gebhart/patrepeval huggingface dataset:
Phase I study of nivolumab combined with IFN-β for patients with advanced melanoma (2017)

The efficacy of nivolumab is greater than that of other anti-melanoma drugs, so nivolumab-based combined therapies that enhance anti-tumor immune responses in patients with metastatic melanoma are of great interest to dermato-oncologists. As we have previously reported, IFN-β enhances the anti-tumor immune response of anti-PD-1 antibodies against B16F10 melanoma <i>in vivo</i>. To explore the potential of this property of IFN-β as part of a combination therapy for the treatment of metastatic melanoma patients, we performed a phase 1 trial, using a traditional rule-based 3 + 3 design, on patients with advanced melanoma. The nivolumab dose was fixed at 2 mg/kg, every 3 weeks. IFN-β was administered to three groups at doses of 1 million, 2 million, and 3 million units, respectively. Dose-limiting toxicities were defined as any grade 3-5 adverse events occurring between day 0 and day 42 that might possibly be related to nivolumab and IFN-β. Of the nine patients who received this combined therapy, none experienced dose-limiting toxicities, and all completed the treatment phase of the study. Patient follow-up continued for 6 months following the final treatment. There were two complete responses (22%) and one partial response (11%), all of which occurred in patients who had received monthly IFN-β immediately prior to the study. In this study, we determined the safe dose of IFN-β, when combined with nivolumab, to be 3 million units. To determine the efficacy of this combination therapy, further phase II trials are required.
Unfolding Pathways of Individual Bacteriorhodopsins (2000)

Atomic force microscopy and single-molecule force spectroscopy were combined to image and manipulate purple membrane patches from Halobacterium salinarum. Individual bacteriorhodopsin molecules were first localized and then extracted from the membrane; the remaining vacancies were imaged again. Anchoring forces between 100 and 200 piconewtons for the different helices were found. Upon extraction, the helices were found to unfold. The force spectra revealed the individuality of the unfolding pathways. Helices G and F as well as helices E and D always unfolded pairwise, whereas helices B and C occasionally unfolded one after the other. Experiments with cleaved loops revealed the origin of the individuality: stabilization of helix B by neighboring helices.
Simultaneous Transmission/Emission Myocardial Perfusion Tomography (1996)

TCT/ECT myocardial perfusion imaging significantly improves the diagnostic accuracy of cardiac SPECT for the detection and localization of CHD. Clinical use of TCT/ECT imaging deserves serious consideration.
TQM in Continuous‐process Manufacturing: Dow‐Corning (Australia) Pty Ltd (1991)

The implementation of Total Quality Management (TQM) principles and practices in continuous‐process manufacturing operations is described from initial consideration through to TQM becoming part of the normal operations of the company. The importance of management‐led project teams in the early phases of implementation and the subsequent shift to operator‐initiated and ‐controlled quality improvements is detailed. Accreditation to international quality system standards (ISO 9002) and the interaction of such accreditation with the cultural change required for successful TQM implementation is discussed. Problems confronting effective TQM implementation or quality‐system accreditation are discussed such as: relationships between the multinational parent company and the domestic subsidiary, and the geographical separation of sections of the company between head offices and manufacturing site. A detailed examination is made of the organisational structure utilised to develop a TQM culture within the company, and the dynamic nature of such an organisational structure in the early phases of implementation is observed. The major requirement for increasing employee involvement in quality‐improvement activities is found to be an increasing commitment to employee training in the areas of: TQM principles; statistical tools; group problem‐solving skills; and leadership skills.
Retinoic Acid Stimulates Chondrocyte Differentiation and Enhances Bone Morphogenetic Protein Effects through Induction of Smad1 and Smad5 (2003)

Whereas bone morphogenetic protein (BMP)-signaling events induce maturational characteristics in vitro, recent evidence suggests that the effects of other regulators might be mediated through BMP-signaling events. The present study examines the mechanism through which retinoic acid (RA) stimulates differentiation in chicken embryonic caudal sternal chondrocyte cultures. Both RA and BMP-2 induced expression of the chondrocyte maturational marker, colX, in chondrocyte cultures by 8 d. Though the RA effect was small, it synergistically enhanced the effect of BMP-2 on colX and phosphatase activity. Inhibition of either RA or BMP signaling, with selective inhibitors, interfered with the inductive effects of these agents but also inhibited the complementary pathway, demonstrating a codependence of RA and BMP signaling during chondrocyte maturation. BMP-2 did not enhance the effects of RA on an RA-responsive reporter construct, but RA enhanced basal activity and synergistically enhanced BMP-2 stimulation of the BMP-responsive chicken type X collagen reporter. A similar synergistic interaction between RA and BMP-2 was observed on colX expression. RA did not increase the expression of the type IA BMP receptor but did markedly up-regulate the expression of Smad1 and Smad5 proteins, important participants in the BMP pathway. Inhibition of RA signaling, with the selective inhibitor AGN 193109, blocked RA-mediated induction of the Smad proteins and chondrocyte differentiation. These findings demonstrate that RA induces the expression of BMP-signaling molecules and enhances BMP effects in chondrocytes.
Immunization against endogenous retroviral tumor-associated antigens. (2001)

Endogenous retroviral gene products have been found in some human tumors, and therefore, may serve as antigens for immunotherapy approaches. The murine colorectal carcinoma CT26 and melanoma B16 have recently been found to express the endogenous retroviral gene products gp70 and p15E, respectively, that can serve as antigens recognized by T cells. To date, though, there has been no demonstration of tumor treatment using an endogenous retroviral protein. In this study, we demonstrate that mice immunized with recombinant vaccinia encoding the gp70 H2-L(d)-restricted minimal determinant were protected from CT26 tumor challenge. Splenocytes from mice immunized with vaccinia gp70 specifically secreted IFN-gamma in response to gp70 peptide-pulsed stimulators. Although this strategy could protect against subsequent tumor challenge, it was ineffective against established tumors. Therefore, to investigate the treatment of established CT26 or B16 lung metastases, mice were treated with cultured dendritic cells (DCs) pulsed with gp70 or p15E peptide. Significant inhibition of established lung metastases required immunization with peptide-pulsed DCs pretreated with CD40 ligand that has been demonstrated to increase the T-cell stimulatory activity of DCs. The ability to immunize against endogenous retroviral tumor antigens may have relevance in the induction of antitumor immunity for some human cancers.
Injection-level dependent surface recombination velocities at the silicon-plasma silicon nitride interface (1995)

Experimental evidence is presented that the effective surface recombination velocity (Seff) at p-silicon surfaces passivated by silicon nitride films (fabricated in a plasma-enhanced chemical vapor deposition system) shows an injection-level dependence similar to the behavior of thermally oxidized silicon surfaces. Using the microwave-detected photoconductance decay method, injection-level dependent Seff measurements were taken on nitride-passivated p-silicon wafers of different resistivities (1.5–3000 Ω cm). The obtained Seff values also show that for low-resistivity substrates (≤2 Ω cm), nitride passivation is as effective as conventional oxide passivation (and even superior at low injection levels) and furthermore offers the advantage of a less pronounced injection-level dependence.
Reduction of isopropylidene acylmalonates, 5-acylbarbituric acids, and 3-acyl-4-hydroxycoumarins to the corresponding alkyl derivatives by sodium cyanoborohydride-acetic acid (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of isopropylidene acylmalonates, 5-acylbarbituric acids, and 3-acyl-4-hydroxycoumarins to the corresponding alkyl derivatives by sodium cyanoborohydride-acetic acidCharles F. Nutaitis, Rose Ann Schultz, Judy Obaza, and Francis X. SmithCite this: J. Org. Chem. 1980, 45, 23, 4606–4608Publication Date (Print):November 1, 1980Publication History Published online1 May 2002Published inissue 1 November 1980https://pubs.acs.org/doi/10.1021/jo01311a011https://doi.org/10.1021/jo01311a011research-articleACS PublicationsRequest reuse permissionsArticle Views837Altmetric-Citations33LEARN 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 Get e-Alerts
Gaze-enhanced scrolling techniques (2007)

Scrolling is an essential part of our everyday computing experience. Contemporary scrolling techniques rely on the explicit initiation of scrolling by the user. The act of scrolling is tightly coupled with the user?s ability to absorb information via the visual channel. The use of eye gaze information is therefore a natural choice for enhancing scrolling techniques. We present several gaze-enhanced scrolling techniques for manual and automatic scrolling which use gaze information as a primary input or as an augmented input. We also introduce the use off-screen gaze-actuated buttons for document navigation and control.
Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes (2001)

The study of human cardiac tissue development is hampered by the lack of a suitable in vitro model. We describe the phenotypic properties of cardiomyocytes derived from human embryonic stem (ES) cells. Human ES cells were cultivated in suspension and plated to form aggregates termed embryoid bodies (EBs). Spontaneously contracting areas appeared in 8.1% of the EBs. Cells from the spontaneously contracting areas within EBs were stained positively with anti-cardiac myosin heavy chain, anti--alpha-actinin, anti-desmin, anti--cardiac troponin I (anti-cTnI), and anti-ANP antibodies. Electron microscopy revealed varying degrees of myofibrillar organization, consistent with early-stage cardiomyocytes. RT-PCR studies demonstrated the expression of several cardiac-specific genes and transcription factors. Extracellular electrograms were characterized by a sharp component lasting 30 +/- 25 milliseconds, followed by a slow component of 347 +/- 120 milliseconds. Intracellular Ca(2+) transients displayed a sharp rise lasting 130 +/- 27 milliseconds and a relaxation component lasting 200--300 milliseconds. Positive and negative chronotropic effects were induced by application of isoproterenol and carbamylcholine, respectively. In conclusion, the human ES cell--derived cardiomyocytes displayed structural and functional properties of early-stage cardiomyocytes. Establishment of this unique differentiation system may have significant impact on the study of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering.
CD134/CD137 dual costimulation‐elicited IFN‐γ maximizes effector T‐cell function but limits Treg expansion (2013)

T-cell tolerance to tumor antigens represents a major hurdle in generating tumor immunity. Combined administration of agonistic monoclonal antibodies (mAbs) to the costimulatory receptors CD134 plus CD137 can program T-cells responding to tolerogenic antigen to undergo expansion, and effector T-cell differentiation, and also elicits tumor immunity. Nevertheless, CD134 and CD137 agonists can also engage inhibitory immune components. To understand how immune stimulatory versus inhibitory components are regulated during CD134 plus CD137 dual costimulation (DCo), the current study utilized a model where DCo programs T-cells encountering a highly tolerogenic self-antigen to undergo effector differentiation. IFN-γ was found to have a pivotal role in maximizing the function of effector T-cells, while simultaneously limiting the expansion of CD4(+)CD25(+)Foxp3(+) Tregs. In antigen-responding effector T-cells, IFN-γ operates via a direct cell-intrinsic mechanism to cooperate with IL-2 to program maximal expression of granzyme B. Simultaneously, IFN-γ limits expression of the IL-2 receptor alpha chain (CD25) and IL-2 signaling through a mechanism that does not involve T-bet-mediated repression of IL-2. IFN-γ also limited CD25 and Foxp3 expression on bystanding CD4(+)Foxp3(+) Tregs, and limited the potential of these Tregs to expand. These effects could not be explained by the ability of IFN-γ to limit IL-2 availability. Taken together, during DCo IFN-γ interacts with IL-2 through distinct mechanisms to program maximal expression of effector molecules in antigen-responding T-cells, while simultaneously limiting Treg expansion.
Fatty Acid-Derived Diisocyanate and Biobased Polyurethane Produced from Vegetable Oil: Synthesis, Polymerization, and Characterization (2009)

A new linear saturated terminal diisocyanate was synthesized from oleic acid via Curtius rearrangement, and its chemical structure was identified by FTIR, (1)H and (13)C NMR, and MS. The feasibility of utilizing this new diisocyanate for the production of polyurethanes (PUs) was demonstrated by reacting it with commercial petroleum-derived polyols and canola oil-derived polyols, respectively. The physical properties of the PUs prepared from fatty acid-derived diisocyanate were compared to those prepared from the same polyols with a similar but petroleum-derived commercially available diisocyanate: 1,6-hexamethylene diisocyanate. It was found that the fatty acid-derived diisocyanate was capable of producing PUs with comparable properties within acceptable tolerances. This work is the first that establishes the production of linear saturated terminal diisocyanate derived from fatty acids and corresponding PUs mostly from lipid feedstock.
HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. (1997)

FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification in the absence of adjuvant therapy is an independent predictor of poor clinical outcome and is a stronger discriminant than tumor size. Women with small tumors that had gene amplification were at increased risk of recurrence and disease-related death.
C++ based System Synthesis of Real-Time Video Processing Systems targeting FPGA Implementation (2007)

Implementing real-time video processing systems put high requirements on computation and memory performance. FPGAs have proven to be effective implementation architecture for these systems. However, the hardware based design flow for FPGAs make the implementation task complex. The system synthesis tool presented in this paper reduces this design complexity. The synthesis is done from a SystemC based coarse grain dataflow graph that captures the video processing system. The data flow graph is optimized and mapped onto an FPGA. The results from real-life video processing systems clearly show that the presented tool produces effective implementations.
Continual electric field stimulation preserves contractile function of adult ventricular myocytes in primary culture (1994)

To model with greater fidelity the electromechanical function of freshly isolated heart muscle cells in primary culture, we describe a technique for the continual electrical stimulation of adult myocytes at physiological frequencies for several days. A reusable plastic cover was constructed to fit standard, disposable 175-cm2 tissue culture flasks and to hold parallel graphite electrodes along the long axis of each flask, which treated a uniform electric field that resulted in a capture efficiency of ventricular myocytes of 75-80%. Computer-controlled amplifiers were designed to be capable of driving a number of flasks concurrently, each containing up to 4 x 10(6) myocytes, over a range of stimulation frequencies (from 0.1 to 7.0 Hz) with reversal of electrode polarity after each stimulus to prevent the development of pH gradients around each electrode. Unlike quiescent, unstimulated myocytes, the amplitude of contraction, and velocities of shortening and relaxation did not change in myocytes paced at 3-5 Hz for up to 72 h. The maintenance of normal contractile function in paced myocytes required mechanical contraction per se, since paced myocytes that remained quiescent due to the inclusion of 2.5 microM verapamil in the culture medium for 48 h also exhibited a decline in contractility when paced after verapamil removal. Similarly, pacing increased peak calcium current compared with quiescent cells that had not been paced. Thus myocyte contraction at physiological frequencies induced by continual uniform electric field stimulation in short-term primary culture in defining medium maintains some biophysical parameters of myocyte phenotype that are similar to those observed in freshly isolated adult ventricular myocytes.
Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis. (1995)

Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. This study demonstrates that purified major extracellular proteins of M. tuberculosis are candidate components of a subunit vaccine against tuberculosis and provides compelling support for the concept that extracellular proteins of intracellular pathogens are key immunoprotective molecules.
논문 : GIS시장과 산업의 실태분석 (2001)

우리나라 GIS시장은 국가GIS구축사업이 시작된 1995년 이후 지난 5년 동안 연평균 40.7%씩 성장해 오고 있다. 이 연구는 이처럼 빠르게 성장하는 GIS시장과 산업에 대한 실태를 조사하고 분석하여 정부의 국가GIS추진전략과 민간기업의 마케팅전략 수립에 필요한 기초자료를 제공하는데 목적을 두고 있다. 실태분석 결과에 따르면, GIS산업은 자본금, 매출액, 고용인력 측면에서 각각 연평균 43.4%, 54.1%, 24.7%씩 성장하고 있다. GIS시장에서 지리공간정보에 대한 수요는 도로망, 도시계획, 지번[주소]좌표, 건물 등의 순서로 높게 나타났다. GIS시장과 산업의 현안과 과제는 규모의 영세성, 구조의 취약성, 지원 법제의 미비 등으로 요약할 수 있다. 2005년까지 GIS시장규모는 2조원에 육박하고, GIS산업인력은 3만 3,800인으로 늘어나며, GIS업체수는 1,140개사로 늘어날 것으로 전망된다.
Daptomycin or teicoplanin in combination with gentamicin for treatment of experimental endocarditis due to a highly glycopeptide-resistant isolate of Enterococcus faecium (1992)

Using an experimental endocarditis model, we studied the activity of daptomycin used alone or in combination with gentamicin against an Enterococcus faecium strain that was highly resistant to glycopeptides and susceptible to gentamicin. In vitro, the MIC of daptomycin was 1 micrograms/ml. In vivo, daptomycin appeared to be effective only when it was used in a high-dose regimen, i.e., 12 mg/kg of body weight every 8 h (-2.5 log10 CFU/g versus controls; P < 0.05), particularly when it was combined with gentamicin (-5.0 log10 CFU/g versus controls; P < 0.01). Since the distribution of daptomycin into cardiac vegetations, as evaluated by autoradiography, appeared to be homogeneous, the poor in vivo activity of daptomycin was considered to be related to its high degree of protein binding, as suggested by killing curves studies. Since the MIC of teicoplanin for the vancomycin-resistant E. faecium strain used in the study was only 64 micrograms/ml and since an in vitro synergy between teicoplanin at high dose and gentamicin was observed, a high-dose regimen of teicoplanin, i.e., 40 mg/kg every 12 h, was also assessed in vivo. This treatment provided marginal activity only when it was combined with gentamicin (-2.3 log10 CFU/g versus controls; P < 0.05). These results suggest that the levels of daptomycin or teicoplanin in serum required to cure experimental endocarditis caused by a highly glycopeptide-resistant strain of E. faecium would not be achievable in humans.
Identification and classification of Oxalobacter formigenes strains by using oligonucleotide probes and primers (1997)

Genomic DNAs of various strains of Oxalobacter formigenes were subjected to restriction endonuclease fragment length polymorphism- and PCR-based amplification analyses with DNA probes and primers complementary to sequences within either the oxc gene, encoding oxalyl coenzyme A (oxalyl-CoA) decarboxylase, or the frc gene, encoding formyl-CoA transferase. Oligonucleotide probes based on nonconserved sequences of oxc or frc were able to divide O. formigenes strains into at least two groups, consistent with the current separation of O. formigenes strains into groups I and II on the basis of 16S rRNA sequence similarities and lipid content. In contrast, an oligonucleotide probe based on the conserved 5' end of oxc appeared to bind all group I and the majority of group II strains. PCR amplification of the oxc gene showed even greater sensitivity in detecting O. formigenes and provided support for further division of the strains into subgroups. In addition, these oligonucleotides failed to hybridize to or amplify PCR products from whole fecal DNA isolated from fresh stool samples from an individual not colonized with O. formigenes, indicating unique specificity. Thus, these DNA analyses permit both detection as well as classification of O. formigenes strains.
Role of miR-10b in breast cancer metastasis (2010)

Ninety percent of cancer-related mortality is caused by metastasis. Current cancer treatments can control many primary tumors but rarely stop the metastatic spread. Accumulating evidence demonstrates that miRNAs are involved in cancer initiation and progression. Furthermore, several miRNAs have been found to regulate metastasis. In particular, recent studies provide the first functional evidence that overexpression of a specific miRNA, miR-10b, can contribute to the development of metastasis, which can be exploited therapeutically in treating breast cancer metastasis in mice. Further in-depth analysis should provide more precise evaluation of the roles, mechanisms, and therapeutic utility of this miRNA in breast cancer.