gebhart/patrepeval huggingface dataset:
The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin (2005)

Scribble (Scrib) is a conserved polarity protein required in Drosophila melanogaster for synaptic function, neuroblast differentiation, and epithelial polarization. It is also a tumor suppressor. In rodents, Scrib has been implicated in receptor recycling and planar polarity but not in apical/basal polarity. We now show that knockdown of Scrib disrupts adhesion between Madin-Darby canine kidney epithelial cells. As a consequence, the cells acquire a mesenchymal appearance, migrate more rapidly, and lose directionality. Although tight junction assembly is delayed, confluent monolayers remain polarized. These effects are independent of Rac activation or Scrib binding to betaPIX. Rather, Scrib depletion disrupts E-cadherin-mediated cell-cell adhesion. The changes in morphology and migration are phenocopied by E-cadherin knockdown. Adhesion is partially rescued by expression of an E-cadherin-alpha-catenin fusion protein but not by E-cadherin-green fluorescent protein. These results suggest that Scrib stabilizes the coupling between E-cadherin and the catenins and are consistent with the idea that mammalian Scrib could behave as a tumor suppressor by regulating epithelial cell adhesion and migration.
Argon plasma coagulation. (2008)

Argon Plasma Coagulation (APC) is an application of gas discharges in argon in electrosurgery, which is increasingly used especially in endoscopy. The major application fields are haemostasis, tissue devitalization and tissue reduction.This review describes the physics and technology of electrosurgery and APC. Some characteristics of the argon discharge are shown and discussed, and thermal effects in biological tissue are described. Subsequently, examples of medical applications are given.
A highly specific l -galactose-1-phosphate phosphatase on the path to ascorbate biosynthesis (2004)

Ascorbate is a critical compound in plants and animals. Humans are unable to synthesize ascorbate, and their main source of this essential vitamin are plants. However, the pathway of synthesis in plants is yet to be established, and several unknown enzymes are only postulated to exist. We describe a specific L-galactose-1-phosphate (L-gal-1-P) phosphatase that we partially purified from young kiwifruit (Actinidia deliciosa) berries. The enzyme had a native molecular mass of approximately 65 kDa, was completely dependent on Mg2+ for activity and was very specific in its ability to hydrolyze L-gal-1-P. The activity had a pH optimum of 7.0, a K(-M(L-gal-1-P) of 20-40 microM and a Ka(Mg2+) of 0.2 mM. The activity was inhibited by Mg2+ at concentrations >2 mM. The enzyme from Arabidopsis thaliana shoots showed similar properties to the kiwifruit enzyme. The Arabidopsis thaliana enzyme preparation was digested with trypsin, and proteins present were identified by using liquid chromatography-MS. One of 24 proteins present in our preparation was an Arabidopsis thaliana protein, At3g02870, annotated myo-inositol-1-phosphate phosphatase in GenBank, that matched the characteristics of the purified l-gal-1-phosphate phosphatase. We then expressed a kiwifruit homologue of this gene in Escherichia coli and found that it showed 14-fold higher maximum velocity for l-gal-1-P than myo-inositol-1-P. The expressed enzyme showed very similar properties to the enzyme purified from kiwifruit and Arabidopsis, except that its KM(L-gal-1-P) and Ka(Mg2+) were higher in the expressed enzyme. The data are discussed in terms of the pathway to ascorbate biosynthesis in plants.
5‐Enolpyruvylshikimate‐3‐phosphate synthase from Staphylococcus aureus is insensitive to glyphosate (2005)

The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes the penultimate step of the shikimate pathway, and is the target of the broad-spectrum herbicide glyphosate. Kinetic analysis of the cloned EPSPS from Staphylococcus aureus revealed that this enzyme exerts a high tolerance to glyphosate, while maintaining a high affinity for its substrate phosphoenolpyruvate. Enzymatic activity is markedly influenced by monovalent cations such as potassium or ammonium, which is due to an increase in catalytic turnover. However, insensitivity to glyphosate appears to be independent from the presence of cations. Therefore, we propose that the Staphylococcus aureus EPSPS should be classified as a class II EPSPS. This research illustrates a critical mechanism of glyphosate resistance naturally occurring in certain pathogenic bacteria.
Metabolic response of granulocytes and platelets to synthetic vascular grafts: Preliminary results with an in vitro technique (1995)

The metabolism of granulocytes as well as platelets evoked by incubation with different synthetic vascular grafts was monitored during 6-h batch experiments using microcalorimetry. Standard knitted Dacron grafts, ePTFE-grafts, knitted Dacron grafts with collagen impregnation, and knitted Dacron grafts with external collagen-coating were used. The heat production per cell was calculated. A rapid increase of metabolic activity followed by a gradual decrease was demonstrated with both granulocyte suspension and platelet concentrate. Significant differences were obtained between the materials with a maximum response of Dacron grafts with collagen impregnation for both granulocyte and platelet response. The materials had different surface morphologies regarding cell adhesion after incubation as demonstrated with scanning electron microscopy with more pronounced adhesion on the collagen-impregnated grafts. The results suggest that microcalorimetry may be useful for the evaluation of cellular reactions on different biomaterials. However, further studies have to reveal the specificity of the reactions.
Establishment of pluripotential cell lines from haploid mouse embryos (1983)

Eggs from 129 SvE and (C57BL x CBA)F1 hybrid female mice were activated parthenogenetically following their exposure to a 7% solution of ethanol in PBS. Only the haploid class which developed a single pronucleus following second polar body extrusion was examined further. These eggs were transferred to suitable recipients and 'delayed' blastocysts subsequently recovered. The 'delayed' blastocysts were explanted into tissue culture and a total of four haploid-derived pluripotent cell lines established from individual embryos. Chromosome analysis of morulae revealed that over 80% contained only haploid mitoses. However, chromosome analysis of early passage cell lines revealed that all were diploid with a modal number of 40 chromosomes. When transplanted into syngeneic hosts, all lines formed well-differentiated teratocarcinomas. This technique provides a source of homozygous diploid cell lines of parthenogenetic origin.
Tissue-Wide Expression Profiling Using cDNA Subtraction and Microarrays to Identify Tumor-Specific Genes (2004)

With the objective of discovering novel putative intervention sites for anticancer therapy, we compared transcriptional profiles of breast cancer, lung squamous cell cancer (LSCC), lung adenocarcinoma (LAC), and renal cell cancer (RCC). Each of these tumor types still needs improvement in medical treatment. Our intention was to search for genes not only highly expressed in the majority of patient samples but which also exhibit very low or even absence of expression in a comprehensive panel of 16 critical (vital) normal tissues. To achieve this goal, we combined two powerful technologies, PCR-based cDNA subtraction and cDNA microarrays. Seven subtractive libraries consisting of approximately 9250 clones were established and enriched for tumor-specific transcripts. These clones, together with approximately 1750 additional tumor-relevant genes, were used for cDNA microarray preparation. Hybridizations were performed using a pool of 16 critical normal tissues as a reference in all experiments. In total, we analyzed 20 samples of breast cancer, 11 of LSCC, 11 of LAC, and 8 of RCC. To select for genes with low or even no expression in normal tissues, expression profiles of 22 different normal tissues were additionally analyzed. Importantly, this tissue-wide expression profiling allowed us to eliminate genes, which exhibit also high expression in normal tissues. Similarly, expression signatures of genes, which are derived from infiltrating cells of the immune system, were eliminated as well. Cluster analysis resulted in the identification of 527 expressed sequence tags specifically up-regulated in these tumors. Gene-wise hierarchical clustering of these clones clearly separated the different tumor types with RCC exhibiting the most homogeneous and LAC the most diverse expression profile. In addition to already known tumor-associated genes, the majority of identified genes have not yet been brought into context with tumorigenesis such as genes involved in bone matrix mineralization (OSN, OPN, and OSF-2) in lung, breast, and kidney cancer or genes controlling Ca(2+) homeostasis (RCN1,CALCA, S100 protein family). EGLN3, which recently has been shown to be involved in regulation of hypoxia-inducible factor, was found to be highly up-regulated in all RCCs and in half of the LSCCs analyzed. Furthermore, 42 genes, the expression level of which correlated with the overall survival of breast cancer patients, were identified. The gene dendogram clearly separates two groups of genes, those up-regulated such as cyclin B1, TGF-beta 3, B-Myb, Erg2, VCAM-1, and CD44 and those down-regulated such as MIG-6, Esp15, and CAK in patients with short survival time.
The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy (2012)

Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis.
Differentiation of Lactotrope Precursor GHFT Cells in Response to Fibroblast Growth Factor-2 (2000)

The mechanisms that control the emergence of different anterior pituitary cells from a common stem cell population are largely unknown. The immortalized GHFT cells derived from targeted expression of SV40 T antigen to mouse pituitary display characteristics of somatolactotropic progenitors in that they express the transcription factor GHF-1 (Pit-1) but not growth hormone (GH) or prolactin (PRL). We searched for factors capable of inducing lactotropic differentiation of GHFT cells. PRL gene expression was not observed in cells subjected to a variety of stimuli, which induce PRL gene expression in mature lactotropes. Only fibroblast growth factor-2 (FGF-2) was able to initiate the transcription, synthesis, and release of PRL in GHFT cells. However, induction of PRL expression was incomplete in FGF-2-treated cells, suggesting that additional factors are necessary to attain high levels of PRL transcription in fully differentiated lactotropes. We also show that the FGF-2 response element is located in the proximal PRL promoter. Stimulation of PRL expression by FGF-2 requires endogenous Ets factors and these factors as well as GHF-1 are expressed at low levels in the committed precursor, suggesting that these low levels are limiting for full PRL expression. Moreover, FGF-2 effect on lactotrope differentiation is mediated, at least partially, by stimulation of the Ras-signaling pathway. Our results suggest that, indeed, GHFT cells represent a valid model for studying lactotropic differentiation and that FGF-2 could play a key role both in initiating lactotrope differentiation and maintaining PRL expression.
Complete cDNA sequences encoding the Chinese hamster P-glycoprotein gene family (1991)

The only function of the transport protein P-glycoprotein (Pgp) that has been identified to date in mammals is its ability to mediate multidrug resistance (MDR) in tumour cell lines. Rodents have three P-glycoprotein (pgp) genes (termed pgp or mdr 1, 2 and 3), and humans have two (mdr1 and mdr3/mdr2). Pgp isoforms differ in their drug transport capabilities: Pgp1 and Pgp2 can mediate MDR, while Pgp3 apparently cannot. The expression of the gene family members is tissue-specific, suggesting that they have unique physiological roles. We report in this paper the complete cDNA sequences for each of the three pgp genes in Chinese hamster. A comparison of the Chinese hamster cDNA sequences with those isolated from human and mouse confirms the identification of the gene family member homologues across these species. An analysis of mammalian Pgp sequences identifies conserved sequences which, it may be speculated, are important for Pgp activity. Previously, three different mdr3 (pgp3 homologous) transcripts, products of alternative splicing, have been reported in humans. Unexpectedly, we find no evidence for a similar alternative splicing event in Chinese hamster: it appears that the expression of pgp3 (mdr3) is different between rodents and humans.
Branched-chain fatty acids produced by mutants of Streptomyces fradiae, putative precursors of the lactone ring of tylosin (1990)

Three branched-chain fatty acids (7-hydroxy-4,6-dimethylnona-2,4-dienoic acid [compound 1], its 7-epimer [compound 2], and 7-keto-4,6-dimethylnona-2,4-dienoic acid [compound 3]) and a ketone (9-hydroxy-6,8-dimethylundeca-4,6-dien-3-one [compound 4]) were isolated from the culture broth of mutants of Streptomyces fradiae which were blocked in the biosynthesis of the macrolide antibiotic tylosin. Two phenotypic classes of mutants of this organism which were blocked in the addition of mycaminose to tylactone (compound 6) accumulated these compounds. These compounds were not produced by mutants which were blocked in lactone synthesis, in steps beyond mycaminose addition, or by the wild-type strain. Synthesis of these compounds, like synthesis of tylosin, was inhibited by the addition of cerulenin. Compounds 1, 2, and 3 were partially interconvertible by these mutants; but they were not produced from the degradation of tylactone and they were not directly incorporated into tylosin by intact cells. The structures of compounds 1 and 2 were equivalent to that of a predicted intermediate (S. Yue, J. S. Duncan, Y. Yamamoto, and C. R. Hutchinson, J. Am. Chem. Soc. 109:1253-1255, 1987) in the biosynthesis of tylactone. The ketone (compound 4) reported previously (N. D. Jones, M. O. Chaney, H. A. Kirst, G. M. Wild, R. H. Baltz, R. L. Hamill, and J. W. Paschal, J. Antibiot. 35:420-425, 1982) appears to be the decarboxylation product of the intermediate following that represented by compound 1. This represents the first report of the isolation of putative precursors of tylactone from tylosin-producing organisms.
Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing beta-galactosidase (1996)

A new drug screening method was devised utilizing Trypanosoma cruzi cells that express the Escherichia coli beta-galactosidase gene. Transfected parasites catalyze a colorimetric reaction with chlorophenol red beta-D-galactopyranoside as substrate. Parasite growth in the presence of drugs in microtiter plates was quantitated with an enzyme-linked immunosorbent assay reader. The assay was performed with the mammalian form of T. cruzi that requires intracellular growth on a monolayer of fibroblast cells. To determine if selective toxicity to the parasites was occurring, the viability of the host cells in the drug was assayed with AlamarBlue. The drugs benznidazole, fluconazole, and amphotericin B were shown to inhibit the parasites at concentrations similar to those previously reported. Several compounds were tested that are inhibitors of glyceraldehyde-3-phosphate dehydrogenase of the related organisms Leishmania mexicana and Trypanosoma brucei. One of these compounds, 2-guanidino-benzimidazole, had an 50% inhibitory concentration of 10 microM in our assay. Two derivatives of this compound were identified with in vitro activity at even lower concentrations. In addition, the assay was modified for testing compounds for lytic activity against the bloodstream form of the parasite under conditions used for storing blood products. Thus, an assay with beta-galactosidase-expressing T. cruzi greatly simplifies screening drugs for selective anti-T. cruzi activity, and three promising new compounds have been identified.
Modulation of Cortical-Limbic Pathways in Major Depression (2004)

Like other antidepressant treatments, CBT seems to affect clinical recovery by modulating the functioning of specific sites in limbic and cortical regions. Unique directional changes in frontal cortex, cingulate, and hippocampus with CBT relative to paroxetine may reflect modality-specific effects with implications for understanding mechanisms underlying different treatment strategies.
Improvement in protein functional site prediction by distinguishing structural and functional constraints on protein family evolution using computational design (2005)

The prediction of functional sites in newly solved protein structures is a challenge for computational structural biology. Most methods for approaching this problem use evolutionary conservation as the primary indicator of the location of functional sites. However, sequence conservation reflects not only evolutionary selection at functional sites to maintain protein function, but also selection throughout the protein to maintain the stability of the folded state. To disentangle sequence conservation due to protein functional constraints from sequence conservation due to protein structural constraints, we use all atom computational protein design methodology to predict sequence profiles expected under solely structural constraints, and to compute the free energy difference between the naturally occurring amino acid and the lowest free energy amino acid at each position. We show that functional sites are more likely than non-functional sites to have computed sequence profiles which differ significantly from the naturally occurring sequence profiles and to have residues with sub-optimal free energies, and that incorporation of these two measures improves sequence based prediction of protein functional sites. The combined sequence and structure based functional site prediction method has been implemented in a publicly available web server.
Achieving yield gains in wheat (2012)

Wheat provides 20% of calories and protein consumed by humans. Recent genetic gains are <1% per annum (p.a.), insufficient to meet future demand. The Wheat Yield Consortium brings expertise in photosynthesis, crop adaptation and genetics to a common breeding platform. Theory suggest radiation use efficiency (RUE) of wheat could be increased ~50%; strategies include modifying specificity, catalytic rate and regulation of Rubisco, up-regulating Calvin cycle enzymes, introducing chloroplast CO(2) concentrating mechanisms, optimizing light and N distribution of canopies while minimizing photoinhibition, and increasing spike photosynthesis. Maximum yield expression will also require dynamic optimization of source: sink so that dry matter partitioning to reproductive structures is not at the cost of the roots, stems and leaves needed to maintain physiological and structural integrity. Crop development should favour spike fertility to maximize harvest index so phenology must be tailored to different photoperiods, and sensitivity to unpredictable weather must be modulated to reduce conservative responses that reduce harvest index. Strategic crossing of complementary physiological traits will be augmented with wide crossing, while genome-wide selection and high throughput phenotyping and genotyping will increase efficiency of progeny screening. To ensure investment in breeding achieves agronomic impact, sustainable crop management must also be promoted through crop improvement networks.
Wave-front interpretation with Zernike polynomials (1980)

Several low-order Zernike modes are photographed for visualization. These polynomials are extended to include both circular and annular pupils through a Gram-Schmidt orthogonalization procedure. Contrary to the traditional understanding, the classical least-squares method of determining the Zernike coefficients from a sampled wave front with measurement noise has been found numerically stable. Furthermore, numerical analysis indicates that the so-called Gram-Schmidt method and the least-squares method give practically identical results. An alternate method using the orthogonal property of the polynomials to determinem their coefficients is also discussed.
<title>Camera motion tracking of real endoscope by using virtual endoscopy system and texture information</title> (2001)

This paper proposes an improved method for camera motion tracking of a real endoscope based on registration endoscopic images and Computerized Tomography (CT) images. Camera motion estimation is a fundamental function of an endoscope navigation system, which provides useful navigation information to medical doctors during endoscopic examinations. Our previous method consists of two steps: (1) rough estimation of camera motion using optical flow information and (2) precise estimation performed by the image based registration technique. The problem of the previous method was that only the forward and the backward motion of the camera were estimated by the optical flow information. To solve this problem, the proposed method effectively uses the change in texture information on real endoscopic video images and estimates the camera motion by mapping the texture to the organ's 3-D shape generated from the CT images. We roughly estimate the all motion of the camera using texture information of the organ's wall, then the precise estimation is performed by using image based registration method. We applied the proposed method to the real bronchoscopic video images and 3-D X-ray CT images. The results sowed that the proposed method was superior to our previous method in many cases.
Two Homologous Apolipoprotein AI Mimetic Peptides (2004)

Two related 18-amino acid, class A, amphipathic helical peptides termed 3F-2 and 3F14 were chosen for this study. Although they have identical amino acid compositions and many similar biophysical properties, 3F-2 is more potent than 3F14 as an apolipoprotein AI mimetic peptide. The two peptides exhibit similar gross conformational properties, forming structures of high helical content on a membrane surface. However, the thermal denaturation transition of 3F-2 is more cooperative, suggesting a higher degree of oligomerization on the membrane. Both 3F-2 and 3F14 promote the segregation of cholesterol in membranes containing phosphatidylcholine and cholesterol, but 3F-2 exhibits a greater selectivity for partitioning into cholesterol-depleted regions of the membrane. Magic angle spinning/NMR studies indicate that the aromatic residues of 3F-2 are stacked in the presence of lipid. The aromatic side chains of this peptide also penetrate more deeply into membranes of phosphatidylcholine with cholesterol compared with 3F14. Using the fluorescent probe, 1,3-dipyrenylpropane, we monitored the properties of the lipid hydrocarbon environment. 3F-2 had a greater effect in altering the properties of the hydrocarbon region of the membrane. The results are consistent with our proposed model of the effect of peptide shape on the nature of the difference in peptide insertion into the bilayer.
Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer (2012)

We developed a new approach to isolate prostate CTCs without significant leukocyte admixture, and to subject them to genome-wide copy number analysis. Our assay may be utilized to explore genomic events involved in cancer progression, e.g. development of castration resistance and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively non-invasive manner.