gebhart/patrepeval huggingface dataset:
Genetic Variation and Evolutionary Origin of the Direct Repeat Locus of Mycobacterium tuberculosis Complex Bacteria (2000)

The direct repeat region in Mycobacterium tuberculosis complex strains is composed of multiple direct variant repeats (DVRs), each of which is composed of a 36-bp direct repeat (DR) plus a nonrepetitive spacer sequence of similar size. It has been shown previously that clinical isolates show extensive polymorphism in the DR region by the variable presence of DVRs, and this polymorphism has been used in the epidemiology of tuberculosis. In an attempt to better understand the evolutionary scenario leading to polymorphic DR loci and to improve strain differentiation by spoligotyping, we characterized and compared the DNA sequences of the complete DR region and its flanking DNA of M. tuberculosis complex strains. We identified 94 different spacer sequences among 26 M. tuberculosis complex strains. No sequence homology was found between any of these spacers and M. tuberculosis DNA outside of the DR region or with any other known bacterial sequence. Although strains differed extensively in the presence or absence of DVRs, the order of the spacers in the DR locus was found to be well conserved. The data strongly suggest that the polymorphism in clinical isolates is the result of successive deletions of single discrete DVRs or of multiple contiguous DVRs from a primordial DR region containing many more DVRs than seen in present day isolates and that virtually no scrambling of DVRs took place during evolution. Because the majority of the novel spacer sequences identified in this study were confined to isolates of the rare Mycobacterium canettii taxon, the use of the novel spacers in spoligotyping led only to a slight improvement of strain differentiation by spoligotyping.
HtrA1: Its future potential as a novel biomarker for cancer (2015)

HtrA1 appears to be involved in several physiological processes as well as in the pathogenesis of conditions such as Alzheimer's disease and osteoarthritis. It has also been hypothesized to play a role as a tumor suppressor. This manuscript reviews the current cancer-related HtrA1 research from the methodological and clinical standpoints including studies regarding its potential role as a tumor marker and/or prognostic factor. PRISMA method was used for study selection. The articles thus collected were examined and selected by two independent reviewers; any disagreement was resolved by a methodologist. A laboratory researcher reviewed the methods and laboratory techniques. Fifteen studies met the inclusion criteria and concerned the following cancer sites: the nervous system, bladder, breast, esophagus, stomach, liver, endometrium, thyroid, ovaries, pleura, lung and skin. Most articles described in vivo studies using a morphological approach and immunohistochemistry, whereas protein expression was quantified as staining intensity scored by two raters. Often the results were not comparable due to the different rating scales and study design. Current research on HtrA1 does not conclusively support its role as a tumor suppressor.
Analysis of the time variant structure of microwave line-of-sight multipath phenomena (2003)

The authors report a novel technique, the SVDP (singular value decomposition prony) algorithm, which has demonstrated its superiority in identifying the multipath rays in line-of-sight microwave links. The technique has been applied to field data and it has proved itself to be a very useful tool in analyzing the time-variant structure of the actual physical mechanism, i.e. the evolution of the delay and amplitude of the multipath rays. The authors present the results of analysis of field measurements made at 11 GHz over a wide bandwidth of 400 MHz on the French CNET at Lannion, using a 50 km link. The major applications of this technique are: the modelling of a multipath channel using the least possible number of rays with the objective of minimizing the RMS error; the analysis of the time-variant structure of a channel and hence the design of adaptive equalizers; and the generation of the statistics of the time-domain multipath parameters, particularly the delay and amplitude distributions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Binding of triton X-100 to diphtheria toxin, crossreacting material 45, and their fragments. (1976)

Binding of the nonionic detergent [3H]Triton X-100 by diphtheria toxin, by the nontoxic serologically related protein crossreacting material (CRM) 45, and by their respective A and B fragments has been studied. If first denatured in 0.1% sodium dodecyl sulfate, all of the proteins with the exception of fragment A bind increasing amounts of Triton X-100, reaching a maximum of more than 40 mol bound per mol of protein when the detergent concentration exceeds its critical micelle concentration. No measurable amount of Triton X-100 is bound by native toxin or its A fragment of any concentration of the detergent. Undenatured CRM45 or its B45 fragment, on the other hand, readily became inserted into Triton X-100 micelles when the detergent reaches its critical micelle concentration. The results show that the toxin molecule contains a hydrophobic domain located on the portion of the B fragment that is linked to A. This region is masked in native toxin. Based on these findings, a model is proposed to describe how fragment B facilitates the transport of the enzymically active hydrophilic fragment A across the plasma membrane to reach the cytoplasm.
Implantable pumps. (1987)

Implantable drug-delivery pumps are being developed to provide the external control of delivery rate or to deliver volumes of drug that are beyond the capabilities of conventional controlled-release formulations. The delivery of insulin to diabetics and chemotherapeutic agents to cancer patients represents the two major applications of such devices, but other applications (chronic pain control, Alzheimer's disease, spasticity, etc.) exist or have been proposed. The most popular device is the Infusaid which is driven by a fluorocarbon vapor-liquid mixture to provide a constant delivery rate. Implantable peristaltic pumps have recently been developed to deliver drugs at variable rates according to a physician-preprogrammed schedule which is actuated with the aid of transcutaneous telemetry. Other devices are available in the literature, if not yet in clinical application.
20 years of DNA-encoded chemical libraries (2011)

The identification of specific binding molecules is a central problem in chemistry, biology and medicine. Therefore, technologies, which facilitate ligand discovery, may substantially contribute to a better understanding of biological processes and to drug discovery. DNA-encoded chemical libraries represent a new inexpensive tool for the fast and efficient identification of ligands to target proteins of choice. Such libraries consist of collections of organic molecules, covalently linked to a unique DNA tag serving as an amplifiable identification bar code. DNA-encoding enables the in vitro selection of ligands by affinity capture at sub-picomolar concentrations on virtually any target protein of interest, in analogy to established selection methodologies like antibody phage display. Multiple strategies have been investigated by several academic and industrial laboratories for the construction of DNA-encoded chemical libraries comprising up to millions of DNA-encoded compounds. The implementation of next generation high-throughput sequencing enabled the rapid identification of binding molecules from DNA-encoded libraries of unprecedented size. This article reviews the development of DNA-encoded library technology and its evolution into a novel drug discovery tool, commenting on challenges, perspectives and opportunities for the different experimental approaches.
Predominant pathogens in hospital infections (1992)

To determine the distribution of pathogens causing nosocomial infections in United States hospitals, we analysed data from the National Nosocomial Infections Surveillance (NNIS) System. From October 1986 to December 1990, amongst hospitals conducting hospital-wide surveillance, the five most commonly reported pathogens were Escherichia coli (13.7%), Staphylococcus aureus (11.2%), enterococci (10.7%), Pseudomonas aeruginosa (10.1%), and coagulase-negative staphylococci (9.7%). The commonest pathogens reported by site included, bloodstream: coagulase-negative staphylococci, S. aureus, enterococci, E. coli, and Candida spp.; lower respiratory tract infection: S. aureus, P. aeruginosa and Enterobacter spp.; surgical wound infection: S. aureus, enterococci and coagulase-negative staphylococci; and urinary tract infection: E. coli, enterococci, and P. aeruginosa. Among hospitals conducting intensive care unit (ICU) surveillance, the commonest pathogens were P. aeruginosa (12.4%), S. aureus (12.3%), coagulase-negative staphylococci (10.2%), Candida spp. (10.1%), Enterobacter spp. and enterococci (8.6% each). In the ICUs, the commonest pathogens found in the bloodstream were coagulase-negative staphylococci, S. aureus, and enterococci; in lower respiratory tract infections P. aeruginosa, S. aureus, and enterococci; in surgical wound infections enterococci, coagulase-negative staphylococci, and Enterobacter spp. and in urinary tract infections Candida spp., E. coli, enterococci, P. aeruginosa, and Enterobacter spp. These data show that S. aureus, E. coli and P. aeruginosa remain important nosocomial pathogens, that coagulase-negative staphylococci, enterococci and C. albicans are pathogens of increasing importance, and that the distribution of pathogens differs by site and hospital location.
Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation (2007)

The emerging potential for the cannabinoid (CB) system in modulating gastrointestinal inflammation has gained momentum over the last few years. Traditional and anecdotal use of marijuana for gastrointestinal disorders, such as diarrhoea and abdominal cramps is recognized, but the therapeutic benefit of cannabinoids in the 21st century is overshadowed by the psychoactive problems associated with CB1 receptor activation. However, the presence and function of the CB2 receptor in the GI tract, whilst not yet well characterized, holds great promise due to its immunomodulatory roles in inflammatory systems and its lack of psychotropic effects. This review of our current knowledge of CB2 receptors in the gastrointestinal tract highlights its role in regulating abnormal motility, modulating intestinal inflammation and limiting visceral sensitivity and pain. CB2 receptors represent a braking system and a pathophysiological mechanism for the resolution of inflammation and many of its symptoms. CB2 receptor activation therefore represents a very promising therapeutic target in gastrointestinal inflammatory states where there is immune activation and motility dysfunction.
An Optimization Approach for Radiosurgery Treatment Planning (2002)

We outline a new approach for radiosurgery treatment planning, based on solving a series of optimization problems. We consider a specific treatment planning problem for a specialized device known as the gamma knife, which provides an advanced stereotactic approach to the treatment of tumors, vascular malformations, and pain disorders within the head. The sequence of optimization problems involves nonlinear and mixed integer programs whose solution is required in a given planning time (typically less than 30 minutes). This paper outlines several modeling decisions that result in more efficient and robust solutions. Furthermore, it outlines a new approach for determining starting points for the nonlinear programs, based on a skeletonization of the target volume. Treatment plans generated for real patient data show the efficiency of the approach.
Elevated levels of osteoprotegerin (OPG) and hepatocyte growth factor (HGF) in rheumatoid arthritis (2001)

Rheumatic diseases are often associated with changes in bone metabolism. Excessive production and release of cytokines and other growth factors due to inflammation, e.g. tumor necrosis factor-alpha (TNF-alpha), receptor activator of NF-kappaB ligand (RANKL), interleukins such as IL-1 and IL-6, may cause alterations in bone homeostasis leading to bone degradation. Other components such as osteoprotegerin (OPG) and possibly the ligand-receptor pair hepatocyte growth factor (HGF) and c-met may counteract this destruction, we have measured the levels of OPG, and HGF c-met, in serum, synovial fluid (SF), and cartilage from patients with rheumatoid arthritis (RA) and other arthritides. We found a) elevated levels of both OPG and HGF in SF from RA patients relative to arthritides of other causes, b) increased levels of both OPG and HGF in SF from seropositive RA patients (RA+) compared to seronegative RA patients (RA-), c) elevated levels or both OPG and HGF in serum from RA patients compared to healthy controls, d) no correlation between severity of inflammation and levels of OPG or HGF, and e) presence of HGF c-met in both cartilage and synovial tissue. The most significant elevations of OPG and HGF were found in patients with RA, the rheumatic disease most frequently associated with the development of secondary osteoporosis.
Cell wall appositions and plant disease resistance: Acoustic microscopy of papillae that block fungal ingress (1980)

Plant cells react to localized stress by forming wall appositions outside their protoplasts on the inner surface of their cellulose walls. For many years it has been inferred that appositions elicited by encroaching fungi, termed "papillae," may subsequently also deter them and thus represent a disease-resistance mechanism. Recently, it has been shown that preformed, oversized papillae, experimentally produced in coleoptile cells of compatible barley, Hordeum vulgare, can completely prevent direct entry of Erysiphe graminis f. sp. hordei that ordinarily penetrates and causes disease. To discover how these papillae may function, acoustic microscopy was used to contrast their in vivo elastic properties with those of ineffective normal papillae and contiguous cell wall. Raster and line scans showed intense acoustic activity at sites of preformed papillae; scans in selected focal planes identified this activity with the papillae, not with subtending cell wall. Minimal acoustic activity was found in normal papillae. It is suggested that some wall appositions could serve in disease resistance as viscoelastic barriers to mechanical forces exerted by the special penetration structures of advancing pathogenic fungi.
Aging, Longevity, Inflammation, and Cancer (2004)

Cancer rates increase sharply with age in both sexes, and the majority of cases of cancer occur in patients over the age of 65 years. However, the incidence and mortality for cancer level off around 85-90 years of age, followed by a plateau, or even a decline in the last decades of life. Therefore, it seems reasonable to conclude that centenarians are endowed with a peculiar resistance to cancer. Tumor progression is a complex process that depends on interactions between tumor and host cells. One aspect of the host response, the inflammatory response, is of particular interest because it includes the release of proinflammatory cytokines, some of which may promote tumor growth and hence influence survival. Data in the literature reviewed in this paper suggest that some kind of solid tumors are affected by regulatory cytokine genotypes. In particular proinflammatory genotypes characterized by a low IL-10 producer or a high IL-6 producer seem to be associated with a worse clinical outcome. On the other hand, recent evidence has linked IL-10 and IL-6 cytokine polymorphisms to longevity. In fact, those individuals who are genetically predisposed to produce high levels of IL-6 have a reduced capacity to reach the extreme limits of human life, whereas the high IL-10-producer genotype is increased among centenarians. This opposite effect of IL-6 and IL-10 common gene polymorphisms in cancer and longevity is intriguing. These data prompt considerations of the role that antagonistic pleiotropy plays in disease and in longevity. Inflammatory genotypes may be both friends and enemies. In fact, they are an important and necessary part of the normal host responses to pathogens, but the overproduction of inflammatory cytokines might cause immune-inflammatory diseases and eventually death. In fact, our immune system has evolved to control pathogens, so proinflammatory responses are likely to be evolutionarily programmed to resist fatal infections, and a high IL-6 or a low IL-10 production is associated with increased resistance to pathogens. However, decreased level of IL-6 or increased level of IL-10 might better control inflammatory responses and cancer development. These conditions might result in an increased chance of long-life survival in an environment with a reduced antigen (i.e., pathogen) load.
Effective Immunoconjugate Therapy in Cancer Models Targeting a Serine Protease of Tumor Fibroblasts (2008)

We show that mAb FAP5-DM1 combines excellent efficacy and tolerability and provides a first assessment of the mode of action of a novel drug candidate for tumor stroma targeting, thus encouraging further development toward clinical testing of this treatment paradigm.
DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor (2005)

The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8(+) T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK- and CD8(+) T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines.
Dissecting the Mechanism of Protein Disulfide Isomerase: Catalysis of Disulfide Bond Formation in a Model Peptide (1994)

As a model for understanding how protein disulfide isomerase (PDI) catalyzes disulfide bond formation in proteins, its action on a 28-residue disordered peptide containing only two cysteine residues has been examined. Disulfide formation in the peptide using the chemical reaction with small molecule thiol/disulfide reagents, such as oxidized and reduced glutathione or cystamine and cysteamine, occurs in two steps, via two alternative intermediate mixed disulfides between the reagent and either peptide cysteine residue. All thiol/disulfide forms of the peptide could be trapped and quantified, so the rates of their interconversion could be measured. Catalytic amounts of PDI increased the rates of these reactions. All rate enhancements were independent of the concentration of the peptide, indicating that it bound to PDI with an apparent Km of less than 3 microM. In the presence of glutathione, PDI accelerated the formation of both single mixed disulfide species, plus their subsequent rearrangement to form the peptide disulfide bond, but not interchange of the mixed disulfide glutathione between the two cysteine residues. In contrast, PDI did not catalyze the reaction of the reagent cystamine with the reduced peptide to form the mixed disulfide, nor the interchange of this mixed disulfide between cysteine residues, but did catalyze the subsequent intramolecular step of peptide disulfide bond formation to a similar extent as with the glutathione mixed disulfide. These effects on the two steps involving the mixed disulfides with glutathione or cystamine accounted for much of the overall catalytic effect of PDI on disulfide bond formation in the peptide, indicating that direct transfer of disulfide bonds from PDI to the peptide occurred less frequently. These findings demonstrate the utility of using such peptides as PDI substrates and have implications for the mechanism of action of PDI.
Electrochemical and Physical Properties of Ti-Substituted Layered Nickel Manganese Cobalt Oxide (NMC) Cathode Materials (2012)

The effect of partial substitution of titanium for cobalt on 3b sites in Li1+z(NixMnxCo1-2x-yTiy)O2 (x = 1/3, 0.4) cathode materials (NMCs) has been investigated for this study. Materials were prepared by glycine-nitrate combustion and co-precipitation methods and solid solutions were observed over a narrow substitution range limited to below about y = 0.07 for both the x = 1/3 and x = 0.4 series, although this depended on the synthesis technique. Increased discharge capacities, lower first cycle inefficiencies and better cycling behavior were observed for several of the Ti-substituted compositions in electrochemical cells. The improved first cycle efficiencies allow higher discharge capacities to be obtained between normal voltage limits, which partly explain the observations. Results from synchrotron X-ray diffraction also indicate that Ti substitution leads to a decreased cell volume change during deintercalation of lithium, which contributes to the improved cycling performance. Magnetic measurements suggest that reduction of some Mn4+ to Mn3+ compensates for the aliovalent substitution in as-made lithium-stoichiometric materials.
Clearing amyloid through the blood–brain barrier (2004)

According to the amyloid hypothesis, accumulation of amyloid beta-peptide (A beta) in the brain is the primary pathogenic event in Alzheimer's disease (AD). Recent evidence indicates that A beta within the intravascular space is linked to A beta deposited in the brain suggesting that transport of A beta between the brain, blood and cerebrospinal fluid, and across the blood-brain barrier, regulates brain A beta. Thus, understanding A beta exchanges between brain and blood, and vice versa, and developing transport-based systemic A beta-lowering strategies may provide new important insights into pathogenesis and therapeutic control of AD.