gebhart/patrepeval huggingface dataset:
Mapping of the human APOB gene to chromosome 2p and demonstration of a two-allele restriction fragment length polymorphism. (1986)

ApoB is a large glycoprotein with an apparent molecular mass of 550 kDa on NaDodSO4/PAGE. It is a major constituent of most lipoproteins and plays an important role in their metabolism. Recently, apoB cDNA clones have been isolated from an expression library made with mRNA from a human hepatoma cell line. These clones, which were all 1.5-1.6 kilobases (kb) long and corresponded to the 3' end of apoB mRNA, were used to demonstrate that hepatic apoB mRNA is approximately 22 kb long. In the current report, a probe derived from one of these cDNA clones, pB8, was used for in situ hybridization experiments to map the human gene for apoB, APOB, to the distal half of the short arm of chromosome 2. This probe was also used to analyze somatic cell hybrids and, in agreement with the in situ hybridization studies, concordancy was demonstrated with chromosome 2. In addition, two hybrids with chromosome 2 translocations that contain only the short arm reacted with the pB8 probe. A third hybrid with a complex rearrangement of chromosome 2, which deleted an interstitial region and the tip of the short arm of chromosome 2, did not react. These data indicate that APOB maps to either 2p21-p23 or 2p24-pter. In further studies, DNA from normal individuals, digested with the restriction endonuclease EcoRI and subjected to Southern blot analysis with the pB8 probe, revealed a two-allele restriction fragment length polymorphism (RFLP). The major allele was 11 kb, and the minor allele was 13 kb. The minor allele was present with a frequency of 20-25%. The inheritance of the two alleles was studied in an informative family, and they segregated in a typical autosomal Mendelian fashion. The mapping studies provide the means for understanding the relationship of the APOB locus to others in the human genome, whereas the demonstration of an APOB RFLP increases our ability to assess the role of this locus in determining plasma lipoprotein levels.
Multiple specificities in the murine CD4+ and CD8+ T-cell response to dengue virus (1996)

The target epitopes, serotype specificity, and cytolytic function of dengue virus-specific T cells may influence their theoretical roles in protection against secondary infection as well as the immunopathogenesis of dengue hemorrhagic fever. To study these factors in an experimental system, we isolated dengue virus-specific CD4+ and CD8+ T-cell clones from dengue-2 virus-immunized BALB/c mice. The T-cell response to dengue virus in this mouse strain was heterogeneous; we identified at least five different CD4+ phenotypes and six different CD8+ phenotypes. Individual T-cell clones recognized epitopes on the dengue virus pre-M, E, NSl/NS2A, and NS3 proteins and were restricted by the I-Ad, I-Ed, Ld, and Kd antigens. Both serotype-specific and serotype-cross-reactive clones were isolated in the CD4+ and CD8+ subsets; among CD8+ clones, those that recognized the dengue virus structural proteins were serotype specific whereas those that recognized the nonstructural proteins were serotype cross-reactive. All of the CD8+ and one of five CD4+ clones lysed dengue virus-infected target cells. Using synthetic peptides, we identified an Ld-restricted epitope on the E protein (residues 331 to 339, SPCKIPFEI) and a Kd-restricted epitope on the NS3 protein (residues 296 to 310, ARGYISTRVEM GEAA). These data parallel previous findings of studies using human dengue virus-specific T-cell clones. This experimental mouse system may be useful for studying the role of the virus serotype and HLA haplotype on T-cell responses after primary dengue virus infection.
Purification of the platelet-derived growth factor receptor by using an anti-phosphotyrosine antibody. (1985)

The platelet-derived growth factor (PDGF) receptor is a 180-kDa membrane glycoprotein. A protein of identical size, lectin affinity, and isoelectric point has been identified as a major substrate for PDGF-activated tyrosine kinase in stimulated 3T3 cells. We have purified this tyrosine-phosphorylated protein to homogeneity by using anti-phosphotyrosine immunoaffinity and lectin affinity steps. Demonstration that this purified tyrosine phosphoprotein is the PDGF receptor necessitated development of an assay capable of identifying specific 125I-labeled PDGF binding activity in soluble receptor preparations. PDGF receptor solubilized from 3T3 cell membranes with the detergent octyl beta-D-glucoside was precipitated on an artificial liposome matrix after receptor aggregation with concanavalin A. Precipitated binding sites display affinity and kinetic characteristics of PDGF receptors in cells and membranes. Preparations of the 180-kDa phosphoprotein that are greater than 90% homogeneous by silver stain and by [35S]methionine protein autoradiography have specific high affinity 125I-labeled PDGF binding sites (equilibrium dissociation constant, 0.1 X 10(-9) M). Binding activity enrichment in this preparation reflects an 11,000-fold purification of binding activity in intact cells. These data demonstrate that the 180-kDa substrate of the PDGF-stimulated tyrosine kinase is the PDGF receptor. Furthermore, these methods provide a means of purifying this and other tyrosine kinase substrates from growth factor-stimulated cells.
Manual of Antibiotics and Infectious Diseases: Treatment and Prevention (2001)

AntibioticsEmpiric Antibiotic TherapyOrganism Directed TherapyAntibiotic ProphylaxisAIDS and HIV InfectionAntibiotic SusceptibilititesImmunobiologic Agents and VaccinesDrugs for Parasitic InfectionsTuberculosisSTD's and Recommendations for the Use of Hepatitis A & Hepatitis B VaccinesHIV Prevention through Early Detection and Treatmentof Other Sexually Transmitted Diseases(STD's)Hospital Epidemiology and Infection ControlInde
Inhibition of SV40 gene expression by microinjected sma antisense RNA and DNA molecules (1991)

We tested the impact of antisense RNA and DNA molecules on SV40 gene expression by microinjection into TC7 cells. Short antisense stretches, complementary to either hairpin or loop structures on the T antigen mRNA, inhibited T antigen synthesis. In contrast, full-length antisense RNA and DNA molecules did not effect T antigen synthesis.
Generation of 10.5 W, 1178 nm Laser Based on Phosphosilicate Raman Fiber Laser (2003)

The phosphorous-doped Raman fiber laser fabricated based on a Fabry-Perot cavity is demonstrated. The fiber length (L) values of 300 m and 700 m, and the reflectivity (R) values of the output fiber Bragg grating (FBG) of 15%, 30% and 50% are adopted. Under the optimum configuration of L=300 m, and R=15%, a 10.5 W, 1178 nm laser is obtained. Considering the pump power of 19.2 W, the optical-optical conversion efficiency is 54.7% and the corresponding slope efficiency is 80%. The 1178 nm light is frequency-doubled to generate 589 nm light as a source for the laser guide star (LGS) for the mesospheric sodium layer.
Formal query languages for secure relational databases (1994)

The addition of stringent security specifications to the list of requirements for an application poses many new problems in DBMS design and implementation, as well as database design, use, and maintenance. Tight security requirements, such as those that result in silent masking of witholding of true information from a user or the introduction of false information into query answers, also raise fundamental questions about the meaning of the database and the semantics of accompanying query languages. In this paper, we propose a belief-based semantics for secure databases, which provides a semantics for databases that can “lie” about the state of the world, or about their knowledge about the state of the world, in order to preserve security. This kind of semantics can be used as a helpful retrofit for the proposals for a “multilevel secure” database model (a particularly stringent form of security), and may be useful for less restrictive security policies as well. We also propose a family of query languages for multilevel secure relational database applications, and base the semantics of those languages on our semantics for secure databases. Our query languages are free of the semantic problems associated with use of ordinary SQL in a multilevel secure context, and should be easy for users to understand and employ.
Thymidine plaque autoradiography of thymidine kinase-positive and thymidine kinase-negative herpesviruses (1983)

Plaques formed by herpes simplex virus (HSV), pseudorabies virus, and varicella-zoster virus were studied by plaque autoradiography after [14C]thymidine labeling. Standard thymidine kinase-positive (TK+) viruses and TK- mutants of HSV types 1 and 2 and pseudorabies virus were studied, including cell cultured viruses and viruses isolated from animals. Autoradiography was performed with X-ray film with an exposure time of 5 days. After development of films, TK+ plaques showed dark rims due to isotope incorporation, whereas TK- plaques were minimally labeled. Plaque autoradiography of stock TK- viruses showed reversion frequencies to the TK+ phenotype of less than 10(-3). Autoradiography indicated that TK- virus retained the TK- phenotype after replication in vivo. In addition, it was shown that TK- HSV could be isolated from mouse trigeminal ganglion tissue after corneal inoculation of TK- HSV together with TK+ HSV. The plaque autoradiographic procedure was very useful to evaluate proportions of TK+ and TK- virus present in TK+-TK- virus mixtures.
4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway (1998)

Growth factors and hormones activate protein translation by phosphorylation and inactivation of the translational repressors, the eIF4E-binding proteins (4E-BPs), through a wortmannin- and rapamycin-sensitive signaling pathway. The mechanism by which signals emanating from extracellular signals lead to phosphorylation of 4E-BPs is not well understood. Here we demonstrate that the activity of the serine/threonine kinase Akt/PKB is required in a signaling cascade that leads to phosphorylation and inactivation of 4E-BP1. PI 3-kinase elicits the phosphorylation of 4E-BP1 in a wortmannin- and rapamycin-sensitive manner, whereas activated Akt-mediated phosphorylation of 4E-BP1 is wortmannin resistant but rapamycin sensitive. A dominant negative mutant of Akt blocks insulin-mediated phosphorylation of 4E-BP1, indicating that Akt is required for the in vivo phosphorylation of 4E-BP1. Importantly, an activated Akt induces phosphorylation of 4E-BP1 on the same sites that are phosphorylated upon serum stimulation. Similar to what has been observed with serum and growth factors, phosphorylation of 4E-BP1 by Akt inhibits the interaction between 4E-BP1 and eIF-4E. Furthermore, phosphorylation of 4E-BP1 by Akt requires the activity of FRAP/mTOR. FRAP/mTOR may lie downstream of Akt in this signaling cascade. These results demonstrate that the PI 3-kinase-Akt signaling pathway, in concert with FRAP/mTOR, induces the phosphorylation of 4E-BP1.
Characterization of the Calmodulin Binding Domain of SIV Transmembrane Glycoprotein by NMR and CD Spectroscopy (1995)

Recent experimental evidence has shown that the C-terminal peptide of the HIV/SIV transmembrane glycoprotein 41 (gp41) can bind very tightly to calmodulin (CaM). These findings imply a potential mechanism for HIV/SIV cytopathogenesis, which involves the uncoupling of some critical cellular signal transduction pathways that are normally mediated by CaM. Here, we present circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy studies of a 28-residue synthetic peptide, SIV-L, corresponding to the C-terminal portion of the SIV transmembrane glycoprotein gp41. CD studies recorded in aqueous solution show a dramatic increase in the amount of alpha-helical structure of the SIV-L peptide upon binding to calcium-CaM. Two-dimensional NMR experiments were performed to determine the secondary structure of the peptide in 25% aqueous trifluoroethanol solution. In this alpha-helix inducing solvent, the observed nuclear Overhauser effects, as well as the alpha 1H and alpha 13C chemical shift changes, demonstrate that a continuous alpha-helix is formed from W3 to L28, although there is some distortion around P17. This result is in accordance with those obtained for many other CaM-binding peptides. Subsequent one-dimensional NMR titration experiments of calcium-CaM and the SIV-L peptide suggest that the peptide can bind to CaM with a 1:1 stoichiometry and that the peptide binding involves both the N- and C-lobe of CaM. However, gel mobility shift assays suggest that the peptide CaM interaction may be more complicated, as oligomeric forms of CaM and the SIV-L peptide were found. These studies provide a potential molecular basis for HIV/SIV cytopathogenesis.
The efficacy of chondroitin sulfate 0.2% in treating interstitial cystitis. (2002)

Intravesical chondroitin sulfate seems to demonstrate some beneficial effects in treatment of interstitial cystitis patients who have positive potassium stimulation test results.
Transform/subband coding of speech with the lapped orthogonal transform (2003)

Efficient transform/subband signal coders can be designed using the lapped orthogonal transform (LOT). With the LOT, blocking effects in the reconstructed signal are absent, as demonstrated previously in image coding contexts. What limited the application of the LOT to a broader class of signals, including speech, was the lack of a fast LOT algorithm for large block sizes. The authors define a new version of the LOT that is fast-computable for any block size. A speech processing example demonstrates the efficiency of the LOT in reducing blocking effects.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Brief Report: Lysyl Oxidase Is a Potential Biomarker of Fibrosis in Systemic Sclerosis (2013)

This study is the first to demonstrate high serum LOX levels in SSc patients that correlate specifically with skin fibrosis. These correlations suggest that LOX levels may serve as a novel biomarker of fibrosis. Future studies are warranted to determine whether LOX is a potential therapeutic target in SSc.
Investigation of co-amplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box gene, DDX1, with N-myc in neuroblastoma. United Kingdom Children's Cancer Study Group. (1996)

Although N-myc amplification is strongly associated with a poor prognosis, not all patients with neuroblastomas having N-myc amplification fare badly. To investigate whether genes other than N-myc are responsible for contributing to the prognosis, we examined seven cell lines and 87 primary tumours for co-amplification of candidate genes known to be present near the normal N-myc locus: ornithine decarboxylase (ODC), ribonucleotide reductase (RRM2), syndecan-1 and a DEAD box protein gene, DDX1. Sequence analysis of the pG21 cDNA clone previously reported to represent an expressed gene frequently co-amplified with N-myc, showed this to be from the DDX1 gene. No co-amplification with the first three genes was found in any of the cell lines or tumour samples. DDX1, however was found to be amplified along with N-myc in 4/6 (67%) cell lines and 6/16 (38%) of the N-myc amplified tumours. Co-amplification of DDX1 and N-myc was found more frequently in stage 4 or 4S tumours than lower stage (1-3) tumours. With the exclusion of a single 4S case, there was a highly significant reduction in the mean disease-free interval from 24.4 +/- 4.7 (SE, n = 10) months for cases with co-amplification of N-myc and DDX1 compared with 9.2 +/- 1.8 (SE, n = 5) months for those cases showing amplification of N-myc alone (P = 0.0056, Welch's unpaired t-test). No amplification of DDX1, ODC, RRM2, or syndecan-1 was found in the absence of N-myc amplification. These observation indicate that the N-myc amplicon is of varied size and/or position relative to the N-myc gene, with DDX1 representing at least one other gene frequently co-amplified with N-myc. Further studies are required to confirm the biological and prognostic significance of DDX1 co-amplification and to elucidate the role that DDX1 plays in tumour genesis and progression.
A phylogenetic analysis of the mycoplasmas: basis for their classification (1989)

Small-subunit rRNA sequences were determined for almost 50 species of mycoplasmas and their walled relatives, providing the basis for a phylogenetic systematic analysis of these organisms. Five groups of mycoplasmas per se were recognized (provisional names are given): the hominis group (which included species such as Mycoplasma hominis, Mycoplasma lipophilum, Mycoplasma pulmonis, and Mycoplasma neurolyticum), the pneumoniae group (which included species such as Mycoplasma pneumoniae and Mycoplasma muris), the spiroplasma group (which included species such as Mycoplasma mycoides, Spiroplasma citri, and Spiroplasma apis), the anaeroplasma group (which encompassed the anaeroplasmas and acholeplasmas), and a group known to contain only the isolated species Asteroleplasma anaerobium. In addition to these five mycoplasma groups, a sixth group of variously named gram-positive, walled organisms (which included lactobacilli, clostridia, and other organisms) was also included in the overall phylogenetic unit. In each of these six primary groups, subgroups were readily recognized and defined. Although the phylogenetic units identified by rRNA comparisons are difficult to recognize on the basis of mutually exclusive phenotypic characters alone, phenotypic justification can be given a posteriori for a number of them.
Phase I Study of Tirapazamine Plus Cisplatin/Etoposide and Concurrent Thoracic Radiotherapy in Limited-Stage Small Cell Lung Cancer (S0004) (2004)

Protocol-defined dose-limiting toxicity was observed at the initial tirapazamine dose, precluding dose escalation. Compared with S9713, the addition of tirapazamine increased the incidence of vomiting, neutropenia, and febrile neutropenia, although the overall toxicity profile remained acceptable. In view of the observed favorable survival, further study of tirapazamine in LSCLC is warranted.
Synthetic Molecules as Antibody Replacements (2004)

Antibodies are by far the most versatile, valuable, and widely used protein-binding agents. They are essential tools in biological research and are increasingly being developed as therapeutic reagents. However, antibodies have a number of practical limitations, and it would be desirable in many applications to replace them with simpler, more robust synthetic molecules. Unfortunately, synthetic protein-binding agents rarely exhibit the high affinity and specificity typical of a good antibody. This article reviews efforts to overcome these limitations and to develop a facile, high-throughput methodology for the isolation of synthetic protein ligands with antibody-like binding characteristics.
Receptor tyrosine kinase inhibitors: Are they real tumor killers? (2015)

Inhibiting tumor growth by targeting the tumor vasculature was first proposed by Judah Folkman almost 40 years ago. Since then, different approaches and numerous drugs and agents have been developed to achieve this goal, either with the aim of inhibiting tumor neoangiogenesis or normalizing the tumor vasculature. Among the most promising therapeutic targets are receptor tyrosine kinases (RTKs), some of which are predominantly expressed on tumor endothelial cells, although they are sometimes also present on tumor cells. The majority of RTK inhibitors investigated over the past two decades competes with ATP at the active site of the kinase and therefore block the phosphorylation of intracellular targets. Some of these drugs have been approved for therapy, whereas others are still in clinical trials. Here, we discuss the scientific basis, current status, problems and future prospects of RTK inhibition in anti-tumor therapy.
Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist (2020)

Interleukin-2 (IL-2) is a component of most protocols of adoptive cell transfer (ACT) therapy for cancer, but is limited by short exposure and high toxicities. NKTR-214 is a kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting of IL-2 conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported by NKTR-214 increases the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in a B16-F10 murine melanoma model. The use of NKTR-214 increases the number of polyfunctional T cells in murine spleens and tumors compared to IL-2, and enhances the polyfunctionality of T and NK cells in the peripheral blood of patients receiving NKTR-214 in a phase 1 trial. In conclusion, NKTR-214 may have the potential to improve the antitumor activity of ACT in humans through increased in vivo expansion and polyfunctionality of the adoptively transferred T cells.
Nonpreserved Human Amniotic Membrane Transplantation in Acute and Chronic Chemical Eye Injuries (2002)

AMT with nonpreserved amniotic membrane promoted epithelial healing, reduced surface inflammation, increased patient comfort, and decreased the extent and severity of vascularization when used in patients with acute chemical burns. When used in limbal stem cell deficiency owing to past chemical burns, AMT alone or in combination with LAT aided in ocular surface reconstruction. Infectious, inflammatory, or toxic/allergic reactions were not encountered in any patient owing to the use of nonpreserved amniotic membrane. Further studies are required to establish the safety and efficacy of preserved and nonpreserved AMT in ocular surface reconstruction.
Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes (2012)

In obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results. (Funded by Ethicon Endo-Surgery and others; ClinicalTrials.gov number, NCT00432809.).
A Design Procedure for All-Digital Phase-Locked Loops Based on a Charge-Pump Phase-Locked-Loop Analogy (2007)

In this brief, a systematic design procedure for a second-order all-digital phase-locked loop (PLL) is proposed. The design procedure is based on the analogy between a type-II second-order analog PLL and an all-digital PLL. The all-digital PLL design inherits the frequency response and stability characteristics of the analog prototype PLL