Miracle-dz/UniFAR-FTUs huggingface dataset:
Pro‐apoptotic activity of transiently expressed BCL‐2 occurs independent of BAX and BAK

BCL‐2 suppresses apoptosis induced by a wide variety of stimuli in multiple cell types. Most of the in vitro studies that have examined the activity of BCL‐2 have employed stable cell lines that ectopically express BCL‐2. We have reported that BCL‐2 is expressed at high levels in the absence of the 5′‐ and 3′‐UTRs of the Bcl‐2 gene and transient high level of expression results in potent cell death (Uhlmann et al., [ 1998 ]: JBC 278:17926–17932). Expression of BCL‐2 under the transcriptional control of the cognate 5′‐ and 3′‐UTRs express lower levels of BCL‐2 and does not cause cell death. Our present results suggest that in contrast to BCL‐2, transient expression of BCL‐xL does not induce cell death and coexpression of BCL‐xL with the pro‐apoptotic BCL‐2 does not suppress cell death. The pro‐apoptotic activity of BCL‐2 appears to involve activation of the cytochrome c/caspase 9/caspase 3 pathway. Elevated levels of BCL‐2 expression results in N‐terminal cleavage of BCL‐2 at a novel site different from a previously identified caspase cleavage site at Asp 34 by a non‐caspase protease. Transient expression of a BCL‐2 mutant lacking aa 51–85 within the loop region induces efficient cell death and N‐terminal cleavage of BCL‐2 while a different deletion mutant lacking aa 30–91 induces reduced levels of cell death in the absence of BCL‐2 cleavage suggesting that N‐terminal processing of BCL‐2 may be an amplification event in BCL‐2‐mediated cell death. Overexpression of BCL‐2 in a Bax‐null human colon cancer cell line (HCT116Bax−/−) induces efficient cell death. The pro‐apoptotic activity of BCL‐2 is also observed in a Bax‐null cells in which BAK expression is inhibited by stable RNAi expression. Our results suggest that BCL‐2 contains an intrinsic pro‐apoptotic activity and can induce apoptosis independent of BAX and BAK under specific conditions. © 2003 Wiley‐Liss, Inc.
In Vitro Study of Mapping Method Interactions in a Name Pattern Landscape

Ontology mapping tools typically employ combinations of methods, the mutual effects of which deserve study. We propose an approach to analysis of such combinations using synthetic ontologies. Initial experiments have been carried out for two string-based and one graphbased method. Most important target of the study was the impact of name patterns over taxonomy paths on the mapping results.
SPIN

Recent GPUs enable Peer-to-Peer Direct Memory Access (p2p) from fast peripheral devices like NVMe SSDs to exclude the CPU from the data path between them for efficiency. Unfortunately, using p2p to access files is challenging because of the subtleties of low-level non-standard interfaces, which bypass the OS file I/O layers and may hurt system performance. Developers must possess intimate knowledge of low-level interfaces to manually handle the subtleties of data consistency and misaligned accesses. We present SPIN, which integrates p2p into the standard OS file I/O stack, dynamically activating p2p where appropriate, transparently to the user. It combines p2p with page cache accesses, re-enables read-ahead for sequential reads, all while maintaining standard POSIX FS consistency, portability across GPUs and SSDs, and compatibility with virtual block devices such as software RAID. We evaluate SPIN on NVIDIA and AMD GPUs using standard file I/O benchmarks, application traces, and end-to-end experiments. SPIN achieves significant performance speedups across a wide range of workloads, exceeding p2p throughput by up to an order of magnitude. It also boosts the performance of an aerial imagery rendering application by 2.6× by dynamically adapting to its input-dependent file access pattern, enables 3.3× higher throughput for a GPU-accelerated log server, and enables 29% faster execution for the highly optimized GPU-accelerated image collage with only 30 changed lines of code.
There Goes the Neighborhood: Pathological Alterations in T-Tubule Morphology and Consequences for Cardiomyocyte Ca2+ Handling

T-tubules are invaginations of the cardiomyocyte membrane into the cell interior which form a tortuous network. T-tubules provide proximity between the electrically excitable cell membrane and the sarcoplasmic reticulum, the main intracellular Ca2+ store. Tight coupling between the rapidly spreading action potential and Ca2+ release units in the SR membrane ensures synchronous Ca2+ release throughout the cardiomyocyte. This is a requirement for rapid and powerful contraction. In recent years, it has become clear that T-tubule structure and composition are altered in several pathological states which may importantly contribute to contractile defects in these conditions. In this review, we describe the “neighborhood” of proteins in the dyadic cleft which locally controls cardiomyocyte Ca2+ homeostasis and how alterations in T-tubule structure and composition may alter this neighborhood during heart failure, atrial fibrillation, and diabetic cardiomyopathy. Based on this evidence, we propose that T-tubules have the potential to serve as novel therapeutic targets.
Neural Attribute Machines for Program Generation

Recurrent neural networks have achieved remarkable success at generating sequences with complex structures, thanks to advances that include richer embeddings of input and cures for vanishing gradients. Trained only on sequences from a known grammar, though, they can still struggle to learn rules and constraints of the grammar. Neural Attribute Machines (NAMs) are equipped with a logical machine that represents the underlying grammar, which is used to teach the constraints to the neural machine by (i) augmenting the input sequence, and (ii) optimizing a custom loss function. Unlike traditional RNNs, NAMs are exposed to the grammar, as well as samples from the language of the grammar. During generation, NAMs make significantly fewer violations of the constraints of the underlying grammar than RNNs trained only on samples from the language of the grammar.
Genetic programming needs better benchmarks

Genetic programming (GP) is not a field noted for the rigor of its benchmarking. Some of its benchmark problems are popular purely through historical contingency, and they can be criticized as too easy or as providing misleading information concerning real-world performance, but they persist largely because of inertia and the lack of good alternatives. Even where the problems themselves are impeccable, comparisons between studies are made more difficult by the lack of standardization. We argue that the definition of standard benchmarks is an essential step in the maturation of the field. We make several contributions towards this goal. We motivate the development of a benchmark suite and define its goals; we survey existing practice; we enumerate many candidate benchmarks; we report progress on reference implementations; and we set out a concrete plan for gathering feedback from the GP community that would, if adopted, lead to a standard set of benchmarks.
Infection with Helicobacter pylori, coronary heart disease, cardiovascular risk factors, and systemic inflammation: the Third National Health and Nutrition Examination Survey.

BACKGROUND Few data have been published on the association of variables of the metabolic syndrome and infection with Helicobacter pylori, a putative risk factor for cardiovascular morbidity, in large, representative samples of total populations. The null hypothesis was no association of prevalent infection with H. pylori with prevalent coronary heart disease (CHD), systemic inflammation, and variables associated with the metabolic syndrome in American men. DESIGN Cross-sectional survey of a large national sample, the Third National Health and Nutrition Examination Survey. METHODS Among men aged 40-74 years, the survey measured history of CHD, glycated hemoglobin percent, and concentrations of fasting serum glucose, insulin, triglycerides, HDL cholesterol, and C-reactive protein (CRP). RESULTS Prevalence of infection with H. pylori increased with age. H. pylori infection was not correlated with serum CRP, prevalence of diagnosed diabetes mellitus, glycated hemoglobin percent, or other risk factors other than age. In diabetic men but not in all men, seropositivity was significantly associated with CHD prevalence. CONCLUSIONS No consistent associations of H. pylon infection with diabetes prevalence or variables of the insulin resistance syndrome were found in American men aged 40-74 years. In diabetic men, H. pylori infection was associated with CHD prevalence.
Efficient hard-switching DC/DC converters for envelope-tracking applications

This paper presents two buck converters switching at 50 MHz and based on Gallium Nitride dice. The first converter features a diode designed for power applications and demonstrates 87.9% peak efficiency. The diode mounted on the second one is aimed at higher-frequency operation and brings this value up above 91% in the same operating conditions. Loss contributions are evaluated, showing the influence of the diode alone on the efficiency of such converters.
A perspective-aware approach to search: visualizing perspectives in news search results

The result set from a search engine for any user's query may exhibit an inherent perspective due to issues with the search engine or issues with the underlying collection. This demonstration paper presents a system that allows users to specify at query time a perspective together with their query. The system then presents results from well-known search engines with a visualization of the results which allows the users to quickly surmise the presence of the perspective in the returned set.
Measurement of Phosphorylated Extracellular Signal–Regulated Kinase 1 and 2 in an Undergraduate Teaching Laboratory with ALPHAscreen Technology

Students use a high-throughput assay to monitor cellular responses to receptor activation. Teaching the practical aspects of signal transduction to large undergraduate classes can be challenging when there is only a finite time frame in which to engage in laboratory activities. This teaching resource describes the use of bead-based ALPHAscreen technology for a class of 300 second-year biochemistry students, exposing the next generation of researchers to cutting-edge technology. Although in this case phosphorylated extracellular signal–regulated kinase 1 and 2 were measured, this technology is applicable to the measurement of many different signaling components. This resource provides a practical guide for instructors and exemplifies how such traditionally high-throughput research technologies can be used as teaching tools.
Practical source-network decoding

When correlated sources are to be communicated over a network to more than one sink, joint source-network coding is, in general, required for information theoretically optimal transmission. Whereas on the encoder side simple randomized schemes based on linear codes suffice, the decoder is required to perform joint source-network decoding which is computationally expensive. Focusing on maximum a-posteriori decoders (or, in the case of continuous sources, conditional mean estimators), we show how to exploit (structural) knowledge about the network topology as well as the source correlations giving rise to an efficient decoder implementation (in some cases even with linear dependency on the number of nodes). In particular, we show how to statistically represent the overall system (including the packets) by a factor-graph on which the sum-product algorithm can be run. A proof-of-concept is provided in the form of a working decoder for the case of three sources and two sinks.
Generating Sparse Representations Using Quantum Annealing: Comparison to Classical Algorithms

We use a quantum annealing D-Wave 2X (1,152-qubit) computer to generate sparse representations of Canny-filtered, center-cropped 30x30 CIFAR-10 images. Each binary neuron (qubit) represents a feature kernel obtained initially by imprinting on a randomly chosen 5x5 image patch and then adapted via an off-line Hebbian learning protocol using the sparse solutions generated by the D-Wave. When using binary neurons, the energy function is non-convex (multiple local-minima) and finding a global minimum is NP-hard. Quantum annealing provides a strategy for finding sparse representations that correspond to good local minima of a non-convex cost function. To overcome the severe coupling restrictions between physical qubits on the D-Wave Chimera graph, we use embedding tools to achieve approximately all-to-all connectivity across a reduced number of logical qubits. We assess the sparse representations generated by the D-Wave using both the total energy as well as classification accuracy on a subset of the CIFAR-10 database. The D-Wave 2X outperforms two classical state-of-the-art binary solvers, GUROBI and Chimera-inspired algorithm Hamze-Freitas-Selby (HFS). Specifically, the D-Wave 2X yields lower energy sparse solutions within seconds while the largest problems take over 10 hours for both GUROBI and HFS. We obtained cross-validation classification of 31.02% for the first 4K images using 47 features on the quantum D- Wave 2X.
Meta-Analysis of Antibiotics and the Risk of Community-Associated Clostridium difficile Infection

ABSTRACT The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.
A subspace method for speech enhancement in the modulation domain

We present a modulation-domain speech enhancement algorithm based on a subspace method. We demonstrate that in the modulation domain, the covariance matrix of clean speech is rank deficient. We also derive a closed-form expression for the modulation-domain covariance matrix of colored noise in each frequency bin that depends on the analysis window shape and the noise power spectral density. Using this, we combine a noise power spectral density estimator with an efficient subspace method using a time domain constrained (TDC) estimator of the clean speech spectral envelope. The performance of the novel enhancement algorithm is evaluated using the PESQ measure and shown to outperform competitive algorithms for colored noise.
Benchmarking image and video retrieval: an overview

Multimedia Information Retrieval (IR)techniques and associated systems are now numerous and justify the development of strategies and actions to objectively evaluate their capabilities. A number of initiatives following this line exist, each with its own peculiarities. In this paper, we take a bird's eye view on benchmarking multimedia IR systems (with the particular case of image and video retrieval)and summarize contributions made to a dedicated special session at the ACM Multimedia Information Retrieval Workshop (ACM MIR2006). From the analysis of a classical IR system, we identify locations of interest for evaluation of performance.We review proposals made in the context of existing benchmarks, each specialized in its own aspect and media.
Historical Antarctic mean sea ice area, sea ice trends, and winds in CMIP5 simulations

In contrast to Arctic sea ice, average Antarctic sea ice area is not retreating but has slowly increased since satellite measurements began in 1979. While most climate models from the Coupled Model Intercomparison Project Phase 5 (CMIP5) archive simulate a decrease in Antarctic sea ice area over the recent past, whether these models can be dismissed as being wrong depends on more than just the sign of change compared to observations. We show that internal sea ice variability is large in the Antarctic region, and both the observed and modeled trends may represent natural variations along with external forcing. While several models show a negative trend, only a few of them actually show a trend that is significant compared to their internal variability on the time scales of available observational data. Furthermore, the ability of the models to simulate the mean state of sea ice is also important. The representations of Antarctic sea ice in CMIP5 models have not improved compared to CMIP3 and show an unrealistic spread in the mean state that may influence future sea ice behavior. Finally, Antarctic climate and sea ice area will be affected not only by ocean and air temperature changes but also by changes in the winds. The majority of the CMIP5 models simulate a shift that is too weak compared to observations. Thus, this study identifies several foci for consideration in evaluating and improving the modeling of climate and climate change in the Antarctic region.
Translational activation maintains germline tissue homeostasis during adulthood

Adult tissue maintenance is achieved through a tightly controlled equilibrium of 2 opposing cell fates: stem cell proliferation and differentiation. In recent years, the germ line emerged as a powerful in vivo model tissue to investigate the underlying gene expression mechanisms regulating this balance. Studies in numerous organisms highlighted the prevalence of post-transcriptional mRNA regulation, which relies on RNA-targeting factors that influence mRNA fates (e.g. decay or translational efficiency). Conserved translational repressors were identified that build negative feedback loops to ensure one or the other cell fate. However, to facilitate a fast and efficient transition between 2 opposing cell fates, translational repression per se appears not to be sufficient, suggesting the involvement of additional modes of gene expression regulation. Cytoplasmic poly(A) polymerases (cytoPAPs) represent a unique class of post-transcriptional mRNA regulators that modify mRNA 3' ends and positively influence cytoplasmic mRNA fates. We recently discovered that the 2 main cytoPAPs, GLD-2 and GLD-4, use distinct mechanisms to promote gene expression and that cytoPAP-mediated mRNA activation is important for regulating the size of the proliferative germ cell pool in the adult Caenorhabditis elegans gonad. Here, we comment on the different mechanisms of the 2 cytoPAPs as translational activators in germ cell development and focus on their biological roles in maintaining the balance between germline stem cell proliferation and differentiation in the Caenorhabditis elegans gonad.
Daytime sleepiness and nasal continuous positive airway pressure therapy in obstructive sleep apnea syndrome patients: effects of chronic treatment and 1-night therapy withdrawal.

A multiple sleep latency test (MSLT) was performed in 30 patients with obstructive sleep apnea syndrome (OSAS) at the time of diagnosis and after 1 year of home therapy with nasal continuous positive airway pressure (nCPAP). The MSLT was administered after two consecutive polysomnographic studies, one with (CPAP) and one without nCPAP (NCPAP) at baseline and at follow-up. After a year of therapy, the MSLT significantly rose from 3.1 +/- 0.3 to 9.8 +/- 1.0 minutes (p = 0.001). The increase in mean sleep latency was significantly correlated with the decrease in the number of arousals during the night (r = -0.48, p = 0.009). On the basis of MSLT value at follow-up, patients were split into two subgroups: the normalized group, in which 15 patients had an MSLT > or = 10 minutes, and the unnormalized group, consisting of 15 patients with an MSLT < 10 minutes. Normalized patients differed for a higher apnea+hypopnea index (AHI) time at baseline, a greater improvement in nocturnal hypoxemia and a greater nCPAP use at follow-up. After 1 night of therapy withdrawal, MSLT fell dramatically to 5.3 +/- 0.6 minutes, even though the subjects said they did not feel sleepy. The changes in MSLT after the night of treatment suspension were not correlated with changes in body mass index (BMI), AHI or nocturnal hypoxemia, whereas they were correlated negatively with changes in AHI time (r = -0.53, p = 0.003) and with the decrease in the number of arousals (r = -0.47, p = 0.009). (ABSTRACT TRUNCATED AT 250 WORDS)
Time Series Tests of Income Convergence with Two Structural Breaks: An Update and Extension

This paper uses newly available long-span data on real per capita incomes from 1900-2001 to test for stochastic convergence in a diverse group of 29 countries. To perform our tests, we utilize the two-break LM unit root test of Lee and Strazicich (2003) and endogenously determine two distinct structural breaks in level and trend for each country. Despite including both OECD and non-OECD countries, we find significant evidence that incomes are stochastically converging. World War II is the most often identified time period of breaks. The results represent slightly more evidence in favor of convergence than reported in the study by Dawson and Sen (forthcoming) using the same sample of countries.
Critically short telomeres and toxicity of chemotherapy in early breast cancer

Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy, fatigue) compromises long-term administration. Preclinical data suggest that the burden of critically short telomeres (< 3 kilobases, CSTs), but not average telomere length by itself, accounts for limited tissue renewal and turnover capacity. The impact of this parameter (which can be modified with different therapies) in chemotherapy-derived toxicity has not been studied. Blood from 115 treatment-naive patients from a clinical trial in early HER2-negative breast cancer that received weekly paclitaxel (80 mg/m2 for 12 weeks) either alone or in combination with nintedanib and from 85 healthy controls was prospectively obtained and individual CSTs and average telomere lenght were determined by HT Q-FISH (high-throughput quantitative FISH). Toxicity was graded according to NCI common toxicity criteria for adverse events (NCI CTCAE V.4.0). The variable under study was “number of toxic episodes” during the 12 weeks of therapy. The percentage of CSTs ranged from 6.5%–49.4% and was directly associated with the number of toxic events (R2 = 0.333; P < 0.001). According to a linear regression model, each 18% increase in the percentage of CSTs was associated to one additional toxic episode during the paclitaxel cycles; this effect was independent of the age or treatment arm. Patients in the upper quartile (> 21.9% CSTs) had 2-fold higher number of neuropathy (P = 0.04) or fatigue (P = 0.019) episodes and >3-fold higher number of myalgia episodes (P = 0.005). The average telomere length was unrelated to the incidence of side effects. The percentage of CSTs, but not the average telomere size, is associated with weekly paclitaxel-derived toxicity.