gebhart/patrepeval huggingface dataset:
Decorin Mimic Inhibits Vascular Smooth Muscle Proliferation and Migration (2013)

Over the past 10 years, the number of percutaneous coronary intervention procedures performed in the United States increased by 33%; however, restenosis, which inhibits complete functional recovery of the vessel wall, complicates this procedure. A wide range of anti-restenotic therapeutics have been developed, although many elicit non-specific effects that compromise vessel healing. Drawing inspiration from biologically-relevant molecules, our lab developed a mimic of the natural proteoglycan decorin, termed DS-SILY, which can mask exposed collagen and thereby effectively decrease platelet activation, thus contributing to suppression of vascular intimal hyperplasia. Here, we characterize the effects of DS-SILY on both proliferative and quiescent human SMCs to evaluate the potential impact of DS-SILY-SMC interaction on restenosis, and further characterize in vivo platelet interactions. DS-SILY decreased proliferative SMC proliferation and pro-inflammatory cytokine secretion in vitro in a concentration dependent manner as compared to untreated controls. The addition of DS-SILY to in vitro SMC cultures decreased SMC migration and protein synthesis by 95% and 37%, respectively. Furthermore, DS-SILY decreased platelet activation, as well as reduced neointimal hyperplasia by 60%, in vivo using Ossabaw swine. These results indicate that DS-SILY demonstrates multiple biological activities that may all synergistically contribute to an improved treatment paradigm for balloon angioplasty.
Synthesis and Cyclic GMP Phosphodiesterase Inhibitory Activity of a Series of 6-Phenylpyrazolo[3,4-d]pyrimidones (1996)

A series of 6-phenylpyrazolo[3,4-d]pyrimidones is described which are specific inhibitors of cGMP specific (type V) phosphodiesterase. Enzymatic and cellular activity as well as in vivo oral antihypertensive activity are evaluated. A n-propoxy group at the 2-position of the phenyl ring is necessary for activity. A series of products substituted at the 5-position in addition to the 2-n-propoxy was prepared and evaluated. This position can accommodate many unrelated groups. Amino derivatives were very potent but lacked metabolic stability. Substitution by carbon-linked small heterocycles provided both high levels of activity and stability. Cellular activity very often correlated with in vivo activity. Among the compounds, 1,3-dimethyl-6(2-propoxy-5-methanesulfonamidophenyl)-1,5-dihydr opyrazolo[3,4-d]pyrimidin-4-one (38) and 1-ethyl-3-methyl-6-(2-propoxy-5-(4-methylthiazol-2-yl)phenyl -1,5-dihy dropyrazolo[3,4-d]pyrimidin-4-one (59) displayed outstanding in vivo activities at 5 mg/kg/os and good metabolic stabilities.
Near-perfect simultaneous measurement of a qubit register (2006)

Simultaneous measurement of multiple qubits stored in hyperfine levels of trapped 111Cd+ ions is realized with an intensified charge-coupled device (CCD) imager. A general theory of fluorescence detection for hyperfine qubits is presented and applied to experimental data. The use of an imager for photon detection allows for multiple qubit state measurement with detection fidelities of greater than 98%. Improvements in readout speed and fidelity are discussed in the context of scalable quantum computation architectures.
Protein Translocation Across Biological Membranes (2005)

Subcellular compartments have unique protein compositions, yet protein synthesis only occurs in the cytosol and in mitochondria and chloroplasts. How do proteins get where they need to go? The first steps are targeting to an organelle and efficient translocation across its limiting membrane. Given that most transport systems are exquisitely substrate specific, how are diverse protein sequences recognized for translocation? Are they translocated as linear polypeptide chains or after folding? During translocation, how are diverse amino acyl side chains accommodated? What are the proteins and the lipid environment that catalyze transport and couple it to energy? How is translocation coordinated with protein synthesis and folding, and how are partially translocated transmembrane proteins released into the lipid bilayer? We review here the marked progress of the past 35 years and salient questions for future work. Subcellular compartments have unique protein compositions, yet protein synthesis only occurs in the cytosol and in mitochondria and chloroplasts. How do proteins get where they need to go? The first steps are targeting to an organelle and efficient translocation across its limiting membrane. Given that most transport systems are exquisitely substrate specific, how are diverse protein sequences recognized for translocation? Are they translocated as linear polypeptide chains or after folding? During translocation, how are diverse amino acyl side chains accommodated? What are the proteins and the lipid environment that catalyze transport and couple it to energy? How is translocation coordinated with protein synthesis and folding, and how are partially translocated transmembrane proteins released into the lipid bilayer? We review here the marked progress of the past 35 years and salient questions for future work.
Enhancement by prostaglandin E2 of bradykinin activation of embryonic rat sensory neurones. (1994)

1. The capacity of prostaglandin E2 (PGE2) to enhance the excitatory response elicited by bradykinin in embryonic rat sensory neurones grown in culture was investigated using the whole-cell patch-clamp recording technique. 2. The focal application of bradykinin (BK) produced a small concentration-dependent depolarization that was associated with an inward current and was described by a ligand-binding isotherm having an EC50 of 230 nM. Typically the depolarization was accompanied by action potentials (APs). 3. After pretreatment with 1 microM PGE2 for 10 min, the number of APs elicited by 100 nM BK was increased by about 3-fold. However, PGE2 had no effect on the amplitude of either the BK-elicited depolarization or inward current. The addition of 1 or 10 microM PGE2 had no effect on the resting membrane potential. 4. In all neurones exhibiting PGE2-enhanced excitability, there was a decrease in the amount of injected current necessary to elicit an AP. 5. The enhanced excitability was not due to repeated exposure to BK since neither the amplitude of the BK-evoked depolarization nor the number of APs was altered by the application of BK at 2 min intervals over a period of 30 min. 6. These results are consistent with the notion that PGE2 acts directly on sensory neurones to enhance the response to chemical excitatory agents, like BK, by lowering the AP firing threshold. The PGE2-mediated sensitization does not result from an alteration of the resting potential or modulation of the neuronal response to the chemical agonist.
The Digital Elliptic Filter--A Compact Sharp-Cutoff Design for Wide Bandstop or Bandpass Requirements (1967)

Detailed design procedures are presented for a practical elliptic-function filter form capable of achieving high selectivity in a very compact configuration. This filter form, called the digital elliptic because of its digital construction and elliptic function response, can provide either bandpass or bandstop characteristics. Examples are given to illustrate typical design procedures for both bandpass and bandstop applications. Experimental results are presented for an octave bandstop design.
Potential Role of Fluoroquinolones in Pediatric Infections (1989)

The fluoroquinolones are new, broad-spectrum, bactericidal antimicrobial agents structurally related to nalidixic acid. They are well absorbed after oral administration, with serum and tissue levels generally in excess of the minimal inhibitory concentrations for susceptible organisms. Their spectrum of activity includes serious pediatric pathogens such as Haemophilus influenzae, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. The potential uses of fluoroquinolones in pediatric diseases include acute and chronic pulmonary infections in children with cystic fibrosis, methicillin-resistant staphylococcal infections, meningitis with resistant bacteria, and prophylaxis in leukemic and immunocompromised children. The toxicity of some quinolone derivatives that involve developing cartilage in sensitive animal species has to be studied further. Clinical trials of fluoroquinolones from Europe and the United States in children show no cartilage or joint toxicity. For the time being and until more clinical experience with fluoroquinolones in children is obtained, their use should be limited to specific cases of therapeutic failure or multiple resistance to other antibiotics.
Chemistry, bioactivity and geographical diversity of steroidal alkaloids from the Liliaceae family (2006)

Plants belonging to the Liliaceae family have been the topic of research in many phytochemical and pharmacological laboratories because they contain structurally complex and biologically fascinating steroidal alkaloids. This review, citing 153 references, summarises the chemistry, bioactivity and geographical diversity of steroidal alkaloids isolated from Veratrum and Fritillaria species, so as to illustrate the chemo-diversity and biological significance of these alkaloids, along with their geographical distribution where this is discernible.
Establishment of a highly sensitive and specific exon-trapping system. (1992)

We have established a highly sensitive and specific exon-trapping system (SETS) with a specific plasmid vector in which an exon in a given DNA segment is identified by its ability to remain as a mature mRNA after splicing. The SETS provides us with the isolation of possible exons rapidly and easily from DNA fragments in chromosomal regions of more than 300 kilobase pairs. Genomic DNA fragments were partially digested and subsequently cloned into plasmid pMHC2, an exon-trapping vector we have constructed. These constructs were transfected into COS-7 cells, and consequent RNA transcripts were spliced in the cells. The resulting mature mRNA was harvested and amplified by using reverse transcription-PCR. Possible exons can be recognized by the sizes of PCR products and cloned into a plasmid vector. The SETS provides a direct means of cloning exons from genomic DNA of more than 300 kilobase pairs within a short period of time. Using this system, we have screened 300-kilobase-pair genomic DNA segments derived from human chromosome 11q13. Human chromosome 11q13 may contain genes responsible for human cancers, because DNA amplification is observed in several malignant tumors. We have successfully identified exon 2 of the HST1 gene and additional transcribed sequences.
Feudal Reinforcement Learning (1992)

One way to speed up reinforcement learning is to enable learning to happen simultaneously at multiple resolutions in space and time. This paper shows how to create a Q-learning managerial hierarchy in which high level managers learn how to set tasks to their sub-managers who, in turn, learn how to satisfy them. Sub-managers need not initially understand their managers&amp;apos; commands. They simply learn to maximise their reinforcement in the context of the current command. We illustrate the system using a simple maze task.. As the system learns how to get around, satisfying commands at the multiple levels, it explores more efficiently than standard, flat, Q-learning and builds a more comprehensive map.
Effects of AST-120 on Blood Concentrations of Protein-Bound Uremic Toxins and Biomarkers of Cardiovascular Risk in Chronic Dialysis Patients (2014)

AST-120 effectively decreased indoxyl sulfate and p-cresol sulfate levels in both total and free forms. AST-120 also improved the profile of cardiovascular biomarkers.
Sequencing Analysis of the Region Encoding the DNA Polymerase of Bovine Adenovirus Serotypes 2 and 3 (1998)

Bovine adenoviruses (BAVs) are important pathogens causing significant economic losses to the cattle industry. We have been interested in the differences among serotypes of these viruses, particularly in their pathogenicity and host range. As part of our efforts to better understand these viruses, we have determined the nucleotide sequences for serotype 3 (BAV3) at map coordinates beween 11.7 and 23.7% and for serotype 2 (BAV2) between 13.1 and 24.0%. Analyses of these sequences revealed large open reading frames (ORFs) encoded within the leftward-reading strand of the viral DNA. The coding capacity of the ORF in BAV3 is 1,167 amino acid residues and 1,138 in BAV2. A search in the GenEMBL protein sequence databank for homology to the predicted polypeptide products of these ORFs established their identity as that for the adenovirus (Ad) DNA polymerase (DNA pol). The deduced polypeptide sequences were aligned with each other and with other known Ad DNA pols to reveal regions of homology and similarity. The comparison at the amino acid sequence level not only showed that the bovine Ad DNA pols from the two serotypes are quite distinct from each other, but also revealed that Ad DNA pols contain multiple domains that are highly conserved among human, canine and bovine Ads. These conserved domains are likely important for the multiple functions attributed to Ad DNA pol, which include catalysis of its own initiation complex, elongation of nascent DNA strand, as well as correction of DNA replication errors.
Combination of Phytosterols and Omega-3 Fatty Acids: A Potential Strategy to Promote Cardiovascular Health (2004)

Phytosterols and omega-3 fatty acids (n-3) are natural food ingredients with potential cardiovascular benefits. Phytosterols inhibit cholesterol absorption, thereby reducing total cholesterol (TC) and LDL-cholesterol levels. Numerous clinical studies have shown that a daily intake of 1.5-2.0 g of phytosterols can result in a 10-15 % reduction in LDL levels, while consumption of n-3 is associated with a significant reduction in plasma triglyceride (TG) concentrations. Furthermore, n-3 may also beneficially modify a number of other risk factors of coronary heart disease (CHD). Thus, it is reasonable to suggest that combination of phytosterols and n-3 may further reduce cardiovascular risk factors. Esterification of phytosterols with non-n-3 fatty acids has substantially improved their incorporation into a variety of foods without affecting the efficacy of phytosterols. Therefore, it is assumed that esterification of phytosterols with n-3 may have advantages for both food industry and health. Evidence suggests that this combination is effective in reducing the levels of several cardiovascular risk factors including TC and TG concentrations, pro-aggregatory factors, arrhythmic eicosanoid and thromboxane A2 levels. In this mini-review, we have critically reviewed and summarized data from clinical and animal studies in which phytosterols and n-3, alone or in combination, were used. We have also provided information on structure-function relationship for these two natural compounds. Biological properties of several phytosterol derivatives including phytosterol-glucoside have been also discussed. Although the animal studies are supportive of this combination therapy, human studies are needed to address its long term effects.
TP53 and liver carcinogenesis (2003)

Primary hepatocellular carcinoma (HCC) is one of the most common malignancies and has the fourth highest mortality rate worldwide. The major risk factors, including chronic infections with the hepatitis B or C virus, are exposure to dietary aflatoxin B1(AFB1), vinyl chloride, or alcohol consumption. Southern China and sub-Saharan Africa have the highest dietary AFB1 exposure, making it and hepatitis B virus (HBV) the major causes of cancer mortality in these geographic areas. Recent studies have discovered genetic and epigenetic changes involved in the molecular pathogenesis of HCC, including somatic mutations in the p53 tumor suppressor gene (TP53). AFB1 induces typical G:C to T:A transversions at the third base in codon 249 of p53. Chronic active hepatitis B and C (HCV) infection, and further inflammatory and oxyradical disorders including Wilson disease (WD) or hemochromatosis, generate reactive oxygen/nitrogen species that can damage DNA and mutate the p53 gene. The X gene of HBV (HBx) is the most common open reading frame integrated into the host genome in HCC. The integrated HBx is frequently mutated and has a diminished ability to function as a transcriptional cotransactivator and to activate the NF-kappa B pathway. However, the mutant HBx proteins still retain their ability to bind to and abrogate p53-mediated apoptosis. In summary, both viruses and chemicals are implicated in the etiology and molecular pathogenesis of HCC. The resultant molecular changes in the ras and Wnt signal-transduction pathways, and the p53 and Rb tumor suppressor pathways significantly contribute to liver carcinogenesis
Inhibition of IGF-1R-Dependent PI3K Activation Sensitizes Colon Cancer Cells Specifically to DR5-Mediated Apoptosis But Not to rhTRAIL (2010)

Background : Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) initiates apoptosis in tumor cells upon binding to its cognate agonistic receptors, death receptors 4 and 5 (DR4 and DR5). The activity of the insulin-like growth factor 1 (IGF-1) survival pathway is often increased in cancer, influencing both cell proliferation and apoptosis. We hypothesized that inhibiting the IGF-1 receptor (IGF-1R) using NVP-AEW541, a small molecular weight tyrosine kinase inhibitor of the IGF-1R, could increase death receptor (DR)-mediated apoptosis in colon cancer cells. Methods : The analyses were performed by caspase assay, flow cytometry, Western blotting, immunoprecipitation and fluorescent microscopy. Results : Preincubation with NVP-AEW541 surprisingly decreased apoptosis induced by recombinant human TRAIL (rhTRAIL) or an agonistic DR4 antibody while sensitivity to an agonistic DR5 antibody was increased. NVP-AEW541 could inhibit IGF-1-induced activation of the phosphatidylinositol 3-kinase (PI3K) pathway. The effects of the PI3K inhibitor LY294002 on TRAIL-induced apoptosis were similar to those of NVP-AEW541, further supporting a role for IGF-1R-mediated activation of PI3K. We show that PI3K inhibition enhances DR5-mediated caspase 8 processing but also lowers DR4 membrane expression and DR4-mediated caspase 8 processing. Inhibition of PI3K reduced rhTRAIL sensitivity independently of the cell line preference for either DR4- or DR5-mediated apoptosis signaling. Conclusion : Our study indicates that individual effects on DR4 and DR5 apoptosis signaling should be taken into consideration when combining DR-ligands with PI3K inhibition.
Dietary Fibers and Glycemic Load, Obesity, and Plasma Adiponectin Levels in Women With Type 2 Diabetes (2006)

Our data indicate that dietary cereal fiber and glycemic load/index are associated with the circulating adiponectin concentration. Such associations were not modified by obesity status.
Cell type-specific methylation of an intronic CpG island controls expression of the MCJ gene (2003)

Over 50% of human genes are associated with CpG islands and DNA methylation within such CpG islands has been clearly correlated with inhibition of expression. Whereas changes in DNA methylation play a key role in a number of human diseases, in particular cancer, in normal DNA CpG islands are nearly always methylation free, regardless of the expression status of the associated gene. Only limited evidence supports a role for DNA methylation in controlling tissue-specific expression in adult somatic tissue. Loss of expression of the MCJ gene has previously been linked to increased chemotherapeutic drug resistance in ovarian cancer. We report that loss of expression of MCJ in drug-resistant ovarian cancer cell lines depends on methylation of a CpG island within its first exon, but is independent of methylation within the promoter region. Furthermore, cell type-specific expression of the MCJ gene in normal cells also depends on the methylation status of the CpG island within its first exon. The MCJ CpG island is methylated and the gene is not expressed in cells of epithelial origin, but unmethylated and expressed in cells of lymphocyte or fibroblast origin. Chromatin immunoprecipitation assays determined that MCJ CpG island methylation was associated with loss of histone acetylation in ovarian epithelial cells compared with unmethylated fibroblast cells. Reduced acetylation was observed not only within the CpG island, but also within the promoter region, suggesting that CpG island methylation may direct alterations in chromatin structure within the promoter region, leading to gene inactivation.
Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma (1999)

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 x 10(6) DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 x 10(6) and 12 x 10(6) DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1-specific CD8(+) cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8(+) T cell infiltration, whereas nonregressing lesions lacked CD8(+) T cells as well as Mage-3 mRNA expression. This study proves the principle that DC "vaccines" can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8(+) CTL-tumor cell interaction in situ as well as escape by lack of tumor antigen expression.
Differential Roles of Interleukin 15 mRNA Isoforms Generated by Alternative Splicing in Immune Responses in Vivo (2000)

At least two types of interleukin (IL)-15 mRNA isoforms are generated by alternative splicing at the 5' upstream of exon 5 in mice. To elucidate the potential roles of IL-15 isoforms in immune responses in vivo, we constructed two groups of transgenic mice using originally described IL-15 cDNA with a normal exon 5 (normal IL-15 transgenic [Tg] mice) and IL-15 cDNA with an alternative exon 5 (alternative IL-15 Tg mice) under the control of an MHC class I promoter. Normal IL-15 Tg mice constitutionally produced a significant level of IL-15 protein and had markedly increased numbers of memory type (CD44(high) Ly6C(+)) of CD8(+) T cells in the LN. These mice showed resistance to Salmonella infection accompanied by the enhanced interferon (IFN)-gamma production, but depletion of CD8(+) T cells exaggerated the bacterial growth, suggesting that the IL-15-dependent CD8(+) T cells with a memory phenotype may serve to protect against Salmonella infection in normal IL-15 Tg mice. On the other hand, a large amount of intracellular IL-15 protein was detected but hardly secreted extracellularly in alternative IL-15 Tg mice. Although most of the T cells developed normally in the alternative IL-15 Tg mice, they showed impaired IFN-gamma production upon TCR engagement. The alternative IL-15 transgenic mice were susceptible to Salmonella accompanied by impaired production of endogenous IL-15 and IFN-gamma. Thus, two groups of IL-15 Tg mice may provide information concerning the different roles of IL-15 isoforms in the immune system in vivo.