gebhart/patrepeval huggingface dataset:
Binocular depth discrimination and estimation beyond interaction space (2009)

The benefits of binocular vision have been debated throughout the history of vision science yet few studies have considered its contribution beyond a viewing distance of a few meters. In the first set of experiments, we compared monocular and binocular performance on depth interval estimation and discrimination tasks at 4.5, 9.0 or 18.0 m. Under monocular conditions, perceived depth was significantly compressed. Binocular depth estimates were much nearer to veridical although also compressed. Regression-based precision measures were much more precise for binocular compared to monocular conditions (ratios between 2.1 and 48). We confirm that stereopsis supports reliable depth discriminations beyond typical laboratory distances. Furthermore, binocular vision can significantly improve both the accuracy and precision of depth estimation to at least 18 m. In another experiment, we used a novel paradigm that allowed the presentation of real binocular disparity stimuli in the presence of rich environmental cues to distance but not interstimulus depth. We found that the presence of environmental cues to distance greatly enhanced stereoscopic depth constancy at distances of 4.5 and 9.0 m. We conclude that stereopsis is an effective cue for depth discrimination and estimation for distances beyond those traditionally assumed. In normal environments, distance information from other sources such as perspective can be effective in scaling depth from disparity.
Two percent of Finnish prostate cancer patients have a germ-line mutation in the hormone-binding domain of the androgen receptor gene. (2000)

Mutations of the androgen receptor (AR) gene have been reported in prostate cancer, usually from tumor tissue specimens from late-stage, androgen-independent cancer. Occasionally, germ-line mutations have been found, but a link between AR mutations and predisposition to human prostate cancer has not been firmly established. Recently, two independent studies reported the same germ-line mutation at codon 726 in exon E (CGC to CTC) in two apparently unrelated Finnish prostate cancer patients. This arginine to leucine substitution was reported to alter the transactivational specificity of the AR protein. In the present study, the R726L mutation was analyzed by allele-specific oligohybridization in DNA specimens from 418 consecutive prostate cancer patients who reported a negative family history (sporadic group) and from 106 patients with a positive family history (hereditary group). The population frequency of the R726L mutation in blood donors was 3 of 900 (0.33%). In contrast, eight (1.91%) mutations (odds ratio = 5.8; P = 0.006) were found in the sporadic group, and two (1.89%) mutations were found in the hereditary group (odds ratio = 5.8; P = 0.09). Suggestive evidence of the segregation of the mutation with prostate cancer was seen in these two families. The present study indicates that the R726L substitution in the AR may confer an up to 6-fold increased risk of prostate cancer and may contribute to cancer development in up to 2% of Finnish prostate cancer patients. These results warrant additional large-scale studies of the significance of rare mutations and polymorphisms in candidate genes along the androgen signaling pathway as risk factors for prostate cancer.
Thermodynamic Analysis of Ligand-Induced Changes in Protein Thermal Unfolding Applied to High-Throughput Determination of Ligand Affinities with Extrinsic Fluorescent Dyes (2010)

The quantification of protein-ligand interactions is essential for systems biology, drug discovery, and bioengineering. Ligand-induced changes in protein thermal stability provide a general, quantifiable signature of binding and may be monitored with dyes such as Sypro Orange (SO), which increase their fluorescence emission intensities upon interaction with the unfolded protein. This method is an experimentally straightforward, economical, and high-throughput approach for observing thermal melts using commonly available real-time polymerase chain reaction instrumentation. However, quantitative analysis requires careful consideration of the dye-mediated reporting mechanism and the underlying thermodynamic model. We determine affinity constants by analysis of ligand-mediated shifts in melting-temperature midpoint values. Ligand affinity is determined in a ligand titration series from shifts in free energies of stability at a common reference temperature. Thermodynamic parameters are obtained by fitting the inverse first derivative of the experimental signal reporting on thermal denaturation with equations that incorporate linear or nonlinear baseline models. We apply these methods to fit protein melts monitored with SO that exhibit prominent nonlinear post-transition baselines. SO can perturb the equilibria on which it is reporting. We analyze cases in which the ligand binds to both the native and denatured state or to the native state only and cases in which protein:ligand stoichiometry needs to treated explicitly.
Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease (2004)

Melatonin is an endogenous antioxidant and free radical scavenger. A transgenic (Tg) mouse model for Alzheimer's disease mimics the accumulation of senile plaques, neuronal apoptosis and memory impairment. Previous studies indicated that melatonin reduced beta-amyloid (Abeta)-induced neurotoxicity. In this study, after giving melatonin at 10 mg/kg to APP 695 transgenic (APP 695 Tg) mice for 4 months, we evaluated the long-term influence of melatonin on behavior, biochemical and neuropathologic changes in APP 695 Tg mice. Step-down and step-through passive avoidance tests suggested that 8-month-old APP 695 Tg mice showed decreases in step-down latency and step-through latency and increases in count of error throughout the entire learning trial and memory session, which suggested learning and memory impairment. However, melatonin alleviated learning and memory deficits. Additionally, choline acetyltransferase (ChAT) activity also decreased in the frontal cortex and hippocampus of APP 695 Tg mice compared with non-Tg littermates. Melatonin supplementation increased ChAT activity in the frontal cortex and hippocampus. DNA fragmentation was present in the frontal cortex of the APP 695 Tg mice; melatonin reduced the number of apoptotic neurons. Congo Red staining and Bielschowsky silver impregnation both showed the apparent extracellular Abeta deposition in frontal cortex of APP 695 Tg mice. However, melatonin decreased the Abeta deposits. Our results indicate that neuroprotection by melatonin is partly related to modulation of apoptosis and protection of the cholinergic system. Early rational melatonin interventions may be one of the most promising strategies in the development of approaches to retard or prevent Abeta-mediated disease progression.
Perceptual interfaces for information interaction: joint processing of audio and visual information for human-computer interaction (2000)

We are exploiting the human perceptual principle of sensory integration (the joint use of audio and visual information) to improve the recognition of human activity (speech recognition, speech event detection and speaker change), intent (intent to speak) and human identity (speaker recognition), particularly in the presence of acoustic degradation due to noise and channel. In this paper, we present experimental results in a variety of contexts that demonstrate the benefit of joint audio-visual processing.
Genomic Evolution, Patterns of Global Dissemination, and Interspecies Transmission of Human and Simian T-cell Leukemia/Lymphotropic Viruses (1999)

Using both env and long terminal repeat (LTR) sequences, with maximal representation of genetic diversity within primate strains, we revise and expand the unique evolutionary history of human and simian T-cell leukemia/lymphotropic viruses (HTLV/STLV). Based on the robust application of three different phylogenetic algorithms of minimum evolution-neighbor joining, maximum parsimony, and maximum likelihood, we address overall levels of genetic diversity, specific rates of mutation within and between different regions of the viral genome, relatedness among viral strains from geographically diverse regions, and estimation of the pattern of divergence of the virus into extant lineages. Despite broad genomic similarities, type I and type II viruses do not share concordant evolutionary histories. HTLV-I/STLV-I are united through distinct phylogeographic patterns, infection of 20 primate species, multiple episodes of interspecies transmission, and exhibition of a range in levels of genetic divergence. In contrast, type II viruses are isolated from only two species (Homo sapiens and Pan paniscus) and are paradoxically endemic to both Amerindian tribes of the New World and human Pygmy villagers in Africa. Furthermore, HTLV-II is spreading rapidly through new host populations of intravenous drug users. Despite such clearly disparate host populations, the resultant HTLV-II/STLV-II phylogeny exhibits little phylogeographic concordance and indicates low levels of transcontinental genetic differentiation. Together, these patterns generate a model of HTLV/STLV emergence marked by an ancient ancestry, differential rates of divergence, and continued global expansion.
Intermodulation Interference in Radio Systems (1953)

Intermodulation interference becomes a serious factor in frequency usage when a block of consecutive channels is provided for a given type of radio service in a confined area. Formulas are presented which show the number of potentially interfering 3rd and 5th order intermodulation products that can be formed in a band of n consecutive channels. The probability of encountering interference when a number of operating channels are picked at random from this band of n channels is developed and the number of interference free operating channels that can be obtained by careful selection in this same band is also derived.
Transcriptional regulation of two serum-induced RNAs in mouse fibroblasts: equivalence of one species to B2 repetitive elements. (1985)

We obtained eight cDNA clones that define five genes whose expression (appearance of transcripts in the cytoplasm) is enhanced when quiescent mouse fibroblasts are stimulated with serum to divide. Two of these clones (designated 49C8 and 16C8) correspond to RNA species that are present in the cytoplasm of quiescent cells at very low levels. After serum stimulation, the level of 16C8 mRNA rose more rapidly than that of 49C8 RNA, reaching a maximum around 6 to 12 h. The data suggest that 49C8 and 16C8 RNAs are induced as a result of independent stimuli. Either fibroblast growth factor or 12-tetradecanoylphorbol-13-acetate alone could induce 16C8 expression almost as effectively as serum; in contrast, 49C8 was not efficiently induced by epidermal growth factor, fibroblast growth factor, insulin, or 12-tetradecanoylphorbol-13-acetate. Inhibitors of transcription and translation diminished the induction of 16C8, while 49C8 expression was sensitive to actinomycin D but not cycloheximide or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. In vitro transcription experiments with isolated nuclei revealed a peak in transcriptional activity of the 16C8 gene at around 3 h after serum stimulation. Sequence analysis of the 49C8 cDNA clone showed greater than 90% homology of a large portion to a consensus rodent B2 repetitive element.
MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma (2013)

We conclude that downregulation of 14q32 miRNA expression is an evolutionarily conserved mechanism that contributes to the biological behavior of osteosarcoma, and that quantification of representative transcripts from this family, such as miR-382, miR-134, and miR-544, provide prognostic and predictive markers that can assist in the management of patients with this disease.
The Role of Plasmin on the Double Antibody Radioimmunoassay of Carcinoembryonic Antigen in Human Blood Samples (1976)

Double antibody radioimmunoassay (RIA) of carcinoembryonic antigen (CEA) on a series of freshly drawn out concurrent plasma and serum samples of normal human blood donors showed that the serum CEA values were invariably higher than the corresponding plasma CEA values. Extraneous addition of fibrinogen brought down the serum-CEA level to a value comparable to or less than the corresponding plasma value. The effect of certain factors associated with blood clotting, particularly Ca++, fibrinogen, and the fibrinolytic enzyme plasmin, was investigated. Ca++ was shown to play no role whereas the effect of fibrinogen was shown to be indirect in that it served as a specific substrate for plasmin, thereby preventing the plasmin degradation of the primary antibody used in the RIA. The finding stresses the role of enzymes like plasmin in double antibody RIA in general and may explain some of the anomalous results obtained when testing biologic material containing plasmin-like substances.
Crystal structure of quinespar, a quinazoline analog of methotrexate (1986)

The molecular structure of quinespar, a quinazoline analogue of methotrexate and aminopterin, has been determined by X-ray crystallography. The molecule displays an extended conformation with the p-aminobenzoyl plane rotated 66 degrees from the plane of the quinazoline. The orientation of the quinazoline ring relative to the rest of the molecule is intermediate between the orientations of the comparable pteridine rings in folic acid and in DHFR-bound methotrexate. Evidence is presented to suggest that 2,4-diaminoquinazolines bind to DHFR in the same manner as do 2,4-diaminopteridines.
Prognostic Value of p53 for Local Failure in Mastectomy-Treated Breast Cancer Patients (2000)

Nuclear accumulation of p53 protein is independently associated with a significantly increased local failure rate in breast cancer patients treated with mastectomy, with or without radiation.
ICA by Minimization of Mutual Information (2001)

An important approach for independent component analysis (ICA) estimation, inspired by information theory, is minimization of mutual information. This approach is the subject of this chapter.
Prognostic importance of serum vascular endothelial growth factor in relation to platelet and leukocyte counts in human renal cell carcinoma (2002)

It has been shown that both serum vascular endothelial growth factor (VEGF) and also platelet counts are associated with survival in renal cell carcinoma (RCC). It is not known, however, whether VEGF in serum relates to the angiogenic activity of the tumour or is derived from circulating blood components. Therefore, the interrelation between serum VEGF, platelet and leukocyte counts compared with health history, clinicopathological findings and outcome was evaluated in patients with RCC. Blood samples were collected before nephrectomy in 161 patients. Serum VEGF165 was assessed by a quantitative ELISA method. Platelet and leukocyte counts were analysed routinely and obtained from medical records. The variables were compared using univariate and multivariate analysis. There were significant correlations between VEGF levels, and platelet (P < 0.001) and leukocyte counts (P < 0.001). Serum VEGF levels, platelet counts, as well as leukocyte counts correlated significantly to stage and grade. Platelet counts were significantly lower in men with medication (P = 0.042), and decreased with age particularly in women (P = 0.001). Age or medication did not affect VEGF levels or leukocyte counts. Both VEGF and platelets gave significant prognostic information in univariate analysis. Using Cox multivariate analysis, VEGF was the last variable to be excluded. Only stage and grade remained as independent prognostic factors. Both VEGF levels and platelet counts gave prognostic information but VEGF was more reliable as predictor of survival in patients with RCC.
Three Isoforms of Synaptic Scaffolding Molecule and Their Characterization (2000)

The synaptic scaffolding molecule (S-SCAM) has been identified as a protein interacting with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/hDLG-associated protein). S-SCAM has six PDZ (we have numbered them PDZ-0 to -5), two WW, and one guanylate kinase (GK) domains and interacts with N-methyl-D-aspartate (NMDA) receptor via PDZ-5 and SAPAP via the GK domain. We have identified here shorter isoforms of S-SCAM that start at the 164th or 224th methionine, and we renamed the original one, S-SCAMalpha, the middle one, S-SCAMbeta, and the shortest one, S-SCAM-gamma. S-SCAMbeta and -gamma have five PDZ (PDZ-1 to -5), two WW, and one GK domains. S-SCAMalpha interacted with S-SCAMbeta and -gamma through the region containing PDZ-4 and -5. The region containing both of PDZ-4 and -5 is sufficient for the clustering of NMDA receptors and forms a dimer in gel filtration, suggesting that S-SCAM forms multimers via the interaction between the C-terminal PDZ domains and assembles NMDA receptors into clusters. S-SCAMbeta and -gamma also interacted with SAPAP, suggesting that the N-terminal region of the GK domain is not necessary for the interaction. Finally, we have identified the interaction of the PDZ domains of S-SCAM with the GK domain of PSD-95/SAP90. S-SCAM, PSD-95/SAP90, and SAPAP are colocalized at least in some part in brain. Therefore, S-SCAM, PSD-95/SAP90, and SAPAP may form a complex in vivo.
Targeted gene deletion of Leishmania major genes encoding developmental stage‐specific leishmanolysin (GP63) (1998)

The major surface glycoprotein of Leishmania major is a zinc metalloproteinase of 63 kDa referred to as leishmanolysin or GP63, which is encoded by a family of seven genes. Targeted gene replacement was used to delete gp63 genes 1-6 encoding the highly expressed promastigote and constitutively expressed GP63. In the L. major homozygous mutants deficient in gp63 genes 1-6, there was no expression of GP63 as detected by reverse transcription-polymerase chain reaction (RT-PCR) or fluorescent staining in promastigotes from the procyclic stage (logarithmic growth phase). The remaining L. major gP63 gene 7 was shown to be developmentally regulated, as it was expressed exclusively in infectious metacyclic stage (late stationary growth phase) promastigotes and in lesion amastigotes. The gp63 genes 1-6-deficient mutants showed increased sensitivity to complement-mediated lysis. The sensitivity to lysis was greater in procyclics than in metacyclics when compared with the equivalent wild-type stages. Increased resistance of the mutant metacyclic promastigotes correlated with the expression of gp63 gene 7 and was restored to the same levels as wild-type promastigotes by transfection with gp63 gene 1. Thus, expression of GP63 is clearly involved in conferring resistance to complement-mediated lysis. The L. major GP63 1-6 mutants were capable of infecting mouse macrophages and differentiating into amastigotes. Similar levels of infection and subsequent intracellular survival were observed when mouse macrophages were infected in vitro with wild type, GP63 1-6 mutants and mutants transfected with gp63 gene 1. The GP63 1-6 mutants were capable of lesion formation in BALB/c mice and, thus, gp63 genes 1-6 do not play a role in the survival of the parasite within mouse macrophages. The role of gp63 genes 1-6 in parasite development within the sandfly vector was studied. GP63 1-6 mutants grew normally in the blood-engorged midgut of both Phlebotomus argentipes and P. papatasi However, both wild-type and mutant promastigotes were lost after 2 days' growth in P. papatasi. The complete developmental pathway in P. argentipes was observed for wild-type promastigotes, GP63 1-6 mutants and mutants transfected with gp63 gene 1. Normal stage differentiation from amastigotes to procyclics, to nectomonads, to haptomonads and to infectious metacyclics was observed. Thus, the highly expressed promastigote forms of GP63, encoded by gp63 genes 1-6, do not appear to be required for nutrient utilization in the bloodmeal during the early stages of development in the sandfly or for midgut attachment and further development. gp63 1-6 genes do, however, play a major protective role against complement-mediated lysis when promastigotes are introduced into the mammalian host.
Induction of Heme Oxygenase-1 Suppresses Venular Leukocyte Adhesion Elicited by Oxidative Stress (1999)

This study aimed to examine whether an elevated activity of heme oxygenase (HO)-1 in the tissue attenuates endothelial cell-leukocyte interactions microvessels in vivo. When rats were pretreated with an intraperitoneal injection of hemin, an HO-1 inducer, mesenteric tissues, including their microvessels, displayed a marked induction of HO-1 concurrent with an increase in plasma concentrations of bilirubin-IXalpha, the product of HO-catalyzed degradation of protoheme IX. In these rats, oxidative stress such as superfusion with H(2)O(2) and ischemia-reperfusion of the tissues neither induced rolling nor exhibited adherent responses of leukocytes in venules. In contrast, the oxidative stresses evoked marked rolling and adhesion of leukocytes in the control rats without HO-1 induction. The HO-1 induction also downregulated leukocyte adhesion elicited by other pro-oxidant stimuli such as N(omega)-nitro-L-arginine methyl ester. The decreases in the oxidant-elicited leukocyte adhesive responses under HO-1-inducing conditions were restored by perfusion with zinc protoporphyrin-IX, an HO inhibitor, but not with copper protoporphyrin-IX, which did not inhibit the enzyme. Furthermore, the effects of zinc protoporphyrin-IX were repressed by superfusion with bilirubin or biliverdin at the micromolar level, but not by the same concentration of carbon monoxide, another product of HO. These results indicate that induction of the HO-1 activity serves as a potential stratagem to prevent oxidant-induced microvascular leukocyte adhesion through the action of bilirubin, a product of HO reaction.
Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor (1991)

The specific cellular receptor for urokinase-type plasminogen activator (uPA) is found on a variety of cell types and has been postulated to play a central role in the mediation of pericellular proteolytic activity. We have studied the kinetics of plasminogen (Plg) activation catalyzed by uPA specifically bound to its receptor on the human monocytoid cell-line U937 and demonstrate this process to have properties differing widely from those observed for uPA in solution. The solution-phase reaction was characterized by a Km of 25 microM and for the cell-associated reaction this fell 40-fold to 0.67 microM, below the physiological Plg concentration of 2 microM. A concomitant 6-fold reduction in kcat resulted in an increase in the overall catalytic efficiency, kcat/Km, of 5.7-fold. This high affinity Plg activation was abolished in the presence of a Plg-binding antagonist. In contrast to intact cells, purified uPA receptor (isolated from phorbol 12-myristate 13-acetate-stimulated U937 cells) was observed to partially inhibit uPA-catalyzed Plg activation, although activity against low molecular weight substrates was retained. Therefore, the cellular binding of Plg appears to be of critical importance for the efficient activation of Plg by receptor-bound uPA. Plasmin generated in the cell-surface Plg activation system described here was also observed to be protected from its principal physiological inhibitor alpha-2-antiplasmin. Together, these data demonstrate that the cell surface constitutes the preferential site for Plg activation when uPA is bound to its specific cellular receptor, which therefore has the necessary characteristics to play an efficient role in the generation of pericellular proteolytic activity.