gebhart/patrepeval huggingface dataset:
Vasopeptidase Inhibitors (2001)

The cardiovascular system is regulated by hemodynamic and neurohumoral mechanisms. These regulatory systems play a key role in modulating cardiac function, vascular tone, and structure. Although neurohumoral systems are essential in vascular homeostasis, they become maladaptive in disease states such as hypertension, coronary disease, and heart failure. The clinical success of ACE inhibitors has led to efforts to block other humoral systems. Neutral endopeptidase (NEP) is an endothelial cell surface zinc metallopeptidase with similar structure and catalytic site. NEP is the major enzymatic pathway for degradation of natriuretic peptides, a secondary enzymatic pathway for degradation of kinins, and adrenomedullin. The natriuretic peptides can be viewed as endogenous inhibitors of the renin angiotensin system. Inhibition of NEP increases levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) of myocardial cell origin, and C-type natriuretic peptide (CNP) of endothelial cell origin as well as bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide and kinin systems, vasopeptidase inhibitors reduce vasoconstriction, enhance vasodilation, improve sodium/water balance, and, in turn, decrease peripheral vascular resistance and blood pressure and improve local blood flow. Within the blood vessel wall, this leads to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II and increased local levels of bradykinin (and, in turn, nitric oxide) and natriuretic peptides. Preliminary clinical experiences with vasopeptidase inhibitors are encouraging. Thus, the combined inhibition of ACE and neutral endopeptidase is a new and promising approach to treat patients with hypertension, atherosclerosis, or heart failure.
Chemoprevention of 1,2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compounds. (1990)

Organosulfur compounds (OSCs) present in garlic and onion oil have been shown to inhibit chemical carcinogenesis. In this study, we compared the chemopreventive efficacy of five lipid- and four water-soluble OSCs using the murine nuclear aberration assay. Administration of diallyl sulfide and S-allyl cysteine p.o. at a dose of 200 mg/kg 3 h prior to i.p. 1,2-dimethylhydrazine (DMH) injection (20 mg/kg) significantly inhibited colonic nuclear damage in female C57Bl/6J mice by 47% and 36%, respectively. The inhibitory effect of S-allyl cysteine was found to be dose dependent. The other OSCs did not affect the level of DMH-induced nuclear toxicity. Furthermore, the incidence and frequency of colonic tumors induced by DMH (20 mg/kg, 10 weekly i.p. injections) in female CF-1 mice were significantly inhibited by S-allyl cysteine pretreatment, given 3 h prior to each carcinogen injection. These data indicate that the allyl group coupled to a single sulfur atom might play an important structural role in inhibition of DMH-induced colonic nuclear toxicity and carcinogenesis. OSCs containing allyl groups stimulated glutathione S-transferase activity in both the liver and colon. However, their saturated analogues stimulated little or no hepatic and colonic glutathione S-transferase activity. Induction of hepatic and colonic glutathione S-transferase might assist in detoxification of carcinogens and could be necessary for some aspects of chemoprevention.
Hodgkin's Disease in Siblings (1977)

An incidence survey of Hodgkin's disease in Greater Boston during 1959-1973 detected five sibling pairs under the age of 45. The expected number is 0.7; thus, siblings of young adults with Hodgkin's disease have about a sevenfold excess risk of the disease (P = 0.0008). Eight sibling pairs, not in the incidence series, were also identified. Among all 13 pairs, 12 were sex concordant; the number expected is 6.8 (P = 0.01). The literature includes 46 sibling pairs under 45 of which 30 are sex concordant. The expected number is 23.9 (P = 0.05). Combining the present and the literature series suggests that siblings of the same sex as an affected person have a risk of Hodgkin's disease double that of siblings of the opposite sex. The sex concordance suggests that the excess Hodgkin's disease among siblings of affected persons is due either to inter-personal transmission of an etiologic agent by prolonged or intimate contact or to common-source exposures.
Macro-materials processing (1982)

Laser macro-materials processing is currently undergoing intense development. Lasers have already offered new processing capabilities, and have gained an important rank as industrials machine tools. This paper outlines the basic methods employed in laser macro-machining, discusses the controlling beam-interaction parameters, and relates progress gained in formulating a better understanding of the underlying physical principles of high-power laser processing of materials. A number of cases in which lasers have offered substantial advantages over competing technologies are illustrated. The evolution of macro-machining of materials continues to lead to new laser-processing capabilities, and even now may have rendered some of the earliest cited laser performance data obsolete.
Differential aspects of consultation-liaison psychiatry in a Saudi hospital. II: knowledge and attitudes of physicians and patients. (2006)

To assess the attitude and knowledge of physicians and patients towards psychiatry, we asked 115 referring doctors and 188 referred patients to complete questionnaires. We examined the results along with the referral rates to try to identify factors that may affect a consultation-liaison psychiatry service. Generally, knowledge was poor and attitudes towards psychiatry negative in both groups. This negatively influenced the referral rates and reflected the lack of integration of psychiatry and medicine at the training level. This is an indication that psychiatrists need to work in collaboration with hospital doctors to integrate psychiatry into medicine at all levels and emphasizes the priority of education of hospital staff, patients and the community in consultation-liaison psychiatry.
The expression of lysyl‐oxidase gene family members in myeloproliferative neoplasms (2013)

Myeloproliferative neoplasms (MPNs) are malignant disorders originating from clonal expansion of a single neoplastic stem cell and characteristically show an increase in bone marrow reticulin fibers. Lysyl oxidases (LOXs) are copper-dependent amine oxidases that play a critical role in the biogenesis of connective tissue by crosslinking extracellular matrix proteins, collagen and elastin. Expression of LOX gene family members is increased in disorders associated with increased fibrosis. To evaluate involvement of LOX gene family in various MPNs. In-situ hybridization was used to detect Lysyl-Oxidase family members in bone marrow biopsies from patients with different MPNs. We compared normal bone marrows and those from patients with polycythemia vera, essential thrombocythemia, chronic myeloid leukemia, and primary myelofibrosis (PMF). Serum levels of lysyl-oxidase from patients with PMF and healthy controls were also examined. LOX gene family was not detected in normal bone marrows. All members of the LOX gene family were over expressed in PMF. In other MPNs a differential pattern of expression was observed. Differences in gene expression were statistically significant (P < 0.010). The medianserum LOX levels in normal controls was 28.4 ± 2.5 ng\ml and 44.6 ± 9.44 ng\ml in PMF (P = 0.02). The varying pattern of expression of LOX genes may reflect differences in the pathophysiology of bone marrow fibrosis in these MPNs. These observations could be used as the basis for future targeted therapy directed against bone marrow fibrosis.
Spin Torque and Field-Driven Perpendicular MRAM Designs Scalable to Multi-Gb/Chip Capacity (2006)

In this paper, we present a micromagnetic analysis of two novel magnetoresistive memory designs, both of which utilize the material-intrinsic perpendicular uniaxial magnetic anisotropy for retaining memory states. The analysis shows that such perpendicular memory element design allows the utilization of thick magnetic film, thereby enabling downsize scalability of each memory element while maintaining sufficient thermal stability. One of the designs is to utilize direct current injection for switching the memory states via the effect of spin momentum transfer. The other design utilizes current-generated field for switching. The performance characteristics of both designs are reported
Genetic structure of avian myeloblastosis virus, released from transformed myeloblasts as a defective virus particle (1980)

Chicken myeloblasts transformed by avian myeloblastosis virus (AMV) in the absence of nondefective helper virus (termed nonproducer cells) were found to release a defective virus particle (DVP) that contains avian tumor viral gag proteins but lacks envelope glycoprotein and a DNA polymerase. Nonproducer cells contain a Pr76 gag precursor protein and also a protein that is indistinguishable from the Pr180 gag-pol protein of nondefective viruses. The RNA of the DVP is 7.5 kilobases (kb) long and is 0.7 kb shorter than the 8.2-kb RNAs of the helper viruses of AMV, MAV-1 and MAV-2. Comparisons based on RNA.cDNA hybridization and mapping of RNase T1-resistant oligonucleotides indicated that DVP RNA shares with MAV RNAs nearly isogenic 5'-terminal gag and pol-related sequences of 5.3 kb and a 3'-terminal c-region of 0.7 kb that is different from that found in other avian tumor viruses. Adjacent to the c-region, DVP RNA contains a contiguous specific sequence of 1.5 kb defined by 14 specific oligonucleotides. Except for two of these oligonucleotides that map at its 5' end, this sequence is unrelated to any sequences of nondefective avian tumor viruses of four different envelope subgroups as well as to the specific sequences of fibroblast-transforming avian acute leukemia and sarcoma viruses of four different RNA subgroups. The specific sequence of the DVP RNA is present in infectious stocks of AMV from this and other laboratories in an AMV-transformed myeloblast line from another laboratory, and it is about 70% related to nucleotide sequences of E26 virus, an independent isolate of an AMV-like virus. Preliminary experiments show DVP to be leukemogenic if fused into susceptible cells in the presence of helper virus. We conclude that DVP RNA is the leukemogenic component of infectious AMV and that its specific sequence, termed AMV, may carry genetic information for oncogenicity. Thus we have found here a transformation-specific RNA sequence, unrelated to helper virus, in a highly oncogenic virus that does not transform fibroblasts.
Diurnal and Ultradian Dynamics of Serum Adiponectin in Healthy Men: Comparison with Leptin, Circulating Soluble Leptin Receptor, and Cortisol Patterns (2003)

Adiponectin is an abundant serum adipokine secreted exclusively from differentiated adipocytes, which plays an important role in regulating insulin sensitivity. The dynamics of circulating adiponectin concentrations have yet to be systematically investigated. We sought to determine whether serum adiponectin levels exhibit diurnal or ultradian rhythms in healthy normal-weight men and to compare the 24-h profile of adiponectin fluctuations with those of leptin, leptin-binding protein (sOB-R), and cortisol. We collected blood samples at 15-min intervals over 24 h from six subjects receiving an isocaloric diet, and we measured adiponectin, leptin, sOB-R, and cortisol levels. Fourier and cross-correlation analyses were performed on these time series to study diurnal variations, and the Cluster7 program was used for pulsatility analysis. Circulating adiponectin and sOB-R levels exhibited ultradian pulsatility as well as a diurnal variation with a significant decline at night, reaching a nadir in the early morning. The 24-h variations of serum adiponectin and sOB-R were nearly identical and followed those of cortisol after a few hours, but were out-of-phase with leptin diurnal rhythms. These data suggest that adiponectin and sOB-R levels might be influenced by common regulatory factors and challenge the notion that cortisol may have a direct inhibitory effect on adiponectin in humans.
A New Series of PDGF Receptor Tyrosine Kinase Inhibitors: 3-Substituted Quinoline Derivatives (1994)

A series of 63 3-substituted quinoline derivatives has been prepared and tested for inhibition of cell-free platelet derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The compounds were generally prepared either by a Friedlander condensation between an aryl-acetaldehyde and an o-aminobenzaldehyde or by a palladium-catalyzed coupling between an aryl bromide or triflate and an organostannane or organozinc chloride. The presence of 6,7-dimethoxy groups on the quinoline ring was found to be advantageous although not essential for potent inhibition of PDGF-RTK. A lipophilic group attached to the quinoline 3-position contributed substantially to activity. The lipophilic groups generally consisted of monocyclic aromatics or small alkynyl, alkenyl, and alkyl groups. Optimum activity of ca. < or = 20 nM (IC50) was observed when 6,7-dimethoxyquinoline was substituted in the 3-position with 4-methoxyphenyl (15d), 3-fluoro-4-methoxyphenyl (17m), 3-fluorophenyl (17b), 4-hydroxyphenyl (24), 6-methoxypyridin-3-yl (15o), 5-pyridin-2(1H)-one (23), trans-beta-styryl (15e), thiophene-3-yl (2e), 5-chlorothiophene-2-yl (15f), or cyclopentenyl (17n) groups. Most of the compounds in the series were tested for inhibition of cell-free epidermal growth factor receptor tyrosine kinase activity and found to be inactive.
Genetic Characterization of a New Type IV-A Pilus Gene Cluster Found in Both Classical and El Tor Biotypes of Vibrio cholerae (1999)

The Vibrio cholerae genome contains a 5.4-kb pil gene cluster that resembles the Aeromonas hydrophila tap gene cluster and other type IV-A pilus assembly operons. The region consists of five complete open reading frames designated pilABCD and yacE, based on the nomenclature of related genes from Pseudomonas aeruginosa and Escherichia coli K-12. This cluster is present in both classical and El Tor biotypes, and the pilA and pilD genes are 100% conserved. The pilA gene encodes a putative type IV pilus subunit. However, deletion of pilA had no effect on either colonization of infant mice or adherence to HEp-2 cells, demonstrating that pilA does not encode the primary subunit of a pilus essential for these processes. The pilD gene product is similar to other type IV prepilin peptidases, proteins that process type IV signal sequences. Mutational analysis of the pilD gene showed that pilD is essential for secretion of cholera toxin and hemagglutinin-protease, mannose-sensitive hemagglutination (MSHA), production of toxin-coregulated pili, and colonization of infant mice. Defects in these functions are likely due to the lack of processing of N termini of four Eps secretion proteins, four proteins of the MSHA cluster, and TcpB, all of which contain type IV-A leader sequences. Some pilD mutants also showed reduced adherence to HEp-2 cells, but this defect could not be complemented in trans, indicating that the defect may not be directly due to a loss of pilD. Taken together, these data demonstrate the effectiveness of the V. cholerae genome project for rapid identification and characterization of potential virulence factors.
Cytokines and oxidative signalling in skeletal muscle (2001)

A growing body of literature indicates that cytokines regulate skeletal muscle function, including gene expression and adaptive responses. Tumour necrosis factor-alpha (TNF-alpha) is the cytokine most prominently linked to muscle pathophysiology and, therefore, has been studied most extensively in muscle-based systems. TNF-alpha is associated with muscle catabolism and loss of muscle function in human diseases that range from cancer to heart failure, from arthritis to AIDS. Recent advances have established that TNF-alpha causes muscle weakness via at least two mechanisms, accelerated protein loss and contractile dysfunction. Protein loss is a chronic response that occurs over days to weeks. Changes in gene expression required for TNF-alpha induced catabolism are regulated by the transcription factor nuclear factor-kappaB which is essential for the net loss of muscle protein caused by chronic TNF-alpha exposure. Contractile dysfunction is an acute response to TNF-alpha stimulation, developing over hours and resulting in decreased force production. Both actions of TNF-alpha involve a rapid rise in endogenous oxidants as an essential step in post-receptor signal transduction. These oxidants appear to include reactive oxygen species derived from mitochondrial electron transport. Such information provides insight into the cellular and molecular mechanisms of TNF-alpha action in skeletal muscle and establishes a scientific basis for continued research into cytokine signalling.
Multiple effects of tumor necrosis factor on lipoprotein lipase in vivo. (1987)

A single dose of recombinant murine tumor necrosis factor (TNF) suppressed lipoprotein lipase activity in adipose tissue of fed rats, mice, and guinea pigs for 48 h, even though TNF itself is rapidly metabolized in vivo. Immunoprecipitation of [35S]lipoprotein lipase from fat pads pulse-labeled with [35S]methionine showed a decrease in relative synthesis of the enzyme, which correlated to the decrease in activity. There was no decrease in general protein synthesis and no change in distribution of the enzyme between adipocytes and extracellular locations in the tissue. This is in contrast to fasting in which case there is redistribution of the enzyme within the tissue, decrease in general protein synthesis, but no change in relative synthesis of lipoprotein lipase. TNF did not decrease lipoprotein lipase activity in any tissue other than the adipose but increased the activity in several cases, most markedly in the liver. No [35S]methionine was incorporated into lipoprotein lipase by liver slices from normal or TNF-treated animals. Thus, the increased activity can not be ascribed to enhanced hepatic synthesis of the enzyme. There was an increase in lipoprotein lipase activity in plasma, which correlated to the increase in liver. Thus, TNF suppresses lipoprotein lipase synthesis in adipocytes, but not in other tissues, and has some as yet undefined effect on lipoprotein lipase turnover in extrahepatic tissues, which results in increased transport of active lipase through plasma to the liver.
CD44 modulates Smad1 activation in the BMP-7 signaling pathway (2004)

Bone morphogenetic protein 7 (BMP-7) regulates cellular metabolism in embryonic and adult tissues. Signal transduction occurs through the activation of intracellular Smad proteins. In this paper, using a yeast two-hybrid screen, Smad1 was found to interact with the cytoplasmic domain of CD44, a receptor for the extracellular matrix macromolecule hyaluronan. Coimmunoprecipitation experiments confirmed the interaction of Smad1 with full-length CD44-interactions that did not occur when CD44 receptors truncated within the cytoplasmic domain were tested. Chondrocytes overexpressing a truncated CD44 on a background of endogenous full-length CD44 no longer exhibited Smad1 nuclear translocation upon BMP-7 stimulation. Further, pretreatment of chondrocytes with Streptomyces hyaluronidase to disrupt extracellular hyaluronan-cell interactions inhibited BMP-7-mediated Smad1 phosphorylation, nuclear translocation of Smad1 or Smad4, and SBE4-luciferase reporter activation. These results support a functional link between the BMP signaling cascade and CD44. Thus, changes in hyaluronan-cell interactions may serve as a means to modulate cellular responsiveness to BMP.
<title>Scene change detection and content-based sampling of video sequences</title> (1995)

Digital images and image sequences (video) are a significant component of multimedia information systems, and by far the most demanding in terms of storage and transmission requirements. Content-based temporal sampling of video frames is proposed as an efficient method for representing the visual information contained in the video sequence by using only a small subset of the video frames. This involves the identification and retention of frames at which the contents of the scene is `significantly' different from the previously retained frames. It is argued that the criteria used to measure the significance of a change in the contents of the video frames are subjective, and performing the task of content-based sampling of image sequences, in general, requires a high level of image understanding. However, a significant subset of the points at which the contextual information in the video frames change significantly can be detected by a `scene change detection' method. The definition of a scene change is generalized to include not only the abrupt transitions between shots, but also gradual transitions between shots resulting from video editing modes, and inter-shot changes induced by camera operations. A method for detecting abrupt and gradual scene changes is discussed. The criteria for detecting camera-induced scene changes from camera operations are proposed. Scene matching is proposed as a means of achieving further reductions in the storage and transmission requirements.
Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity (2011)

The present study demonstrates and highlights the importance of subtle biological changes downstream of primary membrane and endocytosis-associated phenomena resulting from high dose SiO2NP exposure. Increased activation of transcription factors, such as ATF-2, was quantitatively assessed as a function of i) human cell line specific stress-response, ii) SiO2NP size and iii) concentration. Despite the low level of cytotoxicity detected for the amorphous SiO2NP investigated, these findings prompt an in-depth focus for future SiO2NP-cell/tissue investigations based on the combined analysis of more subtle signalling pathways associated with accumulation mechanisms, which is essential for establishing the bio-safety of existing and new nanomaterials.
Antibodies to mouse mammary tumor virus-related antigen in sera of patients with breast carcinoma (1981)

Sera from patients with breast carcinoma, benign breast disease, malignancies other than breast carcinoma, and healthy female controls were analyzed by indirect immunofluorescence for the presence of antibodies directed toward antigens of mouse mammary tumor. Sera from 56 to 137 (40.9%) patients with breast carcinoma were positive. Positive reactivity was also found in sera from 5 to 27 (18.5%) patients with benign breast disease, in 7 of 60 (11.7%) patients with malignancies other than breast carcinoma, and in 2 of 56 (3.6%) female controls. In the group of patients with breast carcinoma a correlation was noted between age and the probability of detection of these antibodies. Histopathologic examination of breast cancers indicated that antibodies to antigens in mouse mammary tumors were more often found in patients with infiltrating ductal carcinoma of the mucinous type than with other types of breast tumors. No correlation was demonstrable between the incidence of detection of these antibodies and the stage of the disease. Immunochemical analyses indicated that the antibody activity was present in IgG and IgM classes of immunoglobulins. The human antibodies to antigens in mouse mammary tumors could be removed from patients' sera by absorption with disrupted mouse mammary tumor virus (MMTV) but not with gp52 or gp34 (52,000 and 34,000 dalton polypeptides) of MMTV, or with Rauscher mouse leukemia virus (MLV).