725 research outputs found

    Segregated tunneling-percolation model for transport nonuniversality

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    We propose a theory of the origin of transport nonuniversality in disordered insulating-conducting compounds based on the interplay between microstructure and tunneling processes between metallic grains dispersed in the insulating host. We show that if the metallic phase is arranged in quasi-one dimensional chains of conducting grains, then the distribution function of the chain conductivities g has a power-law divergence for g -> 0 leading to nonuniversal values of the transport critical exponent t. We evaluate the critical exponent t by Monte Carlo calculations on a cubic lattice and show that our model can describe universal as well nonuniversal behavior of transport depending on the value of few microstructural parameters. Such segregated tunneling-percolation model can describe the microstructure of a quite vast class of materials known as thick-film resistors which display universal or nonuniversal values of t depending on the composition.Comment: 8 pages, 5 figures (Phys. Rev. B - 1 August 2003)(fig1 replaced

    Impact of drying on techno-functional and nutritional properties of food proteins and carbohydrates - A comprehensive review

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    This is the final version. Available on open access from Taylor & Francis via the DOI in this recordData availability statement: There is no data available for this article.Foods comprise of many macromolecules that have varying techno-functional and nutritional properties. The isolated proteins and carbohydrates from them are increasingly being used as potential ingredients in the food industries. Numerous processes like drying for food processing and preservation cause variations in functional and nutritional attributes of proteins and carbohydrates in different degrees in the food products that can ultimately affect their possible applications. This article explores different drying technologies being used in the food industries, including freeze-drying, microwave-assisted drying, infrared drying, vacuum drying, spray drying, and oven drying. Based on the evaluation of multiple studies, it can be inferred that these drying methods have the potential to contribute to low drying performance, high operational costs, and strong environmental impact. Moreover, they can affect the nutritional value of macronutrients such as proteins, starches, gums, and dietary fibers present in foods, the integrity of the food structures, and their functional properties. Understanding the correlation between the drying technique used and the functional and nutritional attributes of macromolecules will help to provide better insight into the importance of the different drying methods. Optimization of the operational parameters of the different drying methods could be vital and needs to be evaluated to avoid the degradation of the proteins and carbohydrates and the loss of their properties

    The Electrical-Thermal Switching in Carbon Black-Polymer Composites as a Local Effect

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    Following the lack of microscopic information about the intriguing well-known electrical-thermal switching mechanism in Carbon Black-Polymer composites, we applied atomic force microscopy in order to reveal the local nature of the process and correlated it with the characteristics of the widely used commercial switches. We conclude that the switching events take place in critical interparticle tunneling junctions that carry most of the current. The macroscopic switched state is then a result of a dynamic-stationary state of fast switching and slow reconnection of the corresponding junctions.Comment: 14 pages, 5 figures,Typographic correctio

    A new differential configuration suitable for realization of high CMRR, all-pass/notch filters

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    #yayıncısurumuyok# ; Tam metin hakemden geçmiş kopyadır.In this paper, a new configuration suitable for realization of differential input-differential output first order, second order all-pass and notch filters with high CMRR is given. The proposed configuration uses two negative type second-generation current conveyors (CCII-), and three admittances. Two first order and one second order all-pass filters and a notch filter (tunable if current controlled conveyor CCCII is used) are extracted from the proposed configuration. Tracking error, element mismatch, sensitivity analysis, simulation and experimental results are included

    Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation

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    More than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantially higher potency than our first-generation AKT degrader (INY-03-041), with both compounds outperforming catalytic AKT inhibition by GDC-0068. Using multiomic profiling and causal network integration in breast cancer cells, we demonstrated that the enhanced efficacy of INY-05-040 was associated with sustained suppression of AKT signaling, which was followed by induction of the stress mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). Further integration of growth inhibition assays with publicly available transcriptomic, proteomic, and reverse phase protein array (RPPA) measurements established low basal JNK signaling as a biomarker for breast cancer sensitivity to AKT degradation. Together, our study presents a framework for mapping the network-wide signaling effects of therapeutically relevant compounds and identifies INY-05-040 as a potent pharmacological suppressor of AKT signaling

    Multiomic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation

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    More than 50% of human tumors display hyperactivation of the serine/threonine kinase AKT. Despite evidence of clinical efficacy, the therapeutic window of the current generation of AKT inhibitors could be improved. Here, we report the development of a second-generation AKT degrader, INY-05-040, which outperformed catalytic AKT inhibition with respect to cellular suppression of AKT-dependent phenotypes in breast cancer cell lines. A growth inhibition screen with 288 cancer cell lines confirmed that INY-05-040 had a substantially higher potency than our first-generation AKT degrader (INY-03-041), with both compounds outperforming catalytic AKT inhibition by GDC-0068. Using multiomic profiling and causal network integration in breast cancer cells, we demonstrated that the enhanced efficacy of INY-05-040 was associated with sustained suppression of AKT signaling, which was followed by induction of the stress mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). Further integration of growth inhibition assays with publicly available transcriptomic, proteomic, and reverse phase protein array (RPPA) measurements established low basal JNK signaling as a biomarker for breast cancer sensitivity to AKT degradation. Together, our study presents a framework for mapping the network-wide signaling effects of therapeutically relevant compounds and identifies INY-05-040 as a potent pharmacological suppressor of AKT signaling

    Mechanisms underlying disorders of consciousness: Bridging gaps to move toward an integrated translational science

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    AIM: In order to successfully detect, classify, prognosticate, and develop targeted therapies for patients with disorders of consciousness (DOC), it is crucial to improve our mechanistic understanding of how severe brain injuries result in these disorders. METHODS: To address this need, the Curing Coma Campaign convened a Mechanisms Sub-Group of the Coma Science Work Group (CSWG), aiming to identify the most pressing knowledge gaps and the most promising approaches to bridge them. RESULTS: We identified a key conceptual gap in the need to differentiate the neural mechanisms of consciousness per se, from those underpinning connectedness to the environment and behavioral responsiveness. Further, we characterised three fundamental gaps in DOC research: (1) a lack of mechanistic integration between structural brain damage and abnormal brain function in DOC; (2) a lack of translational bridges between micro- and macro-scale neural phenomena; and (3) an incomplete exploration of possible synergies between data-driven and theory-driven approaches. CONCLUSION: In this white paper, we discuss research priorities that would enable us to begin to close these knowledge gaps. We propose that a fundamental step towards this goal will be to combine translational, multi-scale, and multimodal data, with new biomarkers, theory-driven approaches, and computational models, to produce an integrated account of neural mechanisms in DOC. Importantly, we envision that reciprocal interaction between domains will establish a virtuous cycle, leading towards a critical vantage point of integrated knowledge that will enable the advancement of the scientific understanding of DOC and consequently, an improvement of clinical practice
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