Miracle-dz/UniFAR-FTUs huggingface dataset:
P3N-PIPO, a Frameshift Product from the P3 Gene, Pleiotropically Determines the Virulence of Clover Yellow Vein Virus in both Resistant and Susceptible Peas

ABSTRACT Peas carrying the cyv1 recessive resistance gene are resistant to clover yellow vein virus (ClYVV) isolates No.30 (Cl-No.30) and 90-1 (Cl-90-1) but can be infected by a derivative of Cl-90-1 (Cl-90-1 Br2). The main determinant for the breaking of cyv1 resistance by Cl-90-1 Br2 is P3N-PIPO produced from the P3 gene via transcriptional slippage, and the higher level of P3N-PIPO produced by Cl-90-1 Br2 than by Cl-No.30 contributes to the breaking of resistance. Here we show that P3N-PIPO is also a major virulence determinant in susceptible peas that possess another resistance gene, Cyn1, which does not inhibit systemic infection with ClYVV but causes hypersensitive reaction-like lethal systemic cell death. We previously assumed that the susceptible pea cultivar PI 226564 has a weak allele of Cyn1. Cl-No.30 did not induce cell death, but Cl-90-1 Br2 killed the plants. Our results suggest that P3N-PIPO is recognized by Cyn1 and induces cell death. Unexpectedly, heterologously strongly expressed P3N-PIPO of Cl-No.30 appears to be recognized by Cyn1 in PI 226564. The level of P3N-PIPO accumulation from the P3 gene of Cl-No.30 was significantly lower than that of Cl-90-1 Br2 in a Nicotiana benthamiana transient assay. Therefore, Cyn1-mediated cell death also appears to be determined by the level of P3N-PIPO. The more efficiently a ClYVV isolate broke cyv1 resistance, the more it induced cell death systemically (resulting in a loss of the environment for virus accumulation) in susceptible peas carrying Cyn1, suggesting that antagonistic pleiotropy of P3N-PIPO controls the resistance breaking of ClYVV. IMPORTANCE Control of plant viral disease has relied on the use of resistant cultivars; however, emerging mutant viruses have broken many types of resistance. Recently, we revealed that Cl-90-1 Br2 breaks the recessive resistance conferred by cyv1, mainly by accumulating a higher level of P3N-PIPO than that of the nonbreaking isolate Cl-No.30. Here we show that a susceptible pea line recognized the increased amount of P3N-PIPO produced by Cl-90-1 Br2 and activated the salicylic acid-mediated defense pathway, inducing lethal systemic cell death. We found a gradation of virulence among ClYVV isolates in a cyv1-carrying pea line and two susceptible pea lines. This study suggests a trade-off between breaking of recessive resistance (cyv1) and host viability; the latter is presumably regulated by the dominant Cyn1 gene, which may impose evolutionary constraints upon P3N-PIPO for overcoming resistance. We propose a working model of the host strategy to sustain the durability of resistance and control fast-evolving viruses.
Self-reported occupational physical activity and cardiorespiratory fitness: Importance for cardiovascular disease and all-cause mortality.

OBJECTIVES This study aimed to investigate whether workers with the combination of high occupational physical activity (OPA) and low cardiorespiratory fitness have an increased risk of cardiovascular disease (CVD) and all-cause mortality. METHODS Using multivariable Cox proportional hazards regression, we analyzed 2190 males and 2534 females from the Copenhagen City Heart Study, aged 20-67 years and with no known CVD at study entry in 1991-1994, for the risk of CVD and all-cause mortality from independent, stratified and combinations of self-reported OPA (ie, low, moderate and high) and cardiorespiratory fitness (low, same and higher as peers) at baseline. RESULTS During a median follow-up of 18.5 years, 257 and 852 individuals died from CVD and any cause, respectively. In the fully-adjusted model, an increased risk for CVD mortality was found for those with low compared to high self-reported cardiorespiratory fitness [hazard ratio (HR) 2.17, 95% confidence interval (95% CI) 1.40-3.38), for those with high compared to low OPA (HR 1.45, 95% CI 1.05-2.00), and for those with high compared to low OPA within the strata of low self-reported cardiorespiratory fitness (HR 2.83, 95% CI 1.24-6.46). Moreover, those with the combination of high OPA and low self-reported cardiorespiratory fitness had an increased risk for CVD mortality compared to those with the combination of low OPA and high self-reported cardiorespiratory fitness (HR 6.22, 95% CI 2.67-14.49). Rather similar, but lower risk estimates were found for all-cause mortality. CONCLUSION These findings may have important implications for CVD prevention among workers with excessive cardiovascular strain at work.
Experimental validation of through-thickness resin flow model in the consolidation of saturated porous media

In this paper, a reliable and reproducible experimental procedure for the study of the through-thickness flow induced by the compaction of a saturated porous media is presented. Experimental fluid pressure data are exploited in the validation of a fully coupled fluid-mechanical model and the verification of the related material parameters. The experimental results show overall good agreement with the numerical solution, for all three configurations tested. In addition, up-scaling rules have been identified, which relate the consolidation time with the fluid viscosity and the number of layers.
YY1 is indispensable for Lgr5+ intestinal stem cell renewal

Significance A subset of our body’s tissues is continuously renewed through cell division. Tissue-specific stem cells support this tissue turnover, and understanding the mechanisms that control the behavior of these stem cells is important to understanding the health of the tissue. In this work, we identify a novel regulator of the intestinal stem cells. We find that, when the transcription factor YY1 is inactivated, intestinal stem cells can no longer renew themselves. We show that YY1 controls mitochondrial gene expression, and loss of YY1 results in loss of mitochondrial structural integrity. This work, therefore, provides a link between a mitochondrial regulator and stem cell function and broadens our appreciation of metabolic regulation in tissue-specific stem cells. The intestinal stem cell fuels the highest rate of tissue turnover in the body and has been implicated in intestinal disease and cancer; understanding the regulatory mechanisms controlling intestinal stem cell physiology is of great importance. Here, we provide evidence that the transcription factor YY1 is essential for intestinal stem cell renewal. We observe that YY1 loss skews normal homeostatic cell turnover, with an increase in proliferating crypt cells and a decrease in their differentiated villous progeny. Increased crypt cell numbers come at the expense of Lgr5+ stem cells. On YY1 deletion, Lgr5+ cells accelerate their commitment to the differentiated population, exhibit increased levels of apoptosis, and fail to maintain stem cell renewal. Loss of Yy1 in the intestine is ultimately fatal. Mechanistically, YY1 seems to play a role in stem cell energy metabolism, with mitochondrial complex I genes bound directly by YY1 and their transcript levels decreasing on YY1 loss. These unappreciated YY1 functions broaden our understanding of metabolic regulation in intestinal stem cell homeostasis.
Bayesian Semi-Supervised Tensor Decomposition using Natural Gradients for Anomaly Detection

Anomaly Detection has several important applications. In this paper, our focus is on detecting anomalies in seller-reviewer data using tensor decomposition. While tensor-decomposition is mostly unsupervised, we formulate Bayesian semi-supervised tensor decomposition to take advantage of sparse labeled data. In addition, we use Pólya-Gamma data augmentation for the semi-supervised Bayesian tensor decomposition. Finally, we show that the Pólya-Gamma formulation simplifies calculation of the Fisher information matrix for partial natural gradient learning. Our experimental results show that our semi-supervised approach outperforms state of the art unsupervised baselines. And that the partial natural gradient learning outperforms stochastic gradient learning and Online-EM with sufficient statistics.
Strength and fracture of Si micropillars: A new scanning electron microscopy-based micro-compression test

A novel method for in situ scanning electron microscope (SEM) micro-compression tests is presented. The direct SEM observation during the instrumented compression testing allows for very efficient positioning and assessment of the failure mechanism. Compression tests on micromachined Si pillars with volumes down to 2 μm^3 are performed inside the SEM, and the results demonstrate the potential of the method. In situ observation shows that small diameter pillars tend to buckle while larger ones tend to crack before failure. Compressive strength increases with decreasing pillar diameter and reaches almost 9 GPa for submicrometer diameter pillars. This result is in agreement with earlier bending experiments on Si. Difficulties associated with precise strain measurements are discussed.
A comparison of quality of life in obese individuals with and without binge eating disorder.

OBJECTIVE This study investigates whether binge eating disorder (BED) in obese individuals is associated with a greater degree of impairment in quality of life (QOL) than obesity alone. METHOD Treatment-seeking obese individuals with and without BED were compared on QOL scores using the Impact of Weight on Quality of Life (IWQOL-Lite) questionnaire. RESULTS With the exception of the Physical Function subscale, obese individuals with BED scored significantly higher than non-BED participants on each of the subscales and on the total scale of the IWQOL-Lite. For all participants, body mass index (BMI) was related significantly to scores on the Physical Function and Public Distress subscales of the IWQOL-Lite. DISCUSSION Obese individuals with BED have impaired functioning on psychosocial aspects of QOL in addition to poorer physical functioning associated with obesity. These findings underscore the pervasive impact of BED in obese individuals, as BED is associated with more impairment than obesity alone.
Impact of competitive strategy and cost-focus on global supplier switching (reshore and relocation) decisions

Abstract This study analyzes how global supplier switching decisions (reshore and relocate) are influenced by the buyers’ cost-focus and competitive strategies. Comprehensive survey data were gathered from US textile and apparel industry. The analysis revealed that the buyers with distinct competitive strategies such as Made-in-USA, speed-to-market are likely to have significantly higher proportions of reshoring activities. Furthermore, large companies and retailers are shown to be more cost-focused than small and manufacturing companies, respectively. Finally, cost-focused companies are shown to be more likely to switch their international suppliers. By analyzing the buyer side of supplier-switching and identifying the common features of companies engaging in reshoring or relocation, our analysis enables us to better interpret international supplier-switching. While other studies have regarded the superior performance of the prospective supplier or the external issues as the main factors, we emphasize the impact of internal dynamics of buyers on the international supplier-switching processes.
Characterization of the Adeno-Associated Virus 1 and 6 Sialic Acid Binding Site

ABSTRACT The adeno-associated viruses (AAVs), which are being developed as gene delivery vectors, display differential cell surface glycan binding and subsequent tissue tropisms. For AAV serotype 1 (AAV1), the first viral vector approved as a gene therapy treatment, and its closely related AAV6, sialic acid (SIA) serves as their primary cellular surface receptor. Toward characterizing the SIA binding site(s), the structure of the AAV1-SIA complex was determined by X-ray crystallography to 3.0 Å. Density consistent with SIA was observed in a pocket located at the base of capsid protrusions surrounding icosahedral 3-fold axes. Site-directed mutagenesis substitution of the amino acids forming this pocket with structurally equivalent residues from AAV2, a heparan sulfate binding serotype, followed by cell binding and transduction assays, further mapped the critical residues conferring SIA binding to AAV1 and AAV6. For both viruses five of the six binding pocket residues mutated (N447S, V473D, N500E, T502S, and W503A) abolished SIA binding, whereas S472R increased binding. All six mutations abolished or decreased transduction by at least 50% in AAV1. Surprisingly, the T502S substitution did not affect transduction efficiency of wild-type AAV6. Furthermore, three of the AAV1 SIA binding site mutants—S472R, V473D, and N500E—escaped recognition by the anti-AAV1 capsid antibody ADK1a. These observations demonstrate that common key capsid surface residues dictate both virus binding and entry processes, as well as antigenic reactivity. This study identifies an important functional capsid surface “hot spot” dictating receptor attachment, transduction efficiency, and antigenicity which could prove useful for vector engineering. IMPORTANCE The adeno-associated virus (AAV) vector gene delivery system has shown promise in several clinical trials and an AAV1-based vector has been approved as the first gene therapy treatment. However, limitations still exist with respect to transduction efficiency and the detrimental effects of preexisting host antibodies. This study aimed to identify key capsid regions which can be engineered to overcome these limitations. A sialic glycan receptor recognition pocket was identified in AAV1 and its closely related AAV6, using X-ray crystallography. The site was confirmed by mutagenesis followed by cell binding and transduction assays. Significantly, residues controlling gene expression efficiency, as well as antibody escape variants, were also identified. This study thus provides, at the amino acid level, information for rational structural engineering of AAV vectors with improved therapeutic efficacy.
Transcranial Magnetic Stimulation to the Frontal Operculum and Supramarginal Gyrus Disrupts Planning of Outcome-Based Hand–Object Interactions

Behavioral data suggest that goals inform the selection of motor commands during planning. We investigated the neural correlates that mediate planning of goal-oriented actions by asking 10 healthy subjects to prepare either a goal-specific movement toward a common object (a cup), with the intent of grasping-to-pour (liquid into it) or grasping-to-move (to another location) the object, or performing a non-object-oriented stimulus-response task (move a finger). Single-pulse transcranial magnetic stimulation was administered on 50% of trials to the supramarginal gyrus (SMG), anterior intraparietal sulcus, inferior frontal gyrus opercularis (IFGo), and triangularis during motor planning. Stimulation to SMG and IFGo caused a significant delay in planning goal-oriented actions but not responses to an arbitrary stimulus. Despite the delay, movement execution was not affected, suggesting that the motor plan remained intact. Our data implicate the SMG and IFGo in planning goal-oriented hand–object interactions.
INTRACELLULAR RECORDING FROM THE GIANT SYNAPSE OF THE SQUID

1. Recording with glass micropipette electrodes inserted close to the synaptic region, in the presynaptic and in the postsynaptic fibers of the giant synapse in the stellate ganglion of the squid, has been accomplished. 2. The forms of the spike and of the synaptic potential are very much like those reported earlier (Bullock, 1948) from macroelectrodes. The crest time and the rate of fall are labile and depend on the state of fatigue, though the time of initiation of the postsynaptic potential does not. 3. It is concluded after examination of both intra- and extracellular recordings that there is a real synaptic delay of the order of 1 or 2 milliseconds at 15–20°C. 4. There is sometimes a very small and sometimes no visible deflection in the intracellular postsynaptic record attributable to the presynaptic spike. It is concluded that transmission cannot be electrical. 5. The amplitude of the postsynaptic potential can be controlled over some range by the amplitude of the presynaptic potential. 6. Hyperpolarization of the postsynaptic membrane results in increase in amplitude of spikes up to 200 millivolts, in increase in the membrane potential level at which the spike flares up, but in no considerable change in the amplitude in postsynaptic potential. 7. The postsynaptic potential can add to the late falling phase and the undershoot of an antidromic spike in the postfiber but cannot add to the crest or early part of the falling phase. The earliest part of the antidromic spike during which the postsynaptic potential can add is probably a period of refractoriness to electrical shock by analogy with the properties of the axon.
Endovascular reperfusion therapies for acute ischemic stroke: dissecting the evidence

ABSTRACT Background: Ischemic stroke is a major cause of death and disability and intravenous thrombolysis has been the only approved acute reperfusion therapy (RT) for many years. Methods: Seven randomized-controlled clinical trials (RCTs) evaluating the safety and efficacy of endovascular therapy in patients with acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) have been recently published. Results: These studies have changed the treatment paradigm by establishing mechanical thrombectomy (MT) as the most effective acute stroke therapy for improving functional outcome in anterior circulation ELVO with a NNT of 6. Conclusions: The present review will critically evaluate the results of these RCTs and of the existing meta-analyses investigating the safety and efficacy of endovascular therapy for AIS. Points of debate such as acute stroke imaging, posterior circulation stroke and general anesthesia will be addressed. We will also discuss health policies aiming to increase the availability of endovascular treatment for stroke patients.
Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture

Colorectal cancer is one of the most common causes of cancer death worldwide. In patients with metastatic colorectal cancer, combination treatment with several anti-cancer drugs is employed and improves overall survival in some patients. Nevertheless, most patients with metastatic disease are not cured owing to the drug resistance. Cancer stem cells are known to regulate resistance to chemotherapy. In the previous study, we established a novel three-dimensional organoid culture model from tumor colorectal tissues of human patients using an air–liquid interface (ALI) method, which contained numerous cancer stem cells and showed resistance to 5-fluorouracil (5-FU) and Irinotecan. Here, we investigate which inhibitor for stem cell-related signal improves the sensitivity for anti-cancer drug treatment in tumor ALI organoids. Treatment with Hedgehog signal inhibitors (AY9944, GANT61) decreases the cell viability of organoids compared with Notch (YO-01027, DAPT) and Wnt (WAV939, Wnt-C59) signal inhibitors. Combination treatment of AY9944 or GANT61 with 5-FU, Irinotecan or Oxaliplatin decreases the cell viability of tumor organoids compared with each anti-cancer drug alone treatment. Treatment with AY9944 or GANT61 inhibits expression of stem cell markers c-Myc, CD44 and Nanog, likely through the decrease of their transcription factor, GLI-1 expression. Combination treatment of AY9944 or GANT61 with 5-FU or Irinotecan also prevents colony formation of colorectal cancer cell lines HCT116 and SW480. These findings suggest that Hedgehog signals mediate anti-cancer drug resistance in colorectal tumor patient-derived ALI organoids and that the inhibitors are useful as a combinational therapeutic strategy against colorectal cancer.
Load Prediction for Energy-Aware Scheduling for Cloud Computing Platforms

We address online scheduling for servers of Cloud service providers. Each server is composed of several variable-speed processors whose power function is convex. The servers may be busy, idle or switched off. The objective of our scheduling is to minimize the energy consumed by a Cloud computing platform. To achieve this goal, we try to anticipate computing demands by predicting a workload, then we modify the set of available servers to fit this prediction and finally we schedule our jobs on the available servers. To schedule jobs we have developed the POD (Predict Optimize Dispatch) algorithm. We evaluate its performance for real-life traces in the presence of different types of prediction. The analysis shows that our scheduling reduces energy consumption considerably.
Notes on Expected Computational Cost of Classifiers Cascade: A Geometric View

A cascade of classifiers, working within a detection procedure, extracts and uses different number of features depending on the window under analysis. Windows with background regions can be typically recognized as negative with just a few features, whereas windows with target objects (or resembling them) might require thousands of features. The central point of attention for this paper is a quantity that describes the average computational cost of an operating cascade, namely — the expected value of the number of features the cascade uses. This quantity can be calculated explicitly knowing the probability distribution underlying the data and the properties of a particular cascade (detection and false alarm rates of its stages), or it can be accurately estimated knowing just the latter. We show three purely geometric examples that demonstrate how training a cascade with sensitivity / FAR constraints imposed per each stage can lead to non-optimality in terms of the computational cost. We do not propose a particular algorithm to overcome the pitfalls of stage-wise training, instead, we sketch an intuition showing that non-greedy approaches can improve the resulting cascades.
Host association influences variation at salivary protein genes in the bat ectoparasite Cimex adjunctus

Parasite–host relationships create strong selection pressures that can lead to adaptation and increasing specialization of parasites to their hosts. Even in relatively loose host–parasite relationships, such as between generalist ectoparasites and their hosts, we may observe some degree of specialization of parasite populations to one of the multiple potential hosts. Salivary proteins are used by blood‐feeding ectoparasites to prevent hemostasis in the host and maximize energy intake. We investigated the influence of association with specific host species on allele frequencies of salivary protein genes in Cimex adjunctus, a generalist blood‐feeding ectoparasite of bats in North America. We analysed two salivary protein genes: an apyrase, which hydrolyses ATP at the feeding site and thus inhibits platelet aggregation, and a nitrophorin, which brings nitrous oxide to the feeding site, inhibiting platelet aggregation and vasoconstriction. We observed more variation at both salivary protein genes among parasite populations associated with different host species than among populations from different spatial locations associated with the same host species. The variation in salivary protein genes among populations on different host species was also greater than expected under a neutral scenario of genetic drift and gene flow. Finally, host species was an important predictor of allelic divergence in genotypes of individual C. adjunctus at both salivary protein genes. Our results suggest differing selection pressures on these two salivary protein genes in C. adjunctus depending on the host species.