gebhart/patrepeval huggingface dataset:
Preferential dependence of autoantibody production in murine lupus on CD86 costimulatory molecule (1995)

Blockade of the interactions between CD28/CTLA-4 and their ligands, CD80 (B7, B7.1)/CD86 (B70, B7.2), seems an attractive means to induce antigen-specific peripheral tolerance in organ transplantation and autoimmune disease. Recently, diversities between CD80 and CD86 in expression, regulation, and function have been reported in certain cell populations and murine experimental disease models. To investigate the possible differential role of CD80 and CD86 in the development of lupus, we treated lupus-prone NZB/W F1 mice with specific monoclonal antibodies (mAb) against CD80, CD86, or both. The treatment with a combination of anti-CD80 and CD86 mAb before the onset of lupus completely prevented autoantibody production and nephritis, and prolonged survival. Interestingly, we found that anti-CD86 mAb alone, but not anti-CD80 mAb, efficiently inhibited autoantibody production. Subclass study on IgG anti-double-stranded (ds) DNA antibody revealed that the treatment with anti-CD86 mAb almost completely inhibited both IgG1 and IgG2b, but not IgG2a production. The incomplete reduction of IgG2a anti-dsDNA antibody by anti-CD86 mAb was compensated by the addition of anti-CD80 mAb. A significant reduction of mRNA for interleukin (IL)-2, interferon-gamma, IL-4 and IL-6 was observed in mice treated with a combination of anti-CD80 and CD86 mAb or anti-CD86 mAb alone. Treatment with both mAb after the onset of lupus resulted in a significantly prolonged survival with reduction of autoantibody production. These results suggest that CD86 plays a more critical role in autoantibody production, and CD86, but not CD80, contributes to Th2-mediated Ig production. However, the blockade of both CD80 and CD86 are required for preventing the development and progression of lupus.
A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene (2006)

The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.
Photochromotropic behaviour of 2-(2?,4?-dinitrobenzyl)-pyridine (1960)

The first page of this article is displayed as the abstract.
Total Synthesis and Biological Evaluation of a Series of Macrocyclic Hybrids and Analogues of the Antimitotic Natural Products Dictyostatin, Discodermolide, and Taxol (2010)

The design, synthesis, and biological evaluation of a series of hybrids and analogues of the microtubule-stabilizing anticancer agents dictyostatin, discodermolide, and taxol is described. A 22-membered macrolide scaffold was prepared by adapting earlier synthetic routes directed towards dictyostatin and discodermolide, taking advantage of the distinctive structural and stereochemical similarities between these two polyketide-derived marine natural products. Initial endeavors towards accessing novel discodermolide/dictyostatin hybrids led to the adoption of a late-stage diversification strategy and the construction of a small library of methyl-ether derivatives, along with the first triple hybrids bearing the side-chain of taxol or taxotere attached through an ester linkage. Biological assays of the anti-proliferative activity of these compounds in a series of human cancer cell lines, including the taxol-resistant NCI/ADR-Res cell line, allowed the proposal of various structure-activity relationships. This led to the identification of a potent macrocyclic discodermolide/dictyostatin hybrid 12 and its C9 methoxy derivative 38, accessible by an efficient total synthesis and with a similar biological profile to dictyostatin.
Overexpression of the Protien Tyrosine Phosphatase PTP1B in Human Breast Cancer: Assocation With p185c-erbB-2 Protein Expression (1994)

Further studies are needed to determine if PTP1B overexpression balances or augments PTK activity. PTP1B overexpression might also be evaluated as a clinical prognostic factor in human breast cancers.
Effects of substrate conductivity on cell morphogenesis and proliferation using tailored, atomic layer deposition-grown ZnO thin films (2015)

We demonstrate that ZnO films grown by atomic layer deposition (ALD) can be employed as a substrate to explore the effects of electrical conductivity on cell adhesion, proliferation, and morphogenesis. ZnO substrates with precisely tunable electrical conductivity were fabricated on glass substrates using ALD deposition. The electrical conductivity of the film increased linearly with increasing duration of the ZnO deposition cycle (thickness), whereas other physical characteristics, such as surface energy and roughness, tended to saturate at a certain value. Differences in conductivity dramatically affected the behavior of SF295 glioblastoma cells grown on ZnO films, with high conductivity (thick) ZnO films causing growth arrest and producing SF295 cell morphologies distinct from those cultured on insulating substrates. Based on simple electrostatic calculations, we propose that cells grown on highly conductive substrates may strongly adhere to the substrate without focal-adhesion complex formation, owing to the enhanced electrostatic interaction between cells and the substrate. Thus, the inactivation of focal adhesions leads to cell proliferation arrest. Taken together, the work presented here confirms that substrates with high conductivity disturb the cell-substrate interaction, producing cascading effects on cellular morphogenesis and disrupting proliferation, and suggests that ALD-grown ZnO offers a single-variable method for uniquely tailoring conductivity.
Near‐IR spectroscopic imaging for skin hydration: The long and the short of it (2002)

Near-IR spectroscopic methods have been developed to determine the degree of hydration of human skin in vivo. Noncontact reflectance spectroscopic imaging was used to investigate the distribution of skin moisture as a function of location. A human study in a clinical setting has generated quantitative data showing the effects of a drying agent and a moisturizer on delineated regions of the forearms of eight volunteers. Two digital imaging systems equipped with liquid-crystal tunable filters were used to collect stacks of monochromatic images at 10-nm intervals over the 650-1050 and 960-1700 nm wavelength bands. Synthetic images generated from measurements of water absorption band areas at three different near-IR wavelengths (970, 1200, and 1450 nm) showed obvious differences in the apparent distribution of water in the skin. Changes resulting from the skin treatments were much more evident in the long-wavelength images than in the short-wavelength ones. The variable sensitivity of the method at different wavelengths has been interpreted as being the result of different penetration depths of the IR light used in the reflectance studies.
Antibiotic magainins exert cytolytic activity against transformed cell lines through channel formation. (1991)

Magainins are an ionophoric class of vertebrate peptides with antibiotic activity against various microorganisms. Here we show that magainin 2 and synthetic analogues can rapidly and irreversibly lyse hematopoietic tumor and solid tumor target cells with a relative cytotoxic potency that parallels their antibacterial efficacy and at concentrations that are relatively nontoxic to well-differentiated cells. The cytotoxicity is prevented by cell depolarization. Magainins represent a natural cytolytic agent in vertebrates and may provide another therapeutic strategy for certain tumors.
Colour coded duplex sonography in suspected deep vein thrombosis of the leg. (1990)

Left: Oblique view of lumbar spine showing LI, L2, L4, and L5 vertebrae with vestiges of posterior elements ofL3 (arrowed). Note codfish appearance ofL2, L4, and LS. Right: lateral view oflumbar spine showing narrowing ofdisc spaces ofT12 and L I and kyphos between L2 and L4, pseudo-Schmorl's nodes at upper and lower surfaces of T12
Analysis of Minor Hysteresis Loops of Cold Rolled Low Carbon Steel (2006)

Minor hysteresis loops of cold rolled low carbon steel have been analyzed in connection with the rolling reduction. We found several simple relations between parameters of minor loops and obtained minor-loop properties that are independent of magnetic field amplitude and magnetic field. The properties increase with increasing rolling reduction and are in proportion to coercive force of the major loop. The present analysis method using minor loops can be applied to quantitative nondestructive evaluation of dislocation density in ferromagnetic materials
A Regulatory Role for RIP140 in Nuclear Receptor Activation (1998)

Transcriptional regulation of gene expression by nuclear receptors requires negatively and positively acting cofactors. Recent models for receptor activation propose that certain receptors in the absence of ligands can recruit corepressors while ligand binding results in conformational changes leading to the recruitment of coactivators. Previous work has established a coactivator role for the SRC-1 family members as well as an involvement of the coactivators CBP/p300 in nuclear receptor signaling. However, in addition to coactivators, ligand-activated nuclear receptors bind a number of different proteins that possibly serve other functions. Using peroxisome proliferator-activated receptor-α (PPARα) as bait in a yeast two-hybrid screening, we have isolated nuclear factor RIP140 whose function in receptor activation is unclear. We now report a detailed characterization of RIP140 action with a focus on the retinoid X receptor (RXR) heterodimeric receptors PPAR and thyroid hormone receptor (TR). We show that putative PPAR ligands enhance the interaction of RIP140 with the rat PPAR subtypes α and γ in solution but not with PPAR/RXR heterodimers on DNA. However, RIP140 forms ternary complexes in the presence of RXR ligands. Similar experiments with TR support the high affinity of RIP140 to the RXR subunit and also suggest that either partner in the TR/RXR heterodimer can independently respond to ligand. Coactivation experiments in yeast and mammalian cells confirm the coactivator role for SRC-1, but not for RIP140. We provide important evidence that the in vitro binding of RIP140 and SRC-1 to nuclear receptors is competitive. Since RIP140 generally down-regulates receptor activity in mammalian cells and specifically down-regulates coactivation mediated by SRC-1, we propose a model in which RIP140 indirectly regulates nuclear receptor AF-2 activity by competition for coactivators such as SRC-1.
Efficient Bioconjugation of Protein Capture Agents to Biosensor Surfaces Using Aniline-Catalyzed Hydrazone Ligation (2010)

Aniline-catalyzed hydrazone ligation between surface-immobilized hydrazines and aldehyde-modified antibodies is shown to be an efficient method for attaching protein capture agents to model oxide-coated biosensor substrates. Silicon photonic microring resonators are used to directly evaluate the efficiency of this surface bioconjugate reaction at various pHs and in the presence or absence of aniline as a nucleophilic catalyst. It is found that aniline significantly increases the net antibody loading for surfaces functionalized over a pH range from 4.5 to 7.4, allowing derivatization of substrates with reduced incubation time and sample consumption. This increase in antibody loading directly results in more sensitive antigen detection when functionalized microrings are employed in a label-free immunoassay. Furthermore, these experiments also reveal an interesting pH-dependent noncovalent binding trend that plays an important role in dictating the amount of antibody attached onto the substrate, highlighting the competing contributions of the bioconjugate reaction rate and the dynamic interactions that control opportunities for a solution-phase biomolecule to react with a substrate-bound reagent.
Military geology in war and peace (1998)

Abstract In warfare military geologists pursue five main categories of work: tactical and strategic terrain analysis, fortifications and tunneling, resource acquisition, defense installations, and field construction and logistics. In peace they train for wartime operations and may be involved in peace-keeping and nation-building exercises. Although many geologists view military geology as a branch of engineering geology, the U.S. military does not include geologists in its force structure and gets geological assistance on an ad hoc basis. The army does, however, include organic terrain teams at division and higher levels to provide routine information for mission planning and execution. The classic dilemma for military geology has been whether support can best be provided by civilian technical-matter experts or by uniformed soldiers who routinely work with the combat units.
Subsurface Mapping and Seismic Modeling from Resistivity Data to Tie Locally Productive Formations of the Wilcox Group in LaSalle Parish, Louisiana to a High-Resolution Shallow Imaging Seismic Dataset (2018)

Located in LaSalle Parish, Louisiana, the area of interest for this study encompasses portions of the Tullos-Urania and Olla oil fields, with their hydrocarbon accumulation stemming from the Wilcox Group. The overall objective of this study is threefold; first, generate structure maps of the strata within this area of investigation and identify the productive formations. Second, utilize seismic modeling from local wells defining the most accurate resistivity-to-sonic transform. The last goal is to generate an accurate seismic-to-well tie employing the most accurate sonic log generated at the wells bounding the high-resolution shallow imaging seismic data. This study must use resistivity data to model sonic logs for the bounding wells which have no sonic logs available. The modeled sonic logs are then used to create time- depth relationships between the acquired seismic data and the wells bounding the seismic line. To use resistivity logs to model a sonic log, this study will compare three equations (Faust, 1953; Kim, 1964; Smiths, 1968) to determine their relative accuracies for a one-step resistivity-to-sonic transform. Accuracy is measured by the absolute average deviation of the modelled sonic data from the measured sonic data from wells within the study area, but distant from the seismic line, which have recorded sonic logs. The results of this study indicate that the one-step resistivity-to- sonic equation proposed by Faust (1953) generates the least amount of error when applied to the short resistivity curve. Throughout the modeled logs, the Faust (1953) equation generates an absolute average deviation of 6.0% for the short resistivity curves while Kim’s (1964) and Smiths (1968) equations produce 9.7% and 12.8% absolute average deviation. By understanding the variability of these models, future studies can ascertain the best fit model for further investigation of shallow hydrocarbon bearing formations within, or similar to, the Paleocene-Eocene aged strata in Central Louisiana.
Intracellular expression of human immunodeficiency virus type 1 (HIV-1) protease variants inhibits replication of wild-type and protease inhibitor-resistant HIV-1 strains in human T-cell lines (1996)

The enzymatic activity of the human immunodeficiency type 1 (HIV-1) protease (PR) is crucial to render HIV-1 virions mature and infectious. Hence, genetic intervention strategies based on trans-dominant (td) variants of the HIV-1 PR might be an alternative to current pharmacological and gene therapy regimens for AIDS. CD4-positive human CEM-SS T-cell lines were generated which constitutively expressed HIV-1 td PR variants. HIV-1 infection experiments demonstrated severely reduced HIV-1 replication in these td PR CEM-SS cell lines compared with control T cells expressing wild-type PR. Furthermore, replication of an HIV-1 isolate bearing a PR inhibitor-resistant PR was blocked, showing that genetic intervention strategies based on td PRs can be effective against HIV-1 isolates containing PR inhibitor-resistant mutants.
Advanced or Metastatic Pancreatic Cancer: Molecular Targeted Therapies (2010)

Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat. However, clinical developments over the past decade have been modest and advances are incremental at most. The core drug and the backbone of treatment in all settings of pancreatic adenocarcinoma-adjuvant, locally advanced, and metastatic-remains gemcitabine. The past decade of research focused initially on combining cytotoxic therapies with gemcitabine, and during that time a large number of studies have been published that aimed to target the molecular abnormalities implicated in pancreatic tumor growth, invasion, metastasis, angiogenesis, and resistance to apoptosis. This research is of particular importance, as data suggest that a large number of genetic alterations affect only a few major signaling pathways and processes involved in pancreatic tumorigenesis. Although laboratory results of targeted therapies have been impressive, until now only erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated marginal survival benefit in combination with gemcitabine in phase III clinical trials. Even though the failures of targeted therapies in the clinical setting are discouraging, it is reasonable to surmise that major progress will evolve as the molecular biology of pancreatic adenocarcinoma continues to be unraveled. This review describes some of the important developments and targeted agents for pancreatic cancer that have been tested in clinical trials.
How Long Should Insulin Be Used Once a Vial Is Started? (2003)

Editor’s comment : The commentary by Dr. Grajower has such important clinical relevance that responses were invited from the three pharmaceutical companies that supply insulin in the U.S. and the American Diabetes Association, and all of these combined in this commentary. The commenting letter and individual responses were authored separately and are completely independent of each other. 

Diabetic patients treated with insulin, whether for type 1 or type 2 diabetes, are prone to often unexplained swings in their blood glucose. These swings can vary from dangerously low to persistently high levels. Most diabetic patients, and most physicians, will adjust insulin regimens so as to avoid hypoglycemia at the expense of hyperglycemia. Among the “textbook” reasons for variable glucose responses to any given insulin regimen are 1 ) site of administration, 2 ) exercise, 3 ) bottles not adequately mixed before drawing the insulin (for NPH, Lente, or Ultralente), and 4 ) duration of treatment with insulin (1).

A new insulin was marketed by Aventis Pharmaceuticals about 1 year ago, insulin glargine (Lantus). The manufacturer seemed to stress that patients not use a started bottle of this insulin for >28 days (2). Two patients of mine highlighted this point.

L.K. is a 76-year-old woman with type 2 diabetes, diagnosed at 55 years of age, and treated with insulin since age 56. Her insulin regimen was changed to Lantus at night together with Novolog before meals. She monitors her blood glucose four times a day. She used a bottle of Lantus until it ran out; therefore, a bottle lasted for 2 months. Her recent HbA1c was 7.6%. I retrospectively analyzed her home glucose readings by averaging her fasting blood glucose levels for the first 15 days of a new bottle and the last 15 days of that same bottle. The results were 137 ± …
Long-Term Treatment With Deutetrabenazine Is Associated With Continued Improvement in Tardive Dyskinesia (TD): Results From an Open-Label Extension Study (S4.009) (2019)

To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Updated results of the responder analysis are reported here.
Escherichia coli maltose‐binding protein is uncommonly effective at promoting the solubility of polypeptides to which it is fused (1999)

Although it is usually possible to achieve a favorable yield of a recombinant protein in Escherichia coli, obtaining the protein in a soluble, biologically active form continues to be a major challenge. Sometimes this problem can be overcome by fusing an aggregation-prone polypeptide to a highly soluble partner. To study this phenomenon in greater detail, we compared the ability of three soluble fusion partners--maltose-binding protein (MBP), glutathione S-transferase (GST), and thioredoxin (TRX)--to inhibit the aggregation of six diverse proteins that normally accumulate in an insoluble form. Remarkably, we found that MBP is a far more effective solubilizing agent than the other two fusion partners. Moreover, we demonstrated that in some cases fusion to MBP can promote the proper folding of the attached protein into its biologically active conformation. Thus, MBP seems to be capable of functioning as a general molecular chaperone in the context of a fusion protein. A model is proposed to explain how MBP promotes the solubility and influences the folding of its fusion partners.
The isolation of cDNA clones for human fibrinogen (1984)

Fibrinogen (factor I) is an acute phase plasma protein which participates in the final steps of the coagulation pathway.Human fibrinogen, like all vertebrate fibrinogens studied to date, is composed of dimers of Aa'-, Bp-and Y-chains which are synthesised in the liver as abundant polypeptides.cDNA clones coding for the Ao(-, Bf-and Y-chains of human fibrinogen were isolated from an adult liver cDNA library.Clones were identified by hybridisation with mixtures of septadecamer oligonucleotides synthesised to regions of the polypeptide sequences showing low ambiguity on codon assignment.Sequencing of cDNA inserts subcloned into M13mp9 and comparision of the cDNA derived protein sequence with published amino acid sequences for fibrinogen polypeptides formed the basis of clone characterisation.cDNA insert sizes are 1,950 bp for AO^-fibrinogen, 1,450 bp for Bp-fibrinogen and 950 bp for Y -f ibrinogen.The recombinants do not share homologous sequences as revealed by the absence of cross-hybridisation.Southern blot hybridisations of human genomic DNA digested with various restriction enzymes gave simple band patterns with each clone suggesting that fibrinogen genes represent a set of unique sequences in the human genome.Expression in adult human liver, examined by Northern blots, showed the clones for B^-and Y -f ibrinogen hybridised to a single RNA sequence.The estimated mRNA sizes are 1.85 kb for Bp-fibrinogen and 1.8 kb for Yfibrinogen.Two mRNA sequences were detected with the clone for A(-fibrinogen, a major band at 2.6 kb and a minor band at about 1.8 kb.Chromosomal regional assignment performed by restriction fragment mapping of Human X CHO somatic cell hybrid DNAs tentatively localises the A</-, Bp-and Y-f ibrinogen genes to human chromosome 4q26-qter.I would like to thank all members of the Biochemistry department (past and present) for their help during the course of my thesis.Thanks to Bob Williamson for his encouragement and advice.To Steve Humphries and Simon Wallis for reading the manuscript and making helpful suggestions.To