Phosphorylated polypeptides represent promising biomimetic macromolecules for various regenerative applications. However to date, large-scale synthesis of phosphorylated polypeptides with controlled degrees of phosphorylation has not been achieved, restricting research in phosphorylated proteins to their central roles in biomineralization pathways. Here, we present a co-polypeptide synthesis strategy based on the Ring-Opening Polymerization (ROP) of N-carboxyanhydrides (NCAs), followed by controlled phosphorylation of serine (Ser) residues. The molecular design, including amino acid composition and molecular weight of polypeptides, mimicked the intriguing phosphorylated protein Pc-3 secreted by the sandcastle tube worm Phragmatopoma californica, which is a major constituent of the glue produced by the animal to bind hard particles together for their protective tubes. Pc-3 is comprised of mostly Ser and tyrosine (Tyr), with up to 70% of Ser residues phosphorylated into phospho-serine (pSer) giving rise to the high net negative charge of Pc-3. Three NCA monomers were synthesized, namely Ser with free –OH groups, and Ser and Tyr with protected –OH groups, and subsequently polymerized with various feeding ratios in order to obtain a broad range of final amino acid compositions. In the final step, phosphorylation targeting free –OH groups of Ser was conducted. With this strategy, the degree of phosphorylation is governed by the initial amount of unprotected –OH groups of the precursor Ser–NCA, and the final co-polypeptides contain relative amounts of Tyr and pSer that can be tailored, yielding a composition and molecular weight (MW) that closely match those of Pc-3. This control of phosphorylation leads to polypeptides exhibiting a wide range of zeta potential values between −20 and −50 mV. Using analytical assays, including Dynamic Light Scattering (DLS), Surface Plasmon Resonance (SPR), and Quartz Crystal Microbalance with Dissipation (QCM-D), we demonstrate that these phosphorylated polypeptides exhibit affinity towards divalent ions such as Ca2+, thus opening the door for their usage as scaffolds for mineralized tissue repair or as a major component of biocompatible adhesives.


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Machine learning is one of the most important subfields of computer science and can be used to solve a variety of interesting artificial intelligence problems. There are different languages, framework and tools to define the data needed to solve machine learning-based problems. However, there is a great number of very diverse alternatives which makes it difficult the intercommunication, portability and re-usability of the definitions, designs or algorithms that any developer may create. In this paper, we take the first step towards a language and a development environment independent of the underlying technologies, allowing developers to design solutions to solve machine learning-based problems in a simple and fast way, automatically generating code for other technologies. That can be considered a transparent bridge among current technologies. We rely on Model-Driven Engineering approach, focusing on the creation of models to abstract the definition of artifacts from the underlying technologies.


Simulation of tunneling electrons excited by the sunlight in TiO2 to surface states is performed for TiO2/Si nanostructure. The tunneling transmission coefficient of the surface states created by organic compounds was calculated by phase function method. Dependence of the transmission coefficient of tunneling electrons on potential barrier parameters is explained by interference of transmitted and reflected waves.


This paper quantifies sediment contamination by heavy metals in four reservoirs and one lake located downstream from major urban areas in Switzerland. The waterbodies include the Wettingen Reservoir (located on the Limmat River downstream from Zurich), the Klingnau Reservoir (on the lower Aare River), the Wohlen Reservoir (downstream from Berne), the Verbois Reservoir (downstream from Geneva) and Vidy Bay (Lake Geneva, city of Lausanne). For all sediment cores and contaminants, a trend is observed from high contaminant values in the lower part of the cores, decreasing to lower concentrations in the upper part of the cores. However, for each site and each element, specific features are recognized. Applying the criteria of the Swiss ordinance on soil protection, all sediment cores must be classified as contaminated by one or more contaminants and at variable levels. From these data, it is concluded that: reservoirs and lakes located downstream from major urban centres in Switzerland have accumulated significant volumes of contaminated sediments in the past, representing the largest, but not the most intensely, contaminated sites on a national scale; the main environmental risk is remobilization of the contaminants and their return to the food chain, particularly by infiltration into the groundwater; and although the processes of remobilization are identified, the conditions of occurrence and the amplitude of the processes are still poorly known. Different options of reservoir and lake sediment management also are discussed and further research topics defined.


We investigate the electronic structure of solution-processed perovskite solar cells using temperature-dependent electroabsorption (EA) spectroscopy. Simultaneous measurements of absorption and electromodulated spectra of semitransparent methylammonium lead iodide solar cells facilitate a direct comparison of the specific features. The EA spectra can be transformed to peak-like line shapes utilizing an approach based on the Kramers–Kronig relations. The resulting peak positions correspond well to the discrete excitonic—rather than the continuum—contribution of the absorption spectra derived from generalized Elliott fits. This indicates the excitonic nature of the observed EA resonance and is found to be consistent over the whole temperature range investigated (from T = 10 K up to room temperature). To further confirm these findings, a line shape analysis of the measured EA spectra was performed. The best agreement was achieved using a first-derivative-like functional form which is expected for excitonic systems and supports the conclusion of an excitonic optical transition. Exciton binding energies EB are estimated for the orthorhombic and tetragonal phases as 26 meV and 19 meV, respectively. Nevertheless, power-conversion efficiencies η up to 13% (11.5% stabilized) demonstrate good charge-carrier separation in the devices due to sufficient thermal dissociation and Sommerfeld-enhanced absorption.


The objective of the study was to examine the hypothesis that some forms of suicidal behavior among adolescents are related to helplessness and depression, whereas others are related to anger and impulsivity. Sixty-five adolescents were studied. Thirty-three had borderline personality disorder (BPD), of whom 17 had made a recent suicide attempt. Thirty-two had major depressive disorder (MDD), of whom 16 had made a recent suicide attempt. Assessments were made with the Child Suicide Potential Scale, the Beck Depression Inventory, the Beck Hopelessness Scale, the Multidimensional Anger Inventory, the Overt Aggression Scale, the Impulsiveness-Control Scale, and the Suicide Intent Scale. Adolescents with BPD had more anger, aggression, and impulsiveness than those with MDD, but similar levels of depression and hopelessness. Suicidal versus nonsuicidal adolescents were more depressed, hopeless, and aggressive, but not more angry or impulsive. There were no significant differences in impulsiveness for the MDD suicidal group versus the MDD nonsuicidal group, but the suicidal BPD adolescents were significantly more impulsive than the nonsuicidal BPD adolescents. In the subjects with BPD, impulsiveness and aggression correlated significantly and positively with suicidal behavior. In the subjects with MDD, no such correlations were seen. In both diagnostic groups, depression and hopelessness correlated positively and significantly with suicidal behavior. Anger did not correlate with suicidal behavior in either of the groups. The suicidal subjects with MDD had significantly higher suicidal intent scores than the suicidal adolescents with BPD. We conclude that the nature of suicidal behavior in adolescents with BPD differs from that seen in MDD with respect to the role of anger and aggression.


Emerging infectious diseases are an increasingly prominent threat to biodiversity. However, traditional methods in conservation generally have limited efficacy in the face of disease threats. Ironically, although unintentional human movement of species has facilitated the spread of pathogens, intentional conservation translocations are a promising approach to combatting disease threats under certain circumstances. Here, we summarize two decades of published literature on translocations of Australian frogs threatened by chytridiomycosis—a fungal disease that has caused amphibian declines and extinctions globally. We identify key motivations, considerations, and factors associated with outcomes, including the role of chytridiomycosis in failures. In an effort to improve success, we then propose a conceptual framework for determining when conservation translocations may be both feasible and beneficial, with a focus on understanding mechanisms favoring host persistence. Lastly, we build on our findings from the review and the conceptual framework to develop a set of recommendations to guide practitioners aiming to translocate amphibians as a conservation strategy in the face of chytridiomycosis. Although diseases pose a unique set of challenges for managing declining species in the wild, we argue that progress is likely with careful and well‐informed adaptive management experiments to refine reintroduction and translocation efforts.


preliminary vehicle design. From a customer perspective, desirability can be mapped to the performance specifications of a design. Desirability drives the customer-perceived value of the vehicle, which when combined with price, serves to drive the vehicle's market share. Such vehicle designs must also be technically feasible from an engineering perspective, ensuring and establishing confidence that they can be realized and manufactured. Traditional analyses of desirability, however, are conducted by presenting discrete performance specifications. Incorporating uncertainty into a preliminary design's performance allows the consumer to be presented with performance specifications characterized by either a mean value or distribution, permitting investigation of variation from a customer's perspective. The goal of this research is to take a set of non-dominated solutions and combine them with a random utility model, to explore how the variance in both models impacts the final solution. This paper explores the impact of uncertainty in vehicle design, with potential vehicles first being created and assessed for feasibility. A Technical Feasibility Model is utilized to narrow down the possible designs to those that are both feasible and Pareto optimal. Capturing customer preference ranges for each objective is made possible with the implementation of utility functions whose coefficients are dictated by a referenced market model. In addition to defining the customer preference ranges for this problem, uncertainty is applied to each performance objective considered within the vehicle model. The vehicle designs are then evaluated, combining the variances associates with uncertainty in vehicle performance and the aspects of a random utility model.


Proteomics and bioinformatics reveal a role for the phosphatase PP6 in opposing phosphorylation by casein kinase 2. Exploring mitotic phosphatase function To study the function of the serine-threonine protein phosphatase PP6, Rusin et al. analyzed the effect of depleting HeLa cells of the catalytic subunit of PP6 on the phosphoproteome when the cells were arrested in mitosis. Motif analysis of the sequences of the sites that changed in the PP6c-depleted cells suggested kinases that PP6 activity may oppose. In addition to the known role of PP6 in reducing the activity of the Aurora kinase A, a kinase that is important for chromosome segregation and spindle formation, network analysis of the proteins that exhibited differences in phosphorylation identified roles for PP6 in the regulation of RNA splicing, rRNA processing, and translation. Biochemical analysis showed that a subunit of the complex necessary for chromosome condensation was phosphorylated by casein kinase 2 and dephosphorylated by PP6. Thus, this study identified a mitotically regulated phosphorylation event in this critical complex and provided many other potential direct substrates of PP6 and pathways regulated by PP6 in mitotic cells. Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry–based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2–dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity.


Following international agreement on the sustainable development goals, governments are now confronting the critical issue of funding the enormous investments - especially in infrastructure - required to meet those goals. Yet governments clearly lack the fiscal space to finance all the investments, as well as the skills needed to design and manage them. So the focus is on how to crowd in private investment and private management. Since not enough private investment is flowing today, donor governments are exploring how to blend public aid money with private finance to make aid spending go further and crowd in more private investment.


"The most urbanized provinces of the Netherlands are North-Holland, South-Holland and Utrecht. In these provinces, the population density (number of inhabitants per square kilometer of land) is five times that of the Northern provinces and Zeeland.... According to the Regional Population Forecasts 1994, up to 2015 all the provinces are expected to have a positive population growth. The population of the youngest province Flevoland will grow most rapidly: by about 50%. The population growth, both in relative and absolute terms, will be small in the Northern provinces and Zeeland (in the South West)." (SUMMARY IN ENG)


The clinical need and historical approaches to tissue engineering as applied to regenerative medicine are introduced, along with comments on activities in this field around Australia, and then the huge advances for tissue culture studies are discussed ( Part A ). Combinations of human stem cells and new approaches for generating bioscaffolds present great opportunities for in vitro studies of basic biology and physiology, drug testing and high throughput screening for the pharmaceutical industry, and the advanced tissue engineering of organs and devices. The future here is bright. The major obstacles arise with in vivo application of these bioengineering advances using animal models and humans ( Part B ), and the complexity of living tissues and the challenges of increased scale required for clinical translation to the large human situation are first discussed. While clinical success seen with implantation of acellular bioscaffolds (with population by host cells) is likely to expand for human use, the major challenge relates to (generally) low survival in vivo of (donor or autologous) cells that are expanded and grown in tissue culture before implantation into the living body. Another major challenge is revascularisation of implanted tissues/organs at the human scale. The innovative approaches and rapid advances in tissue bioengineering hold great promise for overcoming these major obstacles and extending the clinical applications of these technologies.


Vibrational sum frequency spectroscopy has been
used to study the molecular properties upon compression of a highly charged
arachidic acid Langmuir monolayer, which displays a first order phase
transition plateau in the surface pressure - molecular area (p-A) isotherm. By targeting vibrational modes
from the carboxylic acid headgroup, alkyl chain, and interfacial water
molecules, information regarding the surface charge, surface potential, type of
ion pair formed, and conformational order of the monolayer could be extracted. The
monolayer in the liquid expanded phase is found to be fully charged until
reaching the 2D-phase transition plateau, where partial reprotonation, as well
as the formation of COO⎺ Na+ contact-ion
pairs, start to take place. In the condensed phase after the transition, three
headgroup species, mainly hydrated COO⎺, COOH, and COO⎺ Na+ contact-ion pairs could be
identified and their proportions quantified. Comparison with theoretical models
shows that despite the low ionic strengths used (i.e. 10 mM), the predictions
from the Gouy Chapman model are only adequate for the lowest surface densities,
when the surface charge does not exceed -0.1 C/m2. In contrast, a
modified Poisson-Boltzmann (MPB) model that accounts for the steric effects
associated with the finite ion-size, captures many of the experimental
observables, including the partial reprotonation, and surface potential changes
upon compression. The agreement highlights the importance of hydronium ion –
carboxylate interactions, as well as the layer of sodium ions packed at the
steric limit, for explaining the phase transition behavior. The MPB model,
however, does not explicitly consider the formation of contact ion pairs with
the sodium counterion. The experimental results provide a quantitative molecular
insight that could be used to test potential extensions to the theory.


Postoperative delirium (POD) is a major complication following surgery and is considered the most common complication among older adults following cardiac surgery; with up to 87% of patients being affected (Whitlock, Vannucci, & Avidan, 2011). Dexmedetomidine, a highly selective α2 agonist, inhibits the release of norepinephrine presynaptically causing analgesia and inhibits central nervous system stimulation in the postsynaptic neurons causing decreased blood pressure and heart rate; together, contributing to the effects of analgesia, anesthesia, and sedation (Naaz & Ozair, 2014). The purpose of this systematic review was to analyze the current literature and examine the effects of dexmedetomidine on POD in the adult cardiac surgical population. A comprehensive literature review was completed using CINAHL, PubMed, and Medline focusing on the pathology of postoperative delirium, the physiology of cardiac surgery, and the pharmacodynamics of dexmedetomidine. Guidelines set forth by PRISMA and Inouye and Charpentier's multifactorial model were utilized to assist in the identification of eligible studies. Study analysis was completed by creating study specific and data outcome tables. Critical appraisal of individual RCTs was performed utilizing the Critical Appraisal Skills Programme (CASP) checklist. A cross study analysis table was also created comparing the results of all eligible studies against one another. The findings of this systematic review determined that in the adult cardiac surgical population, dexmedetomidine was associated with a decreased incidence of POD; however, the results for time to extubation, ICU LOS (length of stay), and hospital LOS varied amid the studies examined.


PURPOSE
Due to the negative impact of radiation on the patient and the surgical team during percutaneous nephrolithotomy (PCNL), we aimed to evaluate success rate and complications of blind access for PCNL using lumbar notch landmark and compare with conventional fluoroscopy-guided access.

MATERIALS AND METHODS
In a clinical trial, 100 patients who were candidate for PCNL, were randomly assigned into blind group (1) and fluoroscopy-guided group (2). In group 1 the lumbar notch was used to guide percutaneous access and in group 2 fluoroscopy performed after needle insertion, Amplatz placement and at the end of surgery. If the access failed, we would repeat puncturing up to 5 times. In group 2, access was achieved using full fluoroscopy guidance. All patients underwent postoperative assessment including kidney-ureter-bladder X-ray and ultrasonography.

RESULTS
Both mean access time and mean operation time were statically similar in group 1 and group 2 (3.3 ± 0.5 vs. 3.6 ± 0.7 min and 35.2 ± 4.6 vs. 38.9 ± 4.1 min, respectively). A successful puncture was achieved in 86% and 94% of the patients in groups 1 and 2, respectively (P = .18). Total success rate of procedure was 80% and 88% of the patients in groups 1 and 2, respectively (P = .27).

CONCLUSION
According to this study, it seems that blind access is a safe and effective PCNL method, and we recommend employment of this technique by skilled endourologist in urology centers especially for patient with large hydronephrotic kidney.


This thesis systematically investigates the physical, mechanical and chemical properties of the copper oxidation on the copper alloy leadframe that influence the reliability of an IC packaging in semiconductor industries. In this study, the oxidation on the copper alloy leadframe was promoted via heat treatment process. The copper oxidation was investigated and characterized using various advanced analytical techniques by means of Optical Microscopy, Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), Vickers Micro-Indentation, Energy Dispersive X-ray Spectroscopy (EDS), Auger Electron Spectroscopy (AES), Focused Ion Beam (FIB), High Resolution Transmission Electron Microscopy (HRTEM) and Energy Electron Loss Spectroscopy (EELS). The oxidation was found to cause a transformation of physical colour of the leadframe from light brown to dark brown. The changes of the surface texture from fine to coarse granular were also observed as a result of the oxidation process. The coarse granular surface derived from high temperature treatment was found to be hard and brittle resulting to the flaky and crack surface as it is induced by the Vickers micro indentation test. The oxidation was found to be initiated at the heat treatment temperature of 120 °C. The copper oxide thickness shows an increasing trend as the temperature increases. The copper oxide thickness growth was 16 nm, 49 nm, 93 nm and 160 nm at the heat treatment temperature of 150 °C, 180 °C, 210 °C and 240 °C respectively. The activation energy was found to be 41 kJ/mol. At high oxidation temperature, the formation of micro-voids and separations were observed along the interface between the copper oxide and the bulk copper leadframe. Poor adhesion at this interface region due to micro-voids and separation were found to be the root cause of the delamination issue. EELS analysis determined that for the regions with intact interface the oxidation system is CuO/Cu2O/CuO/Cu, however, in regions containing micro-voids or separations the oxidation system is found to be CuO/Cu2O/Cu.


Rights to territory and rights to immigration are usefully theorized together. Our starting point is a Lockean analysis of the moral foundations of territoriality offered by John Simmons. Crucially, this Lockean account makes the legitimacy of a state's claim to its territory dependent on a prior claim to land that individuals may have. However, we will see that this account needs to be amended to give appropriate expression to the view that the earth is common property of humankind, which is central to the Lockean account of ownership. In this way, Locke's thought leads us to notions of over- and under-use of collectively owned resources that might help us understand the moral nature of immigration. However, once we have developed this Lockean account to that point, we will leave it behind to develop our main conclusions in a manner that does not depend on a specifically Lockean account. We will embark on a systematic discussion on the notion of collective ownership and explore various ways of thinking about it, and then derive accounts of immigration and territoriality. In doing so, we will be able to offer more precise accounts of the ideas of over- and under-use of resources, so as to introduce the possibility of resource-based constraints on immigration policy. The account that will emerge in this way will be quite different from Simmons, but in line with the revisions of the Lockean account that we will suggest. We will proceed to use this territorial account as a means of criticizing one pattern of argument frequently invoked to legitimate the state's right to constrain immigration: the survival and preservation of culture. We will conclude with some final reflections on the right to culture more generally, understood here as a right to select immigrants based upon their cultural membership and identity.


The main aim of this project was to find new tools and finishing techniques for designing recyclable, aesthetic 'surfaces' within the context of a 'closed cycle polyester economy' (Livingston, 2003). This can be explained as a mechanism of industrial ecology where all waste can be reused in a perpetual material metabolism or system.

Of the total textile fibre produced globally, up to 65% is lost, post-consumer, to landfill, incineration or composting. Of this, at least 50% is said to be recyclable (Laursen et al, 2005). In particular polyester, a synthetic fibre group derived from oil, is responsible for as much as 79% of the global synthetic fibre market, at 31.9 million tonnes in 2009 (Engelhardt, 2010), and therefore represents a significant proportion of this textile waste. Polyester is a thermoplastic material and as such is fully recyclable, thus making a closed cycle polyester economy a theoretical possibility. Therefore sending it to landfill is an unnecessary waste of a non-renewable resource. However, if this textile fibre is used without an understanding of its material make-up, this inherent recyclability can be inhibited.

Many design approaches to recycling are end-of-life interventions that can be described as 'extended life techniques' rather than 'design for recycling'. In order to design fully recyclable polyester textile products, potential barriers to recycling needed to be identified and 'designed out' at the production stages.

Current processing and finishing methods such as chemical coatings or lamination, commonly used in the industry's ever growing desire for performance and functionality, often create barriers to this continuous cycle, by mixing materials with different reprocessing needs into an irreversible state. These complex hybrid materials leave a legacy of waste and prevent inclusion in future fabrications (Allwood et al, 2006). If polyester textile products are preserved as monomaterials during their production they can be returned for reprocessing into virgin quality material over several cycles through chemical repolymerisation. The research set out to find new, technological alternatives to these traditional finishing techniques which could be employed to preserve monomateriality in polyester materials in order to work within the boundaries of a Cradle to Cradle metabolism (McDonough & Braungart, 2002).

Laser processing was selected as the most appropriate tool for development, because of its ability to manipulate thermoplastic materials through heat and its potential for flexible control through digital means. The resulting prototypes showed that several finishes which would normally need chemical coatings or adhesives could be achieved without any added agents.

In summary, this research contributes to knowledge firstly by proposing a new model for designing 'Cradle-to-cradle (C2C) textile products' that can contribute to a future closed- loop material economy and secondly by presenting a new application of laser-welding technology as a tool for the finishing of 100% polyester textiles which can be repolymerised at end-of-life.


Ultrasound-assisted solventless oxidation/reductive amination of benzyl halides was developed as a facile, efficient, and environmental friendly method toward N-alkylated amines. Aldehydes were formed in situ by oxidation of organic halides with N-methylmorpholine N-oxide (NMO), followed by direct reductive amination with amines using sodium borohydride and montmorillonite K-10 catalyst as the reducing system. This green and simple procedure enables N-alkylated amines to be prepared in good to excellent yields with high selectivity of the monoalkylation.


One of the major developments brought along by the internet during the past years is the
advent of social media. And by extension, this has also entailed the development of network
cooperation via social media. The following study is concerned with one specific application of
network cooperation via social media, namely the Europol Platform for Experts, which is a
social media tool for law enforcement experts. The aim of this paper fourfold: Firstly, to find out
to what extent the EPE is being used by registered users. Secondly, it will be found out for which
purpose(s) the EPE is currently being used. Thirdly, the aim is to find out which factors
influence whether the EPE is or is not being used by the registered users. The fourth aim of the
research is to find out how the registered users evaluate the EPE.
The data for the research was collected through a questionnaire and several interviews among
the registered users and analysed through statistical analysis. The results of the study lead to
the conclusion that the EPE is used only to a very limited extent. When it is used it is mainly for
information seeking purposes, followed by communication and participation purposes. The
analyses show that the factors performance expectancy, effort expectancy, social influence and
facilitating conditions are all positively and significantly related to overall EPE use. The
evaluation of the EPE by the registered users is very mixed and at times even highly
contradictory and revolves around the topics information, community of experts, security, nonuse,
website functionality, accessibility, user-friendliness, and the absence of benefits or
disadvantages.
Based on these findings, it appears that Europol has several ways to bring about an increased
use of system and make the system more successful. Therefore, it is recommended that Europol
focuses on three activities, namely changing performance indicators, and improving the system
and raising awareness.


At the end of the Second World War, Stalin forged the communist regimes in Eastern Europe as satellites of Soviet Union. After ten hard years of Soviet Stalinism, with the changings introduced by the 20th Congress of the CPSU, the leaderships of satellites' communist parties risked to be overthrown by their internal rivals. In Romania, in 1956, Party Secretary Gheorghe Gheorghiu-Dej converted Romania into a Stalinist system guided by Romanians: the Romanian receipe in order to prevent the change included the recovery of the national elite and intellectuals previously ostracized. While presenting itself as communist, the regime increasingly used nationalism for the creation of domestic consensus in anti-Soviet function. Nicolae Ceausescu, came to power in 1965, continued this strategy and led it to its climax, expanding dramatically the propaganda machine, that flooded into the everyday life of the Romanians. In particular, it was the discourse on national history that was manipulated and falsified for mere political needs, and declined in each type of cultural product, both in the academic literature as well as in popular literature and the arts. This book narrates how Romanian culture was subservient to the maintenance of a political system for over forty years and the consequences of this forced regimentation after the demolition of the Berlin Wall.


S. Zeinali Heris*1, M. Khodadadi Yazdi1 1Department of Chemical Engineering, Faculty of Engineering, Ferdowsi University Of Mashhad, Mashhad, Iran; firstname.lastname@example.com Introduction Nanofluids are suspension of metallic or metal-oxide solid nanoparticles with size varying generally from 1 to 100 nm dispersed in heat transfer liquids such as water, ethylene glycol and engine oil. It has been found that important heat transfer enhancement may be achieved using nanofluids instead of conventional fluids. This is of major importance for electronics and microelectronics where liquids cooling systems are necessary and miniaturizing is needed. In this regard, determination of the nanofluids viscosity is essential to establishing adequate pumping power as well as the convective heat transfer coefficient, because the prandtl number and Reynolds number are functions of viscosity. The conventional correlations such as Einstein model [1] consider only the nanoparticles volume concentration on nanofluid viscosity prediction. Nguyen et al. [2, 3] during their experimental investigation studied the influence of temperature and the particle size on dynamic viscosities of water/ Al2O3 and water/CuO suspension. In the present study the various models for nanofluids viscosity determination is studied and the advantage and disadvantage of each models discussed.


We used C57BL/6J and BALB/cJ mice to examine microRNA expression in ischemic hindlimb muscles at a time point when the 2 strains had similar recovery to identify microRNAs that are differentially regulated. We used computational techniques to identify and quantitative real-time Background —MicroRNAs are key regulators of gene expression in response to injury, but there is limited knowledge of their role in ischemia-induced angiogenesis, such as in peripheral arterial disease. Here, we used an unbiased strategy and took advantage of different phenotypic outcomes that follow surgically induced hindlimb ischemia between inbred mouse strains to identify key microRNAs involved in perfusion recovery from hindlimb ischemia. Methods and Results —From comparative microRNA profiling between inbred mouse strains that display profound differences in their extent of perfusion recovery after hindlimb ischemia, we found that the mouse strain with higher levels of microRNA-93 (miR-93) in hindlimb muscle before ischemia and the greater ability to upregulate miR-93 in response to ischemia had better perfusion recovery. In vitro, overexpression of miR-93 attenuated hypoxia-induced apoptosis in both endothelial and skeletal muscle cells and enhanced proliferation in both cell types. In addition, miR-93 overexpression enhanced endothelial cell tube formation. In vivo, miR-93 overexpression enhanced capillary density and perfusion recovery from hindlimb ischemia, and antagomirs to miR-93 attenuated perfusion recovery. Both in vitro and in vivo modulation of miR-93 resulted in alterations in the expression of >1 cell cycle pathway gene in 2 different cell types. Conclusions —Our data indicate that miR-93 enhances perfusion recovery from hindlimb ischemia by modulation of multiple genes that coordinate the functional pathways of cell proliferation and apoptosis. Thus, miR-93 is a strong potential target for pharmacological modulation to promote angiogenesis in ischemic tissue. ( Circulation . 2013;127:1818-1828.) washed with PBS and mounted with Vectashield mounting medium (Vector Lab, Burlingame, CA). Secondary antibody only without primary antibody was used as negative control to assess non-specific binding. Three representative pictures from each section were taken under 400X magnification, using Olympus BX51 high-magnification microscope. Total number of CD31 positive spots/field and total number of muscle fiber/field were counted, and capillaries expressed as CD31 positive spots/muscle fiber.


Prolonged normothermic ex vivo heart perfusion could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via normothermic ex vivo heart perfusion. Standard perfusion (SP; n = 40) utilized red blood cell/plasma perfusate and Langendorff technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-blood; n = 6) or cross-circulated filtered plasma (XC-plasma; n = 7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared with 22 of 40 SP hearts (55%; p = 0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3–12. No significant differences were seen between XC-blood and XC-plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478 ± 700 mm Hg/s vs. 872 ± 500; p = 0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.


In this thesis, the Defrise-Clack (DC) algorithm [4], an exact cone-beam reconstruction algorithm, was implemented in CUDA for the most common geometry used in x-ray C-arm CT systems (flat panel detector geometry). The implementation utilizes the forward gridding method with Kaiser-Bessel kernel to calculate the 2D Radon transform efficiently. Furthermore, a complete image quality evaluation (resolution, noise and artifacts) was carried out on reconstructions from 29 different cone-beam data sets and with 196 different sets of reconstruction parameters (Ns,Nμ,W). The results were compared to the predominantly used cone-beam reconstruction algorithm, Feldkamp-Davis-Kress (FDK) [9]. To improve reconstruction speed, an alternative implementation of the Defrise-Clack algorithm with inverse gridding method was suggested. The inverse gridding method was originally designed to replace the 2D inverse Radon transform [24], however, we showed that this method, with a small modication and without additional processing, can also replace the 2D backprojection operation. The Defrise-Clack algorithm was then implemented in CUDA with the inverse gridding method and the same image quality evaluations were carried out. The inverse gridding implementation utilizes the same Kaiser-Bessel kernel with the same width parameter W as the forward gridding implementation. Results have shown that this method does not degrade image quality if the size of the Kaiser-Bessel kernel is large enough (W > 2). Results indicate that the Defrise-Clack algorithm provides reconstructions with signicant improvements over the short-scan FDK algorithm with respect to cone-beam artifacts. In addition, it was shown that both algorithms have the same resolution-noise characteristics.


This paper describes an efficient lifting based hybrid image coding (LB-HIC) scheme. The proposed scheme is based on using the lifting transform (LT) in conjunction with the discrete cosine transform (DCT) to provide coding performance superior to the popular image coders. The proposed method uses combination of the DCT coding and the high performance of the set partitioning in hierarchical tree (SPIHT) coding. The modification process provides a new subband image data containing almost the same information of the original one but having smaller values of the lifting coefficients. Simulation results of the proposed method demonstrate that, with small addition in the computational complexity of the coding process, the peak signal-to-noise ratio (PSNR) performance of the proposed algorithm is much higher than that of the SPIHT test coder and some of famous image coding techniques.


The common external tariff (CET) for Economic Community of West African States (ECOWAS) was adopted at a Heads of State Summit in October 2013 in Dakar. This paper assesses the potential impact on Nigeria of implementing the new ECOWAS CET. It uses the World Bank's tariff reform impact simulation tool (TRIST) to simulate three scenarios: (i) keeping in place current import bans and levies which are charged in addition to tariffs, while implementing the CET tariff rate on non-banned products, (ii) removing the import bans and implementing the CET rate on all products, but keeping the additional import levies in place, and (iii) fully implementing the CET on all products and completely removing import bans and levies. The paper suggests that implementing the CET will have significant and largely positive effects on Nigerian consumers and producers. This note is intended to enrich the debate by presenting projections on the likely effects of CET implementation. To the extent possible with the limited available data, it gives a comprehensive overview of the effects to be expected on government revenue, the welfare of consumers, and the performance of Nigerian firms. It also discusses new opportunities for Nigerian firms to benefit from the regional market that are likely to arise if the CET is implemented. The note is organized as follows: section one gives introduction. Section two describes Nigeria's current trade profile with a particular focus on trade with the ECOWAS region. Section three makes use of the World Bank's TRIST to analyze the impact of implementing the CET in Nigeria in terms of changes in the level of protection by industry, government revenue from taxes levied at the border, consumer welfare, and the competitiveness of Nigerian firms. Section four shifts the focus beyond Nigeria's borders to look at the regional market within ECOWAS.


Biodeterioration is the least understood decay mechanisms of outdoor stone monuments. Microbial colonisation is largely determined by the properties of the stone and environmental conditions. The literature on microorganisms on outdoor stone monuments and their decay mechanisms was reviewed. For the assessment and quantification of microbial deterioration, methods that can be carried out by cultural heritage conservators with limited microbiological skills were selected and adjusted for the application on outdoor stone monuments. To this end, the total biomass was quantified by a protein assay (Folin-Lowry method), its phototrophic contribution through chlorophyll a absorbance and the amount of extracellular substances (EPS) were assessed by carbohydrate quantification (phenol method). Microbial activity was measured through two different enzyme assays: fluorescein diacetate cleavage and dehydrogenase activity (INT reduction). In order to develop a long-term monitoring strategy, these parameters were tested in the morning (8 am) and in the afternoon (4 pm) on biofilms from a sunny and a shady sampling site on a limestone wall in the south of Mexico. The experiments were performed in the dry season and the rainy season. Changes in biofilm composition and activity during the day were very small, while seasonal changes were more pronounced. The largest differences could be seen in samples from the different sampling sites (sun and shade), where the microbial population had established over years of distinct environmental conditions. Variations in biofilm composition and activity exceeding such natural variation may indicate the necessity for an antimicrobial treatment. The choice of an antimicrobial agent is difficult and the ideal treatment does not exist. Of the various chemical antimicrobial agents tested (Mergal K14, Parmetol DF12, Troysan S97, Preventol R50 hydrogen peroxide and ethanol) on microbial biofilms on stone, ethanol (70%) was the most effective, as revealed by ATP measurements. A flexible, non-invasive in vivo system, employing the bioluminescent bacterium Vibrio fischeri, was developed to assess sub-lethal effects of antimicrobial treatments and to test combined treatments for synergy. Various biocides and ultrasound (267 kHz, 20 kHz), alone and in combination, were tested for their effect on V. fischeri (Mergal K14, Parmetol DF12, Troysan S97, Preventol R50 hydrogen peroxide and ethanol) and a microbial biofilm on stone (Troysan S97, Preventol R50 and ethanol). The tests did not reveal synergistic effects however, a systematic, comprehensive study on chemical and/or physical methods might reveal an innovative approach towards a more environmentally friendly microbial eradication method for outdoor stone monuments. Long-term monitoring of the composition and activity of a microbial biofilm may provide data to determine if an antimicrobial treatment is necessary. If an antimicrobial intervention cannot be avoided, low-toxic substances, such as ethanol, should be considered first. For the evaluation of the success of an antimicrobial treatment, ATP measurement has proven to be a reliable and simple method that does not require specialised skills.


A patient with idiopathic thrombocytopenia purpura who was treated with high dosage corticosteroids for ten years, developed 18 separate lesions of avascular necrosis in 12 different bones. Despite spontaneous revascularization of many of the lesions, subchrondral collapse caused symptomatic secondary degenerative arthritis in many joints. Pathological examination of both resected femoral heads showed no intravascular thrombosis.


For most building materials, the enthalpy-temperature relationship is not linear but contains steep sections at places where latent heat is absorbed as a result of desorption of moisture, dehydration, dissociation, or transformation. Partly associated with these physicochemical changes, and partly independent of them, the thermal conductivity also undergoes considerable variation. These are the main reasons why the usual assumptions are not valid when the heat flow through building elements during fire exposure is to be calculated. A numerical method is described which can be used successfully for solving one-dimensional transient heat flow problems of any complexity. The applica- tion of this method to the calculation of temperature history of building elements during fire exposure is illustrated through some examples. In cases where the building element is not subject to thermal disintegration or collapse the numerical heat flow analysis will yield the fire endurance of the building element. In other cases the heat flow analysis must be coupled with a numerical stress-deformation analysis.


Background This study aims to analyze the changes and significance of organ function indices in patients with severe Coronavirus Disease 2019 (COVID-19) pneumonia for prediction of major organ damages and guiding treatment schemes. Methods 63 patients with severe COVID-19 pneumonia were selected as the severe group and 73 patients with mild syndromes were selected as the mild group. SAS9.4 software was used for statistical analysis of the data. Results Levels of ALT, AST, cTnI, Cr, PT, APTT and Ddimer of the severe group were significantly higher while PLT was lower than those of the mild group. The data of all quantitative variables were converted into categorical variables. Significantly higher levels of AST, ALB, D-dimer and higher proportion of bilateral lung involvement were observed from the severe group comparing to those in the mild group, while the difference in the other indices between the two groups was insignificant in statistical perspective. Conclusions There are significant differences in the levels of multiple organ function indices between the severe group and the mild group of patients with COVID-19 pneumonia infection. Through examining the relevant indices, conditions of patients' multiple organ function damage could be predicted and used as guidance of treatment.


This causal comparitive study examined the effect of early childhood education on social and emotional development in children ages 3-6 years old in Kwara State of Nigeria. Sixty children who were exposed to early childhood education were selected through cluster sampling from six different schools, that is, 30 boys and 30 girls. Also selected through convenient sampling technique were 60 children who were not exposed to early childhood education in the locality, that is, 30 boys and 30 girls. In all, 120 samples participated in the study. Data were obtained from the parent-child questionnaire made up of ten items on social development and ten items on emotional development. Parents reported on their observations of their childs social and emotional development. Two research hypotheses were formulated for the study. The null hypothesis were tested with students t-test statistic of independant samples at 0.05 level of significance. Overall, the research found that there was no significant effect of early childhood education on either social or emotional development. Competent and qualified early childhood educators should be recruited by both the Govemment and private school proprietors to guide and teach they pupils at this level of education so as to lay a strong foundation for each childs future career. Following these findings the study, were recommendation for Early Childhood Education in Nigeria.


The high pressure common rail injection System is one of the most advanced technologies for the diesel engine to reduce fuel consumption exhaust emissions. While the design of the high pressure common rail injector is the key for the whole system. Considering that the working pressure of fuel in the injector, a more accurate injector body model was established with the modeling software Pro/Engineer in this study. Finite element analysis technology in Ansys software was applied to calculate the strength of injector body of the high pressure common rail system under different injection pressures. And then the rationality of structure parameters and material selection of the injector body can be analyzed and verified. The research conclusions can provide the theoretical basis for the optimization design of the injector.


Ankle Foot Orthosis (A.F.O) should endure the uncountable repeating impact and fatigue loadings owing to the gait characteristics. This study investigates the impact deflection and relationship between the absorbed energy and the residual strength rate using the glass/epoxy and the aramid/epoxy for the leaf spring in A.F.O. In conclusion, an equation was suggested to evaluate the absorbed energy and the residual strength rate by the different impact velocities. When the glass/epoxy and the aramid/epoxy was selected for the leaf spring in A.F.O, it was reasonable to use the glass/epoxy of the cross-ply for the parts subject to the large impact and the aramid/epoxy of the woven type for the parts to require the high elastic energy such as the large deformation.


The statistical survey of the electronics industry in the United States, published annually by the Electronic Industries Association, for several years has shown a trend of importance to all IEEE members whose employment and job assignments depend on the markets for electronic systems, equipment, and components. That trend is a decrease in the year-to-year growth of factory sales in two major components of the industry: products sold to the government and to the consuming public. The other major component, sales of industrial products, has shared this trend of arrested growth, but there is an encouraging turnaround that is evident in the projected figures for 1969. Although product sales are by no means the only significant economic factor in these industries, this indicator has a fundamental influence on future product design and development. The statistics reviewed in this article are taken by permission from the recently published ``EIA Yearbook - 1969.'' This 94-page document1 contains detailed data on sales of individual product lines, funding, employment, and related industry statistics. It is recommended highly to IEEE members, in the U.S. and elsewhere, who have an interest in the economic underpinning of our profession.


Cameras are being used everywhere for the safety and security of citizens in different countries. Using a machine to detect humans in a photo or a video frame is a very complicated and challenging task. Various techniques have been developed for this purpose, which mainly rely on Artificial Intelligence. This article aims to provide a comprehensive review and analysis of the literatures from a descriptive perspective, which is its main differentiator from the existing survey papers in this area. Firstly, the vision-based human detection techniques and classifiers are elucidated in conjunction with the variants of feature extraction techniques. Secondly, various pros and cons of such techniques are discussed. Then, an investigation has been conducted and reported based on the state-of-the-art human detection descriptors (e.g. Log-Average Miss Rate and accuracy). Although techniques such as Viola-Jones and Speeded-Up Robust Features can detect objects in real-time and overcome Scale-Invariant Feature Transform (SIFT) limitations, they are still sensitive to illuminated conditions. Other techniques such as SIFT, Bag of Words, Orthogonal Moments, and Histogram of oriented Gradients provide other interesting benefits which include insensitivity to occlusion and clutters, simplicity, low-order element construction and invariance to illuminated conditions; nevertheless, they are computationally expensive and sensitive to image rotation. A meticulous review along similar lines revealed that the Deformable Part-based Model performs relatively better due to its ability to deal with particular pose variations and multiple views, occlusion handling (partial) and is application-free while its counterparts focus on only a single aspect. This article highlights and provides a brief description of each available data-sets for human detection research. Various use-cases of human detection systems are also elaborated. Finally, various conclusions are derived based on the conducted review followed by recommendations for future directions and possibilities to further improve the speed and accuracy of human detection systems.


OBJECTIVE
The goal of this study was to examine the bidirectional relationship of sleep and pain to determine whether changes in sleep complaints over the course of a chronic pain treatment trial predict pain outcomes and vice versa, controlling for changes in depression and anxiety.

METHODS
Data were analyzed from a 12-month randomized, controlled trial that tested the effectiveness of a collaborative care intervention for veterans with chronic musculoskeletal pain. Participants were 250 veterans from 5 primary care clinics in a Veteran Affairs (VA) medical center. Measures of pain, sleep, and depression/anxiety symptoms were collected at baseline, 3 months, and 12 months. Factor analysis was used to clarify the boundaries of these domains, and structural equation modeling was used to examine whether changes in sleep complaints and depression/anxiety during the trial predicted pain at the end of the trial, controlling for covariates. An alternative model was also tested in which changes in pain predicted sleep complaints.

RESULTS
Changes in sleep complaints at 3 months significantly predicted changes in pain at 12 months (standardized path coefficient = .29, p < .001). To a lesser extent, changes in pain predicted changes in sleep (standardized path coefficient = .15, p < .05). Changes in depression/anxiety did not significantly predict changes in pain or sleep. There was also evidence of differential relations of specific sleep complaints with pain.

CONCLUSIONS
This work helps to further disentangle the complex relationship between pain and sleep. This bidirectional relationship may need to be considered to improve pain outcomes.


ABSTRACT Water is essential for human life, yet safe drinking water is a limited resource. Critical to fighting the global water crisis are public awareness campaigns, including Public Service Announcements (PSAs). While YouTube has become a popular medium for disseminating prosocial content such as PSAs, environmental communication efforts on this platform remain largely uninvestigated. This study examines the content and characteristics of global water crisis PSAs on YouTube by applying two communication models: the Extended Parallel Process Model, and the Elaboration Likelihood Model. These models are used to evaluate the potential effectiveness of the PSAs. Content analysis reveals that threat messages often outweigh efficacy messages in the videos, central route processing cues are more prevalent than peripheral route cues, and a focus on quality or quantity issues differed by sponsoring organization (non-profit, for-profit, government). Implications and avenues for potential future research are discussed.


Mycobacterium tuberculosis synthesizes isoprenoids via the nonmevalonate or DOXP pathway. Previous work demonstrated that three enzymes in the pathway (Dxr, IspD, and IspF) are all required for growth in vitro . We demonstrate the essentiality of the key genes dxs1 and gcpE , confirming that the pathway is of central importance and that the second homolog of the synthase ( dxs2 ) cannot compensate for the loss of dxs1 . We looked at the effect of overexpression of Dxr, Dxs1, Dxs2, and GcpE on viability and on growth in M. tuberculosis . Overexpression of dxs1 or dxs2 was inhibitory to growth, whereas overexpression of dxr or gcpE was not. Toxicity is likely to be, at least partially, due to depletion of pyruvate from the cells. Overexpression of dxs1 or gcpE resulted in increased flux through the pathway, as measured by accumulation of the metabolite 4-hydroxy-3-methyl-but-2-enyl pyrophosphate. We identified the functional translational start site and promoter region for dxr and demonstrated that it is expressed as part of a polycistronic mRNA with gcpE and two other genes. Increased expression of this operon was seen in cells overexpressing Dxs1, indicating that transcriptional control is effected by the first enzyme of the pathway via an unknown regulator.


In recent years, water pollution has posed a serious threat to aquatic organisms and humans. Advanced oxidation processes (AOPs) based on activated peroxymonosulfate (PMS) show high oxidation, good selectivity, wide pH range and no secondary pollution in the removal of organic pollutants in water. Carbon-based materials are emerging green catalysts that can effectively activate persulfates to generate radical and non-radical active species to degrade organic pollutants. Compared with transition metal catalysts, carbon-based materials are widely used in SR-AOPs because of their low cost, non-toxicity, acid and alkali resistance, large specific surface area, and scalable surface charge, which can be used for selective control of specific water pollutants. This paper mainly presents several carbon-based materials used to activate PMS, including raw carbon materials and modified carbon materials (heteroatom-doped and metal-doped), analyzes and summarizes the mechanism of activating PMS by carbon-based catalysts, and discusses the influencing factors (temperature, pH, PMS concentration, catalyst concentration, inorganic anions, inorganic cations and dissolved oxygen) in the activation process. Finally, the future challenges and prospects of carbon-based materials in water pollution control are also presented.


The public perception of the existing public transport system in Malaysia has been declining over the years. The challenges in transforming the public transport system into the mode of choice are not limited to increasing infrastructure and capacity. A more integrated and comprehensive approach is required as it is also about improving the regulatory framework, planning structure and level of services delivered. The transformation of the public transport landscape in Malaysia is consistent with principles underlined in the National Physical Plan 2 and guided by the transformation thrusts which form the basis for national policy measures.


The present study is comparing the evaluation cards of the event, related to all the events executed in the experimental phase (363 participants) with those ones achieved in the first and second year of running phase system (321 and 180 participants), with particular reference to the emergent opinions about the five year compulsoriness of the attainment of the credits, imposed by the normative of the Ministry of Health. The analysis of the results underlines the discordance between the evaluations and the opinions expressed in the same ones. Finally, in the organization of a formative event is necessary to consider the not-measured factors that engrave on those measured ones (as the effectiveness). The effectiveness should also be measured at a distance of months, referring them to the possible applications of learned results on the working place, also considering the resistances to individual or collective change.


Purpose: Keratin19 (KRT19) is the smallest known type I intermediate filament and is used as a marker for reverse transcriptase PCR–mediated detection of disseminated tumors. In this study, we investigated the functional analysis of KRT19 in human breast cancer. Experimental Design: Using a short hairpin RNA system, we silenced KRT19 in breast cancer cells. KRT19 silencing was verified by Western blot analysis and immunocytochemistry. We further examined the effect of KRT19 silencing on breast cancer cells by cell proliferation, migration, invasion, colony formation assay, cell-cycle analysis, immunocytochemistry, immunohistochemistry, and mouse xenograft assay. Results: Silencing of KRT19 resulted in increased cell proliferation, migration, invasion, and survival. These effects were mediated by upregulation of Akt signaling as a result of reduced PTEN mRNA expression. Silencing of KRT19 decreased the nuclear import of early growth response-1 (Egr1), a transcriptional factor for PTEN transcription, through reduced association between Egr1 and importin-7. We also confirmed that silencing of KRT19 increased tumor formation in a xenograft model. Conclusions: KRT19 is a potential tumor suppressor that negatively regulates Akt signaling through modulation of Egr1 nuclear localization. Clin Cancer Res; 19(16); 4335–46. ©2013 AACR.


The paper examines global research output (1656 records) on "Impact of Covid-19 on Sleep Disorders", based on publications indexed in Scopus database. The global publications on this theme averaged 15.05 citations per paper. About 19.02% share of its total publications on this theme received external funding support and averaged 34.59 citations per paper. Ninety five countries unevenly partcipitated in global research output on "Impact of Covid-19 on Sleeping Disorders", of which the top 10 most productive countries accounted for 87.62% and more than 100% share in global publications and citations. The USA, China and Italy led in global publications ranking and productivity as against China (2.52), U.K.(2.26) and Italy (1.67) leading in terms of relative citation index.The 527 organizations and 773 authors participated in global research on this theme, with top 15 most productive organizations and authors contributing to 21.62% and 6.28% global publications share and 63.70% and 56.20% global citations share. Huazhong University of Science & Technology, China, and Tongji Medical College, China and Harvard Medical School, USA were the most productive global organizations (with 40, 38 and 33 papers) and Capital Medical University, China (153.85 and 10.22), Wuhan University, China (109.33 and 7.26) and Renmin Hospital of Wuhan University, China (108.10 and 7.18) were the leading most impactful organizations in terms of citation per paper and relative citation index. Z. Liu, S. Grover and G. Wang were the most productive authors (with 9, 8 and, 8). L.Kang (395.17 and 26.26), Y. Wang (395.17 and 26.26) and, S. Ma (322.0 and 21.4) were the most impactful authors. International Journal of Environment Research & Public Health, Sleep Medicine and Frontiers in Psychiatry were the most productive journals (with 73, 69 and 49 papers). Brain, Behavior & Immunity (86.04)., Asian Journal of Psychiatry (46.78), Psychiatry Research (41.15) were the most impactful journals.


Spin electronics is a new research area, which not only uses the electron's charge but also its spin. By using the electron spin dependent properties of magnetic materials one can make devices with a new functionality. This has lead to magnetoresistive devices that can change their resistance by 10 to 50% in small magnetic fields, such as giant magnetoresistance (GMR) devices and the magnetic tunnel junction (MTJ). This large resistance change can be used in applications such as read heads or serve as memory elements in a magnetic random access memory (MRAM). This thesis describes two devices: the spin-valve transistor (SVT) and the magnetic tunnel transistor (MTT). The SVT has an unique property, namely its huge relative collector current change of more than 300% in small magnetic fields at room temperature. This unique property by itself is not enough to warrant the applicability of the SVT. The other properties that are important for the applicability of the SVT are described in this thesis. An alternative to the SVT, the MTT, will also be discussed.

The SVT is a hybrid device that generally has an n-Si/ Pt / Ni82Fe18/ Au/ Co/ Au/ n-Si structure. The Pt / Ni82Fe18/ Au/ Co/ Au multi layer is the base and the two semiconductors on each side are the emitter and the collector respectively. The SVT is used in the common base configuration, where the emitter barrier (Si/Pt) is forward biased and the collector diode is zero or reversed biased. A flow of electrons from the silicon over the Schottky barrier into the metal base starts when the emitter is forward biased. These electrons have an excess energy compared to the Fermi level of the base and move in the direction of the collector. The electrons that are scattered in the base will lose their energy or momentum and make up the base current. Only those electrons that reach the collector with the right momentum and a high enough energy can enter the collector. The collector current is thus extremely sensitive to the scattering conditions in the base. The scattering conditions in the Ni82Fe18 and the Co layer are different for the spin-up and spin-down electrons. This makes the total scattering dependent on the relative magnetizations of the Ni82Fe18 and the Co layer. The collector current is largest when the magnetizations are parallel (I P C ) and smallest when the magnetizations are anti-parallel aligned (I AP C ). The relative change in collector current is called the magnetocurrent (MC = (I P C - I AP C )/I AP C ).

This PhD research started with the development of a reliable process for fabricating spin-valve transistors. The introduction of this process together with the introduction of an ultra-high vacuum metal-evaporation system and the right choice of materials resulted in the SVT's that exhibit an MC of more than 300% at room temperature.

This thesis starts with a study on the size dependence of the magnetic and electrical properties of the SVT. We extended the previously mentioned process by using silicon on insulator (SOI) wafers, a combination of dry and wet etching techniques and SU8 (a negative tone photoresist) as an insulator layer. We were successful in producing SVTs with lateral dimensions that ranged from 300µm by 300µm to 10µm by 10µm. As expected, we saw no influence of the dimensions on the Schottky barrier height. Moreover the reverse current scaled down linearly with area. Both observations show that we have high-quality Schottky diodes. The key property of the SVT, its MC, showed no size dependence and remained constant around 240% for all dimensions. The transfer ratio is the ratio between the applied emitter current and the measured collector current. This ratio showed a slight decrease for transistors with dimensions below 25µm by 25µm. This is attributed to a deterioration of the emitter efficiency. The maximum possible emitter current decreases with transistor dimensions. The limiting factor is the maximum possible current density in the spin-valve base, which is 1.7 × 10 7 A/cm 2 . This value agrees with electromigration failure of spin valves. We have shown that it is possible to scale the lateral dimensions of the SVT down to 10µm by 10 µm. In my view further scaling down is limited to the physical height needed for the emitter, which includes the depletion width for the Schottky barrier and the doping profile needed for the Ohmic contact.

To characterize the noise sources of the SVT we studied the frequency spectrum of three types of transistors that differed only in the type of metal base. The measurement showed that the frequency spectrum of the transistor with only non-magnetic layers in the base was completely dominated by shot noise in the frequency range of the measurement (10 Hz to 100kHz). The inclusion of one or more magnetic layers lowered the collector current and thus the level of the shot noise. It did not however change the nature of the noise or add noise (of magnetic origin) to the collector current. The collector current spectral density (SI) changes linearly with IC in a quasi-static magnetic field as expected for shot noise. We have however not observed 1/f noise in our measurements, not even at the switching fields of the spin valve. With this knowledge we can calculate the signal to noise ratio (SNR) of the SVT. The SNR increases with increasing MC and also with the absolute value collector current.

From the basic relation IC = α IE we see that we can increase the collector current by either increasing the emitter current (IE) or the transfer ratio (alpha). We saw before that the emitter current has an upper limit imposed by device breakdown, therefore the way to enlarge IC is to improve the transfer ratio. We started to improve α by enlarging the energy difference between the emitter and collector barrier. The transfer ratio increased with increasing energy difference due to the larger number of states available at the collector semiconductor when electrons arrive with a higher energy. The transfer ratio also improves when materials with longer attenuation lengths are used in the base, i.e. Au instead of Pt. The influence of the SVT's structural quality on the transfer ratio is demonstrated by the optimum in collector current versus Pt layer thickness. Furthermore, by varying the thickness of the NiFe layer we were able to prove that there is a maximum in the absolute current change for a certain thickness, due to the trade-off between transfer ratio and MC. The same study yielded a value for the attenuation of an interface, which is a factor of 0.55. The influence of crystal orientation on the transfer ratio was found to be negligible. Temperature effects on the transfer ratio are weak and are due to the spatial distribution of Schottky barrier heights and thermal spin wave scattering. Summarizing, we improved the transfer ratio by a factor of 118 from a Si/Pt/NiFe/Au/Co/Pt/Si SVT compared with a Si/Au/NiFe/Au/Co/Cu/Si transistor, while the MC remained constant above 200% and showed only small and non-systematic changes. The latter implies that the collection of both the spin-up and spin-down electrons can be improved, resulting in an increase in collector current without affecting the MC. The best results so far for SVTs are with a Si/ Au (20A)/ Ni82Fe18 (30A)/ Au (70A)/ Co (30A)/ Au (40A)/ Si SVT, it has a transfer ratio of 1.2 × 10 4 and an MC of 230%. Further improvement of the transfer ratio might result from better control over the quality of the complete SVT structure. Another option is to use a tunnel barrier on the emitter side. This not only allows one to further enlarge the energy difference between the injected electrons and the collector Schottky barrier, but also opens up the possibility to remove layers from the base if a ferromagnetic emitter electrode is used, as in an MTT.

Magnetic tunnel transistors have been successfully realized with the use of in situ shadow mask technology. Already we achieved a transfer ratio equal to that of SVTs, while the MCof the MTT is above 100%. The MTT has a Si/ Co/ Al2O3/ CoFe/ IrMn/ Ta structure. We have shown that the MTT can be used to determine a lower limit for the tunnel spin polarization of a ferromagnet/insulator interface. With a MTT this lower limit can be determined in a large temperature and tunnel-barrier bias range. The transfer ratio measured versus tunnel-barrier bias continues to increase, due to the larger number of available states at the collector at higher energies. More research is needed to explain the tunnelbarrier bias dependence of the MC. We expect that MTTs can be improved by using evaporation techniques rather than sputter techniques. Furthermore the quality of the collector diode can be improved with a corresponding increase in transfer ratio by choosing the right materials.

The comparison of the SVT and MTT with tunnel junctions in terms of signal, noise, scalability, frequency response, robustness and of course the ability to study the properties of spin-polarized hot-electrons in magnetic materials justifies the further research of SVTs and MTTs. Last modified: May 16, 2002 by Hans.


Many methods have been proposed for efficient storage of molecular hydrogen for fuel cell applications. However, despite intense research efforts, the twin U.S. Department of Energy goals of 6.5% mass ratio and 62 kg/m3 volume density has not been achieved either experimentally or via theoretical simulations on reversible model systems. Carbon-based materials, such as carbon nanotubes, have always been regarded as the most attractive physisorption substrates for the storage of hydrogen. Theoretical studies on various model graphitic systems, however, failed to reach the elusive goal. Here, we show that insufficiently accurate carbon-H2 interaction potentials, together with the neglect and incomplete treatment of the quantum effects in previous theoretical investigations, led to misleading conclusions for the absorption capacity. A proper account of the contribution of quantum effects to the free energy and the equilibrium constant for hydrogen adsorption suggest that the U.S. Department of Energy specification can be approached in a graphite-based physisorption system. The theoretical prediction can be realized by optimizing the structures of nano-graphite platelets (graphene), which are light-weight, cheap, chemically inert, and environmentally benign.


Introduces a first proposal on how to use semiotics in order to improve software engineering methods, when intelligent autonomous systems are targeted. First we investigate the current flaws in software engineering, concerning intelligent autonomous systems. Then we propose a knowledge taxonomy, based on semiotic ideas, aiming at a tool to understand the information domain of intelligent autonomous systems. Further, we illustrate how to use the notion of knowledge types during the development of a simple intelligent autonomous system, emphasizing the relationship between the described types of knowledge aiming at the understanding on how they are organized into an intelligent autonomous system. After that we review the idea of the generalized subsistence machine (GSM) proposed by Meystel (1996) as a possible tool (not the unique nor the best one) to represent the information domain of intelligent autonomous systems. Finally, it is shown how both ideas might be used in the requirement analysis step of any software engineering method when an intelligent autonomous system is targeted. As a conclusion, we discuss the future works and trends of semiotic intelligent autonomous systems engineering.


PURPOSE
Brachytherapy is a vital part of treating locally advanced cervix cancer. Point-based 2D treatment planning is conventionally used. New CT/MRI-compatible applicators for HDR brachytherapy make 3D conformal planning possible. GEC-ESTRO endorsed the EMBRACE (intErnational study on MRI-guided BRachytherapy in locally Advanced CErvical cancer) protocol which recommends standard-plan-based manual optimization over inverse optimization due to the concern of the uncertainty of high dose in targets and adjacent normal tissue. This study investigated the feasibility of inverse optimization planning.

METHODS
Eight cervix cases using tandem/ring applicators +/- parametrial needles were evaluated. Both manually and inversely optimized 3D conformal plans using Oncentra® Brachy were generated for each case following EMBRACE guidelines. Planning time and DVH parameters including D90 and V100% for HR-CTV, D90 for IR-CTV, D2cc for normal structures (bladder, rectum, sigmoid colon, and small bowel) were compared. Dose was reported in total EQD2 dose, assuming 45Gy in 25 fractions external beam and 28Gy in 4 fractions HDR treatment. Prescription dose (PD) and PD×2 isodose volumes and V100% and V200% for normal tissue (excluding all contoured OARs) were compared to evaluate the high dose volumes.

RESULTS
The average planning time was reduced by 55% with inverse planning. Target coverage between inverse and manual plans differed by <2% for HR-CTV (D90 and V100) and IR-CTV (D90). Inverse planning reduced the D2cc for normal structures by 4.2%-5.7% and the V100% and V200% for normal tissue by 31% and 40%, respectively. For 7 of the 8 cases, small bowel was observed near the target and received significant dose with either approach.

CONCLUSIONS
In this study, inverse planning improved DVH parameters over manual planning, with less planning time. Reporting normal tissue dose should alleviate the concern of undetected high dose regions. Even though small bowel is not often considered in traditional planning, dose should be reported.


We investigated the root distribution and nitrogen fixation activity of American jointvetch (Aeschynomene americana L.) cv. Glenn, under waterlogging treatment. The plants were grown in pots under three different treatments: no waterlogging (control), 30 days of waterlogging (experiment 1), and 40 days of waterlogging (experiment 2). The plants were subjected to the treatments on day 14 after germination. Root dry matter (DM) weight distribution of waterlogged plants was shallower than controls after day 20 of waterlogging. Throughout the study period, the total root DM weight in waterlogged plants was similar to that in the controls. Enhanced rooting (adventitious roots) and nodule formation at the stem base were observed in waterlogged plants after day 20 of waterlogging. The average DM weight of individual nodules on the region of the stem between the soil surface and water surface of waterlogged plants was similar to that of individual taproot nodules in the controls. Waterlogged plants had slightly greater plant DM weight than the controls after 40
days of treatment. The total nitrogenase activity (TNA) of nodules and nodule DM weight were higher in waterlogged plants than in the controls. Waterlogged American jointvetch had roots with nodules both around the soil surface and in the area between the soil surface and water surface after 20 days of waterlogging, and they maintained high nitrogenase activity and net assimilation rate that resulted in an increased growth rate.


The effects of oxygen-derived free radicals on the contractile activity of the mesenteric collecting lymphatics were evaluated in the anesthetized rat. Lymphatic contractions were monitored before, during and after the application of oxyradicals. Contraction frequency (F), stroke volume (SV), ejection fraction (EF), contraction propagation (PC), and lymph pump flow (LPF) were determined from the lymphatic diameter tracings. Oxyradicals were generated using hypoxanthine and xanthine oxidase. Exposure to oxyradicals inhibited the lymphatic pumping mechanism: 1) F fell from 15.5 +/- 0.8 to 0.8 +/- 0.7 beats/min; 2) EF went from 0.44 +/- 0.02 to 0.08 +/- 0.04; 3) PC dropped from 92 +/- 2 to 56 +/- 8%; and 4) LPF fell precipitously from 41.0 +/- 5.2 to 0.7 +/- 0.4 nl/min. The effects of the oxyradicals were attenuated by superoxide dismutase, implicating superoxide anion as one of the predominant causative agents. We conclude that oxyradicals significantly inhibit the lymph pump and that this inhibition could be a factor contributing to the formation of interstitial edema during inflammation.


Influences of culture media and sucrose concentrations on plant regeneration from Easter lily (Lilium longiflorum L. cv. Ace) ovary tissues were investigated. Pistils excised from unopened flower buds (3-5 cm long) were sectioned and cultured on either B-5 medium or Murashige and Skoog (MS) medium containing 2%, 5%, or 10% sucrose, with 1 mg·L -1 2,4-D and 2 mg·L -1 BA. Callus formation was most prolifi c on MS medium containing 5% sucrose. Shoot differentiation was higher on MS medium than on B-5 me- dium. Rooted plants were transferred into soil medium and grown in a greenhouse. Root tip smears showed that 35% of the regenerated plants showed a variation in chromosome numbers from 10 to 25 per cell, while the rest of the regenerants showed the normal 2n = 2x = 24 chromosomes per cell. The mixoploid condition also existed in different root cells of the same regenerated plant. Chemical names used: 2,4-dichlorophenoxyacetic acid (2,4-D); 6-benzylaminopurine (BA).


Nanotechnology has, without a doubt, ushered in a new era of technological convergence and holds the promise of making a profound impact on the way research in physics, chemistry, materials science, biotechnology etc. are conducted. The novel properties of materials at the nanoscale (or nanostructures) make them useful in a variety of applications, from catalysis to the medical field and electronics industry. However, to exploit these properties at the nanoscale, precise control over the morphology and size of nanostructures is required. One strategy that may be explored to tailor nanostructure morphology and size is vapour deposition. A lot of further insight can be gained from computer simulations of the processes governing the growth of nanostructures during vapour deposition. A method that shows promise in simulating thin film growth through vapour deposition is kinetic Monte Carlo (KMC). Therefore, in this study, a KMC model was developed to describe growth through vapour deposition. A gold on graphite system was simulated to test the model. In this KMC model, substantial effort was devoted to developing the model in different stages, each stage being more robust than the previous one. The assumptions made at each stage and possible artefacts (unphysical consequences) arising from them are discussed in order to distinguish real physical effects from artificial ones. In the model, data structures, search algorithms and a random number generator were developed and employed in an object-orientated code to simulate the growth. Several simulations were performed at different growth conditions for each of the stages. The results are interpreted based on the kinetic constraints imposed during the growth.


The trace element composition of zircon, especially in tandem with U-Pb geochronology, has become a powerful tool for tracing magmatic processes associated with the formation of porphyry copper deposits. However, the use of the redox-sensitive Eu and Ce anomalies as a potential mineral exploration proxy is controversial. This study presents a comprehensive, temporally constrained data set of zircon trace element compositions (n = 645) for three compositionally distinct magmatic series identified in the Meghri-Ordubad pluton, southernmost Lesser Caucasus. The 30 million years of Cenozoic magmatism in the Meghri-Ordubad pluton are associated with several ore-forming pulses leading to the formation of porphyry copper deposits and epithermal-style mineralization. Our zircon geochemical data constrain the thermal and chemical evolution of this complex intrusive suite and allow an evaluation of the usefulness of zircon as a mineral exploration proxy for porphyry copper deposits. Our results combined with Rayleigh fractionation modeling indicate that the trace element composition of zircon (Th/U, Hf, Ti, YbN/DyN, Eu anomalies) is influenced by the composition and the water concentration of the parental magma, as well as by co-crystallizing titanite and apatite. In contrast, the variations of Ce anomalies remain difficult to explain by magmatic processes and could rather be ascribed to relative fluctuations of the redox conditions. In the Meghri-Ordubad pluton, we do not observe any systematic patterns between the trace element composition in zircons and the different ore-forming pulses. This questions the reliability of using the trace element composition in zircon as an exploration mineral proxy, and it rather emphasizes that a good knowledge of the entire magmatic evolution of a metallogenic province is required.


We evaluated structural stabilities for A-site-ordered perovskites using the computer program "SPuDS", and succeeded in synthesizing designed AMn3Al4O12 (A=Y, Dy) under high-pressure and high-temperature conditions. Bond Valence Sum calculations with the refined structural parameters revealed that the compounds are represented as ionic A3+Mn3+3Al3+4O2-12. Mn3+ ions at the A' site produce high-spin magnetic moments and they align antiferromagnetically. The A-site Dy spins, on the other hand, behave paramagnetically and show no correlation with the A'-site Mn spins. The antiferromagnetism of the A'-site Mn spins is caused by the nearest neighboring Mn-Mn direct exchange interaction.


The history of the observatory showed a systematic organization in carrying out educational and research studies in astronomy since the early 9th century during the glorious Islamic civilization era. The Syammasiya and Qasiyun Observatory which were the earliest and other observatories during that era had been used as examples to European observatories and observatories worldwide including ones in Malaysia until today. Differences exist between the observatories in the past and at the present in the scopes of research and the instruments in use now which have given rise to the difference in the objectives and functions and the contributions of observatories especially those observatories in Malaysia. Although observatories in Malaysia have progressed, certain issues still prevail especially in matters pertaining to human resource development. Consequently, the research aims at evaluating the history of observatories in Malaysia and analysing issues of human resource development that have resulted from it. This research also puts forward solutions based on human resource theories to the issues of human resource in observatories around Malaysia. Data collection for the qualitative research was conducted using documentation, interviews and observation methods. A comparative analysis of the data was conducted by making comparisons and employing the inductive and deductive methods. The results indicate that although these observatories have contributed towards education and studies of the new moon, weaknesses exist prominently in the field of human resource compared to those observatories during the glorious era of Islamic civilization, in the aspect of expertise development and transfer of experience. Based on analyses on human resource at Malaysian observatories, in general, it was found that these observatories, on the whole,
iv
provide effective training and learning programmes aimed at developing the skills needed by these workers, despite problems that exist in its support system and the environment of these observatories which are not totally capable in providing training and the development of human resource for researchers and the staff at the observatories in Malaysia and the lack of experts who could transform these observatories into research centers. A strategic human resource plan has never been discussed seriously and students of astronomy has not been exposed to opportunities to the optimum. The system of recruitment and transfer of experience practiced in observatories in Malaysia are found to be unsuitable. Among the suggestions are to improve the system of recruitment by hiring workers and researchers with genuine interest, knowledge and skills apart from training these researchers and experts in astronomy to develop observatories as research and educational centres. It is hoped that this study will provide beneficial input for administrators and the staff of observatories and policy makers in the field of science and technology particularly astronomy in efforts to build observatories.


This econometric study assesses the efficiency of the income tax credit system implemented in France in 2005 on households' retrofitting investment decisions, focusing on insulation measures. A logit model with random individual effects is estimated using an unbalanced panel of 23,879 households surveyed over the period 2002-2011. An estimation in difference is performed to identify the impact of the policy. The tax credit had no significant effect during the first two years, suggesting a latency period related to inertia in households' investment decisions, possibly due to the complexity of the tax credit scheme. The tax credit had an increasing, significant positive effect from 2007 to 2010, before slightly decreasing in 2011. This is in line with changes in the tax credit rates, suggesting a correlation with the level of subsidy. Defined as the situation in which the subsidized household would have invested even in the absence of the subsidy, free-riding progressively decreased over the period and was lower for insulation of opaque surfaces (roofs, walls, etc.) than for insulation of windows. The estimated average proportion of free-riders varies between 40% and 85% after 2006. Finally, we assess the potential bias caused by time-varying unobservable variables and conclude that our estimates of the impacts of the policy are conservative.


Ecologists are faced with an over-abundance of ways to measure biodiversity. In this paper, I provide a compilation of and guide through this ticket of diversity metrics. I present a typology for diversity metrics that encompasses the three commonly considered categories of information: abundance, phylogenetic relationships, and traits (i.e., function). I update and expand previous summaries of diversity metrics. The formulas of those 117 metrics are presented in a standard notation and format that makes it easy to see the mathematical similarities and differences among the metrics. Finally, I propose a standard set of symbols for many of the metrics that makes their properties immediately obvious. This compilation will make it easier for researchers to identify the metric(s) most suited to their needs and will help guide future metric development. Disclaimer This manuscript is based on work done while serving at (and furloughed from) the U.S. National Science Foundation. The views expressed in this paper do not necessarily reflect those of the National Science Foundation or the United States Government.


The Research Group on Networks, in which the journal Flux originates, was created in France more than twenty years ago. Gathering researchers from all disciplinary origins as well as people from network utility companies, the group aimed at promoting cross-cutting research on technical networks: water and sanitation, energy, telecommunications and transport systems. Its intellectual origins were twofold: urban planning and urban history; science and technology studies (STS). Policy changes in the 1980s and in the 1990s led members of the group to study processes of liberalization of utility services. Interactions with the llarge technical systemsr research community proved very helpful in analysing the morphogenesis of networks. Conversely, methodological issues were not extensively discussed within the group. And paradoxically, geographers were less involved in the activities of the group than historians, sociologists, economists and engineers.In parallel, the notion of network was experiencing a tremendous success within both academic and professional milieux. Notably under the influence of the spread of the Internet, all spheres of economic and social activities began to function as networks. Some analysts argued that the network was the paradigm of the contemporary world: they were denounced as ideologists. A methodological effort seems the only way to reappropriate the ltoolkitr associated with the notion of network, which coould then be used to shed new light on the grand questions of social sciences. The elements needed to develop a robust socio-economy of technical networks are already available.


A simple optical multichannel analyzer consisting of SIT vidicon camera, videotape recorder, and video digitizer was used to record coherent anti-Stokes Raman scattering N2 spectra for temperature measurements inside a firing internal combustion engine. A high-resolution spectrum was recorded from each engine cycle at a 10-Hz repetition rate. Thousands of spectra were rapidly stored in inexpensive nonvolatile memory (videotape) to be digitized and analyzed later for the generation of temperature histograms. In addition to this spectroscopic application, the same equipment can be used for fluid dynamic and combustion imaging experiments.


The central nervous system (CNS) is considered as largely isolated from the immune system – a status referred to as "immune privilege". But CNS-tissue is constantly surveyed by immune cells and can under certain circumstances, such as viral infections, become a target of inflammatory responses. Cytotoxic T cells (CTLs) combat viruses in peripheral organs as well as the CNS and can contribute to inflammation-induced tissue damage. This concept drives the viral deja vu mouse model, where defined sequences of lymphocytic choriomeningitis virus (LCMV) infections cause severe CNS inflammation. The CTL response targets viral epitopes of persistently infected neurons that are shared by the used viruses.
To better understand the requirements and consequences for CTL:neuron interactions in vivo, different epitope mutants of the immunodominant LCMV epitopes NP396-404 and GP33-41 with different affinities to MHC class I were tested for their contribution in deja vu disease. While the CTL response against the LCMV nucleoprotein epitope NP396-404 was shown to be pivotal for viral deja vu disease, the co-expression of high affinity GP33 mutant epitopes did indeed aggravate disease but could not induce viral deja vu disease in the absence of NP396-404.
Furthermore, the molecular mediators and structural consequences of CTL attack on neurons were investigated by using bone marrow chimeras of CTL effector molecules and their receptors. CTL-derived Interferon-γ (IFN-γ) was identified as key mediator of CTL-induced synapse loss ("deafferentation") in virus-infected neurons. Deafferentation was found to correlate with clinical disability and dependend on the activation of the JAK–STAT1 pathway by IFN-γ-receptor signaling in target neurons. A similar IFN-γ signature was found in human neurons affected by Rasmussen's encephalitis, a CTL-mediated autoimmune disease.
These results provide important insights into the molecular mechanisms operating at the immunological synapse between CTL and neuron in inflammatory diseases of the CNS.


Recent studies have shown that adaptive evolution can be rapid enough to affect contemporary ecological dynamics in nature (i.e. 'rapid evolution'). These studies tend to focus on trait functions relating to interspecific interactions; however, the importance of rapid evolution of stoichiometric traits has been relatively overlooked. Various traits can affect the balance of elements (carbon, nitrogen, and phosphorus) of organisms, and rapid evolution of such stoichiometric traits will not only alter population and community dynamics but also influence ecosystem functions such as nutrient cycling. Multiple environmental changes may exert a selection pressure leading to adaptation of stoichiometrically important traits, such as an organism's growth rate. In this paper, we use theoretical approaches to explore the connections between rapid evolution and ecological stoichiometry at both the population and ecosystem level. First, we incorporate rapid evolution into an ecological stoichiometry model to investigate the effects of rapid evolution of a consumer's stoichiometric phosphorus: carbon ratio on consumer-producer population dynamics. We took two complementary approaches, an asexual clonal genotype model and a quantitative genetic model. Next, we extended these models to explicitly track nutrients in order to evaluate the effect of rapid evolution at the ecosystem level. Our model results indicate rapid evolution of the consumer stoichiometric trait can cause complex dynamics where rapid evolution destabilizes population dynamics and rescues the consumer population from extinction (evolutionary rescue). The model results also show that rapid evolution may influence the level of nutrients available in the environment and the flux of nutrients across trophic levels. Our study represents an important step for theoretical integration of rapid evolution and ecological stoichiometry.