gebhart/patrepeval huggingface dataset:
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1 (2008)

The multiprotein mTORC1 protein kinase complex is the central component of a pathway that promotes growth in response to insulin, energy levels, and amino acids and is deregulated in common cancers. We find that the Rag proteins--a family of four related small guanosine triphosphatases (GTPases)--interact with mTORC1 in an amino acid-sensitive manner and are necessary for the activation of the mTORC1 pathway by amino acids. A Rag mutant that is constitutively bound to guanosine triphosphate interacted strongly with mTORC1, and its expression within cells made the mTORC1 pathway resistant to amino acid deprivation. Conversely, expression of a guanosine diphosphate-bound Rag mutant prevented stimulation of mTORC1 by amino acids. The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb.
Walnut Extract Inhibits the Fibrillization of Amyloid Beta-Protein, and also Defibrillizes its Preformed Fibrils (2004)

Fibrillar amyloid beta-protein (Abeta) is the principal component of amyloid plaques in the brains of patients with Alzheimer's disease. We have studied the effect of walnut extract on Abeta fibrillization by Thioflavin T fluorescence spectroscopy and electron microscopy. The walnut extract not only inhibited Abeta fibril formation in a concentration and time- dependent manner but it was also able to defibrillize Abeta preformed fibrils. Over 90% inhibition of Abeta fibrillization was observed with 5 microl of methanolic extract of walnut (MEOW) both after 2 and 3 days of incubation. The maximum defibrillization (91.6%) was observed when preformed Abeta fibrils were incubated with 10 microl of MEOW for 2 days. These results suggest that walnuts may reduce the risk or delay the onset of Alzheimer's disease by maintaining Abeta in the soluble form. Further studies showed that anti-amyloidogenic compound in walnut is an organic compound of molecular weight less than 10 kDa, which is neither a lipid nor a protein. Chloroform extract of walnut had no effect on Abeta fibrillization while MEOW and its 10 kDa filtrate inhibited Abeta fibrillization equally. It is proposed that polyphenolic compounds (such as flavonoids) present in walnuts may be responsible for its anti-amyloidogenic activity.
Structural requirements of the competitive binding site of recombinant human indoleamine 2,3-dioxygenase (1996)

The structural requirements for substrate/inhibitor binding to the active site of recombinant human IDO are reported in this paper. Tryptophan analogues with substituents at the 5 or 6 positions were found to bind to the tryptophan binding site of IDO and serve as either substrates or inhibitors. Analogues that were more effective as substrates than inhibitors include 5-methyl-D,L-tryptophan 18, 5-methoxy-D,L-tryptophan 19, 5-hydroxy-L-tryptophan 21 and 6-methyl-D,L-tryptophan 24. Interestingly, 5-methyl-D,L-tryptophan appeared to be a better substrate than L-tryptophan. Compounds which were more active as inhibitors than substrates include 5-bromo-D,L-tryptophan 22 and 6-fluoro-D,L-tryptophan 25. 5-Fluoro-D,L-tryptophan 23 was slightly more active as a substrate. The most effective competitive inhibitor of recombinant human IDO was 6-nitro-L-tryptophan 26 which inhibited enzyme activity 52% at 1 mM concentrations (K-i = 180 mu M) and was not active as a substrate. The optical isomer, 6-nitro-D-tryptophan 27 did not inhibit IDO activity indicating that binding to the active site is stereoselective. An analogue with a large substituent at the 5 position, 5-benzyloxy-D,L-tryptophan 20, was excluded from the active site. Compounds with substituents at other positions around the indole ring or the amino acid portion of tryptophan generally have low activity as substrates or inhibitors although the benzofuran analogue 5 gave moderate (43%) inhibition.
From 'Break Out' to 'Breakthrough': Successful Market Strategies of Immigrant Entrepreneurs in the UK (2010)

This paper explores the strategies that enable ethnic minority immigrant entrepreneurs to 'break out' of local ethnic markets and 'break through' into more promising markets with greater opportunities. It analyzes the contextual and personal characteristics of the entrepreneurs that implement those strategies, based on a primary survey of South Asian entrepreneurs in the UK. The analysis suggests that breaking out of co-ethnic customer markets is neither necessary nor sufficient for entrepreneurial expansion. The critical factor is the entrepreneur's ability to break through into customer markets that are larger, by geographical reach or profit margins and value added. Many successful immigrant entrepreneurs leverage market knowledge of their home countries. At the same time, the more successful entrepreneurs break out of ethnic labor markets by hiring non-ethnic employees. The capacity to 'break out' and 'break through' into larger, global markets, is strengthened by the entrepreneur's education, experience, access and ability to leverage international business networks, and agility to move into more promising markets.
Treatment of depression in general practice: a controlled trial of flupenthixol (‘Fluanxol’) (1974)

SummaryOn the basis of an arbitrary definition of depression, 85 general practitioners treated 231 patients during a 2-week period with flupenthixol (‘Fluanxof)d˚ and placebo in a controlled, randomized, double-blind trial. The male. female ratio was 1:5, and the mean age was 42 years. The severity of the symptoms was assessed by a rating scale, and satisfactory improvement was defined as a reduction of 50% or over of the initial individual scores.Improvement was obtained in 65 % of patients treated with flupenthixol and in 50% of those in the placebo group. The difference is statistically significant, X2 = 5.0, d.f.l.,p = 0.025.The two groups were comparable with respect to sex, age, associated diseases, other medication and failure to take the trial drugs, but relevant personal relationships could not be assessed.Patients showed marked improvement during the first week of treatment and few untoward effects were noted. It is concluded that in patients selected according to the criteria of the trial a better effect may be expected from flupenthixol than from placebo, namely 19 ± 12.8%, greater at the end of 1 week and 15 ± 12.8%, at the end of 2 weeks, but that if improvement has not occurred within the first week, little is to be gained from continued treatment.It is pointed out that a great deal of drug effect must be assumed to be connected with general confidence in medicines, the tendency towards spontaneous improvement, and changes in the patient's background situation and the doctor - patient relationship.It is recommended that a larger number of diseases be defined in general practice, so that G.P.s may realize clearly what they are doing, why they are doing it, and what results they are getting. Only thereby is it possible to gain increased knowledge about the value of diagnostic and therapeutic possibilities.
Human fos Gene (1986)

A decade ago it was observed that the transforming gene src of avian sarcoma virus has counterparts in normal chicken chromosomal DNA (Stehlin et al. 1976). Since then src-specific sequences have been detected across all species, from Homo sapiens to yeast (Varmus 1982; Bishop 1983; Weinberg 1983; Hunter 1984). This realization that normal cells harbor genes that have the potential to induce neoplasia was a turning point in modern cancer research. Such genes, collectively called oncogenes or proto-oncogenes, were first discovered through the agency of retroviruses, a group of viruses that cause tumors in experimental animals (Cooper 1982). Since human neoplasias generally do not display viral etiology (human acute T-cell leukemia and AIDS being recent exceptions), the appearance of oncogenes on the tumor biology scene was not greeted with overt enthusiasm.
Quantum dots – a versatile tool in plant science? (2006)

An optically stable, novel class of fluorophores (quantum dots) for in situ hybridisation analysis was tested to investigate their signal stability and intensity in plant chromosome analyses. Detection of hybridisation sites in situ was based on fluorescence from streptavidin-linked inorganic crystals of cadmium selenide. Comparison of quantum dots (QDs) with conventional detection systems (Alexa 488) in immunolabeling experiments demonstrated greater sensitivity than the conventional system. In contrast, detection of QDs in in situ hybridisation of several plant chromosomes, using several high-copy sequences, was less sensitive than Alexa 488. Thus, semiconductor nanocrystal fluorophores are more suitable for immunostaining but not for in situ hybridisation of plant chromosomes.
Omeprazole and lansoprazole suspensions for nasogastric administration (1999)

Journal Article Omeprazole and lansoprazole suspensions for nasogastric administration Get access Kenneth L. McAndrews, Jr., Pharm.D., Kenneth L. McAndrews, Jr., Pharm.D. Clinical Coordinator, Clinical Pharmacist Pharmacy Department Naval Medical Center 34800 Bob Wilson Drive San Diego, CA 92134-5000 wmacal@snd10.med.navy.mil Search for other works by this author on: Oxford Academic Google Scholar John H. Eastham, Pharm.D. John H. Eastham, Pharm.D. Clinical Pharmacist Pharmacy Department Naval Medical Center 34800 Bob Wilson Drive San Diego, CA 92134-5000 Search for other works by this author on: Oxford Academic Google Scholar American Journal of Health-System Pharmacy, Volume 56, Issue 1, 1 January 1999, Page 81, https://doi.org/10.1093/ajhp/56.1.81 Published: 01 January 1999
Human-computer interaction (1996)

All aspects of human-computer interaction, from the high-level concerns of organizational context and system requirements to the conceptual, semantic, syntactic, and lexical levels of user interface design, are ultimately funneled through physical input and output actions and devices. The fundamental task in computer input is to move information from the brain of the user to the computer. Progress in this discipline attempts to increase the useful bandwidth across that interface by seeking faster, more natural, and more convenient means for a user to transmit information to a computer. This article mentions some of the technical background for this area, surveys the range of input devices currently in use and emerging, and considers future trends in input.
Glucocorticoidlike Activity of Megestrol (1997)

Sporadic single case reports linking glucocorticoidlike activity to megestrol acetate have been reported in the literature. These findings have important implications for patient care. Adverse drug experience reports to the US Food and Drug Administration from 1984 through 1996 and a MEDLINE search of the literature from 1984 through 1996 provided the case reports. Five cases of Cushing syndrome, 12 cases of new-onset diabetes, and 16 cases of adrenal insufficiency were identified in association with megestrol therapy. Twelve cases in which preexisting diabetes was exacerbated and 17 cases of possible adrenal insufficiency were identified. Therapy with megestrol can result in clinical manifestations of glucocorticoidlike activity, including Cushing syndrome, diabetes, and adrenal insufficiency. Clinicians need to be aware of this association as these complications can be life-threatening if not recognized. Arch Intern Med. 1997;157:1651-1656
Interleukin-18 and Crohn’s Disease (2001)

The etiology and pathogenesis of inflammatory bowel disease remains an area under intense investigation. Crohn's disease (CD) is characterized by a marked accumulation of activated Th1 type CD4+ T cells and macrophages in inflamed intestinal mucosa. IL-18 is a recently described cytokine that mainly exists in activated macrophages and shares biological activities with IL-12 in driving the development of Th1 type CD4+ T cells by inducing interferon-gamma. To clarify the role of IL-18 in intestinal inflammation in CD, we assessed the functional role of IL-18 in regulating intestinal mucosal lymphocytes in human CD and murine CD model.
Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ (2005)

5-aminosalicylic acid (5-ASA) is an antiinflammatory drug widely used in the treatment of inflammatory bowel diseases. It is known to inhibit the production of cytokines and inflammatory mediators, but the mechanism underlying the intestinal effects of 5-ASA remains unknown. Based on the common activities of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands and 5-ASA, we hypothesized that this nuclear receptor mediates 5-ASA therapeutic action. To test this possibility, colitis was induced in heterozygous PPAR-gamma(+/-) mice and their wild-type littermates, which were then treated with 5-ASA. 5-ASA treatment had a beneficial effect on colitis only in wild-type and not in heterozygous mice. In epithelial cells, 5-ASA increased PPAR-gamma expression, promoted its translocation from the cytoplasm to the nucleus, and induced a modification of its conformation permitting the recruitment of coactivators and the activation of a peroxisome-proliferator response element-driven gene. Validation of these results was obtained with organ cultures of human colonic biopsies. These data identify PPAR-gamma as a target of 5-ASA underlying antiinflammatory effects in the colon.
The experimental induction of whisker growth in the hooded rat by implantation of dermal papillae (1967)

ABSTRACT Dermal papillae are regenerated and whiskers are produced after the experimental removal of up to the lower third of the vibrissa follicle, but if more of the follicle is removed neither event occurs (Oliver, 1966 a, b). Similarly, when lengths of the lower third of the vibrissa follicle wall are transplanted into ear skin, whiskers are again produced, but not if lengths of wall are taken from within the upper two-thirds of the follicle (Oliver, 1967). From these experiments it was clear that the outer root sheath and the adherent mesenchymal layer, from which the new papillae are apparently derived, are the essential tissues in the regeneration process.
Studies on the First DSC Endotherm of Polyurethane Hard Segment Based on 4,4‘-Diphenylmethane Diisocyanate and 1,4-Butanediol (1998)

The first high-temperature endotherm (T1) of polyurethane hard segment based on 4,4‘-diphenylmethane diisocyanate (MDI) and 1,4-butanediol (BD) was studied by differential scanning calorimetry (DSC). The materials contain 69% (w/w) of MDI and BD as the hard segment and hydroxyl-terminated cis-polybutadiene with number average molecular weights of 1650 and 2300, respectively, as the soft segment. The hard segment and the soft segment of these polyurethanes appear to be very completely phase-separated, giving rise to very simplified material structures for this study. Samples under melt-quenched condition gave rise to a highly amorphous phase for the hard phase and a distinct hard-segment glass transition behavior, which enabled us to study the T1 behavior in relation to the amorphous hard-segment Tg (Tgh). Upon annealing below the Tgh of the pure amorphous hard phases, both the T1 temperature and magnitude of the T1 endotherm increased linearly with the increase in logarithmic annealing time (log ta). On the other hand, if the polyurethane were first annealed to form multiple endotherms at noncrystalline T2 region, the annealing above the previous Tgh gave rise to a T1 which also increased linearly in temperature with the increase in log ta. These phenomena are typical of enthalpy relaxations resulting from the physical aging of the amorphous hard segment. Thus, we suggest the long-term confusing nature of T1 is due to an enthalpy relaxation of the amorphous hard segment. On the other hand, we also suggest that T2, which was previously associated with a long-range order of unspecified nature, would disturb the amorphous hard segment and cause a rise in the Tg in different degrees to a higher temperature near T2.
Structural characterization of the fusobacterial non-specific porin FomA suggests a 14-stranded topology, unlike the classical porins (2002)

Native and recombinant FomA proteins were extracted by detergent from the cell envelopes of Fusobacterium nucleatum and Escherichia coli, and purified to near homogeneity by chromatography. Circular dichroism analysis revealed that the FomA protein consists predominantly of beta-sheets, in line with the previously proposed 16-stranded beta-barrel topology model. Results obtained by trypsin treatment of intact cells and cell envelopes of F. nucleatum, and from limited proteolysis of purified FomA protein, indicated that the N-terminal part of the FomA protein is not an integral part of the beta-barrel, but forms a periplasmic domain. Based on these results a new topology model is proposed for the FomA protein, where the C-terminal part forms a 14-stranded beta-barrel separate from the periplasmic N-terminal domain.
Synchronizing web browsing data with Browserver (2010)

People spend a lot of time navigating on the web. When moving from one computer device to another, it would be useful to have access to the navigation data produced in the previous web session. In this article, a synchronization service of navigation data, called Browserver, is presented. It is responsible for keeping user navigation information (tabs, history, forms, cookies, etc.) so that it can be recovered from any device connected to the Internet. Finally, Browserver performance is compared to a similar service, according to hardware and network consumption metrics.
Neurotrophin Small Molecule Mimetics: Candidate Therapeutic Agents for Neurological Disorders (2005)

Neurotrophin proteins bind to p75NTR and Trk receptors to trigger potent biological effects including modulation of neuronal survival, promotion and maintenance of neurite networks, upregulation of neural function and modulation of synaptic plasticity. Factors limiting clinical application include poor stability, restricted nervous system penetration and a wide array of biological activities that may lead to adverse effects. A potential approach for addressing these limitations is the development of synthetic, small molecule, neurotrophin mimetics with favorable profiles of stability, tissue penetration and targeted biological actions. Neurotrophin mimetic strategies include development of agents that act at neurotrophin receptors as agonists, partial agonists, inverse agonists or antagonists to promote, inhibit or modify neurotrophin- related signal transduction. The existence of a two-receptor system for neurotrophins, suggests the possibility that small molecules mimicking p75NTR versus Trk-interacting neurotrophin domains might differentially promote selected neurotrophin functions. Moreover, the principle of differential receptor activation predicts that different mimetics acting at a given neurotrophin receptor might elicit differential signaling patterns and biological effects. For example, prevention of neuronal death in the absence of the neurotrophin effects of upregulation of pain transduction or inflammation might constitute a desired activity profile. Synthesis of active peptide mimetics corresponding to specific neurotrophin domains has established the proof-of-principle that neurotrophin domain mimetics can be created that exhibit antagonist or agonist features and points to the possibility of creating non-peptide, small molecule mimetics with favorable medicinal properties and targeted neurotrophin activities.
Depletion of Human Histone H1 Variants Uncovers Specific Roles in Gene Expression and Cell Growth (2008)

At least six histone H1 variants exist in somatic mammalian cells that bind to the linker DNA and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition, H1 seems to be actively involved in the regulation of gene expression. However, it is not well known whether the different variants have distinct roles or if they regulate specific promoters. We have explored this by inducible shRNA-mediated knock-down of each of the H1 variants in a human breast cancer cell line. Rapid inhibition of each H1 variant was not compensated for by changes of expression of other variants. Microarray experiments have shown a different subset of genes to be altered in each H1 knock-down. Interestingly, H1.2 depletion caused specific effects such as a cell cycle G1-phase arrest, the repressed expression of a number of cell cycle genes, and decreased global nucleosome spacing. On its side, H1.4 depletion caused cell death in T47D cells, providing the first evidence of the essential role of an H1 variant for survival in a human cell type. Thus, specific phenotypes are observed in breast cancer cells depleted of individual histone H1 variants, supporting the theory that distinct roles exist for the linker histone variants.
Cube polarizers by the use of metal particles in anodic alumina films (1994)

Metal columns in an anodic alumina film exhibit a prominent anisotropy in the optical loss near the resonance wavelength. The resonance wavelength depends on the direction of polarization and varies with the volume ratio of the metal columns. Based on the anisotropy, we fabricated cube polarizers and attained an extinction ratio of > 30 dB near the 1-µ m wavelength.
Patient-Controlled Analgesia (1983)

Patient-controlled analgesia is a relatively new and investigational technique that permits patients to treat pain by directly activating doses of intravenous narcotics. The technique was developed in response to the undertreatment of pain in hospitalized patients. Continuous narcotic infusion and intraspinal narcotic administrations also have the potential to provide continuous, uninterrupted analgesia, but do not allow simple dose attentuation to avoid overdosage. Patient-controlled analgesia is used to treat postoperative and labor pain and pain associated with terminal illness; it delivers analgesic more effectively with fewer side effects than conventional parenteral narcotic therapies. The technique is also an ideal investigative instrument for studying equianalgesic states. Several foreign-made devices are now being used under investigational sanctions in this country, and it is anticipated that several American manufacturers will be seeking regulatory approval to market the devices.
Amyloid-like Formation by Self-Assembly of Peptidolipids in Two Dimensions (2004)

The accumulation of beta-amyloid peptide (Abeta) in the human brain is known to be the major cause that drives Alzheimer's disease pathogenesis. Abeta, a 39-42 amino acid peptide, is the cleavage product of amyloid precursor protein in the hydrophobic transmembrane region. The present study employs a two-dimensional (2D) approach. Two synthetic peptidolipids, C18-IIGLM-OH and C18-IIGLM-NH2, are selected based on the fragment 31-35 of Abeta which is recognized as one of the determining segments that induces formation of amyloid fibril plaques. The aliphatic hydrocarbon chain C18 is attached to the N-terminal of the fragment 31-35 to facilitate the 2D study at the air-water interface. The aggregation process is observed by two measurements: (1) surface pressure-area and surface dipole moment-area isotherms and (2) epifluorescence microscopy of the Langmuir films to investigate the topography of the amyloid-like formation.