gebhart/patrepeval huggingface dataset:
sst2 Somatostatin Receptor Mediates Cell Cycle Arrest and Induction of p27 (1999)

Activation of the somatostatin receptor sst2 inhibits cell proliferation by a mechanism involving the stimulation of the protein-tyrosine phosphatase SHP-1. The cell cycle regulatory events leading to sst2-mediated growth arrest are not known. Here, we report that treatment of Chinese hamster ovary cells expressing sst2 with the somatostatin analogue, RC-160, led to G1 cell cycle arrest and inhibition of insulin-induced S-phase entry through induction of the cyclin-dependent kinase inhibitor p27(Kip1). Consequently, a decrease of p27(Kip1)-cdk2 association, an inhibition of insulin-induced cyclin E-cdk2 kinase activity, and an accumulation of hypophosphorylated retinoblastoma gene product (Rb) were observed. However, RC-160 had no effect on the p21(Waf1/Cip1). When sst2 was coexpressed with a catalytically inactive mutant SHP-1 in Chinese hamster ovary cells, mutant SHP-1 induced entry into cell cycle and down-regulation of p27(Kip1) and prevented modulation by insulin and RC-160 of p27(Kip1) expression, p27(Kip1)-cdk2 association, cyclin E-cdk2 kinase activity, and the phosphorylation state of Rb. In mouse pancreatic acini, RC-160 reverted down-regulation of p27(Kip1) induced by a mitogen, and this effect did not occur in acini from viable motheaten (mev/mev) mice expressing a mutant SHP-1 with markedly deficient enzymes. These findings provide the first evidence that sst2 induces cell cycle arrest through the up-regulation of p27(Kip1) and demonstrate that SHP-1 is required for maintaining high inhibitory levels of p27(Kip1) and is a critical target of the insulin, and somatostatin signaling cascade, leading to the modulation of p27(Kip1).
Processing and function of CFTR-ΔF508 are species-dependent (2007)

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis. The most common mutation, a deletion of the phenylalanine at position 508 (DeltaF508), disrupts processing of the protein. Nearly all human CFTR-DeltaF508 is retained in the endoplasmic reticulum and degraded, preventing maturation to the plasma membrane. In addition, the F508 deletion reduces the activity of single CFTR channels. Human CFTR-DeltaF508 has been extensively studied to better understand its defects. Here, we adopted a cross-species comparative approach, examining human, pig, and mouse CFTR-DeltaF508. As with human CFTR-DeltaF508, the DeltaF508 mutation reduced the single-channel activity of the pig and mouse channels. However, the mutant pig and mouse proteins were at least partially processed like their wild-type counterparts. Moreover, pig and mouse CFTR-DeltaF508 partially restored transepithelial Cl(-) transport to CF airway epithelia. Our data, combined with earlier work, suggest that there is a gradient in the severity of the CFTR-DeltaF508 processing defect, with human more severe than pig or mouse. These findings may explain some previously puzzling observations in CF mice, they have important implications for evaluation of potential therapeutics, and they suggest new strategies for discovering the mechanisms that disrupt processing of human CFTR-DeltaF508.
An Augmented Reality System for Military Operations in Urban Terrain (2002)

The self-renewing cancer stem cells (CSCs) represent one of the distinct cell populations occurring in a tumour that can differentiate into multiple lineages. This group of sparsely abundant cells play a vital role in tumour survival and resistance to different treatments during cancer. The lack of exclusive markers associated with CSCs makes diagnosis and prognosis in cancer patients extremely difficult. This calls for the identification of unique regulators and markers for CSCs. Various signalling pathways like the Wnt/β-catenin pathway, Hedgehog pathway, Notch pathway, and TGFβ/BMP play a major role in the regulation and maintenance of CSCs. Epigenetic regulatory mechanisms add another layer of complexity to control these signalling pathways. In this chapter, we discuss about the role of epigenetic mechanisms in regulating the cellular signalling pathways in CSCs. The epigenetic regulatory mechanisms such as DNA methylation, histone modification and microRNAs can modulate the diverse effectors of signalling pathways and consequently the growth, differentiation and tumorigenicity of CSCs. In the end, we briefly discuss the therapeutic potential of targeting these epigenetic regulators and their target genes in CSCs.
A synthetic peptide corresponding to the NH2 terminus of vesicular stomatitis virus glycoprotein is a pH-dependent hemolysin. (1984)

The spike protein of vesicular stomatitis virus, G protein, is a 68,000-Da glycoprotein which mediates viral binding, membrane fusion, and hemolysis. In an attempt to define the protein domain involved in membrane destabilization and fusion, a 25-amino acid peptide corresponding to the NH2 terminus of G protein was synthesized. We show here that this peptide is a pH-dependent hemolysin and that the pH and temperature optima for hemolysis by peptide and virus are similar. Antiserum prepared against this peptide is nonneutralizing and nonreactive with native G protein. Antipeptide antibodies, however, do react with sodium dodecyl sulfate-denatured protein, suggesting that the G protein NH2 terminus is "masked" in the native protein. The hemolytic activity of the synthetic peptide may reflect an analogous function of the NH2 terminus of G protein.
Meta-analysis of Oncogenic Protein Kinase Cι Signaling in Lung Adenocarcinoma (2009)

Meta-analysis of public gene expression data are useful in identifying novel gene targets of oncogenic PKCiota signaling. Our data indicate that both common and cell type-specific signaling mechanisms contribute to PKCiota-dependent transformation.
Prediction of Gene Function in Methylthioadenosine Recycling from Regulatory Signals (2002)

The S-box transcription termination control system, first identified in Bacillus subtilis, is used for regulation of gene expression in response to methionine availability. The presence of the S-box motif provided the first indication that the ykrTS and ykrWXYZ genes could play a role in recycling of 5'-methylthioadenosine, a by-product of polyamine biosynthesis that can be converted to methionine. In this study we demonstrate a role for the ykrTS and ykrWXYZ gene products in this pathway.
L-Dopa− and Dopamine−(R)-α-Lipoic Acid Conjugates as Multifunctional Codrugs with Antioxidant Properties (2006)

A series of multifunctional codrugs (1−4), obtained by joining L-Dopa (LD) and dopamine (DA) with (R)-α-lipoic acid (LA), was synthesized and evaluated as potential codrugs with antioxidant and iron-chelating properties. These multifunctional molecules were synthesized to overcome the pro-oxidant effect associated with LD therapy. The physicochemical properties, together with the chemical and enzymatic stabilities of synthesized compounds, were evaluated in order to determine both their stability in aqueous medium and their sensitivity in undergoing enzymatic cleavage by rat and human plasma to regenerate the original drugs. The new compounds were tested for their radical scavenging activities, using a test involving the Fe (II)−H2O2-induced degradation of deoxyribose, and to evaluate peripheral markers of oxidative stress such as plasmatic activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the plasma. Furthermore, we showed the central effects of compounds 1 and 2 on spontaneous locomotor activity of rats in comparison with LD-treated animals. From the results obtained, compounds 1−4 appeared stable at a pH of 1.3 and in 7.4 buffered solution; in 80% human plasma they were turned into DA and LD. Codrugs 1−4 possess good lipophilicity (log P > 2 for all tested compounds). Compounds 1 and 2 seem to protect partially against the oxidative stress deriving from auto-oxidation and MAO-mediated metabolism of DA. This evidence, together with the “in vivo” dopaminergic activity and a sustained release of the parent drug in human plasma, allowed us to point out the potential advantages of using 1 and 2 rather than LD in treating pathologies such as Parkinson's disease, characterized by an evident decrease of DA concentration in the brain.
Real-time hand gesture recognition system based on Associative Processors (2009)

In this paper, a general-purpose similarity-measure recognition system using Associative Processor (AP) chips for real time hand gesture recognition is proposed. In order to get hand gesture feature vectors, the system adopts a vision-based hand tracking approach by using hand gesture segmentation algorithm. The system downloads those feature vectors data from large hand gesture feature vectors data base into the on-chip cache memory of an AP, then performs gestures matching in an extremely short time. Although gestures recognition processing is computationally very expensive by software, latency free recognition becomes possible due to the highly parallel maximum-likelihood matching architecture of the AP chip. In this study, we propose a solution about hand gestures recognition using large testing/training data and the hardware-accelerated matching architecture for human-computer interaction. Using a prototype AP chip implemented in field-programmable gate arrays (FPGA), the effectiveness of such application systems has been demonstrated.
Potential applications of hierarchical branching nanowires in solar energy conversion (2009)

Nanoscience and nanotechnology can provide many benefits to photovoltaic and photoelectrochemical applications by combining novel nanoscale properties with processability and low cost. Taking advantage of high quality, high efficiency, yet low cost nanomaterials could potentially provide the new and transformative approaches to enable the proposed generation-III solar technologies. Nanowires are interesting because they have a long axis to absorb incident sunlight yet with a short radial distance to separate the photogenerated carriers. In this perspective, we further suggest that more “complex” nanostructures, both in the form of hierarchically branching/hyperbranching nanowire structures and in the form of multi-component nanowire heterostructures of diverse materials, are potentially even more interesting for solar energy harvesting and conversion. The common bottom-up synthetic techniques to induce branching in nanowires to form hierarchical nanowire structures are reviewed. Several potential strategies for their incorporation into solar conversion devices are discussed and some fundamental issues and future directions are identified.
Induction chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by concurrent chemoradiotherapy for unresectable locally advanced head and neck cancer (2010)

This novel combined-modality treatment program, is toxic but feasible, and can be administered for selected patients with advanced and unresectable head and neck cancer. © 2010 Biomedical Imaging and Intervention Journal. All rights reserved.
Expression of B-myb in neuroblastoma tumors is a poor prognostic factor independent from MYCN amplification. (1999)

The transcription factors of the Myb family are expressed in several tissues and play an important role in cell proliferation, differentiation, and survival In this study, the expression of A-myb, B-myb, and c-myb was investigated in a group of 64 neuroblastomas at different dinical stages by a sensitive reverse transcription-PCR tchnique and correlated with patients' survival. All of the myb genes were frequently expressed in neuroblastoma tumors. Interestingly, the expression of B-myb, which was detected in 33 cases, was associated with an increased risk of death (P = 0.027 in a univariate analysis), whereas there was no correlation with A-myb and c-myb expression. In addition, in a multivariate Cox regression analysis that included myb gene expression, MYCN status, age at diagnosis, and tumor staging, MYCN amplification and B-myb expression were independently associated to an increased risk (P < 0.01 and P = 0.015, respectively). In overall survival curves obtained by stratifying the neuroblastoma cases on the basis of MYCN status and B-myb expression, the group of patients without MYCN amplification and positive for B-myb expression had worse survival probability than that without MYCN amplification and nonexpressing B-myb (P < 0.01). In summary, these findings provide the first demonstration that B-myb expression can be a useful prognostic marker in human neuroblastoma. Moreover, B-myb expression has a prognostic value complementary to MYCN amplification and can identify a group of high-risk patients that would not be predicted on the basis of the MYCN status only.
A New Fusion Gene TPM3-ALK in Anaplastic Large Cell Lymphoma Created by a (1;2)(q25;p23) Translocation (1999)

Anaplastic large cell lymphomas (ALCL) are frequently associated with the t(2;5)(p23;q35). This translocation fuses the nucleophosmin (NPM) gene at 5q35, which encodes a nucleolar protein involved in shuttling ribonucleoproteins from the cytoplasm to the nucleus, to the anaplastic lymphoma kinase (ALK) gene at 2p23, encoding a tyrosine kinase receptor. In this report, we describe a typical case of ALCL whose malignant cells exhibited a novel (1;2)(q25;p23) translocation. These cells expressed ALK protein, but, in contrast to t(2;5)-positive ALCL (which show cytoplasmic, nuclear, and nucleolar staining), labeling was restricted to the malignant cell cytoplasm. Using a polymerase chain reaction (PCR)-based technique to walk on chromosome 2 from the known ALK gene across the breakpoint, we showed that the gene involved at 1q25 is TPM3, encoding a nonmuscular tropomyosin. We subsequently identified, using reverse transcription-PCR analysis of cases showing similar ALK cytoplasm-restricted staining, fusion of the ALK and TPM3 genes in 2 other cases of ALCL. The TPM3 gene has been previously found in papillary thyroid carcinomas as a fusion partner with the TRK kinase gene. We showed that TPM3 is constitutively expressed in lymphoid cell lines, suggesting that, in these t(1;2)-bearing ALCL cases, the TPM3 gene contributes an active promoter for ALK expression. Activation of the ALK catalytic domain probably results from homodimerization of the hybrid protein TPM3-ALK, through the TPM3 protein-protein interaction domain. The present cases of ALCL associated with a novel t(1;2)(q25;p23) demonstrate that at least one fusion partner other than NPM can activate the intracytoplasmic domain of the ALK kinase.
Kinetics and Mechanism of 1,3‐Dipolar Cycloadditions (1963)

Abstract Criteria for the mechanism of 1,3‐dipolar cycloadditions which lead to 5‐membered rings are provided by the stereoselectivity observed with cis‐trans isomeric dipolarophiles, by the effect of solvent and substituents on the rate constants, by the activation parameters, and by orientation phenomena. A concerted addition, which can also be described in terms of molecular orbitals and in which the two new σ‐bonds are formed simultaneously, although not necessarily at equal rates, offers the best explanation of the experimental facts.
Orchestration of neuronal migration by activity of ion channels, neurotransmitter receptors, and intracellular Ca2+ fluctuations (1998)

The real-time observation of cell movement in acute cerebellar slices reveals that granule cells alter their shape concomitantly with changes in the mode and rate of migration as they traverse different cortical layers. Although the origin of local environmental cues responsible for these position-specific changes in migratory behavior remains unclear, several signaling mechanisms involved in controlling granule cell movement have emerged. The onset of one such mechanism is marked by the expression of voltage-gated ion channels and neurotransmitter receptors in postmitotic cells prior to the initiation of their migration. Granule cells start their radial migration after the expression of N-type Ca2+ channels and the N-methyl-D-aspartate subtype of glutamate receptors on the plasmalemmal surface. Blockade of the channel or receptor activity significantly decreases the rate of cell movement, indicating that the activation of these membrane constituents provides an essential signal for the translocation of granule cells. Another signal that controls the rate of cell migration is embedded in the combined amplitude and frequency components of Ca2+ fluctuations in the somata of migrating granule cells. Interestingly, each phase of Ca2+ fluctuation controls a separate phase of saltatory movement in the granule cells: The cells move forward during the phase of transient Ca2+ elevation and remain stationary during the troughs. Consequently, the changes in the amplitude and frequency components of Ca2+ fluctuations directly affect granule cell movement: Reducing the amplitude or frequency of Ca2+ fluctuations slows down the speed of cell movement, while the enhancement of these components accelerates migration. These findings suggest that signaling molecules present in the local cellular milieu encountered on the migratory route control the shape and motility of granule cells by modifying Ca2+ fluctuations in the soma through the activation of specific ion channels and neurotransmitter receptors.
Chemopreventive Agents Alters Global Gene Expression Pattern: Predicting their Mode of Action and Targets (2006)

Chemoprevention has the potential to be a major component of colon, breast, prostate and lung cancer control. Epidemiological, experimental, and clinical studies provide evidence that antioxidants, anti-inflammatory agents, n-3 polyunsaturated fatty acids and several other phytochemicals possess unique modes of action against cancer growth. However, the mode of action of several of these agents at the gene transcription level is not completely understood. Completion of the human genome sequence and the advent of DNA microarrays using cDNAs enhanced the detection and identification of hundreds of differentially expressed genes in response to anticancer drugs or chemopreventive agents. In this review, we are presenting an extensive analysis of the key findings from studies using potential chemopreventive agents on global gene expression patterns, which lead to the identification of cancer drug targets. The summary of the study reports discussed in this review explains the extent of gene alterations mediated by more than 20 compounds including antioxidants, fatty acids, NSAIDs, phytochemicals, retinoids, selenium, vitamins, aromatase inhibitor, lovastatin, oltipraz, salvicine, and zinc. The findings from these studies further reveal the utility of DNA microarray in characterizing and quantifying the differentially expressed genes that are possibly reprogrammed by the above agents against colon, breast, prostate, lung, liver, pancreatic and other cancer types. Phenolic antioxidant resveratrol found in berries and grapes inhibits the formation of prostate tumors by acting on the regulatory genes such as p53 while activating a cascade of genes involved in cell cycle and apoptosis including p300, Apaf-1, cdk inhibitor p21, p57 (KIP2), p53 induced Pig 7, Pig 8, Pig 10, cyclin D, DNA fragmentation factor 45. The group of genes significantly altered by selenium includes cyclin D1, cdk5, cdk4, cdk2, cdc25A and GADD 153. Vitamine D shows impact on p21(Waf1/Cip1) p27 cyclin B and cyclin A1. Genomic expression profile with vitamin D indicated differential expression of gene targets such as c-JUN, JUNB, JUND, FREAC-1/FoxF1, ZNF-44/KOX7, plectin, filamin, and keratin-13, involved in antiproliferative, differentiation pathways. The agent UBEIL has a remarkable effect on cyclin D1. Curcumin mediated NrF2 pathway significantly altered p21(Waf1/Cip1) levels. Aromatase inhibitors affected the expression of cyclin D1. Interestingly, few dietary compounds listed in this review also have effect on APC, cdk inhibitors p21(Waf1/Cip1) and p27. Tea polyphenol EGCG has a significant effect on TGF-beta expression, while several other earlier studies have shown its effect on cell cycle regulatory proteins. This review article reveals potential chemoprevention drug targets, which are mainly centered on cell cycle regulatory pathway genes in cancer.
Experience with ventriculo peritoneal shunts at the University of Nigeria Teaching Hospital, Enugu. (1995)

In a study of 212 children at the University of Nigeria Teaching Hospital, Enugu who received ventriculo peritoneal shunt for hydrocephalus over a 13-year period (1977-1989, 14 had infected shunts and one developed shunt nephritis. Staphylococcus aureus was responsible for 36.4% of the positive cultures and was responsible for the only case of shunt nephritis. This is about the fourth case of shunt nephritis associated with Staphylococcus aureus shunt infection, in the literature. The pertinent features of this case were intraventricular haemorrhage as the cause of the hydrocephalus, frequent revision of shunts before the onset of nephritis and full recovery following intravenous antibiotic therapy and reimplantation of a new shunt.
Overproduction of tyrosyl-tRNA synthetase is toxic to Escherichia coli: a genetic analysis (1990)

The tyrS genes from Escherichia coli and Bacillus stearothermophilus were toxic to E. coli when they were carried by plasmids with very high copy numbers (pEMBL8 and pEMBL9). We quantified this effect by comparing the efficiencies of plating of E. coli derivatives harboring recombinant plasmids in various experimental conditions. The toxicity was apparent at both 30 and 37 degrees C. It increased with the growth temperature, the strength of the tyrS promoter, and the copy number of the plasmidic vector. Two- to threefold enhancement of tyrS expression raised the toxicity 300-fold. Point mutations in tyrS that prevent interaction between its product, tyrosyl-tRNA synthetase, and tRNA(Tyr) but do not alter the rate of formation of tyrosyl-adenylate abolished the toxicity. Thus, the toxic effect was due to high cellular levels of synthetase activity. At 30 degrees C, the cellular concentration of tyrosyl-tRNA synthetase reached 55% of that of soluble proteins and led to decreased beta-galactosidase stability. We discuss possible causes of this toxic effect and describe its applications to the study of the recognition and interaction between the synthetase and tRNA(Tyr).
The Orthologous Human and Murine Semaphorin 6A-1 Proteins (SEMA6A-1/Sema6A-1) Bind to the Enabled/Vasodilator-stimulated Phosphoprotein-like Protein (EVL) via a Novel Carboxyl-terminal Zyxin-like Domain (2000)

Neuronal development and apoptosis critically depend on the transformation of extracellular signals to intracellular actions resulting in cytoskeletal rearrangements. Ena/VASP (enabled/vasodilator-stimulated phosphoprotein) proteins play an important role in actin and filament dynamics, whereas members of the semaphorin protein family are guidance signals in embryo- and organogenesis. Here, we report the identification of two novel transmembranous human and murine semaphorins, (HSA)SEMA6A-1 and (MMU)Sema6A-1. These semaphorin 6 variants directly link the Ena/VASP and the semaphorin protein family, since SEMA6A-1/Sema6A-1 is capable of a selective binding to the protein EVL (Ena/VASP-like protein). EVL is the third member of the Ena/VASP family of proteins that was identified sharing the same structural features as Mena (mammalian enabled) and VASP, although its functionality seems to be different from that of the other members. Here we demonstrate that SEMA6A-1/Sema6A-1 is colocalized with EVL via its zyxin-like carboxyl-terminal domain that contains a modified binding motif, which further stresses the existence of functional differences between EVL and Mena/VASP. In addition these findings suggest a completely new role for transmembranous semaphorins such as SEMA6A-1/Sema6A-1 in retrograde signaling.