bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale integrated photonics for high-performance interconnects
Authors: Beausoleil Raymond G.
Published: June 2011

Moore's Law has set great expectations that the performance of information technology will improve exponentially until at least the end of this decade. Although the physics of silicon transistors alone might allow these expectations to be met, the physics of the long metal wires that cross and connect packages almost certainly will not. Global-level interconnects incorporating large-scale integrated photonics fabricated on the same platform as silicon microelectronics hold the promise of revolutionizing computing by enabling parallel many-core and network switch architectures that combine unprecedented performance and ease of use with affordable power consumption.

Over the last decade, remarkable progress has been made in research on low-power silicon photonic devices for interconnect applications, and CMOS-compatible fabrication technologies promise a “Moore's Law for photonics” that could completely change the economics of integrated optics. In this survey, photonic technologies amenable to large-scale CMOS integration are reviewed from the perspective of high-performance interconnects operating over distance scales of 1mm to 100m. An overview of the requirements placed on integrated optical devices by a variety of modern computer applications leads to discussions of active and passive photonic components designed to generate, guide, filter, modulate, and detect light in the telecommunication bands. Critical challenges and prospects for large-scale integration are evaluated with an emphasis on silicon-on-insulator as a platform for photonics.
Passivity-based self-triggered control
Authors: Eyisi Emeka , Koutsoukos Xenofon
Published: June 2011

In this paper we present a case study on the trajectory tracking control of a robotic manipulator over a wireless network. We use passivity and self-triggered control to achieve two important desirable properties of Cyber Physical Systems (CPS), efficient use of resources and stability in the presence of network uncertainties. By using a passivity based approach, our design ensures the stability of the overall system even in the presence of network uncertainties while the self-triggered strategy ensures efficient use of network resources. We present preliminary simulation results to demonstrate our approach for the case study.
The problem with time in mixed continuous/discrete time modelling
Authors: Rovers Kenneth C. , Kuper Jan , Smit Gerard J. M.
Published: June 2011

The design of cyber-physical systems requires the use of mixed continuous time and discrete time models. Current modelling tools have problems with time transformations (such as a time delay) or multi-rate systems.

We will present a novel approach that implements signals as functions of time, directly corresponding to their mathematical representation. This enables an exact implementation of time transformations and as an additional advantage enables local control over time. A representation of components and signals in both domains is provided, together with composition operators to allow the specification of signal flow diagrams.
A logic-based modeling and verification of CPS
Authors: Saeedloei Neda , Gupta Gopal
Published: June 2011

Cyber-physical systems (CPS) consist of perpetually and concurrently executing physical and computational components. The presence of physical components require the computational components to deal with continuous quantities. A formalism that can model discrete and continuous quantities together with concurrent, perpetual execution is lacking. In this paper we report on the development of a formalism based on
logic programming
extended with
co-induction, constraints over reals
, and
coroutining
that allows CPS to be elegantly modeled. This logic programming realization can be used for verifying interesting properties as well as generating implementations of CPS. We illustrate this formalism by applying it to elegant modeling of the
reactor temperature control system
. Interesting properties of the system can be verified merely by posing appropriate
queries
to this model. Precise parametric analysis can also be performed.
Cyber-physical systems for next generation intelligent buildings
Authors: Savvides Andreas , Paschalidis Ioannis , Caramanis Michael
Published: June 2011

The proliferation of the smart grid creates new opportunities for large buildings to act as smart end-points that provide mutually beneficial services for building occupants and the grid. In this article we describe how Cyber-Physical systems that provide rapid access to information and decision-making can enable buildings to autonomously interact with the grid. By participating in new real-time electricity markets on the
utility side of the meter
and day-ahead markets, buildings have the potential of achieving local efficiency and reliability gains while also facilitating the effective utilization of renewables.
Biphasic Calcium Phosphate Bioceramics for Orthopaedic Reconstructions: Clinical Outcomes
Authors: Garrido Carlos A. , Lobo Sonja E. , Turíbio Flávio M. , LeGeros Racquel Z.
Published: June 2011

BCP are considered the most promising biomaterials for bone reconstruction. This study aims at analyzing the outcomes of patients who received BCP as bone substitutes in orthopaedic surgeries. Sixty-six patients were categorized according to the etiology and morphology of the bone defects and received scores after clinical and radiographic evaluations. The final results corresponded to the combination of both parameters and varied from 5 (excellent result) to 2 or lower (poor result). Most of the patients who presented cavitary defects or bone losses due to prosthesis placement or revision, osteotomies, or arthrodesis showed good results, and some of them excellent results. However, patients with segmental defects equal or larger than 3 cm in length were classified as moderate results. This study established clinical parameters where the BCP alone can successfully support the osteogenic process and where the association with other tissue engineering strategies may be considered.
High Levels of Cardiovascular Risk Factors among Pakistanis in Norway Compared to Pakistanis in Pakistan
Authors: Zahid Naeem , Meyer Haakon E. , Kumar Bernadette N. , Claussen Bjørgulf , Hussain Akhtar
Published: June 2011

Objectives. Previous studies have shown that the Norwegian-Pakistanis had considerably higher prevalence for diabetes and obesity compared to Norwegians. We studied the additional risk of obesity, dyslipidemia, and hypertension among Pakistanis in Norway compared to Pakistanis living in Pakistan.Method. 770 Norwegian-Pakistani adults (53.9% men and 46.1% women) born in Pakistan from two surveys conducted in Norway between 2000 and 2002 were compared with a sample of 1230 individuals (29.1% men and 70.9% women) that participated in a survey in Pakistan in 2006.Results. Both populations had similar height, but Norwegian-Pakistanis had considerably higher mean weight. Of the Norwegian-Pakistanis, 56% of the males and 40% of the females had a BMI above 25 kg/m2, as opposed to 30% and 56% in Pakistan, for males and females, respectively. Norwegian-Pakistanis had higher total cholesterol.Conclusion. Obesity and an unfavourable lipid profile were widely prevalent in both populations; the highest level was recorded amongst those living in Norway. The increased risk for obesity and dyslipidemia may be ascribed to change of lifestyle after migration.
Heat Transfer of DE-Series MOSFETs
Authors: Swart Arthur James
Published: June 2011

MOSFET devices have developed significantly over the past few years to become the number one choice for high-power applications in power electronics and electronic communication. Commercially available devices (such as the IXYS RF manufactured) now operate into the VHF range with output RF powers of up to 300 W. They are optimized for linear operation and suitable for broadcast and communication applications. This paper presents the heat transfer out of an IXZ210N50L MOSFET which is sandwiched between two identical heatsinks. The results reveal a linear decrease in heat flowing away from the top of the MOSFET when compared to the bottom of the MOSFET for each step increase of drain current. Two graphs (representing the top and bottom heatsinks connected to the MOSFET device) contrast the temperature rise for the Bisink technique when the drain current through the IXZ210N50L MOSFET is kept constant at 5 A. The Bisink technique has the advantages of lower on-state resistances and higher output powers when compared to the traditional mounting using only one heatsink, resulting in improved reliability and performance. Results further reveal that the ambient temperature must be measured in the vicinity of the heatsink.
An Optimal Lower Eigenvalue System
Authors: Liu Yingfan
Published: June 2011

An optimal lower eigenvalue system is studied, and main theorems including a series of necessary and suffcient conditions concerning existence and a Lipschitz continuity result concerning stability are obtained. As applications, solvability results to some von‐Neumann‐type input‐output inequalities, growth, and optimal growth factors, as well as Leontief‐type balanced and optimal balanced growth paths, are also gotten.
Investigation of the Effects of Titanate as Coupling Agent and Some Inorganic Nanoparticles as Fillers on Mechanical Properties and Morphology of Soft PVC
Authors: Hajian Morteza , Koohmareh Gholam Ali , Mostaghasi Afsaneh
Published: June 2011

The effects of titanate as a coupling agent and some particulate nanoscale particles such as TiO2, CaCO3, and ZnO on thermal and mechanical properties of emulsion polyvinylchloride (E-PVC) were investigated by thermogravimetric analysis (TGA), and mechanical tests. In this research, it was found that, in the presence of nanoparticles of CaCO3, TiO2, and ZnO, the peak temperature of dehydrochlorination of E-PVC was shifted to higher temperatures, and the rate of mass loss was decreased. Also results of differential scanning calorimetry showed that the addition of nanoparticle of CaCO3, TiO2, and ZnO led to an increase in glass transition temperature. The impact strength, elastic modulus and toughness of the samples were enhanced after addition of 0–10 part of filer in hundred parts of resin (phr) nano-CaCO3, nano-TiO2, and nano-ZnO due to improvement of compatibility of the polymer and the nano-particles. Also UV and thermal stability of the samples were enhanced by means of the nanoparticles. It was found that, in the presence of titanate as coupling agent, content of additives that could be used in the composite of PVC shifts to higher amounts.
The Pharmacology of Acute Lung Injury in Sepsis
Authors: Varisco Brian Michael
Published: June 2011

Acute lung injury (ALI) secondary to sepsis is one of the leading causes of death in sepsis. As such, many pharmacologic and nonpharmacologic strategies have been employed to attenuate its course. Very few of these strategies have proven beneficial. In this paper, we discuss the epidemiology and pathophysiology of ALI, commonly employed pharmacologic and nonpharmacologic treatments, and innovative therapeutic modalities that will likely be the focus of future trials.
On Quasi‐ω‐Confluent Mappings
Authors: Qahis Abdo , Noorani Mohd. Salmi Md.
Published: June 2011

We introduce a new class of mappings called quasi‐ω‐confluent maps, and we study the relation between these mappings, and some other forms of confluent maps. Moreover, we prove several results about some operations on quasi‐ω‐confluent mappings such as: composition, factorization, pullbacks, and products.
Simulation of Cerebral Aneurysm Growth and Prediction of Evolving Rupture Risk
Authors: Kroon Martin
Published: June 2011

Cerebral aneurysms are local expansions of blood vessel walls in the brain blood system. The rupture of an aneurysm is a very severe event associated with a high rate of mortality. When cerebral aneurysms are detected, clinicians need to decide if operation is required. The risk of aneurysm rupture is then compared to the risks associated with the medical intervention. In the present paper, a probabilistic framework for a mechanically based rupture risk assessment of cerebral aneurysms is proposed. The method is based on the assumption that the strength of aneurysmal tissues can be described by a statistical distribution. A structural analysis of the aneurysm in question is performed, and the maximum stress experienced by the aneurysm is compared to the strength distribution. The proposed model was compared with clinical results for ruptured aneurysms in terms of rupture density and accumulated rupture risk as a function of aneurysm size. The model was able to reproduce the clinical results well. The proposed framework may potentially be used under in vivo conditions to predict the risk of rupture for diagnosed aneurysms.
A Fold Bifurcation Theorem of Degenerate Solutions in a Perturbed Nonlinear Equation
Authors: Liu Ping , Wang Yuwen
Published: June 2011

We consider a nonlinear equation F(ε, λ, u) = 0, where the parameter ε is a perturbation
parameter, F is a differentiable mapping from R × R × X to Y, and X, Y are Banach spaces. We obtain an abstract bifurcation theorem by using the generalized saddle‐node bifurcation
theorem.
Adaptive Optimal m‐Stage Runge‐Kutta Methods for Solving Reaction‐Diffusion‐Chemotaxis Systems
Authors: Yu Jui-Ling
Published: June 2011

We present a class of numerical methods for the reaction‐diffusion‐chemotaxis system which is significant for biological and chemistry pattern formation problems. To solve reaction‐diffusion‐chemotaxis systems, efficient and reliable numerical algorithms are essential for pattern generations. Along with the implementation
of the method of lines, implicit or semi‐implicit schemes are typical time stepping solvers to reduce the effect on time step constrains due to the stability condition. However, these two schemes are usually difficult to employ. In this paper, we propose an adaptive optimal time stepping strategy for the explicit m‐stage Runge‐Kutta method to solve reaction‐diffusion‐chemotaxis systems. Instead of relying on empirical approaches to control the time step size, variable
time step sizes are given explicitly. Yet, theorems about stability and convergence of the algorithm are provided in analyzing robustness and efficiency. Numerical experiment results on a testing problem and a real application problem are shown.
Minimally Invasive Treatment of Spinal Metastases: Techniques
Authors: Rose Peter S. , Clarke Michelle J. , Dekutoski Mark B.
Published: June 2011

With improved treatments and increasingly life expectancy, the burden of metastatic disease in the spine is expected to rise. The role of conventional surgery for spinal metastases is well established but often involves procedures of large magnitude. We describe minimally invasive techniques for spinal stabilization and decompression in patients with symptomatic metastatic disease of the spine.
Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors
Authors: Miller Claudia P. , Singh Melissa M. , Rivera-Del Valle Nilsa , Manton Christa A. , Chandra Joya
Published: June 2011

Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi) has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS‐generating agents, proteasome inhibitors, and DNA‐damaging compounds that together may provide a therapeutic advantage over single‐agent strategies.
Synthesis of Five-Bar Slider Mechanism with Variable Topology for Finitely Separated Positions
Authors: Daivagna Umesh M. , Balli Shrinivas S.
Published: June 2011

A method to synthesize a five-bar slider mechanism with variable topology is suggested. Synthesis is carried out in two phases for function generation. In Phase I, synthesis is carried out for three finitely separated positions. In Phase II, it is carried outfor two finitely separated positions. A dyadic complex number method is used to write the equations of motion. The method is simple, general and has an increased accuracy over graphical techniques. An application of the five-bar slider mechanism with variable topology is illustrated.
Spatial and Temporal Dynamics in the Ionic Driving Force for GABAAReceptors
Authors: Wright R. , Raimondo J. V. , Akerman C. J.
Published: June 2011

It is becoming increasingly apparent that the strength of GABAergic synaptic transmission is dynamic. One parameter that can establish differences in the actions of GABAergic synapses is the ionic driving force for the chloride-permeable GABAAreceptor (GABAAR). Here we review some of the sophisticated ways in which this ionic driving force can vary within neuronal circuits. This driving force for GABAARs is subject to tight spatial control, with the distribution of Cl−transporter proteins and channels generating regional variation in the strength of GABAAR signalling across a single neuron. GABAAR dynamics can result from short-term changes in their driving force, which involve the temporary accumulation or depletion of intracellular Cl−. In addition, activity-dependent changes in the expression and function of Cl−regulating proteins can result in long-term shifts in the driving force for GABAARs. The multifaceted regulation of the ionic driving force for GABAARs has wide ranging implications for mature brain function, neural circuit development, and disease.
Evaluation of Hole Quality in Hardened Steel with High-Speed Drilling Using Different Cooling Systems
Authors: Brandão Lincoln Cardoso , Neves Frederico Ozanan , Nocelli Gregório Christo
Published: June 2011

This work evaluates the hole quality on AISI H13 hardened steel using high-speed drilling. Specimens were machined with new and worn out drills with 8.6 mm diameter and (TiAl)N coating. Two levels of cutting speed and three levels of cooling/lubrication systems (flooded, minimum lubrication quantity, and dry) were used. The hole quality is evaluated on surface roughness (Ra) parameter, diameter error, circularity, and cylindricity error. A statistical analysis of the results shows that the cooling/lubrication system significantly affects the hole quality for all measured variables. This analysis indicates that dry machining produces the worst results. Higher cutting speeds not only prove beneficial to diameter error and circularity errors, but also show no significant difference on surface roughness and cylindricity errors. The effects of the interaction between the cooling/lubrication systems, tool wear, and cutting speed indicate that only cylindricity error is influenced. Thus, the conclusion is that the best hole quality is produced with a higher cutting speed using flooded or minimum lubrication quantity independent of drill wear.
Asymptotics of Negative Exponential Moments for Annealed Brownian Motion in a Renormalized Poisson Potential
Authors: Chen Xia , Kulik Alexey
Published: June 2011

In (Chen and Kulik, 2009), a method of renormalization was proposed for constructing some more physically realistic random potentials in a Poisson cloud. This paper is devoted to the detailed analysis of the asymptotic behavior of the annealed negative exponential moments for the Brownian motion in a renormalized Poisson potential. The main results of the paper are applied to studying the Lifshitz tails asymptotics of the integrated density of states for random Schrödinger operators with their potential terms represented by renormalized Poisson potentials.
Multiple Positive Solutions for Semilinear Elliptic Equations with Sign‐Changing Weight Functions in ℝN
Authors: Hsu Tsing-San
Published: June 2011

Existence and multiplicity of positive solutions for the following
semilinear elliptic equation: −Δu + u = a(x)|u|p−2u + λb(x)|u|q−2u in ℝN, u ∈ H1(ℝN), are established, where λ > 0, 1 < q < 2 < p < 2*  (2* = 2N/(N − 2) if N ≥ 3,  2* = ∞
if N = 1, 2), a, b satisfy suitable conditions, and b maybe changes sign in ℝN. The study is based on the extraction of the Palais‐Smale sequences in the Nehari manifold.
A Self-Checking Hardware Journal for a Fault-Tolerant Processor Architecture
Authors: Amin Mohsin , Ramazani Abbas , Monteiro Fabrice , Diou Camille , Dandache Abbas
Published: June 2011

We introduce a specialized self-checking hardware journal being used as a centerpiece in our design strategy to build a processor tolerant to transient faults. Fault tolerance here relies on the use of error detection techniques in the processor core together with journalization and rollback execution to recover from erroneous situations. Effective rollback recovery is possible thanks to using a hardware journal and chosing a stack computing architecture for the processor core instead of the usual RISC or CISC. The main objective of the journalization and the hardware self-checking journal is to prevent data not yet validated to be sent to the main memory, and allow to fast rollback execution on faulty situations. The main memory, supposed to be fault secure in our model, only contains valid (uncorrupted) data obtained from fault-free computations. Error control coding techniques are used both in the processor core to detect errors and in the HW journal to protect the temporarily stored data from possible changes induced by transient faults. Implementation results on an FPGA of the Altera Stratix-II family show clearly the relevance of the approach, both in terms of performance/area tradeoff and fault tolerance effectiveness, even for high error rates.
Fatty Acids and Hypoxia Stimulate the Expression and Secretion of the Adipokine ANGPTL4 (Angiopoietin-Like Protein 4/ Fasting-Induced Adipose Factor) by Human Adipocytes
Authors: González-Muniesa Pedro , de Oliveira Cristiane , Pérez de Heredia Fátima , Thompson Mary P. , Trayhurn Paul
Published: June 2011

Background/Aims: Hypoxia occurs in white adipose tissue in obesity, modulating the expression and release of specific inflammation-related adipokines. ANGPTL4 (angiopoietin-like protein 4/fasting-induced adipose factor), which is implicated in angiogenesis, lipid metabolism and glucose homeostasis, is a major hypoxia-sensitive gene; recent studies indicate that ANGPTL4 expression is also regulated by fatty acids. We have examined the effects of hypoxia and fatty acids, alone and together, on the expression and release of ANGPTL4 by human adipocytes. Methods: Human adipocytes were differentiated and incubated with fatty acids (250 µM) in normoxia (21% O2) or hypoxia (1% O2). ANGPTL4 mRNA was measured by real-time PCR and the protein in the medium determined by ELISA. Results: In normoxia, ANGPTL4 gene expression was upregulated by palmitic, oleic, arachidonic and eicosapentaenoic acids, and ANGPTL4 release was increased. In contrast, there was no effect of lauric or myristic acids. Hypoxia alone increased the expression and secretion of ANGPTL4, and lauric, myristic, arachidonic and eicosapentaenoic acids each further increased expression and release in hypoxic adipocytes. Conclusion: The expression and secretion of ANGPTL4 by human adipocytes is upregulated by both hypoxia and fatty acids. The stimulatory effect of fatty acids on ANGPTL4 production is augmented under hypoxic conditions.
Prediction of Silent Ischemic Lesions after Carotid Artery Stenting Using Virtual Histology Intravascular Ultrasound
Authors: Yamada Kiyofumi , Yoshimura Shinichi , Kawasaki Masanori , Enomoto Yukiko , Takano Kyohei , Asano Takahiko , Minatoguchi Shinya , Iwama Toru
Published: June 2011

Background: A major concern with carotid artery stenting (CAS) is the potential for cerebral embolism. The purpose of this study was to determine whether virtual histology intravascular ultrasound (VH-IVUS) can predict the risk of a silent ischemic lesion after CAS. Methods: We performed CAS in 45 patients with carotid stenosis. Before CAS, we assessed plaque characteristics by VH-IVUS. We also performed diffusion-weighted magnetic resonance imaging of the brain before and after CAS to detect newly appearing ipsilateral silent ischemic lesions (NISIL). Results: In the patient group that was positive for NISIL (P group: n = 18), the relative fibrofatty (FF) area identified by VH-IVUS in 5 cross-sections including the most stenotic lesion was significantly larger than that in areas of the NISIL-negative group (N group: n = 27; 32.7 ± 13.2 and 18.3 ± 9.8%, respectively; p < 0.001). The relative fibrous area was significantly lower in the P group than in the N group (59.2 ± 9.5 and 74.6 ± 9.1%, respectively; p < 0.001). There were no differences in the relative dense calcium and necrotic core areas between the P and N groups. From the analysis of receiver operating characteristic curves, most reliable cutoff values for predicting NISIL were a relative FF area of 30% in the most stenotic lesion. In multivariate logistic regression analysis, the relative FF area was an independent predictor of NISIL (p = 0.005). Conclusions: Quantitative tissue characterization of atherosclerotic lesions of carotid arteries using VH-IVUS was useful to predict NISIL after CAS. However, the positive predictive value determined by VH-IVUS was not superior to that determined by a noninvasive method.
Plasma C3 and C3a Levels in Cryptogenic and Large-Vessel Disease Stroke: Associations with Outcome
Authors: Stokowska Anna , Olsson Sandra , Holmegaard Lukas , Jood Katarina , Blomstrand Christian , Jern Christina , Pekna Marcela
Published: June 2011

Background and Purpose: Inflammation seems to be a key player in the pathophysiology of stroke. In this study, we compared plasma C3 and C3a levels in cryptogenic and large-vessel disease (LVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at 3 months and 2 years. Methods: C3 and C3a levels in plasma of 79 cryptogenic stroke and 73 LVD stroke patients, sampled within 10 days and at 3 months after stroke, and age- and sex-matched control subjects from the Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assessed with the modified Rankin Scale. Results: Plasma C3 was increased in both stroke groups at both time points. Systemic elevation of C3a was limited to the acute phase in the cryptogenic stroke group, whereas plasma C3a levels in the LVD group were also elevated at the 3-month follow-up. In the LVD group, plasma C3 levels in the upper third at the 3-month follow-up were associated with an unfavorable outcome after 3 months independently of age and sex: odds ratio (OR) 5.56; 95% confidence interval (CI) 1.03–29.93; p = 0.045; as well as after 2 years: OR 4.75; 95% CI 1.11–20.30; p = 0.036. In the cryptogenic stroke group, high plasma C3a levels in the acute phase were associated with an unfavorable outcome after 3 months: OR 3.75; 95% CI 1.01–13.96; p = 0.049 in univariate analysis but not after adjustment for age and sex (p = 0.050). Conclusions: Plasma C3 and C3a levels are elevated in cryptogenic and LVD stroke and the predictive value of these markers may depend on stroke subtype. Further studies on the role of the complement system in ischemic stroke outcome based on larger patient populations and controlling for the effect of infections, are clearly warranted.
Global Regulatory Systems Operating in Bacilysin Biosynthesis in Bacillus subtilis
Authors: Köroğlu Türkan Ebru , Öğülür İsmail , Mutlu Seval , Yazgan-Karataş Ayten , Özcengiz Gülay
Published: June 2011

In Bacillus subtilis, bacilysin is a nonribosomally synthesized dipeptide antibiotic composed of L-alanine and L-anticapsin. The biosynthesis of bacilysin depends on the bacABCDEywfG operon (bac operon)and the adjacent ywfH gene. To elucidate the effects of global regulatory genes on the expression of bac operon, we used the combination of lacZ fusion analysis and the gel mobility shift assays. The cell density-dependent transition state induction of the bac operon was clearly shown. The basal expression level of the bac operon as well as transition state induction of bac is directly ComA dependent. Three Phr peptides, PhrC, PhrF and PhrK, are required for full-level expression of ComA-dependent bac operon expression, but the most important role seemed to be played by PhrC in stimulating bac expression through a RapC-independent manner. Spo0A is another positive regulator which participates in the transition state induction of bac both directly by interacting with the bac promoter and indirectly by repressing abrB expression. AbrB and CodY proteins do not only directly repress the bac promoter, but they also mutually stimulate the transition state induction of bac indirectly, most likely by antagonizing their repressive effects without preventing each other’s binding since both proteins can bind to the bac promoter simultaneously.
Decreased Kidney Function Is a Significant Factor Associated with Silent Cerebral Infarction and Periventricular Hyperintensities
Authors: Shima Hideaki , Ishimura Eiji , Naganuma Toshihide , Ichii Mitsuru , Yamasaki Takeshi , Mori Katsuhito , Nakatani Tatsuya , Inaba Masaaki
Published: June 2011

Background/Aims: Silent cerebral lacunar infarction (SCI) and periventricular hyperintensities (PVH) have been reported to be markers of ischemic cerebral small-vessel disease and risk factors for future cerebrovascular events in the general population. The relationship between CKD and SCI/PVH is examined. Methods: In this cross-sectional study, brain magnetic resonance imaging was performed with a 1.5-T system in 324 predialysis CKD patients and in 60 normal subjects. Results: SCI was found in 103 CKD patients (31.8%), and PVH was found in 174 CKD patients (53.7%). SCI/PVH were more prevalent in patients with higher blood pressure, advanced age and decreased kidney function. There was a significant association between the prevalence of SCI/PVH and the CKD stage, with greater prevalence of SCI/PVH as the CKD stage advanced (p < 0.0001). PVH grade also advanced as the CKD stage advanced. The estimated glomerular filtration rate was a significant factor associated with the presence of SCI/PVH, independent of any other factors. There was a strong association between the prevalence of SCI/PVH (p < 0.0001). Conclusion: In CKD patients, decreased kidney function is a significant factor associated with SCI/PVH, both of which are significantly associated with each other. These results suggest that CKD patients with SCI/PVH are at greater risk of future cerebrovascular events.
Genetic Evidence for a TatC Dimer at the Core of the Escherichia coli Twin Arginine (Tat) Protein Translocase
Authors: Maldonado Barbara , Buchanan Grant , Müller Matthias , Berks Ben C. , Palmer Tracy
Published: June 2011

The twin arginine protein transport (Tat) system transports folded proteins across the cytoplasmic membranes of prokaryotes and the thylakoid membranes of plant chloroplasts. In Escherichia coli, the TatB and TatC components form a multivalent receptor complex that binds Tat substrates. Here, we have used a genetic fusion approach to construct covalent TatC oligomers in order to probe the organisation of TatC. A fused dimer of TatC supported Tat transport activity and was fully stable in vivo. Inactivating point mutations in one or other of the TatC units in the fused TatC dimer did not inactivate TatC function, indicating that only one TatC protomer in the TatC fused dimer needs to be active. Larger covalent fusions of TatC also supported Tat transport activity but were degraded in vivo to release smaller TatC forms. Taken together, these results strongly suggest that TatC forms a functional dimer, and support the idea that there is an even number of TatC protomers in the TatBC complex.
Association Between Myocardial Infarction and Fractures
Authors: Gerber Yariv , Melton L. Joseph , Weston Susan A. , Roger Véronique L.
Published: June 2011

Background—

Data on the association between myocardial infarction (MI) and fractures are scarce. Recent changes in the epidemiology of MI justify exploring this relationship. We evaluated whether MI constitutes a risk factor for osteoporotic fracture and examined secular trends in this association.

Methods and Results—

Consecutive Olmsted County, Minnesota, residents with incident MI diagnosed in 1979 to 2006 and community control subjects individually matched (1:1) to cases on age, sex, and year of onset (n=6642) were followed up through 2009. Outcome measures were time to osteoporotic fracture, overall and by anatomic site, and death. Fracture incidence rates were stable in controls but increased markedly over time among MI cases. Accordingly, although an overall excess of fracture risk after MI was observed (adjusted hazard ratio, 1.32; 95% confidence interval, 1.12 to 1.56), substantial temporal variations were noted (1979 to 1989: hazard ratio, 0.81; 95% confidence interval, 0.58 to 1.12; 1990 to 1999: hazard ratio, 1.47; 95% confidence interval, 1.10 to 1.96; 2000 to 2006: hazard ratio, 1.73; 95% confidence interval, 1.32 to 2.27;
P
for trend <0.001). Trends were similar regardless of age, sex or fracture site. Conversely, the overall hazard ratio for death in MI cases versus controls did not change materially despite a continuous decline in 30-day case fatality rate (12.5% in 1979 to 1989; 6.7% in 2000 to 2006). Observed changes in the baseline prevalence of cardiovascular risk factors, MI characteristics, and comorbidities did not fully account for the trends in fracture risk.

Conclusions—

Over the past decades, the association between MI and osteoporotic fractures increased steadily. The trend is consistent with the displacement of post-MI outcomes toward noncardiovascular events, highlighting the need for comprehensive prevention strategies to accommodate the changing epidemiology of MI.
Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction
Authors: Guazzi Marco , Vicenzi Marco , Arena Ross , Guazzi Maurizio D.
Published: June 2011

Background—

The prevalence of heart failure with preserved ejection fraction is increasing. The prognosis worsens with pulmonary hypertension and right ventricular (RV) failure development. We targeted pulmonary hypertension and RV burden with the phosphodiesterase-5 inhibitor sildenafil.

Methods and Results—

Forty-four patients with heart failure with preserved ejection fraction (heart failure signs and symptoms, diastolic dysfunction, ejection fraction ≥50%, and pulmonary artery systolic pressure >40 mm Hg) were randomly assigned to placebo or sildenafil (50 mg thrice per day). At 6 months, there was no improvement with placebo, but sildenafil mediated significant improvements in mean pulmonary artery pressure (−42.0±13.0%) and RV function, as suggested by leftward shift of the RV Frank-Starling relationship, increased tricuspid annular systolic excursion (+69.0±19.0%) and ejection rate (+17.0±8.3%), and reduced right atrial pressure (−54.0±7.2%). These effects may have resulted from changes within the lung (reduced lung water content and improved alveolar-capillary gas conductance, +15.8±4.5%), the pulmonary vasculature (arteriolar resistance, −71.0±8.2%), and left-sided cardiac function (wedge pulmonary pressure, −15.7±3.1%; cardiac index, +6.0±0.9%; deceleration time, −13.0±1.9%; isovolumic relaxation time, −14.0±1.7%; septal mitral annulus velocity, −76.4±9.2%). Results were similar at 12 months.

Conclusions—

The multifaceted response to phosphodiesterase-5 inhibition in heart failure with preserved ejection fraction includes improvement in pulmonary pressure and vasomotility, RV function and dimension, left ventricular relaxation and distensibility (structural changes and/or ventricular interdependence), and lung interstitial water metabolism (wedge pulmonary pressure decrease improving hydrostatic balance and right atrial pressure reduction facilitating lung lymphatic drainage). These results enhance our understanding of heart failure with preserved ejection fraction and offer new directions for therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01156636.
Activation of Peroxisome Proliferator-Activated Receptor–δ Enhances Regenerative Capacity of Human Endothelial Progenitor Cells by Stimulating Biosynthesis of Tetrahydrobiopterin
Authors: He Tongrong , Smith Leslie A. , Lu Tong , Joyner Michael J. , Katusic Zvonimir S.
Published: June 2011

The mechanisms underlying the regenerative capacity of endothelial progenitor cells (EPCs) are not fully understood. We hypothesized that biosynthesis of tetrahydrobiopterin is an important mechanism responsible for the stimulatory effects of peroxisome proliferator-activated receptor–δ (PPARδ) activation on regenerative function of human EPCs. Treatment of human EPCs with a selective PPARδ agonist GW501516 for 24 hours increased the levels of mRNA, protein, and enzymatic activity of GTP cyclohydrolase I (GTPCH I), as well as the production of tetrahydrobiopterin. The effects of GW501516 were mediated by suppression of PTEN expression, thereby increasing phosphorylation of AKT. The AKT signaling also mediated GW501516-induced phosphorylation of endothelial NO synthase. In addition, activation of PPARδ significantly enhanced proliferation of EPCs. This effect was abolished by the GTPCH I inhibitor, 2,4-diamino-6-hydroxypyrimidine, or genetic inactivation of GTPCH I with small interfering RNA but not by inhibition of endothelial NO synthase with
N
G
-nitro-
l
-arginine methyl ester. Supplementation of NO did not reverse 2,4-diamino-6-hydroxypyrimidine-inhibited 5-bromodeoxyuridine incorporation. Furthermore, transplantation of human EPCs stimulated re-endothelialization in a mouse model of carotid artery injury. Pretreatment of EPCs with GW501516 significantly enhanced the ability of transplanted EPCs to repair denuded endothelium. GTPCH I-small interfering RNA transfection significantly inhibited in vivo regenerative capacity of EPCs stimulated with GW501516. Thus, in human EPCs, activation of PPARδ stimulates expression and activity of GTPCH I and biosynthesis of tetrahydrobiopterin via PTEN-AKT signaling pathway. This effect enhances the regenerative function of EPCs.
Enhancing Mobility in the European Neighborhood Policy? The Cases of Moldova and Georgia
Authors: Eisele Katharina , Wiesbrock Anja
Published: June 2011

In 2004, the EU launched the European Neighborhood Policy (ENP) with the objective of avoiding new dividing lines between the EU and its neighbors in the East and the South. This was offered as an alternative to full EU membership. The ENP is intended to bring about prosperity, stability, and security. In this context, the EU has agreed on a number of Action Plans on a bilateral basis with twelve ENP partner states. The mobility of persons is a key policy priority in the framework of the ENP, which is substantiated by the conclusion of 'mobility partnerships' with Moldova (2008) and Georgia (2009). Even though the Action Plans have been negotiated on the basis of 'joint ownership', it is arguable that EU interests have come to dominate the cooperation. The question arises to what extent these policy plans are beneficial for the neighboring countries and individual migrants. This article focuses on the rules and policy priorities contained in the Partnership and Cooperation Agreements, the Action Plans, the visa facilitation and readmission agreements, as well as the mobility partnerships concluded with Moldova and Georgia. The analysis unfolds that the main emphasis of the ENP is on border control and the fight against irregular migration, whereas little has been done to enhance legal migration opportunities. Therefore, we argue that the ENP falls short of meeting the objective to create cooperation based on mutual interest and joint ownership.
Evolutionary adaptation of oniscidean isopods to terrestrial life: Structure, physiology and behavior
Authors: Hornung Elisabeth
Published: June 2011

Terrestrial isopods (Oniscidea) are the most successful crustacean colonizers of land habitats. From an evolutionary point of view, they are excellent examples of model organisms that have adaptated to terrestrial life. Th e aquatic-terrestrial branching of the phylogenetic lines of the Oniscidea occurred in the marine littoral zone. Th e most oniscid species-rich areas are found in the circum-Mediterranean region. Studies on the morphology, physiology, ecology and biogeography of Oniscidea highlight the diversity of the group. Th ey successfully colonized a wide range of terrestrial habitats by solving such ecological and physiological challenges as reproduction, respiration, excretion and protection against desiccation. During terrestrial adaptation, they evolved diverse morphological, ecological and behavioral traits. Th is review summarizes our present knowledge of some aspects of the morphology, physiology and behavior as it related to oniscidean adaptation to the terrestrial realm.
Chronicle of a Frustration Foretold? The Implementation of a Broad Protection Agenda in the United Nations
Authors: Carvalho Benjamin de , Sande Lie Jon Harald
Published: June 2011

Although the Protection of Civilians (PoC) today is now loosely embedded in the UN system as a whole, a number of issues remain to be addressed at the institutional level for PoC to inform a shared culture of protection. These include a conceptual clarification of whether protection activities are the mission’s mandate per se or a mere part of its many tasks. If PoC is only one of many tasks, what is the raison d’être of peacekeeping missions? At headquarter level, two main challenges remain. How can PoC become part of a shared interagency culture, rather than remaining the sole prerogative or task of OCHA without thereby losing its institutional momentum, and how can UN DPKO take greater ownership to PoC without narrowing it down to mere physical protection? The process of implementation thus far shows that there is a risk that the rising primacy of a narrow conception of PoC – largely consistent with that held by military segments of peacekeeping – will be institutionalized at the expense of the broad concept advocated by OCHA. Finally, there needs to be clearer institutional mechanisms for learning from experience. As of today, the reporting from the field is largely lost to those drafting resolutions.
Salivary Gland Gene Expression Atlas Identifies a New Regulator of Branching Morphogenesis
Authors: Musselmann K. , Green J.A. , Sone K. , Hsu J.C. , Bothwell I.R. , Johnson S.A. , Harunaga J.S. , Wei Z. , Yamada K.M.
Published: June 2011

During organ development, local changes in gene expression govern morphogenesis and cell fate. We have generated a microanatomical atlas of epithelial gene expression of embryonic salivary glands. The mouse submandibular salivary gland first appears as a single mass of epithelial cells surrounded by mesenchyme, and it undergoes rapid branching morphogenesis to form a complex secretory organ with acini connected to an extensive ductal system. Using laser capture microdissection, we collected samples from 14 distinct epithelial locations at embryonic days 12.5, 13.5, 14, and 15, and characterized their gene expression by microarray analysis. These microarray results were evaluated by qPCR of biological replicates and by comparisons of the gene expression dataset with published expression data. Using this gene expression atlas to search for novel regulators of branching morphogenesis, we found a substantial reduction in mRNA levels of GSK3β at the base of forming clefts. This unexpected finding was confirmed by immunostaining, and inhibition of GSK3β activity enhanced salivary gland branching. This first microanatomical expression atlas of a developing gland characterizes changes in local gene expression during salivary gland development and differentiation, which should facilitate the identification of key genes involved in tissue morphogenesis.
The theoretical foundations of statistical learning theory based on fuzzy random samples in Sugeno measure space
Authors: Minghu Ha , Chao Wang , Pedrycz Witold
Published: June 2011

Statistical learning theory is regarded as an appropriate theory to deal with learning problems on small samples, and it has now become a novel research interest of the machine learning field. However, the theory is based on real-valued random samples and established on probability measure space; it rarely deals with learning problems based on fuzzy random samples and established on Sugeno measure space. It is well known that fuzzy random samples and Sugeno measure space are interesting and important extensions of real-valued random samples and probability measure space, respectively. Therefore, the statistical learning theory based on fuzzy random samples in Sugeno measure space is further discussed in this paper. Firstly, based on definitions of the distribution function and the expected value of fuzzy random variables in Sugeno measure space, the Hoeffding inequality of fuzzy random variables is proved. Secondly, for the sake of completeness of the paper, the key theorem of learning theory based on fuzzy random samples in Sugeno measure space is introduced. Finally, the bounds on the rate of uniform convergence of a learning process based on fuzzy random samples in Sugeno measure space are constructed.
Beyond the Geneticization Thesis
Authors: Pavone Vincenzo , Arias Flor
Published: June 2011

In the last decade, preimplantation genetic testing (preimplantation genetic diagnosis [PGD] and preimplantation genetic screening [PGS]) have become widely used and in 2005 constituted 5 percent of all in vitro fertilization (IVF) cycles performed in Europe. Their diffusion, however, is not homogenous; while in some countries they are prohibited and in others hardly implemented, Spain performs 33 percent of all the PGD/PGS. While policy guidelines and mainstream bioethics address PGD from a patient choice perspective, disability studies insist on PGD’s potentiality for discrimination. Alternatively, other authors have explored PGD/PGS from the perspective of geneticization but little work has been done on how PGD/PGS are framed by the members of national regulatory bodies. Combining the analysis of juridical documents with semistructured interviews with members of the Spanish National Assisted Reproduction Committee (CNRHA), this study suggests that the remarkable diffusion of PGD/PGS in Spain may be largely due to the interaction between the growing momentum enjoyed by embryonic stem cell research and a vibrant expansion of IVF business along the Mediterranean coast. In this process, genetic issues per se seem to play a minor role, although the prevention of genetic diseases now constitutes the master narrative underpinning the extension of PGD from monogenic, early onset, diseases to polygenic, late-onset, ones.