gebhart/patrepeval huggingface dataset:
Endocytosis and Nuclear Trafficking of Adeno-Associated Virus Type 2 Are Controlled by Rac1 and Phosphatidylinositol-3 Kinase Activation (2000)

Adeno-associated virus (AAV) is a single-stranded DNA parvovirus that causes no currently known pathology in humans. Despite the fact that this virus is of increasing interest to molecular medicine as a vector for gene delivery, relatively little is known about the cellular mechanisms controlling infection. In this study, we have examined endocytic and intracellular trafficking of AAV-2 using fluorescent (Cy3)-conjugated viral particles and molecular techniques. Our results demonstrate that internalization of heparan sulfate proteoglycan-bound AAV-2 requires alphaVbeta5 integrin and activation of the small GTP-binding protein Rac1. Following endocytosis, activation of a phosphatidylinositol-3 (PI3) kinase pathway was necessary to initiate intracellular movement of AAV-2 to the nucleus via both microfilaments and microtubules. Inhibition of Rac1 using a dominant N17Rac1 mutant led to a decrease in AAV-2-mediated PI3 kinase activation, indicating that Rac1 may act proximal to PI3 kinase during AAV-2 infection. In summary, our results indicate that alphaVbeta5 integrin-mediated endocytosis of AAV-2 occurs through a Rac1 and PI3 kinase activation cascade, which directs viral movement along the cytoskeletal network to the nucleus.
GATA-3 Dominant Negative Mutant (1995)

The GATA family of transcription factors regulates a wide variety of genes, including those involved in differentiation of erythrocytes and T lymphocytes. We report here the creation of a dominant negative mutant of GATA-3, KRR, which effectively blocks wild-type GATA-1, GATA-2, and GATA-3 transactivation when co-expressed in transient assays. KRR was generated by site-directed mutagenesis while investigating a putative activation domain of GATA-3, located between its two zinc fingers. The GATA-3 KRR mutation does not affect expression, nuclear translocation, or the ability to bind to a consensus GATA sequence. KRR can suppress the activity of the minimal T cell receptor (TCR) alpha and beta enhancers by 12- and 3.4-fold, respectively. However, KRR did not have a significant effect on the activity of larger TCR-alpha and -beta enhancer fragments. Thus, functional redundancy in the TCR-alpha and -beta enhancers can compensate for the loss of GATA-3 activity.
Mortality Among Persons With Obsessive-Compulsive Disorder in Denmark (2016)

The presence of OCD was associated with a significantly increased mortality risk. Comorbid anxiety disorders, depression, or substance use disorders further increased the risk. However, after adjusting for these and somatic comorbidities, we found that the mortality risk remained significantly increased among persons with OCD.
Apoptosis of Bystander T Cells Induced by Human Immunodeficiency Virus Type 1 with Increased Envelope/Receptor Affinity and Coreceptor Binding Site Exposure (2004)

Apoptosis of uninfected bystander CD4(+) T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1) pathogenesis. The viral and host mechanisms that lead to bystander apoptosis are not well understood. To investigate properties of the viral envelope glycoproteins (Env proteins) that influence the ability of HIV-1 to induce bystander apoptosis, we used molecularly cloned viruses that differ only in specific amino acids in Env. The ability of these strains to induce bystander apoptosis was tested in herpesvirus saimiri-immortalized primary CD4(+) T cells (CD4/HVS), which resemble activated primary T cells. Changes in Env that increase affinity for CD4 or CCR5 or increase coreceptor binding site exposure enhanced the capacity of HIV-1 to induce bystander apoptosis following viral infection or exposure to nonreplicating virions. Apoptosis induced by HIV-1 virions was inhibited by CD4, CXCR4, and CCR5 antibodies or by the CXCR4 inhibitor AMD3100, but not the fusion inhibitor T20. HIV-1 virions with mutant Envs that bind CXCR4 but are defective for CD4 binding or membrane fusion induced apoptosis, whereas CXCR4 binding-defective mutants did not. These results demonstrate that HIV-1 virions induce apoptosis through a CXCR4- or CCR5-dependent pathway that does not require Env/CD4 signaling or membrane fusion and suggest that HIV-1 variants with increased envelope/receptor affinity or coreceptor binding site exposure may promote T-cell depletion in vivo by accelerating bystander cell death.
Regulators of G-Protein Signaling 3 and 4 (RGS3, RGS4) Are Associated with Glioma Cell Motility (2004)

Diffuse brain invasion is a major reason for poor prognosis of glioma patients. The molecular mechanisms underlying infiltration are different from those of other cancer types. To detect genes associated with glioma invasion, highly migratory clones were selected from U373MG glioma cells and from primary glioblastoma cells, and the gene expression pattern of these "fast" cells was compared with that of the original ("slow") cells using oligonucleotide microarrays comprising 12,625 genes. A total of 28 genes were differently expressed in both primary and established cell populations, including 19 genes that were upregulated and 9 that were downregulated in fast cells. Most of these genes have not been linked to glioma invasion so far. Specifically, differentially expressed genes included those encoding extracellular matrix components (COL16A1, DPT), proteases (CATD, PRSS11), cytokines (MDK, IL8), transport proteins (SLC1A3, ATP10B), cytoskeleton constituents (ACTA2, ACTSG, NEFL), DNA repair enzymes (WRN, ADPRTL2), and G-protein signaling components (GNA12, RGS3, RGS4). RGS3 and RGS4, which are homologs of the Drosophila glia gene loco, were further functionally analyzed. U373MG glioma cell clones overexpressing RGS3 or RGS4 showed an increase of both adhesion and migration. These findings expand the spectrum of possible molecular pathways underlying the invasion of neoplastic astrocytes. Specifically, they suggest that RGS proteins and G-protein-mediated signal transduction are evolutionary conserved functional players.
Automated identification of changes in electrode contact properties for long-term permanent ERT monitoring experiments (2013)

ABSTRACT Electrical resistivity tomography (ERT) monitoring experiments are being conducted more often to image spatiotemporal changes in soil properties. When conducting long-term ERT monitoring, the identification of suspicious electrodes in a permanent spread is of major importance because changes in electrode contact properties of a single electrode may affect the quality of many measurements on each time-slice. An automated methodology was developed to detect these temporal changes in electrode contact properties, based on a Bayesian approach called “weights of evidence.” Contrasts (CW) and studentized contrasts (CS) are estimators of the influence of each electrode in the global data quality. A consolidated studentized contrast (CCS) is introduced to consider the proportion of rejected quadripoles which contain a single electrode. These estimators are computed for each time-slice using Q-factor (coefficient of variation of repeated measurements) threshold values, from 0 to 10%, to discriminate between selected and rejected quadripoles. An automated detection strategy is proposed to identify suspicious electrodes by comparing the CCS to the MECS (maximum expected CS values when every electrode is good for the given data set). These MECS are computed using Monte-Carlo simulations of a hundred random draws where the distribution of Q-factor values follows a Weibull cumulative distribution, with k=0.421 and λ=1.303, fitted on a background data set filtered using a 5% threshold on absolute reciprocal errors. The efficiency of the methodology and its sensitivity to the selected reciprocal error threshold are assessed on synthetic and field data. Our approach is suitable to detect suspicious electrodes and slowly changing conditions affecting the galvanic contact resistances where classical approaches are shown to be inadequate except when the faulty electrode is disconnected. A data-weighting method is finally proposed to ensure that only good data will be used in the inversion of ERT monitoring data sets.
A micromachined integratable thermal reactor (2002)

This paper presents a micromachined thermal reactor. The silicon substrate remains unheated because of the thermal isolation design during thermal cycling of the reaction chamber. The side-heating concept employed has significantly improved in-chamber temperature uniformity. Finite-element-analysis is carried out to optimise the thermal performance. Experimental results have proved that the thermal reactor can easily be integrated with other non-thermal components. Integration of the device with other components or modules of miniaturised total analysis systems (/spl mu/TAS) is very promising.
Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome (2006)

The association of thrombosis and gestational morbidity with antiphospholipid antibodies is termed antiphospholipid syndrome (APS). Annexin 2 (A2) is a profibrinolytic endothelial cell surface receptor that binds plasminogen, its tissue activator (tPA), and beta(2)-glycoprotein I (beta2GPI), the main antigen for antiphospholipid antibodies. Here, we evaluate A2 as a target antigen in APS. Serum samples from 434 individuals (206 patients with systemic lupus erythematosus without thrombosis, 62 with APS, 21 with nonautoimmune thrombosis, and 145 healthy individuals) were analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblot for antiphospholipid and A2 antibodies. Anti-A2 antibodies (titer > 3 SDs) were significantly more prevalent in patients with APS (22.6%; venous, 17.5%; arterial, 34.3%; and mixed thrombosis, 40.4%) than in healthy individuals (2.1%, P < .001), patients with nonautoimmune thrombosis (0%, P = .017), or patients with lupus without thrombosis (6.3%, P < .001). Anti-A2 IgG enhanced the expression of tissue factor on endothelial cells (6.4-fold +/- 0.13-fold SE), blocked A2-supported plasmin generation in a tPA-dependent generation assay (19%-71%) independently of beta2GPI, and inhibited cell surface plasmin generation on human umbilical vein endothelial cells (HUVECs) by 34% to 83%. We propose that anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome.
Novel reinforcement of corrugated nanofiber tissue-engineered vascular graft to prevent aneurysm formation for arteriovenous shunts in an ovine model (2022)

Reinforcement is required to create grafts that can withstand arterial pressure. Reinforcement with suture materials has the potential to maintain cell infiltration into the graft, which could improve the neotissue formation of the graft.
Functional Connectivity MR Imaging of the Language Network in Patients with Drug-Resistant Epilepsy (2010)

In patients with intractable epilepsy, FC-MRI revealed an overall reduction and reorganization of the connectivity pattern within the language network. FC was reduced in the left hemisphere regardless of the epileptogenic focus side and was positively correlated with linguistic performance only in patients with LE.
FSI of high performance high-lift devices with circulation control via conditioned coandã-jets (2013)

Current transport aircraft are limited to airports with comparatively long runways for take-off and landing. An aircraft with short take-off and landing capabilities is under investigation at the Collaborative Research Center 880. The aircraft employs circulation controlled high lift devices where high velocity air is blown through a slot in front of the flap. These high performance high-lift devices allow take-off and landing of the aircraft at runways of 800 m length. The curved flap leading edge induces a Coandˇa effect with the jet resulting in an attached flow up to the tip of the flap even at high deflection angles of up to 85 . Examination of the aeroelasticity of the wing is of high importance because of the sensitivity of the Coandˇa effect to perturbation through deformation and consequential change in flow. The large pressure gradients can play a significant role in the effective use of this jet system. Preliminary studies have shown an influence on aerodynamic performance due to slot deformation. Small changes in the aerodynamic characteristics can have adverse effects on the stall behavior. A flap section model of the wing is used to analyze the performance for several flight states. This high detail model allows capturing fine effects over the whole wing chord and on the slot region while still including wing deformations. The aerodynamic performance of the aeroelastic flap section model is compared to the characteristics of the rigid airfoil. The analyzed flight states give an insight into the influence of the deformation on the flow. Additionally the effects of jet momentum variation on aerodynamics is shown and the dominant stall phenomena presented. The local relative change in pressure can reach values between 10 and 20 % and has an influence on the stall behavior of the section. The change in aerodynamic performance illustrates the influence of small deformations on the sensitive circulation control.
Effects of Viral Strain, Transgene Position, and Target Cell Type on Replication Kinetics, Genomic Stability, and Transgene Expression of Replication-Competent Murine Leukemia Virus-Based Vectors (2007)

The limited efficiency of in vivo gene transfer by replication-deficient retroviral vectors remains an obstacle to achieving effective gene therapy for solid tumors. One approach to circumvent this problem is the use of replication-competent retroviral vectors. However, the application of such vectors is at a comparatively early stage and the effects which virus strain, transgene cassette position, and target cell can exert on vector spread kinetics, genomic stability, and transgene expression levels remain to be fully elucidated. Thus, in this study a panel of vectors allowing the investigation of different design features on an otherwise genetically identical background were analyzed with respect to these readout parameters in cultures of both murine and human cells and in preformed tumors in nude mice. The obtained data revealed that (i) Moloney murine leukemia virus (Mo-MLV)-based vectors spread with faster kinetics, drive higher levels of transgene expression, and are more stable than equivalent Akv-MLV-based vectors; (ii) vectors containing the transgene cassette directly downstream of the envelope gene are genomically more stable than those containing it within the 3'-long terminal repeat U3 region; and (iii) the genomic stability of both strains seems to be cell line dependent.
Future directions for immunotherapeutic intervention against sarcomas (2006)

As of 2006, few studies are examining the utility of immunotherapy in sarcomas. However, a detailed understanding of the remarkable mechanics of how an immune response is mounted and how T cell activation and/or proliferation can be halted by the tumor will be central to properly design new studies of immunological agents against sarcomas and other cancers.
Ash1p is a site-specific DNA-binding protein that actively represses transcription (2001)

ASH1 encodes a protein that is localized specifically to the daughter cell nucleus, where it has been proposed to repress transcription of the HO gene. Using Ash1p purified from baculovirus-infected insect cells, we have shown that Ash1p binds specific DNA sequences in the HO promoter. DNase I protection analyses showed that Ash1p recognizes a consensus sequence, YTGAT. Mutation of this consensus abolishes Ash1p DNA binding in vitro . We have shown that Ash1p requires an intact zinc-binding domain in its C terminus for repression of HO in vivo and that this domain may be involved in DNA binding. A heterologous DNA-binding domain fused to an N-terminal segment of Ash1p functions as an active repressor of transcription. Our studies indicate that Ash1p is a DNA-binding protein of the GATA family with a separable transcriptional repression domain.
Image enhancement using artificial neural network and fuzzy logic (2015)

Digital images are important source of information used for analysis and interpretation. During image acquisition image is degraded up to some extent. Thus we have to go through the process called image enhancement. It improves the visual appearance of an image. This paper presents a technique for image enhancement using artificial neural network and fuzzy logic. It denoise and enhance an image when it is corrupted by different noises such as salt and pepper, gaussian and non-gaussian noises. In Image analysis, denoising and enhancing are most important pre-processing and post-processing steps. Several filters have been illustrated till date but have many limitations. In the proposed technique, Artificial neural network determines type of noises whereas Fuzzy logic used for denoising and enhancement purpose. Experimental results shows the effectiveness of the proposed method by quantitative analysis and visual illustration. Several parameters like PSNR, MSE, AD, NAE are used for performance evaluation.
Multiplicity of ammonium uptake systems in Corynebacterium glutamicum: role of Amt and AmtB (2001)

In Corynebacterium glutamicum, a Gram-positive soil bacterium widely used in the industrial production of amino acids, two genes encoding (putative) ammonium uptake carriers have been described. The isolation of amt was the first report of the sequence of a gene encoding a bacterial ammonium uptake system combined with the characterization of the corresponding protein. Recently, a second amt gene, amtB, with so far unknown function, was isolated. The isolation of this gene and the suggestion of a new concept for ammonium acquisition prompted the reinvestigation of ammonium transport in C. glutamicum. In this study it is shown that Amt mediates uptake of (methyl)ammonium into the cell with high affinity and strictly depending on the membrane potential. As shown by the determination of K:(m) at different pH values, ammonium/methylammonium, but not ammonia/methylamine, are substrates of Amt. AmtB exclusively accepts ammonium as a transport substrate. In addition, hints of another, until now unknown, low-affinity, ammonium-specific uptake system were found.
Capsule endoscopy： Improving transit time and image view (2005)

AIM: To evaluate the effect of various methods of small bowel preparation on the transit time and the quality of visualization of the entire small bowel mucosa.METHODS: Ninety-five patients underwent capsule endoscopy (CE) by easily swallowing the capsule. They were divided into three study groups according to the preparation used: group A (n = 26) by polyethylene glycol (PEG) liter or with sodium phosphate (SP) 12 h prior to the CE study; group B (n = 29) by erythromycin 1 h prior to the CE study; and group C (n = 40) without any preparation. Visualization ranged from good to satisfactory to poor.RESULTS: The gastric emptying time in the group prepared with erythromycin was shorter but without statistical significance and the small bowel transit time was unaffected. In elderly subjects prepared by PEG or SP, the gastric emptying time was significantly longer (163.7 min, P = 0.05). The transit times of the three sub-groups were not affected by gender or pathology.The grade of cleaning of the entire study group was 3.27±1.1. The erythromycin group presented significantly the worst quality of images (P = 0.05) compared to the other sub-groups. Age, gender, and pathology had no effect on the quality of the cleaning of the small bowel in the sub-groups. One (1.05%) case had no natural excretion.CONCLUSION: Erythromycin markedly reduces gastric emptying time, but has a negative effect on the quality of the image in the small bowel. The preparation of elderly subjects with PEG or SP has a negative effect on the small bowel transit time.
Targeting the Ets Binding Site of the HER2/neuPromoter with Pyrrole-Imidazole Polyamides (2000)

Three DNA binding polyamides () were synthesized that bind with high affinity (K(a) = 8.7. 10(9) m(-1) to 1.4. 10(10) m(-1)) to two 7-base pair sequences overlapping the Ets DNA binding site (EBS; GAGGAA) within the regulatory region of the HER2/neu proximal promoter. As measured by electrophoretic mobility shift assay, polyamides binding to flanking elements upstream () or downstream (2 and 3) of the EBS were one to two orders of magnitude more effective than the natural product distamycin at inhibiting formation of complexes between the purified EBS protein, epithelial restricted with serine box (ESX), and the HER2/neu promoter probe. One polyamide, 2, completely blocked Ets-DNA complex formation at 10 nm ligand concentration, whereas formation of activator protein-2-DNA complexes was unaffected at the activator protein-2 binding site immediately upstream of the HER2/neu EBS, even at 100 nm ligand concentration. At equilibrium, polyamide 1 was equally effective at inhibiting Ets/DNA binding when added before or after in vitro formation of protein-promoter complexes, demonstrating its utility to disrupt endogenous Ets-mediated HER2/neu preinitiation complexes. Polyamide 2, the most potent inhibitor of Ets-DNA complex formation by electrophoretic mobility shift assay, was also the most effective inhibitor of HER2/neu promoter-driven transcription measured in a cell-free system using nuclear extract from an ESX- and HER2/neu-overexpressing human breast cancer cell line, SKBR-3.
Amelioration of the macrothrombocytopenia associated with the murine Bernard-Soulier syndrome (2002)

An absent platelet glycoprotein (GP) Ib-IX receptor results in the Bernard-Soulier syndrome and is characterized by severe bleeding and the laboratory presentation of macrothrombocytopenia. Although the macrothrombocytopenic phenotype is directly linked to an absent GP Ib-IX complex, the disrupted molecular mechanisms that produce the macrothrombocytopenia are unknown. We have utilized a mouse model of the Bernard-Soulier syndrome to engineer platelets expressing an alpha-subunit of GP Ib (GP Ibalpha) in which most of the extracytoplasmic sequence has been replaced by an isolated domain of the alpha-subunit of the human interleukin-4 receptor (IL-4Ralpha). The IL-4Ralpha/GP Ibalpha fusion is membrane expressed in Chinese hamster ovary (CHO) cells, and its expression is facilitated by the presence of human GP IX and the beta-subunit of GP Ib. Transgenic animals expressing a chimeric receptor were generated and bred into the murine Bernard-Soulier syndrome-producing animals devoid of mouse GP Ibalpha but expressing the IL-4Ralpha/GP Ibalpha fusion sequence. The characterization of these mice revealed a 2-fold increase in circulating platelet count and a 50% reduction in platelet size when compared with platelets from the mouse model of the Bernard-Soulier syndrome. Immunoprecipitation confirmed that the IL-4Ralpha/GP Ibalpha subunit interacts with filamin-1 and 14-3-3zeta, known binding proteins to the GP Ibalpha cytoplasmic tail. Mice expressing the chimeric receptor retain a severe bleeding phenotype, confirming a critical role for the GP Ibalpha extracytoplasmic domain in hemostasis. These results provide in vivo insights into the structural elements of the GP Ibalpha subunit that contribute to normal megakaryocyte maturation and thrombopoiesis.
Inactivation of E. coli O157:H7 Using a Pulsed Nonthermal Plasma System (2002)

ABSTRACT: The use of elevated temperatures to pasteurize food products leads to a loss of food quality, which stimulates research into novel nonthermal processes for food preservation. Using nonthermal plasma discharges, applied directly into the food product, proved effective in reducing the number of Escherichia coli O157:H7 cells in apple juice, by up to 7 log units. The pulsed nonthermal plasma system was developed and used to study the effects of different process parameters on the inactivation. The process parameters considered were discharge voltage, pulse number, and pulse frequency. The apple juice used had a pH of 4 and a conductivity of 2.29 mS/cm.