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Nowadays, multi-energy systems play an important role in satisfying the ever-increasing demand for different energy resources. At the same time, the sustainable development of such systems is usually based on the structural and parametric optimization (synthesis) of their infrastructures. There is a large spectrum of specialized optimization tools for the study of single energy systems. At the same time, the problem of modeling the interaction between single energy systems remains challenging. Therefore, it is imperative to develop an efficient experimental environment to effectively implement the synthesis of optimal configurations of multi-energy systems. Microgrids are a special case of multi-energy systems. They provide a higher level of energy supply compared to the main grids and enhance their reliability and resilience. In this context, we propose a framework and subject-oriented environment for the synthesis of optimal microgrid configurations in a reasonable time considering the available computational resources. The basis of the environment is a service-oriented application. The modeling and optimization of the studied systems is performed by means of scientific workflows. Our results complement and develop known approaches to automate the modeling of multi-energy systems using their typical models and specially selected optimization algorithms corresponding to these models. We have successfully tested our approach for the synthesis of optimal microgrid configurations on the case study of a specific microgrid providing heat and electricity to a small settlement. [ABSTRACT FROM AUTHOR]

Implementing high-performance computing (HPC) to solve problems in energy infrastructure resilience research in a heterogeneous environment based on an in-memory data grid (IMDG) presents a challenge to workflow management systems. Large-scale energy infrastructure research needs multi-variant planning and tools to allocate and dispatch distributed computing resources that pool together to let applications share data, taking into account the subject domain specificity, resource characteristics, and quotas for resource use. To that end, we propose an approach to implement HPC-based resilience analysis using our Orlando Tools (OT) framework. To dynamically scale computing resources, we provide their integration with the relevant software, identifying key application parameters that can have a significant impact on the amount of data processed and the amount of resources required. We automate the startup of the IMDG cluster to execute workflows. To demonstrate the advantage of our solution, we apply it to evaluate the resilience of the existing energy infrastructure model. Compared to similar approaches, our solution allows us to investigate large infrastructures by modeling multiple simultaneous failures of different types of elements down to the number of network elements. In terms of task and resource utilization efficiency, we achieve almost linear speedup as the number of nodes of each resource increases. [ABSTRACT FROM AUTHOR]

This article presents a package for analyzing the energy system vulnerability developed with new technology for continuous integration, delivery, and deployment of applied software. It implements a framework that allows combining and optimally using various methods for modelling energy systems and provides the comprehensive assessment of their vulnerability with regard to various uncertainties. The essential principles to identify and rank critical elements of an energy system are considered in the article. The investigations made with the package shown that the principles seem to be logical for the subsequent construction of the invariant set of measures for improving the energy system resilience.

Migraine is a chronic neurologic disease estimated to affect approximately 50 million Americans. It is associated with a range of symptoms, which contribute to disability and substantial negative impacts on quality of life for many patients. Still, migraine continues to be underdiagnosed, undertreated, and optimising treatment for individual patients has proven difficult. As many migraine patients will be seen first in primary care settings, internists and other primary care providers are ideally positioned to improve diagnosis and migraine management for many patients. In this review, we discuss some of the challenges in diagnosing migraine and suggest strategies to overcome them, summarise the current understanding of migraine pathophysiology and clinical evidence on acute and preventive treatment options, and offer practical approaches to diagnosis and contemporary management of migraine in the primary care setting. Migraine is a prevalent disease with substantial impact. Primary care providers are ideally positioned to improve care for migraine patients with streamlined approaches to diagnosis and management. A stepwise diagnostic approach to migraine involves taking a thorough headache history, excluding secondary headache, and identifying primary headache disorder using screening tools or ICHD-3 criteria. The FDA approved seven new migraine therapies from 2018 to 2020 (four monoclonal antibodies, two gepants, one ditan), expanding acute and preventive therapeutic options. [ABSTRACT FROM AUTHOR]

Nowadays, a provision of the computational process fault-tolerance in Grid is a relevant issue. In the paper, we address a fault-tolerance improvement in solving large-scale scientific and applied problems that are implemented through modular programming in heterogeneous distributed computing environments. We describe a computational process by an abstract program (problem-solving scheme) that correlates to a workflow. The problem-solving scheme specifies modules (applied software) and their relations with each other. This paper proposes a new multi-agent algorithm for re-allocating Grid-resources when the computational process fails. The algorithm execution involves forming a residual problem-solving scheme using methods of the abstract program specialization and reallocating its modules between agents that represent computational resources. In comparison to the known algorithms for the same purpose, the proposed algorithm implements an adaptive multi-scenario solving this issue and therefore increases a degree of computational process fault-tolerance. Extensive modeling and practical experiments demonstrate the practicability of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Dual leucine zipper kinase (DLK) promotes growth cone motility and must be restrained to ensure normal development. PHR (Pam/ Highwire/RPM-1) ubiquitin ligases therefore target DLK for degradation unless axon injury occurs. Overall DLK levels decrease during development, but how DLK levels are regulated within a developing growth cone has not been examined. We analyzed the expression of the fly DLK Wallenda (Wnd) in R7 photoreceptor growth cones as they halt at their targets and become presynaptic boutons. We found that Wnd protein levels are repressed by the PHR protein Highwire (Hiw) during R7 growth cone halting, as has been observed in other systems. However, as R7 growth cones become boutons, Wnd levels are further repressed by a temporally expressed transcription factor, Tramtrack69 (Ttk69). Previously unobserved negative feedback from JNK also contributes to Wnd repression at both time points. We conclude that neurons deploy additional mechanisms to downregulate DLK as they form stable, synaptic connections.We use live imaging to probe the effects of Wnd and Ttk69 on R7 bouton development and conclude that Ttk69 coordinates multiple regulators of this process. [ABSTRACT FROM AUTHOR]

The kinesin KIF1C is known to regulate podosomes, actin-rich adhesion structures that remodel the extracellular matrix during physiological processes. Here, we show that KIF1C is a player in the podosome-inducing signaling cascade. Upon induction of podosome formation by protein kinase C (PKC), KIF1C translocation to the cell periphery intensifies and KIF1C accumulates both in the proximity of peripheral microtubules that show enrichment for the plus-tip-associated proteins CLASPs and around podosomes. Importantly, without CLASPs, both KIF1C trafficking and podosome formation are suppressed. Moreover, chimeric mitochondrially targeted CLASP2 recruits KIF1C, suggesting a transient CLASP-KIF1C association. We propose that CLASPs create preferred microtubule tracks for KIF1C to promote podosome induction downstream of PKC. [ABSTRACT FROM AUTHOR]

Highlights: [•] WASP-B (wasB) is a WASP-related protein found in Dictyostelium. [•] F-actin assembly response is increased and prolonged in wasB − cells. [•] wasB − cells exhibit frequent protrusion of pseudopods causing aberrant chemotaxis. [•] wasB − cells exhibit aberrant regulation of RacC activation and localization. [•] Chemotaxis defects of wasB − are likely to result from aberrant regulation of RacC. [ABSTRACT FROM AUTHOR]

We have evaluated the binding of sialylated and desialylated lipoproteins to collagen isolated from the proteoglycan and musculoelastic layers of intima and media of uninvolved human aorta and atherosclerotic lesions. Comparing various collagen preparations from the uninvolved intima-media, the binding of sialylated apoB-containing lipoproteins was best to collagen from the intimal PG-rich layer. Binding of sialylated apoB-containing lipoproteins to collagen from this layer of fatty streak and fibroatheroma was 1.4- and 3.1-fold lower, respectively, in comparison with normal intima. Desialylated VLDL versus sialylated one exhibited a greater binding (1.4- to 3.0-fold) to all the collagen preparations examined. Desialylated IDL and LDL showed a higher binding than sialylated ones when collagen from the intimal layers of fibroatheroma was used. Binding of desialylated HDL to collagen from the intimal PG-rich layer of normal tissue, initial lesion, and fatty streak was 1.2- to 2.0-fold higher compared with sialylated HDL. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess the efficacy of 6 mg subcutaneous (SC) sumatriptan to treat migraine and the relationship between response of migraine and cutaneous allodynia in a population of migraine patients who historically failed to respond to oral triptan medications. This was an openlabel study consisting of patients with migraines who historically failed to respond to oral triptan medications. Forty-three patients were asked to treat three migraine attacks with 6 mg SC sumatriptan. The primary efficacy endpoint was the percentage of patients achieving relief of headache at 2 h. Ninetyone percent of the patients responded to a single dose of SC sumatriptan 6 mg. Fifty percent of all patients were pain-free by 2 h and over 30% had a 24-h sustained pain-free response. When administered within 90 min from the onset of migraine (i.e., during the developing phase of cutaneous allodynia), SC 6 mg sumatriptan proved to be effective despite the occurrence of allodynia in a group of patients, who historically had failed to respond to oral triptan medications. These findings suggest that the window of opportunity to treat allodynic patients with injectable triptans may be longer (up to 2 h) than with oral triptans (up to 1 h). [ABSTRACT FROM AUTHOR]

Nowadays, developing and applying advanced digital technologies for monitoring protected natural territories are critical problems. Collecting, digitalizing, storing, and analyzing spatiotemporal data on various aspects of the life cycle of such territories play a significant role in monitoring. Often, data processing requires the utilization of high-performance computing. To this end, the paper addresses a new approach to automation of implementing resource-intensive computational operations of web processing services in a heterogeneous distributed computing environment. To implement such an operation, we develop a workflow-based scientific application executed under the control of a multi-agent system. Agents represent heterogeneous resources of the environment and distribute the computational load among themselves. Software development is realized in the Orlando Tools framework, which we apply to creating and operating problem-oriented applications. The advantages of the proposed approach are in integrating geographic information services and high-performance computing tools, as well as in increasing computation speedup, balancing computational load, and improving the efficiency of resource use in the heterogeneous distributed computing environment. These advantages are shown in analyzing multidimensional time series. [ABSTRACT FROM AUTHOR]

Nowadays, simulation modeling is a relevant and practically significant means in the field for research of infrastructure object functioning. It forms the basis for studying the most important components of such objects represented by their digital twins. Applying meteorological data, in this context, becomes an important issue. In the paper, we propose a new microservice-based approach for organizing simulation modeling in heterogeneous distributed computing environments. Within the proposed approach, all operations related to data preparing, executing models, and analyzing the obtained results are implemented as microservices. The main advantages of the proposed approach are the parameter sweep computing within simulation modeling and possibility of integrating resources of public access supercomputer centers with cloud and fog platforms. Moreover, we provide automated microservice web forms using special model specifications. We develop and apply the service-oriented tools for studying environmentally friendly equipment of the objects at the Baikal natural territory. Among such objects are recreation tourist centers, children's camps, museums, exhibition centers, etc. As a result, we have evaluated the costs for the possible use of heat pumps in different operational and meteorological conditions for the typical object. The provided comparative analysis has confirmed the aforementioned advantages of the proposed approach. [ABSTRACT FROM AUTHOR]

The article presents a case of a 14-year-old boy who suffered from frequent severe headaches characterized by sharp, throbbing pain behind his left eye and left temple which may last from 30 minutes to two hours in the U.S. A headache specialist noted that aneurysm of a brain blood vessel is the most dangerous cause of a strictly unilateral headache of sudden onset. The patient's history reveals that his headache pain is of comparatively short duration which not triggered by physical exertion.

This article presents a case study of a 47-year-old woman with short-lasting, strictly unilateral headaches. She describes the pain as sharp and stabbing that involves only the right orbital, temporal, and occipital areas. The severe headaches last an average of 15 to 30 minutes and usually occur daily.

The article presents two case studies on episodic migraine. According to the headache specialist, abortive medications are needed to be taken as early as possible and patients who have migraine with aura can use the aura as a signal to begin treatment. The specialist stresses that therapy with corticosteroids may be effective more for episodic migraine with aura. Meanwhile, the specialist recommends an early initiation of treatment with parenteral medications for episodic migraine without aura.

The article presents an interview with Dr. Seymour Diamond, director and founder of the Diamond Headache Clinic in Chicago. Diamond gives his diagnostic approach regarding a patient having a severe, worsening headaches associated with progressive neurologic symptoms. He also classifies the headaches of the patients that started during her teenage years. He cites further workup to be done for the patients that includes magnetic resonance imaging scans of the brain as the first step.

The article presents the dialogue between a primary care doctor and a headache specialist concerning the diagnosis of a patient with chronic daily headache of sudden onset. When asked by the doctor with regard to the diagnosis of the patient, the specialist stated that the sudden onset of the headaches and the lack of some factors that might contribute to his condition suggest new daily persistent headache, citing the International Headache Society's Classification of Headache Disorders.

The article presents a case study of a 32-year-old woman who complains of severe throbbing pain at the top of her; numbness and weakness on the left side of her face and in her left arm and leg; and nausea, vomiting, and light and noise sensitivity. When the pain started, the patient felt light tingling in her lips that slowly spread down to her arm and leg. INSET: FOCUS ON MIGRAINE WITH NEUROLOGIC DEFICITS..

Stem cells depend on intrinsic and local factors to maintain their identity and activity, but they also sense and respond to changing external conditions. We previously showed that germline stem cells (GSCs) and follicle stem cells (FSCs) in the Drosophila ovary respond to diet via insulin signals. Insulin signals directly modulate the GSC cell cycle at the G2 phase, but additional unknown dietary mediators control both G1 and G2. Target of rapamycin, or TOR, is part of a highly conserved nutrient-sensing pathway affecting growth, proliferation, survival and fertility. Here, we show that optimal TOR activity maintains GSCs but does not play a major role in FSC maintenance, suggesting differential regulation of GSCs versus FSCs. TOR promotes GSC proliferation via G2 but independently of insulin signaling, and TOR is required for the proliferation, growth and survival of differentiating germ cells. We also report that TOR controls the proliferation of FSCs but not of their differentiating progeny. Instead, TOR controls follicle cell number by promoting survival, independently of either the apoptotic or autophagic pathways. These results uncover specific TOR functions in the control of stem cells versus their differentiating progeny, and reveal parallels between Drosophila and mammalian follicle growth. [ABSTRACT FROM AUTHOR]

In this paper, we formulate configurable cloud-based VoIP call allocation problem as a special case of dynamic multi-objective bin-packing. We consider voice quality influenced by CPU stress, cost contributed by the number of billing hours for Virtual Machines (VMs) provisioning, and calls placed on hold due to under-provisioning resources. We distinguish call allocation strategies by the type and amount of information used for allocation: knowledge-free, utilization-aware, rental-aware, and load-aware. We propose and study a variety of strategies with static and dynamic policies of VM provisioning. To study realistic scenarios, we consider startup delays for VM provisioning, and three configurable parameters: utilization threshold, rental threshold, and prediction interval. They can be configured and dynamically adapted to cope with different objective preferences, workloads, and cloud properties. We conduct comprehensive simulation on the real workload of the MIXvoip company and show that the proposed strategies outperform ones currently in-use. • We address concepts of simulation visualization as a pedagogical tool for supporting computer science undergraduates. • We demonstrate the practicability and benefits of the proposed approach on allocation of calls in Cloud VoIP model. • We discuss call allocation strategies with different types and amounts of information used for provision on cloud environments with configurable parameters. • We describe how simulation model enhance the decision making of VoIP providers respect to quality of service and cost of infrastructure. [ABSTRACT FROM AUTHOR]

In this paper, we propose a timetable optimization method based on a Multiobjective Cellular genetic algorithm to tackle the multiple vehicle-type problems. The objective is to determine bus assignment in each time period to optimize a quality of service and transport operating cost. The quality of service, represented by the unsatisfied user demand, guarantees a good experience in terms of comfort, safety, availability, improving effects on how passengers perceive wait times. The operational cost contributes to reducing the traffic jams, the flux of unfilled vehicles and fuel consumption, helping to diminish the negative environmental impact. With the operation data of Los Angeles bus route 217 northbound, at peak and off-peak hours, we obtain a set of non-dominated solutions that represent different assignments of vehicles covering a given set of trips in a defined route. The experimental analysis based on several quality indicators, like Hypervolume, Spread, ε -Indicator, and Set Coverage, indicates that our algorithm is a competitive technique comparing with well-known techniques presented in the literature. • An integration of frequency setting and timetabling for multiple vehicle types. • A multiobjective cellular evolutionary algorithm. • Trade-off between the loss of quality of service and operational costs. • A real-world case study based on the route 217 in Los Angles. [ABSTRACT FROM AUTHOR]