bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Characterization of LiMn2O4 Cathodes Surface‐Modified by DC Pulsed Plasma Treatment
Authors: Chen Cheng‐Lun , Chiu Kuo‐Feng , Chen Yan‐Ru , Lin Hsin‐Chih , Chen Chen Chung
Published: June 2012

A study of oxygen dc pulsed plasma irradiation treatment has been carried out on LiMn2O4 powder cathodes to enhance the electrochemical performances of lithium ion batteries. The samples have been characterized by X‐ray diffraction, scanning electron microscope, energy dispersion spectroscope and electrochemical measurements. It is found that after undergoing the plasma treatments, the sharp facets of LiMn2O4 particles become smooth due to plasma ion bombardment. The treated electrodes are partially covered by layers with high atomic percent of element F, indicating the reflow of binders. The electrochemical measurements are carried out under harsh conditions, including deep‐discharge at low cut‐off potential of 2 V and cycling at elevated temperature of 60 °C. The results reveal that moderate oxygen dc pulsed plasma treatment can improve the cycling stability of LiMn2O4 powder electrodes in the above mentioned conditions. The enhanced electrochemical performances are attributed to the dense protection layers on electrode surface, which reduce the capacity fading due to the Mn+2 ions dissolution.
Evolution of past enamel technology and metal conservation issues: the case of two Byzantine style bindings
Authors: Sodo A. , Ricci M. A. , Mangialardo S. , Postorino P. , Micheli M. , Crisostomi P.
Published: June 2012

The results of a Raman spectroscopic study of the cloisonne’ and basse‐taille enamels, which beautify two Byzantine style bindings from the Marciana Library (Venice), namely the Lat. III,111 and the MsGR.I.53 codexes, are presented in this work. The first binding dates back to the 13th century and was subject to an early restoration work in the 14th century, when new enamels substituted four originals. The second binding, from the 15th century, shows a lower number of enamels, all originals, and with a larger color palette. The white and yellow enamels of both codexes were successfully characterized and the red ones, where hematite was not used. Interestingly the white and yellow color of the 13th century enamels of the Lat. III,111 codex has been obtained by an ancient technique of the glass technology, which was already obsolete in the 13th century, and is based on the use of calcium antimonate and Naples yellow. The white color in the other binding's enamels have been instead obtained by using cassiterite, according to the tradition of the time. Cassiterite was also mixed to Naples yellow in the enamels of the MsGR.I.53 codex, to change the yellow hue. The identification of agents determining some colors is instead uncertain or not feasible by Raman spectroscopy. The transparency of the 14th century enamels of the Lat. III,111 codex has allowed the comparison of metal degradation below the enamels and in regions exposed to the atmosphere. Copyright © 2012 John Wiley & Sons, Ltd.
Raman spectroscopy reveals differences in collagen secondary structure which relate to the levels of mineralisation in bones that have evolved for different functions
Authors: Buckley Kevin , Matousek Pavel , Parker Anthony W. , Goodship Allen E.
Published: June 2012

Bone is a composite material comprising a collagen fibril scaffold surrounded by crystals of carbonated‐hydroxyapatite mineral. It is well established that the relative proportions of mineral and collagen in mature bone are not definite and are adapted in order to ‘tune’ its mechanical properties. It is not known, however, how the mineral to collagen ratio is controlled. This paper uses Raman spectroscopy (which permits the probing of both the mineral and the collagen phases of bone) to explore the hypothesis that the control mechanism is related to the nature of the collagen and that bones with different levels of mineralisation have qualitatively different collagen. Raman spectra of functionally adapted bones with varying levels of mineralisation are presented and features that indicate the differences in the collagen's secondary structure (amide I band profiles) and post‐translational modification (hydroxyproline/proline ratios) are highlighted. The study demonstrates that Raman spectroscopy can provide a means to investigate the mechanisms that control the mineral to collagen ratio of bone. Understanding these mechanisms could pave the way towards the therapeutic alteration of the mineral to collagen ratio and, thus, the control of the mechanical properties of bone. Copyright © 2012 John Wiley & Sons, Ltd.
Magnetic separation and SERS observation of analyte molecules on bifunctional silver/iron oxide composite nanostructures
Authors: Gühlke Marina , Selve Sören , Kneipp Janina
Published: June 2012

We report the preparation of bifunctional silver–iron oxide composite nanostructures (Ag@Fe2O3) and demonstrate their magnetic separation with an analyte molecule from silver nanoparticles in a mixed solution. Magnetic and non‐magnetic plasmonic nanostructures and their separation are monitored by the surface‐enhanced Raman scattering (SERS) spectra of two different analytes attached to each kind of particles. In general, such separation experiments can provide insight into basic phenomena of adsorption and exchange of adsorbed molecules which are of strong interest in SERS. The formation of stable Ag@Fe2O3 nanoparticle–molecule complexes suggests small magnetic SERS labels without additional protective layers for application in analytical assays. The magnetic plasmonic nanostructures have great promise for targeted imaging and sensing in biological structures by directing nanosensors to places of interest using magnetic fields. The option of magnetic separation and collection of plasmonic particles improves the analytical capabilities of SERS. Copyright © 2012 John Wiley & Sons, Ltd.
Polarization behaviors of twisted carbon nanotube fibers
Authors: Zhou Jinyuan , Sun Gengzhi , Zhan Zhaoyao , An Jianing , Zhang Yongzhe , Zhang Yani , Zheng Lianxi
Published: June 2012

Polarization behaviors of carbon nanotube (CNT) fibers with different twisting were reported. Scanning electron microscope and polarized Raman spectroscopy were used to investigate the prepared samples. Results indicate that surface twisting angle affects greatly the polarization angle and I///I⊥ ratio of twisted CNT fibers. Raman depth profile measurements imply that the twisted fibers consist of non‐uniform CNT alignments. A simplified two‐CNT‐alignment geometric model was proposed to illuminate the experimental observations. The results suggest that polarized Raman depth profile measurement would be a very useful approach for determining the distribution of CNT alignments in CNT fibers. Copyright © 2012 John Wiley & Sons, Ltd.
Direct measurement of part‐per‐billion levels of dimethyl sulfoxide in water by gas chromatography with stacked injection and chemiluminescence detection
Authors: Luong Jim , Gras Ronda , Shellie Robert A. , Cortes Hernan J.
Published: June 2012

Dimethyl sulfoxide (DMSO) is a chemical of industrial significance with many important applications. DMSO is used as an industrial solvent, in drug delivery and healthcare applications, among others. Analysis of DMSO in water typically involves extensive sample preparation, enrichment, and derivatization to improve solute detectability. A novel gas chromatographic procedure has been developed for the direct measurement of trace levels of DMSO in an aqueous matrix, such as potable water. The technology utilizes stacked injection techniques for in‐column solute enrichment, a precolumn to enhance solute focusing effects, and sulfur chemiluminescence detection for matrix suppression and sensitivity. A detection limit of 2 parts per billion (ppb) (v/v) of DMSO in water was attained. Relative precision of less than 7% at the concentration of 10 ppb (v/v) of DMSO was demonstrated. A correlation coefficient of 0.9988 was obtained over a range of 2 ppb (v/v) to 100 ppb (v/v). No detectable carry‐over was found at the 5 ppb (v/v) level whereas less than 4% carry‐over was observed at the 100 ppb (v/v) level. Various sample storage media including glass, polyethylene, and polycarbonate were also studied to minimize solute loss. Recoveries greater than 84% were achieved with all storage media tested. The method was found to be reliable and simple to implement.
Accurate analysis of trace earthy‐musty odorants in water by headspace solid phase microextraction gas chromatography‐mass spectrometry
Authors: Ma Kang , Zhang Jin Na , Zhao Min , He Ya Juan
Published: June 2012

A simple and sensitive method was developed for the simultaneous separation and determination of trace earthy‐musty compounds including geosmin, 2‐methylisoborneol, 2‐isobutyl‐3‐methoxypyrazine, 2‐isopropyl‐3‐methoxypyrazine, 2,3,4‐trichloroanisole, 2,4,6‐trichloroanisole, and 2,3,6‐trichloroanisole in water samples. This method combined headspace solid‐phase microextraction (HS‐SPME) with gas chromatography‐mass spectrometry and used naphthalene‐d8 as internal standard. A divinylbenzene/carboxen/polydimethylsiloxane fiber exposing at 90°C for 30 min provided effective sample enrichment in HS‐SPME. These compounds were separated by a DB–1701MS capillary column and detected in selected ion monitoring mode within 12 min. The method showed a good linearity from 1 to 100 ng L−1 and detection limits within (0.25–0.61 ng L−1) for all compounds. Using naphthalene‐d8 as the internal standard, the intra‐day relative standard deviation (RSD) was within (2.6–3.4%), while the inter‐day RSD was (3.5–4.9%). Good recoveries were obtained for tap water (80.5–90.6%), river water (81.5–92.4%), and lake water (83.5–95.2%) spiked at 10 ng L−1. Compared with other methods using HS‐SPME for determination of odor compounds in water samples, this present method had more analytes, better precision, and recovery. This method was successfully applied for analysis of earthy‐musty odors in water samples from different sources.
Effect of ion adsorption on CEC separation of small molecules using hypercrosslinked porous polymer monolithic capillary columns
Authors: Chen Xiao‐Jia , Dinh Ngoc Phuoc , Zhao Jing , Wang Yi‐Tao , Li Shao‐Ping , Svec Frantisek
Published: June 2012

Both poly(styrene‐co‐vinylbenzyl chloride‐co‐divinylbenzene) and poly(4‐methylstyrene‐co‐vinylbenzyl chloride‐co‐divinylbenzene) monolithic columns have been hypercrosslinked and for the first time used to achieve capillary electrochromatographic separations. Although these columns do not contain ionizable functionalities, electroosmotic flow was observed due to adsorption of ions from a buffer solution contained in the mobile phase on the surface of the hydrophobic polymer. An increase of more than one order of magnitude was observed with the use of both monolithic polymers. The hypercrosslinking reaction creates a large surface area thus enabling adsorption of a much larger number of ions. Alkylbenzenes were successfully separated using the hypercrosslinked monolithic columns.
Clinical predictors of driving status in Huntington's disease
Authors: Beglinger Leigh J. , Prest Luke , Mills James A. , Paulsen Jane S. , Smith Megan M. , Gonzalez‐Alegre Pedro , Rowe Kelly C. , Nopoulos Peggy , Uc Ergun Y.
Published: June 2012

The aim of this study was to identify the motor, cognitive, and behavioral determinants of driving status and risk factors for driving cessation in Huntington's disease (HD). Seventy‐four patients with HD were evaluated for cognitive, motor, psychiatric, and functional status using a standardized battery (Unified Huntington's Disease Rating Scale [UHDRS] and supplemental neuropsychological testing) during a research clinic visit. Chart review was used to categorize patients into two driving status categories: (1) “currently driving” included those driving and driving but with clinician recommendation to restrict, and (2) “not driving” included those with clinician recommendation to cease driving and those not currently driving because of HD. Multi‐ and univariate logistic regression was used to identify significant clinical predictors of those driving versus not driving. Global cognitive performance and UHDRS Total Functional Capacity scores provided the best predictive model of driving cessation (Nagelkerke R2 = 0.65; P < 0.0001). Measures of learning (P = 0.006) and psychomotor speed/attention (P = 0.003) accounted for the overall cognitive finding. In univariate analyses, numerous cognitive, motor, and daily functioning items were significantly associated with driving. Although driving status is associated with many aspects of the disease, results suggest that the strongest association is with cognitive performance. A detailed cognitive evaluation is an important component of multidisciplinary clinical assessment in patients with HD who are driving. © 2012 Movement Disorder Society
Shell finite elements with different through‐the‐thickness kinematics for the linear analysis of cylindrical multilayered structures
Authors: Cinefra M. , Carrera E.
Published: June 2012

The present paper considers the linear static analysis of composite cylindrical structures by means of a shell finite element with variable through‐the‐thickness kinematic. The refined models used are grouped in the Unified Formulation by Carrera (CUF), and they permit to accurately describe the distribution of displacements and stresses along the thickness of the multilayered shell. The shell element has nine nodes, and the mixed interpolation of tensorial components method is employed to contrast the membrane and shear locking phenomenon. Different composite cylindrical shells are analyzed, with various laminations and thickness ratios. The governing equations are derived from the principle of virtual displacement in order to apply the finite element method. The results, obtained with different theories contained in the CUF, are compared with both the elasticity solutions given in the literature and the analytical solutions obtained using Navier's method. From the analysis, one can conclude that the shell element based on the CUF is very efficient, and its use is mandatory with respect to the classical models in the study of composite structures. Copyright © 2012 John Wiley & Sons, Ltd.
Adherence to transcranial Doppler screening guidelines among children with sickle cell disease
Authors: Eckrich Michael J. , Wang Winfred C. , Yang Elizabeth , Arbogast Patrick G. , Morrow Anthony , Dudley Judith A. , Ray Wayne A. , Cooper William O.
Published: June 2012

Background

Little is known about adherence to guidelines recommending yearly screening with transcranial Doppler (TCD) ultrasonography to detect stroke risk for children with severe sickle cell disease. The objective was to determine the proportion of children with hemoglobin SS (HbSS) or sickle‐β0‐thalassemia (HbSβ0) aged 2–16 years who received recommended TCD screening from 1997 to 2008, and to identify factors associated with adherence.

Procedure

A retrospective cohort study included patients enrolled in Tennessee Medicaid with HbSS or HbSβ0 who received care at the two largest sickle cell centers in Tennessee. The outcome of interest was adherence with guidelines for annual screening TCD's, identified from computer claims and validated through medical record review. The cumulative rate of children who received a TCD per year was calculated using the Kaplan–Meier method. Cox proportional hazards regression was used to examine the association of child, family, and health care use characteristics with receiving a TCD.

Results

Among 338 TCD eligible at‐risk children, 232 (68.6%) had at least one TCD during the study period. The yearly cumulative incidence of annual TCD's increased from 2.5% in 1997 to 68.3% in 2008. In multivariate models, calendar year, maternal education, and increased number of sickle cell related outpatient visits were associated with an increased rate of receiving a TCD.

Conclusions

Publicly insured children with HbSS or HbSβ0 had increasing adherence with TCD screening guidelines between 1997 and 2008, though 31% had no TCD at all during follow‐up. Increasing number of sickle cell related outpatient visits was associated with increasing adherence to screening guidelines. Pediatr Blood Cancer 2013;60:270–274. © 2012 Wiley Periodicals, Inc.
Improved care of rhabdomyosarcoma in Jordan using less intensive therapy
Authors: Al‐Jumaily Usama , Ayyad Omar , Masarweh Main , Ghandour Khalil , Almousa Abdelatif , Al‐Hussaini Maysa , Ferrari Andrea , Sultan Iyad
Published: June 2012

Background

The care of rhabdomyosarcoma (RMS) is complex due to its multimodal nature. By following standard protocols with acceptable toxicity and building local expertise, better outcome should be achievable.

Procedure

A retrospective study was conducted of records of patients (n = 45; 31 males; median age 26 months) with RMS treated at King Hussein Cancer Center in Jordan from January 2004 to December 2008. Patient demographics, tumor characteristics, risk stratification, treatment plan, and outcomes were studied. In June 2006, the cyclophosphamide dose was lowered from 2.2 g/m2 to 1.2 g/m2 per cycle because of the significant toxicity with higher dose. Survival rates, hematological toxicities, period of hospitalization due to febrile neutropenia (FN), and response rate at week 12 of treatment were compared between low‐ and high‐dose cyclophosphamide groups.

Results

Four‐year progression‐free survival (PFS) and overall survival (OS) rates were 61% ± 7.5% and 72% ± 6.9%, respectively. There was a significant difference in outcome by risk group in 4‐year PFS (low‐risk, 88% ± 12%; intermediate‐risk 63% ± 9.3%; high‐risk, 14% ± 13%; P = 0.0001) and OS (low‐risk, 88% ± 12%; intermediate‐risk 79% ± 7.5%; high‐risk, 17% ± 15%; P = 0.0011). There was significant reduction in hematological toxicities, incidence of FN, and period of hospitalization for FN in patients given low‐dose cyclophosphamide but no significant difference in PFS between low‐ and high‐dose cyclophosphamide groups.

Conclusions

Survival rates of patients with RMS in some developing countries can be improved by following or modifying evidence‐based approaches successful in developed countries and establishing multidisciplinary strategies. Therapy intensity should be increased in developing countries only when evidence supports its utility. Pediatr Blood Cancer 2013; 60: 53–58. © 2012 Wiley Periodicals, Inc.
The role of 18F‐FDG PET/CT in the metabolic characterization of lung nodules in pediatric patients with bone sarcoma
Authors: Cistaro Angela , Lopci Egesta , Gastaldo Luca , Fania Piercarlo , Brach del Prever Adalberto , Fagioli Franca
Published: June 2012

Background

The principal aim of this study was to identify the lowest nodule diameter and the SUVmax capable of characterizing lung nodules in pediatric patients with bone sarcoma.

Procedure

Eighteen consecutive bone sarcoma patients (M/F = 11:7; mean age 14 years) with suspicious lung lesions at CT were enrolled. Overall, 63 lung nodules with a mean diameter of 3.35 mm (range 1.2–39.8 mm) were investigated. 18F‐FDG PET was performed according to standard procedure using a hybrid PET/CT system and results were compared with histology and/or clinical/radiological follow‐up. For each lesion, we evaluated SUVmax, SUVratio to the mediastinal blood pool and maximum nodule diameter.

Results

Of the 63 nodules, 32 proved to be benign and 31 malignant. On a visual basis, 18F‐FDG PET had an accuracy of 88.9%, a sensitivity of 90.3%, a specificity of 87.5%, a PPV of 87.5%, and a NPV of 90.3%. ROC curve analysis of SUVmax for all nodules showed a value around 1 (>1.09) to be capable of differentiating metastases from benign lesions: sensitivity and specificity were 90.3% and 93.8%, respectively (accuracy 92.1%). Similar analysis revealed a cut‐off value around 1 (>0.83) for SUVratio (sensitivity and specificity were 90.3% and 90.6%, respectively) and a cut‐off value of ca. 6 mm (>5.8 mm) for nodule diameter (sensitivity and specificity of 90.3% and 81.3%, respectively).

Conclusions

18F‐FDG PET/CT is an accurate modality for the metabolic characterization of lung nodules in the pediatric population with bone sarcoma, and a SUVmax (or SUVratio) >1 is capable of discriminating malignant from benign lesions. Pediatr Blood Cancer 2012; 59: 1206–1210. © 2012 Wiley Periodicals, Inc.
The RC scales predict psychotherapy outcomes: The predictive validity of the MMPI‐2's restructured clinical scales for psychotherapeutic outcomes
Authors: Scholte Wubbo , Tiemens Bea , Verheul Roel , Meerman Anke , Egger Jos , Hutschemaekers Giel
Published: June 2012

This study investigated the capacity of the Minnesota Multiphasic Personality Inventory's (MMPI‐2) restructured clinical (RC) scales to predict treatment outcomes of inpatient psychotherapy concerning long‐term changes in the level of psychopathology for patients with personality disorders. The predictive capacity of the RC scales is compared with that of the clinical scales. The MMPI‐2 was administered at baseline. We followed up 179 patients for 36 months. The Brief Symptom Inventory measured the symptom changes between baseline and the end of the treatment as well as between baseline and 36 months. The RC2 (Low Positive Emotions) scale and RC8 (Aberrant Experiences) scale predicted lower levels of symptomatic improvements at 36 months. These scales did not have a significantly better performance than the original clinical scales. The RC2 and the 2(Depression) scale of the clinical scales predicted less improvement at 36 months. These findings emphasize that the RC scales should not be used alone or as a replacement for the clinical scales. Copyright © 2012 John Wiley & Sons, Ltd.
Prescribing volume and costs for primary care in 2011
Authors: Chaplin Steve
Published: June 2012

Steve Chaplin analyses the latest statistics for prescribing in primary care in 2011, showing no overall change in spending despite continuing growth in prescribing.
What GPs need to know about palliative‐care drugs: ketamine
Authors: Howard Rachel , Howard Paul
Published: June 2012

This is the first in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist‐initiated palliative‐care drugs. This first article summarises the key issues for patients receiving ketamine.
Roughness formation in (100) silicon during low‐energy Cs+ bombardment
Authors: Mansilla C. , Philipp P. , Wirtz T.
Published: June 2012

In secondary ion mass spectrometry, high depth resolution for the characterization of ultra‐shallow junctions can only be obtained when making use of low‐energy primary ion bombardment. However, such analysis conditions often lead to roughness formation at the crater bottoms.

In this paper, roughness formation has been studied on silicon for Cs+ bombardment on the Cameca (Gennevilliers, France)SC‐Ultra instrument. Impact energies have been changed from 250 eV up to 5 keV working in positive secondary ion polarity.

The surface morphology has been characterized by atomic force microscopy. Surface roughening appeared at low primary ion fluence and continued growing at higher fluences. Ripples formed perpendicular to the plane containing the beam and the normal to the surface. Their wavelength and correlation length have been studied as a function of the experimental conditions. Both parameters increase with increasing ion fluence, and higher values of ion energy promoted more ordered rippled structures and lower values of roughness. Copyright © 2012 John Wiley & Sons, Ltd.
Are cultures endangered by climate change? Yes, but…
Authors: Strauss Sarah
Published: June 2012

Culture, from an anthropological perspective, encompasses all learned and shared aspects of life in human societies. Included is not only ‘high culture’—the arts and literature—but also science, technology, and more practical, everyday activities and beliefs: how to plant a potato or pray for rain, to seek good luck in battle or on exams at school. Cultures are not static; they change in response to wars, plagues, new inventions—as well as to environmental and climate variability. Here we look at some of the ‘rules’ of culture, in order to explore the extent to which climate change seriously threatens cultural diversity. The most popular examples of climate change impacts on human societies focus on remote communities in the Arctic or on tropical islands, but we need to keep in mind that the fossil fuel dependent lifeways of those of us residing in the industrialized temperate zones are perhaps even more endangered, and certainly less sustainable. WIREs Clim Change 2012 doi: 10.1002/wcc.181

This article is categorized under:

Vulnerability and Adaptation to Climate Change > Values‐Based Approach to Vulnerability and Adaptation
Probabilistic may/must testing: retaining probabilities by restricted schedulers
Authors: Georgievska Sonja , Andova Suzana
Published: June 2012

This paper considers the probabilistic may/must testing theory for processes having external, internal, and probabilistic choices. We observe that the underlying testing equivalence is too strong and distinguishes between processes that are observationally equivalent. The problem arises from the observation that the classical compose-and-schedule approach yields unrealistic overestimation of the probabilities, a phenomenon that has been recently well studied from the point of view of compositionality, in the context of randomized protocols and in probabilistic model checking. To that end, we propose a new testing theory, aiming at preserving the probability information in a parallel context. The resulting testing equivalence is insensitive to the exact moment the internal and the probabilistic choices occur. We also give an alternative characterization of the testing preorder as a probabilistic ready-trace preorder.
Filter-embedding semiring fusion for programming with MapReduce
Authors: Emoto Kento , Fischer Sebastian , Hu Zhenjiang
Published: June 2012

We show that MapReduce, the de facto standard for large scale data-intensive parallel programming, can be equipped with a programming theory in calculational form. By integrating the generate-and-test programming paradigm and semirings for aggregation of results, we propose a novel parallel programming framework for MapReduce. The framework consists of two important calculation theorems: the shortcut fusion theorem of semiring homomorphisms bridges the gap between specifications and efficient implementations, and the filter-embedding theorem helps to develop parallel programs in a systematic and incremental way.
Using schedulers to test probabilistic distributed systems
Authors: Hierons Robert M. , Núñez Manuel
Published: June 2012

Formal methods are one of the most important approaches to increasing the confidence in the correctness of software systems. A formal specification can be used as an
oracle
in testing since one can determine whether an observed behaviour is allowed by the specification. This is an important feature of formal testing: behaviours of the system observed in testing are compared with the specification and ideally this comparison is automated. In this paper we study a formal testing framework to deal with systems that interact with their environment at physically distributed interfaces, called ports, and where choices between different possibilities are probabilistically quantified. Building on previous work, we introduce two families of schedulers to resolve nondeterministic choices among different actions of the system. The first type of schedulers, which we call
global schedulers
, resolves nondeterministic choices by representing the environment as a single global scheduler. The second type, which we call
localised schedulers
, models the environment as a set of schedulers with there being one scheduler for each port. We formally define the application of schedulers to systems and provide and study different implementation relations in this setting.
A secure voting scheme based on rational self-interest
Authors: Misra Jayadev
Published: June 2012

We propose a scheme for secure voting that involves the candidates themselves in implementing the voting system. It exploits the competing interests (rivalry) and mutual distrust among the candidates to force an honest election.
Checking noninterference in Timed CSP
Authors: Roscoe A. W. , Huang Jian
Published: June 2012

A well-established specification of noninterference in CSP is that, when high-level events are appropriately abstracted, the remaining low-level view is deterministic. This is not a workable definition in Timed CSP, where many processes cannot be refined to deterministic ones. We argue that in fact “deterministic” should be replaced by “maximally refined” in the definition above. We show how to automate the resulting timed noninterference check within the context of the recent extension of FDR to analyse a discrete version of Timed CSP, and how an extended theory of digitisation has the potential both to create more accurate specifications and to infer when processes are noninterfering in the more usual continuous-time semantics.
Stepwise refinement of heap-manipulating code in Chalice
Authors: Leino K. Rustan M. , Yessenov Kuat
Published: June 2012

Stepwise refinement is a well-studied technique for developing a program from an abstract description to a concrete implementation. This paper describes a system with automated tool support for refinement, powered by a state-of-the-art verification engine that uses an SMT solver. Unlike previous refinement systems, users of the presented system interact only via declarations in the programming language. Another aspect of the system is that it accounts for dynamically allocated objects in the heap, so that data representations in an abstract program can be refined into ones that use more objects. Finally, the system uses a language with familiar imperative features, including sequential composition, loops, and recursive calls, offers a syntax with skeletons for describing program changes between refinements, and provides a mechanism for supplying witnesses when refining non-deterministic programs.
Security invariants in discrete transition systems
Authors: Hoang Thai Son
Published: June 2012

The Shadow semantics is a qualitative model for noninterference security for sequential programs. In this paper, we first extend the Shadow semantics to Event-B, to reason about discrete transition systems with noninterference security properties. In particular, we investigate how these security properties can be specified and proved as machine invariants. Next we highlight the role of security invariants during refinement and identify some common patterns in specifying them. Finally, we propose a practical extension to the supporting
Rodin platform
of Event-B, with the possibility of having some properties to be
invariants-by-construction
.
Worldwide Alzheimer's Disease Neuroimaging Initiative
Authors: Carrillo Maria C. , Bain Lisa J. , Frisoni Giovanni B. , Weiner Michael W.
Published: June 2012

The Alzheimer's Disease Neuroimaging Initiative (ADNI) was launched in 2003 to speed drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public–private partnership, the first phase of ADNI (ADNI 1) set a new standard for data sharing without embargo. In addition, it has been extended to 2017 by additional funding (North American‐ADNI Grand Opportunities and ADNI 2) as well as multiple projects around the world, collectively known as Worldwide ADNI (WW‐ADNI). The goal of WW‐ADNI is to harmonize projects and results across different geographical sites and to encourage and harmonize data management and availability to investigators around the world. WW‐ADNI projects are currently underway in North America, Europe, Japan, Australia, Korea, Taiwan, and Argentina, with a nascent program in China and a possible future program in Brazil.
Relationships between net primary productivity and forest stand age in U.S. forests
Authors: He Liming , Chen Jing M. , Pan Yude , Birdsey Richard , Kattge Jens
Published: June 2012

Net primary productivity (NPP) is a key flux in the terrestrial ecosystem carbon balance, as it summarizes the autotrophic input into the system. Forest NPP varies predictably with stand age, and quantitative information on the NPP‐age relationship for different regions and forest types is therefore fundamentally important for forest carbon cycle modeling. We used four terms to calculate NPP: annual accumulation of live biomass, annual mortality of aboveground and belowground biomass, foliage turnover to soil, and fine root turnover in soil. For U.S. forests the first two terms can be reliably estimated from the Forest Inventory and Analysis (FIA) data. Although the last two terms make up more than 50% of total NPP, direct estimates of these fluxes are highly uncertain due to limited availability of empirical relationships between aboveground biomass and foliage or fine root biomass. To resolve this problem, we developed a new approach using maps of leaf area index (LAI) and forest age at 1 km resolution to derive LAI‐age relationships for 18 major forest type groups in the USA. These relationships were then used to derive foliage turnover estimates using species‐specific trait data for leaf specific area and longevity. These turnover estimates were also used to derive the fine root turnover based on reliable relationships between fine root and foliage turnover. This combination of FIA data, remote sensing, and plant trait information allows for the first empirical and reliable NPP‐age relationships for different forest types in the USA. The relationships show a general temporal pattern of rapid increase in NPP in the young ages of forest type groups, peak growth in the middle ages, and slow decline in the mature ages. The predicted patterns are influenced by climate conditions and can be affected by forest management. These relationships were further generalized to three major forest biomes for use by continental‐scale carbon cycle models in conjunction with remotely sensed land cover types.
Inherited strike‐slip faults as an origin for basement‐cored uplifts: Example of the Kungey and Zailiskey ranges, northern Tian Shan
Authors: Selander Jacob , Oskin Michael , Ormukov Cholponbek , Abdrakhmatov Kanatbek
Published: June 2012

Basement‐cored uplifts bounded by steeply dipping reverse faults are mechanically difficult to explain. Reactivation of strike‐slip faults that aid the formation of new, high‐angle reverse faults in the surrounding crust may provide one origin for these structures. This hypothesis is explored by examining the late Miocene to Quaternary evolution of the Kungey and Zailiskey ranges in the northern Tian Shan. These ranges are cored by the Kemin‐Chilik fault (KCF), an inherited Paleozoic structure with sinistral separation of basement terranes. Range growth in response to northward propagation of the Tian Shan has taken place along a network of steeply dipping reverse and oblique‐slip faults surrounding the KCF. Deformation of a low relief unconformity separating Neogene strata from Paleozoic basement records structural growth in response to fault slip. Deformed river terraces surrounding the ranges are correlated to a well preserved chronosequence in the southern Kungey Range. Cosmogenic10Be dating of this chronosequence combined with offset measurements yields slip rates ranging from 0.07 to 0.37 mm/yr for dip‐slip faults, and 1.1 to 1.5 mm/yr for strike‐slip faults Late Quaternary activity in the Kungey‐Zailiskey ranges is consistent with the longer‐term, outward stepping pattern of range growth. Based on cross sections constrained from the folded unconformity surface, deformed Neogene strata and Quaternary terraces, faults building the Kungey Range are inferred to steepen at depth and emanate from a shear zone co‐located with the reactivated KCF. This geometry is consistent with a slip partitioned system developed by an obliquely slipping reactivated fault at depth.
The role of zonal winds in the production of a pre‐reversal enhancement in the vertical ion drift in the low latitude ionosphere
Authors: Heelis R. A. , Crowley G. , Rodrigues F. , Reynolds A. , Wilder R. , Azeem I. , Maute A.
Published: June 2012

The evolution of the pre‐reversal enhancement in the vertical ion drift in the equatorialFregion is described via an examination of the current systems determined from a coupled ionosphere thermosphere model. We find that the pre‐reversal enhancement is produced by a reversal in theF region zonal wind that results in an additional upward current where the E region Pedersen conductivity is declining across the dusk sector. The continuity of the total current is maintained through an enhancement in the eastward zonal current and an associated upward drift of the ions.
Dual Inhibition of Phosphodiesterase-4 and p38 MAP Kinase: A Strategy for Treatment of Chronic Inflammatory Diseases
Authors: ALBRECHT WOLFGANG , LAUFER STEFAN
Published: June 2012

The rationale for selecting p38α MAPK as a target for pharmacological intervention was based on the elucidation of its key role in the regulation of pro-inflammatory cytokine expression, the observations that p38α MAPK is highly activated in inflamed tissue from patients with rheumatoid arthritis, inflammatory bowel disease or chronic obstructive pulmonary disease and on the demonstrated anti-inflammatory efficacy of many p38 MAPK inhibitors in experimental disease models, which was associated with cytokine suppression. Unfortunately, the efficacy of all p38α MAPK inhibitors, which were advanced to clinical trials, was not superior to that of placebo. Although the exact molecular mechanism behind this unexpected outcome has not yet been elucidated, p38 MAPK is generally no longer considered as a valid target for treatment of chronic inflammatory diseases.

Inhibitors of phosphodiesterase 4 (PDE4) are also potent anti-inflammatory drugs and many candidates were advanced to clinical development. However, in vivo, the drug-mediated PDE4-inhibition is associated with nausea and emesis as major side-effects and so far, for most PDE4-inhibitors, the therapeutic window was not big enough to achieve a significant clinical benefit at tolerated doses.

p38 MAPK inhibitors of the chemical class of pyridinylimidazoles have been intensely investigated and, since the discovery of SB203580, many derivatives with substantially improved kinase selectivity and reduced liver toxicity potential have been described. As a matter of serendipity, rather than as a result of rational design, a subset of the class of 2-methanesulfinyl imidazoles, which are less potent p38α/β MAPK inhibitors, also showed affinity to PDE4 and inhibit this target at sub-µM concentrations. Results of first experimental in-vivo models of acute and chronic inflammation suggest that a moderate inhibition of p38α MAPK contributes the anti-inflammatory effect of PDE4-inhibitors, which could translate into clinical efficacy at sub-ematogenic doses.
Bruton's Tyrosine Kinase (Btk)
Authors: SCHNUTE MARK E. , HUANG ADRIAN , SAIAH EDDINE
Published: June 2012

Bruton's tyrosine kinase (Btk) is a non-receptor tyrosine kinase belonging to the Tec family of kinases. Btk is critical for B-cell development, differentiation and signalling through the B-cell antigen receptor (BCR) as is evident by its genetic association to a human primary immunodeficiency disease known as X-linked Agammaglobulinemia (XLA). Btk is also present in specific cells of the myeloid lineage and contributes to the activation of the FcγR and FcεR signalling pathways in macrophages, neutrophils and mast cells. Because of its key role in these pathways, Btk is considered a promising target for therapeutic intervention in autoimmune and inflammatory disease. Numerous research groups are actively working to identify Btk inhibitors through the targeting of inactive kinase conformations or covalent active site inhibition. Both strategies have benefited from the rapid growth in structural biology insight for the target. Recently discovered potent and orally bioavailable Btk inhibitors have shown promising efficacy in several pre-clinical animal models of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). These results, coupled with promising initial findings from the study of Btk inhibitors in human clinical trials for oncology, strongly suggest Btk intervention offers significant potential as a treatment strategy in inflammatory disease.
CCR2 Antagonists for the Treatment of Diseases Associated with Inflammation
Authors: HOU CUIFEN , SUI ZHIHUA
Published: June 2012

The CCR2 and MCP-1 pathway has become one of the most-studied chemokine systems for therapeutic use in inflammatory diseases and conditions. It plays a pivotal role in inflammatory diseases, especially those that are characterized by monocyte-rich infiltration. This chapter reviews the biology of CCR2 and MCP-1, and their roles in diseases and conditions related to inflammation such as rheumatoid arthritis, multiple sclerosis, asthma, obesity, type 2 diabetes, atherosclerosis, nephropathy, cancer, pulmonary fibrosis and pain. Intense drug-discovery efforts over the past 15 years have generated a large number of CCR2 antagonists in diverse structural classes. Mutagenesis studies have elucidated important residues on CCR2 that interact with many classes of these CCR2 antagonists. To facilitate understanding of CCR2 antagonist SAR, a simple pharmacophore model is used to summarize the large number of diverse chemical structures. The majority of published compounds are classified based on their central core structures using this model. Key SAR points in the published literature are briefly discussed for most of the series. Lead compounds in each chemical series are highlighted where information is available. The challenges in drug discovery and development of CCR2 antagonists are briefly discussed. Clinical candidates in various diseases in the public domain are summarized with a brief discussion about the clinical challenges.
Tipping the Balance of Sphingosine 1-Phosphate Production: Sphingosine Kinases and Sphingosine 1-Phosphate Lyase as Immune Therapeutic Targets
Authors: ORAVECZ TAMAS , AUGERI DAVID
Published: June 2012

Sphingolipid metabolism involves the synthesis and degradation of a number of structurally similar molecules that function as building blocks of cell membranes as well as signalling molecules. Sphingosine, derived from the breakdown of ceramide, is phosphorylated by two sphingosine kinases (SK), SK1 and SK2, producing Sphingosine-1-Phosphate (S1P). S1P is an important signalling agent present in all mammalian cells as well as in the circulation. It can serve both as a chemotactic ligand of G-protein coupled receptors and as a second messenger in signal transduction pathways, which control cell differentiation, proliferation and apoptosis. S1P levels are regulated by two other catalytic processes in addition to the kinase activities. Sphingosine 1-phosphate lyase (S1PL) irreversibly degrades S1P through a retro-aldol reaction, and two classes of phosphatases, acting on lipids, dephosphorylate S1P to regenerate sphingosine. It has become evident that tipping the balance of S1P production can augment as well as inhibit inflammation in a context-dependent manner. This dual function places S1P in the company of other secreted factors that display a Yin-Yang role in the inflammatory process, such as INF-γ, TGF-β and members of the IL-17 family of cytokines. Therefore, enzymes of sphingolipid metabolism have become important new drug targets for the control of inflammation, autoimmune disorders and cancer. This chapter covers the immunology of S1PL, SK1 and SK2, and summarizes the drug-discovery efforts aimed at exploiting the potential of these enzymes as novel anti-inflammatory drug targets.
Kupffer cell depletion attenuates leptin-mediated methoxamine-stimulated portal perfusion pressure and thromboxane A2 release in a rodent model of NASH-cirrhosis
Authors: Yang Ying-Ying , Huang Yi-Tsau , Tsai Tung-Hu , Hou Ming-Chih , Lee Fa-Yauh , Lee Shou-Dong , Lin Han-Chieh
Published: June 2012

Cirrhotic portal hypertension is characterized by increased hepatic oxidative stress, AA (arachidonic acid)-derived TXA2 (thromboxane A2) release and exaggerated hepatic response to the α-adrenergic agonist MTX (methoxamine). Besides promoting hepatic fibrosis, the role of hyperleptinaemia in the modulation of vascular response in NASH (non-alcoholic steatohepatitis) rat livers remains unknown. The aim of the present study was to explore the possible links between hyperleptinaemia and the disarrangement in the hepatic microcirculation. NASH-cirrhosis with hyperleptinaemia was induced in lean rats by feeding with an HF/MCD (high-fat/methionine-choline-deficient) diet. Portal haemodynamics, various substances, protein and mRNA expression and PUFA (polyunsaturated fatty acid) composition were measured. Finally, the effects of leptin pre-infusion on TXA2 release and concentration–PPP (portal perfusion pressure) curves in response to MTX were evaluated by simultaneously pre-treatment with the Kupffer cell inactivators GdCl3 (gadolinium chloride) or EC (encapsulated clodronate), the TXS (TXA2 synthase) inhibitor furegrelate, the TP receptor (TXA2 receptor) antagonist SQ29548 and the dual TXS/TP receptor antagonist BM567. In HF/MCD+leptin-lean rats, cirrhosis-induced PPP and MTX hyper-responsiveness were associated with increased hepatic TXA2 production, TBARS (thiobarbituric acid-reacting substances) levels and the AA (arachidonic acid)/n−3 PUFA ratio, and up-regulation of hepatic leptin, FAS (fatty acid synthase), NADPH oxidase subunits, TXS, TP receptor, TGFβ1 (transforming growth factor β1) proteins and mRNAs. Pre-infusion of leptin significantly enhanced MTX-stimulated PPP elevation and TXA2 release, which were attenuated by GdCl3 and EC pre-treatment. Concomitantly pre-incubation with BM567, but not furegrelate or SQ29548, significantly abolished the leptin-enhanced MTX-stimulated increase in PPP in NASH-cirrhotic rats. Hyperleptinaemia plays an important role in hyper-responsiveness to MTX in NASH-cirrhotic rat livers with portal hypertension. The leptin-enhanced MTX-stimulated increase in PPP is mediated by increased oxidative stress and Kupffer-cell-activated AA-derived TXA2 release in NASH-cirrhotic rats.
Adhesion of E. coli to silver- or copper-coated porous clay ceramic surfaces
Authors: Yakub I. , Soboyejo W. O.
Published: June 2012

Porous ceramic water filters (CWFs), produced by sintering a mixture of clay and a combustible material (such as woodchips), are often used in point-of-use water filtration systems that occlude microbes by size exclusion. They are also coated with colloidal silver, which serves as a microbial disinfectant. However, the adhesion of microbes to porous clay surfaces and colloidal silver coated clay surfaces has not been studied. This paper presents the results of atomic force microscopy (AFM) measurements of the adhesion force between Escherichia coli bacteria, colloidal silver, and porous clay-based ceramic surfaces. The adhesion of silver and copper nanoparticles is also studied in control experiments on these alternative disinfectant materials. The adhesive force between the wide range of possible bi-materials was measured using pull-off measurements during force microscopy. These were combined with measurements of AFM tip radii/substrate roughness that were incorporated into adhesion models to obtain the adhesion energies for the pair wise interaction. Of the three antimicrobial metals studied, the colloidal silver had the highest affinity for porous ceramic surface (125 ± 32 nN and ∼0.29 J/m2) while the silver nanoparticles had the highest affinity for E. coli bacteria (133 ± 21 nN and ∼0.39 J/m2). The implications of the results are then discussed for the design of ceramic water filter that can purify water by adsorption and size exclusion.