The Electrostatic Persistence Length Calculated from Monte Carlo, Variational and Perturbation Methods

Monte Carlo simulations and variational calculations using a Gaussian ansatz are applied to a model consisting of a flexible linear polyelectrolyte chain as well as to an intrinsically stiff chain with up to 1000 charged monomers. Addition of salt is treated implicitly through a screened Coulomb potential for the electrostatic interactions. For the flexible model the electrostatic persistence length shows roughly three regimes in its dependence on the Debye-H\"{u}ckel screening length, $\kappa^{-1}$.As long as the salt content is low and $\kappa^{-1}$ is longer than the end-to-end distance, the electrostatic persistence length varies only slowly with $\kappa^{-1}$. Decreasing the screening length, a controversial region is entered. We find that the electrostatic persistence length scales as $sqrt{\xi_p}/\kappa$, in agreement with experiment on flexible polyelectrolytes, where $\xi_p$ is a strength parameter measuring the electrostatic interactions within the polyelectrolyte. For screening lengths much shorter than the bond length, the $\kappa^{-1}$ dependence becomes quadratic in the variational calculation. The simulations suffer from numerical problems in this regime, but seem to give a relationship half-way between linear and quadratic. A low temperature expansion only reproduces the first regime and a high temperature expansion, which treats the electrostatic interactions as a perturbation to a Gaussian chain, gives a quadratic dependence on the Debye length. For a sufficiently stiff chain, the persistence length varies quadratically with $\kappa^{-1}$ in agreement with earlier theories.Comment: 20 pages LaTeX, 9 postscript figure

Analysis of complex contagions in random multiplex networks

We study the diffusion of influence in random multiplex networks where links can be of $r$ different types, and for a given content (e.g., rumor, product, political view), each link type is associated with a content dependent parameter $c_i$ in $[0,\infty]$ that measures the relative bias type-$i$ links have in spreading this content. In this setting, we propose a linear threshold model of contagion where nodes switch state if their "perceived" proportion of active neighbors exceeds a threshold \tau. Namely, a node connected to $m_i$ active neighbors and $k_i-m_i$ inactive neighbors via type-$i$ links will turn active if $\sum{c_i m_i}/\sum{c_i k_i}$ exceeds its threshold \tau. Under this model, we obtain the condition, probability and expected size of global spreading events. Our results extend the existing work on complex contagions in several directions by i) providing solutions for coupled random networks whose vertices are neither identical nor disjoint, (ii) highlighting the effect of content on the dynamics of complex contagions, and (iii) showing that content-dependent propagation over a multiplex network leads to a subtle relation between the giant vulnerable component of the graph and the global cascade condition that is not seen in the existing models in the literature.Comment: Revised 06/08/12. 11 Pages, 3 figure

Local atomic arrangement and martensitic transformation in Ni50_{50}Mn35_{35}In15_{15}: An EXAFS Study

Heusler alloys that undergo martensitic transformation in ferromagnetic state are of increasing scientific and technological interest. These alloys show large magnetic field induced strains upon martensitic phase change thus making it a potential candidate for magneto-mechanical actuation. The crystal structure of martensite is an important factor that affects both the magnetic anisotropy and mechanical properties of such materials. Moreover, the local chemical arrangement of constituent atoms is vital in determining the overall physical properties. Ni$_{50}$Mn$_{35}$In$_{15}$ is one such ferromagnetic shape memory alloy that displays exotic properties like large magnetoresistance at moderate field values. In this work, we present the extended x-ray absorption fine-structure measurements (EXAFS) on the bulk Ni$_{50}$Mn$_{35}$In$_{15}$ which reveal the local structural change that occurs upon phase transformation. The change in the bond lengths between different atomic species helps in understanding the type of hybridization which is an important factor in driving such Ni-Mn based systems towards martensitic transformation

Phase diagram of Fe-doped Ni-Mn-Ga ferromagnetic shape-memory alloys

We have studied the effect of Fe addition on the structural and magnetic transitions in the magnetic shape memory alloy Ni-Mn-Ga by substituting systematically each atomic species by Fe. Calorimetric and AC susceptibility measurements have been carried out in order to study the magnetic and structural transformation properties. We find that the addition of Fe modifies the structural and magnetic transformation temperatures. Magnetic transition temperatures are displaced to higher values when Fe is substituted into Ni-Mn-Ga, while martensitic and premartensitic transformation temperatures shift to lower values. Moreover, it has been found that the electron per atom concentration essentially governs the phase stability in the quaternary system. However, the observed scaling of transition temperatures with $e/a$ differs from that reported in the related ternary system Ni-Mn-Ga.Comment: 8 pages, 8 figures. Accepted for publication in the Physical Review

The effect of microstructure on mechanical properties of HVOF sprayed WC-CoCr composite coatings

This study aims for deeper understanding of the composition and phase changes occurring during HVOF spraying of the powder to WC-CoCr coatings. Also, the effect of lamellar microstructure on the mechanical properties is studied. Compositional and microstructural features are studied by means of X-ray diffraction, XRF, FE-SEM and TEM (EDX, EELS). Mechanical properties are mainly studied by different instrumented indentation and nanoindentation techniques. The use of two new fracture parameters, complementing the fracture toughness value of the coating, are proposed and examined. Higher load range indentations are used to measure cross-sectional and surface hardness, elastic modulus and fracture toughness of the coatings. Mechanical properties of individual phases are studied by nanoindentation. To our knowledge this is the first time that the mechanical properties of this amorphous/nanocrystalline matrix are studied. ICP (In-situ Coating Property) sensor, developed for quality control and residual stress evaluation, is also used to measure the elastic modulus and coefficient of thermal expansion (CTE) of the coatings. Abrasion wear resistance of the coatings are studied according to standard ASTM G 65D. Because of the brittle nature of HVOF coatings, the main focus of this study is in the effects of coating microstructure on fracture toughness, and on crack initiation and propagation resistance. It is shown that even when two similar coatings have equal indentation fracture toughness values, the critical crack initiation loads may be very different. This new parameter is expected to be extremely useful in the evaluation of the coating performance under loading conditions

A preferential attachment model with random initial degrees

In this paper, a random graph process ${G(t)}_{t\geq 1}$ is studied and its degree sequence is analyzed. Let $(W_t)_{t\geq 1}$ be an i.i.d. sequence. The graph process is defined so that, at each integer time $t$, a new vertex, with $W_t$ edges attached to it, is added to the graph. The new edges added at time t are then preferentially connected to older vertices, i.e., conditionally on $G(t-1)$, the probability that a given edge is connected to vertex i is proportional to $d_i(t-1)+\delta$, where $d_i(t-1)$ is the degree of vertex $i$ at time $t-1$, independently of the other edges. The main result is that the asymptotical degree sequence for this process is a power law with exponent $\tau=\min\{\tau_{W}, \tau_{P}\}$, where $\tau_{W}$ is the power-law exponent of the initial degrees $(W_t)_{t\geq 1}$ and $\tau_{P}$ the exponent predicted by pure preferential attachment. This result extends previous work by Cooper and Frieze, which is surveyed.Comment: In the published form of the paper, the proof of Proposition 2.1 is incomplete. This version contains the complete proo

A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma

Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine

Evaluating outcomes of therapies offered by occupational therapists in adult mental health

Background: Attitudes towards the use of outcome measures by professionals working in mental health have been shown to be variable. Occupational therapists appear to have difficulty specifying goals and measuring the outcomes of interventions. Aims: To measure the outcomes of therapies offered by occupational therapists and to assess concurrent validity of the Van du Toit Model of Creative Ability (VdT MoCA) assessment. Method: The Global Assessment of Functioning (GAF), VdT MoCA assessment and Canadian Occupational Performance Measure (COPM) were used. Changes in mean scores on the measures were assessed using appropriate tests. Correlations between measures were assessed using Spearman's non-parametric test. Results: Mean post-therapy scores were significantly higher than pre-therapy scores on all three measures. VdT MoCA assessment scores pre- and post-therapy were highly correlated with GAF scores. The COPM outcome scores were uncorrelated with VdT MoCA assessment and GAF scores. Conclusions: The results offer a promising indication that occupational therapy interventions may increase functioning and thus aid clients' recovery. The VdT MoCA assessment is promising as a measure of improvement in functioning. Further research is needed to confirm these results and to further explore issues around occupational therapists' use of outcome measures

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research