gebhart/patrepeval huggingface dataset:
Endothelial-specific gene expression directed by the tie gene promoter in vivo (1995)

The tie gene encodes a receptor tyrosine kinase that is expressed in the endothelium of blood vessels, particularly during embryonic development and angiogenesis in adults. We have cloned and characterized the mouse tie gene and isolated the human and mouse tie promoters. The promoter activities of human and mouse tie were analyzed using luciferase reporter gene constructs in transfected cell lines and beta-galactosidase constructs in transgenic mice. In transfection assays of cultured cells, both human and mouse promoter DNA fragments showed activity that was not restricted to endothelial cells. In contrast, in transgenic mice both promoters directed expression of the reporter gene to endothelial cells undergoing vasculogenesis and angiogenesis. In adult mice, tie promoter activity in lung and many vessels of the kidney was as high as in the vessels of the corresponding embryonic tissues, whereas in the heart, brain and liver, tie promoter activity was downregulated and restricted to coronaries, cusps, capillaries, and arteries. Our results show that the endothelial cell-type specificity of the tie promoter in vivo can be transferred to heterologous genes by using relatively short promoter fragments. The tie promoter, thus, has useful properties for potential gene therapy.
Receptor-Targeted Nipah Virus Glycoproteins Improve Cell-Type Selective Gene Delivery and Reveal a Preference for Membrane-Proximal Cell Attachment (2016)

Receptor-targeted lentiviral vectors (LVs) can be an effective tool for selective transfer of genes into distinct cell types of choice. Moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. Here we show that LVs pseudotyped with receptor-targeted Nipah virus (NiV) glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell membrane (less than 100 Å distance). Then, they were flexible in receptor usage as demonstrated by successful targeting of EpCAM, CD20, and CD8, and as selective as LVs pseudotyped with receptor-targeted measles virus (MV) glycoproteins, the current standard for cell-type specific gene delivery. Remarkably, NiV-LVs could be produced at up to two orders of magnitude higher titers compared to their MV-based counterparts and were at least 10,000-fold less effectively neutralized than MV glycoprotein pseudotyped LVs by pooled human intravenous immunoglobulin. An important finding for NiV-LVs targeted to Her2/neu was an about 100-fold higher gene transfer activity when particles were targeted to membrane-proximal regions as compared to particles binding to a more membrane-distal epitope. Likewise, the low gene transfer activity mediated by NiV-LV particles bound to the membrane distal domains of CD117 or the glutamate receptor subunit 4 (GluA4) was substantially enhanced by reducing receptor size to below 100 Å. Overall, the data suggest that the NiV glycoproteins are optimally suited for cell-type specific gene delivery with LVs and, in addition, for the first time define which parts of a cell surface protein should be targeted to achieve optimal gene transfer rates with receptor-targeted LVs.
Virtual trip lines for distributed privacy-preserving traffic monitoring (2008)

Automotive traffic monitoring using probe vehicles with Global Positioning System receivers promises significant improvements in cost, coverage, and accuracy. Current approaches, however, raise privacy concerns because they require participants to reveal their positions to an external traffic monitoring server. To address this challenge, we propose a system based on virtual trip lines and an associated cloaking technique. Virtual trip lines are geographic markers that indicate where vehicles should provide location updates. These markers can be placed to avoid particularly privacy sensitive locations. They also allow aggregating and cloaking several location updates based on trip line identifiers, without knowing the actual geographic locations of these trip lines. Thus they facilitate the design of a distributed architecture, where no single entity has a complete knowledge of probe identities and fine-grained location information. We have implemented the system with GPS smartphone clients and conducted a controlled experiment with 20 phone-equipped drivers circling a highway segment. Results show that even with this low number of probe vehicles, travel time estimates can be provided with less than 15% error, and applying the cloaking techniques reduces travel time estimation accuracy by less than 5% compared to a standard periodic sampling approach.
A Surrounding Gate Transistor (SGT) Gain Cell For Ultra High Density Drams (1993)

Conventionally, it is necessary to obtain enough (eg. 30fF per one cell) storage capacitance in as small a area as possible in order to realize high density DRAMs. This leads to the employment of very deep trench-or complicated stacked-capacitors, which elongates fabrication processes.
Protein Profiling with Epstein-Barr Nuclear Antigen-1 Reveals an Interaction with the Herpesvirus-associated Ubiquitin-specific Protease HAUSP/USP7 (2003)

The Epstein-Barr nuclear antigen-1 (EBNA1) protein of Epstein-Barr virus is important for the replication, segregation, and transcriptional activation of latent Epstein-Barr virus genomes; has been implicated in host cell immortalization; and avoids proteasomal processing and cell-surface presentation. To gain insight into how EBNA1 fulfills these functions, we have profiled cellular protein interactions with EBNA1 using EBNA1 affinity chromatography and tandem affinity purification (TAP) of EBNA1 complexes from human cells (TAP-tagging). We discovered several new specific cellular protein interactions with EBNA1, including interactions with HAUSP/USP7, NAP1, template-activating factor-I beta/SET, CK2, and PRMT5, all of which play important cell regulatory roles. The ubiquitin-specific protease USP7 is a known target of herpes simplex virus, and the USP7-binding region of EBNA1 was mapped to amino acids 395-450. A mutation in EBNA1 that selectively disrupted binding to USP7 was found to cause a 4-fold increase in EBNA1 replication activity but had no effect on EBNA1 turnover and cell-surface presentation. The results suggest that USP7 can regulate the replication function of EBNA1 and that EBNA1 may influence cellular events by sequestering key regulatory proteins.
Renal Cyst Development in Mice with Conditional Inactivation of the von Hippel-Lindau Tumor Suppressor (2006)

Inactivation of the von Hippel-Lindau tumor suppressor, pVHL, is associated with both hereditary and sporadic renal cysts and renal cell carcinoma, which are commonly thought to arise from the renal proximal tubule. pVHL regulates the protein stability of hypoxia-inducible factor (HIF)-alpha subunits and loss of pVHL function leads to HIF stabilization. The role of HIF in the development of VHL-associated renal lesions remains to be determined. To investigate the functional consequences of pVHL inactivation and the role of HIF signaling in renal epithelial cells, we used the phosphoenolpyruvate carboxykinase (PEPCK) promoter to generate transgenic mice in which Cre-recombinase is expressed in the renal proximal tubule and in hepatocytes. We found that conditional inactivation of VHL in PEPCK-Cre mutants resulted in renal cyst development that was associated with increased erythropoietin levels and polycythemia. Increased expression of the HIF target gene erythropoietin was limited to the liver, whereas expression of carbonic anhydrase 9 and multidrug resistance gene 1 was up-regulated in the renal cortex of mutant mice. Inactivation of the HIF-alpha binding partner, arylhydrocarbon receptor nuclear translocator (Arnt), but not Hif-1alpha, suppressed the development of renal cysts. Here, we present the first mouse model of VHL-associated renal disease that will provide a basis for further genetic studies to define the molecular events that are required for the progression of VHL-associated renal cysts to clear cell renal cell carcinoma.
Catalytic Cycle for the Asymmetric Hydrogenation of Prochiral Ketones to Chiral Alcohols:  Direct Hydride and Proton Transfer from Chiral Catalysts trans-Ru(H)2(diphosphine)(diamine) to Ketones and Direct Addition of Dihydrogen to the Resulting Hydridoamido Complexes (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCatalytic Cycle for the Asymmetric Hydrogenation of Prochiral Ketones to Chiral Alcohols: Direct Hydride and Proton Transfer from Chiral Catalysts trans-Ru(H)2(diphosphine)(diamine) to Ketones and Direct Addition of Dihydrogen to the Resulting Hydridoamido ComplexesKamaluddin Abdur-Rashid, Michael Faatz, Alan J. Lough, and Robert H. MorrisView Author Information Department of Chemistry, University of Toronto 80 Saint George Street, Toronto Ontario M5S 3H6, Canada Cite this: J. Am. Chem. Soc. 2001, 123, 30, 7473–7474Publication Date (Web):July 7, 2001Publication History Received28 March 2001Revised13 June 2001Published online7 July 2001Published inissue 1 August 2001https://pubs.acs.org/doi/10.1021/ja015902uhttps://doi.org/10.1021/ja015902urapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views3101Altmetric-Citations267LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Alcohols,Anions,Catalysts,Ketones,Precursors Get e-Alerts
Successful Expansion but Not Complete Restriction of Tropism of Adeno-Associated Virus by In Vivo Biopanning of Random Virus Display Peptide Libraries (2009)

Targeting viral vectors to certain tissues in vivo has been a major challenge in gene therapy. Cell type-directed vector capsids can be selected from random peptide libraries displayed on viral capsids in vitro but so far this system could not easily be translated to in vivo applications. Using a novel, PCR-based amplification protocol for peptide libraries displayed on adeno-associated virus (AAV), we selected vectors for optimized transduction of primary tumor cells in vitro. However, these vectors were not suitable for transduction of the same target cells under in vivo conditions. We therefore performed selections of AAV peptide libraries in vivo in living animals after intravenous administration using tumor and lung tissue as prototype targets. Analysis of peptide sequences of AAV clones after several rounds of selection yielded distinct sequence motifs for both tissues. The selected clones indeed conferred gene expression in the target tissue while gene expression was undetectable in animals injected with control vectors. However, all of the vectors selected for tumor transduction also transduced heart tissue and the vectors selected for lung transduction also transduced a number of other tissues, particularly and invariably the heart. This suggests that modification of the heparin binding motif by target-binding peptide insertion is necessary but not sufficient to achieve tissue-specific transgene expression. While the approach presented here does not yield vectors whose expression is confined to one target tissue, it is a useful tool for in vivo tissue transduction when expression in tissues other than the primary target is uncritical.
Laparoscopic Management of Endopelvic Etiologies of Pudendal Pain in 134 Consecutive Patients (2009)

Our findings emphasize that in patients with seemingly inexplicable anogenital pain, especially after failed treatment for Alcock's canal syndrome, laparoscopic exploration of the pelvic nerves must be done for further diagnosis and therapy before prematurely labeling the patients as refractory to treatment.
Recombinant bacteriophage lysins as antibacterials (2010)

With the increasing worldwide prevalence of antibiotic resistant bacteria, bacteriophage endolysins (lysins) represent a very promising novel alternative class of antibacterial in the fight against infectious disease. Lysins are phage-encoded peptidoglycan hydrolases which, when applied exogenously (as purified recombinant proteins) to Gram-positive bacteria, bring about rapid lysis and death of the bacterial cell. A number of studies have recently demonstrated the strong potential of these enzymes in human and veterinary medicine to control and treat pathogens on mucosal surfaces and in systemic infections. They also have potential in diagnostics and detection, bio-defence, elimination of food pathogens and control of phytopathogens. This review discusses the extensive research on recombinant bacteriophage lysins in the context of antibacterials, and looks forward to future development and potential.
Stress Proteins and Immunology (1990)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Synthesis of rotavirus-like particles in insect cells: Comparative and quantitative analysis (1998)

When the three major structural proteins, VP2, VP6, and VP7, of rotavirus are co-expressed in insect cells infected with recombinant baculoviruses, they self-assemble into triple-layered virus-like particles (VLPs) that are similar in morphology to native rotavirus. In order to establish the most favorable conditions for the synthesis of rotavirus VLPs, we have compared the kinetics of 2/6/7-VLP synthesis in two different insect cell lines: High Five cells propagated in Excell 405 medium and Spodoptera frugiperda 9 cells in Excell 400 medium. The majority of VLPs produced in both cell lines were released into the culture medium, and these released VLPs were predominantly triple-layered and were found to be stable for the period of six or seven days examined. The optimal synthesis of VLPs depended upon the cell line and the culture medium used as well as the time of harvesting infected cell cultures. The highest yield of VLPs was obtained from High Five cultures in the late phase of infection when the yield was at least 5-fold higher than that from S. frugiperda 9 cultures on a per cell basis. Our results demonstrate the usefulness of High Five cells for the production of VLPs as potential rotavirus subunit vaccines.
Concentration and detection of bacteria in virtual environmental samples based on non-immunomagnetic separation and quantum dots by using a laboratory-made system (2012)

This study investigated a method that simultaneously detects three bacteria, Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus via an approach that combines un-immunized magnetic nanoparticles for the enrichment and antibody-conjugated quantum dots (QDs) as fluorescence markers, by using a laboratory-made system. In the enrichment procedure, the un-immunized superparamagnetic polymer nanoparticles and the three bacteria formed "beadcell" complex. Magnetic nanoparticles with different size were used and some interferents were added into the bacteria suspension respectively to check the influence on concentration efficiency. In the immuno-fluorescence labeling procedure, QDs with different emission wavelenghs were immobilized with antibody. Antibody conjugated QDs capture the bacteria selectively and specifically so that "sandwich" complex were formed. The suspension of the labeled bacteria was trickled onto a microporous membrane. A 450nm semiconductor laser was used as a part of the laboratory-made system to excite the QDs. Three PMT detectors were utilized to detect the fluorescence intensity. These un-immunized magnetic nanoparticles can be applied in nonspecific separation and enrichment of bacteria from environmental samples, and this method, of which the detection procedures are completed within 2 h, can be applied to the cost-effective and rapid detecting of bacterial contamination.
Social Text Normalization using Contextual Graph Random Walks (2013)

We introduce a social media text normalization system that can be deployed as a preprocessing step for Machine Translation and various NLP applications to handle social media text. The proposed system is based on unsupervised learning of the normalization equivalences from unlabeled text. The proposed approach uses Random Walks on a contextual similarity bipartite graph constructed from n-gram sequences on large unlabeled text corpus. We show that the proposed approach has a very high precision of (92.43) and a reasonable recall of (56.4). When used as a preprocessing step for a state-of-the-art machine translation system, the translation quality on social media text improved by 6%. The proposed approach is domain and language independent and can be deployed as a preprocessing step for any NLP application to handle social media text. 1
Ablation of Gata1 in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis (2008)

The transcription factor Gata1 is expressed in several hematopoietic lineages and plays essential roles in normal hematopoietic development during embryonic stages. The lethality of Gata1-null embryos has precluded determination of its role in adult erythropoiesis. Here we have examined the effects of Gata1 loss in adult erythropoiesis using conditional Gata1 knockout mice expressing either interferon- or tamoxifen-inducible Cre recombinase (Mx-Cre and Tx-Cre, respectively). Mx-Cre-mediated Gata1 recombination, although incomplete, resulted in maturation arrest of Gata1-null erythroid cells at the proerythroblast stage, thrombocytopenia, and excessive proliferation of megakaryocytes in the spleen. Tx-Cre-mediated Gata1 recombination resulted in depletion of the erythroid compartment in bone marrow and spleen. Formation of the early and late erythroid progenitors in bone marrow was significantly reduced in the absence of Gata1. Furthermore, on treatment with a hemolytic agent, these mice failed to activate a stress erythropoietic response, despite the rising erythropoietin levels. These results indicate that, in addition to the requirement of Gata1 in adult megakaryopoiesis, Gata1 is necessary for steady-state erythropoiesis and for erythroid expansion in response to anemia. Thus, ablation of Gata1 in adult mice results in a condition resembling aplastic crisis in human.
Abstract 1395: Role of High Mobility Group Box 1 Protein in Post-Infarction Healing Process and Left Ventricular Remodeling (2007)

Background: The appropriate infarct healing process is prerequisite for preventing left ventricular (LV) remodeling after myocardial infarction (MI). High mobility group box1 protein (HMGB1) is derived from necrotic cells and activated macrophages and involved in tissue repair as immunostimulatory signal. However, the role of HMGB1 in post-MI LV remodeling is unknown. Methods and Results: We examined 35 patients with first ST-elevated acute MI. Peak serum HMGB1 level, determined by serial measurements (q. 6h), did not differ in age, sex, coronary risk factors and infarct site. Its peak level was markedly higher in patients with adverse in-hospital clinical outcomes, including pump failure, cardiac rupture, LV aneurysm and cardiac death, compared with those without (all p&lt;0.05). Then we performed experimental study using rat MI model, induced by permanent left coronary ligation. Anti-HMGB1 antibodies (1 mg/day, MI/antiH, n=20) or control antibodies (MI/C, n=20) were injected subcutaneously every 24 hours for 7 days. Sham-operated rats served as controls (n=10). Quantitative RT-PCR and immunoblotting showed that HMGB1 expression was increased in the infarcted area peaking at day 3 in MI/C compared with sham (p&lt;0.05). Its expression was localized in myocytes and inflammatory cells by immunohistochemistry. The mRNA level of TNF-α (−48%, p=0.03) and IL1-β (−44%, p=0.02) and the number of infiltrated macrophages (p=0.04) in the infarcted area were markedly reduced at day 3 in MI/antiH compared with MI/C. Echocardiographic and hemodynamic studies at day 7 showed increased LV end-diastolic dimension (p=0.03), LVEDP (p=0.03), and decreased LV max dP/dt (p=0.01) in MI/antiH compared with MI/C. Histologically, scar thinning in the infarcted area (0.53±0.23 vs 0.68±0.21 mm, p=0.02) and hypertrophy in the non-infarcted myocardium (2.01±0.23 vs 1.63±0.21 mm, p=0.03) were more prominent in MI/antiH compared with MI/C at day 14. Conclusions: Elevation of serum HMGB1 level is associated with adverse clinical outcomes in patients with acute MI. However, blockade of HMGB1 in rat MI model aggravated early LV remodeling through impaired infarct healing and advanced scar thinning, suggesting an essential role of HMGB1 in the appropriate repairing process after MI.
Efficient genome editing in Caenorhabditis elegans by CRISPR-targeted homologous recombination (2013)

Cas9 is an RNA-guided double-stranded DNA nuclease that participates in clustered regularly interspaced short palindromic repeats (CRISPR)-mediated adaptive immunity in prokaryotes. CRISPR-Cas9 has recently been used to generate insertion and deletion mutations in Caenorhabditis elegans, but not to create tailored changes (knock-ins). We show that the CRISPR-CRISPR-associated (Cas) system can be adapted for efficient and precise editing of the C. elegans genome. The targeted double-strand breaks generated by CRISPR are substrates for transgene-instructed gene conversion. This allows customized changes in the C. elegans genome by homologous recombination: sequences contained in the repair template (the transgene) are copied by gene conversion into the genome. The possibility to edit the C. elegans genome at selected locations will facilitate the systematic study of gene function in this widely used model organism.