University at Buffalo

About: University at Buffalo is a education organization based out in Buffalo, New York, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 33773 authors who have published 63840 publications receiving 2278954 citations. The organization is also known as: UB & State University of New York at Buffalo.

Heterogeneity of eukaryotic replicons, replicon clusters, and replication foci.

Abstract: According to the current paradigm, replication foci are discrete sites in the interphase nucleus where assemblies of DNA replication enzymes simultaneously elongate the replication forks of 10–100 adjacent replicons (each ∼100 kbp). Here we review new results and provide alternative interpretations for old results to show that the current paradigm is in need of further development. In particular, many replicons are larger than previously thought – so large that their complete replication takes much longer (several hours) than the measured average time to complete replication at individual foci (45–60 min). In addition to this large heterogeneity in replicon size, it is now apparent that there is also a corresponding heterogeneity in the size and intensity of individual replication foci. An important property of all replication foci is that they are stable structures that persist, with constant dimensions, during all cell cycle stages including mitosis, and therefore likely represent a fundamental unit of chromatin organization. With this in mind, we present a modified model of replication foci in which many of the foci are composed of clusters of small replicons as previously proposed, but the size and number of replicons per focus is extremely heterogeneous, and a significant proportion of foci are composed of single large replicons. We further speculate that very large replicons may extend over two or more individual foci and that this organization may be important in regulating the replication of such large replicons as the cell proceeds through S-phase.

Once-a-Day Concerta Methylphenidate Versus Three-Times-Daily Methylphenidate in Laboratory and Natural Settings

Abstract: Objective. Methylphenidate (MPH), the most commonly prescribed drug for attention-deficit/hyperactivity disorder (ADHD), has a short half-life, which necessitates multiple daily doses. The need for multiple doses produces problems with medication administration during school and after-school hours, and therefore with compliance. Previous long-acting stimulants and preparations have shown effects equivalent to twice-daily dosing of MPH. This study tests the efficacy and duration of action, in natural and laboratory settings, of an extended-release MPH preparation designed to last 12 hours and therefore be equivalent to 3-times-daily dosing. Methods. Sixty-eight children with ADHD, 6 to 12 years old, participated in a within-subject, double-blind comparison of placebo, immediate-release (IR) MPH 3 times a day (tid), and Concerta, a once-daily MPH formulation. Three dosing levels of medication were used: 5 mg IR MPH tid/18 mg Concerta once a day (qd); 10 mg IR MPH tid/36 mg Concerta qd; and 15 mg IR MPH tid/54 mg Concerta qd. All children were currently medicated with MPH at enrollment, and each child9s dose level was based on that child9s MPH dosing before the study. The doses of Concerta were selected to be comparable to the daily doses of MPH that each child received. To achieve the ascending rate of MPH delivery determined by initial investigations to provide the necessary continuous coverage, Concerta doses were 20% higher on a daily basis than a comparable tid regimen of IR MPH. Children received each medication condition for 7 days. The investigation was conducted in the context of a background clinical behavioral intervention in both the natural environment and the laboratory setting. Parents received behavioral parent training and teachers were taught to establish a school-home daily report card (DRC). A DRC is a list of individual target behaviors that represent a child9s most salient areas of impairment. Teachers set daily goals for each child9s impairment targets, and parents provided rewards at home for goal attainment. Each weekday, teachers completed the DRC, and it was used as a dependent measure of individualized medication response. Teachers and parents also completed weekly standardized ratings of behavior and treatment effectiveness. To evaluate the time course of medication effects, children spent 12 hours in a laboratory setting on Saturdays and medication effects were measured using procedures and methods adapted from our summer treatment program. Measures of classroom behavior and academic productivity/accuracy were taken in a laboratory classroom setting during which children completed independent math and reading worksheets. Measures of social behavior were taken in structured, small-group board game settings and unstructured recess settings. Measures included behavior frequency counts, academic problems completed and accuracy, independent observations, teacher and counselor ratings, and individualized behavioral target goals. Reports of adverse events, sleep quality, and appetite were collected. Results. On virtually all measures in all settings, both drug conditions were significantly different from placebo, and the 2 drugs were not different from each other. In children9s regular school settings, both medications improved behavior as measured by teacher ratings and individualized target behaviors (the DRC); these effects were seen into the evening as measured by parent ratings. In the laboratory setting, effects of Concerta were equivalent to tid MPH and lasted at least through 12 hours after dosing. Concerta was significantly superior to tid MPH on 2 parent rating scores, and when asked, more parents preferred Concerta than preferred tid IR MPH or placebo. Side effects on children9s sleep and appetite were similar for the 2 preparations. In the lab setting, both medications improved productivity and accuracy on arithmetic seatwork assignments, disruptive and on-task behavior, and classroom rule following. Both medications improved children9s rule following and negative behavior in small group board games, as well as in unstructured recess settings. Individual target behaviors also showed significant improvement with medication across domains in the laboratory setting. Children9s behavior across settings deteriorated across the laboratory day, and the primary effect of medication was to prevent this deterioration as the day wore on. Results support the use of background behavioral treatment in clinical trials of stimulant medication, and illustrate the utility of a measure of individualized daily target goals (ie, the DRC) as an objective measure of medication response in both the laboratory and natural school settings. Conclusion. This investigation clearly supports the efficacy of the Concerta long-acting formulation of MPH for parents who desire to have medication benefits for their child throughout the day and early evening. Effects of a single morning dose lasted throughout the school day and into the evening hours, and were present for both social behavior with peers and academic performance in the classroom. Effects on multiple measures, by multiple informants, and in multiple settings, were similar to those of a standard preparation of MPH given 3 times a day. These effects lasted throughout a 12-hour period, providing coverage of school, afternoon, and evening behavior with a single morning dose. Measures of evening behavior in the laboratory setting included arithmetic productivity (analogous to homework), and recess settings (analogous to home and neighborhood recreational activities). Some parents prefer behavioral interventions to medication for use at home, and some children with ADHD neither need nor tolerate medication in the evening. For those who do need a full 12 hours of medication coverage, based on the results of this study, Concerta would seem to be the choice. This study provides a model for clinical trials of new psychoactive drugs for children: assessments by multiple raters, in both natural and ecologically valid laboratory settings, across a range of domains of impairment and settings, examining a large number of objective, reliable measures of behavior, and in a context of ongoing behavioral treatment. attention-deficit/hyperactivity disorder, pharmacological treatment, methylphenidate, long-acting preparations.

Asymmetric Cyclopropanations by Rhodium(II) N-(Arylsulfonyl)prolinate Catalyzed Decomposition of Vinyldiazomethanes in the Presence of Alkenes. Practical Enantioselective Synthesis of the Four Stereoisomers of 2-Phenylcyclopropan-1-amino Acid

Abstract: The rhodium N-(arylsulfonyl)prolinate catalyzed decomposition of vinyldiazomethanes in the presence of alkenes leads to a very general method for the synthesis of functionalized cyclopropanes in a highly diastereoselective and enantioselective mode. A detailed study was undertaken to determine the key factors that control the enantioselectivity of this process. The highest levels of enantioselectivity were obtained using cyclic N-(arylsulfonyl)amino acids as ligands for the dirhodium catalyst, and the optimized catalyst was tetrakis[N-[(4-dodecylphenyl)sulfonyl]-(L)-prolinato]dirhodium. The carbenoid structure has a critical effect on the degree of asymmetric induction, and the combination of a small electron-withdrawing group such as a methyl ester and an electron-donating group such as vinyl or phenyl resulted in the highest levels of enantioselectivity. The use of electron neutral alkenes and pentane as solvent also enhanced the enantioselectivity of the process. The synthetic utility of this chemistry...

Minimal-change integrity maintenance using tuple deletions

Abstract: We address the problem of minimal-change integrity maintenance in the context of integrity constraints in relational databases. We assume that integrity-restoration actions are limited to tuple deletions. We focus on two basic computational issues: repair checking (is a database instance a repair of a given database?) and consistent query answers [in: ACM Symposium on Principles of Database Systems (PODS), 1999, 68] (is a tuple an answer to a given query in every repair of a given database?). We study the computational complexity of both problems, delineating the boundary between the tractable and the intractable cases. We consider denial constraints, general functional and inclusion dependencies, as well as key and foreign key constraints. Our results shed light on the computational feasibility of minimal-change integrity maintenance. The tractable cases should lead to practical implementations. The intractability results highlight the inherent limitations of any integrity enforcement mechanism, e.g., triggers or referential constraint actions, as a way of performing minimal-change integrity maintenance.

Evidence for a potent antiinflammatory effect of rosiglitazone.

Abstract: We have recently demonstrated a potent antiinflammatory effect of troglitazone, an agonist of peroxisome proliferator-activated receptor γ (PPARγ) and a partial agonist of PPARα in both the nondiabetic obese and diabetic obese subjects. We have now investigated the antiinflammatory actions of rosiglitazone, a selective PPARγ agonist. Eleven nondiabetic obese subjects and 11 obese diabetic subjects were each given 4 mg of rosiglitazone daily for a period of 6 wk. Fasting blood samples were obtained at 0, 1, 2, 4, 6, and 12 wk (6 wk after the cessation of rosiglitazone). Eight obese subjects and five obese diabetic subjects were also included in the study as control groups. Fasting blood samples were obtained from the control groups at 0, 1, 2, 4, and 6 wk only. Nuclear factor κB (NFκB)-binding activity in mononuclear cells, plasma monocyte chemoattractant protein-1 (MCP-1), TNF-α, soluble intercellular adhesion molecule-1, C-reactive protein (CRP), and serum amyloid A (SAA) were measured. Blood glucose con...