Modeling supply chain interdependent critical infrastructure systems

While strategies for emergency response to large-scale disasters have been extensively studied, little has been done to map medium- to long-term strategies capable of restoring supply chain infrastructure systems and reconnecting such systems from a local urban area to national supply chain systems. This is, in part, because no comprehensive, data-driven model of supply chain networks exists. Without such models communities cannot re-establish the level of connectivity required for timely restoration of goods and services. This dissertation builds a model of supply chain interdependent critical infrastructure (SCICI) as a complex adaptive systems problem. It defines model elements, data needs/element, the interdependency of critical infrastructures, and suggests metrics for evaluating success. Previous studies do not consider the problem from a systematic view and therefore their solutions are piecemeal, rather than integrated with respect to both the model elements and geospatial data components. This dissertation details a methodology to understand the complexities of SCICI within a real urban framework (St. Louis, MO). Interdependencies between the infrastructures are mapped to evaluate resiliency and a framework for quantifying interdependence is proposed. In addition, this work details the identification, extraction and integration of the data necessary to model infrastructure systems --Abstract, page iv

Effect of Non-Coding RNA on Post-Transcriptional Gene Silencing of Alzheimer Disease

A large amount of hidden biological information is contained in the human genome, which is not expressed or revealed in the form of proteins; the usual end product form of gene expression. Instead, most of such information is in the form of non-coding RNAs (ncRNAs). ncRNAs correspond to genes that are transcribed, but do not get translated into proteins. This part of the genome was, till recently, considered as ‘junk’. The term ‘junk’ implied lack of any discernible function of these RNA. More than 98% of the human genomic size encompasses these non-coding RNAs. But, recent research has evidently brought out the indispensible contribution of non-coding RNA in controlling and regulating gene expression. ncRNA such as siRNAs and microRNAs have been reported to greatly help in causing post-transcriptional gene silencing (PTGS) in cells through RNA interference (RNAi) pathway. In this work, we have investigated the possibility of using siRNAs and microRNAs to aid in gene silencing of early onset Alzheimer’s disease genes. 
Alzheimer’s disease specific mutations and their corresponding positions in mRNA have been identified for six genes; Presenilin-1, Presenilin-2, APP (amyloid beta precursor protein), APBB3, BACE-1 and PSENEN. 

Small interfering RNAs (siRNAs) that can cause PTGS through RNA interference pathway have been designed. RNA analysis has been done to verify complementarity of antisense siRNA sequence with target mRNA sequence. Interaction studies have been done computationally between these antisense siRNA strands and seven Argonaute proteins. From the interaction studies, only one of the seven Argonaute proteins; 1Q8K, was found to have interaction with the siRNAs indicating the importance and uniqueness of this particular protein in RISC (RNA induced silencing complex). 

The interaction studies have been carried out for the microRNAs also. Out of the 700 mature human microRNAs collected, 394 microRNAs have been identified to show partial complementarity with their target sequence on PSEN-1 mRNA. Of these 394, five microRNAs have shown partial complementarity to early onset Alzheimer’s disease specific mutations in PSEN-1 mRNA. Interaction studies have been done between these microRNAs and Argonaute proteins. Thus, design, characterization and analysis of ncRNAs that contribute to post transcriptional gene silencing of Alzheimer’s disease have been achieved.
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Identifying Geographical Interdependency in Critical Infrastructure Systems Using Open Source Geospatial Data in Order to Model Restoration Strategies in the Aftermath of a Large-Scale Disaster

In the wake of a large-scale disaster, strategies for emergency search and rescue, short-term recovery and medium- to long-term restoration are needed. While considerable effort is geared to developing strategies for the former two options, little comprehensive guidance exists on the latter. However, medium- to long-term restoration has a significant effect on local, regional and national economies and is essential to community vitality. In part, the deficit of robust strategies can be linked to the complexity in the data acquisition and limited methodologies to understand the interconnectedness of the relevant systems elements. This research utilizes infrastructure data for Supply Chain Interdependent Critical Infrastructure Systems (SCICI) such as transportation, energy, communications, or water, obtained or derived through open sources (such as The National Map of the U.S. Geological Survey) to identify, understand, and map the interdependencies between these system elements to enable restoration planning. Specifically, internal geographical relationships (herein called the ‘geographical interdependency’) of SCICI elements are mapped. These interdependencies highlight the stress points on the larger SCICI where failures occur and are not included in current built environment models. The mapping of these interdependencies is a key step forward in attempts to optimally restore an urban center’s supply chain in the wake of an extreme event

Post-Disaster Supply Chain Interdependent Critical Infrastructure System Restoration: A Review of Data Necessary and Available for Modeling

The majority of restoration strategies in the wake of large-scale disasters have focused on short-term emergency response solutions. Few consider medium- to long-term restoration strategies to reconnect urban areas to national supply chain interdependent critical infrastructure systems (SCICI). These SCICI promote the effective flow of goods, services, and information vital to the economic vitality of an urban environment. To re-establish the connectivity that has been broken during a disaster between the different SCICI, relationships between these systems must be identified, formulated, and added to a common framework to form a system-level restoration plan. To accomplish this goal, a considerable collection of SCICI data is necessary. The aim of this paper is to review what data are required for model construction, the accessibility of these data, and their integration with each other. While a review of publically available data reveals a dearth of real-time data to assist modeling long-term recovery following an extreme event, a significant amount of static data does exist and these data can be used to model the complex interdependencies needed. For the sake of illustration, a particular SCICI (transportation) is used to highlight the challenges of determining the interdependencies and creating models capable of describing the complexity of an urban environment with the data publically available. Integration of such data as is derived from public domain sources is readily achieved in a geospatial environment, after all geospatial infrastructure data are the most abundant data source and while significant quantities of data can be acquired through public sources, a significant effort is still required to gather, develop, and integrate these data from multiple sources to build a complete model. Therefore, while continued availability of high quality, public information is essential for modeling efforts in academic as well as government communities, a more streamlined approach to a real-time acquisition and integration of these data is essential

Daksha: On Alert for High Energy Transients

We present Daksha, a proposed high energy transients mission for the study of electromagnetic counterparts of gravitational wave sources, and gamma ray bursts. Daksha will comprise of two satellites in low earth equatorial orbits, on opposite sides of earth. Each satellite will carry three types of detectors to cover the entire sky in an energy range from 1 keV to >1 MeV. Any transients detected on-board will be announced publicly within minutes of discovery. All photon data will be downloaded in ground station passes to obtain source positions, spectra, and light curves. In addition, Daksha will address a wide range of science cases including monitoring X-ray pulsars, studies of magnetars, solar flares, searches for fast radio burst counterparts, routine monitoring of bright persistent high energy sources, terrestrial gamma-ray flashes, and probing primordial black hole abundances through lensing. In this paper, we discuss the technical capabilities of Daksha, while the detailed science case is discussed in a separate paper.Comment: 9 pages, 3 figures, 1 table. Additional information about the mission is available at https://www.dakshasat.in

Science with the Daksha High Energy Transients Mission

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Topics in video game technology

Artificial Intelligence has been a critical part of video games for a long time and is becoming increasingly more complex with modern-day games. Gamers look for smarter opponents and tougher bots to engage them and this has led to AI\u27s being a much more important component of a game than it ever was. Our initial work dealt with emergent behaviors and their potential impact on games. We built a Predator-Prey ecosystem simulation and analyzed the Lotka-Volterra model. We then explored its potential uses in resource collection based strategy-games. The second part of this work was an analysis of the relationship between prey and vegetation. We developed a more realistic vegetation growth model and studied the relationship between consumption and growth. The goal of the final part of our work was to build a racing game based on the Graph Camera concept as described by Popescu et al

Modeling supply chain network resiliency in the aftermath of an extreme event

Failure of infrastructure elements due to an extreme event adversely affects the supply chain networks in any urban environment. This study models the resiliency of a supply chain network by integrating geospatial data with critical supply chain elements and graph theory. This model can then be combined with an extreme event simulation to calculate resiliency. Resiliency refers to the time required for services and select economic indicators to approach pre-event levels (in this study, a return to 80% of the pre-event capacity). This research proposes an interdisciplinary approach to develop a comprehensive framework for resiliency modeling. This approach includes the integration of: graph theory, geospatial data, supply chain assessment, and hazards risk analysis. A geographic information system (GIS) is constructed from data extracted or derived from The National Map of the U.S. Geological Survey for Johnson County, Kansas in the Greater Kansas City area. These data are used to generate a combinatorial graph from which resiliency is calculated in the aftermath of a simulated EF-5 tornado. The graph shows the interconnectivity between the different supply chain elements, as well as the inter-dependability among them. Reconstruction in the aftermath of the tornado simulation is manipulated to promote a rapid recovery of the supply chain network. These results are then compared with ground truth data for the EF-5 tornado that devastated Joplin, Missouri on 22 May 2011. Preliminary results show a good level of agreement between the constructed model and real-world events --Abstract, page iii

Framework for Modeling Urban Restoration Resilience Time in the Aftermath of an Extreme Event

The impacts of extreme events continue long after the emergency response has terminated. Effective reconstruction of supply-chain strategic infrastructure (SCSI) elements is essential for postevent recovery and the reconnectivity of a region with the outside. This study uses an interdisciplinary approach to develop a comprehensive framework to model resilience time. The framework is tested by comparing resilience time results for a simulated EF-5 tornado with ground truth data from the tornado that devastated Joplin, Missouri, on May 22, 2011. Data for the simulated tornado were derived for Overland Park, Johnson County, Kansas, in the greater Kansas City, Missouri, area. Given the simulated tornado, a combinatorial graph considering the damages in terms of interconnectivity between different SCSI elements is derived. Reconstruction in the aftermath of the simulated tornado is optimized using the proposed framework to promote a rapid recovery of the SCSI. This research shows promising results when compared with the independent quantifiable data obtained from Joplin, Missouri, returning a resilience time of 22 days compared with 25 days reported by city and state official