gebhart/patrepeval huggingface dataset:
Structure and function of SH2 domains (1994)

In order for cells to respond to their environment, a series of regulated molecular events has to take place. External signalling molecules bind to cellular receptors and thereby trigger the activation of multiple intracellular pathways, which modify cellular phenotypes. The cell-surface receptors for a wide range of polypeptide hormones possess protein tyrosine kinase activity, which is induced by binding of the appropriate extracellular ligand. Tyrosine phosphorylation can act as a molecular switch, by initiating the recruitment of cytoplasmic effector molecules containing Src homology (SH) 2 domains, to activated receptors. These SH2-containing proteins, in turn, regulate intracellular signalling pathways. Here, we discuss the role of tyrosine phosphorylation in triggering signalling pathways, as well as the functions of SH2 domains, which mediate these events through phosphotyrosine-dependent protein-protein interactions.
Enhanced AODV Routing Protocol with Paging in Heterogeneous IP-Based Networks (2010)

As wireless IP-based networks become more popular and larger in size and coverage, simple mobility management protocols cannot deal with the demands. With the growing access to the Internet, mobility can be divided into macro/micro-mobility domains. Macro-mobility can be efficiently handled with Mobile IP and its derivatives but they do not scale that well for the micro-mobility case. An alternative for micro-mobility domains is to use a reactive route discovery mechanism. Ad-hoc routing protocols such as DSR and AODV are the well known protocols that can be used for this purpose. The disadvantage of the reactive approach is that the route discovery process becomes costly in terms of control overhead and latency of the connection setup when done frequently. In this paper, an optimization of the simple AODV route discovery is proposed, introducing a paging extension. The proposed mechanism is somewhat similar to other paging schemes like Cellular IP, but introduces modifications and enhancements for reducing the paging control overhead. Simulation results of AODV and the enhanced route discovery with paging are presented along with the performance evaluation of both schemes. The simulations were performed with the QualNet Network Simulator.
A Novel Cobra Venom Metalloproteinase, Mocarhagin, Cleaves a 10-Amino Acid Peptide from the Mature N Terminus of P-selectin Glycoprotein Ligand Receptor, PSGL-1, and Abolishes P-selectin Binding (1995)

Initial rolling of circulating neutrophils on a blood vessel wall prior to adhesion and transmigration to damaged tissue is dependent upon P-selectin expressed on endothelial cells and its specific neutrophil receptor, the P-selectin glycoprotein ligand-1 (PSGL-1). Pretreatment of neutrophils, HL60 cells, or a recombinant fucosylated soluble form of PSGL-1 (sPSGL-1.T7) with the cobra venom metalloproteinase, mocarhagin, completely abolished binding to purified P-selectin in a time-dependent and EDTA- and diisopropyl fluorophosphate-inhibitable manner consistent with mocarhagin selectively cleaving PSGL-1. A polyclonal antibody against the N-terminal peptide Gln-1-Glu-15 of mature PSGL-1 immunoprecipitated sPSGL-1.T7 but not sPSGL-1.T7 treated with mocarhagin, indicating that the mocarhagin cleavage site was near the N terminus. A single mocarhagin cleavage site between Tyr-10 and Asp-11 of mature PSGL-1 was determined by N-terminal sequencing of mocarhagin fragments of sPSGL-1.T7 and is within a highly negatively charged amino acid sequence 1-QATEYEYLDY decreases DFLPETEPPE, containing three tyrosine residues that are consensus sulfation sites. Consistent with a functional role of this region of PSGL-1 in binding P-selectin, an affinity-purified polyclonal antibody against residues Gln-1-Glu-15 of PSGL-1 strongly inhibited P-selectin binding to neutrophils, whereas an antibody against residues Asp-9-Arg-23 was noninhibitory. These combined data strongly suggest that the N-terminal anionic/sulfated tyrosine motif of PSGL-1 as well as downstream sialylated carbohydrate is essential for binding of P-selectin by neutrophils.
The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer (2001)

Expression of vascular endothelial growth factor (VEGF)-C and that of its receptors were assessed in non-small cell lung cancer. Immunohistochemistry revealed positive VEGF-C expression in 38.7% (24/62) of the patients studied. A significant positive correlation was found between VEGF-C in cancer cells and VEGF receptor-3 (VEGFR-3) in vascular endothelial cells, but not between VEGF-C in cancer cells and VEGFR-2 in endothelial cells. In this cohort of lung cancer patients, VEGF-C expression was significantly associated with lymph node metastasis, lymphatic vessel invasion, and worse outcomes after the operation. Although the independent prognostic impact of VEGF-C and VEGFR-3 was not clear, VEGFR-2 expression in endothelial cells retained the independency as the prognostic indicator. In light of these findings, we conclude that VEGF-C plays an important role in lymphatic invasion/metastasis and tumour progression in non-small cell lung cancer.
Simple bioconjugate chemistry serves great clinical advances: albumin as a versatile platform for diagnosis and precision therapy (2016)

Albumin is the most abundant circulating protein in plasma and has recently emerged as a versatile protein carrier for drug targeting and for improving the pharmacokinetic profile of peptide or protein based drugs. Three drug delivery technologies related to albumin have been developed, which include the coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugating bioactive proteins by albumin fusion technology (AFT), and encapsulation of drugs into albumin nanoparticles. This review article starts with a brief introduction of human serum albumin (HSA), and then summarizes the mainstream chemical strategies of developing HSA binding molecules for coupling with drug molecules. Moreover, we also concisely condense the recent progress of the most important clinical applications of HSA-binding platforms, and specify the current challenges that need to be met for a bright future of HSA-binding.
Factor H and Atypical Hemolytic Uremic Syndrome (2005)

Atypical hemolytic uremic syndrome is a disease that is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations in the complement regulator factor H are associated with the inherited form of the disease, and >60% of the mutations are located within the C terminus of factor H. The C-terminus of factor H, represented by short consensus repeat 19 (SCR19) and SCR20, harbors multiple functions; consequently, this study aimed to examine the functional effects of clinically reported mutations in these SCR. Mutant factor H proteins (W1157R, W1183L, V1197A, R1210C, R1215G, and P1226S) were recombinantly expressed and functionally characterized. All six mutant proteins showed severely reduced heparin, C3b, C3d, and endothelial cell binding. By peptide spot analyses, four linear regions that are involved in heparin, C3b, and C3d binding were localized in SCR19 and SCR20. A three-dimensional homology model of the two domains suggests that these four regions form a common binding site across both domains. In addition, this structural model identifies two types of residues: Type A residues are positioned on the SCR surface and are represented by mutants W1157R, W1183L, R1210C, and R1215G; and type B residues are buried within the SCR structure and affect mutations V1197A and P1226S. Mutations of both types of residue result in the same functional defects, namely the reduced binding of factor H to surface-attached C3b molecules and reduced complement regulatory activity at the cell surfaces. The buried type B mutations seem to affect ligand interaction of factor H more severely than the surface-exposed mutations.
Cytokeratin 20, 34betaE12 and overexpression of HER-2/neu in urine cytology as predictors of recurrences in superficial urothelial carcinoma. (2005)

There were investigated 80 patients with superficial urothelial carcinoma of the urinary bladder (Ta and T1). All cases had a minimum follow-up of 36 months. Patients were selected in order to form two subgroups. The first group (n = 28) had no recurrence during the follow-up, and in the second (n = 52) each patient had a minimum of two recurrences. The pathologic diagnosis was performed on archive slides stained with haematoxylin-eosin. Archive smears performed at the moment of the primary diagnosis from voided urine were discolored, and used for immunocytochemistry. It was investigated the expression of cytokeratin 20, high molecular weight cytokeratin 34betaE12, and overexpression of HER-2/neu protein. Microwave antigen retrieval was performed in all immunocytochemical procedures. The working system was LSAB2 and EnVision, and diaminobenzidine was used as chromogen. The initial conventional cytology was positive for malignant cells in all cases. Cytokeratin 20 was positive in 92.85% of cases without recurrences, and in 94.23% of cases with recurrences. High molecular weight cytokeratin was expressed in 42.85% of cases without recurrence and in 63.46% of patients with recurrences. The overexpression of HER-2/neu protein was found in 7.14% of cases of the first group, and in 84.61% of cases of the second group. Our results support the idea that HER-2/neu and high molecular weight cytokeratin may be used as markers to predict recurrence in superficial urothelial carcinoma.
Multi-frame coding of LPC parameters at 600-800 bps (1991)

Pitch-excited linear predictive coding (LPC) is widely used to code speech at 2400 b/s. The authors describe a method of coding LPC parameters which reduces the required channel bandwidth from 2400 b/s to 600-800 b/s. This method uses a split vector quantizer to code spectral parameters at 18 to 22 b/frame without excessive memory requirements. It also exploits interframe redundancy by block coding the pitch, voicing, and energy parameters, and by selectively interpolating the spectral parameters. When operating at less than 700 b/s, the system achieved as core of 90 for a three-male-speaker DRT (diagnostic rhyme test).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Illumination invariant object recognition (2002)

Varying illumination is severe problem for existing face recognition algorithms. Altering the light direction from left to right, for example, causes a change of contrast in large face regions and causes most face recognition algorithms to fail. Theoretical results, based on the law of incoherent light superposition, provide the solid ground on which a new illumination invariant recognition algorithm is derived. A face recognition experiment demonstrates that this algorithm indeed shows improved recognition performance even if the conditions, for which the theoretical results were derived, do not hold exactly.
Detecting human faces in color images (2002)

We propose a new method to detect human faces in color images. A human skin color model is built to capture the chromatic properties based on multivariate statistical analysis. Given a color image, multiscale segmentation is used to generate homogeneous regions at multiple different scales. From the coarsest to the finest scale, regions of skin color are merged until the shape is approximately elliptic. Postprocessing is performed to determine whether a merged region contains a human face and include the facial features of non-skin color such as eyes and mouth if necessary. Experimental results show that human faces in color images can be detected regardless of size, orientation and viewpoint.
Structural and functional analysis of a cloned segment of Escherichia coli DNA that specifies proteins of a C4 pathway of serine biosynthesis (1987)

The plasmid pDR121 is a pBR322 derivative that contains a 3.7-kilobase-pair EcoRI fragment of DNA from the 81.2-min region of the Escherichia coli chromosome. The genomic insert encodes threonine dehydrogenase and at least one other protein. Several physical and kinetic properties of threonine dehydrogenase, overproduced in cells harboring pDR121, are identical to those of pure threonine dehydrogenase from a haploid mutant of E. coli K-12 that produces this enzyme constitutively. Tester strains with serB or glyA mutations harboring pDR121 are prototrophs. The ability to confer prototrophy on such tester strains is associated with elevated levels of threonine dehydrogenase. The functional roles of various segments of the 3.7-kilobase-pair insert of pDR121 were analyzed by constructing specific deletions and insertions. Certain subclones retained the ability to specify threonine dehydrogenase without conferring prototrophy on tester strains. This suggests that at least one other protein encoded within pDR121 plays an essential role in the conversion of threonine to serine.
Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy. (1993)

Up-regulation of maternal islet function is essential to accommodate the increased demand for insulin during pregnancy. Previously, we suggested that lactogenic activity regulates islet function during pregnancy. However, this hypothesis was based on the effect of homologous PRLs on islets, since the homologous placental lactogens (or islets) were unavailable. In this study we examine the direct effects of homologous placental lactogens (PL), PRL, and GH on insulin secretion and B-cell division in rat, mouse, and human islets in vitro. Neonatal rat islets were cultured for 8 days in the presence of 0-1000 ng/ml rat PL-I (rPL-I), rPRL, or rGH. Media were changed daily, and the insulin concentration was determined. rPL-I and rPRL (500 ng/ml) treatment resulted in a 2-fold increase in insulin secretion. rGH (1000 ng/ml) elicited a 30% increase in insulin secretion. Similarly, cell replication, as indicated by BrdU incorporation into B-cells, was increased 4-fold in the presence of rPL-I and rPRL. The ED50 for insulin secretion and 5'-bromo-2'-deoxyuridine (BrdU) incorporation was 70 ng/ml for rPL-I and 150 ng/ml for rPRL. Similarly, in adult rat islets, insulin secretion was increased 1.6-fold, and B-cell replication increased 3-fold in the presence of the lactogenic hormones. Neonatal mouse islets were cultured for 8 days in the presence of 500 ng/ml mouse (m) PL-I, mPL-II, mPRL, or mGH. mPL-I, mPL-II, and mPRL treatment resulted in a 2-fold increase in insulin secretion. mGH elicited a 30% increase in insulin secretion. BrdU incorporation into B-cells was increased 3-fold in the presence of mPL-I and mPRL and 2-fold in the presence of mPL-II. Adult human islets were cultured for 8 days in the presence of 1 microgram/ml human (h) PL, hPRL, or hGH. For human islets isolated from six pancreata obtained from females, hPL (138 +/- 10%), hPRL (133 +/- 9%), and hGH (117 +/- 3%) significantly increased insulin secretion compared to that from control islets. This study compares the direct effects among homologous PLs, PRLs, and GHs on insulin secretion and B-cell division in rat, mouse, and human islets. The results indicate that placental lactogen directly regulates islet function in several species and is probably the principal hormone responsible for the increased islet function observed during normal pregnancy.
The pattern of gene expression in human CD34 + stem/progenitor cells (2001)

We have analyzed the pattern of gene expression in human primary CD34(+) stem/progenitor cells. We identified 42,399 unique serial analysis of gene expression (SAGE) tags among 106,021 SAGE tags collected from 2.5 x 10(6) CD34(+) cells purified from bone marrow. Of these unique SAGE tags, 21,546 matched known expressed sequences, including 3,687 known genes, and 20,854 were novel without a match. The SAGE tags that matched known sequences tended to be at higher levels, whereas the novel SAGE tags tended to be at lower levels. By using the generation of longer sequences from SAGE tags for gene identification (GLGI) method, we identified the correct gene for 385 of 440 high-copy SAGE tags that matched multiple genes and we generated 198 novel 3' expressed sequence tags from 138 high-copy novel SAGE tags. We observed that many different SAGE tags were derived from the same genes, reflecting the high heterogeneity of the 3' untranslated region in the expressed genes. We compared the quantitative relationship for genes known to be important in hematopoiesis. The qualitative identification and quantitative measure for each known gene, expressed sequence tag, and novel SAGE tag provide a base for studying normal gene expression in hematopoietic stem/progenitor cells and for studying abnormal gene expression in hematopoietic diseases.
Response mechanism of nematic liquid crystals using the in-plane switching mode (1996)

A response mechanism of nematic liquid crystals following the switching-on and off of an in-plane electric field when using the in-plane switching (IPS) mode was investigated. Simplified theoretical expressions, which were derived with an assumption that an in-plane electric field was applied to the liquid crystals, were used to explain the dynamical switching process in the IPS mode. In particular, the relaxation time of the liquid crystals when removing the electric field was described as a proportional relationship to the square of the cell gap. A thinner cell gap also proved to be effective in obtaining a fast response time in the IPS mode. By contrast, the switching-on time when applying the in-plane electric field proved to be inversely proportional to the difference between the square of the electric field strength and the square of the critical electric field strength at which the liquid crystals begin to deform.
Multiple K-ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique. (1991)

By using a modified polymerase chain reaction strategy, we have devised an approach to detect a K-ras oncogene mutated at codon 12 in the presence of 1000 normal alleles. This is a considerable improvement in sensitivity on previous assays. Application of this assay to 15 cholangiocarcinomas showed that all contained a K-ras mutation to codon 12 and that nine of the tumors contained two or more mutations. In 11 cases, mutations were present in less than 10% of the cells in the sample. In common with pancreatic adenocarcinomas, in which 75 to 95% of cases contain a mutation in K-ras, cholangiocarcinomas show a very high frequency of ras gene mutation, but within a tumor only a fraction of cells contain a ras mutation. The presence of multiple mutations and the low frequency of mutant alleles in the samples argue against K-ras mutations being the initiating genetic lesion in this tumor, but suggest that ras gene mutation is involved in the stepwise progression of neoplastic cells to full malignancy.
The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (2001)

During the last 2 years, several novel genes that encode glucose transporter-like proteins have been identified and characterized. Because of their sequence similarity with GLUT1, these genes appear to belong to the family of solute carriers 2A (SLC2A, protein symbol GLUT). Sequence comparisons of all 13 family members allow the definition of characteristic sugar/polyol transporter signatures: (1) the presence of 12 membrane-spanning helices, (2) seven conserved glycine residues in the helices, (3) several basic and acidic residues at the intracellular surface of the proteins, (4) two conserved tryptophan residues, and (5) two conserved tyrosine residues. On the basis of sequence similarities and characteristic elements, the extended GLUT family can be divided into three subfamilies, namely class I (the previously known glucose transporters GLUT1-4), class II (the previously known fructose transporter GLUT5, the GLUT7, GLUT9 and GLUT11), and class III (GLUT6, 8, 10, 12, and the myo-inositol transporter HMIT1). Functional characteristics have been reported for some of the novel GLUTs. Like GLUT1-4, they exhibit a tissue/cell-specific expression (GLUT6, leukocytes, brain; GLUT8, testis, blastocysts, brain, muscle, adipocytes; GLUT9, liver, kidney; GLUT10, liver, pancreas; GLUT11, heart, skeletal muscle). GLUT6 and GLUT8 appear to be regulated by sub-cellular redistribution, because they are targeted to intra-cellular compartments by dileucine motifs in a dynamin dependent manner. Sugar transport has been reported for GLUT6, 8, and 11; HMIT1 has been shown to be a H+/myo-inositol co-transporter. Thus, the members of the extended GLUT family exhibit a surprisingly diverse substrate specificity, and the definition of sequence elements determining this substrate specificity will require a full functional characterization of all members.
The IMiDs targets IKZF-1/3 and IRF4 as novel negative regulators of NK cell-activating ligands expression in multiple myeloma (2015)

Immunomodulatory drugs (IMiDs) have potent anti-tumor activities in multiple myeloma (MM) and are able to enhance the cytotoxic function of natural killer (NK) cells, important effectors of the immune response against MM. Here, we show that these drugs can enhance the expression of the NKG2D and DNAM-1 activating receptor ligands MICA and PVR/CD155 in human MM cell lines and primary malignant plasma cells. Depletion of cereblon (CRBN) by shRNA interference strongly impaired upregulation of these ligands and, more interestingly, IMiDs/CRBN-mediated downregulation of the transcription factors Ikaros (IKZF1), Aiolos (IKZF3) and IRF4 was critical for these regulatory mechanisms. Indeed, shRNA knockdown of IKZF1 or IKZF3 expression was both necessary and sufficient for the upregulation of MICA and PVR/CD155 expression, suggesting that these transcription factors can repress these genes; accordingly, the direct interaction and the negative role of IKZF1 and IKZF3 proteins on MICA and PVR/CD155 promoters were demonstrated. Finally, MICA expression was enhanced in IRF4-silenced cells, indicating a specific suppressive role of this transcription factor on MICA gene expression in MM cells.Taken together, these findings describe novel molecular pathways involved in the regulation of MICA and PVR/CD155 gene expression and identify the transcription factors IKZF-1/IKZF-3 and IRF4 as repressors of these genes in MM cells.
Using relational knowledge discovery to prevent securities fraud (2005)

We describe an application of relational knowledge discovery to a key regulatory mission of the National Association of Securities Dealers (NASD). NASD is the world's largest private-sector securities regulator, with responsibility for preventing and discovering misconduct among securities brokers. Our goal was to help focus NASD's limited regulatory resources on the brokers who are most likely to engage in securities violations. Using statistical relational learning algorithms, we developed models that rank brokers with respect to the probability that they would commit a serious violation of securities regulations in the near future. Our models incorporate organizational relationships among brokers (e.g., past coworker), which domain experts consider important but have not been easily used before now. The learned models were subjected to an extensive evaluation using more than 18 months of data unseen by the model developers and comprising over two person weeks of effort by NASD staff. Model predictions were found to correlate highly with the subjective evaluations of experienced NASD examiners. Furthermore, in all performance measures, our models performed as well as or better than the handcrafted rules that are currently in use at NASD.