gebhart/patrepeval huggingface dataset:
Downregulation of Major Histocompatibility Complex Class I by Human Ubiquitin Ligases Related to Viral Immune Evasion Proteins (2004)

Poxviruses and gamma-2 herpesviruses share the K3 family of viral immune evasion proteins that inhibit the surface expression of glycoproteins such as major histocompatibility complex class I (MHC-I), B7.2, ICAM-1, and CD95(Fas). K3 family proteins contain an amino-terminal PHD/LAP or RING-CH domain followed by two transmembrane domains. To examine whether human homologues are functionally related to the viral immunoevasins, we studied seven membrane-associated RING-CH (MARCH) proteins. All MARCH proteins located to subcellular membranes, and several MARCH proteins reduced surface levels of known substrates of the viral K3 family. Two closely related proteins, MARCH-IV and MARCH-IX, reduced surface expression of MHC-I molecules. In the presence of MARCH-IV or MARCH-IX, MHC-I was ubiquitinated and rapidly internalized by endocytosis, whereas MHC-I molecules lacking lysines in their cytoplasmic tail were resistant to downregulation. The amino-terminal regions containing the RING-CH domain of several MARCH proteins examined catalyzed multiubiquitin formation in vitro, suggesting that MARCH proteins are ubiquitin ligases. The functional similarity of the MARCH family and the K3 family suggests that the viral immune evasion proteins were derived from MARCH proteins, a novel family of transmembrane ubiquitin ligases that seems to target glycoproteins for lysosomal destruction via ubiquitination of the cytoplasmic tail.
Cytokine-induced neutrophil-mediated injury of human endothelial cells (1997)

To understand the pathogenesis of vasculitides, we analyzed how cytokine stimulation of HUVEC in vitro activates the cytotoxic capacity of polymorphonuclear (PMN) granulocytes. IL-1beta, IFN-gamma, or TNF-alpha caused highly significant dose and time-dependent HUVEC injury. TNF-alpha-treated HUVEC activated the PMN by means of phospholipase C-related event, since coincubations conferred PMN to react with a rise of cytosolic calcium concentrations, [Ca2+]i. Ab blockade of ICAM-1 on HUVEC inhibited 50 to 70% of the injury induced by these cytokines, whereas a mAb to E-selectin reduced 45 to 65% of IL-1beta- and TNF-alpha-, but not IFN-gamma-induced cytotoxicity. The role of nitric oxide (NO) was of significance since injury induced by each cytokine was reduced by 60 to 87% by specific NO-synthase inhibitors, as well as by scavenging extracellular NO by oxyhemoglobin. In contrast, injury induced by TNF-alpha was inhibited by neither superoxide dismutase or catalase, alpha1-antitrypsin, alpha2-macroglobulin, nor the platelet-activating factor receptor antagonist WEB-2086. Moreover, PMN from a patient with chronic granulomatous disease were fully capable of mediating cytotoxicity. The possibility that IL-8, produced by HUVEC in response to TNF-alpha, mediated activation of PMN was not corroborated since addition of an IL-8-blocking mAb did not modify HUVEC injury. Nonetheless, the IL-8 mAb (but not WEB-2086) blocked the rise of [Ca2+]i. Thus, in this in vitro model of vasculitis, the effect of IL-1beta, IFN-gamma, and TNF-alpha as promotors of cytokine-mediated neutrophil-dependent injury to HUVEC is a process dependent on expression of adhesion molecules and probably associated with NO produced in the system.
Hydrogen-induced percolation in discontinuous films (2002)

Hydrogen absorption in a metal leads to significant lattice expansion. This effect can be applied for discontinuous films to make them exceed the percolation limit, turning the film from nonconducting to conducting. Furthermore, in a percolating system, the conductivity should depend strongly on the external hydrogen pressure. This letter discusses the idea of a hydrogen-induced percolation mechanism. The process is illustrated by measurements on agglomerated palladium films, showing a maximum decrease of the resistivity by 50% at an exposure of the films to 5×104 to 9×104 Pa. The agglomerated films are prepared by Joule heating, using heat dissipation in the film itself.
Primary Structure Elements of Spider Dragline Silks and Their Contribution to Protein Solubility (2004)

Spider silk proteins have mainly been investigated with regard to their contribution to mechanical properties of the silk thread. However, little is known about the molecular mechanisms of silk assembly. As a first step toward characterizing this process, we aimed to identify primary structure elements of the garden spider's (Araneus diadematus) major dragline silk proteins ADF-3 and ADF-4 that determine protein solubility. In addition, we investigated the influence of conditions involved in mediating natural thread assembly on protein aggregation. Genes encoding spider silk-like proteins were generated using a cloning strategy, which is based on a combination of synthetic DNA modules and PCR-amplified authentic gene sequences. Comparing secondary structure, solubility, and aggregation properties of the synthesized proteins revealed that single primary structure elements have diverse influences on protein characteristics. Repetitive regions representing the largest part of dragline silk proteins determined the solubility of the synthetic proteins, which differed greatly between constructs derived from ADF-3 and ADF-4. Factors, such as acidification and increases in phosphate concentration, which promote silk assembly in vivo generally decreased silk protein solubility in vitro. Strikingly, this effect was pronounced in engineered proteins comprising the carboxyl-terminal nonrepetitive regions of ADF-3 or ADF-4, indicating that these regions might play an important role in initiating assembly of spider silk proteins.
Tyrosine phosphorylation in desmosomes and hemidesmosomes of the corneal epithelium. (1996)

We examined the localization of phosphotyrosine (p-Tyr)-modified proteins in the normal corneal epithelium using affinity-purified rabbit anti-p-Tyr antibody. Normal rat cornea was fixed and semi-thin and ultra-thin frozen sections were prepared. Immunofluorescence microscopy showed that p-Tyr was distributed along the cell membrane of the corneal epithelium. Immunogold electron microscopy revealed that the labeling is exclusively localized in the desmosomes and hemidesmosomes. A fraction enriched with desmosomes was extracted from the bovine corneal epithelium and examined by Western blotting. Immunoblotting for p-Tyr showed eight prominent bands (290, 200, 190, 115, 85, 62, 50, and 47 kD) in the desmosomal fraction. The enrichment of p-Tyr in desmosomes and hemidesmosomes of the corneal epithelium suggests that these cell-to-cell and cell-to-substrate junctions are involved in signal transduction.
Carotid artery stenting : current practice and techniques (2004)

Part One: Clinical Results and Experience Obstructive Carotid Artery Disease and Evidence-Based Benefits of Revascularization Alfredo M. Lopez-Yunez Historical Background: 20 Years of Endovascular Therapy for Obstructive Carotid Artery Disease Klaus Mathias Immediate and Late Outcomes of Carotid Artery Stenting Sumaira McDonald and Peter Gaines Global Carotid Artery Stent Registry Michael Wholey, Nadim Al-Mubarak and Mark H. Wholey Current Indications Nadim Al-Mubarak, Gary S. Roubin and Sriram S. Iyer Stenting for Recurrent Stenosis Following a Carotid Endarterctomy Nadim Al-Mubarak, Gary S. Roubin, Jiri J. Vitek Role of Multi-Specialty Group in Carotid Artery Stenting Michael Wholey Basic Angiographic Anatomy of the Brachiocephalic Vasculature Nadim Al-Mubarak and Jiri J. Vitek Part Two: Carotid Artery Stenting Techniques Carotid Artery Access Techniques Nadim Al-Mubarak, Jiri J. Vitek, Sriram S. Iyer and Gary S. Roubin Step-by-Step Procedural Techniques Sriram S. Iyer, Nadim Al-Mubarak, Jiri J. Vitek and Gary S. Roubin Direct Cervical Carotid Artery Approach Edward B. Dietrich, MD Complications Nadim Al-Mubarak, Sriram S. Iyer, Gary S. Roubin and Jiri J. Vitek Risk of Embolization During Carotid Artery Stenting and the Concept of Anti-Embolization Tako Ohki Microembolization During Carotid Artery Stenting Nadim Al-Mubarak Carotid Stenting with the Distal Occlusion Anti-Embolization Systems Michael Henry Carotid Stenting with Intravascular Filter Anti-Embolization Systems Antonio Colombo Proximal Balloon Protection: The Parodi Anti-Embolization System Joan Parodi Intravascular Filter Anti-Embolization: Illustrative Cases Antonio Colombo Technical Pearls Jiri J. Vitek and Sriram S. Iyer Restenosis Following Carotid Artery Stenting Fayaz Schwal Limitations of Current Equipment and the Future Carotid Stenting Device Horst Sievert Neurorescue Intervention Jiri J. Vitek and Nadim Al-Mubarak Intracranial Angioplasty and Stenting Phillips Meyer Part Three: Future Directions Current Status of Clinical Trials and Implications of Anti-Embolism Protection Robert W. Hobson, MD Statistical Considerations in Investigating the Outcomes of Carotid Artery Stenting Victoria Howard and George Howard
Fuzzy pain demand index from an i-pain system for assessment of postoperative pain via patient-controlled analgesia using a multilayer hierarchical structure (2008)

An advanced multilayer hierarchical structure included a personal digital assistant (PDA) device for an i-pain system is described in this paper. This PDA is like a messenger that not only records visual analog scales (VASs) and side effects but also collects the patient-controlled analgesia (PCA) data via the RS232 port by wire (i.e., cable) or wireless (i.e., Bluetooth) at time of medical staff visits. In our previous study, a novel fuzzy pain demand (FPD) derived from the interval of each bolus of PCA according to a fuzzy modeling algorithm can show the patients’ dynamic demand and past efforts to overcome the postoperative pain. Hence, this study investigated whether FPD index can distinguish the analgesic efficacy using different amounts and combination drugs via six hundred and seventynine patients with upper and lower abdominal, spinal, and extremity procedures.
Relocalized p27Kip1 Tumor Suppressor Functions as a Cytoplasmic Metastatic Oncogene in Melanoma (2007)

The p27 tumor suppressor negatively regulates G1 cell cycle progression. However, human malignancies rarely select for deletion/inactivation of p27, a hallmark of tumor suppressor genes. Instead, p27 is degraded or relocalized to the cytoplasm in aggressive malignancies, supporting the notion that p27 sequestration from its nuclear cyclin:cyclin-dependent kinase (cdk) targets is critical. However, emerging cell biology data suggest a novel cdk-independent cytoplasmic function of p27 in cell migration. Here, we find cytoplasmic p27 in 70% of invasive and metastatic melanomas. In contrast, no cytoplasmic p27 was detected in noninvasive, basement membrane-confined melanoma in situ, suggesting a late oncogenic role for cytoplasmic p27 in metastasis. Targeted cytoplasmic expression of wild-type or non-cdk-binding p27 at subphysiologic levels induced melanoma motility and resulted in numerous metastases to lymph node, lung, and peritoneum. These observations point to a prominent role of cytoplasmic p27 in metastatic disease that is independent of cyclin:cdk regulation or mere nuclear loss.
Synthesis, Characterization, and Field‐Effect Transistor Properties of Carbazolenevinylene Oligomers: From Linear to Cyclic Architectures (2008)

Two cyclic carbazolenevinylene dimers 1 and 2 were synthesized by McMurry coupling reactions. A linear compound 3 was also prepared for comparison. Compounds 1-3 were fully characterized by means of NMR spectroscopy, HRMS, elemental analysis, and UV/Vis absorption spectroscopy. Quantum chemical simulations showed that the cyclic compounds possessed smaller HOMO-LUMO gaps and more extended conjugation. The UV/Vis absorption spectra of the cyclic compounds showed blueshifts compared with that of the linear compound 3. Time-dependent DFT (TD-DFT) analysis revealed that this was due to the different selection rules for molecules with cyclic and linear architectures. The cyclic conformation also significantly affected the molecular ordering in the solid state. The X-ray crystal structure of 1 showed partial pi-pi overlapping between the adjacent molecules. Thin films of 1-3 were fabricated by the vacuum-deposition method on Si/SiO(2) substrates. Multicrystalline thin films were obtained from compounds 1 and 2, but only amorphous thin films could be obtained for the linear compound 3. Another important difference between the cyclic and linear compounds was the reduced reorganization energy for the cyclic compounds. These two facts have resulted in improved field-effect transistor (FET) mobilities for the cyclic compounds compared with the linear compound. In addition, as the substrate temperature has a significant influence on the morphology and the degree of crystallinity of the thin films deposited, the device performance could be optimized by varying the substrate temperature. The FET devices based on 2 gave the highest mobility of 0.013 cm(2) V(-1) s(-1). The results showed that carbazole derivatives with cyclic structures might make better FETs.
Inhibitory Action of the Peptide AcSDKP on the Proliferative State of Hematopoietic Stem Cells in the Presence of Captopril but not Lisinopril (1997)

The effect of Angiotensin I-converting enzyme (ACE) inhibitors on their own and in combination with the peptide AcSDKP on the proliferation of hematopoietic stem cells has been investigated. Hematopoietic stem cells from murine bone marrow induced into cell cycle following exposure to 2 Gy gamma-irradiation were incubated in vitro for up to 24 h in the presence of medium, captopril/lisinopril, AcSDKP, and AcSDKP with either ACE inhibitor. Hematopoietic stem cells were monitored using the high proliferative potential-colony forming cell-1 (HPP-CFC-1) population cloned in the presence of human IL-1 beta, murine IL-3, and murine M-CSF. No significant inhibitory effect was observed in the presence of AcSDKP on its own and AcSDKP in combination with lisinopril. However, there was a significant inhibition of stem cell cycling when AcSDKP and captopril were combined. This suggests that captopril inhibits AcSDKP breakdown better than lisinopril. The combination of AcSDKP and captopril also had an inhibitory effect on cell recruitment into S phase. The fact that a combination of AcSDKP and captopril switches cycling hematopoietic stem cells out of cycle indicates the importance of the N-active catalytic site of ACE in AcSDKP hydrolysis in vitro. Thus, AcSDKP in combination with appropriate ACE inhibitors may be of use in regulating the proliferation of hematopoietic stem cells in vitro.
Downstream Products are Potent Inhibitors of the Heparan Sulfate 2-O-Sulfotransferase (2018)

Heparan Sulfate (HS) is a cell signaling molecule linked to pathological processes ranging from cancer to viral entry, yet fundamental aspects of its biosynthesis remain incompletely understood. Here, the binding preferences of the uronyl 2-O-sulfotransferase (HS2ST) are examined with variably-sulfated hexasaccharides. Surprisingly, heavily sulfated oligosaccharides formed by later-acting sulfotransferases bind more tightly to HS2ST than those corresponding to its natural substrate or product. Inhibition assays also indicate that the IC<sub>50</sub> values correlate simply with degree of oligosaccharide sulfation. Structural analysis predicts a mode of inhibition in which 6-O-sulfate groups located on glucosamine residues present in highly-sulfated oligosaccharides occupy the canonical binding site of the nucleotide cofactor. The unexpected finding that oligosaccharides associated with later stages in HS biosynthesis inhibit HS2ST indicates that the enzyme must be separated temporally and/or spatially from downstream products during biosynthesis in vivo, and highlights a challenge for the enzymatic synthesis of lengthy HS chains in vitro.
The Direct3D 10 system (2006)

We present a system architecture for the 4 th generation of PC-class programmable graphics processing units (GPUs). The new pipeline features significant additions and changes to the prior generation pipeline including a new programmable stage capable of generating additional primitives and streaming primitive data to memory, an expanded, common feature set for all of the programmable stages, generalizations to vertex and image memory resources, and new storage formats. We also describe structural modifications to the API, runtime, and shading language to complement the new pipeline. We motivate the design with descriptions of frequently encountered obstacles in current systems. Throughout the paper we present rationale behind prominent design choices and alternatives that were ultimately rejected, drawing on insights collected during a multi-year collaboration with application developers and hardware designers.
Biomimetic Growth of Hydroxyapatite on Gelatin Films Doped with Sodium Polyacrylate (2000)

Gelatin films were used as biomimetic substrates for the nucleation of hydroxyapatite from simulated body fluid (SBF). Stretching and presence of sodium polyacrylate appear to be essential factors for the specific nucleation and growth of hydroxyapatite crystals inside the films. After soaking in 1.5SBF for periods longer than 4 days, all the films display a completely calcified surface. However, the spherical aggregates on the film surfaces do not give any X-ray diffraction effect and exhibit a low Ca/P molar ratio, typical of amorphous calcium phosphate. The ordered deposition of crystalline hydroxyapatite has been verified to take place only in stretched polyacrylate--gelatin films. The crystals grow as tablets about 2 microns thick among the gelatin layers, with their crystallographic c-axes preferentially oriented parallel to the direction of orientation of the collagen molecules, thus resembling the parallel orientation of apatitic crystals and collagen fibrils in calcified biological tissues.
Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme (2011)

Glioblastoma multiforme (GBM) is the most common and aggressive brain cancer, and despite treatment advances, patient prognosis remains poor. During routine animal studies, we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used to treat pinworm infection, inhibited brain tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the more promising drug for GBM therapy. In GBM cell lines, mebendazole displayed cytotoxicity, with half-maximal inhibitory concentrations ranging from 0.1 to 0.3 µM. Mebendazole disrupted microtubule formation in GBM cells, and in vitro activity was correlated with reduced tubulin polymerization. Subsequently, we showed that mebendazole significantly extended mean survival up to 63% in syngeneic and xenograft orthotopic mouse glioma models. Mebendazole has been approved by the US Food and Drug Administration for parasitic infections, has a long track-record of safe human use, and was effective in our animal models with doses documented as safe in humans. Our findings indicate that mebendazole is a possible novel anti-brain tumor therapeutic that could be further tested in clinical trials.
Prognosis and Gene Expression Profiling of 20q13-Amplified Breast Cancers (2006)

Our results suggest that amplified tumors of types 1 and 2 are two distinct entities resulting from two different mechanisms and associated to different prognosis.
REBASE--restriction enzymes and methylases (1996)

REBASE is a comprehensive database of information about restriction enzymes and their associated methylases, including their recognition and cleavage sites and their commercial availability. Information from REBASE is available via monthly electronic mailings as well as via WAIS, anonymous ftp and through the World Wide Web (http://www.neb.com/rebase). Specialized files are available that can be used directly by many software packages.
Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations (2001)

A Dutch family with autosomal recessive early-onset parkinsonism showed a heterozygous missense mutation in combination with a heterozygous exon deletion in the parkin gene. Although the main clinical syndrome consisted of parkinsonism, the proband clinically had additional mild gait ataxia and pathologically showed neuronal loss in parts of the spinocerebellar system, in addition to selective loss of dopaminergic neurons in the substantia nigra pars compacta. Lewy bodies and neurofibrillary tangles were absent, but tau pathology was found.
On the Design and Analysis of Multiple-Storage Elements (1989)

Abstract : The primary contribution of this thesis is the development of a data storage latch that accepts, stores and provides four-valued logic signals. The latch is implemented in Complementary Metal Oxide Silicon and all logic levels are encoded as voltage. The latch storage state is determined by thresholding operations on its input, and the output is logically restored replica of that (multiple-valued) input. Detailed analysis of an existing current-mode CMOS design is also presented in this study. A comparison between these devices reveals that the voltage-mode data latch provides less stable intermediate logic states, but consumes significantly less static power. In addition, the voltage- mode CMOS design can be implemented with the same number of devices that are required for two binary D flip-flops. Keywords: Logic circuits.
On the physical operation and optimization of the p-GaN gate in normally-off GaN HEMT devices (2017)

In this study, an investigation is undertaken to determine the effect of gate design parameters on the on-state characteristics (threshold voltage and gate turn-on voltage) of pGaN/AlGaN/GaN high electron mobility transistors (HEMTs). Design parameters considered are pGaN doping and gate metal work function. The analysis considers the effects of variations on these parameters using a TCAD model matched with experimental results. A better understanding of the underlying physics governing the operation of these devices is achieved with a view to enable better optimization of such gate designs.
Use of dabigatran etexilate to reduce breast cancer progression (2010)

Coagulation proteases and the generation of thrombin are increased in breast tumor epithelial and stromal cells. Since thrombin can modify tumor cell behavior directly through the activation of protease-activated receptors (PARs) or indirectly by generating fibrin matrices, the effect of dabigatran etexilate, a direct thrombin inhibitor, on breast cancer development was evaluated. Dabigatran inhibited invasiveness of MDA-MB-231 breast carcinoma cells across Matrigel-coated membranes at concentrations that had no effect on the proliferation index of cultured tumor cells. In vivo evaluation of invasiveness of MDA-MB-231 cells in tracheal xenotransplants in nude mice orally administered dabigatran etexilate twice daily at a dose of 45 mg/kg over 4 weeks demonstrated less invasion of tumor cells through the tracheal wall compared to vehicle-treated mice. To evaluate the effect of dabigatran on the development of metastatic foci, 4T1 tumor cells were injected orthotopically in the mammary fat pads of syngeneic Balb/c mice. Dabigatran etexilate treatment exhibited evidence of antitumor activity with a 50% reduction in tumor volume at 4 weeks following orthotopic injection of 4T1 cells in syngeneic Balb/c mice with no weight loss in treated mice. Dabigatran etexilate reduced both 4T1 tumor cells in the blood and liver micrometastases by 50-60%. These results suggest that oral administration of the direct thrombin inhibitor, dabigatran etexilate, inhibits both invasion and metastasis of malignant breast tumors, suggesting that it may be beneficial in not only preventing thrombotic events in cancer patients, but also as adjunct therapy to treat malignant tumors.