Subcritical crack growth and in vitro lifetime prediction of resin composites with different filler distributions

Objectives. Verify the influence of different filler distributions on the subcritical crack growth (SCG) susceptibility, Weibull parameters (m and sigma(0)) and longevity estimated by the strength-probability-time (SPT) diagram of experimental resin composites. Methods. Four composites were prepared, each one containing 59 vol% of glass powder with different filler sizes (d(50) = 0.5; 0.9; 1.2 and 1.9 mu m) and distributions. Granulometric analyses of glass powders were done by a laser diffraction particle size analyzer (Sald-7001, Shimadzu, USA). SCG parameters (n and sigma(f0)) were determined by dynamic fatigue (10(-2) to 10(2) MPa/s) using a biaxial flexural device (12 x 1.2 mm; n = 10). Twenty extra specimens of each composite were tested at 10(0) MPa/s to determine m and sigma(0). Specimens were stored in water at 37 degrees C for 24 h. Fracture surfaces were analyzed under SEM. Results. In general, the composites with broader filler distribution (C0.5 and C1.9) presented better results in terms of SCG susceptibility and longevity. C0.5 and C1.9 presented higher n values (respectively, 31.2 +/- 6.2(a) and 34.7 +/- 7.4(a)). C1.2 (166.42 +/- 0.01(a)) showed the highest and C0.5 (158.40 +/- 0.02(d)) the lowest sigma(f0) value (in MPa). Weibull parameters did not vary significantly (m: 6.6 to 10.6 and sigma(0): 170.6 to 176.4 MPa). Predicted reductions in failure stress (P-f = 5%) for a lifetime of 10 years were approximately 45% for C0.5 and C1.9 and 65% for C0.9 and C1.2. Crack propagation occurred through the polymeric matrix around the fillers and all the fracture surfaces showed brittle fracture features. Significance. Composites with broader granulometric distribution showed higher resistance to SCG and, consequently, higher longevity in vitro. (C) 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Lipophilicity as a determinant of binding of procaine analogs to rat alpha(3)beta(4) nicotinic acetylcholine receptor

Nicotinic acetylcholine receptors (nAChRs) have been studied in detail with regard to their interaction with therapeutic and drug addiction-related compounds. Using a structureactivity approach, we have examined the relationship among the molecular features of a set of eight para-R-substituted N,N-[(dimethylamino)ethyl] benzoate hydrochlorides, structurally related to procaine and their affinity for the a3 beta 4 nAChR heterologously expressed in KXa3 beta 4R2 cells. Affinity values (log[1/IC50]) of these compounds for the a3 beta 4 nAChR were determined by their competition with [3H]TCP binding. Log(1/IC50) values were analyzed considering different hydrophobic and electronic parameters and those related to molar refractivity. These have been experimentally determined or were taken from published literature. In accordance with literature observations, the generated cross-validated quantitative structureactivity relationship (QSAR) equations indicated a significant contribution of hydrophobic term to binding affinity of procaine analogs to the receptor and predicted affinity values for several local anesthetics (LAs) sets taken from the literature. The predicted values by using the QSAR model correlated well with the published values both for neuronal and for electroplaque nAChRs. Our work also reveals the general structure features of LAs that are important for interaction with nAChRs as well as the structural modifications that could be made to enhance binding affinity. (c) 2012 Wiley Periodicals, Inc.

Loss of Interleukin-10 Signaling and Infantile Inflammatory Bowel Disease: Implications for Diagnosis and Therapy

BACKGROUND & AIMS: Homozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder. METHODS: We analyzed 66 patients with early onset IBD (younger than 5 years of age) for mutations in the genes encoding IL-10, IL-10R1, and IL-10R2. IL-10R deficiency was confirmed by functional assays on patients' peripheral blood mononuclear cells (immunoblot and enzyme-linked immunosorbent assay analyses). We assessed the therapeutic effects of standardized allogeneic HSCT. RESULTS: Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. Refractory colitis became manifest in all patients within the first 3 months of life and was associated with perianal disease (16 of 16 patients). Extraintestinal symptoms included folliculitis (11 of 16) and arthritis (4 of 16). Allogeneic HSCT was performed in 5 patients and induced sustained clinical remission with a median follow-up time of 2 years. In vitro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received the transplant. CONCLUSIONS: We identified loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD. These findings indicate that infantile IBD patients with perianal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce remission in those with IL-10R deficiency.

Extrinsic Purinergic Regulation of Neural Stem/Progenitor Cells: Implications for CNS Development and Repair

There has been tremendous progress in understanding neural stem cell (NSC) biology, with genetic and cell biological methods identifying sequential gene expression and molecular interactions guiding NSC specification into distinct neuronal and glial populations during development. Data has emerged on the possible exploitation of NSC-based strategies to repair adult diseased brain. However, despite increased information on lineage specific transcription factors, cell-cycle regulators and epigenetic factors involved in the fate and plasticity of NSCs, understanding of extracellular cues driving the behavior of embryonic and adult NSCs is still very limited. Knowledge of factors regulating brain development is crucial in understanding the pathogenetic mechanisms of brain dysfunction. Since injury-activated repair mechanisms in adult brain often recapitulate ontogenetic events, the identification of these players will also reveal novel regenerative strategies. Here, we highlight the purinergic system as a key emerging player in the endogenous control of NSCs. Purinergic signalling molecules (ATP, UTP and adenosine) act with growth factors in regulating the synchronized proliferation, migration, differentiation and death of NSCs during brain and spinal cord development. At early stages of development, transient and time-specific release of ATP is critical for initiating eye formation; once anatomical CNS structures are defined, purinergic molecules participate in calcium-dependent neuron-glia communication controlling NSC behaviour. When development is complete, some purinergic mechanisms are silenced, but can be re-activated in adult brain after injury, suggesting a role in regeneration and self-repair. Targeting the purinergic system to develop new strategies for neurodevelopmental disorders and neurodegenerative diseases will be also discussed.

Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC

We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.

Description of atmospheric conditions at the Pierre Auger Observatory using the Global Data Assimilation System (GDAS)

Atmospheric conditions at the site of a cosmic ray observatory must be known for reconstructing observed extensive air showers. The Global Data Assimilation System (GDAS) is a global atmospheric model predicated on meteorological measurements and numerical weather predictions. GDAS provides altitude-dependent profiles of the main state variables of the atmosphere like temperature, pressure, and humidity. The original data and their application to the air shower reconstruction of the Pierre Auger Observatory are described. By comparisons with radiosonde and weather station measurements obtained on-site in Malargue and averaged monthly models, the utility of the GDAS data is shown. (C) 2012 Elsevier B.V. All rights reserved.

Immunohistochemical expression of Rho GTPases in ameloblastomas

Rho GTPases are proteins that regulate cell cycle, shape, polarization, invasion, migration, and apoptosis, which are important characteristics of normal and neoplastic cells. Rho GTPases expression has been reported in normal tooth germ and several pathologies; however, it has not been evaluated in ameloblastomas. The aim of this study was to analyze the expression and distribution of RhoA, RhoB, Rac1, and Cdc42 Rho GTPases in solid and unicystic ameloblastomas. Three-micrometer sections from paraffin- embedded specimens were evaluated by using an avidin- biotin immunohistochemical method with antibodies against the proteins mentioned above. RhoA and RhoB staining was observed in a high number of cells (P < 0.05) and greater intensity in non-polarized ones. Rac1 was not observed, andCdc42 didnot showany statistical differences between the number of non-polarized and basal positive cells (P > 0.05). Upon comparing the studied ameloblastomas, a higher number of positive cells in the unicystic variant was observed than that in the solid one (P < 0,05). The results obtained suggest that theseGTPases could play a role in the ameloblastoma neoplastic epithelial cell phenotype determination (polarized or non-polarized), as well as in variant (solid or unicystic) and subtype (follicular or plexiform) determination. Furthermore, they could participate in solid ameloblastoma invasion mechanisms. J Oral Pathol Med (2012) 41: 400-407

Antennas for the detection of radio emission pulses from cosmic-ray induced air showers at the Pierre Auger Observatory

The Pierre Auger Observatory is exploring the potential of the radio detection technique to study extensive air showers induced by ultra-high energy cosmic rays. The Auger Engineering Radio Array (AERA) addresses both technological and scientific aspects of the radio technique. A first phase of AERA has been operating since September 2010 with detector stations observing radio signals at frequencies between 30 and 80 MHz. In this paper we present comparative studies to identify and optimize the antenna design for the final configuration of AERA consisting of 160 individual radio detector stations. The transient nature of the air shower signal requires a detailed description of the antenna sensor. As the ultra-wideband reception of pulses is not widely discussed in antenna literature, we review the relevant antenna characteristics and enhance theoretical considerations towards the impulse response of antennas including polarization effects and multiple signal reflections. On the basis of the vector effective length we study the transient response characteristics of three candidate antennas in the time domain. Observing the variation of the continuous galactic background intensity we rank the antennas with respect to the noise level added to the galactic signal.

Biogenic Potassium Salt Particles as Seeds for Secondary Organic Aerosol in the Amazon

The fine particles serving as cloud condensation nuclei in pristine Amazonian rainforest air consist mostly of secondary organic aerosol. Their origin is enigmatic, however, because new particle formation in the atmosphere is not observed. Here, we show that the growth of organic aerosol particles can be initiated by potassium-salt-rich particles emitted by biota in the rainforest. These particles act as seeds for the condensation of low- or semi-volatile organic compounds from the atmospheric gas phase or multiphase oxidation of isoprene and terpenes. Our findings suggest that the primary emission of biogenic salt particles directly influences the number concentration of cloud condensation nuclei and affects the microphysics of cloud formation and precipitation over the rainforest.

Measurement of electrons from semileptonic heavy-flavor hadron decays in pp collisions at root s=7 TeV

The differential production cross section of electrons from semileptonic heavy-flavor hadron decays has been measured at midrapidity (\y\ < 0.5) in proton-proton collisions at root s = 7 TeV with ALICE at the LHC. Electrons were measured in the transverse momentum range 0.5 < p(t) < 8 GeV/c. Predictions from a fixed-order perturbative QCD calculation with next-to-leading-log resummation agree with the data within the theoretical and experimental uncertainties. DOI: 10.1103/PhysRevD.86.112007

The rapid atmospheric monitoring system of the Pierre Auger Observatory

The Pierre Auger Observatory is a facility built to detect air showers produced by cosmic rays above 10(17) eV. During clear nights with a low illuminated moon fraction, the UV fluorescence light produced by air showers is recorded by optical telescopes at the Observatory. To correct the observations for variations in atmospheric conditions, atmospheric monitoring is performed at regular intervals ranging from several minutes (for cloud identification) to several hours (for aerosol conditions) to several days (for vertical profiles of temperature, pressure, and humidity). In 2009, the monitoring program was upgraded to allow for additional targeted measurements of atmospheric conditions shortly after the detection of air showers of special interest, e. g., showers produced by very high-energy cosmic rays or showers with atypical longitudinal profiles. The former events are of particular importance for the determination of the energy scale of the Observatory, and the latter are characteristic of unusual air shower physics or exotic primary particle types. The purpose of targeted (or "rapid") monitoring is to improve the resolution of the atmospheric measurements for such events. In this paper, we report on the implementation of the rapid monitoring program and its current status. The rapid monitoring data have been analyzed and applied to the reconstruction of air showers of high interest, and indicate that the air fluorescence measurements affected by clouds and aerosols are effectively corrected using measurements from the regular atmospheric monitoring program. We find that the rapid monitoring program has potential for supporting dedicated physics analyses beyond the standard event reconstruction.

Transcorneal Electrical Stimulation Shows Neuroprotective Effects in Retinas of Light-Exposed Rats

PURPOSE. To examine the effects of transcorneal electrical stimulation (TES) on retinal degeneration of light-exposed rats. METHODS. Thirty-three Sprague Dawley albino rats were divided into three groups: STIM (n = 15) received 60 minutes of TES, whereas SHAM (n = 15) received identical sham stimulation 2 hours before exposure to bright light with 16,000 lux; healthy animals (n = 3) served as controls for histology. At baseline and weekly for 3 consecutive weeks, dark-and light-adapted electroretinography was used to assess retinal function. Analysis of the response versus luminance function retrieved the parameters Vmax (saturation amplitude) and k (luminance to reach 1/2Vmax). Retinal morphology was assessed by histology (hematoxylin-eosin [HE] staining; TUNEL assay) and immunohistochemistry (rhodopsin staining). RESULTS. Vmax was higher in the STIM group compared with SHAM 1 week after light damage (mean intra-individual difference between groups 116.06 mu V; P = 0.046). The b-wave implicit time for the rod response (0.01 cd.s/m(2)) was lower in the STIM group compared with the SHAM group 2 weeks after light damage (mean intra-individual difference between groups 5.78 ms; P = 0.023); no other significant differences were found. Histological analyses showed photoreceptor cell death (TUNEL and HE) in SHAM, most pronounced in the superior hemiretina. STIM showed complete outer nuclear layer thickness preservation, reduced photoreceptor cell death, and preserved outer segment length compared with SHAM (HE and rhodopsin). CONCLUSIONS. This sham-controlled study shows that TES can protect retinal cells against mild light-induced degeneration in Sprague Dawley rats. These findings could help to establish TES as a treatment in human forms of retinal degenerative disease. (Invest Ophthalmol Vis Sci. 2012;53:5552-5561) DOI: 10.1167/iovs.12-10037

Incomplete fissures in severe emphysematous patients evaluated with MDCT: Incidence and interobserver agreement among radiologists and pneumologists

Objective: Pulmonary fissures completeness predicts efficacy in endobronchial valves (EBV) implantation, a new lobar volume reduction therapy for severe emphysematous patients. We assessed the incidence of incomplete fissures and the interobserver agreement in its evaluation with MDCT, in severe emphysematous patients prior to EBV implantation. Materials and Methods: Volumetric thin-section CT scans of 35 patients (CODP GOLD 3/4, heterogeneous emphysema) were retrospectively reviewed by 2 pneumologists, 1 general and 2 experienced chest radiologists, independently and blinded for treatment outcome, and the pulmonary fissures were classified as either complete or incomplete. Interobserver agreement was assessed with Kappa index (KI). Results: Agreement between all readers for the left oblique, right oblique and horizontal fissure was, respectively, moderate (KI = 0.53), fair (KI = 0.37) and moderate (KI = 0.42). Highest agreement (99/105 fissures) was observed among experienced radiologists, being for left oblique, right oblique and horizontal, respectively, almost perfect (KI = 0.79), perfect (KI = 1.0) and moderate (KI = 0.52). These 2 reviewers found that all of 35 patients had at least one incomplete fissure, with a proportion of incomplete fissures assigned as 74/65%, 85/85% and 91/88%, respectively for the left oblique, right oblique and horizontal fissures. Conclusions: Pneumologists and radiologists agreed fairly to moderately in fissures analysis, while the experienced chest radiologists reached the highest clinically adequate agreement of 94%. We believe that clinical routine visual analysis of the fissures integrity can be done with a good degree of confidence in MDCT images, and experienced readers might be required. Also, a higher than expected incidence of incomplete fissures was described in our studied population. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Ruthenium(II) complexes with 2-(diphenylphosphinomethyl)aniline

2-(Diphenylphosphinomethyl)aniline. H2L1, reacts with [RuCl2(PPh3)(3)] to yield the monomeric complexes [RuCl2(H2L1)(PPh3)(CH3CN)], [RuCl2(H2L1)(2)]and the chloro-bridged dimer [(H2L1)(PPh3)Ru(mu-Cl)(2)Ru(PPh3) (H2L1)] depending on the conditions applied. Exclusively the monochelate [RuCl2 (H2L1)(dmso)(2)] is formed during reactions of H2L1 with [RuCl2(dmso)(4)]. H2L1 acts as a neutral, bidentate ligand in all complexes. The products are studied spectroscopically and by X-ray diffraction. (C) 2012 Elsevier Ltd. All rights reserved.

Kinin-B2 Receptor Activity Determines the Differentiation Fate of Neural Stem Cells

Bradykinin is not only important for inflammation and blood pressure regulation, but also involved in neuromodulation and neuroprotection. Here we describe novel functions for bradykinin and the kinin-B2 receptor (B2BkR) in differentiation of neural stem cells. In the presence of the B2BkR antagonist HOE-140 during rat neurosphere differentiation, neuron-specific beta 3-tubulin and enolase expression was reduced together with an increase in glial protein expression, indicating that bradykinin- induced receptor activity contributes to neurogenesis. In agreement, HOE-140 affected in the same way expression levels of neural markers during neural differentiation of murine P19 and human iPS cells. Kinin-B1 receptor agonists and antagonists did not affect expression levels of neural markers, suggesting that bradykinin-mediated effects are exclusively mediated via B2BkR. Neurogenesis was augmented by bradykinin in the middle and late stages of the differentiation process. Chronic treatment with HOE-140 diminished eNOS and nNOS as well as M1-M4 muscarinic receptor expression and also affected purinergic receptor expression and activity. Neurogenesis, gliogenesis, and neural migration were altered during differentiation of neurospheres isolated from B2BkR knock-out mice. Whole mount in situ hybridization revealed the presence of B2BkR mRNA throughout the nervous system in mouse embryos, and less beta 3-tubulin and more glial proteins were expressed in developing and adult B2BkR knock-out mice brains. As a underlying transcriptional mechanism for neural fate determination, HOE-140 induced up-regulation of Notch1 and Stat3 gene expression. Because pharmacological treatments did not affect cell viability and proliferation, we conclude that bradykinin-induced signaling provides a switch for neural fate determination and specification of neurotransmitter receptor expression.