gebhart/patrepeval huggingface dataset:
Antiplatelet Agents Based on Cyclooxygenase Inhibition without Ulcerogenesis. Evaluation and Synthesis of 4,5-Bis(4-methoxyphenyl)-2-substituted-thiazoles (1994)

The syntheses, biological evaluations, and structure-activity relationships of a series of 4,5-bis-(4-methoxyphenyl)-2-substituted-thiazoles as potent antiplatelet agents with vasodilatory activity are described. 2-Guanidino-4,5-bis(4-methoxyphenyl)thiazole (3), designed from two parent compounds (itazigrel and timegadine), showed inhibitory activity of malondialdehyde (MDA, IC50 = 31 microM) production which is formed from the cyclooxygenase (CO)-catalyzed oxygenation of arachidonic acid in the synthesis of prostanoids in platelets, with vasodilatory activity (ED50 = 2.0 microM). Further structure-activity relationship studies on 3 culminated in the preparation of 4,5-bis(4-methoxyphenyl)-2-[(1-methylpiperazin-4-yl)carbonyl]thiaz ole (10a, FR122047) which exhibited potent inhibitory activity on MDA synthesis in vitro (IC50 = 0.088 microM) and platelet aggregation in guinea pigs ex vivo (100% inhibition even 6 h after 1.0 mg/kg administration) with vasodilatory activity in vitro (ED50 = 6.2 microM). Moreover, 10a demonstrated no ulcerogenesis effect in rats even at 100 mg/kg dosage (safety margin in rats is more than 70 while that of aspirin is only 1.2) in spite of its potent CO inhibition (IC50 = 0.43 microM14), while the use of aspirin, a CO inhibitor and the most popular thromboembolic drug, is restricted by the side effect. Pharmacokinetic studies on 10a have revealed that 10a is detectable in platelet-rich plasma but not in platelet-poor plasma 1 day after oral administration, which indicates that 10a tends to be localized in platelets. This property could be responsible for its low toxicity and reduction of side effects in clinical studies.
Protocol for Nearly Full-Length Sequencing of HIV-1 RNA from Plasma (2008)

Nearly full-length genome sequencing of HIV-1 using peripheral blood mononuclear cells (PBMC) DNA as a template for PCR is now a relatively routine laboratory procedure. However, this has not been the case when using virion RNA as the template and this has made full genome analysis of circulating viruses difficult. Therefore, a well-developed procedure for sequencing of full-length HIV-1 RNA directly from plasma was needed. Plasma from U.S. donors representing a range of viral loads (VL) was used to develop the assay. RNA was extracted from plasma and reverse-transcribed. Two or three overlapping regions were PCR amplified to cover the entire viral genome and sequenced for verification. The success of the procedure was sensitive to VL but was routinely successful for VL greater than 10(5) and the rate declined in proportion to the VL. While the two-amplicon strategy had an advantage of increasing the possibility of amplifying a single species of HIV-1, the three-amplicon strategy was more successful in amplifying samples with low viral loads. This protocol provides a useful tool for molecular analysis to understand the HIV epidemic and pathogenesis, as well as diagnosis, therapy and future vaccine strategies.
Two key polymorphisms in a newly discovered allele of theVitis vinifera TPS24gene are responsible for the production of the rotundone precursor α-guaiene (2015)

Rotundone was initially identified as a grape-derived compound responsible for the peppery aroma of Shiraz wine varieties. It has subsequently been found in black and white pepper and several other spices. Because of its potent aroma, the molecular basis for rotundone formation is of particular relevance to grape and wine scientists and industry. We have identified and functionally characterized in planta a sesquiterpene synthase, VvGuaS, from developing grape berries, and have demonstrated that it produces the precursor of rotundone, α-guaiene, as its main product. The VvGuaS enzyme is a novel allele of the sesquiterpene synthase gene, VvTPS24, which has previously been reported to encode VvPNSeInt, an enzyme that produces a variety of selinene-type sesquiterpenes. This newly discovered VvTPS24 allele encodes an enzyme 99.5% identical to VvPNSeInt, with the differences comprising just 6 out of the 561 amino acid residues. Molecular modelling of the enzymes revealed that two of these residues, T414 and V530, are located in the active site of VvGuaS within 4 Å of the binding-site of the substrate, farnesyl pyrophosphate. Mutation of these two residues of VvGuaS into the corresponding polymorphisms in VvPNSeInt results in a complete functional conversion of one enzyme into the other, while mutation of each residue individually produces an intermediate change in the product profile. We have therefore demonstrated that VvGuaS, an enzyme responsible for production of the rotundone precursor, α-guaiene, is encoded by a novel allele of the previously characterized grapevine gene VvTPS24 and that two specific polymorphisms are responsible for functional differences between VvTPS24 alleles.
Secure Remote Access with L2TP (2000)

L2TP protocol is a virtual extension of PPP across IP network infrastructure. L2TP makes possible for an access concentrator (LAC) to be near remote clients, while allowing PPP termination server (LNS) to be located in enterprise premises. L2TP allows an enterprise to retain control of RADIUS data base, which is used to control Authentication, Authorization and Accountability (AAA) of dial-in users. The objective of this document is to extend security characteristics of IPsec to remote access users, as they dial-in through the Internet. This is accomplished without creating new protocols and using the existing practices of Remote Access and IPsec. Specifically, the document proposes three new RADIUS parameters for use by the LNS node, acting as Secure Remote Access Server (SRAS) to mandate network level security between remote clients and the enterprise. The document also discusses limitations of the approach.
Impaired Glucose Tolerance and Impaired Fasting Glucose Share Similar Underlying Pathophysiologies (2007)

Both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states. IGT was defined as having normal fasting plasma glucose (< 6.1 mmol/l) and abnormal 2-hr post-challenge plasma glucose. IFG was defined as having abnormal fasting plasma and normal 2-hr post-challenge plasma glucose (< 7.8 mmol/l). To explore whether these two abnormalities share similar underlying pathophysiologies, we evaluated risk factors of IGT and IFT using the models of factor analysis. The present study included 107 subjects with IGT and 52 with IFG. An oral glucose tolerance test and insulin suppression test, which could quantify insulin resistance, were performed on separate days. The risk factors include waist-to-hip ratio (WHR), triglycerides, high-density lipoprotein (HDL)-cholesterol, blood pressure, and fasting plasma glucose, which are associated with metabolic syndrome and insulin resistance. Factor analysis is a commonly used statistical method that could reduce a large number of risk factors into smaller numbers of groups, also called dimension. Accordingly, the complicated data could be interpreted more easily, since the related risk factors are grouped in one dimension. The results showed that the risk factors of IGT and IFG have similar grouping patterns. Triglyceride, insulin resistance, and HDL-cholesterol were grouped in one dimension (the lipid dimension), while WHR, mean blood pressure and fasting plasma glucose were grouped in another dimension (the metabolic dimension). In conclusion, except for WHR, the grouping patterns of the components in both IGT and IFG were nearly identical. These results suggest that IGT and IFG may share similar pathophysiologies.
Potency of inhibitors for gamma-aminobutyric acid uptake by mouse brain subcellular particles at 0 degrees. (1975)

Binding of γ-amino[14C]butyric acid by sucellular particles of mouse brain homogenates at 0° is apparently due to action of the specific transport system for GABA. Although not energy-requiring, this uptake process showed a saturable dependence of GABA concentration, with an apparent Km of 28 ± 3 µM. The process was strictly sodium-dependent and sensitive to osmotic shock, freezing and thawing, and treatment with mild detergents. None of the GABA sequestering had the properties expected of neurotransmitter receptor sites, which probably were present in concentrations too low to be detectable by equilibrium dialysis of filtration assays of ligand binding. The potency of inhibition of GABA uptake at 0° was determined for 13 structural analogues of GABA known to inhibit both the transport of GABA and GABA synapses. No inhibition of GABA uptake occurred with 0.3 mM picrotoxin, but high concentrations (0.3 mM) of bicuculline-like compounds did inhibit the process, indicating that inhibition of the of radioactive GABA to tissue homogenates by bicuculline is not a sufficient criterion by itself to define such binding sites as receptors.
Human mesenchymal stem cells inhibit metastasis of a hepatocellular carcinoma model using the MHCC97‐H cell line (2010)

The effects of mesenchymal stem cells (MSC) on the growth and metastasis of human malignancies including hepatocellular carcinoma (HCC) are controversial, and the underlying mechanisms are not yet understood. The aim of this study was to explore the role of MSC in the progression of HCC. We investigated the effect of MSC on in vitro proliferation and invasion and in vivo tumor growth and pulmonary metastasis of MHCC97-H HCC cells with a high metastatic potential. The mRNA and protein levels of transforming growth factor-beta 1 (TGFβ1) and MMP, and their association with the effects of MSC on HCC cells were also evaluated. Co-culture of MHCC97-H cells with MSC conditioned medium significantly enhanced in vitro proliferation but inhibited invasiveness. Following MSC treatment of a nude mouse model bearing human HCC, the MSC were predominantly located in the HCC tissues. Compared with controls, MSC-treated mice exhibited significantly larger tumors (3080.51 ± 1234.78 mm(3) vs 2223.75 ± 1000.60 mm(3), P = 0.045), but decreased cellular numbers of lung metastases (49.75 ± 18.86 vs 227.22 ± 74.67, P = 0.046). Expression of TGFβ1 and MMP-2 was significantly downregulated in the MSC-treated HCC cells. TGFβ siRNA concurrently downregulated expression of TGFβ and MMP-2 in HCC cells and blocked the MSC-induced proliferation and invasiveness of MHCC97-H cells. The MSC enhanced tumor growth but significantly inhibited the invasiveness and metastasis of HCC, possibly through downregulation of TGFβ1. These findings suggest that MSC could be useful in controlling metastatic recurrence of HCC.
G-band frequency-steering antenna array design and measurements (2011)

This paper discusses design of a micro-fabricated frequency-steered waveguide slot array and its radiation pattern measurements over a 130GHz to 180GHz frequency range. The array is designed in a reduced-height WR-5 waveguide, and the slot spacing, size and position are optimized using HFSS. The array was fabricated in the PolyStrata™ process by Nuvotronics, LLC. The measured return loss of the 20-element travelling-wave array is below 12dB from 130 to 180GHz. The radiation patterns agree well with simulations are exhibit about 1degree/GHz of scanning. The measurements were performed in a calibrated quasi-optical setup.
Brain Inspired Cognitive Model with Attention for Self-Driving Cars (2017)

Perception-driven approach and end-to-end system are two major vision-based frameworks for self-driving cars. However, it is difficult to introduce attention and historical information of autonomous driving process, which are the essential factors for achieving human-like driving into these two methods. In this paper, we propose a novel model for self-driving cars named brain-inspired cognitive model with attention (CMA). This model consists of three parts: a convolutional neural network for simulating human visual cortex, a cognitive map built to describe relationships between objects in complex traffic scene and a recurrent neural network that combines with the real-time updated cognitive map to implement attention mechanism and long-short term memory. The benefit of our model is that can accurately solve three tasks simultaneously:1) detection of the free space and boundaries of the current and adjacent lanes. 2)estimation of obstacle distance and vehicle attitude, and 3) learning of driving behavior and decision making from human driver. More significantly, the proposed model could accept external navigating instructions during an end-to-end driving process. For evaluation, we build a large-scale road-vehicle dataset which contains more than forty thousand labeled road images captured by three cameras on our self-driving car. Moreover, human driving activities and vehicle states are recorded in the meanwhile.
Chemokine C‐C motif receptor 5 and C‐C motif ligand 5 promote cancer cell migration under hypoxia (2012)

The chemokine CC motif receptor 5 (CCR5) and its ligands have been reported to be associated with cancer progression and metastasis. Although recent researches have demonstrated a fundamental role of hypoxia in cancer, the effect of hypoxia on the expression and function of CCR5 and its ligands in cancer cells is unknown. Here, we investigated the status of CCR5 and its ligands in cancer cells under hypoxic conditions. Quantitative polymerase chain reaction, western blotting and immunofluorescence staining showed that hypoxia induced a strong increase of CCR5 expression. Dual luciferase assay and mRNA stability analysis indicated that hypoxia-induced CCR5 mRNA expression relied on both transcriptional and posttranscriptional mechanisms. We detected the expression of CCR5 ligands and found that chemokine CC motif ligand 5 (CCL5) was induced under hypoxia. Recombinant human CCL5 stimulated cell migration rather than cell proliferation under hypoxia, and neutralization of CCL5 inhibited hypoxia-induced migration of cancer cells. Similarly, overexpression of CCR5 increased cell migration, and knockdown of CCR5 attenuated hypoxia-mediated cell migration. We further showed that hypoxia-inducible factor-1α (HIF-1α) was involved in CCR5 and CCL5 regulation under hypoxia. HIF-1α mRNA levels were highly correlated with CCR5 mRNA and CCL5 mRNA levels in clinical samples. CCR5 and CCL5 were highly expressed in breast cancer lymph nodes metastases. Taken together, our data suggest that CCR5-CCL5 interaction promotes cancer cell migration under hypoxia.
Immunogenicity of therapeutic recombinant immunotoxins (2016)

Recombinant immunotoxins (RITs) are chimeric proteins designed to treat cancer. They are made up of an Fv or Fab that targets an antigen on a cancer cell fused to a 38-kDa portion of Pseudomonas exotoxin A (PE38). Because PE38 is a bacterial protein, it is highly immunogenic in patients with solid tumors that have normal immune systems, but much less immunogenic in patients with hematologic malignancies where the immune system is suppressed. RITs have shown efficacy in refractory hairy cell leukemia and in some children with acute lymphoblastic leukemia, but have been much less effective in solid tumors, because neutralizing antibodies develop and prevent additional treatment cycles. In this paper we will (i) review data from clinical trials describing the immunogenicity of PE38 in different patient populations; (ii) review results from clinical trials using different immunosuppressive drugs; and (iii) describe our efforts to make new less-immunogenic RITs by identifying and removing T- and B-cell epitopes to hide the RIT from the immune system.
Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis (2010)

The results indicate for the first time a role for exosomes in human lung disease with possible contributions to the initiation and progression of inflammation in sarcoidosis. This suggests that exosomes may be a new potential target for the clinical treatment of lung diseases.
Autologous anti‐idiotypic antibody response is regulated by the level of circulating complementary idiotype (1996)

BALB/c mice injected with lyophilized vaccine from Streptococcus pneumoniae R36a (Pn) predominantly responded with antibody molecules the vast majority of which expressed the public idiotype T15 and were directed to the immunodominant epitope phosphorylcholine (PC). However, after a single immunization with Pn vaccine young (3-month-old) BALB/c mice did not produce any specific anti-T15 antibody response. In contrast, young D1.LP mice were able to mount a specific anti-T15 response upon primary immunization with pneumococcal vaccine. The anti-PC response in the two mouse strains differed in that the proportion of antibody molecules that expressed the T15 idiotype for Pn-primed D1.LP mice showed a smaller proportion of PC-specific antibody expressing the T15 idiotype. Neonatal injection of anti-T15 monoclonal antibodies led to a long-term suppression of the PC-specific T15+ B-cell clones but at young/adult age these mice maintained the ability to produce a normal amount of PC-specific antibody. Interestingly, the idiotypically-suppressed BALB/c mice mounted a significant anti-T15 response during the primary response to Pn. We interpreted these data as showing that the level of circulating idiotype may regulate the production of the complementary anti-idiotypic antibody. In addition, in vitro experiments demonstrated that the lack of the anti-T15 response during primary antibody response in BALB/c mice is probably because of a state of tolerance that is regulated by T cells.
Green fluorescent antibodies: novel in vitro tools (2000)

We produced a fluorescent antibody as a single recombinant protein in Escherichia coli by fusing a red-shifted mutant of green fluorescent protein (EGFP) to a single-chain antibody variable fragment (scFv) specific for hepatitis B surface antigen (HepBsAg). GFP is a cytoplasmic protein and it was not previously known whether it would fold correctly to form a fluorescent protein in the periplasmic space of E.COLI: In this study we showed that EGFP alone or fused to the N'- and C'-termini of the scFv resulted in fusion proteins that were in fact highly fluorescent in the periplasmic space of E.COLI: cells. Further characterization revealed that the periplasmic N'-terminal EGFP-scFv fusion was the most stable form which retained the fluorescent properties of EGFP and the antigen binding properties of the native scFv; thus representing a fully functional chimeric molecule. We also demonstrated the utility of EGFP-scFv in immunofluorescence studies. The results showed positive staining of COS-7 cells transfected with HepBsAg, with comparable sensitivity to a monoclonal antibody or the scFv alone, probed with conventional fluorescein-labelled second antibodies. In this study, we developed a simple technique to produce fluorescent antibodies which can potentially be applied to any scFv. We demonstrated the utility of an EGFP-scFv fusion protein for immunofluorescence studies, but there are many biological systems to which this technology may be applied.
Value dependence graphs (1994)

The value dependence graph (VDG) is a sparse dataflow-like representation that simplifies program analysis and transformation. It is a functional representation that represents control flow as data flow and makes explicit all machine quantities, such as stores and I/O channels. We are developing a compiler that builds a VDG representing a program, analyzes and transforms the VDG, then produces a control flow graph (CFG) [ASU86] from the optimized VDG. This framework simplifies transformations and improves upon several published results. For example, it enables more powerful code motion than [CLZ86, FOW87], eliminates as many redundancies as [AWZ88, RWZ88] (except for redundant loops), and provides important information to the code scheduler [BR91]. We exhibit a fast, one-pass method for elimination of partial redundancies that never performs redundant code motion [KFS92, DS93] and is simpler than the classical [MR79, Dha91] or SSA [RWZ88] methods. These results accrue from eliminating the CFG from the analysis/transformation phases and using demand dependences in preference to control dependences.
Rapid Diagnosis of Bacteremia by Universal Amplification of 23S Ribosomal DNA Followed by Hybridization to an Oligonucleotide Array (2000)

The rapid identification of bacteria in blood cultures and other clinical specimens is important for patient management and antimicrobial therapy. We describe a rapid (<4 h) detection and identification system that uses universal PCR primers to amplify a variable region of bacterial 23S ribosomal DNA, followed by reverse hybridization of the products to a panel of oligonucleotides. This procedure was successful in discriminating a range of bacteria in pure cultures. When this procedure was applied directly to 158 unselected positive blood culture broths on the day when growth was detected, 125 (79.7%) were correctly identified, including 4 with mixed cultures. Nine (7.2%) yielded bacteria for which no oligonucleotide targets were present in the oligonucleotide panel, and 16 culture-positive broths (10.3%) produced no PCR product. In seven of the remaining eight broths, streptococci were identified but not subsequently grown, and one isolate of Staphylococcus aureus was misidentified as a coagulase-negative staphylococcus. The accuracy, range, and discriminatory power of the assay can be continually extended by adding further oligonucleotides to the panel without significantly increasing complexity or cost.
Targeting ornithine decarboxylase reverses the LIN28/Let-7 axis and inhibits glycolytic metabolism in neuroblastoma (2014)

LIN28 has emerged as an oncogenic driver in a number of cancers, including neuroblastoma (NB). Overexpression of LIN28 correlates with poor outcome in NB, therefore drugs that impact the LIN28/Let-7 pathway could be beneficial in treating NB patients. The LIN28/Let-7 pathway affects many cellular processes including the regulation of cancer stem cells and glycolytic metabolism. Polyamines, regulated by ornithine decarboxylase (ODC) modulate eIF-5A which is a direct regulator of the LIN28/Let-7 axis. We propose that therapy inhibiting ODC will restore balance to the LIN28/Let-7 axis, suppress glycolytic metabolism, and decrease MYCN protein expression in NB. Difluoromethylornithine (DFMO) is an inhibitor of ODC in clinical trials for children with NB. In vitro experiments using NB cell lines, BE(2)-C, SMS-KCNR, and CHLA90 show that DFMO treatment reduced LIN28B and MYCN protein levels and increased Let-7 miRNA and decreased neurosphere formation. Glycolytic metabolic activity decreased with DFMO treatment in vivo. Additionally, sensitivity to DFMO treatment correlated with LIN28B overexpression (BE(2)-C>SMS-KCNR>CHLA90). This is the first study to demonstrate that DFMO treatment restores balance to the LIN28/Let-7 axis and inhibits glycolytic metabolism and neurosphere formation in NB and that PET scans may be a meaningful imaging tool to evaluate the therapeutic effects of DFMO treatment.
Saturable human neopterin response to interferon-α assessed by a pharmacokinetic-pharmacodynamic model (2013)

The PK-PD model of SR-IFN-α developed in this study has presented a quantitative tool to assess the time-course of a saturable neopterin response in humans.