gebhart/patrepeval huggingface dataset:
Inflammatory Cytokines in Heart Failure: Mediators and Markers (2012)

Evidence from both experimental and clinical trials indicates that inflammatory mediators are of importance in the pathogenesis of chronic heart failure (HF) contributing to cardiac remodeling and peripheral vascular disturbances. Several studies have shown raised levels of inflammatory cytokines such as tumor necrosis factor (TNF)α, interleukin (IL)-1β and IL-6 in HF patients in plasma and circulating leukocytes, as well as in the failing myocardium itself. There is strong evidence that these mediators are involved in processes leading to cardiac remodeling such as hypertrophy, fibrosis and apoptosis. Some of these cytokines can also give useful prognostic information as reliable biomarkers in this disorder. In general, immunomodulating treatments have, with a few exceptions, been neutral or even harmful. However, the negative results of anti-TNF studies, for instance, do not necessarily argue against the 'cytokine hypothesis'. These studies just underscore the challenges in developing treatment modalities that can modulate the cytokine network in HF patients and result in beneficial net effects. Future studies should identify the crucial actors and their mechanisms of action in the immunopathogenesis of chronic HF and, in particular, clarify the balance between adaptive and maladaptive effects of these molecules. Such studies are a prerequisite for the development of new treatment strategies that target inflammatory and immunopathogenic mechanisms in HF. In this review article, these issues are thoroughly discussed, and we also argue for the possibility of future therapeutic targets such as mediators in innate immunity, chemokines and mediators in matrix remodeling.
Regulation of Telomerase Activity in Rat Lung Fibroblasts (2002)

Fibroblasts from bleomycin-injured lungs express telomerase activity transiently during the period of active fibrosis, but the signal(s) responsible for its induction is (are) unknown. The objective of this study was to identify potential mediators capable of regulating telomerase activity induction in rat lung fibroblasts during pulmonary fibrosis. Lung fibroblasts from control (NRF) and bleomycin-treated (BRF) rats were isolated and treated in vitro with either basic fibroblast growth factor (bFGF) or interleukin-4 (IL-4). At selected time points after treatment, the cells were analyzed for telomerase activity, as well as telomerase reverse transcriptase (TERT) mRNA and protein by reverse transcriptase/polymerase chain reaction and Western blot, respectively. The results showed that bFGF could induce telomerase activity in NRF and stimulate further the induced activity in BRF. The bFGF effect was accompanied by increased TERT protein expression and a rapid but transient increase in TERT mRNA. In contrast, IL-4 inhibited the induced telomerase activity in BRF, which was accompanied by increased alpha-smooth muscle actin expression, an indicator of myofibroblast differentiation. These findings suggest that telomerase expression could be induced in rat lung fibroblasts by bFGF, but suppressed by IL-4, which promoted myofibroblast differentiation. The latter is consistent with the preferential expression of telomerase activity in fibroblasts relative to myofibroblasts.
Effects of Toxin A fromClostridium difficileon Mast Cell Activation and Survival (1998)

Toxins A and B from Clostridium difficile are the main cause of antibiotic-associated diarrhea and pseudomembranous colitis. They cause fluid accumulation, necrosis, and a strong inflammatory response when inoculated in intestinal loops. Since mast cells are a rich source of inflammatory mediators, abundant in the gut, and known to be involved in C. difficile-induced enteritis, we studied the in vitro effect of toxin A on isolated mast cells. Normal rats sensitized by infection with Nippostrongilus brasiliensis were used to isolate peritoneal mast cells (PMC). PMC from naive rats were stimulated with calcium ionophore A23187 as a model of antigen-independent activation, and PMC from sensitized rats were stimulated with N. brasiliensis antigens to study immunoglobulin E-dependent mast cell activation. After 4 h, toxin A did not induce release of nitric oxide or histamine in naive PMC. However, 10 ng of toxin per ml caused a significant release of tumor necrosis factor alpha (TNF-alpha). In contrast, 1 microg of toxin per ml inhibited antigen or A23187-induced histamine release by PMC. Toxin A at 1 microg/ml for 4 h caused disruption of actin which aggregated in the cytoplasm and around the nucleus. After 24 h, chromatin condensation, cytoplasmic blebbing, and apoptotic-like vesicles were observed; DNA fragmentation was documented also. These results suggest that mast cells may participate in the initial inflammatory response to C. difficile infection by releasing TNF-alpha upon interaction with toxin A. However, longer exposure to toxin A affects the release of inflammatory mediators, perhaps because of the alteration of the cytoskeleton and induction of apoptosis. The impaired functions and survival of mast cells by C. difficile toxin A could hamper the capacity of these cells to counteract the infection, thus prolonging the pathogenic effects of C. difficile toxins.
sst2 somatostatin receptor expression reverses tumorigenicity of human pancreatic cancer cells. (1997)

Among the five cloned somatostatin receptor subtypes (sst1 to sst5), sst2 mediates the antiproliferative effect of somatostatin analogues in vitro. Somatostatin analogues have been shown to inhibit cell growth in vitro and in vivo in pancreatic cancer models that expressed sst2. We recently demonstrated the loss of sst2 gene expression in human pancreatic adenocarcinomas and most of the derived pancreatic cancer cell lines. In the present study, we corrected the sst2 defect in human pancreatic cancer BxPC-3 and Capan-1 cells by stable transfection with human sst2 cDNA. In the absence of exogenous ligand, both BxPC-3 and Capan-1 cells expressing sst2 showed a significant reduction in cell growth. This inhibitory effect was blocked by treatment with antiserum to somatostatin. sst2-expressing cells produced somatostatin-like immunoreactivity that mainly corresponded to somatostatin 14, indicating the induction of a negative autocrine loop. In other respects, sst2 expression in Capan-1 cells induced a significant reduction of clonogenicity in soft agar. Moreover, a significantly reduced (Capan-1 cells) or suppressed (BxPC-3 cells) tumor growth in athymic nude mice was observed. The reversal of tumorigenicity induced by the restoration of sst2 expression suggests that the loss of sst2 contributes to the malignancy of human pancreatic cancers.
Expression of desmosomal proteins in squamous cell carcinomas of the skin (2003)

Desmosomal proteins are highly regulated in cutaneous SCC. Only desmoglein 2 expression correlates with risk of metastasis. Desmosomes may still be functional in metastasizing tumor cells.
Lensless electronic imaging (1997)

A theory is presented for image retrieval when a planar transparency is illuminated by spatially incoherent light that propagates in free space and is then recorded on a CCD array, but without using an imaging lens. Based on Maxwell's equations and Fourier-optical, linear-systems theory, equations are derived for digital processing of this badly blurred image in order to recover a reasonable facsimile of the original. Rigorous impulse responses and their corresponding transfer functions are presented for the cases of general amplitude illumination and for incoherent illumination.
An induced-fit kinetic mechanism for DNA replication fidelity: direct measurement by single-turnover kinetics (1991)

An exonuclease-deficient mutant of T7 DNA polymerase was constructed and utilized in a series of kinetic studies on misincorporation and next correct dNTP incorporation. By using a synthetic oligonucleotide template-primer system for which the kinetic pathway for correct incorporation has been solved [Patel, S.S., Wong, I., & Johnson, K. A. (1991) Biochemistry (first of three papers in this issue)], the kinetic parameters for the incorporation of the incorrect triphosphates dATP, dCTP, and dGTP were determined, giving, respectively, kcat/Km values of 91, 23, and 4.3 M-1 s-1 and a discrimination in the polymerization step of 10(5)-10(6). The rates of misincorporation in all cases were linearly dependent on substrate concentration up to 4 mM, beyond which severe inhibition was observed. Competition of correct incorporation versus dCTP revealed an estimated Ki of approximately 6-8 mM, suggesting a corresponding kcat of 0.14s-1. Moderate elemental effects of 19-, 17-, and 34-fold reduction in rates were measured by substituting the alpha-thiotriphosphate analogues for dATP, dCTP, and dGTP, respectively, indicating that the chemistry step is partially rate-limiting. The absence of a burst of incorporation during the first turnover places the rate-limiting step at a triphosphate binding induced conformational change before chemistry. In contrast, the incorporation of the next correct triphosphate, dCTP, on a mismatched DNA substrate was saturable with a Km of 87 microM for dCTP, 4-fold higher than the Kd for the correct incorporation on duplex DNA, and a kcat of 0.025 s-1. A larger elemental effect of 60, however, suggests a rate-limiting chemistry step. The rate of pyrophosphorolysis on a mismatched 3'-end is undetectable, indicating that pyrophosphorolysis does not play a proofreading role in replication. These results show convincingly that the T7 DNA polymerase discriminates against the incorrect triphosphate by an induced-fit conformational change and that, following misincorporation, the enzyme then selects against the resultant mismatched DNA by a slow, rate-limiting chemistry step, thereby allowing sufficient time for the release of the mismatched DNA from the polymerase active site to be followed by exonucleolytic error correction.
Susceptibility of cats to equine morbillivirus (1996)

This is the first demonstration that animals can be infected with EMV by non-parenteral means, that the virus can transmit naturally between animals and confirms other reports of the similarity of EMV disease in horses and cats.
Improved inference and autotyping in EEG-based BCI typing systems (2013)

The RSVP Keyboard™ is a brain-computer interface (BCI)-based typing system for people with severe physical disabilities, specifically those with locked-in syndrome (LIS). It uses signals from an electroencephalogram (EEG) combined with information from an n-gram language model to select letters to be typed. One characteristic of the system as currently configured is that it does not keep track of past EEG observations, i.e., observations of user intent made while the user was in a different part of a typed message. We present a principled approach for taking all past observations into account, and show that this method results in a 20% increase in simulated typing speed under a variety of conditions on realistic stimuli. We also show that this method allows for a principled and improved estimate of the probability of the backspace symbol, by which mis-typed symbols are corrected. Finally, we demonstrate the utility of automatically typing likely letters in certain contexts, a technique that achieves increased typing speed under our new method, though not under the baseline approach.
Estimating enrichment of repetitive elements from high-throughput sequence data (2010)

We describe computational methods for analysis of repetitive elements from short-read sequencing data, and apply them to study histone modifications associated with the repetitive elements in human and mouse cells. Our results demonstrate that while accurate enrichment estimates can be obtained for individual repeat types and small sets of repeat instances, there are distinct combinatorial patterns of chromatin marks associated with major annotated repeat families, including H3K27me3/H3K9me3 differences among the endogenous retroviral element classes.
Structure and function of prostanoid receptors. (1993)

We have recently cloned cDNAs for the human and mouse TXA2/PGH2 receptors and a cDNA for the mouse PGE receptor. Sequencing, homology and hydrophobicity analyses revealed that they are proteins of 343, 341 and 365 amino acid residues, respectively, and all are rhodopsin-type receptors with putative seven transmembrane domains. Homology between the human and mouse TXA2 receptors is 76% in total and that between the human TXA2 and mouse PGE receptors is 38%. The homology increases in the putative transmembrane regions to 85 and 45%, respectively, and there observed several features common to the three receptors. These results indicate that the prostanoid receptors constitute a family of receptors of similar structure. The cloned PGE receptor showed binding activity specific to so-called EP3 agonists, which verified for the first time that pharmacologically defined PGE receptor subtypes consist of different molecules. This receptor also displayed different efficiency in signal transduction to an EP3 agonist, M & B-28767, and PGE2, providing an interesting model for the analysis of receptor-G protein coupling. In addition to the above biochemical results, these studies have revealed the characteristic tissue distribution of these receptors, which will open up a new biology of these prostanoids.
HELLP syndrome: recognition and perinatal management. (1999)

HELLP, a syndrome characterized by hemolysis, elevated liver enzyme levels and a low platelet count, is an obstetric complication that is frequently misdiagnosed at initial presentation. Many investigators consider the syndrome to be a variant of preeclampsia, but it may be a separate entity. The pathogenesis of HELLP syndrome remains unclear. Early diagnosis is critical because the morbidity and mortality rates associated with the syndrome have been reported to be as high as 25 percent. Platelet count appears to be the most reliable indicator of the presence of HELLP syndrome. The D-dimer test may be a useful tool for the early identification of patients with preeclampsia who may develop severe HELLP syndrome. The mainstay of therapy is supportive management, including seizure prophylaxis and blood pressure control in patients with hypertension. Women remote from term should be considered for conservative management, whereas those at term should be delivered. Some patients require transfusion of blood products, and most benefit from corticosteroid therapy. Rarely, patients with refractory HELLP syndrome require plasmapheresis.
BTS1 Encodes a Geranylgeranyl Diphosphate Synthase in Saccharomyces cerevisiae (1995)

Protein prenylation utilizes different types of isoprenoids groups, namely farnesyl and geranylgeranyl, to modify proteins. These lipophilic moieties attach to carboxyl-terminal cysteine residues to promote the association of soluble proteins to membranes. Most prenylated proteins are geranylgeranylated. Geranylgeranylation is catalyzed by two different prenyltransferases, the type I and type II geranylgeranyl transferases, both of which utilize geranylgeranyl diphosphate as a lipid donor. In the yeast Saccharomyces cerevisiae, the BET2 gene encodes the beta-subunit of the type II geranylgeranyl transferase. Mutations in this gene cause a defect in the geranylgeranylation of small GTP-binding proteins that mediate vesicular traffic. In an attempt to analyze those genes whose products may interact with Bet2, we isolated a suppressor of the bet2-1 mutant. This suppressor gene, called BTS1, encodes the yeast geranylgeranyl diphosphate synthase. BTS1 is not essential for the vegetative growth of cells; however, disrupting it impedes the geranylgeranylation of many cellular proteins and renders cells cold sensitive for growth. Our findings imply that BTS1 suppresses the bet2-1 mutant by increasing the intracellular pool of geranylgeranyl diphosphate.
Deep Vein Thrombosis Treated With Streptokinase or Heparin (1976)

Twenty-seven patients with deep vein thrombosis whose primary therapy was randomized between streptokinase and heparin were reevaluated clinically and by ascending venography after a mean period of 7 months. Normal venograms were found in 6 (40%) of the streptokinase-treated patients and in 1 patient (8%) who had heparin therapy. Segmental valve preservation was found in 1 patient from each group. All patients with complete or partial valve preservation became asymptomatic. Vein recanalization without preservation of valves occurred in 18 patients: 8 (54%) of those on streptokinase, and 10 (83%) of those on heparin. At the time of follow-up, 11 of these 18 patients, including 8 who had had prior thrombosis, reported peripheral edema; the postphlebitic syndrome developed in 1. Factors favoring a good outcome of acute venous thrombosis were (1) no prior thrombotic disease, (2) localized thrombosis, and (3) prompt streptokinase therapy.
Lipopolysaccharide smooth-rough phase variation in bacteria of the genus Chlamydia (1994)

In two strains of Chlamydia psittaci and in Chlamydia trachomatis serotype L1, we have detected a so-far-unknown antigen which (i) is resistant to heat and proteolytic digestion, (ii) can be extracted with phenol-water into the water phase, (iii) gives a ladder-like banding pattern in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (iv) is immunogenic in rabbits and mice, and (v) contains immunoreactivity of lipid A, a common and characteristic component of gram-negative lipopolysaccharides (LPS). Thus, chlamydiae contain, in addition to the known rough-type LPS, another LPS type which is phenotypically smooth (S-LPS). S-LPS was observed preferentially in chlamydiae grown in the yolk sac of embryonated eggs; it was, however, also detected by immunofluorescence in tissue culture-grown chlamydiae with a monoclonal antibody against S-LPS.
Progress in Two-Dimensional Arrays for Real-Time Volumetric Imaging (1998)

The design, fabrication, and evaluation of two dimensional array transducers for real-time volumetric imaging are described. The transducers we have previously described operated at frequencies below 3 MHz and were unwieldy to the operator because of the interconnect schemes used in connecting to the transducer handle. Several new transducers have been developed using new connection technology. A 40 x 40 = 1,600 element, 3.5 MHz array was fabricated with 256 transmit and 256 receive elements. A 60 x 60 = 3,600 element 5.0 MHz array was constructed with 248 transmit and 256 receive elements. An 80 x 80 = 6,400 element, 2.5 MHz array was fabricated with 256 transmit and 208receive elements. 2-D transducer arrays were also developed for volumetric scanning in an intra cardiac catheter, a 10 x 10 = 100 element 5.0 MHz forward-looking array and an 11 x 13 = 143 element 5.0 MHz side-scanning array. The-6dB fractional bandwidths for the different arrays varied from 50% to 63%, and the 50 omega insertion loss for all the transducers was about-64 dB. The transducers were used to generate real-time volumetric images in phantoms and in vivo using the Duke University real time volumetric imaging system, which is capable of generating multiple planes at any desired angle and depth within the pyramidal volume.
Relationship of Specific Vaginal Bacteria and Bacterial Vaginosis Treatment Failure in Women Who Have Sex with Women (2008)

Persistent bacterial vaginosis is associated with several bacteria in the Clostridiales order, Megasphaera phylotype 2, and P. lacrimalis, suggesting that vaginal microbiology at diagnosis may determine risk for antibiotic failure.
An automated pulse labelling method for structure-activity relationship studies with antibacterial oxazolidinones. (1990)

The 3-aryl-2-oxooxazolidinones are a new class of synthetic antibacterial agents that potently inhibit protein synthesis. An automated pulse labelling method with [3H]-lysine was developed with Bacillus subtilis to obtain additional quantitative activity data for structure-activity relationship studies with the oxazolidinones. Inhibition constants were calculated after a Logit fit of the data into the formula: % of control = 100/(1 + e[-B(X - A)]), where B is the slope of the model, X is the natural log of the inhibitor concentration and A is the natural log of the inhibitor concentration required to inhibit protein synthesis by 50% (ln IC50). When substituents at the 5-methyl position of the heterocyclic ring (B-substituent) were NHCOCH3, OH or Cl, the correlation coefficient was 0.87 between the MIC and IC50 values (for all compounds with MICs less than or equal to 16 micrograms/ml). The D-isomers of DuP 721 (A-substituent = CH3CO) and DuP 105 (A-substituent = CH3SO) gave MICs of 128 micrograms/ml and IC50s of greater than or equal to 50 micrograms/ml for protein synthesis, showing that only the L-isomers were active. By MIC testing, oxazolidinones with the B-substituent of NHCOCH3 and the A-substituent of CH3CO, NO2, CH3S, CH3SO2 or (CH3)2CH had comparable antibacterial potency; however, pulse labelling analysis showed that compounds with an A-substituent of CH3CO or NO2 were more potent inhibitors of protein synthesis.
Tissue Engineering and Regenerative Medicine: History, Progress, and Challenges (2011)

The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this effort has been translated to actual therapies, especially in the areas of skin replacement and, to a lesser extent, cartilage repair. A good amount of thoughtful work has also yielded prototypes of other tissue substitutes such as nerve conduits, blood vessels, liver, and even heart. Forward movement to clinical product, however, has been slow. Another offshoot of these efforts has been the incorporation of some new exciting technologies (e.g., microfabrication, 3D printing) that may enable future breakthroughs. In this review we highlight the modest beginnings of the field and then describe three application examples that are in various stages of development, ranging from relatively mature (skin) to ongoing proof-of-concept (cartilage) to early stage (liver). We then discuss some of the major issues that limit the development of complex tissues, some of which are fundamentals-based, whereas others stem from the needs of the end users.