gebhart/patrepeval huggingface dataset:
LsaA, an Antigen Involved in Cell Attachment and Invasion, Is Expressed byLawsonia intracellularisduring Infection In Vitro and In Vivo (2002)

Lawsonia intracellularis has been identified recently as the etiological agent of proliferative enteropathies, which are characterized by intestinal epithelial hyperplasia and associated moderate immune responses. This disease complex has been reported in a broad range of animals, prevalently in pigs, and L. intracellularis has been linked with ulcerative colitis in humans. L. intracellularis is an obligate intracellular bacterium, and the pathogenic mechanisms used to cause disease are unknown. Using in vitro-grown organisms as a source of genomic DNA, we identified a Lawsonia gene which encodes a surface antigen, LsaA (for Lawsonia surface antigen), associated with attachment to and entry into cells. The deduced amino acid sequence of this protein showed some similarity to members of a novel protein family identified in a number of other bacterial pathogens but for which roles are not fully defined. Transcription of this gene was detected by reverse transcription-PCR in L. intracellularis grown in vitro in IEC18 cells and in bacteria present in ileal tissue from infected animals. Immunohistochemistry with specific monoclonal antibody and immunoblotting with sera from infected animals demonstrated that LsaA protein is synthesized by L. intracellularis during infection. Expression of this gene during infection in vitro and in vivo suggests that this surface antigen is involved during infection, and phenotypic analysis indicated a role during L. intracellularis attachment to and entry into intestinal epithelial cells
Optimization of Fibronectin-Assisted Retroviral Gene Transfer into Human CD34 + Hematopoietic Cells (1997)

Efficient retroviral gene transfer into hematopoietic stem and progenitor cells can be achieved by co-localizing retrovirus and target cells on specific adhesion domains of recombinant fibronectin (FN) fragments. In this paper, we further optimize this technology for human CD34+ cells. Investigating the role of cytokine prestimulation in retrovirus-mediated gene transfer on plates coated with the recombinant FN CH-296 revealed that prestimulation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) CD34+ cells was essential to achieve efficient gene transfer into clonogenic cells. The highest gene transfer occurred by prestimulating PB CD34+ cells for 40 hr with a combination of stem cell factor (SCF), G-CSF, and megakaryocyte growth and development factor (MGDF) prior to retroviral infection on CH-296. Surprisingly, a prolonged simultaneous exposure of primary CD34+ PB cells to retrovirus and cytokines in the presence of CH-296 lowered the gene transfer efficiency. Gene transfer into cytokine prestimulated CD34+ bone marrow (BM) cells was not influenced by increasing the coating concentrations of a recombinant FN fragment, CH-296, nor was it adversely influenced by increasing the number of CD34+ target cells, suggesting that the amount of retroviral particles present in the supernatant was not a limiting factor for transduction of CD34+ BM cells on CH-296-coated plates. The polycation Polybrene was not required for efficient transduction of hematopoietic cells in the presence of CH-296. Furthermore, we demonstrated that repeated exposure of CH-296 to retrovirus containing supernatant, called preloading, can be employed to concentrate the amount of retroviral particles bound to CH-296. These findings establish a simple and short clinically applicable transduction protocol that targets up to 68% of BM or G-CSF-mobilized PB CD34+ cells and is capable of genetically modifying up to 17% of CD34+CD38-/dim PB cells.
DNA unwinding induced by photoaddition of psoralen derivatives and determination of dark-binding equilibrium constants by gel electrophoresis (1978)

Derivatives of furo[3,2-g]coumarin (psoralen) can bind to the DNA double helix and, in the presence of long-wavelength UV light, the bound psoralen may react covalently with pyrimidine residues on one or both strands of the helix. By using agarose gel electrophoresis, we have determined the unwinding angle associated with each of four different psoralen derivatives to be 28 degrees +/- 4 degrees . For 4,5',8-trimethylpsoralen (trioxsalen) the unwinding angle was found to be independent of the initial DNA superhelix density in the range that is accessible to agarose gel electrophoresis. Also by using agarose gel electrophoresis, we have determined the unwinding angle for ethidium intercalation. This was done by the total relaxation of supercoiled DNA in the presence of a series of ethidium concentrations. By using published values for the association constant for ethidium binding to DNA and evaluating the final superhelix density (after removal of ethidium) of the DNA on gels, we calculated an unwinding angle of 29 degrees +/- 3 degrees . Assuming an unwinding angle of 28 degrees for the noncovalent intercalation of psoralen derivatives, we used the same procedure to determine intercalation binding constants. The association constants for 4'-aminomethyltrioxsalen were 300-1400 M(-1) in NaCl at 0.2-0.05 M and 300-2500 M(-1) in Mg(2+) at 4-0.5 mM. The association constant for 4'-hydroxymethyltrioxsalen in 0.5 mM Mg(2+) was determined to be 70 M(-1).
Abstract 11: Macrophage Expression of the Notch Ligand Delta-Like 4 Promotes Vein Graft Disease in LDL Receptor--Deficient Mice (2014)

Background: Vein graft failure causes devastating complications in patients with peripheral arterial disease or ischemic heart disease, but its underlying mechanisms remain obscure and no effective therapeutic measures are available. Methods and Results: We tested the hypothesis that Notch signaling triggered by its ligand Delta-like 4 (Dll4) promotes macrophage activation and vein graft disease. Vein graft surgery was performed in high-fat fed LDL receptor-deficient (Ldlr-/-) mice by implanting donor inferior vena cava into recipient right carotid arteries. [Approach 1: Dll4 antibody] Dll4 blocking antibody was administered for 28 days. Dll4 blockade inhibited lesion development and macrophage accumulation (Figures) in vein grafts, and suppressed macrophage expression of genes typical of pro-inflammatory M1 macrophages (e.g., IL-1β, TNF-α). In vivo molecular imaging demonstrated that Dll4 antibody treatment suppressed MMP activity in lesional macrophages. Dll4 blockade concomitantly attenuated collagen thinning. [Approach 2: siRNA delivery to macrophages] To address the relative contribution of macrophages to Dll4-mediated vein graft disease in vivo, we delivered Dll4 siRNA oligos encapsulated in macrophage-targeted lipid nanoparticles. In vivo Dll4 silencing in macrophages reduced lesion development and macrophage burden in vein grafts of Ldlr-/- mice to a similar extent as those of Dll4 antibody therapy. In vitro gain-of-function and loss-of-function studies suggested that Dll4 promotes expression of pro-inflammatory molecules in macrophages. Furthermore, macrophage Dll4 stimulated smooth muscle cell (SMC) proliferation and migration and suppressed their differentiation. Conclusions: These results suggest the novel mechanism that macrophage Dll4 promotes vein graft lesion development by exacerbating inflammation and crosstalk between macrophages and SMC, supporting the Dll4-Notch axis as a potential therapeutic target.
THE MITOCHONDRIAL DEATH/LIFE REGULATOR IN APOPTOSIS AND NECROSIS (1998)

Both physiological cell death (apoptosis) and, in some cases, accidental cell death (necrosis) involve a two-step process. At a first level, numerous physiological and some pathological stimuli trigger an increase in mitochondrial membrane permeability. The mitochondria release apoptogenic factors through the outer membrane and dissipate the electrochemical gradient of the inner membrane. Mitochondrial permeability transition (PT) involves a dynamic multiprotein complex formed in the contact site between the inner and outer mitochondrial membranes. The PT complex can function as a sensor for stress and damage, as well as for certain signals connected to receptors. Inhibition of PT by pharmacological intervention on mitochondrial structures or mitochondrial expression of the apoptosis-inhibitory oncoprotein Bcl-2 prevents cell death, suggesting that PT is a rate-limiting event of the death process. At a second level, the consequences of mitochondrial dysfunction (collapse of the mitochondrial inner transmembrane potential, uncoupling of the respiratory chain, hyperproduction of superoxide anions, disruption of mitochondrial biogenesis, outflow of matrix calcium and glutathione, and release of soluble intermembrane proteins) entails a bioenergetic catastrophe culminating in the disruption of plasma membrane integrity (necrosis) and/or the activation of specific apoptogenic proteases (caspases) by mitochondrial proteins that leak into the cytosol (cytochrome c, apoptosis-inducing factor) with secondary endonuclease activation (apoptosis). The relative rate of these two processes (bioenergetic catastrophe versus protease and endonuclease activation) determines whether a cell will undergo primary necrosis or apoptosis. The acquisition of the biochemical and ultrastructural features of apoptosis critically relies on the liberation of apoptogenic proteases or protease activators from mitochondria. The fact that mitochondrial events control cell death has major implications for the development of cytoprotective and cytotoxic drugs.
Comparison of genomic signatures of non-small cell lung cancer recurrence between two microarray platforms. (2012)

A four-gene signature is associated with survival among patients with early-stage NSCLC. Further validation of these findings is warranted.
A Mutation in a Purported Regulatory Gene Affects Control of Sterol Uptake in Saccharomyces cerevisiae (1998)

Aerobically growing wild-type strains of Saccharomyces cerevisiae are unable to take exogenously supplied sterols from media. This aerobic sterol exclusion is vitiated under anaerobic conditions, in heme-deficient strains, and under some conditions of impaired sterol synthesis. Mutants which can take up sterols aerobically in heme-competent cells have been selected. One of these mutations, designated upc2-1, gives a pleiotropic phenotype in characteristics as diverse as aerobic accumulation of sterols, total lipid storage, sensitivity to metabolic inhibitors, response to altered sterol structures, and cation requirements. During experiments designed to ascertain the effects of various cations on yeast with sterol alterations, it was observed that upc2-1 was hypersensitive to Ca2+. Using resistance to Ca2+ as a screening vehicle, we cloned UPC2 and showed that it is YDR213W, an open reading frame on chromosome IV. This belongs to a fungal regulatory family containing the Zn(II)2Cys6 binuclear cluster DNA binding domain. The single guanine-to-adenine transition in upc2-1 gives a predicted amino acid change from glycine to aspartic acid. The regulatory defect explains the semidominance and pleiotropic effects of upc2-1.
Cardiac-specific Overexpression of Mouse Cardiac Calsequestrin Is Associated with Depressed Cardiovascular Function and Hypertrophy in Transgenic Mice (1998)

Calsequestrin is a high capacity Ca2+-binding protein in the sarcoplasmic reticulum (SR) lumen. To elucidate the functional role of calsequestrin in vivo, transgenic mice were generated that overexpressed mouse cardiac calsequestrin in the heart. Overexpression (20-fold) of calsequestrin was associated with cardiac hypertrophy and induction of a fetal gene expression program. Isolated transgenic cardiomyocytes exhibited diminished shortening fraction (46%), shortening rate (60%), and relengthening rate (60%). The Ca2+ transient amplitude was also depressed (45%), although the SR Ca2+ storage capacity was augmented, as suggested by caffeine application studies. These alterations were associated with a decrease in L-type Ca2+ current density and prolongation of this channel's inactivation kinetics without changes in Na+-Ca2+ exchanger current density. Furthermore, there were increases in protein levels of SR Ca2+-ATPase, phospholamban, and calreticulin and decreases in FKBP12, without alterations in ryanodine receptor, junctin, and triadin levels in transgenic hearts. Left ventricular function analysis in Langendorff perfused hearts and closed-chest anesthetized mice also indicated depressed rates of contraction and relaxation of transgenic hearts. These findings suggest that calsequestrin overexpression is associated with increases in SR Ca2+ capacity, but decreases in Ca2+-induced SR Ca2+ release, leading to depressed contractility in the mammalian heart.
Microbial production of biovanillin (2010)

This review aims at providing an overview on the microbial production of vanillin, a new alternative method for the production of this important flavor of the food industry, which has the potential to become economically competitive in the next future. After a brief description of the applications of vanillin in different industrial sectors and of its physicochemical properties, we described the traditional ways of providing vanillin, specifically extraction and chemical synthesis (mainly oxidation) and compared them with the new biotechnological options, i.e., biotransformations of caffeic acid, veratraldehyde and mainly ferulic acid. In the second part of the review, emphasis has been addressed to the factors most influencing the bioproduction of vanillin, specifically the age of inoculum, pH, temperature, type of co-substrate, as well as the inhibitory effects exerted either by excess substrate or product. The final part of the work summarized the downstream processes and the related unit operations involved in the recovery of vanillin from the bioconversion medium.
Clinical implications of a staging model for bipolar disorders (2009)

A model of staging in the field of bipolar disorder (BD) should offer a means for clinicians to predict response to treatment and more general outcome measures, such as the level of functioning and autonomy. The present staging model emphasizes the assessment of patients in the interepisodic period and includes: latent phase: individuals who present mood and anxiety symptoms and increased risk for developing threshold BD; Stage I--patients with BD who present well established periods of euthymia and absence of overt psychiatric morbidity between episodes; Stage II--patients who present rapid cycling or current axis I or II comorbidities; Stage III--patients who present a clinically relevant pattern of cognitive and functioning deterioration, as well as altered biomarkers; and Stage IV--patients who are unable to live autonomously and present altered brain scans and biomarkers. Such a model implies a longitudinal appraisal of clinical variables, as well as assessment of neurocognition and biomarkers in the interepisodic period. Staging facilitates understanding of the mechanisms underlying progression of the disorder, assists in treatment planning and prognosis and, finally, underscores the imperative for early intervention.
Formation Mechanism and Properties of Electrochemically Etched Trenches in n‐Type Silicon (1990)

Three‐dimensional structures in silicon are increasingly coming into use for the fabrication of mechanical and electrical devices. The fabrication of deep trenches is one of the most important problems in VLSI (very large scale integration) technology. In this study the spontaneous trench formation in n‐type silicon immersed in hydrofluoric acid under anodic bias is demonstrated and the resulting microstructures are characterized. Trenches with arbitrary cross sections and high aspect ratios for microelectronic (e.g., 42 μm depth and 0.6 μm diam) and for power component application (e.g., 60 μm depth and 10 μm diam) have been produced by a standard masking technique. The trench formation is explained by a model which takes into account the conditions of the space charge region the minority carrier current and the crystal orientation. A passivating sidewall layer is not needed in this model. The dimensions and the shape of anodically etched trenches can be varied over a wide range by adjusting the critical parameters.
Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression (1989)

The kinetics of retroviral DNA and RNA synthesis are parameters vital to understanding viral growth, especially for human immunodeficiency virus (HIV), which encodes several of its own regulatory genes. We have established a single-cycle growth condition for HIV in H9 cells, a human CD4+ lymphocyte line. The full-length viral linear DNA is first detectable by 4 h postinfection. During a one-step growth of HIV, amounts of viral DNA gradually increase until 8 to 12 h postinfection and then decrease. The copy number of unintegrated viral DNA is not extraordinarily high even at its peak. Most strikingly, there is a temporal program of RNA accumulation: the earliest RNA is greatly enriched in the 2-kilobase subgenomic mRNA species, while the level of 9.2-kilobase RNA which is both genomic RNA and mRNA remains low until after 24 h of infection. Virus production begins at about 24 h postinfection. Thus, viral DNA synthesis is as rapid as for other retroviruses, but viral RNA synthesis involves temporal alteration in the species that accumulate, presumably as a consequence of viral regulatory genes.
<title>Adaptive trimmed mean filter for computed tomographic imaging</title> (1994)

The image quality of a computed tomography (CT) scan is frequently degraded by severe streaking artifacts resulting from excessive x-ray quantum noise. When this occurs, a patient has to be re-scanned at a higher x-ray technique to obtain an acceptable image for diagnosis. This approach results in not only unnecessary dosage to the patient, but also a delayed patient diagnosis and a reduced patient throughput. In this paper, we propose an adaptive trimmed mean filter (ATMF) in Radon space to combat this problem. The ATMF is an extension to the existing (alpha) -inner mean filter in that both sample size M and the trimming parameter (alpha) are selected based on the local statistics. In addition, the 2D ATMF is unsymmetrical to adapt to the sampling pattern in Radon pace. Phantom studies and clinical evaluations have shown that this type of filter is very effective in reducing or eliminating quantum noise induced artifacts. At the same time, the impact on the image spatial resolution has been kept to a minimum.
Growth inhibition of different human colorectal cancer xenografts after a single intravenous injection of oncolytic vaccinia virus GLV-1h68 (2013)

The anti-tumor activity observed against colorectal cancer cells in these studies was a result of direct viral oncolysis by GLV-1h68 and inflammation-mediated innate immune responses. The therapeutic effects occurred in tumors regardless of the stage of disease from which the cells were derived. Thus, the recombinant vaccinia virus GLV-1h68 has the potential to treat colorectal cancers independently of the stage of progression.
Two novel genital human papillomavirus (HPV) types, HPV68 and HPV70, related to the potentially oncogenic HPV39 (1996)

The genomes of two novel human papillomavirus (HPV) types, HPV68 and HPV70, were cloned from a low-grade cervical intraepithelial neoplasia and a vulvar papilloma, respectively, and partially sequenced. Both types are related to HPV39, a potentially oncogenic virus. HPV68 and HPV70 were also detected in genital intraepithelial neoplasia from three patients and one patient, respectively. Comparison with sequence data in the literature indicates that the subgenomic ME180-HPV DNA fragment, cloned from a carcinoma cell line, corresponds to an HPV68 subtype and that several HPV DNA fragments amplified by PCR from genital neoplasia represent worldwide distributed variants of HPV68 and HPV70.
Preliminary Studies in the Development of a Gastric Battery for Fish (1964)

In 1956 Parker S. Trefethen described an external ultrasonic tag for tracking fish. This tag was designed for use on adult king salmon, Oncorhynchus tshawytsca, and was subsequently used to track these fish above Bonneville Dam (Johnson, 1957). Although this tracking system was the best available at that time several limitations to its use were evident: the transmitter and power supply were large and thus impractical for use on small fish, and the unit was attached externally and was likely to influence movement, and the life of the battery was very short (17 hours). Succeeding transmitters were somewhat longer-lived and smaller (Novotny and Esterberg, 1962). However, they were externally attached to the fish and their use still limited by a short battery life (up to 10 days).
UW is superior to Celsior and HTK in the protection of human liver endothelial cells against preservation injury (2004)

Celsior solution (CS), a new preservation solution in thoracic organ transplantation, was evaluated for its efficacy in cold preservation of human liver endothelial cells (HLEC) and was compared to University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK, Custodiol). HLEC cultures were preserved at 4 degrees C in CS, UW, and HTK, for 2, 6, 12, 24, and 48 hours, with 6 hours of reperfusion. Levels of lactate dehydrogenase (LDH), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and adenosine 5'-triphosphate (ATP) were measured after each interval of ischemia and the respective phase of reperfusion. Preservation injury of HLEC as measured by LDH release, intracellular ATP level, and MTT reduction were overall significantly (P <or= .01, P <or= .01, P < .05, respectively) lower in UW than in CS and HTK. CS demonstrates a modest superiority to HTK in HLEC preservation. Furthermore, cold preservation remains the main cause of preservation injury of HLEC regardless of the preservation solution used. Additionally, the maintenance of a high intracellular ATP level of HLEC after ischemia and reperfusion, as shown by UW, could be taken as a beneficial effect, particularly in long-term ischemia. In conclusion, our cell culture model reveals the order of efficacy to protect HLEC against preservation injury as: UW >> CS > HTK.
Enhancement of CD8+ T Cell Responses by ICOS/B7h Costimulation (2001)

Although the recently identified ICOS/B7h costimulatory counterreceptors are critical regulators of CD4(+) T cell responses, their ability to regulate CD8(+) responses is unclear. Here we report using a tumor-rejection model that ectopic B7h expression can costimulate rejection by CD8(+) T cells in the absence of CD4(+) T cells. Although responses of naive T cells were significantly augmented by priming with B7h, B7h was surprisingly effective in mobilizing recall responses of adoptively transferred T cells. To explore why secondary responses of CD8(+) T cells were particularly enhanced by B7h, kinetics of ICOS up-regulation, proliferative responses, and cytokine production were compared from both naive and rechallenged 2C-transgenic T cells costimulated in vitro. Although B7h costimulated proliferative responses from both CD8(+) populations, rechallenged cells were preferentially costimulated for IL-2 and IFN-gamma production. These results indicate that ICOS/B7h counterreceptors likely function in vivo to enhance secondary responses by CD8(+) T cells.