Miracle-dz/UniFAR-FTUs huggingface dataset:
Regeneration and Tolerance Factor Prevents Bystander T-Cell Death Associated with Human Immunodeficiency Virus Infection

ABSTRACT Human immunodeficiency virus (HIV) infection is characterized by a depletion of T cells. This depletion is caused both by the virus-induced death of infected T cells and by the death of uninfected cells (bystander depletion) by a mechanism which is largely uncharacterized. Regeneration and tolerance factor (RTF) is a subunit of the vacuolar ATPase and a protein that is involved with activation and apoptosis. Anti-RTF antibodies mediate apoptosis in T lymphocytes. When anti-RTF was added to lymphocytes from an HIV-positive individual, they underwent larger amounts of apoptosis than cells taken from healthy controls. When lymphocytes were examined by Western blotting, those from HIV-positive individuals exhibited increased levels of expression of the 50-kDa protein (P < 0.001). A 70-kDa protein was the predominant form of RTF in uninfected control lymphocytes, being expressed in 100% of individuals studied. The expression of the 50-kDa protein in HIV-positive individuals correlated with decreased absolute CD4 counts with a sensitivity of 92% and a positive predictive value of 86%. When uninfected lymphocytes were stimulated with anti-CD3 and anti-CD28, no RTF was detected during early stimulation but a 50-kDa protein was expressed during late stimulation. When the susceptibilities of the lymphocytes to anti-RTF-induced apoptosis were measured, they correlated with the size of the RTF protein expressed. The cells were not susceptible to apoptosis when the 70-kDa RTF was present but were susceptible when the 50-kDa RTF was present. We propose that the increase in the levels of the 50-kDa RTF on cells from HIV-positive individuals is important in preventing the cell from undergoing apoptosis.
Phase-Resolved Properties and Simulation of Partial Discharges in High Voltage Liquid Insulation

High voltage equipments play important roles in electric power systems. In order to obtain the equipments work properly it is essential to keep the high voltage insulation system in good condition. High voltage insulations are classified into gas, liquid and solid insulations as well as their composites. Partial discharges may take place in liquid insulation. The appearance of partial discharges may degrade the performance of the insulation. The occurrence of the partial discharge (PD) is also an indication of insulation abnormality. In order to increase the quality of diagnosis of high voltage equipments it is important to deeply understand the partial discharges in each insulation. This paper reports the measurement, analysis and modeling of partial discharges in liquid insulating material. The partial discharges were generated using needle-plane electrode system. Partial discharge measurement was conducted using phase-resolved measurement system which able to measure the PD magnitude (q), phase of PD occurrence (φ) as well as PD number (n). The analysis of the PD data was conducted by utilizing φ-q-n and φ-n pattern. The experimental results showed that for PD pulses were observed at around the peak of both positive and negative applied voltages. The magnitude as well as pulse number are strongly dependent on the instantaneous applied voltage. Based on experimental the results, computer simulation of PD in liquid insulation was conducted. Simulated phase resolved PD patterns were similar to those obtained from experiment.
Single Sample Face Recognition from Video via Stacked Supervised Auto-Encoder

This work proposes and evaluates strategies based on Stacked Supervised Auto-Encoders (SSAE) for face representation in video surveillance applications. The study focuses on the identification task with a single sample per person (SSPP) in the gallery. Variations in terms of pose, facial expression, illumination and occlusion are approached in two ways. First, the SSAE extracts features from face images, which are robust to such variations. Second, we propose methods to exploit the multiple samples per persons probes (MSPPP) that can be extracted from video sequences. Three variants of the proposed method are compared upon HONDA/UCSD and VIDTIMIT video datasets. The experimental results demonstrate that strategies combining SSAE and MSPPP are able to outperform other SSPP methods, such a local binary patterns, in face recognition from video.
Impact of Line-Edge Roughness on FinFET Matching Performance

As a result of CMOS scaling, the critical dimension (CD) of integrated circuits has been shrinking. At sub-45 nm nodes, in which FinFET is a viable device architecture, line-edge roughness (LER) in current Si-based technologies forms a significant fraction of the line CD. In such cases, analyzing the impact of LER on FinFET performance is vital for meeting various device specifications. The impact of LER on the matching performance of FinFETs is investigated through statistical device simulations, comparing the relative importance of fin- and gate-LER. Fin-LER is shown to significantly degrade FinFET matching performance under DC and transient operations. Combining our device simulation results with experimental data, it is shown that fin-LER will dominate the intra-bit-cell stochastic mismatch in FinFET static random access memories at the LSTP-32-nm node. The electrical performance of spacer-defined fin (SDF) and resist-defined fin (RDF) patterning technologies has been compared. It is shown that, with respect to RDF patterning, the spacer-defined process has the potential to improve FinFET matching performance by 90%.
The effect of indomethacin on acute radiation induced gastrointestinal injury: A morphologic study

Radiation induced intestinal injury is a dose limiting factor in the treatment of pelvic, abdominal, and retroperitoneal malignancies with radiation therapy. In experimental models, radiation has been associated with increased intestinal prostaglandin activity and in clinical trials prostaglandin inhibitors have been demonstrated to improve the symptoms of acute radiation enteritis. This study was conducted to determine if the prostaglandin inhibitor indomethacin could prevent the morphologic changes of acute radiation induced intestinal injury. Twenty‐four male rats received either parenteral indomethacin at doses of 0.5, 1.0, and 3.0 mg/kg per dose every 12 hours or saline from 24 hours pre‐radiation exposure until sacrifice 48 hours later. Twenty‐four control animals received identical drug dosages and anesthesia but no radiation. Radiation produced a decreased villus/crypt ratio and increased acute inflammation and degeneration. Indomethacin treated animals demonstrated significantly less polymorphonuclear leukocyte infiltration and decreased degeneration. Villus/crypt ratio was not affected by indomethacin. © 1992 Wiley‐Liss, Inc.
Inverted Alu repeats unstable in yeast are excluded from the human genome

The nearly one million Alu repeats in human chromosomes are a potential threat to genome integrity. Alus form dense clusters where they frequently appear as inverted repeats, a sequence motif known to cause DNA rearrangements in model organisms. Using a yeast recombination system, we found that inverted Alu pairs can be strong initiators of genetic instability. The highly recombinagenic potential of inverted Alu pairs was dependent on the distance between the repeats and the level of sequence divergence. Even inverted Alus that were 86% homologous could efficiently stimulate recombination when separated by <20 bp. This stimulation was independent of mismatch repair. Mutations in the DNA metabolic genes RAD27 (FEN1), POL3 (polymerase δ) and MMS19 destabilized widely separated and diverged inverted Alus. Having defined factors affecting inverted Alu repeat stability in yeast, we analyzed the distribution of Alu pairs in the human genome. Closely spaced, highly homologous inverted Alus are rare, suggesting that they are unstable in humans. Alu pairs were identified that are potential sites of genetic change.
Mutability in Pseudomonas viridiflava as a programmed balance between antibiotic resistance and pathogenicity.

Mutable bacterial cells are defective in their DNA repair system and often have a phenotype different from that of their wild-type counterparts. In human bacterial pathogens, the mutable and hypermutable phenotypes are often associated with general antibiotic resistance. Here, we quantified the occurrence of mutable cells in Pseudomonas viridiflava, a phytopathogenic bacterium in the P. syringae complex with a broad host range and capacity to live as a saprophyte. Two phenotypic variants (transparent and mucoid) were produced by this bacterium. The transparent variant had a mutator phenotype, showed general antibiotic resistance and could not induce disease on the plant species tested (bean). In contrast, the mucoid variant did not display mutability or resistance to antibiotics and was capable of inducing disease on bean. Both the transparent and mucoid variants were less fit when grown in vitro, whereas, in planta, both of the variants and wild-types attained similar population densities. Given the importance of the methyl-directed mismatch repair system (MMR) in the occurrence of mutable and hypermutable cells in human bacterial pathogens, we investigated whether mutations in mut genes were associated with mutator transparent cells in P. viridiflava. Our results showed no mutations in MMR genes in any of the P. viridiflava cells tested. Here, we report that a high mutation rate and antibiotic resistance are inversely correlated with pathogenicity in P. viridiflava, but are not associated with mutations in MMR. In addition, P. viridiflava variants differ from variants produced by other phytopathogenic bacteria in the absence of reversion to the wild-type phenotype.
Effector T lymphocytes in lymphocytic choriomeningitis virus-infected mice. Cytolytic activity of Lyt-23 spleen cells in vitro does not correlate with elimination of infectious virus from spleens

The T lymphocytes from mice recovering from infection with lymphocytic choriomeningitis virus were selected for subclasses by treatment with anti-Lyt antisera and complement. Lyt-23 cells and mixtures of lyt-1 and Lyt-23 cells caused up to one-half the destruction of cultivated target cells as compared with untreated T lymphocytes; Lyt-1 cells alone were not cytotoxic. Selected and unselected spleen T cells were also inoculated intravenously into previously infected mice. Whereas unselected cells reduced infectious virus in the spleens of the recipients approximately 100-fold, only marginal effects, which were not preferentially associated with one particular subclass, were seen with selected LYT-23 or Lyt-1 lymphocytes or a mixture of both. Apparently the Lyt-23 cells, shown to by cytolytic for infected cells in vitro, did not cause elimination of a measurable quantity of the virus from mice.
Assessing the Impact of Urban Sprawl on Net Primary Productivity of Terrestrial Ecosystems Using a Process-Based Model—A Case Study in Nanjing, China

Urban sprawl/urbanization has large impacts on the structure and function of terrestrial ecosystems. Net primary production (NPP) is an important indicator for estimating the earth's ability to support life and aids the evaluation of sustainable development of the terrestrial ecosystem. In this study, the process-based boreal ecosystem productivity simulator (BEPS) model was used in conjunction with leaf area index (LAI) dataset, land cover, and meteorological and soil data to simulate daily NPP at spatial resolution 250 m in Nanjing, a representative region within the Yangtze Delta, for the period 2001-2010. Effects of urbanization on land-cover change and regional NPP are quantitatively evaluated. The results show that during this period, urbanization caused significant land-cover change. Compared with 2001, urbanized area and area covered by water bodies increased significantly, while vegetated area declined greatly. The greatest loss was cropland, followed by evergreen coniferous and closed deciduous forests. There were obvious spatial differences in NPP variations. The reduction rate of annual NPP in the major city of Nanjing, Jiangning District, and Gaochun County was much higher than that in Pukou and Luhe district, and Lishui County. These results indicate that a process-based model driven by remote sensing is useful in assessing the impact of urban sprawl on NPP, and urbanization, not climate factors, is a main factor for NPP reduction for an urbanizing region.
Finite wordlength design for VLSI FFT processors

Resource efficient FFT processors have become a common requirement for high-speed xDSL and OFDM transceivers. Hardwired VLSI implementations often result in smaller area and lower power consumption than general-purpose DSP processors. For hardwired designs, intelligent wordlength selection can be employed to further reduce hardware resource requirements. This paper describes a technique for quick and accurate estimation of FFT noise performance by modeling the FFT as a series of amplifier stages. The technique is employed to specify wordlengths that provide good tradeoffs between noise performance and hardware requirements. The technique is also used to show that the decimation-in-time radix-2 FFT algorithm has better finite wordlength properties than the decimation-in-frequency radix-2 FFT algorithm.
Analytical evaluation of a tradeoff between energy efficiency and responsiveness of neighbor discovery in self-organizing ad hoc networks

Ad hoc networking enables novel communication paradigms which require the definition of new quality-of-service (QoS) parameters and frameworks for QoS support. The relevant QoS requirements are frequently antagonist and, consequently, an appropriate tradeoff has to be determined and achieved to fit all of them. As an example, the spontaneous networking featured by self-organizing ad hoc networks is possible only if neighboring communication nodes discover each other within a short period of time; however, velocity of discovery is paid in terms of energy consumption. In this paper, an analytical framework is derived which allows an evaluation of the tradeoff between energy efficiency and responsiveness in the discovery process. More specifically, the analytical framework allows either to achieve the highest velocity in the discovery process, given that the energy consumption is lower than a certain threshold, or to minimize the energy consumption given that specific requirements in terms of the discovery velocity are satisfied. The analytical framework is applied to significant case studies to derive design implications on neighbor discovery algorithms.
Tackling the challenges posed by target flexibility in drug design

Importance of the field: Current computational docking methods are often effective in predicting accurate drug-binding geometries in cases of relatively rigid target structures. However, binding of drug-like ligands to protein receptor molecules frequently involves or even requires conformational adaptation. Realistic prediction of ligand–receptor binding geometries and complex stability needs in many cases an appropriate inclusion of conformational changes, not only for the ligand, but also for the receptor molecule. Areas covered in this review: Recent approaches to efficiently account for target receptor flexibility during docking simulations are reviewed. What the reader will gain: The reader will gain insights into methods to efficiently treat protein side-chain flexibility and approaches for continuous adaptation of backbone conformations in pre-calculated essential or soft collective degrees of freedom. In addition, molecular dynamics or Monte Carlo based methods providing simultaneous inclusion of receptor and ligand flexibility are discussed as well as promising new developments to generate conformationally diverse ensembles of a protein structure. The large variety of possible conformational changes in proteins on ligand binding is illustrated for the enzyme reverse transcriptase of HIV-1, which is an important drug target. Take home message: If the backbone conformation of the binding site does not change, current docking programs can perform well by taking side-chain reorientations into account only. Future progress to account for full target flexibility in docking requires both accurate prediction of the essential modes of backbone motion and improvements in scoring to enhance selectivity. Thus, the scoring function should realistically cover energetic and particularly entropic contributions to binding, which would allow more realistic estimates of binding free energies.
Auditory Lexical Decision and Repetition in Children: Effects of Acoustic and Lexical Constraints

Objectives: The objective of this study was to identify factors that may detract from children’s ability to identify words they do and do not know. Factors investigated were acoustic constraints stemming from the presence of hearing loss (HL) or an acoustic competitor, and lexical constraints due to an impoverished or cluttered vocabulary. Design: Eleven children with normal hearing (NH) and 11 children with bilateral, mild to moderately severe sensorineural HL were asked to categorize and repeat two-syllable real and nonsense words. Stimuli were amplified and frequency shaped for each child with HL and presented randomly at a level consistent with average conversational speech (65 dB SPL). About half of the children in each group listened in quiet while the other half listened in multitalker babble. In addition to overall performance, responses were judged based on the word category chosen by the child (real or nonsense), the category of the word produced by the child as judged by an examiner (real or nonsense), and the accuracy of the verbal response compared with the stimulus. From these judgments, 10 discrete types of errors were identified. Analyses were conducted for three different combinations of the 10 error categories to best characterize the effects of acoustic and lexical constraints. Results: Performance was highest for real words presented in quiet and poorest for nonsense words presented in multitalker babble. Also, the performance of the children with HL was poorer than that of the children with NH. Error analyses revealed strong effects of acoustic constraints on performance but few effects of lexical constraints. The two most frequently occurring errors were the same for both children with NH and the children with HL and entailed the misperception of nonsense words and the mistaking of nonsense words for real words. However, while both groups of children exhibited these errors in multitalker babble, the children with HL demonstrated these errors in quiet as well. Conclusions: These results suggest that children’s interactions with real and nonsense words are significantly constrained when the acoustic signal is degraded by HL and/or an acoustic competitor. The children’s tendency to repair unknown words into real words in the presence of acoustic interference may be beneficial when perceiving familiar speech, but could also be detrimental if that tendency causes them to miss opportunities to learn new words.
ErbB2 Potentiates Breast Tumor Proliferation through Modulation of p27Kip1-Cdk2 Complex Formation: Receptor Overexpression Does Not Determine Growth Dependency

ABSTRACT Overexpression of the ErbB2 receptor, a major component of the ErbB receptor signaling network, contributes to the development of a number of human cancers. ErbB2 presents itself, therefore, as a target for antibody-mediated therapies. In this respect, anti-ErbB2 monoclonal antibody 4D5 specifically inhibits the growth of tumor cells overexpressing ErbB2. We have analyzed the effect of 4D5-mediated ErbB2 inhibition on the cell cycle of the breast tumor cell line BT474. 4D5 treatment of BT474 cells resulted in a G1 arrest, preceded by rapid dephosphorylation of ErbB2, inhibition of cytoplasmic signal transduction pathways, accumulation of the cyclin-dependent kinase inhibitor p27Kip1, and inactivation of cyclin-Cdk2 complexes. Time courses demonstrated that 4D5 treatment redirects p27Kip1 onto Cdk2 complexes, an event preceding increased p27Kip1 expression; this correlates with the downregulation of c-Myc and D-type cyclins (proteins involved in p27Kip1sequestration) and the loss of p27Kip1 from Cdk4 complexes. Similar events were observed in ErbB2-overexpressing SKBR3 cells, which exhibited reduced proliferation in response to 4D5 treatment. Here, p27Kip1 redistribution resulted in partial Cdk2 inactivation, consistent with a G1 accumulation. Moreover, p27Kip1 protein levels remained constant. Antisense-mediated inhibition of p27Kip1 expression in 4D5-treated BT474 cells further demonstrated that in the absence of p27Kip1 accumulation, p27Kip1 redirection onto Cdk2 complexes is sufficient to inactivate Cdk2 and establish the G1 block. These data suggest that ErbB2 overexpression leads to potentiation of cyclin E-Cdk2 activity through regulation of p27Kip1 sequestration proteins, thus deregulating the G1/S transition. Moreover, through comparison with an ErbB2-overexpressing cell line insensitive to 4D5 treatment, we demonstrate the specificity of these cell cycle events and show that ErbB2 overexpression alone is insufficient to determine the cellular response to receptor inhibition.
Splicing and missense mutations in the human FXIIIA gene causing FXIII deficiency: effects of these mutations on FXIIIA RNA processing and protein structure

We have investigated the molecular basis of factor XIII (FXIII) deficiency in a family from the north‐west region of the U.K. and identified two sequence changes in the FXIII subunit A (FXIIIA) gene. We report a novel Asn to Lys mutation at codon 541, and a g → a mutation at the intron 5/exon 6 splice junction in the FXIIIA gene. The splicing mutation results in two abnormal FXIIIA transcripts. The Asn541 residue is important for stabilizing an external fold in the FXIIIA barrel 1 domain. The Asn541Lys mutation is expected to result in inappropriate folding and therefore an unstable FXIIIA molecule.
Imatinib as preoperative therapy in Chinese patients with recurrent or metastatic GISTs.

OBJECTIVE Imatinib has dramatically altered the options for management of patients with gastrointestinal stromal tumours. However, it has become clear that secondary resistance to the drug develops during long-term therapy. The purpose of our study was to retrospectively analyze safety and long-term outcomes in Chinese patients with recurrent or metastatic GISTs treated with imatinib preoperatively. METHODS Between June 2003 and June 2011, 22 patients underwent surgery for recurrent or metastatic GISTs after preoperative treatment with imatinib. RESULTS Complete resection was accomplished in 8 of the 10 responsive disease (RD) patients (80%), and in 3 of the 12 patients (25%) who had progression disease (PD). The amount of blood loss during the operation in PD patients was higher than in RD patients. There was 1 hospital death in PD group related to surgery, while the other patients recovered with conservative therapy because complications were mild. The difference in median PFS between patients with RD and those with PD was significant (24.8 vs. 2.81 months, P<0.001). The difference in 2-year OS rate between patients with RD and those with PD was not significant (100% vs. 87.5%, P>0.05). CONCLUSIONS Our study indicates that surgical intervention can improve the PFS of Chinese patients with recurrent or metastatic GISTs responsive to imatinib, but does not prolong OS as well as in patients who develop imatinib resistance. Surgical resection following imatinib treatment is feasible and can be considered for patients with advanced GISTs responsive to imatinib.