gebhart/patrepeval huggingface dataset:
Dengue vaccine design: issues and challenges (1998)

Dengue virus infection is now a global problem affecting tens of millions of people. The spread of the four dengue virus serotypes had led to increased incidence of dengue haemorrhagic fever (DHF) reported and with 2.5 billion people at risk, efforts towards the development of safe and effective vaccines against dengue must be accelerated. This chapter reviews some of the important lessons of pathogenesis which may be learnt from classical studies in the field and place these in the context of current knowledge about the molecular biology of the virus. The issues which have to be addressed in designing a safe vaccine against dengue are raised and the problems of designing subunit as well as whole virus vaccines are pointed out, particularly with regard to the phenomenon of antibody dependent enhancement and, more generally, the problem of immune potentiation of disease. More efforts must be made to understand the basis of pathogenesis in DHF and in finding out what nature has to teach about protection against and recovery from dengue virus infection.
SNARE Protein Structure and Function (2003)

The SNARE superfamily has become, since its discovery approximately a decade ago, the most intensively studied element of the protein machinery involved in intracellular trafficking. Intracellular membrane fusion in eukaryotes requires SNARE (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) proteins that form complexes bridging the two membranes. Although common themes have emerged from structural and functional studies of SNAREs and other components of the eukaryotic membrane fusion machinery, there is still much to learn about how the assembly and activity of this machinery is choreographed in living cells.
音乐彩蝶——科琳·贝利·雷 (2007)

莺歌燕舞,摇滚电音,听得久了,会不会忽然觉得有点索然无味,甚至令你浮躁不安?记得还是大学那会听电台的青乐节目,偶然听到了Norah Jones那舒缓感性的噪音,才知道原来有一种音乐可以让人充分享受铅华洗尽的闲适与安静。喜欢爵士乐带来的那种慵懒沧桑而又玩味深沉的感觉,喜欢爵士歌手们朦胧忧郁地浅吟低唱。当我第一次听Corinne Bailey Rae的成名曲Like A Star时,脑海里马上蹦出一个词——慵懒!不想再赘言赞美她如泉水般舒服自然清澈的噪音,因为于我而言,Corinne最吸引我的就是这种慵懒洒脱的感觉。恬淡不加任何修饰的嗓音,可以让你在一个休闲的周末细细聆听一下午,你阻塞的耳朵将得到彻底冲洗,重新呼吸到音乐的本质。
Determination of the Sequence Alteration in the DNA of the Herpes Simplex Virus Type 1 Temperature-sensitive Mutant ts K (1984)

The alteration in the DNA sequence responsible for the mutant phenotype of the herpes simplex virus type 1 temperature-sensitive mutant ts K has been determined. A single C:G base pair present in the wild-type Vmw 175 immediate-early polypeptide-coding sequence has been replaced by T:A in the mutant gene. This results in the substitution of an alanine by a valine codon. In two revertants the mutant T:A base pair has been resubstituted by C:G.
Ethers and esters derived from apocynin avoid the interaction between p47phox and p22phox subunits of NADPH oxidase: evaluation in vitro and in silico (2013)

NOX (NADPH oxidase) plays an important role during several pathologies because it produces the superoxide anion (O2•-), which reacts with NO (nitric oxide), diminishing its vasodilator effect. Although different isoforms of NOX are expressed in ECs (endothelial cells) of blood vessels, the NOX2 isoform has been considered the principal therapeutic target for vascular diseases because it can be up-regulated by inhibiting the interaction between its p47phox (cytosolic protein) and p22phox (transmembrane protein) subunits. In this research, two ethers, 4-(4-acetyl-2-methoxy-phenoxy)-acetic acid (1) and 4-(4-acetyl-2-methoxy-phenoxy)-butyric acid (2) and two esters, pentanedioic acid mono-(4-acetyl-2-methoxy-phenyl) ester (3) and heptanedioic acid mono-(4-acetyl-2-methoxy-phenyl) ester (4), which are apocynin derivatives were designed, synthesized and evaluated as NOX inhibitors by quantifying O2•- production using EPR (electron paramagnetic resonance) measurements. In addition, the antioxidant activity of apocynin and its derivatives were determined. A docking study was used to identify the interactions between the NOX2's p47phox subunit and apocynin or its derivatives. The results showed that all of the compounds exhibit inhibitory activity on NOX, being 4 the best derivative. However, neither apocynin nor its derivatives were free radical scavengers. On the other hand, the in silico studies demonstrated that the apocynin and its derivatives were recognized by the polybasic SH3A and SH3B domains, which are regions of p47phox that interact with p22phox. Therefore this experimental and theoretical study suggests that compound 4 could prevent the formation of the complex between p47phox and p22phox without needing to be activated by MPO (myeloperoxidase), this being an advantage over apocynin.
Tumor Immunotherapy Using Gene-Modified Human Mesenchymal Stem Cells Loaded into Synthetic Extracellular Matrix Scaffolds (2008)

Mesenchymal stem cells (MSCs) are appealing as gene therapy cell vehicles given their ease of expansion and transduction. However, MSCs exhibit immunomodulatory and proangiogenic properties that may pose a risk in their use in anticancer therapy. For this reason, we looked for a strategy to confine MSCs to a determined location, compatible with a clinical application. Human MSCs genetically modified to express luciferase (MSC(luc)), seeded in a synthetic extracellular matrix (sECM) scaffold (sentinel scaffold) and injected subcutaneously in immunodeficient mice, persisted for more than 40 days, as assessed by bioluminescence imaging in vivo. MSCs modified to express a bispecific alpha-carcinoembryonic antigen (alphaCEA)/alphaCD3 diabody (MSC(dAb)) and seeded in an sECM scaffold (therapeutic scaffolds) supported the release of functional diabody into the bloodstream at detectable levels for at least 6 weeks after implantation. Furthermore, when therapeutic scaffolds were implanted into CEA-positive human colon cancer xenograft-bearing mice and human T lymphocytes were subsequently transferred, circulating alphaCEA/alphaCD3 diabody activated T cells and promoted tumor cell lysis. Reduction of tumor growth in MSC(dAb)-treated mice was statistically significant compared with animals that only received MSC(luc). In summary, we report here for the first time that human MSCs genetically engineered to secrete a bispecific diabody, seeded in an sECM scaffold and implanted in a location distant from the primary tumor, induce an effective antitumor response and tumor regression.
Current Treatment Approaches in Diabetic Macular Edema (2007)

A proper evaluation of the vitreous and retina is fundamental to select the most appropriate treatment approach in DME. While small microaneurysms with focal DME may be treated by conventional focal photocoagulation, diffuse DME which do not respond to grid photocoagulation may benefit from intravitreal injections using triamcinolone acetonide or novel VEGF inhibitors. Eyes with DME and additional vitreous traction may benefit from pars plana vitrectomy without ILM peeling. A combination of laser, pharmacological and surgical treatment modalities may be necessary to maintain central vision in eyes with DME.
Biofilms on Indwelling Urethral Catheters Produce Quorum-Sensing Signal Molecules In Situ and In Vitro (1998)

Acylated homoserine lactones (AHLs) are chemical signals that mediate population density-dependent (quorum-sensing) gene expression in numerous gram-negative bacteria. In this study, gram-negative bacilli isolated from catheters were screened for AHL production by a cross-feeding assay utilizing an AHL-responsive Agrobacterium tumefaciens reporter strain. Positive reactions were obtained from 14 isolates of Pseudomonas aeruginosa; negative or weakly positive reactions were recorded for isolates of five other species. P. aeruginosa biofilms were then produced on catheters in a physical model of the bladder. Sections of colonized all-silicone catheters gave positive reactions for the quorum-sensing signal molecules as did sections that had been cleaned of biofilm and autoclaved. Control sections of unused catheters were negative in the tests. Sections from four of nine catheters that had been freshly removed from patients gave positive reactions for AHLs. Cleaned autoclaved sections of three of these catheters also gave strongly positive reactions for AHLs. These results demonstrate that AHLs are produced by biofilms as they develop on the catheters both in vitro in the model and in vivo in the patient's bladder. They represent the first demonstration of AHL production by biofilms in a clinical setting.
Mitotic degradation of yeast Fkh1 by the Anaphase Promoting Complex is required for normal longevity, genomic stability and stress resistance (2016)

The Saccharomyces cerevisiae Forkhead Box (Fox) orthologs, Forkheads (Fkh) 1 and 2, are conserved transcription factors required for stress response, cell cycle progression and longevity. These yeast proteins play a key role in mitotic progression through activation of the ubiquitin E3 ligase Anaphase Promoting Complex (APC) via transcriptional control. Here, we used genetic and molecular analyses to demonstrate that the APC E3 activity is necessary for mitotic Fkh1 protein degradation and subsequent cell cycle progression. We report that Fkh1 protein degradation occurs specifically during mitosis, requires APCCdc20 and proteasome activity, and that a stable Fkh1 mutant reduces normal chronological lifespan, increases genomic instability, and increases sensitivity to stress. Our data supports a model whereby cell cycle progression through mitosis and G1 requires the targeted degradation of Fkh1 by the APC. This is significant to many fields as these results impact our understanding of the mechanisms underpinning the control of aging and cancer.
Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte implantation for osteochondral defects of the knee (2005)

Autologous chondrocyte implantation (ACI) is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes. We have performed a prospective, randomised comparison of ACI-C and MACI for the treatment of symptomatic chondral defects of the knee in 91 patients, of whom 44 received ACI-C and 47 MACI grafts. Both treatments resulted in improvement of the clinical score after one year. The mean modified Cincinnati knee score increased by 17.6 in the ACI-C group and 19.6 in the MACI group (p = 0.32). Arthroscopic assessments performed after one year showed a good to excellent International Cartilage Repair Society score in 79.2% of ACI-C and 66.6% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in the biopsies of 43.9% of the ACI-C and 36.4% of the MACI grafts after one year. The rate of hypertrophy of the graft was 9% (4 of 44) in the ACI-C group and 6% (3 of 47) in the MACI group. The frequency of re-operation was 9% in each group. We conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI. While MACI is technically attractive, further long-term studies are required before the technique is widely adopted.
Static statistical timing analysis for latch-based pipeline designs (2005)

A latch-based timing analyzer is an essential tool for developing high-speed pipeline designs. As process variations increasingly influence the timing characteristics of DSM designs, a timing analyzer capable of handling process-induced timing variations for latch-based pipeline designs becomes in demand. In this work, we present a static statistical timing analyzer, STAP, for latch-based pipeline designs. Our analyzer propagates statistical worst-case delays as well as critical probabilities across the pipeline stages. We present an efficient method to handle correlations due to re-convergent fanouts. We also demonstrate the impact of not including the analysis of reconvergent fanouts in latch-based pipeline designs. Comparing to a Monte-Carlo based timing analyzer, our experiments show that STAP can accurately evaluate the critical probability that a design violates the timing constraints under a given statistical timing model. The runtime comparison further demonstrates the efficiency of our STAP.
Exosomes Mediate the Cytoprotective Action of Mesenchymal Stromal Cells on Hypoxia-Induced Pulmonary Hypertension (2012)

This study indicates that MEX exert a pleiotropic protective effect on the lung and inhibit pulmonary hypertension through suppression of hyperproliferative pathways, including STAT3-mediated signaling induced by hypoxia.
TiO2 Nanotubes with Open Channels as Deactivation-Resistant Photocatalyst for the Degradation of Volatile Organic Compounds (2016)

We synthesized ordered TiO2 nanotubes (TNT) and compared their photocatalytic activity with that of TiO2 nanoparticles (TNP) film during the repeated cycles of photocatalytic degradation of gaseous toluene and acetaldehyde to test the durability of TNT as an air-purifying photocatalyst. The photocatalytic activity of TNT showed only moderate reduction after the five cycles of toluene degradation, whereas TNP underwent rapid deactivation as the photocatalysis cycles were repeated. Dynamic SIMS analysis showed that carbonaceous deposits were formed on the surface of TNP during the photocatalytic degradation of toluene, which implies that the photocatalyst deactivation should be ascribed to the accumulation of recalcitrant degradation intermediates (carbonaceous residues). In more oxidizing atmosphere (100% O2 under which less carbonaceous residues should form), the photocatalytic activity of TNP still decreased with repeating cycles of toluene degradation, whereas TNT showed no sign of deactivation. Because TNT has a highly ordered open channel structure, O2 molecules can be more easily supplied to the active sites with less mass transfer limitation, which subsequently hinders the accumulation of carbonaceous residues on TNT surface. Contrary to the case of toluene degradation, both TNT and TNP did not exhibit any significant deactivation during the photocatalytic degradation of acetaldehyde, because the generation of recalcitrant intermediates from acetaldehyde degradation is insignificant. The structural characteristics of TNT is highly advantageous in preventing the catalyst deactivation during the photocatalytic degradation of aromatic compounds.
Stereo vision based indoor/outdoor navigation for flying robots (2013)

We introduce our new quadrotor platform for realizing autonomous navigation in unknown indoor/outdoor environments. Autonomous waypoint navigation, obstacle avoidance and flight control is implemented on-board. The system does not require a special environment, artificial markers or an external reference system. We developed a monolithic, mechanically damped perception unit which is equipped with a stereo camera pair, an Inertial Measurement Unit (IMU), two processor-and an FPGA board. Stereo images are processed on the FPGA by the Semi-Global Matching algorithm. Keyframe-based stereo odometry is fused with IMU data compensating for time delays that are induced by the vision pipeline. The system state estimate is used for control and on-board 3D mapping. An operator can set waypoints in the map, while the quadrotor autonomously plans its path avoiding obstacles. We show experiments with the quadrotor flying from inside a building to the outside and vice versa, traversing a window and a door respectively. A video of the experiments is part of this work. To the best of our knowledge, this is the first autonomously flying system with complete on-board processing that performs waypoint navigation with obstacle avoidance in geometrically unconstrained, complex indoor/outdoor environments.
Nanoscale Imaging of Epidermal Growth Factor Receptor Clustering (2009)

The development of some solid tumors is associated with overexpression of the epidermal growth factor receptor (EGFR) and often correlates with poor prognosis. Near field scanning optical microscopy, a technique with subdiffraction-limited optical resolution, was used to examine the influence of two inhibitors (the chimeric 225 antibody and tyrosine phosphorylation inhibitor AG1478) on the nanoscale clustering of EGFR in HeLa cells. The EGFR is organized in small clusters, average diameter of 150 nm, on the plasma membrane for both control and EGF-treated cells. The numbers of receptors in individual clusters vary from as few as one or two proteins to greater than 100. Both inhibitors yield an increased cluster density and an increase in the fraction of clusters with smaller diameters and fewer receptors. Exposure to AG1478 also decreases the fraction of EGFR that colocalizes with both rafts and caveolae. EGF stimulation results in a significant loss of the full-length EGFR from the plasma membrane with the concomitant appearance of low molecular mass proteolytic products. By contrast, AG1478 reduces the level of EGFR degradation. Changes in receptor clustering provide one mechanism for regulating EGFR signaling and are relevant to the design of strategies for therapeutic interventions based on modulating EGFR signaling.
Synthesis and Characterization of Injectable Poly(N-isopropylacrylamide)-Based Hydrogels That Support Tissue Formation in Vitro (1999)

Hydrogels that support tissue formation in vitro were developed using poly(N-isopropylacrylamide) [P(NIPAAm)]. Loosely cross-linked P(NIPAAm) and poly(NIPAAm-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were synthesized with N,N'-methylenebis(acrylamide) cross-linker. At room temperature (RT), the hydrogels were transparent and extremely pliable, while at 37 °C, the matrices became opaque and were significantly more rigid. The P(NIPAAm-co-AAc) hydrogel demonstrated significantly less volume change between RT and 37 °C, contained significantly more water at 37 °C, and had a lower critical solution temperature which was significantly higher, as compared to that of the P(NIPAAm) hydrogel. The hydrogels supported bovine articular chondrocyte viability for at least 28 days of in vitro culture, and cartilage-like tissue was formed in the matrices. These hydrogels can be injected through a small-diameter aperture and offer the benefit of in situ stabilization without the possible deleterious effects of in situ polymerization. Thus, these hydrogels have the potential to be used as injectable scaffolds for tissue engineering applications.
Amygdala–prefrontal dissociation of subliminal and supraliminal fear (2005)

Facial expressions of fear are universally recognized signals of potential threat. Humans may have evolved specialized neural systems for responding to fear in the absence of conscious stimulus detection. We used functional neuroimaging to establish whether the amygdala and the medial prefrontal regions to which it projects are engaged by subliminal fearful faces and whether responses to subliminal fear are distinguished from those to supraliminal fear. We also examined the time course of amygdala-medial prefrontal responses to supraliminal and subliminal fear. Stimuli were fearful and neutral baseline faces, presented under subliminal (16.7 ms and masked) or supraliminal (500 ms) conditions. Skin conductance responses (SCRs) were recorded simultaneously as an objective index of fear perception. SPM2 was used to undertake search region-of-interest (ROI) analyses for the amygdala and medial prefrontal (including anterior cingulate) cortex, and complementary whole-brain analyses. Time series data were extracted from ROIs to examine activity across early versus late phases of the experiment. SCRs and amygdala activity were enhanced in response to both subliminal and supraliminal fear perception. Time series analysis showed a trend toward greater right amygdala responses to subliminal fear, but left-sided responses to supraliminal fear. Cortically, subliminal fear was distinguished by right ventral anterior cingulate activity and supraliminal fear by dorsal anterior cingulate and medial prefrontal activity. Although subcortical amygdala activity was relatively persistent for subliminal fear, supraliminal fear showed more sustained cortical activity. The findings suggest that preverbal processing of fear may occur via a direct rostral-ventral amygdala pathway without the need for conscious surveillance, whereas elaboration of consciously attended signals of fear may rely on higher-order processing within a dorsal cortico-amygdala pathway.
Identification of Novel Inhibitors of the Transforming Growth Factor β1 (TGF-β1) Type 1 Receptor (ALK5) (2002)

Screening of our internal compound collection for inhibitors of the transforming growth factor beta1 (TGF-beta1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3,4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-beta1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay.
A Modified Urokinase Plasminogen Activator Induces Liver Regeneration Without Bleeding (1995)

Direct retrovirus-mediated hepatic gene transfer results in permanent gene expression; however, gene transfer requires surgical hepatectomy (to stimulate cell division) and has been inefficient. We recently used recombinant adenovirus vectors that transiently expressed urokinase from mouse hepatocytes to induce hepatocellular regeneration in place of a partial hepatectomy. The adenovirus method allowed for five-fold more efficient retrovirus transduction in vivo compared to the conventional partial hepatectomy approach. The major problem with the urokinase-mediated hepatic regeneration was the transient secretion of urokinase into the bloodstream that led to hypocoagulation. To circumvent this side-effect, the urokinase protein was modified by adding amino-terminal and carboxy-terminal endoplasmic reticulum retention signals. The recombinant urokinase molecules expressed from adenoviral vectors remained in hepatocytes, were enzymatically active, and resulted in similar rates of hepatic regeneration as found with the secreted urokinase. Modified urokinase-mediated liver regeneration was equally capable of allowing retrovirus-mediated gene transfer in vivo. Thus, the method of direct retrovirus transduction of hepatocytes becomes clinically relevant as the technology becomes safer.
Nucleotide sequence of the transposon Tn7 gene encoding an aminoglycoside-modifying enzyme, 3″(9)-O-nucleotidyltransferase (1985)

The nucleotide sequence of a transposon Tn7 DNA fragment encoding a 3"(9)-O-nucleotidyltransferase, an aminoglycoside-modifying enzyme, which mediates bacterial resistance to spectinomycin and streptomycin, was determined. The aadA structural gene was 786 bases long and predicted a polypeptide of 262 amino acids with a calculated molecular weight of 29,207. Comparison of the DNA sequences of Tn7 and plasmid R538-1 indicated that their aadA genes were nearly identical. Comparison of the polypeptides predicted by the aadA genes of Tn7 and Tn554 indicated that the genes were related.