gebhart/patrepeval huggingface dataset:
Evaluation of a dual bias dual metal oxide‐silicon semiconductor field effect transistor detector as radiation dosimeter (1994)

A new type of direct reading semiconductor dosimeter has been investigated as a radiation detector for photon and electron therapy beams of various energies. The operation of this device is based on the measurement of the threshold voltage shift in a custom-built metal oxide-silicon semiconductor field effect transistor (MOSFET). This voltage is a linear function of absorbed dose. The extent of the linearity region is dependent on the voltage controlled operation during irradiation. Operating two MOSFETS at two different biases simultaneously during irradiation will result in sensitivity (V/Gy) reproducibility better than +/- 3% over a range in dose of 100 Gy and at a dose per fraction greater than 20 x 10(-2) Gy. The modes of operation give this device many advantages, such as continuous monitoring during irradiation, immediate reading, and permanent storage of total dose after irradiation. The availability and ease of use of these MOSFET detectors make them very promising in clinical dosimetry.
Discovery of Potent and Selective Agonists for the Free Fatty Acid Receptor 1 (FFA1/GPR40), a Potential Target for the Treatment of Type II Diabetes (2008)

A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC(50) = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) in metabolic diseases such as diabetes or obesity.
Efficient Preparation of Site-Specific Antibody–Drug Conjugates Using Cysteine Insertion (2017)

Antibody-drug conjugates (ADCs) are a class of biopharmaceuticals that combine the specificity of antibodies with the high-potency of cytotoxic drugs. Engineering cysteine residues in the antibodies using mutagenesis is a common method to prepare site-specific ADCs. With this approach, solvent accessible amino acids in the antibody have been selected for substitution with cysteine for conjugating maleimide-bearing cytotoxic drugs, resulting in homogeneous and stable site-specific ADCs. Here we describe a cysteine engineering approach based on the insertion of cysteines before and after selected sites in the antibody, which can be used for site-specific preparation of ADCs. Cysteine-inserted antibodies have expression level and monomeric content similar to the native antibodies. Conjugation to a pyrrolobenzodiazepine dimer (SG3249) resulted in comparable efficiency of site-specific conjugation between cysteine-inserted and cysteine-substituted antibodies. Cysteine-inserted ADCs were shown to have biophysical properties, FcRn, and antigen binding affinity similar to the cysteine-substituted ADCs. These ADCs were comparable for serum stability to the ADCs prepared using cysteine-mutagenesis and had selective and potent cytotoxicity against human prostate cancer cells. Two of the cysteine-inserted variants abolish binding of the resulting ADCs to FcγRs in vitro, thereby potentially preventing non-target mediated uptake of the ADCs by cells of the innate immune system that express FcγRs, which may result in mitigating off-target toxicities. A selected cysteine-inserted ADC demonstrated potent dose-dependent anti-tumor activity in a xenograph tumor mouse model of human breast adenocarcinoma expressing the oncofetal antigen 5T4.
Atom Transfer Radical Polymerization of 4-Vinylpyridine (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTAtom Transfer Radical Polymerization of 4-VinylpyridineJianhui Xia, Xuan Zhang, and Krzysztof MatyjaszewskiView Author Information Center for Macromolecular Engineering, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213 Cite this: Macromolecules 1999, 32, 10, 3531–3533Publication Date (Web):April 22, 1999Publication History Received29 October 1998Revised23 March 1999Published online22 April 1999Published inissue 1 May 1999https://pubs.acs.org/doi/10.1021/ma9816968https://doi.org/10.1021/ma9816968rapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views5006Altmetric-Citations205LEARN 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:Catalysts,Monomers,Physical and chemical properties,Polymerization,Radical polymerization Get e-Alerts
Analysis of the PLL Jitter Due to Power/Ground and Substrate Noise (2004)

Phase-locked loops (PLL) in radio-frequency (RF) and mixed analog-digital integrated circuits (ICs) experience substrate coupling due to the simultaneous circuit switching and power/ground (P/G) noise which translate to a timing jitter. In this paper. an analysis of the PLL timing jitter due to substrate noise resulting from P/G noise and large-signal switching is presented. A general comprehensive stochastic model of the substrate and P/G noise sources in very large-scale integration (VLSI) circuits is proposed. This is followed by calculation of the phase noise of the constituent voltage-controlled oscillator (VCO) in terms of the statistical properties of substrate and P/G noise. The PLL timing jitter is then predicted in response to the VCO phase noise. Our mathematical method is utilized to study the jitter-induced P/G noise in a CMOS PLL, which is designed and simulated in a 0.25-/spl mu/m standard CMOS process. A comparison between the results obtained by our mathematical model and those obtained by HSPICE simulation prove the accuracy of the predicted model.
Mouse model of arterial injury. (1993)

In the present study, we established an injury model of the mouse carotid artery. Complete removal of the endothelium was achieved with a flexible wire. A platelet monolayer covered the denuded surface, and damage to underlying medial smooth muscle cells (SMCs) was detected. Injection of [3H]thymidine was used to determine the replication index for medial SMCs, which was found to be 1.6% at 2 days after denudation and 9.8% at 5 days. SMCs were observed in the intima by day 8 (replication index, 66%), and by 2 weeks the intimal lesion had a similar cell content as the media. In most animals, repair of the endothelial lining was complete 3 weeks after injury. The present model will allow us to use transgenic animals to address questions relevant to vascular biology and atherosclerosis.
Design and Implementation of a Hybrid Equipment Data Acquisition System(HEDAS) for Equipment Engineering System(EES) Framework (2012)

본 논문은 장비엔지니어링 시스템(EES) 프레임워크에서 반도체와 광전자 제조장비를 위한 새로운 하이브리드 생산설비데이터 습득 시스템을 설계하고 구현한다. 장비엔지니어링 분야에서 장비로부터 수집되는 데이터 량이 급격히 증가하고 있다. 제안된 HEDAS(Hybrid Equipment Data Acquisition System)는 EES 프레임워크에서 발생하는 대용량의 실시간 데이터를 효율적으로 처리한다. 또한, 제안된 시스템은 실시간 EES 응용 뿐만 아니라 비실시간 EES 응용을 지원할 수 있다. 실시간 EES 응용을 위해서 HEDAS는 메모리 기반의 연속질의와 필터링 기술을 이용하여 고속의 실시간 처리를 수행한다. HEADS는 비 실시간 장비 데이터를 HEADS 기반의 데이터베이스 또는 기존의 데이터베이스에 선택적으로 저장할 수 있다. 특히, 급격하게 증가하는 장비 데이터에 대해 디스크 저장 비용을 절감하기 위해 타임스템프 기반의 압축 인덱싱과 질의처리 기법을 제공한다. HEDAS는 EES 프레임워크에서 대용량의 실시간 및 비 실시간 장비 데이터를 수집하여 다양한 EES 응용에 수집된 데이터를 전송할 수 있는 효율적인 시스템이다. In this paper we design and implement a new Hybrid Equipment Data Acquisition System (HEDAS) for data collection of semiconductor and optoelectronic manufacturing equipments in the equipment engineering system(EES) framework. The amount of the data collected from equipments have increased rapidly in equipment engineering system. The proposed HEDAS efficiently handles a large amount of real-time equipment data generated from EES framework. It also can support the real-time ESS applications as well as non real-time ESS applications. For the real-time EES applications, it performs high-speed real-time processing that uses continuous query and filtering techniques based on memory buffers. The HEDAS can optionally store non real-time equipment data using a HEDAS-based database or a traditional DBMS-based database. In particular, The proposed HEDAS offers the compression indexing based on the timestamp of data and query processing technique saving the cost of disks storage against extremely increasing equipment data. The HEDAS is efficient system to collect huge real-time and non real-time equipment data and transmit the collected equipment data to several EES applications in EES framework.
Development of a Fluorescent-Tagged Kinase Assay System for the Detection and Characterization of Allosteric Kinase Inhibitors (2009)

Kinase disregulation disrupts the intricate network of intracellular signaling pathways and contributes to the onset of diseases such as cancer. Although several kinase inhibitors are on the market, inhibitor selectivity and drug resistance mutations persist as fundamental challenges in the development of effective long-term treatments. Chemical entities binding to less conserved allosteric sites would be expected to offer new opportunities for scaffold development. Because no high-throughput method was previously available, we developed a fluorescence-based kinase binding assay for identifying and characterizing ligands which stabilize the inactive kinase conformation. Here, we present a description of the development and validation of this assay using the serine/threonine kinase p38alpha. By covalently attaching fluorophores to the activation loop of the kinase, we were able to detect conformational changes and measure the K(d), k(on), and k(off) associated with the binding and dissociation of ligands to the allosteric pocket. We report the SAR of a synthesized focused library of pyrazolourea derivatives, a scaffold known to bind with high affinity to the allosteric pocket of p38alpha. Additionally, we used protein X-ray crystallography together with our assay to examine the binding and dissociation kinetics to characterize potent quinazoline- and quinoline-based type II inhibitors, which also utilize this binding pocket in p38alpha. Last, we identified the b-Raf inhibitor sorafenib as a potent low nanomolar inhibitor of p38alpha and used protein X-ray crystallography to confirm a unique binding mode to the inactive kinase conformation.
CXCR4 and CXCL12 (SDF-1) in Prostate Cancer (2004)

Ab124 and Ab125 inhibit CXCL12-mediated cellular activities by binding the receptor CXCR4. Recombinant scFv are an efficient mode of targeting tumor antigens. Considering the high incidence of PCa, the development of fully human scFv may be a useful therapeutic approach in the prevention and treatment of PCa metastasis.
Association of thrombin-antithrombin III complex with vitronectin in serum. (1985)

Purification of vitronectin by identical procedures from serum instead of plasma results in the coisolation of an additional protein component with mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of 82 kDa. We show that this component is the thrombin-antithrombin III complex based on the following evidence. Similar to a complex constructed using purified thrombin and antithrombin III, the 82-kDa component has a reduced molecular size of 69 kDa if it is not boiled prior to SDS-PAGE. Upon prolonged boiling in SDS it dissociates into 56- and 32-kDa components which co-migrate in SDS-PAGE with purified antithrombin III and thrombin, respectively. The 82- and 56-kDa components react with an antiserum against antithrombin III, and an antiserum prepared against the 82-kDa complex reacts with purified antithrombin III. Thrombin-antithrombin III complex, from either serum or recalcified clotted plasma, bound to vitronectin immobilized on Sepharose or plastic. However, purified antithrombin III which had not reacted with thrombin lacked affinity for vitronectin as did antithrombin III from citrated plasma. Purified antithrombin III acquired affinity for immobilized vitronectin if it was complexed with thrombin or was modified by radioiodination. Binding of vitronectin to antithrombin III coated on plastic was demonstrated using enzyme-linked immunosorbent assay. These results demonstrate that vitronectin binds thrombin-antithrombin III complexes through a cryptic site in antithrombin III which can be exposed when antithrombin III is radioiodinated, bound to plastic, or complexed with thrombin. Since vitronectin can interact with cells, the binding of vitronectin to the thrombin-antithrombin III complex may serve to facilitate the interaction of this complex with cell surfaces.
Geno2pheno: estimating phenotypic drug resistance from HIV-1 genotypes (2003)

Therapeutic success of anti-HIV therapies is limited by the development of drug resistant viruses. These genetic variants display complex mutational patterns in their pol gene, which codes for protease and reverse transcriptase, the molecular targets of current antiretroviral therapy. Genotypic resistance testing depends on the ability to interpret such sequence data, whereas phenotypic resistance testing directly measures relative in vitro susceptibility to a drug. From a set of 650 matched genotype-phenotype pairs we construct regression models for the prediction of phenotypic drug resistance from genotypes. Since the range of resistance factors varies considerably between different drugs, two scoring functions are derived from different sets of predicted phenotypes. Firstly, we compare predicted values to those of samples derived from 178 treatment-naive patients and report the relative deviance. Secondly, estimation of the probability density of 2000 predicted phenotypes gives rise to an intrinsic definition of a susceptible and a resistant subpopulation. Thus, for a predicted phenotype, we calculate the probability of membership in the resistant subpopulation. Both scores provide standardized measures of resistance that can be calculated from the genotype and are comparable between drugs. The geno2pheno system makes these genotype interpretations available via the Internet (http://www.genafor.org/).
Bryostatin-1 Synergizes with Histone Deacetylase Inhibitors to Reactivate HIV-1 from Latency (2010)

The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication on patients treated with HAART. It has been suggested that successful depletion of such latent reservoirs will require a combination of therapeutic agents that can specifically and efficiently act on cells harboring latent HIV-1 provirus. Using Jurkat-LAT-GFP cells, a tractable model of HIV-1 latency, we have found that bryostatin -1 reactivates HIV-1 through a classical PKC-dependent pathway. Bryostatin-1 also activates MAPKs and NF-κB pathways and synergizes with HDAC inhibitors to reactivate HIV-1 from latency. Bryostatin-1 downregulates the expression of the HIV-1 co-receptors CD4 and CXCR4 and prevented de novo HIV-1 infection in susceptible cells. We applied proteomic methods to investigate major changes in protein expression in Jurkat-LAT-GFP under latency and reactivation conditions. We identified up-regulation of proteins that may be involved in the innate anti-HIV-1 response (NKEF-A and MHD2) and in different cell functions (i.e. cofilin-1 and transgelin-2) of the host cells. PKC agonists may represent a valuable pharmacological approach to purge latent HIV from cellular reservoirs and at the moment, the only clinically available PKC agonist is bryostatin-1. This drug has been tested in numerous clinical trials and its pharmacokinetics and toxicity in humans is well known. Moreover, bryostatin-1 potently synergizes with other HDAC inhibitors commonly used in the medical practice such as valproic acid. Therefore, bryostatin-1, alone or in combination with HDAC inhibitors, could be used in HAART treated patients to validate the hypothesis that reactivating HIV-1 from latency could purge HIV-1 reservoirs.
Prostaglandin E2 and Tumor Necrosis Factor α Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production (1997)

Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investigated the effects of PGE2 on human dendritic cells (DCs) which develop in the presence of GM-CSF and IL-4. We demonstrate that in the absence of LPS, PGE2 dose dependently stimulated the production of IL-12 by DCs. Although PGE2 alone stimulated the production of low amounts of IL-12 only, it synergized with tumor necrosis factor (TNF)-alpha to induce high levels of IL-12 production by DCs. Addition of TNF-alpha in the absence of PGE2 had no effect on IL-12 production. Conversely, in the presence of LPS, PGE2 inhibited IL-12 production by DCs in a dose-dependent manner. The combination of PGE2 and TNF-alpha efficiently silenced mannose receptor-mediated endocytosis in DCs and readily induced neo-expression of the CD83 antigen. In addition, the expression of various surface antigens such as major histocompatibility complex class I and II, adhesion, as well as costimulatory molecules was upregulated by this treatment. The effects of PGE2 on IL-12 synthesis and CD83 expression could be mimicked by dibutyryl-cAMP and forskolin, indicating that they were due to the intracellular elevation of cAMP levels. DC treated with PGE2 and TNF-alpha were most potent in stimulating allogeneic T cell proliferation. Our data demonstrate that PGE2 contributes to the maturation of human DCs and that PGE2 can be a potent enhancer of IL-12 production by human DCs.
A photoemission study of passivated silicon surfaces produced by etching in solutions of HF (1989)

Hydrogen-terminated silicon surfaces produced by etching in solutions of HF have been studied using photoelectron spectroscopy and LEED. They have been found to be remarkably free from contamination, locally ordered and electrically passivated. The hydrogen may be removed from the (100) surface by annealing in UHV at (520+or-10) degrees C. At that temperature, the initial (1*1) structure of the surface changes to a two domain (2*1) reconstruction and the Fermi level becomes pinned by surface states. The relationship between residual contamination and etching parameters such as time, concentration and crystallographic orientation of the sample has been examined, together with the degradation of the hydride surface with exposure to various environments. This has shown that the contamination levels of the surface are sensitive to etching procedure, but with suitable care, a 5% non-aqueous HF solution provides the optimum etch.
Mitochondria and cell death (2000)

Mitochondria play a central role in both apoptosis and necrosis through the opening of the mitochondrial permeability transition pore (MPTP). This is thought to be formed through a Ca(2+)-triggered conformational change of the adenine nucleotide translocase (ANT) bound to matrix cyclophilin-D and we have now demonstrated this directly by reconstitution of the pure components. Opening of the MPTP causes swelling and uncoupling of mitochondria which, unrestrained, leads to necrosis. In ischaemia/reperfusion injury of the heart we have shown MPTP opening directly. Recovery of hearts correlates with subsequent closure, and agents that prevent opening or enhance closure protect from injury. Transient MPTP opening may also be involved in apoptosis by initially causing swelling and rupture of the outer membrane to release cytochrome c (cyt c), which then activates the caspase cascade and sets apoptosis in motion. Subsequent MPTP closure allows ATP levels to be maintained, ensuring that cell death remains apoptotic rather than necrotic. Apoptosis in the hippocampus that occurs after a hypoglycaemic or ischaemic insult is triggered by this means. Other apoptotic stimuli such as cytokines or removal of growth factors also involve mitochondrial cyt c release, but here there is controversy over whether the MPTP is involved. In many cases cyt c release is seen without any mitochondrial depolarization, suggesting that the MPTP does not open. Recent data of our own and others have revealed a specific outer-membrane cyt c-release pathway involving porin that does not release other intermembrane proteins such as adenylate kinase. This is opened by pro-apoptotic members of the Bcl-2 family such as BAX and prevented by anti-apoptotic members such as Bcl-X(L). Our own data suggest that this pathway may interact directly with the ANT in the inner membrane at contact sites.
Laterally coupled solidly mounted BAW resonators at 1.9 GHz (2009)

Laterally coupled bulk acoustic wave resonators fabricated onto an acoustic mirror are studied. The acoustic mirror comprises two W-SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> pairs. Thin-film AlN is used as the piezoelectric material with a Mo bottom electrode and an Al top electrode. Structures consist of laterally acoustically coupled electrodes 2.5 ¿m wide and 300 ¿m long, with gaps of 4 ¿m in-between. Acoustical coupling between the electrodes results in two resonances forming an electrical bandpass response at 1.9 GHz. A device with two coupled electrodes features a 1.5% relative to center frequency bandwidth, 10 dB insertion loss in 50-¿ environment and 3.9 dB insertion loss after matching. Electrical frequency responses are presented and compared to simulations. Mechanical vibration fields in the devices are studied with a laser interferometer.
Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate (2017)

Antibody drug conjugates (ADCs) are no longer an unknown entity in the field of cancer therapy with the success of marketed ADCs like ADCETRIS and KADCYLA and numerous others advancing through clinical trials. The pursuit of novel cytotoxic payloads beyond the mictotubule inhibitors and DNA damaging agents has led us to the recent discovery of an mRNA splicing inhibitor, thailanstatin, as a potent ADC payload. In our previous work, we observed that the potency of this payload was uniquely tied to the method of conjugation, with lysine conjugates showing much superior potency as compared to cysteine conjugates. However, the ADC field is rapidly shifting towards site-specific ADCs due to their advantages in manufacturability, characterization and safety. In this work we report the identification of a highly efficacious site-specific thailanstatin ADC. The site of conjugation played a critical role on both the in vitro and in vivo potency of these ADCs. During the course of this study, we developed a novel methodology of loading a single site with multiple payloads using an in situ generated multi-drug carrying peptidic linker that allowed us to rapidly screen for optimal conjugation sites. Using this methodology, we were able to identify a double-cysteine mutant ADC delivering four-loaded thailanstatin that was very efficacious in a gastric cancer xenograft model at 3mg/kg and was also shown to be efficacious against T-DM1 resistant and MDR1 overexpressing tumor cell lines.