Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual PPARα/γ Ligand TZD18 Either Alone or in Combination with Imatinib Inhibits Proliferation and Induces Apoptosis of Human CML Cell Lines

Despite progress in the treatment of early-stage chronic myeloid leukemia (CML), the accelerated and blastic phases of CML still remain a therapeutic challenge. Persistence of BCR-ABL-positive (bcr-abl+) cells or secondary resistance during imatinib therapy frequently occurs. In this study, we investigated the activity of a novel dual ligand specific for peroxisome proliferator-activated receptor α and γ (PPARα/γ) against CML blast crisis cell lines. Exposure of these cell lines (K562, KU812 and KCL22) to TZD18 resulted in a growth inhibition in a dose- and time-dependent manner. This effect may not be mediated through PPARγ and/or PPARα activation, since antagonists of PPARg and/or PPARa could not reverse this inhibition. Western blotting analysis showed that expression of the cyclin dependent kinase inhibitor (CDKI) p27kip1 was enhanced, whereas levels of cyclin E, cyclin D2 and cyclin dependent kinase 2 (CDK-2) were decreased when these cells were treated with TZD18. Most interestingly, TZD18 synergistically enhanced the antiproliferative and pro-apoptotic effects of imatinib. Overall, our findings strongly suggest that TZD18, either alone or in combination with imatinib may be beneficial for the treatment of CML in myeloid blast crisis.
Base Station-Side Rate Estimation for Threshold-Based Feedback, and Design Implications in Multi-User OFDM Systems

Rate adaptation and scheduling are essential in ensuring that contemporary orthogonal frequency division multiplexing systems achieve high downlink spectral efficiencies. They depend upon reduced feedback schemes to efficiently feedback channel state information from the users to the base station (BS). In the popular threshold-based quantized feedback scheme, a user feeds back to the BS the quantized value of the signal-to-noise ratio for each subchannel. For this scheme, we derive a novel, throughput-optimal discrete rate adaptation (TORA) policy, which enables a system designer to reduce the feedback overhead. We present it in closed form for different multi-antenna diversity modes for the exponentially correlated subchannel gains model. We also develop a computationally simpler suboptimal variant of it. We derive an insightful lower bound for the fading- and user location-averaged throughput gain achieved by TORA over conventional rate adaptation for 1-bit feedback. We present extensive results to benchmark the system-level performance of TORA for different numbers of feedback bits and modulation and coding schemes available at the BS, and various schedulers, quantizers, and multi-antenna modes.
Resolving single-cell heterogeneity from hundreds of thousands of cells through sequential hybrid clustering and NMF

The rapid proliferation of single-cell RNA-Sequencing (scRNA-Seq) technologies has spurred the development of diverse computational approaches to detect transcriptionally coherent populations. While the complexity of the algorithms for detecting heterogeneity have increased, most existing algorithms require significant user-tuning, are heavily reliant on dimensionality reduction techniques and are not scalable to ultra-large datasets. We previously described a multi-step algorithm, Iterative Clustering and Guide-gene selection (ICGS), which applies intra-gene correlation and hybrid clustering to uniquely resolve novel transcriptionally coherent cell populations from an intuitive graphical user interface. Here, we describe a new iteration of ICGS that outperforms state-of-the-art scRNA-Seq detection workflows when applied to well-established benchmarks. This approach combines multiple complementary subtype detection methods (HOPACH, sparse-NMF, cluster “fitness”, SVM) to resolve rare and common cell-states, while minimizing differences due to donor or batch effects. Using data from the Human Cell Atlas, we show that the PageRank algorithm effectively down samples ultra-large scRNA-Seq datasets, without losing extremely rare or transcriptionally similar distinct cell-types and while recovering novel transcriptionally unique cell populations. We believe this new approach holds tremendous promise in reproducibly resolving hidden cell populations in complex datasets. Highlights ICGS2 outperforms alternative approaches in small and ultra-large benchmark datasets Integrates multiple solutions for cell-type detection with supervised refinement Scales effectively to resolve rare cell-states from ultra-large datasets using PageRank sampling with a low memory footprint Integrated into AltAnalyze to enable sophisticated and automated downstream analysis
ECG-based biometrics: A real time classification approach

Behavioral biometrics is one of the areas with growing interest within the biosignal research community. A recent trend in the field is ECG-based biometrics, where electrocardiographic (ECG) signals are used as input to the biometric system. Previous work has shown this to be a promising trait, with the potential to serve as a good complement to other existing, and already more established modalities, due to its intrinsic characteristics. In this paper, we propose a system for ECG biometrics centered on signals acquired at the subject's hand. Our work is based on a previously developed custom, non-intrusive sensing apparatus for data acquisition at the hands, and involved the pre-processing of the ECG signals, and evaluation of two classification approaches targeted at real-time or near real-time applications. Preliminary results show that this system leads to competitive results both for authentication and identification, and further validate the potential of ECG signals as a complementary modality in the toolbox of the biometric system designer.
Low response to a monovalent inactivated unadjuvanted influenza A (H1N1) pdm09 vaccine in pediatricians of a general hospital in Japan

Immunization of health care personnel (HCP) is critically important to reduce healthcare-associated influenza infections substantially. During 2009–2010, 74% of all HCP at Kitano Hospital, Osaka, Japan, including 94% of pediatricians, received the monovalent unadjuvanted influenza A (H1N1) pdm09 vaccine. We evaluated the vaccine’s immunogenicity. Sixteen pediatricians received 15 μg hemagglutinin antigen subcutaneously. Antibody titer assays were conducted using hemagglutination-inhibition antibody assay on days 0 and 21 and at 5 mo after vaccination. Seroprotection rates, seroconversion rates, and geometric mean titer folds at 21 d were, respectively, 43.8%, 43.8% and 5.4 in all subjects, 70.0%, 70.0% and 8.0 in subjects aged 27–34 y, and 0.0%, 0.0% and 8.0 in subjects aged ≥ 35 y. None of the latter group met the European Medicines Agency criteria. We hope to adopt intradermal routes and further the development of the influenza vaccine using new technology to improve immunogenicity in Japan.
Effects of melatonin on photosynthesis and soybean seed growth during grain filling under drought stress

We studied the effects of melatonin on soybean photosynthesis and seed growth at different developmental stages under drought stress induced by polyethylene glycol in the growth medium. Experimental groups were supplied with a normal nutrient solution after seven days of continuous treatment; overall, five treatments were completed when the early maturity stage was reached. Under normal water supply, melatonin supplementation had no significant effect on the photosynthetic characteristics or soybean seed growth. However, drought stress reduced leaf relative water content, chlorophyll content, and relative photosynthetic gas-exchange parameters, while it increased a leaf content of osmoregulatory substances, antioxidant-related enzyme activities, and seed growth-related indicators. Compared to the drought-stressed group, the melatonin treatment under drought stress improved the above indicators; specifically, melatonin effectively increased the photosynthetic rate, 100-seed mass, and total seed mass per plant. All the effects were most significant during the first seven days after the early seed-filling stage.
Associations between pre‐kidney‐transplant risk factors and post‐transplant cardiovascular events and death

The prevalence of cardiovascular risk factors in renal transplant candidates is high. A better understanding of the relation between these risk factors and cardiovascular morbidity and mortality is mandatory to improve transplantation outcome. In this retrospective cohort study 2187 adult patients who received a first kidney transplant between 1984 and 1997 were included. We analyzed the incidence of post‐transplant cardiovascular events and tried to identify independent pretransplant risk factors for post‐transplant cardiovascular events and all‐cause mortality. The cumulative incidence of post‐transplant cardiovascular events was 40%. The incidence was highest in the first 3 months after transplantation. Independent pretransplant risk factors for a post‐transplant cardiovascular event were diabetic nephropathy [Hazard ratio (HR) 3.02; 95% CI 2.85–3.98], claudication [HR 2.17 (1.42–3.31)], cardiac event [HR 1.76 (1.32–2.33)], cerebrovascular accident HR 1.53 (1.03–2.28), time‐on‐dialysis [HR 1.06 (1.02–1.11)], recipient age [HR 1.04 (1.04–1.05)], and body mass index [HR 1.03 (1.00–1.05)]. Diabetic nephropathy and cardiovascular disease were also important predictors for all‐cause mortality. Diabetic nephropathy and cardiovascular disease were the most important predictors for cardiovascular events and all‐cause mortality after renal transplantation. Early treatment of cardiovascular risk factors and pretransplant cardiovascular evaluation might improve transplantation outcome.
Comment on “Positive Selection of Tyrosine Loss in Metazoan Evolution”

Tan et al. (Reports, 25 September 2009, p. 1686) argued that loss of tyrosine residues from proteins in metazoans was driven by positive selection to remove potentially deleterious phosphorylation sites. We challenge this hypothesis, providing evidence that the high guanine-cytosine (GC) content of metazoan genomes was the primary driver in the loss of tyrosine residues.
Application of geostatistics tools to evaluate droplets spectrum of a common spray atomizer using several additives

The objective of this work was to evaluate the spectrum of droplets and syrup deposition of motorized costal atomizer, using additives in spraying solution. For this purpose geostatistical approach was applied. The treatments such as water (witness) and different additives (mineral oil, siliconized polymer and ethoxylated nonylphenol) were applied. Just before application, collectors (glass plates and hydrosensitive labels) were distributed at seven distances from the center of the spray circumference with different radius (3.0, 6.0, 9.0, 12.0, 15.0, 18.0 and 20.0 m), in the directions of the cardinal and collateral points, totaling 56 sample points. The deposition parameters, volumetric median diameter (VMD), relative amplitude (RA) and coverage were evaluated by means of aqueous solution (spray liquids + dye) to verify deposition by spectrophotometry and hydrosensitive paper label for the spectrum of drops. Descriptive analysis of the data was performed and geostatistics used as a tool for the analysis of spatial variability. The values for non-sampled locations were estimated using the ordinary kriging interpolation method. It allowed mapping that defined the application zones for the calculation of drift. The results showed that the VMD of the droplets was 136 μm. The application maps showed that there was a drift of 71.50% of the volume of syrup applied. The geostatistical tool made it possible to evaluate the droplet and deposition spectrum by means of the application maps. The proposed climatic recommendations for the application of agricultural pesticides do not apply to cost atomizers.
125Iodine monotherapy for Japanese men with low- and intermediate-risk prostate cancer: outcomes after 5 years of follow-up

Data from 305 Japanese men with low-risk (n = 175) or intermediate-risk (n = 130) prostate cancer who underwent 125I monotherapy were retrospectively analyzed. Of the 305 patients, 93 received hormonal therapy for a median of 6 months (range, 1–33 months) before implantation. The prescribed dose to the prostate plus 3- to 5-mm margin was set at 145 Gy. The mean dose to 90% of the prostate volume at 1 month (D90) and the prostate volume receiving at least 100% dose at 1 month (V100) were 173.4 Gy and 95.8%, respectively. The median follow-up was 66 months (range, 12–94 months). The 5-year biochemical non-evidence of disease rate was 95.5% (low-risk, 94.2%; intermediate-risk, 97.3%). The 5-year freedom from clinical failure rate was 98.9% (low-risk, 98.9%; intermediate-risk, 99.2%). The initial prostate-specific antigen level was identified as a significant predictive factor for biochemical recurrence (P = 0.029). The late Grade 3 genitourinary toxicity rate was 2.0%. No patients displayed late gastrointestinal toxicity of Grade 3 or worse. Monotherapy with 125I showed excellent outcomes with limited morbidity for Japanese men with low- and intermediate-risk prostate cancer after 5 years of follow-up.
Advances in G Protein-Coupled Receptor Allostery: From Function to Structure

It is now widely accepted that G protein-coupled receptors (GPCRs) are highly dynamic proteins that adopt multiple active states linked to distinct functional outcomes. Furthermore, these states can be differentially stabilized not only by orthosteric ligands but also by allosteric ligands acting at spatially distinct binding sites. The key pharmacologic characteristics of GPCR allostery include improved selectivity due to either greater sequence divergence between receptor subtypes and/or subtype-selective cooperativity, a ceiling level to the effect, probe dependence (whereby the magnitude and direction of the allosteric effect change with the nature of the interacting ligands), and the potential for biased signaling. Recent chemical biology developments are beginning to demonstrate how the incorporation of analytical pharmacology and operational modeling into the experimental workflow can enrich structure-activity studies of allostery and bias, and have also led to the discovery of a new class of hybrid orthosteric/allosteric (bitopic) molecules. The potential for endogenous allosteric modulators to play a role in physiology and disease remains to be fully appreciated but will likely represent an important area for future studies. Finally, breakthroughs in structural and computational biology are beginning to unravel the mechanistic basis of GPCR allosteric modulation at the molecular level.
Divorce Laws and the Structure of the American Family

This paper investigates the impact of no‐fault divorce laws on marriage and divorce in the United States. I propose a theory that captures the key stylized facts of the rising then declining divorce rates and the apparent convergence of divorce rates across the different divorce regimes. The empirical results suggest that a shift from fault to no‐fault divorce increased the odds of divorcing for those couples who married before the shift. The analysis further suggests that those couples who marry after the shift to a no‐fault regime, in turn, sort themselves better upon marriage, which offsets the direct effect of the law on divorce rates. Consistent with that selectivity argument, after a switch to a no‐fault divorce regime, women get married later in life. These results hold for the law that governs property division and spousal support. The law that governs divorce grounds does not seem to matter significantly.
Effects of inducer intake kinetics on the dynamics of gene expression

Many genes are only active following the intake of an inducer by the cell, via passive diffusive, positive, or negative feedback intake mechanisms. Based on measurements of the in vivo kinetics of intake and subsequent transcription events in Escherichia coli, we use stochastic models to investigate how the kinetics of intake affects both transient and nearequilibrium dynamics of gene expression. We find that the intake kinetics affects mean and variability of the transient time to reach the steady state of proteins numbers and also the degree of fluctuations in these numbers. Fluctuations in the extracellular number of inducers affects the variability of protein numbers at steady state in a degree that differs with the intake kinetics. Finally, changing the intake kinetics of an inducer of a genetic switch allows tuning the bias in the choice of noisy attractor. We conclude that the kinetics of inducer intake affects transient and near-equilibrium gene expression dynamics and, consequently, the phenotypic diversity of organisms in fluctuating environments.
Cardiac Depression Produced by L-Arginine and Phosphodiestrase Inhibitor on Isolated Mammalian Rabbit Heart: Function of Cyclic Guanosine Monophosphate (cGMP)

Problem statement: Cyclic guanosine 3',5'-monophosphate cGMP is one the important second messengers that determines the cardiomyocyte activity and its role in healthy and diseased cardiac muscle is still controversial. We are reporting the effect of adding L-arginine, the NO donor that stimulates cGMP production and Sildenafil citrate (phosphodiestrase inhibitor) that inhibits cGMP hydrolyis on isolated rabbit's heart to answer: Is it safe to prescribe phosphodiestrase inhibitors for men with low cardiac output? Approach: Isolated hearts from 6 rabbits were perfused using Langendorff's apparatus in which the perfusion fluid was ringer-Locke solution, applied at constant flow rate and was continuously bubbled with a mixture of 95% oxygen and 5% carbon dioxide. Each heart served as its own control before infusion of L-arginine in concentration of 3 m mol L −1 and Sildenafil citrate 1.5 mg L −1 simultaneously. Their effects were recorded after 1, 3, 5 and 10 min. The effluent fluid was collected for cardiac enzymes assay after 5 and 10 min. Results: Data showed that the infusion of L-arginine and Sildenafil citrate produced negative inotrpic and chronotropic effects. Also, the cardiac enzymes were significantly elevated. Conclusion: The present study, which was carried out on the isolated rabbit's heart, demonstrated that increased cGMP could produce a cardioprotective role by decreasing the cardiac work, although it might be hazardous to men with depressed cardiac function.
A novel electromigration characterization method based on low-frequency noise measurements

A new electromigration (EM) test method, based on low-frequency noise (LFN) measurements is demonstrated and validated for advanced nano-interconnects, conformable to the 10 nm semiconductor technology nodes and beyond. For the first time, the methodology is applied to electromigration test structures where different metal layers are connected by vias. Firstly, it is established that LFN can be used to calculate electromigration activation energies in via-containing nano-interconnects. This finding is verified by comparing the activation energy obtained by LFN with the one calculated using standard accelerated EM tests on a wide variety of interconnect types. The large correlation between both values (≥90%) indicates that LFN can indeed be applied to successfully determine EM activation energies. Secondly, LFN is shown to provide an indication of electromigration damage in nano-interconnects, which allows linking the noise magnitude with a defect concentration. The first two findings are then combined to provide qualitative predictions of electromigration lifetimes. Two models are proposed: one for void nucleation (the time to form a critical void that will thereafter start growing) and one for void growth (the time between the formation of the critical void and failure, i.e. when the void spans the entire line thickness). Also in this case very strong correlations between LFN measurements and EM experiments were found (≥90% for single metal lines and ≥80% for via-containing structures). The main advantages of using LFN measurements over standard tests for electromigration characterization are that they are non-destructive (no electromigration damage is induced during the test), much faster (a 300 mm wafer can be characterized in a matter of days, as opposed to the weeks it can take using standard EM tests), and that they can be done at test conditions closer to actual operation of the interconnects, such that inducing different mechanisms due to over-stress is avoided.
Field measurements on the generation and emission characteristics of PM2.5 from industrial fluidized bed boilers

ABSTRACT This study presented new field measurement data on the particle size distributions, morphological characteristics, and elemental composition of particulate matter (PM)2.5 (particle diameter less than 2.5 mm) from 12 industrial boilers, including eight circulating fluidized bed boilers (CFB) and four bubbling fluidized bed boilers (BFB). Measurement in situ was taken with an electrical low-pressure impactor equipped with a two-stage dilution sampling system. Morphological characteristics were determinded by electron microscope (SEM), and elemental compositions of the samples were determinded by X-ray fluorescence (XRF) and inductively coupled plasma (ICP). The results show that before and after the dust removal, the number concentration distributions of PM2.5 display bimodal distributions, one peak is between 0.07 and 0.12 μm, and the other peak is between 0.32 and 0.48 μm. And the particle concentrations of PM2.5 depended mainly on submicron particles (less than 1 µm in diameter), formed by gasification-condensation mechanisms. The mass concentration distributions of PM2.5 showing no peak distribution and increase with the particle size. Compared to electrostatic precipitators (ESPs) and fabric filters (FFs) , the ESPs has a lower removal efficiency of PM2.5. The morphological characteristics of PM2.5 before and after dust removal contain irregular particles and spherical particles. The mass percentages of Na, K, and Fe in PM2.5 after the dust removal are nearly the same as those before the dust removal, but Si, Ca, and Al in PM2.5 decreased after dust removal and S in PM2.5 increased after dust removal. Although the hazardous elements Cr, V, Mn, and Ni in PM2.5 after dust removal did not change significantly, the Pb, Cd, As, Se, and Hg increased after dust removal. These data clearly show that the composition of PM2.5 changes as dust are removed by air pollution control devices.
Pip: Detecting the Unexpected in Distributed Systems

Bugs in distributed systems are often hard to find. Many bugs reflect discrepancies between a system's behavior and the programmer's assumptions about that behavior. We present Pip, an infrastructure for comparing actual behavior and expected behavior to expose structural errors and performance problems in distributed systems. Pip allows programmers to express, in a declarative language, expectations about the system's communications structure, timing, and resource consumption. Pip includes system instrumentation and annotation tools to log actual system behavior, and visualization and query tools for exploring expected and unexpected behavior. Pip allows a developer to quickly understand and debug both familiar and unfamiliar systems. We applied Pip to several applications, including FAB, SplitStream, Bullet, and RanSub. We generated most of the instrumentation for all four applications automatically. We found the needed expectations easy to write, starting in each case with automatically generated expectations. Pip found unexpected behavior in each application, and helped to isolate the causes of poor performance and incorrect behavior.