bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of ITPA Gene Polymorphisms and the Risk of Ribavirin-Induced Anemia in HIV/Hepatitis C Virus (HCV)-Coinfected Patients Receiving HCV Combination Therapy
Authors: Domingo Pere , Guardiola Josep M. , Salazar Juliana , Torres Ferran , Mateo M. Gracia , Pacho Cristina , del Mar Gutierrez M. , Lamarca Karuna , Fontanet Angels , Martin Jordi , Muñoz Jessica , Vidal Francesc , Baiget Montserrat
Published: March 2012

Polymorphisms of the ITPA gene have been associated with anemia during combination therapy in hepatitis C virus (HCV)-monoinfected patients. Our aim was to confirm this association in HIV/HCV-coinfected patients. In this prospective, observational study, 73 HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin (RBV) were enrolled. Two single nucleotide polymorphisms within or adjacent to the ITPA gene (rs1127354 and rs7270101) were genotyped. The associations between the ITPA genotype and anemia or treatment outcome were examined. Fifty-nine patients (80.8%) had CC at rs1127354, whereas 14 (19.2%) had a CA/AA ITPA genotype. Percent decreases from baseline hemoglobin level were significantly greater in patients with the CC genotype than in those with the CA/AA genotype at week 4 (
P
= 0.0003), week 12 (
P
< 0.0001), and week 36 (
P
= 0.0102) but not at the end of treatment. RBV dose reduction was more often needed in patients with the CC genotype than in those with the CA/AA genotype (odds ratio [OR] = 11.81; 95% confidence interval [CI] = 1.45 to 256.17;
P
= 0.0039), as was erythropoietin therapy (OR = 8.28; 95% CI = 1.04 to 371.12;
P
= 0.0057). Risk factors independently associated with percent hemoglobin nadir decrease were RBV dose reduction (OR = 11.72; 95% CI = 6.82 to 16.63;
P
< 0.001), baseline hemoglobin (OR = 1.69; 95% CI = 0.23 to 3.15;
P
= 0.024), and body mass index (OR = −0.7; 95% CI = −1.43 to 0.03;
P
= 0.061). ITPA polymorphism was not an independent predictor of sustained virological response. Polymorphisms at rs1127354 in the ITPA gene influence hemoglobin levels during combination HCV therapy and the need for RBV dose reduction and erythropoietin use in HIV/HCV-coinfected patients.
Mycobacterium tuberculosis Lacking All Mycolic Acid Cyclopropanation Is Viable but Highly Attenuated and Hyperinflammatory in Mice
Authors: Barkan Daniel , Hedhli Dorsaf , Yan Han-Guang , Huygen Kris , Glickman Michael S.
Published: March 2012

Mycolic acids, the major lipid of theMycobacterium tuberculosiscell wall, are modified by cyclopropane rings, methyl branches, and oxygenation through the action of eightS-adenosylmethionine (SAM)-dependent mycolic acid methyltransferases (MAMTs), encoded at four genetic loci. Mycolic acid modification has been shown to be important forM. tuberculosispathogenesis, in part through effects on the inflammatory activity of trehalose dimycolate (cord factor). Studies using the MAMT inhibitor dioctylamine have suggested that the MAMT enzyme class is essential forM. tuberculosisviability. However, it is unknown whether a cyclopropane-deficient strain ofM. tuberculosiswould be viable and what the effect of cyclopropane deficiency on virulence would be. We addressed these questions by creating and characterizingM. tuberculosisstrains lacking all functional MAMTs. Our results show thatM. tuberculosisis viable either without cyclopropanation or without cyclopropanation and any oxygenated mycolates. Characterization of these strains revealed that MAMTs are required for acid fastness and resistance to detergent stress. Complete lack of cyclopropanation confers severe attenuation during the first week after aerosol infection of the mouse, whereas complete loss of MAMTs confers attenuation in the second week of infection. Characterization of immune responses to the cyclopropane- and MAMT-deficient strains indicated that the net effect of mycolate cyclopropanation is to dampen host immunity. Taken together, our findings establish the immunomodulatory function of the mycolic acid modification pathway in pathogenesis and buttress this enzyme class as an attractive target for antimycobacterial drug development.
Receptor-Dependent and -Independent Immunomodulatory Effects of Phenol-Soluble Modulin Peptides from Staphylococcus aureus on Human Neutrophils Are Abrogated through Peptide Inactivation by Reactive Oxygen Species
Authors: Forsman Huamei , Christenson Karin , Bylund Johan , Dahlgren Claes
Published: March 2012

The virulence and pathogenesis mechanisms of community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) strains depend on a newly described group of phenol-soluble modulin (PSM) peptides (the PSMα peptides) with cytolytic activity. These toxins are α-helical peptides with a formyl group at the N terminus, and they activate neutrophils through formyl peptide receptor 2 (FPR2), a function closely correlated to the capacity of staphylococcal species to cause invasive infections. The effects of two synthetic PSMα peptides were investigated, and we show that they utilize FPR2 and promote neutrophils to produce reactive oxygen species (ROS) which in turn trigger inactivation of the peptides. Independently of FPR2, the PSMα peptides also downregulate the neutrophil response to other stimuli and exert a cytolytic effect to which apoptotic neutrophils are more sensitive than viable cells. The novel immunomodulatory functions of the PSMα peptides were sensitive to ROS generated by the neutrophil myeloperoxidase (MPO)-H2O2system, suggesting a role for this enzyme system in counteracting bacterial virulence.
Multigene Families in Trypanosoma cruzi and Their Role in Infectivity
Authors: De Pablos Luis Miguel , Osuna Antonio
Published: March 2012

TheTrypanosoma cruzigenome contains the most widely expanded content (∼12,000 genes) of the trypanosomatids sequenced to date. This expansion is reflected in the high number of repetitive sequences and particularly in the large quantity of genes that make up its multigene families. Recently it was discovered that the contents of these families vary between phylogenetically unrelated strains. We review the basic characteristics of trans-sialidases and mucins as part of the mechanisms of immune evasion ofT. cruziand as ligands and factors involved in the cross talk between the host cell and the parasite. We also show recently published data describing two new multigene families, DGF-1 and MASP, that form an important part of the scenario representing the complex biology ofT. cruzi.
PmpG
303-311
, a Protective Vaccine Epitope That Elicits Persistent Cellular Immune Responses in Chlamydia muridarum-Immune Mice
Authors: Johnson Raymond M. , Yu Hong , Kerr Micah S. , Slaven James E. , Karunakaran Karuna P. , Brunham Robert C.
Published: March 2012

Urogenital
Chlamydia
serovars replicating in reproductive epithelium pose a unique challenge to host immunity and vaccine development. Previous studies have shown that CD4 T cells are necessary and sufficient to clear primary
Chlamydia muridarum
genital tract infections in the mouse model, making a protective CD4 T cell response a logical endpoint for vaccine development. Our previous proteomics studies identified 13 candidate
Chlamydia
proteins for subunit vaccines. Of those, PmpG-1 is the most promising vaccine candidate. To further that work, we derived a PmpG
303-311
-specific multifunctional Th1 T cell clone, designated PmpG1.1, from an immune C57BL/6 mouse and used it to investigate the presentation of the PmpG
303-311
epitope by infected epithelial cells. Epithelial presentation of the PmpG
303-311
epitope required bacterial replication, occurred 15 to 18 h postinfection, and was unaffected by gamma interferon (IFN-γ) pretreatment. Unlike epitopes recognized by other
Chlamydia
-specific CD4 T cell clones, the PmpG
303-311
epitope persisted on splenic antigen-presenting cells (APC) of mice that cleared primary genital tract infections. PmpG1.1 was activated by unmanipulated irradiated splenocytes from immune mice without addition of exogenous
Chlamydia
antigen, and remarkably, activation of PmpG1.1 by unmanipulated immune splenocytes was stronger 6 months postinfection than it was 3 weeks postinfection. Enhanced presentation of PmpG
303-311
epitope on splenic APC 6 months postinfection reflects some type of “consolidation” of a protective immune response. Understanding the antigen-presenting cell populations responsible for presenting PmpG
303-311
early (3 weeks) and late (6 months) postinfection will likely provide important insights into stable protective immunity against
Chlamydia
infections of the genital tract.
A case–control study examining whether neurological deficits and PTSD in combat veterans are related to episodes of mild TBI
Authors: Ruff Robert Louis , Riechers Ronald George , Wang Xiao-Feng , Piero Traci , Ruff Suzanne Smith
Published: March 2012

Background

Mild traumatic brain injury (mTBI) is a common injury among military personnel serving in Iraq or Afghanistan. The impact of repeated episodes of combat mTBI is unknown.

Objective

To evaluate relationships among mTBI, post-traumatic stress disorder (PTSD) and neurological deficits (NDs) in US veterans who served in Iraq or Afghanistan.

Methods

This was a case–control study. From 2091 veterans screened for traumatic brain injury, the authors studied 126 who sustained mTBI with one or more episodes of loss of consciousness (LOC) in combat. Comparison groups: 21 combat veterans who had definite or possible episodes of mTBI without LOC and 21 veterans who sustained mTBI with LOC as civilians.

Results

Among combat veterans with mTBI, 52% had NDs, 66% had PTSD and 50% had PTSD and an ND. Impaired olfaction was the most common ND, found in 65 veterans. The prevalence of an ND or PTSD correlated with the number of mTBI exposures with LOC. The prevalence of an ND or PTSD was >90% for more than five episodes of LOC. Severity of PTSD and impairment of olfaction increased with number of LOC episodes. The prevalence of an ND for the 34 combat veterans with one episode of LOC (4/34=11.8%) was similar to that of the 21 veterans of similar age and educational background who sustained civilian mTBI with one episode of LOC (2/21=9.5%, p-NS).

Conclusions

Impaired olfaction was the most frequently recognised ND. Repeated episodes of combat mTBI were associated with increased likelihood of PTSD and an ND. Combat setting may not increase the likelihood of an ND. Two possible connections between mTBI and PTSD are (1) that circumstances leading to combat mTBI likely involve severe psychological trauma and (2) that altered cerebral functioning following mTBI may increase the likelihood that a traumatic event results in PTSD.
PARALLEL ALGORITHMS FOR MAPPING SHORT DEGENERATE AND WEIGHTED DNA SEQUENCES TO A REFERENCE GENOME
Authors: ILIOPOULOS COSTAS S. , MILLER MIRKA , PISSIS SOLON P.
Published: March 2012

One of the most ambitious trends in current biomedical research is the large-scale genomic sequencing of patients. Novel high-throughput (or next-generation) sequencing technologies have redefined the way genome sequencing is performed. They are able to produce millions of short sequences (reads) in a single experiment, and with a much lower cost than previously possible. Due to this massive amount of data, efficient algorithms for mapping these sequences to a reference genome are in great demand, and recently, there has been ample work for publishing such algorithms. One important feature of these algorithms is the support of multithreaded parallel computing in order to speedup the mapping process. In this paper, we design parallel algorithms, which make use of the message-passing parallelism model, to address this problem efficiently. The proposed algorithms also take into consideration the probability scores assigned to each base for occurring in a specific position of a sequence. In particular, we present parallel algorithms for mapping short degenerate and weighted DNA sequences to a reference genome.
FINDING CHARACTERISTIC SUBSTRINGS FROM COMPRESSED TEXTS
Authors: INENAGA SHUNSUKE , BANNAI HIDEO
Published: March 2012

Text mining from large scaled data is of great importance in computer science. In this paper, we consider fundamental problems on text mining from compressed strings, i.e., computing a longest repeating substring, longest non-overlapping repeating substring, most frequent substring, and most frequent non-overlapping substring from a given compressed string. Also, we tackle the following novel problem: given a compressed text and compressed pattern, compute the representative of the equivalence class of the pattern w.r.t. the text. We present algorithms that solve the above problems in time polynomial in the size of input compressed strings. The compression scheme we consider is straight line program (SLP) which has exponential compression, and therefore our algorithms are more efficient than any existing algorithms that require decompression of given SLPs.
ASYMPTOTIC BEHAVIOUR OF THE MAXIMAL NUMBER OF SQUARES IN STANDARD STURMIAN WORDS
Authors: PIATKOWSKI MARCIN , RYTTER WOJCIECH
Published: March 2012

Denote by sq(w) the number of distinct squares in a string w and let [Formula: see text] be the class of standard Sturmian words. They are generalizations of Fibonacci words and are important in combinatorics on words. For Fibonacci words the asymptotic behaviour of the number of runs and the number of squares is the same. We show that for Sturmian words the situation is quite different. The tight bound [Formula: see text] for the number of runs was given in [3]. In this paper we show that the tight bound for the maximal number of squares is [Formula: see text]. We use the results of [11], where exact (but not closed) complicated formulas were given for sq(w) for [Formula: see text]. We show that for all [Formula: see text] we have [Formula: see text] and there is an infinite sequence of words [Formula: see text] such that lim k→∞ |wk| = ∞ and [Formula: see text].

Surprisingly the maximal number of squares is reached by the words with recurrences of length only 5. This contrasts with the situation of Fibonacci words, though standard Sturmian words are natural extension of Fibonacci words. If this length drops to 4, the asymptotic behaviour of the maximal number of squares falls down significantly below [Formula: see text]. The structure of Sturmian words rich in squares has been discovered by us experimentally and verified theoretically. The upper bound is much harder, its proof is not a matter of simple calculations. The summation formulas for the number of squares are complicated, no closed formula is known. Some nontrivial reductions were necessary.
DIRECT RECIPROCITY-BASED COOPERATION IN MOBILE AD HOC NETWORKS
Authors: SEREDYNSKI MARCIN , BOUVRY PASCAL
Published: March 2012

A distributed nature of a wireless mobile ad hoc network, lack of a single authority, and limited battery resources of participating devices may lead its users to be reluctant to packet relaying duties. This paper investigates potential networking conditions that could lead to a direct reciprocity-based cooperation on packet relaying. Simulation of behaviour of the network is carried out using an evolutionary game-theoretical approach. A game-based model of nodes' interactions coupled with a genetic algorithm is used to find successful relaying strategies for various networking conditions. Computational experiments demonstrate that the reciprocity-based packet relaying is an efficient way to overcome the social dilemma present in such a network. However, in the presence of a large number of unconditionally cooperatives nodes a selfish permanent defection strategy is more efficient than a reciprocal tit-for-tat strategy. Nevertheless the switch from cooperative to selfish behaviour among some users does not change significantly the overall performance of the network as the negative consequences of the switch are compensated by the generous packet relaying contribution of unconditionally cooperative nodes.
COMPARATIVE STUDY OF DIFFERENT MICRO-THERMAL ACTUATORS FOR MICRO-ELECTRO-MECHANICAL-SYSTEM APPLICATION
Authors: PATOWARI P. K. , NATH M. M. , BHARALI A. S. , GOGOI J. , SINGH C. K.
Published: March 2012

This paper presents a comparative study of three micro-thermal actuators, which differ in their construction and material being used. Model-I is the basic model and Model-II and Model-III are developed with a view to achieve improved performance over Model-I. The main objective of this analysis is to achieve greater deflection from the considered actuator models under a range of applied voltages. Apart from deflection analysis, analyses for temperature distribution and stress developed in the actuator models are also carried out for feasibility study. The materials under consideration are poly-silicon, single crystal silicon, and titanium. The software used for modeling and simulation is Comsol Multiphysics.
MOLTEN SALT ASSISTED SYNTHESIS OF LUTETIUM SILICATE NANOPARTICLES
Authors: TANG XIAOPING , GAO YANFENG , CHEN HONGFEI , LUO HONGJIE
Published: March 2012

Lutetium disilicate (Lu2Si2O7) powders were prepared by a molten salt synthesis method. The effects of calcination temperature, reaction time, and surfactants on the properties of powders were investigated. The results revealed that with molten salts Lu2Si2O7 can be formed at 800°C. The particle size and morphology can be controlled by adding surfactants and changing reaction times. The formation mechanism and stability of Lu2Si2O7 structures were also discussed. The developed method for the synthesis of Lu2Si2O7 may pave the way for its application as environmental barrier coating materials.
SELF-ASSEMBLY OF BISMUTH SELENIDE TWO-DIMENSIONAL SUPERSTRUCTURE FROM HEXAGONAL NANOSHEETS
Authors: SHEN JUNJIE , SUN QIAN , ZHU TIEJUN , ZHAO XINBING
Published: March 2012

A kind of novel superstructure array composed of hexagonal Bi2Se3 nanosheets were fabricated via a facile hydrothermal method. The structure was characterized by X-ray diffraction and field emission scanning electron micrioscopy. It is suggested that the two dimensional superstructure was self-assembled by sheet-like Bi2Se3 building blocks on naturally-formed Bi2SeO2 precusor template. The present result indicates one promising way in design and growth of self-assembled superstructures by controllable crystal growth from deoxided substrates with good lattice match.
EFFECT OF Nd-DOPING ON THE NANOCRYSTALLITE SIZE AND MICROWAVE ABSORPTION PROPERTIES OF Sr-HEXAFERRITE
Authors: KHANMOHAMMADI H. , EBRAHIMI S. A. SEYYED
Published: March 2012

Nd -doped M -type Strontium hexaferrite powders with composition of Sr 1-x Nd x Fe 12 O 19(x = 0, 0.1, 0.2) were prepared by conventional ceramic method at various calcination temperatures. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used for characterization of the obtained powders. The results showed that by increasing Nd doping, the single phase magnetoplumbite structure has been formed at higher temperatures. The average crystallite size of the samples calculated by the Scherrer formula indicates that Nd -doping resulted in a significant decrease in the mean crystallite size. The hexaferrite-polymer bulk composites in epoxy resin matrix, with ferrite ratio of 90 wt.%, were also prepared. The microwave absorption properties of these composites were investigated in 8–12 GHz frequency range by means of a vector network analyzer. Due to the reflection loss measurements, Nd -doped Sr -hexaferrite could be a promising material for microwave absorption applications in X-band.
Er3+ INFRARED PHOTO- AND ELECTRO-LUMINESCENCE FROM Er-DOPED Si-RICH SILICON NITRIDE FILMS WITH VARYING Si AND Er CONTENTS
Authors: YIN YANG , XU WANJIN , RAN GUANGZHAO , QIN GUOGANG , ZHANG BIN
Published: March 2012

Both Er -doped Si -rich silicon nitride ( Er : Si 3(1+x) N 4) films and electroluminescence (EL) devices with structure of indium tin oxide/ Er : Si 3(1+x) N 4/ p-Si with varying Si and Er contents have been fabricated by reactive magnetron sputtering technique. We have investigated the effects of the excess Si content in a wide range (x from 0 to 2.1) on the Er3+ 1.54 μm photoluminescence (PL), EL and the electrical transport of the Er : Si 3(1+x) N 4 films. It is found that the Er 3+ 1.54 μm PL intensity of the Er : Si 3(1+x) N 4 films and the EL power efficiency of the Er : Si 3(1+x) N 4 devices exhibit strong dependences on x and are enhanced by one to two orders of magnitude around x = 0.27 and x = 0.53, respectively. The Er concentration also has a great influence on both Er 3+ 1.54 μm PL and EL of the Er:Si 3(1+x) N 4 films. The optimum Er concentrations for PL and EL in the Er:Si 3(1+x) N 4 films with x = 0.53 are both ~3 at.%.
ELECTRICAL ACTIVATION OF THERMO-RESPONSIVE PVC-CFRP LAMINATE ACTUATORS
Authors: TAMAGAWA HIROHISA , LIN WENYI , SASAKI MINORU
Published: March 2012

A bimorph actuator of PVC-CFRP laminate (PVC: polyvinylchloride; CFRP: carbon fiber reinforced plastic) is fabricated, where its bending results from the large disparity between the coefficients of thermal expansion of PVC and CFRP. Thermal expansion is brought about by applying a voltage to the CFRP layer of the PVC-CFRP laminate to generate Joule heat. Thus, the PVC-CFRP laminate acts as an electroactive polymer actuator. The authors experimentally confirmed that laminate temperature due to Joule heat completely determines laminate deflection curvature, and also demonstrated that temperature determines the blocking force generated by PVC-CFRP laminate.
PHASE STRUCTURE, PIEZOELECTRIC AND MULTIFERRIOC BEHAVIOR OF (K0.48Na0.52)NbO3-Co2O3 PIEZOELECTRIC CERAMICS
Authors: WU WENJUAN , XIAO DINGQUAN , WU JIAGANG , LI JING , ZHU JIANGUO
Published: March 2012

( K 0.48 Na 0.52) NbO 3-x% Co 2 O 3 (x = 0, 0.03 and 0.05) (KNN-x% Co2O3 ) lead-free piezoelectric ceramics were prepared by the conventional solid-state sintering method. An orthorhombic phase was observed for all KNN-x% Co2O3 ceramics at room temperature, and two phase transitions were confirmed by the high temperature X-ray diffraction and the temperature dependence of the dielectric constant. The Co2O3 greatly improves the density and decreases the sintering temperature of KNN ceramics. The KNN-0.05 mol%Co2O3 ceramic exhibits good properties (d33 = 120 pC/N , k p = 0.41, Q m = 213 and T c = 407°C) and a good age stability. The multiferroic behavior was also observed at room temperature for the KNN-0.05 mol%Co2O3 ceramic, as confirmed by P–E loops and magnetic behavior.
Variations in rifting style and structure of the Scotian margin, Atlantic Canada, from 3D gravity inversion
Authors: Dehler S. A. , Welford J. K.
Published: March 2012

Regional gravity data and a three-dimensional (3D) inversion approach were used to examine variations in crustal thickness and to extend seismic-based interpretations along the Scotian margin, Atlantic Canada. Constraints on Moho, crust and sedimentary layers were based on seismic refraction models and profiles of deep multichannel seismic data. A subsurface 3D density anomaly distribution was developed, using initial constraints from bathymetric data and seismic basement depth estimates, and inverting for crustal and subcrustal geometries. Predictions from the model include regional maps of Moho structure, crustal thickness and stretching factor. Depth slices allow comparison with seismic interpretations along three transects. The model predictions of variable width of crustal extension and northward thinning of oceanic crust agree with the seismic profiles. The density anomaly model shows significantly greater thinning and numerous block faulting beneath the northern margin and more uniform thinning to the SW. The fairly sharp transition between the two regions may be explained by a transfer zone separating different rifting regimes.
A Precise Method-Method Interaction-Based Cohesion Metric for Object-Oriented Classes
Authors: Al Dallal Jehad , Briand Lionel C.
Published: March 2012

The building of highly cohesive classes is an important objective in object-oriented design. Class cohesion refers to the relatedness of the class members, and it indicates one important aspect of the class design quality. A meaningful class cohesion metric helps object-oriented software developers detect class design weaknesses and refactor classes accordingly. Several class cohesion metrics have been proposed in the literature. Most of these metrics are applicable based on low-level design information such as attribute references in methods. Some of these metrics capture class cohesion by counting the number of method pairs that share common attributes. A few metrics measure cohesion more precisely by considering the degree of interaction, through attribute references, between each pair of methods. However, the formulas applied by these metrics to measure the degree of interaction cause the metrics to violate important mathematical properties, thus undermining their construct validity and leading to misleading cohesion measurement. In this paper, we propose a formula that precisely measures the degree of interaction between each pair of methods, and we use it as a basis to introduce a low-level design class cohesion metric (LSCC). We verify that the proposed formula does not cause the metric to violate important mathematical properties. In addition, we provide a mechanism to use this metric as a useful indicator for refactoring weakly cohesive classes, thus showing its usefulness in improving class cohesion. Finally, we empirically validate LSCC. Using four open source software systems and eleven cohesion metrics, we investigate the relationship between LSCC, other cohesion metrics, and fault occurrences in classes. Our results show that LSCC is one of three metrics that explains more accurately the presence of faults in classes. LSCC is the only one among the three metrics to comply with important mathematical properties, and statistical analysis shows it captures a measurement dimension of its own. This suggests that LSCC is a better alternative, when taking into account both theoretical and empirical results, as a measure to guide the refactoring of classes. From a more general standpoint, the results suggest that class quality, as measured in terms of fault occurrences, can be more accurately explained by cohesion metrics that account for the degree of interaction between each pair of methods.
Weak Alphabet Merging of Partial Behavior Models
Authors: Fischbein Dario , D’Ippolito Nicolas , Brunet Greg , Chechik Marsha , Uchitel Sebastian
Published: March 2012

Constructing comprehensive operational models of intended system behavior is a complex and costly task, which can be mitigated by the construction of partial behavior models, providing early feedback and subsequently elaborating them iteratively. However, how should partial behavior models with different viewpoints covering different aspects of behavior be composed? How should partial models of component instances of the same type be put together? In this article, we propose
model merging
of modal transition systems (MTSs) as a solution to these questions. MTS models are a natural extension of labelled transition systems that support explicit modeling of what is currently unknown about system behavior. We formally define model merging based on weak alphabet refinement, which guarantees property preservation, and show that merging consistent models is a process that should result in a minimal common weak alphabet refinement (MCR). In this article, we provide theoretical results and algorithms that support such a process. Finally, because in practice MTS merging is likely to be combined with other operations over MTSs such as parallel composition, we also study the algebraic properties of merging and apply these, together with the algorithms that support MTS merging, in a case study.
An Approach for Modeling Architectural Design Rules in UML and its Application to Embedded Software
Authors: Mattsson Anders , Fitzgerald Brian , Lundell Björn , Lings Brian
Published: March 2012

Current techniques for modeling software architecture do not provide sufficient support for modeling architectural design rules. This is a problem in the context of model-driven development in which it is assumed that major design artifacts are represented as formal or semi-formal models. This article addresses this problem by presenting an approach to modeling architectural design rules in UML at the abstraction level of the meaning of the rules. The high abstraction level and the use of UML makes the rules both amenable to automation and easy to understand for both architects and developers, which is crucial to deployment in an organization. To provide a proof-of-concept, a tool was developed that validates a system model against the architectural rules in a separate UML model. To demonstrate the feasibility of the approach, the architectural design rules of an existing live industrial-strength system were modeled according to the approach.
Symbolic Message Sequence Charts
Authors: Roychoudhury Abhik , Goel Ankit , Sengupta Bikram
Published: March 2012

Message sequence charts (MSCs) are a widely used visual formalism for scenario-based specifications of distributed reactive systems. In its conventional usage, an MSC captures an interaction snippet between
concrete
objects in the system. This leads to voluminous specifications when the system contains several objects that are behaviorally similar. MSCs also play an important role in the model-based testing of reactive systems, where they may be used for specifying (partial) system behaviors, describing test generation criteria, or representing test cases. However, since the number of processes in a MSC specification are fixed, model-based testing of systems consisting of process classes may involve a significant amount of rework: for example, reconstructing system models, or regenerating test cases for systems differing only in the number of processes of various types.

In this article we propose a scenario-based notation, called symbolic message sequence charts (SMSCs), for modeling, simulation, and testing of process classes. SMSCs are a lightweight syntactic and semantic extension of MSCs where, unlike MSCs, a SMSC lifeline can denote some/all objects from a collection. Our extensions give us substantially more modeling power. Moreover, we present an abstract execution semantics for (structured collections of) SMSCs. This allows us to validate MSC-based system models capturing interactions between large, or even unbounded, number of objects. Finally, we describe a SMSC-based testing methodology for process classes, which allows generation of test cases for new object configurations with minimal rework.

Since our SMSC extensions are only concerned with MSC lifelines, we believe that they can be integrated into existing standards such as UML 2.0. We illustrate our SMSC-based framework for modeling, simulation, and testing of process classes using a weather-update controller case-study from NASA.
Verification and Validation of UML Conceptual Schemas with OCL Constraints
Authors: Queralt Anna , Teniente Ernest
Published: March 2012

To ensure the quality of an information system, it is essential that the conceptual schema that represents the knowledge about its domain is semantically correct. The semantic correctness of a conceptual schema can be seen from two different perspectives. On the one hand, from the point of view of its definition, a conceptual schema must be
right
. This is ensured by means of verification techniques that check whether the schema satisfies several correctness properties. On the other hand, from the point of view of the requirements that the information system should satisfy, a schema must also be
the right one
. This is ensured by means of validation techniques, which help the designer understand the exact meaning of a schema and to see whether it corresponds to the requirements. In this article we propose an approach to verify and validate UML conceptual schemas, with arbitrary constraints formalized in OCL. We have also implemented our approach to show its feasibility.
On the exploitation of a high-throughput SHA-256 FPGA design for HMAC
Authors: Michail Harris E. , Athanasiou George S. , Kelefouras Vasilis , Theodoridis George , Goutis Costas E.
Published: March 2012

High-throughput and area-efficient designs of hash functions and corresponding mechanisms for Message Authentication Codes (MACs) are in high demand due to new security protocols that have arisen and call for security services in every transmitted data packet. For instance, IPv6 incorporates the IPSec protocol for secure data transmission. However, the IPSec's performance bottleneck is the HMAC mechanism which is responsible for authenticating the transmitted data. HMAC's performance bottleneck in its turn is the underlying hash function. In this article a high-throughput and small-size SHA-256 hash function FPGA design and the corresponding HMAC FPGA design is presented. Advanced optimization techniques have been deployed leading to a SHA-256 hashing core which performs more than 30% better, compared to the next better design. This improvement is achieved both in terms of throughput as well as in terms of throughput/area cost factor. It is the first reported SHA-256 hashing core that exceeds 11Gbps (after place and route in Xilinx Virtex 6 board).
A novel framework for exploring 3-D FPGAs with heterogeneous interconnect fabric
Authors: Siozios Kostas , Pavlidis Vasilis F. , Soudris Dimitrios
Published: March 2012

A heterogeneous interconnect architecture can be a useful approach for the design of 3-D FPGAs. A methodology to investigate heterogeneous interconnection schemes for 3-D FPGAs under different 3-D fabrication technologies is proposed. Application of the proposed methodology on benchmark circuits demonstrates an improvement in delay, power consumption, and total wire-length of approximately 41%, 32%, and 36%, respectively, as compared to 2-D FPGAs. These improvements are additional to reducing the number of interlayer connections. The fewer interlayer connections are traded off for a higher yield. An area model to evaluate this trade-off is presented. Results indicate that a heterogeneous 3-D FPGA requires 37% less area as compared to a homogeneous 3-D FPGA. Consequently, the heterogeneous FPGAs can exhibit a higher manufacturing yield. A design toolset is also developed to support the design and exploration of various performance metrics for the proposed 3-D FPGAs.
Dark innovation
Authors: Denning Peter J.
Published: March 2012

As computing technologists, we tend to think of innovations in terms of new products or services supported by, or made of, computing technologies. But there are other types of innovation besides products. There are process innovations, such as McDonald's method of making hamburgers fast; social innovations, such as Mothers Against Drunk Driving; and business model innovations, such as Starbucks replacing a coffee shop with an Internet cafe. In all these categories, we tend to think of innovations as new ways of doing things that positively impact many people.
Systems Science Methods in Public Health: Dynamics, Networks, and Agents
Authors: Luke Douglas A. , Stamatakis Katherine A.
Published: March 2012

Complex systems abound in public health. Complex systems are made up of heterogeneous elements that interact with one another, have emergent properties that are not explained by understanding the individual elements of the system, persist over time, and adapt to changing circumstances. Public health is starting to use results from systems science studies to shape practice and policy, for example in preparing for global pandemics. However, systems science study designs and analytic methods remain underutilized and are not widely featured in public health curricula or training. In this review we present an argument for the utility of systems science methods in public health, introduce three important systems science methods (system dynamics, network analysis, and agent-based modeling), and provide three case studies in which these methods have been used to answer important public health science questions in the areas of infectious disease, tobacco control, and obesity.
Toward a Systems Approach to Enteric Pathogen Transmission: From Individual Independence to Community Interdependence
Authors: Eisenberg Joseph N.S. , Trostle James , Sorensen Reed J.D. , Shields Katherine F.
Published: March 2012

Diarrheal disease is still a major cause of mortality and morbidity worldwide; thus a large body of research has been produced describing its risks. We review more than four decades of literature on diarrheal disease epidemiology. These studies detail a progression in the conceptual understanding of transmission of enteric pathogens and demonstrate that diarrheal disease is caused by many interdependent pathways. However, arguments by diarrheal disease researchers in favor of attending to interaction and interdependencies have only recently yielded more formal systems-level approaches. Therefore, interdependence has not yet been highlighted in significant new research initiatives or policy decisions. We argue for a systems-level framework that will contextualize transmission and inform prevention and control efforts so that they can integrate transmission pathways. These systems approaches should be employed to account for community effects (i.e., interactions among individuals and/or households).
Conceptual Approaches to the Study of Health Disparities
Authors: Diez Roux Ana V.
Published: March 2012

Scientific and policy interest in health disparities, defined as systematic, plausibly avoidable health differences adversely affecting socially disadvantaged groups, has increased markedly over the past few decades. Like other research, research in health disparities is strongly influenced by the underlying conceptual model of the hypothetical causes of disparities. Conceptual models are important and a major source of debate because multiple types of factors and processes may be involved in generating disparities, because different disciplines emphasize different types of factors, and because the conceptual model often drives what is studied, how results are interpreted, and which interventions are identified as most promising. This article reviews common conceptual approaches to health disparities including the genetic model, the fundamental cause model, the pathways model, and the interaction model. Strengths and limitations of the approaches are highlighted. The article concludes by outlining key elements and implications of an integrative systems-based conceptual model.
Advertising of Prescription-Only Medicines to the Public: Does Evidence of Benefit Counterbalance Harm?
Authors: Mintzes Barbara
Published: March 2012

Since the global withdrawal of rofecoxib (Vioxx) in 2004, concerns about public health effects of direct-to-consumer advertising (DTCA) have grown. A systematic review of the research evidence on behavioral, health, and cost effects, published in 2005, found four studies meeting inclusion criteria, which showed that DTCA increases prescribing volume and patient demand, and shifts prescribing. From 2005 to 2010, nine studies met similar criteria. These largely confirm previous results. Additional effects include a shift to less appropriate prescribing, differential effects by patient price sensitivity and drug type, switches to less cost-effective treatment, and sustained sales despite a price increase. Claimed effects on adherence do not stand up to scrutiny and are based mainly on negative trials. There is no evidence of improved treatment quality or early provision of needed care. If policy is to be informed by evidence, the strength of research methods and ability to assess causality need to be considered.
Early Intervention to Reduce the Global Health and Economic Burden of Major Depression in Older Adults
Authors: Reynolds Charles F. , Cuijpers Pim , Patel Vikram , Cohen Alex , Dias Amit , Chowdhary Neerja , Okereke Olivia I. , Amanda Dew Mary , Anderson Stewart J. , Mazumdar Sati , Lotrich Frank , Albert Steven M.
Published: March 2012

Randomized trials for selective and indicated prevention of depression in both mixed-aged and older adult samples, conducted in high-income countries (HICs), show that rates of incident depression can be reduced by 20–25% over 1–2 years through the use of psychoeducational and psychological interventions designed to increase protective factors. Recurrence of major depression can also be substantially reduced through both psychological and psychopharmacological strategies. Additional research is needed, however, to address the specific issues of depression prevention in older adults in low- and middle-income countries (LMICs). The growing number of older adults globally, as well as workforce issues and the expense of interventions, makes it important to develop rational, targeted, and cost-effective risk-reduction strategies. In our opinion, one strategy to address these issues entails the use of lay health counselors (LHCs), a form of task shifting already shown to be effective in the treatment of common mental disorders in LMICs. We suggest in this review that the time is right for research into the translation of depression-prevention strategies for use in LMICs.
The Methods of Comparative Effectiveness Research
Authors: Sox Harold C. , Goodman Steven N.
Published: March 2012

This review describes methods used in comparative effectiveness research (CER). The aim of CER is to improve decisions that affect medical care at the levels of both policy and the individual. The key elements of CER are (a) head-to-head comparisons of active treatments, (b) study populations typical of day-to-day clinical practice, and (c) a focus on evidence to inform care tailored to the characteristics of individual patients. These requirements will stress the principal methods of CER: observational research, randomized trials, and decision analysis. Observational studies are especially vulnerable because they use data that directly reflect the decisions made in usual practice. CER will challenge researchers and policy makers to think deeply about how to extract more actionable information from the vast enterprise of the daily practice of medicine. Fortunately, the methods are largely applicable to research in the public health system, which should therefore benefit from the intense interest in CER.
Public Health and the Epidemic of Incarceration
Authors: Dumont Dora M. , Brockmann Brad , Dickman Samuel , Alexander Nicole , Rich Josiah D.
Published: March 2012

An unprecedented number of Americans have been incarcerated in the past generation. In addition, arrests are concentrated in low-income, predominantly nonwhite communities where people are more likely to be medically underserved. As a result, rates of physical and mental illnesses are far higher among prison and jail inmates than among the general public. We review the health profiles of the incarcerated; health care in correctional facilities; and incarceration's repercussions for public health in the communities to which inmates return upon release. The review concludes with recommendations that public health and medical practitioners capitalize on the public health opportunities provided by correctional settings to reach medically underserved communities, while simultaneously advocating for fundamental system change to reduce unnecessary incarceration.
Speed Limits, Enforcement, and Health Consequences
Authors: Elvik Rune
Published: March 2012

This review summarizes current knowledge regarding the effects of speed limit enforcement on public health. Speed limits are commonly used around the world to regulate the maximum speed at which motor vehicles can be operated on public roads. Speed limits are statutory, and violations of them are normally sanctioned by means of fixed penalties (traffic tickets) or, in the event of serious violations, suspension of the driver's license and imposition of prison sentences. Speed limit violations are widespread in all countries for which statistics can be found. Speeding contributes more to the risk of traffic injury than do other risk factors for which estimates of population-attributable risk are available. Traffic speed strongly influences impact speed in crashes and therefore has major implications for public health.
The Hurrider I Go the Behinder I Get: The Deteriorating International Ranking of U.S. Health Status
Authors: Bezruchka Stephen
Published: March 2012

The health of societies can be measured by a range of mortality indicators, and comparisons of national parameters with those of other societies can be symbolic of health status and progress. Over the past century, health outcomes have been steadily improving almost everywhere in the world, but the rates of improvements have varied. In the 1950s, the United States, having among the lowest mortality and other indicators of good health, ranked well among nations. Since then, the United States has not seen the scale of improvements in health outcomes enjoyed by most other developed countries, despite spending increasing amounts of its economy on health care services. Trends in personal health-related behaviors are only part of the explanation. Structural factors related to inequality and conditions of early life are important reasons for the relative stagnation in health. Reversing this relative decline would require a major national coordinated long-term effort to expose the problem and create the political will to address it.
Health Disparities Research in Global Perspective: New Insights and New Directions
Authors: Kumanyika Shiriki
Published: March 2012

This commentary introduces this volume's symposium on “Comparative Approaches to Reducing Health Disparities.” Disparities in the health of socially and economically disadvantaged compared with more advantaged populations are observed worldwide. The lack of progress in addressing these disparities compels a continuing search for new ideas and evidence about potential solutions as well as efforts to understand when and where these solutions work and how they work. The symposium consists of five in-depth reviews led by established scholars who approach the topic from their different disciplinary and topical perspectives. Taken together, these reviews point out the conceptual and methodological opportunities for generating more effective disparities research within biomedical, public health, and health services approaches, the value of also applying theory and methods from disciplines such as political science and economics to health disparities research, and insights to be gained from comparisons of how disparities occur and are remedied in different societies.