gebhart/patrepeval huggingface dataset:
Characterization of a cDNA encoding the 43-kDa membrane-associated inositol-polyphosphate 5-phosphatase. (1994)

Agonist stimulation of cells results in phosphatidylinositol turnover and the generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), which mobilizes intracellular calcium. The inositol-polyphosphate 5-phosphatase (5-phosphatase) enzymes hydrolyze Ins(1,4,5)P3 in a signal-terminating reaction. We have isolated a 2.7-kilobase (kb) composite cDNA, encoding the 43-kDa membrane-associated 5-phosphatase, by screening a human placental lambda gt11 library, using degenerate oligonucleotides. The 2.7-kb cDNA contains a 1.1-kb open reading frame, comprising 363 amino acids, which encodes a protein of a predicted molecular mass of 42 kDa. Amino acid sequence analysis demonstrates a number of potential sites for phosphorylation by protein kinase C and a CAAX motif in the COOH terminus, which may mediate membrane localization. The recombinant enzyme was expressed in COS-7 cells, resulting in a 50-fold increase in enzyme activity in the detergent-soluble membrane fraction of the cell (nanomole of Ins(1,4,5)P3 hydrolyzed per min/mg), but only a 2.5-fold increase in 5-phosphatase activity in the total cell homogenate. Sequence analysis demonstrated a 73-amino acid domain in the COOH terminus of the 43-kDa membrane-associated 5-phosphatase, which had 30% sequence identity and 67% similarity to a region in the 75-kDa 5-phosphatase and 34% identity and 70% similarity to a sequence in the protein that is encoded by the gene, defective in Lowe's oculocerebrorenal syndrome. As shown by RNA analysis the 43-kDa membrane-associated 5-phosphatase appears to be predominantly expressed in heart, brain, and skeletal muscle.
A network of yeast basic helix-loop-helix interactions (2000)

The Ino4 protein belongs to the basic helix-loop-helix (bHLH) family of proteins. It is known to form a dimer with Ino2p, which regulates phospholipid biosynthetic genes. Mammalian bHLH proteins have been shown to form multiple dimer combinations. However, this flexibility in dimerization had not been documented for yeast bHLH proteins. Using the yeast two-hybrid assay and a biochemical assay we show that Ino4p dimerizes with the Pho4p, Rtg1p, Rtg3p and Sgc1p bHLH proteins. Screening a yeast cDNA library identified three additional proteins that interact with Ino4p: Bck2p, YLR422W and YNR064C. The interaction with Bck2p prompted us to examine if any of the Bck2p-associated functions affect expression of phospholipid biosynthetic genes. We found that hyperosmotic growth conditions altered the growth phase regulation of a phospholipid biosynthetic gene, CHO1. There are two recent reports of initial whole genome yeast two-hybrid interactions. Interestingly, one of these reports identified five proteins that interact with Ino4p: Ino2p, Hcs1p, Apl2p, YMR317W and YNL279W. Ino2p is the only protein in common with the data presented here. Our finding that Ino4p interacts with five bHLH proteins suggests that Ino4p is likely to be a central player in the coordination of multiple biological processes.
Human Amnion-Isolated Cells Normalize Blood Glucose in Streptozotocin-Induced Diabetic Mice (2003)

Whole pancreas or beta-cell transplantation has opened the way for the treatment of advanced stage of diabetes mellitus. However, it is always limited by the scarcity of transplantation materials. The amniotic membrane is part of the fetal membrane and is composed of amniotic epithelium (HAE) and mesenchymal (HAM) cells that are derived from the inner cell mass in the blastocyst. Thus, HAE and HAM cells may have the potential to differentiate into various organs. The aim of our study was to assess the possibility of HAE cells differentiating into insulin-producing cells. In vitro, HAE cells stimulated with nicotinamide induced insulin mRNA in the culture cells. In vivo, HAE cells were capable of normalizing the blood glucose level of diabetic mice after several weeks of implantation into streptozotocin-induced diabetic mice. The distribution of human cells and human insulin secretion in mouse tissue studied by immunohistochemistry for anti-human-specific beta-2-microglobulin and anti-human-specific insulin shows the same location in mouse tissue. These studies suggest that HAE cells have the potential to differentiate into beta-cells in vivo, and hence that HAE cells have therapeutic potential for the treatment of type I diabetes mellitus.
Variations in PET/CT Methodology for Oncologic Imaging at U.S. Academic Medical Centers: An Imaging Response Assessment Team Survey (2011)

There is considerable variability in the way PET/CT scans are performed at academic institutions that are part of the IRAT network. This variability likely makes it difficult to quantitatively compare studies performed at different centers. These data suggest that additional standardization in methodology will be required so that PET/CT studies, especially those performed quantitatively, are more comparable across sites.
Effects of Bradykinin on Pial Arteries and Arteriolesin vitroandin situ (1983)

The effect of bradykinin on cerebrovascular resistance vessels was investigated by the use of in vitro and in situ preparations. Bradykinin, in the range of 10(-10) to 10(-5) M, elicited a concentration-dependent vasodilatation on both feline and human pial arteries in vitro; the half-maximal response was found to be approximately at 2.8 X 10(-7) M and 1.3 X 10(-8) M (EC50), respectively. This dilatatory effect of bradykinin in vitro was found only in arteries preconstricted with prostaglandin F2 alpha or 5-hydroxytryptamine. In order to determine the effects of bradykinin on the diameter of cat pial arteries in situ, perivascular microapplication was employed. The dose-response curves obtained showed vasodilatation; the EC50 and the maximal response (EAm) were 4.4 X 10(-7) M and 45.5% at 10(-5) M, respectively. Statistically significant (p less than 0.01) reactions were observed at 10(-7) M and higher concentrations of bradykinin. The observed effects were independent of initial vessel size (80-260 microns). These in situ findings are very similar to those found in vitro. The isolated guinea pig ileum was used to check the stability of the bradykinin solutions. In this instance, a concentration-dependent contraction was found when "freshly prepared" or "5 hours stored" bradykinin was applied, indicating no measureable degradation of bradykinin. We conclude that bradykinin is a powerful vasodilator of both human and feline pial arteries.
Immunoglobulin heavy chain and binding protein complexes are dissociated in vivo by light chain addition. (1990)

Immunoglobulin heavy chain binding protein (BiP, GRP78) associates stably with the free, nonsecreted Ig heavy chains synthesized by Abelson virus transformed pre-B cell lines. In cells synthesizing both Ig heavy and light chains, the Ig subunits assemble rapidly and are secreted. Only incompletely assembled Ig molecules can be found bound to BiP in these cells. In addition to Ig heavy chains, a number of mutant and incompletely glycosylated transport-defective proteins are stably complexed with BiP. When normal proteins are examined for combination with BiP, only a small fraction of the intracellular pool of nascent, unfolded, or unassembled proteins can be found associated. It has been difficult to determine whether these BiP-associated molecules represent assembly intermediates which will be displaced from BiP and transported from the cell, or whether these are aberrant proteins that are ultimately degraded. In order for BiP to monitor and aid in normal protein transport, its association with these proteins must be reversible and the released proteins should be transport competent. In the studies described here, transient heterokaryons were formed between a myeloma line producing BiP-associated heavy chains and a myeloma line synthesizing the complementary light chain. Introduction of light chain synthesis resulted in assembly of prelabeled heavy chains with light chains, displacement of BiP from heavy chains, and secretion of Ig into the culture supernatant. These data demonstrate that BiP association can be reversible, with concordant release of transportable proteins. Thus, BiP can be considered a component of the exocytic secretory pathway, regulating the transport of both normal and abnormal proteins.
Stealthy malware detection through vmm-based "out-of-the-box" semantic view reconstruction (2007)

An alarming trend in malware attacks is that they are armed with stealthy techniques to detect, evade, and subvert malware detection facilities of the victim. On the defensive side, a fundamental limitation of traditional host-based anti-malware systems is that they run inside the very hosts they are protecting ("in the box"), making them vulnerable to counter-detection and subversion by malware. To address this limitation, recent solutions based on virtual machine (VM) technologies advocate placing the malware detection facilities outside of the protected VM ("out of the box"). However, they gain tamper resistance at the cost of losing the native, semantic view of the host which is enjoyed by the "in the box" approach, thus leading to a technical challenge known as the semantic gap.
Specific human cytotoxic T cells recognize B-cell lines persistently infected with respiratory syncytial virus. (1986)

The T-lymphocyte response to respiratory syncytial (RS) virus has been invoked to explain the bronchiolitis and pneumonia caused by RS virus in human infants. However, T cells also appear to play a role in protection against RS virus infection. Although RS virus-specific human lymphocytes have been demonstrated, neither the phenotype nor the function of the lymphocytes was characterized. We describe here the induction of anti-RS virus cytotoxic T lymphocytes, in both bulk culture and restimulated cell lines, from human peripheral blood. Infection of Epstein-Barr virus-transformed human B-cell lines with RS virus in vitro readily caused a persistent infection; these cells continued to synthesize RS viral proteins and secrete infectious RS virus 4 months after infection. The persistently infected cells were used both to restimulate cytotoxic-T-cell precursors and as targets for RS virus-specific cytotoxic T cells.
Complexity of cyanobacterial exopolysaccharides: composition, structures, inducing factors and putative genes involved in their biosynthesis and assembly (2009)

Cyanobacterial extracellular polymeric substances (EPS) are mainly composed of high-molecular-mass heteropolysaccharides, with variable composition and roles according to the microorganism and the environmental conditions. The number of constituents - both saccharidic and nonsaccharidic - and the complexity of structures give rise to speculations on how intricate their biosynthetic pathways could be, and how many genes may be involved in their production. However, little is known regarding the cyanobacterial EPS biosynthetic pathways and regulating factors. This review organizes available information on cyanobacterial EPS, including their composition, function and factors affecting their synthesis, and from the in silico analysis of available cyanobacterial genome sequences, proposes a putative mechanism for their biosynthesis.
Self-powered signal processing using vibration-based power generation (1998)

Low power design trends raise the possibility of using ambient energy to power future digital systems. A chip has been designed and tested to demonstrate the feasibility of operating a digital system from power generated by vibrations in its environment. A moving coil electromagnetic transducer was used as a power generator. Calculations show that power on the order of 400 /spl mu/W can be generated. The test chip integrates an ultra-low power controller to regulate the generator voltage using delay feedback techniques, and a low power subband filter DSP load circuit. Tests verify 500 kHz self-powered operation of the subband filter, a level of performance suitable for sensor applications. The entire system, including the DSP load, consumes 18 /spl mu/W of power. The chip is implemented in a standard 0.8 /spl mu/m CMOS process. A single generator excitation produced 23 ms of valid DSP operation at a 500 kHz clock frequency, corresponding to 11,700 cycles.
Expression of infectious woodchuck hepatitis virus in murine and avian fibroblasts (1989)

The liver is the primary site for replication of the hepadnavirus genome. We asked whether the posttranscriptional phase of the viral replication cycle would depend on hepatocyte-specific functions. For this purpose, we assayed a previously constructed chimera between sequences of the cytomegalovirus immediate-early promoter-enhancer region and woodchuck hepatitis virus (WHV) (C. Seeger and J. Maragos, J. Virol. 63:1907-1915, 1989) for its ability to direct the synthesis of infectious WHV in hepatoma cells and in murine and avian fibroblast cells. Viruslike particles containing WHV DNA were produced transiently in transfected hepatoma cells and in fibroblasts. Inoculation of woodchucks with culture medium from hepatoma cells or fibroblasts transfected with viral DNA led to productive WHV infection, as observed following infection of woodchucks with serum from WHV-infected animals. These results demonstrate that posttranscriptional events of the hepadnavirus replication cycle are not dependent on hepatocyte-specific functions.
Immunoblockade of PSGL-1 attenuates established experimental murine colitis by reduction of leukocyte rolling (2004)

Recruitment of circulating leukocytes into the colonic tissue is a key feature of intestinal inflammation. P-selectin glycoprotein ligand-1 (PSGL-1) and very late antigen-4 (VLA-4) are expressed on leukocytes and play an important role in leukocyte-endothelial cell adhesive interactions. We examined the effects of immunoneutralization of PSGL-1 and VLA-4 on leukocyte recruitment in vivo in the development and treatment of experimental colitis. Chronic colitis was induced in balb/c mice by oral administration of dextran sodium sulfate (DSS). Monoclonal antibodies 2PH1 (anti-PSGL-1) and PS/2 (anti-VLA-4) or the combination of both were injected intravenously, and leukocyte adhesion was observed for 60 min in colonic submucosal venules by intravital microscopy (IVM) under isoflurane/N(2)O anesthesia. In addition, mice with established colitis were treated by daily intraperitoneal injections of 2PH1, PS/2, or the combination of both over 5 days. Disease activity index (DAI), histology, and myeloperoxidase (MPO) levels were compared with sham-treated DSS controls. We found that 2PH1 reduced the number of rolling leukocytes (148.7 +/- 29.8 vs. 36.9 +/- 8.7/0.01 mm(2)/30 s, P < 0.05), whereas leukocyte velocity was increased (24.0 +/- 3.6 vs. 127.8 +/- 11.7 microm/s, P < 0.05). PS/2 reduced leukocyte rolling to a lesser extent. Leukocyte firm adhesion was not influenced by 2PH1 but was strongly reduced by PS/2 (24.1 +/- 2 vs. 4.4 +/- 0.9/0.01 mm(2)/30 s, P < 0.05). Combined application did not cause additional effects on leukocyte adhesion. Treatment of chronic colitis with 2PH1 or PS/2 reduced DAI, mucosal injury, and MPO levels significantly. Combined treatment led to a significantly better reduction of DAI (0.4 +/- 0.1 vs. 2.1 +/- 0.2 points) and histology (9.7 +/- 0.9 vs. 21.4 +/- 4.6 points). In conclusion, PSGL-1 and VLA-4 play an important role for leukocyte recruitment during intestinal inflammation. Therapeutic strategies designed to disrupt interactions mediated by PSGL-1 and/or VLA-4 may prove beneficial in treatment of chronic colitis.
Silicon Diffused-Element Piezoresistive Diaphragms (1962)

The properties of a pressure transducer consisting of a single-crystal silicon diaphragm having stress-sensitive piezoresistive regions formed by the localized diffusion of impurities have been theoretically and experimentally investigated. The longitudinal and transverse piezoresistance effects are discussed and the results are applied to the stress pattern of a deformed diaphragm. The conditions under which the stress in the diaphragm varies linearly with applied pressure are discussed and good agreement between the predicted and measured sensitivity is found in both the linear and nonlinear cases.
Copper-Free Click Chemistry for Highly Luminescent Quantum Dot Conjugates: Application to in Vivo Metabolic Imaging (2010)

Quantum dots (QD) are inorganic nanocrystals with outstanding optical properties, specially suited for biological imaging applications. Their attachment to biomolecules in mild aqueous conditions for the design of bioconjugates is therefore highly desirable. 1,3-dipolar [3 + 2] cycloaddition between azides and terminal alkynes ("click chemistry") could represent an attractive QD functionalization method. Unfortunately, the use of the popular Cu(I)-catalyzed version of this reaction is not applicable for achieving this goal, since the presence of copper dramatically alters the luminescence properties of QD dispersions. We demonstrate here that copper-free click chemistry, between strained cyclooctyne functionalized QD and azido-biomolecules, leads to highly luminescent conjugates. In addition, we show that QD-cyclooctyne can be used at previously unreported low concentration (250 nM) for imaging the incorporation of azido-modified sialic acid in cell membrane glycoproteins.
Pose Estimation for Augmented Reality: A Hands-On Survey (2015)

Augmented reality (AR) allows to seamlessly insert virtual objects in an image sequence. In order to accomplish this goal, it is important that synthetic elements are rendered and aligned in the scene in an accurate and visually acceptable way. The solution of this problem can be related to a pose estimation or, equivalently, a camera localization process. This paper aims at presenting a brief but almost self-contented introduction to the most important approaches dedicated to vision-based camera localization along with a survey of several extension proposed in the recent years. For most of the presented approaches, we also provide links to code of short examples. This should allow readers to easily bridge the gap between theoretical aspects and practical implementations.
Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers (2017)

Immunotherapy induces durable responses in a subset of patients with cancer. High tumor mutational burden (TMB) may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non-small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. We reviewed data on 1,638 patients who had undergone comprehensive genomic profiling and had TMB assessment. Immunotherapy-treated patients (<i>N</i> = 151) were analyzed for response rate (RR), progression-free survival (PFS), and overall survival (OS). Higher TMB was independently associated with better outcome parameters (multivariable analysis). The RR for patients with high (≥20 mutations/mb) versus low to intermediate TMB was 22/38 (58%) versus 23/113 (20%; <i>P</i> = 0.0001); median PFS, 12.8 months vs. 3.3 months (<i>P</i> ≤ 0.0001); median OS, not reached versus 16.3 months (<i>P</i> = 0.0036). Results were similar when anti-PD-1/PD-L1 monotherapy was analyzed (<i>N</i> = 102 patients), with a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders versus nonresponders treated with anti-PD-1/PD-L1 monotherapy was 18.0 versus 5.0 mutations/mb (<i>P</i> < 0.0001). Interestingly, anti-CTLA4/anti-PD-1/PD-L1 combinations versus anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%; <i>P</i> = 0.004) and PFS (<i>P</i> = 0.024). Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. Benefit from dual checkpoint blockade did not show a similarly strong dependence on TMB. <i>Mol Cancer Ther; 16(11); 2598-608. ©2017 AACR</i>.
Therapy with GAD in diabetes (2009)

The enzyme glutamic acid decarboxylase (GAD) is of great importance for the neurotransmission in the central nervous system, and therefore of interest for treatment of pain and neurological disease. However, it is also released in pancreas although its role is not quite clear. GAD is a major auto-antigen in the process leading to type 1 diabetes with both a clear cell-mediated immune response to GAD and auto-antibodies to GAD (GADA), which can be used as a predictor of diabetes. Administration of the isoform GAD65 can prevent autoimmune destruction of pancreatic beta cells in non-obese diabetic (NOD) mice and the subsequent need for exogenous insulin replacement. In Phase I and II studies an alum-formulated vaccine (Diamyd) has shown to be safe, and in a dose-finding study in Latent Autoimmune Diabetes in Adults (LADA) patients 20-microg was given subcutaneously one month apart indicating preservation of residual insulin secretion. A double-blind randomized Phase II trial in 70 patients (10-18 years old) with recent-onset type 1 diabetes showed significant preservation of residual insulin secretion and a GAD-specific immune response, both humoral and cell-mediated, but no treatment-related adverse events. With this promising background further studies are on their way, both intervention in newly diagnosed type 1 diabetic patients, and trials to prevent the disease.
Elevation of free beta subunit of human choriogonadotropin and core beta fragment of human choriogonadotropin in the serum and urine of patients with malignant pancreatic and biliary disease. (1992)

Human choriogonadotropin (hCG), its free beta subunit (beta hCG), and the core beta hCG fragment (c beta hCG) were measured by highly sensitive time-resolved immunofluorometric assays in the serum and urine of 29 patients with pancreatic cancer, 7 patients with biliary cancer, and 45 patients with benign pancreatic or biliary diseases. The results were compared with those of an age- and sex-matched reference population of nonpregnant women and men. Of the various forms of hCG assayed in serum, beta hCG showed the best diagnostic accuracy, and c beta hCG was the best marker in urine. Elevated serum concentrations of beta hCG were observed in 72% of the patients with pancreatic cancer, in 6 of 7 patients with biliary cancer, and in 9% of those with benign disorders. The serum concentrations of c beta hCG were elevated in 45%, 57%, and 2%, respectively, and those in urine in 55%, 71%, and 11%, respectively. The molar concentrations of c beta hCG in serum were mostly lower than those of beta hCG. Thus beta hCG secreted into serum appears to be the main source of c beta hCG in urine. Provided that they are measured by sufficiently sensitive and specific assays, beta hCG in serum and c beta hCG in urine appear to be useful markers for pancreatic and biliary cancer.