gebhart/patrepeval huggingface dataset:
Safety, immunogenicity, and transmissibility in humans of CVD 1203, a live oral Shigella flexneri 2a vaccine candidate attenuated by deletions in aroA and virG (1996)

We evaluated the safety and immunogenicity of attenuated Shigella flexneri 2a vaccine candidate CVD 1203, which harbors precise deletions in the plasmid gene virG and in the chromosomal gene aroA. CVD 1203 invades epithelial cells but undergoes minimal intracellular proliferation and cell-to-cell spread. Fasting healthy volunteers, aged 18 to 40 years, were randomly allocated (double-blind design) to receive either CVD 1203 vaccine or placebo, along with sodium bicarbonate buffer, on days 0 and 14, as follows. At the time of the first inoculation, 10 subjects received placebo (group 1) and 22 subjects received either 1.5 x 10(8) (group 2; 11 subjects) or 1.5 x 10(9) (group 3; 11 subjects) CFU of CVD 1203. Fourteen days later, subjects from group 1 received 1.2 x 10(6) CFU of CVD 1203 and subjects from groups 2 and 3 received 1.2 x 10(8) vaccine organisms. Clinical tolerance was dose dependent. After a single dose of CVD 1203 at 10(6), 10(8), or 10(9) CFU, self-limited (<48-h duration) objective reactogenicity (fever, diarrhea, or dysentery) developed in 0, 18, and 72% of subjects, respectively, and in no placebo recipients. CVD 1203 induced immunoglobulin G seroconversion to S. flexneri 2a lipopolysaccharide (LPS) in 30, 45, and 36% of subjects from groups 1, 2, and 3, respectively, and stimulated immunoglobulin A-producing anti-LPS antibody-secreting cells in 60, 91, and 100% of subjects, respectively. After vaccination, significant rises in tumor necrosis factor alpha concentration in serum (groups 1, 2, and 3) and stool (group 2) samples were observed. We conclude that engineered deletions in virG and aroA markedly attenuate wild-type S. flexneri but preserve immunogenicity; however, less reactogenic vaccines are needed.
Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway (2016)

Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance. Furthermore, it was also observed that IL-11 induced STAT3 phosphorylation and increased anti-apoptotic protein Bcl-2 and Survivin expression in cancer cells. The effect could be abrogated by suppressing STAT3 phosphorylation or silencing IL-11Rα expression in cancer cells. In conclusion, chemotherapy-induced IL-11 upregulation in CAF promotes lung adenocarcinoma cell chemoresistance by activating IL-11R/STAT3 anti-apoptotic signaling pathway.
FoldingZero: Protein Folding from Scratch in Hydrophobic-Polar Model (2018)

De novo protein structure prediction from amino acid sequence is one of the most challenging problems in computational biology. As one of the extensively explored mathematical models for protein folding, Hydrophobic-Polar (HP) model enables thorough investigation of protein structure formation and evolution. Although HP model discretizes the conformational space and simplifies the folding energy function, it has been proven to be an NP-complete problem. In this paper, we propose a novel protein folding framework FoldingZero, self-folding a de novo protein 2D HP structure from scratch based on deep reinforcement learning. FoldingZero features the coupled approach of a two-head (policy and value heads) deep convolutional neural network (HPNet) and a regularized Upper Confidence Bounds for Trees (R-UCT). It is trained solely by a reinforcement learning algorithm, which improves HPNet and R-UCT iteratively through iterative policy optimization. Without any supervision and domain knowledge, FoldingZero not only achieves comparable results, but also learns the latent folding knowledge to stabilize the structure. Without exponential computation, FoldingZero shows promising potential to be adopted for real-world protein properties prediction.
Use of Compatible Polymer Blends To Fabricate Arrays of Carbon Black−Polymer Composite Vapor Detectors (1998)

Compatible blends of poly(vinyl acetate) and poly(methyl methacrylate) have been used to produce a series of electrically conducting carbon black composites whose resistance is sensitive to the nature and concentration of an analyte in the vapor phase. The dc electrical resistance response of the composites was found to be a nonlinear function of the mole fraction of poly(vinyl acetate) in the blend. These compatible blend composite detectors provided additional analyte discrimination information relative to a reference detector array that only contained composites formed using the pure polymer phases. The added discrimination power provided by the compatible blend detectors, and thus the added diversity of the enhanced detector array, was quantified through use of a statistical metric to assess the performance of detector arrays in various vapor classification tasks.
Understanding Consequences of Concurrent Therapies (1993)

In 1989, the occurrence of a rare, life-threatening ventricular arrhythmia (torsades de pointes) in an otherwise healthy young woman led alert clinicians at the Naval Hospital in Bethesda, Md, to consider the possibility that the patient's near-fatal arrhythmia was triggered by a drug-drug interaction involving her antihistamine (terfenadine) and her antifungal (ketoconazole) medications.<sup>1</sup>Consulting clinical pharmacologists from the Uniformed Services University of the Health Sciences and the US Food and Drug Administration (FDA) suggested that ketoconazole inhibited the oxidative metabolism of terfenadine. Analysis of blood samples revealed that the patient had high levels of unmetabolized terfenadine, a compound not usually detectable in blood because it is metabolized so quickly. Review of reports to the FDA's spontaneous reporting system revealed that among additional cases of torsades de pointes in patients receiving terfenadine, many were also receiving ketoconazole. This evidence led the FDA to ask Marion Merrill Dow, Kansas City, Mo,
Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair (2006)

Interleukin-6 (IL-6) is an important mediator of liver regeneration and repair that is also elevated in chronic liver diseases, including fatty liver of obesity and cirrhosis. IL-6 has been reported both to delay and accelerate liver regeneration. We examined the effects on liver injury and regeneration of a continuous administration of exogenous IL-6 to mice by injection of an IL-6-expressing CHO-cell line in athymic nude mice and by osmotic mini-pump delivery of recombinant murine IL-6. Short-term IL-6 administration (1-2 days) accelerated early recovery of liver mass, whereas more long-term administration (5-7 days) markedly impaired liver regeneration. Similarly, short-term IL-6 treatment increased hepatic resistance to the lethal effects of the Fas agonist Jo-2, but on more prolonged IL-6 exposure the Jo-2 resistance vanished. IL-6 administration initially induced expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, correlating with protection against Fas-mediated cell death. More prolonged IL-6 administration, however, resulted in marked induction of the pro-apoptotic protein Bax. This result coincided with increased activation of the type II or intrinsic, mitochondrial path to cell death, manifested by increased caspase-9 activation and increased cytochrome c release after Jo-2 exposure. These data demonstrate that IL-6 can function acutely to improve hepatic regeneration and repair, but that more chronic exposure not only abolishes the protective effects of IL-6, but actually sensitizes the liver to injury and death. In conclusion, elevated IL-6 in certain chronic liver diseases contributes to an increased likelihood of liver failure after injury.
In vitro catalysis of oxidative folding of disulfide-bonded proteins by the Escherichia coli dsbA (ppfA) gene product. (1992)

It was shown previously that the Escherichia coli gene ppfA (dsbA) encodes a periplasmic protein, and its inactivation leads to a deficiency in disulfide bond formation of envelope proteins (Kamitani, S., Akiyama, Y., and Ito, K. (1992) EMBO J. 11, 57-62; Bardwell, J. C. A., McGovern, K., and Beckwith, J. (1991) Cell 67, 581-589). The DsbA/PpfA protein was overproduced, purified, and examined for its activities in vitro. Its abundance in a wild-type cell was estimated to be about 850 molecules which probably exist as homodimers as suggested by size exclusion chromatography. Purified DsbA markedly stimulated disulfide bond formation of E. coli alkaline phosphatase, either in vitro synthesized or purified and denatured, as well as of reduced bovine ribonuclease A. The DsbA-catalyzed rapid disulfide bond formation occurred after a lag period which appeared to be determined by the redox state of the reaction mixture and concentration of DsbA. Inclusion of higher concentrations of oxidized glutathione or DsbA shortened the lag period. We propose that DsbA, which proved to directly catalyze disulfide bond formation, may also have a role in maintaining the bacterial periplasm oxidative.
Spray-Layer-by-Layer Assembly Can More Rapidly Produce Optical-Quality Multistack Heterostructures (2011)

Automated spray-layer-by-layer (LbL) assembly was used to create highly reflective structurally colored thin films with high reflectance at near-UV light wavelengths. Reflectance peaks were tuned by fabricating alternating stacks of high (TiO(2) nanoparticles) and low (SiO(2) nanoparticles) refractive index materials using a non-quarter-wave design. Spray-assembled multilayer heterostructures fabricated with up to 840 individual polymer or nanoparticle deposition steps presented similar roughness and refractive index values compared to Bragg stacks obtained via immersion LbL assembly. Such complex multilayer heterostructures, however, could be fabricated in significantly shorter times; the time required to deposit a complete bilayer was only about 90 s, compared to 36 min for the immersion assembly of the same system. Optimization of the experimental parameters was performed to achieve uniform coatings and relatively smooth interfaces and surfaces. We observed that the spraying times of the nanoparticle and polymer solutions are the main parameters that determine the thickness, optical properties, and uniformity of the assembled films. Ellipsometry, atomic force microscopy (AFM), UV-vis spectroscopy, and transmission electron microscopy (TEM) were used to characterize the samples. The nanoparticle thin films were iridescent and presented relatively narrow peaks of high reflectance (∼90%) at visible and near-UV wavelengths of light.
GM-CSF-induced, bone-marrow-derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms (2010)

In our earlier work, we had shown that GM-CSF treatment of CBA/J mice can suppress ongoing thyroiditis by inducing tolerogenic CD8α(-) DCs, which helped expand and/or induce CD4(+)Foxp3(+) Tregs. To identify the primary cell type that was affected by the GM-CSF treatment and understand the mechanism by which Tregs were induced, we compared the effect of GM-CSF on matured spDCs and BMDC precursors in vitro. Matured spDCs exposed to GM-CSF ex vivo induced only a modest increase in the percentage of Foxp3-expressing T cells in cocultures. In contrast, BM cells, when cultured in the presence of GM-CSF, gave rise to a population of CD11c(+)CD11b(Hi)CD8α(-) DCs (BMDCs), which were able to expand Foxp3(+) Tregs upon coculture with CD4(+) T cells. This contact-dependent expansion occurred in the absence of TCR stimulation and was abrogated by OX40L blockage. Additionally, the BMDCs secreted high levels of TGF-β, which was required and sufficient for adaptive differentiation of T cells to Foxp3(+) Tregs, only upon TCR stimulation. These results strongly suggest that the BMDCs differentiated by GM-CSF can expand nTregs and induce adaptive Tregs through different mechanisms.
Crotonase Catalysis Enables Flexible Production of Functionalized Prolines and Carbapenams (2011)

The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5-carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl-coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5-carboxymethyl-prolines were converted into the corresponding bicyclic β-lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic β-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers.
Bandwidth, SAR, and Efficiency of Internal Mobile Phone Antennas (2004)

This paper presents a thorough investigation into the effects of several phone chassis-related parameters-length, width, thickness, and distance between the head and phone-on the bandwidth, efficiency, and specific absorption rate (SAR) characteristics of internal mobile phone antennas. The studied antenna-chassis combinations are located beside an anatomical head model in a position of actual handset use. The effect of the user's hand is also studied with two different hand models. The main part of the study is based on FDTD simulations, but also experimental results, which support the computationally obtained conclusions, are given. The presented analysis provides novel and useful information for future design of mobile handset antennas. The results show the general trends of bandwidth, SAR, and efficiency with different chassis parameters. The results also reveal a connection between these three performance parameters: an increase in SARs and a decrease in radiation efficiency occur compared to the general trend when the bandwidth reaches its maximum. This happens when the resonant frequency of the chassis equals that of the antenna.
Improving grid behaviour (1999)

In this paper, the author describes how the inglorious Summer-of-1996 blackouts taught the Western USA to improve emergency grid control and protection and to sharpen power network simulation techniques.
Quantifying Turfgrass Color Using Digital Image Analysis (2003)

Color is a major component of the aesthetic quality of turf and often evaluated in field studies. Digital image analysis may be an improved, objective method to quantify turf color. Studies were conducted to determine if digital image analysis with SigmaScan software (SPSS, Chicago, IL) was capable of: (i) accurately determining the hue, saturation, and brightness (HSB) levels of Munsell Plant Tissue color chips, (ii) quantifying visual color differences among zoysiagrass ( Zoysia japonica Steud.) and creeping bentgrass { Agrostis palustris Huds. [= A. stolonifera var. palustris (Huds.) Farw.]} plots receiving various N treatments, and (iii) quantifying genetic color differences among bermudagrass ( Cynodon spp.) cultivars. Digital images of turf plots were analyzed with SigmaScan software to determine average HSB levels for each image. A dark green color index (DGCI) was created from HSB values for direct comparison with visual ratings. Digital image analysis accurately quantified the HSB levels ( r 2 = 0.99, 0.96, and 0.97, respectively) of Munsell color chips corresponding to turf colors. Significant HSB differences were present among N treatments in creeping bentgrass, while only significant hue differences existed in zoysiagrass. Significant hue and saturation differences were present among bermudagrass cultivars. There was strong agreement between DGCI values and visual ratings. The relative variances of the HSB and DGCI were significantly less than the variance associated with multiple raters. This evaluation technique may facilitate objective comparisons of turf color across researchers, locations, and years when images are collected under equal lighting conditions (i.e., the use of an artificial light source at night or in an enclosed system).
LC/ESI‐MS/MS characterisation of lipopeptide biosurfactants produced by the Bacillus licheniformis V9T14 strain (2010)

Lipopeptide biosurfactants produced by the Bacillus licheniformis V9T14 strain showed an interesting anti-adhesion activity against biofilm formation of human pathogenic bacterial strains. The chemical characterisation of the crude extract of V9T14 strain was first developed through electrospray ionisation mass spectrometry (ESI-MS) and ESI-MS/MS direct infusions: two sets of molecular ion species belonging to the fengycin and surfactin families were revealed and their structures defined, interpreting their product ion spectra. The LC/ESI-MS analysis of the crude extract allowed to separate in different chromatogram ranges the homologues and the isoforms of the two lipopeptide families. The extract was then fractionated by silica gel chromatography in two main fractions, I and II. The purified biosurfactants were analysed through a new, rapid and suitable LC/ESI-MS/MS method, which allowed characterising the composition and the structures of the produced lipopeptides. LC/ESI-MS/MS analysis of fraction I showed the presence of C(13), C(14) and C(15) surfactin homologues, whose structures were confirmed by the product ion spectra of the sodiated molecules [M + Na](+) at m/z 1030, 1044 and 1058. LC/ESI-MS/MS analysis of fraction II confirmed the presence of two main fengycin isoforms, with the protonated molecules [M + H](+) at m/z 1478 and 1506 corresponding to C(17) fengycin A and C(17) fengycin B, respectively. Other homologues (C(14) to C(16)) were revealed and confirmed as belonging to fengycin A or B according to the retention times and the product ions generated, although with the same nominal mass. Finally, a relative percentage content of each homologue for both lipopeptides families in the whole extract was proposed.
Accuracy of reflectance photoplethysmography on detecting cuff-induced vascular occlusions (2015)

Photoplethysmography (PPG) is a noninvasive optical technique, which can also be used to derive important parameters other than arterial oxygen saturation (SpO2). In this work, the accuracy of the technique on detecting changes in blood perfusion during different levels of vascular occlusions has been explored. A dual-wavelength, reflectance PPG probe was applied on the left forearm of 10 healthy volunteers and raw PPG signals were acquired by a research PPG processing system. The raw PPG signals were separated into pulsatile AC and continuous DC PPG components. The signals were used to estimate SpO2 and changes in concentration of oxygenated, deoxygenated, and total haemoglobin. Different levels of occlusions, from 20 mmHg to total occlusion were induced by a pressure-cuff on the left arm. The system was able to indicate all the occlusions. In particular, the haemoglobin concentration changes estimated from PPG were in high agreement with Near Infrared Spectroscopy measurements.
KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78 (2015)

Recent advances in genome and transcriptome analysis have contributed to the identification of many potential cancer-related genes. Furthermore, biological and clinical investigations of the candidate genes provide us with a better understanding of carcinogenesis and development of cancer treatment. Here, we report a novel role of KIAA1324 as a tumor suppressor in gastric cancer. We observed that KIAA1324 was downregulated in most gastric cancers from transcriptome sequencing data and found that histone deacetylase was involved in the suppression of KIAA1324. Low KIAA1324 levels were associated with poor prognosis in gastric cancer patients. In the xenograft model, KIAA1324 significantly reduced tumor formation of gastric cancer cells and decreased development of preformed tumors. KIAA1324 also suppressed proliferation, invasion, and drug resistance and induced apoptosis in gastric cancer cells. Through protein interaction analysis, we identified GRP78 (glucose-regulated protein 78 kDa) as a KIAA1324-binding partner. KIAA1324 blocked oncogenic activities of GRP78 by inhibiting GRP78-caspase-7 interaction and suppressing GRP78-mediated AKT activation, thereby inducing apoptosis. In conclusion, our study reveals a tumor suppressive role of KIAA1324 via inhibition of GRP78 oncoprotein activities and provides new insight into the diagnosis and treatment of gastric cancer.
Purification of a putative precursor of globin messenger RNA from mouse nucleated erythroid cells. (1977)

Nucleated erythroid cells were incubated for 10 min in the presence of [5-3H]uridine, and the total RNA was isolated by three different extraction procedures. RNA containing globin messenger RNA sequences was purified from other cellular RNAs by selective hybridization to globin complementary DNA cellulose. Depending upon the extraction procedure employed, 0.4-0.6% of the radioactively-labeled total cellular RNA applied to the column annealed to globin complementary DNA cellulose. The annealed RNA was treated with formaldehyde and analyzed by formaldehyde/polyacrylamide gel electrophoresis. Mature globin mRNA and an RNA migrating at approximately 15 S were observed. No globin mRNA containing sequences larger than 20 S were present. The 15S RNA was partially resolved from mature globin mRNA by neutral sucrose density gradient centrifugation. The RNA isolated from the heavy region of this gradient migrated as 15 S in the formaldehyde/polyacrylamide gels and retained its ability to quantitatively anneal to globin complementary DNA cellulose. On the basis of these observations, we conclude that nucleated erythroid cells obtained from the spleens of anemic mice have a 15S RNA which contains globin mRNA sequences. The 15S RNA is not an aggregate and is a good candidate for a globin mRNA precursor.