gebhart/patrepeval huggingface dataset:
Tumor necrosis factor-induced endothelial tissue factor is associated with subendothelial matrix vesicles but is not expressed on the apical surface (1992)

Cultured endothelial cells can be induced by tumor necrosis factor/cachectin (TNF) and other cytokines to synthesize the procoagulant cofactor tissue factor (TF). Intact monolayers of TNF- treated endothelial cells showed only minimal TF activity. In contrast, after permeabilization of these monolayers with detergent (saponin, 0.02%), there was approximately 10- to 20-fold increase in TF-mediated, factor VIIa-dependent factor Xa formation. Extracellular matrix derived from TNF-treated endothelium, prepared after removing the cells by hypotonic lysis or ammonium hydroxide (0.1 N), also had similarly enhanced TF activity. Incubation with a blocking monoclonal antibody to TF inhibited the procoagulant activity of both TNF-stimulated endothelial cells, whether they were intact or permeabilized, and of their matrices. However, when the apical cell surface was pretreated with anti-TF antibody, washed, and then cells were lysed with water or permeabilized with saponin, similar augmentation of TF activity was still observed, suggesting the presence of a pool of TF to which the antibody did not initially gain access. Consistent with this concept, the presence of TF in the matrix of TNF-treated endothelial cells was shown by immunoblotting and morphologic studies; cultured endothelial monolayers and the native endothelium of aortic segments after exposure to TNF showed TF in extracellular matrix, associated with vesicles. In contrast, TF was virtually undetectable on the apical endothelial surface. Taken together, these findings suggest that endothelial TF can be present in a cryptic pool that only gains access to the blood after alteration in the integrity of the endothelial monolayer.
Effects of pancreatic polypeptide, caerulein, and bombesin on satiety in obese mice (1985)

Congenitally obese mice are hyperphagic, suggesting that their obesity is secondary to defects in normal satiety mechanisms. The present study compares the effects of caerulein, bombesin, and pancreatic polypeptide (three equimolar doses each of 3, 9, and 27 nmol/kg) on food intake in 10 pairs of lean and obese mice. After the intraperitoneal injection of saline, obese mice eat 240% more of a liquid meal (Magnacal) than their lean littermates (P less than 0.01). All three doses of caerulein significantly inhibited food intake in both obese and lean mice. Although the highest dose of bombesin significantly decreased food intake in both obese and lean mice, the lowest dose was only effective in obese mice. In contrast, none of these doses of pancreatic polypeptide had a significant effect on food intake in either lean or obese mice. A dose of bovine pancreatic polypeptide of 200 nmol/kg was required to significantly reduce food intake in lean and obese mice. This study demonstrates that obese mice respond to satiety signals and may even be more sensitive than their lean littermates to some messengers. In addition, the previously described reversal of this obesity syndrome by pancreatic polypeptide in doses of approximately 2.5 and 25 nmol X kg-1 X day-1 is unlikely to be due to effects of this peptide on food intake.
Immune-mediated neurodegeneration and neuroprotection in MS. (2003)

It has become evident that multiple sclerosis (MS) has significant neurodegenerative components. An increasing number of reports show neuronal and axonal damage in MS patients and experimental allergic encephalomyelitis (EAE) in an animal model of MS. The mechanisms behind this neurodegeneration are unknown, but evidence suggests immune-mediated damage. In this review we analyse the findings of immune-mediated injury in MS and focus on axonal and neuronal injury. The potential neuroprotective role of some currently available MS drug treatments is also discussed.
Differences between outward currents of human atrial and subepicardial ventricular myocytes. (1996)

1. Outward currents were studied in myocytes isolated from human atrial and subepicardial ventricular myocardium using the whole-cell voltage clamp technique at 22 degrees C. The Na+ current was inactivated with prepulses to -40 mV and the Ca2+ current was eliminated by both reducing extracellular [Ca2+] to 0.5 mM and addition of 100 microM CdCl2 to the bath solution. 2. In human myocytes, three different outward currents were observed. A slowly inactivating sustained outward current, I(so), was found in atrial but not ventricular myocytes. A rapidly inactivating outward current, I(to), of similar current density was observed in cells from the two tissues. An additional uncharacterized non-inactivating background current of similar size was observed in atrial and in ventricular myocytes. 3. I(to) and I(so) could be differentiated in atrial myocytes by their different kinetics and potential dependence of inactivation, and their different sensitivities to block by 4-amino-pyridine, suggesting that two individual channel types were involved. 4. In atrial cells, inactivation of I(to) was more rapid and steady-state inactivation occurred at more negative membrane potentials than in ventricular cells. Furthermore, the recovery of I(to) from inactivation was slower and without overshoot in atrial myocytes. In addition, 4-aminopyridine-induced block of I(to) was more efficient in atrial than in ventricular cells. These observations suggest that the channels responsible for atrial and ventricular I(to) were not identical. 5. We conclude that the differences in outward currents substantially contribute to the particular shapes of human atrial and ventricular action potentials. The existence of I(so) in atrial cells only provides a clinically interesting target for anti-arrhythmic drug action, since blockers of I(so) would selectively prolong the atrial refractory period, leaving ventricular refractoriness unaltered.
Synthesis of Deoxy and Deoxyhalogeno Analogues of myo-Inositol (1987)

Abstract A number of deoxy and deoxyhalogeno analogues of moyo-inositol of Interest 1n Investigating the biochemical processes of the phosphoinositide pathway were synthesized. Syntheses Include those deoxyinositols (cyclohexane pentols) which correspond to myo-inositol deoxygenated at positions 1, 4 and 5, as well as a set of 5-deoxyhalogeno (F, Cl, Br, I) myo- and epimeric neo-inositols. Configurational assignments are based primarily on 1H NMR spectroscopy.
Charging Behavior of Single-Stranded DNA Polyelectrolyte Brushes (2006)

DNA monolayers are widely used in fundamental and applied genomics and are versatile experimental models for elucidating the behavior of charged polymers at interfaces. The physical behavior of these systems is to a large extent governed by their internal ionic microenvironment, which is investigated here for layers of end-tethered, single-stranded DNA oligonucleotides (DNA brushes). Retention of counterions by the DNA brush manifests as lowered susceptibility of the interfacial capacitance to external salt conditions. A physical model based on concepts adapted from polymer science was used to further elucidate the connection between monolayer organization and its charging behavior. The data indicate a reorganization of the monolayer with changes in ionic strength and strand coverage that is consistent with that expected for a polyelectrolyte brush. A method for electrochemical quantification of strand coverage, based on shift of reduction potential for redox counterions associated with the DNA monolayer, is also described. These results provide guidance for development of label-free electrochemical diagnostics employing DNA monolayers and formulate a description of monolayer behavior within a polymer science framework.
Monoclonal antibody technology. (1986)

The development, production, limitations, and uses of monoclonal antibody (MoAb) technology are presented. The first MoAbs were developed in 1975 using a process whereby the antibody-producing spleen cells of mice that had been immunized against sheep red blood cells were fused with the cells of a mouse myeloma cell line, producing hybridomas. These hybridoma cells are used to produce MoAbs, which are antibodies that will bind to only one specific target site on an antigen. Large quantities of MoAbs are grown, either in cell cultures or in the peritoneum of mice, and harvested. Although large quantities of MoAbs can be produced, these techniques are limited because of the potential for contamination by mouse viruses and the inability of the hybridomas to yield sufficient quantities of MoAbs. MoAbs are currently used in diagnostic techniques, including pregnancy tests and drug assays, as well as in tests for detecting viral and bacterial infections and cancer. MoAbs, coupled with dyes or radioactive isotopes, can be used in imaging techniques. Other possible applications of MoAbs include tissue typing, purification, therapy of cancer and autoimmune diseases, and treatment of drug toxicities. As the use of MoAbs in health care increases, pharmacists will need to have a good understanding of the functions and applications of these agents.
Vinculin acts as a sensor in lipid regulation of adhesion-site turnover (2005)

The dynamics of cell adhesion sites control cell morphology and motility. Adhesion-site turnover is thought to depend on the local availability of the acidic phospholipid phosphatidylinositol-4,5-bisphosphate (PIP(2)). PIP(2) can bind to many cell adhesion proteins such as vinculin and talin, but the consequences of this interaction are poorly understood. To study the significance of phospholipid binding to vinculin for adhesion-site turnover and cell motility, we constructed a mutant, vinculin-LD, deficient in acidic phospholipid binding yet with functional actin-binding sites. When expressed in cells, vinculin-LD was readily recruited to adhesion sites, as judged by fluorescence recovery after photobleaching (FRAP) analysis, but cell spreading and migration were strongly impaired, and PIP(2)-dependent disassembly of adhesions was suppressed. Thus, PIP(2) binding is not essential for vinculin activation and recruitment, as previously suggested. Instead, we propose that PIP(2) levels can regulate the uncoupling of adhesion sites from the actin cytoskeleton, with vinculin functioning as a sensor.
Morphine Alkaloids, CXVII: Investigation of the Azidolysis of Tertiary Alcohols of Thebaine Derivatives with Bridged Ring C (1993)

Abstract Replacement of the C‐19 tertiary hydroxyl group of some thebaine and oripavine derivatives with bridged ring C (so‐called Bentley 's compounds) for an azido group has been performed with hydrazoic acid. In case the hydroxyl group was connected to a centre of chirality, substitution resulted in the formation of diastereomeric mixture of azides and elimination took place as well, the extent of which was dependent mainly on steric factors. Configuration of the C‐19 has been determined by 1 H‐NMR spectra and calculated proton‐proton distances of amines 13a and 13b obtained by the reduction of 10c followed by separation.
Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-Prone CD8 T cells in persistent hepatitis B virus infection (2011)

CTLA-4 is expressed by HBV-specific CD8 T cells with high levels of Bim and helps to drive this proapoptotic phenotype. CTLA-4 blockade could form one arm of a therapeutic approach to modulate the diverse patterns of coregulation of T-cell exhaustion in this heterogeneous disease.
Molecular cloning and characterization of winter flounder antifreeze cDNA. (1981)

Double-stranded cDNA was synthesized from partially purified winter flounder antifreeze mRNA and inserted into the endonuclease Pst I site of plasmid pBR322 by the poly(dG).poly(dC) homopolymer extension technique. The recombinant plasmids wee used to transform Escherichia coli. Clones containing antifreeze cDNA inserts were identified by the hybridization-selection technique. One of the inserts, 380 nucleotides in length, was digested with endonucleases Sau3AI and HinfI, which cleaved the insert into three fragments. The nucleotide sequences of these fragments were determined. The cDNA contains the entire coding sequence for a possible antifreeze peptide, including the leader sequence. The predicted amino acid sequence is similar to but not identical to one of the known sequences of antifreeze peptide. Within the cDNA are three segments of repeating sequences. The basic repeating sequence of 11 amino acids is maintained in the amino acid sequence coded by the cDNA and in the antifreeze peptide.
Bacterial production of poly(.beta.-hydroxyalkanoates) containing unsaturated repeating units by Rhodospirillum rubrum (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBacterial production of poly(.beta.-hydroxyalkanoates) containing unsaturated repeating units by Rhodospirillum rubrumHerbert W. Ulmer, Richard A. Gross, Mario Posada, Paul Weisbach, R. Clinton Fuller, and Robert W. LenzCite this: Macromolecules 1994, 27, 7, 1675–1679Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/ma00085a002https://doi.org/10.1021/ma00085a002research-articleACS PublicationsRequest reuse permissionsArticle Views202Altmetric-Citations37LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Nanoliter Dispensing Method by Degassed Poly(dimethylsiloxane) Microchannels and Its Application in Protein Crystallization (2007)

This paper describes a method of dispensing a nanoliter volume of liquid into arrays of microwells through degassed poly(dimethylsiloxane) (PDMS) microchannels. In this method, the PDMS microchannels were reversibly bound to arrays of microwells. The PDMS elastomer was predegassed and served as an internal vacuum pumping source. Various aqueous solutions were infused into arrays of microwells through the reversibly sealed PDMS microchannels. Microwells fabricated in PDMS, poly(methyl methacrylate) (PMMA), and glass were all compatible with this dispensing method. By removing the PDMS microchannels, arrays of droplets confined in the microwells were obtained. Multiplex reaction and screening at the nanoliter scale were carried out by binding two such arrays of microwells to form microchambers. We applied this method to screening the crystallization conditions of four known proteins. Long-term incubation of over 2 months was achieved by employing glass microwells. An unknown protein was then crystallized using the screening method in microwells. The crystals with sufficient size were harvested from the reversibly bound microwells. X-ray diffraction with a resolution of 3.1 Angstrom was obtained.
Application of a microscope to Brillouin scattering spectroscopy (1992)

In order to make a microscopic observation of the surface elastic wave on inhomogeneous opaque materials, an apparatus for Brillouin scattering spectroscopy was constructed utilizing a commercial microscope. An optical system which serves both as an inlet of a laser beam and as an outlet of the scattered light was made and incorporated in the microscope. The apparatus was proved to be particularly useful to make microscopic-scale observations of surface elastic waves on metal films.
Formulation of a stable parenteral product; Clonidine Hydrochloride Injection. (1999)

Clonidine Hydrochloride Injection (Duraclon) is a clear, colorless, preservative-free, pyrogen free, aqueous solution of clonidine hydrochloride. The indication for this product is for use as an adjunct in pain management, administered epidurally, when opiates are insufficient. The drug formulation was evaluated under both normal and stress conditions in the preformulation/formulation studies. The list of studies conducted includes a light sensitivity study, an oxygen sensitivity study, a pH/stability study, a stopper compatibility evaluation, a freeze-thaw study, and a stability study. Samples from the light, oxygen, pH/stability, and stability studies were evaluated for color, visual clarity, pH, potency, and chromatographic purity. Samples from the freeze-thaw study were evaluated for all of the above except chromatographic purity. The results for these studies demonstrate the stability of the product as formulated. The pH of this unbuffered product was consistently within the acceptance criteria. The product remained clear and colorless for the duration of each study. The values obtained for the potency and chromatographic purity assays showed no evidence of degradation. The reasons for the lack of degradation can be found in the molecular structure of the drug substance and the formulation of the drug product. Since the molecular structure is that of a Schiff base, it is theoretically possible, although difficult, to cleave the molecule. A catalyst would be required, and none of the possible catalysts are present in the formulation. The molecule could also be cleaved upon exposure to light, and the evidence indicates that the molecule does interact with light. This interaction is not to the degree, however, that product stability is affected. The formulation contains only the active drug substance and sodium chloride in water for injection with a pH of approximately 6. Although the product is unbuffered, the influence of the stoppers and glass vials upon the formulation pH was minimal. In addition, the stopper compatibility of the product is enhanced by the absence of chelating agents, preservatives, acids, and bases. Since the dilute concentrations of both the active and excipient are well below their solubility limits, no solubility related issues would be expected upon freezing and subsequent thawing. Clonidine Hydrochloride Injection, as formulated, does not require protection from light, oxygen, or freezing. The product shows acceptable stability within the pH range, and the rubber closure is compatible with the product. Real time stability data combined with statistical projections support a 36-month expiration date.
Two minimal Tat translocases in Bacillus (2004)

Summary Activity of the Tat machinery for protein transport across the inner membrane of Escherichia coli and the chloroplast thylakoidal membrane requires the presence of three membrane proteins: TatA, TatB and TatC. Here, we show that the Tat machinery of the Gram‐positive bacterium Bacillus subtilis is very different because it contains at least two minimal Tat translocases, each composed of one specific TatA and one specific TatC component. A third, TatB‐like component is apparently not required. This implies that TatA proteins of B. subtilis perform the functions of both TatA and TatB of E. coli and thylakoids. Notably, the two B. subtilis translocases named TatAdCd and TatAyCy both function as individual, substrate‐specific translocases for the twin‐arginine preproteins PhoD and YwbN, respectively. Importantly, these minimal TatAC translocases of B. subtilis are representative for the Tat machinery of the vast majority of Gram‐positive bacteria, Streptomycetes being the only known exception with TatABC translocases.
Endometrial Cancer in Tamoxifen-Treated Breast Cancer Patients: Findings From the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 * (1994)

Tamoxifen treatment for breast cancer should continue. In addition, the relative risk of endometrial cancer observed in B-14 tamoxifen-treated patients is consistent with the twofold relative risk used in the initial risk-benefit computation for the NSABP breast cancer prevention trial.
MEMS: Enabled Drug Delivery Systems (2015)

Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed.
PROGRESS IN DEVELOPMENT OF A LIVE-ATTENUATED, TETRAVALENT DENGUE VIRUS VACCINE BY THE UNITED STATES ARMY MEDICAL RESEARCH AND MATERIEL COMMAND (2003)

"PROGRESS IN DEVELOPMENT OF A LIVE-ATTENUATED, TETRAVALENT DENGUE VIRUS VACCINE BY THE UNITED STATES ARMY MEDICAL RESEARCH AND MATERIEL COMMAND" published on Dec 2003 by American Society of Tropical Medicine and Hygiene.
Biomarkers in Colorectal Cancer. (2016)

Colorectal cancer is the third most common cancer worldwide, with 1.36 million people diagnosed in 2012. The prognosis of colorectal cancer is better with an earlier diagnosis. The outcome of colorectal cancer may also be improved by targeting pathways involved in colorectal cancer formation, such as anti-epidermal growth factor receptor (EGFR) therapy. An understanding of colorectal carcinogenesis is essential for the design of molecular targeting. Recent advances in the molecular subtypes of colorectal cancer, methylation of DNA in colorectal cancer, and micro-RNA biogenesis, and their involvement in colorectal cancer have resulted in the identification of many new colorectal biomarkers. Such biomarkers may be used for earlier diagnosis of, selection of 'personalised' therapy for, and prognosis of colorectal cancer. Many of these biomarkers appear promising in small-scale studies. However, validation of their effectiveness with large-scale clinical trials is needed before routine clinical application. To this end, the recently established consensus molecular subtypes of colorectal cancer would enable like-for-like comparisons of the treatment outcomes of clinical trials.