On the density and multiplicity of solutions to the fractional Nirenberg problem

This paper is devoted to establishing some results on the density and multiplicity of solutions to the fractional Nirenberg problem which is equivalent to studying the conformally invariant equation $P_\sigma(v)=K v^{\frac{n+2\sigma}{n-2\sigma}}$ on the standard unit sphere $(\mathbb{S}^n,g_0)$ with $\sigma\in (0,1)$ and $n\geq 2$, where $P_\sigma$ is the intertwining operator of order $2\sigma$ and $K$ is the prescribed curvature function. More specifically, by using the variational gluing method, refined analysis of bubbling behavior, extension formula, as well as the blow up analysis arguments, we obtain the existence of infinitely many multi-bump solutions. In particular, we show the smooth curvature functions of metrics conformal to $g_0$ are dense in the $C^{0}$ topology. Moreover, the related fractional Laplacian equations $(-\Delta)^{\sigma} u=K(x) u^{\frac{n+2\sigma}{n-2\sigma}}$ in $\mathbb{R}^n$, with $K(x)$ being asymptotically periodic in one of the variables, are also studied and infinitely many solutions are obtained under natural flatness assumptions

Diffusion Conditional Expectation Model for Efficient and Robust Target Speech Extraction

Target Speech Extraction (TSE) is a crucial task in speech processing that focuses on isolating the clean speech of a specific speaker from complex mixtures. While discriminative methods are commonly used for TSE, they can introduce distortion in terms of speech perception quality. On the other hand, generative approaches, particularly diffusion-based methods, can enhance speech quality perceptually but suffer from slower inference speed. We propose an efficient generative approach named Diffusion Conditional Expectation Model (DCEM) for TSE. It can handle multi- and single-speaker scenarios in both noisy and clean conditions. Additionally, we introduce Regenerate-DCEM (R-DCEM) that can regenerate and optimize speech quality based on pre-processed speech from a discriminative model. Our method outperforms conventional methods in terms of both intrusive and non-intrusive metrics and demonstrates notable strengths in inference efficiency and robustness to unseen tasks. Audio examples are available online (https://vivian556123.github.io/dcem).Comment: Submitted to ICASSP 202

Study on the trend of congenital heart disease inpatient costs and its influencing factors in economically underdeveloped areas of China, 2015–2020: a case study of Gansu Province

BackgroundEconomic data on congenital heart disease are scarce in economically underdeveloped areas of China. Therefore, this study aimed to shed light on the level and changing trend of congenital heart disease inpatients' economic burden in underdeveloped areas.MethodThis study used a multi-stage stratified cluster sampling method to select 11,055 inpatients with congenital heart disease from 197 medical and health institutions in Gansu Province. Their medical records and expenses were obtained from the Hospital Information System. Univariate analysis was conducted using the rank sum test and Spearman rank correlation. Quantile regression and random forest were used to analyze the influencing factors.ResultsFrom 2015 to 2020, the average length of stay for congenital heart disease patients in Gansu Province was 10.09 days, with an average inpatient cost of USD 3,274.57. During this period, the average inpatient costs per time increased from USD 3,214.85 to USD 3,403.41, while the average daily inpatient costs increased from USD 330.05 to USD 376.56. The average out-of-pocket costs per time decreased from USD 2,305.96 to USD 754.77. The main factors that affected the inpatient costs included length of stay, cardiac procedure, proportion of medications, age, and hospital level.ConclusionCongenital heart disease causes a significant economic burden on both families and society. Therefore, to further reduce the patient's financial burden, the length of stay should be reasonably reduced, and the rational distribution of medical resources should be continuously promoted to ensure equitable access to healthcare services

Universal isocontours for dissipative Kerr solitons

Dissipative Kerr solitons can be generated within an existence region defined on a space of normalized pumping power versus cavity-pump detuning frequency. The contours of constant soliton power and constant pulse width in this region are studied through measurement and simulation. Such isocontours impart structure to the existence region and improve understanding of soliton locking and stabilization methods. As part of the study, dimensionless, closed-form expressions for soliton power and pulse width are developed (including Raman contributions). They provide isocontours in close agreement with those from the full simulation, and, as universal expressions, can simplify the estimation of soliton properties across a wide range of systems

Expression of the Pupal Determinant broad during Metamorphic and Neotenic Development of the Strepsipteran Xenos vesparum Rossi

Derived members of the endoparasitic order Strepsiptera have acquired an extreme form of sexual dimorphism whereby males undergo metamorphosis and exist as free-living adults while females remain larviform, reaching sexual maturity within their hosts. Expression of the transcription factor, broad (br) has been shown to be required for pupal development in insects in which both sexes progress through metamorphosis. A surge of br expression appears in the last larval instar, as the epidermis begins pupal development. Here we ask if br is also up-regulated in the last larval instar of male Xenos vesparum Rossi (Stylopidae), and whether such expression is lost in neotenic larviform females. We clone three isoforms of br from X. vesparum (Xv′br), and show that they share greatest similarity to the Z1, Z3 and Z4 isoforms of other insect species. By monitoring Xv′br expression throughout development, we detect elevated levels of total br expression and the Xv′Z1, Xv′Z3, and Xv′Z4 isoforms in the last larval instar of males, but not females. By focusing on Xv′br expression in individual samples, we show that the levels of Xv′BTB and Xv′Z3 in the last larval instar of males are bimodal, with some males expressing 3X greater levels of Xv′br than fourth instar femlaes. Taken together, these data suggest that neoteny (and endoparasitism) in females of Strepsiptera Stylopidia could be linked to the suppression of pupal determination. Our work identifies a difference in metamorphic gene expression that is associated with neoteny, and thus provides insights into the relationship between metamorphic and neotenic development. © 2014 Erezyilmaz et al

Single-Trait and Multi-Trait Genome-Wide Association Analyses Identify Novel Loci for Blood Pressure in African-Ancestry Populations

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P \u3c 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension

Oral Passive Immunization With Plasma-Derived Polyreactive Secretory-Like IgA/M Partially Protects Mice Against Experimental Salmonellosis.

Secretory immunoglobulins have a critical role in defense of the gastrointestinal tract and are known to act by preventing bacterial acquisition. A stringent murine model of bacterial infection with Salmonella enterica Typhimurium was used to examine protection mediated by oral passive immunization with human plasma-derived polyreactive IgA and IgM antibodies (Abs) reconstituted as secretory-like immunoglobulins (SCIgA/M). This reagent has been shown to trigger Salmonella agglutination and to limit the entry of bacterium into intestinal Peyer's patches via immune exclusion. We now demonstrate that upon administration into ligated intestinal loops, SCIgA/M properly anchors in the mucus and is protected from degradation to a better extent that IgA/M or IgG. Moreover, prophylactic oral administration of SCIgA/M before intragastric infection of mice with a virulent strain of S. enterica Typhimurium allows to protect infected animals, as reflected by reduced colonization of both mucosal and systemic compartments, and conserved integrity of intestinal tissues. In comparison with IgA/M or IgG administration, SCIgA/M provided the highest degree of protection. Moreover, such protective efficacy is also observed after therapeutic oral delivery of SCIgA/M. Either prophylactic or therapeutic treatment with passively delivered SCIgA/M ensured survival of up to 50% of infected mice, while untreated animals all died. Our findings unravel the potential of oral passive immunization with plasma-derived polyreactive SCIgA/M Abs to fight gastrointestinal infections

Biological and clinical insights from genetics of insomnia symptoms

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P <5 x 10(-8), false discovery rate <0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.Peer reviewe