gebhart/patrepeval huggingface dataset:
Reverse transcriptase incorporation of 1,5-anhydrohexitol nucleotides (2001)

Several reverse transcriptases were studied for their ability to accept anhydrohexitol triphosphates, having a conformationally restricted six-membered ring, as substrate for template-directed synthesis of HNA. It was found that AMV, M-MLV, M-MLV (H(-)), RAV2 and HIV-1 reverse transcriptases were able to recognise the anhydrohexitol triphosphate as substrate and to efficiently catalyse the incorporation of one non-natural anhydrohexitol nucleotide opposite a natural complementary nucleotide. However, only the dimeric enzymes, the RAV2 and HIV-1 reverse transcriptases, seemed to be able to further extend the primer with another anhydrohexitol building block. Subsequently, several HIV-1 mutants (4xAZT, 4xAZT/L100I, L74V, M184V and K65A) were likewise analysed, resulting in selection of K65A and, in particular, M184V as the most succesful mutant HIV-1 reverse transcriptases capable of elongating a DNA primer with several 1,5-anhydrohexitol adenines in an efficient way. Results of kinetic experiments in the presence of this enzyme revealed that incorporation of one anhydrohexitol nucleotide of adenine or thymine gave an increased (for 1,5-anhydrohexitol-ATP) and a slightly decreased (for 1,5-anhydrohexitol-TTP) K(m) value in comparison to that of their natural counterparts. However, no more than four analogues could be inserted under the experimental conditions required for selective incorporation. Investigation of incorporation of the altritol anhydrohexitol nucleotide of adenine in the presence of M184V and Vent (exo(-)) DNA polymerase proved that an adjacent hydroxyl group on C3 of 1,5-anhydrohexitol-ATP has a detrimental effect on the substrate activity of the six-ring analogue. These results could be rationalised based on the X-ray structure of HIV-1 reverse transcriptase.
The importance of distributed, component-based healthcare information systems: the role of a service-based architecture (2002)

The high cost of healthcare information systems (HISs) is driven by a number of factors. Proprietary systems drive the cost of interchanging data much higher than if the systems implemented standard interfaces, by not being able to leverage competitive reusable components. The HL7 data standards have been an excellent help, but provide only partial solutions, because of the normal customization that occurs at each organization. The monolithic nature of most large HISs makes it difficult for them to be best-of-breed in an area and very expensive to upgrade or replace. Service-oriented component-based technologies enable systems to be constructed of replaceable, best-of-breed components. This enables much more competition on lower-cost components, with the promise of much lower overall costs. This lower cost is driven not just by competition but also by providing a mechanism to deal with change, by replacing software parts as newer more powerful ones become available without having to replace the entire system. The value of components is not just in their modularity but also in the use of standard interfaces to facilitate interoperability. In addition, the ultimate value to the consumer of components is to enable the ad-hoc assembly of a patient's virtual medical record over the Internet across multiple healthcare organizations. This paper describes the successful implementation of standard components in an open-source system, called OpenEMed, which can be used for a variety of healthcare-related applications.
An empirical study of the robustness of Windows NT applications using random testing (2000)

We report on the third in a series of studies on the reliability of application programs in the face of random input. In 1990 and 1995, we studied the reliability of UNIX application programs, both command line and X-Window based (GUI). In this study, we apply our testing techniques to applications running on the Windows NT operating system. Our testing is simple black-box random input testing; by any measure, it is a crude technique, but it seems to be effective at locating bugs in real programs. We tested over 30 GUI-based applications by subjecting them to two kinds of random input: (1) streams of valid keyboard and mouse events and (2) streams of random Win32 messages. We have built a tool that helps automate the testing of Windows NT applications. With a few simple parameters, any application can be tested. Using our random testing techniques, our previous UNIXbased studies showed that we could crash a wide variety of command-line and X-window based applications on several UNIX platforms. The test results are similar for NT-based applications. When subjected to random valid input that could be produced by using the mouse and keyboard, we crashed 21% of applications that we tested and hung an additional 24 % of applications. When subjected to raw random Win32 messages, we crashed or hung all the applications that we tested. We report which applications failed under which tests, and provide some analysis of the failures. 1INTRODUCTION We report on the third in a series of studies on the reliability of application programs in the face of random input. In 1990 and 1995, we studied the reliability of UNIX command line and X-Window based (GUI) application programs[8,9]. In this study, we apply our techniques to applications running on the Windows NT operating system. Our testing, called fuzz testing, uses simple black-box random input; no knowledge of the application is used in generating the random input. Our 1990 study evaluated the reliability of standard UNIX command line utilities. It showed that 25-33 % of such applications crashed or hung when reading random input. The 1995 study evaluated a larger collection of
Identification of Small-Molecule Inhibitors against Human Leukocyte Antigen-Death Receptor 4 (HLA-DR4) Through a Comprehensive Strategy (2011)

Rheumatoid arthritis (RA) is an autoimmune disease mediated by T-lymphocytes and associated with the human leukocyte antigen-death receptor 4 (HLA-DR4). The HLA-DR4 protein selectively interacts with the antigenic peptides on the cell surface and presents them to the T cell receptor (TCR) on CD4+ T cells. The HLA-DR4-antigen-TCR complex initiates the autoimmune response and eventually causes the chronic inflammation within patients bodies. To inhibit HLA-DR4-restricted T cell activation, an ideal approach is to discover non-T cell stimulating substrates that specifically bind to HLA-DR4. In this paper, a comprehensive structure-based design strategy involved de novo design approach, pharmacophore search, and dock method was presented and applied to "simplify" the known binding peptide ligand of HLA-DR4 and identified specific small-molecule inhibitors for HLA-DR4. The designed three-step strategy successfully identified five nonpeptide ligands with novel scaffolds from a chemical library containing 4 × 10(6) commercially available compounds within a tolerable computing time. The identified five chemicals, BAS-0219606, T0506-2494, 6436645, 3S-71981, and KM 11073, are all non-T cell stimulators and are able to significantly inhibit HLA-DR4-restricted T cell activation induced by type II collagen (CII) 263-272 peptide. IC(50) for the best two potentials, BAS-0219606 and T0506-2494, was 31 and 17 μM, respectively, which is equivalent or better than the known peptide ligands. It is hopeful that they can be used as effective therapeutic means for further treatment of RA patients. In addition, the comprehensive strategy presented in this paper exhibited itself to be an effective flow line from peptide ligands to small-molecule inhibitors and will have applications to other targets.
A least-squares approach to joint diagonalization (1997)

We present a new least-squares-based approach for the joint diagonalization problem arising in blind beamforming. The resulting estimation criterion turns out to coincide with that proposed by Cardoso and Souloumaic (see IEE Proc. F, Radar Signal Process., vol.140, no.6, p.362-70, Dec. 1993) on intuitive grounds, thus establishing the optimality of their criterion in the least-squares (LS) sense.
Rheological Behavior of Nasal Sprays in Shear and Extension (2000)

The rheological profiles of commercial corticosteroid nasal spray suspensions (Beconase, Nasacort, Flixonase, and Nasonex) were compared using shear and extensional techniques. Thixotropy/shear thinning was investigated (Carri-Med CSL100, concentric cylinder geometry) by (a) the generation of flow curves at low (100 sec-1) and high (1200 sec-1) maximum shear rates and (b) determination of equilibrium shear viscosities at constant shear rates of 10 sec-1, 100 sec-1, or 1200 sec-1. Extensional properties, on which droplet breakup and size depend, were examined using digital camera photography of droplet evolution and the length any trailing filament formed when the suspension was extruded from a 10-ml syringe at 500 microliters/min. All the nasal suspensions were shear thinning and were also thixotropic to varying degrees. The absence of significant thixotropic recovery at short times (5 min) for all the sprays implies that thixotropy is not necessarily the controlling factor for prolonged residence of the spray in the nasal cavity, but rather that it is the high viscosities present in all four sprays, even after structure breakdown. Preliminary extensional flow data identified differences among the four sprays, with extensional filament lengths increasing in the same rank order as the lowest shear rate (10 sec-1) equilibrium viscosities.
Food Markets with Live Birds as Source of Avian Influenza (2006)

A patient may have been infected with highly pathogenic avian influenza virus H5N1 in Guangzhou, People's Republic of China, at a food market that had live birds. Virus genes were detected in 1 of 79 wire cages for birds at 9 markets. One of 110 persons in the poultry business at markets had neutralizing antibody against H5N1.
정신장애인 동료지지활동 프로그램이 동료지원가의 회복에 미치는 효과 (2014)

본 연구의 목적은 정신장애인 동료지지활동 프로그램이 동료지원가의 회복에 미치는 효과를 검증하는 것이다. 동료지지활동을 통해 서비스를 제공한 동료지원가의 회복과 정신과적 증상이 어떠한 변화를 나타내는지 실증적으로 검증하였다. 이를 위해 동료지원가 33명을 대상으로 활동 전후, 그리고 6개월 사후의 변화를 측정하였으며, 활동 지속여부에 따라 차이가 있는지를...
Concerted Reactions That Produce Diradicals and Zwitterions: Electronic, Steric, Conformational, and Kinetic Control of Cycloaromatization Processes (2013)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTConcerted Reactions That Produce Diradicals and Zwitterions: Electronic, Steric, Conformational, and Kinetic Control of Cycloaromatization ProcessesRana K. Mohamed, Paul W. Peterson, and Igor V. Alabugin*View Author Information Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4390, United States*E-mail: [email protected]Cite this: Chem. Rev. 2013, 113, 9, 7089–7129Publication Date (Web):April 19, 2013Publication History Received1 February 2013Published online19 April 2013Published inissue 11 September 2013https://pubs.acs.org/doi/10.1021/cr4000682https://doi.org/10.1021/cr4000682review-articleACS PublicationsCopyright © 2013 American Chemical SocietyRequest reuse permissionsArticle Views6658Altmetric-Citations179LEARN 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-Alertsclose SUBJECTS:Aromatic compounds,Cyclization,Hydrocarbons,Stabilization,Substituents Get e-Alerts
Individualized Therapy for Childhood Acute Lymphoblastic Leukemia (2005)

In the field of oncology, a growing emphasis is now being placed on individualizing treatment in a way that maximizes chance for cure while minimizing unwanted side effects. In childhood acute lymphoblastic leukemia (ALL), several well-established clinical and biologic prognostic variables have traditionally been used to risk stratify therapy for individual patients. While this approach has been very successful, many relapses still occur unpredictably in patients characterized as having favorable features of their disease at diagnosis. Furthermore, it is likely that other children are overtreated. Therefore, current initiatives in childhood leukemia have focused on identifying new prognostic markers to refine treatment decision-making. Recent advances, which include the sequencing of the human genome, and technical developments in high-throughput genomics and proteomics, have facilitated these efforts. This review will chart the evolution of individualized therapy for ALL, the most common malignancy of children.
Global Expression of Cell Surface Proteins in Embryonic Stem Cells (2010)

Our results indicate that global gene expression is not simply a result of leaky gene expression, which could be attributed to the loose chromatin structure of ES cells; it is also propagated to the functional level. ES cells may use diverse surface proteins to receive signals from the diverse extracellular stimuli that initiate differentiation. Moreover, the promiscuous expression of tissue specific surface proteins illuminate new insights into the strategies of cell surface marker screening.
Staufen‐mediated <scp>mRNA</scp> decay (2013)

Staufen1 (STAU1)-mediated mRNA decay (SMD) is an mRNA degradation process in mammalian cells that is mediated by the binding of STAU1 to a STAU1-binding site (SBS) within the 3'-untranslated region (3'-UTR) of target mRNAs. During SMD, STAU1, a double-stranded (ds) RNA-binding protein, recognizes dsRNA structures formed either by intramolecular base pairing of 3'-UTR sequences or by intermolecular base pairing of 3'-UTR sequences with a long-noncoding RNA (lncRNA) via partially complementary Alu elements. Recently, STAU2, a paralog of STAU1, has also been reported to mediate SMD. Both STAU1 and STAU2 interact directly with the ATP-dependent RNA helicase UPF1, a key SMD factor, enhancing its helicase activity to promote effective SMD. Moreover, STAU1 and STAU2 form homodimeric and heterodimeric interactions via domain-swapping. Because both SMD and the mechanistically related nonsense-mediated mRNA decay (NMD) employ UPF1; SMD and NMD are competitive pathways. Competition contributes to cellular differentiation processes, such as myogenesis and adipogenesis, placing SMD at the heart of various physiologically important mechanisms.
New CD1d agonists: Synthesis and biological activity of 6″-triazole-substituted α-galactosyl ceramides (2012)

Huisgen [3+2] dipolar cycloaddition of 6″-azido-6″-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activate iNKT cells and stimulate IL-2 cytokine secretion in vitro, and IFN-γ and IL-4 cytokine secretion in vivo. Some of these analogues, specifically 11, 12b, 12f and 13, were more potent IL-2 stimulators than the prototypical CD1d agonist, α-GalCer 1. In terms of any cytokine bias, most of the triazole-containing analogues exhibited a small Th2 cytokine-biasing response relative to that shown by α-GalCer 1. In contrast, the cycloaddition precursor, namely azide 11, provided a small Th1 cytokine-biasing response.
Some outstanding issues in pion scattering at energies above the [Delta] resonance (1993)

The [Delta](1232) resonance dominates pion-nucleon scattering at energies below 300 MeV, the region in which pion-nucleus scattering has been well studied using spectrometers at the meson factories. Above this energy region little pion-nucleus scattering data exists. Recently, spectrometers at Brookhaven, LAMPF, KEK, and DUBNA have been used to obtain initial data for pion-nucleus scattering in this energy region. In this talk we review some data that have been obtained using the LAS spectrometer at LAMPF.
Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors (2006)

Three mammalian nuclear lamin proteins, lamin B(1), lamin B(2) and the lamin A precursor, prelamin A, undergo canonical farnesylation and processing at CAAX motifs. In the case of prelamin A, there is an additional farnesylation-dependent endoproteolysis, which is defective in two congenital diseases: Hutchinson-Gilford progeria (HGPS) and restrictive dermopathy (RD). These two diseases arise respectively from defects in the prelamin A substrate and the enzyme (ZmpSte24) that processes it. Recent work has shed light on the roles of the lamin proteins and the enzymes involved in their farnesylation-dependent maturation. Other experimental work, including mouse model studies, have examined the possibility that farnesyl transferase inhibitors can represent effective treatment for HGPS. However, there are concerns about their use for this purpose given the potential for alternative prenylation pathways.
Low loss/Large tolerance mode converter between SiN waveguide and cleaved single mode fiber (2014)

A mode converter is fabricated with SiON to reduce the coupling loss between SiN waveguide and cleaved single-mode-fiber. The coupling loss is 1.2dB/facet and 1.4dB/facet for TE and TM mode, respectively, with 3dB alignment tolerance of ±3.5µm.
Fog computing dynamic load balancing mechanism based on graph repartitioning (2016)

Because of cloud computing's high degree of polymerization calculation mode, it can't give full play to the resources of the edge device such as computing, storage, etc. Fog computing can improve the resource utilization efficiency of the edge device, and solve the problem about service computing of the delay-sensitive applications. This paper researches on the framework of the fog computing, and adopts Cloud Atomization Technology to turn physical nodes in different levels into virtual machine nodes. On this basis, this paper uses the graph partitioning theory to build the fog computing's load balancing algorithm based on dynamic graph partitioning. The simulation results show that the framework of the fog computing after Cloud Atomization can build the system network flexibly, and dynamic load balancing mechanism can effectively configure system resources as well as reducing the consumption of node migration brought by system changes.
Prescribing Pattern of Antidepressants in Children and Adolescents: Findings from the Research on Asia Psychotropic Prescription Pattern. (2016)

Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.
Total parenteral nutrition as an adjunct to chemotherapy of metastatic colorectal cancer. (1981)

A randomized study was performed in advanced cancer to test the effectiveness of total parenteral nutrition (TPN) in maintaining and improving nutrition, to examine the effects of TPN on tumor growth, and to determine if TPN altered chemotherapy response rates, treatment tolerance, and survival. Forty-five patients on identical chemotherapy were randomized to TPN versus ad libitum feeding. TPN was well tolerated. No clinical or tumor marker evidence suggesting neoplastic growth stimulation was obtained. Chemotherapy-related complications and chemotherapy responses did not differ between the two groups. TPN had little effect on performance status. TPN patients gained an average of 2.8 kg before chemotherapy, but triceps skinfold and mid-arm muscle area did not change significantly during TPN. Survival did not improve with TPN. We conclude that current techniques of TPN are of limited benefit in advanced colon cancer. A small subset of patients with short-gut malabsorption may be helped. Further study is needed to determine the mechanisms of cancer undernutrition and to refine nutritional supplementation techniques on the basis of these mechanisms.
Interferon-β regulates cytokines and BDNF: greater effect in relapsing than in progressive multiple sclerosis (2007)

The mechanism of action of interferon (IFN)-beta therapy in multiple sclerosis (MS) is only partially known, and its efficacy changes with disease stage. In different forms of MS, we determined how IFN-beta regulates mononuclear cell production of the important anti-inflammatory Th2 cytokine - IL-10, the Th1 cytokine - IFN-gamma, and the brain-derived neurotrophic protein - BDNF. Activated T cells and monocytes from therapy-naïve patients secreted more IL-10 than healthy controls. During IFN-beta therapy, however, T cells produced less IL-10. In vitro, IFN-beta stimulated IL-10 production by activated T cells, but inhibited IL-10 secretion by activated monocytes, a richer source of IL-10 than T cells. The form of MS also affected cytokine production. IL-10 and BDNF levels in MNC were high during relapsing/remitting (RR) MS, but low in progressive MS. Surprisingly, IFN-beta therapy increased BDNF levels in antidepressant-naïve patients, but BDNF was lower during concurrent antidepressant drug therapy, suggesting an interaction between MS, depression, and neurodegeneration. IFN-beta in vitro strongly induced IL-10 and IFN-gamma in activated T cells in RRMS, but not in progressive MS, suggesting IFN resistance. IFN-beta effects are specific for disease state and immune subsets, possibly explaining why IFN-beta therapy is most effective in early T cell-regulated RRMS, but less beneficial in progressive MS, where chronic plaques contain few T cells and high numbers of monocytes.
Terpenoid Indole Alkaloids Biosynthesis and Metabolic Engineering in <i>Catharanthus roseus</i> (2007)

Abstract Catharanthus roseus L. (Madagascar periwinkle) biosynthesizes a diverse array of secondary metabolites including anticancer dimeric alkaloids (vinblastine and vincristine) and antihypertensive alkaloids (ajmalicine and serpentine). The multi‐step terpenoid indole alkaloids (TIAs) biosynthetic pathway in C. roseus is complex and is under strict molecular regulation. Many enzymes and genes involved in the TIAs biosynthesis have been studied in recent decades. Moreover, some regulatory proteins were found recently to control the production of TIAs in C. roseus . Based on mastering the rough scheme of the pathway and cloning the related genes, metabolic engineering of TIAs biosynthesis has been studied in C. roseus aiming at increasing the desired secondary metabolites in the past few years. The present article summarizes recent advances in isolation and characterization of TIAs biosynthesis genes and transcriptional regulators involved in the second metabolic control in C. roseus . Metabolic engineering applications in TIAs pathway via overexpression of these genes and regulators in C. roseus are also discussed.
Triacetone Triperoxide: Its Chemical Destruction (1999)

Abstract Due to the known use of triacetone triperoxide (TATP) as an improvized explosive by terrorist organizations, it is essential that those involved in dealing with suspect materials should be aware of the characteristic properties of TATP, and have a means for disposing of it. This paper evaluates possible methods for disposing of TATP and describes in detail a convenient chemical reduction method. The risks involved in handling this sensitive explosive are shown to be considerably reduced by dissolving it in toluene.