gebhart/patrepeval huggingface dataset:
Tumor suppressor genes (1990)

The retinoblastoma sensitivity protein (Rb) and the p53 gene product both appear to function as negative regulators of cell division or abnormal cellular growth in some differentiated cell types. Several types of cancers have been shown to be derived from cells that have extensively mutated both alleles of one or both of these genes, resulting in a loss-of-function mutation. In the case of the p53 gene, this mutational process appears to occur in two steps, with the first mutation at the p53 locus resulting in a trans-dominant phenotype. The mutant p53 gene product enters into an oligomeric protein complex with the wild-type p53 protein derived from the other normal allele and such a complex is inactive or less efficient in its negative regulation of growth control. This intermediate stage of carcinogenesis selects for the proliferation of cells with one mutant allele, enhancing the probability of obtaining a cancer cell with both alleles damaged. The DNA tumor viruses have evolved mechanisms to interact with the Rb and p53 negative regulators of cellular growth in order to enhance their own replication in growing cells. SV40 and adenovirus type 5 produce viral encoded proteins that also form oligomeric protein complexes with p53 and Rb, presumably inactivating their functions. These viral proteins are also the oncogene products of these viruses. Thus, the mechanisms by which cancer may arise in a host, via mutations or virus infections, have fundamental common pathways effecting the same cellular genes and gene products; Rb and p53.
Photoreactive Polymers Bearing a Zwitterionic Phosphorylcholine Group for Surface Modification of Biomaterials (2015)

Photoreactive polymers bearing zwitterionic phosphorylcholine and benzophenone groups on the side chain were synthesized and used as surface modification reagents for biomaterials. A photoreactive methacrylate containing the benzophenone group, 3-methacryloyloxy-2-hydroxypropyl-4-oxybenzophenone (MHPBP), was synthesized via a ring-opening and addition reaction between glycidyl methacrylate and 4-hydroxybenzophenone. Then, water-soluble, amphiphilic polymers poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-MHPBP) (PMH) and poly(MPC-co-n-butyl methacrylate-co-MHPBP), with different monomer unit compositions, were synthesized through radical polymerization. Ultraviolet-visible (UV/vis) absorption spectra of these polymer solutions showed that these polymers have maximum absorption peaks at 254 and 289 nm that can be attributed to the benzophenone unit. The intensity of UV adsorption at 289 nm was decreased with increased UV irradiation time, and it was saturated within a few minutes, indicating that the polymers are highly sensitive to UV irradiation. A commercial material (i.e., cyclic polyolefin) was simply modified by a UV irradiation for 1.0 min. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analysis results indicated that the stability of the polymer on the surface was dramatically enhanced because of the photochemical reaction of the benzophenone moiety. The air contact angles of PMH surfaces measured in water were up to 160°. Thus, highly hydrophilic surfaces were obtained. The critical surface tension of the PMH-modified surface was 45.7 mN/m. By evaluating the biological reactivity of the treated surface, protein adsorption and cell adhesion were completely inhibited on the surface, which was prepared using a photopatterning procedure using PMH. In conclusion, photoreactive MPC polymers with a benzophenone moiety could be used as a novel and effective surface modifier.
Severe combined immunodeficiency caused by deficiency in either the δ or the ε subunit of CD3 (2004)

We investigated the molecular mechanism underlying a severe combined immunodeficiency characterized by the selective and complete absence of T cells. The condition was found in 5 patients and 2 fetuses from 3 consanguineous families. Linkage analysis performed on the 3 families revealed that the patients were carrying homozygous haplotypes within the 11q23 region, in which the genes encoding the γ, δ, and ε subunits of CD3 are located. Patients and affected fetuses from 2 families were homozygous for a mutation in the CD3D gene, and patients from the third family were homozygous for a mutation in the CD3E gene. The thymus from a CD3δ-deficient fetus was analyzed and revealed that T cell differentiation was blocked at entry into the double positive (CD4+CD8+) stage with the accumulation of intermediate CD4–single positive cells. This indicates that CD3δ plays an essential role in promoting progression of early thymocytes toward double-positive stage. Altogether, these findings extend the known molecular mechanisms underlying severe combined immunodeficiency to a new deficiency, i.e., CD3ε deficiency, and emphasize the essential roles played by the CD3ε and CD3δ subunits in human thymocyte development, since these subunits associate with both the pre-TCR and the TCR.
Uncertainty in Health Risks from Artificial Lighting due to Disruption of Circadian Rhythm and Melatonin Secretion: A Review (2012)

ABSTRACT Incandescent lighting in many domestic and commercial applications is in the process of replacement by more efficient light sources, such as the compact fluorescent light (CFL) and the light emitting diode (LED). For household use, both CFL and LED sources have a significant blue component in the emitted spectrum in comparison to the warmer incandescent globes and this has been the cause of emerging health concerns. Recent research suggests that the blue light bandwidth in the visible spectrum has a significant impact on physical health, including disruption of the internal body clock and suppression of melatonin secretion at night. This disruptive effect has been linked to a range of illnesses, including breast cancer, prostate cancer, heart disease, obesity, and diabetes. There have also been positive effects observed, including re-setting the body clock to the required sleep pattern, boosting mood, alertness, cognitive performance, and alleviating seasonal affective depression (SAD). In this article, an introduction and review of recent research is provided, relevant health issues are highlighted and discussed, and uncertainty analysis completed for the dose–response curve for melatonin suppression as a function of incident photon density.
Safety, efficacy, and duration of immunity induced in swine by use of an avirulent live Salmonella choleraesuis-containing vaccine (1995)

An avirulent live Salmonella choleraesuis culture (SC-54) was evaluated for use as an effective vaccine in preventing salmonellosis caused by S. choleraesuis in pigs. Eighty-two pigs, 3 to 4 weeks old, were randomly assigned to 1 of 2 treatment groups, which were designated as either vaccinates or controls. After vaccination, all pigs were examined for fecal shedding of S choleraesuis, rectal temperature, and 10 clinical variables. Significant difference was not detected between vaccinated and nonvaccinated pigs for 14 days (phase I) after intranasal administration of the vaccine. Efficacy and duration of immunity were examined by intranasally challenge exposing respective pigs from either treatment group with a virulent field isolate of S choleraesuis at 2, 8, or 20 weeks after vaccination (phases II-IV). Pigs were again evaluated for 14 days after challenge exposure, and 10 clinical variables and rectal temperature were monitored. Surviving pigs were euthanatized and evaluated for gross lesions, and samples of 7 organs were collected. These organs samples were homogenized, and level of S choleraesuis infection was determined. After virulent challenge exposure during phases II-IV, the clinical status of the SC-54 vaccinates was significantly (P < 0.05) superior to that of nonvaccinates for rectal temperature, feces consistency, behavior, appetite, body condition, and mean score for the 10 clinical variables. Quantitative bacteriologic culture of the tonsil, lung, liver, spleen, mesenteric lymph nodes, ileum, and colon samples indicated consistent reduction of organ colonization in vaccinates; bacteria numbers in the mesenteric lymph nodes, lungs, and ileum were significantly (P < 0.05) reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluating Structural Similarity in XML Documents (2002)

XML documents on the web are often found without DTDs, particularly when these documents have been created from legacy HTML. Yet having knowledge of the DTD can be valuable in querying and manipulating such documents. Recent work (XTRACT) has given us a means to (re-)construct a DTD to describe the structure common to a given set of document instances. However, given a collection of documents with unknown DTDs, it may not be appropriate to construct a single DTD to describe every document in the collection. Instead, we would wish to partition the collection into smaller sets of &amp;quot;similar&amp;quot; documents, and then induce a separate DTD for each such set. It is this partitioning problem that we address in this paper.
THE VALUE OF VALUE PRICING (2001)

The federal government has been sponsoring demonstrations of toll roads and value pricing to try to win over a highly resistant public. Two of the demonstrations in California show that the mechanisms and software programs work well, that transactions and enforcement are manageable and that drivers are adjusting. In one, drivers pay fees based on the time of day and day of the week, with carpools getting a discount. In the second, single drivers can pay a premium to ride in what were under-used carpool lanes. A key flaw in current approaches is the requirement that there be a free alternative. That means that congestion on the free portion must not improve so much that the paying alternative is no longer attractive. Computer simulations of different methods of value pricing show that fine tuning of the prices charged can go a long way toward eliminating the need for a free alternative, because the benefits increase dramatically. But it is hard to do it right.
Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging (2010)

Identifying factors that accelerate the aging process can provide important therapeutic targets for slowing down this process. Misregulation of phosphate homeostasis has been noted in various skeletal, cardiac, and renal diseases, but the exact role of phosphate toxicity in mammalian aging is not clearly defined. Phosphate is widely distributed in the body and is involved in cell signaling, energy metabolism, nucleic acid synthesis, and the maintenance of acid-base balance by urinary buffering. In this study, we used an in vivo genetic approach to determine the role of phosphate toxicity in mammalian aging. Klotho-knockout mice (klotho(-/-)) have a short life span and show numerous physical, biochemical, and morphological features consistent with premature aging, including kyphosis, uncoordinated movement, hypogonadism, infertility, severe skeletal muscle wasting, emphysema, and osteopenia, as well as generalized atrophy of the skin, intestine, thymus, and spleen. Molecular and biochemical analyses suggest that increased renal activity of sodium-phosphate cotransporters (NaPi2a) leads to severe hyperphosphatemia in klotho(-/-) mice. Genetically reducing serum phosphate levels in klotho(-/-) mice by generating a NaPi2a and klotho double-knockout (NaPi2a(-/-)/klotho(-/-)) strain resulted in amelioration of premature aging-like features. The NaPi2a(-/-)/klotho(-/-) double-knockout mice regained reproductive ability, recovered their body weight, reduced their organ atrophy, and suppressed ectopic calcifications, with the resulting effect being prolonged survival. More important, when hyperphosphatemia was induced in NaPi2a(-/-)/klotho(-/-) mice by feeding with a high-phosphate diet, premature aging-like features reappeared, clearly suggesting that phosphate toxicity is the main cause of premature aging in klotho(-/-) mice. The results of our dietary and genetic manipulation studies provide in vivo evidence for phosphate toxicity accelerating the aging process and suggest a novel role for phosphate in mammalian aging.
Home Nebuliser Use in Children with Asthma in Two Scottish Health Board Areas (1995)

Re-organisation of resources and arrangements could improve the service and bring it in line with recognised standards of care.
Effect of the Cu thickness on the stability of a Ni/Cu bilayer UBM of lead free microbumps during liquid and solid state aging (2005)

The present study focuses on liquid and solid phase reactions between an electrodeposited bilayer UBM and Sn, which is chosen as worst case solder material for lead free bumping. Small sized bumps were realized by electrodeposition using one lithographic mask for electrodepositing the UBM and the solder. The bilayer UBM consists of an electrodeposited Ni and Cu layer (Ni/sub ed/, Cu/sub ed/) on a sputtered Cu seedlayer (Cu/sub sp/) and a sputtered TiWN diffusion barrier. The Cu/sub ed/ layer is situated between solder and the Ni/sub ed/ layer and is suitable to act as a sacrificial layer forming a diffusion barrier layer between Ni and the solder. This barrier layer avoids or decreases the degradation of the Ni/sub ed/ layer during solid or liquid phase reaction with the solder. Rules for a proper design of the Cu layer thickness are deduced taking into account the solubility of Cu in the solder material as well as the formation and growth of intermetallic phases between solder and UBM. Electrodeposition of the UBM is suitable to realize small sized bump sizes up to 50 /spl mu/m diameter.
Lactoferrin is a lipid A-binding protein (1994)

Lactoferrin (LF), a cationic 80-kDa protein present in polymorphonuclear leukocytes and in mucosal secretions, is known to have antibacterial effects on gram-negative bacteria, with a concomitant release of lipopolysaccharides (LPS, endotoxin). In addition, LF is known to decrease LPS-induced cytokine release by monocytes and LPS priming of polymorphonuclear leukocytes. Its mechanism of action is incompletely understood. We have now demonstrated by in vitro-binding studies that LF binds directly to isolated lipid A and intact LPS of clinically relevant serotypes of the species which most frequently cause bacteremia (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), as well as to lipid A and LPS of mucosal pathogens (among others, Neisseria meningitides and Haemophilus influenzae). Binding to LPS was inhibitable by lipid A and polymyxin B but not by KDO (3-deoxy-D-manno-octulosonate), a glycoside residue present in the inner core of LPS. Binding of LF to lipid A was saturable, and an affinity constant of 2 x 10(9) M-1 was calculated for the LF-lipid A interaction. Our data may explain, in part, the mechanism whereby LF exerts its antibacterial and anti-endotoxic effects. Further studies on the ability of LF to block the detrimental effects of LPS, both in vitro and in vivo, are warranted.
Exposure to ELF magnetic field tuned to Zn inhibits growth of cancer cells (2005)

The effects of ELF alternating magnetic fields tuned to Zn(2+) on the growth of cancer cells with different status of p53 were investigated using a cell proliferation assay. Human cancer cells HeLa (cervix cancer, p53(+/+)), Saos-2 and Saos-2-His-273 (osteosarcoma, p53(-/-) and p53 His-273 mutant, respectively), H1299tTA and H1299tTA-His175 (lung carcinoma, p53(-/-) and p53 His-175 mutant), and normal human fibroblasts VH-10 (p53(+/+)) were used. Exposure parameters were calculated for the first harmonic of Zn(2+) based either on the magnetic parametric resonance (MPR) model of Lednev or the ion parametric resonance (IPR) model of Blanchard and Blackman. ELF exposure was for 72 and 96 h. The vertical alternating field was 20 Hz at amplitudes of either 38.7 or 77.4 microT (peaks, IPR or MPR, respectively). The vertical static magnetic field was 43 microT, and the horizontal static magnetic field was zeroed. Treatments of cells with PRIMA-1 and gamma-rays were used as positive controls. Growth inhibition was observed in cells after exposure to ELF at 38.7 microT. Inhibition of HeLa, VH-10, and Saos-2-His-273 cells was statistically significant, P=0.0003, 0.02, and 0.006, respectively. No consistent ELF effects following exposure 77.4 microT were seen. PRIMA-1 inhibited the growth of all cell lines with the strongest effect in mutant p53-carrying cell line H1299tTA-His175. The effects of gamma-rays were relatively weak, suggesting that the cell proliferation assay under conditions employed in this study is not very sensitive to apoptosis. In conclusion, ELF under conditions of exposure tuned to Zn(2+) according to the IPR model inhibited the growth of cancer and normal cells. No clear relationship of the observed growth inhibition to p53 status was found. Further experiments, using complementary techniques, are required to test whether p53 reactivation by ELF is feasible.
Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice (2013)

The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.
Glyceryl trinitrate triggers premonitory symptoms in migraineurs (2004)

Studying attacks of migraine is considerably hampered by its fundamentally episodic nature. Developing approaches to triggering migraine reliably is important for advancing understanding of the disorder by facilitating its study. Based on the work of the Copenhagen Group we administered an intravenous infusion of 0.5 μg/kg/min glyceryl trinitrate (GTN) to 44 migraineurs, 23 migraine without aura, 21 migraine with aura, and to 12 healthy controls. We sought to characterise the GTN-induced migraine in terms of the clinical features of the attacks and reproducibility of triggering, and included a non-migraine control group for the purpose of comparing any effects to exclude an ordering effect. Of the 44 patients administered GTN, 33 had a migraine attack fulfilling International Headache Society criteria. Thirty-two attacks were of migraine without aura and one of migraine with aura. Twelve patients described typical premonitory symptoms, which have not been previously documented with GTN-induced migraine. A repeat attack was triggered in all subjects but one. In one case a visual aura was also triggered both times. Our study shows that GTN-induced triggering is common in our patients, and remarkably reproducible. The data will facilitate the use of the GTN model in studies requiring extensive planning, such as brain imaging, or where preventive questions are at issue. We also report the first patient with a reproducible GTN-triggered migraine with aura.
Synthetic methodology for alkyl substituted hydrazines (2001)

Substituted hydrazines have found many technical and commercial applications and this is reflected in the immense number of such compounds synthesized to date. In this review an attempt has been made to supplement the existing comprehensive literature by presenting only a selection of synthetic methods, judged to be of particular principal or practical interest, together with some additional, recent approaches. The important steps in the development from simple substituted hydrazines to rational synthesis of multisubstituted derivatives are recapitulated.
Characteristics of waveguides for long-distance transmission (1961)

Discussion of a "'aveguide communication system is given and t he syste m is co mpared with ex isting commun ication medi a. The principal prope rties of waveguide-the mcdium of communication-are disc ussed in some detail. The particular sig nificance of heli cal a nd coated waveguides is pointed out and the design formulas in cludcd. The p lwnomenon of mode conversion-reconversion , which is pec uliar to a waveg uide communicat io n systcm , is di sc ussed in general and the basic theory as app li cab le to d es ign is also discussed . D esig n feat ures of components such as be nds, tra nsduce rs, tapers, etc., a re analyzed . The effect of waveguide di sco nt inui t ies is a nal yzed in so me detail and \'a riou ~ aspects of signa l d istort ion are a lso conside red . I I bY FIG U RE 1. A possible communication syslem 1lsing waveguide.
Physiological Characteris tics of Spontaneously Developed Diabetes in Male WBN/Kob Rat and Prevention of Development of Diabetes by Chronic Oral Administration of Synthetic Trypsin Inhibitor (FOY-305) (1993)

The male WBN/Kob rats spontaneously develop diabetes mellitus with age. In this study, we examined how glucose tolerance, potency of insulin release, and histology of the pancreas were changed with age in this model. Furthermore, we examined the effect of FOY-305, a synthetic trypsin inhibitor, on this model. Male WBN/Kob rats were divided into two groups: one group fed on standard pellet diet (STD group) and the other on pellet containing 0.1% FOY-305 (FOY group) for 56 weeks after age 4 weeks. Oral glucose (2 g/kg) tolerance test, histology of the pancreas, and glucose (8.3 mM)- and arginine (10 mM)-stimulated insulin release from the isolated perfused pancreas were examined at 8, 20, 40, and 60 weeks of age in both groups. Pancreatic insulin content was examined at 60 weeks. In the STD group, impairment of glucose tolerance and destruction and fibrosis of pancreatic tissues progressed with age. Glucose-stimulated insulin release was remarkably reduced with age, while arginine-stimulated insulin release was preserved. By contrast, in the FOY group, development of glucose intolerance was delayed and the pancreas showed fewer pathologic changes compared with the STD group. Insulin releases in response to both glucose and arginine were preserved at all ages examined. Total pancreatic insulin content at 60 weeks of age was significantly greater than that of the STD group. The male WBN/Kob rat is a new type of diabetic model that shows a similar pattern of insulin release to that in rat with non-insulin-dependent diabetes mellitus and also shows unique histopathological changes in exocrine pancreas. FOY-305 was effective in preventing the development of diabetes in this model, although its mechanism is still unknown.
Attenuation of fibrosis in vitro and in vivo with SPARC siRNA (2010)

Specific inhibition of SPARC effectively reduced fibrotic changes in vitro and in vivo. SPARC inhibition may represent a potential therapeutic approach to fibrotic diseases.