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6,414 results on '"Krier, A."'

1. On the decay properties of the neutron-deficient isotope 242Es

Author

Khuyagbaatar, J., Cantemir, R. A., Duellmann, Ch. E., Jaeger, E., Kindler, B., Krier, J., Kurz, N., Lommel, B., Schausten, B., and Yakushev, A.

Subjects
Nuclear Experiment
Abstract

The radioactive decay properties of $^{242}$Es were studied with significantly improved statistics compared to available literature data. This isotope was produced in the 3n evaporation channel of the fusion reaction of $^{48}$Ca+$^{197}$Au. A half-life of 16.9(8)~s was deduced from 662 $\alpha$ decays of $^{242}$Es, resulting in an $\alpha$-decay branching of 41(3)\%. Twenty-six fission events with a half-life of 18.2$^{+4.5}_{-3.0}$~s were assigned to originate from the electron-capture delayed fission of $^{242}$Es. The probability for the electron-capture delayed fission was measured to be 0.015(4), which improves and resolves ambiguities in available experimental data. We discuss all known cases for electron-capture delayed fission in Es, Bk, and Am isotopes and compare experimental data with predictions from a recent semi-empirical model. A cross section of 27(3)~nb was measured for the production of $^{242}$Es.

Published
2024
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2. The Ethics of Advanced AI Assistants

Author

Gabriel, Iason, Manzini, Arianna, Keeling, Geoff, Hendricks, Lisa Anne, Rieser, Verena, Iqbal, Hasan, Tomašev, Nenad, Ktena, Ira, Kenton, Zachary, Rodriguez, Mikel, El-Sayed, Seliem, Brown, Sasha, Akbulut, Canfer, Trask, Andrew, Hughes, Edward, Bergman, A. Stevie, Shelby, Renee, Marchal, Nahema, Griffin, Conor, Mateos-Garcia, Juan, Weidinger, Laura, Street, Winnie, Lange, Benjamin, Ingerman, Alex, Lentz, Alison, Enger, Reed, Barakat, Andrew, Krakovna, Victoria, Siy, John Oliver, Kurth-Nelson, Zeb, McCroskery, Amanda, Bolina, Vijay, Law, Harry, Shanahan, Murray, Alberts, Lize, Balle, Borja, de Haas, Sarah, Ibitoye, Yetunde, Dafoe, Allan, Goldberg, Beth, Krier, Sébastien, Reese, Alexander, Witherspoon, Sims, Hawkins, Will, Rauh, Maribeth, Wallace, Don, Franklin, Matija, Goldstein, Josh A., Lehman, Joel, Klenk, Michael, Vallor, Shannon, Biles, Courtney, Morris, Meredith Ringel, King, Helen, Arcas, Blaise Agüera y, Isaac, William, and Manyika, James

Subjects
Computer Science - Computers and Society
Abstract

This paper focuses on the opportunities and the ethical and societal risks posed by advanced AI assistants. We define advanced AI assistants as artificial agents with natural language interfaces, whose function is to plan and execute sequences of actions on behalf of a user, across one or more domains, in line with the user's expectations. The paper starts by considering the technology itself, providing an overview of AI assistants, their technical foundations and potential range of applications. It then explores questions around AI value alignment, well-being, safety and malicious uses. Extending the circle of inquiry further, we next consider the relationship between advanced AI assistants and individual users in more detail, exploring topics such as manipulation and persuasion, anthropomorphism, appropriate relationships, trust and privacy. With this analysis in place, we consider the deployment of advanced assistants at a societal scale, focusing on cooperation, equity and access, misinformation, economic impact, the environment and how best to evaluate advanced AI assistants. Finally, we conclude by providing a range of recommendations for researchers, developers, policymakers and public stakeholders.

Published
2024

3. A Learning Organization in Action: Applying Senge's Five Disciplines to a Collections Diversity Audit

Author

Kaitlin Springmier, Catherine Fonseca, Laura Krier, Rita Premo, Hilary Smith, and Mary Wegmann

Abstract

For more than 30 years, Peter Senge's theory of learning organizations has influenced the study of leadership and organizations. Researchers have studied various components of his framework: team cognition and mental models, team learning, shared vision, systems thinking, and personal mastery. But few articles have explored what it looks like in practice when the five disciplines of the learning organization are enacted in an organization. This article explores the ways in which these disciplines influenced the implementation and outcomes of a collection diversity audit at Sonoma State University Library. The authors discuss the ways that Senge's learning organization framework enabled them to create a sustainable model for evaluating diversity in selection and acquisition practices.

Published
2024
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4. Asymptotically proved numerical coupling of a 2D flexural porous plate with the 3D Stokes fluid

Author

Krier, Maxime, Orlik, Julia, Panasenko, Grigory, and Steiner, Konrad

Subjects
Mathematics - Numerical Analysis, Mathematics - Functional Analysis
Abstract

This paper presents an efficient coupling of the 3D Stokes flow interacting with an effective perforated periodic heterogeneous anisotropic 2D plate. The effective model was obtained by the asymptotic analysis in earlier works and here an effective numerical algorithm is given. By $Q_3$ or bi-cubic spacial interpolation the time-dependent problem was reduced to an algebraic system of ordinary differential equation in time. Different examples were given, demonstrating the influence of the structural plate parameters on the solution.

Published
2023

8. The impact of hypoxia preconditioning on mesenchymal stem cells performance in hypertensive kidney disease

Author

Gurparneet Kaur Sohi, Naba Farooqui, Arjunmohan Mohan, Kamalnath Sankaran Rajagopalan, Li Xing, Xiang Y. Zhu, Kyra Jordan, James D. Krier, Ishran M. Saadiq, Hui Tang, LaTonya J. Hickson, Alfonso Eirin, Lilach O. Lerman, and Sandra M. Herrmann

Subjects
Hypertensive kidney disease, Adipose mesenchymal stem cells, Hypoxia preconditioning, Angiogenesis, Senescence, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract

Abstract Background Autologous mesenchymal stem cells (MSCs) have emerged as a therapeutic option for many diseases. Hypertensive kidney disease (HKD) might impair MSCs’ reparative ability by altering the biomolecular properties, but the characteristics of this impairment are unclear. In our previous pre-clinical studies, we found hypoxic preconditioning (HPC) enhanced angiogenesis and suppressed senescence gene expression. Thus, we hypothesize that HPC would improve human MSCs by enhancing their functionality and angiogenesis, creating an anti-inflammatory and anti-senescence environment. Methods MSC samples (n = 12 each) were collected from the abdominal fat of healthy kidney donors (HC), hypertensive patients (HTN), and patients with hypertensive kidney disease (HKD). MSCs were harvested and cultured in Normoxic (20% O2) or Hypoxic (1% O2) conditions. MSC functionality was measured by proliferation assays and cytokine released in conditioned media. Senescence was evaluated by senescence-associated beta-galactosidase (SA-beta-gal) activity. Additionally, transcriptome analysis using RNA-sequencing and quantitative PCR (qPCR) were performed. Results At baseline, normoxic HTN-MSCs had higher proliferation capacity compared to HC. However, HPC augmented proliferation in HC. HPC did not affect the release of pro-angiogenic protein VEGF, but increased EGF in HC-MSC, and decreased HGF in HC and HKD MSCs. Under HPC, SA-β-gal activity tended to decrease, particularly in HC group. HPC upregulated mostly the pro-angiogenic and inflammatory genes in HC and HKD and a few senescence genes in HKD. Conclusions HPC has a more favorable functional effect on HC- than on HKD-MSC, reflected in increased proliferation and EGF release, and modest decrease in senescence, whereas it has little effect on HTN or HKD MSCs.

Published
2024
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9. Case Report: Methimazole-Induced Parotitis - An Unusual Presentation [version 2; peer review: 1 approved with reservations]

Author

Ricky Rana, Emily Krier, Abubakar Tauseef, and Jalal Dufani

Subjects
Case Report, Articles, methimazole, drug-induced reaction, parotitis, hyperthyroidsm
Abstract

A 56-year-old female with a medical history of unspecified hyperthyroidism and a recent thyroid storm presented to the ED with tachycardia, hypertension, and bilateral enlarged parotid glands. During a previous hospitalization, she was diagnosed with unspecified hyperthyroidism and started on methimazole. During hospitalization, laboratory findings suggested Graves’ disease with an acute thyroid storm. The patient also complained of enlarged parotid glands bilaterally. CT tomography of the neck revealed no calculi of the parotid glands but showed extensive fatty replacement, possibly related to methimazole use. Treatment with propranolol and IV hydrocortisone improved thyroid function. Due to the suspicion of methimazole-induced parotitis, she was transitioned to a reduced methimazole dosage for treatment of Graves’ disease, which subsequently improved her parotitis. Methimazole, the standard initial treatment for Graves’ disease, is generally well-tolerated. It can cause adverse reactions; however, parotitis is very rare and has been documented in only a few case reports. Owing to the limited number of reports, its incidence is currently unknown. Here, we present a case of methimazole-induced parotitis as an unusual presentation of thyroid storm. Drug-induced reactions can only be considered once common causes of parotitis such as viral infection, obstruction, and autoimmune diseases are ruled out. Treatment involves dosage adjustments and supportive care. Methimazole-induced parotitis is often misdiagnosed and overlooked because of the lack of reported cases. This necessitates future research into the reaction mechanisms and optimal treatment.

Published
2024
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10. A Phase I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic NSCLC

Author

Jyoti Malhotra, MD, MPH, Yong Lin, PhD, Malini Patel, MD, Michael J. Yellin, MD, Emmanuel Zachariah, PhD, Curtis Krier, PhD, Ankit Saxena, PhD, and Salma K. Jabbour, MD

Subjects
Immunotherapy, anti-CD27, radiation, NSCLC, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT). Methods: We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy. On day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2. Results: A total of 15 patients were enrolled (one patient did not start treatment). The median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (AE) and 7 (50%) had at least one grade III or worse treatment-related AE. There was only one grade III immune-related AE requiring steroids (1 diarrhea and colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, three patients had stable disease (2 with stable disease > 4 mo) and the clinical benefit rate was 25%. The median progression-free survival was two months and the median overall survival was 6.4 months. Conclusions: Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.

Published
2024
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11. Human liver derived mesenchymal stromal cells ameliorate murine ischemia-induced inflammation through macrophage polarization

Author

Yun Liang, Elif Ozdogan, Michael J. Hansen, Hui Tang, Ishran Saadiq, Kyra L. Jordan, James D. Krier, Deep B. Gandhi, Joseph P. Grande, Lilach O. Lerman, and Timucin Taner

Subjects
mesenchymal stromal cells, immunomodulation, renal artery stenosis, liver tolerance, inflammation, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionThe immunomodulatory properties of mesenchymal stromal cells (MSC) have been well-characterized in in-vitro and in-vivo models. We have previously shown that liver MSC (L-MSC) are superior inhibitors of T-cell activation/proliferation, NK cell cytolytic function, and macrophage activation compared to adipose (A-MSC) and bone marrow MSC (BM-MSC) in-vitro.MethodTo test these observations in-vivo, we infused these types of MSC into mice with unilateral renal artery stenosis (RAS), an established model of kidney inflammation. Unilateral RAS was induced via laparotomy in 11-week-old, male 129-S1 mice under general anesthesia. Control mice had sham operations. Human L-MSC, AMSC, and BM-MSC (5x105 cells each) or PBS vehicle were injected intra-arterially 2 weeks after surgery. Kidney morphology was studied 2 weeks after infusion using micro-MRI imaging. Renal inflammation, apoptosis, fibrosis, and MSC retention were studied ex-vivo utilizing western blot, immunofluorescence, and immunohistological analyses.ResultsThe stenotic kidney volume was smaller in all RAS mice, confirming significant injury, and was improved by infusion of all MSC types. All MSC-infused groups had lower levels of plasma renin and proteinuria compared to untreated RAS. Serum creatinine improved in micetreated with BM- and L-MSC. All types of MSC located to and were retained within the stenotic kidneys, but L-MSC retention was significantly higher than A- and BM-MSC. While all groups of MSC-treated mice displayed reduced overall inflammation and macrophage counts, L-MSC showed superior potency in-vivo at localizing to the site of inflammation and inducing M2 (reparative) macrophage polarization to reduce inflammatory changes.DiscussionThese in-vivo findings extend our in-vitro studies and suggest that L-MSC possess unique anti-inflammatory properties that may play a role in liver-induced tolerance and lend further support to their use as therapeutic agents for diseases with underlying inflammatory pathophysiology.

Published
2024
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12. Case Report: Methimazole-Induced Parotitis - An Unusual and Rare Presentation of Thyroid Storm [version 1; peer review: awaiting peer review]

Author

Ricky Rana, Emily Krier, Abubakar Tauseef, and Jalal Dufani

Subjects
Case Report, Articles, methimazole, drug-induced reaction, parotitis, hyperthyroidsm
Abstract

A 56-year-old female with a medical history of unspecified hyperthyroidism and a recent thyroid storm presented to the ED with tachycardia, hypertension, and bilateral enlarged parotid glands. During a previous hospitalization, she was diagnosed with unspecified hyperthyroidism and started on methimazole. During hospitalization, laboratory findings suggested Graves’ disease with an acute thyroid storm. The patient also complained of enlarged parotid glands bilaterally. CT tomography of the neck revealed no calculi of the parotid glands but showed extensive fatty replacement, possibly related to methimazole use. Treatment with propranolol and IV hydrocortisone improved thyroid function. Due to the suspicion of methimazole-induced parotitis, she was transitioned to a reduced methimazole dosage for treatment of Graves’ disease, which subsequently improved her parotitis. Methimazole, the standard initial treatment for Graves’ disease, is generally well-tolerated. It can cause adverse reactions; however, parotitis is very rare and has been documented in only a few case reports. Owing to the limited number of reports, its incidence is currently unknown. Here, we present a case of methimazole-induced parotitis as an unusual presentation of thyroid storm. Drug-induced reactions can only be considered once common causes of parotitis such as viral infection, obstruction, and autoimmune diseases are ruled out. Treatment involves dosage adjustments and supportive care. Methimazole-induced parotitis is often misdiagnosed and overlooked because of the lack of reported cases. This necessitates future research into the reaction mechanisms and optimal treatment.

Published
2024
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13. A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder

Author

Shankar, Suma P, Grimsrud, Kristin, Lanoue, Louise, Egense, Alena, Willis, Brandon, Hörberg, Johanna, AlAbdi, Mayer, Klaus, Ütkür, Koray, Monaghan, Kristin G, Krier, Joel, Stoler, Joan, Alnemer, Maha, Shankar, Prabhu R, Schaffrath, Raffael, Alkuraya, Fowzan S, Brinkmann, Ulrich, Eriksson, Leif A, Lloyd, Kent, Rauen, Katherine A, Network, Undiagnosed Diseases, Acosta, Maria T, Adam, Margaret, Adams, David R, Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A, Azamian, Mahshid S, Bacino, Carlos A, Bademci, Guney, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H, Behrens, Edward, Bejerano, Gill, Bennet, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A, Berry, Gerard T, Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C, Brokamp, Elly, Brown, Gabrielle, Burke, Elizabeth A, Burrage, Lindsay C, Butte, Manish J, Byers, Peter, Byrd, William E, Carey, John, Carrasquillo, Olveen, Cassini, Thomas, Chang, Ta Chen Peter, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D, Coakley, Terra R, Cobban, Laurel A, Cogan, Joy D, Coggins, Matthew, Cole, F Sessions, Colley, Heather A, Cooper, Cynthia M, Cope, Heidi, Craigen, William J, Crouse, Andrew B, Cunningham, Michael, D'Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davis, Joie, Dayal, Jyoti G, Deardorff, Matthew, Dell'Angelica, Esteban C, Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Doss, Argenia L, Douine, Emilie D, Duncan, Laura, Earl, Dawn, Eckstein, David J, Emrick, Lisa T, Eng, Christine M, Esteves, Cecilia, Falk, Marni, Fernandez, Liliana, Fieg, Elizabeth L, and Fisher, Paul G

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Pediatric, Human Genome, 2.1 Biological and endogenous factors, Adenosine Diphosphate, Animals, Histidine, Humans, Methyltransferases, Mice, Mice, Inbred C57BL, Neurodevelopmental Disorders, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Syndrome, Nonverbal neurodevelopment delays, Novel gene discovery, Precision animal modeling, Precision genomics, Translational genetics, Undiagnosed Diseases Network, Clinical Sciences, Genetics & Heredity
Abstract

PurposeDiphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).MethodsMolecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants.ResultsDPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2.ConclusionWe provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.

Published
2022

14. Solvability of a fluid-structure interaction problem with semigroup theory

Author

Maxime Krier and Julia Orlik

Subjects
fluid-structure interaction, asymptotic analysis, homogenization, dimension reduction, semigroup theory, Mathematics, QA1-939
Abstract

Continuous semigroup theory is applied to proof the existence and uniqueness of a solution to a fluid-structure interaction (FSI) problem of non-stationary Stokes flow in two bulk domains, separated by a 2D elastic, permeable plate. The plate's curvature is proportional to the jump of fluid stresses across the plate and the flow resistance is modeled by Darcy's law. In the weak formulation of the considered physical problem, a linear operator in space is associated with a sum of two bilinear forms on the fluid and the interface domains, respectively. One attains a system of equations in operator form, corresponding to the weak problem formulation. Utilizing the sufficient conditions in the Lumer-Phillips theorem, we show that the linear operator is a generator of a contraction semigroup, and give the existence proof to the FSI problem.

Published
2023
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17. The Ethics of Advanced AI Assistants.

Author

Iason Gabriel, Arianna Manzini, Geoff Keeling, Lisa Anne Hendricks, Verena Rieser, Hasan Iqbal, Nenad Tomasev, Ira Ktena, Zachary Kenton, Mikel Rodriguez, Seliem El-Sayed, Sasha Brown, Canfer Akbulut, Andrew Trask, Edward Hughes 0001, A. Stevie Bergman, Renee Shelby, Nahema Marchal, Conor Griffin, Juan Mateos-Garcia, Laura Weidinger, Winnie Street, Benjamin Lange, Alex Ingerman, Alison Lentz, Reed Enger, Andrew Barakat, Victoria Krakovna, John Oliver Siy, Zeb Kurth-Nelson, Amanda McCroskery, Vijay Bolina, Harry Law, Murray Shanahan, Lize Alberts, Borja Balle, Sarah de Haas, Yetunde Ibitoye, Allan Dafoe, Beth Goldberg, Sébastien Krier, Alexander Reese, Sims Witherspoon, Will Hawkins, Maribeth Rauh, Don Wallace, Matija Franklin, Josh A. Goldstein, Joel Lehman, Michael Klenk, Shannon Vallor, Courtney Biles, Meredith Ringel Morris, Helen King, Blaise Agüera y Arcas, William Isaac 0001, and James Manyika

Published
2024
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18. Complementing the United States Household Food Security Survey Module with Items Reflecting Social Unacceptability

Author

Frongillo, Edward A, Bethancourt, Hilary J, Norcini Pala, Andrea, Maya, Sigal, Wu, Katherine C, Kizer, Jorge R, Tien, Phyllis C, Kempf, Mirjam-Colette, Hanna, David B, Appleton, Allison A, Merenstein, Daniel, D’Souza, Gypsyamber, Ofotokun, Igho, Konkle-Parker, Deborah, Michos, Erin D, Krier, Sarah, Stosor, Valentina, Turan, Bulent, and Weiser, Sheri D

Published
2024
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19. Processes and outcomes from a clinical genetics e-consultation service managed by a primary care physician champion

Author

Benjamin J. Kerman, Carrie B.L. Zawatsky, Elizabeth Fieg, Natasha Y. Frank, Roseann S. Donnelly, Robert C. Green, John C. Kennedy, Neal Lakdawala, Adam M. Licurse, Emma F. Perez, Charlene L. Preys, Joel B. Krier, Huma Q. Rana, Bethany Zettler, and Jason L. Vassy

Subjects
Clinical genetics, e-consultation, Outcomes, Primary care, Genetics, QH426-470, Medicine
Abstract

Purpose: Timely access to clinical genetics consultations remains a barrier to timely genomic medicine services, which new service delivery models might help address. Methods: We implemented a genetics electronic consultation (eConsult) service staffed by a primary care physician (PCP) champion, supervised by genetics specialists. Chart reviews from July 2018 to January 2022 examined categories of questions received, e-consultant’s recommendations, and outcomes of any conventional genetics referrals. Providers were surveyed on likelihood of ordering a conventional genetics consultation before eConsult and satisfaction with eConsult responses. Results: Conventional genetics consultation was recommended for 338 out of 462 (73%) eConsults received, among whom 254 out of 338 (75%) had an order placed for a conventional consult by the provider requesting the eConsult. Among all 462 eConsults, including in cases which conventional consult was not recommended, 279 (60%) were referred for conventional genetics consultation, of which 171 out of 279 (61%) completed a consult. Of these, 122 out of 171 (71%) were recommended for genetic testing, and 84 out of 122 (69%) completed testing. The genetic testing of 23 out of 84 (27%) patients identified informative actionable findings. Supervising genetics specialists made substantive revisions to PCP draft responses for only 8% (36/462) of eConsults. Conclusion: This case series demonstrates that a PCP champion eConsult model can feasibly triage and respond to genetics questions with PCP-relevant content and yield high provider satisfaction. Such a model warrants further evaluation as an addition to the genetic services of health care systems.

Published
2024
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21. Low-frequency inherited complement receptor variants are associated with purpura fulminans

Author

Bendapudi, Pavan K., Nazeen, Sumaiya, Ryu, Justine, Söylemez, Onuralp, Robbins, Alissa, Rouaisnel, Betty, O’Neil, Jillian K., Pokhriyal, Ruchika, Yang, Moua, Colling, Meaghan, Pasko, Bryce, Bouzinier, Michael, Tomczak, Lindsay, Collier, Lindsay, Barrios, David, Ram, Sanjay, Toth-Petroczy, Agnes, Krier, Joel, Fieg, Elizabeth, Dzik, Walter H., Hudspeth, James C., Pozdnyakova, Olga, Nardi, Valentina, Knight, James, Maas, Richard, Sunyaev, Shamil, and Losman, Julie-Aurore

Published
2024
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24. Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections

Author

Borras, Silvia, Clark, Caroline, Dean, John, Miedzybrodzka, Zosia, Ross, Alison, Tennant, Stephen, Dabir, Tabib, Donnelly, Deirdre, Humphreys, Mervyn, Magee, Alex, McConnell, Vivienne, McKee, Shane, McNerlan, Susan, Morrison, Patrick J., Rea, Gillian, Stewart, Fiona, Cole, Trevor, Cooper, Nicola, Cooper-Charles, Lisa, Cox, Helen, Islam, Lily, Jarvis, Joanna, Keelagher, Rebecca, Lim, Derek, McMullan, Dominic, Morton, Jenny, Naik, Swati, O’Driscoll, Mary, Ong, Kai-Ren, Osio, Deborah, Ragge, Nicola, Turton, Sarah, Vogt, Julie, Williams, Denise, Bodek, Simon, Donaldson, Alan, Hills, Alison, Low, Karen, Newbury-Ecob, Ruth, Norman, Andrew M., Roberts, Eileen, Scurr, Ingrid, Smithson, Sarah, Tooley, Madeleine, Abbs, Steve, Armstrong, Ruth, Dunn, Carolyn, Holden, Simon, Park, Soo-Mi, Paterson, Joan, Raymond, Lucy, Reid, Evan, Sandford, Richard, Simonic, Ingrid, Tischkowitz, Marc, Woods, Geoff, Bradley, Lisa, Comerford, Joanne, Green, Andrew, Lynch, Sally, McQuaid, Shirley, Mullaney, Brendan, Berg, Jonathan, Goudie, David, Mavrak, Eleni, McLean, Joanne, McWilliam, Catherine, Reavey, Eleanor, Azam, Tara, Cleary, Elaine, Jackson, Andrew, Lam, Wayne, Lampe, Anne, Moore, David, Porteous, Mary, Baple, Emma, Baptista, Júlia, Brewer, Carole, Castle, Bruce, Kivuva, Emma, Owens, Martina, Rankin, Julia, Shaw-Smith, Charles, Turner, Claire, Turnpenny, Peter, Tysoe, Carolyn, Bradley, Therese, Davidson, Rosemarie, Gardiner, Carol, Joss, Shelagh, Kinning, Esther, Longman, Cheryl, McGowan, Ruth, Murday, Victoria, Pilz, Daniela, Tobias, Edward, Whiteford, Margo, Williams, Nicola, Barnicoat, Angela, Clement, Emma, Faravelli, Francesca, Hurst, Jane, Jenkins, Lucy, Jones, Wendy, Ajith Kumar, V.K., Lees, Melissa, Loughlin, Sam, Male, Alison, Morrogh, Deborah, Rosser, Elisabeth, Scott, Richard, Wilson, Louise, Beleza, Ana, Deshpande, Charu, Flinter, Frances, Holder, Muriel, Irving, Melita, Izatt, Louise, Josifova, Dragana, Mohammed, Shehla, Molenda, Aneta, Robert, Leema, Roworth, Wendy, Ruddy, Deborah, Ryten, Mina, Yau, Shu, Bennett, Christopher, Blyth, Moira, Campbell, Jennifer, Coates, Andrea, Dobbie, Angus, Hewitt, Sarah, Hobson, Emma, Jackson, Eilidh, Jewell, Rosalyn, Kraus, Alison, Prescott, Katrina, Sheridan, Eamonn, Thomson, Jenny, Bradshaw, Kirsty, Dixit, Abhijit, Eason, Jacqueline, Haines, Rebecca, Harrison, Rachel, Mutch, Stacey, Sarkar, Ajoy, Searle, Claire, Shannon, Nora, Sharif, Abid, Suri, Mohnish, Vasudevan, Pradeep, Canham, Natalie, Ellis, Ian, Greenhalgh, Lynn, Howard, Emma, Stinton, Victoria, Swale, Andrew, Weber, Astrid, Banka, Siddharth, Breen, Catherine, Briggs, Tracy, Burkitt-Wright, Emma, Chandler, Kate, Clayton-Smith, Jill, Donnai, Dian, Douzgou, Sofia, Gaunt, Lorraine, Jones, Elizabeth, Kerr, Bronwyn, Langley, Claire, Metcalfe, Kay, Smith, Audrey, Wright, Ronnie, Bourn, David, Burn, John, Fisher, Richard, Hellens, Steve, Henderson, Alex, Montgomery, Tara, Splitt, Miranda, Straub, Volker, Wright, Michael, Zwolinski, Simon, Allen, Zoe, Bernhard, Birgitta, Brady, Angela, Brooks, Claire, Busby, Louise, Clowes, Virginia, Ghali, Neeti, Holder, Susan, Ibitoye, Rita, Wakeling, Emma, Blair, Edward, Carmichael, Jenny, Cilliers, Deirdre, Clasper, Susan, Gibbons, Richard, Kini, Usha, Lester, Tracy, Nemeth, Andrea, Poulton, Joanna, Price, Sue, Shears, Debbie, Stewart, Helen, Wilkie, Andrew, Albaba, Shadi, Baker, Duncan, Balasubramanian, Meena, Johnson, Diana, Parker, Michael, Quarrell, Oliver, Stewart, Alison, Willoughby, Josh, Crosby, Charlene, Elmslie, Frances, Homfray, Tessa, Jin, Huilin, Lahiri, Nayana, Mansour, Sahar, Marks, Karen, McEntagart, Meriel, Saggar, Anand, Tatton-Brown, Kate, Butler, Rachel, Clarke, Angus, Corrin, Sian, Fry, Andrew, Kamath, Arveen, McCann, Emma, Mugalaasi, Hood, Pottinger, Caroline, Procter, Annie, Sampson, Julian, Sansbury, Francis, Varghese, Vinod, Baralle, Diana, Callaway, Alison, Cassidy, Emma J., Daniels, Stacey, Douglas, Andrew, Foulds, Nicola, Hunt, David, Kharbanda, Mira, Lachlan, Katherine, Mercer, Catherine, Side, Lucy, Temple, I. Karen, Wellesley, Diana, Ambrose, J.C., Arumugam, P., Baple, E.L., Bleda, M., Boardman-Pretty, F., Boissiere, J.M., Boustred, C.R., Caulfield, M.J., Chan, G.C., Craig, C.E.H., Daugherty, L.C., de Burca, A., Devereau, A., Elgar, G., Foulger, R.E., Fowler, T., FurióTarí, P., Hackett, J.M., Halai, D., Hamblin, A., Henderson, S., Holman, J.E., Hubbard, T.J.P., Ibáñez, K., Jackson, R., Jones, L.J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S.E.A., Leong, I.U.S., Lopez, F.J., MaleadyCrowe, F., Mason, J., McDonagh, E.M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A.C., Odhams, C.A., Patch, C., Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Scott, R.H., Siddiq, A., Sieghart, A., Smedley, D., Smith, K.R., Sosinsky, A., Spooner, W., Stevens, H.E., Stuckey, A., Sultana, R., Thomas, E.R.A., Thompson, S.R., Tucci, A., Walsh, E., Watters, S.A., Welland, M.J., Williams, E., Witkowska, K., Acosta, Maria T., Adam, Margaret, Adams, David R., Agrawal, Pankaj B., Alejandro, Mercedes E., Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A., Azamian, Mahshid S., Bacino, Carlos A., Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H., Behrens, Edward, Bejerano, Gill, Bennet, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonnenmann, Carsten, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C., Brokamp, Elly, Brown, Gabrielle, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Byers, Peter, Byrd, William E., Carey, John, Carrasquillo, Olveen, Peter Chang, Ta Chen, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Coggins, Matthew, Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Craigen, William J., Crouse, Andrew B., Cunningham, Michael, D'Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davids, Mariska, Dayal, Jyoti G., Deardorff, Matthew, Dell'Angelica, Esteban C., Dhar, Shweta U., Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Douine, Emilie D., Draper, David D., Duncan, Laura, Earl, Dawn, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Esteves, Cecilia, Estwick, Tyra, Falk, Marni, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L., Findley, Laurie C., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Fresard, Laure, Gahl, William A., Glass, Ian, Godfrey, Rena A., Golden-Grant, Katie, Goldman, Alica M., Goldstein, David B., Grajewski, Alana, Groden, Catherine A., Gropman, Andrea L., Gutierrez, Irma, Hahn, Sihoun, Hamid, Rizwan, Hanchard, Neil A., Hassey, Kelly, Hayes, Nichole, High, Frances, Hing, Anne, Hisama, Fuki M., Holm, Ingrid A., Hom, Jason, Horike-Pyne, Martha, Huang, Alden, Huang, Yong, Isasi, Rosario, Jamal, Fariha, Jarvik, Gail P., Jarvik, Jeffrey, Jayadev, Suman, Johnston, Jean M., Karaviti, Lefkothea, Kelley, Emily G., Kennedy, Jennifer, Kiley, Dana, Kohane, Isaac S., Kohler, Jennefer N., Krakow, Deborah, Krasnewich, Donna M., Kravets, Elijah, Korrick, Susan, Koziura, Mary, Krier, Joel B., Lalani, Seema R., Lam, Byron, Lam, Christina, Lanpher, Brendan C., Lanza, Ian R., Lau, C. Christopher, LeBlanc, Kimberly, Lee, Brendan H., Lee, Hane, Levitt, Roy, Lewis, Richard A., Lincoln, Sharyn A., Liu, Pengfei, Liu, Xue Zhong, Longo, Nicola, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Majcherska, Marta M., Mak, Bryan, Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Mao, Rong, Maravilla, Kenneth, Markello, Thomas C., Marom, Ronit, Marth, Gabor, Martin, Beth A., Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, McCauley, Jacob, McCormack, Colleen E., McCray, Alexa T., McGee, Elisabeth, Mefford, Heather, Merritt, J. Lawrence, Might, Matthew, Mirzaa, Ghayda, Morava, Eva, Moretti, Paolo M., Morimoto, Marie, Mulvihill, John J., Murdock, David R., Nakano-Okuno, Mariko, Nath, Avi, Nelson, Stan F., Newman, John H., Nicholas, Sarah K., Nickerson, Deborah, Nieves-Rodriguez, Shirley, Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pace, Laura, Pak, Stephen, Pallais, J. Carl, Papp, Jeanette C., Parker, Neil H., Phillips, John A., Posey, Jennifer E., Potocki, Lorraine, Pusey, Barbara N., Quinlan, Aaron, Raskind, Wendy, Raja, Archana N., Rao, Deepak A., Renteria, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rosenwasser, Natalie, Ruzhnikov, Maura, Sacco, Ralph, Sampson, Jacinda B., Samson, Susan L., Saporta, Mario, Scott, C. Ron, Schaechter, Judy, Schedl, Timothy, Scott, Daryl A., Sharma, Prashant, Shin, Jimann, Signer, Rebecca, Sillari, Catherine H., Silverman, Edwin K., Sinsheimer, Janet S., Sisco, Kathy, Smith, Edward C., Smith, Kevin S., Solem, Emily, Solnica-Krezel, Lilianna, Stoler, Joan M., Stong, Nicholas, Sullivan, Jennifer A., Sun, Angela, Sutton, Shirley, Sweetser, David A., Sybert, Virginia, Tabor, Holly K., Tamburro, Cecelia P., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Tucker, Brianna M., Urv, Tiina K., Vanderver, Adeline, Velinder, Matt, Viskochil, Dave, Vogel, Tiphanie P., Wahl, Colleen E., Wallace, Stephanie, Walley, Nicole M., Walsh, Chris A., Walker, Melissa, Wambach, Jennifer, Wan, Jijun, Wang, Lee-Kai, Wangler, Michael F., Ward, Patricia A., Wegner, Daniel, Wener, Mark, Wenger, Tara, Perry, Katherine Wesseling, Westerfield, Monte, Wheeler, Matthew T., Whitlock, Jordan, Wolfe, Lynne A., Woods, Jeremy D., Yamamoto, Shinya, Yang, John, Yu, Guoyun, Zastrow, Diane B., Zhao, Chunli, Zuchner, Stephan, Jeffries, Lauren, Mis, Emily K., McWalter, Kirsty, Donkervoort, Sandra, Brodsky, Nina N., Carpier, Jean-Marie, Ji, Weizhen, Ionita, Cristian, Roy, Bhaskar, Morrow, Jon S., Darbinyan, Armine, Iyer, Krishna, Aul, Ritu B., Chao, Katherine R., Cobbold, Laura, Cohen, Stacey, Custodio, Helena M., Drummond-Borg, Margaret, Finanger, Erika, Hainline, Bryan E., Helbig, Ingo, Hewson, Stacy, Hu, Ying, Jackson, Adam, Konstantino, Monica, Leach, Meganne E., McCormick, David, Nelson, Stanley, Nguyen, Joanne, Nugent, Kimberly, Ortega, Lucy, Goodkin, Howard P., Roeder, Elizabeth, Roy, Sani, Sapp, Katie, Saade, Dimah, Sisodiya, Sanjay M., Stals, Karen, Towner, Shelley, Wilson, William, Khokha, Mustafa K., Bönnemann, Carsten G., Lucas, Carrie L., and Lakhani, Saquib A.

Published
2024
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26. Heterozygous loss-of-function variants significantly expand the phenotypes associated with loss of GDF11

Author

Ravenscroft, Thomas A, Phillips, Jennifer B, Fieg, Elizabeth, Bajikar, Sameer S, Peirce, Judy, Wegner, Jeremy, Luna, Alia A, Fox, Eric J, Yan, Yi-Lin, Rosenfeld, Jill A, Zirin, Jonathan, Kanca, Oguz, Benke, Paul J, Cameron, Eric S, Strehlow, Vincent, Platzer, Konrad, Jamra, Rami Abou, Klöckner, Chiara, Osmond, Matthew, Licata, Thomas, Rojas, Samantha, Dyment, David, Chong, Josephine SC, Lincoln, Sharyn, Stoler, Joan M, Postlethwait, John H, Wangler, Michael F, Yamamoto, Shinya, Krier, Joel, Westerfield, Monte, and Bellen, Hugo J

Subjects
Congenital Structural Anomalies, Genetics, Pediatric, 2.1 Biological and endogenous factors, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Aetiology, Animals, Bone Morphogenetic Proteins, Craniofacial Abnormalities, Growth Differentiation Factors, Humans, Mutation, Missense, Phenotype, Spine, Zebrafish, Undiagnosed Diseases Network, Clinical Sciences, Genetics & Heredity
Abstract

PurposeGrowth differentiation factor 11 (GDF11) is a key signaling protein required for proper development of many organ systems. Only one prior study has associated an inherited GDF11 variant with a dominant human disease in a family with variable craniofacial and vertebral abnormalities. Here, we expand the phenotypic spectrum associated with GDF11 variants and document the nature of the variants.MethodsWe present a cohort of six probands with de novo and inherited nonsense/frameshift (4/6 patients) and missense (2/6) variants in GDF11. We generated gdf11 mutant zebrafish to model loss of gdf11 phenotypes and used an overexpression screen in Drosophila to test variant functionality.ResultsPatients with variants in GDF11 presented with craniofacial (5/6), vertebral (5/6), neurological (6/6), visual (4/6), cardiac (3/6), auditory (3/6), and connective tissue abnormalities (3/6). gdf11 mutant zebrafish show craniofacial abnormalities and body segmentation defects that match some patient phenotypes. Expression of the patients' variants in the fly showed that one nonsense variant in GDF11 is a severe loss-of-function (LOF) allele whereas the missense variants in our cohort are partial LOF variants.ConclusionGDF11 is needed for human development, particularly neuronal development, and LOF GDF11 alleles can affect the development of numerous organs and tissues.

Published
2021

27. First Results From the Retrieved Column O/N2 Ratio From the Ionospheric Connection Explorer (ICON): Evidence of the Impacts of Nonmigrating Tides

Author

England, Scott L, Meier, RR, Frey, Harald U, Mende, Stephen B, Stephan, Andrew W, Krier, Christopher S, Cullens, Chihoko Y, Wu, Yen‐Jung J, Triplett, Colin C, Sirk, Martin M, Korpela, Eric J, Harding, Brian J, Englert, Christoph R, and Immel, Thomas J

Subjects
Earth Sciences, Atmospheric Sciences, thermosphere, atmospheric composition, atmospheric tides, airglow, Astronomical and Space Sciences, Geophysics, Astronomical sciences, Space sciences
Abstract

In near-Earth space, variations in thermospheric composition have important implications for thermosphere-ionosphere coupling. The ratio of O to N2 is often measured using far-UV airglow observations. Taking such airglow observations from space, looking below the Earth's limb allows for the total column of O and N2 in the ionosphere to be determined. While these observations have enabled many previous studies, determining the impact of non-migrating tides on thermospheric composition has proved difficult, owing to a small contamination of the signal by recombination of ionospheric O+. New ICON observations of far UV are presented here, and their general characteristics are shown. Using these, along with other observations and a global circulation model we show that during the morning hours and at latitudes away from the peak of the equatorial ionospheric anomaly, the impact of non-migrating tides on thermospheric composition can be observed. During March - April 2020, the column O/N2 ratio was seen to vary by 3 - 4 % of the zonal mean. By comparing the amplitude of the variation observed with that in the model, both the utility of these observations and a pathway to enable future studies is shown.

Published
2021

30. Commonalities across computational workflows for uncovering explanatory variants in undiagnosed cases.

Author

Kobren, Shilpa Nadimpalli, Baldridge, Dustin, Velinder, Matt, Krier, Joel B, LeBlanc, Kimberly, Esteves, Cecilia, Pusey, Barbara N, Züchner, Stephan, Blue, Elizabeth, Lee, Hane, Huang, Alden, Bastarache, Lisa, Bican, Anna, Cogan, Joy, Marwaha, Shruti, Alkelai, Anna, Murdock, David R, Liu, Pengfei, Wegner, Daniel J, Paul, Alexander J, Undiagnosed Diseases Network, Sunyaev, Shamil R, and Kohane, Isaac S

Subjects
Undiagnosed Diseases Network, Humans, Computational Biology, Genomics, Genome, Software, Genetic Testing, Workflow, Undiagnosed Diseases, Genetics, Human Genome, Genetics & Heredity, Clinical Sciences
Abstract

PurposeGenomic sequencing has become an increasingly powerful and relevant tool to be leveraged for the discovery of genetic aberrations underlying rare, Mendelian conditions. Although the computational tools incorporated into diagnostic workflows for this task are continually evolving and improving, we nevertheless sought to investigate commonalities across sequencing processing workflows to reveal consensus and standard practice tools and highlight exploratory analyses where technical and theoretical method improvements would be most impactful.MethodsWe collected details regarding the computational approaches used by a genetic testing laboratory and 11 clinical research sites in the United States participating in the Undiagnosed Diseases Network via meetings with bioinformaticians, online survey forms, and analyses of internal protocols.ResultsWe found that tools for processing genomic sequencing data can be grouped into four distinct categories. Whereas well-established practices exist for initial variant calling and quality control steps, there is substantial divergence across sites in later stages for variant prioritization and multimodal data integration, demonstrating a diversity of approaches for solving the most mysterious undiagnosed cases.ConclusionThe largest differences across diagnostic workflows suggest that advances in structural variant detection, noncoding variant interpretation, and integration of additional biomedical data may be especially promising for solving chronically undiagnosed cases.

Published
2021

31. Understanding the Impact of Resident Assistant Experiences on Their Professional Quality of Life: The Case for Increased Institutional Supports

Author

McClure, Caitlyn, Birong, Gretchen, Anderson, Jennifer, Brunn, Paul, Jang, Eun Young, and Krier-Jenkins, Amanda

Abstract

The role of a resident assistant is complex and multi-faceted, requiring a unique blend of strong interpersonal skills and professional decorum. By contrast, little is known about the depth of self-care needed to mitigate the impact of the role on resident assistants' quality of life. This exploratory mixed-methods research project seeks to determine the Professional Quality of Life (ProQOL) for resident assistants. They were surveyed using a pre- (n = 106) and post-test (n = 115) across a spring semester. Findings suggest that resident assistants experienced significant ProQOL score changes across all three indicators: compassion satisfaction, burnout, and secondary traumatic stress. [Discussion questions developed by Tracey Mason-Innes.]

Published
2022

32. Spectroscopy along Flerovium Decay Chains: Discovery of Ds280 and an Excited State in Cn282

Author

Såmark-Roth, A, Cox, DM, Rudolph, D, Sarmiento, LG, Carlsson, BG, Egido, JL, Golubev, P, Heery, J, Yakushev, A, Åberg, S, Albers, HM, Albertsson, M, Block, M, Brand, H, Calverley, T, Cantemir, R, Clark, RM, Düllmann, Ch E, Eberth, J, Fahlander, C, Forsberg, U, Gates, JM, Giacoppo, F, Götz, M, Götz, S, Herzberg, R-D, Hrabar, Y, Jäger, E, Judson, D, Khuyagbaatar, J, Kindler, B, Kojouharov, I, Kratz, JV, Krier, J, Kurz, N, Lens, L, Ljungberg, J, Lommel, B, Louko, J, Meyer, C-C, Mistry, A, Mokry, C, Papadakis, P, Parr, E, Pore, JL, Ragnarsson, I, Runke, J, Schädel, M, Schaffner, H, Schausten, B, Shaughnessy, DA, Thörle-Pospiech, P, Trautmann, N, and Uusitalo, J

Subjects
Nuclear and Plasma Physics, Synchrotrons and Accelerators, Physical Sciences, Mathematical Sciences, Engineering, General Physics, Mathematical sciences, Physical sciences
Abstract

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1)  MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518  μs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

Published
2021

33. Spectroscopy along Flerovium Decay Chains: Discovery of ^{280}Ds and an Excited State in ^{282}Cn.

Author

Såmark-Roth, A, Cox, DM, Rudolph, D, Sarmiento, LG, Carlsson, BG, Egido, JL, Golubev, P, Heery, J, Yakushev, A, Åberg, S, Albers, HM, Albertsson, M, Block, M, Brand, H, Calverley, T, Cantemir, R, Clark, RM, Düllmann, Ch E, Eberth, J, Fahlander, C, Forsberg, U, Gates, JM, Giacoppo, F, Götz, M, Götz, S, Herzberg, R-D, Hrabar, Y, Jäger, E, Judson, D, Khuyagbaatar, J, Kindler, B, Kojouharov, I, Kratz, JV, Krier, J, Kurz, N, Lens, L, Ljungberg, J, Lommel, B, Louko, J, Meyer, C-C, Mistry, A, Mokry, C, Papadakis, P, Parr, E, Pore, JL, Ragnarsson, I, Runke, J, Schädel, M, Schaffner, H, Schausten, B, Shaughnessy, DA, Thörle-Pospiech, P, Trautmann, N, and Uusitalo, J

Subjects
General Physics, Mathematical Sciences, Physical Sciences, Engineering
Abstract

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1)  MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518  μs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

Published
2021

35. The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies

Author

Attié-Bitach, Tania, Comier-Daire, Valerie, Rozet, Jean-Michel, Frishberg, Yaacov, Llanas, Brigitte, Broyer, Michel, Mohsin, Nabil, Macher, Marie-Alice, Philip, Nicole, Baudouin, Véronique, Brackman, Damian, Loirat, Chantal, Charbit, Marina, Dehennault, Maud, Guyot, Claude, Bataille, Pierre, Elting, Mariet, Deschenes, Georges, Gropman, Andrea, Guest, Geneviève, Gagnadoux, Marie-France, Nicoud, Philippe, Cochat, Pierre, Ranchin, Bruno, Bensman, Albert, Guerrot, Anne-Marie, Knebelmann, Bertrand, Bilge, Ilmay, Bruno, Danièle, Burtey, Stéphane, Rouvière, Caroline Rousset, Caudwell, Valérie, Morin, Denis, Dollfus, Hélène, Maisin, Anne, Hamel, Christian, Bieth, Eric, Gie, Sophie, Goodship, Judith, Roussey, Gwenaelle, La Selve, Hermine, Nivet, Hubert, Bessenay, Lucie, Caillez, Mathilde, Palcoux, Jean Bernard, Benoît, Stéphane, Dubot, Philippe, Fila, Marc, Giuliano, Fabienne, Iftene, Daouya, Kessler, Michele, Kwon, Theresa, Lahoche, Anine, Laurent, Audrey, Leclerc, Anne-Laure, Milford, David, Neuhaus, Thomas, Odent, Sylvie, Eckart, Philippe, Chauveau, Dominique, Niaudet, Patrick, Repetto, Horacio, Taque, Sophie, Bruel, Alexandra, Noel-Botte, Alexandra, Launay, Emma Allain, Allard, Lisa, Anlicheau, Dany, Adra, Anne-Laure, Garnier, Arnaud, Nagra, Arvind, Baatard, Remy, Bacchetta, Justine, Sadikoglu, Banu, Barnerias, Christine, Barthelemy, Anne, Basel, Lina, Bassilios, Nader, Ben Maiz, Hedi, Ben Moussa, Fatma, Benmati, Faïza, Berthaud, Romain, Bertholet, Aurélia, Blanchier, Dominique, Boffa, Jean Jacques, Bouchireb, Karim, Bouhabel, Ihab, Boukerroucha, Zakaria, Bourdat-Michel, Guylhène, Boute, Odile, Brochard, Karine, Caumes, Roseline, Elalaoui, Siham Chafai, Chamontin, Bernard, Chastang, Marie Caroline, Pietrement, Christine, Richer, Christine, Legendre, Christophe, Dahan, Karin, Dalla-Vale, Fabienne, Thibaudin, Damien, Dauvergne, Maxime, Davourie, Salandre, Debeukelaer, Martin, Delbet, Jean Daniel, Deltas, Constantinos, Graber, Denis, Devillars, Nadège, Diouf, Boucar, Fenzy, Martine Doco, André, Jean-Luc, Joly, Dominique, Fryer, Alan, Albano, Laetitia, Cassuto, Elisabeth, Pincon, Aline, Medeira, Ana, Chaussenot, Annabelle, Mensire-Marinier, Anne, Bouissou, Francois, Decramer, Stephane, Bottani, Armand, Hummel, Aurélie, Karras, Alexandre, Katz, Avi, Azema, Christine, Janbon, Bénédicte, Roussel, Bernard, Bonniol, Claude, Mariat, Christiophe, Champion, Gérard, Chantreuil, Deborah, Chassaing, Nicolas, Mousson, Christiane, Baudeau, Christine, Cuntz, Delphine Hafdar, Mignot, Cyril, Dehoux, Laurene, Lacombe, Didier, Hannedouche, Thierry, Mérieau, Elodie, Charlin, Emmanuelle, Gauthier, Eric, Plasse, Florent, Faguer, Stanislas, Lebas, Fanny, Demurger, Florence, Emma, Francesco, Cartault, François, Dumont, Geneviève, Godefroid, Nathalie, Guigonis, Vincent, Hillaire, Sophie, Groothoff, Jaap, Dudley, Jan, Jourde-Chiche, Noémie, El Karoui, Khalil, Krid, Saoussen, Coudert, Krier, Bencheick, Larbi, Yver, Laurent, Lavocat, Marie-Pierre, De Sagazan, Le Monies, Leroy, Valerie, Thibaudin, Lise, Ingulli, Liz, Gwanmesia, Lorraine, Burglen, Lydie, Saïd-Menthon, Marie-Hélène, Carrera, Marta, Nizon, Mathilde, Melander, Catherine, Foulard, Michel, Blayo, Monique, Prinseau, Jacques, Jay, Nadine, Brun, Nathalie, Camille, Nicolas, Nobili, François, Devuyst, Olivier, Ben Brahim, Ouafa, Parvex, Paloma, Sabourin, Laurence Perrin, Blanc, Philippe, Vanhille, Philippe, Galichon, Pierre, Pierrepont, Sophie, Planquois, Vincent, Poussard, Gwenaelle, Noble, Claire Pouteil, Allal, Radia, Bernard, Raphaelle, Mounet, Raynaud, Cahen, Rémi, Touraine, Renaud, Rigothier, Claire, Ryckewaert, Amélie, Sacquepee, Mathieu, El Chehadeh, Salima, Samaille, Charlotte, Haq, Shuman, Simckes, Ari, Lanoiselée, Stéphanie, Tellier, Stephanie, Subra, Jean-François, Cloarec, Sylvie, Tenenbam, Julie, Lamy, Thomas, Garraud, Valérie Drouin, Valette, Huguette, Meyssonnier, Vanina, Vargas-Poussou, Rosa, Snajer, Yves, Durault, Sandrine, Plaisier, Emmanuelle, Berard, Etienne, Fakhouri, Fadi, Louillet, Ferielle, Finielz, Paul, Fischbach, Michel, Foliguet, Bernard, Francois-Pradier, Hélène, Garaix, Florentine, Gerard, Marion, Rizzoni, Gianfranco, Gilbert, Brigitte, Glotz, Denis, Dubrasquet, Astrid Godron, Grünfeld, Jean-Pierre, Bollee, Guillaume, Hall, Michelle, Hansson, Sverker, Haye, Damien, Taffin, Hélène, Hildebrandt, Friedhelm, Hourmand, Maryvonne, Kayserili, Hümya, Tack, Ivan, Jacquemont, Marie Line, Fabre-Teste, Jennifer, Kashtan, Cliff, Van Hoeck, Kkoen, Klein, Alexandre, Knefati, Yannick, Knoers, Nine, Konrad, Martin, Lachaux, Alain, Landru, Isabelle, Landthaler, Gilbert, Lang, Philippe, Le Pogamp, Patrick, Legris, Tristan, Didailler, Catherine, Lobbedez, Thierry, de Parscau, Loïc, Pinson, Lucile, Maheut, Hervé, Duval-Arnould, Marc, Rio, Marlène, Gubler, Marie-Claire, Merville, Pierre, Mestrallet, Guillaume, Meunier, Maite, Moreau, Karine, Harambat, Jérôme, Morgan, Graeme, Mourad, Georges, Stuber, Niksic, Boespflug-Tanguy, Odile, Dunand, Olivier, Niel, Olivier, Ouali, Nacera, Malvezzi, Paolo, Jaoude, Pauline Abou, Pelletier, Solenne, Peltier, Julie, Petersen, M.B., Michel, Philippe, Rémy, Philippe, Philit, Jean-Baptiste, Pichault, Valérie, Billette de Villemeur, Thierry, Boudailliez, Bernard, Leheup, Bruno, Dossier, Claire, Djeddi, Djamal-Dine, Berland, Yves, Hurault de Ligny, Bruno, Rigden, Susan, Robino, Christophe, Rossi, Annick, Sarnacki, Sabine, Saidani, Messaoud, Sartorius, Albane Brodin, Schäfer, Elise, Laszlo, Sztriha, Thouret, Marie-Christine, Thuillier-Lecouf, Angélique, Trachtman, Howard, Trivin, Claire, Tsimaratos, Michel, Van Damme-Lombaerts, Rita, Willems, Marjolaine, Youssef, Michel, Zaloszyc, Ariane, Zawodnik, Alexis, Ziliotis, Marie-Julia, Petzold, Friederike, Billot, Katy, Chen, Xiaoyi, Henry, Charline, Filhol, Emilie, Martin, Yoann, Avramescu, Marina, Douillet, Maxime, Morinière, Vincent, Krug, Pauline, Jeanpierre, Cécile, Tory, Kalman, Boyer, Olivia, Burgun, Anita, Servais, Aude, Salomon, Remi, Benmerah, Alexandre, Heidet, Laurence, Garcelon, Nicolas, Antignac, Corinne, Zaidan, Mohamad, and Saunier, Sophie

Published
2023
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40. Spectroscopic Tools Applied to Flerovium Decay Chains

Author

Cox, DM, Såmark-Roth, A, Rudolph, D, Sarmiento, LG, Fahlander, C, Forsberg, U, Golubev, P, Heery, JAM, Yakushev, A, Albers, HM, Block, M, Brand, H, Clark, RM, Düllmann, Ch E, Eberth, J, Gates, JM, Giacoppo, F, Götz, M, Götz, S, Herzberg, R-D, Jäger, E, Kindler, B, Khuyagbaatar, J, Kojouharov, I, Kratz, JV, Krier, J, Kurz, N, Lens, L, Lommel, B, Mistry, A, Meyer, C-C, Mokry, C, Papadakis, P, Pore, JL, Runke, J, Thörle-Pospiech, P, Trautmann, N, Schaffner, H, Schausten, B, and Uusitalo, J

Subjects
Nuclear and Plasma Physics, Synchrotrons and Accelerators, Physical Sciences, Atomic, Molecular, Nuclear, Particle and Plasma Physics, Condensed Matter Physics, Other Physical Sciences, Physical sciences
Abstract

An upgraded TASISpec setup, with the addition of a veto DSSD and the new Compex detector-germanium array, has been employed with the gas-filled recoil separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, to study flerovium (element 114) decay chains. The detector upgrades along with development of new analytical techniques have improved the sensitivity of the TASISpec setup for measuring α-photon coincidences. These improvements have been assessed with test reactions. The reaction 48Ca+206,207Pb was used for verification of experimental parameters such as transmission to implantation DSSD and target-segment to α-decay correlations. The reaction 48Ca+ nat Hf was used to produce several short-lived nuclei with multiple-α decay chains to investigate pile-up event deconvolution.

Published
2020

42. Morphology-assisted galaxy mass-to-light predictions using deep learning

Author

Dobbels, Wouter, Krier, Serge, Pirson, Stephan, Viaene, Sébastien, De Geyter, Gert, Salim, Samir, and Baes, Maarten

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

One of the most important properties of a galaxy is the total stellar mass, or equivalently the stellar mass-to-light ratio (M/L). It is not directly observable, but can be estimated from stellar population synthesis. Currently, a galaxy's M/L is typically estimated from global fluxes. For example, a single global g - i colour correlates well with the stellar M/L. Spectral energy distribution (SED) fitting can make use of all available fluxes and their errors to make a Bayesian estimate of the M/L. We want to investigate the possibility of using morphology information to assist predictions of M/L. Our first goal is to develop and train a method that only requires a g-band image and redshift as input. This will allows us to study the correlation between M/L and morphology. Next, we can also include the i-band flux, and determine if morphology provides additional constraints compared to a method that only uses g- and i-band fluxes. We used a machine learning pipeline that can be split in two steps. First, we detected morphology features with a convolutional neural network. These are then combined with redshift, pixel size and g-band luminosity features in a gradient boosting machine. Our training target was the M/L acquired from the GALEX-SDSS-WISE Legacy Catalog, which uses global SED fitting and contains galaxies with z ~ 0.1. Morphology is a useful attribute when no colour information is available, but can not outperform colour methods on its own. When we combine the morphology features with global g- and i-band luminosities, we find an improved estimate compared to a model which does not make use of morphology. While our method was trained to reproduce global SED fitted M/L, galaxy morphology gives us an important additional constraint when using one or two bands. Our framework can be extended to other problems to make use of morphological information., Comment: 17 pages, 8 figures, accepted by A&A

Published
2019
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43. De Novo Variants in the ATPase Module of MORC2 Cause a Neurodevelopmental Disorder with Growth Retardation and Variable Craniofacial Dysmorphism

Author

Sacoto, Maria J Guillen, Tchasovnikarova, Iva A, Torti, Erin, Forster, Cara, Andrew, E Hallie, Anselm, Irina, Baranano, Kristin W, Briere, Lauren C, Cohen, Julie S, Craigen, William J, Cytrynbaum, Cheryl, Ekhilevitch, Nina, Elrick, Matthew J, Fatemi, Ali, Fraser, Jamie L, Gallagher, Renata C, Guerin, Andrea, Haynes, Devon, High, Frances A, Inglese, Cara N, Kiss, Courtney, Koenig, Mary Kay, Krier, Joel, Lindstrom, Kristin, Marble, Michael, Meddaugh, Hannah, Moran, Ellen S, Morel, Chantal F, Mu, Weiyi, Muller, Eric A, Nance, Jessica, Natowicz, Marvin R, Numis, Adam L, Ostrem, Bridget, Pappas, John, Stafstrom, Carl E, Streff, Haley, Sweetser, David A, Szybowska, Marta, Network, Undiagnosed Diseases, Walker, Melissa A, Wang, Wei, Weiss, Karin, Weksberg, Rosanna, Wheeler, Patricia G, Yoon, Grace, Kingston, Robert E, and Juusola, Jane

Subjects
Neurodegenerative, Rare Diseases, Pediatric, Genetics, Brain Disorders, Intellectual and Developmental Disabilities (IDD), Neurosciences, Congenital Structural Anomalies, Clinical Research, Dental/Oral and Craniofacial Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adenosine Triphosphatases, Adolescent, Adult, Child, Child, Preschool, Craniofacial Abnormalities, Female, Genetic Diseases, Inborn, Growth Disorders, Heterozygote, Humans, Infant, Intellectual Disability, Male, Microcephaly, Middle Aged, Mutation, Neurodevelopmental Disorders, Phenotype, Transcription Factors, Young Adult, Undiagnosed Diseases Network, CMT2Z, Leigh-like disease, MORC2, developmental delay, intellectual disability, microcephaly, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

MORC2 encodes an ATPase that plays a role in chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous variants in MORC2 have been reported in individuals with autosomal-dominant Charcot-Marie-Tooth disease type 2Z and spinal muscular atrophy, and the onset of symptoms ranges from infancy to the second decade of life. Here, we present a cohort of 20 individuals referred for exome sequencing who harbor pathogenic variants in the ATPase module of MORC2. Individuals presented with a similar phenotype consisting of developmental delay, intellectual disability, growth retardation, microcephaly, and variable craniofacial dysmorphism. Weakness, hyporeflexia, and electrophysiologic abnormalities suggestive of neuropathy were frequently observed but were not the predominant feature. Five of 18 individuals for whom brain imaging was available had lesions reminiscent of those observed in Leigh syndrome, and five of six individuals who had dilated eye exams had retinal pigmentary abnormalities. Functional assays revealed that these MORC2 variants result in hyperactivation of epigenetic silencing by the HUSH complex, supporting their pathogenicity. The described set of morphological, growth, developmental, and neurological findings and medical concerns expands the spectrum of genetic disorders resulting from pathogenic variants in MORC2.

Published
2020

44. Quantifying Downstream Healthcare Utilization in Studies of Genomic Testing

Author

Mackay, Zoë P, Dukhovny, Dmitry, Phillips, Kathryn A, Beggs, Alan H, Green, Robert C, Parad, Richard B, Christensen, Kurt D, Team, BabySeq Project, Agrawal, Pankaj B, Ceyhan-Birsoy, Ozge, Fayer, Shawn, Frankel, Leslie A, Genetti, Casie A, Gutierrez, Amanda M, Harden, Maegan, Holm, Ingrid A, Krier, Joel B, Lebo, Matthew S, Machini, Kalotina, McGuire, Amy L, Naik, Medha, Nguyen, Tiffany T, Pereira, Stacey, Ramanathan, Vivek, Rehm, Heidi L, Roberts, Amy, Robinson, Jill O, Roumiantsev, Sergei, Schwartz, Talia S, Truong, Tina K, VanNoy, Grace E, Waisbren, Susan E, and Yu, Timothy W

Subjects
Health Services and Systems, Health Sciences, Clinical Research, Human Genome, Health Services, Genetics, Patient Safety, Health and social care services research, 8.1 Organisation and delivery of services, Good Health and Well Being, Female, Genetic Testing, Genomics, Humans, Infant, Longitudinal Studies, Male, Parents, Patient Acceptance of Health Care, Risk Factors, Surveys and Questionnaires, Telephone, genetic testing, genomics, healthcare utilization, health services, humans, infant, newborn, medical records, risk factors, surveys and questionnaires, whole exome sequencing, BabySeq Project Team, Public Health and Health Services, Applied Economics, Health Policy & Services, Applied economics, Health services and systems, Policy and administration
Abstract

ObjectivesThe challenges of understanding how interventions influence follow-up medical care are magnified during genomic testing because few patients have received it to date and because the scope of information it provides is complex and often unexpected. We tested a novel strategy for quantifying downstream healthcare utilization after genomic testing to more comprehensively and efficiently identify related services. We also evaluated the effectiveness of different methods for collecting these data.MethodsWe developed a risk-based approach for a trial of newborn genomic sequencing in which we defined primary conditions based on existing diagnoses and family histories of disease and defined secondary conditions based on unexpected findings. We then created patient-specific lists of services associated with managing primary and secondary conditions. Services were quantified based on medical record reviews, surveys, and telephone check-ins with parents.ResultsBy focusing on services that genomic testing would most likely influence in the short-term, we reduced the number of services in our analyses by more than 90% compared with analyses of all observed services. We also identified the same services that were ordered in response to unexpected findings as were identified during expert review and by confirming whether recommendations were completed. Data also showed that quantifying healthcare utilization with surveys and telephone check-ins alone would have missed the majority of attributable services.ConclusionsOur risk-based strategy provides an improved approach for assessing the short-term impact of genomic testing and other interventions on healthcare utilization while conforming as much as possible to existing best-practice recommendations.

Published
2020

45. Optical properties of metamorphic type-I InAs$_{1-x}$Sb$_{x}$/Al$_{y}$In$_{1-y}$As quantum wells grown on GaAs for the mid-infrared spectral range

Author

Repiso, Eva, Broderick, Christopher A., de la Mata, Maria, Arkani, Reza, Lu, Qi, Marshall, Andrew R. J., Molina, Sergio I., O'Reilly, Eoin P., Carrington, Peter J., and Krier, Anthony

Subjects
Condensed Matter - Materials Science
Abstract

We analyse the optical properties of InAs$_{1-x}$Sb$_{x}$/Al$_{y}$In$_{1-y}$As quantum wells (QWs) grown by molecular beam epitaxy on relaxed Al$_{y}$In$_{1-y}$As metamorphic buffer layers (MBLs) using GaAs substrates. The use of Al$_{y}$In$_{1-y}$As MBLs allows for the growth of QWs having large type-I band offsets, and emission wavelengths $> 3$ $\mu$m. Photoluminescence (PL) measurements for QWs having Sb compositions up to $x = 10$\% demonstrate strong room temperature emission up to 3.4 $\mu$m, as well as enhancement of the PL intensity with increasing wavelength. To quantify the trends in the measured PL we calculate the QW spontaneous emission, using a theoretical model based on an 8-band $\vec{k} \cdot \vec{p}$ Hamiltonian. The theoretical calculations, which are in good agreement with experiment, identify that the observed enhancement in PL intensity with increasing wavelength is associated with the impact of compressive strain on the QW valence band structure. Our results highlight the potential of type-I InAs$_{1-x}$Sb$_{x}$/Al$_{y}$In$_{1-y}$As metamorphic QWs to address several limitations associated with existing heterostructures operating in the mid-infrared, establishing these novel heterostructures as a suitable platform for the development of mid-infrared light-emitting diodes.

Published
2018
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46. De Novo Pathogenic Variants in N-cadherin Cause a Syndromic Neurodevelopmental Disorder with Corpus Collosum, Axon, Cardiac, Ocular, and Genital Defects

Author

Accogli, Andrea, Calabretta, Sara, St-Onge, Judith, Boudrahem-Addour, Nassima, Dionne-Laporte, Alexandre, Joset, Pascal, Azzarello-Burri, Silvia, Rauch, Anita, Krier, Joel, Fieg, Elizabeth, Pallais, Juan C, Network, Undiagnosed Diseases, Acosta, Maria T, Adams, David R, Agrawal, Pankaj, Alejandro, Mercedes E, Allard, Patrick, Alvey, Justin, Andrews, Ashley, Ashley, Euan A, Azamian, Mahshid S, Bacino, Carlos A, Bademci, Guney, Baker, Eva, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Barbouth, Deborah, Batzli, Gabriel F, Bayrak-Toydemir, Pinar, Beggs, Alan H, Bejerano, Gill, Bellen, Hugo J, Bernstein, Jonathan A, Berry, Gerard T, Bican, Anna, Bick, David P, Birch, Camille L, Bivona, Stephanie, Bohnsack, John, Bonnenmann, Carsten, Bonner, Devon, Boone, Braden E, Bostwick, Bret L, Botto, Lorenzo, Briere, Lauren C, Brokamp, Elly, Brown, Donna M, Brush, Matthew, Burke, Elizabeth A, Burrage, Lindsay C, Butte, Manish J, Carey, John, Carrasquillo, Olveen, Chang, Ta Chen Peter, Chao, Hsiao-Tuan, Clark, Gary D, Coakley, Terra R, Cobban, Laurel A, Cogan, Joy D, Cole, F Sessions, Colley, Heather A, Cooper, Cynthia M, Cope, Heidi, Craigen, William J, D’Souza, Precilla, Dasari, Surendra, Davids, Mariska, Dayal, Jyoti G, Dell’Angelica, Esteban C, Dhar, Shweta U, Dorrani, Naghmeh, Dorset, Daniel C, Douine, Emilie D, Draper, David D, Duncan, Laura, Eckstein, David J, Emrick, Lisa T, Eng, Christine M, Esteves, Cecilia, Estwick, Tyra, Fernandez, Liliana, Ferreira, Carlos, Fieg, Elizabeth L, Fisher, Paul G, Fogel, Brent L, Forghani, Irman, Fresard, Laure, Gahl, William A, Godfrey, Rena A, Goldman, Alica M, Goldstein, David B, Gourdine, Jean-Philippe F, Grajewski, Alana, Groden, Catherine A, Gropman, Andrea L, Haendel, Melissa, Hamid, Rizwan, Hanchard, Neil A, and Hayes, Nichole

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Genetics, Biological Sciences, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Axons, Cadherins, Corpus Callosum, Eye, Frameshift Mutation, Genitalia, Heart Defects, Congenital, Heterozygote, Humans, Neurodevelopmental Disorders, Undiagnosed Diseases Network, ACOG, CDH2, N-cadherin, cardiac defects, cell-cell adhesion, corpus callosum, eye defects, genital defects, intellectual disability, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Cadherins constitute a family of transmembrane proteins that mediate calcium-dependent cell-cell adhesion. The extracellular domain of cadherins consists of extracellular cadherin (EC) domains, separated by calcium binding sites. The EC interacts with other cadherin molecules in cis and in trans to mechanically hold apposing cell surfaces together. CDH2 encodes N-cadherin, whose essential roles in neural development include neuronal migration and axon pathfinding. However, CDH2 has not yet been linked to a Mendelian neurodevelopmental disorder. Here, we report de novo heterozygous pathogenic variants (seven missense, two frameshift) in CDH2 in nine individuals with a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, variable axon pathfinding defects (corpus callosum agenesis or hypoplasia, mirror movements, Duane anomaly), and ocular, cardiac, and genital anomalies. All seven missense variants (c.1057G>A [p.Asp353Asn]; c.1789G>A [p.Asp597Asn]; c.1789G>T [p.Asp597Tyr]; c.1802A>C [p.Asn601Thr]; c.1839C>G [p.Cys613Trp]; c.1880A>G [p.Asp627Gly]; c.2027A>G [p.Tyr676Cys]) result in substitution of highly conserved residues, and six of seven cluster within EC domains 4 and 5. Four of the substitutions affect the calcium-binding site in the EC4-EC5 interdomain. We show that cells expressing these variants in the EC4-EC5 domains have a defect in cell-cell adhesion; this defect includes impaired binding in trans with N-cadherin-WT expressed on apposing cells. The two frameshift variants (c.2563_2564delCT [p.Leu855Valfs∗4]; c.2564_2567dupTGTT [p.Leu856Phefs∗5]) are predicted to lead to a truncated cytoplasmic domain. Our study demonstrates that de novo heterozygous variants in CDH2 impair the adhesive activity of N-cadherin, resulting in a multisystemic developmental disorder, that could be named ACOG syndrome (agenesis of corpus callosum, axon pathfinding, cardiac, ocular, and genital defects).

Published
2019

47. Platform-based food delivery in Paris before and during the pandemic: profile, motivations and mobility patterns of couriers

Author

Anne Aguilera, Laetitia Dablanc, Camille Krier, and Nicolas Louvet

Subjects
Delivery, Platforms, Couriers, Bikes, Shared mobility, Accidents, Transportation engineering, TA1001-1280, Transportation and communications, HE1-9990
Abstract

Abstract Background Platform-based fast delivery is developing rapidly in many cities across the world, especially in the food sector. Yet knowledge about the characteristics and the activity patterns of delivery couriers is scarce, especially in terms of their mobility behavior. Methodology Based on two questionnaire surveys conducted in 2020 and 2021 with 300 and 500 couriers respectively, this article analyses the profiles, motivations and mobility patterns of couriers working in Paris (France), with a focus on the impacts of the pandemic. Results First, the analysis of the profiles and motivations of couriers reveals that platform-based delivery is largely a temporary activity performed by young males of foreign origin, and undertaken as a student job or an entry to the labor market. Second, data on mobility patterns confirm that platform-based delivery is a dangerous activity with a high risk of road accidents. Moreover, many couriers break the law in order to increase their income by using motorized two-wheelers that are not legally permitted in France. We also show the use of shared bikes, which seems to be a great support tool for couriers who are starting work in this sector or have a problem with their own bikes. Third, the pandemic prompted many students to become platform-based delivery couriers in order to compensate for the lack of student jobs. It also worsened the working conditions of the majority of platform-based couriers. These findings raise new urban policy challenges and also new avenues for research in terms of topics and methods.

Published
2022
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50. Synthesis and crystal structure of rac-2-(1,3-dioxoisoindolin-2-yl)ethyl 4-methyl-N-phenyl-N′-(triisopropylsilyl)benzenesulfondiimidoate: the first member of a new substance class

Author

Erik Friedrich, Timo Heinrich, Lara Rosenberger, Mireille Krier, Stephanie Marek, and Michael Reggelin

Subjects
sulfondiimidoate, sulfondiimidate, crystal structure, bioisosters, Crystallography, QD901-999
Abstract

The title compound {systematic name: rac-2-[7-methyl-4-(4-methylphenyl)-4-(phenylimino)-6,6-bis(propan-2-yl)-3-oxa-4λ6-thia-5-aza-6-silaoct-4-en-1-yl]-2,3-dihydro-1H-isoindole-1,3-dione}, C32H41N3O3SSi, was synthesized by desoxychlorination of 4-methyl-N-phenyl-N′-(triisopropylsilyl)benzenesulfonimidamide and subsequent reaction with 2-(2-hydroxyethyl)isoindoline-1,3-dione. The racemic compound was crystallized from isopropanol. The structural characterization by single-crystal X-ray diffraction revealed two double-bonded nitrogen atoms to the central sulfur atom and an overall crystal packing driven by its aromatic interactions.

Published
2022
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