Cancer somatic mutations can generate neoantigens that distinguish malignant from normal cells. However, the personalized identification and validation of neoantigens remains a major challenge. Here ...we discover neoantigens in human mantle-cell lymphomas by using an integrated genomic and proteomic strategy that interrogates tumour antigen peptides presented by major histocompatibility complex (MHC) class I and class II molecules. We applied this approach to systematically characterize MHC ligands from 17 patients. Remarkably, all discovered neoantigenic peptides were exclusively derived from the lymphoma immunoglobulin heavy- or light-chain variable regions. Although we identified MHC presentation of private polymorphic germline alleles, no mutated peptides were recovered from non-immunoglobulin somatically mutated genes. Somatic mutations within the immunoglobulin variable region were almost exclusively presented by MHC class II. We isolated circulating CD4
T cells specific for immunoglobulin-derived neoantigens and found these cells could mediate killing of autologous lymphoma cells. These results demonstrate that an integrative approach combining MHC isolation, peptide identification, and exome sequencing is an effective platform to uncover tumour neoantigens. Application of this strategy to human lymphoma implicates immunoglobulin neoantigens as targets for lymphoma immunotherapy.
Hyperons and quarks in proto-neutron stars Roark, J; Du, X; Constantinou, C ...
Monthly notices of the Royal Astronomical Society,
07/2019, Letnik:
486, Številka:
4
Journal Article
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ABSTRACT
In this work, we study matter in the cores of proto-neutron stars, focusing on the impact of their composition on the stellar structure. We begin by examining the effects of finite ...temperature (through a fixed entropy per baryon) and lepton fraction on purely nucleonic matter by making use of the DSH (Du, Steiner & Holt) model. We then turn our attention to a relativistic mean-field model containing exotic degrees of freedom, the Chiral Mean Field (CMF) model, again, under the conditions of finite temperature and trapped neutrinos. In the latter, since both hyperons and quarks are found in the cores of large-mass stars, their interplay and the possibility of mixtures of phases is taken into account and analysed. Finally, we discuss how stellar rotation can affect our results.
We review the calculation of the equation of state of pure neutron matter using quantum Monte Carlo (QMC) methods. QMC algorithms permit the study of many-body nuclear systems using realistic two- ...and three-body forces in a non-perturbative framework. We present the results for the equation of state of neutron matter, and focus on the role of three-neutron forces at supranuclear density. We discuss the correlation between the symmetry energy, the neutron star radius and the symmetry energy. We also combine QMC and theoretical models of the three-nucleon interactions, and recent neutron star observations to constrain the value of the symmetry energy and its density dependence.
The temperature in the crust of an accreting neutron star, which comprises its outermost kilometre, is set by heating from nuclear reactions at large densities, neutrino cooling and heat transport ...from the interior. The heated crust has been thought to affect observable phenomena at shallower depths, such as thermonuclear bursts in the accreted envelope. Here we report that cycles of electron capture and its inverse, β(-) decay, involving neutron-rich nuclei at a typical depth of about 150 metres, cool the outer neutron star crust by emitting neutrinos while also thermally decoupling the surface layers from the deeper crust. This 'Urca' mechanism has been studied in the context of white dwarfs and type Ia supernovae, but hitherto was not considered in neutron stars, because previous models computed the crust reactions using a zero-temperature approximation and assumed that only a single nuclear species was present at any given depth. The thermal decoupling means that X-ray bursts and other surface phenomena are largely independent of the strength of deep crustal heating. The unexpectedly short recurrence times, of the order of years, observed for very energetic thermonuclear superbursts are therefore not an indicator of a hot crust, but may point instead to an unknown local heating mechanism near the neutron star surface.
Descriptive epidemiology of total joint replacement procedures is limited to annual procedure volumes (incidence). The prevalence of the growing number of individuals living with a total hip or total ...knee replacement is currently unknown. Our objective was to estimate the prevalence of total hip and total knee replacement in the United States.
Prevalence was estimated using the counting method by combining historical incidence data from the National Hospital Discharge Survey and the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases from 1969 to 2010 with general population census and mortality counts. We accounted for relative differences in mortality rates between those who have had total hip or knee replacement and the general population.
The 2010 prevalence of total hip and total knee replacement in the total U.S. population was 0.83% and 1.52%, respectively. Prevalence was higher among women than among men and increased with age, reaching 5.26% for total hip replacement and 10.38% for total knee replacement at eighty years. These estimates corresponded to 2.5 million individuals (1.4 million women and 1.1 million men) with total hip replacement and 4.7 million individuals (3.0 million women and 1.7 million men) with total knee replacement in 2010. Secular trends indicated a substantial rise in prevalence over time and a shift to younger ages.
Around 7 million Americans are living with a hip or knee replacement, and consequently, in most cases, are mobile, despite advanced arthritis. These numbers underscore the substantial public health impact of total hip and knee arthroplasties.
For concentrator photovoltaic modules, a promising approach is the miniaturization of the solar cell and optics. In solar cells, the perimeter is a source for the recombination of minority charge ...carriers, which leads to a voltage loss. With decreasing cell size, the ratio between perimeter and solar cell area increases and therefore the perimeter recombination becomes more relevant. In this work, we quantify this loss using the open-circuit voltages derived from I–V measurements of triple-junction concentrator solar cells of different sizes under varying irradiances. For the simulations, a one-dimensional diode model with two parallel interconnected diodes is applied with ideality factors of n1 = 3 and n2 = 6 for the triple-junction solar cell. As we compare solar cell designs that differ in size and fraction of the metallized area, we must take into account that the parallel resistance and the dark saturation currents differ. In the model, this discrepancy is conveyed by a dependency on the perimeter-to-area ratio and incorporating the ratio between the active and total areas into the model. Therefore, the areas need to be determined. For small solar cells, the uncertainty of the measurement is high. We account for this uncertainty by investigating areas derived from the photolithography masks and measurements. The model is applied to investigate the influence of the voltage loss on solar cells smaller than 3 mm in diameter. We show that, despite the simplification of the ideality factors, the model agrees well with the measurements. It is shown that for high concentrations (C > 500), the voltage loss is below 2% even for small cells with P/A up to 120 cm−1. We show that the dark area voltage loss for this cell and concentration is of the same order of magnitude as the loss due to the perimeter.
•Our model is based on two diodes considering saturation current of the solar cell, the perimeter and dark area recombination and the parallel resistance.•We discuss the influence of the uncertainty introduced by the area measurements.•Model validated by I–V measurements with very good agreement to the simulation.•Investigation of triple-junction solar cells for a commercial epitaxial structure from AZUR.•Quantification of loss in open-circuit voltage for micro-CPV cells.•VOC losses are very low for high concentration even when the solar cell has a diameter of 300 µm.
Mothers vary in duration of breastfeeding. These individual differences are related to a variety of demographic and individual maternal factors including maternal hormones, mood and early ...experiences. However, little is known about the role of genetic factors. We studied single‐nucleotide polymorphisms (SNPs) in the OXT peptide gene (rs2740210; rs4813627) and the OXT receptor gene (OXTR rs237885) in two samples of mothers from the Maternal adversity, Vulnerability and Neurodevelopment study (MAVAN), a multicenter (Hamilton and Montreal, Canada) study following mothers and their children from pregnancy until 7 years of age. Data from the Hamilton site was the primary sample (n = 201) and data from Montreal was the replication sample (n = 151). Breastfeeding duration, maternal mood (measured by the CES‐D scale) and early life adversity (measured by the CTQ scale) were established during 12 months postpartum. In our primary sample, polymorphisms in OXT rs2740210, but not the other SNPs, interacted with early life adversity to predict variation in breastfeeding duration (overall F8,125 = 2.361, P = 0.021; interaction effect b = −8.12, t = −2.3, P = 0.023) and depression (overall F8,118 = 5.751, P ≤ 0.001; interaction effect b = 6.06, t = 3.13, P = 0.002). A moderated mediation model showed that higher levels of depression mediated the inverse relation of high levels of early life adversity to breastfeeding duration, but only in women possessing the CC genotype effect a′ = −3.3401, 95% confidence interval (CI) = −7.9466 to −0.0015 of the OXT SNP and not in women with the AA/AC genotype (a′ = −1.2942, ns). The latter findings (moderated mediation model) were replicated in our Montreal sample (a′ = −0.277, 95% CI = −0.7987 to −0.0348 for CC; a′ = −0.1820, ns for AA/AC).
Depression mediates the inverse relation of early adversity to breastfeeding duration, but only in women with the CC genotype of OXT rs2740210.
The roles of isospin asymmetry in nuclei and neutron stars are investigated using a range of potential and field-theoretical models of nucleonic matter. The parameters of these models are fixed by ...fitting the properties of homogeneous bulk matter and closed-shell nuclei. We discuss and unravel the causes of correlations among the neutron skin thickness in heavy nuclei, the pressure of beta-equilibrated matter at a density of
0.1
fm
-
3
, the derivative of the nuclear symmetry energy at the same density and the radii of moderate mass neutron stars. Constraints on the symmetry properties of nuclear matter from the binding energies of nuclei are examined. The extent to which forthcoming neutron skin measurements will further delimit the symmetry properties is investigated. The impact of symmetry energy constraints for the mass and moment of inertia contained within neutron star crusts and the threshold density for the nucleon direct Urca process, all of which are potentially measurable, is explored. We also comment on the minimum neutron star radius, assuming that only nucleonic matter exists within the star.
Neutrinos emitted during the collapse, bounce, and subsequent explosion provide information about supernova dynamics. The neutrino spectra are determined by weak interactions with nuclei and nucleons ...in the inner regions of the star, and thus the neutrino spectra are determined by the composition of matter. The composition of stellar matter at temperature ranging from T = 1-3 MeV and densities ranging from 10-5 to 0.1 times the saturation density is explored. We examine the single-nucleus approximation commonly used in describing dense matter in supernova simulations and show that while the approximation is accurate for predicting the energy and pressure at most densities, the predicted compositions are less accurate, varying by 50% or more at the largest densities. We find that as the temperature and density increase, the single nucleus approximation systematically overpredicts the mass number of nuclei that are actually present and underestimates the contribution from lighter nuclei which are present in significant amounts.
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