bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian Morphology Is a Marker of Heritable Biochemical Traits in Sisters with Polycystic Ovaries
Authors: Franks Stephen , Webber Lisa J. , Goh Micaela , Valentine Anne , White Davinia M. , Conway Gerard S. , Wiltshire Steven , McCarthy Mark I.
Published: June 2008

Context: Polycystic ovary syndrome (PCOS) is a common endocrinopathy of uncertain etiology but with strong evidence for a genetic contribution.

Objective: The objective of the study was to test the hypothesis that the typical polycystic ovarian morphology is a marker of inherited biochemical features in families of women with PCOS.

Design: A study of probands with PCOS and their sisters.

Patients: Patients included 125 probands and 214 sisters. All probands had PCOS, defined by symptoms of anovulation and/or hyperandrogenism with polycystic ovaries on ultrasound. Affected sisters were defined by polycystic ovaries, regardless of symptoms, and unaffected sisters defined by normal ovarian morphology.

Setting: This was a clinic-based study.

Main Outcome Measures: Clinical, endocrine, and metabolic features in the various groups were compared, and estimates of broad-sense heritability were obtained using the quantitative transmission disequilibrium test.

Results: Although affected sisters had fewer symptoms than probands (30% had no symptoms of PCOS), serum testosterone, androstenedione, LH, and fasting insulin and insulin sensitivity were similar in the two groups with polycystic ovaries but significantly different from those in unaffected sisters or controls. We observed moderate to high heritabilities for all traits studied in affected sister pairs, whereas heritabilities calculated from discordant siblings were substantially lower.

Conclusions: These data provide further evidence for a genetic basis of PCOS. The high heritability of biochemical features in probands and affected sisters, despite wide variation in symptoms, shows that not only are these biochemical traits strongly influenced by genetic factors but also, importantly, that polycystic ovarian morphology is an index of inherited traits in families with PCOS.
The Type 5 Phosphodiesterase Inhibitor Tadalafil Influences Salivary Cortisol, Testosterone, and Dehydroepiandrosterone Sulphate Responses to Maximal Exercise in Healthy Men
Authors: Di Luigi Luigi , Baldari Carlo , Sgrò Paolo , Emerenziani Gian Pietro , Gallotta Maria Chiara , Bianchini Serena , Romanelli Francesco , Pigozzi Fabio , Lenzi Andrea , Guidetti Laura
Published: June 2008

Context: Physical exercise-related stress activates hypothalamus-pituitary-adrenal (HPA) axis; nitric oxide is one of the mediators of the HPA axis response to stress, and phosphodiesterase type 5 inhibitors influences nitric oxide-linked biological activities.

Objective: The objective of the study was to investigate whether a single oral long half-life phosphodiesterase type 5 inhibitor (tadalafil) administration influences the HPA axis response to exercise-related stress.

Design: This was a double-blind, cross-over trial.

Participants: Participants included nine healthy male athletes.

Interventions: All subjects performed a maximal exercise test in normoxia, after which they received a single oral administration of tadalafil or placebo. Then after a 2-wk washout period, they were crossed over and repeated the exercise test. Each subject was his own control. Salivary collections, for steroid evaluations [cortisol, dehydroepiandrosterone sulphate (DHEAS), testosterone] and respective ratio calculation (DHEAS to cortisol, testosterone to cortisol, testosterone to DHEAS), were performed before each exercise (Pre-Ex), immediately after (Post-Ex), and at 30 min during recovery.

Results: As expected, mean salivary cortisol concentration increased immediately after exercise after both tadalafil and placebo (P = 0.014 and P =0.036 vs. Pre-Ex, respectively); however, the cortisol increase was significantly higher after tadalafil administration (P = 0.034 vs. placebo). Furthermore, an increased salivary testosterone after exercise was observed only after tadalafil administration (P = 0.029 vs. Pre-Ex). No effects of either exercise and/or tadalafil administration on salivary DHEAS concentrations were observed. DHEAS to cortisol and testosterone to cortisol ratios significantly decreased after exercise after tadalafil administration (P = 0.037, and P = 0.02 vs. placebo, respectively).

Conclusion: Tadalafil administration amplified the salivary cortisol and testosterone responses to a maximal exercise-related stress in healthy trained humans.
(ING): A VERNACULAR BASELINE FOR ENGLISH IN APPALACHIA
Authors: Hazen Kirk
Published: June 2008

In order to provide a contemporary description of Appalachian English, this article investigates the (ING) variable in Appalachian speech, explaining both the linguistic and social constraints on variation. Data from 67 West Virginia speakers are qualitatively and quantitatively analyzed for grammatical context, preceding and following place of articulation, sociogeographic orientation, age, sex, ethnicity, social class, and interview context. Results indicate that the only linguistic conditioning factor for this speech community is the syntactic category. Socially, the patterns of variation are considerably more complex than the grammatical patterns. Reflecting the sociogeographic boundary found by previous scholars, a Southern-Northern divide exists in the production of variants: the Southern speakers have a higher rate of the alveolar variant than the Northern speakers. The other social factors work within this sociogeographic divide. Yet, contrary to most references to Appalachian rates of (ING), speakers in this sample are far from categorical, with rates ranging from 1% to 96% for the alveolar variant.
MIDDLE-CLASS AFRICAN AMERICANS: REACTIONS AND ATTITUDES TOWARD AFRICAN AMERICAN ENGLISH
Authors: Rahman Jacquelyn
Published: June 2008

This article examines the attitudes of a group of middle-class African Americans toward varieties that are available to them for helping to project the attitudes, stances, and affiliations that they perceive as effective in negotiating social and professional environments where vastly distinct linguistic norms may prevail. The research uses subjective reaction tests, interviews, and an online survey to ask questions about the significance of “sounding black” in judgments the participants make about standardness, social class, and appropriateness of speech styles for various environments. The research also examines linguistic features that contribute to the social judgments. Results show a correlation between the perception of African American identity and judgments that occur in other areas; the consultants value AAVE as their heritage language, but see standard African American English as the one variety that can meet the demands of all environments.
The role of adherens junctions and VE-cadherin in the control of vascular permeability
Authors: Dejana Elisabetta , Orsenigo Fabrizio , Lampugnani Maria Grazia
Published: June 2008

Endothelial cells control the passage of plasma constituents and circulating cells from blood to the underlying tissues. This specialized function is lost or impaired in several pathological conditions – including inflammation, sepsis, ischemia and diabetes – which leads to severe, and sometimes fatal, organ dysfunction. Endothelial permeability is regulated in part by the dynamic opening and closure of cell-cell adherens junctions (AJs). In endothelial cells, AJs are largely composed of vascular endothelial cadherin (VE-cadherin), an endothelium-specific member of the cadherin family of adhesion proteins that binds, via its cytoplasmic domain, to several protein partners, including p120, β-catenin and plakoglobin. Endogenous pathways that increase vascular permeability affect the function and organization of VE-cadherin and other proteins at AJs in diverse ways. For instance, several factors, including vascular endothelial growth factor (VEGF), induce the tyrosine phosphorylation of VE-cadherin, which accompanies an increase in vascular permeability and leukocyte diapedesis; in addition, the internalization and cleavage of VE-cadherin can cause AJs to be dismantled. From the knowledge of how AJ organization can be modulated, it is possible to formulate several pharmacological strategies to control the barrier function of the endothelium. We discuss the possible use of inhibitors of SRC and other kinases, of agents that increase cAMP levels, and of inhibitors of lytic enzymes as pharmacological tools for decreasing endothelial permeability.
A novel small-molecule inhibitor reveals a possible role of kinesin-5 in anastral spindle-pole assembly
Authors: Groen Aaron C. , Needleman Daniel , Brangwynne Clifford , Gradinaru Christain , Fowler Brandon , Mazitschek Ralph , Mitchison Timothy J.
Published: June 2008

The tetrameric plus-end-directed motor, kinesin-5, is essential for bipolar spindle assembly. Small-molecule inhibitors of kinesin-5 have been important tools for investigating its function, and some are currently under evaluation as anti-cancer drugs. Most inhibitors reported to date are `non-competitive' and bind to a specific site on the motor head, trapping the motor in an ADP-bound state in which it has a weak but non-zero affinity for microtubules. Here, we used a novel ATP-competitive inhibitor, FCPT, developed at Merck (USA). We found that it induced tight binding of kinesin-5 onto microtubules in vitro. Using Xenopus egg-extract spindles, we found that FCPT not only blocked poleward microtubule sliding but also selectively induced loss of microtubules at the poles of bipolar spindles (and not asters or monoasters). We also found that the spindle-pole proteins TPX2 and γ-tubulin became redistributed to the spindle equator, suggesting that proper kinesin-5 function is required for pole assembly.
Initiation and execution of lipotoxic ER stress in pancreatic β-cells
Authors: Cunha Daniel A. , Hekerman Paul , Ladrière Laurence , Bazarra-Castro Angie , Ortis Fernanda , Wakeham Marion C. , Moore Fabrice , Rasschaert Joanne , Cardozo Alessandra K. , Bellomo Elisa , Overbergh Lutgart , Mathieu Chantal , Lupi Roberto , Hai Tsonwin , Herchuelz Andre , Marchetti Piero , Rutter Guy A. , Eizirik Décio L. , Cnop Miriam
Published: June 2008

Free fatty acids (FFA) cause apoptosis of pancreatic β-cells and might contribute to β-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. We studied here the molecular mechanisms implicated in FFA-induced ER stress initiation and apoptosis in INS-1E cells, FACS-purified primary β-cells and human islets exposed to oleate and/or palmitate. Treatment with saturated and/or unsaturated FFA led to differential ER stress signaling. Palmitate induced more apoptosis and markedly activated the IRE1, PERK and ATF6 pathways, owing to a sustained depletion of ER Ca2+ stores, whereas the unsaturated FFA oleate led to milder PERK and IRE1 activation and comparable ATF6 signaling. Non-metabolizable methyl-FFA analogs induced neither ER stress nor β-cell apoptosis. The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary β-cells is primarily lipotoxic, and not glucolipotoxic. Palmitate, but not oleate, activated JNK. JNK inhibitors reduced palmitate-mediated AP-1 activation and apoptosis. Blocking the transcription factor CHOP delayed palmitate-induced β-cell apoptosis. In conclusion, saturated FFA induce ER stress via ER Ca2+ depletion. The IRE1 and resulting JNK activation contribute to β-cell apoptosis. PERK activation by palmitate also contributes to β-cell apoptosis via CHOP.
TRPC6 channels promote dendritic growth via the CaMKIV-CREB pathway
Authors: Tai Yilin , Feng Shengjie , Ge Ruiliang , Du Wanlu , Zhang Xiaoxing , He Zhuohao , Wang Yizheng
Published: June 2008

The canonical transient receptor potential channels (TRPCs) are Ca2+-permeable nonselective cation channels with various physiological functions. Here, we report that TRPC6, a member of the TRPC family, promotes hippocampal neuron dendritic growth. The peak expression of TRPC6 in rat hippocampus was between postnatal day 7 and 14, a period known to be important for maximal dendritic growth. Overexpression of TRPC6 increased phosphorylation of Ca2+/calmodulin-dependent kinase IV (CaMKIV) and cAMP-response-element binding protein (CREB) and promoted dendritic growth in hippocampal cultures. Downregulation of TRPC6 by short hairpin RNA interference against TRPC6 suppressed phosphorylation of both CaMKIV and CREB and impaired dendritic growth. Expressing a dominant-negative form of CaMKIV or CREB blocked the TRPC6-induced dendritic growth. Furthermore, inhibition of Ca2+ influx suppressed the TRPC6 effect on dendritic growth. Finally, in TRPC6 transgenic mice, the phosphorylation of CaMKIV and CREB was enhanced and the dendritic growth was also increased. In conclusion, TRPC6 promoted dendritic growth via the CaMKIV-CREB pathway. Our results thus revealed a novel role of TRPC6 during the development of the central nervous system (CNS).
Dual role for microtubules in regulating cortical contractility during cytokinesis
Authors: Murthy Kausalya , Wadsworth Patricia
Published: June 2008

Microtubules stimulate contractile-ring formation in the equatorial cortex and simultaneously suppress contractility in the polar cortex; how they accomplish these differing activities is incompletely understood. We measured the behavior of GFP-actin in mammalian cells treated with nocodazole under conditions that either completely eliminate microtubules or selectively disassemble astral microtubules. Selective disassembly of astral microtubules resulted in functional contractile rings that were wider than controls and had altered dynamic activity, as measured by FRAP. Complete microtubule disassembly or selective loss of astral microtubules resulted in wave-like contractile behavior of actin in the non-equatorial cortex, and mislocalization of myosin II and Rho. FRAP experiments showed that both contractility and actin polymerization contributed to the wave-like behavior of actin. Wave-like contractile behavior in anaphase cells was Rho-dependent. We conclude that dynamic astral microtubules function to suppress Rho activation in the nonequatorial cortex, limiting the contractile activity of the polar cortex.
Tyrosine phosphorylation of annexin A2 regulates Rho-mediated actin rearrangement and cell adhesion
Authors: Rescher Ursula , Ludwig Carsten , Konietzko Vera , Kharitonenkov Alexei , Gerke Volker
Published: June 2008

Cell adhesion and motility require a dynamic remodelling of the membrane-associated actin cytoskeleton in response to extracellular stimuli that are primarily transmitted through receptor tyrosine kinases. In a cellular model system for tyrosine phosphorylation-based growth factor signaling, we observed that annexin A2 is tyrosine-phosphorylated upon insulin receptor activation. The phosphorylation precedes peripheral actin accumulations and subsequent cell detachment. These morphological changes are inhibited by annexin A2 depletion and require Rho/ROCK signaling downstream of tyrosine-phosphorylated annexin A2. A phospho-mimicking annexin A2 mutant is sufficient to drive peripheral actin accumulation and the resulting cell detachment in the absence of insulin stimulation. Thus, a tyrosine phosphorylation switch in annexin A2 is an important event in triggering Rho/ROCK-dependent and actin-mediated changes in cell morphology associated with the control of cell adhesion.
Chromosome cohesion – rings, knots, orcs and fellowship
Authors: Díaz-Martínez Laura A. , Giménez-Abián Juan F. , Clarke Duncan J.
Published: June 2008

Sister-chromatid cohesion is essential for accurate chromosome segregation. A key discovery towards our understanding of sister-chromatid cohesion was made 10 years ago with the identification of cohesins. Since then, cohesins have been shown to be involved in cohesion in numerous organisms, from yeast to mammals. Studies of the composition, regulation and structure of the cohesin complex led to a model in which cohesin loading during S-phase establishes cohesion, and cohesin cleavage at the onset of anaphase allows sister-chromatid separation. However, recent studies have revealed activities that provide cohesion in the absence of cohesin. Here we review these advances and propose an integrative model in which chromatid cohesion is a result of the combined activities of multiple cohesion mechanisms.
Exceptional mechanical and structural stability of HSV-1 unveiled with fluid atomic force microscopy
Authors: Liashkovich Ivan , Hafezi Wali , Kühn Joachim E. , Oberleithner Hans , Kramer Armin , Shahin Victor
Published: June 2008

Evidence is emerging that changes in the structural and mechanical properties of viral particles are closely linked and that such changes are essential to infectivity. Here, applying the nanostructural and nanomechanical approach of atomic force microscopy, we visualised capsids of the ubiquitous human pathogen herpes simplex virus type 1 (HSV-1) at nano-scale resolution in physiologically relevant conditions. Simultaneously performed nano-indentation measurements on genome-containing and genome-free capsids revealed that genome-containing HSV-1 capsids withstand an exceptionally large mechanical force of ∼6 nN, which is three times larger than the highest values previously reported for other viruses. Greater mechanical forces, however, led to a release of the viral genome. The resulting genome-free capsids, which largely retained their overall structure, were found to be utterly elastic. HSV-1 capsids thus exhibit an exceptional structural and mechanical stability, which is largely provided by the densely packaged genome. This stability might be the key determinant for capsid survival over long distances in the axonal cytoplasm where it is exposed to mechanical forces by molecular motors before it reaches the nuclear pore for crucial genome uncoating.
A Two-Sided, Empirical Model of Television Advertising and Viewing Markets
Authors: Wilbur Kenneth C.
Published: June 2008

For marketers, television remains the most important advertising medium. This paper proposes a two-sided model of the television industry. We estimate viewer demand for programs on one side and advertiser demand for audiences on the other. The primary objective is to understand how each group's program usage influences the other group.

Four main conclusions emerge. First, viewers tend to be averse to advertising. When a highly rated network decreases its advertising time by 10%, our model predicts a median audience gain of about 25% (assuming no competitive reactions). Second, we find the price elasticity of advertising demand is −2.9, substantially more price elastic than 30 years ago.

Third, we compare our estimates of advertiser and viewer preferences for program characteristics to networks' observed program choices. Our results suggest that advertiser preferences influence network choices more strongly than viewer preferences. Viewers' two most preferred program genres, Action and News, account for just 16% of network program hours. Advertisers' two most preferred genres, Reality and Comedy, account for 47% of network program hours.

Fourth, we perform a counterfactual experiment in which some viewers gain access to a hypothetical advertisement avoidance technology. The results suggest that ad avoidance tends to increase equilibrium advertising quantities and decrease network revenues.
Informing, Transforming, and Persuading: Disentangling the Multiple Effects of Advertising on Brand Choice Decisions
Authors: Mehta Nitin , Chen Xinlei (Jack) , Narasimhan Om
Published: June 2008

Prior behavioral research has suggested that advertising can influence a consumer's quality evaluation through informative and transformative effects. The informative effect acts directly to inform a consumer of product attributes and hence shapes her evaluations of brand quality. The transformative effect affects the consumer's evaluation of brand quality by enhancing her assessment of her subsequent consumption experience. In addition, advertising may influence a consumer's utility directly, even without providing any explicit information—this is the persuasive effect.

In this paper, we propose a framework that formally models the processes through which all three effects of advertisements impact consumers' brand evaluations and their subsequent brand choice decisions. In particular, we model source credibility, confirmatory bias, and bounded rationality on the part of consumers, by appropriately modifying the standard Bayesian learning approach. Our model conforms closely to prior behavioral literature and the experimental findings therein. In our empirical analysis, we get significant estimates of both informative and transformative effects across brands. We find interesting temporal patterns across the effects; for instance, the importance of transformative effects seem to grow over time, while that of informative effects diminishes. Finally, we conduct policy experiments to examine the impact of increased ad intensity on advertising effects, as well as the role played by consumption ambiguity.
Research Note—Vertical Information Sharing in a Volatile Market
Authors: He Chuan , Marklund Johan , Vossen Thomas
Published: June 2008

When demand is uncertain, manufacturers and retailers often have private information on future demand, and such information asymmetry impacts strategic interaction in distribution channels. In this paper, we investigate a channel consisting of a manufacturer and a downstream retailer facing a product market characterized by short product life, uncertain demand, and price rigidity. Assuming the firms have asymmetric information about the demand volatility, we examine the potential benefits of sharing information and contracts that facilitate such cooperation. We conclude that under a wholesale price regime, information sharing might not improve channel profits when the retailer underestimates the demand volatility but the manufacturer does not. Although information sharing is always beneficial under a two-part tariff regime, it is in general not sufficient to achieve sharing, and additional contractual arrangements are necessary. The contract types we consider to facilitate sharing are profit sharing and buyback contracts.
Publish and Prosper: The Financial Impact of Publishing by Marketing Faculty
Authors: Mittal Vikas , Feick Lawrence , Murshed Feisal
Published: June 2008

This paper investigates the impact of research productivity on the salaries of marketing faculty members. We examine how the number of articles published in various types of publications affects faculty members' nine-month salary using a sample of three years of information on 298 marketing professors from 33 research-oriented, public universities. Consistent with research conducted in other disciplines, we find a positive impact of publishing on salary. We estimate the individual salary impact for each of the four top-tier journals in marketing, finding that the biggest impact on salary comes from publishing in Marketing Science. Further, we find that publishing in Tier 1 journals in marketing has a bigger salary impact than in Tier 1 journals outside marketing. Finally, we find that faculty and department characteristics also affect salary. For example, being from a higher ranked research university and being a full professor are each associated with higher salary.
Cross-Brand Pass-Through in Supermarket Pricing
Authors: Dubé Jean-Pierre , Gupta Sachin
Published: June 2008

We investigate the sensitivity of cross-brand pass-through estimates to two types of pooling: across stores, and across regular price and promotional price weeks. Using the category data from Besanko, Dubé, and Gupta (2005), hereafter BDG, we find consistent support across all 11 categories for the predictive power of the wholesale prices of substitute products for retail shelf prices. A Bayesian procedure is used to address the small sample issues that arise in the absence of pooling. Even though the unpooled results render our inferences for specific cross-brand pass-through magnitudes reported in BDG as imprecise, consistent with McAlister (2007), we do find significant empirical support for cross-brand pass-through.

We next assess the sensitivity of cross-brand pass-through estimates to pooling. This requires us to construct a much longer time series of 224 weeks for the refrigerated orange juice category, in contrast with the 52-week samples used in BDG and McAlister (2007). We find strong empirical support for the predictive power of wholesale prices of substitute products for retail shelf prices. In addition, we find evidence of nonzero own- and cross-brand pass-through elasticities for which our inferences are much more precise. These findings are robust to the separation of regular and promotional price weeks. However, the magnitudes of own-brand and cross-brand pass-through are quite different during promotional and regular price weeks. Our results clearly show that with longer data series and more robust models that can handle small sample sizes, there is evidence of cross-brand pass-through, substantiating the findings in BDG. Finally, we comment on why our results are entirely consistent with both the theoretical and empirical literatures on category pricing and retailer behavior.
Total Dual Integrality of Rothblum's Description of the Stable-Marriage Polyhedron
Authors: Király Tamás , Pap Júlia
Published: June 2008

Rothblum showed that the convex hull of the stable matchings of a bipartite preference system can be described by an elegant system of linear inequalities. In this paper we prove that the description given by Rothblum is totally dual integral. We give a constructive proof based on the results of Gusfield and Irving on rotations, which gives rise to a strongly polynomial algorithm for finding an integer optimal dual solution.
An Asymptotically Optimal Policy for a Quantity-Based Network Revenue Management Problem
Authors: Reiman Martin I. , Wang Qiong
Published: June 2008

We consider a canonical revenue management problem in a network setting where the goal is to find a customer admission policy to maximize the total expected revenue over a fixed finite horizon. There is a set of resources, each of which has a fixed capacity. There are several customer classes, each with an associated arrival process, price, and resource consumption vector. If a customer is accepted, it effectively removes the resources that it consumes from the system. The exact solution cannot be obtained for reasonable-sized problems due to the curse of dimensionality. Several (approximate) solution techniques have been proposed in the literature. One way to analytically compare policies is via an asymptotic analysis where both resource sizes and arrival rates grow large. Many of the proposed policies are asymptotically optimal on the fluid scale. However, as we demonstrate in this paper, these policies may fail to be optimal on the more sensitive diffusion scale even for quite simple problem instances. We develop a new policy that achieves diffusion-scale optimality. The policy starts with a probabilistic admission rule derived from the optimization of the fluid model, embeds a trigger function that tracks the difference between the actual and expected customer acceptance, and sets threshold values for the trigger function, the violation of which invokes the reoptimization of the admission rule. We show that re-solving the fluid model, which needs to be performed at most once, is required for extending the asymptotic optimality from the fluid scale to the diffusion scale. We demonstrate the implementation of the policy by numerical examples.
Lattice Theory and the Consumer's Problem
Authors: Mirman Leonard J. , Ruble Richard
Published: June 2008

This paper explores and explains the application of the lattice theoretic approach to classic comparative statics in consumer theory. Through examples of preferences that are not quasiconcave, or not differentiable, or not continuous, the approach is shown to characterize income effects more powerfully than the standard approach. The underlying partial order is key to applying the method. Therefore, several adapted partial orders are introduced and discussed.
An Analysis of Monotone Follower Problems for Diffusion Processes
Authors: Bayraktar Erhan , Egami Masahiko
Published: June 2008

We consider a singular stochastic control problem, which is called the monotone follower stochastic control problem, and give sufficient conditions for the existence and uniqueness of a local-time type optimal control. To establish this result, we use a methodology that has not been employed to solve singular control problems. We first confine ourselves to local-time strategies. We then apply a transformation to the total reward accrued by reflecting the diffusion at a given boundary and show that it is linear in its continuation region. Now, the problem of finding the optimal boundary becomes a nonlinear optimization problem: The slope of the linear function and an obstacle function need to be simultaneously maximized. The necessary conditions of optimality come from first-order derivative conditions. We show that under some weak assumptions these conditions become sufficient. We also show that the local-time strategies are optimal in the class of all monotone increasing controls.

As a by-product of our analysis, we give sufficient conditions for the value function to be C2 on all of its domain. We solve two dividend payment problems to show that our sufficient conditions are satisfied by the examples considered in the mainstream literature. We show that our assumptions are satisfied not only when capital of a company is modeled by a Brownian motion with drift, but also when we change the modeling assumptions and use a square root process to model the capital.
Fluid Limits for Processor-Sharing Queues with Impatience
Authors: Gromoll H. Christian , Robert Philippe , Zwart Bert
Published: June 2008

We investigate a processor-sharing queue with renewal arrivals and generally distributed service times. Impatient jobs may abandon the queue or renege before completing service. The random time representing a job's patience has a general distribution and may be dependent on its initial service time requirement. A scaling procedure that gives rise to a fluid model with nontrivial yet tractable steady state behavior is presented. This fluid model captures many essential features of the underlying stochastic model, and it is used to analyze the impact of impatience in processor-sharing queues.
Local Indices for Degenerate Variational Inequalities
Authors: Simsek Alp , Ozdaglar Asuman , Acemoglu Daron
Published: June 2008

We provide an index formula for solutions of variational inequality problems defined by a continuously differentiable function F over a convex set M represented by a finite number of inequality constraints. Our index formula can be applied when the solutions are nonsingular and possibly degenerate, as long as they also satisfy the injective normal map (INM) property, which is implied by strong stability. We show that when the INM property holds, the degeneracy in a solution can be removed by perturbing the function F slightly, i.e., the index of a degenerate solution is equal to the index of a nondegenerate solution of a slightly perturbed variational inequality problem. We further show that our definition of the index is equivalent to the topological index of the normal map at the zero corresponding to the solution. As an application of our index formula, we provide a global index theorem for variational inequalities which holds even when the solutions are degenerate.
Löwner's Operator and Spectral Functions in Euclidean Jordan Algebras
Authors: Sun Defeng , Sun Jie
Published: June 2008

We study analyticity, differentiability, and semismoothness of Löwner's operator and spectral functions under the framework of Euclidean Jordan algebras. In particular, we show that many optimization-related classical results in the symmetric matrix space can be generalized within this framework. For example, the metric projection operator over any symmetric cone defined in a Euclidean Jordan algebra is shown to be strongly semismooth. The research also raises several open questions, whose answers would be of strong interest for optimization research.
Stochastic Games on a Product State Space
Authors: Flesch János , Schoenmakers Gijs , Vrieze Koos
Published: June 2008

We examine so-called product-games with an aperiodic transition structure, with respect to the average reward, for which we present an approach based on communicating states. For the general n-player case, we establish the existence of 0-equilibria. In addition, for the special case of two-player zero-sum games of this type, we show that both players have stationary 0-optimal strategies.
Approximation Algorithms for the Capacitated Multi-Item Lot-Sizing Problem via Flow-Cover Inequalities
Authors: Levi Retsef , Lodi Andrea , Sviridenko Maxim
Published: June 2008

We study the classical capacitated multi-item lot-sizing problem with hard capacities. There are N items, each of which has a specified sequence of demands over a finite planning horizon of T discrete periods; the demands are known in advance but can vary from period to period. All demands must be satisfied on time. Each order incurs a time-dependent fixed ordering cost regardless of the combination of items or the number of units ordered, but the total number of units ordered cannot exceed a given capacity C. On the other hand, carrying inventory from period to period incurs holding costs. The goal is to find a feasible solution with minimum overall ordering and holding costs.

We show that the problem is strongly NP-hard, and then propose a novel facility location type LP relaxation that is based on an exponentially large subset of the well-known flow-cover inequalities; the proposed LP can be solved to optimality in polynomial time via an efficient separation procedure for this subset of inequalities. Moreover, the optimal solution of the LP can be rounded to a feasible integer solution with cost that is at most twice the optimal cost; this provides a 2-approximation algorithm which is the first constant approximation algorithm for the problem. We also describe an interesting on-the-fly variant of the algorithm that does not require solving the LP a priori with all the flow-cover inequalities. As a by-product we obtain the first theoretical proof regarding the strength of flow-cover inequalities in capacitated inventory models.
A Characterization of Box-Mengerian Matroid Ports
Authors: Chen Xujin , Ding Guoli , Zang Wenan
Published: June 2008

Let M be a matroid on E∪{l}, where l ∉ E is a distinguished element of M. The l-port of M is the set 𝒫= {P: P ⊆ E with P∪{l} a circuit of M}. Let A be the 𝒫-E incidence matrix. Let U2, 4 be the uniform matroid on four elements of rank two, let F7 be the Fano matroid, let F7* be the dual of F7, and let F7+ be the unique series extension of F7. In this paper, we prove that the system Ax≥1, x≥0 is box-totally dual integral (box-TDI) if and only if M has no U2, 4-minor using l, no F7*-minor using l, and no F7+-minor using l as a series element. Our characterization yields a number of interesting results in combinatorial optimization.
Bayesian Sequential Change Diagnosis
Authors: Dayanik Savas , Goulding Christian , Poor H. Vincent
Published: June 2008

Sequential change diagnosis is the joint problem of detection and identification of a sudden and unobservable change in the distribution of a random sequence. In this problem, the common probability law of a sequence of i.i.d. random variables suddenly changes at some disorder time to one of finitely many alternatives. This disorder time marks the start of a new regime, whose fingerprint is the new law of observations. Both the disorder time and the identity of the new regime are unknown and unobservable. The objective is to detect the regime-change as soon as possible, and, at the same time, to determine its identity as accurately as possible. Prompt and correct diagnosis is crucial for quick execution of the most appropriate measures in response to the new regime, as in fault detection and isolation in industrial processes, and target detection and identification in national defense. The problem is formulated in a Bayesian framework. An optimal sequential decision strategy is found, and an accurate numerical scheme is described for its implementation. Geometrical properties of the optimal strategy are illustrated via numerical examples. The traditional problems of Bayesian change-detection and Bayesian sequential multi-hypothesis testing are solved as special cases. In addition, a solution is obtained for the problem of detection and identification of component failure(s) in a system with suspended animation.
Assessment of Clinical Pharmacists' Interventions in French Hospitals: Results of a Multicenter Study
Authors: Bedouch Pierrick , Charpiat Bruno , Conort Ornella , Rose François-Xavier , Escofier Laurence , Juste Michel , Roubille Renaud , Allenet Benoît
Published: June 2008

Background:

The development of clinical pharmacy activities in most European countries is underway; however, data on these activities are still poorly reported. Multicenter studies are necessary to standardize and demonstrate the value of clinical pharmacy activities in these countries.

Objective:

To document clinical pharmacists' daily routine interventions (Pls) to identify trends of intervention, drugs, and situations most frequently associated with drug-related problems (DRPs) and to estimate physicians' acceptance of PI.

Methods:

A prospective study of Pls was conducted in 6 French hospitals. The sample consisted of 300 randomized Pls par hospital, recorded during the medication order validation process when a DRP was identified. We recorded patients' demographic characteristics, drugs involved, wards, DRP description, pharmacists' recommendations, and whether or not the recommendations were accepted by the physicians.

Results:

A total of 38, 626 medication orders were analyzed by 28 clinical pharmacists, leading to 1800 Pls (4.66 Pls per 100 medication orders). Of the 1800 Pls, 25.9% targeted psychotropic drugs, 15.9% targeted antithrombotic drugs. 15.5% targeted digestive and metabolic drugs, and 15.0% targeted cardiovascular drugs. The most commonly identified DRPs were nonconformity to guidelines or contraindication (21.3%), followed by improper administration (20.6%), supratherapeutic dose (19.2%), and drug interaction (12.6%). Nearly half (42.2%) of the pharmacists' recommendations were related to drug choice (drug switch 22.2%, drug discontinuation 16.3%, addition of a new drug 3.7%) followed by dose adjustment (23.8%), optimization of administration (21, 9%; change of administration route 10.3%, administration modalities 11.6%), and need for drug monitoring (12.2%). The rate of physicians' acceptance was 73.4% (15.3% refusals, 11.3% not assessable).

Conclusions:

In French hospitals, pharmacists contribute to preventing DRPs during medication order validation. This study suggests that a few types of drugs and errors constitute a substantial proportion of Pls. Knowledge of the most frequent DRPs could significantly increase the efficiency of clinical Pls.
Delivery of Optimized Anticoagulant Therapy: Consensus Statement from the Anticoagulation Forum
Authors: Garcia David A , Witt Daniel M , Hylek Elaine , Wittkowsky Ann K , Nutescu Edith A , Jacobson Alan , Moll Stephan , Merli Geno J , Crowther Mark , Earl Laura , Becker Richard C , Oertel Lynn , Jaffer Amir , Ansell Jack E
Published: June 2008

Objective:

To provide recommendations, policies, and procedures pertaining to the provision of optimized anticoagulation therapy designed to achieve desired clinical endpoints while minimizing the risk of anticoagulant-related adverse outcomes (principally bleeding and thrombosis).

Study Selection and Data Extraction:

Due to this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors who constitute the Board of Directors of The Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The Board is composed of physicians, pharmacists, and nurses with demonstrated expertise and significant collective experience in the management of patients receiving anticoagulation therapy.

Data Synthesis:

Recommendations for delivering optimized anticoagulation therapy were developed collaboratively by the authors and are summarized in 9 key areas: (I) Qualifications of Personnel, (II) Supervision, (III) Care Management and Coordination, (IV) Documentation. (V) Patient Education, (VI) Patient Selection and Assessment, (VII) Laboratory Monitoring, (VIII) Initiation and Stabilization of Warfarin Therapy, and (IX) Maintenance of Therapy. Recommendations are intended to inform the development of care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized anticoagulation therapy are intended to apply to all clinicians involved in the care of outpatients receiving anticoagulation therapy, regardless of the structure and setting in which that care is delivered.

Conclusions:

Anticoagulation therapy, although potentially life-saving, has inherent risks. Whether a patient is managed in a solo practice or a specialized anticoagulation management service, a systematic approach to the key elements outlined herein will reduce the likelihood of adverse events. The need for continued research to validate optimal practices for managing anticoagulation therapy is acknowledged.
CaV1.2 rather than CaV1.3 is coupled to glucose-stimulated insulin secretion in INS-1 832/13 cells
Authors: Nitert Marloes Dekker , Nagorny Cecilia L F , Wendt Anna , Eliasson Lena , Mulder Hindrik
Published: June 2008

In clonal β-cell lines and islets from different species, a variety of calcium channels are coupled to glucose-stimulated insulin secretion. The aim of this study was to identify the voltage-gated calcium channels that control insulin secretion in insulinoma (INS)-1 832/13 cells. The mRNA level of CaV1.2 exceeded that of CaV1.3 and CaV2.3 two-fold. Insulin secretion, which rose tenfold in response to 16.7 mM glucose, was completely abolished by 5 μM isradipine that blocks CaV1.2 and CaV1.3. Similarly, the increase in intracellular calcium in response to 15 mM glucose was decreased in the presence of 5 μM isradipine, and the frequency of calcium spikes was decreased to the level seen at 2.8 mM glucose. By contrast, inhibition of CaV2.3 with 100 nM SNX-482 did not significantly affect insulin secretion or intracellular calcium. Using RNA interference, CaV1.2 mRNA and protein levels were knocked down by ∼65% and ∼34% respectively, which reduced insulin secretion in response to 16.7 mM glucose by 50%. Similar reductions in calcium currents and cell capacitance were seen in standard whole-cell patch-clamp experiments. The remaining secretion of insulin could be reduced to the basal level by 5 μM isradipine. Calcium influx underlying this residual insulin secretion could result from persisting CaV1.2 expression in transfected cells since knock-down of CaV1.3 did not affect glucose-stimulated insulin secretion. In summary, our results suggest that CaV1.2 is critical for insulin secretion in INS-1 832/13 cells.
The role of thyroid hormone receptor DNA binding in negative thyroid hormone-mediated gene transcription
Authors: Wulf Anne , Wetzel Marianne G , Kebenko Maxim , Kröger Meike , Harneit Angelika , Merz Jennifer , Weitzel Joachim M
Published: June 2008

Thyroid hormone 3,3′,5-tri-iodothyronine (T3) regulates gene expression in a positive and negative manner. Here, we analyzed the regulation of a positively (mitochondrial glycerol-3-phosphate dehydrogenase) and negatively T3-regulated target gene (TSHα). Thyroid hormone receptor (TR) activates mGPDH but not TSH promoter fragments in a mammalian one-hybrid assay. Furthermore, we investigated functional consequences of targeting TR to DNA independent of its own DNA-binding domain (DBD). Using a chimeric fusion protein of the DBD of yeast transcription factor Gal4 with TR, we demonstrated a positive regulation of gene transcription in response to T3. T3-mediated activation of this chimeric protein is further increased after an introduction of point mutations within the DBD of TR. Moreover, we investigated the capacity of TR to negatively regulate gene transcription on a DNA-tethered cofactor platform. A direct binding of TR to DNA via its own DBD is dispensable in this assay. We investigated functional consequences of point mutations affecting different domains of TR. Our data indicate that the DBD of TR plays a key role in direct DNA binding on positively but not on negatively T3-regulated target genes. Nevertheless, the DBD is involved in mediating negative gene regulation independent of its capacity to bind DNA.
Can artificial soil be used in the vegetative vigor test for US pesticide registration?
Authors: Bidelspach Conor , Olszyk David , Pfleeger Thomas
Published: June 2008

Current testing guidelines for pesticide registration for the protection of nontarget plants calls for the use of sterilized, standardized soil consisting of primarily sandy loam, loamy sand, loamy clay, or clay loam that contains up to 3% organic matter. Low organic matter soils can be difficult to manage in a greenhouse setting because when soils dry, they contract, causing impeded water infiltration, or when overwatered, poor drainage increases the chances of anaerobic conditions. The purpose of this study was to determine if the results for the vegetative vigor test differed when using either natural or artificial soils. The herbicide sulfometuron methyl was applied 14 d after emergence at 0.1 and 0.0032 of the suggested field application rate. Six plant species were tested, 4 of the common test species, Zea mays (corn), Glycine max (soybean), Avena sativa (oat), and Lactuca sativa (lettuce), and 2 native plants of the Willamette Valley, Oregon prairie, Bromus carinatus (California brome) and Ranunculus occidentalis (western buttercup). Herbicide application rate was the most significant factor in the experiment regardless of soil type. The different soils generally produced different results, even though the 2 native soils, one from Oregon and the other from Maryland, are both acceptable soils for the pesticide registration tests. The plants grown on artificial soil produced results generally between the Oregon and Maryland soil results. This study indicates that artificial soils may produce results similar to or more sensitive than soils currently used in the vegetative vigor test.
Effect of protamine sulfate on the isolated mesenteric arteries of normotensive and spontaneously hypertensive rats
Authors: Orescanin-Dusic Zorana , Milovanovic S. , Spasic M. , Radojicic R. , Blagojevic D.
Published: June 2008

We tested the relaxant effect of increased protamine sulfate (PS) amounts (10, 20, 50, 100 and 150 ?g/ml) on the isolated mesenteric arteries of normotensive and spontaneously hypertensive (SH) rats, with or without endothelium. PS caused concentration-dependent relaxation of isolated mesenteric arteries in both types of rats. The relaxation effect of PS was lower in SH rats than in normotensive ones. Our results indicate that the vascular smooth muscles play a significant role in PS-mediated relaxation.