gebhart/patrepeval huggingface dataset:
Peptide binding prediction for the human class II MHC allele HLA-DP2: a molecular docking approach (2011)

Abstract Background MHC class II proteins bind oligopeptide fragments derived from proteolysis of pathogen antigens, presenting them at the cell surface for recognition by CD4+ T cells. Human MHC class II alleles are grouped into three loci: HLA-DP, HLA-DQ and HLA-DR. In contrast to HLA-DR and HLA-DQ, HLA-DP proteins have not been studied extensively, as they have been viewed as less important in immune responses than DRs and DQs. However, it is now known that HLA-DP alleles are associated with many autoimmune diseases. Quite recently, the X-ray structure of the HLA-DP2 molecule (DPA*0103, DPB1*0201) in complex with a self-peptide derived from the HLA-DR α-chain has been determined. In the present study, we applied a validated molecular docking protocol to a library of 247 modelled peptide-DP2 complexes, seeking to assess the contribution made by each of the 20 naturally occurred amino acids at each of the nine binding core peptide positions and the four flanking residues (two on both sides). Results The free binding energies (FBEs) derived from the docking experiments were normalized on a position-dependent (npp) and on an overall basis (nap), and two docking score-based quantitative matrices (DS-QMs) were derived: QMnpp and QMnap. They reveal the amino acid preferences at each of the 13 positions considered in the study. Apart from the leading role of anchor positions p1 and p6, the binding to HLA-DP2 depends on the preferences at p2. No effect of the flanking residues was found on the peptide binding predictions to DP2, although all four of them show strong preferences for particular amino acids. The predictive ability of the DS-QMs was tested using a set of 457 known binders to HLA-DP2, originating from 24 proteins. The sensitivities of the predictions at five different thresholds (5%, 10%, 15%, 20% and 25%) were calculated and compared to the predictions made by the NetMHCII and IEDB servers. Analysis of the DS-QMs indicated an improvement in performance. Additionally, DS-QMs identified the binding cores of several known DP2 binders. Conclusions The molecular docking protocol, as applied to a combinatorial library of peptides, models the peptide-HLA-DP2 protein interaction effectively, generating reliable predictions in a quantitative assessment. The method is structure-based and does not require extensive experimental sequence-based data. Thus, it is universal and can be applied to model any peptide - protein interaction.
Transport of LDL-derived cholesterol from the NPC1 compartment to the ER involves the trans-Golgi network and the SNARE protein complex (2008)

Mammalian cells acquire cholesterol mainly from LDL. LDL enter the endosomes, allowing cholesteryl esters to be hydrolyzed by acid lipase. The hydrolyzed cholesterol (LDL-CHOL) enters the Niemann-Pick type C1 (NPC1)-containing endosomal compartment en route to various destinations. Whether the Golgi is involved in LDL-CHOL transport downstream of the NPC1 compartment has not been demonstrated. Using subcellular fractionation and immunoadsorption to enrich for specific membrane fractions, here we show that, when parental Chinese hamster ovary (CHO) cells are briefly exposed to (3)H-cholesteryl linoleate (CL) labeled-LDL, newly liberated (3)H-LDL-CHOL appears in membranes rich in trans-Golgi network (TGN) long before it becomes available for re-esterification at the endoplasmic reticulum (ER) or for efflux at the plasma membrane. In mutant cells lacking NPC1, the appearance of newly liberated (3)H-LDL-CHOL in the TGN-rich fractions is much reduced. We next report a reconstituted transport system that recapitulates the transport of LDL-CHOL to the TGN and to the ER. The transport system requires ATP and cytosolic factors and depends on functionality of NPC1. We demonstrate that knockdown by RNAi of 3 TGN-specific SNAREs (VAMP4, syntaxin 6, and syntaxin 16) reduces >/=50% of the LDL-CHOL transport in intact cells and in vitro. These results show that vesicular trafficking is involved in transporting a significant portion of LDL-CHOL from the NPC1-containing endosomal compartment to the TGN before its arrival at the ER.
Lysophospholipid Receptors (2001)

Lysophospholipids (LPs), including lysophosphatidic acid and sphingosine 1-phosphate, produce many cellular effects. However, the prolonged absence of any cloned and identified LP receptor has left open the question of how these lipids actually bring about these effects. The cloning and functional identification of the first LP receptor, lp(A1)/vzg-1, has led rapidly to the identification and classification of multiple orphan receptors/expression sequence tags known by many names (e.g. edg, mrec1.3, gpcr26, H218, AGR16, nrg-1) as members of a common cognate G protein-coupled receptor family. We review features of the LP receptor family, including molecular characteristics, genomics, signaling properties, and gene expression. A major question for which only partial answers are available concerns the biological significance of receptor-mediated LP signaling. Recent studies that demonstrate the role of receptor-mediated LP signaling in the nervous system, cardiovascular system, and other organ systems indicate the importance of this signaling in development, function, and pathophysiology and portend an exciting time ahead for this growing field.
Allosteric properties of hemoglobin and the plasma membrane of the erythrocyte: New insights in gas transport and metabolic modulation (2008)

Within the red blood cell the hemoglobin molecule is subjected to modulation mechanisms, namely homo- and heterotropic interactions, which optimize its functional behavior to the specific physiological requirements. At the cellular level, these modulation mechanisms are utilized to perform a number of other functions that are not minor with respect to the basic function of oxygen transport. Here we report some key examples concerning: (i) the interaction of hemoglobin with band 3 and its influence on glucose metabolism; (ii) the role of the ligand-linked quaternary transition of hemoglobin in the control of "NO bioactivity" and of gas diffusion; (iii) the interaction of plasma membrane with the various oxidative derivatives of the hemoglobin molecule.
Lactate dehydrogenase a in cancer: A promising target for diagnosis and therapy (2013)

One of the principal biochemical characteristics of malignant cells compared to normal cells is a metabolic switch from oxidative phosphorylation to increased glycolysis, even under hypoxic conditions, and is termed the Warburg effect. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. It is elevated in many types of cancers and has been linked to tumor growth, maintenance, and invasion; therefore, its inhibition may restrict the energy supply in tumors and thereby reduce the metastatic and invasive potential of cancer cells. This enzyme is receiving a great deal of attention as a potential diagnostic marker or a predictive biomarker for many types of cancer and as a therapeutic target for new anticancer treatments. In this review, we summarize the role of LDHA in cancer, discuss its potential significance in clinical diagnosis and prognosis of cancer, and propose LDHA as a novel target for the inhibition of tumor growth and invasiveness.
TAK1–TAB2 Signaling Contributes to Bone Destruction by Breast Carcinoma Cells (2011)

Advanced-stage breast cancers frequently metastasize to the bones and cause bone destruction, but the underlying mechanism is not fully understood. This study presents evidence that TGF-β-activated protein kinase 1 (TAK1) signaling in tumor cells promotes bone destruction by metastatic breast carcinoma cells, controlling expression of prometastatic factors including matrix metalloproteinase (MMP) 9 and COX2. Suppression of TAK1 signaling by dominant-negative TAK1 (dn-TAK1) in breast carcinoma MDA-MB-231 cells impairs bone colonization by carcinoma cells and bone osteolysis in the intracardiac injection model. Mechanistic studies showed that inhibition of TAK1 by dn-TAK1 or siRNA blocked expression of factors implicated in bone metastasis, such as MMP-9, COX2/PTGS2, parathyroid hormone-related protein (PTHrP) and interleukin 8 (IL-8), but did not affect activation of p38MAPK by TGF-β. TAK1 signaling is mediated by TAK1-binding partners TAB1, TAB2, and TAB3. Carcinoma cells express elevated mRNA levels of TAB2 and TAB3, whereas the TAB1 expression is noticeably low. Accordingly, depletion of TAB2 by siRNA reduced expression of MMP-9 and COX2. Together, these studies show that the TAK1-TAB2-TAB3 signaling axis is critical for carcinoma-induced bone lesions, mediating expression of proinvasive and osteolytic factors. These findings identify the TAK1-TAB2 axis as a potential therapeutic target in bone metastasis.
Coiled Tubing in Horizontal Wells (1988)

ABSTRACT Coiled tubing is an effective tool in logging and workover applications of horizontal wells. Several operators have taken advantage of using coiled tubing to log or perforate wells which could not have been performed with conventional wireline methods. Specialized surface and subsurface equipment has been developed to facilitate the use of wireline tools with coiled tubing. Production logging data, particularly multiphase flow testing, in horizontal wells have proved difficult to interpret. The use of coiled tubing packers and flow diverters to help isolate flow rates has improved production profile data. Coiled tubing has been used to selectively place stimulation fluids over long sections of horizontal hole, i.e., 1,200ft (366m) and greater. It has also been used in zone isolation, cement squeezing, and setting of bridge plugs. Several cases are presented where the use of coiled tubing eliminated or reduced conventional rig expense.
Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors (2013)

The adenosine 5'-triphosphate (ATP)-gated Ca(2+)-permeable channel P2X7 receptor (P2X7R) is strongly upregulated in many tumors and cancer cells, and has an important role in cancer cell invasion associated with metastases. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an anthraquinone derivative originally isolated from Rheum officinale Baill known for decades to possess anticancer properties. In this study, we examined the effects of emodin on P2X7R-dependent Ca(2+) signaling, extracellular matrix degradation, and in vitro and in vivo cancer cell invasiveness using highly aggressive human cancer cells. Inclusion of emodin at doses ≤10 µM in cell culture had no or very mild effect on the cell viability. ATP elicited increases in intracellular Ca(2+) concentration were reduced by 35 and 60% by 1 and 10 µM emodin, respectively. Emodin specifically inhibited P2X7R-mediated currents with an IC50 of 3 µM and did not inhibit the currents mediated by the other human P2X receptors heterologously expressed in human embryonic kidney (HEK293T) cells. ATP-induced increase in gelatinolytic activity, in cancer cell invasiveness in vitro and in cell morphology changes were prevented by 1 µM emodin. Furthermore, such ATP-evoked effects and inhibition by emodin were almost completely ablated in cancer cells transfected with P2X7R-specific small interfering RNA (siRNA) but not with scrambled siRNA. Finally, the in vivo invasiveness of the P2X7R-positive MDA-MB-435s breast cancer cells, assessed using a zebrafish model of micrometastases, was suppressed by 40 and 50% by 1 and 10 µM emodin. Taken together, these results provide consistent evidence to indicate that emodin inhibits human cancer cell invasiveness by specifically antagonizing the P2X7R.
Robots and manufacturing automation (1985)

From the Publisher:
Surveys the wide spectrum of automated systems available to improve manufacturing productivity including robots, numerical control machines, programmable controllers, computer controllers and microprocessor-based automated systems. Completely updated, it features industry case studies, revised and expanded problem sections and new material on product design, CAD, Karnaugh Maps and CIM.
Neuregulin in Cardiac Hypertrophy in Rats With Aortic Stenosis (1999)

The neuregulin receptors erbB2 and erbB4 are downregulated at both the message and protein levels at the stage of early failure in animals with chronic hypertrophy secondary to aortic stenosis. These data suggest a role for disabled erbB receptor signaling in the transition from compensatory hypertrophy to failure.
Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells (1995)

The BCR/ABL oncogenic tyrosine kinase is responsible for initiating and maintaining the leukemic phenotype of Philadelphia chromosome (Ph1)-positive cells. Phosphatidylinositol-3 (PI-3) kinase is known to interact with and be activated by receptor and nonreceptor tyrosine kinases. We investigated whether PI-3 kinase associates with and/or is regulated by BCR/ABL, whether this interaction is functionally significant for Ph1 cell proliferation, and, if so, whether inhibition of PI-3 kinase activity can be exploited to eliminate Ph1-positive cells from bone marrow. We show that the p85 alpha subunit of PI-3 kinase associates with BCR/ABL and that transient expression of BCR/ABL in fibroblasts and down-regulation of BCR/ABL expression using antisense oligodeoxynucleotides (ODNs) in Ph1 cells activates and inhibits, respectively, PI-3 kinase enzymatic activity. The use of specific ODNs or antisense constructs to downregulate p85 alpha expression showed a requirement for p85 alpha subunit in the proliferation of BCR/ABL-dependent cell lines and chronic myelogenous leukemia (CML) primary cells. Similarly, wortmannin, a specific inhibitor of the enzymatic activity of the p110 subunit of PI-3 kinase, inhibited growth of these cells. The growth of normal bone marrow and erythromyeloid, but not megakaryocyte, progenitors was inhibited by p85 alpha antisense [S]ODNs, but wortmannin, at the concentrations tested, did not affect normal hematopoiesis. The proliferation of two BCR/ABL- and growth factor-independent cell lines was not affected by downregulation of the expression of the p85 alpha subunit or inhibition of p110 enzymatic activity, confirming the specificity of the observed effects on Ph1 cells. Thus, PI-3 kinase is one of the downstream effectors of BCR/ABL tyrosine kinase in CML cells. Moreover, reverse transcriptase-polymerase chain reaction performed on single colonies to detect BCR-ABL transcripts showed that wortmannin was able to eliminate selectively CML-blast crisis cells from a mixture of normal bone marrow and Ph1 cells.
Novel Catalyst System for Treating Exhaust Gases from Internal Combustion and Stationary Source Engines (1993)

&lt;div class="htmlview paragraph"&gt;A major challenge facing the automotive industry today is substantially lower emissions from internal combustion engines. In the face of the 1990 Clean Air Act passed by the US Government, various approaches are being researched and developed to meet that challenge. A simple solution can result if one has available a high temperature stable catalyst system that can be installed close to the engine exhaust manifold. Such a simple catalyst system has been discovered&lt;sup&gt;(&lt;span class="xref"&gt;1&lt;/span&gt;)&lt;span class="xref"&gt;*&lt;/span&gt;&lt;/sup&gt; and is being developed for commercial use. This system is based on a thermodynamically stable, alpha-alumina monolith onto which are deposited noble metals. These alpha-alumina monoliths do not require a wash-coat. The noble metal loadings are typically equal to or less than those currently employed in commercial automotive catalysts. In standard engine dynamometer (V-8 Chevrolet, 350 CID, 5.7 liter) tests done at Southwest Research Institute, it has been demonstrated that these catalysts have equivalent initial performance for HC and CO combustion and NO&lt;sub&gt;x&lt;/sub&gt; reduction without the need for rhodium. However, they excel in superior high temperature stability, and a surprisingly excellent NO&lt;sub&gt;x&lt;/sub&gt; reduction activity equivalent to the commercial rhodium containing catalysts. This paper will highlight the results of catalyst performance testing and also show the ability of the new catalyst system to withstand greater than 1200°C (likely about 1400+°C) temperature experienced during engine misfire-conditions under which a commercial Honda Ac-&lt;/div&gt;
<title>New methods for detection, analysis, and isolation of rare cell populations</title> (1996)

New methods for flow cytometric detection, analysis and cell sorting of rare (< 0.001 percent) cell subpopulations have been developed. A 2-stage system of high-speed cell (and data) classification (U.S. Patent 5,204,884) allows first-stage cell classifications and error-Checking at rates in excess of 100 000 cells/sec. Multi-queuing, secondary-stage electronic processing on the basis of up to 11 parameters, including mathematical functions such as principal components calculated in real-time using lookup tables, allows for reduction of false-positive cells multiply-labeled with positive- and negative-selection fluorescent markers. This has allowed detection of rare cell subpopulations with frequencies below 10<SUP>-6</SUP>. Special "flexible sorting" hardware and software (U.S. Patent 5,199,576) permits sorting of cell subpopulations on the basis of mathematical algorithms which are not limited to conventional rectilinear or bitmap sort boundaries. Both high-speed enrichment sorting of live cells and high-resolution sorting for single-cell molecular characterizations are supported. New sampling statistics software allows for prediction of required sorting times for rare cell subpopulations. Home-built "bridging" software facilitates analysis of rare cells by a number of home-built (e.g. PC/Biplot) and commercial software packages (e.g. S-Plus for Windows). 3D stereo visualization and interactive software provide viewing of three raw and/or mathematically transformed or constructed data parameters, to aid in subsequent selection of optimal sort criteria. Special software has been developed for improved data analysis and selection of sort boundaries through the use of cell classification-tagged listmode data mixtures. This permits comparison of different classification algorithms (e.g. cluster analysis, neural networks, or recursive partitioning) for rare cells.
Cell cycle regulation of human DNA repair and chromatin remodeling genes (2015)

Maintenance of a genome requires DNA repair integrated with chromatin remodeling. We have analyzed six transcriptome data sets and one data set on translational regulation of known DNA repair and remodeling genes in synchronized human cells. These data are available through our new database: www.dnarepairgenes.com. Genes that have similar transcription profiles in at least two of our data sets generally agree well with known protein profiles. In brief, long patch base excision repair (BER) is enriched for S phase genes, whereas short patch BER uses genes essentially equally expressed in all cell cycle phases. Furthermore, most genes related to DNA mismatch repair, Fanconi anemia and homologous recombination have their highest expression in the S phase. In contrast, genes specific for direct repair, nucleotide excision repair, as well as non-homologous end joining do not show cell cycle-related expression. Cell cycle regulated chromatin remodeling genes were most frequently confined to G1/S and S. These include e.g. genes for chromatin assembly factor 1 (CAF-1) major subunits CHAF1A and CHAF1B; the putative helicases HELLS and ATAD2 that both co-activate E2F transcription factors central in G1/S-transition and recruit DNA repair and chromatin-modifying proteins and DNA double strand break repair proteins; and RAD54L and RAD54B involved in double strand break repair. TOP2A was consistently most highly expressed in G2, but also expressed in late S phase, supporting a role in regulating entry into mitosis. Translational regulation complements transcriptional regulation and appears to be a relatively common cell cycle regulatory mechanism for DNA repair genes. Our results identify cell cycle phases in which different pathways have highest activity, and demonstrate that periodically expressed genes in a pathway are frequently co-expressed. Furthermore, the data suggest that S phase expression and over-expression of some multifunctional chromatin remodeling proteins may set up feedback loops driving cancer cell proliferation.
Seismic Stratigraphy and Global Changes of Sea Level, Part 2<subtitle>The Depositional Sequence as a Basic Unit for Stratigraphic Analysis<xref ref-type="fn" rid="ch03-2fn1"><sup>1</sup></xref></subtitle> (1977)

Papers from a research symposium at the 1975 American Association of Petroleum Geologists and supplemented by later reports became “Seismic Stratigraphy Applications to Hydrocarbon Exploration”, one of AAPG’s best-selling book publications. Dramatic improvements in seismic imaging were demonstrated, a result of developments in seismic data quality and the processing capability of electronic technology. Twenty-eight articles are grouped into three sections. The first describes principles that both permit and also limit interpretations. The second section presents sixteen articles that describe the qualitative approach to stratigraphic interpretations of reflection records, and the final section presents techniques and examples of modeling. Of particular interest are a series of eleven papers in the second section under the subject heading of “Seismic stratigraphy and global changes of sea level”. Prepared by P. R. Vail, R. M. Mitchum and others from Exxon, they describe the regional unconformities and stratigraphic changes resulting from sea level fluctuations, and the manner in which these changes can be interpreted from seismic surveys. For many individuals within the oil industry who purchased this book, it was their first introduction to the modern concept of sequence stratigraphy that would have a major impact on the methodology of petroleum exploration.
Electrospun Silk Fibroin Nanofiber Tubes for Peripheral Nerve Regeneration (2010)

Silk fibroin (SF) has been extensively studied for application in wound dressing, bone, vessel and nerve regeneration. We have previously reported on good in vitro biocompatibility of SF nanofibers with neuronal cell. In the present study, we prepared SF nanofiber-based artificial nerve conduit to bridge 10mm long sciatic nerve defect of rats. We evaluated the peripheral nerve regeneration outcome by a combination of electrophysiological assessment, the percentage of wet weight loss of tibialis anterior muscle and histological investigation. These results showed that SF nanofibrous conduit could promote peripheral nerve regeneration and would be a promising alternative to nerve autografts, especially TSF nanofibrous conduit.
Cyclic ADP-Ribose Analogues Containing the Methylenebisphosphonate Linkage:  Effect of Pyrophosphate Modifications on Ca2+ Release Activity (2005)

Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate linkage in the place of the pyrophosphate have been synthesized from nicotinamide adenine dinucleotide analogues enzymatically using Aplysia californica ADP-ribosyl cyclase. Methylenebisphosphonate cyclic ADP-ribose (cADPR[CH(2)]) and methylenebisphosphonate cyclic 3-deaza-ADP-ribose (3-deaza-cADPR[CH(2)]) showed full agonist activity for release of Ca(2+) ions from sea urchin egg homogenates. The EC(50) for cADPR[CH(2)] was 856 nM and that for 3-deaza-cADPR[CH(2)] was 300 nM, about 15- and 5-fold less potent than cADPR, respectively.