gebhart/patrepeval huggingface dataset:
Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload (2006)

Cardiac hypertrophy is associated with upregulation of vascular endothelial growth factor (VEGF) in the myocardium. Here, we evaluated the effects of a decoy VEGF receptor on heart morphology and function to a murine model of pressure overload hypertrophy. Mice were administered adenoviral vector encoding a decoy VEGF receptor (Ad-Flk), and their hearts were subjected to pressure overload by transverse aortic constriction (TAC). Treatment with Ad-Flk led to a net reduction in capillary density in hearts subjected to TAC. Ad-Flk also led to a reduction in TAC-induced cardiac hypertrophy and promoted left ventricle dilatation and a loss in contractile function. Treatment with Ad-Flk markedly increased myocardial fibrosis and collagen gene upregulation. In contrast, Ad-Flk had no effect on any of these parameters in sham-treated mice. Administration of a VEGF trap reagent diminished pressure overload cardiac hypertrophy and promoted the progression to heart failure but had no effect on sham-treated animals. These findings suggest that VEGF is required to maintain myocardial capillary density and that reductions in the vascular bed are associated with the transition from compensatory hypertrophy to failure.
Os impasses do G-8 e a reforma da governança global (2010)

Este artigo propõe uma análise sobre os\nimpasses do G-8 e sua relação com o G-20 e demais\nfóruns informais.
Barley Aleurone Layers Secrete a Nuclease in Response to Gibberellic Acid (1986)

Incubation of barley (Hordeum vulgare L. cv Himalaya) half-seeds with gibberellic acid enhances the secretion of ribonuclease and deoxyribonuclease from aleurone tissue (MJ Chrispeels, JE Varner 1967 Plant Physiol 42: 398-406; L Taiz, JE Starks 1977 Plant Physiol 60: 182-189). These activities were over 50-fold greater in medium of half-seeds incubated with gibberellic acid than in control medium. Ribonuclease and deoxyribonuclease activities initially appeared in the medium 24 to 48 hours after hormone induction and increased for up to 96 hours. Both activities had a pH optimum of 6.0 and a temperature optimum of 55 degrees C. When the medium from gibberellic acid-treated half-seeds was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, the major ribonuclease and deoxyribonuclease activity bands comigrated. The two enzyme activities remained associated throughout a 2,700-fold purification employing ammonium sulfate fractionation, Heparin-Agarose affinity chromatography, and Reactive Blue 2-Agarose affinity chromatography. Also accompanying the ribonuclease and deoxyribonuclease activities throughout purification was the ability to hydrolyze the 3'-phosphoester linkage of 3'-AMP. The purified protein was composed of a single polypeptide with an apparent molecular weight of 36 kilodaltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It is concluded that in response to gibberellic acid, barley aleurone tissue secretes a nuclease having ribonuclease, deoxyribonuclease, and 3'-nucleotidase activities.
Coronaviruses: Structure and Genome Expression (1988)

Introduction. Progress in coronavirology is illustrated by the number of workshops convened and reviews written. International meetings have been held in Germany (1980), the Netherlands (1983) and the U.S.A. (1986), and the Fourth Coronavirus Symposium will be organized by one of us (D.C.) in Cambridge, U.K. in July 1989. In addition, reviews have appeared which highlighted particularly interesting characteristics of the family, e.g. the replication strategy (Lai, 1986) and the glycoproteins (Sturman &amp; Holmes, 1985). As the last general accounts were published some 5 years ago (Siddell et al., 1983; Sturman &amp; Holmes, 1983) an update is timely. The present article is based on the large amount of sequence data accumulated in these years and focuses on the viral nucleic acids and proteins and their function. Coronaviruses cause infections in man, other mammals and birds. Most experimental data have been obtained from studies of mouse hepatitis virus (MHV) and infectious bronchitis virus of chickens (IBV).
Genetic basis for p53 overexpression in human breast cancer. (1991)

Overexpression of an activated form of the p53 protein may be involved in neoplastic transformation. We found widespread overexpression of p53 by immunohistochemical staining in 11 (22%) of 49 primary invasive human breast cancers. Northern blot analysis showed that this overexpression was not due to an increase in the steady-state level of p53 mRNA. The p53 gene was directly sequenced in 7 of these tumors with elevated levels of the protein and, in each case, a mutation that altered the coding sequence for p53 was found in a highly conserved region of the gene. Whereas 4 of these tumors contained only a mutant p53 allele, the other 3 tumors exhibited coding sequences from both a mutant and a wild-type allele. p53 mutations have previously been correlated with allelic loss of part of chromosome 17p that contains the p53 locus. Examination of all 49 breast tumors revealed a 61% frequency of deletion at or near the p53 locus. However, the presence of allelic deletion did not correlate with overexpression of the protein. Six tumors that were deleted but did not express high levels of the protein were sequenced and all retained a wild-type p53 allele. In this series of human breast cancers, overexpression of the p53 protein, not allelic loss on chromosome 17p, was always associated with mutation of the p53 gene.
Large-Scale Selection of CD34+ Peripheral Blood Progenitors and Expansion of Neutrophil Precursors for Clinical Applications (1996)

Hematopoietic recovery after high-dose chemotherapy is characterized by an obligate period of neutropenia of approximately 8-10 days. It is postulated that if a pool of neutrophil precursors and progenitors were expanded in vitro and reinfused, the duration of neutropenia may be substantially shortened by these cells capable of providing mature neutrophils within days of reinfusion. In this study, peripheral blood progenitor cell products were obtained from six normal donors mobilized with rhG-CSF and two patients mobilized with cyclophosphamide and rhG-CSF. CD34+ cells were isolated using the Isolex immunomagnetic bead method. A mean of 8.26 x 10(7) CD34+ cells with a mean purity of 74.5% were seeded at a concentration of 1 x 10(5)/ml into a 12 day stroma-free liquid culture using gas-permeable bags. A serum-free growth medium supplemented with PIXY321 was used. On day 7, there was a mean cellular expansion of fourfold, at which time the cells were resuspended at the initial concentration, yielding a mean culture volume of 3L (1-6 L). On day 12, there was an additional mean fold cellular expansion of 10 x, achieving an overall mean fold expansion of 41 +/- 16. Cellular characterization of the expanded cells revealed predominantly neutrophil precursors by morphology (mean 70.1%) and flow cytometric analysis. A mean of 52.3% of the expanded cells expressed CD15. Immunohistochemical staining revealed a mean of 7.1% CD41a+ megakaryocytic progenitors in the final cultured cell product. Detectable CD34+ cells were maintained only in those cultures initiated with greater than 90% CD34+ cells. Colony-forming units-granulocyte-macrophage (CFU-GM) were maintained in the 12 day culture at a level similar to the preculture number, whereas CFU mixed were depleted in all samples. On day 0, there were few CFU clusters (colonies containing fewer than 50 cells) identified, but by day 12, a mean total of 8.3 x 10(6) CFU clusters were identified. On day 12, the expanded cells were harvested and pooled using the Fenwal CS3000 Plus blood cell separator and resuspended in Plasma-Lyte-A with 1% human serum albumin. The mean harvest recovery of expanded progenitors was 91%, with a mean viability of 86%.
Phase I trial of targeted therapy with PSA-TRICOM vaccine (V) and ipilimumab (ipi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (2009)

5144 Background: There are few treatment options for mCRPC pts. Immunotherapy + adjuvant immunomodulators is a promising modality. PSA-TRICOM V is composed of poxviral vectors encoding PSA and 3 costimulatory molecules (ICAM-I, LFA-3, and B7.1) and has clinical activity in mCRPC. Ipi blocks CTLA-4, a T-cell downregulatory receptor, has clinical activity in mCRPC as monotherapy and has also been shown to enhance anti-tumor responses in combination with V in preclinical studies. Methods: Pts received V and GM-CSF q 4 weeks in 4 sequential cohorts of escalating doses of ipi at 1, 3, 5, and 10 mg/kg (DL1–4 respectively). After 6 courses of ipi, pts could receive a maintenance dose q 3 months (mo) until progression. Results: Study accrual is complete with 30 pts. There was no DLT and no &gt; G2 adverse event (AE) attributed to V. There were 20 ≥ G2 immune-related AE (irAE): 0/3, 2/6, 5/6 and 13/15 pts on DL1–4, respectively. There was no evidence of clinical benefit in the 6 pts who had prior chemo on DL1 and 2, so subsequently we excluded pts with prior chemo. Median TTP for 9 chemo-naïve pts treated on DL2 and 3 was 6.1 mo (2.9–11.6 mo). Median PSA doubling time (DT) ↑ from 2.2 mo at baseline to 3.7 on study (p = 0.17). 5 of 9 had ≥ 50% ↓ in PSA from peak during study and 1 had a sustained ↓ PSA &gt; 95% from baseline. 4 of these pts had stable disease (SD) for ≥ 6 mo and 2 had unconfirmed partial responses by RECIST. Of the 15 pts on DL4, to date 9 have had SD for ≥ 6 mo (2 ≥ 12 mo); 4 remain on trial. 1 had a sustained ↓ in PSA &gt; 99% from baseline and is still on study after 12 mo. Median PSA DT ↑ &gt; 3-fold from 2.6 mo at baseline to 8.2 on study (p = 0.01) in DL4. The 24 chemo-naïve pts had PSA DT ↑ from 2.5 to 6 mo (p = 0.003). 14 of 30 pts had a PSA ↓ from baseline or peak PSA on study. 2 of 14 had no irAE, 12 showed ≥ G2 irAE temporally associated with PSA ↓. 5 of 9 pts had &gt; 2–5 fold ↑ in T-cell responses by ELISPOT assay and 4 of 13 had significant ↓ in their IL-6 levels. Immune responses appeared to correlate with clinical activity. Conclusions: This combination has clinical activity in pts with chemo-naïve mCRPC and seems to correlate with immune responses. It is associated with manageable side effects; however, further studies are required to see if the combination is more effective than either agent alone. No significant financial relationships to disclose.
Loss of susceptibility as a novel breeding strategy for durable and broad-spectrum resistance (2009)

Recent studies on plant immunity have suggested that a pathogen should suppress induced plant defense in order to infect a plant species, which otherwise would have been a nonhost to the pathogen. For this purpose, pathogens exploit effector molecules to interfere with different layers of plant defense responses. In this review, we summarize the latest findings on plant factors that are activated by pathogen effectors to suppress plant immunity. By looking from a different point of view into host and nonhost resistance, we propose a novel breeding strategy: disabling plant disease susceptibility genes (S-genes) to achieve durable and broad-spectrum resistance.
Autoimmunity and ALS (1996)

Significant evidence has accrued suggesting that antibodies to voltage-gated calcium channel are observed in at least some patients with sporadic ALS (SALS) and that such antibodies alter the function of these ion channels in vitro and in vivo. Further, passive transfer of these immunoglobulin-containing fractions into mice produces changes at the neuromuscular junction that are very similar to changes observed in patients with SALS. These changes reflect local alterations in intracellular Ca2+ homeostasis and, in animal models, may also evidence early changes of motoneuron injury, such as Golgi apparatus swelling and fragmentation. Although not yet documented to induce motoneuron death in vivo, SALS immunoglobulins induce Ca(2+)-dependent apoptosis in a differentiated motoneuron hybrid cell line via a mechanism that involves oxidative injury. SALS immunoglobulin-mediated apoptosis in these cells is regulated by the presence of the same calcium-binding proteins that may modulate selective motoneuron vulnerability in SALS.
Cone‐beam CT with megavoltage beams and an amorphous silicon electronic portal imaging device: Potential for verification of radiotherapy of lung cancer (2002)

We investigate the potential of megavoltage (MV) cone-beam CT with an amorphous silicon electronic portal imaging device (EPID) as a tool for patient position verification and tumor/organ motion studies in radiation treatment of lung tumors. We acquire 25 to 200 projection images using a 22 x 29 cm EPID. The acquisition is automatic and requires 7 minutes for 100 projections; it can be synchronized with respiratory gating. From these images, volumetric reconstruction is accomplished with a filtered backprojection in the cone-beam geometry. Several important prereconstruction image corrections, such as detector sag, must be applied. Tests with a contrast phantom indicate that differences in electron density of 2% can be detected with 100 projections, 200 cGy total dose. The contrast-to-noise ratio improves as the number of projections is increased. With 50 projections (100 cGy), high contrast objects are visible, and as few as 25 projections yield images with discernible features. We identify a technique of acquiring projection images with conformal beam apertures, shaped by a multileaf collimator, to reduce the dose to surrounding normal tissue. Tests of this technique on an anthropomorphic phantom demonstrate that a gross tumor volume in the lung can be accurately localized in three dimensions with scans using 88 monitor units. As such, conformal megavoltage cone-beam CT can provide three-dimensional imaging of lung tumors and may be used, for example, in verifying respiratory gated treatments.
A syntactic approach to discourse semantics (1984)

A correct structural analysis of a discourse is a prerequisite for understanding it. This paper sketches the outline of a discourse grammar which acknowledges several different levels of structure. This grammar, the "Dynamic Discourse Model", uses an Augmented Transition Network parsing mechanism to build a representation of the semantics of a discourse in a stepwise fashion, from left to right, on the basis of the semantic representations of the individual clauses which constitute the discourse. The intermediate states of the parser model the intermediate states of the social situation which generates the discourse.The paper attempts to demonstrate that a discourse may indeed be viewed as constructed by means of sequencing and recursive nesting of discourse constituents. It gives rather detailed examples of discourse structures at various levels, and shows how these structures are described in the framework proposed here.
The influence of biological and fungicidal seed treatments on chickpea (Cicer arietinum) damping off (2009)

Damping off of chickpea (Cicer arietinum) can lead to stand loss and yield reduction. Fungicide seed treatments are able to successfully control chickpea damping off, but the effectiveness of many commercially available biological seed treatments has not been well tested. The objective of this study was to test the effect of commercially available biological and fungicide seed treatments on damping off of cultivars of kabuli and desi chickpea types. The biological seed treatments Bacillus pumilus GB34 (Yield Shield), Bacillus subtilis GB03 (Kodiak), B. subtilis MBI 600 (Subtilex), Streptomyces lydicus WYEC 108 (Actinovate), Streptomyces griseoviridis K61 (Mycostop), Trichoderma harzianum Rifai strain KRL-AG2 (T-22 Planter Box), the fungicide treatments fludioxonil (Maxim) and mefenoxam (Apron XL LS), as well as combined biological and fungicide seed treatments were tested in greenhouse and field experiments. The desi cultivar exhibited lower incidence of damping off in greenhouse and field trials than the kabuli cultivar. Several biological seed treatments inhibited germination and growth of the kabuli cultivar in the absence of pathogens in greenhouse experiments but not in field trials. In greenhouse experiments where soil was artificially infested with the damping off pathogen Pythium ultimum, the kabuli cultivar emergence was increased by the application of mefenoxam but not by biological seed treatments. Mefenoxam was the most effective seed treatment in field trials at three locations in Montana in the spring of 2007. Biological seed treatments were ineffective for reducing damping off and increasing plant growth measurements above untreated controls, even in combination with fungicides. These results indicate the use of mefenoxam is critical for controlling Pythium damping off in Montana and that biological seed treatments are not effective.
Phase 1 evaluation of a local delivery device releasing silver ions in periodontal pockets: safety, pharmacokinetics and bioavailability (2001)

A new local delivery device (LDD) capable of releasing silver in periodontal pockets has been developed and tested pre-clinically. Silver has potent antimicrobial effects on Gram-negative periodontal pathogens with a mean in vitro minimum bactericidal concentration (MBC) < or =0.5 microg/ml. This phase 1 study assessed the safety, pharmacokinetics and bioavailability of silver ions delivered intracrevicularly with a resorbable LDD (PocketGuard) in a group of 9 volunteers affected with periodontitis. In each subject, a PLGA/PEG LDD loaded with 12% silver nitrate (w/w) was inserted in each of 4 selected pockets > or =5 mm. Serum, gingival fluid and subgingival plaque samples were evaluated before and at various time points after LDD placement for 21 days. At each time point, the concentration of silver in gingival crevicular fluid (GCF) was quantified with an Inductively Coupled Plasma-Mass Spectrometer. Subgingival plaque samples were processed for evaluation of total anaerobic and aerobic counts (CFU/ml). The maximum mean silver concentration in GCF was 1,493 +/- 709 microg/ml (range 589-2,245). It decayed exponentially with a half-life of 7.1 +/- 6.1 days (2.7-20.4). Average silver concentrations in excess of 10 microg/ml were detected in each patient for 14 days after LDD placement with the average concentration for all patients in excess of 25 microg/mL at day 21. Total anaerobic counts decreased an average of 1.7 +/- 1.9 x 10(6) CFU/ml (p= 0.0078) from baseline to day 7, indicating that the silver was biologically active. A mild increase in cervical root discoloration was observed at day 21:0.25 +/- 0.31 stain index units. Discoloration that did not resolve spontaneously could be removed at the end of the study with polishing. No systemic effects were observed. It is concluded that local silver concentrations above the MBC in serum were maintained for at least 21 days. A specific microbiologic effect was also observed.
A 3-D Model for Concentrator Solar Cells Based on Distributed Circuit Units (2005)

A three-dimensional (3-D) distributed model for high-concentrator solar cells based on elementary units made up of electrical circuits is presented. The recombination mechanisms are dealt with in detail, paying special attention to the perimeter properties. No ohmic effect is omitted making this a powerful simulation tool for concentrator solar cells. A shunt resistance is also included. The model allows the simulation of the external connections and nonuniform illumination profiles making this model very useful for optimizing future structures and technological processes. The proposed 3-D model is compared with a lumped, two-diode model in the simulation of a GaAs solar cell operating from 1 to 2000 suns. It is found that the 3-D distributed model agrees satisfactorily with the experimental data for all concentrations. The agreement cannot be made simultaneously for both low and high concentrations for the lumped model.
Structural studies on urethane elastomers (1968)

Abstract A number of techniques have been used to study structural organization and transitions in polyether- and polyester-based urethane elastomers. Scanning thermal methods reveal three characteristic transitions common to samples of varying composition, namely, the major glass transition and two higher transitions believed due to disruption of different types of hydrogen bonding. Other transitions are assigned to melting of ester and of urethane crystallites. Light-scattering measurements on turbid polyether-based samples indicate both isotropic and anisotropic contributions to scattered intensity, the latter reflecting structural ordering on a small scale. X-Ray diffraction studies of stress-induced crystallization in the polyetherbased elastomer show reflections attributed to crystallites of polyether segments. It is concluded that separation into a domain structure occurs in both types of elastomers, but to a higher degree in the polyether-based polymers than in the polyester-based polymers, possibly due to restrictions in the latter imposed by interaction of the ester and urethane groups.
Cyclosporin A inhibits induction of IL-2 receptor alpha chain expression by affecting activation of NF-kB-like factor(s) in cultured human T lymphocytes. (1991)

We have examined the effect and potential mechanism of Cyclosporin A (CsA) on the Interleukin-2-receptor alpha chain (IL-2R alpha) expression in human T-lymphocytes. CsA pretreatment of PHA-activated T-cells led to 30-50% decrease in Tac antigen surface expression and a concomitant decrease in the steady state IL-2R alpha mRNA levels. Transacting factors which recognize a kB-like sequence present in the IL-2R alpha chain regulatory region have been suggested to participate in the transcriptional regulation of the IL-2R alpha gene. Using oligonucleotides corresponding to the 5' regulatory region of the IL-2R alpha gene (i.e. 245 to 291 bp upstream of the start codon) and nuclear extract from resting T lymphocytes, we detected two specific bands by gel mobility shift assay. One of these bands is specifically increased after stimulation with phytohemagglutinin (PHA) and it is inhibited by CsA pretreatment. The same pattern of binding activity has been observed with the tandem repeat of NF-kB binding site present in the enhancer element of the human immunodeficiency virus long terminal repeat (HIV-1 LTR). These data suggest that CsA affects IL-2R receptor alpha chain expression by inhibiting the interaction of transacting factors to kB-like sequences after PHA activation. These findings may be of some relevance for the understanding of the immunosuppressive effects of CsA in normal human T lymphocytes.
Microbial Profile and Antimicrobial Susceptibility of Bacteria Found in Inflammatory Hidradenitis Suppurativa Lesions (2016)

Our findings on bacterial species and their topographical distribution revealed that the microbial flora in HS lesions reflects commensal flora of the skin. Due to the susceptibility rate and immunomodulatory and anti-inflammatory properties, cotrimoxazole may represent an alternative antibiotic agent and should be considered for therapy in HS patients.
X-Chromosome Inactivation in Cloned Mouse Embryos (2000)

To study whether cloning resets the epigenetic differences between the two X chromosomes of a somatic female nucleus, we monitored X inactivation in cloned mouse embryos. Both X chromosomes were active during cleavage of cloned embryos, followed by random X inactivation in the embryo proper. In the trophectoderm (TE), X inactivation was nonrandom with the inactivated X of the somatic donor being chosen for inactivation. When female embryonic stem cells with two active X chromosomes were used as donors, random X inactivation was seen in the TE and embryo. These results demonstrate that epigenetic marks can be removed and reestablished on either X chromosome during cloning. Our results also suggest that the epigenetic marks imposed on the X chromosomes during gametogenesis, responsible for normal imprinted X inactivation in the TE, are functionally equivalent to the marks imposed on the chromosomes during somatic X inactivation.