Miracle-dz/UniFAR-FTUs huggingface dataset:
National polarization and international agreements

Significance Why are so many postwar experiments in international governance now being challenged? We consider how polarization of political parties and stakeholders on the issues addressed by international environment agreements affects commitment to those agreements. We also consider how changes in national obligations under agreements affect polarization. We show that while there is good cause to think that party polarization is associated with reduced support for international agreements, stakeholder engagement that penalizes parties adopting positions too distant from their own has an important moderating affect. An understanding of the way that the political environment conditions national commitment to international agreements may, in turn, help in understanding the way in which national decisions ramify through the international treaty system. The network of international environmental agreements (IEAs) has been characterized as a complex adaptive system (CAS) in which the uncoordinated responses of nation states to changes in the conditions addressed by particular agreements may generate seemingly coordinated patterns of behavior at the level of the system. Unfortunately, since the rules governing national responses are ill understood, it is not currently possible to implement a CAS approach. Polarization of both political parties and the electorate has been implicated in a secular decline in national commitment to some IEAs, but the causal mechanisms are not clear. In this paper, we explore the impact of polarization on the rules underpinning national responses. We identify the degree to which responsibility for national decisions is shared across political parties and calculate the electoral cost of party positions as national obligations under an agreement change. We find that polarization typically affects the degree but not the direction of national responses. Whether national commitment to IEAs strengthens or weakens as national obligations increase depends more on the change in national obligations than on polarization per se. Where the rules governing national responses are conditioned by the current political environment, so are the dynamic consequences both for the agreement itself and for the network to which it belongs. Any CAS analysis requires an understanding of such conditioning effects on the rules governing national responses.
Radar cross section reduction of wideband antenna with a novel wideband radar absorbing materials

This study introduces a novel method to reduce the radar cross section (RCS) of wideband antennas. A novel wideband radar absorbing material (RAM) with frequency selective surfaces (FSSs) is proposed. The wideband RAM is used as the ground plane of a Yagi-Uda and a Vivaldi antenna for in-band RCS reduction. The measurement result shows that the radiation pattern of the antennas over the whole band is preserved when wideband RAM is used. The RCS of the Yagi-Uda and Vivaldi antenna with RAM can be reduced by more than 10 dB over the operating band with this method.
A genotype-phenotype correlation matrix for ABCA4 disease based on long-term prognostic outcomes

Background More than 1500 variants in the ATP-binding cassette, sub-family A, member 4 (ABCA4), locus underlie a heterogeneous spectrum of retinal disorders ranging from aggressive childhood-onset chorioretinopathy to milder late-onset macular disease. Genotype-phenotype correlation studies have been limited in clinical applicability as patient cohorts are typically small and seldom capture the full natural history of individual genotypes. To overcome these limitations, we constructed a genotype-phenotype correlation matrix that provides quantifiable probabilities of long-term disease outcomes associated with specific ABCA4 genotypes from a large, age-restricted patient cohort. Methods The study included 112 unrelated patients at least 50 years of age in whom 2 pathogenic variants were identified after sequencing of the ABCA4 locus. Clinical characterization was performed using the results of best corrected visual acuity, retinal imaging, and full-field electroretinogram testing. Results Four distinct prognostic groups were defined according to the spatial severity of disease features across the fundus. Recurring genotypes were observed in milder prognoses, including a newly defined class of rare hypomorphic alleles. PVS1 (predicted null) variants were enriched in the most severe prognoses; however, missense variants were present in a larger-than-expected fraction of these patients. Analysis of allele combinations and their respective prognostic severity showed that certain variants, such as p.(Gly1961Glu), and both rare and frequent hypomorphic alleles, were “clinically dominant” with respect to patient phenotypes irrespective of the allele in trans. Conclusion These results provide much-needed structure to the complex genetic and clinical landscape of ABCA4 disease and add a tool to the clinical repertoire to quantitatively assess individual genotype-specific prognoses in patients. FUNDING National Eye Institute, NIH, grants R01 EY028203, R01 EY028954, R01 EY029315, P30 19007 (Core Grant for Vision Research); the Foundation Fighting Blindness USA, grant no. PPA-1218-0751-COLU; and Research to Prevent Blindness.
A phase 2 evaluation of pembrolizumab for recurrent Lynch‐like versus sporadic endometrial cancers with microsatellite instability

Microsatellite instability–high (MSI‐H)/mismatch repair deficiency (dMMR) is a biomarker for responses to immune checkpoint inhibitors (ICIs). Whether mechanisms underlying microsatellite instability alter responses to ICIs is unclear. This article reports data from a prospective phase 2 pilot study of pembrolizumab in patients with recurrent MSI‐H endometrial cancer (EC) analyzed by whole exome sequencing (WES) and potential mechanisms of primary/secondary ICI resistance (NCT02899793).
Microtopographical guidance of macropinocytic signaling patches

Significance Morphologies of amoebae and immune cells are highly deformable and dynamic, which facilitates migration in various terrains, as well as ingestion of extracellular solutes and particles. It remains largely unexplored whether and how the underlying membrane protrusions are triggered and guided by the geometry of the surface in contact. In this study, we show that in Dictyostelium, the precursor of a structure called macropinocytic cup, which has been thought to be a constitutive process for the uptake of extracellular fluid, is triggered by micrometer-scale surface features. Imaging analysis and computational simulations demonstrate how the topographical dependence of the self-organizing dynamics supports efficient guidance and capturing of the membrane protrusion and hence movement of an entire cell along such surface features. In fast-moving cells such as amoeba and immune cells, dendritic actin filaments are spatiotemporally regulated to shape large-scale plasma membrane protrusions. Despite their importance in migration, as well as in particle and liquid ingestion, how their dynamics are affected by micrometer-scale features of the contact surface is still poorly understood. Here, through quantitative image analysis of Dictyostelium on microfabricated surfaces, we show that there is a distinct mode of topographical guidance directed by the macropinocytic membrane cup. Unlike other topographical guidance known to date that depends on nanometer-scale curvature sensing protein or stress fibers, the macropinocytic membrane cup is driven by the Ras/PI3K/F-actin signaling patch and its dependency on the micrometer-scale topographical features, namely PI3K/F-actin–independent accumulation of Ras-GTP at the convex curved surface, PI3K-dependent patch propagation along the convex edge, and its actomyosin-dependent constriction at the concave edge. Mathematical model simulations demonstrate that the topographically dependent initiation, in combination with the mutually defining patch patterning and the membrane deformation, gives rise to the topographical guidance. Our results suggest that the macropinocytic cup is a self-enclosing structure that can support liquid ingestion by default; however, in the presence of structured surfaces, it is directed to faithfully trace bent and bifurcating ridges for particle ingestion and cell guidance.
The representation of time windows in primate auditory cortex

Abstract Whether human and nonhuman primates process the temporal dimension of sound similarly remains an open question. We examined the brain basis for the processing of acoustic time windows in rhesus macaques using stimuli simulating the spectrotemporal complexity of vocalizations. We conducted functional magnetic resonance imaging in awake macaques to identify the functional anatomy of response patterns to different time windows. We then contrasted it against the responses to identical stimuli used previously in humans. Despite a similar overall pattern, ranging from the processing of shorter time windows in core areas to longer time windows in lateral belt and parabelt areas, monkeys exhibited lower sensitivity to longer time windows than humans. This difference in neuronal sensitivity might be explained by a specialization of the human brain for processing longer time windows in speech.
The Cardiac Caval Index: Improving Noninvasive Assessment of Cardiac Preload

Inferior vena cava (IVC) pulsatility quantified by the Caval Index (CI) is characterized by poor reliability, also due to the irregular magnitude of spontaneous respiratory activity generating the major pulsatile component. The aim of this study was to test whether the IVC cardiac oscillatory component could provide a more stable index (Cardiac CI‐CCI) compared to CI or respiratory CI (RCI).
Field-level inference of galaxy intrinsic alignment from the SDSS-III BOSS survey

As a large-scale overdensity collapses, it affects the orientation and shape of galaxies that form, by exerting tidal shear along their axes. Therefore, the shapes of elliptical galaxies align with the tidal field of cosmic structures. This intrinsic alignment provides insights into galaxy formation and the primordial universe, complements late-time cosmological probes and constitutes a significant systematic effect for weak gravitational lensing observations. In the present study, we provide constraints on the linear alignment model using a fully Bayesian field-level approach, using galaxy shape measurements from the SDSS-III BOSS LOWZ sample and three-dimensional tidal fields constrained with the LOWZ and CMASS galaxy samples of the SDSS-III BOSS survey. We find 4σ evidence of intrinsic alignment, with an amplitude of AI = 2.9 ± 0.7 at 20 Mpch.
SeaPlace: Process Variation Aware Placement for Reliable Combinational Circuits against SETs and METs

Nowadays nanoscale combinational circuits are facing significant reliability challenges including soft errors and process variations. This paper presents novel process variation-aware placement strategies that include two algorithms to increase the reliability of combinational circuits against both Single Event Transients (SETs) and Multiple Event Transients (METs). The first proposed algorithm is a global placement method (called SeaPlace-G) that places the cells for hardening the circuit against SETs by solving a quadratic formulation. Afterwards, a detailed placement algorithm (named SeaPlace-D) is proposed to increase the circuit reliability against METs by solving a linear programming optimization problem. Experimental results show that SeaPlace-G and SeaPlace-D averagely achieve 41.78% and 32.04% soft error reliability improvement against SET and MET, respectively. Moreover, when SeaPlace-D is followed by SeaPlace-G, MET reduction can be improved by up to 53.3%.
Soluble PD-L1 works as a decoy in lung cancer immunotherapy via alternative polyadenylation

Immune checkpoint therapy targeting the PD-1/PD-L1 axis is a potentially novel development in anticancer therapy and has been applied to clinical medicine. However, there are still some problems, including a relatively low response rate, innate mechanisms of resistance against immune checkpoint blockades, and the absence of reliable biomarkers to predict responsiveness. In this study of in vitro and in vivo models, we demonstrate that PD-L1–vInt4, a splicing variant of PD-L1, plays a role as a decoy in anti–PD-L1 antibody treatment. First, we showed that PD-L1–vInt4 was detectable in clinical samples and that it was possible to visualize the secreting variants with IHC. By overexpressing the PD-L1–secreted splicing variant on MC38 cells, we observed that an immune-suppressing effect was not induced by their secretion alone. We then demonstrated that PD-L1–vInt4 secretion resisted anti–PD-L1 antibody treatment, compared with WT PD-L1, which was explicable by the PD-L1–vInt4’s decoying of the anti–PD-L1 antibody. The decoying function of PD-L1 splicing variants may be one of the reasons for cancers being resistant to anti–PD-L1 therapy. Measuring serum PD-L1 levels might be helpful in deciding the therapeutic strategy.
Systematic review and meta-analysis of the predictive power of MTHFR polymorphisms for pemetrexed drug efficacy and toxicity in non-small cell lung cancer patients

Abstract We conducted a meta-analysis to determine if MTHFR polymorphisms are effective biomarkers for non-small cell lung cancer (NSCLC) patient survival and pemetrexed (PEM) treatment toxicity. Because of data heterogeneity, fixed or random effects models were chosen, and pooled HRs and 95% confidence intervals (CIs) were calculated. No correlation between MTHFR 677 C > T polymorphism and progression-free survival (PFS) or overall survival (OS) was detected in NSCLC patients; however, patients with the T allele benefited more than those with the wild-type allele. Two papers reported hematologic toxicity of single-agent PEM treatment in patients with the MTHFR 677 C > T polymorphism. However, data on MTHFR polymorphisms and toxicity could not be combined, even though publication bias and sensitivity analysis results were stable and reliable. We conclude that the MTHFR 677 C > T polymorphism could not predict PEM efficacy in NSCLC patients; however, the T allele may increase the risk of haematological toxicity. A large-scale clinical trial is recommended.
Identifying the temporal electrophysiological and molecular changes that contribute to TSC-associated epileptogenesis

Tuberous sclerosis complex (TSC), caused by heterozygous mutations in TSC1 or TSC2, frequently results in intractable epilepsy. Here, we made use of an inducible Tsc1-knockout mouse model, allowing us to study electrophysiological and molecular changes of Tsc1-induced epileptogenesis over time. We recorded from pyramidal neurons in the hippocampus and somatosensory cortex (L2/L3) and combined this with an analysis of transcriptome changes during epileptogenesis. Deletion of Tsc1 resulted in hippocampus-specific changes in excitability and adaptation, which emerged before seizure onset and progressed over time. All phenotypes were rescued after early treatment with rapamycin, an mTOR inhibitor. Later in epileptogenesis, we observed a hippocampal increase of excitation-to-inhibition ratio. These cellular changes were accompanied by dramatic transcriptional changes, especially after seizure onset. Most of these changes were rescued upon rapamycin treatment. Of the genes encoding ion channels or belonging to the Gene Ontology term action potential, 27 were differentially expressed just before seizure onset, suggesting a potential driving role in epileptogenesis. Our data highlight the complex changes driving epileptogenesis in TSC, including the changed expression of multiple ion channels. Our study emphasizes inhibition of the TSC/mTOR signaling pathway as a promising therapeutic approach to target epilepsy in patients with TSC.
Chronic Urticaria: A Swedish Registry-based Cohort Study on Population, Comorbidities and Treatment Characteristics

Swedish databases present unique opportunities to research population data on diseases and treatments. The current study is, to our knowledge, the most comprehensive registry-based study on a chronic urticaria population in Sweden to date. The aim of this study was to describe the chronic urticaria population in Stockholm County regarding epidemiology, demographics, comorbidity, healthcare usage and treatment patterns in relation to current international guidelines. Real-world data were extracted between 2013 and 2019, yielding 10,642 adult patients. Study period prevalence of chronic urticaria was 0.53%, the mean annual incidence was approximately 0.08%, and 68% of patients were female. Regarding diagnosis, 58% were first diagnosed in primary care, approximately 50% were diagnosed before the age of 40 years. Regarding type of urticaria, 89% had chronic spontaneous urticaria, 11% had chronic inducible urticaria, and 5% of patients with chronic urticaria had coexisting angioedema. Common coexisting diagnoses were, for example, asthma, allergy, psychiatric and behavioural disorders and cardiometabolic disorders. Treatment patterns generally followed guidelines, yet data indicated that guidelines were not fully implemented, especially in primary care.
Functional Short-Term Outcomes and Mortality in Children with Severe Traumatic Brain Injury: Comparing Decompressive Craniectomy and Medical Management

The effect of decompressive craniectomy (DC) on functional outcomes and mortality in children after severe head trauma is strongly debated. The lack of high-quality evidence poses a serious challenge to neurosurgeons' and pediatric intensive care physicians' decision making in critically ill children after head trauma. This study was conducted to compare DC and medical management in severely head-injured children with respect to short-term outcomes and mortality. Data on patients <18 years of age treated in Germany, Austria, and Switzerland during a 10-year period were extracted from TraumaRegister DGU®, forming a retrospective multi-center cohort study. Descriptive and multi-variable analyses were performed to compare outcomes and mortality after DC and medical management. Of 2507 patients, 402 (16.0%) received DC. Mortality was 20.6% after DC and 13.7% after medical management. Poor outcome (death or vegetative state) occurred in 27.6% after DC and in 16.1% after medical management. After risk adjustment by logistic regression modeling, the odds ratio was 1.56 (95% confidence interval 1.01-2.40) for poor outcome at intensive care unit discharge and 1.20 (0.74-1.95) for mortality after DC. In summary, DC was associated with increased odds for poor short-term outcomes in children with severe head trauma. This finding should temper enthusiasm for DC in children until a large randomized controlled trial has answered more precisely if DC in children is beneficial or increases rates of vegetative state.
Anti-vaccination attitudes are associated with less analytical and more intuitive reasoning

ABSTRACT Online anti-vaccination rhetoric has produced far reaching negative health consequences. Persons who endorse anti-vaccination attitudes may employ less analytical reasoning when problem solving. Considering limitations in previous research, we used an online web-based survey (n = 760; mean age = 47.69; 388 males, 372 females) to address this question. Analytical reasoning was negatively correlated with anti-vaccination attitudes (r = −.18, p < .0001). This relationship remained significant after statistically controlling for potential confounders, including age, sex, education, and religiosity (r = −.16, p < .0001). We hope that elucidating the cognitive, non-information-based aspects of anti-vaccination attitudes will help to guide effective educational interventions aimed at improving public health in the future.
Large Area >8 kV SiC GTO Thyristors with Innovative Anode-Gate Designs

This study is focused on the design and fabrication of large-area (4.1x4.1 mm2 and 8.2x8.2 mm2), 8.1 kV 4H-SiC GTO Thyristors. The anode and gate fingers of Thyristors were designed with involute, cellular or hexagonal patterns. Forward blocking voltages as high as 8106 V and On-state voltage drop (Von) and differential specific on-resistance (Ron,sp) as low as 3.8 V and 6 mΩ-cm2 at 100 A/cm2 were measured on these devices. About 59% of 4.1 x4.1 mm2 and 29% of 8.2x8. 2 mm2 Thyristors blocked voltages in excess of 6 kV. Detailed investigations revealed the impact of different anode/gate finger geometries on the device characteristics. Preliminary pulsed power characterization of the GTO Thyristors was also performed.
The impact of perfluoroalkyl substances on pregnancy, birth outcomes, and offspring development: a review of data from mouse models

Abstract Per- and polyfluoroalkyl substances (PFASs) such as perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are persistent in the environment and bioaccumulate in wildlife and humans, potentially causing adverse health effects at all stages of life. Studies from human pregnancy have shown that exposure to these contaminants are associated with placental dysfunction and fetal growth restriction; however, studies in humans are confounded by genetic and environmental factors. Here, we synthesize the available results from mouse models of pregnancy to show the causal effects of prenatal exposure to PFOA and PFOS on placental and fetal development and on neurocognitive function and metabolic disorders in offspring. We also propose gaps in the present knowledge and provide suggestions for future research studies. Summary Sentence Using mouse models of pregnancy, maternal exposure to perfluoroalkyl substances has been shown to have significant impact on placental development, fetal growth, neurocognitive function, and risk for disease in both mother and offspring.
Sharpening the probabilistic Arithmetic-Geometric Mean Inequality

We consider the $p$-generalized arithmetic-geometric mean inequality for vectors chosen randomly from the $\ell_p^n$-ball in $\mathbb{R}^n$. In this setting the inequality can be improved or reversed up to a respective scalar constant with high probability, and central limit theorems and large deviation results with respect to this constant have been shown. We sharpen these large deviation results in the spirit of Bahadur and Ranga Rao, thereby providing concrete and asymptotically exact estimates on a non-logarithmic scale for the probability of the inequality being improvable or reversible up to a constant, respectively.