gebhart/patrepeval huggingface dataset:
Establishment of New Transmissible and Drug-Sensitive Human Immunodeficiency Virus Type 1 Wild Types due to Transmission of Nucleoside Analogue-Resistant Virus (2001)

Sequence analysis of human immunodeficiency virus type 1 (HIV-1) from 74 persons with acute infections identified eight strains with mutations in the reverse transcriptase (RT) gene at positions 41, 67, 68, 70, 215, and 219 associated with resistance to the nucleoside analogue zidovudine (AZT). Follow-up of the fate of these resistant HIV-1 strains in four newly infected individuals revealed that they were readily replaced by sensitive strains. The RT of the resistant viruses changed at amino acid 215 from tyrosine (Y) to aspartic acid (D) or serine (S), with asparagine (N) as a transient intermediate, indicating the establishment of new wild types. When we introduced these mutations and the original threonine (T)-containing wild type into infectious molecular clones and assessed their competitive advantage in vitro, the order of fitness was in accord with the in vivo observations: 215Y < 215D = 215S = 215T. As detected by real-time nucleic acid sequence-based amplification with two molecular beacons, the addition of AZT or stavudine (d4T) to the viral cultures favored the 215Y mutant in a dose-dependent manner. Our results illustrate that infection with nucleoside analogue-resistant HIV leads in newly infected individuals to mutants that are sensitive to nucleoside analogues, but only a single mutation removed from drug-resistant HIV. Such mutants were shown to be transmissible, stable, and prone to rapid selection for resistance to AZT or d4T as soon as antiretroviral therapy was administered. Monitoring of patients for the presence of new HIV-1 wild types with D, S, or N residues at position 215 may be warranted in order to estimate the threat to long-term efficacy of regimens including nucleoside analogues.
New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control (2004)

The expression of certain genes involved in fundamental metabolism is regulated by metabolite-binding "riboswitch" elements embedded within their corresponding mRNAs. We have identified at least six additional elements within the Bacillus subtilis genome that exhibit characteristics of riboswitch function (glmS, gcvT, ydaO/yuaA, ykkC/yxkD, ykoK, and yybP/ykoY). These motifs exhibit extensive sequence and secondary-structure conservation among many bacterial species and occur upstream of related genes. The element located upstream of the glmS gene in Gram-positive organisms functions as a metabolite-dependent ribozyme that responds to glucosamine-6-phosphate. Other motifs form complex folded structures when transcribed as RNA molecules and carry intrinsic terminator structures. These findings indicate that riboswitches serve as a major genetic regulatory mechanism for the control of metabolic genes in many microbial species.
Hypothesis: microtubules, a key to Alzheimer disease. (1989)

Alzheimer disease (AD) is a clinicopathologic syndrome of unknown etiology with numerous abnormalities in neuronal and nonneuronal cells. A review of the literature suggests that a common basic intracellular defect may underlie many of the reported abnormalities. We hypothesize impairment of the microtubule (MT) system as one explanation for the pathogenesis of AD. Evidence in support of the hypothesis includes the following: MTs are ubiquitous and vital cell components, unequally distributed, with the highest concentration in the brain; various abnormalities, including the key neuropathologic lesions, can be explained by impairments of the MT system; and experiments utilizing pharmacologic agents known to disrupt MTs have reproduced certain abnormalities observed in AD. The hypothesis provides a framework for systematic investigations of MTs at the cellular and molecular levels as well as the basis for in vivo diagnostic tests for AD.
Ion-beam-assisted deposition of nonhydrogenated a-Si:C films (1996)

Amorphous silicon carbide (a-Si:C) films were prepared by low-energy ion-beam-assisted deposition (IBAD) in an attempt to remove structural defects in the "lattice" and improve the electrical characteristics of the film. The ion beam was generated by electron cyclotron resonance from an ultra-high-purity argon plasma. The deposition environment was first evacuated to a very high vacuum to eliminate all but trace amounts of water vapour and other gases so that improvements in the electrical and (or) structural properties of the film would be attributable to the influence of the densification by ion bombardment and not to contaminants. The IBAD process does improve the film characteristics by reducing the density of localized states at the Fermi level and the porosity of the film. However, even though these films have the best electrical characteristics obtained thus far for these kind of films, none of them exhibited device quality and none were observed to be photoconducting. A large density (≈1 at.%) of implanted argon atoms may be limiting the reduction in the defect density that might otherwise be achievable.
ERYTHROPOIETIN ATTENUATES THE TISSUE INJURY ASSOCIATED WITH HEMORRHAGIC SHOCK AND MYOCARDIAL ISCHEMIA (2004)

Here we investigate the effects of erythropoietin (EPO) on the tissue/organ injury caused by hemorrhagic shock (HS), endotoxic shock, and regional myocardial ischemia and reperfusion in anesthetized rats. Male Wistar rats were anesthetized with thiopental sodium (85 mg/kg i.p.) and subjected to hemorrhagic shock (HS; i.e., mean arterial blood pressure reduced to 45 mmHg for 90 min, followed by resuscitation with shed blood for 4 h), endotoxemia (for 6 h), or left anterior descending coronary artery occlusion (25 min) and reperfusion (2 h). HS and endotoxemia resulted in renal dysfunction and liver injury. Administration of EPO (300 IU/kg i.v., n = 10) before resuscitation abolished the renal dysfunction and liver injury in hemorrhagic, but not endotoxic, shock. HS also resulted in significant increases in the kidney of the activities of caspases 3, 8, and 9. This increase in caspase activity was not seen in HS rats treated with EPO. In cultured human proximal tubule cells, EPO concentration-dependently reduced the cell death and increase in caspase-3 activity caused by either ATP depletion (simulated ischemia) or hydrogen peroxide (oxidative stress). In the heart, administration of EPO (300 IU/kg i.v., n = 10) before reperfusion also caused a significant reduction in infarct size. In cultured rat cardiac myoblasts (H9C2 cells), EPO also reduced the increase in DNA fragmentation caused by either serum deprivation (simulated ischemia) or hydrogen peroxide (oxidative stress). We propose that the acute administration of EPO on reperfusion and/or resuscitation will reduce the tissue injury caused by ischemia-reperfusion of the heart (and other organs) and hemorrhagic shock.
Transmitter Architectures Based on Near-Field Direct Antenna Modulation (2008)

A near-field direct antenna modulation (NFDAM) technique is introduced, where the radiated far-field signal is modulated by time-varying changes in the antenna near-field electromagnetic (EM) boundary conditions. This enables the transmitter to send data in a direction-dependent fashion producing a secure communication link. Near-field direct antenna modulation (NFDAM) can be performed by using either switches or varactors. Two fully-integrated proof-of-concept NFDAM transmitters operating at 60 GHz using switches and varactors are demonstrated in silicon proving the feasibility of this approach.
High KIF18A expression correlates with unfavorable prognosis in primary hepatocellular carcinoma (2014)

This study aimed to investigate KIF18A expression in hepatocellular carcinoma (HCC) and to determine the possibility of KIF18A expression being a biomarker in HCC diagnosis or being an independent predictor of disease-free survival (DFS) and overall survival (OS) in HCC patients underwent surgical resection. KIF18AmRNA was detected in 216 cases of HCC tissues by quantitative real-time PCR (qRT-PCR) and in 20 cases of HCC tissues by semi-quantitative RT-PCR. KIF18A protein was determined in 32 cases of HCC tissues by immunohistochemistry (IHC). The survival probability was analyzed by Kaplan-Meier method, and survival curves between groups were obtained by using the log-rank test. Independent predictors associated with DFS were analyzed with Stepwise Cox proportional hazard models. High KIF18A mRNA level was detected in 154 out of 216 (71.3%) cases of HCC. The positive rate of KIF18A expression was significantly higher in liver cancer tissues than that in adjacent normal liver tissues (ANLT) from HCC patients [65.6% (21 of 32) vs. 25.0% (8 of 32), P=0.001]. The KIF18A expression level had positive relevance to the alpha-fetoprotein (AFP) (≥ 200 ng/ml), tumor size (≥ 5 cm), clinical tumor-node-metastasis (TNM) stage and portal vein tumor thrombus (PVTT) in HCC (all P <0.05). A survival analysis indicated that HCC patients with higher KIF18A expression had a significantly shorter DFS and OS after resection. A multivariate analysis suggested that KIF18A upregualtion was an independent factor for DFS [hazard risk (HR)=1.602; 95% confidence interval (CI), 1.029-2.579; P=0.031] and OS (HR=1.682; 95% CI, 1.089-2.600; P=0.019). KIF18A might be a biomarker for HCC diagnosis and an independent predictor of DFS and OS after surgical resection.
The Thy Pol-2 intein of Thermococcus hydrothermalis is an isoschizomer of PI-TliI and PI-TfuII endonucleases (2000)

THY Pol-2 intein, from Thermococcus hydrothermalis, belongs to the same allelic family as TLI Pol-2 (PI-TLII), Tfu Pol-2 (PI-TFUII) and TspTY Pol-3 mini-intein, all inserted at the pol-c site of archaeal DNA polymerase genes. This new intein was cloned, expressed in Escherichia coli and purified. The intein is a specific endonuclease (PI-THY:I) which cleaves the inteinless sequence of the THY DNA pol gene. Moreover, PI-TLII, PI-TFUII and PI-THYI are very similar endonucleases which cleave DNA in the same optimal conditions at 70 degrees C yielding similar 3'-hydroxyl overhangs of 4 bp and the reaction is subject to product inhibition. The three enzymes are able to cleave the three DNA sequences spanning the pol-c site and a 24 bp consensus cleavage site was defined for the three isoschizomers. However, the exact size of the minimal cleavage site depends both on the substrate sequence and the endonuclease. The inability of the isoschizomers to cleave the inteinless DNA polymerase gene from Pyrococcus spp. KOD is due to point substitutions on the 5' side of the pol-c site, suggesting that the absence of inteins of this allelic family in DNA polymerase genes from Pyrococcus spp. can be linked to small differences in the target site sequence.
THE MICROBIAL CONTRIBUTION TO HUMAN FAECAL MASS (1980)

A method has been developed, based on techniques used for isolating bacteria from the rumen, that enables human faeces to be fractionated into three major components. The method requires repeated, vigorous agitation of a suspension of faecal solids with detergent, the use of a stomacher, and high-speed centrifugation. By this means the faecal microflora are separated from faecal dietary-fibre residues. These two components, with water-soluble material in the stool, comprise 98.3 +/- 0.9% of faecal solids. The purity of the microbial fraction was demonstrated by Gram and plant stains and by scanning electron microscopy. Microscopic counts of the bacteria in each fraction of the stool showed that the microbial fraction contained 95% of the total bacteria. Chemical analysis of the component sugars indicated 6-7% possible contamination by non-bacterial polysaccharides. The bacterial pellet was 6% nitrogen, and accounted for 60% of the total faecal nitrogen. When faeces from nine healthy subjects on a metabolically controlled British-type diet were studied, bacteria comprised 54.7 +/- 1.7% of the total solids, fibre 16.7 +/- 0.8% and soluble material 24.0 +/- 1.3%. Bacteria therefore represent a much larger proportion of the faecal mass than was previously thought.
Characterization of primary T cell subsets mediating rejection of pancreatic islet grafts. (1989)

The cellular mechanisms by which pancreatic islet grafts are rejected have not been clearly defined. In order to address the roles of CD4+ and CD8+ T cells in pancreatic islet rejection, we used an adoptive transfer model in which H-2b nude mice were reconstituted with negatively selected H-2b CD4+ or CD8+ T cell subpopulations and engrafted with fully allogeneic pancreatic islet grafts. We found that primary (unprimed) CD4+ T cells mediated the rejection of pancreatic islet grafts, whereas, primary CD8+ T cells failed to do so, even though both T cell subpopulations were competent to reject skin allografts. These data indicate that primary CD4+ T cells are necessary for rejection of allogeneic pancreatic islet grafts, whereas primary CD8+ T lymphocytes are not. Implications concerning the nature of the APC involved in the initiation of the rejection response to islet allografts and the expression of MHC Ag by pancreatic islet cells are discussed.
P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro (1997)

To identify novel inhibitors of transcriptional activation by the HIV Tat protein, we used a combination of in vitro and in vivo Tat-dependent transcription assays to screen >100,000 compounds. All compounds identified blocked Tat-dependent stimulation of transcriptional elongation. Analysis of a panel of structurally diverse inhibitors indicated that their target is the human homolog of Drosophila positive transcription elongation factor b (P-TEFb). Loss of Tat transactivation in extracts depleted of the kinase subunit of human P-TEFb, PITALRE, was reversed by addition of partially purified human P-TEFb. Transfection experiments with wild-type or kinase knockout PITALRE demonstrated that P-TEFb is required for Tat function. Our results suggest that P-TEFb represents an attractive target for the development of novel HIV therapeutics.
Enzyme-catalyzed processes in organic solvents. (1985)

Three different lipases (porcine pancreatic, yeast, and mold) can vigorously act as catalysts in a number of nearly anhydrous organic solvents. Various transesterification reactions catalyzed by porcine pancreatic lipase in hexane obey Michaelis-Menten kinetics. The dependence of the catalytic activity of the enzyme in organic media on the pH of the aqueous solution from which it was recovered is bell-shaped, with the maximum coinciding with the pH optimum of the enzymatic activity in water. The catalytic power exhibited by the lipases in organic solvents is comparable to that displayed in water. In addition to transesterification, lipases can catalyze several other processes in organic media including esterification, aminolysis, acyl exchange, thiotransesterification, and oximolysis; some of these reactions proceed to an appreciable extent only in nonaqueous solvents.
Amplification of Nucleic Acids by Polymerase Chain Reaction (PCR) and Other Methods and their Applications (1991)

The in vitro replication of DNA, principally using the polymerase chain reaction (PCR), permits the amplification of defined sequences of DNA. By exponentially amplifying a target sequence, PCR significantly enhances the probability of detecting target gene sequences in complex mixtures of DNA. It also facilitates the cloning and sequencing of genes. Amplification of DNA by PCR and other newly developed methods has been applied in many areas of biological research, including molecular biology, biotechnology, and medicine, permitting studies that were not possible before. Nucleic acid amplification has added a new and revolutionary dimension to molecular biology. This review examines PCR and other in vitro nucleic acid amplification methodologies--examining the critical parameters and variations and their widespread applications--giving the strengths and limitations of these methodologies.
Long-Term Outcomes of Urgency-Frequency Syndrome Due to Painful Bladder Syndrome Treated With Sacral Neuromodulation and Analysis of Failures (2009)

These patients appear to respond best to permanent quadripolar lead placement but long-term results do not appear to be independently affected by the method of test stimulation. Loss of benefit over time is not common.
Plinabulin, a Novel Small Molecule That Ameliorates Chemotherapy-Induced Neutropenia, Is Administered on the Same Day of Chemotherapy and Has Anticancer Efficacy (2016)

Abstract Plinabulin is a small molecule with tumor-inhibiting and immune-enhancing effects. Plinabulin induces dendritic cell maturation and cytokines interleukin-1β (IL-1β), IL-6, and IL-12 production, all of which are important in neutrophil survival. In preclinical studies, plinabulin prevented docetaxel- or cyclophosphamide-induced neutropenia via a mechanism of action different from that of granulocyte colony-stimulating factor (G-CSF) analogues. In phase 1 and 2 solid tumor trials of plinabulin, which included &gt;140 patients, routine safety laboratory assessments revealed an unexpected protective effect against neutropenia. In the phase 2 clinical trial, patients were randomized to receive docetaxel 75 mg/m2 alone (n=73) or docetaxel 75 mg/m2 followed by plinabulin (NPI-2358-101) at 30 mg/m2 (n=50) or at 20 mg/m2 (n=40), repeated every 3 weeks (clinicaltrials.gov NCT00630110). Plinabulin was given by a 30-minute intravenous (IV) infusion, starting 1 hour after administration of docetaxel. The primary efficacy endpoint was median overall survival. Secondary endpoints included safety assessments, such as complete blood count measurements, on Days 1, 8, and 15 of each cycle. Compared to docetaxel treatment alone, the addition of plinabulin to docetaxel significantly (p&lt;0.0003) reduced the proportion of patients with grade 4 neutropenia from 33.3% to 4.6% in Cycle 1. The figure shows the proportions of patients with grade 4 neutropenia (absolute neutrophil count [ANC] &lt;0.5x109/L) on Day 8, the approximate day after docetaxel administration corresponding to the largest reduction in neutrophil count (Blackwell Ann Oncol 2015). Plinabulin also reduced the clinical sequelae associated with docetaxel-induced neutropenia (sepsis, infections, hospitalizations, need for docetaxel dose reduction, and G-CSF use). Bone pain was reported in 4% of patients receiving plinabulin. Plinabulin had a favorable safety profile; the most prominent finding was grade 3 transient hypertension in 20% and 5% of patients receiving 30 mg/m2 and 20 mg/m2 plinabulin, respectively. Docetaxel (n=65) vs plinabulin 20 mg/m2 (n=39): p = 0.00026 Docetaxel (n=65) vs plinabulin 30 mg/m2 (n=47): p = 0.00018 Plinabulin 20 mg/m2 (n=39) vs plinabulin 30 mg/m2 (n=47): p = 0.68 Plinabulin is a novel small molecule that is being developed for the mitigation of chemotherapy-induced neutropenia. Administered by IV infusion on the same day of (approximately 1 h after) chemotherapy, plinabulin will be given in a single dose of 20 mg/m2 per cycle. Plinabulin has the potential to be an effective, safe (with much less bone pain), cost-effective, and convenient alternative to G-CSF for the prevention of chemotherapy-induced neutropenia. Figure Figure. Disclosures Blayney: BeyondSpring: Other: Travel and lodging to develop clinical trial protocol. Lloyd:BeyondSpring: Consultancy. Huang:BeyondSpring: Employment. Mohanlal:BeyondSpring: Employment.
Toxicity and management in CAR T-cell therapy (2016)

T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. However, CAR T cells also have the capacity to elicit expected and unexpected toxicities including: cytokine release syndrome, neurologic toxicity, "on target/off tumor" recognition, and anaphylaxis. Theoretical toxicities including clonal expansion secondary to insertional oncogenesis, graft versus host disease, and off-target antigen recognition have not been clinically evident. Abrogating toxicity has become a critical step in the successful application of this emerging technology. To this end, we review the reported and theoretical toxicities of CAR T cells and their management.
Continuous Positive Airway Pressure via the Boussignac System Immediately after Extubation Improves Lung Function in Morbidly Obese Patients with Obstructive Sleep Apnea Undergoing Laparoscopic Bariatric Surgery (2009)

Administration of continuous positive airway pressure immediately after extubation maintains spirometric lung function at 24 h after laparoscopic bariatric surgery better than continuous positive airway pressure started in the postanesthesia care unit.
Akt-Dependent Phosphorylation Specifically Regulates Cot Induction of NF-κB-Dependent Transcription (2002)

The Akt (or protein kinase B) and Cot (or Tpl-2) serine/threonine kinases are associated with cellular transformation. These kinases have also been implicated in the induction of NF-kappa B-dependent transcription. As a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, Cot can also activate MAP kinase signaling pathways that target AP-1 and NFAT family transcription factors. Here we show that Akt and Cot physically associate and functionally cooperate. Akt appears to function upstream of Cot, as Akt can enhance Cot induction of NF-kappa B-dependent transcription, and dominant-negative Cot blocks the activation of this element by Akt. Furthermore, deletion analysis shows that binding to Akt is critical for Cot function. The regulation of NF-kappa B-dependent transcription by Cot requires Akt-dependent phosphorylation of serine 400 (S400), near the carboxy terminus of Cot. However, phosphorylation at this site is not required for Cot kinase activity or AP-1 induction, suggesting it specifically regulates Cot effector function at the level of the NF-kappa B pathway. Mutation of S400 in Cot does indeed abolish its ability to activate I kappa B-kinase (IKK) complexes, but paradoxically it allows for increased Cot association with the IKK complex. This mutated form of Cot also acts as a dominant negative for T-cell antigen receptor/CD28- or Akt/phorbol myristate acetate-induced NF-kappa B induction, while having relatively little effect on tumor necrosis factor induction of NF-kappa B. These findings suggest that the activation of different signaling pathways by MAP3Ks may be regulated separately and may provide evidence for how such discrimination by one member of this kinase family occurs.
Advances in Skin Regeneration Using Tissue Engineering (2017)

Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application.
Realtime Data Processing at Facebook (2016)

Realtime data processing powers many use cases at Facebook, including realtime reporting of the aggregated, anonymized voice of Facebook users, analytics for mobile applications, and insights for Facebook page administrators. Many companies have developed their own systems; we have a realtime data processing ecosystem at Facebook that handles hundreds of Gigabytes per second across hundreds of data pipelines.