The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli. RESULTS: No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli. CONCLUSION: These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.

Design of non-Gaussian multispectral shortwave infrared filters assessed by surface spectral reflectances on the ECOSTRESS library.

This paper addresses the multispectral filter design problem for spectral ranges where a viewing subspace is not defined. The methodology of color filter design is extended to this case, which allows the optimization of custom filter transmittance that meets the physical constraints of available fabrication methods. Multispectral shortwave infrared filters are then designed for two scenarios: spectral reconstruction and false-color representation. The Monte Carlo method is used to verify the filter performance degradation due to deviations in fabrication. The results obtained indicate that the proposed method is useful for designing multispectral filters to be fabricated using generic processes without any additional constraints.

An Overview of Emergent Order in Far-from-Equilibrium Driven Systems: From Kuramoto Oscillators to Rayleigh-Bénard Convection.

Soft-matter systems when driven out of equilibrium often give rise to structures that usually lie in between the macroscopic scale of the material and microscopic scale of its constituents. In this paper we review three such systems, the two-dimensional square-lattice Ising model, the Kuramoto model and the Rayleigh-Bénard convection system which when driven out of equilibrium give rise to emergent spatio-temporal order through self-organization. A common feature of these systems is that the entities that self-organize are coupled to one another in some way, either through local interactions or through a continuous media. Therefore, the general nature of non-equilibrium fluctuations of the intrinsic variables in these systems are found to follow similar trends as order emerges. Through this paper, we attempt to find connections between these systems, and systems in general which give rise to emergent order when driven out of equilibrium. This study, thus acts as a foundation for modeling a complex system as a two-state system, where the states: order and disorder can coexist as the system is driven away from equilibrium.

Concentration-driven phase transition and self-assembly in drying droplets of diluting whole blood.

Multi-colloidal systems exhibit a variety of structural and functional complexity owing to their ability to interact amongst different components into self-assembled structures. This paper presents experimental confirmations that reveal an interesting sharp phase transition during the drying state and in the dried film as a function of diluting concentrations ranging from 100% (undiluted whole blood) to 12.5% (diluted concentrations). An additional complementary contact angle measurement exhibits a monotonic decrease with a peak as a function of drying. This peak is related to a change in visco-elasticity that decreases with dilution, and disappears at the dilution concentration for the observed phase transition equivalent to 62% (v/v). This unique behavior is clearly commensurate with the optical image statistics and morphological analysis; and it is driven by the decrease in the interactions between various components within this bio-colloid. The implications of these phenomenal systems may address many open-ended questions of complex hierarchical structures.

A comparative study of the drying evolution and dried morphology of two globular proteins in de-ionized water solutions.

Pattern formation in drying protein droplets continues to attract considerable research attention because it can be linked to specific protein-protein interactions. An extensive study of the drying evolution and the final crack patterns is presented, highlighting the concentration dependence (from 1 to 13 wt%) of two globular proteins, lysozyme (Lys) and bovine serum albumin (BSA), in de-ionized water. The drying evolution starts with a constant contact radius mode and shifts to a mixed mode where both fluid front and contact angle changes. The contact angle monotonically decreases, whereas, the fluid front exhibits two regimes: an initial linear regime and a later non-linear regime. Unlike the linear regime, the non-linear regime is faster for Lys droplets. This results in the formation of a "mound"-like structure in the central region. A new feature, a "dimple" is observed in this mound which is found to be dependent on the initial concentration. The different crack morphology of BSA and Lys depends strongly on the initial state of the solution and can be interpreted using a simple mechanical model. In fact, when dried under uniform conditions (surface, humidity, temperature, droplet diameter, etc.), the evolution and the final pattern displays as a fingerprint of the initial state.

Phase diagrams and dynamics of a computationally efficient map-based neuron model.

We introduce a new map-based neuron model derived from the dynamical perceptron family that has the best compromise between computational efficiency, analytical tractability, reduced parameter space and many dynamical behaviors. We calculate bifurcation and phase diagrams analytically and computationally that underpins a rich repertoire of autonomous and excitable dynamical behaviors. We report the existence of a new regime of cardiac spikes corresponding to nonchaotic aperiodic behavior. We compare the features of our model to standard neuron models currently available in the literature.

Treatment planning systems dosimetry auditing project in Portugal.

BACKGROUND AND PURPOSE: The Medical Physics Division of the Portuguese Physics Society (DFM_SPF) in collaboration with the IAEA, carried out a national auditing project in radiotherapy, between September 2011 and April 2012. The objective of this audit was to ensure the optimal usage of treatment planning systems. The national results are presented in this paper. MATERIAL AND METHODS: The audit methodology simulated all steps of external beam radiotherapy workflow, from image acquisition to treatment planning and dose delivery. A thorax CIRS phantom lend by IAEA was used in 8 planning test-cases for photon beams corresponding to 15 measuring points (33 point dose results, including individual fields in multi-field test cases and 5 sum results) in different phantom materials covering a set of typical clinical delivery techniques in 3D Conformal Radiotherapy. RESULTS: All 24 radiotherapy centers in Portugal have participated. 50 photon beams with energies 4-18 MV have been audited using 25 linear accelerators and 32 calculation algorithms. In general a very good consistency was observed for the same type of algorithm in all centres and for each beam quality. CONCLUSIONS: The overall results confirmed that the national status of TPS calculations and dose delivery for 3D conformal radiotherapy is generally acceptable with no major causes for concern. This project contributed to the strengthening of the cooperation between the centres and professionals, paving the way to further national collaborations.

Calorimetric study of phase transitions in ocylcyanobiphenyl-barium titanate nanoparticle dispersions.

High-resolution ac-calorimetry is reported on the weakly first-order isotropic to nematic (I-N) and the continuous nematic to smectic-A (N-SmA) phase transitions in the liquid crystal octylcyanobiphenyl (8CB) doped with a ferroelectric nanoparticle barium titanate, BaTiO3 (BT). Measurements were performed as a function of BT concentration and over a wide temperature range well above and below the two transitions. From the thermal scans of all samples (having BT mass fraction φ(m) = 0.001 to 0.014 and pure 8CB), both the I-N and the N-SmA transitions evolve in character. Specifically, there appears an unusual change of the I-N specific heat peak shape on heating as φ(m) increases. Both the transitions shift to lower temperature at a different rate for φ(m)<φ(m)(c)=0.002 as compared to that for φ(m)>φ(m)(c). The effective transition enthalpies are essentially constant and similar to that seen in the bulk. Using a simple geometric model, the mean distance between the BT particles at the cross-over φ(m)(c) is found to be x(c)~3 µm, which is consistent with an estimated surface extrapolation length b for the nematic director. This suggests that the low φ(m) regime is dominated by an impurity/disorder effect while for φ(m)>φ(m)(c) the mean distance is small enough for the LC to mediate coupling between the BT ferroelectric nanoparticles.

Study of the isotropic to smectic-A phase transition in liquid crystal and acetone binary mixtures.

The first-order transition from the isotropic (I) to smectic-A (Sm A) phase in the liquid crystal 4-cyano-4(')-decylbiphenyl (10CB) doped with the polar solvent acetone (ace) has been studied as a function of solvent concentration by high-resolution ac-calorimetry. Heating and cooling scans were performed for miscible 10CB+ace samples having acetone mole fractions from x(ace)=0.05 (1 wt %) to 0.36 (10%) over a wide temperature range from 310 to 327 K. Two distinct first-order phase transition features are observed in the mixture whereas there is only one transition (I-Sm A) in the pure 10CB for that particular temperature range. Both calorimetric features reproduce on repeated heating and cooling scans and evolve with increasing x(ace) with the high-temperature feature relatively stable in temperature but reduced in size while the low-temperature feature shifts dramatically to lower temperature and exhibits increased dispersion. The coexistence region increases for the low-temperature feature but remains fairly constant for the high-temperature feature as a function of x(ace). Polarizing optical microscopy supports the identification of a smectic phase below the high-temperature heat capacity signature indicating that the low-temperature feature represents an injected smectic-smectic phase transition. These effects may be the consequence of screening the intermolecular potential of the liquid crystals by the solvent that stabilizes a weak smectic phase intermediate of the isotropic and pure smectic-A.

Orientational coupling enhancement in a carbon nanotube dispersed liquid crystal.

We present a detailed study of a dilute suspension of carbon nanotubes (CNTs) in a pentylcyanobiphenyl (5CB) liquid crystal (LC) by probing the dielectric properties as a function of applied ac voltage and frequency. In principle, to minimize the elastic distortion in the nematic matrix, the monodispersed CNTs follow the nematic director without disturbing the director field significantly. A strong anchoring energy due to π-π electron stacking between LC-CNT molecules results in an increase in the dielectric anisotropy for the hybrid system, indicating a significant enhancement in the orientational order parameter. The frequency-dependent dielectric anisotropy for the composite system reveals the intrinsic frequency response of the LC-CNT anchoring mechanism. As a matter of consequence, the extracted value of splay elastic constant suggests that LC-CNT anchoring has an impact on the structural modification of the hybrid LC+CNT system. This strong anchoring energy stabilizes local pseudonematic domains, giving rise to a nonzero dielectric anisotropy in the isotropic phase that also shows an intrinsic frequency response.

Calorimetric study of the nematic to smectic-A phase transition in octylcyanobiphenyl-hexane binary mixtures.

The continuous nematic to smectic-A (N-SmA) phase transition has been studied by high-resolution ac-calorimetry in binary mixtures of the liquid crystal octylcyanobiphenyl (8CB) and a nonmesogenic, low-molecular weight, solvent n-hexane (hex) as a function of temperature and solvent concentration. Heating and cooling scans about the N-SmA transition temperature were repeatedly performed on pure and six 8CB+hex samples having hexane molar concentration ranging from x(hex)=0.02 to 0.12. All 8CB+hex samples in this range of x(hex) remain macroscopically miscible and exhibit an N-SmA heat capacity peak that shifts nonmonotonically to lower temperature and evolves in shape, with a reproducible hysteresis, as x(hex) increases. The imaginary part of heat capacity remains zero up to x(hex)(TCP) ≃ 0.07 above which the distinct peak is observed, corresponding to a jump in both the real and imaginary enthalpy, indicating the onset of first-order behavior. A simple power-law analysis reveals an effective exponent that increases smoothly from 0.30 to 0.50 with an amplitude ratio A-/A+→1 as x(hex)→x(hex)(TCP). This observed crossover of the N-SmA toward a tricritical point driven by solvent concentration is consistent with previous results and can be understood as a solvent softening of the liquid crystal and concument promoting of nematic fluctuations.

TMEM25, REPS2 and Meis 1: favourable prognostic and predictive biomarkers for breast cancer.

BACKGROUND/AIMS: A panel of prognostic and predictive biomarkers would contribute to personalized treatment of breast cancer patients. However, many such biomarkers have yet to be identified and evaluated. The aim of this study was to investigate the relevance of 3 such putative biomarkers. METHODS: TMEM25, REPS2 and Meis 1 expression was investigated by qRT-PCR, in triplicate, in 103 breast tumour biopsies procured in 1993-1994. Normal breast tissue specimens were also analysed for comparative purposes. Univariate and multivariate analyses were used to identify associations between expression of these transcripts as well as patients' clinicopathological and survival data. RESULTS: TMEM25, REPS2 and Meis 1 transcripts were detected in approximately 52, 78 and 40% of tumour specimens, respectively. Expression of each of the 3 genes was indicative of extended survival times from diagnosis [association between relapse-free survival (RFS) and TMEM25, p = 0.0002; REPS2, p = 0.0287; association between overall survival (OS) and TMEM25, p = 0.001; REPS2, p = 0.0131; Meis 1, p = 0.0255]. Presence of TMEM25 and Meis 1 was associated with oestrogen receptor-positive (TMEM25, p < 0.0005; Meis 1, p = 0.011), lower-grade (TMEM25, p = 0.002; Meis 1, p = 0.001) tumours. Multivariate analysis indicated TMEM25 expression to be an independent prognostic factor for extended RFS (p = 0.011) and OS (p = 0.001). Furthermore, for patients who received adjuvant chemotherapy, significantly longer survival times were achieved if their tumours expressed TMEM25 (OS, p = 0.031; RFS, p = 0.0181) and REPS2 (OS, p = 0.011). While expression of these mRNAs was generally absent from triple-negative breast tumours, statistical significance was not achieved. CONCLUSION: Our results suggest that TMEM25, REPS2 and Meis 1 mRNAs may be useful members of a panel of favourable prognostic and predictive markers for breast cancer and an understanding of their function may provide useful information about this disease.

Evidence for directed self-assembly of quantum dots in a nematic liquid crystal.

Assembling quantum dots (QDs) into nanoscale configurations over macroscopic dimensions is an important goal to realizing their electro-optical potential. In this Rapid Communication, we present a detailed study of a pentylcyanobiphenyl liquid crystal (LC) and a CdS QD colloidal dispersion by probing the dielectric property epsilon and relaxation as a function of an applied ac electric field Eac. In principle, dispersing QDs in a nematic LC medium can direct the dots to align in nearly one-dimensional chainlike structures along the nematic director and these assemblies of QDs can be directed by external electric fields. In a uniform planar aligned cell, the Fréedericksz switching of the LC+QDs appears as a two-step process with the same initial switching field as the bulk but with the final epsilon value larger than that for an aligned bulk LC. The relaxation of epsilon immediately following the removal of Eac follows a single-exponential decay to its original value that is slower than the bulk but becomes progressively faster with increasing Eac, eventually saturating. These results suggest that the arrangement of the QDs is mediated by the LC.

Breast cancer: understanding sensitivity and resistance to chemotherapy and targeted therapies to aid in personalised medicine.

Breast cancer is the second leading cause of cancer deaths. This disease is estimated to be diagnosed in over one million people worldwide and to cause more than 400,000 deaths each year. This is a significant health problem in terms of both morbidity and mortality. Chemotherapy forms part of a successful treatment regime in many cases; however, as few as half of the patients treated may benefit from this, as a result of intrinsic or acquired multiple drug resistance (MDR). A range of mechanisms of MDR has been identified using in vitro cell culture models; many, if not all, of which may contribute to breast cancer resistance in the clinical setting. This phenomenon is complicated by the heterogenous nature of breast cancer and the likely multi-factorial nature of clinical resistance. It has been very well established that a "one treatment fits all" approach is not relevant and significant advances have been made through identifying and appropriately treating sub-groups of patients; particularly with newer rationally-targeted therapies, such as the HER2-targeted monoclonal antibody, Trastuzumab, and the dual HER2 and EGFR tyrosine kinase inhibitor, Lapatinab. Furthermore, large defined collaborative studies, using standardised global profiling approaches to study mRNA, microRNAs and proteins, followed by functional genomics studies, by ourselves and others, are underway in order to definitively establish the degree of complexity contributing to drug resistance. The overall vision is to identify the optimum therapeutic regime for individual patients -possibly involving novel targeted therapies, drug resistance modulators, and chemotherapy- to overcome breast cancer.

Erionite and asbestos differently cause transformation of human mesothelial cells.

Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-kappaB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation.

Induced thermal dynamics in the melt of glycerol and aerosil dispersions.

A high-resolution calorimetric spectroscopy study has been performed on pure glycerol and colloidal dispersions of an aerosil gel in glycerol covering a wide range of temperatures from 300 to 380 K, deep in the liquid phase of glycerol. The colloidal glycerol+aerosil samples with 0.07, 0.14, and 0.32 g of silica per cm3 of glycerol reveal activated energy (thermal) dynamics at temperatures well above the Tg of the pure glycerol. The onset of these dynamics appears to be due to the frustration or pinning imposed by the silica gel on the glycerol liquid and is apparently a long-range, cooperative phenomena. Since this behavior begins to manifest itself at relatively low silica densities (large mean void length compared to the size of a glycerol molecule) and speeds up with increasing density, these induced dynamics are likely due to a coupling between the flexible aerosil gel and large groups of glycerol molecules mediated by mutual hydrogen bonding. This is supported by the lack of such thermal dynamics in pure aerosil gels, pure glycerol, or aerosil gels dispersed in a non-glass-forming, non-hydrogen-bonding, liquid crystal under nearly identical experimental conditions. The study of such frustrated colloids may provide a unique avenue for illuminating the physics of glasses.

Role of aerosil dispersion on the activated kinetics of the LC1-xSilx system.

This study explores the role of aerosil dispersion on activated phase transitions of bulk octylcyanobiphenyl (8CB) liquid crystals by performing heating rate-dependent experiments. Differential scanning calorimetry (DSC) was used at various heating ramp rates in order to probe the activated phase dynamics of the system. The system, LC1-xSilx, was prepared by mixing aerosil nanoparticles (7 nm in diameter) in the bulk 8CB by the solvent dispersion method (SDM). LC represents bulk 8CB, and Sil represents aerosil nanoparticles with concentration x in percent. The concentration of the aerosil nanoparticles (x) varied from 0 to 0.2 g/cm3 in the bulk 8CB. Well-defined, endothermic peaks were found on a heating scan at melting and at the smectic-A to nematic (SmA-N) and nematic to isotropic (N-I) transitions. These peaks show a temperature shift and a change in their shapes and sizes in the presence of aerosil nanoparticles. In addition, an exothermic peak also appeared before the melting peak during the heating scan in the presence of aerosil nanoparticles. All transitions shifted significantly with different heating ramp rates, following an Arrhenius behavior, showing activated kinetics. The presence of aerosil nanoparticles caused a significant increase in the enthalpy and a decrease in the activation energy compared to the results found in bulk 8CB. This behavior can be explained by aerosil dispersion in the LC1-xSilx, inducing a disorder in the bulk 8CB. Infrared (IR) spectroscopy shows a shift to higher frequency for the broad peak at 1082 cm-1, corresponding to an Si-O bond as the density of the aerosil increases, and can be explained in terms of surface and molecular interactions between aerosil nanoparticles and 8CB liquid crystal molecules.

Thermodynamics of activated phase transitions of 8CB: DSC and MC calorimetry.

The present paper reports the heating rate effect on the phase transitions of a pure liquid crystal octylcyanobiphenyl (8CB) with use of Differential Scanning Calorimetry (DSC) and Modulation Calorimetry (MC) techniques. The DSC runs were taken at various temperature ramp rates from 20 to 0.5 K/min for heating and cooling scans. Well-defined endothermic/exothermic peaks were found at the melting/crystallization, smectic-A to nematic (SmA-N), and nematic to isotropic (N-I) transitions on heating/cooling scans, respectively. All transitions shift in temperature significantly with different ramp rates. The temperature shift of C(p) peaks between heating and cooling scans indicates the order of the transitions. In addition, all transitions follow an Arrhenius behavior. The activation energy of a transition increases as the total energy involved in the transition decreases. The respective enthalpy and entropy change of each transition provides information on the Gibbs free energy. The significance of the results is discussed in terms of the order of transitions. A comparative analysis of MC and DSC techniques highlights the significance of the two techniques. MC is a practicable tool for observing the phase dynamics whereas DSC is a good tool for studying the rate kinematics of the transitions.

Accidente cerebro-vascular: análisis de la población reclutada durante 20 años. Su relación con factores de riesgo y evolución intrahospitalaira / Stroke: analysis of a population studied during a 20-year period

831 pacientes mayores de 18 años con accidente cerebro-vascular (ACV) fueron analizados durante el período 1985-2005. A todos se realizó tomografía axial computada a su ingreso lo que permitió identificar los ACV isquémicos de los hemorrágicos...En esta serie consecutiva se encontró peor evolución en los ACV hemorrágicos, sin diferencia con respecto a edad o sexo. El análisis de los factores de riesgo ubica a la diabetes, la hipertensión, la cardiopatía isquémica concomitante, el sexo masculino y la hipertrofia ventricular izquierda como determinantes de mayor mortalidad

Smectic ordering in liquid-crystal-aerosil dispersions. II. Scaling analysis.

Liquid crystals offer many unique opportunities to study various phase transitions with continuous symmetry in the presence of quenched random disorder (QRD). The QRD arises from the presence of porous solids in the form of a random gel network. Experimental and theoretical work supports the view that for fixed (static) inclusions, quasi-long-range smectic order is destroyed for arbitrarily small volume fractions of the solid. However, the presence of porous solids indicates that finite-size effects could play some role in limiting long-range order. In an earlier work, the nematic-smectic-A transition region of octylcyanobiphenyl (8CB) and silica aerosils was investigated calorimetrically. A detailed x-ray study of this system is presented in the preceding paper, which indicates that pseudocritical scaling behavior is observed. In the present paper, the role of finite-size scaling and two-scale universality aspects of the 8CB+aerosil system are presented and the dependence of the QRD strength on the aerosil density is discussed.