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International audience; This paper presents a method to identify wave equations' parameters using wave dispersion characteristics (k-space) on two-dimensional domains. The proposed approach uses the minimization of the difference of an analytic formulation of the dispersion relation to wavenumbers calculated from solution fields. The implementation of partial differential equations (PDE) resolution on finite element software is explained and tested with analytic solutions in order to generate the test solution fields for the identification process. The coefficient identification is tested on solution fields generated by finite element solver for some 2 ndand 4 th-order equations. In particular the test cases are the equations at different frequencies of deflection of isotropic and orthotropic membrane, flexion of isotropic and orthotropic plate and an original model of orthotropic plate equivalent to a bi-directional ribbed plate. In the limits of the spatial sampling rate and the domain size, the process allows an accurate retrieval of the wave equation parameters.

The mechanism of action of CD8+CD25High+FOXP3+ T cells in hepatocellular carcinoma (HCC) has not been fully understood. Herein, the role of CD8+CD25High+FOXP3+ T cells in HCC was compared with that of CD4+CD25High+FOXP3+ regulatory T cells (conventional Tregs). Thirty-five patients with HCC and twenty age and sex-matched healthy adults (controls) were enrolled. The percentage of CD8+CD25High+FOXP3+ T cells and conventional Tregs in peripheral blood was measured by flow cytometry. Our results revealed that the percentage of peripheral CD8+CD25High+FOXP3+ T cells in HCC patients was significantly higher than controls (P = 0.005). The conventional Tregs showed the same trend with a higher level in HCC than controls (P

Background Till now, pooled data about the safety and efficacy of different direct-acting antiviral (DAAs) regimens in different renal situations are still under evaluation. Aim To evaluate a real-life experience of the efficacy and safety of ombitasvir/paritaprevir/ritonavir plus ribavirin (OBV/PTV/r plus RIB) in patients with end-stage kidney disease (ESKD). Patients and methods Between January 2017 and January 2018, an open-label multicenter prospective study was designed to enroll all consecutive patients with proven CHC genotype 4 infections and concomitant ESKD based on estimated glomerular filtration rate (eGFR) with (HD group) or without hemodialysis (non-HD group). Patients were given a co-formula of OBV/PTV/r (25/150/100 mg) once-daily plus RIB was given for 12 weeks. Sustained virologic response (SVR 12) was the primary endpoint. Results A total of 110 patients were enrolled. An overall SVR 12 was reported in 104 (94.5%) patients, and treatment failure were reported in 6 patients [2 patients (1.8%) were relapsed, and 4 patients (3.6%) patients were non-responders]. SVR12 was 96% in HD and 91.4% in non-HD patients (P = 0.286). There were no reported serious adverse events. Anemia was reported in 66.6% (n = 50) in HD group and in 31.4% (n = 11) in non-HD group. Conclusion Although it is still challenging, achievement of SVR12 in patients with chronic HCV and concomitant end-stage kidney disease in the era of DAAs became possible with a 12 weeks course of a co-formula of ombitasvir/paritaprevir /ritonavir plus ribavirin. ClinicalTrials.gov ID NCT03341988.

Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer.We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype.Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P = .015), larger tumors (P = .004), lymph node (LN) positivity (P .001), high tumor grade (P = .012), and HER2 positivity (P .001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P = .003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P .001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P = .049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P .001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P = .007), shorter relapse-free interval (P .001), and lung metastasis (P .001).Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome.

We develop a stochastic model for a carve-out appointment system for a single physician in a primary care facility that allocates certain slots for same-day requests while reserving the rest for appointments requested in advance. Several slots are double-booked to mitigate the negative impacts from no-shows. Our model takes into account the stochastic demands of both routine patients and same-day requests as well as no-shows and optimizes the overall system performance, which includes the primary care provider’s utility and patients’ waiting time. We derive the optimal number of open slots, the maximum number of patients allowed to be double-booked, and where these open slots and double-booked slots should be placed. A key contribution of our approach is that both capacity decisions and scheduling decisions are obtained simultaneously. Moreover, our approach allows the optimal schedules to be analytically characterized by the demand distribution of same-day requests, the no-show rate, and the ratio of overtime cost to waiting cost for the special case where it is optimal to leave one open slot and one double-booked slot. Numerical results are used for more general cases to provide managerial insights on the usage of open slots and double-booked slots. The optimal schedule should start with a few open slots. If the no-show rate is low, single-booked slots should be placed before the first double-booked slots. On the other hand, if the no-show rate is high, a double-booked slot should be placed immediately after the series of open slots. Additional open slots should be inserted either between two double-booked slots or between one double-booked slot and a series of single-booked slots. The strategic placement of open slots not only increases the physician’s utilization but also improves patients’ aggregated waiting time.

Melanocyte homoeostasis and their response to ultraviolet radiation (UVR) are mediated to a large extent by keratinocyte-derived factors, many of which have been well-characterized. Lee et al. describe novel effects of adenosine 5'-triphosphate (ATP), which is secreted by keratinocytes and can stimulate melanogenesis by melanocytes following UVA exposure. The investigators attribute the melanogenic effect of ATP to binding purinergic receptors type 2 X7 (P2X7), which are expressed on human melanocytes, leading to activation of the protein kinase C pathway. This report is the first to identify expression of specific purinergic receptors on human melanocytes, and it suggests ATP as a signaling molecule that stimulates pigmentation. Follow up on these results should clarify the physiological role of ATP in mediating the tanning response to solar UVR.

Melanin synthesis occurs within a specialized organelle called the melanosome. Traditional methods for measuring melanin levels rely on the detection of chemical degradation products of melanin by high-performance liquid chromatography. Although these methods are robust, they are unable to distinguish between melanin synthesis and degradation and are best suited to measure melanin changes over long periods of time. We developed a method that actively measures both eumelanin and pheomelanin synthesis by fate tracing [U-13C] L-tyrosine using liquid chromatography-mass spectrometry. Using this method, we confirmed the previous reports of the differences in melanin synthesis between melanocytes derived from individuals with different skin colors and MC1R genotype and uncovered new information regarding the differential de novo synthesis of eumelanin and pheomelanin, also called mixed melanogenesis. We also revealed that distinct mechanisms that alter melanosomal pH differentially induce new eumelanin and pheomelanin synthesis. Finally, we revealed that the synthesis of L-3,4-dihydroxyphenylalanine, an important metabolite of L-tyrosine, is differentially controlled by multiple factors. Because L-tyrosine fate tracing is compatible with untargeted liquid chromatography-mass spectrometry‒based metabolomics, this approach enables the broad measurement of cellular metabolism in combination with melanin metabolism, and we anticipate that this approach will shed new light on multiple mechanisms of melanogenesis.

The Millimeter Wave (mmWave) spectrum band, with its high bandwidth, will significantly satisfy the need for high data-demand of the next-generation communication networks. However, transmission over the mmWave band suffers from a short communication range due to its high frequency. Such short-range communication can dramatically affect the network connectivity in mesh-based networks, leading to excessive packet loss. To improve the network connectivity and thus the throughput, Unmanned Aerial Vehicles (UAVs)/drones can be utilized as relays. Along with UAVs, multi-path routing is needed to ensure better network reliability through different routes. In this paper, we propose maximizing mmWave-based mesh network connectivity via optimally deploying a number of UAVs/drones and enabling multiple parallel paths at the upper network layers. We model the optimization problem for minimizing end-to-end delay with a minimum number of drones, we further perform a delay analysis for the received queues and obtain the link layer end-to-end delay. The evaluation is first performed through MATLAB and then verified using a realistic scenario in the NS-3 simulator by assuming an IEEE 802.11ad-based wireless mesh network. The results show that the proposed UAV-assisted schemes achieve higher throughput and shorter delay compared to baselines scenario with no deployment of UAVs or single transmissions.

I argue that a method situated in the everyday visceral experience of food preparation and consumption awakens the senses into being, opening up the body in different ways in relation to materials, senses, and other bodies, offering new insight into emotion and affect. While using ‘the body as an instrument of research’ (Longhurst et al., 2008) in this manner begins with the discussion of affective relations with food, the visceral serves as a gateway to further uncovering other affective relations with place. Affect can be understood as ‘sticky’, arising from encounters between bodies and objects in the environment and influenced by history (Ahmed, 2004). Migrants undergo considerable changes in their affective response as they encounter, contemplate, and embody new experiences – making them ‘stick’. I offer a methodological examination of a visceral approach to inform our understanding of the affective response to migration through interviews with 11 Egyptian migrant women in the Region of Waterloo, Ontario, Canada as we prepare and consume a traditional Egyptian meal together. This study is a stepping stone to addressing affect as a significant place-making factor and to providing a method to access the visceral, emotional, and affective geographies of home.

Ductile fracture is an important field in dynamic materials research. The simulation of ductile failure by means of numerical codes requires accurate material models that are validated with data obtained from precise high-rate mechanical testing. In this work, a high strength quenched and tempered steel is studied over a wide range of strain rates using different test methods to achieve a range of stress states with numerical computations being used to determine the precise stress and strain rate states for the multiaxial GISSMO model. The consideration of stress state, not only in tensile triaxiality 0.33 and above but also in shear, tension/shear and compression/shear, will lead to greater accuracy in failure predictions for a wide range of applications involving complex multiaxial stress states, particularly for thick and high strength materials.

The analysis of nonlinear fractional-order circuits is a challenging problem. This is due to the lack of nonlinear circuit theorems and designs particularly in the presence of memristive elements. The response of a series connection of a simple resistor with fractional order capacitor and its analytical formulation in both charging and discharging phases is considered. The numerical simulation of fractional order HP memristor in series with a fractional order capacitor is also discussed. It is a demonstration of a simple nonlinear fractional-order memristive circuit in both charging and discharging cases. Furthermore, this paper introduces an approach to approximate nonlinear fractional-order memrisitve circuits by linear circuits using a minimax optimization technique. Hence, the new circuit can be analyzed using the conventional linear circuit theorems. The charging and discharging of a series fractional-order memristor with a fractional-order capacitor are discussed numerically. The effect of fractional-order parameters and memristor polarity are also investigated. Using a suitable optimization technique, an accurate approximation by a circuit that include a resistor and a fractional-capacitor is obtained for both charging and discharging cases. A great matching was observed between the frequency responses of the fractional-order nonlinear low pass filter based on fractional-order memristor and fractional-order capacitor and that of the optimized linear fractional order case. Similar matching is observed for the nonlinear and optimized cases when a periodic triangular waveform is applied using Fourier series expansion.

Successful use of artificial neural network (ANN) to simulate human model motion.Experimentation results of using ANN to simulate the tasks of walking and jumping.The use of ANN reduces the simulation time from 1-40?min to a fraction of a second. Digital human models (DHMs) are critical for improved designs, injury prevention, and a better understanding of human behavior. Although many capabilities in the field are maturing, there are still opportunities for improvement, especially in motion prediction. Thus, this work investigates the use of an artificial neural network (ANN), specifically a general regression neural network (GRNN), to provide real-time computation of DHM motion prediction, where the underlying optimization problems are large and computationally complex. In initial experimentation, a GRNN is used successfully to simulate walking and jumping on a box while using physics-based human simulations as training data. Compared to direct computational simulations of dynamic motion, use of GRNN reduces the calculation time for each predicted motion from 1-40?min to a fraction of a second with no noticeable reduction in accuracy. This work lays the foundation for studying the effects of changes to training regiments on human performance.

In today’s global environment supply chains should be agile and responsive. Ideally, suppliers would like to know the order quantities with enough lead-time to set up the production process and schedule for delivery. However, retailers cannot predict demand accurately and thus both suppliers and retailers may incur significant losses due to under-stocking and/or over-stocking. To attenuate this effect, one of the viable practices is that suppliers impose minimum Order Quantity Commitments (OQC) for regular orders and penalties for reduced orders, while providing retailers with expedited-delivery options at premium costs if needs arise. In this paper, we introduce a methodology to assist in developing inventory management policies to optimize the expected profit. Our model considers a two-period setting where retailers place orders according to pre-sale forecasts but then have the opportunity to update their orders just prior to the season according to the most recent forecasts and the current inventory level. Utilizing the newsvendor model and dynamic programming methods, we obtain the optimal ordering and replenishing policies that maximize the expected profits of retailers. We then analyze the impacts of these flexible terms on the performance of both the retailer and the supplier.

Motivated by the increase in students’ enrollment in Arabic as a foreign language (AFL) classes and a lack of specified pedagogies aligned with the American Council on the Teaching of Foreign Languages Performance Guidelines for Language Learners ( ACTFL, 2017 ), this study investigated a genre-based approach (GBA) informed by systemic functional linguistics (SFL) to teach and assess the written Arabic recount of habitual events. The purpose of this article is to show how the GBA empowered novice Arabic learners to make meaning when portraying the main participant in the written Arabic recount of habitual events. The study quantitatively observed the changes in the writing of 15 students over the course of a unit of study, and qualitatively an in-depth observation of two students using SFL as the framework for analysis. The results indicate that the students improved on using interpersonal meanings to portray the main participant associated with the Arabic written recount of habitual events. The results suggest that SFL genre-informed pedagogy empowers AFL students to expand their linguistic repertoire to address the socio-culturally purpose of the recount of habitual events. Further implications on the teaching of AFL learners and on AFL pedagogy will be discussed.

Rofecoxib (ROF), a potent selective COX-II inhibitor NSAID, has been withdrawn from the market due to its high risk on patients with cardiovascular disorders (CVD). In the current study, an attempted to re-introduce ROF into the market via co-formulation with the antiplatelet drug, Aspirin, to neutralize ROF effect on the platelet function has been investigated. Solubility and dissolution profiles of ROF were studied and improved through formulation into solid dispersions with Soluplus® before being mixed with a low dose of Aspirin. The novel drug combination was incorporated into oral tablets with various compositions to optimize the tablets physico-chemical performance. In addition, a new validated HPLC method was developed for simultaneous assessment of both drugs in the tablets. The optimized tablets demonstrated satisfactory physico-chemical performance. The developed HPLC method was accurate, precise, robust and sensitive with limits of detection (LODs) of 2.96 and 0.25 μg/mL and limits of quantitation (LOQs) of 8.77 and 0.77 μg/mL for Aspirin and ROF, respectively. The novel co-therapy showed normal platelet function in rabbits in opposite to ROF monothrapy. The data presented in this study can be promising to re-utilize ROF as an effective and selective NSAID, to satisfy the market's demand, while ensuring its safety in CVD patients.