University of Oklahoma

About: University of Oklahoma is a education organization based out in Norman, Oklahoma, United States. It is known for research contribution in the topics: Population & Radar. The organization has 25269 authors who have published 52609 publications receiving 1821706 citations. The organization is also known as: OU & Oklahoma University.

Ecto‐enzyme and signaling functions of lymphocyte CD 7 3

Abstract: CD73 or ecto-5'-nucleotidase (5'-NT) is a widely expressed ecto-enzyme which catalyzes the dephosphorylation of AMP and other nucleoside monophosphates. CD73 participates in purine salvage through this enzymatic activity, supplying cells with precursors for energy metabolism and nucleic acid biosynthesis. As an enzyme that produces adenosine, CD73 can also regulate adenosine receptor engagement in many tissues. However, CD73 also has functions independent of its enzyme activity. Like many glycosyl phosphatidylinositol (GPI)-anchored molecules, it transmits potent activation signals in T cells when ligated by antibodies. Less compelling evidence suggests that CD73 may function as a cell adhesion molecule. In the human immune system, CD73 is expressed on subsets of T and B cells, on germinal center follicular dendritic cells, and on thymic medullary reticular fibroblasts and epithelial cells. Many challenging areas remain to be explored before the role of CD73 in the immune system will be fully understood. These include an evaluation of the role of adenosine receptors in lymphoid development, the identification of physiological CD73 ligands, a functional assessment of the GPI anchor, and an analysis of the intricate cell-type-specific and developmental regulation of CD73 expression.

RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development

Abstract: Regulation of patterning and morphogenesis during embryonic development depends on tissue-specific signaling by retinoic acid (RA), the active form of Vitamin A (retinol). The first enzymatic step in RA synthesis, the oxidation of retinol to retinal, is thought to be carried out by the ubiquitous or overlapping activities of redundant alcohol dehydrogenases. The second oxidation step, the conversion of retinal to RA, is performed by retinaldehyde dehydrogenases. Thus, the specific spatiotemporal distribution of retinoid synthesis is believed to be controlled exclusively at the level of the second oxidation reaction. In an N-ethyl-N-nitrosourea (ENU)-induced forward genetic screen we discovered a new midgestation lethal mouse mutant, called trex, which displays craniofacial, limb, and organ abnormalities. The trex phenotype is caused by a mutation in the short-chain dehydrogenase/reductase, RDH10. Using protein modeling, enzymatic assays, and mutant embryos, we determined that RDH10trex mutant protein lacks the ability to oxidize retinol to retinal, resulting in insufficient RA signaling. Thus, we show that the first oxidative step of Vitamin A metabolism, which is catalyzed in large part by the retinol dehydrogenase RDH10, is critical for the spatiotemporal synthesis of RA. Furthermore, these results identify a new nodal point in RA metabolism during embryogenesis.

Signaling in Venture Capitalist—New Venture Team Funding Decisions: Does It Indicate Long-Term Venture Outcomes?

Abstract: According to signaling theory, new venture teams (NVTs) can communicate to venture capitalists and other potential investors both a “value” signal and a “commitment” signal, based on the level of personal investment in a venture. Venture capitalists (VCs) typically want to know if a NVT is really committed to a venture and if its members truly believe that a venture has wealth creating potential. Team members can convey signals via their investment behavior. We test our hypotheses based on a sample of 183 VC-backed ventures that we tracked over a ten-year time period. These data indicate that the signals sent to VCs in the early stages of the funding process do not appear to have any significant relationship with long-term venture outcomes. We explore possible explanations for these findings, as well as their implications for signaling theory and future research.

Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial

Abstract: Summary Background Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10%, and median overall survival after third-line therapy of 5–9 months. In this study (QUADRA), we investigated the activity of niraparib monotherapy as the fourth or later line of therapy. Methods QUADRA was a multicentre, open-label, single-arm, phase 2 study that evaluated the safety and activity of niraparib in adult patients (≥18 years) with relapsed, high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube, or primary peritoneal cancer who had been treated with three or more previous chemotherapy regimens. The study was done in the USA and Canada, and 56 sites screened patients (50 sites treated at least one patient). Patients received oral niraparib 300 mg once daily continuously, beginning on day 1 and every cycle (28 days) thereafter until disease progression. The primary objective was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with homologous recombination deficiency (HRD)-positive tumours (including patients with BRCA and without BRCA mutations) sensitive to their last platinum-based therapy who had received three or four previous anticancer therapy regimens (primary efficacy population). Efficacy analyses were additionally done in all dosed patients with measurable disease at baseline. Findings Between April 1, 2015 and Nov 1, 2017, we screened 729 patients for eligibility and enrolled 463 patients, who were initiated on niraparib therapy. At the time of database lock (April 11, 2018), enrolment had closed and the study was ongoing, with 21 patients still on treatment. Patients had received a median of four (IQR 3–5) previous lines of therapy, and the median follow-up for overall survival was 12·2 months (IQR 3·7–22·1). 151 (33%) of 463 patients were resistant and 161 (35%) of 463 patients were refractory to the last administered platinum therapy. 13 (28%) of 47 patients in the primary efficacy population achieved an overall response according to RECIST (95% CI 15·6–42·6; one-sided p=0·00053). The most common drug-related grade 3 or worse treatment-emergent adverse events were anaemia (113 [24%] of 463 patients) and thrombocytopenia (95 [21%] of 463 patients). The most common treatment-emergent serious adverse events were small intestinal obstruction (34 [7%] of 463 patients), thrombocytopenia (34 [7%] of 463 patients), and vomiting (27 [6%] of 463 patients). One death due to gastric haemorrhage was considered treatment related. Interpretation We observed clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive platinum-sensitive disease, which includes not only patients with a BRCA mutation but also a population with BRCA wild-type disease. We identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. Funding Tesaro.

Relations of Different Types of Numerical Magnitude Representations to Each Other and to Mathematics Achievement.

Abstract: We examined relations between symbolic and non-symbolic numerical magnitude representations, between whole number and fraction representations, and between these representations and overall mathematics achievement in fifth graders. Fraction and whole number symbolic and non-symbolic numerical magnitude understandings were measured using both magnitude comparison and number line estimation tasks. After controlling for non-mathematical cognitive proficiency, both symbolic and nonsymbolic numerical magnitude understandings were uniquely related to mathematics achievement, but the relation was much stronger for symbolic numbers. A meta-analysis of 19 published studies indicated that relations between non-symbolic numerical magnitude knowledge and mathematics achievement are present but tend to be weak, especially beyond 6 years of age.