gebhart/patrepeval huggingface dataset:
TUTORIAL ON NETWORK GENOMICS. (2001)

With the ever-increasing genomic information pouring into the databases researchers start to look for pattern in genomes. Key questions are the identification of function. In the past function was mainly understood to be assigned to a single gene isolated from other cellular components or mechanisms. Sequence comparison fo single genes and their products (proteins) as well as of intergenic space are a consequence of a well established one-gene one-function interpretation. prediction of function solely by sequence similarity searches are powerful techniques that initiated the advent of bioinformatics and computational biology. Seminal work on sequence alignment by Temple Smith and Michael Waterman [33] and sequence searches with the BLAST algorithm by Altschul et al. [2] provide essential methods for sequence based determination of function. Similar outstanding contributions to determination of function have been archived in the area of structure prediction, molecular modeling and molecular dynamics. Techniques covering ab initio and homology modeling up to biophysical interpretation of long-run molecular dynamics simulations are mentioned ehre. With the ever-increasing number of information of different genetic/genomic origin, new aspect are looked for that deviate from the single gene at a time method. Especially with the identification of surprisingly few human genes the emerging perception in the scientific community that the concept of function has to be extended to include other sequence based as well as non-sequenced based information. A schema of determination of function by different concepts is shown in Figure 1. The tutorial is comprised of the following sections: The first two sections discuss the differences between genomic and non-genomic based context information, section three will cover combined methods. Finally, section four lsits web-resources and databases. All presented approaches extensively employ comparative methods.
The cancer anorexia-cachexia syndrome. (2000)

The cancer anorexia-cachexia syndrome is one of the most common causes of death among cancer patients and is present in 80% at death. It is a complex example of metabolic chaos effecting protein, carbohydrate, and fat metabolism. Tumors produce both direct and indirect abnormalities, resulting in anorexia and weight loss. The disease burden does not correlate with the degree of cachexia. Although there is no treatment to control or reverse the process, appetite stimulants may promote increased food intake and enhance quality of life.
Survey of Network on Chip (NoC) Architectures & Contributions (2009)

Multiprocessor architectures and platforms have been introduced to extend the applicability of Moore’s law. They depend on concurrency and synchronization in both software and hardware to enhance the design productivity and system performance. These platforms will also have to incorporate highly scalable, reusable, predictable, cost- and energy-efficient architectures. With the rapidly approaching billion transistors era, some of the main problems in deep sub-micron technologies which are characterized by gate lengths in the range of 60-90 nm, will arise from non-scalable wire delays, errors in signal integrity and unsynchronized communications. These problems may be overcome by the use of Network on Chip (NOC) architecture. In this paper, we have summarized over sixty research papers and contributions in NOC area.
Immunogenicity of Pasteurella multocida and Mannheimia haemolytica outer membrane vesicles (2013)

Pasteurella multocida is able to cause disease in humans and in a wide range of animal hosts, including fowl cholera in birds, atrophic rhinitis in pigs, and snuffles in rabbits. Together with Mannheimia haemolytica, P. multocida also represents a major bacterial causative agent of bovine respiratory disease (BRD), which is one of the most important causes for economic losses for the cattle backgrounding and feedlot industry. Commercially available vaccines only partially prevent infections caused by P. multocida and M. haemolytica. Thus, this study characterized the immunogenicity of P. multocida and M. haemolytica outer membrane vesicles (OMVs) upon intranasal immunization of BALB/c mice. Enzyme-linked immunosorbent assays (ELISA) revealed that OMVs derived from P. multocida or M. haemolytica are able to induce robust humoral and mucosal immune responses against the respective donor strain. In addition, also significant cross-immunogenic potential was observed for both OMV types. Colonization studies showed that a potential protective immune response against P. multocida is not only achieved by immunization with P. multocida OMVs, but also by immunization with OMVs derived from M. haemolytica. Immunoblot and immunoprecipitation analyses demonstrated that M. haemolytica OMVs induce a more complex immune response compared to P. multocida OMVs. The outer membrane proteins OmpA, OmpH, and P6 were identified as the three major immunogenic proteins of P. multocida OMVs. Amongst others, the serotype 1-specific antigen, an uncharacterized outer membrane protein, as well as the outer membrane proteins P2 and OmpA were found to be the most important antigens of M. haemolytica OMVs. These findings are useful for the future development of broad-spectrum OMV based vaccines against BRD and other infections caused by P. multocida or M. haemolytica.
COLORIMETRIC ESTIMATION OF INDOLEACETIC ACID (1951)

The wide use of the auxin, indoleacetic acid, in physiological and biochemical experiments has promoted interest in methods for its colorimetrie estimation. Mitchell and Brunstetteb (1) have proposed both the nitrite and the ferric chloride-sulphuric acid tests for the quantitative estimation of indoleacetic acid (IAA) in aqueous solutions, basing their suggested procedures upon a study of optimal reaction conditions for these two reagents. According to them, the nitrite method is sensitive to 10 /tig. IAA/ml. and develops a red color that is stable after two hours. In several attempts to duplicate their nitrite method using solutions of IAA varying from 20 to 45 /tg./ml., we could not obtain a stable red color with IAA at the two hours proposed, or at any other time. A faint pink develops almost immediately which rapidly fades to orange or yellow, depending on IAA concentrations, within i hour. If the concentration of nitrite is reduced, the red color becomes sufficiently persistent to be read. Indole likewise gives a strong, relatively stable, red color in this test (cf. table II)?a reaction which is sometimes used as a qualitative test for indole (Nitroso-Indole reaction). Tang and Bonner (2) have modified the ferric chloride-sulphuric acid method for IAA, combining the iron and sulphuric acid as a single reagent to yield improved sensitivity. However, the color produced is also unstable, rapidly developing and then fading. We have found, as have these workers, that the fading color can be practically dealt with by adopting a standard time between addition of reagent and reading of absorbancy or transmittance. Both of the methods discussed above possess disadvantages, lacking either specificity, sensitivity, or stability of color complex formed. During a study of the inactivation of IAA in aqueous solutions, it was frequently necessary to assay at one time many samples where the IAA concentrations were low, or where the degree of significance of small differences in concentrations between experimental unite required evaluation. Hence, we considered it desirable 'to re-examine the ferric chloride-sulphuric acid procedure. Several alterations have been made which produce a more stable color, of increased specificity, which changes in density more rapidly with variation in IAA concentration. 1. The procedure of Tang and Bonner can be improved somewhat by reading at 15 minutes after addition of reagent (instead of 30 minutes as they suggest), since the transient color reaches a maximum at the former time. Maximum absorption was found to occur at 530 ???.
Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. (1990)

To investigate the effect that human wild-type p53 (wt-p53) expression has on cell proliferation we constructed a recombinant plasmid, pM47, in which wt-p53 cDNA is under transcriptional control of the hormone-inducible mouse mammary tumor virus promoter linked to the dominant biochemical selection marker gene Eco gpt. The pM47 plasmid was introduced into T98G cells derived from a human glioblastoma multiforme tumor, and a stable clonal cell line, GM47.23, was derived that conditionally expressed wt-p53 following exposure to dexamethasone. We show that induction of wt-p53 expression in exponentially growing cells inhibits cell cycle progression and that the inhibitory effect is reversible upon removal of the inducer or infection with simian virus 40. Moreover, when growth-arrested cells are stimulated to proliferate, induction of wt-p53 expression inhibits G0/G1 progression into S phase and the cells accumulate with a DNA content equivalent to cells arrested in the G0/G1 phase of the cell cycle. Taken together, these studies suggest that wt-p53 may play a negative role in growth regulation.
Configurations of Diastereomeric Hydroxyethylene Isosteres Strongly Affect Biological Activities of a Series of Specific Inhibitors of Human‐Immunodeficiency‐Virus Proteinase (1997)

Human immunodeficiency virus (HIV) proteinase (PR) represents an important target for antiviral chemotherapy. We present an analysis of inhibitory activities of a series of pseudopeptide inhibitors of HIV-1 PR. All inhibitors were N-protected tetrapeptides with the scissile bond replaced by a nonhydrolysable hydroxyethylene or hydroxyethylamine isostere. To elucidate subtle structural requirements of the PR binding cleft, we synthesised inhibitors with four combinations of configurations at the asymmetric carbons of the isostere. Compounds were tested in vitro using purified recombinant enzyme and a chromogenic peptide substrate. The differences in inhibition constants between individual diastereoisomers reached three orders of magnitude. The most active hydroxyethylene-containing inhibitor possessed the 2R,4S,5S configuration at the isostere. Inhibitor activity was also tested in mammalian cell culture by analysing reduction of viral polyprotein processing and virus infectivity. The results obtained in tissue culture were generally in agreement with the in vitro data, giving a similar order of potency for the individual diastereoisomers. The most active compounds completely blocked production of infectious virus. A simulation method for interaction was employed to build a model of the inhibitors in the PR active site, to identify the interactions responsible for the differences in activities of individual stereoisomers, and to estimate the relative contribution of individual structural features to the overall inhibitory activity.
Dengue in Travelers (2005)

Dengue infection may be the most common infection other than malaria among travelers to tropical areas. This flavivirus infection is transmitted by mosquitoes. Although it often is asymptomatic, dengue infection can lead to leukopenia, thrombocytopenia, and even hemorrhagic complications and shock. This review summarizes the current approaches to establishing the diagnosis, managing the complications, and preventing this potentially dangerous infection.
Aberrant expression of homeobox gene HOXA7 is associated with müllerian-like differentiation of epithelial ovarian tumors and the generation of a specific autologous antibody response (2001)

Autologous serum antibodies to molecules that are aberrantly expressed in tumors represent potential biomarkers for early diagnosis of cancer. In this study, we identified the homeobox gene HOXA7 as encoding an antigen in epithelial tumors of the ovary. These tumors are thought to arise from the simple epithelium lining the ovarian surface, but they often resemble the specialized epithelia derived from the müllerian ducts. Expression of HOXA7 was detected in ovarian tumors exhibiting müllerian-like features and correlated with the generation of anti-HOXA7 antibodies by patients. In contrast, it was observed that healthy women lack anti-HOXA7 antibodies (P < 0.0001) and that HOXA7 expression is absent from normal ovarian surface epithelium. Interestingly, HOXA7 expression was detected in the müllerian-like epithelium lining inclusion cysts in normal ovaries and in the müllerian duct-derived epithelium of normal fallopian tubes. Furthermore, ectopic expression of HOXA7 enhanced the epithelial phenotype of immortalized ovarian surface epithelial cells, as indicated by the appearance of cobblestone morphology, induction of E-cadherin expression, and down-regulation of vimentin. These findings associate aberrant HOXA7 expression with the müllerian-like differentiation of epithelial ovarian tumors and suggest diagnostic utility of serum antibodies to HOXA7.
Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis? (1999)

It is generally believed that most T2-weighted (T2) lesions in the central white matter of patients with multiple sclerosis begin with a variable period of T1-weighted (T1) gadolinium (Gd) enhancement and that T1 Gd-enhancing and T2 lesions represent stages of a single pathological process. Lesion probability maps can be used to test this hypothesis by providing a quantitative description of the spatial distribution of these two types of lesions across a patient population. The simplest prediction of this hypothesis would be that the spatial distributions of T1 Gd-enhancing and T2 lesions are identical. We generated T1 Gd-enhancing and T2 lesion probability maps from 19 patients with relapsing-remitting multiple sclerosis. There was a significantly higher probability (P = 0.001) for T2 lesions to be found in the central relative to the peripheral white matter (risk ratio 4.5), although the relative distribution of T1 Gd-enhancing lesions was not significantly different (P = 0.7) between central and peripheral white matter regions (risk ratio 0.6). Longitudinal data on the same population were used to demonstrate a similar distribution asymmetry between new T1 Gd-enhancing and new T2 lesions that developed over the course of 1 year. Alternative hypotheses to explain this observation were tested. We found no spatial difference in the likelihood of development of persistent T2 lesions following T1 Gd enhancement. The relative distribution of T1 Gd-enhancing lesions was shown to be independent of the dose of Gd contrast agent and the frequency of scanning. Our findings suggest that a proportion of the periventricular T2 lesion volume may arise from mechanisms other than those associated with early breakdown of the blood-brain barrier leading to T1 Gd enhancement.
Comparison of standard exponential and linear techniques to amplify small cDNA samples for microarrays (2005)

Amplification with T7 transcription better reflects the variation of the unamplified transcriptome than PCR based methods owing to the better representation of long transcripts. If transcripts of particular interest are known to have high GC content and are of limited length, however, PCR-based methods may be preferable.
Development of immunity to porcine rotavirus in piglets protected from disease by bovine colostrum (1981)

Bovine colostrum with rotavirus-neutralizing activity was fed for 10 days to two groups of piglets, one of which was inoculated intranasally with a rotavirus of porcine origin. A third group, which did not receive colostrum, was also inoculated with the virus, and these piglets developed diarrhea, excreted rotavirus in the feces, and died 6 days after infection. In contrast, the infected piglets fed with bovine colostrum remained healthy, although they developed antibody to rotavirus. Twenty-seven days after the primary inoculation, piglets in the colostrum-fed groups were inoculated intranasally with virus. Those in the previously unexposed group became clinically ill and excreted rotavirus, whereas those which had experienced a previous subclinical infection (the colostrum-fed, virus-inoculated group) remained healthy. It was concluded that bovine colostrum protected piglets from the clinical effects of a porcine rotavirus and that these animals developed an immunity which prevented subsequent disease.
Neuroprotective and Neurotrophic Actions of the Mood Stabilizer Lithium: Can It Be Used to Treat Neurodegenerative Diseases? (2004)

The mood stabilizing drug lithium has emerged as a robust neuroprotective agent in preventing apoptosis of neurons. Long-term treatment with lithium effectively protects primary cultures of rat brain neurons from glutamate-induced, NMDA receptor-mediated excitotoxicity. This neuroprotection is accompanied by an inhibition of NMDA-receptor-mediated calcium influx, upregulation of anti-apoptotic Bcl-2, downregulation of pro-apoptotic p53 and Bax, and activation of cell survival factors. Lithium treatment antagonizes glutamate-induced activation of c-Jun-N-terminal kinase (JNK), p38 kinase, and AP-1 binding, which has a major role in cytotoxicity, and suppresses glutamate-induced loss of phosphorylated cAMP responsive element binding protein (CREB). Lithium also induces the expression of brain-derived neurotrophic factor (BDNF) and subsequent activation TrkB, the receptor for BDNF, in cortical neurons. The activation of BDNF/TrkB signaling is essential for the neuroprotective effects of this drug. In addition, lithium stimulates the proliferation of neuroblasts in primary cultures of CNS neurons. Lithium also shows neuroprotective effects in rodent models of diseases. In a rat model of stroke, post-insult treatment with lithium or valproate, another mood stabilizer, at therapeutic doses markedly reduces brain infarction and neurological deficits. This neuroprotection is associated with suppression of caspase-3 activation and induction of chaperone proteins such as heat shock protein 70. In a rat model of Huntington's disease (HD) in which an excitotoxin is unilaterally infused into the striatum, both long- and short-term pretreatment with lithium reduces DNA damage, caspase-3 activation, and loss of striatal neurons. This neuroprotection is associated with upregulation of Bcl-2. Lithium also induces cell proliferation near the injury site with a concomitant loss of proliferating cells in the subventricular zone. Some of these proliferating cells display neuronal or astroglial phenotypes. These results corroborate our findings obtained in primary neuronal cultures. The neuroprotective and neurotrophic actions of lithium have profound clinical implications. In addition to its present use in bipolar patients, lithium could be used to treat acute brain injuries such as stroke and chronic progressive neurodegenerative diseases.
Strategies for the reduction of 3‐MCPD esters and related compounds in vegetable oils (2011)

Abstract For the reduction of 3‐monochloro‐1,2‐propanediol fatty acid esters (3‐MCPD esters) and related compounds in edible fats and oils three different strategies are conceivable: removal of critical reactants from the raw material, changing of the refining process or removal of formed 3‐MCPD esters and related compounds from the refined product. This paper discusses these possibilities and shows that different raw materials have different capabilities to form 3‐MCPD esters and related compounds, whereas palm oil, but also corn oil or coconut oil possess the highest potential for the formation. Washing of the raw material before the refining process with water or ethanol (75%) reduced the capability for the formation of 3‐MCPD esters and related compounds in palm oil for about 20 and 25%, respectively. The paper shows that chloride and DAGs seem to be important precursors for the formation of 3‐MCPD esters and related compounds. A hypothesis was defined that a content of 4% DAGs could be a threshold for a higher potential of the raw material for the formation of the esters. Using acid solutions (formic acid) instead of water for the generation of strip steam during deodorization resulted in a reduction of the formation of glycidyl esters for about 35%. Practical application: In a first statement the German Federal Institute for Risk Assessment (BfR) but also others recommended to search for alternative techniques for the production of edible oils to ensure lower levels of 3‐MCPD esters and related compound. Changing the selection criteria for the raw material, improving the raw material before refining or removal of 3‐MCPD esters and related compounds after refining have the advantage that the refining process which has been optimized over the last 100 years regarding oil quality does not need to be changed.
Coagulation factors V and VIII and ceruloplasmin constitute a family of structurally related proteins. (1984)

Computer searches of the National Biomedical Research Foundation protein and nucleic acid sequence data bases using the NH2 terminus of the bovine factor Va 94-kilodalton heavy chain, the NH2 terminus of the 74-kilodalton factor Va light chain, and an internal 98-residue segment of porcine factor VIII revealed that both bovine factor V and porcine factor VIII are statistically homologous to human ceruloplasmin. The NH2-terminal segment of bovine factor Va heavy chain is homologous to three segments of ceruloplasmin sequence starting at residues 1, 351, and 713; the NH2-terminal sequence of bovine factor Va light chain is homologous to the same human ceruloplasmin sequence segments beginning at residues 1, 349, and 711. The longer porcine factor VIII sequence is homologous to three segments of human ceruloplasmin, residues 1-77, 400-433, and 683-791. These data indicate that factor V, factor VIII, and ceruloplasmin comprise a group of evolutionarily linked protein structures that possibly resulted from multiplication of ancestral precursor genes.
Novel Nucleotide Analogues as Potential Substrates for TMPK, a Key Enzyme in the Metabolism of AZT (2003)

Novel cyclic and acyclic analogues of dTMP and AZTMP were synthesized from the corresponding cycloSal-phosphotriesters. This method yielded the nucleotides in good yields with a simple work-up. Investigation of the substrate properties of the modified nucleotides towards TmpK showed, that they are very poor substrates for this key enzyme in the bioactivation of AZT.
Managed Care Forum (1996)

Journal Article Managed Care Forum Get access Perry Cohen, Pharm.D., Perry Cohen, Pharm.D. Senior Vice President Systemed Pharmacy Inc. 140 Glastonbury Boulevard Glastonbury, CT 06033 Search for other works by this author on: Oxford Academic Google Scholar Gene T. Jay, Gene T. Jay Manager, Pharmaceutical Policy Systemed Pharmacy Inc. 140 Glastonbury Boulevard Glastonbury, CT 06033 Search for other works by this author on: Oxford Academic Google Scholar Thomas B. Kayo, FASHP Thomas B. Kayo, FASHP General Manager Option Care of Tulsa 6666 S. Sheridan, Suite 100 Tulsa. OK 74133-1750 Search for other works by this author on: Oxford Academic Google Scholar American Journal of Health-System Pharmacy, Volume 53, Issue 13, 1 July 1996, Pages 1534–1537, https://doi.org/10.1093/ajhp/53.13.1534 Published: 01 July 1996