Abstract Tumor necrosis factor (TNF) is a critical cytokine, which contributes to both physiological and pathological processes. This mini-review will briefly touch the history of TNF discovery, its ...family members and its biological and pathological functions. Then, it will focus on new findings on the molecular mechanisms of how TNF triggers activation of the NF-κB and AP-1 pathways, which are critical for expression of pro-inflammatory cytokines, as well as the MLKL cascade, which is critical for the generation of ROS in response to TNF. Finally, this review will briefly summarize recent advances in understanding TNF-induced cell survival, apoptosis and necrosis (also called necroptosis). Understanding new findings and emerging concepts will impact future research on the molecular mechanisms of TNF signaling in immune disorders and cancer-related inflammation.
Automatic facial action unit (AU) and expression detection from videos is a long-standing problem. The problem is challenging in part because classifiers must generalize to previously unknown ...subjects that differ markedly in behavior and facial morphology (e.g., heavy versus delicate brows, smooth versus deeply etched wrinkles) from those on which the classifiers are trained. While some progress has been achieved through improvements in choices of features and classifiers, the challenge occasioned by individual differences among people remains. Person-specific classifiers would be a possible solution but for a paucity of training data. Sufficient training data for person-specific classifiers typically is unavailable. This paper addresses the problem of how to personalize a generic classifier without additional labels from the test subject. We propose a transductive learning method, which we refer to as a Selective Transfer Machine (STM), to personalize a generic classifier by attenuating person-specific mismatches. STM achieves this effect by simultaneously learning a classifier and re-weighting the training samples that are most relevant to the test subject. We compared STM to both generic classifiers and cross-domain learning methods on four benchmarks: CK+ 44, GEMEP-FERA 67, RUFACS 4 and GFT 57. STM outperformed generic classifiers in all.
SWR is a member of chromatin remodeler family and participates the replacement of histone H2A with H2A.Z. One of the SWR subunits, Swc5, has an intrinsically disordered region and binds to H2A‐H2B ...dimer. Though the binding structure of Swc5 and H2A‐H2B has been resolved recently, it is still challenging to investigate the binding mechanism as well as the role of the charge interactions between Swc5 and H2A‐H2B. Here we developed a coarse‐grained structure‐based model and performed molecular dynamics simulations to investigate the binding processes of two Swc5 regions with different lengths (swc5‐a and swc5‐b) to H2A‐H2B. The simulation results suggest a different role of electrostatic interactions between swc5‐a/swc5‐b and H2A‐H2B on binding. The electrostatic interactions between swc5‐a/swc5‐b and H2A‐H2B can not only accelerate the initial capture step of binding, but can also trap the swc5‐a/swc5‐b at the wrong binding site on H2A. Besides, the conserved DEF/Y‐2 motif of Swc5 is important for the binding affinity and the recognition with H2A‐H2B at the initial step. Both swc5‐a and swc5‐b undergo a structural shift before reaching the final bound state. This theoretical study provides important details and the underlying physical mechanisms of the binding processes of swc5‐a/swc5‐b and H2A‐H2B.
•The airflow management technologies in data centers are classified as long and short distance in the present review.•Hot-air recirculation, cold-air bypass, leakages, and airflow distributions are ...the most critical factors.•Strategies on improving airflow uniformity and preventing bypass and hot-air recirculation are reviewed.•Computational fluid dynamics plays essential role but requires prior calibration before further implementation.
This study provides a review upon airflow management in data centers. Based on the available airflow path, cooling systems in data centers are categorized as long-distance cooling or short-distance cooling systems. Investigations on airflow management include tests in real data center or in simulated data center. Besides, the computational fluid dynamics (CFD) had been widely employed upon the thermal and airflow management of the data centers. For the long-distance cooling system, the airflow management normally adopts raised-floor configuration and hot/cold aisle arrangement. The major problems in airflow management include hot-air recirculation, cold-air bypass, leakages, over-provisioned and under-provisioned air supply, and airflow/temperature non-uniformity. The aforementioned effects often interact with the geometry layout of the data center. Related literatures regarding the effect of plenum depth, perforated tiles, enhanced facility such as induced bypass fans, infrastructure layout, aisle containment and leakage are discussed and compared. In addition, studies on the overhead air supply method are also examined and compared with the raised-floor ones. For the short-distance cooling system, the effect of server layout and heat exchanger layout concerning the airflow uniformity are investigated. It is found that the appropriate management of the original design into centralized server layout can ease the mal-distribution of airflow into the severs by 30%. This review aims to emphasize the criteria of implementing airflow management to data centers that serve as a reference guide for energy saving in data center as far as airflow arrangement is concerned. Moreover, some recommended future research efforts are also addressed.
The removal of antibiotics from the aquatic environment has received great interest. The aim of this study is to examine degradation of oxytetracycline (OTC), tetracycline (TC), chlortetracycline ...(CTC), amoxicillin (AMO), sulfamethazine (SMZ), sulfamethoxazole (SMX), sulfadimethoxine (SDM) in sludge. Four antibiotic-degrading bacterial strains, SF1 (Pseudmonas sp.), A12 (Pseudmonas sp.), strains B (Bacillus sp.), and SANA (Clostridium sp.), were isolated, identified and tested under aerobic and anaerobic conditions in this study. Batch experiments indicated that the addition of SF1 and A12 under aerobic conditions and the addition of B and SANA under anaerobic conditions increased the biodegradation of antibiotics in sludge. Moreover, the results of repeated addition experiments indicated that the efficiency of the biodegradation of antibiotics using the isolated bacterial strains could be maintained for three degradation cycles. Two groups of potential microbial communities associated with the aerobic and anaerobic degradation of SMX, AMO and CTC in sludge were revealed. Twenty-four reported antibiotics-degrading bacterial genera (Achromobacter, Acidovorax, Acinetobacter, Alcaligenes, Bacillus, Burkholderia, Castellaniella, Comamonas, Corynebacterium, Cupriavidus, Dechloromonas, Geobacter, Gordonia, Klebsiella, Mycobacterium, Novosphingobium, Pandoraea, Pseudomonas, Rhodococcus, Sphingomonas, Thauera, Treponema, Vibrio and Xanthobacter) were found in both the aerobic and anaerobic groups, suggesting that these 24 bacterial genera may be the major antibiotic-degrading bacteria in sludge.
In our recent publication, we have proposed a revised base excision repair pathway in which DNA polymerase β (Polβ) catalyzes Schiff base formation prior to the gap-filling DNA synthesis followed by ...β-elimination. In addition, the polymerase activity of Polβ employs the "three-metal ion mechanism" instead of the long-standing "two-metal ion mechanism" to catalyze phosphodiester bond formation based on the fact derived from time-resolved x-ray crystallography that a third Mg2+ was captured in the polymerase active site after the chemical reaction was initiated. In this study, we develop the models of the uncross-linked and cross-linked Polβ complexes and investigate the "three-metal ion mechanism" vs the "two-metal ion mechanism" by using the quantum mechanics/molecular mechanics molecular dynamics simulations. Our results suggest that the presence of the third Mg2+ ion stabilizes the reaction-state structures, strengthens correct nucleotide binding, and accelerates phosphodiester bond formation. The improved understanding of Polβ's catalytic mechanism provides valuable insights into DNA replication and damage repair.
Most action unit (AU) detection methods use one-versus-all classifiers without considering dependences between features or AUs. In this paper, we introduce a joint patch and multi-label learning ...(JPML) framework that models the structured joint dependence behind features, AUs, and their interplay. In particular, JPML leverages group sparsity to identify important facial patches, and learns a multi-label classifier constrained by the likelihood of co-occurring AUs. To describe such likelihood, we derive two AU relations, positive correlation and negative competition, by statistically analyzing more than 350,000 video frames annotated with multiple AUs. To the best of our knowledge, this is the first work that jointly addresses patch learning and multi-label learning for AU detection. In addition, we show that JPML can be extended to recognize holistic expressions by learning common and specific patches, which afford a more compact representation than the standard expression recognition methods. We evaluate JPML on three benchmark datasets CK+, BP4D, and GFT, using within-and cross-dataset scenarios. In four of five experiments, JPML achieved the highest averaged F1 scores in comparison with baseline and alternative methods that use either patch learning or multi-label learning alone.
Liquid-liquid phase separation (LLPS) of some IDPs/IDRs can lead to the formation of the membraneless organelles in vitro and in vivo, which are essential for many biological processes in the cell. ...Here we select three different IDR segments of chaperon Swc5 and develop a polymeric slab model at the residue-level. By performing the molecular dynamics simulations, LLPS can be observed at low temperatures even without charge interactions and disappear at high temperatures. Both the sequence length and the charge pattern of the Swc5 segments can influence the critical temperature of LLPS. The results suggest that the effects of the electrostatic interactions on the LLPS behaviors can change significantly with the ratios and distributions of the charged residues, especially the sequence charge decoration (SCD) values. In addition, three different forms of swc conformation can be distinguished on the phase diagram, which is different from the conventional behavior of the free IDP/IDR. Both the packed form (the condensed-phase) and the dispersed form (the dilute-phase) of swc chains are found to be coexisted when LLPS occurs. They change to the fully-spread form at high temperatures. These findings will be helpful for the investigation of the IDP/IDR ensemble behaviors as well as the fundamental mechanism of the LLPS process in bio-systems.
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