gebhart/patrepeval huggingface dataset:
AIDS-associated Kaposi's sarcoma (KS) cells express oncostatin M (OM)-specific receptor but not leukemia inhibitory factor/OM receptor or interleukin-6 receptor. Complete block of OM-induced KS cell growth and OM binding by anti-gp130 antibodies. (1995)

Oncostatin M (OM), which shares functional similarity and structural homology to leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), functions as a potent growth fac- tor for AIDS-associated Kaposi's sarcoma-derived cells (AIDS-KS cells). OM was also suggested to bind to the LIF receptor (LIF/OM receptor), which consists of a signal transducing subunit for LIF and IL-6 (gpl30) and a LIF receptor a-subunit. Recent studies indicate that IL-6 has growth-stimulating activity for AIDS-KS cells. However, we find that AIDS-KS cell growth is exclusively induced by OM and not by LIF or IL-6. We also observed the lack of binding properties of AIDS-KS cells for LIF and IL-6. Scatchard plots revealed the existence of two affinity classes of OM receptor sites on AIDS-KS cells, with Kd values of 6-12 pM (high affinity) and 521-815 pM (low affinity). In competition binding studies, we find that the OM-specific receptor, but not the LIF/OM receptor, contributes to the OM-spe- cific growth stimulation of AIDS-KS cells. We also noted that anti-gpl30 antibodies can completely abolish OM-in- duced growth stimulation of AIDS-KS cells as well as OM binding to AIDS-KS cells. PCR amplification clearly re- vealed high levels of gpl30 expression in AIDS-KS cells, while the transcript of LWF receptor a-subunit or IL-6 recep- tor a-subunit was not observed. Therefore, we conclude that (a) AIDS-KS cells express the OM-specific receptor with high and low affinity, but not the LIF/OM receptor; (b) gpl30 on AIDS-KS cells plays a key role in OM binding and signaling on the OM-specific receptor; and (c) the lack of biological response of AIDS-KS cells to IL-6 and LWF can be explained by the absence of the IL-6 and LI/OM receptors. All this evidence shows the correlation of OM- specific biological activity with expression of the OM-specific receptor and the involvement of gpl30 on this receptor, as based on findings in in vitro growth assays and binding experiments for AIDS-KS cells. (
High‐throughput screening of chromatographic separations: III. Monoclonal antibodies on ceramic hydroxyapatite (2008)

High-throughput screening (HTS) of chromatography resins for identifying optimal protein purification conditions is becoming an integral part of industrial process development. In this work, ceramic hydroxyapatite (cHA) chromatography of 15 humanized monoclonal antibodies (mAbs) was examined by HTS. MAb binding, as quantified by partition coefficient (K(p)), was measured under 92 combinations of sodium chloride, phosphate, and pH. Binding varied inversely with these variables for all mAbs tested. However, the magnitudes of binding among mAbs under identical conditions varied significantly, showing a >1.5 log range in K(p). Analysis of variance (ANOVA) techniques were used to describe the binding of each mAb as a function of the three screen variables. Linear models relating log K(p) to the pH, log[sodium chloride], and log[phosphate] fit the data for each antibody with 93-96% accuracy. From these models, characteristic charge values for the cation exchange and metal coordination components of the multi-modal mAb/cHA interaction varied twofold across the mAbs, reflecting inherent variability in the number of contacts between a particular mAb and the cHA surface. Furthermore, we reduced the number of test conditions required from 92 to 8 while maintaining an accurate representation of the full binding response surface. This eight-point modeling method accurately predicted the binding behavior of mAbs as well as mAb aggregates, a common impurity in crude mAb preparations. Using this eight-point modeling method, binding and selectivity information for mAb and aggregate can be obtained from less than two milligrams of protein, making the method attractive for early manufacturability assessments.
Building a performance model of streaming media applications in utility data center environment (2003)

Utility Data Center (UDC) provides a flexible, cost-effective infrastructure to support the hosting of applications for Internet services. In order to enable the design of a "utility-aware" streaming media service which automatically requests the necessary resources from UDC infrastructure, we introduce a set of benchmarks for measuring the basic capacities of streaming media systems. The benchmarks allow one to derive the scaling rules of server capacity for delivering media files which are: i) encoded at different bit rates, ii) streamed from memory vs disk. Using an experimental testbed, we show that these scaling rules are non-trivial. In this paper, we develop a workload-aware, media server performance model which is based on a cost function derived from the set of basic benchmark measurements. We validate this performance model by comparing the predicted and measured media server capacities for a set of synthetic workloads.
Novel Regulators of Bone Formation: Molecular Clones and Activities (1988)

Protein extracts derived from bone can initiate the process that begins with cartilage formation and ends in de novo bone formation. The critical components of this extract, termed bone morphogenetic protein (BMP), that direct cartilage and bone formation as well as the constitutive elements supplied by the animal during this process have long remained unclear. Amino acid sequence has been derived from a highly purified preparation of BMP from bovine bone. Now, human complementary DNA clones corresponding to three polypeptides present in this BMP preparation have been isolated, and expression of the recombinant human proteins have been obtained. Each of the three (BMP-1, BMP-2A, and BMP-3) appears to be independently capable of inducing the formation of cartilage in vivo. Two of the encoded proteins (BMP-2A and BMP-3) are new members of the TGF-beta supergene family, while the third, BMP-1, appears to be a novel regulatory molecule.
Organic semiconductor heterointerfaces containing bathocuproine (1999)

The four organic–organic heterointerfaces formed by depositing the organic semiconductor bathocuproine on tris(8-hydroxy-quinoline)aluminum (Alq3), N,N′-diphenyl-N,N′-bis(1-naphthyl)-1,1′ biphenyl-4,4″ diamine (α-NPD), 4,4′-N,N′-dicarbazolyl-biphenyl (CBP), and copper phthalocyanine (CuPc) have been studied using ultraviolet photoelectron spectroscopy. The relative positions of the vacuum levels and highest occupied molecular orbital levels of the organics were measured at each interface. Within our experimental uncertainty of 100 meV, the vacuum levels were found to align at all four interfaces.
Investigating the influence of chromatic aberration and optical illumination bandwidth on fundus imaging in rats (2015)

Abstract. Rodent models are indispensable in studying various retinal diseases. Noninvasive, high-resolution retinal imaging of rodent models is highly desired for longitudinally investigating the pathogenesis and therapeutic strategies. However, due to severe aberrations, the retinal image quality in rodents can be much worse than that in humans. We numerically and experimentally investigated the influence of chromatic aberration and optical illumination bandwidth on retinal imaging. We confirmed that the rat retinal image quality decreased with increasing illumination bandwidth. We achieved the retinal image resolution of 10 μm using a 19 nm illumination bandwidth centered at 580 nm in a home-built fundus camera. Furthermore, we observed higher chromatic aberration in albino rat eyes than in pigmented rat eyes. This study provides a design guide for high-resolution fundus camera for rodents. Our method is also beneficial to dispersion compensation in multiwavelength retinal imaging applications.
Identification of plant cytoskeletal, cell cycle‐related and polarity‐related proteins using Schizosaccharomyces pombe (1996)

The fission yeast Schizosaccharomyces pombe has been used to identify Arabidopsis thaliana proteins that may play a role in cell shape maintenance or cell cycle regulation. An Arabidopsis thaliana cDNA library was constructed in pREP5N vector under the control of the inducible nmt1 promoter and transformed into S. pombe. Expression of the A. thaliana sequences was induced and clones showing severe morphological changes were identified and analysed. Comparison of the sequences of the inserts with the sequence data bases revealed that several cDNAs encode proteins known to play a role in function of the cytoskeleton, the cell cycle and establishment of cell polarity. These include alpha-1, alpha-2, alpha-6 and beta-6 tubulins, myosin heavy chain-like protein, ubiquitin conjugating enzymes UBC9 (E2), 26S protease subunits, Ranbinding protein, myb protein, PRL1 gene product and rho protein. Approximately 30% of the clones encode novel sequences. The results suggest that S. pombe phenotypic screening can be used to identify plant proteins involved in cell shape maintenance and regulation during cell cycle and development.
Site-specific mutagenesis of human apolipoprotein E. Receptor binding activity of variants with single amino acid substitutions. (1988)

Apolipoprotein (apo) E, an important protein involved in cholesterol transport in the plasma, binds with high specificity and high affinity to the apoB, E (low density lipoprotein) receptor. Several lines of evidence have indicated that key basic residues in the vicinity of residues 140-160 of apoE are important in mediating binding to the receptor. Furthermore, apoE variants exhibiting defective receptor binding are associated with the genetic lipid disorder type III hyperlipoproteinemia. To determine whether other basic amino acids in this region of apoE also affect receptor binding activity, site-specific mutagenesis of apoE in a bacterial expression system was undertaken. This system had been used successfully to produce apoE3 that was structurally and functionally equivalent to human plasma apoE3. Variants of apoE in which neutral amino acids were substituted for basic residues at positions 136, 140, 143, and 150 were produced. The variants all displayed defective binding; their activity ranged from 9 to 52% of normal (a range similar to that seen with naturally occurring variants of human apoE). In addition, to determine whether the conformation of this region is important for receptor binding, we designed variants in which proline was substituted for leucine 144 or alanine 152. Both variants were defective, exhibiting 13 and 27% of normal binding, respectively. In contrast, a double mutant in which arginine was substituted for serine 139 and alanine for leucine 149 displayed slightly enhanced receptor binding activity. These studies confirm that the middle of the apoE molecule is important in receptor binding and indicate that only certain amino acid substitutions in this region interfere with receptor binding activity.
DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. (1988)

The mating pheromone alpha-factor arrests Saccharomyces cerevisiae MATa cells in the G1 phase of the cell cycle. Size control is also exerted in G1, since cells do not exit G1 until they have attained a critical size. A dominant mutation (DAF1-1) which causes both alpha-factor resistance and small cell size (volume about 0.6-fold that of the wild type) has been isolated and characterized genetically and by molecular cloning. Several alpha-factor-induced mRNAs were induced equivalently in daf1+ and DAF1-1 cells. The DAF1-1 mutation consisted of a termination codon two-thirds of the way through the daf1+ coding sequence. A chromosomal deletion of DAF1 produced by gene transplacement increased cell volume about 1.5-fold; thus, DAF1-1 may be a hyperactive or deregulated allele of a nonessential gene involved in G1 size control. Multiple copies of DAF1-1 also greatly reduced the duration of the G1 phase of the cell cycle.
TensorFlow: Large-Scale Machine Learning on Heterogeneous Distributed Systems (2016)

TensorFlow is an interface for expressing machine learning algorithms, and an implementation for executing such algorithms. A computation expressed using TensorFlow can be executed with little or no change on a wide variety of heterogeneous systems, ranging from mobile devices such as phones and tablets up to large-scale distributed systems of hundreds of machines and thousands of computational devices such as GPU cards. The system is flexible and can be used to express a wide variety of algorithms, including training and inference algorithms for deep neural network models, and it has been used for conducting research and for deploying machine learning systems into production across more than a dozen areas of computer science and other fields, including speech recognition, computer vision, robotics, information retrieval, natural language processing, geographic information extraction, and computational drug discovery. This paper describes the TensorFlow interface and an implementation of that interface that we have built at Google. The TensorFlow API and a reference implementation were released as an open-source package under the Apache 2.0 license in November, 2015 and are available at www.tensorflow.org.
Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas (2004)

PTEN is a tumor suppressor gene mutated in many human cancers, and its expression is reduced or absent in almost half of hepatoma patients. We used the Cre-loxP system to generate a hepatocyte-specific null mutation of Pten in mice (AlbCrePten(flox/flox) mice). AlbCrePten(flox/flox) mice showed massive hepatomegaly and steatohepatitis with triglyceride accumulation, a phenotype similar to human nonalcoholic steatohepatitis. Adipocyte-specific genes were induced in mutant hepatocytes, implying adipogenic-like transformation of these cells. Genes involved in lipogenesis and beta-oxidation were also induced, possibly as a result of elevated levels of the transactivating factors PPARgamma and SREBP1c. Importantly, the loss of Pten function in the liver led to tumorigenesis, with 47% of AlbCrePten(flox/flox) livers developing liver cell adenomas by 44 weeks of age. By 74-78 weeks of age, 100% of AlbCrePten(flox/flox) livers showed adenomas and 66% had hepatocellular carcinomas. AlbCrePten(flox/flox) mice also showed insulin hypersensitivity. In vitro, AlbCrePten(flox/flox) hepatocytes were hyperproliferative and showed increased hyperoxidation with abnormal activation of protein kinase B and MAPK. Pten is thus an important regulator of lipogenesis, glucose metabolism, hepatocyte homeostasis, and tumorigenesis in the liver.
P2-purinergic receptor agonists inhibit the growth of androgen-independent prostate carcinoma cells. (1992)

To develop a new approach to the treatment of advanced, hormone-refractory prostate cancer, the signal transductions regulating the growth of human androgen-independent prostate carcinoma cell lines were studied. Agonist-stimulated Ca2+ mobilization, a critical regulatory event in other secretory cell types, was studied as a means of identifying previously undescribed plasma membrane receptors that may transduce a growth inhibitory signal. In all of the cell lines tested, P2-purinergic receptor agonists, including ATP and certain hydrolysis-resistant adenine nucleotides, induced a rapid, transient increase in cytoplasmic free Ca2+ that was detectable at 50 to 100 nM ATP, was maximal at 100 microM ATP, and was inhibited approximately 50% by chelation of extracellular Ca2+. Within 8 s after addition, ATP stimulated accumulation of the polyphosphatidylinositol products inositol (1, 4, 5) trisphosphate, inositol (1, 3, 4) trisphosphate, and inositol tetrakisphosphate. In addition to stimulating phosphatidylinositol turnover and Ca2+ mobilization, ATP and hydrolysis-resistant ATP analogues induced greater than 90% inhibition of the growth of all lines tested. These data demonstrate that human androgen-independent prostate carcinoma cells express functional P2-purinergic receptors linked to phospholipase C, and that agonists of this receptor are markedly growth inhibitory, suggesting a novel therapeutic approach to this common adult neoplasm.
Developmental, Stage-Specific, and Hormonally Regulated Expression of Growth Hormone Secretagogue Receptor Messenger RNA in Rat Testis1 (2003)

Recent evidence from our research suggested the direct role of ghrelin in the control of testicular function. However, the pattern of expression and hormonal regulation of the gene encoding its cognate receptor (i.e., the growth hormone-secretagogue receptor [GHS-R]) in the male gonad remains to be fully elucidated. In this paper, overall expression of GHS-R mRNA in rat testis was compared with that of the functional receptor form, namely GHS-R type 1a, in different developmental and experimental settings. In addition, cellular distribution of GHS-R within adult testis tissue was assessed. Our analyses demonstrated persistent expression of the GHS-R gene in rat testis throughout postnatal development. In contrast, testicular expression of GHS-R type 1a mRNA remained undetectable before puberty and sharply increased thereafter. In adult testis, GHS-R1a mRNA expression presented a scattered pattern of cellular distribution, including Sertoli and Leydig cells that also showed specific GHS-R1a immunoreactivity. Expression of total GHS-R and specific GHS-R1a mRNAs was detected in isolated seminiferous tubule preparations, with varying levels throughout the defined stages of the spermatogenic cycle. In addition, testicular expression of total GHS-R and GHS-R1a mRNAs was up-regulated by exposure to ghrelin in vitro and after stimulation with FSH in vivo. In conclusion, our data demonstrate that expression of the GHS-R gene in rat testis takes place in a developmental, stage-specific, and hormonally regulated manner. Divergent expression of total GHS-R and type 1a specific mRNAs was detected at certain stages of postnatal development and spermatogenic cycle, thus raising the possibility that, in addition to net changes in GHS-R gene expression, the balance between receptor subtypes may represent a novel mechanism for the tuning of ghrelin sensitivity in rat testis.
Targeting the molecular basis for tumour hypoxia (2005)

Tumour hypoxia stems from impaired oxygen delivery as a result of a disorganised tumour vasculature and inadequate blood supply. Hypoxic tumours are highly resistant to chemotherapy and radiation therapy and correlate with a poor patient prognosis. Hypoxia is a powerful stimulus for the expression of genes involved in cell survival and angiogenesis. A key factor in this process is hypoxia-inducible factor (HIF), which regulates transcription of hypoxia-activated genes. Efforts are currently under way to develop targeted cancer therapeutics to hypoxia-activated pathways, and in particular to the transcription factor HIF.
PPAR and Liver Injury in HIV‐Infected Patients (2009)

Due to the introduction of active HIV antiretroviral treatment, AIDS-related morbidity and mortality have markedly decreased and liver diseases are now a major cause of morbidity and mortality in HIV-infected patients. Chronic liver injury encompasses a wide spectrum of diseases due to HCV and HBV coinfection, drug-related toxicity, and NASH. HIV-infected patients who are receiving treatment present with a high prevalence of metabolic complications and lipodystrophy. Those patients are at high risk of nonalcoholic fatty liver disease, the liver feature of the metabolic syndrome. This review will focus on (1) the liver injuries in HIV-infected patients; (2) both the current experimental and human data regarding PPAR and liver diseases; (3) the interactions between HIV and PPAR; (4) the potential use of PPAR agonists for the management of HIV-related liver diseases.
Osteogenic Differentiation of Human Bone Marrow Stromal Cells on Partially Demineralized Bone Scaffolds in Vitro (2004)

Tissue engineering has been used to enhance the utility of biomaterials for clinical bone repair by the incorporation of an osteogenic cell source into a scaffold followed by the in vitro promotion of osteogenic differentiation before host implantation. In this study, three-dimensional, partially demineralized bone scaffolds were investigated for their ability to support osteogenic differentiation of human bone marrow stromal cells (BMSCs) in vitro. Dynamic cell seeding resulted in homogeneous cell attachment and infiltration within the matrix and produced significantly higher seeding efficiencies when compared with a conventional static seeding method. Dynamically seeded scaffolds were cultured for 7 and 14 days in the presence of dexamethasone and evaluated on biochemical, molecular, and morphological levels for osteogenic differentiation. Significant elevation in alkaline phosphatase activity was observed versus controls over the 14-day culture, with a transient peak indicative of early mineralization on day 7. On the basis of RT-PCR, dexamethasone-treated samples showed elevations in alkaline phosphatase and osteocalcin expression levels at 7 and 14 days over nontreated controls, while bone sialoprotein was produced only in the presence of dexamethasone at 14 days. Scanning electron microscopy evaluation of dexamethasone-treated samples at 14 days revealed primarily cuboidal cells indicative of mature osteoblasts, in contrast to nontreated controls displaying a majority of cells with a fibroblastic cell morphology. These results demonstrate that partially demineralized bone can be successfully used with human BMSCs to support osteogenic differentiation in vitro. This osseous biomaterial may offer new potential benefits as a tool for clinical bone replacement.
Gate length scaling accelerated to 30 nm regime using ultra-thin film PD-SOI technology (2002)

High performance SOI CMOS designed for the 100 nm technology node is presented. At 1 V supply voltage, the 33 nm devices give a drive current of 1000 (1100) /spl mu/A//spl mu/m DC (dynamic) for NFET and 445 (457) /spl mu/A//spl mu/m for PFET at an off current of 300 nA//spl mu/m. The intrinsic gate delays are 0.55 ps and 1.19 ps. The NFET delay is further reduced to 0.45 ps at gate length scaled to 25 nm. The delay and current values are the best ever reported at 1.0 V. The excellent result is accomplished by using super-HALO design on 45 nm SOI substrate.
Asthmatic changes in mice lacking T-bet are mediated by IL-13 (2005)

Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway hyperresponsiveness (AHR), airway inflammation, enhanced recovery of T(h)2 cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition and myofibroblast transformation. Here we analyze the mechanisms responsible for the chronic airway remodeling observed in these mice. CD4+ T cells isolated from the lung of T-bet-deficient mice were spontaneously activated CD44(high)CD69(high) memory T cells, with a typical T(h)2 cytokine profile. Neutralization of IL-13 but not IL-4 resulted in amelioration of AHR in airways of mice lacking T-bet. IL-13 blockade also led to reduced eosinophilia and decreased vimentin, transforming growth factor beta (TGF-beta) and alpha smooth muscle actin (alphaSMA) levels. T-bet(-/-) lung fibroblasts proliferated very rapidly and released increased amounts of TGF-beta. Interestingly, neutralization of TGF-beta ameliorated aspects of the chronic airway remodeling phenotype but did not reduce AHR. These data highlight a T-bet-directed function for IL-13 in controlling lung remodeling that is both dependent on and independent of its interaction with TGF-beta in the asthmatic airway.