bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of intense short pulse laser shapes on generating of the optimum wakefield and dissociation of methane molecule
Authors: Irani E. , Zare S. , Navid H.A. , Dehghani Z. , Sadighi-Bonabi R.
Published: May 2012

The optimum convolution of dual short pulse for producing the maximum wakefield and the highest dissociation probability of CH4has been investigated. By using three fundamental shapes of pulses though four different arrangements, the generated wake are considered in plasma. It is found that when the first and second pulses were rectangular–triangular and sinusoidal pulse shapes, respectively, the resultant wakefield amplitude is the highest. This effect opens up a new novel way by pulse shaping mechanism in the photo dissociation dynamics of molecules and controlling of chemical reactions in the desired channels by short pulse intense lasers for reducing the computation time of genetic algorithm model. Using field assisted dissociation model, the dissociation probability for a CH4+molecule exposed to a 100 femtosecond 8 Jcm−2Ti:Sapphire laser pulse is calculated. Here, the highest possible dissociation probability of the methane ion is calculated by the gradient optimization method in which the gradient of a function should be in the direction of the local extremes. The C-H molecular bond of CH4+ion is assumed to be in the same direction as the electric field component of the laser pulse. These results show that there is an excellent match with experimental data. The remarkable feature of this work is that the sensitivity of the dissociation probability of the initial bond lengthq, is studied and the desired product channel is controlled by variation of the laser intensity and it's time evolution by introducing a characteristic vectored space for intensity and duration of two tailored rectangular femtosecond laser pulses.
Repetitive nanosecond-pulse discharge in a highly nonuniform electric field in atmospheric air: X-ray emission and runaway electron generation
Authors: Shao Tao , Tarasenko Victor F. , Zhang Cheng , Baksht Evgeni KH. , Yan Ping , Shut'Ko Yuliya V.
Published: May 2012

Repetitive nanosecond-pulse discharge with a highly inhomogeneous electric field was investigated in air at atmospheric pressure. Three repetitive nanosecond generators were used, and the rise times of the voltage pulses were 15, 1, and 0.2 ns, respectively. Under different experimental conditions, X-rays and runaway electron beams were directly measured using various setups. The variables affecting X-rays and runaway electrons, including gap distance, pulse repetition frequency, anode geometry, and material, were investigated. It was shown that it was significantly easier to record the X-rays than the runaway electrons in the repetitive nanosecond-pulse discharge. It was confirmed that a volume diffuse discharge was attributed to the generation of runaway electrons and the corresponding X-rays.
The Contribution of IslamicWaqfto Managing the Conservation of Buildings in the Historic Stone Town of Zanzibar
Authors: Khalfan Khalfan Amour , Ogura Nobuyuki
Published: May 2012

The conservation of historic buildings depends on their physical maintenance as much as it depends upon their protection against external threats resulting from economic forces, the political climate, and human interference. Although physical conservation is what keeps the buildings standing, protecting buildings from these external threats can be considered more important because, without such protection, the buildings might not survive for any maintenance to be performed. To achieve the envisaged protection, proper management techniques are required. This article draws management inspirations from the unique and long-enduring tradition of the Islamicwaqf, as practiced in the historic Stone Town of Zanzibar, now a World Heritage Site. The structure ofwaqfmanagement is examined, along with aspects of finance and building maintenance. It was found that the ability of a management system to evolve according to prevailing conditions can be an effective shield against the external threats mentioned here.
Epidemiological and clinical description of the top three reportable parasitic diseases in a Canadian community
Authors: RAVEL A. , NESBITT A. , PINTAR K. , MACARTHUR A. , WANG H.-L. , MARSHALL B. , POLLARI F.
Published: May 2012

This study provides a comprehensive epidemio-clinical picture of sporadic, domestically acquired cases of amoebiasis, cryptosporidiosis and giardiasis in one Canadian community based on patient symptom, outcome and exposure data from an enhanced surveillance system. It yields valuable data for estimating the burden of those diseases including the proportion of bloody diarrhoea, hospitalization, and disease duration. Age differences were observed by incidence rate and for some clinical information and exposures to risk factors. For each of the three diseases, the animal/environment-to-person route was the most common possible main transmission route according to the exposure reported, whereas the person-to-person route was the least common. Exposure was higher for the 10–24 years age group of giardiasis cases for swimming in recreational waters (79%) and attending a barbeque (50%). Therefore, comparisons between groups of cases or extrapolation of results when estimating the burden of illness should be adjusted for age.
Numerical analysis of a piezoelectric bone remodelling problem
Authors: FERNÁNDEZ J. R. , GARCÍA-AZNAR J. M. , MARTÍNEZ R.
Published: May 2012

Although in recent years bone piezoelectricity has been normally neglected, lately a new interest has appeared to show the importance of bone piezoelectricity in wet bone's complex response to loading. Here we numerically study a problem, including a strain-adaptive bone remodelling and the piezoelectricity. Its variational formulation leads to a coupled system composed of two linear variational equations for displacements and electric potential, and a parabolic variational inequality for the apparent density. Fully discrete approximations are now introduced by using the finite element method to approximate spatial variable and the explicit Euler scheme to discretise time derivatives. Somea priorierror estimates are proved and the linear convergence of the algorithm is deduced under additional regularity conditions. Finally, some one- and two-dimensional numerical simulations are described to show the accuracy of the proposed algorithm and the behaviour of the solution.
The Case: Starving for Perfection
Authors: MISHRA RUCHIKA
Published: May 2012

To submit a case that has been reviewed by an ethics committee or to submit papers on related topics in clinical ethics, readers are invited to contact Ruchika Mishra, editor of “Ethics Committees and Consultants at Work,” at: ruchika.mishra@gmail.com.
Differences in Danish children's diet quality on weekdays v. weekend days
Authors: Rothausen Berit W , Matthiessen Jeppe , Hoppe Camilla , Brockhoff Per B , Andersen Lene F , Tetens Inge
Published: May 2012

Objective

To compare differences in children's diet quality on weekdays (Monday–Thursday), Fridays and weekend days.

Design

A representative cross-sectional study in which participants completed a 7 d pre-coded food record. Mean intakes of energy, macronutrients and selected food items (g/10 MJ) as well as energy density were compared between weekdays, Fridays and weekend days for each gender in three age groups (4–6, 7–10 and 11–14 years) using Tobit analysis to account for zero intakes.

Setting

The Danish National Survey of Dietary Habits and Physical Activity 2003–2008.

Subjects

Children (n 784; 49·9 % boys) aged 4–14 years.

Results

For both genders in all age groups (P < 0·05), energy intake was higher during weekends than on weekdays, and intakes of sugar-sweetened beverages and white bread were higher, whereas intake of rye bread was lower. This contributed to a higher percentage of energy from added sugars, a lower fibre content and a higher energy density on weekend days v. weekdays. In children aged 4–6 and 7–10 years, the diet on weekend days was also characterized by higher intakes of sweets and chocolate and lower intakes of fruit and vegetables. Overall, the diet on Fridays appeared as a mix of the diets on weekdays and weekend days.

Conclusions

Significant differences and distinct characteristic patterns were found in children's diet quality during weekdays, Fridays and weekend days. The present study suggests that in prevention of childhood overweight and obesity, more attention should be paid to the higher energy intake, especially from sugar-rich foods and beverages, on Fridays and weekend days.
Correlates of Omani adults’ physical inactivity and sitting time
Authors: Mabry Ruth M , Winkler Elisabeth AH , Reeves Marina M , Eakin Elizabeth G , Owen Neville
Published: May 2012

Objective

To inform public health approaches for chronic disease prevention, the present study identified sociodemographic, anthropometric and behavioural correlates of work, transport and leisure physical inactivity and sitting time among adults in Oman.

Design

Cross-sectional study using the WHO STEPwise study methodology.

Setting

Sur City, Oman.

Subjects

Men and women aged 20 years and older (n 1335) in the Sur City Healthy Lifestyle Study who had complete data for demographic variables (gender, age, education, work status and marital status), BMI and behavioural risk factors – smoking and dietary habits plus physical inactivity and sitting time (the outcome variables).

Results

The highest level of physical inactivity was in the leisure domain (55·4 %); median sitting time was about 2 h/d. Gender-stratified logistic regression models found that the statistically significant (P < 0·05) correlates of inactivity (in one or more domains) were age, work status and fruit and vegetable intake in women, and age, education, work status, marital status and BMI in men. Gender-stratified linear regression models found that the statistically significant correlates of sitting time were age, work status and BMI in women and education in men.

Conclusions

Findings suggest that public health interventions need to be gender responsive and focus on domain-specific physical inactivity. In the Omani context, this might include gender-segregated exercise facilities to promote leisure physical activity among women and walking-friendly environmental initiatives to promote transport physical activity among men. Further evidence on barriers to physical activity and factors that influence prolonged sitting is required to develop relevant public health interventions.
Metal acquisition and virulence inBrucella
Authors: Roop R. Martin
Published: May 2012

Similar to other bacteria,Brucellastrains require several biologically essential metals for their survivalin vitroandin vivo. Acquiring sufficient levels of some of these metals, particularly iron, manganese and zinc, is especially challenging in the mammalian host, where sequestration of these micronutrients is a well-documented component of both the innate and acquired immune responses. This review describes theBrucellametal transporters that have been shown to play critical roles in the virulence of these bacteria in experimental and natural hosts.
States, Insurgents, and Wartime Political Orders
Authors: Staniland Paul
Published: May 2012

Bargains, deals, and tacit understandings between states and insurgents are common in civil wars. This fascinating mix of conflict and cooperation shapes patterns of politics, governance, and violence. Building on recent findings about state formation, I offer a conceptual typology of political orders amidst civil war. Wartime political orders vary according to the distribution of territorial control and the level of cooperation between states and insurgents. Orders range from collusion and shared sovereignty to spheres of influence and tacit coexistence to clashing monopolies and guerrilla disorder. Examples from contemporary South Asian conflicts illustrate these concepts, which are scalable and portable across contexts. Scholars need to think more creatively about the political-military arrangements that emerge and evolve during war. A key policy implication is that there are many ways of forging stability without creating a counterinsurgent Leviathan.
Can There Be a Political Science of the Holocaust?
Authors: King Charles
Published: May 2012

The substantial literature on mass violence, from ethnic cleansing to civil wars, has paid surprisingly little attention to the largest instance of mass violence in human history: the Holocaust. When political scientists have approached the subject, the trend has been to treat the Holocaust as a single case, comparing it—sometimes controversially—with other instances of genocide such as Rwanda or Cambodia. But historically grounded work on the destruction of European Jewry can help illuminate the microfoundations of violent politics, unpack the relationship between a ubiquitous violence-inducing ideology (antisemitism) and highly variable murder, and recast old questions about the origins and evolution of the Holocaust itself. After reviewing new trends in history-writing, I highlight opportunities for social-scientifically oriented research centered on the interaction of state power, local communities, and violent mobilization in five areas: military occupation, repertoires of violence, alliance politics, genocidal policymaking, and resistance. My conclusion addresses thorny issues of comparison, morality, and memory.
Response to James L. Gibson's Review of Skeletons in the Closet: Transitional Justice in Post-Communist Europe
Authors: Nalepa Monika
Published: May 2012

Vigorous exchanges between those who study charged topics like transitional justice using different approaches can be very helpful in progressing our understanding of the complex issues. But those reading this exchange between James Gibson and me could be left puzzled. While my review of Gibson's work shows how our two approaches can be harmonized, Gibson's review of Skeletons may urge readers to question whether, given such seemingly irreconcilable differences, transitional justice remains one field.
SpICE: A program to study small‐scale disturbances in the ionosphere
Authors: Harris T. J. , Cervera M. A. , Meehan D. H.
Published: May 2012

Ionospheric disturbances observed by bottom‐side soundings of the ionosphere appear at many temporal and spatial scales. Australia has many simultaneous observations from vertically orientated ionospheric sounders with spatial separations on the scale of 1000 km. However, with this spatial sampling only large scale ionospheric disturbances can be mapped and subsequently modeled. DSTO has an experimental program in progress to investigate the smaller spatial scale disturbances. These are often seen on vertical incidence soundings and are uncorrelated with soundings from greater than 500 km away. They can also be uncorrelated with soundings from the same site only 15 min later. The DSTO program to investigate these ionospheric disturbances is called SpICE, for Spatial Ionospheric Correlation Experiment. SpICE uses a small set of transmitters and receivers with varying separations to achieve a geographically spread set of near‐vertical incidence ionospheric “reflection” points separated by 50–150 km, allowing us to probe disturbances at this spatial scale. Using the latest digital receiver technology we can collect amplitude and phase information from the ionospheric returns of the continuous wave transmissions of a nearby transmitter that is rapidly sweeping through the HF band. The returned signal is processed at a very high resolution to achieve good signal‐to‐noise complex ionograms at better than one‐minute time updates. To date there have been three SpICE campaigns. This paper will discuss the SpICE program goals and highlight some of the unusual features observed in the first campaign. Following papers will look more closely at this data set and the subsequent campaigns.
The development of magmatism along the Cameroon Volcanic Line: Evidence from teleseismic receiver functions
Authors: Gallacher R. J. , Bastow I. D.
Published: May 2012

The Cameroon Volcanic Line (CVL) in West Africa is a chain of Cenozoic volcanism with no clear age progression. The reasons for its existence are unclear, and the nature of its magmatic plumbing system is poorly understood. Specifically, whether or not the CVL crust presently contains melt and/or mafic intrusions, as is often observed at hot spots and rifts elsewhere, is presently unknown. To address this issue, we present a receiver function study of crustal structure using earthquakes recorded by the Cameroon Broadband Seismic Experiment. In regions of the CVL unaffected by Cretaceous extension associated with the breakup of Gondwana (e.g., the Garoua rift), Vp/Vs ratios are markedly low (network average ∼1.74) compared to hot spots elsewhere, providing no evidence for either melt or cooled mafic crustal intrusions due to CVL magmatism. The character of P‐to‐S conversions from beneath the CVL also indicates that lower‐crustal intrusions (often termed underplate) are not present beneath the region. Our observations thus corroborate earlier petrological studies that show CVL alkaline magmas fractionate in the mantle, not the crust, prior to eruption. Hypotheses for the formation of the CVL should not include markedly elevated upper‐mantle potential temperatures, or large volumes of partial melt, both of which can explain observations at hot spots and rifts worldwide. The protracted, yet sporadic, development of small‐volume alkali melts beneath the CVL may instead be explained better by lower melt volume mechanisms such as shear zone reactivation or lithospheric delamination.
Late Paleozoic to Early Mesozoic tectonic evolution of northeast Tibet: Evidence from the Triassic composite western Jinsha‐Garzê‐Litang suture
Authors: Yang T.‐N. , Hou Z.‐Q. , Wang Y. , Zhang H.‐R. , Wang Z.‐L.
Published: May 2012

The Paleotethyan tectonic history of northeast Tibet remains hotly debated, particularly regarding the nature of the Jinsha suture. Different interpretations of the Jinsha suture lead to different tectonic reconstructions of northeast Tibet, southern Eurasian continent. We identified three tectonic units along the western segment of the Jinsha suture in the Yushu–Zhiduo region: the Bayan Har–Songpan–Garzê fold belt (BSB), the Yushu mélange, and the eastern portion of the Qiangtang block (EQ). New geochemical and geochronological studies help to identify a Triassic continental magmatic arc (the Yushu arc) that developed upon the EQ and that is geochemically similar to magmatism in the Yidun arc. Structural studies, combined with40Ar/39Ar analyses, reveal a complex deformational history of the Yushu–Zhiduo region: earlier‐stage top‐to‐the‐north asymmetrical fabrics are preserved exclusively in the Yushu mélange, which yields a phengite40Ar/39Ar age of 230.5 ± 0.8 Ma; later‐stage orthogonal fabrics developed in the BSB and EQ (superposed upon the earlier fabrics in the Yushu mélange), likely resulted from a collision between the BSB and the Yushu arc that continued until ∼195 Ma. The structural patterns and deformation history of Yushu arc region are comparable with those recorded in the Yidun arc region. Thus, the previously defined Jinsha suture should be subdivided into western and southern segments. The western Jinsha suture is continuous with the Garzê‐Litang suture, while the southern Jinsha‐Ailaoshan suture marks the site of the closure of several intracontinental rift basins that have likely been overprinted by intra or back‐arc extension.
Ar‐Ar dating of K‐feldspar in low grade metamorphic rocks: Example of an exhumed Mesozoic accretionary wedge and forearc, South Island, New Zealand
Authors: Mortimer N. , McLaren S. , Dunlap W. J.
Published: May 2012

New40Ar/39Ar ages from detrital K‐feldspars and metamorphic white micas from the Eastern Province terranes of New Zealand have been used to investigate the thermo‐tectonic history of different parts of an exhumed Mesozoic forearc basin and accretionary wedge. K‐feldspars from barely metamorphosed sedimentary host rocks mainly record detrital source area ages whereas those from zeolite and prehnite‐pumpellyite facies host rocks have textures and argon age spectra that indicate recrystallization during regional low‐temperature metamorphism. The results contribute to a model that genetically links thermo‐tectonic events across the accretionary wedge and forearc basin elements of the convergent margin, and into the Median Batholith arc probably by the Early Cretaceous and possibly by the Middle Jurassic. Thus, even though multidiffusion domain (MDD) models cannot be used to make inference on cooling histories in such situations, the K‐feldspar argon thermochronometer can provide useful information on the timing of geological events in sub‐greenschist facies rocks.
Unraveling the apparent magnitude threshold of remote earthquake triggering using full wavefield surface wave simulation
Authors: Parsons Tom , Kaven J. Ole , Velasco Aaron A. , Gonzalez‐Huizar Hector
Published: May 2012

Empirical studies with earthquake catalogs suggest that large events (M > 5) are rarely triggered in significant numbers by passing surface waves at remote distances from main shocks. Triggered, small (M < 5) earthquakes are routinely associated with the passage of surface waves from large (M > 7) main shocks. Since large earthquakes involve larger rupture areas, we study the spatial and temporal characteristics of dynamic stress change for clues. Using a 3D finite element method, we model the complete wavefield from the 2002 M= 7.9 Denali earthquake recorded near the Wasatch Front in Utah, where details about triggered seismicity are known. In particular, we load our model with a displacement seismogram to acquire a time series of the stress change tensor and model failure of a representative normal fault based on these stress changes. We note that the stress‐change regime varies rapidly between favoring strike‐slip, thrust, and normal faulting, with durations lasting ∼1–4 s. We find that these stress regimes usually affect only some fraction of a fault surface at any given time. Stress amplitudes also vary, meaning that ideal conditions for triggering are short‐lived and spatially limited. Stress conditions can also rapidly reverse to regimes that inhibit slip. Given these stressing conditions, we conclude that it may be difficult for a larger rupture area to experience the temporally and spatially coherent stress change necessary to develop into a large magnitude earthquake.
Signatures of sea level changes on tidal geomorphology: Experiments on network incision and retreat
Authors: Stefanon Luana , Carniello Luca , D'Alpaos Andrea , Rinaldo Andrea
Published: May 2012

How do tidal networks respond to changes in relative mean sea level (RMSL)? The question on whether the morphological features of a tidal landscape retain signatures of past environmental forcings, or are in equilibrium with current ones, is critical to our prediction of the fate of residual tidal landforms. In the case of tidal networks, the issue is quite relevant owing to their fundamental role on landscape eco‐morphodynamic evolution. Here we explore the response of tidal networks to cyclic variations in RMSL triggering tidal prism changes on the basis of laboratory experiments carried out in a synthetic lagoonal environment. A decrease in the tidal prism leads to network retreat and contraction of channel cross sections. Conversely, an increase in the tidal prism promotes network re‐incision and re‐expansion of channel cross sections: Network retreat and expansion tend to occur within the same planar blueprint. Our results show that the drainage density of tidal channels is linearly related to the landscape‐forming prism, although this relation is speculated to hold with reasonable approximation as a statistical tendency rather than as a pointwise, instantaneous adaptation. Changes in tidal prism rapidly influence network efficiency in draining the intertidal platform and the related transport of water, sediments, nutrients and pollutants. This bears important consequences for quantitative predictions of the long‐term ecomorphological adaptation of the tidal landscape to RMSL changes.
Dynamics of the region 1 Birkeland current oval derived from the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE)
Authors: Clausen L. B. N. , Baker J. B. H. , Ruohoniemi J. M. , Milan S. E. , Anderson B. J.
Published: May 2012

The region 1 (R1) and region 2 current systems typically form concentric rings of field‐aligned currents in the polar ionospheres; we term the inner ring the R1 oval. We apply an automated fitting scheme to field‐aligned current densities provided by the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) and identify the latitude of maximum R1 current at all magnetic local times to yield the size of the R1 oval. We investigate the dynamics of the R1 oval size in response to geomagnetic activity for two cases corresponding to: repeated substorm activations with a minimally enhanced ring current; a significant ring current enhancement with multiple substorms. During the first event the dynamics of the R1 oval size reflected an expanding‐contracting polar cap: during substorm growth phase dayside reconnection added open magnetic flux to the polar cap, expanding the R1 oval equatorward. Tail reconnection during the substorm expansion phase converted open into closed magnetic flux and the polar cap contracts as reflected by the poleward retreat of the R1 oval. During the period of enhanced ring current intensity the R1 oval grew to larger sizes during each substorm growth phase than it did during the other event, consistent with the suggestion that a stronger ring current stabilizes the magnetospheric tail to the onset of magnetic reconnection. The presented methodology allows AMPERE data to be condensed into a single parameter, the R1 oval size, which reflects magnetospheric dynamics and provides a convenient measure of the instantaneous magnetospheric system state in both hemispheres.
The need to consider ion Bernstein waves as a dissipation channel of solar wind turbulence
Authors: Podesta John J.
Published: May 2012

Kinetic Alfvén waves (KAWs) with highly oblique wave vectors, k⊥ ≫ k∥, are believed to form an integral part of the turbulent energy cascade in the solar wind near the proton gyroradius scale k⊥ρi ∼ 1. At wave numbers k⊥ρi > 1, where linear theory predicts kinetic Alfvén waves undergo strong Landau damping, mode coupling with ion‐Bernstein waves (IBWs) occurs. This mode coupling enables energy exchange between KAWs and IBWs that may be relevant for turbulent dissipation processes in the solar wind and other collisionless plasmas. It is pointed out that for plasmas having Gaussian velocity distributions, also known as Maxwellian plasmas, the dispersion relation of IBWs exhibits a fine structure or splitting into multiple branches that causes the dispersion relation of IBWs to intersect a given branch of the KAW dispersion relation several times, thus providing multiple channels of energy exchange between KAWs and IBWs (for a given angle of wave propagation). It is also shown that the collisionless damping rate of IBWs can exceed that of KAWs in certain regions of parameter space and that IBWs exhibit different ratios of proton to electron heating than KAWs. Consequently, the role of IBWs in the dissipation of solar wind turbulence requires more careful study. Gyrokinetic theory, gyrokinetic simulations, and other physical models of solar wind dissipation processes which ignore the coupling between KAWs and IBWs may be missing important physics.
Aerosol control on depth of warm rain in convective clouds
Authors: Konwar Mahen , Maheskumar R. S. , Kulkarni J. R. , Freud E. , Goswami B. N. , Rosenfeld D.
Published: May 2012

Aircraft measurements of cloud condensation nuclei (CCN) and microphysics of clouds at various altitudes were conducted over India during CAIPEEX (Cloud Aerosol Interaction and Precipitation Enhancement Experiment) phase I and II in 2009 and 2010 respectively. As expected, greater CCN concentrations gave rise to clouds with smaller drops with greater number concentrations (Nc). The cloud drop effective radius (re) increased with distance above cloud base (D). Warm rain became detectable, i.e., rain water content >0.01 g/Kg, at the tops of growing convective clouds when re exceeded 12 μm. The re is determined by the number of activated CCN, Nad, and D. The Nad can be approximated by the maximum measured values of Nc. Higher Nc resulted in greater D for reaching the re threshold for onset of warm rain, re*, denoted as D*. In extreme cases of highly polluted and moist air that formed the monsoon clouds over the Indo‐Gangetic plains, D* exceeded 6 km, well above the 0°C isotherm level. The precipitation particles were initiated there as supercooled raindrops at a temperature of −8°C. Giant CCN reduced re* and D*, by initiating raindrops closer to cloud base. This effect was found mainly in dusty air masses over the Arabian Sea. Besides, the aerosol effect on D*, D* was found to decrease with increase in cloud water path.
Immunoexcitotoxicity as a Central Mechanism of Chronic Traumatic Encephalopathy – A Unifying Hypothesis
Authors: Blaylock, Russell L. , Maroon, MD Joseph C.
Published: May 2012

Some individuals suffering from mild traumatic brain injuries, especially repetitive mild concussions, are thought to develop a slowly progressive encephalopathy characterized by a number of the neuropathological elements shared with various neurodegenerative diseases. A central pathological mechanism explaining the development of progressive neurodegeneration in this subset of individuals has not been elucidated. Yet, a large number of studies indicate that a process called immunoexcitotoxicity may be playing a central role in many neurodegenerative diseases including chronic traumatic encephalopathy (CTE). The term immunoexcitotoxicity was first coined by the lead author to explain the evolving pathological and neurodevelopmental changes in autism and the Gulf War Syndrome, yet it can be applied to a number of neurodegenerative disorders. The interaction between immune receptors within the central nervous system (CNS) and excitatory glutamate receptors trigger a series of events, such as extensive reactive oxygen species/reactive nitrogen species generation, accumulation of lipid peroxidation products, and prostaglandin activation, which then leads to dendritic retraction, synaptic injury, damage to microtubules, and mitochondrial suppression. In this chapter, we discuss the mechanism of immunoexcitotoxicity and its link to each of the pathophysiological and neurochemical events previously described with CTE, with special emphasis on the observed accumulation of hyperphosphorylated tau.
Astroglial Proteins as Biomarkers of Intracerebral Hemorrhage
Authors: Foerch CHRISTIAN
Published: May 2012

The astrocytic glial fibrillary acidic protein (GFAP) has recently been identified as a blood biomarker candidate indicating acute intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. Following the rupture of an arterial vessel, the expansion of a hematoma into the brain tissue causes a rapid destruction of astrocytes and the blood-brain barrier with an immediate release of GFAP into the bloodstream. In contrast, in ischemic stroke, necrosis and structural disintegration of astroglial cells do not occur until 6 to 12 hours after symptom onset. Thus, a time window exists in which elevated blood GFAP values indicate ICH. Explorative clinical studies have shown that GFAP is detectable in the blood of patients with acute ICH, whereas patients with acute ischemic stroke (<6hours after symptom onset) do not have measurable GFAP serum values. A sensitivity of 80% to 85% and a specificity of >95% for diagnosing ICH (versus ischemic stroke) has been reported. This chapter provides an overview on the pathophysiological background and evidence derived from clinical trials to date. Furthermore, potential clinical applications of a GFAP point-of-care test are discussed.
Molecular Dynamics Simulations of RNA Molecules
Authors: Šponer J. , Otyepka M. , Banáš P. , Réblová K. , Walter N. G.
Published: May 2012

The experimental techniques available to study structural dynamics and function of RNA are efficiently complemented by advanced computational methods. Molecular dynamics (MD) simulation is particularly useful as an auxiliary technique to provide deeper insights into known structures derived primarily from atomic-resolution crystal structures of RNAs in functionally relevant states. Careful analysis of MD simulations can identify problematic aspects of an experimental RNA structure, unveil structural characteristics masked by experimental constraints, reveal functionally significant stochastic fluctuations, evaluate the structural impact of base substitutions, modifications and ionization, and predict structurally and potentially functionally important details of the solvent behavior, including the presence of tightly bound water molecules. In contrast, reliable predictions of structure from sequence information remain beyond the applicability of MD tools. MD relies on simple atomistic force fields while high-quality starting structures are required. We comment here on the two latest refinements of the AMBER force field, i.e., parmbsc0 and parmOL. Parmbsc0 is an essential reparametrization of the α/γ torsional profiles. ParmOL is reparametrization of the χ region that suppresses high-anti χ states while also modifying the anti versus syn balance and the shape of the syn region. Still, even with these improvements, MD simulations are far from perfect. Hybrid QM/MM approaches help in the assessment of the plausibility of chemical mechanisms in RNA enzymes. The ultimate utility of computational studies in understanding RNA function requires that the results are neither blindly accepted nor flatly rejected, but rather considered in the context of all available experimental data.
Structure and Dynamics of Supercoiled DNA Knots and Catenanes
Authors: Witz Guillaume , Stasiak Andrzej
Published: May 2012

Circular DNA molecules in vivo form catenanes and knots during such processes as replication or recombination. In addition, DNA molecules are often subjected to a torsional tension, which results in their supercoiling. The interplay between catenation, knotting and supercoiling leads to unexpected conformational changes of entire DNA molecules, and this has interesting physical and biological consequences. We show in this chapter how modelling DNA as a semi-flexible ribbon can be applied to get information about the molecular conformation of DNA molecules with complex topologies. In particular, our results highlight the importance of the chirality of knots and catenanes in the structural changes induced by DNA supercoiling. For example, strongly linked right-handed toroidal DNA catenanes undergo a specific folding that can be reversed by the introduction of negative supercoiling in each chain, or the shape of negatively supercoiled DNA trefoil knots depends on their chirality. In each case, we perform dynamical simulations including hydrodynamics, to investigate the consequences of these structural changes on the sedimentation and gel electrophoretic behaviour of the modelled knotted and catenated DNA molecules.
Sliding Dynamics Along DNA: A Molecular Perspective
Authors: Marcovitz Amir , Levy Yaakov
Published: May 2012

Rapid recognition of DNA target sites involves facilitated diffusion through which alternative sites are searched on genomic DNA. One of the key mechanisms in the localization of the target by a DNA binding protein is one-dimensional diffusion (sliding) in which the protein is attracted to the DNA by electrostatic forces. During the search, the protein faces both a thermodynamic and a kinetic challenge, as it needs to rapidly recognize and tightly bind a specific DNA sequence within an enormous background of nonspecific genomic sites and competing macromolecular species. Understanding the nature of interactions between regulatory proteins and nonspecific DNA sequences is required in order to decipher the structural and dynamic features that underlie protein–DNA recognition processes. In this review, we discuss a simplified computational approach that represents protein–DNA interactions by electrostatic forces. We provide structural criteria that distinguish between different search mechanisms and show that the protein makes use of similar binding interfaces for both nonspecific and specific interactions. The presented model captures various experimental features of facilitated diffusion and has the potency to address other questions regarding the nature of DNA search, such as the sliding characteristics of oligomeric and multidomain DNA binding proteins that are ubiquitous in the cell.
Structure-based Design Technology CONTOUR and its Application to Drug Discovery
Authors: Liu Zhijie , Lindblom Peter , Claremon David A. , Singh Suresh B.
Published: May 2012

Structure-based design has had a significant impact on the drug discovery process over the past two decades by identifying novel and efficacious molecules for a variety of therapeutic targets. Among the approaches used for structure-based drug design, the de novo design approach has a great potential to generate novel molecules that best complement a protein binding site, but had failed to meet expectations in its initial attempts. More recently this approach has met with success due to algorithmic developments in the methodologies. In this chapter we introduce a state-of-the-art de novo design technology called CONTOUR®, provide details of the algorithmic enhancements we have implemented and show improvements in performance over past methods. CONTOUR was developed to grow novel drug like molecules by assembling fragments in the context of the binding site using a high resolution crystal structure of a protein as a starting point. The technology comprises a sophisticated growth algorithm that works in concert with an effective scoring function. The growth algorithm creates molecules in a context sensitive manner by assembling fragments that are dynamically selected from a fragment library and screened to optimally complement features of a given binding site. The scoring function was developed to capture essential elements of the binding interactions and to rank order grown molecules with a high probability of exhibiting activity against a protein target of interest. The application of CONTOUR to identify inhibitors against human 11β HSD1 enzyme will be discussed here.
Molecular Simulation in Computer-aided Drug Design: Algorithms and Applications
Authors: Swift Robert V. , Amaro Rommie E.
Published: May 2012

Molecular simulations have made substantial contributions in the area of drug discovery over the past two decades. These contributions have been facilitated by increases in raw compute power and the availability of high-resolution structures, as well as improvements in general methods and algorithms. In this chapter, the contributions of molecular simulations, in particular molecular dynamics (MD) and Monte Carlo (MC) simulation methods, to the discovery and design of novel therapeutic agents will be discussed. After a brief introduction to drug discovery and pharmacology jargon, the reader is introduced to the concepts of using of molecular simulation to: investigate structure-dynamics-function relationships in clinically-relevant targets, perform predictive ensemble-based virtual screening experiments, estimate free energies of binding and perform hit-to-lead optimization. Advice on presented algorithms and future prospects are also discussed.
Derivative discontinuity, bandgap and lowest unoccupied molecular orbital in density functional theory
Authors: Yang Weitao , Cohen Aron J. , Mori-Sánchez Paula
Published: May 2012

The conventional analysis of Perdew and Levy, and Sham and Schlüter shows that the functional derivative discontinuity of the exchange-correlation density functional plays a critical role in the correct prediction of bandgaps, or the chemical hardness. In a recent work by the present authors, explicit expressions for bandgap prediction with all common types of exchange-correlation functionals have been derived without invoking the concept of exchange-correlation energy functional derivative discontinuity at all. We here analyze the two approaches and establish their connection and difference. The present analysis further leads to several important results: (1) The lowest unoccupied molecular orbital (LUMO) in DFT has as much meaning in describing electron addition as the highest occupied molecular orbital (HOMO) in describing electron removal. (2) Every term in the total energy functional contributes to the energy gap because of the discontinuity of the derivative of the density (or density matrix) with respect to the number of electrons, \documentclass[12pt]{minimal}\begin{document}$((\partial \rho _{s}(\mathbf {r^{\prime }},\mathbf {r}))/\partial N )_{v_{s}}$\end{document}((∂ρs(r′,r))/∂N)vs, at integers. (3) Consistent with the Perdew-Levy-Sham-Schlüter conclusion that the exact Kohn-Sham energy gap differs from the fundamental bandgap by a finite correction due to the functional derivative discontinuity of the exchange-correlation energy, we show that the exchange-correlation functional cannot be an explicit and differentiable functional of the electron density, either local or nonlocal. The last result is further strengthened when we consider Mott insulators. There, the exact exchange-correlation functional needs to have an explicitly discontinuous (nondifferentiable) dependence on the density or the density matrix. (4) We obtain exact conditions on the derivatives of total energy with respect to the spin-up and spin-down number of electrons.
Experimental determination of thermal profiles during laser spike annealing with quantitative comparison to 3-dimensional simulations
Authors: Iyengar Krishna , Jung Byungki , Willemann Michael , Clancy Paulette , Thompson Michael O.
Published: May 2012

Thin film platinum resistors were used to directly measure temperature profiles during laser spike annealing (LSA) with high spatial and temporal resolution. Observed resistance changes were calibrated to absolute temperatures using the melting points of the substrate silicon and thin gold films. Both the time-dependent temperature experienced by the sample during passage of the focussed laser beam and profiles across the spatially dependent laser intensity were obtained with sub-millisecond time resolution and 50 µm spatial resolution. Full 3-dimensional simulations incorporating both optical and thermal variations of material parameters were compared with these results. Accounting properly for the specific material parameters, good agreement between experiments and simulations was achieved. Future temperature measurements in complex environments will permit critical evaluation of LSA simulations methodologies.
Effect of oxygen vacancy on the dielectric relaxation of BaTiO3 thin films in a quenched state
Authors: Yao Sheng-Hong , Yuan Jin-Kai , Gonon Patrice , Bai Jinbo , Pairis Sébastien , Sylvestre Alain
Published: May 2012

A thermal treatment below the crystallization temperature followed by rapid cooling down was adopted onto as-deposited BaTiO3 (BTO) amorphous films to freeze the microstructure activated at annealed temperature. A large increase of dielectric constant from 19 to 329 was observed at 0.1 Hz for the BTO film annealed at 600 °C for 60 min. Subsequently, three separated dielectric relaxations were exploited as a function of the frequency and temperature. Such dielectric responses were analyzed in terms of the activation energy. The evolution of oxygen vacancy with temperature can be invoked as being responsible for the observed dielectric relaxations.
B4C thin films for neutron detection
Authors: Höglund Carina , Birch Jens , Andersen Ken , Bigault Thierry , Buffet Jean-Claude , Correa Jonathan , van Esch Patrick , Guerard Bruno , Hall-Wilton Richard , Jensen Jens , Khaplanov Anton , Piscitelli Francesco , Vettier Christian , Vollenberg Wilhelmus , Hultman Lars
Published: May 2012

Due to the very limited availability of 3He, new kinds of neutron detectors, not based on 3He, are urgently needed. Here, we present a method to produce thin films of 10B4C, with maximized detection efficiency, intended to be part of a new generation of large area neutron detectors. B4C thin films have been deposited onto Al-blade and Si wafer substrates by dc magnetron sputtering from natB4C and 10B4C targets in an Ar discharge, using an industrial deposition system. The films were characterized with scanning electron microscopy, elastic recoil detection analysis, x-ray reflectivity, and neutron radiography. We show that the film-substrate adhesion and film purity are improved by increased substrate temperature and deposition rate. A deposition rate of 3.8 Å/s and substrate temperature of 400 °C result in films with a density close to bulk values and good adhesion to film thickness above 3 μm. Boron-10 contents of almost 80 at. % are obtained in 6.3 m2 of 1 μm thick 10B4C thin films coated on Al-blades. Initial neutron absorption measurements agree with Monte Carlo simulations and show that the layer thickness, number of layers, neutron wavelength, and amount of impurities are determining factors. The study also shows the importance of having uniform layer thicknesses over large areas, which for a full-scale detector could be in total ∼1000 m2 of two-side coated Al-blades with ∼1 μm thick 10B4C films.
Perturbative treatment of triple excitations in internally contracted multireference coupled cluster theory
Authors: Hanauer Matthias , Köhn Andreas
Published: May 2012

Internally contracted multireference coupled cluster (ic-MRCC) methods with perturbative treatment of triple excitations are formulated based on Dyall's definition of a zeroth-order Hamiltonian. The iterative models ic-MRCCSDT-1, ic-MRCC3, and their variants ic-MRCCSD(T), ic-MRCC(3) which determine the energy correction from triples by a non-iterative step are consistent in the single-reference limit with CCSDT-1a, CC3, CCSD(T), and CC(3), respectively. Numerical tests on the potential energy surfaces of BeH2, H2O, and N2 as well as on the structure and harmonic vibrational frequencies of the ozone molecule show that these methods account very well for higher order correlation effects. The ic-MRCCSD(T) method is further applied to the geometry optimization and harmonic frequencies of the symmetric vibrational modes of the binuclear transition metal oxide Ni2O2, to the singlet-triplet splittings of o-, m-, and p-benzyne and to a ring-opening reaction of an azirine compound with the molecular formula C6H7NO. The size of the active spaces used in this study ranges from CAS(2,2) to CAS(8,8). Comparisons of results based on differently sized active spaces indicate that the ic-MRCCSD(T) method provides a highly accurate and efficient treatment of both static and dynamic electron correlation in connection with minimal active spaces.