gebhart/patrepeval huggingface dataset:
Detection of bladder cancer using a novel nuclear matrix protein, BLCA-4. (2000)

We have identified previously six nuclear matrix proteins (NMPs) that are bladder cancer specific. In this study, we analyzed the expression of one of these proteins, BLCA-4, in bladder tumors and normal bladder tissue. We also examined the appearance of BLCA-4 in the urine as a biomarker for bladder cancer. BLCA-4 was isolated from nuclear matrix preparations of bladder tumors, and its peptide sequence was determined. The antibodies generated against the resulting BLCA-4 peptides were then used to detect its presence in immunoblots and in urine samples by immunoassay. We analyzed tissue samples of bladder tumor and normal donor bladders and urine obtained from 51 normal individuals and 54 patients with pathologically confirmed bladder cancer. The BLCA-4 peptide sequences do not resemble any known human protein sequences. On immunoblot analysis, BLCA-4 expression was detectable in tumor and normal tissues from patients with bladder cancer but not in any of the normal bladder tissue obtained from organ donors. Using a prospectively determined cutoff level of 13 A (absorbance) units/microg protein, all 51 normal individuals tested were negative for BLCA-4 expression, whereas 53 of 55 samples from patients with bladder cancer were positive. These results suggest that BLCA-4 is present throughout the bladder in both the tumor and morphologically normal areas in bladder cancer patients. BLCA-4 is a very sensitive (96.4%) and specific (100%) marker for bladder cancer. BLCA-4 is a bladder cancer-specific marker that can be detected using a urine-based assay and can be used in the diagnosis of bladder cancer.
Magnetic and surface plasmon resonances for periodic lattices of plasmonic split-ring resonators (2008)

In this study, the author investigates magnetic and surface plasmon resonances for periodic lattices of plasmonic split-ring resonators by the use of the interface matching method. Magnetic resonance is characterized by a special frequency branch and illustrated with the localized eigenmode patterns. The basic features associated with magnetic resonance are present at the long wavelength as well as at the Bloch wavelength comparable to the size of a unit cell with minor distinctions. Near the surface plasma frequency, a large number of highly resonant branches appear and surface plasmon resonance gradually becomes the dominated feature. By varying the ratio of lattice constant to plasma wavelength, the influence of plasmonic property on magnetic resonance is examined for rather small and large skin depths.
Split-Face Comparison of Photodynamic Therapy with 5-Aminolevulinic Acid and Intense Pulsed Light Versus Intense Pulsed Light Alone for Photodamage (2006)

Short-contact ALA-PDT-IPL brings about greater improvement in photodamaged skin and greater clearance of AK lesions than IPL alone, further confirming the usefulness of ALA-PDT in photorejuvenation.
Evaluation of Safety and Efficacy of 3TC (Lamivudine) in Patients with Asymptomatic or Mildly Symptomatic Human Immunodeficiency Virus Infection: A Phase I/II Study (1995)

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts < or = 400 x 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta 2-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.
Bispecific CD3/HER2 Targeting FynomAb Induces Redirected T Cell-Mediated Cytolysis with High Potency and Enhanced Tumor Selectivity (2015)

CD3 bispecific therapies retargeting T cells to tumors have recently demonstrated striking activity in patients. Several CD3 bispecific antibodies directed against various tumor targets are currently being investigated in the clinic across different tumors. One limitation of these therapies is the risk of target-related toxicity due to low-level expression of tumor antigen in normal tissue. In this study we have engineered a bispecific CD3/HER2 FynomAb, COVA420, which redirects T cells with high potency and selectivity to tumor cells with high HER2 expression in vitro and in vivo. COVA420 activity depends on high HER2 density as no activity was observed on cells with lower HER2 levels as found in human normal tissue. These results suggest that COVA420 may spare normal tissue expressing low levels of HER2 while still having uncompromised efficacy on tumor cells with high HER2 expression. This concept may be applied to other cancer antigens that otherwise cannot be targeted by T cell redirecting approaches, and may therefore expand the applicability of CD3 bispecific FynomAbs to a larger number of solid tumors.
Electrophysiological characterization of Na+ currents in acutely isolated human hippocampal dentate granule cells (1998)

1. Properties of voltage-dependent Na+ currents were investigated in forty-two dentate granule cells (DGCs) acutely isolated from the resected hippocampus of twenty patients with therapy-refractory temporal lobe epilepsy (TLE) using the whole-cell patch-clamp technique. 2. Depolarizing voltage commands elicited large, rapidly activating and inactivating Na+ currents (140 pS microm-2; 163 mM extracellular Na+) that were reduced in amplitude by lowering the Na+ gradient (43 mM extracellular Na+). At low temperatures (8-12 C), the time course of Na+ currents slowed and could be well described by the model of Hodgkin & Huxley. 3. Na+ currents were reversibly blocked by tetrodotoxin (TTX) and saxitoxin (STX) with a half-maximal block of 4.7 and 2.6 nM, respectively. In order to reduce series resistance errors, the Na+ current was partially blocked by low toxin concentrations (10-15 nM) in the experiments described below. Under these conditions, Na+ currents showed a threshold of activation of about -50 mV, and the voltages of half-maximal activation and inactivation were -29 and -55 mV, respectively. 4. The time course of recovery from inactivation could be described with a double-exponential function (time constants, 3-20 and 60-200 ms). The rapid and slow time constants showed a distinct voltage dependence with maximal values around -55 and -80 mV, respectively. These properties contributed to a reduction of the Na+ currents during repetitive stimulation that was more pronounced with higher stimulation frequencies and also showed a dependence on the holding potential. 5. In summary, the most striking features of DGC Na+ currents were the large current density and the presence of a current component showing a slow recovery from inactivation. Our data provide a basis for comparison with properties of Na+ currents in animal models of epilepsy, and for the study of drug actions in therapy-refractory epilepsy.
An in vivo screen for the luciferase transgene in zebrafish. (1994)

A simple and economical large-scale in vivo screen for firefly luciferase expression in transgenic zebrafish is described. The screen is a film assay of luminescence during embryogenesis. Either luciferin substrate can be microinjected into the embryo, or the embryo can be raised in a luciferin solution. In a test of transient expression in the G0 (microinjected) generation, a construct with the human cytomegalovirus (CMV) promoter gave higher levels of expression than three other constructs. Using the CMV promoter, injection of supercoiled or linear DNA led to approximately equivalent amounts of expression. Although G0 transient luciferase expression is high enough to be reliably screened, G1 integrated expression is either low or nonexistent, and therefore unscreenable. In the G1 and G2 generations, low-level expression was increased with application of 5-azacytidine. The fact that both transgene methylation and 5-azacytidine activation of expression occurred suggests that methylation is involved in either reducing or eliminating integrated luciferase expression. This in vivo luciferase screen may be useful for insertional mutagenesis, promoter, gene, or enhancer traps, promoter analysis, and optimization of conditions for gene transfer.
The Elastic Deformation of Lubricated Carbon Fiber Bundles: Comparison of Theory and Experiments (1992)

During typical composites manufacturing processes, fibers are deformed in ways that alter their processing characteristics (e.g., permeability, stresses and resin pressure, etc.) and their resulting microstructure (fiber volume fraction, void fraction, etc.). In this paper, we review all available data for the deformation behavior of lubricated carbon fiber bundles and compared it to a recently developed 3-D theory [15]. Most of the data, which is for transverse compression, exhibits very large scatter, but can be collapsed by shifting along the fiber volume fraction axis. It is hypothesized that the shifts represent different "states" for the fiber bundle, which can be represented in the model by a single variable, the available fiber volume fraction V a . It is then shown that all available aligned carbon fiber bundle data, including bulk compression, axial extension, and coupling be havior can be fit to the modified model by only adjusting V a . In one case (the coupling be havior), the available fiber volume fraction was directly measured. Observations on how the "state" of the fiber bundle can be modified by the processing conditions are included. On the basis of this analysis, a simple, practical test to determine V a is proposed.
Capacity Control of Residential Heat Pump Heating Systems (2007)

Heat pumps used for space and sanitary hot water heating of residential buildings are increasingly popular in northern Europe. As they compete with other heating equipment and in order to limit the environmental impact of their use, it is very important that heat pumps are energy efficient. The scope of this thesis is to investigate the potential for increased energy efficiency of heat pumps by applying variable-speed capacity control to compressor, pumps and fans, as well as an overall optimisation strategy for on-line optimisation of the operation. Focus has been on ground-source heat pumps connected to hydronic heating systems but the same principles apply also to other types of heat pumps. For air-source heat pumps the defrost function adds one extra parameter to consider and this is partly investigated by the evaluation of a proposal for optimised defrost initiation. Two prototype heat pumps with variable-speed compressors were designed and evaluated by laboratory measurements. The results from these measurements were used as input to models for calculating the energy efficiency of different heat pump systems. The models were used to compare the annual performance of the two prototype heat pumps to the performance of a state-of-the-art intermittently operated ground-source heat pump. One major result is that for the comparison between variable-speed and intermittent operation it is important to consider the transient behaviour of the heating system. In a separate study the possible benefits of using variable-speed controlled circulators were investigated. Results show that the use of efficient circulators is of primary importance, especially for heat pumps with a variable-speed capacity controlled compressor. Of secondary importance comes the variable-speed operation and optimisation of circulator and compressor capacities. Most important in this respect is to control the capacity of the circulator for the bore hole system. Capacity control of the circulators can be implemented by a simple strategy with results very close to an optimised control. Comparing the Seasonal Performance Factor (SPF) of an all variable-speed controlled heat pump (variable-speed pumps and compressor) with optimised pump and compressor capacities to the state-of-the-art intermittently controlled heat pump shows that the SPF could be increased by approximately 30 %. However, this requires improved compressor and system design compared to the two prototype heat pumps.
Renal Afferent Denervation Prevents Hypertension in Rats With Chronic Renal Failure (1995)

Increased activity of the sympathetic nervous system has been described in chronic renal failure, but its role in the genesis and maintenance of hypertension associated with this condition has not been established. The kidney has an intense network of chemoreceptors and baroreceptors that send impulses to the brain. To what extent activation of these receptors by the scarred kidney or the uremic milieu may contribute to this model of hypertension is unknown. In the present study, we evaluated the effect of bilateral dorsal rhizotomy on the development of hypertension and neuroadrenergic activity in the anterior, lateral, and posterior hypothalamic nuclei, in the locus ceruleus, and in the nucleus tractus solitarius of Sprague-Dawley rats that underwent 5/6 nephrectomy or were sham operated. Neuroadrenergic activity was determined by calculating norepinephrine turnover rate after inhibition of norepinephrine synthesis with alpha-methyl-DL-p-tyrosine methyl ester hydrochloride. The endogenous norepinephrine concentration was significantly greater in the posterior and lateral hypothalamic nuclei and the locus ceruleus, but not in the nucleus tractus solitarius, and the anterior hypothalamic nuclei of uremic rats compared with control rats. In rats with chronic renal failure and sham rhizotomy, the turnover rate of norepinephrine in the posterior (15.3 +/- 1.61 nmol.g-1.h-1) and lateral hypothalamic nuclei (11.7 +/- 2.12 nmol.g-1.h-1) and in the locus ceruleus (26.6 +/- 2.42 nmol.g-1.h-1) was significantly faster (P < .01) than in rats with renal failure and dorsal rhizotomy (4.1 +/- 0.51, 4.7 +/- 0.77, and 5.1 +/- 1.13 nmol.g-1.h-1, respectively) or control animals with or without rhizotomy.(ABSTRACT TRUNCATED AT 250 WORDS)
Engineering Herbicide Metabolism in Tobacco and Arabidopsis with CYP76B1, a Cytochrome P450 Enzyme from Jerusalem Artichoke (2002)

The Jerusalem artichoke (Helianthus tuberosus) xenobiotic inducible cytochrome P450, CYP76B1, catalyzes rapid oxidative dealkylation of various phenylurea herbicides to yield nonphytotoxic metabolites. We have found that increased herbicide metabolism and tolerance can be achieved by ectopic constitutive expression of CYP76B1 in tobacco (Nicotiana tabacum) and Arabidopsis. Transformation with CYP76B1 conferred on tobacco and Arabidopsis a 20-fold increase in tolerance to linuron, a compound detoxified by a single dealkylation, and a 10-fold increase in tolerance to isoproturon or chlortoluron, which need successive catalytic steps for detoxification. Two constructs for expression of translational fusions of CYP76B1 with P450 reductase were prepared to test if they would yield even greater herbicide tolerance. Plants expressing these constructs had lower herbicide tolerance than CYP76B1 alone, which is apparently a consequence of reduced stability of the fusion proteins. In all cases, increased herbicide tolerance results from more extensive metabolism, as demonstrated with exogenously fed phenylurea. Beside increased herbicide tolerance, expression of CYP76B1 has no other visible phenotype in the transgenic plants. Our data indicate that CYP76B1 can function as a selectable marker for plant transformation, allowing efficient selection in vitro and in soil-grown plants. Plants expressing CYP76B1 may also be a potential tool for phytoremediation of contaminated sites.
TRPC1, a human homolog of a Drosophila store-operated channel. (1995)

In many vertebrate and invertebrate cells, inositol 1,4,5-trisphospate production induces a biphasic Ca2+ signal. Mobilization of Ca2+ from internal stores drives the initial burst. The second phase, referred to as store-operated Ca2+ entry (formerly capacitative Ca2+ entry), occurs when depletion of intracellular Ca2+ pools activates a non-voltage-sensitive plasma membrane Ca2+ conductance. Despite the prevalence of store-operated Ca2+ entry, no vertebrate channel responsible for store-operated Ca2+ entry has been reported. trp (transient receptor potential), a Drosophila gene required in phototransduction, encodes the only known candidate for such a channel throughout phylogeny. In this report, we describe the molecular characterization of a human homolog of trp, TRPC1. TRPC1 (transient receptor potential channel-related protein 1) was 40% identical to Drosophila TRP over most of the protein and lacked the charged residues in the S4 transmembrane region proposed to be required for the voltage sensor in many voltage-gated ion channels. TRPC1 was expressed at the highest levels in the fetal brain and in the adult heart, brain, testis, and ovaries. Evidence is also presented that TRPC1 represents the archetype of a family of related human proteins.
Lectin derivatives of methotrexate and chlorambucil as chemotherapeutic agents. (1981)

Methotrexate and chlorambucil, each covalently linked to either abrus agglutinin, abrin, ricinus agglutinin, ricin, or concanavalin A, were prepared. A single dose of the derivative injected ip into sarcoma 180-bearing noninbred N:NIH(S) white mice resulted in prolongation of the survival time and was more effective than an equivalent dose of free drug and lectin. Drug-lectin also showed a higher inhibitory effect on the DNA biosynthesis of the tumor cell than did an equivalent dose of the free drug and lectin.
The Drosophila splicing regulator sex-lethal directly inhibits translation of male-specific-lethal 2 mRNA. (1998)

Male-specific expression of the protein male-specific-lethal 2 (MSL-2) controls dosage compensation in Drosophila. msl-2 gene expression is inhibited in females by Sex-lethal (SXL), an RNA binding protein known to regulate pre-mRNA splicing. An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains putative SXL binding sites and is retained in female flies. Here we show that SXL plays a dual role in the inhibition of msl-2 expression. Cotransfection of Drosophila Schneider cells with an SXL expression vector and a reporter containing the 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron and efficient accumulation of the unspliced mRNA in the cytoplasm, where its translation was blocked by SXL, but not by the intron per se. Both splicing and translation inhibition by SXL were recapitulated in vitro and found to be dependent upon SXL binding to high-affinity sites within the intron, showing that SXL directly regulates these events. Our data reveal a coordinated mechanism for the regulation of msl-2 expression by the same regulatory factor: SXL enforces intron retention in the nucleus and subsequent translation inhibition in the cytoplasm.
Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men (2005)

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. Injection of hypocretin-1 acutely suppresses TRH and TSH release in rats. In contrast, subchronic administration does not appear to affect the hypothalamo-pituitary-thyroid ensemble in animals. We explored (in 7 patients and 7 controls) whether hypocretin deficiency impacts circulating TSH levels and circadian timing of TSH release in narcoleptic humans. Plasma TSH concentration profiles (blood samples taken at 10-min intervals during 24 h) and TSH levels in response to TRH injection were analyzed by Cluster, robust regression, approximate entropy (ApEn), and deconvolution. Circulating TSH levels were lower in patients, which was primarily attributable to lower pulse amplitude and nadir concentrations. TSH secretion correlated positively with mean 24-h leptin levels (R2 = 0.46, P = 0.02) and negatively with amount of sleep (R2 = 0.29, P = 0.048). Pattern-synchrony between 24-h leptin and TSH concentrations was demonstrated by significant cross-correlation and cross-ApEn analyses with no differences between controls and patients. Sleep onset was closely associated with a fall in circulating TSH. Features of diurnal rhythmicity of circulating TSH fluctuations were similar in patients and controls, with the acrophase occurring shortly after midnight. Thyroxine and triiodothyronine concentrations were similar in patients and controls and did not display a diurnal rhythm. The response of plasma TSH levels to TRH was also similar in both groups. Sleep patterns in narcoleptics were significantly disorderly compared with controls, as measured by ApEn (P = 0.006). In summary, circulating TSH concentrations are low in hypocretin-deficient narcoleptic men, which could be attributable to their low plasma leptin levels and/or their abnormal sleep-wake cycle.
Genetic Requirements for the Single-Strand Annealing Pathway of Double-Strand Break Repair in Saccharomyces cerevisiae (1996)

HO endonuclease-induced double-strand breaks (DSBs) within a direct duplication of Escherichia coli lacZ genes are repaired either by gene conversion or by single-strand annealing (SSA), with > 80% being SSA. Previously it was demonstrated that the RAD52 gene is required for DSB-induced SSA. In the present study, the effects of other genes belonging to the RAD52 epistasis group were analyzed. We show that RAD51, RAD54, RAD55, and RAD57 genes are not required for SSA irrespective of whether recombination occurred in plasmid or chromosomal DNA. In both plasmid and chromosomal constructs with homologous sequences in direct orientation, the proportion of SSA events over gene conversion was significantly elevated in the mutant strains. However, gene conversion was not affected when the two lacZ sequences were in inverted orientation. These results suggest that there is a competition between SSA and gene conversion processes that favors SSA in the absence of RAD51, RAD54, RAD55 and RAD57. Mutations in RAD50 and XRS2 genes do not prevent the completion, but markedly retard the kinetics, of DSB repair by both mechanisms in the lacZ direct repeat plasmid, a result resembling the effects of these genes during mating-type (MAT) switching.
Subsets of the Major Tyrosine Phosphorylation Sites in Crk-associated Substrate (CAS) Are Sufficient to Promote Cell Migration (2004)

Crk-associated substrate (p130(CAS) or CAS) is a major integrin-associated Src substrate that undergoes tyrosine phosphorylation at multiple YXXP motifs in its substrate domain (SD) to create docking sites for SH2-containing signaling effectors. Notably, recruitment of Crk adaptor proteins to the CAS SD sites is implicated in promoting cell migration. However, it is unclear which or how many of the 15 CAS SD YXXP tyrosines are critically involved. To gain a better understanding of CAS SD function, we assessed the signaling capacity of individual YXXP motifs. Using site-directed mutagenesis combined with tryptic phosphopeptide mapping, we determined that the ten tyrosines in YXXP motifs 6-15 are the major sites of CAS SD phosphorylation by Src. Phosphopeptide binding assays showed that all of these sites are capable of binding the Crk SH2 domain. To evaluate the requirement for CAS YXXP sites in stimulating cell migration, a series of phenylalanine substitution variants were expressed in CAS -/- mouse embryo fibroblasts. CAS expression enhanced the rate of cell migration into a monolayer wound in a manner dependent on the major sites of Src phosphorylation. Effective wound healing was achieved by CAS variants containing as few as four of the major sites, indicating sufficiency of partial SD signaling function in this cell migration response.