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At least 73 records · Page 4

A clinically and genomically annotated nerve sheath tumor biospecimen repository

Nerve sheath tumors occur as a heterogeneous group of neoplasms in patients with neurofibromatosis type 1 (NF1). The malignant form represents the most common cause of death in people with NF1, and even when benign, these tumors can result in significant disfigurement, neurologic dysfunction, and a range of profound symptoms. Lack of human tissue across the peripheral nerve tumors common in NF1 has been a major limitation in the development of new therapies. To address this unmet need, we have created an annotated collection of patient tumor samples, patient-derived cell lines, and patient-derived xenografts, and carried out high-throughput genomic and transcriptomic characterization to serve as a resource for further biologic and preclinical therapeutic studies. In this work, we release genomic and transcriptomic datasets comprised of 55 tumor samples derived from 23 individuals, complete with clinical annotation. All data are publicly available through the NF Data Portal and at http://synapse.org/jhubiobank.

60 APPLIED LIFE SCIENCES↗

Genetics of varicose veins reveals polygenic architecture and genetic overlap with arterial and venous disease

Varicose veins represent a common cause of cardiovascular morbidity, with limited available medical therapies. Although varicose veins are heritable and epidemiologic studies have identified several candidate varicose vein risk factors, the molecular and genetic basis remains uncertain. Here we analyzed the contribution of common genetic variants to varicose veins using data from the Veterans Affairs Million Veteran Program and four other large biobanks. Among 49,765 individuals with varicose veins and 1,334,301 disease-free controls, we identified 139 risk loci. We identified genetic overlap between varicose veins, other vascular diseases and dozens of anthropometric factors. Using Mendelian randomization, we prioritized therapeutic targets via integration of proteomic and transcriptomic data. Finally, topological enrichment analyses confirmed the biologic roles of endothelial shear flow disruption, inflammation, vascular remodeling and angiogenesis. Further, these findings may facilitate future efforts to develop nonsurgical therapies for varicose veins.

59 BASIC BIOLOGICAL SCIENCES↗

Inappropriate antibiotic access practices at the community level in Eastern Ethiopia

Access to antibiotic medications is critical to achieving the Sustainable Development Goal for good health and well-being. However, non-prescribed and informal sources are implicated as the most common causes of inappropriate antibiotic access practices, resulting in untargeted therapy, which leads to antibiotic resistance. Hence, knowing antibiotic access practices at the community level is essential to target misuse sources. In this study, 2256 household representatives were surveyed between July and September 2023 to examine their antibiotic access practices. Of 1245 household members who received antibiotics, 45.6% did so inappropriately. Non-prescribed antibiotic access was more common among urban residents and individuals not enrolled in health insurance schemes. This means of antibiotic access was also more common among individuals concerned about distance, drug availability, and healthcare convenience at public facilities. In addition, women and rural individuals were more likely to get antibiotics from unauthorized sources. Unrestricted antibiotic dispensing practices in urban areas enabled their non-prescribed access, while unlicensed providers prevailed with this access practice in rural areas. In this regard, personal behaviors and healthcare-related gaps such as the lack of health insurance, inconvenience, and drug unavailability have led community members to seek antibiotics from unofficial and non-prescribed sources. Targeting the identified behavioral and institutional factors can enhance antibiotic access through prescriptions, hence reducing antibiotic resistance.

60 APPLIED LIFE SCIENCES↗

Multi-version software reliability through fault-avoidance and fault-tolerance

A number of experimental and theoretical issues associated with the practical use of multi-version software to provide run-time tolerance to software faults were investigated. A specialized tool was developed and evaluated for measuring testing coverage for a variety of metrics. The tool was used to collect information on the relationships between software faults and coverage provided by the testing process as measured by different metrics (including data flow metrics). Considerable correlation was found between coverage provided by some higher metrics and the elimination of faults in the code. Back-to-back testing was continued as an efficient mechanism for removal of un-correlated faults, and common-cause faults of variable span. Software reliability estimation methods was also continued based on non-random sampling, and the relationship between software reliability and code coverage provided through testing. New fault tolerance models were formulated. Simulation studies of the Acceptance Voting and Multi-stage Voting algorithms were finished and it was found that these two schemes for software fault tolerance are superior in many respects to some commonly used schemes. Particularly encouraging are the safety properties of the Acceptance testing scheme.

Vouk, Mladen A.↗

Quasi-biennial geomagnetic variation caused by the sun

Clear evidence for the existence of a quasi-biennial geomagnetic variation is shown by an analysis of annual averages of the horizontal (H) component of the geomagnetic field observed at five observatories. The analysis uses a numerical filter, which is equivalent to taking the second order time derivative of the time series. The cause for the variation is external to the earth because its amplitude depends on magnetic activity. The second order time derivative of H is well correlated with the corresponding time derivatives of the relative sunspot number and 10.7 cm solar flux. It is suggested that quasi-biennial oscillations observed in the geomagnetic field, cosmic rays, stratospheric zonal wind and temperature, total ozone, and other meteorological parameters could be produced by a common cause on the sun.

Sugiura, M.↗

Evaluation of Hardware and Software Bill of Materials (HBOMs/SBOMs) Extraction Methods

Hardware and software bills of materials (HBOMs and SBOMs) provide important visibility into the components, dependencies, and supply chain relationships within programmable digital devices. This visibility is critical for advanced nuclear reactor applications, where use of common or shared hardware components, software libraries, suppliers, or manufacturing processes may create common cause failure (CCF) vulnerabilities despite apparent diversity. This paper evaluates current approaches for obtaining and analyzing HBOMs and SBOMs in support of CCF, diversity and defense-in-depth (D3) assessments, and begins to explore potential methods for artificial intelligence/machine learning-based analysis. The availability of BOM information from advanced reactor manufacturers and vendors, representative hardware and software categories found in advanced reactor systems continues to limit research [13]. This paper compares commonly used BOM formats, including CycloneDX, SPDX, and SWID. It also surveys publicly available tools for generating BOMs from source code, compiled binaries, and hardware-related information, noting limitations in language coverage, system age, and format interoperability. Finally, this paper evaluates methods for correlating BOM data with vulnerability and exploitability information, including VEX, CVE, and CWE resources. The findings indicate that publicly available nuclear-vendor BOMs are limited, making third-party extraction and research into novel analysis techniques necessary.

Cybersecurity↗

Multiversion software reliability through fault-avoidance and fault-tolerance

In this project we have proposed to investigate a number of experimental and theoretical issues associated with the practical use of multi-version software in providing dependable software through fault-avoidance and fault-elimination, as well as run-time tolerance of software faults. In the period reported here we have working on the following: We have continued collection of data on the relationships between software faults and reliability, and the coverage provided by the testing process as measured by different metrics (including data flow metrics). We continued work on software reliability estimation methods based on non-random sampling, and the relationship between software reliability and code coverage provided through testing. We have continued studying back-to-back testing as an efficient mechanism for removal of uncorrelated faults, and common-cause faults of variable span. We have also been studying back-to-back testing as a tool for improvement of the software change process, including regression testing. We continued investigating existing, and worked on formulation of new fault-tolerance models. In particular, we have partly finished evaluation of Consensus Voting in the presence of correlated failures, and are in the process of finishing evaluation of Consensus Recovery Block (CRB) under failure correlation. We find both approaches far superior to commonly employed fixed agreement number voting (usually majority voting). We have also finished a cost analysis of the CRB approach.

Vouk, Mladen A.↗

Genetic and behavioral adaptation of Candida parapsilosis to the microbiome of hospitalized infants revealed by in situ genomics, transcriptomics, and proteomics

Background Candida parapsilosis is a common cause of invasive candidiasis, especially in newborn infants, and infections have been increasing over the past two decades. C. parapsilosis has been primarily studied in pure culture, leaving gaps in understanding of its function in a microbiome context. Results. Here, we compare five unique C. parapsilosis genomes assembled from premature infant fecal samples, three of which are newly reconstructed, and analyze their genome structure, population diversity, and in situ activity relative to reference strains in pure culture. All five genomes contain hotspots of single nucleotide variants, some of which are shared by strains from multiple hospitals. A subset of environmental and hospital-derived genomes share variants within these hotspots suggesting derivation of that region from a common ancestor. Four of the newly reconstructed C. parapsilosis genomes have 4 to 16 copies of the gene RTA3, which encodes a lipid translocase and is implicated in antifungal resistance, potentially indicating adaptation to hospital antifungal use. Time course metatranscriptomics and metaproteomics on fecal samples from a premature infant with a C. parapsilosis blood infection revealed highly variable in situ expression patterns that are distinct from those of similar strains in pure cultures. For example, biofilm formation genes were relatively less expressed in situ, whereas genes linked to oxygen utilization were more highly expressed, indicative of growth in a relatively aerobic environment. In gut microbiome samples, C. parapsilosis co-existed with Enterococcus faecalis that shifted in relative abundance over time, accompanied by changes in bacterial and fungal gene expression and proteome composition. Conclusions The results reveal potentially medically relevant differences in Candida function in gut vs. laboratory environments, and constrain evolutionary processes that could contribute to hospital strain persistence and transfer into premature infant microbiomes.

59 BASIC BIOLOGICAL SCIENCES↗

GEFSv12 High- and Low-Skill Day-10 Tornado Forecasts

Abstract On average, modern numerical weather prediction forecasts for daily tornado frequency exhibit no skill beyond day 10. However, in this extended-range lead window, there are particular model cycles that have exceptionally high forecast skill for tornadoes because of their ability to correctly simulate the future synoptic pattern. Here, model initial conditions that produced a more skillful forecast for tornadoes over the United States were exploited while also highlighting potential causes for low-skill cycles within the Global Ensemble Forecasting System, version 12 (GEFSv12). There were 88 high-skill and 91 low-skill forecasts in which the verifying day-10 synoptic pattern for tornado conditions revealed a western U.S. thermal trough and an eastern U.S. thermal ridge, a favorable configuration for tornadic storm occurrence. Initial conditions for high skill forecasts tended to exhibit warmer sea surface temperatures throughout the tropical Pacific Ocean and Gulf of Mexico, an active Madden–Julian oscillation, and significant modulation of Earth-relative atmospheric angular momentum. Low-skill forecasts were often initialized during La Niña and negative Pacific decadal oscillation conditions. Significant atmospheric blocking over eastern Russia—in which the GEFSv12 overforecast the duration and characteristics of the downstream flow—was a common physical process associated with low-skill forecasts. This work helps to increase our understanding of the common causes of high- or low-skill extended-range tornado forecasts and could serve as a helpful tool for operational forecasters. Significance Statement This research provides a framework for the anticipation of a more (or less) skillful 10-day tornado forecast in an operational numerical weather prediction system. High-skill forecasts were associated with substantial tropical convection and warm sea surface temperature throughout the Pacific Ocean and Gulf of Mexico, whereas the underlying cause of low-skill forecasts were typically associated with a blocking anticyclone over eastern Russia. These findings are important because they permit increased or decreased confidence in a long-range forecast of tornado occurrence based on a dynamical prediction system.

Meteorology & Atmospheric Sciences↗

Conical Seat Shut-Off Valve

A moveable valve for controlling flow of a pressurized working fluid was designed. This valve consists of a hollow, moveable floating piston pressed against a stationary solid seat, and can use the working fluid to seal the valve. This open/closed, novel valve is able to use metal-to-metal seats, without requiring seat sliding action; therefore there are no associated damaging effects. During use, existing standard high-pressure ball valve seats tend to become damaged during rotation of the ball. Additionally, forces acting on the ball and stem create large amounts of friction. The combination of these effects can lead to system failure. In an attempt to reduce damaging effects and seat failures, soft seats in the ball valve have been eliminated; however, the sliding action of the ball across the highly loaded seat still tends to scratch the seat, causing failure. Also, in order to operate, ball valves require the use of large actuators. Positioning the metal-to-metal seats requires more loading, which tends to increase the size of the required actuator, and can also lead to other failures in other areas such as the stem and bearing mechanisms, thus increasing cost and maintenance. This novel non-sliding seat surface valve allows metal-to-metal seats without the damaging effects that can lead to failure, and enables large seating forces without damaging the valve. Additionally, this valve design, even when used with large, high-pressure applications, does not require large conventional valve actuators and the valve stem itself is eliminated. Actuation is achieved with the use of a small, simple solenoid valve. This design also eliminates the need for many seals used with existing ball valve and globe valve designs, which commonly cause failure, too. This, coupled with the elimination of the valve stem and conventional valve actuator, improves valve reliability and seat life. Other mechanical liftoff seats have been designed; however, they have only resulted in increased cost, and incurred other reliability issues. With this novel design, the seat is lifted by simply removing the working fluid pressure that presses it against the seat and no external force is required. By eliminating variables associated with existing ball and globe configurations that can have damaging effects upon a valve, this novel design reduces downtime in rocket engine test schedules and maintenance costs.

Farner, Bruce↗

An Integrated Framework for Risk Assessment of Safety-related Digital Instrumentation and Control Systems in Nuclear Power Plants: Methodology Refinement and Exploration

This report documents activities performed by Idaho National Laboratory (INL) during Fiscal Year (FY) 2023 for the U.S. Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) Program, Risk Informed Systems Analysis (RISA) Pathway, digital instrumentation and control (DI&C) risk assessment project. In FY 2019, the RISA Pathway initiated a project to develop a risk assessment strategy for delivering a technical basis to support effective, and secure DI&C technologies for digital upgrades/designs. A risk assessment-informed framework was proposed for this strategy, which aims to (1) provide a best-estimate, risk informed capability to quantitatively estimate the safety margin obtained from plant modernization, especially for safety-related DI&C systems, (2) support and supplement existing risk informed DI&C design guides by providing quantitative risk information and evidence, (3) offer a capability of design architecture evaluation of various DI&C systems, (4) assure the long-term safety and reliability of safety-related DI&C systems, and (5) reduce uncertainty in costs and support integration of DI&C systems in the plant. To achieve these technical goals, the LWRS-developed framework provides a means to address relevant technical issues by: (1) defining a risk informed analysis process for DI&C upgrade that integrates hazard analysis, reliability analysis, and consequence analysis, (2) applying risk informed tools to address common cause failures (CCFs) and quantify corresponding failure probabilities for DI&C technologies, particularly software CCFs, (3) evaluating the impact of digital failures at the component level, system level, and plant level, and (4) providing insights and suggestions on designs to manage the risks, thus to support the development and deployment of advanced DI&C technologies in nuclear power plants (NPPs). Adding diversity within a system or components is the primary means to eliminate and mitigate CCFs, but diversity also increases system complexity and may not address all sources of systematic failures. Optimization of diversity and redundancy applications for the safety-critical DI&C systems remains a challenge. To deal with the technical issues in addressing potential software CCFs in safety-related DI&C systems of NPPs and supporting relevant design optimization, the proposed framework provides: (a) A best-estimate, risk informed capability to address new technical digital issues quantitatively, focusing on software CCFs in safety-related DI&C systems of NPPs; (b) A common and a modularized platform for DI&C designers, software developers, cybersecurity analysts, and plant engineers to predict and prevent risk in the early design stage of DI&C systems; (c) Technical bases and risk informed insights to assist users address the risk informed alternatives for evaluation of CCFs in safety-related DI&C systems of NPPs; and (d) A risk informed tool that offers a capability of design architecture evaluation of various DI&C systems to support system design decisions in diversity and redundancy applications. The research and development efforts of this project in FY 2023 are focused on refining current methods on software CCF modeling and estimation and exploring additional innovative approaches to risk assessment of DI&C systems to enable a more comprehensive and complete assessment of various safety-related DI&C design architectures. The primary audience of this report are DI&C designers, engineers, and probabilistic risk assessment (PRA) practitioners. This includes stakeholders, such as the nuclear utilities and regulators who consider the deployment and upgrade of DI&C systems, DI&C software developers and reviewers, and cybersecurity specialists. It should be noted that all the analyses are performed for the demonstration of the methodology, not for the evaluation of an actual digital control system. Results are obtained based on limited design information and testing data.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Risk Analysis of Various Design Architectures for High Safety-significant Safety-related Digital Instrumentation and Control Systems of Nuclear Power Plants during Accident Scenarios

This report documents the plus-up activities performed by Idaho National Laboratory (INL) during Fiscal Year (FY) 2022 for the U.S. Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) Program, Risk Informed Systems Analysis (RISA) Pathway, digital instrumentation and control (DI&C) risk assessment project. In FY 2019, the RISA Pathway initiated a project to develop a risk assessment strategy for delivering a strong technical basis to support effective, licensable, and secure DI&C technologies for digital upgrades/designs. An integrated risk assessment technology for the DI&C systems was proposed for this strategy, which aims to (1) provide a best-estimate, risk-informed capability to quantitatively and accurately estimate the safety margin obtained from plant modernization, especially for the high safety-significant safety-related (HSSSR) DI&C systems, (2) support and supplement existing advanced risk-informed DI&C design guides by providing quantitative risk information and evidence, (3) offer a capability of design architecture evaluation of various DI&C systems to support system design decisions and diversity and redundancy applications, (4) assure the long-term safety and reliability of HSSSR DI&C systems, and (5) reduce uncertainty in costs and support integration of DI&C systems in the plant. To achieve these technical goals and deal with the expensive licensing justifications from regulatory insights, the LWRS-developed framework instructs nuclear vendors and utilities on how to effectively lower the costs associated with digital compliance and speed industry advances by: (1) defining an integrated risk-informed analysis process for DI&C upgrade, including hazard analysis, reliability analysis, and consequence analysis, (2) applying systematic and risk-informed tools to address common cause failures (CCFs) and quantify corresponding failure probabilities for DI&C technologies, particularly software CCFs, (3) evaluating the impact of digital failures at the component level, system level, and plant level, and (4) providing insights and suggestions on designs to manage the risks, thus to support the development, licensing, and deployment of advanced DI&C technologies on nuclear power plant (NPPs). Adding diversity within system or components is the main means to eliminate and mitigate CCFs, but diversity also increases plant complexity and errors and may not address all sources of systematic failures. How to optimize the diversity and redundancy applications for the safety-critical DI&C systems remains a challenge. To deal with the technical issues in addressing potential software CCFs in HSSSR DI&C systems of NPPs and supporting relevant design optimization, the framework provides: ? An integrated best-estimate, risk-informed capability to address new technical digital issues quantitatively, accurately, and efficiently in plan modernization progress, such as software CCFs in HSSSR DI&C systems of NPPs ? A common and a modularized platform for DI&C designers, software developers, cybersecurity analysts, and plant engineers to efficiently predict and prevent risk in the early design stage of DI&C systems ? Technical bases and risk-informed insights to assist U.S. Nuclear Regulatory Commission (NRC) and industry to address and fulfill the risk-informed alternatives for evaluation of CCFs in HSSSR DI&C systems of NPPs ? An integrated risk-informed tool that offers a capability of design architecture evaluation of various DI&C systems to support system design decisions in diversity and redundancy applications. The plus-up research and development efforts of this project in FY 2022 are focused on methodology improvement of software CCF modeling and estimation, prevention analysis, importance analysis and risk analysis of various design architectures of HSSSR DI&C systems. This work greatly enhances the capability of the LWRS-developed framework for the risk assessment and design optimization of safety-critical DI&C systems. It should be noted that all the analyses are performed for the demonstration of the LWRS-developed framework, not for the evaluation of relevant systems. Results are obtained based on very limited design information and testing data.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Large Charge Moment Change Lightning in an Oklahoma Mesoscale Convective System

On 31 May 2013, a line of severe thunderstorms developed during the local afternoon in central Oklahoma, USA. One of the supercells produced the El Reno tornado, which caused significant damage and killed several people. During the 2300 UTC hour (during the mature supercell stage and just after the tornado began), the storm produced several positive cloud-to-ground (+CG) lightning strokes that featured large (> 100 C km) impulse charge moment changes (iCMCs; charge moment during the first 2 ms after the return stroke). These discharges occurred mainly in convection, in contrast to the typical pattern of large-CMC and sprite-parent +CGs occurring mainly in stratiform precipitation regions. After this time, the line of thunderstorms evolved over several hours into a large mesoscale convective system (MCS). By the 0700 UTC hour on 1 June 2013, the large-CMC pattern had changed markedly. Large-CMC negative CGs, which were absent early in the storm's lifetime, occurred frequently within convection. Meanwhile, large-CMC +CGs had switched to occurring mainly within the broad stratiform region that had developed during the intervening period. The evolution of the large-CMC lightning in this case will be examined using a mix of national mosaics of radar reflectivity, the Oklahoma Lightning Mapping Array (OKLMA), the Charge Moment Change Network (CMCN), and the National Lightning Detection Network (NLDN). A major goal of this study is understanding how storm structure and evolution affected the production of large-CMC lightning. It is anticipated that this will lead to further insight into how and why storms produce the powerful lightning that commonly causes sprites in the upper atmosphere.

Lang, Timothy J.↗

Large Charge Moment Change Lightning in an Oklahoma Mesoscale Convective System

On 31 May 2013, a line of severe thunderstorms developed during the local afternoon in central Oklahoma, USA. One of the supercells produced the El Reno tornado, which caused significant damage and killed several people. During the 2300 UTC hour (during the mature supercell stage and just after the tornado began), the storm produced several positive cloud-to-ground (+CG) lightning strokes that featured large (> 75 C km) impulse charge moment changes (iCMCs - charge moment during the first 2 ms after the return stroke). These discharges occurred mainly in convection, in contrast to the typical pattern of large-CMC and sprite-parent +CGs occurring mainly in stratiform precipitation regions. After this time, the line of thunderstorms evolved over several hours into a large mesoscale convective system (MCS). By the 0700 UTC hour on 1 June 2013, the large- CMC pattern had changed markedly. Large-CMC negative CGs, which were absent early in the storm's lifetime, occurred frequently within convection. Meanwhile, large- CMC +CGs had switched to occurring mainly within the broad stratiform region that had developed during the intervening period. The evolution of the large-CMC lightning in this case will be examined using a mix of polarimetric data from individual radars, national mosaics of radar reflectivity, the Oklahoma Lightning Mapping Array (OKLMA), the Charge Moment Change Network (CMCN), and the National Lightning Detection Network (NLDN). A major goal of this study is understanding how storm structure and evolution affected the production of large-CMC lightning. It is anticipated that this will lead to further insight into how and why storms produce the powerful lightning that commonly causes sprites in the upper atmosphere.

Lang, Timothy J.↗

Mineralogical and microstructural alterations in a portland cement paste after an accelerated decalcification process

Cement paste leaching and concomitant decalcification is a common cause of concrete structure deterioration. Such alterations entail microstructural changes that condition concrete durability. This study analysed those changes in cement pastes exposed to accelerated decalcification, layer-by-layer, from the surface in contact with the leaching agent, 6 M NH{sub 4}NO{sub 3,} to the unaltered area. The microstructural changes were analysed with BSEM, MIP and BET whilst the mineralogical and nanostructural alterations in each layer were assessed with XRD, FTIR, {sup 29}Si and {sup 27}Al MAS NMR and BSD. Decalcification affected not only portlandite and CSH gel, but also the anhydrous clinker and ettringite, inducing major micro- and nano-structural changes, particularly in the two layers closest to the leaching agent. CSH gel decalcification was more intense in the outer layers where long chain gels co-existed with silicon rich gels. BDS, in turn, revealed differences between the amount of bound water in the surface interfacing with the leaching agent and in the leaching front. More specifically, larger numbers of water molecules were tightly bound to silanol groups in the outer, whereas hydroxyl group distribution was more orderly in the inner layers.

36 MATERIALS SCIENCE↗

Modulation of Neuroinflammation by Low-Dose Radiation Therapy in an Animal Model of Alzheimer's Disease

Recently, several studies have reported that low-dose radiation therapy (RT) suppresses the release of proinflammatory cytokines in inflammatory-degenerative disorders, including Alzheimer disease (AD). AD is the most common cause of dementia, and neuroinflammation is one of the major contributing factors in AD pathogenesis. Therefore, low-dose RT may be used clinically for treating AD. However, the appropriate doses, effects, and underlying mechanisms of RT in AD have not been determined. In this study, we aimed to determine the appropriate RT dose and schedule for AD treatment and to investigate the therapeutic effects and mechanisms of low-dose RT in AD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Stochastic pre-event preparation for enhancing resilience of distribution systems

Extreme weather events are the common causes for power supply interruptions and power outages in electrical distribution systems. Improving the distribution system and enhancing its resilience is becoming crucial due to the increased frequency of extreme weather events. Preparation and allocation of multiple flexible resources, such as mobile resources, fuel resources, and labor resources before extreme weather events can mitigate the effects of extreme weather events and enhance the resilience of power distribution systems. Here, in this paper, a two-stage stochastic mixed-integer linear programming (SMILP) is proposed to optimize the preparation and resource allocation process for upcoming extreme weather events, which leads to faster and more efficient post-event restoration. The objective of the proposed two-stage SMILP is to maximize the served load and minimize the operating cost of flexible resources. The first stage in the optimization problem selects the amounts and locations of different resources. The second stage considers the operational constraints of the distribution system and repair crew scheduling constraints. The proposed stochastic pre-event preparation model is solved by a scenario decomposition method, Progressive Hedging (PH), to ease the computational complexity introduced by a large number of scenarios. Furthermore, to show the impact of solar photovoltaic (PV) generation on system resilience, three types of PV systems are considered during a power outage and the resilience improvements with different PV penetration levels are compared. Numerical results from simulations on a large-scale (more than 10,000 nodes) distribution feeder have been used to validate the effectiveness and scalability of the proposed method.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Genetically engineered mouse models of esophageal cancer

Esophageal cancer is the most common cause of cancer-related death worldwide with a diverse geographical distribution, poor prognosis, and diagnosis in advanced stages of the disease. Identification of the mechanisms involved in esophageal cancer development is evaluative to improve outcomes for patients. Genetically engineered mouse models (GEMMs) of cancer provide the physiologic, molecular, and histologic features of the human tumors to determine the pathogenesis and treatments for cancer, hence exhibiting a source of tremendous potential for oncology research. The advancement of cancer modeling in mice has improved to the extent that researchers can observe and manipulate the disease process in a specific manner. Despite the significant differences between mice and humans, mice can be great models for human oncology researches due to similarities between them at the molecular and physiological levels. Due to most of the existing esophageal cancer GEMMs do not propose an ideal system for pathogenesis of the disease, genetic risks, and microenvironment exposure, so identification of challenges in GEM modeling and well-developed technologies are required to obtain the most value for patients. In this review, we describe the biology of human and mouse, followed by the exciting esophageal cancer mouse models with a discussion of applicability and challenges of these models for generating new GEMMs in future studies.

60 APPLIED LIFE SCIENCES↗