gebhart/patrepeval huggingface dataset:
Mechanisms of diabetic vasculopathy: an overview (2001)

Diabetes is commonly associated with both microvascular and macrovascular complications. These vascular complications are accelerated in the context of systemic hypertension. During the past few years the underlying molecular mechanisms responsible for diabetic vascular complications have begun to be clarified. It appears that both metabolic and hemodynamic factors interact to stimulate the expression of cytokines and growth factors in the various vascular trees. Overexpression of the prosclerotic cytokine transforming growth factor-beta has been observed in glomeruli and tubules from the diabetic kidney. In the retina the angiogenic cytokine vascular endothelial growth factor and its receptor, vascular endothelial growth factor R-2 are increased in experimental diabetes. These changes in growth factors are viewed to be responsible for the extracellular matrix accumulation in the diabetic kidney and new vessel formation in the diabetic retina. Changes in cytokines have also been observed at other vascular sites including the mesenteric vascular tree. Vasoactive hormones, such as angiotensin II and endothelin, are potent stimulators of cytokines with recent studies showing that inhibitors of these vasoactive hormone pathways may confer organ protection in diabetes by inhibition of growth factor expression. Glucose-dependent factors, such as the formation of advanced glycation end products that interact with specific receptors and lead to overexpression of a range of cytokines, may play an important role in diabetic vascular complications including atherosclerosis. It is likely that the effects of inhibitors of this pathway such as aminoguanidine on cytokine production may play a pivotal role in mediating the renal, retinal, and vasoprotective effects observed with this agent in experimental diabetes. It is anticipated that the advent of specific inhibitors of cytokine formation or action will provide new approaches for the prevention and treatment of diabetic vascular complications.
Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein (1997)

The LAZ3/BCL6 (lymphoma-associated zinc finger 3/B cell lymphomas 6) gene frequently is altered in non-Hodgkin lymphomas. It encodes a sequence-specific DNA binding transcriptional repressor that contains a conserved N-terminal domain, termed BTB/POZ (bric-à-brac tramtrack broad complex/pox viruses and zinc fingers). Using a yeast two-hybrid screen, we show here that the LAZ3/BCL6 BTB/POZ domain interacts with the SMRT (silencing mediator of retinoid and thyroid receptor) protein. SMRT originally was identified as a corepressor of unliganded retinoic acid and thyroid receptors and forms a repressive complex with a mammalian homolog of the yeast transcriptional repressor SIN3 and the HDAC-1 histone deacetylase. Protein binding assays demonstrate that the LAZ3/BCL6 BTB/POZ domain directly interacts with SMRT in vitro. Furthermore, DNA-bound LAZ3/BCL6 recruits SMRT in vivo, and both overexpressed proteins completely colocalize in nuclear dots. Finally, overexpression of SMRT enhances the LAZ3/BCL6-mediated repression. These results define SMRT as a corepressor of LAZ3/BCL6 and suggest that LAZ3/BCL6 and nuclear hormone receptors repress transcription through shared mechanisms involving SMRT recruitment and histone deacetylation.
A hematopoietic protein tyrosine phosphatase (HePTP) gene that is amplified and overexpressed in myeloid malignancies maps to chromosome 1q32.1. (1994)

Tyrosine phosphorylation is an important regulator of cell growth and differentiation reflecting the interaction of protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP). Although excessive PTK activity can result in hematopoietic cell transformation, perturbation of either of these two modulators may result in uncontrolled cell growth. Myeloid cells are responsive to growth factors and cytokines that induce tyrosine phosphorylation and can become ligand independent when endogenous PTKs become dysregulated. Specific PTPs, through mutation or altered expression, may enhance PTK activities and also cause myeloid ligand independence, though this has not yet been demonstrated. We have previously reported the isolation of a hematopoietic specific cytoplasmic PTP (HePTP). We now report that this gene maps to chromosome 1q32.1 utilizing fluorescent in situ chromosomal hybridization (FISH). This site is frequently amplified in preleukemic myeloproliferative diseases. FISH analysis of a patient with myelodysplastic syndrome characterized by myeloid hypoplasia and monocytosis reveals triplication of the HePTP gene on one allele with elevated protein expression in neoplastic myelomonocytic cells. Elevated expression is also identified in blasts from some patients with acute leukemia. These observations prompted us to examine the experimental effects on cell growth of HePTP overexpression. Though normal myeloid cells show minimal HePTP expression, all hematopoietic cell lines tested show high expression of HePTP. Gene transfer of HePTP into NIH 3T3 cells was therefore performed, which caused altered cell morphology, disorganized growth, anchorage independent colony formation and subtle differences in the pattern of tyrosine phosphoproteins compared to control cell lines. We conclude that amplification and overexpression of HePTP may be an important cofactor contributing to abnormal myeloid cell growth.
Establishment of an IL-12-responsive T cell clone: its characterization and utilization in the quantitation of IL-12 activity (1997)

We previously demonstrated that proliferation of terminally differentiated Th1 clones depends primarily on an interleukin-12 (IL-12)-paracrine mechanism mediated by their interactions with antigen-presenting cells (APC) rather than on an IL-2-autocrine mechanism. Such a Th1 clone (4-86, C57BL/6 origin) was cultured with recombinant IL-12 (rIL-12) in the absence of either antigen or APC. Some cells survived for several passages of culture with only rIL-12, and by limiting dilution, several clones highly reactive to rIL-12 alone were obtained. One of these clones, designated 2D6, was found to proliferate strongly in response to less than 1 pg/mL of rIL-12. This clone exhibited the following surface phenotypes: CD3+, T cell receptor (TCR) alpha beta+, Vbeta11+, NK-1.1-; CD4-CD8-; LFA-1+, ICAM-1+; and CD28+, CD80+, CD86+, CTLA-4-. In accordance with high responsiveness to IL-12, 2D6 cells were also found to express IL-12 receptor (IL-12R) as detected by incubation with rIL-12 and then staining with anti-IL-12 monoclonal antibody (mAb). Stimulation of 2D6 with rIL-12 resulted in the expression of interferon-gamma (IFN-gamma) and IL-10 mRNAs and production of these cytokines. The 2D6 clone responded to IL-2 (vigorously), IL-7 (moderately), and IL-4 (mildly) in addition to IL-12. However, the Ab capture assay using anti-IL-12 mAb enabled us to quantify IL-12-specific activity contained in a given sample. Thus, this study describes the unique features of the IL-12-responsive T cell clone and demonstrates the utilization of this clone in the quantitation of a specific IL-12 activity.
Highly specific in vivo tumor targeting by monovalent and divalent forms of 741F8 anti-c-erbB-2 single-chain Fv. (1993)

The in vivo properties of monovalent and divalent single-chain Fv (sFv)-based molecules with the specificity of the anti-c-erbB-2 monoclonal antibody 741F8 were examined in scid mice bearing SK-OV-3 tumor xenografts. 741F8 sFv monomers exhibited rapid, biphasic clearance from blood, while a slightly slower clearance was observed with the divalent 741F8 (sFv')2 comprising a pair of 741F8 sFv' with a C-terminal Gly4Cys joined by a disulfide bond. Following i.v. injection, the 741F8 sFv monomer was selectively retained in c-erbB-2-overexpressing SK-OV-3 tumor, with excellent tumor:normal organ ratios uniformly exceeding 10:1 by 24 h. The specificity of this effect was demonstrated by the lack of retention of the anti-digoxin 26-10 sFv monomer, as evaluated by biodistribution studies, gamma camera imaging, and cryomacroautoradiography studies. The specificity index (741F8 sFv retention/26-10 sFv retention) of 741F8 monomer binding, measured by the percentage of injected dose per g of tissue, was 13.2:1 for tumor, and 0.8 to 2.1 for all tested normal organs, with specificity indices for tumor:organ ratios ranging from 7.0 (kidneys) to 16.7 (intestines). Comparing divalent 741F8 (sFv')2 with the 26-10 (sFv')2, similar patterns emerged, with specificity indices for retention in tumor of 16.9 for the Gly4Cys-linked (sFv')2. These data demonstrate that, following their i.v. administration, both monovalent and divalent forms of 741F8 sFv are specifically retained by SK-OV-3 tumors. This antigen-specific binding, in conjunction with the 26-10 sFv controls, precludes the possibility that passive diffusion and pooling in the tumor interstitium contributes significantly to long-term tumor localization. 741F8 (sFv')2 species with peptide spacers exhibited divalent binding and increased retention in tumors as compared with 741F8 sFv monomers. Since the blood retention of the (sFv')2 is slightly more prolonged than that of the monomer, it was necessary to demonstrate that the increased tumor localization of the peptide-linked (sFv')2 was due to its divalent nature. The significantly greater localization of the divalent bismalimidohexane-linked 741F8 (sFv')2 as compared with a monovalent 741F8 Fab fragment of approximately the same size suggests that the increased avidity of the (sFv')2 is a factor in its improved tumor retention. This is the first report of successful specific in vivo targeting of tumors by divalent forms of sFv molecules. The improved retention of specific divalent (sFv')2 by tumors may have important consequences for targeted diagnostic or therapeutic strategies.
Off-axis sensor rosettes for measurement of the piezoresistive coefficients of silicon (1993)

Experimental calibration results for the piezoresistive coefficients of silicon as a function of temperatures are presented. Measurements have been performed using a test chip incorporating a new off-axis 0-45 degrees -90 degrees rosette design. This rosette requires the application of only uniaxial stress for measurement of the three individual piezoresistive coefficients of silicon: pi /sub 11/, pi /sub 12/, and pi /sub 44/. Of even greater potential import, this rosette yields inherently temperature compensated values of the coefficients pi /sub 44/ and pi /sub D/=( pi /sub 11/- pi /sub 12/). P-type off-axis rosettes have been characterized as a function of temperature, and values for the temperature dependencies of pi /sub 44/ and pi /sub D/ are reported. The coefficients pi /sub 44/ in p-type silicon and pi /sub D/ in n-type silicon are needed for an optimized stress sensor on
The cyclophilin inhibitor Debio 025 normalizes mitochondrial function, muscle apoptosis and ultrastructural defects inCol6a1−/−myopathic mice (2009)

Desensitization of the mitochondrial permeability transition pore can be achieved by selective inhibition of matrix cyclophilin D without inhibition of calcineurin, resulting in an effective therapy of Col6a1(-/-) myopathic mice. These findings provide an important proof of principle that collagen VI muscular dystrophies can be treated with Debio 025. They represent an essential step towards an effective therapy for Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy, because Debio 025 does not expose patients to the potentially harmful effects of immunosuppression.
STAT1 signaling is associated with acquired crossresistance to doxorubicin and radiation in myeloma cell lines (2006)

The myeloma cell line RPMI 8226/S and its doxorubicin resistant subline 8226/Dox40 were used as models to explore the potential importance of the STAT1 signaling pathway in drug and radiation resistance. The 40-fold doxorubicin resistant subline 8226/Dox40 was found to be crossresistant to single doses of 4 and 8 Gy of radiation. A genome-wide mRNA expression study comparing the 8226/Dox40 cell line to its parental line was performed to identify the underlying molecular mechanisms. Seventeen of the top 50 overexpressed genes have previously been implicated in the STAT1 signaling pathway. STAT1 was over expressed both at the mRNA and protein level. Moreover, analyses of nuclear extracts showed higher abundance of phosphorylated STAT1 (Tyr 701) in the resistant subline. Preexposure of the crossresistant cells to the STAT1 inhibiting drug fludarabine reduced expression of overexpressed genes and enhanced the effects of both doxorubicin and radiation. These results show that resistance to doxorubicin and radiation is associated with increased STAT1 signaling and can be modulated by fludarabine. The data support further development of therapies combining fludarabine and radiation.
The nucleotide sequence of pathogenesis-related (PR) 1b protein gene of tobacco (1990)

A genomic clone encoding the pathogenesis-related (PR) lb protein was cloned from Nicotiana tabacum cv. Samsun NN genomic library screening with cDNA clone of PR la protein gene (1). The following nucleotide sequence contains coding and its flanking regions. The nucleotide sequence of PRlb protein gene is highly similar to that of PR la (2-5). Coding region is from 457 to 963 without intron and capping site is identified at 428. TATA-box is underlined.
Preparation and Photoelectrochemical Properties of Two-Dimensionally Organized CdS Nanoparticle Thin Films (1999)

Two-dimensionally organized CdS nanoparticle films were prepared with the use of the Langmuir−Blodgett (LB) technique. 2-Aminoethanethiol-modified CdS nanoparticles were spread on a water subphase which contained glutaraldehyde as a cross-linking agent for binding the surface-modified CdS nanoparticles with each other, and the cross-linking reaction was undertaken under several different compressions of the CdS nanoparticle layer spread on the water subphase. Surface pressure−area isotherms of the CdS monoparticulate layer taken after the cross-linking were largely different depending on the area used for the cross-linking. By transfer of the CdS monoparticulate film prepared at the air−water interface to the 2-aminoethanethiol-modified gold substrate using the LB technique, CdS monoparticulate films containing different surface concentrations were prepared on the gold substrate. It was easily done to cumulate the monoparticulate film on the gold substrate using the same transfer technique. The prepared CdS nanoparticles films showed n-type photosensitivities which were enhanced by increasing the number of cumulation of monoparticulate films.
Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium (1997)

Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each) cardioplegia ameliorated cytosolic calcium ([Ca2+]i) accumulation and was associated with enhanced functional recovery after surgically induced global ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic cytochrome oxidase I activity and mRNA levels, suggesting that enhanced functional recovery may involve the preservation of high-energy phosphates. To investigate this hypothesis, 31P nuclear magnetic resonance was used to measure serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH (pHi) in Langendorff-perfused, aged (135 wk) rabbit hearts during preischemia, global ischemia (30 min), and reperfusion (30 min). K-Mg cardioplegia retarded PCr depletion (P < 0.05) and significantly enhanced NTP preservation (P < 0.05) during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase in Mgf during ischemia (P < 0.05). These results were correlated with amelioration of [Ca2+]i accumulation during ischemia and preservation of left ventricular function after reperfusion and suggest that optimal functional recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the aged myocardium.
Bowling alone: the collapse and revival of American community (2000)

BOWLING ALONE warns Americans that their stock of social capital, the very fabric of their connections with each other, has been accelerating down. Putnam describes the resulting impoverishment of their lives and communities. Drawing on evidence that includes nearly half a million interviews conducted over a quarter of a century in America, Putnam shows how changes in work, family structure, age, suburban life, television, computers, women's roles and other factors are isolating Americans from each other in a trend whose reflection can clearly be seen in British society. We sign 30 percent fewer petitions than we did ten years ago. Membership in organisations- from the Boy Scouts to political parties and the Church is falling. Ties with friends and relatives are fraying: we're 35 percent less likely to visit our neighbours or have dinner with our families than we were thirty years ago. We watch sport alone instead of with our friends. A century ago, American citizens' means of connecting were at a low point after decades of urbanisation, industrialisation and immigration uprooted them from families and friends. That generation demonstrated a capacity for renewal by creating the organisations that pulled Americans together. Putnam shows how we can learn from them and reinvent common enterprises that will make us secure, productive, happy and hopeful.
Iterative message passing techniques for rapid code acquisition (2004)

Iterative message passing algorithms (MPAs) have found application in a wide range of data detection problems because they can provide near optimal performance and significant complexity reduction. In this paper, we demonstrate that they can be used to efficiently solve the pseudo random code acquisition problem as well. To do this, we represent good pseudo-noise (PN) patterns using sparse graphical models, and then apply the standard iterative message passing algorithm over this graph to approximate maximum likelihood synchronization. Simulation results show that this algorithm achieves better performance than traditional serial search code acquisition in the sense that it works at low signal-to-noise ratios (SNRs) and is much faster. Compared to full parallel search, this approach typically provides significant complexity reduction.
Cytotoxic-T-Cell Responses, Viral Load, and Disease Progression in Early Human Immunodeficiency Virus Type 1 Infection (1997)

In early HIV-1 infection, the induction of memory cytotoxic T lymphocytes, particularly those specific for Env, helps control viral replication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease.
In situ polymerase chain reaction-based localization studies support role of human herpesvirus-8 as the cause of two AIDS-related neoplasms: Kaposi's sarcoma and body cavity lymphoma. (1997)

Several lines of investigation point to a new herpesvirus, human herpesvirus-8 (HHV-8), as the cause of two different neoplasms seen in AIDS patients-Kaposi's sarcoma (KS) and body cavity B cell lymphoma. If this virus is the etiological agent, rather than another opportunistic infectious agent, it should be present in the earliest detectable clinical lesions on a temporal basis, and localize to specific target cells in a spatial pattern consistent with tumorigenic pathways. In this study, we take advantage of the clinical accessibility to biopsy early (patch stage) skin lesions of KS to address the temporal issue, combined with in situ PCR and dual immunostaining using a marker identifying malignant cells, to address the spatial localization issue. 21 different tissue samples were subjected to PCR analysis and in situ PCR with and without simultaneous immunostaining. In normal skin from healthy individuals, no HHV-8 DNA was detected by PCR or in situ PCR. However, in all PCR-positive tissues, distinct and specific in situ PCR staining was observed. In four different patch stage KS lesions, in situ PCR staining localized to nuclei of endothelial cells and perivascular spindle-shaped tumor cells. Later stage KS lesions (plaques and nodules) revealed additional positive cells, including epidermal keratinocytes (four of five), and eccrine epithelia (two of four). These patterns were nonrestricted to skin, as pulmonary KS also revealed HHV-8-specific infection of endothelial cells and KS tumor cells, as well as epithelioid pneumocytes (two of two). In body cavity B cell lymphoma by dual staining, HHV-8 was present in malignant tumor cells (EMA immunostained positive) and not in reactive lymphocytes. These results reveal an early temporal onset and nonrandom tissue and cellular distribution pattern for HHV-8 infection that is consistent with a causal link between this DNA virus and two AIDS-related neoplasms.
Micro Review tRNA‐dircted transcription antitermination (1994)

At least 18 aminoacyl-tRNA synthetase and amino acid biosynthesis genes in several Gram-positive genera appear to be regulated by a common transcription antitermination mechanism. Each gene is induced by limitation for the appropriate amino acid, and not by general amino acid limitation. The mRNA leader regions of these genes exhibit extensive structural conservation. Characterization of the Bacillus subtilis tyrS gene revealed that uncharged tyrosyl-tRNA promotes readthrough of a leader-region terminator; a conformational switch in the leader mRNA between a terminator structure and an antiterminator structure is postulated to mediate antitermination. Two sites of interaction between the tRNA and the leader have been identified by genetic analysis: the tRNA anticodon interacts with a single codon displayed at a precise position in the leader-region structure, and the acceptor end of the tRNA interacts with a side-bulge on the antiterminator.
Radiation sensitization of glioblastoma by cilengitide has unanticipated schedule‐dependency (2008)

We investigated whether cilengitide could amplify the antitumor effects of radiotherapy in an orthotopic rat glioma xenograft model. Cilengitide is a specific inhibitor of alphav series integrins, and acts as an antiangiogenic. U251 human glioma cells express alphavbeta3 and alphavbeta5 integrins. We used in vitro assays of adhesion and growth of tumor and endothelial cells to evaluate cytotoxicity and the potential for cilengitide to enhance radiation toxicity. Treatment was then evaluated in an orthotopic model to evaluate synergy with therapeutic radiation in vivo. In vitro, cilengitide blocked cell adhesion, but did not influence the effects of radiation on U251 cells; cilengitide strongly amplified radiation effects on endothelial cell survival. In vivo, radiotherapy prolonged the survival of U251 tumor-bearing rats from 50 to over 110 days. Cotreatment with cilengitide and radiation dramatically amplified the effects of radiation, producing survival over 200 days and triggering an enhanced apoptotic response and suppression of tumor growth by histology at necropsy. Signaling pathways activated in the tumor included NFkappab, a documented mediator of cellular response to radiation. Because cilengitide has a short plasma half-life (t((1/2)) approximately 20 min), antiangiogenic scheduling typically uses daily injections. We found that a single dose of cilengitide (4 mg/kg) given between 4 and 12 hr prior to radiation was sufficient to produce the same effect. Our results demonstrate that blockade of alphav integrins mediates an unanticipated rapid potentiation of radiation, and suggests possible clinical translation for glioma therapy.