gebhart/patrepeval huggingface dataset:
Peroxynitrite oxidation of sulfhydryls. (1991)

Peroxynitrite anion (ONOO-) is a potent oxidant that mediates oxidation of both nonprotein and protein sulfhydryls. Endothelial cells, macrophages, and neutrophils can generate superoxide as well as nitric oxide, leading to the production of peroxynitrite anion in vivo. Apparent second order rate constants were 5,900 M-1.s-1 and 2,600-2,800 M-1.s-1 for the reaction of peroxynitrite anion with free cysteine and the single thiol of albumin, respectively, at pH 7.4 and 37 degrees C. These rate constants are 3 orders of magnitude greater than the corresponding rate constants for the reaction of hydrogen peroxide with sulfhydryls at pH 7.4. Unlike hydrogen peroxide, which oxidizes thiolate anion, peroxynitrite anion reacts preferentially with the undissociated form of the thiol group. Peroxynitrite oxidizes cysteine to cystine and the bovine serum albumin thiol group to an arsenite nonreducible product, suggesting oxidation beyond sulfenic acid. Peroxynitrous acid was a less effective thiol-oxidizing agent than its anion, with oxidation presumably mediated by the decomposition products, hydroxyl radical and nitrogen dioxide. The reactive peroxynitrite anion may exert cytotoxic effects in part by oxidizing tissue sulfhydryls.
Niemann-Pick C disease and mobilization of lysosomal cholesterol by cyclodextrin (2014)

Niemann-Pick type C (NPC) disease is a lysosomal storage disease in which endocytosed cholesterol becomes sequestered in late endosomes/lysosomes (LEs/Ls) because of mutations in either the NPC1 or NPC2 gene. Mutations in either of these genes can lead to impaired functions of the NPC1 or NPC2 proteins and progressive neurodegeneration as well as liver and lung disease. NPC1 is a polytopic protein of the LE/L limiting membrane, whereas NPC2 is a soluble protein in the LE/L lumen. These two proteins act in tandem and promote the export of cholesterol from LEs/Ls. Consequently, a defect in either NPC1 or NPC2 causes cholesterol accumulation in LEs/Ls. In this review, we summarize the molecular mechanisms leading to NPC disease, particularly in the CNS. Recent exciting data on the mechanism by which the cholesterol-sequestering agent cyclodextrin can bypass the functions of NPC1 and NPC2 in the LEs/Ls, and mobilize cholesterol from LEs/Ls, will be highlighted. Moreover, the possible use of cyclodextrin as a valuable therapeutic agent for treatment of NPC patients will be considered.
Gene therapy for hepatocellular carcinoma: chemosensitivity conferred by adenovirus-mediated transfer of the HSV-1 thymidine kinase gene. (1995)

We have investigated whether adenovirally mediated gene transfer of the herpes simplex thymidine kinase gene to human hepatocellular carcinoma (HCC) cell lines can sensitize these cells to the prodrug ganciclovir and thereby provide a therapeutic option for this intractable cancer. Two replication-deficient adenoviruses encoding for the herpes simplex virus type-1 (HSV) thymidine kinase (TK) gene were generated in which expression of TK is under the control of either the human cytomegalovirus immediate early promoter (CMV) or the human alpha-fetoprotein (AFP) promoter/enhancer. We demonstrate that the combination of adenovirally mediated TK gene transfer and ganciclovir treatment effectively inhibits proliferation and causes cell death of HCC cells in vitro and that in vivo TK gene transfer and ganciclovir treatment inhibits hepatocellular tumor growth in a mouse model of this cancer. Furthermore, we show that expression of the TK gene can be restricted to those HCCs that express the tumor marker AFP through the incorporation of the AFP enhancer/promoter within an adenoviral vector.
Multilevel Linc System Design for Power Efficiency Enhancement (2007)

Linear amplifier with nonlinear components (LINC) is a power amplifier (PA) linearization technique which offers both high PA efficiency and high linearity of wireless transmitters. But at the output stage, LINC uses a power combiner which results in low system efficiency. To solve this problem, we propose a multilevel out-phasing (MOP) scheme and a corresponding architecture, multilevel LINC (MLINC), to increase power combiner efficiency of wireless transmitters. Under WCDMA system linearity requirements, we demonstrate the 3-level MLINC as a design example which enhances power combiner efficiency from 44.5% to 75.5%.
FSL-1, a bacterial-derived toll-like receptor 2/6 agonist, enhances resistance to experimental HSV-2 infection (2009)

The results showed, for the first time, that the bacterial-derived TLR2/6 agonist FSL-1 induced significant resistance to HSV-2 infection when applied in mice or human vaginal EC cultures. Cytokine evaluation illustrated that anti-herpetic activity correlated with induction of a specific profile. The identified anti-herpetic profile provides an invaluable resource for the future design of novel compounds to reduce genital HSV-2 transmission and improves understanding of the complex innate immune response to potential pathogens elicited by the vaginal mucosa.
Detection of Antibodies to Helicobacter pylori Cell Surface Antigens (1990)

Serum IgG antibodies of Helicobacter pylori were detected in single-dilution ELISA using glycine extracted material. Among 148 endoscopy patients 59% displayed antibodies; as expected, a higher occurrence (90%) was found in patients with positive gastric culture for H. pylori than in culture negative patients (37%). Among 68 blood donors the frequency of H. pylori antibodies was 28%. In 73 children less than 15 years of age examined for unrelated disorders the occurrence was 4%. By immunoblotting using the same extract, 3 prominent bands, 29K, 54K and 60K and several weak bands were identified. These were formed by 57%, 92%, and 65%, respectively, of the ELISA positive patient sera. Comparing culture positive and negative patients, the 3 bands occurred more often among the culture positive subjects though between 18 and 61% of the sera from culture negative patients gave either of the bands. When comparing the glycine extracts of 4 different H. pylori strains with separate haemagglutinating patterns no differences in the position of the major bands emerged. By absorption experiments no immunological cross-reactivity with components of Escherichia coli, Klebsiella pneumoniae, Campylobacter jejuni or C. fetus was found. Thus, the glycine extract seemed specific for the detection of antibodies to H. pylori.
Reactive oxygen species, antioxidants, and acquired immunodeficiency syndrome. Sense or speculation? (1991)

A cquired immunodeficiency syndrome (AIDS) results from A infection with a human immunodeficiency virus (HIV-1 or HIV-2) that eventually destroys a specific subset (CD4+) of helper T lymphocytes, so that the patient ultimately succumbs to opportunistic infections and/or certain neoplasms.<sup>1</sup>A high proportion of, and perhaps all, HIV-seropositive patients will show disease progression. Thus, of a cohort of HIV-1—positive subjects who were followed up for 3 years, 19% developed AIDS-related complex (ARC) and 26% developed AIDS.<sup>2</sup>Also, 41% of those who remained asymptomatic showed laboratory evidence of decline of immunologic status.<sup>2</sup>The only drug currently approved for the treatment of AIDS is 3'-azido-3'-deoxythymidine (azidothymidine, or AZT, now called zidovudine), which is therapeutically effective but has significant time- and dose-related toxicity.<sup>3,4</sup> Recent reports have implicated<i>reactive oxygen species</i>both in the pathogenesis of HIV infection and in some of the side effects of drugs such as zidovudine.
Adventist Health System: after the break-up. (1991)

The demise of the Adventist Health System a year ago marked the end of an eight-year experiment. Part of its problems stemmed from disagreement between regional group presidents and AHS executives over consolidated financing and poor diversification decisions that cost the Adventists more than $100 million between 1984 and 1989. But what ultimately sank the system was a rift among Adventist regional group presidents, hospital executives and church leaders over authority and control.
The maternal age effect: a hypothesis based on oxidative phosphorylation (2005)

The 'maternal age effect' in human reproduction, characterized by a negative relationship between maternal age and reproductive efficiency, remains a poorly understood phenomenon. Current data suggest that oocyte physiology determines this relationship. In this review, we present a hypothesis of a mitochondrial role in the physiology of ageing in human oocytes. We suggest that the efficiency of oxidative phosphorylation in the ageing human oocyte is degraded by free radical attack on the primordial oocytes residing in the ovary. Although deficiencies in oxidative phosphorylation can be accounted for in the short term by anaerobic respiration, we suggest that, in the long term, the level of oxidative phosphorylation strongly influences oocyte quality.
User Mode Linux (2006)

User-mode Linux [2](UML) is the port of the Linux kernel to Linux. It implements a Linux virtual machine running on a Linux host. Its hardware is virtual, being constructed from resources provided by the host. UML can run essentially any application that can run on the host.

The design and implementation of UML has been previously described[1]. This paper will describe the work that has taken place during the last year, including changes to what was described in the previous paper. This paper will also discuss new applications of UML involving integration of the virtual and host environments, along with other possibilties such as using UML as a clustering platform.
Live Data Visualization of IoT Sensors Using Augmented Reality (AR) and BIM (2019)

Live Data Visualization of IoT Sensors Using Augmented Reality (AR) and BIM Worawan Natephra and Ali Motamedi Pages 632-638 (2019 Proceedings of the 36th ISARC, Banff, Canada, ISBN 978-952-69524-0-6, ISSN 2413-5844) Abstract: Recently, the integration of Building Information Modeling (BIM) technology and Virtual and Augmented Reality (VR/AR) technologies during the operation and maintenance phase has been increasingly adopted. There has also been a surge of interest in the exploitation of Internet of Things (IoT) for constructed facilities, in the form of wireless networks connecting physical objects (e.g., sensing devices, facility assets, equipment, etc.). Recent IoT systems offer data management and visualization solutions. However, to improve issues such as safety and indoor comfort conditions for facilities, most of the existing IoT deployment do not benefit from the enriched digital representations of BIM and its graphical visualization capabilities. Although the integration of sensor data with BIM models has been investigated in academia, storing such real-time data in a standard and structured manner remains to be further investigated. This research aims to visualize live environmental data collected by IoT agents in the AR environment built upon existing BIM models. In our case study, the environmental data, such as indoor air temperature, light intensity, and humidity are captured by sensors connected to Arduino microcontrollers. Sensor reading are then stored in the BIM model and visualized in both the BIM platform and the AR application in a real-time manner. Keywords: BIM; sensors; thermal comfort; Augmented Reality; Arduino; Internet of Things (IoT); Visualization DOI: https://doi.org/10.22260/ISARC2019/0084 Download fulltext Download BibTex Download Endnote (RIS) TeX Import to Mendeley
Ku Autoantigen: A Multifunctional DNA-Binding Protein (2000)

Ku is a heterodimeric protein composed of approximately 70- and approximately 80-kDa subunits (Ku70 and Ku80) originally identified as an autoantigen recognized by the sera of patients with autoimmune diseases. Ku has high binding affinity for DNA ends and that is why originally it was known as a DNA end binding protein, but now it is known to also bind the DNA structure at nicks, gaps, hairpins, as well as the ends of telomeres. It has been reported also to bind with sequence specificity to DNA and with weak affinity to RNA. Ku is an abundant nuclear protein and is present in vertebrates, insects, yeast, and worms. Ku contains ssDNA-dependent ATPase and ATP-dependent DNA helicase activities. It is the regulatory subunit of the DNA-dependent protein kinase that phosphorylates many proteins, including SV-40 large T antigen, p53, RNA-polymerase II, RP-A, topoisomerases, hsp90, and many transcription factors such as c-Jun, c-Fos, oct-1, sp-1, c-Myc, TFIID, and many more. It seems to be a multifunctional protein that has been implicated to be involved directly or indirectly in many important cellular metabolic processes such as DNA double-strand break repair, V(D)J recombination of immunoglobulins and T-cell receptor genes, immunoglobulin isotype switching, DNA replication, transcription regulation, regulation of heat shock-induced responses, regulation of the precise structure of telomeric termini, and it also plays a novel role in G2 and M phases of the cell cycle. The mechanism underlying the regulation of all the diverse functions of Ku is still obscure.
The epidermal growth factor receptor pathway and its inhibition as anticancer therapy. (2003)

Epidermal growth factor receptor (EGFR) is commonly overexpressed in a number of epithelial malignancies and is often associated with an aggressive phenotype [e.g., non-small cell lung cancer (NSCLC) and bladder cancer]. EGFR is present in over 50% of cases of NSCLC, head and neck squamous cell carcinomas (HNSCC) and colon cancer. Several EGFR-targeting agents have been recently developed (C225, ABX-EGF, E7.6.3, EMD 55900, ICR62, ZD1839, CP358774, PD168393, CGP75166/PKI166, CGP59326A, BIBX1382). The two most advanced EGFR inhibitors in development are C225 and ZD1839. C225 is an antibody directed against the ligand-binding domain of human EGFR, which competes for receptor binding with EGF and other ligands. In vitro, C225 inhibits EGFR tyrosine kinase activity and proliferation of EGFR-overexpressing squamous cell carcinoma cell lines. Synergy was observed with doxorubicin, cisplatin and radiation in preclinical models. In phase I trials, major toxicity has been dermatological (rash and acneic skin reactions); allergic reactions have also been observed in about 3% of cases. This agent, administered intravenously once weekly, is presently in phase III trials in HNSCC and colon cancer. ZD1839, a synthetic molecule which targets the EGFR ATP binding site, is a very specific inhibitor of EGFR tyrosine kinase activity. Synergy has been observed with paclitaxel and cisplatin. In phase I trials, responses were seen in advanced NSCLC, and cutaneous toxicity and diarrhea were the most important side effects. Oral chronic daily administration is feasible. Two large randomized trials have been completed in advanced NSCLC in combination with chemotherapy. A large phase II study in second and third line has demonstrated a single agent activity of 18.5%. Another large phase II study in patients who received prior platinum and docetaxel obtained a response rate of 11%. There was no difference in response rate between the 250 and the 500 mg/day doses, but side effects were higher in patients who received the 500 mg dose. A very similar small molecule, OSI-774, has also shown activity in this setting. Two large randomized phase III studies of ZD1839 have recently been completed and analyzed in which two doses of ZD1839 (250 or 500 mg/day) or placebo were given in combination with two different chemotherapy regimens (carboplatin-paclitaxel or carboplatin-gemcitabine). These studies failed to demonstrate an increase in survival by adding ZD1839 together with chemotherapy in patients with advanced NSCLC.
Protection against transplanted and spontaneous lymphoma by inoculation of heat-altered syngeneic tumor cells in splenectomized mice (1974)

AKR mice with a high incidence of spontaneous lymphoma and leukemia were treated with various combinations of heat-altered syngeneic tumor cells, BCG, and splenectomy. It was found that the combination of heat-altered tumor cells and splenectomy markedly inhibited death secondary to both transplanted and spontaneous disease. BCG in combination with altered tumor cells was moderately effective in suppressing transplanted tumors but had no protective effect against spontaneous tumors. Neither splenectomy nor BCG alone offered any protection against spontaneous disease. The results are especially interesting in view of the evidence that there may be immunological tolerance to tumor specific antigens on these leukemia cells. The results may represent the induction of immune materials against an altered tumor antigen which cross-reacts with unaltered tumor antigens on viable leukemic cells and aids in their destruction. Splenectomy may exert its beneficial effect by reducing circulating enhancing antibodies.
Aptamers in the virologists' toolkit (2007)

Aptamers are artificial nucleic acid ligands that can be generated in vitro against a wide range of molecules, including the gene products of viruses. Aptamers are isolated from complex libraries of synthetic nucleic acids by an iterative, cell-free process that involves repetitively reducing the complexity of the library by partitioning on the basis of selective binding to the target molecule, followed by reamplification. For virologists, aptamers have potential uses as tools to help to analyse the molecular biology of virus replication, as a complement to the more familiar monoclonal antibodies. They also have potential applications as diagnostic biosensors and in the development of antiviral agents. In recent years, these two promising avenues have been explored increasingly by virologists; here, the progress that has been made is reviewed.
The Life-Cycle of the HIV-1 Gag–RNA Complex (2016)

Human immunodeficiency virus type 1 (HIV-1) replication is a highly regulated process requiring the recruitment of viral and cellular components to the plasma membrane for assembly into infectious particles. This review highlights the recent process of understanding the selection of the genomic RNA (gRNA) by the viral Pr55(Gag) precursor polyprotein, and the processes leading to its incorporation into viral particles.
Computed Tomographic Virtual Colonoscopy to Screen for Colorectal Neoplasia in Asymptomatic Adults (2003)

CT virtual colonoscopy with the use of a three-dimensional approach is an accurate screening method for the detection of colorectal neoplasia in asymptomatic average-risk adults and compares favorably with optical colonoscopy in terms of the detection of clinically relevant lesions.
Efficient gene targeted random mutagenesis in genetically stable Escherichia coli strains (2000)

We describe a method to generate in vivo collections of mutants orders of magnitude larger than previously possible. The method favors accumulation of mutations in the target gene, rather than in the host chromosome. This is achieved by propagating the target gene on a plasmid, in Escherichia coli cells, within the region preferentially replicated by DNA polymerase I (Pol I), which replicates only a minor fraction of the chromosome. Mutagenesis is enhanced by a conjunction of a Pol I variant that has a low replication fidelity and the absence of the mutHLS system that corrects replication errors. The method was tested with two reporter genes, encoding lactose repressor or lipase. The proportion of mutants in the collection was estimated to reach 1% after one cycle of growth and 10% upon prolonged cell cultivation, resulting in collections of 1012–1013 mutants per liter of cell culture. The extended cultivation did not affect growth properties of the cells. We suggest that our method is well suited for generating protein variants too rare to be present in the collections established by methods used previously and for isolating the genes that encode such variants by submitting the cells of the collections to appropriate selection protocols.
Copper-62-ATSM: a new hypoxia imaging agent with high membrane permeability and low redox potential. (1997)

Thus, retention of 62Cu-ATSM was studied serially in perfused rat hearts under conditions of normoxia (95% O2 + 5% CO2), hypoxia (95% N2 + 5% CO2) and reoxygenation (95% O2 + 5% CO2). In normoxia and reoxygenation, 62Cu-ATSM injected as a single bolus showed low retention (23.77% and 22.80%, respectively) 15 min after injection, but retention was increased markedly under hypoxic conditions (81.10%). Also, in the in vivo left anterior descending occluded rat heart model, 62Cu-ATSM retention was inversely correlated with accumulation of 201Tl, a relative myocardial blood flow marker.
Low rhodamine 123 retention identifies long-term human hematopoietic stem cells within the Lin−CD34+CD38− population (2006)

Progress to uncover the molecular and cellular regulators that govern human hematopoietic stem cell (HSC) fate has been impeded by an inability to obtain highly purified fractions of HSCs. We report that the rhodamine 123 (Rho 123) dye effluxing fraction of the Lin-CD34+CD38- population contains SCID-repopulating cells (SRCs) capable of long-term repopulation in primary nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Purification based on Rho uptake led to a 4-fold enrichment of SRCs in the Lin-CD34+CD38- fraction, with a frequency of 1 SRC in 30 Lin-CD34+CD38-Rholo cells. The Lin-CD34+CD38-Rholo fraction also possesses long-term self-renewal capacity as measured by serial transplantation totaling more than 20 weeks. We conclude that Rho dye efflux provides an additional means of purifying human HSCs in the quest to achieve homogeneous populations of primitive cells for both experimental and therapeutic applications.
Intermolecular Conformational Coupling and Free Energy Exchange Enhance the Catalytic Efficiency of Cardiac Muscle SERCA2a following the Relief of Phospholamban Inhibition (2005)

Activation of cardiac muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) by beta1-agonists involves cAMP- and PKA-dependent phosphorylation of phospholamban (PLB), which relieves the inhibitory effects of PLB on SERCA2a. To investigate the mechanism of SERCA2a activation, we compared the kinetic properties of SERCA2a expressed with (+) and without (-) PLB in High Five insect cell microsomes to those of SERCA1 and SERCA2a in native skeletal and cardiac muscle SR. Both native SERCA1 and expressed SERCA2a without PLB exhibited high-affinity (10-50 microM) activation of pre-steady-state catalytic site dephosphorylation by ATP, steady-state accumulation of the ADP-sensitive phosphoenzyme (E1P), and a rapid phase of EGTA-induced phosphoenzyme (E2P) hydrolysis. In contrast, SERCA2a in native cardiac SR vesicles and expressed SERCA2a with PLB lacked the high-affinity activation by ATP and the rapid phase of E2P hydrolysis, and exhibited low steady-state levels of E1P. The results indicate that the kinetic differences in Ca2+ transport between skeletal and cardiac SR are due to the presence of phospholamban in cardiac SR, and not due to isoform-dependent differences between SERCA1 and SERCA2a. Therefore, the results are discussed in terms of a model in which PLB interferes with SERCA2a oligomeric interactions, which are important for the mechanism of Ca2+ transport in skeletal muscle SERCA1 [Mahaney, J. E., Thomas, D. D., and Froehlich, J. P. (2004) Biochemistry 43, 4400-4416]. We propose that intermolecular coupling of SERCA2a molecules during catalytic cycling is obligatory for the changes in Ca2+ transport activity that accompany the relief of PLB inhibition of the cardiac SR Ca2+-ATPase.