188 results on '"Schmidt, Brian P."'
Search Results
2. SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19
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Beckman, Danielle, Bonillas, Alyssa, Diniz, Giovanne B, Ott, Sean, Roh, Jamin W, Elizaldi, Sonny R, Schmidt, Brian A, Sammak, Rebecca L, Van Rompay, Koen KA, Iyer, Smita S, and Morrison, John H
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Biological Sciences ,Infectious Diseases ,Coronaviruses ,Emerging Infectious Diseases ,Lung ,Neurosciences ,Brain Disorders ,Neurological ,Good Health and Well Being ,Animals ,SARS-CoV-2 ,COVID-19 ,Neuroinflammatory Diseases ,Nervous System Diseases ,Neurons ,Primates ,CP: Microbiology ,CP: Neuroscience ,NHP ,astrocytes ,coronavirus ,macaque ,microglia ,neurotropism ,rhesus ,neuroinflammation ,high-resolution microscopy ,Biochemistry and Cell Biology ,Medical Physiology ,Biological sciences - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can induce a plethora of neurological complications in some patients. However, it is still under debate whether SARS-CoV-2 directly infects the brain or whether CNS sequelae result from systemic inflammatory responses triggered in the periphery. By using high-resolution microscopy, we investigated whether SARS-CoV-2 reaches the brain and how viral neurotropism can be modulated by aging in a non-human primate model of COVID-19. Seven days after infection, SARS-CoV-2 was detected in the olfactory cortex and interconnected regions and was accompanied by robust neuroinflammation and neuronal damage exacerbated in aged, diabetic animals. Our study provides an initial framework for identifying the molecular and cellular mechanisms underlying SARS-CoV-2 neurological complications, which will be essential to reducing both the short- and long-term burden of COVID-19.
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- 2022
3. Rendering Spatial Sound for Interoperable Experiences in the Audio Metaverse
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Jot, Jean-Marc, Audfray, Rémi, Hertensteiner, Mark, and Schmidt, Brian
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Computer Science - Sound ,Electrical Engineering and Systems Science - Audio and Speech Processing - Abstract
Interactive audio spatialization technology previously developed for video game authoring and rendering has evolved into an essential component of platforms enabling shared immersive virtual experiences for future co-presence, remote collaboration and entertainment applications. New wearable virtual and augmented reality displays employ real-time binaural audio computing engines rendering multiple digital objects and supporting the free navigation of networked participants or their avatars through a juxtaposition of environments, real and virtual, often referred to as the Metaverse. These applications require a parametric audio scene programming interface to facilitate the creation and deployment of shared, dynamic and realistic virtual 3D worlds on mobile computing platforms and remote servers. We propose a practical approach for designing parametric 6-degree-of-freedom object-based interactive audio engines to deliver the perceptually relevant binaural cues necessary for audio/visual and virtual/real congruence in Metaverse experiences. We address the effects of room reverberation, acoustic reflectors, and obstacles in both the virtual and real environments, and discuss how such effects may be driven by combinations of pre-computed and real-time acoustic propagation solvers. We envision an open scene description model distilled to facilitate the development of interoperable applications distributed across multiple platforms, where each audio object represents, to the user, a natural sound source having controllable distance, size, orientation, and acoustic radiation properties., Comment: International Conference on Immersive and 3D Audio (i3DA), September 2021
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- 2021
4. Mice expressing fluorescent PAR2 reveal that endocytosis mediates colonic inflammation and pain
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Latorre, Rocco, Hegron, Alan, Peach, Chloe J, Teng, Shavonne, Tonello, Raquel, Retamal, Jeffri S, Klein-Cloud, Rafael, Bok, Diana, Jensen, Dane D, Gottesman-Katz, Lena, Rientjes, Jeanette, Veldhuis, Nicholas A, Poole, Daniel P, Thomsen, Alex RB, Schmidt, Brian L, Pothoulakis, Charalabos H, Rankin, Carl, Xie, Ying, Koon, Wai, and Bunnett, Nigel W
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Digestive Diseases ,Biotechnology ,Pain Research ,Chronic Pain ,Neurosciences ,2.1 Biological and endogenous factors ,Aetiology ,Animals ,Arrestins ,Cell Membrane ,Colon ,Endocytosis ,Endosomes ,Female ,Fluorescent Dyes ,Ganglia ,Spinal ,Humans ,Inflammation ,Mice ,Mice ,Inbred C57BL ,Nociception ,Pain ,Receptor ,PAR-2 ,Signal Transduction ,signaling ,receptors ,proteases ,endocytosis ,inflammation - Abstract
G protein-coupled receptors (GPCRs) regulate many pathophysiological processes and are major therapeutic targets. The impact of disease on the subcellular distribution and function of GPCRs is poorly understood. We investigated trafficking and signaling of protease-activated receptor 2 (PAR2) in colitis. To localize PAR2 and assess redistribution during disease, we generated knockin mice expressing PAR2 fused to monomeric ultrastable green fluorescent protein (muGFP). PAR2-muGFP signaled and trafficked normally. PAR2 messenger RNA was detected at similar levels in Par2-mugfp and wild-type mice. Immunostaining with a GFP antibody and RNAScope in situ hybridization using F2rl1 (PAR2) and Gfp probes revealed that PAR2-muGFP was expressed in epithelial cells of the small and large intestine and in subsets of enteric and dorsal root ganglia neurons. In healthy mice, PAR2-muGFP was prominently localized to the basolateral membrane of colonocytes. In mice with colitis, PAR2-muGFP was depleted from the plasma membrane of colonocytes and redistributed to early endosomes, consistent with generation of proinflammatory proteases that activate PAR2 PAR2 agonists stimulated endocytosis of PAR2 and recruitment of Gαq, Gαi, and β-arrestin to early endosomes of T84 colon carcinoma cells. PAR2 agonists increased paracellular permeability of colonic epithelial cells, induced colonic inflammation and hyperalgesia in mice, and stimulated proinflammatory cytokine release from segments of human colon. Knockdown of dynamin-2 (Dnm2), the major colonocyte isoform, and Dnm inhibition attenuated PAR2 endocytosis, signaling complex assembly and colonic inflammation and hyperalgesia. Thus, PAR2 endocytosis sustains protease-evoked inflammation and nociception and PAR2 in endosomes is a potential therapeutic target for colitis.
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- 2022
5. Early post-infection treatment of SARS-CoV-2 infected macaques with human convalescent plasma with high neutralizing activity had no antiviral effects but moderately reduced lung inflammation
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Van Rompay, Koen KA, Olstad, Katherine J, Sammak, Rebecca L, Dutra, Joseph, Watanabe, Jennifer K, Usachenko, Jodie L, Immareddy, Ramya, Roh, Jamin W, Verma, Anil, Lakshmanappa, Yashavanth Shaan, Schmidt, Brian A, Di Germanio, Clara, Rizvi, Nabeela, Liu, Hongwei, Ma, Zhong-Min, Stone, Mars, Simmons, Graham, Dumont, Larry J, Allen, A Mark, Lockwood, Sarah, Pollard, Rachel E, de Assis, Rafael Ramiro, Yee, JoAnn L, Nham, Peter B, Ardeshir, Amir, Deere, Jesse D, Jain, Aarti, Felgner, Philip L, Coffey, Lark L, Iyer, Smita S, Hartigan-O’Connor, Dennis J, Busch, Michael P, and Reader, J Rachel
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Pneumonia & Influenza ,Infectious Diseases ,Coronaviruses Therapeutics and Interventions ,Immunization ,Emerging Infectious Diseases ,Coronaviruses ,Lung ,Infection ,Good Health and Well Being ,Animals ,Antibodies ,Neutralizing ,Antiviral Agents ,COVID-19 ,Humans ,Immunization ,Passive ,Macaca mulatta ,RNA ,Viral ,SARS-CoV-2 ,COVID-19 Serotherapy ,Microbiology ,Virology ,Medical microbiology - Abstract
Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable but low levels of antiviral antibodies after infusion. In comparison to the control animals, CCP-treated animals had similar levels of viral RNA in upper and lower respiratory tract secretions, similar detection of viral RNA in lung tissues by in situ hybridization, but lower amounts of infectious virus in the lungs. CCP-treated animals had a moderate, but statistically significant reduction in interstitial pneumonia, as measured by comprehensive lung histology. Thus overall, therapeutic benefits of CCP were marginal and inferior to results obtained earlier with monoclonal antibodies in this animal model. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses.
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- 2022
6. SkyMapper Optical Follow-up of Gravitational Wave Triggers: Alert Science Data Pipeline and LIGO/Virgo O3 Run
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Chang, Seo-Won, Onken, Christopher A., Wolf, Christian, Luvaul, Lance, Möller, Anais, Scalzo, Richard, Schmidt, Brian P., Scott, Susan M., Sura, Nikunj, and Yuan, Fang
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
We present an overview of the SkyMapper optical follow-up program for gravitational-wave event triggers from the LIGO/Virgo observatories, which aims at identifying early GW170817-like kilonovae out to $\sim 200$ Mpc distance. We describe our robotic facility for rapid transient follow-up, which can target most of the sky at $\delta<+10\deg $ to a depth of $i_\mathrm{AB}\approx 20$ mag. We have implemented a new software pipeline to receive LIGO/Virgo alerts, schedule observations and examine the incoming real-time data stream for transient candidates. We adopt a real-bogus classifier using ensemble-based machine learning techniques, attaining high completeness ($\sim$98%) and purity ($\sim$91%) over our whole magnitude range. Applying further filtering to remove common image artefacts and known sources of transients, such as asteroids and variable stars, reduces the number of candidates by a factor of more than 10. We demonstrate the system performance with data obtained for GW190425, a binary neutron star merger detected during the LIGO/Virgo O3 observing campaign. In time for the LIGO/Virgo O4 run, we will have deeper reference images allowing transient detection to $i_\mathrm{AB}\approx $21 mag., Comment: 13 pages, 6 figures, Accepted for publication in PASA
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- 2021
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7. SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma
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Deere, Jesse D, Carroll, Timothy D, Dutra, Joseph, Fritts, Linda, Sammak, Rebecca Lee, Yee, JoAnn L, Olstad, Katherine J, Reader, J Rachel, Kistler, Amy, Kamm, Jack, Di Germanio, Clara, Lakshmanappa, Yashavanth Shaan, Elizaldi, Sonny R, Roh, Jamin W, Simmons, Graham, Watanabe, Jennifer, Pollard, Rachel E, Usachenko, Jodie, Immareddy, Ramya, Schmidt, Brian A, O’Connor, Shelby L, DeRisi, Joseph, Busch, Michael P, Iyer, Smita S, Van Rompay, Koen KA, Hartigan-O’Connor, Dennis J, and Miller, Christopher J
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Microbiology ,Biological Sciences ,Coronaviruses Therapeutics and Interventions ,Coronaviruses ,Lung ,Vaccine Related ,Immunization ,Emerging Infectious Diseases ,Infectious Diseases ,Infection ,Good Health and Well Being ,Animals ,Antibodies ,Neutralizing ,Antibodies ,Viral ,Antiviral Agents ,COVID-19 ,Disease Models ,Animal ,Humans ,Immunity ,Immunization ,Passive ,Macaca mulatta ,Pandemics ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,Viral Load ,Virus Replication ,convalescent plasma ,passive immunization ,nonhuman primate ,animal models of infectious diseases ,microbial pathogenesis ,virology - Abstract
Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection.
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- 2021
8. Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation.
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Verma, Anil, Hawes, Chase E, Lakshmanappa, Yashavanth Shaan, Roh, Jamin W, Schmidt, Brian A, Dutra, Joseph, Louie, William, Liu, Hongwei, Ma, Zhong-Min, Watanabe, Jennifer K, Usachenko, Jodie L, Immareddy, Ramya, Sammak, Rebecca L, Pollard, Rachel, Reader, J Rachel, Olstad, Katherine J, Coffey, Lark L, Kozlowski, Pamela A, Hartigan-O'Connor, Dennis J, Nussenzweig, Michel, Van Rompay, Koen KA, Morrison, John H, and Iyer, Smita S
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NeuroCOVID ,inflammation ,SARS-CoV-2 ,cerebrospinal fluid ,effector CD4 T cells ,interstitial pneumonia ,lymph node ,neuroinflammation ,pathogenesis ,rhesus macaques ,Aging ,Animals ,Antibodies ,Monoclonal ,COVID-19 ,Diabetes Complications ,Diabetes Mellitus ,Experimental ,Female ,Humans ,Lymphocyte Activation ,Macaca mulatta ,Male ,Neuritis ,Pre-Exposure Prophylaxis ,T-Lymphocytes ,Virus Replication ,Prevention ,Biodefense ,Infectious Diseases ,Pneumonia ,Immunization ,Biotechnology ,Pneumonia & Influenza ,Emerging Infectious Diseases ,Lung ,Diabetes ,Vaccine Related ,receptor binding domain ,aged ,type 2 diabetic ,neutrophils ,mucosal-associated invariant T cells ,Biochemistry and Cell Biology ,Medical Physiology - Abstract
Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure.
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- 2021
9. Early treatment with a combination of two potent neutralizing antibodies improves clinical outcomes and reduces virus replication and lung inflammation in SARS-CoV-2 infected macaques.
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Van Rompay, Koen KA, Olstad, Katherine J, Sammak, Rebecca L, Dutra, Joseph, Watanabe, Jennifer K, Usachenko, Jodie L, Immareddy, Ramya, Verma, Anil, Shaan Lakshmanappa, Yashavanth, Schmidt, Brian A, Roh, Jamin W, Elizaldi, Sonny R, Allen, A Mark, Muecksch, Frauke, Lorenzi, Julio CC, Lockwood, Sarah, Pollard, Rachel E, Yee, JoAnn L, Nham, Peter B, Ardeshir, Amir, Deere, Jesse D, Patterson, Jean, Dang, Que, Hatziioannou, Theodora, Bieniasz, Paul D, Iyer, Smita S, Hartigan-O'Connor, Dennis J, Nussenzweig, Michel C, and Reader, J Rachel
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Virology ,Microbiology ,Immunology ,Medical Microbiology - Abstract
There is an urgent need for effective therapeutic interventions against SARS-CoV-2, including new variants that continue to arise. Neutralizing monoclonal antibodies have shown promise in clinical studies. We investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, C135-LS and C144-LS that carry half-life extension mutations, in the rhesus macaque model of COVID-19. Twelve young adult macaques (three groups of four animals) were inoculated intranasally and intra-tracheally with a high dose of SARS-CoV-2 and 24 hours later, treated intravenously with a high (40 mg/kg) or low (12 mg/kg) dose of the C135-LS and C144-LS antibody combination, or a control monoclonal antibody. Animals were monitored for 7 days. Compared to the control animals, animals treated with either dose of the anti-SARS-CoV-2 antibodies showed similarly improved clinical scores, lower levels of virus replication in upper and lower respiratory tract, and significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. In conclusion, this study provides proof-of-concept in support of further clinical development of these monoclonal antibodies against COVID-19 during early infection.
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- 2021
10. SkyMapper Southern Survey: Second Data Release (DR2)
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Onken, Christopher A., Wolf, Christian, Bessell, Michael S., Chang, Seo-Won, Da Costa, Gary S., Luvaul, Lance C., Mackey, Dougal, Schmidt, Brian P., and Shao, Li
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Astrophysics of Galaxies ,Astrophysics - Solar and Stellar Astrophysics - Abstract
We present the second data release (DR2) of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia, using six optical filters: $u,v,g,r,i,z$. DR2 is the first release to go beyond the $\sim$18mag (10${\sigma}$) limit of the Shallow Survey released in DR1, and includes portions of the sky at full survey depth that reach >21mag in $g$ and $r$ filters. The DR2 photometry has a precision as measured by internal reproducibility of 1% in $u$ and $v$, and 0.7% in $griz$. More than 21 000 deg$^2$ have data in some filters (at either Shallow or Main Survey depth) and over 7 000 deg$^2$ have deep Main Survey coverage in all six filters. Finally, about 18 000 deg$^2$ have Main Survey data in $i$ and $z$ filters, albeit not yet at full depth. The release contains over 120 000 images, as well as catalogues with over 500 million unique astrophysical objects and nearly 5 billion individual detections. It also contains cross-matches with a range of external catalogues such as Gaia DR2, Pan-STARRS1 DR1, GALEX GUVcat, 2MASS, and AllWISE, as well as spectroscopic surveys such as 2MRS, GALAH, 6dFGS, and 2dFLenS., Comment: 21 pages, 17 figures. As of 25 Aug 2020, DR2 is available to the world at http://skymapper.anu.edu.au
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- 2020
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11. Ultra-luminous quasars at redshift $z>4.5$ from SkyMapper
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Wolf, Christian, Hon, Wei Jeat, Bian, Fuyan, Onken, Christopher A., Alonzi, Noura, Bessell, Michael A., Li, Zefeng, Schmidt, Brian P., and Tisserand, Patrick
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Astrophysics - Astrophysics of Galaxies - Abstract
The most luminous quasars at high redshift harbour the fastest-growing and most massive black holes in the early Universe. They are exceedingly rare and hard to find. Here, we present our search for the most luminous quasars in the redshift range from $z=4.5$ to $5$ using data from SkyMapper, Gaia and WISE. We use colours to select likely high-redshift quasars and reduce the stellar contamination of the candidate set with parallax and proper motion data. In $\sim$12,500~deg$^2$ of Southern sky, we find 92 candidates brighter than $R_p=18.2$. Spectroscopic follow-up has revealed 21 quasars at $z\ge 4$ (16 of which are within $z=[4.5,5]$), as well as several red quasars, BAL quasars and objects with unusual spectra, which we tentatively label OFeLoBALQSOs at redshifts of $z\approx 1$ to $2$. This work lifts the number of known bright $z\ge 4.5$ quasars in the Southern hemisphere from 10 to 26 and brings the total number of quasars known at $R_p<18.2$ and $z\ge 4.5$ to 42., Comment: Submitted to MNRAS, 10 pages
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- 2019
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12. SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques.
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Shaan Lakshmanappa, Yashavanth, Elizaldi, Sonny R, Roh, Jamin W, Schmidt, Brian A, Carroll, Timothy D, Weaver, Kourtney D, Smith, Justin C, Verma, Anil, Deere, Jesse D, Dutra, Joseph, Stone, Mars, Franz, Sergej, Sammak, Rebecca Lee, Olstad, Katherine J, Rachel Reader, J, Ma, Zhong-Min, Nguyen, Nancy K, Watanabe, Jennifer, Usachenko, Jodie, Immareddy, Ramya, Yee, JoAnn L, Weiskopf, Daniela, Sette, Alessandro, Hartigan-O'Connor, Dennis, McSorley, Stephen J, Morrison, John H, Tran, Nam K, Simmons, Graham, Busch, Michael P, Kozlowski, Pamela A, Van Rompay, Koen KA, Miller, Christopher J, and Iyer, Smita S
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Germinal Center ,Th1 Cells ,Cell Line ,Vero Cells ,Animals ,Macaca mulatta ,Humans ,Disease Models ,Animal ,Immunoglobulin G ,Phosphoproteins ,Antibodies ,Viral ,Immunization ,Passive ,Female ,Male ,Immunity ,Humoral ,Spike Glycoprotein ,Coronavirus ,Immunogenicity ,Vaccine ,Chlorocebus aethiops ,COVID-19 ,SARS-CoV-2 ,Coronavirus Nucleocapsid Proteins ,T Follicular Helper Cells ,Disease Models ,Animal ,Antibodies ,Viral ,Immunization ,Passive ,Immunity ,Humoral ,Spike Glycoprotein ,Coronavirus ,Immunogenicity ,Vaccine - Abstract
CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC Tfh cells specific for the SARS-CoV-2 spike and nucleocapsid proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Collectively, the data show induction of GC responses in a rhesus model of mild COVID-19.
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- 2021
13. Oral health-related quality of life after radiation therapy for head and neck cancer: the OraRad study
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Patton, Lauren L., Helgeson, Erika S., Brennan, Michael T., Treister, Nathaniel S., Sollecito, Thomas P., Schmidt, Brian L., Lin, Alexander, Chera, Bhishamjit S., and Lalla, Rajesh V.
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- 2023
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14. Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.
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Verma, Anil, Schmidt, Brian A, Elizaldi, Sonny R, Nguyen, Nancy K, Walter, Korey A, Beck, Zoltan, Trinh, Hung V, Dinasarapu, Ashok R, Lakshmanappa, Yashavanth Shaan, Rane, Niharika N, Matyas, Gary R, Rao, Mangala, Shen, Xiaoying, Tomaras, Georgia D, LaBranche, Celia C, Reimann, Keith A, Foehl, David H, Gach, Johannes S, Forthal, Donald N, Kozlowski, Pamela A, Amara, Rama R, and Iyer, Smita S
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Germinal Center ,B-Lymphocytes ,Th1 Cells ,Animals ,Macaca mulatta ,Humans ,HIV-1 ,Saponins ,Lipid A ,Immunoglobulin G ,AIDS Vaccines ,Adjuvants ,Immunologic ,HIV Antibodies ,Immunization ,Secondary ,Female ,CD4 ,Tfh ,adjuvant ,antibody ,vaccine ,T-fh ,Infectious Diseases ,Vaccine Related (AIDS) ,Prevention ,HIV/AIDS ,Immunization ,Biotechnology ,Vaccine Related ,3.4 Vaccines ,Infection ,Virology ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences - Abstract
Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine.
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- 2020
15. Carnegie Supernova Project-II: Extending the Near-Infrared Hubble Diagram for Type Ia Supernovae to $z\sim0.1$
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Phillips, M. M., Contreras, Carlos, Hsiao, E. Y., Morrell, Nidia, Burns, Christopher R., Stritzinger, Maximilian, Ashall, C., Freedman, Wendy L., Hoeflich, P., Persson, S. E., Piro, Anthony L., Suntzeff, Nicholas B., Uddin, Syed A., Anais, Jorge, Baron, E., Busta, Luis, Campillay, Abdo, Castellón, Sergio, Corco, Carlos, Diamond, T., Gall, Christa, Gonzalez, Consuelo, Holmbo, Simon, Krisciunas, Kevin, Roth, Miguel, Serón, Jacqueline, Taddia, F., Torres, Simón, Anderson, J. P., Baltay, C., Folatelli, Gastón, Galbany, L., Goobar, A., Hadjiyska, Ellie, Hamuy, Mario, Kasliwal, Mansi, Lidman, C., Nugent, Peter E., Perlmutter, S., Rabinowitz, David, Ryder, Stuart D., Schmidt, Brian P., Shappee, B. J., and Walker, Emma S.
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Astrophysics - High Energy Astrophysical Phenomena - Abstract
The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a "Cosmology" sample of $\sim100$ Type Ia supernovae located in the smooth Hubble flow ($0.03 \lesssim z \lesssim 0.10$). Light curves were also obtained of a "Physics" sample composed of 90 nearby Type Ia supernovae at $z \leq 0.04$ selected for near-infrared spectroscopic time-series observations. The primary emphasis of the CSP-II is to use the combination of optical and near-infrared photometry to achieve a distance precision of better than 5%. In this paper, details of the supernova sample, the observational strategy, and the characteristics of the photometric data are provided. In a companion paper, the near-infrared spectroscopy component of the project is presented., Comment: 43 pages, 10 figures, accepted for publication in PASP
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- 2018
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16. Discovery of the most ultra-luminous QSO using Gaia, SkyMapper and WISE
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Wolf, Christian, Bian, Fuyan, Onken, Christopher A., Schmidt, Brian P., Tisserand, Patrick, Alonzi, Noura, Hon, Wei Jeat, and Tonry, John L.
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We report the discovery of the ultra-luminous QSO SMSS~J215728.21-360215.1 with magnitude $z=16.9$ and W4$=7.42$ at redshift 4.75. Given absolute magnitudes of $M_{145,\rm AB}=-29.3$, $M_{300,\rm AB}=-30.12$ and $\log L_{\rm bol}/L_{\rm bol,\odot} = 14.84$, it is the QSO with the highest unlensed UV-optical luminosity currently known in the Universe. It was found by combining proper-motion data from Gaia DR2 with photometry from SkyMapper DR1 and the Wide-field Infrared Survey Explorer (WISE). In the Gaia database it is an isolated single source and thus unlikely to be strongly gravitationally lensed. It is also unlikely to be a beamed source as it is not discovered in the radio domain by either NVSS or SUMSS. It is classed as a weak-emission-line QSO and possesses broad absorption line features. A lightcurve from ATLAS spanning the time from October 2015 to December 2017 shows little sign of variability., Comment: 6 pages, 4 figures, accepted for publication in PASA
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- 2018
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17. Discovery of two bright $z\sim5$ quasars with SkyMapper, Pan-STARRS1 and WISE
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Li, Zefeng, Wolf, Christian, Bian, Fuyan, Onken, Christopher A., Schmidt, Brian P., Tisserand, Patrick, Alonzi, Noura, and Hon, Wei Jeat
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Astrophysics - Astrophysics of Galaxies - Abstract
We present a search for bright $z\sim5$ quasars using imaging data from SkyMapper Southern Survey, Pan-STARRS1 and the Wide-field Infrared Survey Explorer (WISE). We select two sets of candidates using WISE with optical bands from SkyMapper and alternatively from Pan-STARRS1, limited to a magnitude of $i<18.2$. We follow up several candidates with spectroscopy and find that the four candidates common to both lists are quasars, while others turned out to be cool stars. Two of the four quasars, SMSS J013539.27-212628.4 at $z=4.86$ and SMSS J093032.58-221207.7 at $z=4.94$, are new discoveries and ranked among the dozen brightest known $z>4.5$ QSOs in the $i$-band., Comment: 7 pages, 4 figures; submitted to PASA, couple of typos fixed in the arXiv version
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- 2018
18. SN 2012fr: Ultraviolet, Optical, and Near-Infrared Light Curves of a Type Ia Supernova Observed Within a Day of Explosion
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Contreras, Carlos, Phillips, M. M., Burns, Christopher R., Piro, Anthony L., Shappee, B. J., Stritzinger, Maximilian D., Baltay, C., Brown, Peter J., Conseil, Emmanuel, Klotz, Alain, Nugent, Peter E., Turpin, Damien, Parker, Stu, Rabinowitz, D., Hsiao, Eric Y., Morrell, Nidia, Campillay, Abdo, Castellón, Sergio, Corco, Carlos, González, Consuelo, Krisciunas, Kevin, Serón, Jacqueline, Tucker, Brad E., Walker, E. S., Baron, E., Cain, C., Childress, Michael J., Folatelli, Gastón, Freedman, Wendy L., Hamuy, Mario, Hoeflich, P., Persson, S. E., Scalzo, Richard, Schmidt, Brian, and Suntzeff, Nicholas B.
- Subjects
Astrophysics - High Energy Astrophysical Phenomena - Abstract
We present detailed ultraviolet, optical and near-infrared light curves of the Type Ia supernova (SN) 2012fr, which exploded in the Fornax cluster member NGC 1365. These precise high-cadence light curves provide a dense coverage of the flux evolution from $-$12 to $+$140 days with respect to the epoch of $B$-band maximum (\tmax). Supplementary imaging at the earliest epochs reveals an initial slow, nearly linear rise in luminosity with a duration of $\sim$2.5 days, followed by a faster rising phase that is well reproduced by an explosion model with a moderate amount of $^{56}$Ni mixing in the ejecta. From an analysis of the light curves, we conclude: $(i)$ explosion occurred $< 22$ hours before the first detection of the supernova, $(ii)$ the rise time to peak bolometric ($\lambda > 1800 $\AA) luminosity was $16.5 \pm 0.6$ days, $(iii)$ the supernova suffered little or no host-galaxy dust reddening, $(iv)$ the peak luminosity in both the optical and near-infrared was consistent with the bright end of normal Type Ia diversity, and $(v)$ $0.60 \pm 0.15 M_{\odot}$ of $^{56}$Ni was synthesized in the explosion. Despite its normal luminosity, SN 2012fr displayed unusually prevalent high-velocity \ion{Ca}{2} and \ion{Si}{2} absorption features, and a nearly constant photospheric velocity of the \ion{Si}{2} $\lambda$6355 line at $\sim$12,000 \kms\ beginning $\sim$5 days before \tmax. Other peculiarities in the early phase photometry and the spectral evolution are highlighted. SN 2012fr also adds to a growing number of Type Ia supernovae hosted by galaxies with direct Cepheid distance measurements., Comment: 88 pages, 29 figures, 12 tables
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- 2018
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19. SkyMapper Southern Survey: First Data Release (DR1)
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Wolf, Christian, Onken, Christopher A., Luvaul, Lance C., Schmidt, Brian P., Bessell, Michael S., Chang, Seo-Won, Da Costa, Gary S., Mackey, Dougal, Martin-Jones, Tony, Murphy, Simon J., Preston, Tim, Scalzo, Richard A., Shao, Li, Smillie, Jon, Tisserand, Patrick, White, Marc C., and Yuan, Fang
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Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
We present the first data release (DR1) of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia. Here, we present the survey strategy, data processing, catalogue construction and database schema. The DR1 dataset includes over 66,000 images from the Shallow Survey component, covering an area of 17,200 deg$^2$ in all six SkyMapper passbands $uvgriz$, while the full area covered by any passband exceeds 20,000 deg$^2$. The catalogues contain over 285 million unique astrophysical objects, complete to roughly 18 mag in all bands. We compare our $griz$ point-source photometry with PanSTARRS1 DR1 and note an RMS scatter of 2%. The internal reproducibility of SkyMapper photometry is on the order of 1%. Astrometric precision is better than 0.2 arcsec based on comparison with Gaia DR1. We describe the end-user database, through which data are presented to the world community, and provide some illustrative science queries., Comment: 31 pages, 19 figures, 10 tables, PASA, accepted
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- 2018
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20. Comparison of sampling methods for profiling cervicovaginal microbiome in rhesus macaques
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Schmidt, Brian A, Phillips, Ronald, Rolston, Matthew, Raeman, Reben, and Iyer, Smita S
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Veterinary Sciences ,Agricultural ,Veterinary and Food Sciences ,Genetics ,Vaccine Related ,Immunization ,Human Genome ,Biotechnology ,Prevention ,HIV/AIDS ,Good Health and Well Being ,Animals ,Bacteria ,Cervix Uteri ,Female ,Macaca mulatta ,Microbiota ,Specimen Handling ,Vagina ,16S rRNA ,HIV ,lavage ,swab ,Zoology ,Virology ,Veterinary sciences - Abstract
Cervicovaginal bacteria cause inflammation which in turn increases HIV risk. Profiling the cervicovaginal microbiome, therefore, is instrumental for vaccine development. We show that the microbiome profile captured by cervicovaginal lavage is comparable to samples obtained by vaginal swabs. Thus, lavage may serve as a sampling strategy in NHP vaccine studies.
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- 2019
21. Spatial summation of individual cones in human color vision.
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Schmidt, Brian, Boehm, Alexandra, Tuten, William, and Roorda, Austin
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Adult ,Color ,Color Perception ,Color Vision ,Female ,Fovea Centralis ,Humans ,Male ,Retina ,Retinal Cone Photoreceptor Cells - Abstract
The human retina contains three classes of cone photoreceptors each sensitive to different portions of the visual spectrum: long (L), medium (M) and short (S) wavelengths. Color information is computed by downstream neurons that compare relative activity across the three cone types. How cone signals are combined at a cellular scale has been more difficult to resolve. This is especially true near the fovea, where spectrally-opponent neurons in the parvocellular pathway draw excitatory input from a single cone and thus even the smallest stimulus projected through natural optics will engage multiple color-signaling neurons. We used an adaptive optics microstimulator to target individual and pairs of cones with light. Consistent with prior work, we found that color percepts elicited from individual cones were predicted by their spectral sensitivity, although there was considerable variability even between cones within the same spectral class. The appearance of spots targeted at two cones were predicted by an average of their individual activations. However, two cones of the same subclass elicited percepts that were systematically more saturated than predicted by an average. Together, these observations suggest both spectral opponency and prior experience influence the appearance of small spots.
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- 2019
22. Carnegie Supernova Project-II: Extending the Near-infrared Hubble Diagram for Type Ia Supernovae to z ∼ 0.1∗ ∗ This paper includes data gathered with the 6.5 meter Magellan telescopes at Las Campanas Observatory, Chile.
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Phillips, MM, Contreras, Carlos, Hsiao, EY, Morrell, Nidia, Burns, Christopher R, Stritzinger, Maximilian, Ashall, C, Freedman, Wendy L, Hoeflich, P, Persson, SE, Piro, Anthony L, Suntzeff, Nicholas B, Uddin, Syed A, Anais, Jorge, Baron, E, Busta, Luis, Campillay, Abdo, Castellón, Sergio, Corco, Carlos, Diamond, T, Gall, Christa, Gonzalez, Consuelo, Holmbo, Simon, Krisciunas, Kevin, Roth, Miguel, Serón, Jacqueline, Taddia, F, Torres, Simón, Anderson, JP, Baltay, C, Folatelli, Gastón, Galbany, L, Goobar, A, Hadjiyska, Ellie, Hamuy, Mario, Kasliwal, Mansi, Lidman, C, Nugent, Peter E, Perlmutter, S, Rabinowitz, David, Ryder, Stuart D, Schmidt, Brian P, Shappee, BJ, and Walker, Emma S
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Space Sciences ,Physical Sciences ,cosmology: observations ,galaxies: distances and redshifts ,(stars:) supernovae: general Online material: color figures ,astro-ph.HE ,Astronomical and Space Sciences ,Astronomy & Astrophysics ,Astronomical sciences ,Particle and high energy physics - Abstract
The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a “Cosmology” sample of ∼100 TypeIa supernovae located in the smooth Hubble flow (0.03
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- 2019
23. Review of applications and challenges of quantitative systems pharmacology modeling and machine learning for heart failure
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Cheng, Limei, Qiu, Yuchi, Schmidt, Brian J., and Wei, Guo-Wei
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- 2022
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24. Oral cancer induced TRPV1 sensitization is mediated by PAR2 signaling in primary afferent neurons innervating the cancer microenvironment
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Scheff, Nicole N., Wall, Ian M., Nicholson, Sam, Williams, Hannah, Chen, Elyssa, Tu, Nguyen H., Dolan, John C., Liu, Cheng Z., Janal, Malvin N., Bunnett, Nigel W., and Schmidt, Brian L.
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- 2022
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25. Oral cancer patients experience mechanical and chemical sensitivity at the site of the cancer
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Sawicki, Caroline M., Janal, Malvin N., Nicholson, Samuel J., Wu, Angie K., Schmidt, Brian L., and Albertson, Donna G.
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- 2022
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26. Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice
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De Logu, Francesco, Nassini, Romina, Hegron, Alan, Landini, Lorenzo, Jensen, Dane D., Latorre, Rocco, Ding, Julia, Marini, Matilde, Souza Monteiro de Araujo, Daniel, Ramírez-Garcia, Paulina, Whittaker, Michael, Retamal, Jeffri, Titiz, Mustafa, Innocenti, Alessandro, Davis, Thomas P., Veldhuis, Nicholas, Schmidt, Brian L., Bunnett, Nigel W., and Geppetti, Pierangelo
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- 2022
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27. A blinded determination of $H_0$ from low-redshift Type Ia supernovae, calibrated by Cepheid variables
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Zhang, Bonnie R., Childress, Michael J., Davis, Tamara M., Karpenka, Natallia V., Lidman, Chris, Schmidt, Brian P., and Smith, Mathew
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Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
Presently a ${>}3\sigma$ tension exists between values of the Hubble constant $H_0$ derived from analysis of fluctuations in the Cosmic Microwave Background by Planck, and local measurements of the expansion using calibrators of type Ia supernovae (SNe Ia). We perform a blinded reanalysis of Riess et al. 2011 to measure $H_0$ from low-redshift SNe Ia, calibrated by Cepheid variables and geometric distances including to NGC 4258. This paper is a demonstration of techniques to be applied to the Riess et at. 2016 data. Our end-to-end analysis starts from available CfA3 and LOSS photometry, providing an independent validation of Riess et al. 2011. We obscure the value of $H_0$ throughout our analysis and the first stage of the referee process, because calibration of SNe Ia requires a series of often subtle choices, and the potential for results to be affected by human bias is significant. Our analysis departs from that of Riess et al. 2011 by incorporating the covariance matrix method adopted in SNLS and JLA to quantify SN Ia systematics, and by including a simultaneous fit of all SN Ia and Cepheid data. We find $H_0 = 72.5 \pm 3.1$ (stat) $\pm 0.77$ (sys) km s$^{-1}$ Mpc$^{-1}$ with a three-galaxy (NGC 4258+LMC+MW) anchor. The relative uncertainties are 4.3% statistical, 1.1% systematic, and 4.4% total, larger than in Riess et al. 2011 (3.3% total) and the Efstathiou 2014 reanalysis (3.4% total). Our error budget for $H_0$ is dominated by statistical errors due to the small size of the supernova sample, whilst the systematic contribution is dominated by variation in the Cepheid fits, and for the SNe Ia, uncertainties in the host galaxy mass dependence and Malmquist bias., Comment: 38 pages, 13 figures, 13 tables; accepted for publication in MNRAS
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- 2017
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28. The SkyMapper Transient Survey
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Scalzo, Richard, Yuan, Fang, Childress, Michael J., Moller, Anais, Schmidt, Brian, Tucker, Brad E., Zhang, Bonnie, Astier, Pierre, Betoule, Marc, and Regnault, Nicolas
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Cosmology and Nongalactic Astrophysics ,Astrophysics - High Energy Astrophysical Phenomena - Abstract
The SkyMapper 1.3 m telescope at Siding Spring Observatory has now begun regular operations. Alongside the Southern Sky Survey, a comprehensive digital survey of the entire southern sky, SkyMapper will carry out a search for supernovae and other transients. The search strategy, covering a total footprint area of ~2000 deg2 with a cadence of $\leq 5$ days, is optimised for discovery and follow-up of low-redshift type Ia supernovae to constrain cosmic expansion and peculiar velocities. We describe the search operations and infrastructure, including a parallelised software pipeline to discover variable objects in difference imaging; simulations of the performance of the survey over its lifetime; public access to discovered transients; and some first results from the Science Verification data., Comment: 13 pages, 11 figures; submitted to PASA
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- 2017
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29. Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation
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Mulpuri, Yatendra, Marty, Vincent N, Munier, Joseph J, Mackie, Ken, Schmidt, Brian L, Seltzman, Herbert H, and Spigelman, Igor
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Neurodegenerative ,Cancer ,Peripheral Neuropathy ,Chronic Pain ,Pain Research ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Analgesics ,Non-Narcotic ,Animals ,Antineoplastic Agents ,Cannabinoid Receptor Modulators ,Cannabinoids ,Cisplatin ,Cold Temperature ,Dose-Response Relationship ,Drug ,Drug Tolerance ,Female ,Ganglia ,Spinal ,Gene Expression Regulation ,Hyperalgesia ,Male ,Peripheral Nervous System Diseases ,RNA ,Messenger ,Rats ,Sprague-Dawley ,Receptor ,Cannabinoid ,CB1 ,Receptor ,Cannabinoid ,CB2 ,Touch ,Chemotherapy neuropathy ,Allodynia ,CB1 receptor ,CB2 receptor ,Endocannabinoid enzymes ,Operant behavior ,Tolerance ,Psychology ,Neurology & Neurosurgery ,Pharmacology and pharmaceutical sciences ,Biological psychology - Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy. Results show that local or systemic administration of 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI) dose-dependently suppressed CIPN mechanical and cold allodynia. Orally administered PrNMI also dose-dependently suppressed CIPN allodynia symptoms in both male and female rats without any CNS side effects. Co-administration with selective cannabinoid receptor subtype blockers revealed that PrNMI's anti-allodynic effects are mediated by CB1 receptor (CB1R) activation. Expression of CB2Rs was reduced in dorsal root ganglia from CIPN rats, whereas expression of CB1Rs and various endocannabinoid synthesizing and metabolizing enzymes was unaffected. Daily PrNMI treatment of CIPN rats for two weeks showed a lack of appreciable tolerance to PrNMI's anti-allodynic effects. In an operant task which reflects cerebral processing of pain, PrNMI also dose-dependently suppressed CIPN pain behaviors. Our results demonstrate that PRCBs exemplified by PrNMI may represent a viable option for the treatment of CIPN pain symptoms.
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- 2018
30. Sensations from a single M-cone depend on the activity of surrounding S-cones.
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Schmidt, Brian, Sabesan, Ramkumar, Tuten, William, Neitz, Jay, and Roorda, Austin
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Adult ,Color Perception ,Eye Movements ,Humans ,Male ,Retinal Cone Photoreceptor Cells - Abstract
Color vision requires the activity of cone photoreceptors to be compared in post-receptoral circuitry. Decades of psychophysical measurements have quantified the nature of these comparative interactions on a coarse scale. How such findings generalize to a cellular scale remains unclear. To answer that question, we quantified the influence of surrounding light on the appearance of spots targeted to individual cones. The eyes aberrations were corrected with adaptive optics and retinal position was precisely tracked in real-time to compensate for natural movement. Subjects reported the color appearance of each spot. A majority of L-and M-cones consistently gave rise to the sensation of white, while a smaller group repeatedly elicited hue sensations. When blue sensations were reported they were more likely mediated by M- than L-cones. Blue sensations were elicited from M-cones against a short-wavelength light that preferentially elevated the quantal catch in surrounding S-cones, while stimulation of the same cones against a white background elicited green sensations. In one of two subjects, proximity to S-cones increased the probability of blue reports when M-cones were probed. We propose that M-cone increments excited both green and blue opponent pathways, but the relative activity of neighboring cones favored one pathway over the other.
- Published
- 2018
31. SN 2012fr: Ultraviolet, Optical, and Near-infrared Light Curves of a Type Ia Supernova Observed within a Day of Explosion* * This paper includes data gathered with the 6.5 m Magellan Baade Telescope, located at Las Campanas Observatory, Chile.
- Author
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Contreras, Carlos, Phillips, MM, Burns, Christopher R, Piro, Anthony L, Shappee, BJ, Stritzinger, Maximilian D, Baltay, C, Brown, Peter J, Conseil, Emmanuel, Klotz, Alain, Nugent, Peter E, Turpin, Damien, Parker, Stu, Rabinowitz, D, Hsiao, Eric Y, Morrell, Nidia, Campillay, Abdo, Castellón, Sergio, Corco, Carlos, González, Consuelo, Krisciunas, Kevin, Serón, Jacqueline, Tucker, Brad E, Walker, ES, Baron, E, Cain, C, Childress, Michael J, Folatelli, Gastón, Freedman, Wendy L, Hamuy, Mario, Hoeflich, P, Persson, SE, Scalzo, Richard, Schmidt, Brian, and Suntzeff, Nicholas B
- Subjects
Astronomical Sciences ,Physical Sciences ,supernovae: general ,supernovae: individual ,astro-ph.HE ,Astronomical and Space Sciences ,Atomic ,Molecular ,Nuclear ,Particle and Plasma Physics ,Physical Chemistry (incl. Structural) ,Astronomy & Astrophysics ,Astronomical sciences ,Particle and high energy physics ,Space sciences - Abstract
We present detailed ultraviolet, optical, and near-infrared light curves of the Type Ia supernova (SN) 2012fr, which exploded in the Fornax cluster member NGC 1365. These precise high-cadence light curves provide a dense coverage of the flux evolution from -12 to +140 days with respect to the epoch of B-band maximum (). Supplementary imaging at the earliest epochs reveals an initial slow and nearly linear rise in luminosity with a duration of ∼2.5 days, followed by a faster rising phase that is well reproduced by an explosion model with a moderate amount of 56Ni mixing in the ejecta. From our analysis of the light curves, we conclude that: (i) the explosion occurred 1800) luminosity was 16.5 ±0.6 days, (iii) the supernova suffered little or no host-galaxy dust reddening, (iv) the peak luminosity in both the optical and near-infrared was consistent with the bright end of normal Type Ia diversity, and (v) 0.60 ±0.15 M o of 56Ni was synthesized in the explosion. Despite its normal luminosity, SN 2012fr displayed unusually prevalent high-velocity Ca ii and Si ii absorption features, and a nearly constant photospheric velocity of the Si ii λ6355 line at ∼12,000 that began ∼5 days before . We also highlight some of the other peculiarities in the early phase photometry and the spectral evolution. SN 2012fr also adds to a growing number of Type Ia supernovae that are hosted by galaxies with direct Cepheid distance measurements.
- Published
- 2018
32. Alterations in opioid inhibition cause widespread nociception but do not affect anxiety-like behavior in oral cancer mice
- Author
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Ye, Yi, Bernabé, Daniel G, Salvo, Elizabeth, Viet, Chi T, Ono, Kentaro, Dolan, John C, Janal, Malvin, Aouizerat, Brad E, Miaskowski, Christine, and Schmidt, Brian L
- Subjects
Biomedical and Clinical Sciences ,Biological Psychology ,Neurosciences ,Psychology ,Pharmacology and Pharmaceutical Sciences ,Pain Research ,Behavioral and Social Science ,Dental/Oral and Craniofacial Disease ,Cancer ,Chronic Pain ,Animals ,Anxiety ,Cancer Pain ,Carcinoma ,Squamous Cell ,Cell Line ,Tumor ,Female ,Head and Neck Neoplasms ,Heterografts ,Humans ,Mice ,Mice ,Inbred BALB C ,Nociceptive Pain ,Receptors ,Opioid ,Spinal Cord ,Squamous Cell Carcinoma of Head and Neck ,Tongue Neoplasms ,allodynia ,cancer pain ,anxiety ,head and neck ,widespread pain ,nociception ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
Widespread pain and anxiety are commonly reported in cancer patients. We hypothesize that cancer is accompanied by attenuation of endogenous opioid-mediated inhibition, which subsequently causes widespread pain and anxiety. To test this hypothesis we used a mouse model of oral squamous cell carcinoma (SCC) in the tongue. We found that mice with tongue SCC exhibited widespread nociceptive behaviors in addition to behaviors associated with local nociception that we reported previously. Tongue SCC mice exhibited a pattern of reduced opioid receptor expression in the spinal cord; intrathecal administration of respective mu (MOR), delta (DOR), and kappa (KOR) opioid receptor agonists reduced widespread nociception in mice, except for the fail flick assay following administration of the MOR agonist. We infer from these findings that opioid receptors contribute to widespread nociception in oral cancer mice. Despite significant nociception, mice with tongue SCC did not differ from sham mice in anxiety-like behaviors as measured by the open field assay and elevated maze. No significant differences in c-Fos staining were found in anxiety-associated brain regions in cancer relative to control mice. No correlation was found between nociceptive and anxiety-like behaviors. Moreover, opioid receptor agonists did not yield a statistically significant effect on behaviors measured in the open field and elevated maze in cancer mice. Lastly, we used an acute cancer pain model (injection of cancer supernatant into the mouse tongue) to test whether adaptation to chronic pain is responsible for the absence of greater anxiety-like behavior in cancer mice. No changes in anxiety-like behavior were observed in mice with acute cancer pain.
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- 2017
33. The ANU WiFeS SuperNovA Program (AWSNAP)
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Childress, Michael J., Tucker, Brad E., Yuan, Fang, Scalzo, Richard, Ruiter, Ashley, Seitenzahl, Ivo, Zhang, Bonnie, Schmidt, Brian, Anguiano, Borja, Aniyan, Suryashree, Bayliss, Daniel D. R., Bento, Joao, Bessell, Michael, Bian, Fuyan, Davies, Rebecca, Dopita, Michael, Fogarty, Lisa, Fraser-McKelvie, Amelia, Freeman, Ken, Kuruwita, Rajika, Medling, Anne M., Murphy, Simon J., Owers, Matthew, Panther, Fiona, Sweet, Sarah M., Thomas, Adam D., and Zhou, George
- Subjects
Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Cosmology and Nongalactic Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
This paper presents the first major data release and survey description for the ANU WiFeS SuperNovA Program (AWSNAP). AWSNAP is an ongoing supernova spectroscopy campaign utilising the Wide Field Spectrograph (WiFeS) on the Australian National University (ANU) 2.3m telescope. The first and primary data release of this program (AWSNAP-DR1) releases 357 spectra of 175 unique objects collected over 82 equivalent full nights of observing from July 2012 to August 2015. These spectra have been made publicly available via the WISeREP supernova spectroscopy repository. We analyse the AWSNAP sample of Type Ia supernova spectra, including measurements of narrow sodium absorption features afforded by the high spectral resolution of the WiFeS instrument. In some cases we were able to use the integral-field nature of the WiFeS instrument to measure the rotation velocity of the SN host galaxy near the SN location in order to obtain precision sodium absorption velocities. We also present an extensive time series of SN 2012dn, including a near-nebular spectrum which both confirms its "super-Chandrasekhar" status and enables measurement of the sub-solar host metallicity at the SN site., Comment: Submitted to Publications of the Astronomical Society of Australia (PASA). Spectra publicly released via WISeREP at http://wiserep.weizmann.ac.il/
- Published
- 2016
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34. HATS-22b, HATS-23b and HATS-24b: Three new transiting Super-Jupiters from the HATSouth Project
- Author
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Bento, Joao, Schmidt, Brian, Hartman, Joel, Bakos, Gaspar, Ciceri, Simona, Brahm, Rafael, Bayliss, Daniel, Espinoza, Nestor, Zhou, George, Rabus, Markus, Bhatti, Waqas, Penev, Kaloyan, Csubry, Zoltan, Jordan, Andres, Mancini, Luigi, Henning, Thomas, de Val-Borro, Miguel, Tinney, Chris, Wright, Duncan, Durkan, Stephen, Suc, Vincent, Noyes, Robert, Lazar, Jozsef, Papp, Istvan, and Sari, Pal
- Subjects
Astrophysics - Earth and Planetary Astrophysics - Abstract
We report the discovery of three moderately high-mass transiting hot Jupiters from the HATSouth survey: HATS-22b, HATS-23b and HATS-24b. These planets add to the numbers of known planets in the ~2MJ regime. HATS-22b is a 2.74+/-0.11 MJ mass and 0.953+0.048/-0.029 RJ radius planet orbiting a V = 13.455 +/- 0.040 sub-silar mass (M_star = 0.759+/-0.019 M_sun; R_star = 0.759+/-0.019 R_sun) K-dwarf host star on an eccentric (e = 0.079 +/- 0.026) orbit. This planet's high planet-to-stellar mass ratio is further evidence that migration mechanisms for hot Jupiters may rely on exciting orbital eccentricities that bring planets closer to their parent stars followed by tidal circularisation. HATS-23b is a 1.478 +/- 0.080 MJ mass and 1.69 +/- 0.24 RJ radius planet on a grazing orbit around a V = 13.901 +/- 0.010 G-dwarf with properties very similar to those of the Sun (M_star = 1.115 +/- 0.054 M_sun; R_star = 1.145 +/- 0.070 R_sun). HATS-24b orbits a moderately bright V = 12.830 +/- 0.010 F-dwarf star (M_star = 1.218 +/- 0.036 M_sun; R_star = 1.194+0.066/-0.041 R_sun). This planet has a mass of 2.39 +0.21/-0.12 MJ and an inflated radius of 1.516 +0.085/-0.065 RJ., Comment: 14 pages, 8 figures, MNRAS Accepted for publication
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- 2016
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35. HATS-18 b: An Extreme Short--Period Massive Transiting Planet Spinning Up Its Star
- Author
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Penev, Kaloyan M., Hartman, Joel D., Bakos, Gaspar A., Ciceri, Simona, Brahm, Rafael, Bayliss, Daniel, Bento, Joao, Jord'an, Andr'es, Csubry, Zoltan, Bhatti, W., de Val-Borro, Miguel, Espinoza, Néstor, Zhou, George, Mancini, Luigi, Rabus, Markus, Suc, Vincent, Henning, Thomas, Schmidt, Brian P., Noyes, Robert W., L'az'ar, J., Papp, Istvan, and S'ari, P.
- Subjects
Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
We report the discovery by the HATSouth network of HATS-18 b: a 1.980 +/- 0.077 Mj, 1.337 +0.102 -0.049 Rj planet in a 0.8378 day orbit, around a solar analog star (mass 1.037 +/- 0.047 Msun, and radius 1.020 +0.057 -0.031 Rsun) with V=14.067 +/- 0.040 mag. The high planet mass, combined with its short orbital period, implies strong tidal coupling between the planetary orbit and the star. In fact, given its inferred age, HATS-18 shows evidence of significant tidal spin up, which together with WASP-19 (a very similar system) allows us to constrain the tidal quality factor for Sun-like stars to be in the range 6.5 <= lg(Q*/k_2) <= 7 even after allowing for extremely pessimistic model uncertainties. In addition, the HATS-18 system is among the best systems (and often the best system) for testing a multitude of star--planet interactions, be they gravitational, magnetic or radiative, as well as planet formation and migration theories., Comment: Submitted. 12 pages, 9 figures, 5 tables
- Published
- 2016
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36. The EMBLA Survey -- Metal-poor stars in the Galactic bulge
- Author
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Howes, Louise M., Asplund, Martin, Keller, Stefan C., Casey, Andrew R., Yong, David, Lind, Karin, Frebel, Anna, Hays, Austin, Alves-Brito, Alan, Bessell, Michael S., Casagrande, Luca, Marino, Anna F., Nataf, David M., Owen, Christopher I., Da Costa, Gary S., Schmidt, Brian P., and Tisserand, Patrick
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - Solar and Stellar Astrophysics - Abstract
Cosmological models predict the oldest stars in the Galaxy should be found closest to the centre of the potential well, in the bulge. The EMBLA Survey successfully searched for these old, metal-poor stars by making use of the distinctive SkyMapper photometric filters to discover candidate metal-poor stars in the bulge. Their metal-poor nature was then confirmed using the AAOmega spectrograph on the AAT. Here we present an abundance analysis of 10 bulge stars with -2.8<[Fe/H]<-1.7 from MIKE/Magellan observations, in total determining the abundances of 22 elements. Combining these results with our previous high-resolution data taken as part of the Gaia-ESO Survey, we have started to put together a picture of the chemical and kinematic nature of the most metal-poor stars in the bulge. The currently available kinematic data is consistent with the stars belonging to the bulge, although more accurate measurements are needed to constrain the stars' orbits. The chemistry of these bulge stars deviates from that found in halo stars of the same metallicity. Two notable differences are the absence of carbon-enhanced metal-poor bulge stars, and the alpha-element abundances exhibit a large intrinsic scatter and include stars which are underabundant in these typically enhanced elements., Comment: 20 pages, 16 figures. Accepted to Monthly Notices of the Royal Astronomical Society. Online tables can be found at http://www.astro.lu.se/~louise/data
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- 2016
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37. Light Curves of 213 Type Ia Supernovae from the ESSENCE Survey
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Narayan, Gautham, Rest, Armin, Tucker, Brad E., Foley, Ryan J., Wood-Vasey, W. Michael, Challis, Peter, Stubbs, Christopher W., Kirshner, Robert P., Aguilera, Claudio, Becker, Andrew C., Blondin, Stephane, Clocchiatti, Alejandro, Covarrubias, Ricardo, Damke, Guillermo, Davis, Tamara M., Filippenko, Alexei V., Ganeshalingam, Mohan, Garg, Arti, Garnavich, Peter M., Hicken, Malcolm, Jha, Saurabh W., Krisciunas, Kevin, Leibundgut, Bruno, Li, Weidong, Matheson, Thomas, Miknaitis, Gajus, Pignata, Guiliano, Prieto, Jose Luis, Riess, Adam G., Schmidt, Brian P., Silverman, Jeffrey M., Smith, R. Chris, Sollerman, Jesper, Spyromilio, Jason, Suntzeff, Nicholas B., Tonry, John L., and Zenteno, Alfredo
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Astrophysics - Cosmology and Nongalactic Astrophysics ,Astrophysics - Astrophysics of Galaxies - Abstract
The ESSENCE survey discovered 213 Type Ia supernovae at redshifts 0.1 < z < 0.81 between 2002 and 2008. We present their R and I-band photometry, measured from images obtained using the MOSAIC II camera at the CTIO 4 m Blanco telescope, along with rapid-response spectroscopy for each object. We use our spectroscopic follow-up observations to determine an accurate, quantitative classification and a precise redshift. Through an extensive calibration program we have improved the precision of the CTIO Blanco natural photometric system. We use several empirical metrics to measure our internal photometric consistency and our absolute calibration of the survey. We assess the effect of various potential sources of systematic bias on our measured fluxes, and we estimate that the dominant term in the systematic error budget from the photometric calibration on our absolute fluxes is ~1%., Comment: (40 pages, 21 figures, accepted for publication in ApJS)
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- 2016
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38. UBVRIz Light Curves of 51 Type II Supernovae
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Galbany, Lluís, Hamuy, Mario, Phillips, Mark M., Suntzeff, Nicholas B., Maza, José, de Jaeger, Thomas, Moraga, Tania, González-Gaitán, Santiago, Krisciunas, Kevin, Morrell, Nidia I., Thomas-Osip, Joanna, Krzeminski, Wojtek, González, Luis, Antezana, Roberto, Wischnjewski, Marina, McCarthy, Patrick, Anderson, Joseph P., Gutiérrez, Claudia P., Stritzinger, Maximilian, Folatelli, Gastón, Anguita, Claudio, Galaz, Gaspar, Green, Elisabeth M., Impey, Chris, Kim, Yong-Cheol, Kirhakos, Sofia, Malkan, Mathew A., Mulchaey, John S., Phillips, Andrew C., Pizzella, Alessandro, Prosser, Charles F., Schmidt, Brian P., Schommer, Robert A., Sherry, William, Strolger, Louis-Gregory, Wells, Lisa A., and Williger, Gerard M.
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - High Energy Astrophysical Phenomena - Abstract
We present a compilation of UBV RIz light curves of 51 type II supernovae discovered during the course of four different surveys during 1986 to 2003: the Cerro Tololo Supernova Survey, the Calan/Tololo Supernova Program (C&T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernova Survey (CATS). The photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination, and calibrated from foreground stars. This work presents these photometric data, studies the color evolution using different bands, and explores the relation between the magnitude at maximum brightness and the brightness decline parameter (s) from maximum light through the end of the recombination phase. This parameter is found to be shallower for redder bands and appears to have the best correlation in the B band. In addition, it also correlates with the plateau duration, being thus shorter (longer) for larger (smaller) s values., Comment: 110 pages, 9 Figures, 6 Tables, accepted in AJ
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- 2015
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39. OPRM1 Methylation Contributes to Opioid Tolerance in Cancer Patients
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Viet, Chi T, Dang, Dongmin, Aouizerat, Bradley E, Miaskowski, Christine, Ye, Yi, Viet, Dan T, Ono, Kentaro, and Schmidt, Brian L
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Cancer ,Genetics ,Pain Research ,Chronic Pain ,Drug Abuse (NIDA only) ,Substance Misuse ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Aged ,Analgesics ,Opioid ,Animals ,Cancer Pain ,Cell Line ,Tumor ,Cohort Studies ,DNA Methylation ,Drug Tolerance ,Epigenesis ,Genetic ,Female ,Humans ,Male ,Mice ,Inbred BALB C ,Middle Aged ,Morphine ,Neoplasm Transplantation ,Neoplasms ,Nociceptive Pain ,Opioid-Related Disorders ,Pain Management ,Patient Education as Topic ,Pharmacogenomic Testing ,Receptors ,Opioid ,mu ,Methylation ,cancer pain ,mu-opioid receptor ,OPRM1 ,opioid tolerance ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Anesthesiology ,Clinical sciences ,Epidemiology - Abstract
Cancer patients in pain require high doses of opioids and quickly become opioid-tolerant. Previous studies have shown that chronic cancer pain as well as high-dose opioid use lead to mu-opioid receptor downregulation. In this study we explore downregulation of the mu-opioid receptor gene (OPRM1), as a mechanism for opioid tolerance in the setting of opioid use for cancer pain. We demonstrate in a cohort of 84 cancer patients that high-dose opioid use correlates with OPRM1 hypermethylation in peripheral leukocytes of these patients. We then reverse-translate our clinical findings by creating a mouse cancer pain model; we create opioid tolerance in the mouse cancer model to mimic opioid tolerance in the cancer patients. Using this model we determine the functional significance of OPRM1 methylation on cancer pain and opioid tolerance. We focus on 2 main cells within the cancer microenvironment: the cancer cell and the neuron. We show that targeted re-expression of mu-opioid receptor on cancer cells inhibits mechanical and thermal hypersensitivity, and prevents opioid tolerance, in the mouse model. The resultant analgesia and protection against opioid tolerance are likely due to preservation of mu-opioid receptor expression on the cancer-associated neurons.PerspectiveWe demonstrate that epigenetic regulation of OPRM1 contributes to opioid tolerance in cancer patients, and that targeted gene therapy could treat cancer-induced nociception and opioid tolerance in a mouse cancer model.
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- 2017
40. AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions
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Paice, Judith A, Mulvey, Matt, Bennett, Michael, Dougherty, Patrick M, Farrar, John T, Mantyh, Patrick W, Miaskowski, Christine, Schmidt, Brian, and Smith, Thomas J
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Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Chronic Pain ,Peripheral Neuropathy ,Digestive Diseases ,Substance Misuse ,Pain Research ,Pancreatic Cancer ,Cancer ,Rare Diseases ,Cancer Pain ,Evidence-Based Medicine ,Humans ,Pain Measurement ,Public-Private Sector Partnerships ,Societies ,Medical ,United States ,Cancer pain ,taxonomy ,bone pain ,chemotherapy-induced peripheral neuropathy ,pancreatic cancer ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Anesthesiology ,Clinical sciences ,Epidemiology - Abstract
Chronic cancer pain is a serious complication of malignancy or its treatment. Currently, no comprehensive, universally accepted cancer pain classification system exists. Clarity in classification of common cancer pain syndromes would improve clinical assessment and management. Moreover, an evidence-based taxonomy would enhance cancer pain research efforts by providing consistent diagnostic criteria, ensuring comparability across clinical trials. As part of a collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) and the American Pain Society (APS), the ACTTION-APS Pain Taxonomy initiative worked to develop the characteristics of an optimal diagnostic system. After the establishment of these characteristics, a working group consisting of clinicians and clinical and basic scientists with expertise in cancer and cancer-related pain was convened to generate core diagnostic criteria for an illustrative sample of 3 chronic pain syndromes associated with cancer (ie, bone pain and pancreatic cancer pain as models of pain related to a tumor) or its treatment (ie, chemotherapy-induced peripheral neuropathy). A systematic review and synthesis was conducted to provide evidence for the dimensions that comprise this cancer pain taxonomy. Future efforts will subject these diagnostic categories and criteria to systematic empirical evaluation of their feasibility, reliability, and validity and extension to other cancer-related pain syndromes.PerspectiveThe ACTTION-APS chronic cancer pain taxonomy provides an evidence-based classification for 3 prevalent syndromes, namely malignant bone pain, pancreatic cancer pain, and chemotherapy-induced peripheral neuropathy. This taxonomy provides consistent diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms for these potentially serious cancer pain conditions that can be extended and applied with other cancer-related pain syndromes.
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- 2017
41. Measuring nickel masses in Type Ia supernovae using cobalt emission in nebular phase spectra
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Childress, Michael J., Hillier, D. John, Seitenzahl, Ivo, Sullivan, Mark, Maguire, Kate, Taubenberger, Stefan, Scalzo, Richard, Ruiter, Ashley, Blagorodnova, Nadejda, Camacho, Yssavo, Castillo, Jayden, Elias-Rosa, Nancy, Fraser, Morgan, Gal-Yam, Avishay, Graham, Melissa, Howell, D. Andrew, Inserra, Cosimo, Jha, Saurabh W., Kumar, Sahana, Mazzali, Paolo A., McCully, Curtis, Morales-Garoffolo, Antonia, Pandya, Viraj, Polshaw, Joe, Schmidt, Brian, Smartt, Stephen, Smith, Ken W., Sollerman, Jesper, Spyromilio, Jason, Tucker, Brad, Valenti, Stefano, Walton, Nicholas, Wolf, Christian, Yaron, Ofer, Young, D. R., Yuan, Fang, and Zhang, Bonnie
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Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Solar and Stellar Astrophysics - Abstract
The light curves of Type Ia supernovae (SNe Ia) are powered by the radioactive decay of $^{56}$Ni to $^{56}$Co at early times, and the decay of $^{56}$Co to $^{56}$Fe from ~60 days after explosion. We examine the evolution of the [Co III] 5892 A emission complex during the nebular phase for SNe Ia with multiple nebular spectra and show that the line flux follows the square of the mass of $^{56}$Co as a function of time. This result indicates both efficient local energy deposition from positrons produced in $^{56}$Co decay, and long-term stability of the ionization state of the nebula. We compile 77 nebular spectra of 25 SN Ia from the literature and present 17 new nebular spectra of 7 SNe Ia, including SN2014J. From these we measure the flux in the [Co III] 5892 A line and remove its well-behaved time dependence to infer the initial mass of $^{56}$Ni ($M_{Ni}$) produced in the explosion. We then examine $^{56}$Ni yields for different SN Ia ejected masses ($M_{ej}$ - calculated using the relation between light curve width and ejected mass) and find the $^{56}$Ni masses of SNe Ia fall into two regimes: for narrow light curves (low stretch s~0.7-0.9), $M_{Ni}$ is clustered near $M_{Ni}$ ~ 0.4$M_\odot$ and shows a shallow increase as $M_{ej}$ increases from ~1-1.4$M_\odot$; at high stretch, $M_{ej}$ clusters at the Chandrasekhar mass (1.4$M_\odot$) while $M_{Ni}$ spans a broad range from 0.6-1.2$M_\odot$. This could constitute evidence for two distinct SN Ia explosion mechanisms., Comment: 16 pages, 12 figures (main text), plus data tables in appendix. Spectra released on WISeREP. Submitted to MNRAS, comments welcome
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- 2015
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42. Nucleosynthesis in a Primordial Supernova: Carbon and Oxygen Abundances in SMSS J031300.36-670839.31
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Bessell, Michael, Collett, Remo, Keller, Stefan, Frebel, Anna, Heger, Alexander, Casey, Andrew, Masseron, Thomas, Asplund, Martin, Jacobson, Heather, Lind, Karin, Marino, Anna, Norris, John, Yong, David, Da Costa, Gary, Chan, Conrad, Magic, Zazralt, Schmidt, Brian, and Tisserand, Patrick
- Subjects
Astrophysics - Solar and Stellar Astrophysics - Abstract
SMSS J031300.36-670839.3 (hereafter SM0313-6708) is a sub-giant halo star, with no detectable Fe lines and large overabundances of C and Mg relative to Ca. We obtained VLT-UVES spectra extending to 3060 Angstroms showing strong OH A-X band lines enabling an oxygen abundance to be derived. The OH A-X band lines in SM0313-6708 are much stronger than the CH C-X band lines. Spectrum synthesis fits indicate an [O/C] ratio of 0.02 +- 0.175. Our high S/N UVES data also enabled us to lower the Fe abundance limit to [Fe/H]{3D},NLTE < -7.52 (3 sigma). These data support our previous suggestion that the star formed from the iron-poor ejecta of a single massive star Population III supernova., Comment: 23 pages, 4 figures, 1 table
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- 2015
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43. High-Resolution Spectroscopic Study of Extremely Metal-Poor Star Candidates from the SkyMapper Survey
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Jacobson, Heather. R., Keller, Stefan, Frebel, Anna, Casey, Andrew R., Asplund, Martin, Bessell, Michael S., Da Costa, Gary S., Lind, Karin, Marino, Anna F., Norris, John E., Pena, Jose M., Schmidt, Brian P., Tisserand, Patrick, Walsh, Jennifer M., Yong, David, and Yu, Qinsi
- Subjects
Astrophysics - Solar and Stellar Astrophysics - Abstract
The SkyMapper Southern Sky Survey is carrying out a search for the most metal-poor stars in the Galaxy. It identifies candidates by way of its unique filter set that allows for estimation of stellar atmospheric parameters. The set includes a narrow filter centered on the Ca II K 3933A line, enabling a robust estimate of stellar metallicity. Promising candidates are then confirmed with spectroscopy. We present the analysis of Magellan-MIKE high-resolution spectroscopy of 122 metal-poor stars found by SkyMapper in the first two years of commissioning observations. 41 stars have [Fe/H] <= -3.0. Nine have [Fe/H] <= -3.5, with three at [Fe/H] ~ -4. A 1D LTE abundance analysis of the elements Li, C, Na, Mg, Al, Si, Ca, Sc, Ti, Cr, Mn, Co, Ni, Zn, Sr, Ba and Eu shows these stars have [X/Fe] ratios typical of other halo stars. One star with low [X/Fe] values appears to be "Fe-enhanced," while another star has an extremely large [Sr/Ba] ratio: >2. Only one other star is known to have a comparable value. Seven stars are "CEMP-no" stars ([C/Fe] > 0.7, [Ba/Fe] < 0). 21 stars exhibit mild r-process element enhancements (0.3 <=[Eu/Fe] < 1.0), while four stars have [Eu/Fe] >= 1.0. These results demonstrate the ability to identify extremely metal-poor stars from SkyMapper photometry, pointing to increased sample sizes and a better characterization of the metal-poor tail of the halo metallicity distribution function in the future., Comment: Minor corrections to text, missing data added to Tables 3 and 4; updated to match published version. Complete tables included in source
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- 2015
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44. The elementary representation of spatial and color vision in the human retina.
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Sabesan, Ramkumar, Schmidt, Brian P, Tuten, William S, and Roorda, Austin
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Visual Pathways ,Neurons ,Retina ,Humans ,Photic Stimulation ,Color Perception ,Light ,Vision ,Ocular ,Retinal Cone Photoreceptor Cells ,Color Vision ,Color vision ,adaptive optics ,imaging ,perception ,photoreceptors ,retina ,Vision ,Ocular - Abstract
The retina is the most accessible element of the central nervous system for linking behavior to the activity of isolated neurons. We unraveled behavior at the elementary level of single input units-the visual sensation generated by stimulating individual long (L), middle (M), and short (S) wavelength-sensitive cones with light. Spectrally identified cones near the fovea of human observers were targeted with small spots of light, and the type, proportion, and repeatability of the elicited sensations were recorded. Two distinct populations of cones were observed: a smaller group predominantly associated with signaling chromatic sensations and a second, more numerous population linked to achromatic percepts. Red and green sensations were mainly driven by L- and M-cones, respectively, although both cone types elicited achromatic percepts. Sensations generated by cones were rarely stochastic; rather, they were consistent over many months and were dominated by one specific perceptual category. Cones lying in the midst of a pure spectrally opponent neighborhood, an arrangement purported to be most efficient in producing chromatic signals in downstream neurons, were no more likely to signal chromatic percepts. Overall, the results are consistent with the idea that the nervous system encodes high-resolution achromatic information and lower-resolution color signals in separate pathways that emerge as early as the first synapse. The lower proportion of cones eliciting color sensations may reflect a lack of evolutionary pressure for the chromatic system to be as fine-grained as the high-acuity achromatic system.
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- 2016
45. Predictors of Altered Upper Extremity Function During the First Year After Breast Cancer Treatment
- Author
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Smoot, Betty, Paul, Steven M, Aouizerat, Bradley E, Dunn, Laura, Elboim, Charles, Schmidt, Brian, Hamolsky, Deborah, Levine, Jon D, Abrams, Gary, Mastick, Judy, Topp, Kimberly, and Miaskowski, Christine
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Rehabilitation ,Clinical Research ,Patient Safety ,Breast Cancer ,Cancer ,Age Factors ,Axilla ,Breast Neoplasms ,Chemotherapy ,Adjuvant ,Female ,Hand Strength ,Humans ,Longitudinal Studies ,Lymph Node Excision ,Mammaplasty ,Mastectomy ,Mastodynia ,Middle Aged ,Neoadjuvant Therapy ,Postoperative Complications ,Prospective Studies ,Racial Groups ,Range of Motion ,Articular ,Upper Extremity ,Mobility ,Function ,Grip Strength ,Range of Motion ,Human Movement and Sports Sciences ,Clinical sciences ,Allied health and rehabilitation science ,Sports science and exercise - Abstract
ObjectiveThe purpose of this study was to evaluate trajectories of and predictors for changes in upper extremity (UE) function in women (n = 396) during the first year after breast cancer treatment.DesignProspective, longitudinal assessments of shoulder range of motion (ROM), grip strength, and perceived interference of function were performed before and for 1 year after surgery. Demographic, clinical, and treatment characteristics were evaluated as predictors of postoperative function.ResultsWomen had a mean (SD) age of 54.9 (11.6) years, and 64% were white. Small but statistically significant reductions in shoulder ROM were found on the affected side over 12 months (P < 0.001). Predictors of interindividual differences in ROM at the 1-month assessment were ethnicity, neoadjuvant chemotherapy, type of surgery, axillary lymph node dissection, and preoperative ROM. Predictors of interindividual differences in changes over time in postoperative ROM were living alone, type of surgery, axillary lymph node dissection, and adjuvant chemotherapy. Declines in mean grip strength from before through 1 month after surgery were small and not clinically meaningful. Women with greater preoperative breast pain interference scores had higher postoperative interference scores at all postoperative assessments.ConclusionSome of the modifiable risk factors identified in this study can be targeted for intervention to improve UE function in these women.
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- 2016
46. Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice
- Author
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Peterson, Douglas E, O'Shaughnessy, Joyce A, Rugo, Hope S, Elad, Sharon, Schubert, Mark M, Viet, Chi T, Campbell‐Baird, Cynthia, Hronek, Jan, Seery, Virginia, Divers, Josephine, Glaspy, John, Schmidt, Brian L, and Meiller, Timothy F
- Subjects
Dental/Oral and Craniofacial Disease ,Chronic Pain ,Cancer ,Pain Research ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Antineoplastic Agents ,Breast Neoplasms ,Female ,Humans ,Incidence ,Pain ,Stomatitis ,TOR Serine-Threonine Kinases ,mTOR inhibitor ,oral mucosal injury ,oral mucositis ,stomatitis ,Biochemistry and Cell Biology ,Oncology and Carcinogenesis - Abstract
In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2-78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR-associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high-dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop.
- Published
- 2016
47. Gene Expression Profiling of Evening Fatigue in Women Undergoing Chemotherapy for Breast Cancer.
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Kober, Kord M, Dunn, Laura, Mastick, Judy, Cooper, Bruce, Langford, Dale, Melisko, Michelle, Venook, Alan, Chen, Lee-May, Wright, Fay, Hammer, Marilyn, Schmidt, Brian L, Levine, Jon, Miaskowski, Christine, and Aouizerat, Bradley E
- Subjects
Humans ,Breast Neoplasms ,Fatigue ,Antineoplastic Agents ,Gene Expression Profiling ,Gene Expression Regulation ,Neoplastic ,Periodicity ,Circadian Rhythm ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,breast cancer ,cancer ,chemotherapy ,diurnal variations in fatigue ,fatigue ,gene expression ,inflammation ,Breast Cancer ,Genetics ,Clinical Research ,Cancer ,Nursing - Abstract
Moderate-to-severe fatigue occurs in up to 94% of oncology patients undergoing active treatment. Current interventions for fatigue are not efficacious. A major impediment to the development of effective treatments is a lack of understanding of the fundamental mechanisms underlying fatigue. In the current study, differences in phenotypic characteristics and gene expression profiles were evaluated in a sample of breast cancer patients undergoing chemotherapy (CTX) who reported low (n = 19) and high (n = 25) levels of evening fatigue. Compared to the low group, patients in the high evening fatigue group reported lower functional status scores, higher comorbidity scores, and fewer prior cancer treatments. One gene was identified as upregulated and 11 as downregulated in the high evening fatigue group. Gene set analysis found 24 downregulated and 94 simultaneously up- and downregulated pathways between the two fatigue groups. Transcript origin analysis found that differential expression (DE) originated primarily from monocytes and dendritic cell types. Query of public data sources found 18 gene expression experiments with similar DE profiles. Our analyses revealed that inflammation, neurotransmitter regulation, and energy metabolism are likely mechanisms associated with evening fatigue severity; that CTX may contribute to fatigue seen in oncology patients; and that the patterns of gene expression may be shared with other models of fatigue (e.g., physical exercise and pathogen-induced sickness behavior). These results suggest that the mechanisms that underlie fatigue in oncology patients are multifactorial.
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- 2016
48. UBVRIz LIGHT CURVES OF 51 TYPE II SUPERNOVAE
- Author
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Galbany, Lluís, Hamuy, Mario, Phillips, Mark M, Suntzeff, Nicholas B, Maza, José, de Jaeger, Thomas, Moraga, Tania, González-Gaitán, Santiago, Krisciunas, Kevin, Morrell, Nidia I, Thomas-Osip, Joanna, Krzeminski, Wojtek, González, Luis, Antezana, Roberto, Wishnjewski, Marina, McCarthy, Patrick, Anderson, Joseph P, Gutiérrez, Claudia P, Stritzinger, Maximilian, Folatelli, Gastón, Anguita, Claudio, Galaz, Gaspar, Green, Elisabeth M, Impey, Chris, Kim, Yong-Cheol, Kirhakos, Sofia, Malkan, Mathew A, Mulchaey, John S, Phillips, Andrew C, Pizzella, Alessandro, Prosser, Charles F, Schmidt, Brian P, Schommer, Robert A, Sherry, William, Strolger, Louis-Gregory, Wells, Lisa A, and Williger, Gerard M
- Subjects
supernovae: general ,surveys ,techniques: photometric ,astro-ph.SR ,astro-ph.HE ,Astronomical and Space Sciences ,Astronomy & Astrophysics - Abstract
We present a compilation of UBVRIz light curves of 51 type II supernovae discovered during the course of four different surveys during 1986-2003: the Cerro Tololo Supernova Survey, the Calán/Tololo Supernova Program (C&T), the Supernova Optical and Infrared Survey (SOIRS), and the Carnegie Type II Supernova Survey (CATS). The photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination, and calibrated from foreground stars. This work presents these photometric data, studies the color evolution using different bands, and explores the relation between the magnitude at maximum brightness and the brightness decline parameter (s) from maximum light through the end of the recombination phase. This parameter is found to be shallower for redder bands and appears to have the best correlation in the B band. In addition, it also correlates with the plateau duration, being shorter (longer) for larger (smaller) s values.
- Published
- 2016
49. Predictors and Trajectories of Morning Fatigue Are Distinct From Evening Fatigue.
- Author
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Wright, Fay, D'Eramo Melkus, Gail, Hammer, Marilyn, Schmidt, Brian L, Knobf, M Tish, Paul, Steven M, Cartwright, Frances, Mastick, Judy, Cooper, Bruce A, Chen, Lee-May, Melisko, Michelle, Levine, Jon D, Kober, Kord, Aouizerat, Bradley E, and Miaskowski, Christine
- Subjects
Humans ,Neoplasms ,Disease Progression ,Fatigue ,Antineoplastic Agents ,Body Mass Index ,Severity of Illness Index ,Linear Models ,Risk Factors ,Depression ,Periodicity ,Photoperiod ,Middle Aged ,Outpatients ,Female ,Male ,Sleep Wake Disorders ,Morning fatigue ,cancer ,chemotherapy ,diurnal variations ,evening fatigue ,hierarchical linear modeling ,oncology ,symptom trajectories ,Prevention ,Mental Health ,Behavioral and Social Science ,Clinical Research ,Sleep Research ,Cancer ,Medical and Health Sciences ,Anesthesiology - Abstract
ContextFatigue is the most common symptom in oncology patients during chemotherapy. Little is known about the predictors of interindividual variability in initial levels and trajectories of morning fatigue severity in these patients.ObjectivesAn evaluation was done to determine which demographic, clinical, and symptom characteristics were associated with initial levels as well as the trajectories of morning fatigue and to compare findings with our companion paper on evening fatigue.MethodsA sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (n = 586) completed demographic and symptom questionnaires a total of six times over two cycles of chemotherapy. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling was used to answer the study objectives.ResultsA large amount of interindividual variability was found in the morning fatigue trajectories. A piecewise model fit the data best. Patients with higher body mass index, who did not exercise regularly, with a lower functional status, and who had higher levels of state anxiety, sleep disturbance, and depressive symptoms reported higher levels of morning fatigue at enrollment. Variations in the trajectories of morning fatigue were predicted by the patients' ethnicity and younger age.ConclusionThe modifiable risk factors that were associated with only morning fatigue were body mass index, exercise, and state anxiety. Modifiable risk factors that were associated with both morning and evening fatigue included functional status, depressive symptoms, and sleep disturbance. Using this information, clinicians can identify patients at higher risk for more severe morning fatigue and evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors.
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- 2015
50. Trajectories of Evening Fatigue in Oncology Outpatients Receiving Chemotherapy.
- Author
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Wright, Fay, D'Eramo Melkus, Gail, Hammer, Marilyn, Schmidt, Brian L, Knobf, M Tish, Paul, Steven M, Cartwright, Frances, Mastick, Judy, Cooper, Bruce A, Chen, Lee-May, Melisko, Michelle, Levine, Jon D, Kober, Kord, Aouizerat, Bradley E, and Miaskowski, Christine
- Subjects
Humans ,Neoplasms ,Disease Progression ,Fatigue ,Antineoplastic Agents ,Severity of Illness Index ,Linear Models ,Risk Factors ,Longitudinal Studies ,Periodicity ,Photoperiod ,Middle Aged ,Outpatients ,Female ,Male ,Evening fatigue ,breast cancer ,chemotherapy ,diurnal variations ,gastrointestinal cancer ,gynecological cancer ,hierarchical linear modeling ,lung cancer ,symptom patterns ,symptom trajectories ,Mental Health ,Cancer ,Clinical Research ,Lung ,Breast Cancer ,Depression ,Medical and Health Sciences ,Anesthesiology - Abstract
ContextFatigue is a distressing persistent sense of physical tiredness that is not proportional to a person's recent activity. Fatigue impacts patients' treatment decisions and can limit their self-care activities. Although significant interindividual variability in fatigue severity has been noted, little is known about predictors of interindividual variability in initial levels and trajectories of evening fatigue severity in oncology patients receiving chemotherapy.ObjectivesTo determine whether demographic, clinical, and symptom characteristics were associated with initial levels and the trajectories of evening fatigue.MethodsA sample of outpatients with breast, gastrointestinal, gynecological, and lung cancer (N = 586) completed demographic and symptom questionnaires a total of six times over two cycles of chemotherapy. Fatigue severity was evaluated using the Lee Fatigue Scale. Hierarchical linear modeling was used to answer the study objectives.ResultsA large amount of interindividual variability was found in the evening fatigue trajectories. A piecewise model fit the data best. Patients who were white, diagnosed with breast, gynecological, or lung cancer, and who had more years of education, childcare responsibilities, lower functional status, and higher levels of sleep disturbance and depression reported higher levels of evening fatigue at enrollment.ConclusionThis study identified both nonmodifiable (e.g., ethnicity) and modifiable (e.g., childcare responsibilities, depressive symptoms, sleep disturbance) risk factors for more severe evening fatigue. Using this information, clinicians can identify patients at higher risk for more severe evening fatigue, provide individualized patient education, and tailor interventions to address the modifiable risk factors.
- Published
- 2015
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