gebhart/patrepeval huggingface dataset:
Association of Epstein-Barr virus with undifferentiated gastric carcinomas with intense lymphoid infiltration. Lymphoepithelioma-like carcinoma. (1991)

Some undifferentiated gastric carcinomas with intense lymphoid infiltration have a striking resemblance to nasopharyngeal lymphoepithelioma. The authors identified eight such cases (seven patients from Japan and one from the United States) of undifferentiated gastric carcinoma (lymphoepithelioma-like carcinoma [LELC]) and examined them for Epstein-Barr (EBV) viral sequences using polymerase chain reaction (PCR) and in situ hybridization (ISH) techniques. EBV was detected in seven of the eight cases by PCR, including a lymph-node metastasis. ISH that was performed in six of these cases showed EBV genomes to be uniformly present in the carcinoma cells and not present in the reactive lymphoid infiltrate or normal gastric mucosa. PCR of a polymorphic EBV locus (lymphocyte-determined membrane antigen) showed that a single genotype was present in each gastric LELC, consistent with a clonal process. These findings suggest that some undifferentiated gastric carcinomas are EBV-related and that focal EBV infection occurs before transformation.
Role of Phosphoinositide 3-Kinase in the Aggressive Tumor Growth of HT1080 Human Fibrosarcoma Cells (2001)

We have developed a model system of human fibrosarcoma cell lines that do or do not possess and express an oncogenic mutant allele of N-ras. HT1080 cells contain an endogenous mutant allele of N-ras, whereas the derivative MCH603 cell line contains only wild-type N-ras. In an earlier study (S. Gupta et al., Mol. Cell. Biol. 20:9294-9306, 2000), we had shown that HT1080 cells produce rapidly growing, aggressive tumors in athymic nude mice, whereas MCH603 cells produced more slowly growing tumors and was termed weakly tumorigenic. An extensive analysis of the Ras signaling pathways (Raf, Rac1, and RhoA) provided evidence for a potential novel pathway that was critical for the aggressive tumorigenic phenotype and could be activated by elevated levels of constitutively active MEK. In this study we examined the role of phosphoinositide 3-kinase (PI 3-kinase) in the regulation of the transformed and aggressive tumorigenic phenotypes expressed in HT1080 cells. Both HT1080 (mutant N-ras) and MCH603 (wild-type N-ras) have similar levels of constitutively active Akt, a downstream target of activated PI 3-kinase. We find that both cell lines constitutively express platelet-derived growth factor (PDGF) and PDGF receptors. Transfection with tumor suppressor PTEN cDNA into HT1080 and constitutively active PI 3-kinase-CAAX cDNA into MCH603 cells, respectively, resulted in several interesting and novel observations. Activation of the PI 3-kinase/Akt pathway, including NF-kappaB, is not required for the aggressive tumorigenic phenotype in HT1080 cells. Activation of NF-kappaB is complex: in MCH603 cells it is mediated by Akt, whereas in HT1080 cells activation also involves other pathway(s) that are activated by mutant Ras. A threshold level of activation of PI 3-kinase is required in MCH603 cells before stimulatory cross talk to the RhoA, Rac1, and Raf pathways occurs, without a corresponding activation of Ras. The increased levels of activation seen were similar to those observed in HT1080 cells, except for Raf and MEK, which were more active than HT1080 levels. This cross talk results in conversion to the aggressive tumorigenic phenotype. This latter observation is consistent with our previous observation that overstimulation of the activity of endogenous members of Ras signaling pathways, activated MEK in particular, is a prerequisite for aggressive tumorigenic growth.
Adenovirus vector-transduced hepatocytes implanted via a preformed collagen/PTFE support persist for at least 4 weeks in vivo. (1996)

Liver-directed gene therapy has the potential to provide an effective adjutant to conventional treatments for liver diseases. In vivo gene transfer is promising but still effectively out of reach with conventional gene delivery techniques. Ex vivo gene therapy using hepatocyte transplantation, however, has been encouraging. We describe and approach toward treatment of liver-related diseases by combining several of the advantageous properties of current liver-directed therapies. Primary hepatocytes were isolated, transduced with an adenovirus vector encoding a reporter gene, embedded in a collagen/polytetrafluoroethylene (PTFE) lattice, and implanted in mice. Recovered 'hepatocyte-organoids' were assayed for the presence and viability of the implanted hepatocytes, duration of transgene expression and presence of the adenovirus vector. In an initial attempt, we demonstrate that genetically modified hepatocytes can survive and express a transgene for at least 4 weeks in vivo when embedded in a collagen/PTFE support and implanted in the intraperitoneal cavity. This approach takes advantage of hepatocyte-specific functions in order to treat diseases where a fraction of the normal enzymatic activity is sufficient to alleviate a disease phenotype.
Characterization of a mitochondrial transport system for branched chain alpha-keto acids. (1985)

Efflux of branched chain alpha-keto acids from preloaded rat heart mitochondria was slow at low external pH. Efflux was first order, and measured rate constants, kappa efflux, were 0.104 +/- 0.005 and 0.115 +/- 0.006 min-1 for alpha-ketoisovalerate and alpha-ketoisocaproate (KIC), respectively. Efflux was stimulated significantly by branched chain alpha-keto acids and related carboxylates such as alpha-ketocaproate and alpha-ketovalerate, but not by substrates for the pyruvate transporter. KIC was the preferred substrate, and the apparent exchange K0.5 for KIC was 0.14 +/- 0.10 mM. Exchange was 7-8-fold faster than efflux, and the maximal rate of exchange at saturating concentrations of alpha-ketoisovalerate and KIC appeared to be independent of the metabolite used. It is proposed that branched chain alpha-keto acids cross the inner mitochondrial membrane on a specific transporter. Transport occurs with a proton, i.e. by proton symport, and is sensitive to inhibition by cinnamic acid derivatives.
Constitutively activated FLT3 phosphorylates BAD partially through Pim‐1 (2006)

Constitutively activating internal tandem duplication (ITD) mutations of the receptor tyrosine kinase FLT3 (Fms-like tyrosine kinase 3) play an important role in leukaemogenesis and their presence is associated with a poor prognosis in acute myeloid leukaemia (AML). Examining the anti- and proapoptotic proteins in constitutively activated FLT3 signalling in BaF3/ITD and MV4-11 cells, we found that the level of Bcl-2 antagonist of cell death (BAD) phosphorylation was greatly decreased in response to FLT3 inhibition. Both Ser-112 and Ser-136 of BAD are rapidly dephosphorylated after treatment with the FLT3 inhibitor CEP-701 in BaF3/ITD and MV4-11 cells. In confirmation of the cell line data, BAD was highly phosphorylated in both constitutively activated wild-type and mutant FLT3 primary AML samples, and rapidly dephosphorylated after treatment of the primary samples with CEP-701. Upstream proteins known to phosphorylate BAD include Akt, extracellular signal-regulated kinase/mitogen-activated protein kinase (Erk/ MAPK), Pim-1 and Pim-2. We and other groups have shown that constitutively activated FLT3 induces multiple signalling pathways, including phosphatidylinositol 3-kinase (PI3K)/Akt, Erk/MAPK and Janus kinase/signal transducers and activators of transcription (Jak/STAT). Thus, BAD may be a nexus point upon which these multiple signalling pathways converge in FLT3-mediated cell survival. In support of this, siRNA knockdown of BAD expression in MV4-11 cells conferred resistance to CEP-701-mediated apoptosis. Our data suggests that Pim-1 is one of the principal kinases mediating the anti-apoptotic function of FLT3/ITD signalling via the phosphorylation of BAD.
Sensory Neuropathy from Pyridoxine Abuse (1983)

We describe seven adults who had ataxia and severe sensory-nervous-system dysfunction after daily high-level pyridoxine (vitamin B6) consumption. Four were severely disabled; all improved after withdrawal. Weakness was not a feature of this condition, and the central nervous system was clinically spared. Although consumption of large doses of pyridoxine has gained wide public acceptance, this report indicates that it can cause sensory neuropathy or neuronopathy syndromes and that safe guidelines should be established for the use of this widely abused vitamin.
Isolation of a Polyubiquitin Promoter and Its Expression in Transgenic Potato Plants (1995)

A polyubiquitin clone (ubi7) was isolated from a potato (Solanum tuberosum) genomic library using a copy-specific probe from a stress-induced ubiquitin cDNA. The genomic clone contained a 569-bp intron immediately 5' to the initiation codon for the first ubiquitin-coding unit. Two chimeric beta-glucuronidase (GUS) fusion transgenes were introduced into potato. The first contained GUS fused to a 1156-bp promoter fragment containing only 5' flanking and 5' untranslated sequences from ubi7. The second transgene contained GUS translationally fused to the carboxy terminus of the first ubiquitin-coding unit and thus included the intron present in the 5' untranslated region of the polyubiquitin gene. Both ubi7-GUS transgenes were activated by wounding in tuber tissue and in leaves by application of exogenous methyl jasmonate. They were also expressed constitutively in the potato tuber peel (outer 1-2 mm). Both transgenes were actively expressed in mature leaves. Exceptionally high levels of expression were observed in senescent leaves. Transgenic clones containing the ubi7 intron and the first ubiquitin-coding unit showed GUS expression levels at least 10 times higher than clones containing GUS fused to the intronless promoter.
Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin (2007)

The small GTPase Rab7 controls late endocytic transport by the minus end-directed motor protein complex dynein-dynactin, but how it does this is unclear. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein-related protein 1L (ORP1L) are two effectors of Rab7. We show that GTP-bound Rab7 simultaneously binds RILP and ORP1L to form a RILP-Rab7-ORP1L complex. RILP interacts directly with the C-terminal 25-kD region of the dynactin projecting arm p150(Glued), which is required for dynein motor recruitment to late endocytic compartments (LEs). Still, p150(Glued) recruitment by Rab7-RILP does not suffice to induce dynein-driven minus-end transport of LEs. ORP1L, as well as betaIII spectrin, which is the general receptor for dynactin on vesicles, are essential for dynein motor activity. Our results illustrate that the assembly of microtubule motors on endosomes involves a cascade of linked events. First, Rab7 recruits two effectors, RILP and ORP1L, to form a tripartite complex. Next, RILP directly binds to the p150(Glued) dynactin subunit to recruit the dynein motor. Finally, the specific dynein motor receptor Rab7-RILP is transferred by ORP1L to betaIII spectrin. Dynein will initiate translocation of late endosomes to microtubule minus ends only after interacting with betaIII spectrin, which requires the activities of Rab7-RILP and ORP1L.
Detection of 1, N2-propanodeoxyguanosine adducts as potential endogenous DNA lesions in rodent and human tissues. (1996)

Our previous study (R.G. Nath and F-L. Chung; Proc. Natl. Acad. Sci. USA, 91: 7491-7495, 1994), using a 32P postlabeling method combined with high-performance liquid chromatography specifically developed for exocyclic adducts, has shown that acrolein- and crotonaldehyde-derived 1,N2-propanodeoxyguanosine adducts (AdG and CdG, respectively) are present in the liver DNA from humans and rodents without carcinogen treatment. Those findings raised important questions regarding their role as potential endogenous DNA lesions in carcinogenesis. In this study, using a similar assay, we examined a variety of tissues from untreated rats and mice (lung, kidney, brain, breast, prostate, colon, skin, and leukocytes) and detected AdG and CdG in the DNA of these tissues. More significantly, we also obtained evidence for the presence of these adducts in the DNA of human leukocytes and mammary glands. The identities of these adducts were verified by comigration of 3', 5' -bisphosphates of the 32P-labeled adduct from DNA with the synthetic standards in a reversed-phased high-performance liquid chromatography. Additional proof of identities was provided by enzymatic conversion of AdG and CdG 3',5' -bisphosphates to the corresponding 5'-monophosphates, followed by comigration with their synthetic standards. The estimated ranges of total AdG and CdG modifications in DNA of various tissues were from 0.10 to 1.60 mumol/mol guanine for humans, based on the recoveries of external standards. This study demonstrated the ubiquity of these adducts in various tissues, suggesting their potential role as endogeneous DNA lesions in rodents and humans.
Binding of Pyridoxal 5‘-Phosphate to the Heme Protein Human Cystathionine β-Synthase (1999)

Cystathionine beta-synthase (CBS), a pyridoxal 5'-phosphate (PLP) dependent enzyme, catalyzes the condensation of serine and homocysteine to form cystathionine. Mammalian CBS was recently shown to be a heme protein. While the role of heme in CBS is unknown, catalysis by CBS can be explained solely by participation of PLP in the reaction mechanism. In this study, treatment of CBS with sodium borohydride selectively reduced the Schiff base but did not affect the heme. Purification and sequencing of the PLP-cross-linked peptide from a trypsin digest of the reduced enzyme revealed the evolutionarily conserved Lys119 to be the residue forming the Schiff base. Serine and hydroxylamine form an alpha-aminoacrylate and an oxime with PLP in CBS, respectively. The sulfhydryl-containing substrate, homocysteine, disturbs the heme environment but does not interact with PLP. In contrast to other PLP-dependent enzymes, CBS emits no PLP-related fluorescence when excited at 296 or 330 nm. PLP but not heme dissociates from the enzyme in the presence of hydroxylamine. The dissociation of PLP is a multistage process involving a short approximately 500 s lag phase, followed by a rapid inactivation and a slower PLP-oxime formation. PLP-free CBS exhibits a decrease of secondary structure as well as loss of CBS activity that can be only partially restored by PLP. This study constitutes the first comprehensive investigation of PLP interaction with a heme protein.
An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. (1994)

In the preceding paper (Hajjar, K. A., Jacovina, A. T., and Chacko, J. (1994) J. Biol. Chem. 269, 21191-21197), we identified a M(r) = 40,000 endothelial cell receptor for tissue plasminogen activator (t-PA) and plasminogen (PLG) as the calcium- and phospholipid-binding protein, annexin II (Ann-II). Here, we examined the effect of Ann-II on t-PA-dependent plasminogen activation in a purified system. Purified native Ann-II bound t-PA, plasminogen, and plasmin with high affinity (Kd = 25 nM, 161 nM, and 75 nM, respectively). At fixed plasminogen concentrations, preincubation with purified native Ann-II was associated with an approximately 21-fold increase in the rate of Glu-PLG activation and an approximately 14-fold increase in activation of Lys-PLG. Three irrelevant proteins had no effect on plasmin formation, while fibrinogen increased the rate of Glu-PLG activation by approximately 4-fold. Annexin-II-mediated enhancement of t-PA-dependent plasminogen activation was 90-95% inhibited by epsilon-aminocaproic acid or by pretreatment of Ann-II with carboxypeptidase B, indicating a carboxyl-terminal lysine-dependent interaction. Kinetic analyses revealed that Ann-II conferred an approximately 60-fold increase in catalytic efficiency upon t-PA-dependent activation of either Glu-PLG or Lys-PLG. Thus, Ann-II-mediated assembly of plasminogen and t-PA may promote and localize constitutive plasmin generation on the surface of the blood vessel wall.
The Complete Genome Sequence of Escherichia coli K-12 (1997)

The 4,639,221-base pair sequence of Escherichia coli K-12 is presented. Of 4288 protein-coding genes annotated, 38 percent have no attributed function. Comparison with five other sequenced microbes reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within E. coli are also evident. The largest family of paralogous proteins contains 80 ABC transporters. The genome as a whole is strikingly organized with respect to the local direction of replication; guanines, oligonucleotides possibly related to replication and recombination, and most genes are so oriented. The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer.
Learning Spatio-Temporal Representation with Pseudo-3D Residual Networks (2017)

Convolutional Neural Networks (CNN) have been regarded as a powerful class of models for image recognition problems. Nevertheless, it is not trivial when utilizing a CNN for learning spatio-temporal video representation. A few studies have shown that performing 3D convolutions is a rewarding approach to capture both spatial and temporal dimensions in videos. However, the development of a very deep 3D CNN from scratch results in expensive computational cost and memory demand. A valid question is why not recycle off-the-shelf 2D networks for a 3D CNN. In this paper, we devise multiple variants of bottleneck building blocks in a residual learning framework by simulating $3\times3\times3$ convolutions with $1\times3\times3$ convolutional filters on spatial domain (equivalent to 2D CNN) plus $3\times1\times1$ convolutions to construct temporal connections on adjacent feature maps in time. Furthermore, we propose a new architecture, named Pseudo-3D Residual Net (P3D ResNet), that exploits all the variants of blocks but composes each in different placement of ResNet, following the philosophy that enhancing structural diversity with going deep could improve the power of neural networks. Our P3D ResNet achieves clear improvements on Sports-1M video classification dataset against 3D CNN and frame-based 2D CNN by 5.3% and 1.8%, respectively. We further examine the generalization performance of video representation produced by our pre-trained P3D ResNet on five different benchmarks and three different tasks, demonstrating superior performances over several state-of-the-art techniques.
Tau proteins: the molecular structure and mode of binding on microtubules. (1988)

Tau is a family of closely related proteins (55,000-62,000 mol wt) which are contained in the nerve cells and copolymerize with tubulin to induce the formation of microtubules in vitro. All information so far has indicated that tau is closely apposed to the microtubule lattice, and there was no indication of domains projecting from the microtubule polymer lattice. We have studied the molecular structure of the tau factor and its mode of binding on microtubules using the quick-freeze, deep-etch method (QF.DE) and low angle rotary shadowing technique. Phosphocellulose column-purified tubulin from porcine brain was polymerized with tau and the centrifuged pellets were processed by QF.DE. We observed periodic armlike elements (18.7 +/- 4.8 nm long) projecting from the microtubule surface. Most of the projections appeared to cross-link adjacent microtubules. We measured the longitudinal periodicity of tau projections on the microtubules and found it to match the 6-dimer pattern better than the 12-dimer pattern. The stoichiometry of tau versus tubulin in preparations of tau saturated microtubules was 1:approximately 5.0 (molar ratio). Tau molecules adsorbed on mica took on rodlike forms (56.1 +/- 14.1 nm long). Although both tau and MAP1 are contained in axons, competitive binding studies demonstrated that the binding sites of tau and MAP1A on the microtubule surfaces are most distinct, although they may partially overlap.
Selective functionalization of calix[4]arenes at the upper rim (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective functionalization of calix[4]arenes at the upper rimJan Dirk Van Loon, Arturo Arduini, Laura Coppi, Willem Verboom, Andrea Pochini, Rocco Ungaro, Sybolt Harkema, and David N. ReinhoudtCite this: J. Org. Chem. 1990, 55, 21, 5639–5646Publication Date (Print):October 1, 1990Publication History Published online1 May 2002Published inissue 1 October 1990https://pubs.acs.org/doi/10.1021/jo00308a024https://doi.org/10.1021/jo00308a024research-articleACS PublicationsRequest reuse permissionsArticle Views2085Altmetric-Citations263LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Expression of cell cycle-regulated proteins in prostate cancer. (1996)

Markers of cellular proliferation have proven to be useful prognostic markers in several tumor types. Recently, immunoreactivity for cyclins was found to provide an independent marker of tumor proliferation in breast cancer. In this study, we sought to determine the pattern of immunoreactivity for cyclins A, B, E, and Ki-67 in surgically resected prostate cancer and to determine their possible prognostic significance. Twenty-eight tumors of American Urological Association stages B and C were selected for study. Immunoreactivity for cyclins A and B was detected in most tumors and was present at significantly reduced levels as compared with breast cancer. Staining for cyclin E was present in four tumors and was present only in focal areas in two of the four. Such focal variation in expression of cell cycle regulators may reflect genetic instability in a tumor. Immunoreactivity for cyclins A and B was correlated with both Ki-67 index (the percentage of cells with Ki-67 immunoreactivity) and with each other. A Ki-67 index greater than 4.0 was associated with shorter time to prostate-specific antigen-detected relapse (P = 0.026). The fraction of cells staining for cyclins A and B divided by the fraction of cells staining for Ki-67 [(A+B)/K] was highly predictive of relapse, with values less than 0.50 associated with more rapid progression (P < 0.001). This latter result remained statistically significant after controlling for Gleason score by stratification. Our results suggest that immunoreactivity for markers of cellular proliferation may provide useful prognostic information in localized prostate cancer, and they need to be validated in a larger numbers of patients.