gebhart/patrepeval huggingface dataset:
Factor XIa Inhibitors as New Anticoagulants (2018)

With the introduction of thrombin and factor Xa inhibitors to the oral anticoagulant market, significant improvements in both efficacy and safety have been achieved. Early clinical and preclinical data suggest that inhibitors of factor XIa can provide a still safer alternative, with expanded efficacy for arterial indications. This Perspective provides an overview of target rationale and details of the discovery and development of inhibitors of factor XIa as next generation antithrombotic agents.
Introduction of spacer peptides N-terminal to a cleavage recognition motif in recombinant fusion proteins can improve site-specific cleavage (1997)

To improve site-specific cleavage of a methionyl porcine growth hormone [[Met1]-pGH(1-46)-IGF-II] fusion protein by the enzyme H64A subtilisin, a series of flexible, unstructured spacer peptides were introduced N-terminal to the cleavage site. When enzymatic digestion preceded refolding of the fusion proteins, IGF-II could only be liberated from substrates which contained spacer peptides. Compared with the parent construct, the yield of IGF-II from refolded fusion proteins containing spacers was improved up to two-fold. Furthermore, this cleavage rate was improved by removing a competing protease recognition motif from the fusion partner. These data show that fusion partners can influence site-specific proteolysis of fusion proteins. Introduction of flexible spacers between the moieties can alleviate these interactions.
Multiple type workflow model for enterprise application integration (2005)

The business environment is changing rapidly everyday. Enterprise information systems must be able to adapt to changes in markets quickly and flexibly. Enterprises control large amounts of software resources and these software resources must be integrated. One solution that is attracting a great deal of attention is the concept of enterprise application integration (EAI). EAI can adapt to changes in markets quickly and flexibly. As a method for implementing EAI, we are proposing business process-based integration using workflow techniques. Business process-based integration divides an enterprise information system into business processes and the work logic that comprises the system. We propose a new type of workflow for EAI. The new workflow for EAI uses a CORBA interface to integrate different types of systems and uses a state transition model based on a database to dynamically control processes. An organization can define business processes and rules so that the business processes can flexibly adapt to changes in the organization and applications. We have confirmed the effectiveness of this new workflow management system for EAI by applying it in an actual test case.
Advances in the understanding of myeloma bone disease and tumour growth (2010)

Advances in multiple myeloma support the notion that the associated bone disease, characterized by increased osteoclastogenesis and suppressed osteoblastogenesis, is both a consequence and necessity of tumour progression. Osteoblastogenesis is suppressed by secreted inhibitors and dysregulation of cell-surface 'coupling' factors on osteogenic cells. Osteoclastogenesis is increased as a consequence of osteoblast deactivation and of production of osteoclast-activating factors. Osteoclasts express soluble and cell-surface factors that stimulate myeloma growth, while osteoblasts produce bone-building factors that restrain growth of myeloma cells that are dependent on the microenvironment; detailed molecular mechanisms are discussed. Experimental and clinical findings indicate that pharmacological and experimental osteoblast-activating agents that effectively promote bone formation also reduce growth of myeloma cells within bone, seemingly by simultaneously stimulating osteoblastogenesis and restraining osteoclastogenesis. Unravelling mechanisms of myeloma bone disease expands horizons for developing novel interventions and also facilitates better understanding of the association between induction of osteolysis and disease progression.
Resilience in shock and swim stress models of depression (2013)

Experimental models of depression often entail exposing a rodent to a stressor and subsequently characterizing changes in learning and anhedonia, which may reflect symptoms of human depression. Importantly, not all people, and not all laboratory rats, exposed to stressors develop depressed behavior; these "resilient" individuals are the focus of our review. Herein we describe research from the "learned helplessness" and "intermittent swim stress" (ISS) models of depression in which rats that were allowed to control the offset of the aversive stimulus with a behavioral response, and in a subset of rats that were not allowed to control the stressor that appeared to be behaviorally and neurochemically similar to rats that were either naive to stress or had controllability over the stressor. For example, rats exposed to inescapable tailshock, but do not develop learned helplessness, exhibit altered sensitivity to the behavioral effects of GABAA receptor antagonists and reduced in vitro benzodiazepine receptor ligand binding. This pattern suggested that resilience might involve activation of an endogenous benzodiazepine-like compound, possibly an allostatic modulator of the GABAA receptor like allopregnanolone. From the ISS model, we have observed in resilient rats protection from stressor-induced glucocorticoid increases and immune activation. In order to identify the neural mediators of these correlates of resilience, non-invasive measures are needed to predict the resilient or vulnerable phenotype prior to analysis of neural endpoints. To this end, we found that ultrasonic vocalizations (USVs) appear to predict the resilient phenotype in the ISS paradigm. We propose that combining non-invasive predictive measures, such as USVs with biological endpoint measures, will facilitate future research into the neural correlates of resilience.
Zirconium oxide based gate dielectrics with equivalent oxide thickness of less than 1.0 nm and performance of submicron MOSFET using a nitride gate replacement process (2003)

Zirconium oxide is investigated as a possible replacement for SiO/sub 2/ gate dielectric thinner than 1.5 nm. A maximum capacitance of 31 fF//spl mu/m/sup 2/ (measured in accumulation at -2 V) is obtained for a 3.9 nm ZrO/sub 2/ film with leakage current of /spl sim/1 mA/cm/sup 2/ at -1.0 V, yielding an equivalent oxide thickness of less than 1.0 nm. Doping with Al produced amorphous films with better uniformity, but slightly lower dielectric constant. Submicron MOSFETs with TiN gate electrode and ZrO/sub 2/ or Al doped ZrO/sub 2/ gate dielectrics have been fabricated and good device performance is obtained.
Improving threading algorithms for remote homology modeling by combining fragment and template comparisons (2010)

In this work, we develop a method called fragment comparison and the template comparison (FTCOM) for assessing the global quality of protein structural models for targets of medium and hard difficulty (remote homology) produced by structure prediction approaches such as threading or ab initio structure prediction. FTCOM requires the C(alpha) coordinates of full length models and assesses model quality based on fragment comparison and a score derived from comparison of the model to top threading templates. On a set of 361 medium/hard targets, FTCOM was applied to and assessed for its ability to improve on the results from the SP(3), SPARKS, PROSPECTOR_3, and PRO-SP(3)-TASSER threading algorithms. The average TM-score improves by 5-10% for the first selected model by the new method over models obtained by the original selection procedure in the respective threading methods. Moreover, the number of foldable targets (TM-score >or= 0.4) increases from least 7.6% for SP(3) to 54% for SPARKS. Thus, FTCOM is a promising approach to template selection. Proteins 2010. (c) 2010 Wiley-Liss, Inc.
Epigenetic suppression of secreted frizzled related protein 1 (SFRP1) expression in human breast cancer (2006)

Expression of Secreted frizzled related protein 1 (SFRP1), a recently identified tumor suppressor gene encoding a WNT signaling antagonist, has been found to be frequently down-regulated in breast cancer and is associated with disease progression and poor prognosis. Here, we investigated the role of epigenetic silencing of SFRP1 in breast cancer cell lines and primary breast tumors. Through analyses by methylation-specific PCR and bisulfite sequencing, promoter methylation of SFRP1 was detected in 88% (7/8) of breast cancer cell lines, 17% (1/6) of grade 1 of ductal carcinoma in situ (DCIS), 69% (9/13) of grade 2 and 3 of DCIS, 68% (19/28) of invasive ductal carcinomas (IDC) and 33% (6/18) of lobular carcinomas but not in any (0/14) of normal mammoplasty specimens and mammary epithelial organoids examined. Real-time RT-PCR studies indicated that loss or downregulation of SFRP1 expression in tumors is frequently associated with promoter hypermethylation. In addition, breast cancer cell lines with SFRP1 promoter hypermethylation reexpressed SFRP1 mRNA after treatment with 5-azaC, implying that DNA methylation is the predominant epigenetic mechanism for SFRP1 gene silencing. These findings suggest that frequent downregulation of SFRP1 expression in breast cancer can be attributed, in large part, to aberrant promoter hypermethylation in conjunction with or without histone deacetylation. Based on the frequency of tumor-specific hypermethylation in this gene, SFRP1 could provide a valuable marker for breast cancer.
Spontaneous release of the Leu-2 (T8) molecule from human T cells. (1983)

Sensitive enzyme-linked immunosorbent assays (ELISA) for the detection of human T cell antigens in soluble form have been developed. The assays use mouse monoclonal antibodies and specific anti-Leu sera prepared in rabbits by immunizing with Leu antigens absorbed to monoclonal antibody affinity columns. With these assays, Leu-1, -2, and -3 antigen signals from extracts of as few as 5 X 10(3) cells could be detected. When culture supernatants from various cell lines were tested, Leu-2 antigen, but not Leu-1 or Leu-3, was found to be present. Leu-2 antigen was present only in supernatants from T cell lines that expressed Leu-2 on their cell surface. Leu-2 antigen accumulated progressively in the supernatant of low density culture and its presence did not depend on cell proliferation or on fetal calf serum in the culture medium. The Leu-2 antigen in the supernatant was found to have only one Leu-2a determinant, whereas Leu-2 antigen from cell extracts had at least two determinants. The Leu-2 molecule was effectively purified from supernatant with an anti-Leu-2a affinity column. The purified Leu-2 antigen from supernatant of HPB-ALL cells was a single polypeptide chain of 27,000 mol wt, whereas Leu-2 antigen present on HPB-ALL cell surface was composed of two or more identical polypeptide chains of 33,000 mol wt linked by disulfide bonds. Normal human sera and sera from leukemia patients were also examined for the presence of the Leu-2 antigen. Normal human sera contained low levels of Leu-2 antigen but sera from Leu-2-positive leukemia patients had high levels. These results indicate that Leu-2 antigen is released from human T cells under physiological conditions.
Comparative Analysis of the Entropy of Radiative Heat Transfer and Heat Conduction (2007)

Many thermodynamic texts incorrectly imply that the entropy flux of thermal radiation (TR) is the same as that for heat conduction, the heat flux divided by the local temperature (q/T). However, for blackbody radiation (BR) emission a 4/3 factor occurs. BR represents the maximum entropy for all radiation with the same emission temperature, as well as all radiation with the same energy radiance. However, using Planck’s formulas it is shown that BR emission has the lowest entropy-to-energy ratio, and thus the lowest entropy factor, for all radiation with the same emission temperature or radiation with an enclosed energy spectrum. In practice, analysis of radiative transfer includes incident, reflected and emitted fluxes. Case-specific integration, based on Planck’s entropy formula, can be used to determine the net radiative entropy flux. However, this net entropy flux can be put in the form n(q/T), where n is a coefficient unique to the radiative fluxes involved. This allows the net entropy flux to be easily calculated given the energy flux and the temperature of the opaque absorbing material. This entropy coefficient can vary greatly, taking on values less than unity, and values greater than unity. This implies that the misuse of the heat conduction entropy flux expression can vary from overestimating (n 1) the net radiative entropy flux. Graphical tools and simplified approximate expressions are presented that allow the entropy coefficient n to be quickly determined in certain general scenarios of radiative transfer encountered in practice.
Effects of subgingival chlorhexidine irrigation on periodontal inflammation (1982)

The purposes of this study were to investigate the effect of direct application of chlorhexidine to periodontal pockets and the practicability of patient self-therapy using a technique of subgingival irrigation. Patients received no other oral hygiene instruction. After initial assessment of parameters, patients were given scaling and polishing and then instruction in the irrigation of designated pockets with chlorhexidine or a placebo using a disposable syringe and blunt needle. During the 28-day irrigation period with chlorhexidine there was highly significant reduction in periodontal inflammation which was maintained at levels significantly below the baseline values for a further 28-day period without irrigation. There was a deterioration in the periodontal state of those patients who had used the placebo, The irrigation technique itself caused no discernible injury in this group of routine periodontal patients. Also, staining in the chlorhexidine group was minimal. It is concluded that subgingival irrigation with chlorhexidine is effective in reducing periodontal inflammation and in controlling subgingival plaque. Intermittent treatment of this kind by the patient at home might reduce to more manageable levels the frequency of hygiene visits and the need for rigorous interdental oral hygiene.
Preparation and characterization of immunoliposomes for targeting of antiviral agents. (1991)

Antibodies specific to avian myeloblastosis virus envelope glycoprotein gp80 were raised. Immunoliposomes were prepared using anti-avian myeloblastosis virus envelope glycoprotein gp80 antibody. The antibody was palmitoylated to facilitate its incorporation into lipid bilayers of liposomes. The fluorescence emission spectra of palmitoylated IgG have exhibited a shift in emission maximum from 330 to 370 nm when it was incorporated into the liposomes. At least 50% of the incorporated antibody molecules were found to be oriented towards the outside in the liposomes. The average size of the liposome was found to be 300 A, and on an average, 15 antibody molecules were shown to be present in a liposome. When adriamycin encapsulated in immunoliposomes was incubated in a medium containing serum for 72 h, about 75% of the drug was retained in liposomes. In vivo localization studies, revealed an enhanced delivery of drug encapsulated in immunoliposomes to the target tissue, as compared to free drug or drug encapsulated in free liposomes. These data suggest a possible use of the drugs encapsulated in immunoliposomes to deliver the drugs in target areas, thereby reducing side effects caused by antiviral agents.
Efficacy of Pinosylvins against White-Rot and Brown-Rot Fungi (1999)

Summary Three stilbenes, pinosylvin (PS), pinosylvin monomethyl ether (PSM) and pinosylvin dimethyl ether (PSD), were extracted from white spruce (Picea glauca) , jack pine (Pinus banksiana) , and red pine (Pinus resinosa) pine cones, and their structures were confirmed by spectroscopic and chromatographic (HPLC, GC/MS, NMR and FTIR) analysis. PS, PSM, PSD or a 1:1:1 mixture of these stilbenes at concentrations of 0.1 % and 1.0 % were examined for their fungal inhibitory activity by two bioassay methods. Growth of white-rot fungi (Trametes versicolor and Phanerochaete chrysosporium) , and brown-rot fungi (Neolentinus lepideus, Gloeophyllum trabeum and Postia placenta) on agar media in the presence of each of the stilbenes or a 1:1:1 mixture inhibited growth of white-rot fungi, but slightly stimulated growth of brown-rot fungi. Soil-block assays, conditions more representative of those found in nature, did not correlate with those from the screening on agar media. PS, PSM, PSD or a 1:1:1 mixture of the three compounds at concentrations of 0.1 % and 1.0 % did not impart any significant decay resistance to white-rot fungi inoculated on a hardwood (Red maple). However under the same conditions, decay resistance was observed against brown-rot fungi on a softwood (Southern yellow pine). It appears that stilbenes at least partially contribute to wood decay resistance against brown-rot fungi.
4-Gb/s PSK homodyne transmission system using phase-locked semiconductor lasers (1990)

Homodyne detection of 4-Gb/s pilot-carrier binary-phase-shift-keyed (BPSK) optical signals using external-cavity semiconductor lasers synchronized by a linear phase-locked loop is discussed. A 2/sup 15/-1 pseudorandom binary sequence (PRBS) has been transmitted through a short fiber with a receiver sensitivity of -44.2 dBm or 72 photons/bit. After transmission through 167 km of standard single-mode fiber, the sensitivity is -43.6 dBm or 83 photons/bit. A balanced PIN/HEMT transimpedance receiver which has a 3-dB bandwidth from 100 kHz to 10.1 GHz and an average equivalent input noise current of 10.8 pA/ square root Hz is used.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cell Type and Culture Condition–Dependent Alternative Splicing in Human Breast Cancer Cells Revealed by Splicing-Sensitive Microarrays (2006)

Growing evidence indicates that alternative or aberrant pre-mRNA splicing takes place during the development, progression, and metastasis of breast cancer. However, which splicing changes that might contribute directly to tumorigenesis or cancer progression remain to be elucidated. We used splicing-sensitive microarrays to detect differences in alternative splicing between two breast cancer cell lines, MCF7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor negative), as well as cultured human mammary epithelial cells. Several splicing alterations in genes, including CD44, FAS, RBM9, hnRNPA/B, APLP2, and MYL6, were detected by the microarray and verified by reverse transcription-PCR. We also compared splicing in these breast cancer cells cultured in either two-dimensional flat dishes or in three-dimensional Matrigel conditions. Only a subset of the splicing differences that distinguish MCF7 cells from MDA-MB-231 cells under two-dimensional culture condition is retained under three-dimensional conditions, suggesting that alternative splicing events are influenced by the geometry of the culture conditions of these cells. Further characterization of splicing patterns of several genes in MCF7 cells grown in Matrigel and in xenograft in nude mice shows that splicing is similar under both conditions. Thus, our oligonucleotide microarray can effectively detect changes in alternative splicing in different cells or in the same cells grown in different environments. Our findings also illustrate the potential for understanding gene expression with resolution of alternative splicing in the study of breast cancer.
Endocrine assessment of impotence—pitfalls of measuring serum testosterone without sex-hormone-binding globulin (1994)

The pitfalls of measuring only total serum testosterone are illustrated by a 52 year old man whose hyperprolactinaemia was associated with normal total serum testosterone but a raised sex-hormone-binding globulin, giving a low free testosterone. Prolactin suppression with bromocriptine normalized sex-hormone-binding globulin and free testosterone, and restored potency and energy after 30 years of impotence and tiredness.
An MRI study of the differences in the rate of thrombolysis between red blood cell‐rich and platelet‐rich components of venous thrombi ex vivo (2011)

Venous thrombi are most often composed of interspersed platelet-rich and RBC-rich regions. T(1) -weighted MRI is capable of noninvasive discrimination between those two components of venous thrombi ex vivo which have a different susceptibility to thrombolysis by rt-PA.
A solution of the mask overlay problem in microelectromechanical CAD (MEMCAD) (1992)

The authors present a computationally efficient algorithm for the processing of data from multiple multi-featured masks to produce a planar map of the device topography in a format compatible with mechanical CAD systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reversal of Experimental Parkinsonism by Lesions of the Subthalamic Nucleus (1990)

Although it is known that Parkinson's disease results from a loss of dopaminergic neurons in the substantia nigra, the resulting alterations in activity in the basal ganglia responsible for parkinsonian motor deficits are still poorly characterized. Recently, increased activity in the subthalamic nucleus has been implicated in the motor abnormalities. To test this hypothesis, the effects of lesions of the subthalamic nucleus were evaluated in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor. This result supports the postulated role of excessive activity in the subthalamic nucleus in Parkinson's disease.
Security Services Using Crowdsourcing (2014)

Abstract Security-as-a-service is an emerging area in cloud computing. Traditionally, security approaches are service provider-centric and provider-driven. In this paper, we propose a model for security-as-a-service using “crowdsourcing”. Though crowdsourcing has been used to provide specific security services like browser security, detecting phishing attacks, detecting cybersecurity threats, there has been no work which provides a unified framework to provide different types of security verification. Dispersed computing power of devices is used to perform security verifications. This is done by subscribers in a collaborative way, using their idle resources, in exchange of certain incentives. Our architecture guarantees anonymity of users who request service and the crowd who contribute in verification by using virtualization concepts and virtual machines. Moreover, we propose an approach for managing these security verification jobs, subscribers in a fault tolerant manner. To the best of our knowledge, we are the first to propose a unified security-as-a-service framework using crowdsourcing, thus introducing a new research problem. We discuss a number of applications, challenges and problems of crowdsourcing in security verification.
ZW10 links mitotic checkpoint signaling to the structural kinetochore (2005)

The mitotic checkpoint ensures that chromosomes are divided equally between daughter cells and is a primary mechanism preventing the chromosome instability often seen in aneuploid human tumors. ZW10 and Rod play an essential role in this checkpoint. We show that in mitotic human cells ZW10 resides in a complex with Rod and Zwilch, whereas another ZW10 partner, Zwint-1, is part of a separate complex of structural kinetochore components including Mis12 and Ndc80-Hec1. Zwint-1 is critical for recruiting ZW10 to unattached kinetochores. Depletion from human cells or Xenopus egg extracts is used to demonstrate that the ZW10 complex is essential for stable binding of a Mad1-Mad2 complex to unattached kinetochores. Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor.