465 research outputs found

    Characterization of a raspberry Pi as the core for a low-cost multimodal EEG-fNIRS platform.

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    Poor understanding of brain recovery after injury, sparsity of evaluations and limited availability of healthcare services hinders the success of neurorehabilitation programs in rural communities. The availability of neuroimaging ca-pacities in remote communities can alleviate this scenario supporting neurorehabilitation programs in remote settings. This research aims at building a multimodal EEG-fNIRS neuroimaging platform deployable to rural communities to support neurorehabilitation efforts. A Raspberry Pi 4 is chosen as the CPU for the platform responsible for presenting the neurorehabilitation stimuli, acquiring, processing and storing concurrent neuroimaging records as well as the proper synchronization between the neuroimaging streams. We present here two experiments to assess the feasibility and characterization of the Raspberry Pi as the core for a multimodal EEG-fNIRS neuroimaging platform; one over controlled conditions using a combination of synthetic and real data, and another from a full test during resting state. CPU usage, RAM usage and operation temperature were measured during the tests with mean operational records below 40% for CPU cores, 13.6% for memory and 58.85 ° C for temperatures. Package loss was inexistent on synthetic data and negligible on experimental data. Current consumption can be satisfied with a 1000 mAh 5V battery. The Raspberry Pi 4 was able to cope with the required workload in conditions of operation similar to those needed to support a neurorehabilitation evaluation

    Bounded Temporal Fairness for FIFO Financial Markets

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    Financial exchange operators cater to the needs of their users while simultaneously ensuring compliance with the financial regulations. In this work, we focus on the operators' commitment for fair treatment of all competing participants. We first discuss unbounded temporal fairness and then investigate its implementation and infrastructure requirements for exchanges. We find that these requirements can be fully met only under ideal conditions and argue that unbounded fairness in FIFO markets is unrealistic. To further support this claim, we analyse several real-world incidents and show that subtle implementation inefficiencies and technical optimizations suffice to give unfair advantages to a minority of the participants. We finally introduce, {\epsilon}-fairness, a bounded definition of temporal fairness and discuss how it can be combined with non-continuous market designs to provide equal participant treatment with minimum divergence from the existing market operation

    PCR clonality detection in Hodgkin lymphoma

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    B-cell clonality detection in whole tissue is considered indicative of B-cell non-Hodgkin lymphoma (NHL). We tested frozen tissue of 24 classical Hodgkin lymphomas (cHL) with a varying tumor cell load with the multiplex polymerase chain reaction (PCR) primer sets for IGH and IGK gene rearrangement (BIOMED-2). A clonal population was found in 13 cases with the IGH FR1 and/or FR2/FR3 PCRs. Using the IGK-VJ and IGK-DE PCRs, an additional six cases had a dominant clonal cell population, resulting in a detection rate of 79% in frozen tissue. Of 12 cases, also the formalin-fixed and paraffin-embedded (FFPE) tissue was tested. Surprisingly, in eight of the 12 FFPE cases with acceptable DNA quality (allowing PCR amplification of >200 nt fragments), the IGK multiplex PCRs performed better in detecting clonality (six out of eight clonal IGK rearrangements) than the IGH PCRs (four out of nine clonal rearrangements), despite a rather large amplicon size. There was no evidence of B-cell lymphoma during follow-up of 1 to 6 years and no correlation was found between the presence of a clonal result and Epstein–Barr virus in the tumor cells. Our results indicate that the present routine PCR methods are sensitive enough to detect small numbers of malignant cells in cHL. Therefore, the presence of a clonal B-cell population does not differentiate between cHL and NHL

    Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

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    Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

    D-brane Instantons as Gauge Instantons in Orientifolds of Chiral Quiver Theories

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    Systems of D3-branes at orientifold singularities can receive non-perturbative D-brane instanton corrections, inducing field theory operators in the 4d effective theory. In certain non-chiral examples, these systems have been realized as the infrared endpoint of a Seiberg duality cascade, in which the D-brane instanton effects arise from strong gauge theory dynamics. We present the first UV duality cascade completion of chiral D3-brane theories, in which the D-brane instantons arise from gauge theory dynamics. Chiral examples are interesting because the instanton fermion zero mode sector is topologically protected, and therefore lead to more robust setups. As an application of our results, we provide a UV completion of certain D-brane orientifold systems recently claimed to produce conformal field theories with conformal invariance broken only by D-brane instantons.Comment: 50 pages, 32 figures. v2: version published in JHEP with references adde

    The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

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    The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

    Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

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    PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

    Distribution and diel vertical movements of mesopelagic scattering layers in the Red Sea

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    © The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Biology 159 (2012): 1833-1841, doi:10.1007/s00227-012-1973-y.The mesopelagic zone of the Red Sea represents an extreme environment due to low food concentrations, high temperatures and low oxygen waters. Nevertheless, a 38 kHz echosounder identified at least four distinct scattering layers during the daytime, of which the 2 deepest layers resided entirely within the mesopelagic zone. Two of the acoustic layers were found above a mesopelagic oxygen minimum zone (OMZ), one layer overlapped with the OMZ, and one layer was found below the OMZ. Almost all organisms in the deep layers migrated to the near-surface waters during the night. Backscatter from a 300 kHz lowered Acoustic Doppler Current Profiler indicated a layer of zooplankton within the OMZ. They carried out DVM, yet a portion remained at mesopelagic depths during the night. Our acoustic measurements showed that the bulk of the acoustic backscatter was restricted to waters shallower than 800 m, suggesting that most of the biomass in the Red Sea resides above this depth.This research is based in part on work supported by Award Nos. USA 00002, KSA 00011 and KSA 00011/02 made by KAUST to the Woods Hole Oceanographic Institution
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