bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediating Among Scientists: A Mental Model of Expert Practice
Authors: Kressel Kenneth , Gadlin Howard
Published: October 2009

Despite the considerable research on mediator behavior, the cognitive structures and processes that presumably guide the strategic and tactical choices of professional mediators are poorly understood. The current study made use of a reflective case study method to explore in considerable detail the strategic thinking of five experienced mediators. The project was conducted at the National Institutes of Health whose Office of the Ombudsman (OO) mediates disputes among the institute’s scientists. Eighteen cases were studied. The thinking of the mediators in these cases displayed regularities that are described in terms of the ombuds team’s working mental model of mediation. The mental model consists of two strongly contrasting intervention scripts: a deep problem‐solving script (DPS) focused on identifying and addressing latent issues of an interpersonal or systemic kind and a tactical problem‐solving script (TPS) focusing instead on the issues as presented by the parties. The tactical script was applied in either an integrative bargaining mode or a more distributive quasi‐arbitration approach. The choice of which script to follow in a given case is determined by first order decision rules concerning the existence and nature of any latent problems that may be present, and second order decision rules concerning the parties’ capacity to engage in “deep” problem‐solving. Despite their very different foci, both DPS and TPS appear to follow the same metascript of problem‐solving stages, beginning with an intensive diagnostic phase during which the decision rules are applied and a script “selection” is made. DPS is the preferred intervention mode of team members. Every case began with at least a preliminary effort to search for and address latent causes, and team members expressed dissatisfaction if they could not apply DPS in cases where latent problems were thought to be fueling the conflict. However, ombudsmen used the scripts flexibly and switched to TPS if DPS was unnecessary or impractical. Both scripts produced agreements that were useful to the parties and to the institution’s scientific purposes, particularly the fostering of scientific competence. The mental model is heavily shaped by the social context in which the ombudsmen function. Thus, the primacy of DPS in the model appears to be due to the fact that the ombudsmen are “repeat players” in the life of the NIH and therefore in a position to become adept at recognizing the latent sources of its dysfunctional conflicts, are under a strong role mandate as ombudsmen to pay attention to covert patterns of organizational dysfunction, and deal with disputants pressed to address latent issues blocking scientific work.
Systematic positions of Lamiophlomis and Paraphlomis (Lamiaceae) based on nuclear and chloroplast sequences
Authors: PAN Yue‐Zhi , FANG Li‐Qin , HAO Gang , CAI Jie , GONG Xun
Published: October 2009

Abstract  Genera Lamiophlomis and Paraphlomis were originally separated from genus Phlomis s.l. on the basis of particular morphological characteristics. However, their relationship was highly contentious, as evidenced by the literature. In the present paper, the systematic positions of Lamiophlomis, Paraphlomis, and their related genera were assessed based on nuclear internal transcribed spacer (ITS) and chloroplast rpl16 and trnL‐F sequence data using maximum parsimony (MP) and Bayesian methods. In total, 24 species representing six genera of the ingroup and outgroup were sampled. Analyses of both separate and combined sequence data were conducted to resolve the systematic relationships of these genera. The results reveal that Lamiophlomis is nested within Phlomis sect. Phlomoides and its generic status is not supported. With the inclusion of Lamiophlomis rotata in sect. Phlomoides, sections Phlomis and Phlomoides of Phlomis were resolved as monophyletic. Paraphlomis was supported as an independent genus. However, the resolution of its monophyly conflicted between MP and Bayesian analyses, suggesting the need for expended sampling and further evidence.
Coupling of CO
2
and Ice Sheet Stability Over Major Climate Transitions of the Last 20 Million Years
Authors: Tripati Aradhna K. , Roberts Christopher D. , Eagle Robert A.
Published: October 2009

CO
2
and Miocene Climate Change

Atmospheric carbon dioxide is a powerful greenhouse gas believed to be one of the most important determinants of climate. Ice cores provide a detailed and direct record of CO
2
concentrations over the past 800,000 years, but not earlier.

Tripati
et al.

(p.
1394
, published online 8 October) report B/Ca measurements of planktonic foraminifera, from which they can infer atmospheric CO
2
concentrations, for the past 20 million years. The concentration of atmospheric CO
2
was similar to preindustrial values for the past 10 millions years, but between 15 and 20 million years ago, during the warm lower Miocene epoch, CO
2
was more abundant, and major climate transitions toward cooler conditions occurred when CO
2
decreased substantially.
The myth of the Brooks method of embolization: a brief history of the endovascular treatment of carotid–cavernous sinus fistula
Authors: Vitek J J , Smith M J
Published: October 2009

Objective

To correct the historical notion that permeates throughout the neurointerventional surgical literature that Dr Barney Brooks was the founder of the specialty.

Material and methods

Both articles written by Dr B Brooks and all pertinent literature dealing with neurointerventional treatment of the carotid–cavernous sinus fistula (CCSF) were reviewed.

Results

The notion that Dr B Brooks was the first to use the embolization method to treat the CCSF was based on misinterpretation of his papers published in 1930 and on ‘second generation’ references used by subsequent authors.

Conclusion

Dr B Brooks never described embolization of the CCSF by a ‘free’ piece of muscle introduced into the internal carotid artery (ICA).
PAIRWISE FINAL STATE INTERACTIONS IN THE p d→p dη REACTION NEAR THRESHOLD
Authors: UPADHYAY N. J. , JAIN B. K. , KHEMCHANDANI K. P. , KELKAR N. G.
Published: October 2009

A model for the p d→p dη reaction published earlier, including the final state interaction (FSI) of all particles, is revisited to investigate the low energy data on this reaction. The three-body problem of p–d–η scattering in the final state is approximated in terms of pairwise interactions between the three particles in the final state. Apart from a comparison with some preliminary data, two new findings relevant to the near threshold data analysis are reported. The first one points toward the limitations of an FSI factor used conventionally to extract the eta-deuteron scattering length and infer subsequently on the existence of eta-mesic states. The second result emphasizes the role of the p–d FSI and the strong Coulomb repulsion near threshold. Finally, a comparison of the above model calculation with low energy data, excludes very large eta-nucleon scattering lengths.
THE STRUCTURE OF COLD DARK MATTER HALOS: RECENT INSIGHTS FROM HIGH RESOLUTION SIMULATIONS
Authors: ZEMP MARCEL
Published: October 2009

We review results from recent high resolution cosmological structure formation simulations, namely the Via Lactea I & II and GHALO projects. These simulations study the formation of Milky Way sized objects within a cosmological framework. We discuss the general properties of cold dark matter halos at redshift z = 0 and focus on new insights into the structure of halos we got due to the unprecedented high resolution in these simulations.
SOCIALIZATION FOR ENTREPRENEURSHIP: THE SECOND GENERATION
Authors: AVIRAM ARIE
Published: October 2009

For the first generation of immigrants, entrepreneurship might be a reasonable answer to their employment problems. Unfortunately, in addition to objective problems such as language, the socialization for entrepreneurship of these immigrants does not always meet the requirements of their new country. This hindrance is overcome by the second generation which, through a different process of socialization, is closing the gap.
FINANCIAL INTERMINGLING IN KOREAN-AMERICAN AND MEXICAN-AMERICAN SMALL BUSINESSES
Authors: HAYNES GEORGE W. , ONOCHIE JOSEPH I. , LEE MYUNG-SOO , PURYEAR AlVIN N. , ROGOFF EDWARD G. , HECK RAMONA K. Z.
Published: October 2009

This study explores the financial intermingling behavior of Mexican-American and Korean-American owned and operated small businesses. It posits that ethnically-owned and -operated small businesses with strong familial ties and more limited access to financial capital are more likely to intermingle financial resources than other small businesses. Mexican-American small business owners typically have very strong familial ties, while Korean-American small business owners typically have very strong community ties. Perhaps more importantly, Mexican-American small business owners have less access to pools of community capital than Korean-American small business owners. Therefore, it is expected that Mexican-American small business owners are more likely to intermingle financial resources than Korean-American small business owners. Even when controlling for the time in United States and English language spoken in the household, this study suggests Mexican-American small business owners are more likely to intermingle financial resources than Korean-American small business owners. Within these two ethnic groups, similar factors contribute to intermingling. Small business owners living in rural areas and borrowers are more likely to intermingle financial resources for both ethnic groups.
IMMIGRANT AND US-BORN MEXICAN-OWNED BUSINESSES: MOTIVATIONS AND MANAGEMENT
Authors: SHINNAR RACHEL S. , CARDON MELISSA S. , EISENMAN MICKI , ZUIKER VIRGINIA SOLIS , LEE MYUNG-SOO
Published: October 2009

In this study, we seek to understand the key differences between the entrepreneurial experience for Mexican immigrant and US-born Mexican entrepreneurs. We focus on differences in motivation for start-up, reliance on ethnic enclaves and business management practices. Using data from the 2005 National Minority Business Owner Survey, our sample consisted of 156 Mexican American entrepreneurs (55 immigrants and 101 US-born). Results suggest that even within a particular minority group, there are key distinctions between immigrant and US-born entrepreneurs. For example, US-born Mexican entrepreneurs are more motivated by the individualistic financial benefits of being an entrepreneur, while Mexican immigrant entrepreneurs are more motivated by serving society and their co-ethnic community. Implications are discussed.
CREDIT RATIONING AND BLACK-OWNED FIRMS: IS THERE EVIDENCE OF DISCRIMINATION?
Authors: PARK YONGJIN , COLEMAN SUSAN
Published: October 2009

This article uses data from the 2003 Survey of Small Business Finances to determine if banks ration credit more severely to black-owned firms. Our results reveal this is the case. Using the Heckman two-step procedure, we determined that black- and white-owned firms have a comparable demand for credit as measured by their actual use of lines of credit. Controlling for firm and owner characteristics, however, black-owned firms had lower line of credit limits suggesting constraints in supply. Further, our findings suggest the supply of credit to black-owned firms is even more severely constrained than other minority-owned firms. These findings highlight the possibility of discrimination against black-owned firms in the form of credit rationing.
SMALL FAMILY BUSINESS SURVIVAL: STRATEGIES FOR COPING WITH OVERLAPPING FAMILY AND BUSINESS DEMANDS
Authors: NIEHM LINDA S. , MILLER NANCY J. , SHELLEY MACK C. , FITZGERALD MARGARET A.
Published: October 2009

This study identified 14 adjustment strategies employed by household and business managers to cope with overlapping work and family demands using data from 1997 and 2000 versions of the National Family Business Survey (NFBS). Significant differences were found between surviving small family firms by managerial role (single or dual) regarding gross income, gender, number of children under age 18, community size and trade sector. Both surviving and non-surviving enterprises tended to bring household work to the business field when times were hectic and demanding, and took care of family responsibilities while at the business. However, in non-surviving businesses, business managers reported a greater tendency to bring work home, demonstrating that work entered the family field more frequently than in surviving businesses. Managers of surviving businesses were more likely to make financial adjustments by hiring temporary help for the business or home, and less likely to ask others to help in the business without pay. Significant differences were also noted regarding the use of non-financial adjustments; managers of surviving family businesses were able to shift away from business work to spend time on family aspects, and to spend less time sleeping to help the business.
Author verification by linguistic profiling
Authors: Halteren Hans Van
Published: October 2009

This article explores the effects of parameter settings in linguistic profiling, a technique in which large numbers of counts of linguistic features are used as a text profile which can then be compared to average profiles for groups of texts. Although the technique proves to be quite effective for authorship verification, with the best overall parameter settings yielding an equal error rate of 3% on a test corpus of student essays, the optimal parameters vary greatly depending on author and evaluation criterion.
A statistical model for near-synonym choice
Authors: Inkpen Diana
Published: October 2009

We present an unsupervised statistical method for automatic choice of near-synonyms when the context is given. The method uses the Web as a corpus to compute scores based on mutual information. Our evaluation experiments show that this method performs better than two previous methods on the same task. We also describe experiments in using supervised learning for this task. We present an application to an intelligent thesaurus. This work is also useful in machine translation and natural language generation.
System-level performance/power analysis for platform-based design of multimedia applications
Authors: Zamora Nicholas H. , Hu Xiaoping , Marculescu Radu
Published: October 2009

The objective of this article is to introduce the use of Stochastic Automata Networks (SANs) as an effective formalism for application-architecture modeling in system-level average-case analysis for platform-based design. By platform, we mean a family of heterogeneous architectures that satisfy a set of architectural constraints imposed to allow re-use of hardware and software components. More precisely, we show how SANs can be used early in the design cycle to identify the best performance/power trade-offs among several application-architecture combinations. Having this information available not only helps avoid lengthy simulations for predicting power and performance figures, but also enables efficient mapping of different applications onto a chosen platform. We illustrate the benefits of our methodology by using the “Picture-in-Picture” video decoder as a driver application.
Area reduction by deadspace utilization on interconnect optimized floorplan
Authors: Sham Chiu-Wing , Young Evangeline F. Y.
Published: October 2009

Interconnect optimization has become the major concern in floorplanning. Many approaches would use simulated annealing (SA) with a cost function composed of a weighted sum of area, wirelength, and interconnect cost. These approaches can reduce the interconnect cost efficiently but the area penalty of the interconnect optimized floorplan is usually quite large. In this article, we propose an approach called
deadspace utilization
(DSU) to reclaim the unused area of an interconnect optimized floorplan by linear programming. Since modules are not necessarily rectangular in shape in floorplanning, some deadspace can be redistributed to the modules to increase the area occupied by each module. If the area of each module can be expanded by the same ratio, the whole floorplan can be compacted by that ratio to give a smaller floorplan. However, we will limit the compaction ratio to prevent overcongestion. Experiments show that we can apply this deadspace utilization technique to reduce the area and total wirelength of an interconnect optimized floorplan further while the routability can be maintained at the same time.
A hierarchical modeling framework for on-chip communication architectures of multiprocessing SoCs
Authors: Zhu Xinping , Malik Sharad
Published: October 2009

In multiprocessor-based SoCs, optimizing the communication architecture is often as important, if not more important, than optimizing the computation architecture. While there are mature platforms and techniques for the modeling and evaluation of architectures of processing elements, the same is not true for the communication architectures. This article presents an application-driven retargetable prototyping platform that fills this gap. This environment aims to facilitate the design exploration of the communication subsystem through application-level execution-driven simulations and quantitative analysis. Based on an analysis of a wide range of on-chip communication architectures, we describe how a specific hierarchical class library can be used to develop new on-chip communication architectures, or variants of existing ones with relatively little incremental effort. We demonstrate this through three case studies including two commercial on-chip bus systems and an on-chip packet switching network. Here we show that, through careful analysis and construction, it is possible for the modeling environment to support the common features of these architectures as part of the library and permit instantiation of the individual architectures as variants of the library design. Consequently, system-level design choices regarding the communication architecture can be made with high confidence in the early stages of design. In addition to improving design quality, this methodology also results in significantly shortening design-time.
Hierarchical partitioning of VLSI floorplans by staircases
Authors: Majumder Subhashis , Sur-Kolay Susmita , Bhattacharya Bhargab B. , Das Swarup Kumar
Published: October 2009

This article addresses the problem of recursively bipartitioning a given floorplan
F
using monotone staircases. At each level of the hierarchy, a monotone staircase from one corner of
F
to its opposite corner is identified, such that (i) the two parts of the bipartition are nearly equal in area (or in the number of blocks), and (ii) the number of nets crossing the staircase is minimal. The problem of area-balanced bipartitioning is shown to be NP-hard, and a maxflow-based heuristic is proposed. Such a hierarchy may be useful to repeater placement in deep-submicron physical design, and also to global routing.
Measuring the strength of information flows in programs
Authors: Masri Wes , Podgurski Andy
Published: October 2009

Dynamic information flow analysis
(DIFA) was devised to enable the flow of information among variables in an executing program to be monitored and possibly regulated. It is related to techniques like
dynamic slicing
and
dynamic impact analysis
. To better understand the basis for DIFA, we conducted an empirical study in which we measured the
strength
of information flows identified by DIFA, using information theoretic and correlation-based methods. The results indicate that in most cases the occurrence of a chain of dynamic program dependences between two variables does
not
indicate a measurable information flow between them. We also explored the relationship between the strength of an information flow and the
length
of the corresponding dependence chain, and we obtained results indicating that no consistent relationship exists between the length of an information flow and its strength. Finally, we investigated whether data dependence and control dependence makes equal or unequal contributions to flow strength. The results indicate that flows due to data dependences alone are stronger, on average, than flows due to control dependences alone. We present the details of our study and consider the implications of the results for applications of DIFA and related techniques.
Distribution fairness in Internet-scale networks
Authors: Pitoura Theoni , Triantafillou Peter
Published: October 2009

We address the issue of measuring distribution fairness in Internet-scale networks. This problem has several interesting instances encountered in different applications, ranging from assessing the distribution of load between network nodes for load balancing purposes, to measuring node utilization for optimal resource exploitation, and to guiding autonomous decisions of nodes in networks built with market-based economic principles. Although some metrics have been proposed, particularly for assessing load balancing algorithms, they fall short. We first study the appropriateness of various known and previously proposed statistical metrics for measuring distribution fairness. We put forward a number of required characteristics for appropriate metrics. We propose and comparatively study the appropriateness of the Gini coefficient (G) for this task. Our study reveals as most appropriate the metrics ofG, the fairness index (FI), and the coefficient of variation (CV) in this order. Second, we develop six distributed sampling algorithms to estimate metrics online efficiently, accurately, and scalably. One of these algorithms (2-PRWS) is based on two effective optimizations of a basic algorithm, and the other two (the sequential sampling algorithm,LBS-HL, and the clustered sampling one,EBSS) are novel, developed especially to estimateG. Third, we show how these metrics, and especiallyG, can be readily utilized online by higher-level algorithms, which can now know when to best intervene to correct unfair distributions (in particular, load imbalances). We conclude with a comprehensive experimentation which comparatively evaluates both the various proposed estimation algorithms and the three most appropriate metrics (G,CV, andFI). Specifically, the evaluation quantifies the efficiency (in terms of number of the messages and a latency indicator), precision, and accuracy achieved by the proposed algorithms when estimating the competing fairness metrics. The central conclusion is that the proposed metric,G, can be estimated with a small number of messages and latency, regardless of the skew of the underlying distribution.
Improving text categorization bootstrapping via unsupervised learning
Authors: Gliozzo Alfio , Strapparava Carlo , Dagan Ido
Published: October 2009

We propose a text-categorization bootstrapping algorithm in which categories are described by relevant seed words. Our method introduces two unsupervised techniques to improve the initial categorization step of the bootstrapping scheme: (i) using latent semantic spaces to estimate the similarity among documents and words, and (ii) the Gaussian mixture algorithm, which differentiates relevant and nonrelevant category information using statistics from unlabeled examples. In particular, this second step maps the similarity scores to class posterior probabilities, and therefore reduces sensitivity to keyword-dependent variations in scores. The algorithm was evaluated on two text categorization tasks, and obtained good performance using only the category names as initial seeds. In particular, the performance of the proposed method proved to be equivalent to a pure supervised approach trained on 70--160 labeled documents per category.
Cilostazol, a specific PDE-3 inhibitor, ameliorates chronic ileitis via suppression of interaction of platelets with monocytes
Authors: Matsunaga Hisayuki , Hokari Ryota , Higashiyama Masaaki , Kurihara Chie , Okada Yoshikiyo , Watanabe Chikako , Komoto Shunsuke , Nakamura Mitsuyasu , Kawaguchi Atsushi , Nagao Shigeaki , Miura Soichiro
Published: October 2009

Excessive migration of monocytes to a site of intestinal inflammation contributes to tissue damage in Crohn's disease. It is known that cilostazol, a specific phosphodiesterase-3 (PDE-3) inhibitor of platelets, decreases monocyte recruitment to intestinal mucosa through suppression of platelet-monocyte interactions. The objective of this study was to clarify whether cilostazol ameliorates murine ileitis by suppression of monocyte migration. Significant inflammation was induced in the ileum of SAMP1/Yit mice at 23 wk of age after piroxicam treatment for 3 wk. Weight of the terminal ileum of mice was significantly greater with inflammatory cell infiltration in SAMP1/Yit mice than in control mice (AKR-J). Treatment of SAMP1/Yit mice with cilostazol-containing food (200 ppm) for 3 wk significantly attenuated the increase in intestinal weight and the histological changes, including invasion of F4/80-positive macrophages. A significant increase in migration of monocytes and platelets to microvessels of the ileal mucosa was observed in SAMP/Yit mice in vivo by using an intravital fluorescence microscope. Pretreatment with cilostazol significantly attenuated the increased migration of monocytes, possibly through suppression of platelet-monocyte interactions. In conclusion, a PDE-3 inhibitor ameliorates murine ileitis through attenuating migration of monocytes to the intestinal mucosa, suggesting a potential usefulness of antiplatelet drugs for treatment of Crohn's disease.
Mediators released from LPS-challenged lungs induce inflammatory responses in liver vascular endothelial cells and neutrophilic leukocytes
Authors: Markovic N. , McCaig L. A. , Stephen J. , Mizuguchi S. , Veldhuizen R. A. W. , Lewis J. F. , Cepinskas G.
Published: October 2009

The systemic inflammatory response plays an important role in the progression of acute lung injury (ALI) to multiple organ dysfunction syndrome (MODS). However, the role of lung-derived inflammatory mediators in induction of the inflammatory response in remote organs is poorly understood. To address the above, we investigated the effects of lung inflammation on induction of inflammatory response(s) in the liver in vitro. Inflammation in mouse lungs was induced by intranasal administration of lipopolysaccharide (LPS; 1 mg/ml) followed by mechanical ventilation using the isolated perfused mouse lung method to obtain and characterize lung perfusate from the pulmonary circulation. LPS administration to mouse lungs resulted in an increased release of inflammation-relevant cytokines and chemokines into the perfusate (Luminex assay) compared with the saline-controls. Subsequently, primary mouse liver vascular endothelial cells (LVEC) or mouse polymorphonuclear leukocytes (PMN) in vitro were stimulated with the perfusate obtained from saline- or LPS-challenged lungs and assessed for various inflammation-relevant end points. The obtained results indicate that stimulation of LVEC with perfusate obtained from LPS-challenged lungs results in 1) reactive oxygen species (ROS) production; 2) activation of NF-κB; and 3) expression of E-selectin, ICAM-1, and VCAM-1 and a subsequent increase in PMN rolling and adhesion to LVEC. In addition, perfusate from LPS-challenged lung induced activation of PMN with respect to increased ROS production and upregulation of cell surface levels of adhesion molecules MAC-1 and VLA-4. Heat-inactivation of the perfusate obtained from LPS-challenged lungs was very effective in suppressing increased proadhesive phenotype (i.e., E-selectin and ICAM-1 expression) in LVEC, whereas targeted inhibition (immunoneutralization) of TNF-α and/or IL-6 in LPS-lung perfusate had no effect. Taken together, these findings indicate that multiple proinflammatory mediators (proteinaceous in nature) released from inflamed lungs act synergistically to induce systemic activation of circulating PMN and promote inflammatory responses in liver vascular endothelial cells.
Increased phase synchronization and decreased cerebral autoregulation during fainting in the young
Authors: Ocon Anthony J. , Kulesa John , Clarke Debbie , Taneja Indu , Medow Marvin S. , Stewart Julian M.
Published: October 2009

Vasovagal syncope may be due to a transient cerebral hypoperfusion that accompanies frequency entrainment between arterial pressure (AP) and cerebral blood flow velocity (CBFV). We hypothesized that cerebral autoregulation fails during fainting; a phase synchronization index (PhSI) between AP and CBFV was used as a nonlinear, nonstationary, time-dependent measurement of cerebral autoregulation. Twelve healthy control subjects and twelve subjects with a history of vasovagal syncope underwent 10-min tilt table testing with the continuous measurement of AP, CBFV, heart rate (HR), end-tidal CO2 (ETco2), and respiratory frequency. Time intervals were defined to compare physiologically equivalent periods in fainters and control subjects. A PhSI value of 0 corresponds to an absence of phase synchronization and efficient cerebral autoregulation, whereas a PhSI value of 1 corresponds to complete phase synchronization and inefficient cerebral autoregulation. During supine baseline conditions, both control and syncope groups demonstrated similar oscillatory changes in phase, with mean PhSI values of 0.58 ± 0.04 and 0.54 ± 0.02, respectively. Throughout tilt, control subjects demonstrated similar PhSI values compared with supine conditions. Approximately 2 min before fainting, syncopal subjects demonstrated a sharp decrease in PhSI (0.23 ± 0.06), representing efficient cerebral autoregulation. Immediately after this period, PhSI increased sharply, suggesting inefficient cerebral autoregulation, and remained elevated at the time of faint (0.92 ± 0.02) and during the early recovery period (0.79 ± 0.04) immediately after the return to the supine position. Our data demonstrate rapid, biphasic changes in cerebral autoregulation, which are temporally related to vasovagal syncope. Thus, a sudden period of highly efficient cerebral autoregulation precedes the virtual loss of autoregulation, which continued during and after the faint.
Contrasting effects of simulated microgravity with and without daily −Gxgravitation on structure and function of cerebral and mesenteric small arteries in rats
Authors: Lin Le-Jian , Gao Fang , Bai Yun-Gang , Bao Jun-Xiang , Huang Xiao-Feng , Ma Jin , Zhang Li-Fan
Published: October 2009

This study was designed to test the hypothesis that a 28-day tail suspension (SUS) could induce hypertrophy and enhanced myogenic and vasoconstrictor reactivity in middle cerebral arteries (MCAs), whereas atrophy and decreased myogenic and vasoconstrictor responses in mesenteric third-order arterioles (MSAs). Also, in addition to the functional enhancement in MCAs, structural changes in both kinds of arteries and functional decrement in MSAs could all be prevented by the intervention of daily 1-h dorsoventral (−Gx) gravitation by restoring to standing posture. To test this hypothesis, vessel diameters to pressure alterations and nonreceptor- and receptor-mediated agonists were determined using a pressure arteriograph with a procedure to measure in vivo length and decrease hysteresis of vessel segments and longitudinal middlemost sections of vessels fixed at maximally dilated state were examined using electron microscopy and histomorphometry. Functional studies showed that 28-day tail-suspended, head-down tilt (SUS) resulted in enhanced and decreased myogenic tone and vasoconstrictor responses, respectively, in MCAs and MSAs. Histomorphometric data revealed that SUS-induced hypertrophic changes in MCAs characterized by increases in thickness (T) and cross-sectional area (CSA) of the media and the number of vascular smooth-muscle-cell layers (NCL), whereas in MSAs, it induced decreases in medial CSA and T and NCL. Daily 1-h −Gxover 28 days can fully prevent these differential structural changes in both kinds of small arteries and the functional decrement in MSAs, but not the augmented myogenic tone and increased vasoreactivity in the MCAs. These findings have revealed special features of small resistance arteries during adaptation to microgravity with and without gravity-based countermeasure.
Increased HDL Cholesterol and ApoA-I in Humans and Mice Treated With a Novel SR-BI Inhibitor
Authors: Masson David , Koseki Masahiro , Ishibashi Minako , Larson Christopher J. , Miller Stephen G. , King Bernard D. , Tall Alan R.
Published: October 2009

Objectives—

Increasing HDL levels is a potential strategy for the treatment of atherosclerosis.

Methods and Results—

ITX5061, a molecule initially characterized as a p38 MAPK inhibitor, increased HDL-C levels by 20% in a human population of hypertriglyceridemic subjects with low HDL levels. ITX5061 also moderately increased apoA-I but did not affect VLDL/LDL cholesterol or plasma triglyceride concentrations. ITX5061 increased HDL-C in WT and human apoA-I transgenic mice, and kinetic experiments showed that ITX5061 decreased the fractional catabolic rate of HDL-CE and reduced its hepatic uptake. In transfected cells, ITX5061 inhibited SR-BI–dependent uptake of HDL-CE. Moreover, ITX5061 failed to increase HDL-C levels in
SR-BI
−/−
mice. To assess effects on atherosclerosis, ITX5061 was given to atherogenic diet–fed
Ldlr
+/−
mice with or without CETP expression for 18 weeks. In both the control and CETP-expressing groups, ITX5061-treated mice displayed reductions of early atherosclerotic lesions in the aortic arch −40%,
P
<0.05), and a nonsignificant trend to reduced lesion area in the proximal aorta.

Conclusions—

Our data indicate that ITX5061 increases HDL-C levels by inhibition of SR-BI activity. This suggests that pharmacological inhibition of SR-BI has the potential to raise HDL-C and apoA-I levels without adverse effects on VLDL/LDL cholesterol levels in humans.
Chylomicronemia Elicits Atherosclerosis in Mice—Brief Report
Authors: Weinstein Michael M. , Yin Liya , Tu Yiping , Wang Xuping , Wu Xiaohui , Castellani Lawrence W. , Walzem Rosemary L. , Lusis Aldons J. , Fong Loren G. , Beigneux Anne P. , Young Stephen G.
Published: October 2009

Objective—

The risk of atherosclerosis in the setting of chylomicronemia has been a topic of debate. In this study, we examined susceptibility to atherosclerosis in
Gpihbp1
-deficient mice (
Gpihbp1
−/−
), which manifest severe chylomicronemia as a result of defective lipolysis.

Methods and Results—

Gpihbp1
−/−
mice on a chow diet have plasma triglyceride and cholesterol levels of 2812±209 and 319±27 mg/dL, respectively. Even though nearly all of the lipids were contained in large lipoproteins (50 to 135 nm), the mice developed progressive aortic atherosclerosis. In other experiments, we found that both
Gpihbp1
-deficient “apo-B48–only” mice and
Gpihbp1
-deficient “apo-B100–only” mice manifest severe chylomicronemia. Thus, GPIHBP1 is required for the processing of both apo-B48– and apo-B100–containing lipoproteins.

Conclusions—

Chylomicronemia causes atherosclerosis in mice. Also, we found that GPIHBP1 is required for the lipolytic processing of both apo-B48– and apo-B100–containing lipoproteins.
Spiral Waves and Reentry Dynamics in an In Vitro Model of the Healed Infarct Border Zone
Authors: Chang Marvin G. , Zhang Yibing , Chang Connie Y. , Xu Linmiao , Emokpae Roland , Tung Leslie , Marbán Eduardo , Abraham M. Roselle
Published: October 2009

Rationale:Reentry underlies most ventricular tachycardias (VTs) seen postmyocardial infarction (MI). Mapping studies reveal that the majority of VTs late post-MI arise from the infarct border zone (IBZ).

Objective:To investigate reentry dynamics and the role of individual ion channels on reentry in in vitro models of the “healed” IBZ.

Methods and Results:We designed in vitro models of the healed IBZ by coculturing skeletal myotubes with neonatal rat ventricular myocytes and performed optical mapping at high temporal and spatial resolution.

In culture, neonatal rat ventricular myocytes mature to form striated myocytes and electrically uncoupled skeletal myotubes simulate fibrosis seen in the healed IBZ. High resolution mapping revealed that skeletal myotubes produced localized slowing of conduction velocity (CV), increased dispersion of CV and directional-dependence of activation delay without affecting myocyte excitability. Reentry was easily induced by rapid pacing in cocultures; treatment with lidocaine, a Na+channel blocker, significantly decreased reentry rate and CV, increased reentry path length and terminated 30% of reentrant arrhythmias (n=18). In contrast, nitrendipine, an L-type Ca2+channel blocker terminated 100% of reentry episodes while increasing reentry cycle length and path length and decreasing reentry CV (n=16). K+channel blockers increased reentry action potential duration but infrequently terminated reentry (n=12).

Conclusions:Cocultures reproduce several architectural and electrophysiological features of the healed IBZ. Reentry termination by L-type Ca2+channel, but not Na+channel, blockers suggests a greater Ca2+-dependence of propagation. These results may help explain the low efficacy of pure Na+channel blockers in preventing and terminating clinical VTs late after MI.
Complement-Dependent Inflammation and Injury in a Murine Model of Brain Dead Donor Hearts
Authors: Atkinson Carl , Varela Juan C. , Tomlinson Stephen
Published: October 2009

Rationale
:

Donor brain death (BD) is an unavoidable occurrence in heart transplantation and results in profound physiological derangements that render the heart more susceptible to ischemia/reperfusion injury in the recipient and likely has negative long-term consequences to allograft survival.

Objective
:

We developed a novel mouse model of BD and investigated the role of complement in BD-induced myocardial inflammation and injury.

Methods and Results
:

BD was induced by inflation of a balloon catheter in the cranial cavity. BD in wild-type mice resulted in a significant increase in serum concentrations of the complement activation product complement component (C)3a, and immunohistochemical analysis of heart sections demonstrated C3 deposition on the vascular endothelium and surrounding myocytes. Following induction of BD in complement (C3)-deficient mice, cardiac troponin levels, and histological evidence of injury were significantly reduced compared to wild-type mice. C3 deficiency was also associated with reduced myocardial leukocyte infiltration and reduced or absent expression of P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-α, and interleukin-1β.

Conclusions
:

These data indicate an important role for complement in BD-induced inflammation and injury and suggest that a complement inhibitory strategy applied to the donor (in addition to the recipient) may provide graft protection.
Conditional Ablation of Nonmuscle Myosin II-B Delineates Heart Defects in Adult Mice
Authors: Ma Xuefei , Takeda Kazuyo , Singh Aman , Yu Zu-Xi , Zerfas Patricia , Blount Anthony , Liu Chengyu , Towbin Jeffrey A. , Schneider Michael D. , Adelstein Robert S. , Wei Qize
Published: October 2009

Rationale
:

Germline ablation of the cytoskeletal protein nonmuscle myosin II (NMII)-B results in embryonic lethality, with defects in both the brain and heart. Tissue-specific ablation of NMII-B by a Cre recombinase strategy should prevent embryonic lethality and permit study of the function of NMII-B in adult hearts.

Objective
:

We sought to understand the function of NMII-B in adult mouse hearts and to see whether the brain defects found in germline-ablated mice influence cardiac development.

Methods and Results
:

We used a loxP/Cre recombinase strategy to specifically ablate NMII-B in the brains or hearts of mice. Mice ablated for NMII-B in neural tissues die between postnatal day 12 and 22 without showing cardiac defects. Mice deficient in NMII-B only in cardiac myocytes (B
αMHC
/B
αMHC
mice) do not show brain defects. However, B
αMHC
/B
αMHC
mice display novel cardiac defects not seen in NMII-B germline-ablated mice. Most of the B
αMHC
/B
αMHC
mice are born with enlarged cardiac myocytes, some of which are multinucleated, reflecting a defect in cytokinesis. Between 6 to 10 months, they develop a cardiomyopathy that includes interstitial fibrosis and infiltration of the myocardium and pericardium with inflammatory cells. Four of 5 B
αMHC
/B
αMHC
hearts develop marked widening of intercalated discs.

Conclusions
:

By avoiding the embryonic lethality found in germline-ablated mice, we were able to study the function of NMII-B in adult mice and show that absence of NMII-B in cardiac myocytes results in cardiomyopathy in the adult heart. We also define a role for NMII-B in maintaining the integrity of intercalated discs.
ASK1 Regulates Cardiomyocyte Death but Not Hypertrophy in Transgenic Mice
Authors: Liu Qinghang , Sargent Michelle A. , York Allen J. , Molkentin Jeffery D.
Published: October 2009

Rationale
:

Apoptosis signal-regulating kinase (ASK)1 is a central upstream kinase in the greater mitogen-activated protein kinase cascade that mediates growth and death decisions in cardiac myocytes in response to diverse pathological stimuli.

Objective
:

However, the role that ASK1 plays in regulating the cardiac hypertrophic response in vivo remains controversial.

Methods and Results
:

Here, we generated mice with cardiac-specific and inducible overexpression of ASK1 in the heart to assess its gain-of-function effect. ASK1 transgenic mice exhibited no induction of cardiac hypertrophy or pathology at 3 and 12 months of age, and these mice showed an identical hypertrophic response to controls following 2 weeks of pressure-overload stimulation or isoproterenol infusion. Although ASK1 overexpression did not alter the cardiac hypertrophic response, it promoted cardiomyopathy and greater TUNEL following pressure-overload stimulation and myocardial infarction. Indeed, ASK1 transgenic mice showed a greater than 2-fold increase in ischemia reperfusion-induced injury to the heart compared with controls. Examination of downstream signaling showed a prominent activation of mitogen-activated protein kinase kinase 4/6 and c-Jun NH
2
-terminal kinase (JNK)1/2 (but not p38 or extracellular signal-regulated kinases [ERKs]), inhibition of calcineurin-NFAT (nuclear factor of activated T cells), and induction of Bax in the hearts of ASK1 transgenic mice following 1 and 8 weeks of pressure-overload stimulation. Mechanistically, cardiomyopathy associated with ASK1 overexpression after 8 weeks of pressure overload was significantly reduced in the calcineurin Aβ–null (
CnA
β
−/−
) background.

Conclusions
:

These results indicate that ASK1 does not directly regulate the cardiac hypertrophic response in vivo, but it does alter cell death and propensity to cardiomyopathy, in part, through a calcineurin-dependent mechanism.
Metabolic Remodeling Induced by Mitochondrial Aldehyde Stress Stimulates Tolerance to Oxidative Stress in the Heart
Authors: Endo Jin , Sano Motoaki , Katayama Takaharu , Hishiki Takako , Shinmura Ken , Morizane Shintaro , Matsuhashi Tomohiro , Katsumata Yoshinori , Zhang Yan , Ito Hideyuki , Nagahata Yoshiko , Marchitti Satori , Nishimaki Kiyomi , Wolf Alexander Martin , Nakanishi Hiroki , Hattori Fumiyuki , Vasiliou Vasilis , Adachi Takeshi , Ohsawa Ikuroh , Taguchi Ryo , Hirabayashi Yoshio , Ohta Shigeo , Suematsu Makoto , Ogawa Satoshi , Fukuda Keiichi
Published: October 2009

Rationale
:

Aldehyde accumulation is regarded as a pathognomonic feature of oxidative stress–associated cardiovascular disease.

Objective
:

We investigated how the heart compensates for the accelerated accumulation of aldehydes.

Methods and Results
:

Aldehyde dehydrogenase 2 (ALDH2) has a major role in aldehyde detoxification in the mitochondria, a major source of aldehydes. Transgenic (Tg) mice carrying an
Aldh2
gene with a single nucleotide polymorphism (
Aldh2*2
) were developed. This polymorphism has a dominant-negative effect and the Tg mice exhibited impaired ALDH activity against a broad range of aldehydes. Despite a shift toward the oxidative state in mitochondrial matrices,
Aldh2*2
Tg hearts displayed normal left ventricular function by echocardiography and, because of metabolic remodeling, an unexpected tolerance to oxidative stress induced by ischemia/reperfusion injury. Mitochondrial aldehyde stress stimulated eukaryotic translation initiation factor 2α phosphorylation. Subsequent translational and transcriptional activation of activating transcription factor-4 promoted the expression of enzymes involved in amino acid biosynthesis and transport, ultimately providing precursor amino acids for glutathione biosynthesis. Intracellular glutathione levels were increased 1.37-fold in
Aldh2*2
Tg hearts compared with wild-type controls. Heterozygous knockout of
Atf4
blunted the increase in intracellular glutathione levels in
Aldh2*2
Tg hearts, thereby attenuating the oxidative stress–resistant phenotype. Furthermore, glycolysis and NADPH generation via the pentose phosphate pathway were activated in
Aldh2*2
Tg hearts. (NADPH is required for the recycling of oxidized glutathione.)

Conclusions
:

The findings of the present study indicate that mitochondrial aldehyde stress in the heart induces metabolic remodeling, leading to activation of the glutathione–redox cycle, which confers resistance against acute oxidative stress induced by ischemia/reperfusion.
Retinal Vascular Caliber and Extracranial Carotid Disease in Patients With Acute Ischemic Stroke
Authors: De Silva Deidre A. , Liew Gerald , Wong Meng-Cheong , Chang Hui-Meng , Chen Christopher , Wang Jie Jin , Baker Michelle L. , Hand Peter J. , Rochtchina Elena , Liu Erica Yang , Mitchell Paul , Lindley Richard I. , Wong Tien Yin
Published: October 2009

Background and Purpose—

Previous studies show that both retinal vascular caliber and carotid disease predict incident stroke in the general population, but the exact relationship between these 2 microvascular and macrovascular structural risk factors is unclear. We studied the relationship between retinal vascular caliber and carotid disease in patients presenting with acute ischemic stroke.

Methods—

We conducted a cross-sectional study of patients with acute ischemic stroke recruited from 3 centers (Melbourne, Sydney, Singapore). The caliber of retinal arterioles and venules was measured from digital retinal photographs. Severe extracranial carotid disease was defined as stenosis ≥75% or occlusion determined by carotid Doppler using North American Symptomatic Carotid Endarterectomy Trial-based criteria.

Results—

Among the 1029 patients with acute stroke studied, 7% of the population had severe extracranial carotid disease. Retinal venular caliber was associated with ipsilateral severe carotid disease (
P
<0.001 in multivariate models). Patients with wider retinal venular caliber were more likely to have severe ipsilateral carotid disease (multivariable-adjusted OR, 3.81; 95% CI, 1.80 to 8.07, comparing the largest and smallest venular caliber quartiles). The retinal venular caliber–carotid disease association remained significant in patients with large artery stroke.

Conclusions—

In patients with acute stroke, retinal venular widening was strongly associated with ipsilateral severe extracranial carotid disease. Our findings suggest concomitant retinal and cerebral microvascular disease may be present in patients with carotid stenosis or occlusion disease. The pathogenesis of stroke due to carotid disease may thus be partially mediated by microvascular disease.