gebhart/patrepeval huggingface dataset:
Effects of Telomerase and Telomere Length on Epidermal Stem Cell Behavior (2005)

A key process in organ homeostasis is the mobilization of stem cells out of their niches. We show through analysis of mouse models that telomere length, as well as the catalytic component of telomerase, Tert, are critical determinants in the mobilization of epidermal stem cells. Telomere shortening inhibited mobilization of stem cells out of their niche, impaired hair growth, and resulted in suppression of stem cell proliferative capacity in vitro. In contrast, Tert overexpression in the absence of changes in telomere length promoted stem cell mobilization, hair growth, and stem cell proliferation in vitro. The effects of telomeres and telomerase on stem cell biology anticipate their role in cancer and aging.
Recognizing nucleotides by cross-tunneling currents for DNA sequencing (2011)

Using first-principles calculations, we study electron transport through nucleotides inside a rectangular nanogap formed by two pairs of gold electrodes which are perpendicular and parallel to the nucleobase plane. We propose that this setup will enhance the nucleotide selectivity of tunneling signals to a great extent. Information from three electrical probing processes offers full nucleotide recognition, which survives the noise from neighboring nucleotides and configuration fluctuations.
High resolution two-dimensional electrophoresis of proteins. (1975)

A technique has been developed for the separation of proteins by two-dimensional polyacrylamide gel electrophoresis. Due to its resolution and sensitivity, this technique is a powerful tool for the analysis and detection of proteins from complex biological sources. Proteins are separated according to isoelectric point by isoelectric focusing in the first dimension, and according to molecular weight by sodium dodecyl sulfate electrophoresis in the second dimension. Since these two parameters are unrelated, it is possible to obtain an almost uniform distribution of protein spots across a two-diminsional gel. This technique has resolved 1100 different components from Escherichia coli and should be capable of resolving a maximum of 5000 proteins. A protein containing as little as one disintegration per min of either 14C or 35S can be detected by autoradiography. A protein which constitutes 10 minus 4 to 10 minus 5% of the total protein can be detected and quantified by autoradiography. The reproducibility of the separation is sufficient to permit each spot on one separation to be matched with a spot on a different separation. This technique provides a method for estimation (at the described sensitivities) of the number of proteins made by any biological system. This system can resolve proteins differing in a single charge and consequently can be used in the analysis of in vivo modifications resulting in a change in charge. Proteins whose charge is changed by missense mutations can be identified. A detailed description of the methods as well as the characteristics of this system are presented.
Identification of overlapping epitopes in mutant ras oncogene peptides that activate CD4+ and CD8+ T cell responses (1996)

Mutant ras p21 proteins contain sequences which distinguish them from normal endogenous ras and, thus, may represent unique epitopes for T cell recognition of antigen bearing tumor cells. Here, we examined the capacity of a mutant K-ras 9-mer peptide to induce in vivo CD8+ cytotoxic T lymphocytes (CTL). The peptide chosen reflected positions 4-12 of the point-mutated sequence of the K-ras oncogene encoding the Gly to Val substitution at codon 12. The overall rationale for selecting this particular 9-mer sequence was threefold: the mutant peptide contained a putative major histocompatibility complex (MHC) class I consensus anchor motif for murine H-2Kd; specific binding to MHC class I may then create an immunogenic complex for the induction of anti-ras CD8+ CTL; and finally, the mutant sequence overlapped with a newly characterized anti-ras CD4+ T helper type 1 epitope, which may have implications for the coordination and activation of both anti-ras immune mechanisms against the same target cell antigenic determinant. A functional interaction with H-2Kd was demonstrated with the mutant ras4-12(V12) peptide, but not the normal ras4-12(G12) peptide, which specifically inhibited an H-2Kd-restricted, anti-nucleoprotein NP147-155 CTL response in a dose-dependent fashion. An anti-ras CD8+ T cell line was then established from immune splenocytes of BALB/c (H-2d) mice injected with ras4-12 (V12) in adjuvant, which mediated peptide-specific lysis of syngeneic P815 tumor targets. Cytotoxicity was restricted by H-2Kd and strongly specific for the mutant ras peptide. Importantly, these anti-ras CTL specifically lysed a syngeneic tumor line (i.e. A20 lymphoma) transduced with the corresponding point-mutated ras oncogene, suggesting T cell receptor recognition of endogenously derived antigen. Overall, these data demonstrated that mutant ras p21 at codon 12(Gly-->Val) contained a peptide sequence which exhibited specific functional binding to a murine MHC class I molecule; the ability of the mutant, but not the normal sequence to bind selectively to murine MHC class I likely reflected the generation of a C-terminal anchor residue; and the ras4-12(V12) peptide was immunogenic for the production of antigen-specific CD8+ CTL, which lysed in vitro a syngeneic tumor cell line harboring the mutant K-ras oncogene.
The significance of mild traumatic brain injury to cognition and self-reported symptoms in long-term recovery from injury (2008)

The aim of this study was to evaluate neurocognition and self-reported symptoms in long-term recovery from mild traumatic brain injury (mild TBI). Participants' time since injury ranged from 3 to 72 (M = 36.75) months. Relative to orthopedic injury controls (n = 63), mild TBI participants (n = 63) did not demonstrate cognitive impairment in any domains examined, or differences in self-report of postconcussive or psychiatric symptoms. However, postconcussive and psychiatric symptoms were strongly related (r = .50, p < .05). Results provide additional evidence that neurological injury in single-incident mild TBI is of little clinical significance to long-term cognitive and symptom outcome.
Effects of testosterone replacement therapy on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men (1998)

Loss of bone and muscle mass are major findings of male hypogonadism. In order to determine the long-term effect of testosterone replacement therapy on spinal bone and muscles, the trabecular and cortical bone mineral density, vertebral body area and paraspinal muscle area were assessed by quantitative computed tomography in 32 testosterone-substituted patients, aged 18-74 years, with idiopathic hypogonadotropic hypogonadism (n=6), pituitary insufficiency (n=5), Klinefelter syndrome (n=12) or other forms of primary hypogonadism (n=9). They were followed for a mean period of 3.2+/-1.7 years (mean+/-S.D.), ranging from 1 to 7 years. A significant correlation between initial serum testosterone levels and bone mineral density was found in patients with congenital forms (r=0.58; P<0.05) but not in those with acquired forms. A significant increase in trabecular and cortical bone mineral density (P<0.001) was documented in the course of replacement therapy in all patients regardless of the type of hypogonadism and age of patients. A slight but significant increase in paraspinal muscle area was observed if all patients were taken together (P<0.01). The area of paraspinal muscle correlated with body weight (r=0.58; P<0.001) and moderately with trabecular bone mineral density (r=0.4; P<0.01). Its increase did not correspond to the change observed for trabecular and cortical bone mineral density. Vertebral body area did not change over time. It correlated only with height and weight but not with bone mineral density. In conclusion, testosterone therapy of hypogonadal men improves both trabecular and cortical bone mineral density of the spine independently of age and type of hypogonadism while vertebral area remains unchanged. The effects seen on paraspinal muscles emphasize the clinical benefit of adequate replacement therapy for the physical fitness of hypogonadal men.
Acceleration of the G 1 /S Phase Transition by Expression of Cyclins Dl and E with an Inducible System (1994)

Conditional overexpression of human cyclins B1, D1, and E was accomplished by using a synthetic cDNA expression system based on the Escherichia coli tetracycline repressor. After induction of these cyclins in asynchronous Rat-1 fibroblasts, a decrease in the length of the G1 interval was observed for cyclins D1 and E, consistent with an acceleration of the G1/S phase transition. We observed, in addition, a compensatory lengthening of S phase and G2 so that the mean cell cycle length in populations constitutively expressing these cyclins was unchanged relative to those of their uninduced counterparts. We found that expression of cyclin B1 had no effect on cell cycle dynamics, despite elevated levels of cyclin B-associated histone H1 kinase activity. Induction of cyclins D1 and E also accelerated entry into S phase for synchronized cultures emerging from quiescence. However, whereas cyclin E exerted a greater effect than cyclin D1 in asynchronous cycling cells, cyclin D1 conferred a greater effect upon stimulation from quiescence, suggesting a specific role for cyclin D1 in the G0-to-G1 transition. Overexpression of cyclins did not prevent cells from entering into quiescence upon serum starvation, although a slight delay in attainment of quiescence was observed for cells expressing either cyclin D1 or cyclin E. These results suggest that cyclins D1 and E are rate-limiting activators of the G1-to-S phase transition and that cyclin D1 might play a specialized role in facilitating emergence from quiescence.
Braf mutations are associated with increased mortality in colorectal cancer (2004)

Gimbel, Mark I. MD; Nash, Garrett MD; Ndubuisi, Mackevin PhD; Wong, Douglas MD; Barany, Francis PhD; Paty, Philip MD, FACS Author Information
Chronic epidural bupivacaine-opioid infusion in intractable cancer pain (1992)

This study examined the efficacy and toxicity associated with chronic epidural opioid-bupivacaine infusions. In a series of 68 patients with cancer pain refractory to epidural opioids alone, analgesia was effectively regained by infusing a opioid-bupivacaine combination. Sixty-one patients (90%) were considered treatment successes, according to conventional criteria. Median length of therapy was 60-120 days, with the longest infusion lasting 277 days. Chronic bupivacaine infusion concentrations ranged from 0.1 to 0.5% with infusion rates varying from 4 to 18 ml/h. The majority of patients experienced pain relief with little or no sympathetic or sensorimotor impairment after the first 24 h at bupivacaine concentrations of 0.125-0.25% and were managed in home or chronic care settings without the need for re-hospitalization. In patients receiving higher bupivacaine concentrations, sympathetic, sensory and motor blockade were well tolerated during chronic infusion. Sensory loss was consistently observed only at bupivacaine concentrations exceeding 0.25%, and motor impairment occurred only at concentrations exceeding 0.35%. Postural hypotension was observed in 6 patients (9%) for the first 24 h only, which supports the requirement for monitoring and fluid therapy during initiation of the bupivacaine infusion. No patient experienced CNS or systemic toxicity, despite plasma total bupivacaine concentrations as high as 10.8 micrograms/ml. Serial plasma bupivacaine levels were measured in 15 patients during chronic infusion. There was considerable inter- and intra-individual variability in plasma bupivacaine concentrations and bupivacaine clearance. We conclude that epidural opioid-bupivacaine infusion is an effective and safe technique for long-term administration of analgesics in the refractory cancer patient.
Demonstration of insulin-responsive trafficking of GLUT4 and vpTR in fibroblasts (2000)

Insulin-responsive trafficking of the GLUT4 glucose transporter and the insulin-regulated aminopeptidase (IRAP) in adipose and muscle cells is well established. Insulin regulation of GLUT4 trafficking in these cells underlies the role that adipose tissue and muscle play in the maintenance of whole body glucose homeostasis. GLUT4 is expressed in a very limited number of tissues, most highly in adipose and muscle, while IRAP is expressed in many tissues. IRAP's physiological role in any of the tissues in which it is expressed, however, is unknown. The fact that IRAP, which traffics by the same insulin-regulated pathway as GLUT4, is expressed in 'non-insulin responsive' tissues raises the question of whether these other cell types also have a specialized insulin-regulated trafficking pathway. The existence of an insulin-responsive pathway in other cell types would allow regulation of IRAP activity at the plasma membrane as a potentially important physiological function of insulin. To address this question we use reporter molecules for both GLUT4 and IRAP trafficking to measure insulin-stimulated translocation in undifferentiated cells by quantitative fluorescence microscopy. One reporter (vpTR), a chimera between the intracellular domain of IRAP and the extracellular and transmembrane domains of the transferrin receptor, has been previously characterized. The other is a GLUT4 construct with an exofacial HA epitope and a C-terminal GFP. By comparing these reporters to the transferrin receptor, a marker for general endocytic trafficking, we demonstrate the existence of a specialized, insulin-regulated trafficking pathway in two undifferentiated cell types, neither of which normally express GLUT4. The magnitude of translocation in these undifferentiated cells (approximately threefold) is similar to that reported for the translocation of GLUT4 in muscle cells. Thus, undifferentiated cells have the necessary retention and translocation machinery for an insulin response that is large enough to be physiologically important.
Sedation Using Dexmedetomidine in Pediatric Burn Patients (2006)

Maintaining appropriate sedation and analgesia in pediatric burn patients can be quite challenging and often requires high doses of analgesics and anxiolytics because tolerance quickly develops. Escalating doses of opioids and benzodiazepines provide little additional benefit while increasing the incidence of side effects. Dexmedetomidine (DEX) is a novel alpha2-adrenergic agonist that provides sedation, anxiolysis, and analgesia with much less respiratory depression than other sedatives. In addition, DEX stimulation of alpha2 receptors on pancreatic beta cells may inhibit insulin secretion. Hyperglycemia has not been studied specifically in patients receiving DEX. Therefore, we hypothesized that DEX would improve sedation compared with our standard sedation regimen. In addition, we studied the effects of DEX on blood glucose levels. We performed a retrospective chart review of 65 pediatric burn patients (42 boys, 23 girls) in the intensive care unit admitted between 2001 and 2004 who received DEX infusion because of failure to achieve adequate sedation with our standard regimen of opioids and benzodiazepines. We recorded age, TBSA burn size, weight, dose and duration of infusion, adequacy of sedation before and after initiation of DEX, blood glucose levels before and after DEX, and the presence or absence of mechanical ventilation. The mean age was 5 years (range, 0.6-17), burn size was 36% TBSA (range, 3-94), and weight was 26 kg (range, 8-100). All patients were rated "inadequately sedate" before DEX infusion was initiated at 0.2 mug/kg/hr and titrated to effect. Twenty-six patients received a loading dose of 1 mug/kg. The average duration of DEX infusion was 11 days (range, 2-50), and no tachyphylaxis was noted. The mean dose was 0.5 mug/kg/hr (range, 0.1-2). Infusions were weaned over the course of 12 to 24 hours without evidence of rebound hypertension or withdrawal. With DEX titration, all patients were rated "adequately sedate," even though all were sedation failures with opioids and benzodiazepines. Eleven of 42 patients receiving ventilatory support were extubated while on DEX infusion, and no patient showed evidence of DEX induced respiratory depression. Patient's blood glucose levels averaged 121.2 +/- 8.9 mg/dl while on DEX infusion and 117.1 +/- 12.1 mg/dl while off, a nonsignificant difference.
Delivery Challenges for Fluoride, Chlorhexidine and Xylitol (2006)

The progression or reversal of dental caries is determined by the balance between pathological and protective factors. It is well established that a) fluoride inhibits demineralization and enhances remineralization, b) chlorhexidine reduces the cariogenic bacterial challenge, and c) xylitol is non-cariogenic and has antibacterial properties. The challenge that we face is how best to deliver these anti-caries entities at true therapeutic levels, over time, to favorably tip the caries balance. High caries risk people, including children with Early Childhood Caries (ECC), are a special challenge, since high cariogenic bacterial activity can override fluoride therapy. Current fluoride and chlorhexidine varnishes deliver all their activity within about 24 hours. Early studies with experimental slow release fluoride devices retained elevated levels of fluoride for months in a therapeutic range but have not been pursued. Preventive dentistry has largely ignored the benefits of reducing the bacterial challenge, partially due to primitive and inadequate delivery systems. For example, Chlorhexidine applied as a rinse partially reduces some bacteria but not others that are hiding within the biofilm. Better antibacterials and better delivery systems are needed. Xylitol delivered by gum or lozenge appears to be effective clinically in reducing cariogenic bacteria and caries levels, but novel systems that deliver therapeutic amounts when needed would be a major advance, especially for young children. Reducing the cariogenic bacterial challenge and enhancing the effect of fluoride by the use of new sustained-delivery systems would have a major effect on dealing with caries as a disease.
Suppression of Listeria monocytogenes colonization following adsorption of nisin onto silica surfaces (1995)

Nisin is an antimicrobial peptide proven to be an effective inhibitor of gram-positive bacteria. It is known that nisin can adsorb to various surfaces and still retain much of its original activity (M. A. Daeschel, J. McGuire, and H. Al-Makhlafi, J. Food Prot. 55:731-735, 1992). In this study, nisin films were allowed to form on silanized silica surfaces and then exposed to medium containing Listeria monocytogenes. Representative areas were selected from each surface, and images of resident listeriae were obtained at 4-h intervals for 12 h. During this time, cells on surfaces that had been in contact with a high concentration of nisin (1.0 mg/ml) exhibited no signs of growth and many displayed evidence of cellular deterioration. Surfaces treated with a lower concentration of nisin (0.1 mg/ml) had a smaller degree of inhibition. In contrast, both protein-free surfaces and those with films of heat-inactivated nisin allowed attached L. monocytogenes cells to grow and reproduce. These studies, when repeated with a nisin-resistant strain of L. monocytogenes, resulted in no inhibition of growth on surfaces with adsorbed nisin. The bactericidal effect of adsorbed nisin was also studied with iodonitrotetrazolium violet, a tetrazolium salt, which is reduced to a red formazan crystal by viable bacteria. Crystals were visible in 95% of the cells adhered to control surfaces but were present in less than 20% of the cells on surfaces with adsorbed nisin. These data indicate that adsorbed nisin may have potential for use as a food grade antimicrobial agent on food contact surfaces.
HTTP Extensions for Web Distributed Authoring and Versioning (WebDAV) (2007)

WebDAV consists of a set of methods, headers, and content-types
ancillary to HTTP/1.1 for the management of resource properties,
creation and management of resource collections, namespace
manipulation, and resource locking (collision avoidance). RFC2518 was
published in February 1998, and this draft makes minor revisions
mostly due to interoperability experience.
HIC1 hypermethylation is a late event in hematopoietic neoplasms. (1997)

HIC1, a candidate tumor suppressor gene on 17p13.3, is hypermethylated and silenced in a large number of solid tumors. To determine its potential role in leukemias, we studied its methylation status in normal and neoplastic hematopoietic cells. We found HIC1 to be unmethylated in peripheral blood cells, bone marrow cells, and CD34+ cells. HIC1 was rarely methylated in newly diagnosed acute myelogenous leukemias (10%) but was relatively frequently methylated in newly diagnosed non-Hodgkin's lymphoma (25%), acute lymphocytic leukemia (ALL; 53%), and chronic-phase chronic myelogenous leukemia (50%). By contrast, HIC1 was hypermethylated in 100% of recurrent ALL and 100% of blast crisis chronic myelogenous leukemia. In two patients with ALL for whom paired diagnosis/relapse samples were available, HIC1 was unmethylated at diagnosis but was highly methylated at relapse after a chemotherapy-induced complete remission. HIC1 methylation, therefore, seems to be a progression event in hematopoietic neoplasms.
Do new cellulolytic enzyme preparations affect the industrial strategies for high solids lignocellulosic ethanol production? (2013)

Production of ethanol from lignocellulosic materials has a promising market potential, but the process is still only at pilot/demonstration scale due to the technical and economical difficulties of the process. Operating the process at very high solids concentrations (above 20% dry matter-DM) has proven essential for economic feasibility at industrial scale. Historically, simultaneous saccharification and fermentation (SSF) was found to give better ethanol yields compared to separate hydrolysis and fermentation (SHF), but data in literature are typically based on operating the process at low dry matter conditions. In this work the impact of selected enzyme preparation and processing strategy (SHF, presaccharification and simultaneous saccharification and fermentation-PSSF, and SSF) on final ethanol yield and overall performance was investigated with pretreated wheat straw up to 30% DM. The experiments revealed that an SSF strategy was indeed better than SHF when applying an older generation enzyme cocktail (Celluclast-Novozym 188). In case of the newer product Cellic CTec 2, SHF resulted in 20% higher final ethanol yield compared to SSF. It was possible to close the mass balance around cellulose to around 94%, revealing that the most relevant products could be accounted for. One observation was the presence of oxidized sugar (gluconic acid) upon enzymatic hydrolysis with the latest enzyme preparation. Experiments showed gluconic acid formation by recently discovered enzymatic class of lytic polysaccharides monoxygenases (LPMO's) to be depending on the processing strategy. The lowest concentration was achieved in SSF, which could be correlated with less available oxygen due to simultaneous oxygen consumption by the yeast. Quantity of glycerol and cell mass was also depending on the selected processing strategy.