gebhart/patrepeval huggingface dataset:
Proopiomelanocortin Processing in the Pituitary, Central Nervous System, and Peripheral Tissues (1988)

More than 20 yr ago, in an elegant series of pulsechase studies, Steiner and Oyer (1) demonstrated that insulin is synthesized in pancreatic islet cells as part of a larger molecule, proinsulin. Since that time, the concept that bioactive peptides are derived from larger precursors has become firmly established (2–4). Over the same period, the definitive structures of the majority of precursors of biologically active peptides have been fully characterized, both by classical protein sequence studies and more recently by recombinant DNA techniques (for reviews see Refs. 4–6). To yield biologically active products, precursors commonly undergo a series of highly organized posttranslational events, including selective proteolytic cleavage and other enzymatic modifications (e.g., phosphorylation, α-amidation, acetylation) which take place within specific membrane-bounded compartments. A number of precursor polypeptides contain within their structure amino acid sequences which have quite diverse biological actions depending on the extent of processing. Second, different precursor molecules can contain identical or very similar sequences. A striking example of both these phenomena is found in the family of prohormones which are processed to yield the opioid peptides, POMC, proenkephalin A (proenkephalin), and proenkephalin B (prodynorphin) (for reviews see Refs. 6–8). A third common feature of precursor processing, and again one described for all three opioid prohormones, is that of tissue-specific differences in their patterns of maturation. Proenkephalin in the brain is largely processed to the pentapeptide enkephalins (9), whereas in the adrenal the majority of enkephalin-like immunoreactivity appears to be of higher molecular weight (4–10 K) (9). Similarly, prodynorphin in the hypothalamus and pituitary neural lobe is processed to smaller forms, principally dynorphin 1-8 and dynorphin 1-17 (10), while in the anterior pituitary larger immunoreactive forms (4–6 K) predominate. These tissue-specific patterns of precursor processing perhaps reflect quite distinct neurotransmitter (central nervous system) and endocrine/paracrine (peripheral tissue) physiological roles for these peptides.
The binding mode of drugs to the TAR RNA of HIV-1 studied by electric linear dichroism (1996)

For the first time, the interaction between a series of small molecules and the TAR RNA of HIV-1 has been investigated by electric linear dichroism (ELD). The compounds tested include the DNA intercalating drugs proflavine and ethidium bromide and an amsacrine-4-carboxamide DNA-threading intercalator as well as the AT-specific DNA minor groove binders netropsin, Hoechst 33258, berenil and DAPI. In all cases except for netropsin, negative reduced dichroism signals were measured in the drug absorption band. In agreement with previous studies, the results indicate that both classical and threading intercalation can occur with the TAR RNA. The ELD data show that the mode of binding of the drugs Hoechst 33258, berenil and DAPI to the TAR RNA is similar to their binding mode in GC-rich regions of DNA and likely involves intercalation into the A-form TAR RNA helix. The wide and shallow minor groove of the TAR RNA is apparently not accessible to DNA minor groove binding drugs such as netropsin. The ELD technique appears uniquely valuable as a means of investigating the interaction of drugs with the TAR RNA.
Encoders, Decoders, Compressors, Decompressors, Viewers, and Helper Utilities for an Internet Tool Box (1996)

No abstract available for this article.
A Plant-specific Cyclin-dependent Kinase Is Involved in the Control of G2/M Progression in Plants (2001)

Cyclin-dependent kinases (CDKs) control the key transitions in the eukaryotic cell cycle. All the CDKs known to control G(2)/M progression in yeast and animals are distinguished by the characteristic PSTAIRE motif in their cyclin-binding domain and are closely related. Higher plants contain in addition a number of more divergent non-PSTAIRE CDKs with still obscure functions. We show that a plant-specific type of non-PSTAIRE CDKs is involved in the control of the G(2)/M progression. In synchronized tobacco BY-2 cells, the corresponding protein, accumulated in a cell cycle-regulated fashion, peaking at the G(2)/M transition. The associated histone H1 kinase activity reached a maximum in mitosis and required a yet unidentified subunit to be fully active. Down-regulation of the associated kinase activity in transgenic tobacco plants using a dominant-negative mutation delayed G(2)/M transition. These results provide the first evidence that non-PSTAIRE CDKs are involved in the control of the G(2)/M progression in plants.
Donna Interactive Chat-bot acting as a Personal Assistant (2016)

Chat-bots are computer programs coded to have a textual or verbal conversation which is logical or intelligent.Chat-bots are designed to make humans believe that they are talking to a human; but instead they are in fact talking to a machine.Taking advantage of this transparency property of chat-bot, an artificial character and personality can be given to a chat-bot which acts like a person of a specific profession.This paper describes an approach to the idea of implementing web-based artificially intelligent chat-bot as a personal assistant of the user, which stimulates setting and initiating meetings of user with his clients.The exchange of information happens through email conversations whereas its evaluation happens through natural language procession and natural language generation and AIML files.
B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide (1999)

While the pathology of multiple sclerosis implicates a role for B cells and antibodies in the disease process, results from animal models have yielded conflicting results. To further characterize the role of B cells in experimental allergic encephalomyelitis (EAE), wild-type and B cell-deficient C57BL/6 mice were immunized with either a recombinant form of myelin oligodendrocyte glycoprotein (MOG) or with the encephalitogenic MOG(35-55) peptide. B cell-deficient mice did not develop EAE when immunized with MOG, although they were susceptible to MOG(35-55)-induced disease. In contrast, wild-type mice were fully susceptible to both MOG and MOG(35-55)-induced EAE. B cell-deficient mice immunized with MOG were primed to the encephalitogenic MOG(35- 55) epitope, as their spleen cells responded with Th1 cytokine production in a fashion similar to WT cells when challenged in vitro with MOG protein or MOG(35-55) peptide. These results demonstrate that the form of inducing antigen (protein vs. peptide) plays a role in the pathogenesis of EAE and may be relevant when applying results from the EAE model to multiple sclerosis.
THE SIGNIFICANT IMMUNOSUPPRESSIVE EFFECT OF GANGLIOSIDE GM3 IN HEART TRANSPLANTATION (1993)

HACHIDA, MITSUHIRO; UWABE, KAZUHIKO; NONOYAMA, MASAKI; IMAMAKI, MIZUHO; NEMOTO, SHINTAROU; HOSHI, HIRONOBU; KATSUMATA, TAKAHIRO; ENDO, MASAHIRO; KOYANAGI, HITOSHI Author Information
Correction of steal syndrome secondary to hemodialysis access fistulas: a simplified quantitative technique. (1992)

Correction of symptomatic vascular steal distal to an arteriovenous fistula requires either fistula ligation or banding. Ligation carries the obvious disadvantage of destruction of a functioning angioaccess, whereas banding procedures have been plagued by the complexity of many of the reported techniques and by the difficulty of balancing fistula flow with distal perfusion. In this study a simple plication technique is described that avoids the introduction of any additional foreign material and that quantifies distal perfusion by means of intraoperative pulse volume recordings. Five patients have been treated by this method, two with autologous vein fistulas and three with bridge fistulas using polytetrafluorethylene. All five have had resolution of their ischemic symptoms with an increase in intraoperative pulse volume recordings of 5 mm or more. Only three of the patients had restoration of the radial pulse, which was not a specific end point of the banding procedure. Furthermore, all fistulas remained patent for at least 6 months and continued to provide adequate flows for hemodialysis. Banding/plication is clearly preferable to fistula closure for the management of steal syndrome. The method described herein is simple and hemodynamically identifies the minimal constriction that will resolve symptoms and preserve fistula flow.
Indoleamine 2,3‐dioxygenase in T‐cell tolerance and tumoral immune escape (2008)

Indoleamine 2, 3-dioxygenase (IDO) degrades the essential amino acid tryptophan in mammals, catalyzing the initial and rate-limiting step in the de novo biosynthesis nicotinamide adenine dinucleotide (NAD). Broad evidence implicates IDO and the tryptophan catabolic pathway in generation of immune tolerance to foreign antigens in tissue microenvironments. In particular, recent findings have established that IDO is overexpressed in both tumor cells and antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the normal physiologic state, IDO is important in creating an environment that limits damage to tissues due to an overactive immune system. However, by fostering immune suppression, IDO can facilitate the survival and growth of tumor cells expressing unique antigens that would be recognized normally as foreign. In preclinical studies, small-molecule inhibitors of IDO can reverse this mechanism of immunosuppression, complementing classical cytotoxic cancer chemotherapeutic agents' ability to trigger regression of treatment-resistant tumors. These results have encouraged the clinical translation of IDO inhibitors, the first of which entered phase I clinical trials in the fall of 2007. In this article, we survey the work defining IDO as an important mediator of peripheral tolerance, review evidence of IDO dysregulation in cancer cells, and provide an overview of the development of IDO inhibitors as a new immunoregulatory treatment modality for clinical trials.
De Novo Design, Expression, and Characterization of Felix: a Four-Helix Bundle Protein of Native-Like Sequence (1990)

The protein Felix was designed de novo to fold into an antiparallel four-helix bundle of specific topology. Its sequence of 79 amino acid residues is not homologous to any known protein sequence, but is "native-like" in that it is nonrepetitive and contains 19 of the 20 naturally occurring amino acids. Felix has been expressed from a synthetic gene cloned in Escherichia coli, and the protein has been purified to homogeneity. Physical characterization of the purified protein indicates that Felix (i) is monomeric in solution, (ii) is predominantly alpha-helical, (iii) contains a designed intramolecular disulfide bond linking the first and fourth helices, and (iv) buries its single tryptophan in an apolar environment and probably in close proximity with the disulfide bond. These physical properties rule out several alternative structures and indicate that Felix indeed folds into approximately the designed three-dimensional structure.
The Neurochip-2: An Autonomous Head-Fixed Computer for Recording and Stimulating in Freely Behaving Monkeys (2011)

The Neurochip-2 is a second generation, battery-powered device for neural recording and stimulating that is small enough to be carried in a chamber on a monkey's head. It has three recording channels, with user-adjustable gains, filters, and sampling rates, that can be optimized for recording single unit activity, local field potentials, electrocorticography, electromyography, arm acceleration, etc. Recorded data are stored on a removable, flash memory card. The Neurochip-2 also has three separate stimulation channels. Two "programmable-system-on-chips" (PSoCs) control the data acquisition and stimulus output. The PSoCs permit flexible real-time processing of the recorded data, such as digital filtering and time-amplitude window discrimination. The PSoCs can be programmed to deliver stimulation contingent on neural events or deliver preprogrammed stimuli. Access pins to the microcontroller are also available to connect external devices, such as accelerometers. The Neurochip-2 can record and stimulate autonomously for up to several days in freely behaving monkeys, enabling a wide range of novel neurophysiological and neuroengineering experiments.
Neutralizing Antibodies to Adenovirus Serotype 5 Vaccine Vectors Are Directed Primarily against the Adenovirus Hexon Protein (2005)

The utility of recombinant adenovirus serotype 5 (rAd5) vector-based vaccines for HIV-1 and other pathogens will likely be limited by the high prevalence of pre-existing Ad5-specific neutralizing Abs (NAbs) in human populations. However, the immunodominant targets of Ad5-specific NAbs in humans remain poorly characterized. In this study, we assess the titers and primary determinants of Ad5-specific NAbs in individuals from both the United States and the developing world. Importantly, median Ad5-specific NAb titers were >10-fold higher in sub-Saharan Africa compared with the United States. Moreover, hexon-specific NAb titers were 4- to 10-fold higher than fiber-specific NAb titers in these cohorts by virus neutralization assays using capsid chimeric viruses. We next performed adoptive transfer studies in mice to evaluate the functional capacity of hexon- and fiber-specific NAbs to suppress the immunogenicity of a prototype rAd5-Env vaccine. Hexon-specific NAbs were remarkably efficient at suppressing Env-specific immune responses elicited by the rAd5 vaccine. In contrast, fiber-specific NAbs exerted only minimal suppressive effects on rAd5 vaccine immunogenicity. These data demonstrate that functionally significant Ad5-specific NAbs are directed primarily against the Ad5 hexon protein in both humans and mice. These studies suggest a potential strategy for engineering novel Ad5 vectors to evade dominant Ad5-specific NAbs.
Clinicopathological significance of core 2 beta1,6-N-acetylglucosaminyltransferase messenger RNA expressed in the pulmonary adenocarcinoma determined by in situ hybridization. (2001)

Cell surface carbohydrates of epithelial cells play important roles in tumor progression. Previously, we have shown that expression of core 2 branched O-glycans in colorectal cancer is closely correlated with the vessel invasion and depth of invasion (K. Shimodaira et al., Cancer Res., 57: 5201-5206, 1997). To test whether this is also the case in human lung cancer, we have examined the expression pattern of core 2 beta1,6-N-acetylglucosaminyltransferase (C2GnT) mRNA responsible for the biosynthesis of core 2 branched O-glycans in 41 cases of lung cancer. Using in situ hybridization, C2GnT mRNA was detected in 73.2% of the lung cancer cells, irrespective of the histopathological type; whereas in normal lung tissues, its expression was restricted to the basal cells of bronchial mucosa. These results indicate that the expression level of C2GnT mRNA was significantly enhanced in association with malignant transformation. Statistical analysis between the C2GnT mRNA expressed in pulmonary adenocarcinoma and clinicopathological variables revealed that the expression of C2GnT was correlated with vessel invasion and lymph node metastasis with significant difference (P < 0.05), but expression of sialyl Le(x), which is frequently expressed in the adenocarcinoma, was not significantly correlated with lymph node metastasis. These results indicate that C2GnT mRNA detected by in situ hybridization reflects the malignant potentials of pulmonary adenocarcinoma, because lymph node metastasis is the most affecting factor to the patients' prognosis.
Chemosensitivity (2005)

Chemosensitivity testing is an ex vivo means of determining or enhancing the cytotoxic and/or cytostatic, or apoptosis-inducing effects of anticancer drugs. In Chemosensitivity, leading researchers and physicians working in academia and biotech companies describe their best laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains today's best protocols for classifying tumors into response categories and for customizing therapy to individuals. These techniques allow measurements of DNA damage, apoptotic cell death, and the molecular and cellular regulators of cytotoxicity, as well as in vivo animal modeling of chemosensitivity. Highlights include genomic and proteomic approaches to assess chemosensivity, in vivo imaging approaches to assess early response to therapy, and methods to statistically analyze data from in vivo therapy. The protocols follow the successful Methods in Molecular Medicine™ series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. The authors also provide guidance on how best to analyze the data derived from the protocols. A companion volume, Volume 1: In Vitro Assays contains in vitro and in vivo techniques to identify which new agents or combination of agents are effective for each type of tumor. Cutting-edge and highly practical, the two volumes of Chemosensitivity provide a comprehensive collection of readily reproducible techniques for the in vitro and in vivo screening of new agents and a set of proven approaches to understand mechanistically why certain cancer cell lines (in vitro) of tumors (in vivo) are more or less sensitive to a particular agent
THE EFFECT OF HYDRODYNAMIC SHEAR ON THE DEOXYRIBONUCLEIC ACID FROM T 2 AND T 4 BACTERIOPHAGES (1959)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Application of interferometric broadband imaging alignment on an experimental x-ray stepper (1998)

A series of experiments were performed with an interferometric-broadband imaging (IBBI) alignment system on an experimental x-ray lithography stepper. These experiments demonstrated sub-1 nm consistency of independent IBBI measurements and the ability to feedback lock the mask relative to a wafer to within a mean of 0.0 nm and a standard deviation of 1.4 nm. Comparisons of displacement measurements made with IBBI and closed-loop piezo drives confirmed scale consistency to within about 1.5%. In the absence of feedback control, spurious relative displacements were observed, due to temperature gradients and the nonrigid mechanics. This argues in favor of feedback control during exposure. The robustness of IBBI in allowing nanometer-level alignment measurements during x-ray exposure, with remotely located long-working-distance, low-cost microscopes should enable it to be used as a stand-alone alignment system or as an adjunct to global alignment.
Fetal damage due to maternal phenylketonuria: Effects of dietary treatment and maternal phenylalanine concentrations around the time of conception (1990)

In 94 infants born to women with PKU, birth weight and head circumference were inversely and linearly related to the mothers' phenylalanine concentrations close to conception; with each 200 mumols/L rise in phenylalanine concentrations, birth weight fell by 98 g and head circumference by 0.46 cm. This relationship was highly significant and appeared to be the same whether or not the mother received a low phenylalanine diet. Even in the 28 infants whose mothers conceived on a strict low phenylalanine diet, birth weights and head circumferences, corrected for sex and gestation, were a little below the population norms (3421 g and 34.7 cm compared with 3600 g and 35.2 cm respectively) although the differences were not statistically significant. Optimal fetal growth occurred only in infants whose mothers had phenylalanine concentrations close to the normal range at conception. Dietary treatment started after conception did not appear to confer any benefit.
The repression of the growth factor-inducible genes JE, c-myc and stromelysin by adenovirus E1A is mediated by conserved region 1. (1989)

The growth factor-inducible cellular genes JE, c-myc and stromelysin (sml) are strongly repressed upon transformation by adenovirus E1A. As E1A proteins are multifunctional and apparently contain distinct domains (conserved regions 1, 2 and 3), each with a specific effect on gene regulation and cell-transformation, we have investigated which of the three conserved regions are responsible for the reduced expression of these genes. To this end, we monitored the expression of the JE, sml and c-myc genes in a panel of normal rat kidney (NRK) cells expressing different mutant E1A genes. Only CR1, and not CR2 or CR3 were found to be essential for the repression of the genes, indicating that CR1, one of the regions essential for cell transformation, represents an autonomous gene regulatory function that can operate in the absence of CR2. We also show that the association of E1A proteins to a 300 kD cellular protein in NRK cells coincides with the ability to repress these genes.
Two Glyceraldehyde-3-phosphate Dehydrogenases with Opposite Physiological Roles in a Nonphotosynthetic Bacterium (2000)

Bacillus subtilis possesses two similar putative phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPDH) encoding genes, gap (renamed gapA) and gapB. A gapA mutant was unable to grow on glycolytic carbon sources, although it developed as well as the wild-type strain on gluconeogenic carbon sources. A gapB mutant showed the opposite phenotype. Purified GapB showed a 50-fold higher GAPDHase activity with NADP(+) than with NAD(+), with K(m) values of 0.86 and 5.7 mm, respectively. lacZ reporter gene fusions revealed that the gapB gene is transcribed during gluconeogenesis and repressed during glycolysis. Conversely, gapA transcription is 5-fold higher under glycolytic conditions than during gluconeogenesis. GAPDH activity assays in crude extracts of wild-type and mutant strains confirmed this differential expression pattern at the enzymatic level. Genetic analyses demonstrated that gapA transcription is repressed by the yvbQ (renamed cggR) gene product and indirectly stimulated by CcpA. Thus, the same enzymatic step is catalyzed in B. subtilis by two enzymes specialized, through the regulation of their synthesis and their enzymatic characteristics, either in catabolism (GapA) or in anabolism (GapB). Such a dual enzymatic system for this step of the central carbon metabolism is described for the first time in a nonphotosynthetic eubacterium, but genomic analyses suggest that it could be a widespread feature.
Organic solvent changes the chymotrypsin specificity with respect to nucleophiles (1992)

In alpha-chymotrypsin-catalyzed acyl-transfer reactions in water the specificity of the enzyme (the nucleophile reactivity of amino acid amides) is correlated with the substrate hydrophobicity and increases as the hydrophobicity of the side chain of the amino acid amides is increased. In a low water system (4% H2O) bulky amino acid amides are less efficient nucleophiles. The specificity of alpha-chymotrypsin towards the amino acid amides in acyl transfer reactions in this case does not depend on the hydrophobicity of the amino acid side chains but correlates with their size. Therefore, different factors can be responsible for the specificity of enzymes in water and in a mainly organic medium.