gebhart/patrepeval huggingface dataset:
Identification and characterization of glucagon‐like peptide‐1 7–36 amide‐binding sites in the rat brain and lung (1988)

High-affinity binding sites for glucagon-like peptide-1 7-36 amide (GLP-1 7-36 NH2) were identified in rat brain and lung membranes. Binding of [125I]GLP-1 7-36 NH2 was rapid, reversible, specific, saturable and pH dependent. Specific binding in the central nervous system was particularly high in the hypothalamus and the brain stem. Oxyntomodulin, glucagon-like peptide-1, glucagon-like peptide-2 and glucagon were 100-1000-fold less potent than GLP-1 7-36 NH2 in competition for this binding site.
ALTERATIONS IN GLYCOSYLTRANSFERASES DURING MYELOID AND MONOCYTOID DIFFERENTIATION OF HL‐60 CELLS (1998)

HL-60, a human promyelocytic leukemia cell line, can be differentiated to myeloid lineage by all- trans retinoic acid (ATRA), dimethylsulfoxide (DMSO) and n -butyric acid (n -BA), or to monocytoid(monocytic/macrophagic) lineage by phorbol-12-myristate-13-acetate (PMA) and ganglioside GM(3). The activity alterations of N -acetylglucosaminyltransferase III and V (GnT-III, GnT-V) as well as alpha-1,6-fucosyl-tranferase (alpha1,6 Fuc T) were studied during the differentiation of HL-60 cells by the above-mentioned five inducers using the fluorescence (PA)-labeled glycan-HPLC method for GnT assays and biotin-labeled glycan-LCA affinity chromatography combined with the HRP-avidin colorimetric method for alpha1,6 Fuc T assay. It was observed that after 3 days, all three enzymes decreased in HL-60 cells induced by 1 micromol/l ATRA and 0.6 mmol/l n-BA, while GnT-III and alpha1,6 Fuc T increased, but GnT-V still decreased after induction by 1% DMSO. GnT-V and alpha1,6 Fuc T declined, while GnT-III was elevated after induction by 0.1 micromol/l PMA for 3 days. In contrast, GnT-III increased after the treatment with 50 micromol/l GM(3)for 3 or 6 days, but GnT-V was not appreciably changed and alpha1,6 FucT was elevated after 6 days of GM(3)treatment. It may be concluded that the decrease of GnT-V is the common change in myeloid differentiation and the increase of GnT-III is the general alteration in monocytoid differentiation. The changes in the activities of glycosyltransferases were consistent with the structural changes in surface N -glycans previously found in our laboratory, i.e. that the antennary number of N -glycans decreased during myeloid differentiation by ATRA, and the amount of bisecting GlcNAc in N -glycans increased during monocytoid differentiation by PMA.
[Clinical study of termination of early pregnancy by combination of dl-15-methyl-prostaglandin F2 alpha and RU 486]. (1993)

In order to study the appropriate dosage in using RU 486 for induced abortion, 80 women of or = 49 days of pregnancy were randomly assigned to 3 groups. 20 women in Group I took 175 mg of RU486 in 3 1/2 days and were given 1 mg injection of prostaglandin (PG) on the 4th day. 20 women in Group II took the same amount of RU486 as group I and were given 0.5 mg of PG injection on the 4th day. 40 women in Group III took 100 mg of RU486 in 2 days and were given 0.5 mg of PG on the 3rd day. The duration of induced abortion and bleeding and the side effects were observed. The outcome of induced abortion was classified as complete abortion, incomplete abortion, and failure. No failures occurred. About 95% of the women in each group had a complete abortion, and the differences among the 3 groups were not statistically significant. Those who had an incomplete abortion received a medical abortion. A small number of women experienced the side effects of dizziness, nausea, vomiting, and diarrhea. Compared with studies with a similar proportion of complete abortion, the dosage of RU486 in this study is 2-4 times smaller, and the dosage of PG is also reduced by 5 to 14 times that used in earlier studies. Signs of incomplete abortion should be closely observed, and action should be taken to avoid excessive bleeding or infection. Drug-induced abortion is gradually gaining acceptance; nevertheless, appropriate medical attention is necessary to guard against complications.
Interleukin-6 Stimulates LDL Receptor Gene Expression via Activation of Sterol-Responsive and Sp1 Binding Elements (2000)

Inflammatory or malignant diseases are associated with elevated levels of cytokines and abnormal low density lipoprotein (LDL) cholesterol metabolism. In the acute-phase response to myocardial injury or other trauma or surgery, total and LDL cholesterol levels are markedly decreased. We investigated the effects of the proinflammatory cytokine interleukin (IL)-6 on LDL receptor (LDL-R) function and gene expression in HepG2 cells. IL-6 dose-dependently increased the binding, internalization, and degradation of (125)I-LDL. IL-6-stimulated HepG2 cells revealed increased steady-state levels of LDL-R mRNA. In HepG2 cells transiently transfected with reporter gene constructs harboring the sequence of the LDL-R promoter extending from nucleotide -1563 (or from nucleotide -234) through -58 relative to the translation start site, IL-6 dose-dependently increased promoter activity. In the presence of LDL, a similar relative stimulatory effect of IL-6 was observed. Studies using a reporter plasmid with a functionally disrupted sterol-responsive element (SRE)-1 revealed a reduced stimulatory response to IL-6. In gel-shift assays, nuclear extracts of IL-6-treated HepG2 cells showed an induced binding of SRE binding protein (SREBP)-1a and SRE binding protein(SREBP)-2 to the SRE-1 that was independent of the cellular sterol content and an induced binding of Sp1 and Sp3 to repeat 3 of the LDL-R promoter. Our data indicate that IL-6 induces stimulation of the LDL-R gene, resulting in enhanced gene transcription and LDL-R activity. This effect is sterol independent and involves, on the molecular level, activation of nuclear factors binding to SRE-1 and the Sp1 binding site in repeat 2 and repeat 3 of the LDL-R promoter, respectively.
Federated Authentication and Authorisation in the Social Science Domain (2011)

The use of Shibboleth as a mechanism for implementing federated authentication is commonplace in many countries. The ability of Shibboleth to transmit extra information about a user, including licenses, roles and other attributes, is not exploited for many reasons, mainly because institional Identity Providers (IdPs) are not maintainable sources of fine grained authorisation information. The JlSC-funded Shintau project has produced an extension to the Shibboleth profile which allows a user to link information from more than one IdP together utilising a custom Linking Service (LS). This paper describes both the application and independent evaluation of this software by the National e-Science Centre (NeSC) at the University of Glasgow within the context of the ESRC-funded Data Management through e-Social Science (DAMES) project.
Developing MicroRNA Therapeutics (2012)

Rarely a new research area has gotten such an overwhelming amount of attention as have microRNAs. Although several basic questions regarding their biological principles still remain to be answered, many specific characteristics of microRNAs in combination with compelling therapeutic efficacy data and a clear involvement in human disease have triggered the biotechnology community to start exploring the possibilities of viewing microRNAs as therapeutic entities. This review serves to provide some general insight into some of the current microRNAs targets, how one goes from the initial bench discovery to actually developing a therapeutically useful modality, and will briefly summarize the current patent landscape and the companies that have started to explore microRNAs as the next drug target.
Hollow Metal Microneedles for Insulin Delivery to Diabetic Rats (2005)

The goal of this study was to design, fabricate, and test arrays of hollow microneedles for minimally invasive and continuous delivery of insulin in vivo. As a simple, robust fabrication method suitable for inexpensive mass production, we developed a modified-LIGA process to micromachine molds out of polyethylene terephthalate using an ultraviolet laser, coated those molds with nickel by electrodepostion onto a sputter-deposited seed layer, and released the resulting metal microneedle arrays by selectively etching the polymer mold. Mechanical testing showed that these microneedles were sufficiently strong to pierce living skin without breaking. Arrays containing 16 microneedles measuring 500 microm in length with a 75 microm tip diameter were then inserted into the skin of anesthetized, diabetic, hairless rats. Insulin delivery through microneedles caused blood glucose levels to drop steadily to 47% of pretreatment values over a 4-h insulin delivery period and were then approximately constant over a 4-h postdelivery monitoring period. Direct measurement of plasma insulin levels showed a peak value of 0.43 ng/ml. Together, these data suggest that microneedles can be fabricated and used for in vivo insulin delivery.
Collection of Sputum for Cytologic Examination (1960)

A PREREQUISITE for the successful detection of cancer cells in sputum is an adequate specimen, the microscopical criterion for which is the presence of alveolar histiocytes ("dust" cells). Although most patients with disease of the lower respiratory tract cough, their sputum may consist only of saliva, oral squamous cells, mouth organisms and food particles. Other specimens, especially first morning sputum, consist of "postnasal drip" that accumulated during the night and is characterized microscopically by mucopurulent exudate, with or without large ciliated columnar cells from the upper respiratory passages.Most patients who have lung disease can produce suitable specimens after adequate . . .
Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization (2017)

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit.
Clonal V alpha 12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients. (1993)

Rheumatoid arthritis (RA) represents a heterogenous disease characterized by chronic polyarthritis. Most patients with adult RA inherit HLA-DR4 or -DR1 major histocompatibility complex (MHC) genes. While the molecular basis for this genetic predisposition is unknown, the major function of these MHC-encoded molecules is to present peptides to T lymphocytes. It is hypothesized that an endogenous or environmental antigen initiates a MHC-restricted immune response mediated by T lymphocytes, which is followed by a chronic inflammatory reaction involving many cell types. In chronic RA, previous or ongoing antigenic activation might result in detectable skewing of the peripheral alpha/beta T cell receptor (TCR) repertoire. Here we demonstrate a marked expansion of V alpha 12.1-bearing CD8+ T cells in the peripheral blood (mean, 22%; range, 10-43%) of > 15% of RA patients. A major proportion of these patients shared HLA-DQ2 in addition to the expected high frequency DR1 and DR4 alleles. Detailed molecular analysis in three of the RA patients with elevated V alpha 12.1+ T cells identified repeated TCR alpha chain sequences consistent with clonal V alpha 12.1+,CD8+ T cell expansion. In addition to shared TCR V alpha 12.1 germline gene usage among unrelated subjects, a conserved J alpha motif was also detected. Together, these results suggest an antigen-driven mechanism of T cell expansion in these patients and may offer a new approach in examining specific antigen that stimulate T cells in RA.
Structural characterization of gelonin: evidence for separate antigenic and cytotoxic domains. (1993)

The N-terminal sequence of the three isoforms of gelonin is identical. Cyanogen bromide cleavage of gelonin produced fragments of Mr 17,000, 13,000, 11,000 and 7,000. The apparent Mr 17,000 component was identified as the N-terminal fragment and represents the major antigenic domain of the protein as it reacted with antibody to the native protein but this fragment did not inhibit protein synthesis in the in vitro translation assay. Our data may suggest possibilities for separation of antigenic and catalytic domains of this ribosome inactivating protein.
Practical medical applications of quantitative MR relaxometry (2012)

Conventional MR images are qualitative, and their signal intensity is dependent on several complementary contrast mechanisms that are manipulated by the MR hardware and software. In the absence of a quantitative metric for absolute interpretation of pixel signal intensities, one that is independent of scanner hardware and sequences, it is difficult to perform comparisons of MR images across subjects or longitudinally in the same subject. Quantitative relaxometry isolates the contributions of individual MR contrast mechanisms (T1, T2, T2) and provides maps, which are independent of the MR protocol and have a physical interpretation often expressed in absolute units. In addition to providing an unbiased metric for comparing MR scans, quantitative relaxometry uses the relationship between MR maps and physiology to provide a noninvasive surrogate for biopsy and histology. This study provides an overview of some promising clinical applications of quantitative relaxometry, followed by a description of the methods and challenges of acquiring accurate and precise quantitative MR maps. It concludes with three case studies of quantitative relaxometry applied to studying multiple sclerosis, liver iron, and acute myocardial infarction.
Electronic structure calculations of doped organic materials for electroluminescent devices (1997)

Recent very promising fabrication advances in organic light emitting diodes have brought out the need for a microscopic understanding of the interaction of light emitters, hole blockers, hole transporters, dopants, and their electroluminescence. We report exploratory quantum calculations on spectra with and without the presence of an external electric field, with different “guest-host” arrangements of emitter and dopant molecules. These calculations, when suitably extended, could be used for predictive optimization of candidate materials, and for the design of optimal layer-structure and layer-ordering etc., in diodes and other proposed structures. The molecules studied are: Scandium 8-hydroxyquinoline as the light emitter, a 1,2,4-triazole molecule as a typical hole blocker, and triphenyl diamine derivatives as hole transporters. The dopant or “guest” molecule was selected to be Nile Red. Studies on the use of a highly conjugated system such as C60 as an element of layer structure are also presented here. The results give an insight into the physical processes at the molecular level and provide guidance in designing optimized material for use in “organic” light emitting diodes.
Suppressed circadian heart rate dynamics in temporal lobe epilepsy (2005)

TLE was associated with reduced HR variability, which was more pronounced during night than day, and the nocturnal increase in HR variability was abolished in patients with TLE. The alteration in autonomic regulation of HR variability was similar in patients with both refractory and well controlled TLE.
T Cell Receptor Internalization from the Immunological Synapse is Mediated by TC21 and RhoG GTPase-Dependent Phagocytosis (2011)

The immunological synapse (IS) serves a dual role for sustained T cell receptor (TCR) signaling and for TCR downregulation. TC21 (Rras2) is a RRas subfamily GTPase that constitutively associates with the TCR and is implicated in tonic TCR signaling by activating phosphatidylinositol 3-kinase. In this study, we demonstrate that TC21 both co-translocates with the TCR to the IS and is necessary for TCR internalization from the IS through a mechanism dependent on RhoG, a small GTPase previously been associated with phagocytosis. Indeed, we found that the TCR triggers T cells to phagocytose 1-6 μm beads through a TC21- and RhoG-dependent pathway. We further show that TC21 and RhoG are necessary for the TCR-promoted uptake of major histocompatibility complex (MHC) from antigen presenting cells. Therefore, TC21- and RhoG-dependence underlie the existence of a common phagocytic mechanism that drives TCR internalization from the IS together with its peptide-MHC ligand.
Structure of 3,4-Dichloroisocoumarin-Inhibited Factor D (1998)

Factor D (D) is a serine protease essential in the activation of the alternative complement pathway. Only a few of the common serine protease inhibitors inhibit D, binding covalently to the serine hydroxyl of the catalytic triad. 3,4-Dichloroisocoumarin (DCI) is a mechanism-based inhibitor which inhibits most serine proteases and many esterases, including D. The structure of the enzyme:inhibitor covalent adduct of D with DCI, DCI:D, to a resolution of 1.8 A is described, which represents the first structural analysis of D with a mechanism-based inhibitor. The side chain of the ring-opened DCI moiety of the protein adduct undergoes chemical modification in the buffered solution, resulting in the formation of an alpha-hydroxy acid moiety through the nucleophilic substitution of both Cl atoms. The inhibited enzyme is similar in overall structure to the native enzyme, as well as to a variety of isocoumarin-inhibited trypsin and porcine pancreatic elastase (PPE) structures, yet notable differences are observed in the active site and binding mode of these small-molecule inhibitors. One region of the active site (residues 189-195) is relatively conserved between factor D, trypsin, and elastase with respect to amino-acid sequence and to conformation. Another region (residues 214-220) reflects the amino-acid substitutions and conformational flexibility between these enzymes. The carbonyl O atom of the DCI moiety was found to be oriented away from the oxyanion hole, which greatly contributes to the stability of the DCI:D adduct. The comparisons of the active sites between native factor D, DCI-inhibited factor D, and various inhibited trypsin and elastase (PPE) molecules are providing the chemical bases directing our design of novel, small-molecule pharmaceutical agents capable of modulating the alternative complement pathway.
Reverse transcriptase and its associated ribonuclease H: interplay of two enzyme activities controls the yield of single-stranded cDNA (1983)

The synthesis of single-stranded globin cDNA by the RNA-directed DNA polymerase activity of reverse transcriptase in the presence of oligothymidylate primers was investigated in order to determine the limitations to higher yields. The results indicated that the associated ribonuclease H activity, an integral part of reverse transcriptase, plays a large role in the synthesis of the first strand of cDNA and that the interplay of the two enzyme activities for any specific set of conditions determines the yield of single-stranded products. In both the presence and the absence of polymerization, the associated ribonuclease H catalyzed the deadenylation of mRNA, producing molecules that were somewhat shorter, highly homogeneous in size, and fully translatable into globin protein. They were also entirely lacking in the ability to serve as templates for cDNA synthesis. The reaction was completely dependent on oligothymidylate and completely independent of deoxyribonucleoside triphosphates. The initial rate of deadenylation was one-fourth the initial rate of initiation of polymerization when saturating levels of deoxyribonucleoside triphosphates were used in the polymerase reaction. In the presence of ribonuclease H activity, the DNA polymerase catalyzed the synthesis of an array of cDNAs including some that were full length. The initiation of polymerization was rate limiting: once synthesis had begun, it required 1-1.5 min to transcribe globin mRNA. However, most primers that were elongated were aborted prematurely. Maximum synthesis of full-length cDNA required stoichiometric levels of enzyme and high triphosphate levels, but regardless of conditions, the sum of completed cDNA and deadenylated mRNA accounted for only 50% of the input mRNA. The data fit a model in which synthesis of full-length cDNA molecules depends on the arrangement of primers and transcription initiation complexes on the poly(A) "tail" of mRNA.
PROGRAM OVERVIEW: RUN-OFF-ROAD COLLISION AVOIDANCE USING IVHS COUNTERMEASURES (1996)

The Run-Off-Road Collision Avoidance Using IVHS Countermeasures program is a four year program sponsored by the National Highway Traffic Safety Administration (NHTSA). The prime contractor for this effort is Carnegie Mellon University (CMU). The primary goal of the program is to develop practical performance specifications for roadway departure collision avoidance systems. The program is divided into three phases. Phase I was recently completed, and involved analyzing the roadway departure crash population, identifying opportunities for intervention, testing existing systems for preventing roadway departure crashes, and developing mathematical models of potential countermeasure systems and using these models to develop preliminary performance specifications. Phase II consists of two primary activities: reviewing state-of-the-art sensing, processing and driver interface technologies for their applicability to run-off-road collision prevention, and designing an advanced testbed vehicle for evaluating alternative countermeasures. Phase III will involve constructing the testbed, conducting and documenting tests of alternative countermeasure systems, and developing and publishing technology independent performance specifications for roadway departure collision avoidance systems based on test results. This paper provides information on run-off-road problem characterization, countermeasure functional goals, tests of existing technology, mathematical modeling, and preliminary performance specifications.