Strain-induced kinetics of intergrain defects as the mechanism of slow dynamics in the nonlinear resonant response of humid sandstone bars

A closed-form description is proposed to explain nonlinear and slow dynamics effects exhibited by sandstone bars in longitudinal resonance experiments. Along with the fast subsystem of longitudinal nonlinear displacements we examine the strain-dependent slow subsystem of broken intergrain and interlamina cohesive bonds. We show that even the simplest but phenomenologically correct modelling of their mutual feedback elucidates the main experimental findings typical for forced longitudinal oscillations of sandstone bars, namely, (i) hysteretic behavior of a resonance curve on both its up- and down-slopes, (ii) linear softening of resonant frequency with increase of driving level, and (iii) gradual recovery (increase) of resonant frequency at low dynamical strains after the sample was conditioned by high strains. In order to reproduce the highly nonlinear elastic features of sandstone grained structure a realistic non-perturbative form of strain potential energy was adopted. In our theory slow dynamics associated with the experimentally observed memory of peak strain history is attributed to strain-induced kinetic changes in concentration of ruptured inter-grain and inter-lamina cohesive bonds causing a net hysteretic effect on the elastic Young's modulus. Finally, we explain how enhancement of hysteretic phenomena originates from an increase in equilibrium concentration of ruptured cohesive bonds that are due to water saturation.Comment: 5 pages, 3 figure

Generator coordinate method calculations of one-nucleon removal reactions on 40^{40}Ca

An approach to the Generator Coordinate Method (GCM) using Skyrme-type effective forces and Woods-Saxon construction potential is applied to calculate the single-particle proton and neutron overlap functions in $^{40}$Ca. The relationship between the bound-state overlap functions and the one-body density matrix has been used. These overlap functions are applied to calculate the cross sections of one-nucleon removal reactions such as ($e,e'p$), ($\gamma,p$) and ($p,d$) on $^{40}$Ca on the same theoretical footing. A consistent description of data for the different reactions is achieved. The shapes of the experimental cross sections for transitions to the $3/2^{+}$ ground state and the first $1/2^{+}$ excited state of the residual nuclei are well reproduced by the overlap functions obtained within the GCM. An additional spectroscopic factor accounting for correlations not included in the overlap function must be applied to the calculated results to reproduce the size of the experimental cross sections.Comment: 16 pages, 6 figures, to be published in Phys. Rev.

Multimodal analysis of GRC ageing process using Nonlinear Impact Resonance acoustic Spectroscopy

Glass fibre Reinforced Cement (GRC) is a composite material composed of Portland cement mortar with low w/c (water/cement) ratio and high proportion of glass fibres. This material suffers from the ageing process by losing its strength with time because of its exposure to severe weather conditions. Ageing process damages the fibre surface and decreases the mechanical properties of the structural components made of this material. It reduces the elastic modulus and toughness of GRC. Fracture toughness is traditionally measured by four point bending tests. In a previous study by the authors it was observed that ageing related deterioration or damage of GRC could be monitored by Non Destructive Testing (NDT) techniques such as Non-linear Impact Resonance Acoustic Spectroscopy (NIRAS) and other ultrasonic techniques. The scope of this paper is to corroborate previous investigations and offer early damage detection capability by generating more experimental data points by optimizing location of the point of strike and thus generating more resonance vibration modes in NIRAS tests.The authors acknowledge the financial support of the Ministerio de Ciencia e Innovacion MICINN, Spain, and FEDER funding (Ondacem Project: BIA 2010-19933).Genovés Gómez, V.; Riestra García-San Miguel, C.; Borrachero Rosado, MV.; Eiras Fernández, JN.; Kundu, T.; Paya Bernabeu, JJ. (2015). Multimodal analysis of GRC ageing process using Nonlinear Impact Resonance acoustic Spectroscopy. Composites Part B: Engineering. 76:105-111. https://doi.org/10.1016/j.compositesb.2015.02.020S1051117

Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT)

Background: Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS. Patients and methods: An open-label prospective phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma. Results: Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS +). The 1-year OS rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response (GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile. Conclusion: Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study. This study is registered at www.clinicatrials.gov NCT00942162

TRPV6 Determines the Effect of Vitamin D3 on Prostate Cancer Cell Growth

Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007). However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enchances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies

Ambient-aware continuous care through semantic context dissemination

Background: The ultimate ambient-intelligent care room contains numerous sensors and devices to monitor the patient, sense and adjust the environment and support the staff. This sensor-based approach results in a large amount of data, which can be processed by current and future applications, e. g., task management and alerting systems. Today, nurses are responsible for coordinating all these applications and supplied information, which reduces the added value and slows down the adoption rate. The aim of the presented research is the design of a pervasive and scalable framework that is able to optimize continuous care processes by intelligently reasoning on the large amount of heterogeneous care data. Methods: The developed Ontology-based Care Platform (OCarePlatform) consists of modular components that perform a specific reasoning task. Consequently, they can easily be replicated and distributed. Complex reasoning is achieved by combining the results of different components. To ensure that the components only receive information, which is of interest to them at that time, they are able to dynamically generate and register filter rules with a Semantic Communication Bus (SCB). This SCB semantically filters all the heterogeneous care data according to the registered rules by using a continuous care ontology. The SCB can be distributed and a cache can be employed to ensure scalability. Results: A prototype implementation is presented consisting of a new-generation nurse call system supported by a localization and a home automation component. The amount of data that is filtered and the performance of the SCB are evaluated by testing the prototype in a living lab. The delay introduced by processing the filter rules is negligible when 10 or fewer rules are registered. Conclusions: The OCarePlatform allows disseminating relevant care data for the different applications and additionally supports composing complex applications from a set of smaller independent components. This way, the platform significantly reduces the amount of information that needs to be processed by the nurses. The delay resulting from processing the filter rules is linear in the amount of rules. Distributed deployment of the SCB and using a cache allows further improvement of these performance results

Adaptation of eye and hand movements to target displacements of different size

Previous work has documented that the direction of eye and hand movements can be adaptively modified using the double-step paradigm. Here we report that both motor systems adapt not only to small direction steps (5° gaze angle) but also to large ones (28° gaze angle). However, the magnitude of adaptation did not increase with step size, and the relative magnitude of adaptation therefore decreased from 67% with small steps to 15% with large steps. This decreasing efficiency of adaptation may reflect the participation of directionally selective neural circuits in double-step adaptation

Orai1 contributes to the establishment of an apoptosis-resistant phenotype in prostate cancer cells

The molecular nature of calcium (Ca2+)-dependent mechanisms and the ion channels having a major role in the apoptosis of cancer cells remain a subject of debate. Here, we show that the recently identified Orai1 protein represents the major molecular component of endogenous store-operated Ca2+ entry (SOCE) in human prostate cancer (PCa) cells, and constitutes the principal source of Ca2+ influx used by the cell to trigger apoptosis. The downregulation of Orai1, and consequently SOCE, protects the cells from diverse apoptosis-inducing pathways, such as those induced by thapsigargin (Tg), tumor necrosis factor α, and cisplatin/oxaliplatin. The transfection of functional Orai1 mutants, such as R91W, a selectivity mutant, and L273S, a coiled-coil mutant, into the cells significantly decreased both SOCE and the rate of Tg-induced apoptosis. This suggests that the functional coupling of STIM1 to Orai1, as well as Orai1 Ca2+-selectivity as a channel, is required for its pro-apoptotic effects. We have also shown that the apoptosis resistance of androgen-independent PCa cells is associated with the downregulation of Orai1 expression as well as SOCE. Orai1 rescue, following Orai1 transfection of steroid-deprived cells, re-established the store-operated channel current and restored the normal rate of apoptosis. Thus, Orai1 has a pivotal role in the triggering of apoptosis, irrespective of apoptosis-inducing stimuli, and in the establishment of an apoptosis-resistant phenotype in PCa cells