bluuebunny/crossref_metadata_2025 huggingface dataset:
MODELING AND ANALYSIS OF NANOTIPS FOR THERMOELECTRIC COOLERS
Authors: TAN KWONG-LUCK , PADMANABHAN PRASHANT , ILIESCU CIPRIAN , TAY FRANCIS E. H.
Published: May 2005

Thermoelectric cooling system can be used in many applications. The properties of structured point contact at the cold end affect the performance of thermoelectric cooling. The performance of metal point junctions as a function of tip radius show that the smaller the tip radius, the better the figure of merit. This paper presents the modeling and analysis of the nanotips. Each nanotip will have to carry some fraction of the weight of the thermoelectric material and the silicon slabs. The small apical area of each nanotip causes a very high pressure build up. The device may be loaded externally to ensure proper nanotip and thermoelectric material contact. A deformation of approximately 10 to 15 nm would be ideal. Finite Element Analysis (FEA) needed to be applied to determine how tall each nanotip must be to maximize soft and hard tip contacts. FEA was also needed to approximate the amount of external loading that will be necessary. ANSYS software was used in the modeling and analysis of the nanotips.
THEORETICAL ANALYSIS AND EXPERIMENT OF A NOVEL DEP CHIP WITH 3-D SILICON ELECTRODES
Authors: YU LIMING , TAY FRANCIS E. H. , XU GUOLIN , ILIESCU CIPRIAN , AVRAM MARIOARA
Published: May 2005

This paper presents a novel dielectrophoresis (DEP) device where the DEP electrodes define the channel walls. This is achieved by fabricating microfluidic channel walls from highly doped silicon so that they can also function as DEP electrodes. Compared with planar electrodes, this device increases the exhibited dielectrophoretic force on the particle, therefore decreases the applied potential and reduces the heating of the solution. A DEP device with triangle electrodes has been designed and fabricated. Compared with the other two configurations, semi-circular and square, triangle electrode presents an increased force, which can decrease the applied voltage and reduce the Joule effect. Yeast cells have been used to for testing the performance of the device.
LTCC TECHNOLOGY FOR PHOTONIC AND MILLIMETER WAVE MODULE INTEGRATION
Authors: KERÄNEN KIMMO , KARPPINEN MIKKO , LENKKERI JAAKKO , MÄKINEN JUKKA-TAPANI , OLLILA JYRKI , KARIOJA PENTTI
Published: May 2005

In the module integration process, lower level packaging elements such as devices, sub-mounts and components are combined as a functional block. Embedded sub-system consists of modules whose operations are controlled by a specific algorithm. Typically, the control algorithm is realized in a form of system software in a processor unit, which controls individual module operations and combines separate module operations as a system operation. In the creation of a cost-efficient embedded system it is essential that reliable, reproducible and cost-efficient building blocks of systems, modules, can be manufactured. We have studied Low Temperature Co-fired Ceramics (LTCC) substrate technology and its possibilities to produce reliable, reproducible and cost-efficient photonic and millimeter wave modules.

In this paper we introduce our contribution to the development of LTCC photonic and millimeter wave modules. Most of the papers written on LTCC packaging are in the field of RF and millimeter wave modules and are shortly reviewed in this paper. Photonic modules utilizing LTCC substrates are almost missing in the literature. Several photonic modules based on the use of LTCC substrates developed by our group are introduced in this paper, including hermetic fiber pigtailed power laser, wavelength tunable laser and 10 GBit/s/ch optical interconnects board for photonic applications. In addition, front-end module for 24 GHz transceiver for millimeter wave applications is introduced.
DESIGN OF SEAMLESS PROTOCOL SWITCHING LAYER FOR VOICE OVER INTERNET PROTOCOL (VOIP) THAT SWITCHES BETWEEN BLUETOOTH AND IEEE 802.11
Authors: TAN YUNG HAN , THAMPI ARUN KRISHNAN , SEBASTIAN DALEY JOSEPH , HA YAJUN
Published: May 2005

The capability of seamlessly switching between two communication protocols will be very important for communication devices of the future, since it allows the end users to judiciously use whichever network is appropriate, depending on cost, signal strength or other factors such as the amount of battery life left on the device. This paper presents the groundbreaking idea of a Seamless Protocol Switching Layer (SPSL) on a hardware and software level to solve this problem. In addition, the SPSL concept is implemented by developing a prototype application, a Smart Video Phone, built using Intel XScale-based PXA255 board and ARM Linux as the operating system that can seamlessly switch between IEEE 802.11 and Bluetooth technologies. Experiments show that if the signal of the Bluetooth signal goes below 40%, the switching to Wireless-Fidelity (Wi-Fi) happens if it is available.
PDA BASED HUMAN MOTION RECOGNITION SYSTEM
Authors: LEMAN K. , ANKIT G. , TAN T.
Published: May 2005

This paper describes the design and implementation of autonomous real-time motion recognition on a Personal Digital Assistant. All previous such applications have been non real-time and required user interaction. The motivation to use a PDA is to test the viability of performing complex video processing on an embedded platform. The application was constructed using a representation and recognition technique for identifying patterns using Hu Moments. The approach is based upon temporal templates (Motion Energy and History Images) and their matching in time. The implementation was done using Intel Integrated Performance Primitives functions in order to reduce the complexity of the application. Tests were conducted using 5 different motion actions like arm waving, walking from left and right of the camera, head tilting and bending forward. Suggestions were also made on how to improve the performance of the system and possible applications.
MODEL AND APPLICATION OF IMPACT WAVE IN MEASURING THE DYNAMIC CHARACTERISTIC OF MICROSTRUCTURE
Authors: BAI YANPING , WANG JIANZHONG , JIN ZHEN
Published: May 2005

The model of transient axially symmetric wave propagation in a circular elastic bar is studied by using the elastic wave propagation theory and the methods of integral transform. The numerical results of the model of longitudinal impact wave velocity are shown using a method of numerical analysis. This theoretical formula and methods of analysis is used in an experimental system to measure the dynamic characteristic of microstructure. Curves of the wave peak emulation of Davies bar are obtained by using theoretical formulation.
PARETO SIMULATED ANNEALING (SA)-BASED MULTI-OBJECTIVE OPTIMIZATION FOR MEMS DESIGN AND APPLICATION
Authors: ONGKODJOJO ONG ANDOJO , TAY FRANCIS E. H.
Published: May 2005

In this paper we present a global optimization method for multiple objective functions using the Pareto Simulated Annealing (SA). This novel optimization method is very useful and promising for design and application in the field of Micro-Electro-Mechanical Systems (MEMS). Previously published global optimization method has been reported by us for only single objective function. The proposed method automatically assigns different objective weights to each objective functions so that it can generate multiple solutions simultaneously. It also offers the trade-off between the objective functions so that we will be able to select the most suitable solution for MEMS design and applications. Based on the global Pareto ranking of the solutions, the optimization method can provide the best solution (the first Pareto ranking) as well.
SLEEP MONITORING DEVICES USING ELECTRIC FIELD (E-FIELD) MATTRESS FOR CHILDREN WITH ECZEMA
Authors: TAN KWONG-LUCK , TAY FRANCIS E. H. , VAN BEVER HUGO
Published: May 2005

This paper presents the concept of implementing different dielectric properties of surroundings to monitor the sleep of eczema patients through the use of an electric field mattress. Different sensor methods, as well as different arrangements of electrodes in the E-field mattress, are discussed to find out which would achieve optimum results. This paper also explains how readings taken from the electrodes can be used to analyze the sleep pattern of eczema patients.
DESIGN ANALYSIS OF THE PROPULSION AND CONTROL SYSTEM OF AN UNDERACTUATED REMOTELY OPERATED VEHICLE USING AXIOMATIC DESIGN THEORY — PART 1
Authors: KOH T. H. , TAY F. E. H. , LAU M. W. S. , LOW E. , SEET G.
Published: May 2005

In this paper, the system design issues of the Propulsion and Control System of the ROV II are analyzed and addressed. The design concept, some of the upgraded features of the ROV II in comparison to ROV I and the unified pilot training and control system developed, will also be briefly discussed in this paper.
FORMAL MODELS IN INDUSTRY STANDARD TOOLS: AN ARGOS BLOCK WITHIN SIMULINK
Authors: BOURKE T. , SOWMYA A.
Published: May 2005

Simulink is widely used within the industry for simulation and model-driven development, and reactive behaviors are often modeled using an add-on called Stateflow. Argos is one of the synchronous languages that have been proposed for the specification, validation and implementation of reactive systems. It is a rigorously defined graphical notation which, though not as powerful as Stateflow, is much less complicated. This paper describes the implementation of an Argos block for Simulink.
MOBILE COMPUTING WITH PERSONAL AREA NETWORK AND HUMAN POWER GENERATION
Authors: CHEOK ADRIAN DAVID , HO MAN FUNG , YUSTINA EVA , LEE SHANG PING
Published: May 2005

For mobile computing system such as wearable computer, one of the most critical hardware issues is the provision of electric power. Various different sources of power for wearable computer have been investigated; however, we are interested only in power that can be generated in-situ, such as human power. This paper describes a novel mean of multiple source human power generation for small wearable electronic devices, and then demonstrates the digital information transfer between wearable computing devices by using human skin as "antenna".

There are a wide range of peripheral devices in a mobile computing system, such as sensors and identification memory tags. As the amount of such devices increases in a mobile computing design, there is a need for these devices to communicate efficiently with the central processing unit. Also, it is highly desirable that these devices could be conveniently connected to the wearable computer without many dangling wires. We developed a personal area network (PAN) system which attempts to interconnect such devices, and at the same time uses human body as communication channel. This system is in a way novel because it is totally powered by human motion.
PREDICTIVE TRACES IN HYBRID SYSTEMS
Authors: v. MOHRENSCHILDT MARTIN
Published: May 2005

Hybrid systems are ideal models of real control systems where the discrete controller interacts with the continuous system on a closed loop via A/D converters and digitally controlled actuators. We extend the notion of a predictive controller to hybrid systems by introducing the notion of predictive traces, the set of all possible traces of a hybrid system starting in some state and mode into the future. A control algorithm is developed that explores this set of predictive traces to determine the next control action.
Learning Transfer of Computer Skills: Examining the Impact of Multilevel Computer Self-Efficacy Beliefs
Authors: Hasan Bassam
Published: May 2005

The information systems literature has demonstrated a positive relationship between an individual's computer self-efficacy (CSE) and his/her ability to learn new computing skills. However, most past studies have overlooked the multilevel nature of the CSE construct and have not differentiated between near-transfer and far-transfer learning of computing skills. Accordingly, this study focuses on these two issues by investigating the impact of two levels of CSE (general and software specific) on two types of learning (near- and far-transfer) in computer training. The results of an experiment conducted to empirically test the relationships hypothesised among the study variables showed that software-specific CSE had significant effects on near-transfer and far-transfer learning and software-specific self-efficacy. In contrast, general CSE was found to have a significant effect on far-transfer learning only. The results provide valuable implications of computer training practice and research.
A Conceptualisation of the Relationship Between Organisational Culture and Knowledge Management
Authors: Zheng Wei
Published: May 2005

Organisational culture has been regarded as an important factor affecting knowledge management practices. This paper is an initial effort in constructing a new conceptualisation of the relationship between organisational culture and knowledge management. In view of this conceptualisation, organisational culture, rather than a mutually exclusive concept from organisational knowledge, overlaps with the concept of knowledge management. It highlights the absolute necessity to view organisational culture and knowledge management simultaneously. It also suggests new directions for managing organisational culture in the context of knowledge management.
A META ANALYSIS APPROACH ON THE DETERMINANT FACTORS OF INCUBATORS' PERFORMANCE
Authors: SOETANTO D. P.
Published: May 2005

Today there are hundreds of new incubators established. The figure is still rising drastically, especially for incubators focusing on technology development. This phenomenal trend acknowledges the importance of incubation policy as one of the means of job creation and accumulation of knowledge in regions. Receiving vast attention as a significant instrument, incubators have convinced many policy makers who rush into applying the strategy in their own regions. Nevertheless, our knowledge about how incubators work to accomplish their objectives is rather inadequate. In this paper, we would like to argue that there are some factors playing a role in the development of incubators. The findings disclose the different factors contributing to the incubators' performance at different times of establishment. Among these factors are: Actors' involvement, regional economy, entrepreneurial culture and types of incubator support.
THE MAXIMUM ACHIEVABLE PROFIT METHOD OF PATENT VALUATION
Authors: CARTE NORMAN
Published: May 2005

The maximum achievable profit method of patent valuation mitigates problems associated with the contemporary discounted cash flows method. According to this new method, the maximum incremental profit that commercialization of a patent can achieve under ideal circumstances is determined. The present value of this profit is the highest valuation that the patent can receive. All of the factors that are known to affect the value of a patent are graded to provide a score. A transfer function uses the score, the present value of the maximum achievable incremental profit, and an investment amount to determine a valuation.
EFFECT OF FIRM CONTINGENCIES ON CONTINUOUS INNOVATION
Authors: SOOSAY CLAUDINE A. , HYLAND PAUL W.
Published: May 2005

Innovation within logistics organizations does not occur in isolation. Most innovation occurs in response to environmental factors outside the direct control of management. Factors such as the location of the organizations, the available technologies, the accessibility of knowledge and globalization can all have an impact on how a business responds in innovative ways that ensure it can remain competitive. The logistics function is increasing in its strategic importance as more and more firms in developed economies such as Singapore and Australia are forced to complete globally to survive. In such a dynamic environment, logistics business must innovate; and to benefit from innovative technologies, systems, processes and practices they must consider the external contingencies that will have the greatest impact on the business operation. This paper provides important lessons from managers in logistics organisations in Australia and Singapore; and demonstrates how contingent factors can affect how firms differ in their strategies and capacities to innovate.
ORGANIZATIONAL STRATEGIC INNOVATION — HOW IS GOVERNMENT POLICY HELPING?
Authors: McGUIGAN MARTIN , HENDERSON JOAN
Published: May 2005

Organizations are looking for new ways to compete within increasingly turbulent business environments. At the macro level, governments are challenged to develop strategic innovation policies that seek to support business competitiveness in this new era. At the same time at a micro level, companies are struggling to re-orientate themselves and become strategically innovative so that they can effectively overcome threats presented by, for example, new emerging low wage economies. This paper aims to develop a clearer understanding of the interface between innovation policy at a macro (regional) level and strategic innovation development at an organizational (micro) level.
STRATEGIC GROUPS, PERFORMANCE, AND ISSUES RELATED TO PRODUCT DESIGN STRATEGY
Authors: CHANG WEN-CHIH , HSU YEN
Published: May 2005

This study examined design cases involving new product development related to Taiwanese home appliance firms for exploring the strategic groups formed by local firms and their performance in new product development and other issues related to product design strategy. The questionnaire survey demonstrates that Taiwanese home appliance firms, in terms of product design strategy, can be grouped into passive response, aggressive response, and R&D focus groups. In their response to the challenges faced following Taiwan joining the WTO, firms in different strategic groups exhibited different financial and non-financial performance. Furthermore, they differed significantly in dealing with product design activities, particularly new product development types, product design features, motivations, and design appeals. Differences in these aspects may be the reason for their differences in new product development performance.
GETTING THE MEASURE OF THE ELECTRONIC GAMES INDUSTRY: DEVELOPERS AND THE MANAGEMENT OF INNOVATION
Authors: GRANTHAM ANDREW , KAPLINSKY RAPHAEL
Published: May 2005

The electronic games industry has grown within the space of a decade to a $40bn global industry. Yet, at least in the UK, the management of innovation in the software development sector reflects the industry's bedroom origins. Visits to major buyers in the US by UK games developers show that publishers increasingly require more sophisticated management procedures from developers, including that with respect to the management of innovation. This paper reports on the development of industry-specific indicators to be used in processes of innovation management, benchmarking innovation practices and performance within the framework of value chain analysis. This provides the sector with a framework for more routinised innovation practices, and is also of relevance to the management of innovation in other software-intensive sectors.
OPPORTUNITIES IN CORPORATE VENTURING — ACTORS CREATING PASSAGEWAYS
Authors: VINTERGAARD CHRISTIAN
Published: May 2005

This paper develops a conceptual understanding of how corporate venture managers recognise and discover opportunities in a network environment. In an effort to create a better understanding of who is involved in the process, this paper reports on the development path of several entrepreneurial opportunities of the Danish corporate venture capitalist, Danfoss A/S. This paper distinguishes itself from previous research done on entrepreneurial opportunities by creating a holistic and conceptual framework, which broadens and expands the perception of the market participants involved in processes of recognition and discovery. Consequently the paper offers insight into a diversified group of actors who mix and match technological and market capabilities in a constant process of recognition and discovery.
Dietary protein intake impacts human skeletal muscle protein fractional synthetic rates after endurance exercise
Authors: Bolster Douglas R. , Pikosky Matthew A. , Gaine P. Courtney , Martin William , Wolfe Robert R. , Tipton Kevin D. , Maclean David , Maresh Carl M. , Rodriguez Nancy R.
Published: May 2005

This investigation evaluated the physiological impact of different dietary protein intakes on skeletal muscle protein synthesis postexercise in endurance runners. Five endurance-trained, male runners participated in a randomized, crossover design diet intervention, where they consumed either a low (0.8 g/kg; LP)-, moderate (1.8 g/kg; MP)-, or high (3.6 g/kg; HP)-protein diet for 4 wk. Diets were designed to be eucaloric with carbohydrate, fat, and protein approximating 60, 30, and 10%; 55, 30, and 15%; and 40, 30, and 30% for LP, MP, and HP, respectively. Substrate oxidation was assessed via indirect calorimetry at 3 wk of the dietary interventions. Mixed-muscle protein fractional synthetic rate (FSR) was measured after an endurance run (75 min at 70% V̇o2 peak) using a primed, continuous infusion of [2H5]phenylalanine. Protein oxidation increased with increasing protein intake, with each trial being significantly different from the other ( P < 0.01). FSR after exercise was significantly greater for LP (0.083%/h) and MP (0.078%/h) than for HP (0.052%/h; P < 0.05). There was no difference in FSR between LP and MP. This is the first investigation to establish that habitual dietary protein intake in humans modulates skeletal muscle protein synthesis after an endurance exercise bout. Future studies directed at mechanisms by which level of protein intake influences skeletal muscle turnover are needed.
Vascular ENaC proteins are required for renal myogenic constriction
Authors: Jernigan Nikki L. , Drummond Heather A.
Published: May 2005

The myogenic response is an essential component of renal blood flow autoregulation and is the inherent ability of vascular smooth muscle cells (VSMCs) to contract in response to increases in intraluminal pressure. Although mechanosensitive ion channels are thought to initiate VSMC stretch-induced contraction, their molecular identity is unknown. Recent reports suggest degenerin/epithelial Na+ channels (DEG/ENaC) may form mechanotransducers in sensory neurons and VSMCs; however, the role of DEG/ENaC proteins in myogenic constriction of mouse renal arteries has not been established. To test the hypothesis that DEG/ENaC proteins are required for myogenic constriction in renal vessels, we first determined expression of ENaC transcripts and proteins in mouse renal VSMCs. Then, we determined pressure- and agonist-induced constriction and changes in vascular smooth muscle cytosolic Ca2+ and Na+ in isolated mouse renal interlobar arteries following DEG/ENaC inhibition with amiloride and benzamil. We detect α-, β-, and γENaC transcript and protein expression in cultured mouse renal VSMC. In contrast, we detect only β- and γ- but not αENaC protein in freshly dispersed mrVMSC. Selective DEG/ENaC inhibition, with low doses of amiloride and benzamil, abolishes pressure-induced constriction and increases in cytosolic Ca2+ and Na+ without diminishing agonist-induced responses in isolated mouse interlobar arteries. Our findings indicate that DEG/ENaC proteins are required for myogenic constriction in mouse interlobar arteries and are consistent with our hypothesis that DEG/ENaC proteins may be components of mechanosensitive ion channel complexes required for myogenic vasoconstriction.
Treadmill running causes significant fiber damage in skeletal muscle of KATP channel-deficient mice
Authors: Thabet M. , Miki T. , Seino S. , Renaud J.-M.
Published: May 2005

Although it has been suggested that the ATP-sensitive K+ (KATP) channel protects muscle against function impairment, most studies have so far given little evidence for significant perturbation in the integrity and function of skeletal muscle fibers from inactive mice that lack KATP channel activity in their cell membrane. The objective was, therefore, to test the hypothesis that KATP channel-deficient skeletal muscle fibers become damaged when mice are subjected to stress. Wild-type and KATP channel-deficient mice (Kir6.2−/− mice) were subjected to 4–5 wk of treadmill running at either 20 m/min with 0° inclination or at 24 m/min with 20° uphill inclination. Muscles of all wild-type mice and of nonexercised Kir6.2−/− mice had very few fibers with internal nuclei. After 4–5 wk of treadmill running, there was little evidence for connective tissues and mononucleated cells in Kir6.2−/− hindlimb muscles, whereas the number of fibers with internal nuclei, which appear when damaged fibers are regenerated by satellite cells, was significantly higher in Kir6.2−/− than wild-type mice. Between 5% and 25% of the total number of fibers in Kir6.2−/− extensor digitum longus, plantaris, and tibialis muscles had internal nuclei, and most of such fibers were type IIB fibers. Contrary to hindlimb muscles, diaphragms of Kir6.2−/− mice that had run at 24 m/min had few fibers with internal nuclei, but mild to severe fiber damage was observed. In conclusion, the study provides for the first time evidence 1) that the KATP channels of skeletal muscle are essential to prevent fiber damage, and thus muscle dysfunction; and 2) that the extent of fiber damage is greater and the capacity of fiber regeneration is less in Kir6.2−/− diaphragm muscles compared with hindlimb muscles.
cMet and Fas Receptor Interaction Inhibits Death-Inducing Signaling Complex Formation in Endothelial Cells
Authors: Smyth Lesley Ann , Brady Hugh J.M.
Published: May 2005

Fas receptor is constitutively expressed on endothelial cells; however, these cells are highly resistant to Fas-mediated apoptosis. In this study, we examined death-inducing signaling complex (DISC) formation in endothelial cells after Fas receptor stimulation. Nonfunctional DISC formation was observed in human umbilical vein endothelial cells (HUVECs). Fas-associated death domain (FADD) and large amounts of FADD-like interleukin-1–converting enzyme–inhibitory protein-L were recruited to the receptor; however, no caspase 8 recruitment was observed. A role for the cell surface molecule cMet in controlling Fas sensitivity in endothelial cells was observed. Here, we report that Fas is associated with cMet in HUVECs. Such an interaction may inhibit self-association of Fas in these cells, as suggested by the fact that monomeric Fas is expressed in these cells. Endothelial cells undergoing cell matrix detachment, anoikis, are sensitive to Fas-mediated apoptosis. Despite upregulating the level of Fas receptor, endothelial cells undergoing anoikis have reduced cMet/Fas interaction, in part because of cMet being cleaved in these cells. Dimeric Fas was observed on anoikis cells. These data suggest that cMet/Fas interaction may inhibit self-association of Fas receptor such that reduced DISC formation occurs in these cells after Fas receptor ligation. cMet/Fas interaction may help explain why endothelial cells are resistant to Fas-mediated apoptosis.
Relationship Between Aortic Stiffening and Microvascular Disease in Brain and Kidney
Authors: O’Rourke Michael F. , Safar Michel E.
Published: May 2005

A close relationship has been established between microvascular damage in brain and kidney and indices of age and hypertension (pulse pressure, aortic pulse wave velocity, and augmentation index). The mechanism of such association has not been established, nor has rationale for prevention and treatment of microvascular damage. A logical pathophysiological explanation can be offered on the basis of differential input impedance in the brain and kidney compared with other systemic vascular beds. Torrential flow and low resistance to flow in these organs exposes small arterial vessels to the high-pressure fluctuations that exist in the carotid, vertebral, and renal arteries. Such fluctuations, measurable as central pulse pressure, increase 3- to 4-fold with age. Exposure of small vessels to highly pulsatile pressure and flow explains microvascular damage and resulting renal insufficiency and intellectual deterioration, according to the mechanism established by Byrom >50 years ago. The logical approach to prevention and treatment requires reduction of central pulse pressure. Because the aorta and large arteries are not directly affected by drugs, this entails reduction of wave reflection by dilation of conduit arteries elsewhere in the body. This can be accomplished by regular exercise and by drugs such as nitrates, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. The explanation given here accounts for greater and earlier vascular damage in diabetes mellitus (relative microvascular fragility) and is similar to that given for vascular changes of pulmonary hypertension caused by ventricular septal defects and other congenital vascular shunts.
Major Clinical Trials of Hypertension
Authors:   The National Heart, Lung, and Blood Institute Working Group on Future Directions in Hypertension Treatment Trials
Published: May 2005

The National Heart, Lung, and Blood Institute assembled an ad hoc working group to evaluate opportunities for new major clinical trials in the field of hypertension. The mandate of this working group was to consider the possible designs of major randomized clinical trials focused on clinical outcomes that might merit significant investment by the National Institutes of Health. The group concluded that the ideal pragmatic clinical trial would have a factorial design and include a population at elevated risk of cardiovascular disease events. Subjects would be randomized to a target of systolic blood pressure <130 versus 130 to 150 mm Hg for adequate separation of means. Initial treatment with thiazide diuretic would be followed by randomization to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, β-blocker, calcium channel blocker, or aldosterone antagonist. A third drug could be added according to a protocol. DNA, proteins, and metabolites would be collected in a sample adequate to assess differential impact of treatment on outcome as a function of genotype, proteomic, and metabolomic expression. Subclinical markers and images would also be measured in a sample of patients to develop evidence of ability to predict ultimate effect on clinical outcomes. This ideal trial would take place within a network, funded for at least a decade, aimed at connecting primary care providers with hypertension specialists. Within the network, substudies or independent studies would be coordinated to develop a continuously improving base of knowledge about the effective delivery of hypertension care.
Chronic Tumor Necrosis Factor-α Inhibition Enhances NO Modulation of Vascular Function in Estrogen-Deficient Rats
Authors: Arenas Ivan A. , Armstrong Stephen J. , Xu Yi , Davidge Sandra T.
Published: May 2005

Tumor necrosis factor-α (TNF-α) is involved in the pathogenesis of vascular disease. Clinical studies have shown that postmenopausal women have higher serum TNF-α levels; however, whether this increase in TNF-α is associated with vascular dysfunction is unknown. We investigated whether estrogen deficiency is associated with increased serum TNF-α levels and tested the effects of in vivo TNF-α inhibition on vascular reactivity. Aged (12 to 15 months) Sprague-Dawley rats were ovariectomized and treated with placebo, estrogen, or a TNF-α inhibitor (Etanercept; 0.3 mg/kg) for 4 weeks. Serum TNF-α was determined by a bioassay, and vascular function was evaluated in the myograph system. Estrogen-deficient animals had higher serum levels of TNF-α compared with either estrogen-replaced animals or animals treated with Etanercept. Moreover, in estrogen-deficient rats, TNF-α inhibition reduced the constriction of mesenteric arteries to phenylephrine, increased the modulation of this vasoconstriction by the NO synthase inhibitor nitro-
l
-arginine methyl ester, and decreased the modulation by a superoxide scavenger (Mn(III)tetrakis(4-benzoic acid) porphyrin chloride). Furthermore, endothelium-dependent relaxation was also enhanced by TNF-α antagonism. Additionally, vascular expression of endothelial NO synthase was increased in animals treated with Etanercept, whereas the expression of NAD(P)H oxidase gp91phox and p22phox subunits was decreased. These data show that estrogen-deficient female rats have higher bioactive serum TNF-α levels compared with estrogen-replaced animals. Moreover, a decrease in serum bioactive TNF-α by a soluble TNF-α receptor (Etanercept) results in increased modulation of vascular function by NO. These observations suggest that TNF-α could be a mediator of vascular dysfunction associated with estrogen deficiency.
High-Density Lipoproteins Induce Transforming Growth Factor-β
2
Expression in Endothelial Cells
Authors: Norata Giuseppe D. , Callegari Elisa , Marchesi Marta , Chiesa Giulia , Eriksson Per , Catapano Alberico L.
Published: May 2005

Background—

HDL is endowed with cardiovascular protective activities. In addition to its role in reverse cholesterol transport, HDL influences different functions of endothelial cells. In the present study, we investigated in endothelial cells the genes involved in inflammation modulated by HDL.

Methods and Results—

Through cDNA array analysis, transforming growth factor (TGF)-β
2
appeared to be a gene responsive to HDL treatment in endothelial cells. Quantitative real-time polymerase chain reaction confirmed that HDL subfraction 3 selectively induces TGF-β
2
mRNA expression and protein release, whereas TGF-β
1
and TGF-β
3
were not affected. This effect was mainly PI3K/Akt dependent. Lysosphingolipids present in HDL such as sphingosine 1 phosphate and sphingosylphosphorylcholine mimicked the effects of the whole HDL. These results were confirmed in vivo in transgenic mice overexpressing human apolipoprotein (apo) A-I. Compared with apoA-I–knockout mice, phospho-Akt, phospho-ERK1/2, and TGF-β
2
expression was increased in the aorta of transgenic mice overexpressing human apoA-I. In addition, the expression of phospho-Smad2/3, the transcription factor activated by TGF-β, is increased in transgenic mice compared with knockout mice.

Conclusions—

Because TGF-β possesses antiinflammatory properties and stabilizes the plaque, the results of the present work suggest a novel target for the antiatherosclerotic effect of HDL.
Cellular Mechanisms Underlying the Development of Catecholaminergic Ventricular Tachycardia
Authors: Nam Gi-Byoung , Burashnikov Alexander , Antzelevitch Charles
Published: May 2005

Background—

Mutations in the ryanodine 2 receptor (RyR2) gene have been identified in patients with catecholaminergic polymorphic ventricular tachycardia. We examined the cellular basis for the ECG features and arrhythmia mechanisms using low-dose caffeine to mimic the defective calcium homeostasis encountered under these conditions.

Methods and Results—

A transmural ECG and action potentials were recorded simultaneously from epicardial, M, and endocardial cells in arterially perfused canine ventricular wedge preparations. Caffeine alone produced no change (10 to 100 μmol/L) or a slight abbreviation (300 μmol/L) of the QT interval and no change in transmural dispersion of repolarization. Isoproterenol (100 nmol/L) alone induced sustained monomorphic ventricular tachycardia (VT) that originated in the epicardium in 3 of 14 wedge preparations. Isoproterenol in the presence of caffeine (100 to 300 μmol/L) induced epicardial VT in 9 of 16 wedge preparations. Delayed afterdepolarization–induced triggered beats that originated in the epicardium were associated with an increased T
peak
-T
end
interval and transmural dispersion of repolarization. Bidirectional VT developed in 11 of 16 wedge preparations as a consequence of alternation in the origin of ectopic activity between endocardial, M, and epicardial regions. Single extrastimuli delivered during sustained epicardial VT induced a rapid polymorphic VT/ventricular fibrillation (VF) in 3 of 9 wedges. Spontaneous polymorphic VT was observed in 3 of 16 preparations. Propranolol (1.0 μmol/L) or verapamil (1.0 μmol/L) completely suppressed ectopic activity that arose from the epicardium and prevented induction of polymorphic VT.

Conclusions—

Our data suggest delayed afterdepolarization–induced extrasystolic activity serves to trigger catecholamine-induced VT/VF under conditions of defective calcium handling. Epicardial origin of the ectopic beats increases transmural dispersion of repolarization, thus providing the substrate for the development of reentrant tachyarrhythmias that underlie rapid polymorphic VT/VF.
Ultrasound Measurement of the Fibrous Cap in Symptomatic and Asymptomatic Atheromatous Carotid Plaques
Authors: Devuyst Gérald , Ruchat Patrick , Karapanayiotides Theodoros , Jonasson Lisa , Cuisinaire Olivier , Lobrinus Johannes-Alexander , Pusztaszeri Marc , Kalangos Askenadios , Despland Paul-André , Thiran Jean-Philippe , Bogousslavsky Julien
Published: May 2005

Background—

Fibrous cap thickness (FCT) is an important determinant of atheroma stability. We evaluated the feasibility and potential clinical implications of measuring the FCT of internal carotid artery plaques with a new ultrasound system based on boundary detection by dynamic programming.

Methods and Results—

We assessed agreement between ultrasound-obtained FCT values and those measured histologically in 20 patients (symptomatic [S]=9, asymptomatic [AS]=11) who underwent carotid endarterectomy for stenosing (>70%) carotid atheromas. We subsequently measured in vivo the FCT of 58 stenosing internal carotid artery plaques (S=22, AS=36) in 54 patients. The accuracy in discriminating symptomatic from asymptomatic plaques was assessed by receiver operating characteristic curves for the minimal, mean, and maximal FCT. Decision FCT thresholds that provided the best correct classification rates were identified. Agreement between ultrasound and histology was excellent, and interobserver variability was small. Ultrasound showed that symptomatic atheromas had thinner fibrous caps (S versus AS, median [95% CI]: minimal FCT=0.42 [0.34 to 0.48] versus 0.50 [0.44 to 0.53] mm,
P
=0.024; mean FCT=0.58 [0.52 to 0.63] versus 0.79 [0.69 to 0.85] mm,
P
<0.0001; maximal FCT=0.73 [0.66 to 0.92] versus 1.04 [0.94 to 1.20] mm,
P
<0.0001). Mean FCT measurement demonstrated the best discriminatory accuracy (area under the curve [95% CI]: minimal 0.74 [0.61 to 0.87]; mean 0.88 [0.79 to 0.97]; maximal 0.82 [0.71 to 0.93]). The decision threshold of 0.65 mm (mean FTC) demonstrated the best correct classification rate (82.8%; positive predictive value 75%, negative predictive value 88.2%).

Conclusions—

FCT measurement of carotid atheroma with ultrasound is feasible. Discrimination of symptomatic from asymptomatic plaques with mean FCT values is good. Prospective studies should determine whether this ultrasound marker is reliable.
Placental Growth Factor Promotes Atherosclerotic Intimal Thickening and Macrophage Accumulation
Authors: Khurana Rohit , Moons Lieve , Shafi Shahida , Luttun Aernout , Collen Désiré , Martin John F. , Carmeliet Peter , Zachary Ian C.
Published: May 2005

Background—

Placental growth factor (PlGF) has been implicated in the pathophysiological angiogenesis and monocyte recruitment that underlie chronic inflammatory disease, but its role in atherosclerosis has not been examined. We investigated the effects of exogenous PlGF, delivered by adenoviral gene transfer, on atherogenic intimal thickening and macrophage accumulation induced by collar placement around the rabbit carotid artery and examined the effects of PlGF deficiency on atherosclerosis in apolipoprotein E–deficient (apoE
−/−
) mice.

Methods and Results—

Periadventitial transfer of PlGF2-encoding adenoviruses significantly increased intimal thickening, macrophage accumulation, endothelial vascular cell adhesion molecule-1 expression, and adventitial neovascularization in the collared arteries of hypercholesterolemic rabbits and increased the intima-to-media ratio in rabbits fed a normal diet. Neointimal macrophages were associated with increased expression of the PlGF receptor Flt-1. The size and macrophage content of early atherosclerotic lesions were reduced in mice deficient in both apoE and PlGF compared with apoE-deficient mice.

Conclusions—

Local adenoviral PlGF2 delivery promotes atherogenic neointima formation in hypercholesterolemic rabbits, and PlGF is required for macrophage infiltration in early atherosclerotic lesions in apoE
−/−
mice. These findings support a novel role for PlGF in the pathogenesis of atherosclerotic disease.
Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome
Authors: Raj Satish R. , Black Bonnie K. , Biaggioni Italo , Harris Paul A. , Robertson David
Published: May 2005

Background—

Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance notable for an excessive increase in heart rate that occurs on standing. Many current therapeutic strategies focus on sympatholysis, but the alternative strategy of enhancing cardiovagal tone has not been studied. The objective of this study was to test the hypothesis that acetylcholinesterase inhibitors will attenuate the tachycardia and improve symptom burden in patients with POTS.

Methods and Results—

Seventeen patients with POTS underwent acute drug trials of pyridostigmine 30 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressures, heart rate, and symptoms were assessed while patients were seated and after they had been standing for up to 10 minutes both before the study drug was given and at 2 and 4 hours after study drug. The heart rate was significantly lower at 2 hours after pyridostigmine than after placebo (100±16 versus 111±14 bpm,
P
=0.001). Pyridostigmine significantly decreased the standing heart rate from baseline (119±16 bpm) at 2 hours (104±16 bpm,
P
<0.001) and 4 hours (100±16 bpm,
P
<0.001) after administration. There was no significant change in blood pressure. The decrease in symptom burden within 4 hours after study drug was significantly greater with pyridostigmine than placebo (−10.4±14.0 AU versus 0.6±7.5 AU,
P
<0.025).

Conclusions—

Acute acetylcholinesterase inhibition significantly attenuated tachycardia in POTS. There was also an improvement in symptom burden with this promising therapy.
Weder Höhepunkt der Geschichte noch Schrei ins Leere. Grundriß der deutsch-jüdischen Symbiose
Authors: Voigts Manfred
Published: May 2005

This essay attempts to explain the German-Jewish symbiosis by examining the history of the German 'Bildungsbürgertum' and the peculiarity of the German Geistesgeschichte', which was shaped by the delay in national unification. On the one hand, the lack of political competence in German intellectual life conformed to Jewish peculiarities; on the other hand, it failed to engage in a critical discussion and rejection of anti-Judaic tendencies.
Total Surface Area Estimates for Individual Ice Particles and Particle Populations
Authors: Schmitt C. G. , Heymsfield A. J.
Published: May 2005

Representations for the surface area of ice particles in terms of the projected area have been developed using two different methods. The first method uses ice particles that are imaged in situ and geometric calculations that are based on the outline of the two-dimensional image of the particle. The second method uses computer-generated ice particle shapes and calculates the total surface area analytically. The results of the second method compare reasonably well with the results of the first method. Surface area estimates for individual particles were combined with particle size distribution and projected area measurements from the Cirrus Regional Study of Tropical Anvils and Cirrus Layers (CRYSTAL)–Florida Area Cirrus Experiment (FACE) field project to give total surface area estimates for observed ice particle populations. Population surface area estimates were also made from balloon-borne replicator data collected during the First International Satellite Cloud Climatology Project (ISCCP) Regional Experiment, phase II (FIRE-II). A relationship between the particle population surface area and projected area (cloud extinction) has been derived. The total particle surface area for particle populations is estimated to be between 8 and 10 times the projected area or between 4 and 5 times the extinction and has a small dependence on the properties of the particle size distribution for particles observed in random orientations.
A Bulk Microphysics Parameterization with Multiple Ice Precipitation Categories
Authors: Straka Jerry M. , Mansell Edward R.
Published: May 2005

A single-moment bulk microphysics scheme with multiple ice precipitation categories is described. It has 2 liquid hydrometeor categories (cloud droplets and rain) and 10 ice categories that are characterized by habit, size, and density—two ice crystal habits (column and plate), rimed cloud ice, snow (ice crystal aggregates), three categories of graupel with different densities and intercepts, frozen drops, small hail, and large hail. The concept of riming history is implemented for conversions among the graupel and frozen drops categories. The multiple precipitation ice categories allow a range of particle densities and fall velocities for simulating a variety of convective storms with minimal parameter tuning. The scheme is applied to two cases—an idealized continental multicell storm that demonstrates the ice precipitation process, and a small Florida maritime storm in which the warm rain process is important.
Simulation of Crop Yields Using ERA-40: Limits to Skill and Nonstationarity in Weather–Yield Relationships
Authors: Challinor A. J. , Wheeler T. R. , Slingo J. M. , Craufurd P. Q. , Grimes D. I. F.
Published: May 2005

Reanalysis data provide an excellent test bed for impacts prediction systems, because they represent an upper limit on the skill of climate models. Indian groundnut (Arachis hypogaea L.) yields have been simulated using the General Large-Area Model (GLAM) for annual crops and the European Centre for Medium-Range Weather Forecasts (ECMWF) 40-yr reanalysis (ERA-40). The ability of ERA-40 to represent the Indian summer monsoon has been examined. The ability of GLAM, when driven with daily ERA-40 data, to model both observed yields and observed relationships between subseasonal weather and yield has been assessed. Mean yields were simulated well across much of India. Correlations between observed and modeled yields, where these are significant, are comparable to correlations between observed yields and ERA-40 rainfall. Uncertainties due to the input planting window, crop duration, and weather data have been examined. A reduction in the root-mean-square error of simulated yields was achieved by applying bias correction techniques to the precipitation. The stability of the relationship between weather and yield over time has been examined. Weather–yield correlations vary on decadal time scales, and this has direct implications for the accuracy of yield simulations. Analysis of the skewness of both detrended yields and precipitation suggest that nonclimatic factors are partly responsible for this nonstationarity. Evidence from other studies, including data on cereal and pulse yields, indicates that this result is not particular to groundnut yield. The detection and modeling of nonstationary weather–yield relationships emerges from this study as an important part of the process of understanding and predicting the impacts of climate variability and change on crop yields.