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Fully understanding the complex mechanical function of temporomandibular joint (TMJ) cartilage and the compositional and structural organization that underlie it is a persistent challenge. Changes to composition, structure, and mechanics take place in naturally occurring disease in humans and canines as well as in disease models, such as in pigs. This study combined histology, Fourier transform infrared (FTIR) microscopy, Fast Fourier transform (FFT), and confocal elastography to quantify the relationship between the microscale composition, structure, and shear mechanics of porcine, canine, and human TMJ cartilage. All three species had distinct zonal mechanics and similarly high stiffness of 105~106 Pa in the hypertrophic zone. Notably, porcine tissue had a thick, compliant fibrous zone (~ 200 µm) (G* < 104 Pa) that was absent in canine and human tissue. The hypertrophic zone of all three species had high proteoglycan content, while the surface regions showed higher collagen content and fiber orientation. Small changes (two-fold) in composition led to large changes (twenty-fold) in modulus. Structural orientation of the fibers showed that high fiber orientation led to more compliant tissue mechanics while the angle of orientation was not predictive of the shear mechanics. The relationship between local composition, structure, and mechanics were similar in all three species. Despite this similarity, the immature pigs used most frequently in disease models have a very thick compliant surface region, the presence of which is likely to alter the degenerative process.

We report a measurement of the nuclear polarization of laser-cooled, optically pumped ^37 K atoms which will allow us to precisely measure angular correlation parameters in the ${\beta }^{+}$ -decay of the same atoms. These results will be used to test the V − A framework of the weak interaction at high precision. At the Triumf neutral atom trap ( Trinat ), a magneto-optical trap confines and cools neutral ^37 K atoms and optical pumping spin-polarizes them. We monitor the nuclear polarization of the same atoms that are decaying in situ by photoionizing a small fraction of the partially polarized atoms and then use the standard optical Bloch equations to model their population distribution. We obtain an average nuclear polarization of $\bar{P}=0.9913\pm 0.0009$ , which is significantly more precise than previous measurements with this technique. Since our current measurement of the β -asymmetry has $0.2 \% $ statistical uncertainty, the polarization measurement reported here will not limit its overall uncertainty. This result also demonstrates the capability to measure the polarization to $\lt 0.1 \% $ , allowing for a measurement of angular correlation parameters to this level of precision, which would be competitive in searches for new physics.

We present a new method of constructing a fully robust qubit in a three-level system. By the application of continuous driving fields, robustness to both external and controller noise is achieved. Specifically, magnetic noise and power fluctuations do not operate within the robust qubit subspace. Whereas all the continuous driving based constructions of such a fully robust qubit considered so far have required at least four levels, we show that in fact only three levels are necessary. This paves the way for simple constructions of a fully robust qubit in many atomic and solid state systems that are controlled by either microwave or optical fields. We focus on the NV-center in diamond and analyze the implementation of the scheme, by utilizing the electronic spin sub-levels of its ground state. In current state-of-the-art experimental setups the scheme leads to improvement of more than two orders of magnitude in coherence time, pushing it towards the lifetime limit. We show how the fully robust qubit can be used to implement quantum sensing, and in particular, the sensing of high frequency signals.

A proposal for a phase gate and a Mølmer–Sørensen gate in the dressed state basis is presented. In order to perform the multi-qubit interaction, a strong magnetic field gradient is required to couple the phonon-bus to the qubit states. The gate is performed using resonant microwave driving fields together with either a radio-frequency (RF) driving field, or additional detuned microwave driving fields. The gate is robust to ambient magnetic field fluctuations due to an applied resonant microwave driving field. Furthermore, the gate is robust to fluctuations in the microwave Rabi frequency and is decoupled from phonon dephasing due to a resonant RF or a detuned microwave driving field. This makes this new gate an attractive candidate for the implementation of high-fidelity microwave based multi-qubit gates. The proposal can also be realized in laser-based set-ups.

Haemodialysis is the most used among the different renal function replacement methods. Although the survival is acceptable the mobility is important; intradialytic hypotension is a main cause of such mobility. In this study which included stable chronic haemodialysis patients, the authors evaluate risk factors for IDH. Advanced age, female sex and autonomic insufficiency are risk factors for IDH. Patients with IDH had more serious ventricular arrhythmias, but a cause-effect relationship was not demonstrated.

Abstract Seven viruses cause at least 15% of the total cancer burden. Viral cancers have been described as the “low-hanging fruit” that can be potentially prevented or treated by new vaccines that would alter the course of global human cancer. Kaposi sarcoma herpesvirus (KSHV or HHV8) is the sole cause of Kaposi sarcoma, which primarily afflicts resource-poor and socially marginalized populations. This review summarizes a recent NIH-sponsored workshop’s findings on the epidemiology and biology of KSHV as an overlooked but potentially vaccine-preventable infection. The unique epidemiology of this virus provides opportunities to prevent its cancers if an effective, inexpensive, and well-tolerated vaccine can be developed and delivered.

Abstract The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.

Abstract In the United States, the transition from unchecked hunting, habitat loss, and species endangerment to an ongoing environmental awakening has been examined through various lenses. Despite this gradual perspective shift, recent reports continue to warn of global declines in species and habitat diversity. As the need for biodiversity conservation grows, nations lag behind in their conservation obligations, creating a funding gap. This paper addresses an untapped potential for funding available from stamp revenue as generated in the United States. We begin with an historical summary of wildlife philatelics and end with specialized stamps providing for biodiversity revenue generation. After the publication of Silent Spring, stamp diversification increased due to the recognition of additional environmental and conservation needs, leading to stamp-based revenue as one means to mitigate funding gaps. Having introduced this term, we provide evidence of its potential to fund biodiversity and animal conservation. Historically, stamp-based revenues began with Migratory Bird Hunting license stamps, followed by the semi-postal Amur tiger cub stamp, and eventually local and state stamps whose purchase provides funding for local conservation needs. Specific successful philatelic funding mechanisms are discussed from the United State, with an eye to future development and expansion intentionally in support of conservation and biodiversity.

There is increasing evidence suggesting that Epstein-Barr virus infection is a causative factor of multiple sclerosis (MS). Epstein-Barr virus (EBV) is a human herpesvirus, Human Gammaherpesvirus 4. EBV infection shows two peaks: firstly, during early childhood and, secondly during the teenage years. Approximately, 90–95% of adults have been infected with EBV and for many this will have been a subclinical event. EBV infection can be associated with significant morbidity and mortality; for example, primary infection in older children or adults is the leading cause of infectious mononucleosis (IM). A disrupted immune response either iatrogenically induced or through genetic defects can result in lymphoproliferative disease. Finally, EBV is oncogenic and is associated with several malignancies. For these reasons, vaccination to prevent the damaging aspects of EBV infection is an attractive intervention. No EBV vaccines have been licensed and the prophylactic vaccine furthest along in clinical trials contains the major virus glycoprotein gp350. In a phase 2 study, the vaccine reduced the rate of IM by 78% but did not prevent EBV infection. An EBV vaccine to prevent IM in adolescence or young adulthood is the most likely population-based vaccine strategy to be tested and adopted. National registry studies will need to be done to track the incidence of MS in EBV-vaccinated and unvaccinated people to see an effect of the vaccine on MS. Assessment of vaccine efficacy with MS being a delayed consequence of EBV infection with the average age of onset being approximately 30 years of age represents multiple challenges.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

BackgroundDespite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. We hypothesized that these differences in presentation are related to differences in the magnitude and/or antigen specificity of SARS-CoV-2-specific T cell (CST) responses between adults and children. We therefore set out to measure the CST response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection.MethodsCSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay.FindingsTwenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses in MIS-C patients were significantly higher than children with uncomplicated SARS-CoV-2 infection, but weaker than CST responses in convalescent adults.InterpretationAge-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults post uncomplicated infection. Children with MIS-C have CST responses that are stronger than children with uncomplicated SARS-CoV-2 infection and weaker than convalescent adults, despite near uniform seropositivity.

This article provides a concise review of the main physical structures and processes involved in space weather’s interconnected systems, emphasizing the critical roles played by magnetic topology and connectivity. The review covers solar drivers of space weather activity, the heliospheric environment, and the magnetospheric response, and is intended to address a growing cross-disciplinary audience interested in applied aspects of modern space weather research and forecasting. The review paper includes fundamental facts about the structure of space weather subsystems and special attention is paid to extreme space weather events associated with major solar flares, large coronal mass ejections, solar energetic particle events, and intense geomagnetic perturbations and their ionospheric footprints. This paper aims to be a first step towards understanding the magnetically connected space weather system for individuals new to the field of space weather who are interested in the basics of the space weather system and how it affects our daily lives.

Human cytomegalovirus (HCMV) can persist for the life of a host in the face of robust immune responses owing to a wide range of immune evasion strategies. Here Liu and colleagues show that HCMV evades the IgG-mediated response by the endoplasmic reticulum-associated degradation of the neonatal Fc receptor for IgG.

Background The impact of immune-related adverse events (irAEs) occurring from adjuvant use of immunotherapy and of their management on relapse-free survival (RFS) and overall survival (OS) outcomes is currently not well understood.Patients and methods E1609 enrolled 1673 patients with resected high-risk melanoma and evaluated adjuvant ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus interferon-α. We investigated the association of irAEs and of use of immunosuppressants with RFS and OS for patients treated with ipilimumab (n=1034).Results Occurrence of grades 1–2 irAEs was associated with RFS (5 years: 52% (95% CI 47% to 56%) vs 41% (95% CI 31% to 50%) with no AE; p=0.006) and a trend toward improved OS (5 years: 75% (95% CI 71% to 79%) compared with 67% (95% CI 56% to 75%) with no AE; p=0.064). Among specific irAEs, grades 1–2 rash was most significantly associated with RFS (p=0.002) and OS (p=0.003). In multivariate models adjusting for prognostic factors, the most significant associations were seen for grades 1–2 rash with RFS (p

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN–, type II IFN–, and NF-κB–dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients’ first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

White-nose syndrome is a fungal disease responsible for the rapid decline of North American bat populations. This study addressed a novel method for inactivating Pseudogymnoascus destructans, the causative agent of WNS, using ultraviolet A (UVA) or B (UVB) radiation in combination with methoxsalen, a photosensitizer from the furanocoumarin family of compounds. Fungal spore suspensions were diluted in micromolar concentrations of methoxsalen (50-500 μM), then exposed to fixed doses of UVA radiation (500-5000 mJ/cm2), followed by plating on germination media. These plates were examined for two to four weeks for evidence of spore germination or inactivation, along with resultant growth or inhibition of P. destructans colonies. Pretreatment of fungal spores with low doses of methoxsalen resulted in a UVA dose-dependent inactivation of the P. destructans spores. All doses of methoxsalen paired with 500 mJ/cm2 of UVA led to an approximate two-log10 (~99%) reduction in spore viability, and when paired with 1000 mJ/cm2, a four-log10 or greater (>99.99%) reduction in spore viability was observed. Additionally, actively growing P. destructans colonies treated directly with methoxsalen and either UVA or UVB radiation demonstrated UV dose-dependent inhibition and termination of colony growth. This novel approach of using a photosensitizer in combination with UV radiation to control fungal growth may have broad, practical application in the future.

The new normal is a conceptual situation where economic and political agents are economically convinced and politically motivated to adapt to temporary austerity in economic growth and political participation. The concept entails a remarkable and rare mix of economics and politics. The alternative is to actively plan towards changing the underlying benchmark. Focusing on Russia, the paper draws on re sults from two studies that reflect on underlying weak links in the benchmark economy. One study examines the tendency and causes for slow growth and sticky distribution in Russia (when compared to other leading countries), making use of social accounting matrix multipliers. The tendencies are partly due to structural imbalances inherited from the past economy with its state-led and parallel shadow counterparts. The other study looks forward into the future and examines Russian prospects for a leading role and influence potential in the global economy. The study makes use of a dominance index composed of the relative sizes of transforming agents (i.e. population) and transformed value (i.e. GDP). Results for Russia suggest that in a few decades global marginalization is imminent, unless agents and production change course and actively link and substantially integrate with other world blocs.