Superiority of Dynamic Weights against Fixed Weights in Merging Multi-Satellite Precipitation Datasets over Pakistan

Data Availability Statement: The data utilized in this study were acquired through purchase from the Pakistan Meteorology Department (PMD) and the Water and Power Development Authority. Information about the data is available at https://www.pmd.gov.pk/en/ (accessed on 1 January 2023) and http://www.wapda.gov.pk/ (accessed on 1 January 2023), respectively.Satellite precipitation products (SPPs) are undeniably subject to uncertainty due to retrieval algorithms and sampling issues. Many research efforts have concentrated on merging SPPs to create high-quality merged precipitation datasets (MPDs) in order to reduce these uncertainties. This study investigates the efficacy of dynamically weighted MPDs in contrast to those using static weights. The analysis focuses on comparing MPDs generated using the “dynamic clustered Bayesian averaging (DCBA)” approach with those utilizing the “regional principal component analysis (RPCA)” under fixed-weight conditions. These MPDs were merged from SPPs and reanalysis precipitation data, including TRMM (Tropical Rainfall Measurement Mission) Multi-satellite Precipitation Analysis (TMPA) 3B42V7, PERSIANN-CDR, CMORPH, and the ERA-Interim reanalysis precipitation data. The performance of these datasets was evaluated in Pakistan’s diverse climatic zones—glacial, humid, arid, and hyper-arid—employing data from 102 rain gauge stations. The effectiveness of the DCBA model was quantified using Theil’s U statistic, demonstrating its superiority over the RPCA model and other individual merging methods in the study area The comparative performances of DCBA and RPCA in these regions, as measured by Theil’s U, are 0.49 to 0.53, 0.38 to 0.45, 0.37 to 0.42, and 0.36 to 0.43 in glacial, humid, arid, and hyper-arid zones, respectively. The evaluation of DCBA and RPCA compared with SPPs at different elevations showed poorer performance at high altitudes (>4000 m). The comparison of MPDs with the best performance of SPP (i.e., TMPA) showed significant improvement of DCBA even at altitudes above 4000 m. The improvements are reported as 49.83% for mean absolute error (MAE), 42.31% for root-mean-square error (RMSE), 27.94% for correlation coefficient (CC), 40.15% for standard deviation (SD), and 13.21% for Theil’s U. Relatively smaller improvements are observed for RPCA at 13.04%, 1.56%, 10.91%, 1.67%, and 5.66% in the above indices, respectively. Overall, this study demonstrated the superiority of DCBA over RPCA with static weight. Therefore, it is strongly recommended to use dynamic variation of weights in the development of MPDs.National Natural Science Foundation of China (grant numbers 51839006 and 52250410336)

Effects of low intensity pulsed ultrasound with and without increased cortical porosity on structural bone allograft incorporation

<p>Abstract</p> <p>Background</p> <p>Though used for over a century, structural bone allografts suffer from a high rate of mechanical failure due to limited graft revitalization even after extended periods <it>in vivo</it>. Novel strategies that aim to improve graft incorporation are lacking but necessary to improve the long-term clinical outcome of patients receiving bone allografts. The current study evaluated the effect of low-intensity pulsed ultrasound (LIPUS), a potent exogenous biophysical stimulus used clinically to accelerate the course of fresh fracture healing, and longitudinal allograft perforations (LAP) as non-invasive therapies to improve revitalization of intercalary allografts in a sheep model.</p> <p>Methods</p> <p>Fifteen skeletally-mature ewes were assigned to five experimental groups based on allograft type and treatment: +CTL, -CTL, LIPUS, LAP, LIPUS+LAP. The +CTL animals (n = 3) received a tibial ostectomy with immediate replacement of the resected autologous graft. The -CTL group (n = 3) received fresh frozen ovine tibial allografts. The +CTL and -CTL groups did not receive LAP or LIPUS treatments. The LIPUS treatment group (n = 3), following grafting with fresh frozen ovine tibial allografts, received ultrasound stimulation for 20 minutes/day, 5 days/week, for the duration of the healing period. The LAP treatment group (n = 3) received fresh frozen ovine allografts with 500 μm longitudinal perforations that extended 10 mm into the graft. The LIPUS+LAP treatment group (n = 3) received both LIPUS and LAP interventions. All animals were humanely euthanized four months following graft transplantation for biomechanical and histological analysis.</p> <p>Results</p> <p>After four months of healing, daily LIPUS stimulation of the host-allograft junctions, alone or in combination with LAP, resulted in 30% increases in reconstruction stiffness, paralleled by significant increases (p < 0.001) in callus maturity and periosteal bridging across the host/allograft interfaces. Longitudinal perforations extending 10 mm into the proximal and distal endplates filled to varying degrees with new appositional bone and significantly accelerated revitalization of the allografts compared to controls.</p> <p>Conclusion</p> <p>The current study has demonstrated in a large animal model the potential of both LIPUS and LAP therapy to improve the degree of allograft incorporation. LAP may provide an option for increasing porosity, and thus potential <it>in vivo </it>osseous apposition and revitalization, without adversely affecting the structural integrity of the graft.</p

Controlling Curie temperature in (Ga,Ms)As through location of the Fermi level within the impurity band

The ferromagnetic semiconductor (Ga,Mn)As has emerged as the most studied material for prototype applications in semiconductor spintronics. Because ferromagnetism in (Ga,Mn)As is hole-mediated, the nature of the hole states has direct and crucial bearing on its Curie temperature TC. It is vigorously debated, however, whether holes in (Ga,Mn)As reside in the valence band or in an impurity band. In this paper we combine results of channeling experiments, which measure the concentrations both of Mn ions and of holes relevant to the ferromagnetic order, with magnetization, transport, and magneto-optical data to address this issue. Taken together, these measurements provide strong evidence that it is the location of the Fermi level within the impurity band that determines TC through determining the degree of hole localization. This finding differs drastically from the often accepted view that TC is controlled by valence band holes, thus opening new avenues for achieving higher values of TC.Comment: 5 figures, supplementary material include

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Urine-based testing for Chlamydia trachomatis among young adults in a population-based survey in Croatia: Feasibility and prevalence

<p>Abstract</p> <p>Background</p> <p>We assessed the feasibility of collecting urine samples for testing on genital <it>Chlamydia trachomatis </it>infection in a population-based survey, and prevalence of this infection among young people aged 18-25 in Croatia. In Croatia, as in the other countries of Eastern Europe, there is a lack of data on prevalence of <it>C trachomatis </it>in the general population, including young adults.</p> <p>Methods</p> <p>We sampled participants using a nationally representative, multi-stage stratified probability sample of young men and women. Detection of <it>C trachomatis </it>DNA in urine samples was performed by using a real-time PCR assay COBAS^®TaqMan^®CT Test, v2.0.</p> <p>Results</p> <p>Overall, 1005 young adults participated in the behavioural part of the survey, and 27.9% men and 37.5% women who were sexually experienced agreed to provide urine samples for testing on <it>C trachomatis</it>. Using multivariate analysis, women were significantly more likely to provide urine samples than men (aOR = 1.53, 95% CI 1.14-2.06) as were those who reported no condom use at last intercourse (aOR = 1.95, 95% CI 1.44-2.62). Prevalence of <it>C trachomatis </it>infection among those who were sexually experienced was 7.3% in men and 5.3% in women.</p> <p>Conclusions</p> <p>Population-based surveys that use probabilistic sampling are a feasible way to obtain population estimates of <it>C trachomatis </it>prevalence among young adults in Croatia, but it is challenging to obtain an adequate response rate. The prevalence of <it>C trachomatis </it>among young adults in Croatia found in this study was higher than that found in other European countries with similar survey response rates.</p

Persistence of tumor-infiltrating CD8 T cells is tumor-dependent but antigen-independent

How tumor-infiltrating lymphocytes (TILs) that are tumor-specific but functionally tolerant persist in the antigen-expressing tumor tissue is largely unknown. We have previously developed a modified TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model where prostate cancer cells express the T-cell epitope SIYRYYGL (SIY) recognized by CD8 T cells expressing the 2C T-cell receptor (TCR) (referred to as TRP-SIY mice). In TRP-SIY mice, activated 2C T cells rapidly become tolerant following infiltration into the prostate tumor. In this study, we show that tolerant 2C T cells persist in the prostate tumor of TRP-SIY mice by proliferating slowly in a tumor-dependent, but antigen-, interleukin (IL)-7- and IL-15-independent manner. We also show that disappearance of 2C T cells from the lymphoid organs of TRP-SIY mice are due to antigen-induced T-cell contraction rather than altered trafficking or generalized T-cell depletion in the mice. Finally, we show that clonal T cells unreactive to SIY are equally capable of persisting in the prostate tumor. These findings suggest that while functional tolerance of TILs is induced by antigen, persistence of tolerant TILs in the tumor tissue is mediated by a novel mechanism: slow proliferation independent of antigen and homeostatic cytokines. These results also allow CD8 T-cell survival in the tumor environment to be compared with T-cell survival in chronic infection

An IFN-γ-IL-18 Signaling Loop Accelerates Memory CD8+ T Cell Proliferation

Rapid proliferation is one of the important features of memory CD8+ T cells, ensuring rapid clearance of reinfection. Although several cytokines such as IL-15 and IL-7 regulate relatively slow homeostatic proliferation of memory T cells during the maintenance phase, it is unknown how memory T cells can proliferate more quickly than naïve T cells upon antigen stimulation. To examine antigen-specific CD8+ T cell proliferation in recall responses in vivo, we targeted a model antigen, ovalbumin(OVA), to DEC-205+ dendritic cells (DCs) with a CD40 maturation stimulus. This led to the induction of functional memory CD8+ T cells, which showed rapid proliferation and multiple cytokine production (IFN-γ, IL-2, TNF-α) during the secondary challenge to DC-targeted antigen. Upon antigen-presentation, IL-18, an IFN-γ-inducing factor, accumulated at the DC:T cell synapse. Surprisingly, IFN-γ receptors were required to augment IL-18 production from DCs. Mice genetically deficient for IL-18 or IFN-γ-receptor 1 also showed delayed expansion of memory CD8+ T cells in vivo. These results indicate that a positive regulatory loop involving IFN-γ and IL-18 signaling contributes to the accelerated memory CD8+ T cell proliferation during a recall response to antigen presented by DCs

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Yoga-Based Cardiac Rehabilitation After Acute Myocardial Infarction: A Randomized Trial

Background: Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). Objectives: This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. Methods: The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life–5 Dimensions–5 Level visual analogue scale at 12 weeks. Results: MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). Conclusions: Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408)

Increased Memory Conversion of Naïve CD8 T Cells Activated during Late Phases of Acute Virus Infection Due to Decreased Cumulative Antigen Exposure

Background: Memory CD8 T cells form an essential part of protective immunity against viral infections. Antigenic load, costimulation, CD4-help, cytokines and chemokines fluctuate during the course of an antiviral immune response thus affecting CD8 T cell activation and memory conversion. Methodology/Principal Findings: In the present study, naïve TCR transgenic LCMV-specific P14 CD8 T cells engaged at a late stage during the acute antiviral LCMV response showed reduced expansion kinetics but greater memory conversion in the spleen. Such late activated cells displayed a memory precursor effector phenotype already at the peak of the systemic antiviral response, suggesting that the environment determined their fate during antigen encounter. In the spleen, the majority of late transferred cells exhibited a central memory phenotype compared to the effector memory displayed by the early transferred cells. Increasing the inflammatory response by exogenous administration of IFNc, PolyI:C or CpG did not affect memory conversion in the late transferred group, suggesting that the diverging antigen load early versus later during acute infection had determined their fate. In agreement, reduction in the LCMV antigenic load after ribavirin treatment enhanced the contribution of early transferred cells to the long lasting memory pool. Conclusions/Significance: Our results show that naïve CD8 cells, exposed to reduced duration or concentration of antigen during viral infection convert into memory more efficiently, an observation that could have significant implications fo