gebhart/patrepeval huggingface dataset:
CopA: An Escherichia coli Cu(I)-translocating P-type ATPase (2000)

The copA gene product, a putative copper-translocating P-type ATPase, has been shown to be involved in copper resistance in Escherichia coli. The copA gene was disrupted by insertion of a kanamycin gene through homologous recombination. The mutant strain was more sensitive to copper salts but not to salts of other metals, suggesting a role in copper homeostasis. The copper-sensitive phenotype could be rescued by complementation by a plasmid carrying copA from E. coli or copB from Enterococcus hirae. Expression of copA was induced by salts of copper or silver but not zinc or cobalt. Everted membrane vesicles from cells expressing copA exhibited ATP-coupled accumulation of copper, presumably as Cu(I). The results indicate that CopA is a Cu(I)-translocating efflux pump that is similar to the copper pumps related to Menkes and Wilson diseases and provides a useful prokaryotic model for these human diseases.
Selective internalization of monoclonal antibodies by B‐cell chronic lymphocytic leukaemia cells (2003)

B-cell chronic lymphocytic leukaemia (B-CLL) cannot be cured by conventional chemotherapy, therefore, toxin-linked therapeutic monoclonal antibodies (mAbs) are increasingly examined for their potential to improve clinical outcome. The current study aimed to identify mAbs that were internalized by the B-CLL cells of 14 patients, using both flow cytometry and confocal laser scanning microscopy. Anti-CD5, CD22 and CD40 mAbs were effectively taken up by B-CLL cells, whereas mAbs against CD19, CD20, CD23 and CD45 were not. This study may form a basis for further research to identify antibodies that may serve as carriers for toxins to treat B-CLL.
Cardiovascular effects of timolol maleate, brimonidine or brimonidine/timolol maleate in concomitant therapy (2002)

This study suggests that both timolol and brimonidine, used alone and concomitantly, cause cardiovascular effects consistent with their pharmacology.
Vascular Smooth Muscle Cells: Isolation, Culture, and Characterization (2003)

In blood vessel development (vasculogenesis) smooth muscle cells (SMCs) are derived by differentiation of mesenchymal cells under the influence of mediators secreted by the endothelial cells (ECs) composing newly formed vessels. In angiogenesis, SMCs can be formed in the same way or by proliferation of existing SMCs (1). Key events in the development of atherosclerotic lesions and restenosis of arteries are now recognized to include vascular SMC migration, hyperplasia, and hypertrophy (2). This has led to an increase in studies of SMC function in response to growth factors, extracellular matrix, and lipoproteins, under controlled in vitro conditions, to address the cellular mechanisms in atherogenesis. Most of the methodology used for vascular smooth muscle culture has been developed for such studies (3).
Clinical Adenoviral Gene Therapy for Prostate Cancer (2009)

Prostate cancer is at present the most common malignancy in men in the Western world. When localized to the prostate, this disease can be treated by curative therapy such as surgery and radiotherapy. However, a substantial number of patients experience a recurrence, resulting in spreading of tumor cells to other parts of the body. In this advanced stage of the disease only palliative treatment is available. Therefore, there is a clear clinical need for new treatment modalities that can, on the one hand, enhance the cure rate of primary therapy for localized prostate cancer and, on the other hand, improve the treatment of metastasized disease. Gene therapy is now being explored in the clinic as a treatment option for the various stages of prostate cancer. Current clinical experiences are based predominantly on trials with adenoviral vectors. As the first of a trilogy of reviews on the state of the art and future prospects of gene therapy in prostate cancer, this review focuses on the clinical experiences and progress of adenovirus-mediated gene therapy for this disease.
Crystal Structure of Unliganded Influenza B Virus Hemagglutinin (2008)

Here we report the crystal structure of hemagglutinin (HA) from influenza B/Hong Kong/8/73 (B/HK) virus determined to 2.8 A. At a sequence identity of approximately 25% to influenza A virus HAs, B/HK HA shares a similar overall structure and domain organization. More than two dozen amino acid substitutions on influenza B virus HAs have been identified to cause antigenicity alteration in site-specific mutants, monoclonal antibody escape mutants, or field isolates. Mapping these substitutions on the structure of B/HK HA reveals four major epitopes, the 120 loop, the 150 loop, the 160 loop, and the 190 helix, that are located close in space to form a large, continuous antigenic site. Moreover, a systematic comparison of known HA structures across the entire influenza virus family reveals evolutionarily conserved ionizable residues at all regions along the chain and subunit interfaces. These ionizable residues are likely the structural basis for the pH dependence and sensitivity to ionic strength of influenza HA and hemagglutinin-esterase fusion proteins.
[PP.36.16] (2015)

Objective: Prescribing of novel anticoagulation therapy (NOAC) is expensive and is limited by the rules of insurance company. The study objective was to evaluate other factors infuenting the choice of NOAC u the patients with atrial fibrillation and arterial hypertension and chronic heart failure. Design and method: Clinical and laboratory parameters, and CHADS2, CHADS VASc and HAS-BLED scores were analyzed and calculated in a cohort of consecutive patients having a regular follow-up visit at tertiary care arterial hypertension a chronic heart failure clinics. Of 89 subject, total number of 52 subjects were indicated to NOAC (group N) and 37 patients stayed on warfarin (W). Results: Mean age in N was 69 years and 73 in W (p = 0.024), with higher proportion of patients > 75 years in W group (p = 0.021). There was higher prevalence of heart failure and vascular disease in group W compared to N (92 % vs. 77 % p = 0.048 and 70 % vs. 48% p = 0.035 respectively). Patients N had lower risk of stroke (CHADS2 score 2,4 vs. 3.0, p = 0.02, CHADS-VASc 3.75 vs. 4.70, p = 0.011) but higher risk of bleeding (HAS-BLED (2.55 vs. 2.13, p = 0.049). Patients from W group had lower ejection fraction (LV EF, 41 vs 49%, p = 0.038), higher creatinine level (p = 0.042), lower estimated glomerular filtration rate (eGFR, p = 0.017) and lower mean hemoglobin level (p = 0.018). CHADS2 score correlated with body mass index (BMI, r = 0.477) and LV EF (r = −0.659) and HAS-BLED score correlated with eGFR (r = −0.442) only in N group. Conclusions: Patients indicated for NOAC were surprisingly younger, with lower prevalence of heart failure and vascular disease, with lower risk of stroke but significantly higher risk of bleeding than patients continuing warfarin therapy. BMI, LV EF and eGFR are other parameters which should be used in the decision making in the choice of anticoagulation therapy.
Real-time fingertip tracking and gesture recognition (2002)

Augmented desk interfaces and other virtual reality systems depend on accurate, real-time hand and fingertip tracking for seamless integration between real objects and associated digital information. We introduce a method for discerning fingertip locations in image frames and measuring fingertip trajectories across image frames. We also propose a mechanism for combining direct manipulation and symbolic gestures based on multiple fingertip motions. Our method uses a filtering technique, in addition to detecting fingertips in each image frame, to predict fingertip locations in successive image frames and to examine the correspondences between the predicted locations and detected fingertips. This lets us obtain multiple complex fingertip trajectories in real time and improves fingertip tracking. This method can track multiple fingertips reliably even on a complex background under changing lighting conditions without invasive devices or color markers.
Localization of the Precursor and Peptide Products Using Electron Microscopic-Immunogold Methods (1987)

Antibodies to different peptides produced from the gastrin precursor have been used in light micro­ scopic- and electron microscopic-immunogo1d stud­ ies of gastrinoma tissue and normal antral mucosa. Antibodies to the C terminus of progastrin, which are known to react with the intact precursor, re­ vealed immunoreactive material in the rough endo­ plasmic reticulum, Go1gi region, and electron-dense granules in gastrinoma cells. In normal antrum these antibodies again revealed the Go1gi region and a population of electron-dense granules. Other anti­ bodies that react with the products of progastrin processing, but not the precursor, e.g., C-termina1 and N-termina1 gastrin 17 specific antibodies, re­ vealed only granules. In addition to electron-dense granules already mentioned, the latter antibodies also revealed electron-lucent and intermediate gran­ ule populations, which in antrum were the major granule types. It is proposed that the intact precur­ sor occurs in rough endoplasmic reticulum and Go1gi; thereafter, in the immature electron-dense granules, and subsequently in electron-lucent gran­ ules, biosynthetic processing liberates gastrin 17 and gastrin 34, which are the major active products of gastrin gene expression. Small biologically active peptides are now known to be synthesized initially as large precursor molecules
Protonated nanostructured aluminosilicate (NSAS) reduces plasma cholesterol concentrations and atherosclerotic lesions in Apolipoprotein E deficient mice fed a high cholesterol and high fat diet (2009)

The aim of this work was to assess the effect of chronic administration of protonated nanostructured aluminosilicate (NSAS) on the plasma cholesterol levels and development of atherosclerotic lesions in Apolipoprotein (ApoE) deficient mice fed a high cholesterol and high fat diet. Apolipoprotein E (ApoE) deficient mice were divided into the following treatment groups: protonated NSAS 1.4% (w/w), untreated control and 2% (w/w) stigmastanol mixed with high-cholesterol/high-fat diet. Animals were treated for 12 weeks, blood samples were withdrawn every 4 weeks for determination of plasma cholesterol and triglyceride levels. At the end of the study the aortic roots were harvested for assessment of atherosclerotic lesions. NSAS at 1.4% (w/w) and stigmastanol at 2% (w/w) treatment groups showed significant decreases in plasma cholesterol concentrations at all time points relative to the control animals. The lesion sum area in 1.4% (w/w) NSAS and 2% (w/w) stigmastanol groups were significantly less from the control animals. In conclusion, in this study, the effectiveness of chronic administration of protonated NSAS material in the reduction of plasma cholesterol levels and decrease in development of atherosclerotic lesions was demonstrated in Apo-E deficient mice model.
MOLECULAR MECHANISMS OF DRUG RESISTANCE IN MYCOBACTERIUM TUBERCULOSIS (1996)

In spite of forty years of effective chemotherapy for tuberculosis, the molecular mechanisms of antibacterial compounds in Mycobacterium tuberculosis have only recently been revealed. Broad spectrum antibacterials, including streptomycin, rifampicin, and fluoroquinolones have been demonstrated to act on the same targets in M. tuberculosis as they do in E. coli. Resistance to these agents results from single mutagenic events that lead to amino acid substitutions in their target proteins. The mechanisms of action of the unique antitubercular drugs, including isoniazid, ethambutol, and pyrazinamide have also recently been defined. Resistance to isoniazid can be caused either by mutations in the katG-encoded catalase-peroxidase, the enzyme responsible for drug activation, or by the molecular target, the inhA-encoded long chain enoyl-ACP reductase. Ethambutol appears to block specifically the biosynthesis of the arabinogalactan component of the mycobacterial cell envelope, and pyrazinamide has no known target. With the resurgence of tuberculosis and the appearance of strains which are multiply resistant to the above compounds, present tuberculosis chemotherapies are threatened. New approaches to the treatment of multi drug-resistant tuberculosis are needed.
Use of Antistaphylococcal -Lactams to Increase Daptomycin Activity in Eradicating Persistent Bacteremia Due to Methicillin-Resistant Staphylococcus aureus: Role of Enhanced Daptomycin Binding (2011)

We used daptomycin plus antistaphylococcal β-lactams (ASBL) to clear refractory MRSA bacteremia. In vitro studies showed enhanced daptomycin bactericidal activity, increased membrane daptomycin binding, and decrease in positive surface charge induced by ASBLs against daptomycin nonsusceptible MRSA. Addition of ASBLs to daptomycin may be of benefit in refractory MRSA bacteremia. (Although the official designation is "daptomycin nonsusceptiblity," we will use the term "daptomycin-resistance" in this paper for facility of presentation.).
Pomegranate Juice and Extracts Provide Similar Levels of Plasma and Urinary Ellagitannin Metabolites in Human Subjects (2008)

Pomegranate juice (PJ), a rich source of polyphenols including ellagitannins, has attracted much attention due to its reported health benefits. This has resulted in the consumption of liquid and powder pomegranate extracts as alternatives to PJ. Therefore establishing the bioavailability of polyphenols from these extract preparations is necessary. Sixteen healthy volunteers sequentially consumed, with a 1-week washout period between treatments, PJ (8 ounces, Wonderful fruit variety), a pomegranate polyphenol liquid extract (POMxl, 8 ounces), and a pomegranate polyphenol powder extract (POMxp, 1,000 mg). The three interventions provided 857, 776, and 755 mg of polyphenols as gallic acid equivalents, respectively. Plasma bioavailability, judged based on ellagic acid levels over a 6-hour period, did not show statistical differences in area under the curve for the three interventions: 0.14 +/- 0.05, 0.11 +/- 0.03, and 0.11 +/- 0.04 micromol . hour/L for PJ, POMxl, and POMxp, respectively. The time of maximum concentration was delayed for POMxp (2.58 +/- 0.42 hours) compared to PJ (0.65 +/- 0.23 hours) and POMxl (0.94 +/- 0.06 hours). Urolithin-A glucuronide, a urinary metabolite of ellagic acid, was not significantly different with the three interventions, reaching levels of approximately 1,000 ng/mL. This study demonstrates that ellagitannin metabolites, delivered from pomegranate fruits, as PJ, POMxl, and POMxp, reach equivalent levels with a delay in time of maximum concentration of POMxp compared to PJ and POMxl.
Genetically-engineered proteins and enzymes from yeasts : production control (1991)

Editor's introduction comparative genetics of important yeasts genetic engineering techniques in yeast time-profiling and environmental design in computer-controlled fermentation and enzyme production introducing heterologous gene expression in yeast as fermentations approach maximal biomass.
Two faces of microbiota in inflammatory and autoimmune diseases: triggers and drugs (2012)

The prevalence of chronic autoimmune and inflammatory diseases, such as inflammatory bowel disease, allergies, or rheumatic diseases, is steadily increasing in developed countries. This increase is probably accelerated by environmental factors, such as decrease in infectious burden or changes in food processing. These lifestyle changes then strongly influence the strongest stimulus for the immune system – commensal microbiota. Despite the differences in the affected organ, the immune‐mediated diseases have one or more factors in common – microbe either as a trigger or as a protector, mucosal barrier dysfunction, and dysregulation of the immune system. The core questions, which microbes are involved and how these diseases can be cured or even prevented still remain unsolved. Powered by the recent progress in technology, by new insights into the function of immune system, by advances in microbiome research, and extended use of gnotobiological techniques, these mechanisms are now being unravelled and new therapeutic possibilities are emerging. To secure their niche, the microbes devised many ingenious ways, how to dampen the inflammation. Nonpathogenic microorganisms or microbial components isolated from probiotic, commensal or even pathogenic microbes could be, therefore, used to interfere with the pathogenetic mechanisms of immune‐mediated diseases.
Mechanical Stiffness Grades Metastatic Potential in Patient Tumor Cells and in Cancer Cell Lines (2011)

Cancer cells are defined by their ability to invade through the basement membrane, a critical step during metastasis. While increased secretion of proteases, which facilitates degradation of the basement membrane, and alterations in the cytoskeletal architecture of cancer cells have been previously studied, the contribution of the mechanical properties of cells in invasion is unclear. Here, we applied a magnetic tweezer system to establish that stiffness of patient tumor cells and cancer cell lines inversely correlates with migration and invasion through three-dimensional basement membranes, a correlation known as a power law. We found that cancer cells with the highest migratory and invasive potential are five times less stiff than cells with the lowest migration and invasion potential. Moreover, decreasing cell stiffness by pharmacologic inhibition of myosin II increases invasiveness, whereas increasing cell stiffness by restoring expression of the metastasis suppressor TβRIII/betaglycan decreases invasiveness. These findings are the first demonstration of the power-law relation between the stiffness and the invasiveness of cancer cells and show that mechanical phenotypes can be used to grade the metastatic potential of cell populations with the potential for single cell grading. The measurement of a mechanical phenotype, taking minutes rather than hours needed for invasion assays, is promising as a quantitative diagnostic method and as a discovery tool for therapeutics. By showing that altering stiffness predictably alters invasiveness, our results indicate that pathways regulating these mechanical phenotypes are novel targets for molecular therapy of cancer.
Germ-line affinity and germ-line variable-region genes in the B cell response. (1987)

The predominance of germ-line genes in IgM expression was evaluated from the nucleotide sequences of mRNA, derived from 10 hybridoma cell lines, coding for the VH and VL regions of anti-5-dimethylaminonaphthalene-1-sulfonyl (anti-Dns) IgM antibody. At least six germ-line VH gene segments distributed among four families are used in this response. Seven of the 10 independently rear-ranged VH genes were identified as germ line, with the other three possibly germ line. In all of them the D and JH portions retained the germ-line sequences of the D and JH segments from which they were derived. Maximum diversity was found in the D segments and the use of noncoded nucleotides at the VH-D and D-JH junctions. Of the eight cell lines expressing the lambda light chains, all were germ line and involved the three subtypes. Maximum affinity for the homologous ligand was found among the seven cell lines identified as expressing germ-line gene segments. Thus any somatic mutation among the remaining 3 cell lines did not provide enhanced affinity and the observed affinity of each cell line can be described as germ-line affinity. It is further suggested that the anti-Dns selectivity of the IgM antibodies is associated primarily with the CDR3 regions.
Managed Care and the Role and Training of Psychiatrists (1995)

While each sector of medical practice and academic medicine confronts the reality of a changing economic environment driven by managed care, psychiatry faces some of the most difficult challenges in defining the future roles and training of psychiatrists. In this paper we describe the challenges and opportunities for psychiatry in this new era, as well as some of the unique problems facing academic psychiatry departments as they seek to fund their academic mission.
Biologically active polymeric sequestrants: Design, synthesis, and therapeutic applications (2007)

Abstract In recent years, functional polymers exhibiting inherently biological activities have been receiving increasing attention as polymer-based human therapeutic agents. These polymeric drugs exhibit unique pharmaceutical properties that are fundamentally different from their traditional small-molecule counterparts. However, unlike polymeric drug delivery systems, examples of polymers possessing intrinsically therapeutic properties are relatively scarce. By virtue of their high-molecular-weight characteristics, these polymeric drugs can be confined to the gastrointestinal (GI) tract, where they can selectively recognize, bind, and remove target disease-causing substances from the body. Being confined to the GI tract and non-biodegradable, these polymeric drugs are free from toxic effects that are associated with traditional systemic drugs. This report highlights recent developments in the rational design and synthesis of appropriate functional polymers that have resulted in a number of promising polymer-based therapeutic agents, including some marketed products.
The5ESSSwitching System: System Test, First-Office Application, and Early Field Experience (1985)

Comprehensive system testing and verification of feature design at a “first-office”-application site are integral parts of the design and development methodology for the 5ESS™ system. The strict enforcement of this methodology has led to a product that has exhibited high quality and reliability in the field. This paper describes the activities associated with the integration and system testing of 5ESS system generics, as well as the procedures used at the first-office-application site to verify operational compatibility prior to release for service. The operational experience with in-service 5ESS systems is also described.
The merger of a single oscillating-beam smart antenna and MC-CDMA: transmit diversity, frequency diversity and directionality (2003)

In this paper, we introduce a novel merger of a single smart antenna array and MC-CDMA (multi-carrier code division multiple access) systems. Here, all carriers in the MC-CDMA system are applied to one smart antenna at the base station (BS). Applying proper time-varying phases to array elements of the smart antenna array, the beam pattern is carefully controlled to generate a mainlobe at the position of the intended user and small oscillations in the beam pattern. This beam pattern oscillation creates a time varying channel with a controllable coherence time and a time diversity benefit at the receiver. Employing MC-CDMA with the proposed antenna array at the BS, we achieve: (1) directionality which supports space division multiple access (SDMA); (2) a time diversity gain using only a single antenna at the receiver in the mobile unit; and (3) increased capacity and performance via MC-CDMA's ability to support both code division multiple access and frequency diversity benefits. Hence, merging MC-CDMA and BS single antenna array in an innovative fashion, we achieve high performance at the mobile via joint frequency-time diversity, and high network capacity via joint space-code division multiple access.