gebhart/patrepeval huggingface dataset:
Building bone to reverse osteoporosis and repair fractures (2008)

An important, unfilled clinical need is the development of new approaches to improve fracture healing and to treat osteoporosis by increasing bone mass. Recombinant forms of bone morphogenetic protein 2 (BMP2) and BMP7 are FDA approved to promote spinal fusion and fracture healing, respectively, and the first FDA-approved anabolic drug for osteoporosis, parathyroid hormone, increases bone mass when administered intermittently but can only be given to patients in the US for two years. As we discuss here, the tremendous explosion over the last two decades in our fundamental understanding of the mechanisms of bone remodeling has led to the prospect of mechanism-based anabolic therapies for bone disorders.
Acoustic positioning of oceanographic instruments (1974)

An acoustic technique for positioning oceanographic instruments in three dimensions at any point in the water column or on the ocean floor is described. The system utilizes an array of acoustic transponders on the sea floor and an acoustic source controlled by an internal clock installed on the device to be positioned. Particular consideration is given to the problem of operating such a system in areas of very rugged topography where direct acoustic paths from instrument to transponder may be obscured. Accuracy and repeatability of the technique utilizing both direct and surface reflected acoustic paths between instrument and transponder are examined experimentally. Results of an experiment to position a bottom sampling device utilizing such a multipath are presented.
ASAAM: aspectual software architecture analysis method (2004)

Software architecture analysis methods aim to predict the quality of a system before it has been developed. In general, the quality of the architecture is validated by analyzing the impact of predefined scenarios on architectural components. Hereby, it is implicitly assumed that an appropriate refactoring of the architecture design can help in coping with critical scenarios and mending the architecture. This paper shows that there are also concerns at the architecture design level which inherently crosscut multiple architectural components, which cannot be localized in one architectural component and which, as such, can not be easily managed by using conventional abstraction mechanisms. We propose the aspectual software architecture analysis method (ASAAM) to explicitly identify and specify these architectural aspects and make them transparent early in the software development life cycle. ASAAM introduces a set of heuristic rules that help to derive architectural aspects and the corresponding tangled architectural components from scenarios. The approach is illustrated for architectural aspect identification in the architecture design of a window management system.
Borane Chain Transfer Agent in Metallocene-Mediated Olefin Polymerization. Synthesis of Borane-Terminated Polyethylene and Diblock Copolymers Containing Polyethylene and Polar Polymer (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTBorane Chain Transfer Agent in Metallocene-Mediated Olefin Polymerization. Synthesis of Borane-Terminated Polyethylene and Diblock Copolymers Containing Polyethylene and Polar PolymerGuangxue Xu and T. C. ChungView Author Information Department of Material Science and Engineering The Pennsylvania State University University Park, Pennsylvania 16802 Cite this: J. Am. Chem. Soc. 1999, 121, 28, 6763–6764Publication Date (Web):July 3, 1999Publication History Received26 April 1999Published online3 July 1999Published inissue 1 July 1999https://doi.org/10.1021/ja9913232Copyright © 1999 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1063Altmetric-Citations99LEARN 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 InReddit Read OnlinePDF (91 KB) Get e-AlertsSUBJECTS:Copolymers,Group 13 compounds,Hydrocarbons,Polymers,Transfer reactions Get e-Alerts
Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. (1991)

Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities [Straus, S.E. (1988) J. Inf. Dis. 157, 405-412]. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology. We evaluated 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymearse chain reaction, and in situ hybridization of blood samples. The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.
Dual Therapy of Ovarian Cancer Using Measles Viruses Expressing Carcinoembryonic Antigen and Sodium Iodide Symporter (2006)

Dual therapy with MV-CEA and MV-NIS is superior to treatment with either virus alone, and it allows noninvasive monitoring of virotherapy via soluble marker peptide and gamma camera imaging. This has important implications for the clinical development of oncolytic measles viruses.
Biochemical studies of three Saccharomyces cerevisiae acyl-CoA synthetases, Faa1p, Faa2p, and Faa3p. (1994)

The efficiency and specificity of protein N-myristoylation appear to be influenced by the availability of myristoyl-CoA and other potential acyl-CoA substrates of myristoyl-CoA:protein N-myristoyltransferase. Recent studies have revealed that Saccharomyces cerevisiae contains at least three acyl-CoA synthetase genes (FAA for fatty acid activation). We have expressed Faa1p, Faa2p, and Faa3p in a strain of Escherichia coli that lacks its own endogenous acyl-CoA synthetase (FadD). Each S. cerevisiae acyl-CoA synthetase contained a carboxyl-terminal His tag so that it could be purified to homogeneity in a single step using nickel chelate affinity chromatography. In vitro assays of C3:0-C24:0 fatty acids indicate that Faa1p prefers C12:0-C16:0, with myristic and pentadecanoic acid (C15:0) having the highest activities. Faa2p can accommodate a wider range of acyl chain lengths: C9:0-C13:0 are preferred and have equivalent activities, although C7:0-C17:0 fatty acids are tolerated as substrates with no greater than a 2-fold variation in specific activity. The myristoyl-CoA synthetase activities of Faa1p and Faa2p are 2 orders of magnitude greater than that of Faa3p in vitro. Faa3p has a preference for C16 and C18 fatty acids with a cis-double bond at C-9-C-10. The temperature optimum for Faa1p is 30 degrees C, while Faa2p and Faa3p have the greatest activities at 25 degrees C. These in vitro observations were confirmed using two in vivo assays: (i) measurement of the ability of each S. cerevisiae acyl-CoA synthetase to direct the incorporation of exogenously derived tritiated myristate, palmitate, or oleate into cellular phospholipids produced in a fadD- strain of E. coli during exponential growth at 24 or 37 degrees C and (ii) measurement of the incorporation of [3H]myristate into a yeast N-myristoylprotein coexpressed with Nmt1p and Faa1p, Faa2p, or Faa3p in the fadD- strain.
Pathway of rhinovirus disruption by soluble intercellular adhesion molecule 1 (ICAM-1): an intermediate in which ICAM-1 is bound and RNA is released (1994)

We have examined the pathway of rhinovirus interaction with soluble intercellular adhesion molecule 1 (sICAM-1). Binding of sICAM-1 to rhinovirus serotypes 3 and 14 gives particles with sedimentation coefficients from 145 to 120S, depending on the amount of sICAM-1 bound. The formation of 120S particles is faster and more extensive at a neutral pH than at an acidic pH. A large number of receptors (> 30) can bind to human rhinovirus 3 without disruption. Disruption by sICAM-1 of rhinovirus that yields 80S particles is strongly temperature dependent and is antagonized by a low pH. Interestingly, sICAM-1 remains bound to the viral capsid after RNA is released, although in smaller amounts than those observed for the native virus. We have found heterogeneity both between and within 80S particle preparations in the VP4 content and number of bound receptors. The ability of the virus to remain bound to its receptor during the uncoating process may facilitate the transport of the viral genome into the cytoplasm in vivo.
Endocytosis in alveolar type II cells: effect of charge and size of tracers. (1984)

The type II cell of the alveolar epithelium of adult rats has been studied by electron microscopy to determine its ability to endocytose electron-dense tracers of differing molecular charge and size. The tracers studied were native (anionic) ferritin, cationic ferritin, 70-kilodalton dextran, and colloidal carbon. Alveolar macrophages ingested all tracers in large amounts, while type II cells took up significant amounts of cationic ferritin only. This tracer was observed, in sequence, within small pinocytic vesicles, large electron-lucent multivesicular bodies, small electron-dense multivesicular bodies, and, by 30 min after instillation, within the nonlamellar matrix of lamellar bodies. By 2 hr all lamellar bodies in any labeled cell contained cationic ferritin. Cationic ferritin also appeared to be transported from alveoli to interstitium by vesicles of type II, but not type I, cells. Native ferritin and dextran were observed in the same organelles as cationic ferritin but in much smaller amounts; colloidal carbon was not taken up by type II cells. These tracers were not observed in the alveolar interstitium. Type II cells therefore appear to internalize preferentially the tracer that binds to the cell membrane. Once within the cell, the tracer may enter a pathway that terminates in a lamellar body or, in the case of cationic ferritin, may be ferried across the cell.
NASICs: A nanoscale fabric for nanoscale microprocessors (2008)

The rapid progress of manufacturing nanoscale devices is pushing researchers to explore appropriate nanoscale computing architectures for high density beyond the physical limitations of conventional lithography. However, manufacturing and layout constraints, as well as high defect/fault rates expected in nanoscale fabrics, could make most device density lost when integrated into computing systems. Therefore, a nanoscale architecture that can deal with those constraints and tolerate defects/faults at expected rates, while still retaining the density advantage, is highly desirable. In this paper, we describe a novel nanoscale architecture based on semiconductor nanowires: NASICs (nanoscale application specific ICs). NASIC is a tile-based fabric built on 2-D nanowire grids and NW FETs. WISP-0 (wire streaming processor) is a processor design built on NASIC fabric where NASIC design principles and optimizations are applied. Built-in fault tolerance techniques are applied on NASICs designs to tolerate defects/faults on-the-fly. Evaluations show that compared with the equivalent CMOS design with 18 nm process (the most advanced technology expected in 2018), WISP-0 with combined built-in redundancy could be still 2~3X denser. Its yield would be 98% if the defect rate of transistors is 5%, and 77% for 10% defective transistors.
Transduction of Notch2 in feline leukemia virus-induced thymic lymphoma (1996)

Feline leukemia virus (FeLV) is thought to induce neoplastic diseases in infected cats by a variety of mechanisms, including the transduction of host proto-oncogenes. While FeLV recombinants that encode cellular sequences have been isolated from tumors of naturally infected animals, the acquisition of an unrelated host gene has never been documented in an experimental FeLV infection. We isolated recombinant FeLV proviruses encoding feline Notch2 sequences from thymic lymphoma DNA of two cats inoculated with the molecularly cloned virus FeLV-61E. Four recombinant genomes were identified, three in one cat and one in the other. Each had similar but distinct transduction junctions, and in all cases, the insertions replaced most of the envelope gene with a region of Notch2 that included the intracellular ankyrin repeat functional domain. The product of the FeLV/Notch2 recombinant provirus was a novel, truncated 65- to 70-kD Notch2 protein that was targeted to the cell nucleus. This virally encoded Notch2 protein, which resembles previously constructed, constitutively activated forms of Notch, was apparently expressed from a subgenomic transcript spliced at the normal envelope donor and acceptor sequences. The data reported here implicate a nuclear, activated Notch2 protein in FeLV-induced leukemogenesis.
Modulation by proinflammatory cytokines of Fas/Fas ligand-mediated apoptotic cell death of synovial cells in patients with rheumatoid arthritis (RA) (1998)

Synovial cell hyperplasia is a characteristic of patients with RA. Excessive proliferation of RA synovial cells is, in part, responsible for the synovial cell hyperplasia. In addition, synovial cell death that would reduce synovial cell number may be defective, leading to the hyperplasia. Thus, the defective control of cell death as well as cell proliferation may be of central importance in the pathogenesis of RA. In this study we analysed effects of proinflammatory cytokines on Fas/Fas ligand (FasL)-induced synovial cell apoptosis, and evaluated apoptosis-associated protein expression in the synovial cells in patients with RA. RA synovial cells expressed Fas antigen and lymphocytes infiltrating into RA synovium expressed FasL. Apoptotic synovial cells were detected within the sublining layer of RA synovium. Anti-Fas MoAb induced apoptosis of RA synovial cells in vitro, and proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-1beta, but not IL-6 or IL-8, inhibited the anti-Fas-induced apoptosis accompanying up-regulation of Bcl-2 protein expression and reduced expression of CPP32 and ICH-1L. Immunohistochemical study revealed that CPP32 and ICH-1L were expressed weakly in the RA synovial lining cells compared with osteoarthritis (OA) synovial lining cells. Thus, we found that although RA synovial cells could die via apoptosis through Fas/FasL pathway, apoptosis of synovial cells was inhibited by proinflammatory cytokines present within the synovium. Inhibition of apoptosis by the proinflammatory cytokines may contribute outgrowth of synovial cells that leads to pannus formation and the destruction of joints in patients with RA.
Biomimetic Chemosensor: Designing Peptide Recognition Elements for Surface Functionalization of Carbon Nanotube Field Effect Transistors (2009)

Single-wall carbon nanotube field effect transistors (SWNT-FETs) are ideal candidates for fabricating sensors due to their unique electronic properties and have been widely investigated for chemical and biological sensing applications. The lack of selectivity of SWNT-FETs has prompted extensive research on developing ligands that exhibit specific binding as selective surface coating for SWNTs. Herein we describe the rational design of a peptide recognition element (PRE) that is capable of noncovalently attaching to SWNTs as well as binding to trinitrotoluene (TNT). The PRE contains two domains, a TNT binding domain derived from the binding pocket of the honeybee odor binding protein ASP1, and a SWNT binding domain previously identified from the phage peptide display library. The PRE structure in the presence of SWNT was investigated by performing classical all-atom molecular dynamics simulations, circular dichroism spectroscopy, and atomic force microscopy. Both computational and experimental analyses demonstrate that the peptide retains two functional domains for SWNT and TNT binding. The binding motif of the peptide to SWNT and to TNT was revealed from interaction energy calculations by molecular dynamics simulations. The potential application of the peptide for the detection of TNT is theoretically predicted and experimentally validated using a SWNT-FET sensor functionalized with a designer PRE. Results from this study demonstrate the creation of chemosensors using designed PRE as selective surface coatings for targeted analytes.
The NADH oxidase of Streptococcus pneumoniae : its involvement in competence and virulence (1999)

A soluble flavoprotein that reoxidizes NADH and reduces molecular oxygen to water was purified from the facultative anaerobic human pathogen Streptococcus pneumoniae. The nucleotide sequence of nox, the gene which encodes it, has been determined and was characterized at the functional and physiological level. Several nox mutants were obtained by insertion, nonsense or missense mutation. In extracts from these strains, no NADH oxidase activity could be measured, suggesting that a single enzyme encoded by nox, having a C44 in its active site, was utilizing O2 to oxidize NADH in S. pneumoniae. The growth rate and yield of the NADH oxidase-deficient strains were not changed under aerobic or anaerobic conditions, but the efficiency of development of competence for genetic transformation during growth was markedly altered. Conditions that triggered competence induction did not affect the amount of Nox, as measured using Western blotting, indicating that nox does not belong to the competence-regulated genetic network. The decrease in competence efficiency due to the nox mutations was similar to that due to the absence of oxygen in the nox+ strain, suggesting that input of oxygen into the metabolism via NADH oxidase was important for controlling competence development throughout growth. This was not related to regulation of nox expression by O2. Interestingly, the virulence and persistence in mice of a blood isolate was attenuated by a nox insertion mutation. Global cellular responses of S. pneumoniae, such as competence for genetic exchange or virulence in a mammalian host, could thus be modulated by oxygen via the NADH oxidase activity of the bacteria, although the bacterial energetic metabolism is essentially anaerobic. The enzymatic activity of the NADH oxidase coded by nox was probably involved in transducing the external signal, corresponding to O2 availability, to the cell metabolism and physiology; thus, this enzyme may function as an oxygen sensor. This work establishes, for the first time, the role of O2 in the regulation of pneumococcal transformability and virulence.
Infection Due to Actinobacillus actinomycetemcomitans: 15 Cases and Review (1989)

Actinobacillus actinomycetemcomitans is a small fastidious gram-negative coccobacillus that fails to grow on MacConkey's agar. Slow growth in broth may lead to delays in diagnosis. First described in 1912, A. actinomycetemcomitans has been recognized since 1962 as capable of causing serious infections in humans. Such infections include periodontal infection, soft tissue abscess (often in association with Actinomyces species), and systemic infection, most commonly endocarditis. Fifteen cases and a review of the English-language literature are presented to define the epidemiology and clinical features of infection due to A. actinomycetemcomitans. Therapy for infection due to A. actinomycetemcomitans has most commonly involved ampicillin or penicillin, often in conjunction with an aminoglycoside. However, resistance to penicillin or ampicillin is common. Antimicrobial agents with a high degree of in vitro activity included cefazolin, cefotaxime, cetriaxone, aminoglycosides, and chloramphenicol. Therapy should be guided by clinical response and in vitro susceptibility testing.
Parthenogenetic Stem Cells (2006)

One of the most exciting and contentious issues in biomedical science today is the potential use of stem cells as a therapeutic intervention for a wide range of diseases with pathologies that involve cellular destruction. Stem cell therapy is currently practiced, or under active research, to repair the effects of neuromuscular degeneration, autoimmune response, ischemic attack, malignant carcinoma, congenital defects, metabolic disorders, and alcohol-related pathologies. When stimulated in a proliferative environment, stem cells may also provide the raw material for large-scale ex vivo tissue regeneration. There are several sources of human stem cells for laboratory culture, but the primary source of pluripotent human embryonic stem cells is the inner cell mass of in vitro fertilized embryos. Despite the potential rewards to medicine, experimentation using cells from viable human fetuses has triggered global political and ethical controversy that has slowed down the pace of research. An alternative source of human embryonic stem cells that circumvents some of these issues would significantly enhance research in this area. Parthenogenetically derived stem cells may represent such a resource. Parthenogenesis involves activation of the oocyte without sperm, and produces a nonviable blastocyst. That is, the activated egg develops to the blastocyst (and so can be used to generate stem cells), but it will not produce a viable pregnancy in mammals. The unique genesis of the embryo, and its arrested development at blastocyst, may afford sufficient moral and political latitude to enable its acceptance as an experimental entity. Research is ongoing to assess the genetic and phenotypic similarity of parthenogenetic stem cells (PSCs) to other stem cell types from mammalian models and to human stem cells derived from fertilized embryos.


Keywords:

Chimera;
Genomic Imprinting;
Parthenogenesis;
Parthenote;
Teratoma;
Uniparental Disomy
Influence of the pKa value of the buried, active‐site cysteine on the redox properties of thioredoxin‐like oxidoreductases (2000)

Thioredoxin constitutes the prototype of the thiol-disulfide oxidoreductase family. These enzymes contain an active-site disulfide bridge with the consensus sequence Cys-Xaa-Xaa-Cys. The more N-terminal active-site cysteine is generally a strong nucleophile with an abnormal low pK(a) value. In contrast, the more C-terminal cysteine is buried and only little is known about its effective pK(a) during catalysis of disulfide exchange reactions. Here we have analyzed the pK(a) values of the active-site thiols in wild type thioredoxin and a 400-fold more oxidizing thioredoxin variant by NMR spectroscopy, using selectively (13)C(beta)-Cys-labeled proteins. We find that the effective pK(a) of the buried cysteine (pK(b)) of the variant is increased, while the pK(a) of the more N-terminal cysteine (pK(N)) is decreased relative to the corresponding pK(a) values in the wild type. We propose two empirical models which exclusively require the knowledge of pK(N) to predict the redox properties of thiol-disulfide oxidoreductases with reasonable accuracy.