gebhart/patrepeval huggingface dataset:
N- versus O-Alkylation of 2,3'-anhydrothymidine: reaction of the obtained pyrimidinium salts with azide ion (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN- versus O-Alkylation of 2,3'-anhydrothymidine: reaction of the obtained pyrimidinium salts with azide ionCatherine Goulaouic, David R. Adams, Angele Chiaroni, Claude Riche, and David S. GriersonCite this: J. Org. Chem. 1993, 58, 11, 3030–3037Publication Date (Print):May 1, 1993Publication History Published online1 May 2002Published inissue 1 May 1993https://pubs.acs.org/doi/10.1021/jo00063a021https://doi.org/10.1021/jo00063a021research-articleACS PublicationsRequest reuse permissionsArticle Views257Altmetric-Citations13LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Fabrication of extremely short length fiber Bragg gratings for sensor applications (2003)

A new technique and a physical model for writing extremely short length Bragg gratings in optical fibers have been developed. The model describes the effects of diffraction on the spatial spectra and therefore, the wavelength spectra of the Bragg gratings. Using an interferometric technique and a variable aperture, short gratings of various lengths and center wavelengths were written in optical fibers. By selecting the related parameters, the Bragg gratings with typical length of several hundred microns and bandwidth of several nanometers can be obtained. These short gratings can be apodized with selected diffraction patterns and hence their broadband spectra have a well-defined bell shape. They are suitable for use as miniaturized distributed strain sensors, which have broad applications to aerospace research and industry as well.
Activation of Pluripotency Genes in Human Fibroblast Cells by a Novel mRNA Based Approach (2010)

Our results demonstrate that mRNA transfection can be a useful approach to precisely control the protein expression level and short-term expression of reprogramming factors is sufficient to activate pluripotency genes in differentiated cells.
Quantum Devices from the Assembly of Zero- and One-Dimensional Building Blocks (2003)

This thesis describes novel methods for the fabrication of nanometer-scale electronic devices, such as single-electron transistors and resonant tunneling diodes, from wire- and dot-shaped building blocks. The first part of the thesis describes the manipulation of metal nanoparticles and carbon nanotubes using an atomic force microscope. Single-electron transistors were realized by moving nanotubes and nanoparticles in electrical contact with metal electrodes. It is shown that various forms of carbon nanotubes can be used as mobile electrodes resulting in very small electrical switches. In particular, the use of carbon nanotubes as electrodes was demonstrated by electrically contacting a sub-10 nm gold particle with two nanotubes. This device showed single-electron charging effects up to 200 K. The second part of the thesis deals with the fabrication and electrical characterization of semiconductor nanowire devices. Nanowires in the InAs/InP material system were grown by chemical beam epitaxy from size-selected nanoparticle catalysts. The heterostructure interfaces between the InAs and InP regions were determined to be almost atomically abrupt from high-resolution transmission electron microscopy investigations. Ohmic contacts, showing linear I-V characteristics down to 4.2 K, were developed to homogeneous InAs nanowires, and transport in these wires was investigated. From electrical characterization of InAs nanowires containing a thick InP barrier, the InP barrier height was estimated to be ~0.6 eV relative to the InAs conduction band edge. Resonant tunneling diodes were fabricated by incorporating a 15 nm InAs dot between two thin InP tunnel barriers. These devices showed peak-to-valley ratios up to 50:1 at 4.2 K. It is also shown that if the InAs dot is extended to a length of 100 nm, the nanowires work as ideal single-electron transistors at 4.2 K.
Induction of Noxa Sensitizes Human Colorectal Cancer Cells Expressing Mcl-1 to the Small-Molecule Bcl-2/Bcl-xL Inhibitor, ABT-737 (2008)

Induction of Noxa by CPT-11 or bortezomib can sensitize colorectal cancer cells expressing Mcl-1 to ABT-737. Up-regulation of Noxa may therefore represent an important strategy to enhance the therapeutic efficacy of ABT-737 against colorectal cancer and other solid tumors.
OspA, a lipoprotein antigen of the obligate intracellular bacterial pathogen Piscirickettsia salmonis. (2001)

No effective recombinant vaccines are currently available for any rickettsial diseases. In this regard the first non-ribosomal DNA sequences from the obligate intracellular pathogen Piscirickettsia salmonis are presented. Genomic DNA isolated from Percoll density gradient purified P. salmonis, was used to construct an expression library in lambda ZAP II. In the absence of preexisting DNA sequence, rabbit polyclonal antiserum raised against P. salmonis, with a bias toward P. salmonis surface antigens, was used to identify immunoreactive clones. Catabolite repression of the lac promoter was required to obtain a stable clone of a 4,983 bp insert in Escherichia coli due to insert toxicity exerted by the accompanying radA open reading frame (ORF). DNA sequence analysis of the insert revealed 1 partial and 4 intact predicted ORF's. A 486 bp ORF, ospA, encoded a 17 kDa antigenic outer surface protein (OspA) with 62% amino acid sequence homology to the genus common 17 kDa outer membrane lipoprotein of Rickettsia prowazekii, previously thought confined to members of the genus Rickettsia. Palmitate incorporation demonstrated that OspA is posttranslationally lipidated in E. coli, albeit poorly expressed as a lipoprotein even after replacement of the signal sequence with the signal sequence from lpp (Braun lipoprotein) or the rickettsial 17 kDa homologue. To enhance expression, ospA was optimized for codon usage in E. coli by PCR synthesis. Expression of ospA was ultimately improved (approximately 13% of total protein) with a truncated variant lacking a signal sequence. High level expression (approximately 42% tot. prot.) was attained as an N-terminal fusion protein with the fusion product recovered as inclusion bodies in E. coli BL21. Expression of OspA in P. salmonis was confirmed by immunoblot analysis using polyclonal antibodies generated against a synthetic peptide of OspA (110-129) and a strong antibody response against OspA was detected in convalescent sera from coho salmon (Oncorhynchus kisutch).
Identification of a conserved membrane localization domain within numerous large bacterial protein toxins (2010)

Vibrio cholerae is the causative agent of the diarrheal disease cholera. Many virulence factors contribute to intestinal colonization and disease including the Multifunctional Autoprocessing RTX toxin (MARTX(Vc)). The Rho-inactivation domain (RID) of MARTX(Vc) is responsible for inactivating the Rho-family of small GTPases, which leads to depolymerization of the actin cytoskeleton. Based on a deletion analysis of RID to determine the minimal functional domain, we have identified a subdomain at the N terminus of RID that is homologous to the membrane targeting C1 domain of Pasteurella multocida toxin. A GFP fusion to this subdomain from RID colocalized with a plasma membrane marker when transiently expressed within HeLa cells and can be found in the membrane fraction following subcellular fractionation. This C1-like subdomain is present in multiple families of bacterial toxins, including all of the clostridial glucosyltransferase toxins and various MARTX toxins. GFP-fusions to these homologous domains are also membrane associated, indicating that this is a conserved membrane localization domain (MLD). We have identified three residues (Y23, S68, R70) as necessary for proper localization of one but not all MLDs. In addition, we found that substitution of the RID MLD with the MLDs from two different effector domains from the Vibrio vulnificus MARTX toxin restored RID activity, indicating that there is functional overlap between these MLDs. This study describes the initial recognition of a family of conserved plasma membrane-targeting domains found in multiple large bacterial toxins.
Recent Progress in Glass-Based Materials for Biomedical Applications (1991)

Since discovery of Bioglass in 1971, various kinds of bioactive glasses and glass-ceramics with different functions such as high mechanical strength, high machinability, fast-setting ability and ferrimagnetism have been developed. Some of them are already clinically used as important bone-repairing implants and also have been proved to be useful even for cancer treatments. Factors governing the bioactivity have been considerably revealed. On the basis of these findings, new kinds of bioactive materials with other different functions such as high fracture toughness as well as low elastic modulus also might be developed from glasses in near future. Non-bioactive but inert glasses and glass-ceramics with various functions such as good workability, natural appearance and radioactivity also have been shown to be useful for biomedical applications such as dental crown and radioactive carrier for a cancer treatment. Glass-based materials will occupy more important positions in biomedical materials in the next decade.
The Quantitative Imaging Network in Precision Medicine (2016)

Precision medicine is a healthcare model that seeks to incorporate a wealth of patient information to identify and classify disease progression and to provide tailored therapeutic solutions for individual patients. Interventions are based on knowledge of molecular and mechanistic causes, pathogenesis and pathology of disease. Individual characteristics of the patients are then used to select appropriate healthcare options. Imaging is playing an increasingly important role in identifying relevant characteristics that help to stratify patients for different interventions. However, lack of standards, limitations in image-processing interoperability, and errors in data collection can limit the applicability of imaging in clinical decision support. Quantitative imaging is the attempt to extract reliable, numerical information from images to eliminate qualitative judgments and errors for providing accurate measures of tumor response to therapy or for predicting future response. This issue of <i>Tomography</i> reports quantitative imaging developments made by several members of the National Cancer Institute Quantitative Imaging Network, a program dedicated to the promotion of quantitative imaging methods for clinical decision support.
Abstract 18906: ACTRIIA-Fc Rebalances BMP and Activin/TGF-β Signaling to Attenuate Experimental Pulmonary Hypertension (2017)

Introduction: Therapies targeting underlying mechanisms of pulmonary arterial hypertension (PAH) could modify disease progression and improve outcomes. The genetics of PAH implicate deficient bone ...
Prostaglandin E-Prostanoid 4 Receptor Mediates Angiotensin II–Induced (Pro)Renin Receptor Expression in the Rat Renal Medulla (2014)

Angiotensin II (Ang II) stimulates (pro)renin receptor (PRR) expression in the renal collecting duct, triggering the local renin response in the distal nephron. Our recent study provided evidence for involvement of cyclooxygenase-2-prostaglandin E2 pathway in Ang II-dependent stimulation of PRR expression in the collecting duct. Here, we tested the role of E-prostanoid (EP) subtypes acting downstream of cyclooxygenase-2 in this phenomenon. In primary rat inner medullary collecting duct cells, Ang II treatment for 12 hours induced a 1.8-fold increase in the full-length PRR protein expression. To assess the contribution of EP receptor, the cell was pretreated with specific EP receptor antagonists: SC-51382 (for EP1), L-798106 (for EP3), L-161982 (for EP4), and ONO-AE3-208 (ONO, a structurally distinct EP4 antagonist). The upregulation of PRR expression by Ang II was consistently abolished by L-161982 and ONO and partially suppressed by SC-51382 but was unaffected by L-798106. The PRR expression was also significantly elevated by the EP4 agonist CAY10598 in the absence of Ang II. Sprague-Dawley rats were subsequently infused for 1 or 2 weeks with vehicle, Ang II alone, or in combination with ONO. Ang II infusion induced parallel increases in renal medullary PRR protein and renal medullary and urinary renin activity and total renin content, all of which were blunted by ONO. Both tail cuff plethysmography and telemetry demonstrated attenuation of Ang II hypertension by ONO. Overall, these results have established a crucial role of the EP4 receptor in mediating the upregulation of renal medullary PRR expression and renin activity during Ang II hypertension.
Hypertriglyceridemia and Ischemic Stroke (2008)

There are no conclusive data regarding the association between dyslipidemia and the risk of ischemic stroke (IS). Clinical investigations have primarily focused on the association between elevated levels of low-density lipoprotein cholesterol and low levels of high-density lipoprotein cholesterol as stroke risk factors. Much less scientific attention has been aimed at elevated levels of triglycerides. Consequently the potential role of hypertriglyceridemia as an independent risk factor for IS remains controversial. However, accumulating evidence has shown that hypertriglyceridemia is associated with pathophysiological processes such as endothelial dysfunction, atherosclerosis and the production of a prothrombotic state, which could contribute to IS risk. The aim of this review is to critically analyze the contribution of hypertriglyceridemia to the occurrence of IS.
Human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome (1994)

Harvard Medical School From Surgical Services, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Shriners Burns Institute, Boston, MA. Address requests for reprints to: Ronald G. Tompkins, MD, Surgical Services, Massachusetts General Hospital, Boston, MA 02114.
Site-specific glycan analysis of the SARS-CoV-2 spike (2020)

The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
A new bioassay for human granulocyte colony-stimulating factor (hG-CSF) using murine myeloblastic NFS-60 cells as targets and estimation of its levels in sera from normal healthy persons and patients with infectious and hematological disorders. (1989)

[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human colony-stimulating factors such as granulocyte-macrophage colony-stimulating factor (hGM-CSF) or macrophage colony-stimulating factor (hM-CSF). Based on these findings, sera from normal persons and patients with severe infections or various hematological disorders were tested after dialysis using this system in order to determine whether G-CSF levels in sera can be estimated or not. In ten normal persons, five patients with acute myelogenous leukemia (AML M1, M2, and M3), five with myelodysplastic syndrome, and four with chronic myelogenous leukemia, no increases in [3H]thymidine uptake were found within the dose range of 0.4 microliters to 50 microliters. In contrast, linear dose responses parallel to a G-CSF standard curve were observed in one patient with a severe bacterial infection, four with aplastic anemia, two with acute myelomonocytic leukemia (AMMoL) (M4), and two with idiopathic neutropenia tested. From the standard curve, the probable levels of G-CSF were calculated as follows: approximately 200 pg/ml with infection, 130-220 pg/ml with aplastic anemia, 150 and 200 pg/ml with AMMoL, and 1120 and 1200 pg/ml with idiopathic neutropenia. The activities of sera were reduced by the anti-rhG-CSF serum pretreatment in the same way as documented in the case of rhG-CSF. Furthermore, the level in a patient with a severe infection became undetectable soon after elimination of the infection and blood neutrophil counts had returned to normal. These findings indicate that the microbioassay system will be useful for measuring circulating G-CSF levels which would fluctuate in accord with requirements for stimulating neutrophil production or with abnormal production of hG-CSF.
Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of hepatitis C virus infection (2015)

Hepatitis C virus (HCV) infection affects an estimated 185 million people worldwide, with chronic infection often leading to liver cirrhosis and hepatocellular carcinoma. Although HCV is curable, there is an unmet need for the development of effective and affordable treatment options. Through a cell-based high-throughput screen, we identified chlorcyclizine HCl (CCZ), an over-the-counter drug for allergy symptoms, as a potent inhibitor of HCV infection. CCZ inhibited HCV infection in human hepatoma cells and primary human hepatocytes. The mode of action of CCZ is mediated by inhibiting an early stage of HCV infection, probably targeting viral entry into host cells. The in vitro antiviral effect of CCZ was synergistic with other anti-HCV drugs, including ribavirin, interferon-α, telaprevir, boceprevir, sofosbuvir, daclatasvir, and cyclosporin A, without significant cytotoxicity, suggesting its potential in combination therapy of hepatitis C. In the mouse pharmacokinetic model, CCZ showed preferential liver distribution. In chimeric mice engrafted with primary human hepatocytes, CCZ significantly inhibited infection of HCV genotypes 1b and 2a, without evidence of emergence of drug resistance, during 4 and 6 weeks of treatment, respectively. With its established clinical safety profile as an allergy medication, affordability, and a simple chemical structure for optimization, CCZ represents a promising candidate for drug repurposing and further development as an effective and accessible agent for treatment of HCV infection.
Consensus molecular subtype (CMS) as a novel integral biomarker in colorectal cancer: A phase II trial of bintrafusp alfa in CMS4 metastatic CRC. (2020)

4084 Background: Consensus Molecular Subtype 4 (CMS4) colorectal cancer (CRC) features increased TGFβ signaling, which may account for de novo resistance to immunotherapy for patients (pts) with microsatellite stable mCRC. To date, no prior trial has incorporated CMS status as an integral biomarker. Bintrafusp alfa (M7824) is a dual PD-L1 antibody/TGFβ trap with acceptable safety. Methods: Primary tumors from pts with metastatic CRC underwent CMS testing in a CLIA setting. In this Simon two-stage phase II trial (Ho: p &lt; .05; Ha: p≥.25) for CMS4 mCRC, pts received bintrafusp alfa 1200mg IV every 14 days. RT (8Gy/day x 3 days) to a single metastatic lesion with abscopal intent was administered between doses 2 and 3. The primary objective was to estimate response rate (RR) per iRECIST. Correlative studies including RNA sequencing were performed on pre- and on-treatment biopsies. Results: 53 of 137 tested pts (39%) between June 2018-December 2019 had CMS4 mCRC. 13 of 15 treated pts received the agent with RT. All pts were evaluable for toxicity, and 13 for response. Median number of doses was 3 (IQR, 2-4). There was one grade 3 immune-related adverse event (colitis) requiring study discontinuation. There were 2 pts with stable disease and 11 with progressive disease as best response (RR 0%, 95% CI 0-22%). Enrollment was stopped after first stage for futility. Median PFS and OS were 1.6 months and 5.0 months, respectively. In paired samples, treatment with bintrafusp alfa resulted in an increase in the expression of IFNγ signature in nonirradiated metastatic lesions ( p&lt; .001, q&lt; .001). Updated results will be presented. Conclusions: This is the first reported clinical trial to utilize CMS status as an integral biomarker for pts with metastatic CRC and capitalizes on treating CRC subpopulations with targeted agents based upon validated RNA-based signatures. Although the efficacy for bintrafusp alfa and RT is low, changes in IFNγ signature provides a potential signal for refining therapeutic strategies based upon TGFβ enrichment in pts with mCRC. Clinical trial information: NCT03436563 .
Eyes 'n ears face detection (2002)

We present a robust and portable visual-based skin and face detection system developed for use in a multiple speaker teleconferencing system, employing both audio and video cues. An omni-directional video sensor is used to provide a view of the entire visual hemisphere, thereby allowing for multiple dynamic views of all the participants. Regions of skin are detected using simple statistical methods, along with histogram color models for both skin and non-skin color classes. Regions of skin belonging to the same person are grouped together, and using simple spatial properties, the position of each person's face is inferred. Preliminary results suggest the system is capable of detecting human faces present in an omni-directional image despite the poor resolution inherent with such an omni-directional sensor.
Mamu-B * 08 -Positive Macaques Control Simian Immunodeficiency Virus Replication (2007)

Certain major histocompatibility complex (MHC) class I alleles are associated with the control of human immunodeficiency virus and simian immunodeficiency virus (SIV) replication. We have designed sequence-specific primers for detection of the rhesus macaque MHC class I allele Mamu-B*08 by PCR and screened a cohort of SIV-infected macaques for this allele. Analysis of 196 SIV(mac)239-infected Indian rhesus macaques revealed that Mamu-B*08 was significantly overrepresented in elite controllers; 38% of elite controllers were Mamu-B*08 positive compared to 3% of progressors (P = 0.00001). Mamu-B*08 was also associated with a 7.34-fold decrease in chronic phase viremia (P = 0.002). Mamu-B*08-positive macaques may, therefore, provide a good model to understand the correlates of MHC class I allele-associated immune protection and viral containment in human elite controllers.