gebhart/patrepeval huggingface dataset:
Direct detection of nucleic acid hybridization on the surface of a charge coupled device (1994)

A method is described for the detection of DNA hybrids formed on a solid support, based upon the pairing of oligonucleotide chemistry and the technologies of electronic microdevice design. Surface matrices have been created in which oligonucleotide probes are covalently linked to a thin SiO2 film. 32P labeled target nucleic acid is then hybridized to this probe matrix under conditions of high stringency. The salient feature of the method is that to achieve the highest possible collection efficiency, the hybridization matrix is placed directly on the surface of a charge coupled device (CCD), which is used to detect 32P decay from hybridized target molecules (1, Eggers, M.D., Hogan, M.E., Reich, R.K., Lamture, J.B., Beattie, K.L., Hollis, M.A., Ehrilich, D.J., Kosicki, B.B., Shumaker, J.M., Varma, R.S., Burke, B.E., Murphy, A., and Rathman, D.D., (1993), Advances in DNA Sequencing Technology, Proc. SPIE, 1891, 13-26). Two implementations of the technology have been employed. The first involves direct attachment of the matrix to the surface of a CCD. The second involves attachment of the matrix to a disposible SiO2 coated chip, which is then placed face to face upon the CCD surface. As can be predicted from this favorable collection geometry and the known characteristics of a CCD, it is found that as measured by the time required to obtain equivalent signal to noise ratios, 32P detection speed by the direct CCD approach is at least 10 fold greater than can be obtained with a commercial gas phase array detector, and at least 100 fold greater than when X-ray film is used for 32P detection. Thus, it is shown that excellent quality hybridization signals can be obtained from a standard hybridization reaction, after only 1 second of CCD data acquisition.
Real-world outcomes of US employees with type 2 diabetes mellitus treated with insulin glargine or neutral protamine Hagedorn insulin: a comparative retrospective database study (2013)

Insulin GLA results in better persistence and adherence, compared with NPH insulin, with no overall cost disadvantages. Better persistence and adherence may lead to long-term health benefits for employees with T2DM.
Efficacy of Antimicrobial Peptoids against Mycobacterium tuberculosis (2011)

Tuberculosis is a leading cause of death worldwide. Resistance of Mycobacterium to antibiotics can make treatments less effective in some cases. We tested selected oligopeptoids--previously reported as mimics of natural host defense peptides--for activity against Mycobacterium tuberculosis and assessed their cytotoxicity. A tetrameric, alkylated, cationic peptoid (1-C13(4mer)) was most potent against M. tuberculosis and least cytotoxic, whereas an unalkylated analogue, peptoid 1(4mer), was inactive. Peptoid 1-C13(4mer) thus merits further study as a potential antituberculosis drug.
Self-shunted Nb/AlO/sub x//Nb Josephson junctions (1999)

We describe the fabrication and properties of high critical current density (J/sub c/) Nb/AlO/sub x//Nb Josephson junctions with deep-submicron dimensions. The junctions are fabricated using a planarized process in which all levels are patterned using a combination of optical and electron-beam lithography. The base and counter electrodes are defined by reactive ion etching using quartz etch masks to give a minimum feature size of 0.2 microns. For J/sub c/=2.1 mA//spl mu/m/sup 2/ and junction area less than 0.1 /spl mu/m/sup 2/ the devices are self-shunted and exhibit nonhysteretic I-V characteristics. A small hysteresis in the larger junctions is caused by heating in the electrodes.
Raman Chirped Adiabatic Passage: a New Method for Selective Excitation of High Vibrational States (1997)

It is demonstrated that efficient and high vibrational excitation can be achieved using non-resonant stimulated Raman transitions for subsequent step by step climbing of vibrational levels. The pump laser (or both the pump and Stokes laser) frequency are to be swept in such a way that the frequency difference sweeping allows molecular anharmonicities of the final states to be matched. It is shown that amplitudes of successive Raman transitions can be quantitatively described with the help of the effective Raman two-level systems. This selective scheme of vibrational excitation, called Raman chirped adiabatic passage (RCAP), should be useful in controlling excited-state populations and chemical reactions. The limitations of another well known adiabatic scheme of population transfer, stimulated Raman adiabatic passage (STIRAP), are outlined and it is shown that RCAP is a complementary method to STIRAP. RCAP should be useful for selective excitation of highly polarizable symmetric bonds such as metal–metal bonds. © 1997 John Wiley & Sons, Ltd.
Constraint-based hypertext for argumentation (1987)

In this paper we describe a hypertext system we are developing for the support of reasoned argumentation: the EUCLID project. We use the project to address two general problems arising with hypertext: the problems of controlling user/document interaction, and the problem of controlling the screen. We suggest that guiding users' interaction with hypertext is difficult because of the unique form of discourse that hypertext represents, and that structuring user/document interaction can be achieved through specializing to a particular type of material and designing the hypertext system to respect the particular discourse structure characteristic of that material. EUCLID's design is tuned to the structure of reasoned discourse. The problem of screen management in EUCLID is a serious one, because our presentation of complex arguments requires mapping the complex logical relations between parts of realistic arguments onto complex spatial relations between items in the display. We describe a general system we are developing which provides this high degree of control for hypertext screen management. This system represents a constraint-based approach to hypertext, in which the items from the underlying database that are to be displayed may each contribute a number of constraints on the layout; a general constraint-satisfier then computes a screen layout that simultaneously satisfies these constraints. Each time an item is to be added to or deleted from the screen, the constraint set is adjusted and the screen layout is recomputed; thus the spatial relationships on the screen provide at all times a veridical representation of the underlying relations between displayed database items. This kind of strong screen control is demanded by hypertext applications which, like ours, are fine grained: the number of nodes and links being displayed number in the hundreds.
Telomerase-Specific Replication-Selective Virotherapy for Human Cancer (2004)

Our results suggest that the hTERT promoter confers competence for selective replication of TRAD in human cancer cells, an outcome that has important implications for the treatment of human cancers.
Protective effects of tumor necrosis factor on murine hematopoiesis during cycle-specific cytotoxic chemotherapy. (1990)

Tumor necrosis factor (TNF) is a pleiotropic cytokine which exerts a wide range of effects when administered in vivo. Using a murine model, we have investigated the effect of pretreatment with 1 microgram (2.6 x 10(4) units) per mouse of recombinant murine TNF-alpha on hematopoietic recovery following administration of cyclophosphamide, 5-fluorouracil, methotrexate, or vinblastine. TNF pretreatment results in enhanced regeneration of circulating neutrophils and hematopoietic progenitors, as measured by in vivo and in vitro assays, in animals given cycle-specific chemotherapeutic agents. The results may suggest that TNF affects cycle kinetics in hematopoietic progenitor cell populations, thus making these cells less prone to the cytocidal effects of the chemotherapeutic agents. As myeloablation is a frequent and often critical side effect following cancer treatment, these findings may have clinical implications.
Endothelial cell integrin α5β1 expression is modulated by cytokines and during migration in vitro (1999)

Alterations in endothelial cell-extracellular matrix interactions are central to the process of angiogenesis. We have investigated the effect of wound-induced two-dimensional migration, basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGF-beta1) and leukemia inhibitory factor (LIF) on expression of the alpha5beta1 integrin in endothelial cells. In multiple-wounded monolayers of bovine microvascular endothelial (BME) cells, an increase in mRNA and total protein for both alpha5 and beta1 subunits was observed, and this could be correlated with a reduction in cell density but not proliferation, both of which are induced following wounding. Although as previously reported, the alpha5 subunit was increased when cells were exposed to TGF-beta1 alone, co-addition of bFGF and TGF-beta1 resulted in a striking synergistic induction of alpha5, with no significant changes in the expression of beta1. In contrast, the alpha5 subunit was decreased by LIF in bovine aortic endothelial but not in BME cells. These findings suggest that quantitative alterations in alpha5 and beta1 integrin subunit expression modulate the adhesive and migratory properties of endothelial cells during angiogenesis.
Inhibitors of cyclic nucleotide phosphodiesterase isozymes type-III and type-IV suppress mitogenesis of rat mesangial cells. (1995)

We studied interactions between the mitogen-activated protein kinase (MAPK) signalling pathway and cAMP-protein kinase (PKA) signaling pathway in regulation of mitogenesis of mesangial cells (MC) determined by [3H]thymidine incorporation, with or without added EGF. Forskolin or dibutyryl cAMP strongly (by 60-70%) inhibited [3H]thymidine incorporation into MC. Cilostamide, lixazinone or cilostazol selective inhibitors of cAMP-phosphodiesterase (PDE) isozyme PDE-III, inhibited mitogenesis to similar extent as forskolin and DBcAMP and activated in situ PKA, but without detectable increase in cAMP levels. Cilostamide and cilostazol were more than three times more effective at inhibiting mesangial mitogenesis than rolipram and denbufylline, inhibitors of isozyme PDE-IV, even though PDE-IV was two times more abundant in MC than was PDE-III. On the other hand, when incubated with forskolin, rolipram-enhanced cAMP accumulation was far greater (10-100x) than with cilostamide. EGF increased MAPK activity (+300%); PDE isozyme inhibitors which suppressed mitogenesis also inhibited MAPK. PDE isozyme inhibitors also suppressed PDGF-stimulated MC proliferation. We conclude that cAMP inhibits the mitogen-dependent MAPK-signaling pathway probably by decreasing the activity of Raf-1 due to PKA-catalyzed phosphorylation. Further, we surmise that minor increase in the cAMP pool metabolized by PDE-III is intimately related to regulation of mesangial proliferation. Thus, PDE isozyme inhibitors have the potential to suppress MC proliferation by a focused effect upon signaling pathways.
Incorporation of Fowl Plague Virus Hemagglutinin into Murine Leukemia Virus Particles and Analysis of the Infectivity of the Pseudotyped Retroviruses (1998)

We describe retrovirus particles carrying the fowl plague virus (FPV) hemagglutinin (HA). When expressed in cells providing Moloney murine leukemia virus (MoMLV) Gag and Pol proteins and a lacZ retroviral vector, FPV HA was found to be efficiently expressed, correctly processed, and stably incorporated into retroviral particles. HA-bearing retroviruses were infectious with a wide host range and were only 10-fold less infectious than retroviruses carrying wild-type MLV retroviral envelopes. We also coexpressed HA proteins in retroviral particles with chimeric MoMLV-derived envelope glycoproteins that efficiently retarget virus attachment but are only weakly fusogenic. Our results suggest that HA can in some cases enhance the fusion ability of these retroviral particles, depending on the cell surface molecule that is used as a receptor.
Isolated thrombosis due to the cystathionine β‐synthase mutation c.833T>C (I278T) (2003)

Hereditary homocystinuria due to cystathionine beta-synthase (CBS) deficiency is a rare disease (about 1:20000 in Germany) often complicated by thromboembolism. Single mutations, which affect the C-terminal region of the CBS enzyme, lead to isolated thrombosis without further symptoms typical for homocystinuria such as atherosclerosis, psychomotor retardation, and dislocation of the ocular lenses. In this study, DNA samples of patients with stroke (n = 225) and sinus thrombosis (n = 46) were screened for the most common homocystinuria mutation, CBS 1278T. In each group one homozygous patient was identified. Thus, not only C-terminal mutations but also the most common mutation in classical homocystinuria, CBS 1278T, can lead to isolated thrombophilic events. These data support the hypothesis that homocystinuria is an underdiagnosed disease.
Antivascular Therapy of Oral Tongue Squamous Cell Carcinoma with PTK787 (2005)

These results suggest that targeting VEGF-R tyrosine kinase activity can be an effective therapeutic approach in squamous cell carcinoma of the oral tongue.
Growth Inhibition of Hepatoma Cells Induced by Vitamin K and Its Analogs (1995)

Congeners of vitamin K are known to inhibit cell growth, although the precise mechanisms of growth inhibition are not well understood. To investigate the mechanisms involved, we synthesized several vitamin K analogs and examined their growth inhibitory activities for a human hepatoma cell line (Hep3B). The analogs included 2-methyl-1,4-naphthoquinone and trimethyl-benzoquinone, with and without aliphatic side chains at position 3. The side chains were all-carbon, thioethers, or O-ethers. Growth inhibition was potent in the compounds with short chains. The presence of a sulfur (thioether) or oxygen atom (O-ether) at the site of attachment of the side chain to the ring potentiated the activity. Apoptotic cell death was induced by the potent growth inhibitory compounds at low concentrations (20-60 microM), whereas necrotic cell death followed treatment with the same compounds at high concentrations. Expression of c-myc, which is thought to be associated with apoptosis, was increased by most of the compounds tested. Both reduced glutathione and cysteine almost completely abrogated the growth inhibitory effects of the thioether analogs as well as of vitamin K3. The effect of glutathione was less prominent for the all-carbon and O-ether analogs, and cysteine had no effect on these analogs. Catalase and deferoxamine mesylate had no significant effect on the thioether analogs, although they showed partial antagonistic effects on the growth inhibition of vitamin K3 and the all-carbon and O-ether analogs. Other non-thiol antioxidants tested had no effect on any of the analogs. Our results indicated that vitamin K-related quinoid compounds cause growth inhibition and both apoptotic and necrotic cell death and that the effects may be mediated by interaction at position 3 of their quinoid nuclei with cellular thiols.
YSZ‐SrCo0.4Fe0.6O3‐δ membranes for the partial oxidation of methane to syngas (2002)

Abstract The perovskite‐related yttria‐stabilized zirconia promoted SrCo 0.4 Fe 0.6 O 3‐δ (SCFZ) oxides were used to construct membrane reactors for the partial oxidation of methane to syngas (POM). The oxygen permeability study of the SCFZ membrane in the air/helium gradient showed that the apparent activation energy was about 69±5 kJ/mol at 1,023∼1,223 K, and the oxygen flux was controlled by the bulk diffusion and surface exchange rate. In a cofeed reactor packed with SCFZ pellets and a blank SCFZ membrane reactor without any catalyst packing, the SCFZ oxides showed low catalytic activity for POM in the fixed‐bed reactor and no POM catalytic activity in the membrane reactor. An SCFZ membrane reactor with NiO/Al 2 O 3 catalyst was continuously running for over 220 h under constant operational conditions. While about 64% of methane was converted with 100% CO selectivity after reaching the steady state, the oxygen flux was about 10 times the value of the air/helium gradient, in the reactor packed with the catalyst. The oxygen flux of SCFZ membranes in the reducing atmosphere could be limited by the surface reaction rate at the reaction side.
1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1,3-dihydroimidazol-2-one:  A Selective High-Affinity Antagonist for the Human Dopamine D4Receptor with Excellent Selectivity over Ion Channels (1999)

After the requirement of pseudocycle formation in the ureas 3 and 7 for hD(4) binding and selectivity was confirmed, structural hybridization with the known hD(4) ligand 2 led to the design and identification of the lead 4-(2-oxo-1, 3-dihydroimidazol-2-yl)piperidine 8. Optimization studies were carried out on 8 with the aim of achieving 1000-fold selectivity for hD(4) over all other receptors while retaining the good pharmacokinetic properties of the lead. After initial preparation of 8 as a minor component in a low-yielding reaction, a novel and regioselective "four-step/one-pot" procedure was developed which proved to be applicable to rapid investigation of the SAR of the 1, 3-dihydroimidazol-2-one ring. Various changes to substituents attached to the 3-, 4-, or 5-position of the 1, 3-dihydroimidazol-2-one core of 8 did not significantly improve selectivity for hD(4) over hD(2) and hD(3). Greater selectivity (>1000-fold) was ultimately achieved by meta substitution of the benzyl group of 8 with various substituents. Compounds 28, 31, and 32 all possess the required selectivity for hD(4) over the other dopamine subtypes, but only 32 has >1000-fold selectivity over all the key counterscreens we tested against. Compound 32 is an antagonist at hD(4) and has a good pharmacokinetic profile in the rat, with excellent estimated in vivo receptor occupancy, thus making it a potentially useful pharmacological tool to investigate the role of the D(4) receptor.
Prognostic and predictive value of PDL1 expression in breast cancer (2014)

Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in breast cancer. Recently PD1/PDL1-inhibitors have shown promising results in different carcinomas with correlation between PDL1 tumor expression and responses. We retrospectively analyzed PDL1 mRNA expression in 45 breast cancer cell lines and 5,454 breast cancers profiled using DNA microarrays. Compared to normal breast samples, PDL1 expression was upregulated in 20% of clinical samples and 38% of basal tumors. High expression was associated with poor-prognosis features (large tumor size, high grade, ER-negative, PR-negative, ERBB2-positive status, high proliferation, basal and ERBB2-enriched subtypes). PDL1 upregulation was associated with biological signs of strong cytotoxic local immune response. PDL1 upregulation was not associated with survival in the whole population, but was associated with better metastasis-free and overall specific survivals in basal tumors, independently of clinicopathological features. Pathological complete response after neoadjuvant chemotherapy was higher in case of PDL1 upregulation (50% versus 21%). In conclusion, PDL1 upregulation, more frequent in basal breast cancers, was associated with increased T-cell cytotoxic immune response. In this aggressive subtype, upregulation was associated with better survival and response to chemotherapy. Reactivation of dormant tumor-infiltrating lymphocytes by PDL1-inhibitors could represent promising strategy in PDL1-upregulated basal breast cancer.
Combined Use Of Proteases And Mass Spectrometry In Structural Biology (1998)

Proteolysis and mass spectrometry methods have been extended to the analysis of higherorder protein structure. Proteases have long been used as probes of native structure, and this approach has been rejuvenated and used in concert with various mass spectrometry techniques. We discuss the application of protease as probes of native structure, delineate the mass spectrometry methods that are appropriate in these studies, and offer several innovative case studies to illustrate key concepts in the combined use of proteolysis and mass spectometry in studies of biomolecular assemblies. ability of uniquely identifying the target protein. The success of this strategy relies on the existence of the protein sequence within the database, and with the sequences of whole genomes for several organisms complete (eg, A. fulgidus, Bacillus subtilis, Caenorhabditis elegans, Escherichia coli, Saccharomyces cerevisiae) and others well underway (eg, Schizosaccharomyces pombe, Homo sapiens), the likelihood for matches is reasonably high. Exact matches are readily identified, and homologous proteins are identified, albeit with lower statistical significance, placing a target protein within a particular family in the absence of an exact match. Methods developed for primary sequence identification and elucidation using MS are particularly well suited for the analysis of higher-order, native protein structure. MS protocols used in primary structure analysis are directly transferable to the analysis of native structure, because they are used in the readout of information that is indirectly related to structure after the proteolysis reactions are performed. Analysis methods, however, must be modified to take into account the added spectral complexity resulting from incomplete proteolysis under limiting conditions. Proteases have long been used as probes of native structure, and this approach has been rejuvenated because powerful MS-based methods allow virtually complete identification of proteolysis reaction products. We review the application of protease as probes of native structure and discuss the MS methods that are appropriate in these studies. We provide several innovative case studies that illustrate key concepts in the combined use of proteolysis and MS in studies of biomolecular assemblies.
Micro-channel filling flow considering surface tension effect (2002)

Understanding filling flow into micro-channels is important in designing micro-injection molding, micro-fluidic devices and an MIMIC (micromolding in capillaries) process. In this paper, we investigated, both experimentally and numerically, &amp;apos;transient filling&amp;apos; flow into micro-channels, which differs from steady-state completely &amp;apos;filled&amp;apos; flow in micro-channels. An experimental flow visualization system was devised to facilitate observation of flow characteristics in filling into micro-channels. Three sets of micro-channels of various widths of different thicknesses (20, 30, and 40 p in) were fabricated using SU-8 on the silicon substrate to find a geometric effect with regard to pressure gradient, viscous force and, in particular, surface tension. A numerical analysis system has also been developed taking into account the surface tension effect with a contact angle concept. Experimental observations indicate that surface tension significantly affects the filling flow to such an extent that even a flow blockage phenomenon was observed at channels of small width and thickness. A numerical analysis system also confirms that the flow blockage phenomenon could take place due to the flow hindrance effect of surface tension, which is consistent with experimental observation. For proper numerical simulations, two correction factors have also been proposed to correct the conventional hydraulic radius for the filling flow in rectangular cross-sectioned channels.