gebhart/patrepeval huggingface dataset:
High-Throughput Real-Time Reverse Transcription-PCR Quantitation of Hepatitis C Virus RNA (1999)

We describe a rapid and reproducible method for assessment of the hepatitis C virus (HCV) load in serum samples. The method combines Taqman technology (Roche) and the ABI Prism 7700 (Perkin Elmer) real-time sequence detection system. We have optimized a single-tube reverse transcription-PCR (RT-PCR) that contains a dual-labeled fluorogenic probe to quantify the 5' noncoding region (5' NCR) of HCV. The probe contains a fluorescent reporter at the 5' end and a fluorescent quencher at the 3' end. The use of such a probe combined with the 5'-3' nuclease activity of Taq polymerase allows direct quantitation of the PCR product by the detection of a fluorescent reporter released in the course of the exponential phase of the PCR. For accurate quantitation of the number of copies of HCV in samples containing unknown quantities, we have used serial dilutions of a synthetic 5' NCR RNA standard of HCV that was previously quantified with an isotopic tracer. The method has a 5-log dynamic range (10(3) to 10(7)). The coefficient of regression of the standard curve was, on average, 0.98. The intra-assay and the interassay coefficients of variation of the threshold cycle were 1% and 6.2%, respectively. Seventy-nine RNA samples from the sera of infected patients were quantified by this method. Comparison of the results with those obtained by other quantitation methods (the Quantiplex 2.0 branched-DNA assay and the Superquant assay from the National Genetics Institute) revealed a significant correlation with all of the results. The mean values were also statistically comparable. In conclusion, the high sensitivity, simplicity, and reproducibility of the real-time HCV RNA quantitation which allows the screening of large numbers of samples, combined with its wide dynamic range, make this method especially suitable for monitoring of the viral load during therapy and tailoring of treatment schedules.
ChemInform Abstract: Boron‐Modified MCM‐41 Mesoporous Molecular Sieves. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Characterization of mouse clonogenic megakaryocyte progenitors (2002)

Although it has been shown that unfractionated bone marrow, hematopoietic stem cells, common myeloid progenitors, and bipotent megakaryocyteerythrocyte progenitors can give rise to megakaryocyte colonies in culture, monopotent megakaryocyte-committed progenitors (MKP) have never been prospectively isolated from the bone marrow of adult mice. Here, we use a monoclonal antibody to the megakaryocyte-associated surface protein, CD9, to purify MKPs from the c-kit(+)Sca-1(-)IL7Ralpha(-)Thy1.1(-)Lin(-) fraction of adult C57BLKa-Thy1.1 bone marrow. The CD9(+) fraction contained a subset of CD41(+)FcgammaR(lo)CD34(+)CD38(+) cells that represent approximately 0.01% of the total nucleated bone marrow cells. They give rise mainly to colony-forming unit-megakaryocytes and occasionally burst-forming unit-megakaryocytes, with a plating efficiency >60% at the single-cell level. In vivo, MKPs do not have spleen colony-forming activity nor do they contribute to long-term multilineage hematopoiesis; they give rise only to platelets for approximately 3 weeks. Common myeloid progenitors and megakaryocyteerythrocyte progenitors can differentiate into MKPs after 72 h in stromal cultures, indicating that MKPs are downstream of these two progenitors. These isolatable MKPs will be very useful for further studies of megakaryopoiesis as well as the elucidation of their gene expression patterns.
Critical Role of P2Y12 Receptor in Regulation of Th17 Differentiation and Experimental Autoimmune Encephalomyelitis Pathogenesis (2017)

Adenosine 5'-diphosphate is a key endogenous cell-signaling molecule that can activate P2 purinergic receptor family members. ADP-P2Y signaling is reported to be associated with inflammation, but its function in T cell differentiation and autoimmune diseases pathogenesis is unclear. In this study, we found that the P2Y<sub>12</sub> receptor was upregulated in the peripheral immune tissues of experimental autoimmune encephalomyelitis (EAE) mice. Deficiency of P2Y<sub>12</sub> led to a reduced peak severity and cumulative disease score in EAE mice, followed by a dramatic reduction of leukocyte infiltration and less extensive demyelination. The percentage of Th17, one of the main pathogenic T cells in EAE, was sharply decreased in P2Y<sub>12</sub> knockout mice, accompanied by decreased IL-17A production and a low mRNA level of Th17-related genes. In vitro culture assay further verified that P2Y<sub>12</sub> directly regulated Th17 differentiation. More interestingly, clopidogrel and ticagrelor, two P2Y<sub>12</sub>-specific antagonists, effectively alleviated the disease severity of EAE and inhibited Th17 differentiation both in vivo and in vitro. Further study demonstrated that blocking the P2Y<sub>12</sub> receptor also ameliorated the symptoms of 2,4,6-trinitrobenzenesulfonic acid-induced colitis and multiple low-dose streptozocin-induced type 1 diabetes. Our findings not only revealed the critical role of P2Y<sub>12</sub> in Th17 differentiation and EAE pathogenesis, but also suggested the promising potential of P2Y<sub>12</sub> antagonists in the treatment of autoimmune diseases.
Structures of the Tyrosine Kinase Domain of Fibroblast Growth Factor Receptor in Complex with Inhibitors (1997)

A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.
Measurement errors and their consequences in protein crystallography (2003)

This article analyzes the relative impact of various types of measurement uncertainties on different stages of structure determination. The treatment of errors is an important part of the experimental process and becomes critical when data quality is barely sufficient to solve and/or answer detailed questions about the structure. The sources and types of experimental errors are described and methods of minimizing their impact are discussed. Practical calculations of sigma estimates in DENZO and SCALEPACK are presented.
An Approach to Core−Shell-Type Architectures in Hyperbranched Polyglycerols by Selective Chemical Differentiation (2000)

In contrast to dendrimers, hyperbranched polymers show no distinguishable interior and periphery. Hyperbranched polyglycerol, however, possesses two types of OH functionalities (arising from linear and terminal glycerol units), which can be chemically differentiated. To generate a core−shell-type architecture in hyperbranched polyglycerol (Mn = 5000, Mw/Mn = 1.5), the 1,2-diols of the terminal glycerol units have been selectively converted into the corresponding acetals or ketals. This allows one to distinguish between interior (closer to the focal unit) and periphery (distant from the focal unit) of the macromolecule, since the remaining linear glycerol units remain unaffected by this transformation. In subsequent reactions, the linear units were functionalized with alkyl halides, such as allyl chloride or benzyl chloride, under phase transfer conditions to obtain the corresponding polyether polyketals. Selective deprotection of the 1,2-ketals was achieved with an acidic ion-exchange resin to give “core”-functionalized polyglycerols. By this procedure, hyperbranched polymers can be selectively tailored to contain hydrophobic substituents in the interior or in the periphery. Distribution coefficients (CHCl3/H2O), unusual thermal behavior, and spectroscopic properties of these macromolecules corroborate their core−shell-type architectures. Structural inversion of the architecture (apolar periphery with polar core vs polar periphery with apolar core) leads to striking changes in physical properties. Furthermore, the presented synthetic methods permit the preparation of a fully alkylated polyglycerol, which was obtained by phase transfer alkylation of polyglycerol. To demonstrate that the linear “core” units of polygylcerol are suitable for further selective functionalization, a polyglycerol pseudo-dendrimer, containing exclusively dendritic and terminal units, has been prepared by selective transformation of all linear into dendritic units.
Lithography: Small 7/2009 (2009)

The cover picture shows how vacuum-assisted capillary force lithography allows the gap between microstructures to be bridged by partial curing and vacuum-assisted hydraulic filling. In the first step, the surface of molded microstructures is incompletely cured by exposure to ultraviolet light, owing to the high oxygen permeability of the poly(dimethyl siloxane) mold. During the curing process, oxygen inhibits crosslinking by scavenging initiator radicals in free-radical polymerization. Consequently, a small portion of the base microstructure (<4 µm) is molded to create a monolithic bridge structure by simply applying a nanoscale mold under a slight pressure (≈0.1–0.5 bar) with the impression of channels, meshes, or circles without collapse. In the second step, a low vacuum facilitates migration of the partially cured polymer into the void spaces imposed by the nanoscale mold, thereby forming a dual-scale bridge structure. For more information, please read the Communication “Fabrication of Monolithic Bridge Structures by Vacuum-Assisted Capillary-Force Lithography” by K. Y. Suh et al. beginning on page 790.
[Simultaneous determination of germanium and molybdenum in mixtures by complexation with 5'-nitrosalicyfluorone and dual-wavelength standard addition spectrophotometry]. (1998)

In the presence of hexadecyltrimethylammonium bromide and in a medium of 0.3-0.9mol/L sulfuric acid, germanium (IV) and molybdenum (VI) react with 2,6,7-trihydroxy-9 (2'-hydroxy-5'-nitro) phenylfluorone-3, i.e., 5'-nitrosalicyfluorone, to develop red complexes, respectively. The spectra of the two complexes overlap seriously each other, and the additivity of their absorbances is good in the wavelength range of 490-548nm. So a new method for simultaneous spectrophotometric determination of germanium and molybdenum by dual-wavelegth standard addition method has been investigated in detail. The analytical results of five standard mixtures are more accuracy than those obtained by isobestic-point dual-wavelength method. The method has been applied to the analysis of traditional chinese medicine and mineral water with satisfactory results.
Influence of surfactants, polymer and doxorubicin loading on the anti-tumour effect of poly(butyl cyanoacrylate) nanoparticles in a rat glioma model (2006)

Poly(n-butyl cyanoacrylate) nanoparticles coated with polysorbate-80 can enable the transport of bound drugs across the blood-brain barrier (BBB) after i.v. injection. In the present study the influence of different formulation parameters on the anti-tumoural effects of doxorubicin nanoparticles against glioblastoma 101/8 was investigated. The manufacturing parameters of poly(alkyl cyanoacrylate) doxorubicin-loaded nanoparticles were optimized concerning drug loading. The nanoparticles were coated with different surfactants and injected intravenously on days 2, 5 and 8 after intra-cranial implantation of glioblastoma 101/8 to rats. The survival times of all doxorubicin containing preparations, including a doxorubicin solution, increased the survival times significantly compared to untreated tumour-bearing rats. The most pronounced increase in survival was obtained with the poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80 and 35% of these animals survived for over 180 days (termination of the experiments). The other nanoparticle preparations yielded lower survival times. Poly(n-butyl cyanoacrylate) doxorubicin-loaded nanoparticles coated with polysorbate 80-coated proved to be very efficient against glioblastoma 101/8. The data suggest that the interaction of nanoparticles with the blood after injection as well as the enhanced permeability and retention effect (EPR effect) contributed differently to the anti-tumoural efficacy depending on nanoparticle formulation and surface properties.
High quality ultra-thin (1.5 nm) TiO/sub 2/-Si/sub 3/N/sub 4/ gate dielectric for deep sub-micron CMOS technology (2003)

This paper presents the physical and electrical properties of ultra-thin (/spl sim/1.5 nm EOT) TiO/sub 2//Si/sub 3/N/sub 4/ gate dielectrics fabricated by the jet-vapor deposition (JVD) process for both n- and p-channel field-effect transistors. It will be shown that the use of TiO/sub 2//Si/sub 3/N/sub 4/ to replace SiO/sub 2/ as gate dielectric can reduce the gate leakage current by several orders of magnitude while maintaining excellent interface quality, high reliability, low trap density, and competitive n-and p-channel MOSFET performance.
alpha 5 Subunit alters desensitization, pharmacology, Ca++ permeability and Ca++ modulation of human neuronal alpha 3 nicotinic receptors. (1998)

Functional effects of human alpha 5 nicotinic ACh receptor (AChR) subunits coassembled with alpha 3 and beta 2 or with alpha 3 and beta 4 subunits, were investigated in Xenopus oocytes. The presence of alpha 5 subunits altered some properties of both alpha 3 AChRs and differentially altered other properties of alpha 3 beta 2 AChRs vs. alpha 3 beta 4 AChRs. alpha 5 subunits increased desensitization and Ca++ permeability of all alpha 3 AChRs. The Ca++ permeabilities of both alpha 3 beta 2 alpha 5 and alpha 3 beta 4 alpha 5 AChRs were comparable to that of alpha 7 AChRs. As we have shown previously, alpha 5 subunits increased the ACh sensitivity of alpha 3 beta 2 AChRs 50-fold but had little effect on alpha 3 beta 4 AChRs. alpha 5 caused only subtle changes in the activation potencies of alpha 3 AChRs for nicotine, cytisine and 1,1-dimethyl-4-plenylpiperazinium (DMPP). However, alpha 5 increased the efficacies of nicotine and DMPP on alpha 3 beta 2 AChRs but decreased them on alpha 3 beta 4 AChRs. Immunoisolation of cloned human AChRs expressed in oocytes showed that alpha 5 efficiently coassembled with alpha 3 plus beta 2 and/or beta 4 subunits. As expected, human AChRs immunoisolated from SH-SY5Y neuroblastoma cells showed that AChRs containing alpha 3 and probably alpha 5 subunits were present, but alpha 4 AChRs were not. In brain, by contrast, alpha 4 beta 2 AChRs were shown to predominate over alpha 3 AChRs. Some of the brain alpha 4 beta 2 AChRs were found to contain alpha 5 subunits.
Speech recognition in noisy environments (1996)

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Chapter 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 1.1. Thesis goals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 1.2. Dissertation Outline . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Chapter 2 The SPHINX-II Recognition System . . . . . . . . . . . . . . . . . . . . . . 17 2.1. An Overview of the SPHINX-II System . . . . . . . . . . . . . . . . . . 17 2.1.1. Signal Processing . . . . . . . . . . . . . . . . . . . . . . . . . 17 2.1.2. Hidden Markov Models . . . . . . . . . . . . . . . . . . . . . . 20 2.1.3. Recognition Unit . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.1.4. Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 2.1.5. Recognition . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 2.2. Experimental Tasks and Corpora . ...
Cold-induced microtubule disruption and relocalization of membrane proteins in kidney epithelial cells. (1998)

Cold preservation of kidneys is commonly used in human transplantation and in vitro studies. However, although disruption of the cytoskeleton by cold has been demonstrated in cultured cells, the effect of cold treatment on intact kidney is poorly understood. In this study, specific antibodies were used to examine the effect of hypothermia on the cytoskeletal network and the trafficking of some membrane proteins in the urinary tubule. Rat kidneys were cut into thin slices (approximately 0.5 mm) that were divided into several groups: (1) some were immediately fixed in paraformaldehyde, sodium periodate, and lysine (PLP); (2) some were stored at 4 degrees C for 15 min or 4 h before being fixed in cold PLP; or (3) after 4 h cold treatment, some slices were rewarmed to 37 degrees C for 15, 30, and 60 min in a physiologic solution, pH 7.4, and were then fixed in warm PLP. Immunofluorescence staining revealed an almost complete disruption of the microtubule network in proximal tubules after 15 min cold treatment, whereas microtubules in other segments were affected after 4 h. A partial recovery of the microtubule network was observed after 60 min rewarming. In contrast, actin filaments seemed to be resistant to cold treatment. gp330, aquaporin-2, H+ ATPase, and the AE1 anion exchanger were all relocated into numerous vesicles that were distributed throughout the cytoplasm after hypothermia followed by rewarming, whereas Na-K-ATPase retained its basolateral localization. The vasopressin-stimulated insertion of aquaporin-2 water channels into the apical membrane was inhibited during the initial rewarming period after cold exposure. Thus, cold preservation of tissues might impair, at least transiently, the polarized membrane expression and function of some transport proteins in renal epithelial cells.
Krüppel-like factor 4 regulates macrophage polarization (2011)

Current paradigms suggest that two macrophage subsets, termed M1 and M2, are involved in inflammation and host defense. While the distinct functions of M1 and M2 macrophages have been intensively studied - the former are considered proinflammatory and the latter antiinflammatory - the determinants of their speciation are incompletely understood. Here we report our studies that identify Krüppel-like factor 4 (KLF4) as a critical regulator of macrophage polarization. Macrophage KLF4 expression was robustly induced in M2 macrophages and strongly reduced in M1 macrophages, observations that were recapitulated in human inflammatory paradigms in vivo. Mechanistically, KLF4 was found to cooperate with Stat6 to induce an M2 genetic program and inhibit M1 targets via sequestration of coactivators required for NF-κB activation. KLF4-deficient macrophages demonstrated increased proinflammatory gene expression, enhanced bactericidal activity, and altered metabolism. Furthermore, mice bearing myeloid-specific deletion of KLF4 exhibited delayed wound healing and were predisposed to developing diet-induced obesity, glucose intolerance, and insulin resistance. Collectively, these data identify KLF4 as what we believe to be a novel regulator of macrophage polarization.
Conservation of low-frequency hearing in cochlear implantation (2004)

This study reports successful conservation of hearing after cochlear implantation using a modified surgical technique. Even high levels of hearing could be maintained, showing that implantation of an intracochlear electrode can be performed atraumatically with preservation of functional structures.
A Cineradiographic Study of Bottle Feeding (1958)

Cineradiographic films have been taken of babies, lambs and kid goats, taking a mixture of milk and barium from a bottle. The various types of teat supplied for feeding babies were comparatively ineffective when compared with the soft veterinary rubber teats used for feeding the animals; the performance of the babies was thus not so good as that of the lambs or kid goats. Our conclusions are: 1. The influence of gravity is important in bottle feeding. It ensures that the bulb of the teat fills. If the hole in the teat is large anough milk drips into the mouth; when rigid teats are used this may be the only way the child can obtain an adequate supply of milk. 2. The lambs and kid goats take one teat full of milk with each jaw and tongue movement; the neck of the teat is completely occluded by approximation of the jaws and the contents of the bulb are expressed into the mouth by elevation of the tongue towards the soft palate, the tongue indenting the bulb from before backwards. Babies usually attempt this movement but in most instances are only partly successful; the teats normally supplied are too rigid and the hole is too small. 3. Following compression of the bulb of the teat by the squeezing action of the tongue, the lowering of the jaw and tongue must cause some degree of suction which may aid in the refilling of the bulb and it may also draw milk into the mouth; the amount of milk obtained in this manner may in favourable circumstances equal the amount obtained by expression. 4. During the phase of compression of the bulb of the teat by elevation of the tongue in the forepart of the mouth there is also taking place simultaneously a lowering of the tongue behind the teat which must cause some suction. 5. Factors relating to the design of different teats have been considered. 6. When milk is swallowed, naso-pharyngeal closure is made by elevation of the soft palate against the adenoidal pad on the roof of the epipharynix, the mode of closure differing from that seen in adults. The relevant variations in anatomy between infants and adults are discussed. 7. The bolus passes through the pharynx on both sides of the superior laryngeal aperture. The larynx is closed as each bolus is expressed from the pharynx and reopened just before the next bolus enters. The theory that young babies and members of the herbivora are able to continue feeding by passing food down into the oesophagus on either side of the laryngeal aperture without closing the airway is disproved.
Dynamics of chronic myeloid leukemia response to long-term targeted therapy reveal treatment effects on leukemic stem cells (2011)

Treatment of chronic myeloid leukemia (CML) with the tyrosine kinase inhibitors (TKIs) imatinib mesylate and nilotinib represents a successful application of molecularly targeted anticancer therapy. However, the effect of TKIs on leukemic stem cells remains incompletely understood. On the basis of a statistical modeling approach that used the 10-year imatinib mesylate treatment response of patients with CML and a patient cohort receiving first-line nilotinib therapy, we found that successful long-term therapy results in a triphasic exponential decline of BCR-ABL1 transcripts in many patients. Within our framework, the first slope of -0.052 ± 0.018 (imatinib mesylate) and -0.042 ± 0.015 (nilotinib) per day represents the turnover rate of leukemic differentiated cells, whereas the second slope of -0.0057 ± 0.0038 (imatinib mesylate) and -0.0019 ± 0.0013 (nilotinib) per day represents the turnover rate of leukemic progenitor cells. The third slope allows an inference of the behavior of immature leukemic cells, potentially stem cells. This third slope is negative in most patients, positive in others, and not observable in some patients. This variability in response may be because of insufficient follow-up, missing data, disease heterogeneity, inconsistent compliance to drug, or acquired resistance. Our approach suggests that long-term TKI therapy may reduce the abundance of leukemic stem cells in some patients.