gebhart/patrepeval huggingface dataset:
Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. (1991)

NADPH diaphorase staining neurons, uniquely resistant to toxic insults and neurodegenerative disorders, have been colocalized with neurons in the brain and peripheral tissue containing nitric oxide synthase (EC 1.14.23.-), which generates nitric oxide (NO), a recently identified neuronal messenger molecule. In the corpus striatum and cerebral cortex, NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in medium to large aspiny neurons. These same neurons colocalize with somatostatin and neuropeptide Y immunoreactivity. NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in the pedunculopontine nucleus with choline acetyltransferase-containing cells and are also colocalized in amacrine cells of the inner nuclear layer and ganglion cells of the retina, myenteric plexus neurons of the intestine, and ganglion cells of the adrenal medulla. Transfection of human kidney cells with NO synthase cDNA elicits NADPH diaphorase staining. The ratio of NO synthase to NADPH diaphorase staining in the transfected cells is the same as in neurons, indicating that NO synthase fully accounts for observed NADPH staining. The identity of neuronal NO synthase and NADPH diaphorase suggests a role for NO in modulating neurotoxicity.
Influence of macromer molecular weight and chemistry on poly(β‐amino ester) network properties and initial cell interactions (2007)

A library of photocrosslinkable poly(beta-amino ester)s (PBAEs) was recently synthesized to expand the number of degradable polymers that can be screened and developed for a variety of biological applications. In this work, the influence of variations in macromer chemistry and macromer molecular weight (MMW) on network reaction behavior, overall bulk properties, and cell interactions were investigated. The MMW was controlled through alterations in the initial diacrylate to amine ratio (> or =1) during synthesis and decreased with an increase in this ratio. Lower MMWs reacted more quickly and to higher double bond conversions than higher MMWs, potentially due to the higher concentration of reactive groups. Additionally, the lower MMWs led to networks with higher compressive and tensile moduli that degraded slower than networks formed from higher MMWs because of an increase in the crosslinking density and decrease in the number of degradable units per crosslink. The adhesion and spreading of osteoblast-like cells on polymer films was found to be dependent on both the macromer chemistry and the MMW. In general, the number of cells was similar on networks formed from a range of MMWs, but the spreading was dramatically influenced by MMW (higher spreading with lower MMWs). These results illustrate further diversity in photocrosslinkable PBAE properties and that the chemistry and macromer structure must be carefully selected for the desired application.
Estimating Linear Models for Compositional Distributional Semantics (2010)

In distributional semantics studies, there is a growing attention in compositionally determining the distributional meaning of word sequences. Yet, compositional distributional models depend on a large set of parameters that have not been explored. In this paper we propose a novel approach to estimate parameters for a class of compositional distributional models: the additive models. Our approach leverages on two main ideas. Firstly, a novel idea for extracting compositional distributional semantics examples. Secondly, an estimation method based on regression models for multiple dependent variables. Experiments demonstrate that our approach outperforms existing methods for determining a good model for compositional distributional semantics. 1
Expression of miR‐155 and miR‐126 in situ in cutaneous T‐cell lymphoma (2013)

Recently, miR-155 has been implicated in cutaneous T-cell lymphoma (CTCL). Thus, elevated levels of miR-155 were observed in skin lesions from CTCL patients as judged from qPCR and micro-array analysis and aberrant, high miR-155 expression was associated with severe disease. Moreover, miR-155 promoted proliferation of malignant T cells in vitro. Little is, however, known about which cell types express miR-155 in vivo in CTCL skin lesions. Here, we study miR-155 expression using in situ hybridization (ISH) with a miR-155 probe, a negative control (scrambled), and a miR-126 probe as a positive control in nine patients with mycosis fungoides, the most frequent subtype of CTCL. We provide evidence that both malignant and non-malignant T cells stain weakly to moderately positive with the miR-155 probe, but generally negative with the miR-126 and negative control probes. Reversely, endothelial cells stain positive for miR-126 and negative for miR-155 and the control probe. Solitary T cells with a malignant morphology display brighter staining with the miR-155 probe. Taken together, our findings suggest that both malignant and non-malignant T cells express miR-155 in situ in CTCL. Moreover, they indicate heterogeneity in miR-155 expression among malignant T cells.
Characteristic CD103 and CD123 Expression Pattern Defines Hairy Cell Leukemia (2011)

By using flow cytometry, we studied CD103 and CD123 expression by the malignant cells in 300 B-cell lymphoproliferative disorder (BC-LPD) cases, including 114 hairy cell leukemia (HCL), 20 HCL variant (HCLv), 9 splenic marginal zone lymphoma (SMZL; in 5, only CD103 was evaluated), 133 chronic lymphocytic leukemia (CLL), 3 follicular lymphoma (FL), and 21 mantle cell lymphoma (MCL). All HCLs expressed uniform CD103 and bright CD123. Among the 20 HCLv cases, 20 (100%) were CD103+ and 8 (40%) were CD123+ (partial or dim). CD103 was negative in all MCL, FL, CLL, and SMZL cases. CD123 was positive in 1 (25%) of 4 SMZL, 3.8% of CLL (5/133), 7 (33%) of 21 MCL, and 1 (33%) of 3 FL cases. CD103 is specific for HCL and HCLv. CD123 expression is more widespread in BC-LPDs but is useful in conjunction with CD25 to differentiate HCLv from HCL. These findings support the usefulness of CD123 and CD103 to aid in the differential diagnosis of BC-LPDs.
Structural analysis of α-satellite DNA and centromere proteins using extended chromatin and chromosomes (1994)

Human centromeres are characterized by distinct subsets of alpha-satellite DNA and by a number of centromeric proteins (CENPs) at least one of which, CENP-B, binds specifically to alpha-satellite DNA sequences. When the centromeres of metaphase chromosomes are mechanically stretched to five to 20 times their normal length, CENPs specifically recognized by CREST autoantibodies extend over the entire length of the linear alpha-satellite array. For higher resolution analysis we spread interphase chromatin across a slide resulting in highly extended chromatin fibers. By fluorescence in situ hybridization (FISH) with human alpha-satellite DNA and an oligomer specific for the CENP-B box sequence, the regular spacing of CENP-B binding motifs within arrays of alpha-satellite DNA was visualized directly. FISH with elongated chromatin structures released from interphase nuclei with the drug N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulfonamide shows that D7Z1 and D7Z2, two distinct alpha-satellite arrays on chromosome 7, are not interspersed with each other but are separated by as little as several hundred kilobases, consistent with previous long-range mapping data. The D7Z2 array, which does not bind detectable amounts of CENPs, can be assigned to the short arm side of the D7Z1 array using artificially stretched chromosomes. In interphase nuclei unreplicated segments give a singlet hybridization signal, whereas fully replicated loci appear as doublets. Although D7Z1 is replicated prior to D7Z2 in the majority of cells, the replication timing of one array relative to the other is variable. The replication of alpha-satellite arrays on homologous chromosomes is highly asynchronous. The newly replicated alpha-satellite lacks the CENP component.
648. Mitigating Tumor Escape: Tandem Anti-CD20- and CD19 SCFV-Based Chimeric Antigen Receptors (CARs) in Leukemia/Lymphoma (2016)

In recent years, adoptive cell therapy using T cells engineered with chimeric antigen receptors (CAR T) specific for CD19 has shown marked clinical efficacy. Nevertheless, cases of tumor escape due to tumor escape in B cell malignancies could be mitigated by CAR T the loss of CD19 antigen have been reported. We hypothesized that approaches that target the CD19 and CD20 tumor antigens simultaneously. Second generation CARs containing scFv specific for CD19 and CD20 were generated by lentiviral transduction of human primary T cells. The configurations were: a) single targeting domain, b) tandem targeting domains, or c) two full-length CAR receptors co-expressed bicistronically in the same T cell. CAR T expression for all constructs confirmed by Western blotting and protein L flow cytometry. CAR T cytolytic activity and IFN gamma secretion were evaluated by killing assays and ELISA, respectively. Single, tandem, and bicistronic CAR T cells exhibited CAR surface expression of 50-70%. All anti- CD19, anti-CD20 CAR T cells demonstrated target-specific cells lysis and induction of IFN-gamma. Interestingly, bicistronic CAR19, CAR20 construct yielded high CAR T surface expression and IFN-gamma production, but inferior in vitro cytolytic activity. To confirm CAR T specificity, K562 CD19+ and K562 CD20+ cell lines were generated. In flow-based 1h killing assays, CAR19 and CAR20 lysed their respective target lines only, whereas tandem CAR constructs lysed both K562 CD19+ and K562 CD20+ cells, but not K562 control. In a subsequent series of co-culture experiments, Raji target cells were combined with very low ratios of CAR T cells, to allow for the evolution of escape variants. On day 5 of co-incubation in the presence of CAR19 T cells, the surviving Raji cells numbers were comparable to control (85,000 cells/well vs 77, 000 cells/well in sham transduction). In comparison, viable Raji numbers decreased drastically post co-incubation with CAR20-, CAR19_20- and CAR20_19-T cells (546, 1,355 and 1,543 cells/well, respectively). Among the surviving Raji population, CD19 surface expression was reduced to 1.6%, vs 93.29% for sham control, whereas the expression of CD20 and CD22 remained high (97% and 78%, respectively). By contrast, the CD20 surface marker was less prone to down-regulation by CAR-T cells expressing anti-CD20 scFv. Similar results were seen when experiments were of longer, 7 days, or shorter, 1 day, duration. Thus, targeting two tumor antigens simultaneously using tandem CAR T cells is a promising new strategy for mitigation of tumor escape via antigen down-regulation. Moreover, expression of two scFv in a single CAR format is superior to expression of two independent CARs from a bicitsronic vector. It also appears that the order of the targeting domains within the tandem CAR impacts anti-tumor activity. These findings are currently being explored further in animal model systems.
Biologically active peptides of the vesicular stomatitis virus glycoprotein (1985)

A peptide corresponding to the amino-terminal 25 amino acids of the mature vesicular stomatitis virus glycoprotein has recently been shown to be a pH-dependent hemolysin. In the present study, we analyzed smaller constituent peptides and found that the hemolytic domain resides within the six amino-terminal amino acids. Synthesis of variant peptides indicates that the amino-terminal lysine can be replaced by another positively charged amino acid (arginine) but that substitution with glutamic acid results in the total loss of the hemolytic function. Peptide-induced hemolysis was dependent upon buffer conditions and was inhibited when isotonicity was maintained with mannitol, sucrose, or raffinose. In sucrose, all hemolytic peptides were also observed to mediate hemagglutination. The large 25-amino acid peptide is also a pH-dependent cytotoxin for mammalian cells and appears to effect gross changes in cell permeability. Conservation of the amino terminus of vesicular stomatitis virus and rabies virus suggests that the membrane-destabilizing properties of this domain may be important for glycoprotein function.
Towards magnetic liquid crystals (1999)

In this paper, we present the results of studies on the synthesis and properties of a series of liquid–crystalline lanthanide complexes of imine ligands. We describe the liquid–crystalline behaviour as a function of the metal, ligand and anion employed and we report on the nature of the coordination between different ligand types and the metal centre.
Luteinizing Hormone and Estradiol in Peripheral Blood of Mares during Estrous Cycle1 (1974)

Blood was obtained from mares and rectal palpation performed daily in six mares of mixed breeds. Blood samples were taken via venipuncture
Chemoprevention of rat prostate carcinogenesis by early and delayed administration of dehydroepiandrosterone. (1999)

Two in vivo bioassays were conducted to evaluate the efficacy of dehydroepiandrosterone (DHEA) as an inhibitor of prostate carcinogenesis in rats. Prostate adenocarcinomas were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate and testosterone propionate, followed by a single i.v. injection of N-methyl-N-nitrosourea (MNU) and chronic androgen stimulation. In the first experiment, DHEA (1000 or 2000 mg/kg diet) was administered continuously to rats beginning 1 week before MNU exposure. In the second experiment, continuous administration of DHEA (2000 mg/kg diet) was begun either 1 week before, 20 weeks after, or 40 weeks after MNU exposure. Controls received basal diet without added DHEA. Studies were terminated at 13 months after MNU administration, and prostate cancer incidence was determined by histopathological evaluation of step sections of accessory sex glands. In the first study, continuous dietary administration of DHEA beginning 1 week before MNU resulted in a dose-related inhibition of prostate cancer induction. In the second experiment, comparable reductions in prostate cancer incidence were observed in groups exposed to DHEA beginning 1 week before, 20 weeks after, and 40 weeks after carcinogen exposure. These data demonstrate that nontoxic doses of DHEA confer significant protection against prostate carcinogenesis in rats. The efficacy of delayed administration of DHEA suggests that the compound confers protection against later stages of prostate cancer induction and can suppress the progression of existing preneoplastic lesions to invasive disease.
Driven to Distraction: Self-Supervised Distractor Learning for Robust Monocular Visual Odometry in Urban Environments (2017)

We present a self-supervised approach to ignoring "distractors" in camera images for the purposes of robustly estimating vehicle motion in cluttered urban environments. We leverage offline multi-session mapping approaches to automatically generate a per-pixel ephemerality mask and depth map for each input image, which we use to train a deep convolutional network. At run-time we use the predicted ephemerality and depth as an input to a monocular visual odometry (VO) pipeline, using either sparse features or dense photometric matching. Our approach yields metric-scale VO using only a single camera and can recover the correct egomotion even when 90% of the image is obscured by dynamic, independently moving objects. We evaluate our robust VO methods on more than 400km of driving from the Oxford RobotCar Dataset and demonstrate reduced odometry drift and significantly improved egomotion estimation in the presence of large moving vehicles in urban traffic.
Inhibition of bladder overactivity by duloxetine in combination with foot stimulation or WAY-100635 treatment in cats (2013)

The purpose of this study was to determine whether duloxetine [a serotonin (5-HT)-norepinephrine reuptake inhibitor] combined with transcutaneous foot stimulation or WAY-100635 (a 5-HT1A antagonist) can enhance inhibition of bladder overactivity in cats. Cystometrograms were performed on eight cats under α-chloralose anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder overactivity. To inhibit bladder overactivity, foot stimulation (5 Hz) was applied via transcutaneous pad electrodes to the right hindfoot at two and four times the threshold intensity for inducing a toe twitch. Duloxetine (0.003-3 mg/kg) was administered intravenously to determine the effect of combination treatment. After the 3 mg/kg dose of duloxetine, WAY-100635 (0.5 mg/kg) was given intravenously. AA irritation significantly (P < 0.0001) reduced bladder capacity to 42.7 ± 7.4% of the saline control capacity. Foot stimulation alone at both two and four times the threshold intensity significantly (P < 0.0001) inhibited bladder overactivity and increased bladder capacity to 66.7 ± 6.3% and 85.7 ± 6.5% of the saline control, respectively. Duloxetine alone dose dependently inhibited bladder overactivity and completely restored bladder capacity to the saline control (109 ± 15.5%) at 3 mg/kg. Although duloxetine combined with foot stimulation did not further enhance inhibition, WAY-100635 (0.5 mg/kg) given after 3 mg/kg duloxetine further increased (P = 0.008) bladder capacity to 162.2 ± 22.5% of the saline control. Although duloxetine and foot stimulation independently inhibited bladder overactivity, combined treatment did not enhance inhibition. Duloxetine combined with WAY-100635, however, synergistically enhanced bladder inhibition, indicating a potential novel treatment for overactive bladder if duloxetine is combined with a 5-HT1A receptor antagonist drug.
Abstract 5323: Targeting PIM1 and CDK4/6 kinases in renal cell carcinoma (2015)

Abstract In this study we examine the hypothesis that combination therapy targeting the VEGFR, PIM1, and CDK4/6 kinases improves the efficacy of VEGFR-directed monotherapy in renal cell carcinoma (RCC). Two RCC cell lines, 786-O and Caki-1 (chosen for differences in VHL), were evaluated and the ED50s of SGI-1776 (PIM1 inhibitor), PD0332991 (CDK4/6 inhibitor), and LY2835219 (dual PIM1 and CDK4/6 inhibitor) assessed with an MTT assay. Cell Titer-Glo® was used to determine the effects of each of the inhibitors on cellular viability alone and in combination with sunitinib (VEFGR tyrosine kinase inhibitor). The effect of LY2835219 on phosphorylation of BAD, a PIM1 substrate, was assessed by Western blot. PIM1 and dual PIM1-CDK4/6 inhibition showed more potent effects on cellular viability than CDK4/6 inhibition. ED50 values of each inhibitor for RCC cells are reported in Table 1. Further assays showed greater decreased cellular viability in cells treated with the combination of a PIM1 inhibitor and sunitinib than in cells treated with either a PIM1 inhibitor or sunitinib alone. When combined with sunitinib, dual PIM1-CDK4/6 inhibition was more effective than PIM1 inhibition in 786-O cells. Sunitinib in combination with a CDK4/6 inhibitor was not as effective as in combination with either a PIM1 inhibitor or a dual PIM1-CDK4/6 inhibitor. Western blot analysis showed a decrease in phospho-BAD in cells treated with a dual PIM1-CDK4/6 inhibitor. Table 1.Potency of Kinase Inhibitors Against RCC Cell LinesInhibitorED50 (786-O; uM)ED50 (Caki-1; uM)SGI-17768.67 (8.13 - 9.25)6.94 (5.05 - 9.53)PD0332991Indeterminate*Indeterminate*LY28352197.46 (6.32 - 8.81)1.18 (1.02 - 1.36)95% confidence intervals are presented in parenthesis. *Highest dose level did not result in a sufficient response to allow for reliable curve fitting to determine the ED50 Our data reveal that targeting PIM1 in combination with sunitinib is superior to sunitinib alone in RCC cell lines. Additionally, in 786-O cells, added CDK4/6 inhibition further improves the efficacy of the combination therapy. Dual PIM1-CDK4/6 kinase targeted therapy in combination with sunitinib is an attractive therapeutic regimen with good potential for translation to the clinic. Ongoing studies include further characterization of the molecular events involved including apoptosis, cell cycle regulation, PIM1 kinase and CDK4/6 kinase activity, and evaluation of the combination therapy in a mouse xenograft model of RCC. Citation Format: Jeffery S. Small, Sheldon L. Holder. Targeting PIM1 and CDK4/6 kinases in renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5323. doi:10.1158/1538-7445.AM2015-5323
Comparison of incidence of insulin-dependent diabetes mellitus in children and young adults in the Province of Turin, Italy, 1984-91 (1997)

To document the incidence of IDDM in the Province of Turin (Italy) in the 8-year period 1984-91 in children (0-14 years) and young adults (15-29 years), in relation to age, sex, monthly-seasonal variability, calendar year and urban/rural area, (all newly diagnosed cases (502) were ascertained through primary and secondary data sources and completeness of ascertainment estimated with the two sample capture-recapture method (99% in childhood and 95% in young adults). The independent effect of age, sex, calendar year, and urban/rural area was estimated with a Poisson regression model. Age-specific incidence rates were 8.42/100,000 (95% CI 7.37-9.62) and 6.72/100,000 (95% CI 5.96-7.58), respectively, in the age groups 0-14 and 15-29 years. Sex differences were evident in young adults, with an almost 1.5-fold increased risk in men (8.37/100,000, 95% CI 7.21-9.71 vs 5.00/100,000, CI 4.09-6.10). Seasonal trend was evident in childhood. Predictors of incidence rates were age, place of residence and interaction between sex and age; no temporal trend was detected. No significant differences were found in the two age-groups with respect to glycaemia, glycosuria, ketonuria, and fasting C-peptide levels. In conclusion, this study shows sex differences in IDDM risk in young adults; 55% of incident cases occurring in young adults; an independent contribution of urban/rural differences to IDDM risk; no temporal trend in 1984-91; a seasonal pattern of incidence in children; no significant differences in clinical presentation between age groups.
Studies of the uricosuric action of the hypolipidemic drug halofenate (1973)

Six hyperuricemic patients, with a high incidence of hypertriglyceridemia, were placed on a purine‐free maintenance diet during a 2 week single‐blind study of the uricosuric activity of halofenate (MK‐185). In a single dose‐response study, halofenate, given in a dose of 1 gm orally, produced a uricosuric effect of 48 hours' duration and a peak response 6 to 8 hours after administration, with a significant fall in serum urate. In a 3 day trial of the drug, a progressive increase in urate excretion occurred with a further fall in serum urate. During the study, the mean triglyceride concentration fell by 26% and cholesterol by 15% of the pretreatment values.