568 research outputs found
Similarity of nuclear structure in 132Sn and 208Pb regions: proton-neutron multiplets
Starting from the striking similarity of proton-neutron multiplets in 134Sb
and 210Bi, we perform a shell-model study of nuclei with two additional protons
or neutrons to find out to what extent this analogy persists. We employ
effective interactions derived from the CD-Bonn nucleon-nucleon potential
renormalized by use of the V-low-k approach. The calculated results for 136Sb,
212Bi, 136I, and 212At are in very good agreement with the available
experimental data. The similarity between 132Sn and 208Pb regions is discussed
in connection with the effective interaction, emphasizing the role of core
polarization effects.Comment: 4 pages, 3 figures, 2 table
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A Potent and Effective Suicidal Listeria Vaccine Platform.
Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8+ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection
Commensal Bacteria Modulate Innate Immune Responses of Vaginal Epithelial Cell Multilayer Cultures
The human vaginal microbiome plays a critical but poorly defined role in reproductive health. Vaginal microbiome alterations are associated with increased susceptibility to sexually-transmitted infections (STI) possibly due to related changes in innate defense responses from epithelial cells. Study of the impact of commensal bacteria on the vaginal mucosal surface has been hindered by current vaginal epithelial cell (VEC) culture systems that lack an appropriate interface between the apical surface of stratified squamous epithelium and the air-filled vaginal lumen. Therefore we developed a reproducible multilayer VEC culture system with an apical (luminal) air-interface that supported colonization with selected commensal bacteria. Multilayer VEC developed tight-junctions and other hallmarks of the vaginal mucosa including predictable proinflammatory cytokine secretion following TLR stimulation. Colonization of multilayers by common vaginal commensals including Lactobacillus crispatus, L. jensenii, and L. rhamnosus led to intimate associations with the VEC exclusively on the apical surface. Vaginal commensals did not trigger cytokine secretion but Staphylococcus epidermidis, a skin commensal, was inflammatory. Lactobacilli reduced cytokine secretion in an isolate-specific fashion following TLR stimulation. This tempering of inflammation offers a potential explanation for increased susceptibility to STI in the absence of common commensals and has implications for testing of potential STI preventatives
Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.
Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM
Computer simulations show that Neanderthal facial morphology represents adaptation to cold and high energy demands, but not heavy biting
Three adaptive hypotheses have been forwarded to explain the distinctive Neanderthal face: (i) an improved ability to accommodate high anterior bite forces, (ii) more effective conditioning of cold and/or dry air and, (iii) adaptation to facilitate greater ventilatory demands. We test these hypotheses using three-dimensional models of Neanderthals, modern humans, and a close outgroup (Homo heidelbergensis), applying finite-element analysis (FEA) and computational fluid dynamics (CFD). This is the most comprehensive application of either approach applied to date and the first to include both. FEA reveals few differences between H. heidelbergensis, modern humans, and Neanderthals in their capacities to sustain high anterior tooth loadings. CFD shows that the nasal cavities of Neanderthals and especially modern humans condition air more efficiently than does that of H. heidelbergensis, suggesting that both evolved to better withstand cold and/or dry climates than less derived Homo. We further find that Neanderthals could move considerably more air through the nasal pathway than could H. heidelbergensis or modern humans, consistent with the propositions that, relative to our outgroup Homo, Neanderthal facial morphology evolved to reflect improved capacities to better condition cold, dry air, and, to move greater air volumes in response to higher energetic requirements
Persistent starspot signals on M dwarfs: multi-wavelength Doppler observations with the Habitable-zone Planet Finder and Keck/HIRES
Young, rapidly-rotating M dwarfs exhibit prominent starspots, which create
quasiperiodic signals in their photometric and Doppler spectroscopic
measurements. The periodic Doppler signals can mimic radial velocity (RV)
changes expected from orbiting exoplanets. Exoplanets can be distinguished from
activity-induced false positives by the chromaticity and long-term incoherence
of starspot signals, but these qualities are poorly constrained for
fully-convective M stars. Coherent photometric starspot signals on M dwarfs may
persist for hundreds of rotations, and the wavelength dependence of starspot RV
signals may not be consistent between stars due to differences in their
magnetic fields and active regions. We obtained precise multi-wavelength RVs of
four rapidly-rotating M dwarfs (AD Leo, G 227-22, GJ 1245B, GJ 3959) using the
near-infrared (NIR) Habitable-zone Planet Finder, and the optical Keck/HIRES
spectrometer. Our RVs are complemented by photometry from Kepler, TESS, and the
Las Cumbres Observatory (LCO) network of telescopes. We found that all four
stars exhibit large spot-induced Doppler signals at their rotation periods, and
investigated the longevity and optical-to-NIR chromaticity for these signals.
The phase curves remain coherent much longer than is typical for Sunlike stars.
Their chromaticity varies, and one star (GJ 3959) exhibits optical and NIR RV
modulation consistent in both phase and amplitude. In general, though, we find
that the NIR amplitudes are lower than their optical counterparts. We conclude
that starspot modulation for rapidly-rotating M stars frequently remains
coherent for hundreds of stellar rotations, and gives rise to Doppler signals
that, due to this coherence, may be mistaken for exoplanets.Comment: Accepted for publication in the Astrophysical Journa
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High sensitivity of summer temperatures to stratospheric sulfur loading from volcanoes in the Northern Hemisphere
This work was funded by an ERC (European Research Council) Marie Curie Career Integration Grant (CIG14-631752) and a Philip Leverhulme prize in Earth Sciences (PLP-2021-167) from the Leverhulme Trust awarded to A.B. WH is funded by a UKRI Future Leaders Fellowship (MR/S033505/1). M.S. acknowledges the support of the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement 820047). H.M.I. and L.C. were both funded by IAPETUS and IAPETUS2 NERC Doctoral Training Partnership. The Tunu2013 and NEEM_2011_S1 ice cores were collected and analyzed for sulfur and other chemical species used to establish the ice core chronologies with funding from NSF grants 1204176 and 0909541 to J.R.M., respectively, and ice cores were sampled with funding from NSF grant 1340174.The 540s, 1450s, and 1600s represent three of the five coldest decades in the Common Era (CE). In each of these cases, the cause of these cold pulses has been attributed to large volcanic eruptions. However, the provenance of the eruption and magnitude of the volcanic forcing remains uncertain. Here, we use high-resolution sulfur isotopes in Greenland and Antarctic ice cores measured across these events to provide a means of improving sulfur loading estimates for these eruptions. In each case, the largest reconstructed tree-ring cooling is associated with an extratropical eruption, and the high-altitude stratospheric sulfate loading of these events is substantially smaller than previous estimates (by up to a factor of two). These results suggest an increased sensitivity of the reconstructed Northern Hemisphere summer temperature response to extratropical eruptions. This highlights the importance of climate feedbacks and processes that amplify and prolong the cooling signal from high latitudes, such as changes in sea ice extent and ocean heat content.Publisher PDFPeer reviewe
Parameter Diagrams of the GRW and CSL Theories of Wave Function Collapse
It has been hypothesized that the time evolution of wave functions might
include collapses, rather than being governed by the Schroedinger equation. The
leading models of such an evolution, GRW and CSL, both have two parameters (or
new constants of nature), the collapse width sigma and the collapse rate
lambda. We draw a diagram of the sigma-lambda-plane showing the region that is
empirically refuted and the region that is philosophically unsatisfactory.Comment: 17 pages LaTeX, 7 figure
Introducing a secondary segmentation to construct a radiomics model for pulmonary tuberculosis cavities
PURPOSE: Accurate segmentation (separating diseased portions of the lung from normal appearing lung) is a challenge in radiomic studies of non-neoplastic diseases, such as pulmonary tuberculosis (PTB). In this study, we developed a segmentation
method, applicable to chest X-rays (CXR), that can eliminate the need for precise disease delineation, and that is effective
for constructing radiomic models for automatic PTB cavity classification.
METHODS: This retrospective study used a dataset of 266 posteroanterior CXR of patients diagnosed with laboratory confirmed
PTB. The lungs were segmented using a U-net-based in-house automatic segmentation model. A secondary segmentation
was developed using a sliding window, superimposed on the primary lung segmentation. Pyradiomics was used for feature
extraction from every window which increased the dimensionality of the data, but this allowed us to accurately capture the
spread of the features across the lung. Two separate measures (standard-deviation and variance) were used to consolidate
the features. Pearson’s correlation analysis (with a 0.8 cut-of value) was then applied for dimensionality reduction followed
by the construction of Random Forest radiomic models.
RESULTS: Two almost identical radiomic signatures consisting of 10 texture features each (9 were the same plus 1 other feature)
were identified using the two separate consolidation measures. Two well performing random forest models were constructed
from these signatures. The standard-deviation model (AUC=0.9444 (95% CI, 0.8762; 0.9814)) performed marginally better
than the variance model (AUC=0.9288 (95% CI, 0.9046; 0.9843)).
CONCLUSION: The introduction of the secondary sliding window segmentation on CXR could eliminate the need for disease
delineation in pulmonary radiomic studies, and it could improve the accuracy of CXR reporting currently regaining prominence as a high-volume screening tool as the developed radiomic models correctly classify cavities from normal CXR.Open access funding provided by University of Pretoria.https://www.springer.com/journal/11547Nuclear MedicineStatisticsSDG-03:Good heatlh and well-bein
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