Surface-Potential-Based Drain Current Analytical Model for Triple-Gate Junctionless Nanowire Transistors

This paper proposes a drain current model for triple-gate n-type junctionless nanowire transistors. The model is based on the solution of the Poisson equation. First, the 2-D Poisson equation is used to obtain the effective surface potential for long-channel devices, which is used to calculate the charge density along the channel and the drain current. The solution of the 3-D Laplace equation is added to the 2-D model in order to account for the short-channel effects. The proposed model is validated using 3-D TCAD simulations where the drain current and its derivatives, the potential, and the charge density have been compared, showing a good agreement for all parameters. Experimental data of short- channel devices down to 30 nm at different temperatures have been also used to validate the model.

DNA-Interactive Properties of Crotamine, a Cell-Penetrating Polypeptide and a Potential Drug Carrier

Crotamine, a 42-residue polypeptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, has been shown to be a cell-penetrating protein that targets chromosomes, carries plasmid DNA into cells, and shows specificity for actively proliferating cells. Given this potential role as a nucleic acid-delivery vector, we have studied in detail the binding of crotamine to single- and double-stranded DNAs of different lengths and base compositions over a range of ionic conditions. Agarose gel electrophoresis and ultraviolet spectrophotometry analysis indicate that complexes of crotamine with long-chain DNAs readily aggregate and precipitate at low ionic strength. This aggregation, which may be important for cellular uptake of DNA, becomes less likely with shorter chain length. 25-mer oligonucleotides do not show any evidence of such aggregation, permitting the determination of affinities and size via fluorescence quenching experiments. The polypeptide binds non-cooperatively to DNA, covering about 5 nucleotide residues when it binds to single (ss) or (ds) double stranded molecules. The affinities of the protein for ss-vs. ds-DNA are comparable, and inversely proportional to salt levels. Analysis of the dependence of affinity on [NaCl] indicates that there are a maximum of,3 ionic interactions between the protein and DNA, with some of the binding affinity attributable to non-ionic interactions. Inspection of the three-dimensional structure of the protein suggests that residues 31 to 35, Arg-Trp-Arg-Trp-Lys, could serve as a potential DNA-binding site. A hexapeptide containing this sequence displayed a lower DNA binding affinity and salt dependence as compared to the full-length protein, likely indicative of a more suitable 3D structure and the presence of accessory binding sites in the native crotamine. Taken together, the data presented here describing crotamine-DNA interactions may lend support to the design of more effective nucleic acid drug delivery vehicles which take advantage of crotamine as a carrier with specificity for actively proliferating cells. Citation: Chen P-C, Hayashi MAF, Oliveira EB, Karpel RL (2012) DNA-Interactive Properties of Crotamine, a Cell-Penetrating Polypeptide and a Potential Drug Carrier. PLoS ONE 7(11): e48913. doi:10.1371/journal.pone.0048913

Analysis of confinement potential fluctuation and band-gap renormalization effects on excitonic transition in GaAs/AlGaAs multiquantum wells grown on (100) and (311)A GaAs surfaces

The competition between confinement potential fluctuations and band-gap renormalization (BGR) in GaAs/AlxGa1-xAs quantum wells grown on [1 0 0] and [3 1 1]A GaAs substrates is evaluated. The results clearly demonstrate the coexistence of the band-tail states filling related to potential fluctuations and the band-gap renormalization caused by an increase in the density of photogenerated carriers during the photoluminescence (PL) experiments. Both phenomena have strong influence on temperature dependence of the PL-peak energy (E-PL(T)). As the photon density increases, the E-PL can shift to either higher or lower energies, depending on the sample temperature. The temperature at which the displacement changes from a blueshift to a redshift is governed by the magnitude of the potential fluctuations and by the variation of BGR with excitation density. A simple band-tail model with a Gaussian-like distribution of the density of state was used to describe the competition between the band-tail filling and the BGR effects on E-PL(T). (C) 2012 Elsevier B.V. All rights reserved.

Synthesis and Characterization of Gold/Alanine Nanocomposites with Potential Properties for Medical Application as Radiation Sensors

Radiation dose assessment is essential for several medical treatments and diagnostic procedures. In this context, nanotechnology has been used in the development of improved radiation sensors, with higher sensitivity as well as smaller sizes and energy dependence. This paper deals with the synthesis and characterization of gold/alanine nanocomposites with varying mass percentage of gold, for application as radiation sensors. Alanine is an excellent stabilizing agent for gold nanoparticles because the size of the nanoparticles does not augment with increasing mass percentage of gold, as evidenced by UV-vis spectroscopy, dynamic light scattering, and transmission electron microscopy. X-ray diffraction patterns suggest that the alanine crystalline orientation undergoes alterations upon the addition of gold nanoparticles. Fourier transform infrared spectroscopy indicates that there is interaction between the gold nanoparticles and the amine group of the alanine molecules, which may be the reason for the enhanced stability of the nanocomposite. The application of the nanocomposites as radiation detectors was evaluated by the electron spin resonance technique. The sensitivity is improved almost 3 times in the case of the nanocomposite containing 3% (w/w) gold, so it can be easily tuned by changing the amount of gold nanoparticles in the nanocomposites, without the size of the nanoparticles influencing the radiation absorption. In conclusion, the featured properties, such as homogeneity, nanoparticle size stability, and enhanced sensitivity, make these nanocomposites potential candidates for the construction of small-sized radiation sensors with tunable sensitivity for application in several medical procedures.

Soil-mediated effects on potential Euterpe edulis (Arecaceae) fruit and palm heart sustainable management in the Brazilian Atlantic Forest

Euterpe edulis is an endangered species due to palm heart overharvesting, the most important non-timber forest product of the Brazilian Atlantic Forest, and fruit exploitation has been introduced as a low impacting alternative. However, E. edulis is a keystone species for frugivores birds, and even the impact of fruit exploitation needs to be better investigated. Since this species occurs over contrasting habitats, the establishment of site-specific standards and limits for exploitation may also be essential to achieve truly sustainable management. In this context, we sought to investigate how soil chemical composition would potentially affect E. edulis (Arecaceae) palm heart and fruit exploitation considering current standards of management. We studied natural populations found in Restinga Forest and Atlantic Rainforest remnants established within Natural Reserves of Sao Paulo State, SE Brazil, where 10.24 ha permanent plots, composed of a grid of 256 subplots (20 m x 20 m), were located. In each of these subplots, we evaluated soil chemical composition and diameter at breast height of E. edulis individuals. Additionally, we evaluated fruit yield in 2008 and 2009 in 20 individuals per year. The Atlantic Rainforest population had a much higher proportion of larger diameter individuals than the population from the Restinga Forest, as a result of habitat-mediated effects, especially those related to soil. Sodium and potassium concentration in Restinga Forest soils, which have strong negative and positive effect on palm growth, respectively, played a key role in determining those differences. Overall, the number of fruits that could be exploited in the Atlantic Rainforest was four times higher than in Restinga Forest. If current rules for palm heart and fruit harvesting were followed without any restriction to different habitats, Restinga Forest populations are under severe threat, as this study shows that they are not suitable for sustainable management of both fruits and palm heart. Hence, a habitat-specific approach of sustainable management is needed for this species in order to respect the demographic and ecological dynamics of each population to be managed. These findings suggest that any effort to create general management standards of low impacting harvesting may be unsuccessful if the species of interest occur over a wide range of ecosystems. (C) 2012 Elsevier B.V. All rights reserved.

Spatial variability of soil fertility and its relationship with seed physiological potential in a soybean production area

The correlation of soil fertility x seed physiological potential is very important in the area of seed technology but results published with that theme are contradictory. For this reason, this study to evaluate the correlations between soil chemical properties and physiological potential of soybean seeds. On georeferenced points, both soil and seeds were sampled for analysis of soil fertility and seed physiological potential. Data were assessed by the following analyses: descriptive statistics; Pearson's linear correlation; and geostatistics. The adjusted parameters of the semivariograms were used to produce maps of spatial distribution for each variable. Organic matter content, Mn and Cu showed significant effects on seed germination. Most variables studied presented moderate to high spatial dependence. Germination and accelerated aging of seeds, and P, Ca, Mg, Mn, Cu and Zn showed a better fit to spherical semivariogram: organic matter, pH and K had a better fit to Gaussian model; and V% and Fe showed a better fit to the linear model. The values for range of spatial dependence varied from 89.9 m for P until 651.4 m for Fe. These values should be considered when new samples are collected for assessing soil fertility in this production area.

A partial dependence factorial analysis to deal with selection bias in observational studis

This thesis presents a creative and practical approach to dealing with the problem of selection bias. Selection bias may be the most important vexing problem in program evaluation or in any line of research that attempts to assert causality. Some of the greatest minds in economics and statistics have scrutinized the problem of selection bias, with the resulting approaches – Rubin’s Potential Outcome Approach(Rosenbaum and Rubin,1983; Rubin, 1991,2001,2004) or Heckman’s Selection model (Heckman, 1979) – being widely accepted and used as the best fixes. These solutions to the bias that arises in particular from self selection are imperfect, and many researchers, when feasible, reserve their strongest causal inference for data from experimental rather than observational studies. The innovative aspect of this thesis is to propose a data transformation that allows measuring and testing in an automatic and multivariate way the presence of selection bias. The approach involves the construction of a multi-dimensional conditional space of the X matrix in which the bias associated with the treatment assignment has been eliminated. Specifically, we propose the use of a partial dependence analysis of the X-space as a tool for investigating the dependence relationship between a set of observable pre-treatment categorical covariates X and a treatment indicator variable T, in order to obtain a measure of bias according to their dependence structure. The measure of selection bias is then expressed in terms of inertia due to the dependence between X and T that has been eliminated. Given the measure of selection bias, we propose a multivariate test of imbalance in order to check if the detected bias is significant, by using the asymptotical distribution of inertia due to T (Estadella et al. 2005) , and by preserving the multivariate nature of data. Further, we propose the use of a clustering procedure as a tool to find groups of comparable units on which estimate local causal effects, and the use of the multivariate test of imbalance as a stopping rule in choosing the best cluster solution set. The method is non parametric, it does not call for modeling the data, based on some underlying theory or assumption about the selection process, but instead it calls for using the existing variability within the data and letting the data to speak. The idea of proposing this multivariate approach to measure selection bias and test balance comes from the consideration that in applied research all aspects of multivariate balance, not represented in the univariate variable- by-variable summaries, are ignored. The first part contains an introduction to evaluation methods as part of public and private decision process and a review of the literature of evaluation methods. The attention is focused on Rubin Potential Outcome Approach, matching methods, and briefly on Heckman’s Selection Model. The second part focuses on some resulting limitations of conventional methods, with particular attention to the problem of how testing in the correct way balancing. The third part contains the original contribution proposed , a simulation study that allows to check the performance of the method for a given dependence setting and an application to a real data set. Finally, we discuss, conclude and explain our future perspectives.

The Dynamics of a Small Model Glass Former as Viewed from Its Potential Energy Landscape

Despite intensive research during the last decades, thetheoreticalunderstanding of supercooled liquids and the glasstransition is stillfar from being complete. Besides analytical investigations,theso-called energy-landscape approach has turned out to beveryfruitful. In the literature, many numerical studies havedemonstratedthat, at sufficiently low temperatures, all thermodynamicquantities can be predicted with the help of the propertiesof localminima in the potential-energy-landscape (PEL). The main purpose of this thesis is to strive for anunderstanding ofdynamics in terms of the potential energy landscape. Incontrast to the study of static quantities, this requirestheknowledge of barriers separating the minima.Up to now, it has been the general viewpoint that thermallyactivatedprocesses ('hopping') determine the dynamics only belowTc(the critical temperature of mode-coupling theory), in thesense that relaxation rates follow from local energybarriers.As we show here, this viewpoint should be revisedsince the temperature dependence of dynamics is governed byhoppingprocesses already below 1.5Tc.At the example of a binary mixture of Lennard-Jonesparticles (BMLJ),we establish a quantitative link from the diffusioncoefficient,D(T), to the PEL topology. This is achieved in three steps:First, we show that it is essential to consider wholesuperstructuresof many PEL minima, called metabasins, rather than singleminima. Thisis a consequence of strong correlations within groups of PELminima.Second, we show that D(T) is inversely proportional to theaverageresidence time in these metabasins. Third, the temperaturedependenceof the residence times is related to the depths of themetabasins, asgiven by the surrounding energy barriers. We further discuss that the study of small (but not toosmall) systemsis essential, in that one deals with a less complex energylandscapethan in large systems. In a detailed analysis of differentsystemsizes, we show that the small BMLJ system consideredthroughout thethesis is free of major finite-size-related artifacts.

Mathematical Modeling to Investigate Antiarrhythmic Drug Side Effects: Rate-Dependence Role in Ionic Currents and Action Potentials Shape in the O’Hara Model

Sudden cardiac death due to ventricular arrhythmia is one of the leading causes of mortality in the world. In the last decades, it has proven that anti-arrhythmic drugs, which prolong the refractory period by means of prolongation of the cardiac action potential duration (APD), play a good role in preventing of relevant human arrhythmias. However, it has long been observed that the “class III antiarrhythmic effect” diminish at faster heart rates and that this phenomenon represent a big weakness, since it is the precise situation when arrhythmias are most prone to occur. It is well known that mathematical modeling is a useful tool for investigating cardiac cell behavior. In the last 60 years, a multitude of cardiac models has been created; from the pioneering work of Hodgkin and Huxley (1952), who first described the ionic currents of the squid giant axon quantitatively, mathematical modeling has made great strides. The O’Hara model, that I employed in this research work, is one of the modern computational models of ventricular myocyte, a new generation began in 1991 with ventricular cell model by Noble et al. Successful of these models is that you can generate novel predictions, suggest experiments and provide a quantitative understanding of underlying mechanism. Obviously, the drawback is that they remain simple models, they don’t represent the real system. The overall goal of this research is to give an additional tool, through mathematical modeling, to understand the behavior of the main ionic currents involved during the action potential (AP), especially underlining the differences between slower and faster heart rates. In particular to evaluate the rate-dependence role on the action potential duration, to implement a new method for interpreting ionic currents behavior after a perturbation effect and to verify the validity of the work proposed by Antonio Zaza using an injected current as a perturbing effect.

Affective and linguistic processing of speech prosody: DC potential studies

Speech melody or prosody subserves linguistic, emotional, and pragmatic functions in speech communication. Prosodic perception is based on the decoding of acoustic cues with a predominant function of frequency-related information perceived as speaker's pitch. Evaluation of prosodic meaning is a cognitive function implemented in cortical and subcortical networks that generate continuously updated affective or linguistic speaker impressions. Various brain-imaging methods allow delineation of neural structures involved in prosody processing. In contrast to functional magnetic resonance imaging techniques, DC (direct current, slow) components of the EEG directly measure cortical activation without temporal delay. Activation patterns obtained with this method are highly task specific and intraindividually reproducible. Studies presented here investigated the topography of prosodic stimulus processing in dependence on acoustic stimulus structure and linguistic or affective task demands, respectively. Data obtained from measuring DC potentials demonstrated that the right hemisphere has a predominant role in processing emotions from the tone of voice, irrespective of emotional valence. However, right hemisphere involvement is modulated by diverse speech and language-related conditions that are associated with a left hemisphere participation in prosody processing. The degree of left hemisphere involvement depends on several factors such as (i) articulatory demands on the perceiver of prosody (possibly, also the poser), (ii) a relative left hemisphere specialization in processing temporal cues mediating prosodic meaning, and (iii) the propensity of prosody to act on the segment level in order to modulate word or sentence meaning. The specific role of top-down effects in terms of either linguistically or affectively oriented attention on lateralization of stimulus processing is not clear and requires further investigations.

Characterisation of Gas Transport Properties of the Opalinus Clay, a Potential Host Rock Formation for Radioactive Waste Disposal

The Opalinus Clay in Northern Switzerland has been identified as a potential host rock formation for the disposal of radioactive waste. Comprehensive understanding of gas transport processes through this low-permeability formation forms a key issue in the assessment of repository performance. Field investigations and laboratory experiments suggest an intrinsic permeability of the Opalinus Clay in the order of 10(-20) to 10(-21) m(2) and a moderate anisotropy ratio < 10. Porosity depends on clay content and burial depth; values of similar to 0.12 are reported for the region of interest. Porosimetry indicates that about 10-30 of voids can be classed as macropores, corresponding to an equivalent pore radius > 25 nm. The determined entry pressures are in the range of 0.4-10 MPa and exhibit a marked dependence on intrinsic permeability. Both in situ gas tests and gas permeameter tests on drillcores demonstrate that gas transport through the rock is accompanied by porewater displacement, suggesting that classical flow concepts of immiscible displacement in porous media can be applied when the gas entry pressure (i.e. capillary threshold pressure) is less than the minimum principal stress acting within the rock. Essentially, the pore space accessible to gas flow is restricted to the network of connected macropores, which implies a very low degree of desaturation of the rock during the gas imbibition process. At elevated gas pressures (i.e. when gas pressure approaches the level of total stress that acts on the rock body), evidence was seen for dilatancy controlled gas transport mechanisms. Further field experiments were aimed at creating extended tensile fractures with high fracture transmissivity (hydro- or gasfracs). The test results lead to the conclusion that gas fracturing can be largely ruled out as a risk for post-closure repository performance.

A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence.

BACKGROUND: Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co-morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence. METHODS: Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed. RESULTS: The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends (p < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence. CONCLUSIONS: Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.

Temporal variability of damage potential on roads as a conceptual contribution towards a short-term avalanche risk simulation

The fatality risk caused by avalanches on road networks can be analysed using a long-term approach, resulting in a mean value of risk, and with emphasis on short-term fluctuations due to the temporal variability of both, the hazard potential and the damage potential. In this study, the approach for analysing the long-term fatality risk has been adapted by modelling the highly variable short-term risk. The emphasis was on the temporal variability of the damage potential and the related risk peaks. For defined hazard scenarios resulting from classified amounts of snow accumulation, the fatality risk was calculated by modelling the hazard potential and observing the traffic volume. The avalanche occurrence probability was calculated using a statistical relationship between new snow height and observed avalanche releases. The number of persons at risk was determined from the recorded traffic density. The method resulted in a value for the fatality risk within the observed time frame for the studied road segment. The long-term fatality risk due to snow avalanches as well as the short-term fatality risk was compared to the average fatality risk due to traffic accidents. The application of the method had shown that the long-term avalanche risk is lower than the fatality risk due to traffic accidents. The analyses of short-term avalanche-induced fatality risk provided risk peaks that were 50 times higher than the statistical accident risk. Apart from situations with high hazard level and high traffic density, risk peaks result from both, a high hazard level combined with a low traffic density and a high traffic density combined with a low hazard level. This provided evidence for the importance of the temporal variability of the damage potential for risk simulations on road networks. The assumed dependence of the risk calculation on the sum of precipitation within three days is a simplified model. Thus, further research is needed for an improved determination of the diurnal avalanche probability. Nevertheless, the presented approach may contribute as a conceptual step towards a risk-based decision-making in risk management.

A heteromeric potassium channel involved in the modulation of the plasma membrane potential is essential for the survival of African trypanosomes.

Discovery of novel drug targets may lead to improved treatment of trypanosomiasis. We characterize here 2 gene products of Trypanosoma brucei that are essential for the growth of bloodstream form (BSF) parasites, as shown by RNA interference (RNAi)-mediated down-regulation of the individual mRNAs. The primary sequences of the 2 proteins--protein encoded by gene Tb927.1.4450 (TbK1) and protein encoded by gene Tb927.9.4820 (TbK2)--indicate that both belong to the family of putative, Ca(2+)-activated potassium channels. The proteins were expressed in Xenopus laevis oocytes and their functions investigated by use of electrophysiological techniques. Only combined expression of TbK1 and TbK2 results in the formation of sizeable currents, indicating that these proteins probably assemble into a heteromeric ion channel. The current mediated by this channel shows little time and voltage dependence and displays a permeability ratio of K(+)/Na(+) of >20. The known potassium channel blocker barium inhibits this channel with a half-maximal inhibitory concentration (IC50) of 98 ± 15 μM. The membrane potential of trypanosomes was measured with a fluorescent dye. Individual RNAi-mediated down-regulation of TbK1 or TbK2 eliminates a potassium conductance in the plasma membrane of BSF. Thus, this heteromeric potassium channel is involved in the modulation of the plasma membrane potential and represents a novel drug target in T. brucei.

The opioid antagonist naltrexone and its pharmacological role in treating alcohol dependence: A literature review

Naltrexone, an opioid antagonist, was the second drug approved for treatment of alcohol dependence in the U.S. Its approval followed two landmark studies published in the U.S. in 1992. [1, 2] These studies showed that a combined treatment of naltrexone and behavioral therapy reduced alcohol consumption in alcoholics. Opioid antagonists decrease craving for alcohol and help to reduce drinking by blocking opioid peptide receptors in the body that are active in a dopamine chemical reward system. ^ Despite their usefulness, opioid antagonists have been underutilized. Health providers not educated in the use of opioid antagonists hold the view that opioid antagonist therapy is ineffective. However, it is apparent from the relevant literature that this therapy, when properly understood and targeted, has the potential to make a positive contribution in treating alcohol dependent patients. ^ This thesis will review the scientific literature and the present body of knowledge regarding opioid antagonists (naltrexone) and their pharmacological role in treating alcohol dependence.^