gebhart/patrepeval huggingface dataset:
Selection of RNAi-based inhibitors for anti-HIV gene therapy (2012)

In the last decade, RNA interference (RNAi) advanced to one of the most widely applied techniques in the biomedical research field and several RNAi therapeutic clinical trials have been launched. We focus on RNAi-based inhibitors against the chronic infection with human immunodeficiency virus type 1 (HIV-1). A lentiviral gene therapy is proposed for HIV-infected patients that will protect and reconstitute the vital immune cell pool. The RNAi-based inhibitors that have been developed are short hairpin RNA molecules (shRNAs), of which multiple are needed to prevent viral escape. In ten distinct steps, we describe the selection process that started with 135 shRNA candidates, from the initial design criteria, via testing of the in vitro and in vivo antiviral activity and cytotoxicity to the final design of a combinatorial therapy with three shRNAs. These shRNAs satisfied all 10 selection criteria such as targeting conserved regions of the HIV-1 RNA genome, exhibiting robust inhibition of HIV-1 replication and having no impact on cell physiology. This combinatorial shRNA vector will soon move forward to the first clinical studies.
Relationship between p53 overexpression and the proliferative activity in hepatocellular carcinoma. (2000)

Relationship between p53 protein overexpression and clinicopathological findings and the proliferative activity was studied in 50 cases of hepatocellular carcinoma (34 biopsy and 16 surgically resected cases) using immunohistochemistry. Overexpression of p53 was observed in 26.5% of biopsy cases and 31. 3% of surgically resected cases. Investigation of the relationship between the p53-positive rate and the clinical stage of HCC showed that it was significantly higher in Stage IV (the most advanced cancer; 54.5%) than in Stage I/II/III (13.0%) (p<0.05). Examination of the relationship between the p53-positive rate and tumor differentiation in the biopsy cases showed that p53 was positive in 9.1% of well differentiated carcinomas, 21.4% of moderately differentiated carcinomas, and 55.6% of poorly differentiated carcinomas, indicating that p53 positivity increased as tumors became less differentiated. The p53-positive rate of poorly differentiated carcinoma (55.6%) was significantly higher than that of well and moderately differentiated carcinoma (16.0%) (p<0.05). In the surgically resected cases, p53 overexpression tended to be more frequent in the less differentiated parts of each tumor nodule. In cases with nodule in nodule pattern of HCC, the p53-positive rate was different among nodules with the same level of differentiation. Examination of tumor cell proliferative activity using the proliferating cell nuclear antigen L.I. showed that this indicator was significantly higher in the p53-positive tumors than in the p53-negative tumors (52.7+/-32.4% vs. 32.4+/-15.3%: p<0.05). These results suggest that p53 overexpression may be involved in determining the dedifferentiation and the proliferative activity of HCC. Examination of the surgically resected cases confirmed that p53 overexpression became heterogeneous during the multistep carcinogenesis and growth process of HCC, which is considered to develop from a single cell. This finding suggests that p53 overexpression may be involved in tumor progression.
Improved High-Temperature Leakage in High-Density MIM Capacitors by Using a TiLaO Dielectric and an Ir Electrode (2007)

We have fabricated high-kappa TaN/Ir/TiLaO/TaN metal-insulator-metal capacitors. A low leakage current of 6.6 times 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-7</sup> A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> was obtained at 125degC for 24-fF/mum2 density capacitors. The excellent device performance is due to the combined effects of the high-kappa TiLaO dielectric, a high work-function Ir electrode, and large conduction band offset.
Clustering acronyms in biomedical text for disambiguation (2006)

Given the increasing number of neologisms in biomedicine (names of genes, diseases, molecules, etc.), the rate of acronyms used in literature also increases. Existing acronym dictionaries cannot keep up with the rate of new creations. Thus, discovering and disambiguating acronyms and their expanded forms are essential aspects of text mining and terminology management. We present a method for clustering long forms identified by an acronym recognition method. Applying the acronym recognition method to MEDLINE abstracts, we obtained a list of short/long forms. The recognized short/long forms were classified by a biologist to construct an evaluation set for clustering sets of similar long forms. We observed five types of term variation in the evaluation set and defined four similarity measures to gathers the similar long forms (i.e., orthographic, morphological, syntactic, lexico semantic variants, nested abbreviations). The complete-link clustering with the four similarity measures achieved 87.5% precision and 84.9% recall on the evaluation set.
Surface-enhanced resonance Raman scattering imaging of Langmuir-Blodgett monolayers of bis(benzimidazo)perylene on silver island films (2000)

The point-by-point mapping and global images of the surface-enhanced resonance Raman scattering (SERRS) spectra obtained from Langmuir–Blodgett (LB) monolayers of bis(benzimidazo)perylene (AzoPTCD) on silver island films are reported. The mapping and global Raman images of the LB-coated silver surfaces were obtained using 514.5 nm laser radiation. Visualization of the variation of the SERRS intensity across a 40 × 40 µm rough metal surface is achieved. Absorption UV–VIS and emission spectra of AzoPTCD solutions and monolayers on glass and silver islands are discussed. Surface-enhanced fluorescence (SEF) of the excimer emission from aggregates in LB film has been observed. The enhancement factors for SEF and SERS are discussed. Copyright © 2000 John Wiley & Sons, Ltd.
A Five-Gene Molecular Grade Index and HOXB13:IL17BR Are Complementary Prognostic Factors in Early Stage Breast Cancer (2008)

Abstract Purpose: Histologic tumor grade is a well-established prognostic factor for breast cancer, and tumor grade–associated genes are the common denominator of many prognostic gene signatures. The objectives of this study are as follows: (a) to develop a simple gene expression index for tumor grade (molecular grade index or MGI), and (b) to determine whether MGI and our previously described HOXB13:IL17BR index together provide improved prognostic information. Experimental Design: From our previously published list of genes whose expression correlates with both tumor grade and tumor stage progression, we selected five cell cycle–related genes to build MGI and evaluated MGI in two publicly available microarray data sets totaling 410 patients. Using two additional cohorts (n = 323), we developed a real-time reverse transcription PCR assay for MGI, validated its prognostic utility, and examined its interaction with HOXB13:IL17BR. Results: MGI performed consistently as a strong prognostic factor and was comparable with a more complex 97-gene genomic grade index in multiple data sets. In patients treated with endocrine therapy, MGI and HOXB13:IL17BR modified each other's prognostic performance. High MGI was associated with significantly worse outcome only in combination with high HOXB13:IL17BR, and likewise, high HOXB13:IL17BR was significantly associated with poor outcome only in combination with high MGI. Conclusions: We developed and validated a five-gene reverse transcription PCR assay for MGI suitable for analyzing routine formalin-fixed paraffin-embedded clinical samples. The combination of MGI and HOXB13:IL17BR outperforms either alone and identifies a subgroup (∼30%) of early stage estrogen receptor–positive breast cancer patients with very poor outcome despite endocrine therapy.
Neutron-capture therapy of human cancer: in vitro results on the preparation of boron-labeled antibodies to carcinoembryonic antigen. (1982)

Two samples of 2-phenyl-1,2-dicarba-closo-[1-3H]dodecaborane(12) were prepared by treating 1-lithio-2-phenyl-1,2-dicarba-closo-dodecaborane(12) with 3H2O (0.1 and 5.0 Ci/ml, respectively). These tritiated phenylcarborane samples were subsequently converted to corresponding samples of p-[1,2-dicarba-closo-[1-3H]dodecaboran(12)-2-yl]benzenediazonium ion ([3H]DBD) suitable for azo-coupling reactions. Reaction of the two tritiated diazonium ion samples with 2-napthol resulted in the formation of an azo dye (epsilon = 1.98 X 10(4) M-1 cm-1 at 485 nm). Experiments relating absorbance to 3H activity proved the two [3H]DBD sources to have 3.81 X 10(11) and 2.45 X 10(13) cpm of 3H per mol of tritiated carborane substituent. Purified antibodies to carcinoembryonic antigen were coupled to the [3H]DBD and, after extensive dialysis, the average number of carborane moieties per antibody molecule was determined by measuring the 3H activity associated with a known protein concentration. Further examination of these tritiated carborane-labeled antibodies by affinity chromatography proved that boron labeling did not destroy their immunoreactivity. Correlations of azo-coupling conditions (reactant ratios, pH) with immunoreactivity and antibody protein recovery are presented.
Recent Advances in the Synthesis and Catalytic Applications of Pillared Clays (2000)

New methods have been developed in recent years that are now being successfully applied in the preparation of pillared interlayered clays (PILCs). Variations in the procedures concern different parameters involved in the synthesis, such as the starting clay, the intercalating solution, the intercalation process, and the drying and calcination steps of the pillared solids, among others. In the present article, the latest results obtained when introducing modifications in the chemical aspects of PILC synthesis are reviewed. These include (1) pillaring with mixed solutions containing two or more cations, (2) using coordination or organometallic compounds, (3) using polymers and surfactants, (4) pillaring of acid-activated clays, and (5) enhancement of PILC acidity. A separate section is devoted to the specific features of preparing these solids in amounts large enough to make their manufacture on an industrial scale economically feasible. Recent developments in the catalytic applications of PILCs are also reviewed, with emphasis on the progressively more extended use of these materials as catalytic supports.
Molecular Engineering of the Autographa californica Nuclear Polyhedrosis Virus Genome: Deletion Mutations Within the Polyhedrin Gene (1983)

We describe a method to introduce site-specific mutations into the genome of Autographa californica nuclear polyhedrosis virus. Specifically, the A. californica nuclear polyhedrosis virus gene for polyhedrin, the major protein that forms viral occlusions in infected cells, was mutagenized by introducing deletions into the cloned DNA fragment containing the gene. The mutagenized polyhedrin gene was transferred to the intact viral DNA by mixing fragment and viral DNAs, cotransfecting Spodoptera frugiperda cells, and screening for viral recombinants that had undergone allelic exchange. Recombinant viruses with mutant polyhedrin genes were obtained by selecting the progeny virus that did not produce viral occlusions in infected cells (occlusion-negative mutants). Analyses of occlusion-negative mutants demonstrated that the polyhedrin gene was not essential for the production of infectious virus and that deletion of certain sequences within the gene did not alter the control, or decrease the level of expression, of polyhedrin. An early viral protein of 25,000 molecular weight was apparently not essential for virus replication in vitro, as the synthesis of this protein was not detected in cells infected with a mutant virus.
Oncogenic activity of Tiam1 and Rac1 in NIH3T3 cells. (1995)

We have recently identified the invasion-inducing Tiam1 gene by proviral insertional mutagenesis. The Tiam1 protein shares a Dbl homology (DH) domain with an increasing number of oncoproteins, some of which have been shown to function as GDP dissociation stimulators (GDS) for small GTPases of the Rho family. In vitro and in vivo analyses indicate that Tiam1 activates the Rho like GTPase Rac1. Here we have analysed the consequences of overexpression of several mutant Tiam1 proteins in NIH3T3 fibroblasts. Similar to other proteins containing a DH domain, N-terminal truncation of the Tiam1 protein activates its oncogenic potential, establishing Tiam1 as a proto-oncogene. In addition, we show the sequences N-terminal of the catalytic DH domain are required for morphological transformation accompanied by the formation of membrane ruffling, but not for the induction of an oncogenic phenotype. Overexpression of constitutively active Rac1 (V12Rac1) in NIH3T3 cells produces a similar oncogenic phenotype, suggesting that the oncogenic effects of Tiam1 are a consequence of Rac activation.
Primary Structures of Cytotoxic Factors Isolated from Habu (Trimeresurus flavoviridis) Venom (1991)

The amino acid sequence of a cytotoxic factor, CTF-I, isolated from the venom of the Japanese habu snake (Trimeresurus flavoviridis) has been determined through automatic phenylisothiocyanate degradation of the PE-protein and derived proteolytic peptides. CTF-I consists of 72 amino acids and contains an Arg-Gly-Asp sequence present in trigramin-like peptides isolated from other snake venoms. The primary structure of another cytotoxic factor, CTF-II, consisting of 75 amino acids, was deduced to comprise that of CTF-1 with an additional Glu-Leu-Leu-sequence at its N-terminal.
Targeted Gene Disruption Demonstrates That P-Selectin Glycoprotein Ligand 1 (Psgl-1) Is Required for P-Selectin–Mediated but Not E-Selectin–Mediated Neutrophil Rolling and Migration (1999)

P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like selectin counterreceptor that binds to P-selectin, E-selectin, and L-selectin. To determine its physiological role in cell adhesion as a mediator of leukocyte rolling and migration during inflammation, we prepared mice genetically deficient in PSGL-1 by targeted disruption of the PSGL-1 gene. The homozygous PSGL-1-deficient mouse was viable and fertile. The blood neutrophil count was modestly elevated. There was no evidence of spontaneous development of skin ulcerations or infections. Leukocyte infiltration in the chemical peritonitis model was significantly delayed. Leukocyte rolling in vivo, studied by intravital microscopy in postcapillary venules of the cremaster muscle, was markedly decreased 30 min after trauma in the PSGL-1-deficient mouse. In contrast, leukocyte rolling 2 h after tumor necrosis factor alpha stimulation was only modestly reduced, but blocking antibodies to E-selectin infused into the PSGL-1-deficient mouse almost completely eliminated leukocyte rolling. These results indicate that PSGL-1 is required for the early inflammatory responses but not for E-selectin-mediated responses. These kinetics are consistent with a model in which PSGL-1 is the predominant neutrophil P-selectin ligand but is not a required counterreceptor for E-selectin under in vivo physiological conditions.
Inhibition of a major NAD(P)-linked oxidoreductase from rat liver cytosol by steroidal and nonsteroidal anti-inflammatory agents and by prostaglandins. (1983)

A NAD(P)-linked 3 alpha-hydroxysteroid dehydrogenase [3 alpha-hydroxysteroid: NAD(P) oxidoreductase, EC 1.1.1.50], purified to homogeneity from male rat liver cytosol, accounts for most of the oxidative activity for 3 alpha-hydroxysteroids and for benzenedihydrodiol (trans-1,2-dihydroxy-3,5-cyclohexadiene) of this tissue. This enzyme, which also promotes the reduction of quinones and certain aromatic aldehydes and ketones, is powerfully inhibited by the major types of nonsteroidal and steroidal anti-inflammatory drugs. The IC50 values for indomethacin and for betamethasone are in the low micromolar range. The rank order of the inhibitory potencies of a series of these agents paralleled closely that reported for the inhibition of cyclooxygenase by nonsteroidal anti-inflammatory agents or the indirect inhibition of phospholipase A2 by anti-inflammatory steroids. A good correlation is found also between the logarithm of the concentrations of these drugs required to inhibit 3 alpha-hydroxysteroid dehydrogenase and the human anti-inflammatory dose. The suggestion that this enzyme may play a role in mediating inflammation is further strengthened by the observation that the dehydrogenase binds arachidonic acid and is also potentially inhibited by certain prostaglandins. This enzyme may be of use in the evaluation of anti-inflammatory activity.
An indirect response model of homocysteine suppression by betaine: optimising the dosage regimen of betaine in homocystinuria (2002)

PK-PD modelling allows recommendations for optimal dosage of betaine in the treatment of homocystinuria, that have the potential for improved patient compliance and both therapeutic and pharmacoeconomic benefit.
Inhibition of casein kinase 1-epsilon induces cancer-cell-selective, PERIOD2-dependent growth arrest (2008)

We identified CK1epsilon as a potential target for developing anticancer reagents with a high therapeutic index. These data support the hypothesis that circadian clock genes can control the cell cycle and cell survival signaling, and emphasize a central role of CK1epsilon and PERIOD2 in linking these systems.
The Psychological Correlates of Treatment Efficacy in Acne (2002)

Background: Acne is a common disfiguring skin condition that affects approximately 15% of the people in the UK. This study investigates the psychological and emotional impact of acne. Material and Methods: The study was conducted at the dermatology out-patient department of the Stirling Royal Infirmary in Stirling and at the dermatology out-patient department of Falkirk Royal Infirmary in Falkirk (Scotland). Patients were assessed pre-treatment, post-treatment (5 months) and follow-up (8 months). Clinical severity was assessed by a dermatologist at all three assessment time-points using the Leeds Acne Severity Grading Technique. The psychological well-being of acne patients was assessed using the following self-report psychological test measures: The Skindex, the Hospital Anxiety and Depression Scale (HADS), the Rosenberg Self-esteem Scale, and the Positive and Negative Affectivity Scales (PANAS). Patients were also asked to self-rate the severity of their skin disease. 34 acne patients completed all 3 assessments. Results: Results demonstrate that the clinical grade of acne improved significantly over treatment time, and at follow-up assessment. This indicates that the treatment prescribed by the dermatologists was generally effective, and that this improvement in the clinical severity of acne was maintained at the 8-month follow-up assessment, even though medical intervention had ceased. There was also evidence of moderate psychological distress pre-treatment, based on the psychological test measures employed. Treatment outcome results obtained from acne patients showed that there was a significant improvement over treatment time on how patients self-rated their self-esteem and positive affectivity, and a significant decrease on how patients selfrated their anxiety, depression, negative affectivity and Skindex scores. Conclusion: In conclusion this study has demonstrated that the psychological profile exhibited by acne patients pretreatment may be largely reversed over treatment time, and that this psychological improvement is generally maintained at follow-up assessment.
Discovery of Novel Hypermethylated Genes in Prostate Cancer Using Genomic CpG Island Microarrays (2009)

This study identifies novel epigenetic biomarkers of prostate cancer and prostate cancer progression, and provides a global assessment of DNA methylation in prostate cancer.
Targeted therapies in the treatment of advanced non-small-cell lung cancer: update. (2009)

After several years of clinical trials in the setting of advanced non-small-cell lung cancer (NSCLC) that were characterized by a lack of efficacy of chemotherapy over best supportive care, we have more recently seen meaningful clinical benefits realized from selected targeted therapies. In their constant development, the survival advantage of these new anti-cancer therapies has been demonstrated not only in the first-line setting, but, lately, even in patients with recurrent disease after failure of one or two previous chemotherapy lines. The first agents in this broad class to demonstrate clinical efficacy were the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors. Erlotinib, an EGFR, and bevacizumab, a vascular endothelial growth factor receptor (VEGFR), are the best representative new drugs for tumour control and palliation. This article reviews the most promising new targeted agents including those that have already been approved and are currently used in the medical practice.
Biological characterization of recombinant human follicle stimulating hormone isoforms (1999)

It has been established that follicle stimulating hormone (FSH) circulates in the bloodstream as a heterogeneous population of molecules. Individual FSH isoforms, while displaying identical amino acid sequences, differ in their extent of post-translational modification. As a result of these variations, the FSH isoforms exhibit differences in overall charge, degree of sialic acid or sulphate incorporation, receptor binding affinity and plasma half-life. Taking advantage of the fact that these forms can be separated from each other on the basis of their charge, we have evaluated in rats the metabolic clearance rates of the acidic [with an isoelectric point (pI) </=ISOdia</= 4.8] and the less acidic (pI > 4.8) isoforms of recombinant human FSH (rhFSH) obtained after chromatofocusing. The less acidic isoform group was found to have a faster clearance from the circulation in rats as compared with the acidic isoform group. This finding is in agreement with the lower bioactivity in vivo (as determined by the Steelman-Pohley assay) of the less acidic isoform group, compared with the acidic one. The mass spectra of the two groups of isoforms showed a difference in the sialic acid content thus highlighting the importance of these residues on the in-vivo activity of FSH. Conversely, when the two groups of isoforms were tested in vitro by using the Y1 human FSH receptor (Y1 hFSHR) assay and a reporter gene assay, no significant differences in the biological activities between these preparations were detected when test concentrations were based on mass.
The P2Y1 receptor is an ADP receptor antagonized by ATP and expressed in platelets and megakaryoblastic cells (1997)

The human P2Y1 purinoceptor has been expressed in Jurkat cells and the effects of HPLC purified nucleotides on calcium movements were measured. The most potent agonist was 2-methylthio-ADP followed by ADP. ATP, Sp-ATPalphaS and beta,gamma-methylene-ATP were competitive antagonists. Suramin and PPADS inhibited the effects of ADP. This pharmacological profile is the same as that of the so-called P2T purinoceptor responsible for platelet aggregation, which has not yet been identified. Using PCR we found the P2Y1 receptor to be present in blood platelets and megakaryoblastic cell lines. These data suggest that the P2Y1 receptor may be the elusive P2T receptor.
Stone-Wales defects in graphene and other planarsp2-bonded materials (2009)

Density functional theory and quantum Monte Carlo simulations reveal that the structure of the Stone-Wales (SW) defect in graphene is more complex than hitherto appreciated. Rather than being a simple in-plane transformation of two carbon atoms, out-of-plane wavelike defect structures that extend over several nanometers are predicted. Equivalent wavelike SW reconstructions are predicted for hexagonal boron-nitride and polycyclic aromatic hydrocarbons above a critical size, demonstrating the relevance of these predictions to $s{p}^{2}$-bonded materials in general.