An Online Decision-Theoretic Pipeline for Responder Dispatch

The problem of dispatching emergency responders to service traffic accidents, fire, distress calls and crimes plagues urban areas across the globe. While such problems have been extensively looked at, most approaches are offline. Such methodologies fail to capture the dynamically changing environments under which critical emergency response occurs, and therefore, fail to be implemented in practice. Any holistic approach towards creating a pipeline for effective emergency response must also look at other challenges that it subsumes - predicting when and where incidents happen and understanding the changing environmental dynamics. We describe a system that collectively deals with all these problems in an online manner, meaning that the models get updated with streaming data sources. We highlight why such an approach is crucial to the effectiveness of emergency response, and present an algorithmic framework that can compute promising actions for a given decision-theoretic model for responder dispatch. We argue that carefully crafted heuristic measures can balance the trade-off between computational time and the quality of solutions achieved and highlight why such an approach is more scalable and tractable than traditional approaches. We also present an online mechanism for incident prediction, as well as an approach based on recurrent neural networks for learning and predicting environmental features that affect responder dispatch. We compare our methodology with prior state-of-the-art and existing dispatch strategies in the field, which show that our approach results in a reduction in response time with a drastic reduction in computational time.Comment: Appeared in ICCPS 201

Nicotinic Receptors Underlying Nicotine Dependence: Evidence from Transgenic Mouse Models.

Nicotine underlies the reinforcing properties of tobacco cigarettes and e-cigarettes. After inhalation and absorption, nicotine binds to various nicotinic acetylcholine receptor (nAChR) subtypes localized on the pre- and postsynaptic membranes of cells, which subsequently leads to the modulation of cellular function and neurotransmitter signaling. In this chapter, we begin by briefly reviewing the current understanding of nicotine's actions on nAChRs and highlight considerations regarding nAChR subtype localization and pharmacodynamics. Thereafter, we discuss the seminal discoveries derived from genetically modified mouse models, which have greatly contributed to our understanding of nicotine's effects on the reward-related mesolimbic pathway and the aversion-related habenulo-interpeduncular pathway. Thereafter, emerging areas of research focusing on modulation of nAChR expression and/or function are considered. Taken together, these discoveries have provided a foundational understanding of various genetic, neurobiological, and behavioral factors underlying the motivation to use nicotine and related dependence processes, which are thereby advancing drug discovery efforts to promote long-term abstinence

Diffusion tensor imaging and fiber tractography of the median nerve at 1.5T: optimization of b value

OBJECTIVE: The objective of this study was to systematically assess the optimal b value for diffusion tensor imaging and fiber tractography of the median nerve at 1.5 T. MATERIALS AND METHODS: This is a prospective study which was carried out with institutional review board approval and written informed consent from the study subjects. Fifteen healthy volunteers (seven men, eight women; mean age, 31.2 years) underwent diffusion tensor imaging of the wrist. A single-shot spin-echo-based echo-planar imaging sequence (TR/TE, 7000/103 ms) was performed in each subject at eight different b values ranging from 325 to 1,550 s/mm(2). Number and length of reconstructed fiber tracts, fiber density index (FDi), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were calculated for the median nerve. Signal-to-noise ratio (SNR) was also calculated for each acquisition. The overall image quality was assessed by two readers in consensus by ranking representative fiber tract images for each subject using a scale range from 1 to 8 (1 = best to 8 = worst image quality). RESULTS: Longest fibers were observed for b values between 675 and 1,025 s/mm(2). Maximum FDi was found at b values of 1,025 s/mm(2). FA was between 0.5 and 0.6 for all b values. ADC gradually decreased from 1.44 x 10(-3) to 0.92 x 10(-3) mm(2)/s with increasing b values. Maximum SNR +/- standard deviation (175.4 +/- 72.6) was observed at the lowest b value and decreased with increasing b values. SNR at b values of 1,025 s/mm(2) was 48.5% of the maximum SNR. Optimal fiber tract image quality was found for b values of 1,025 s/mm(2). CONCLUSIONS: The optimal b value for diffusion tensor imaging and fiber tractography of the median nerve at 1.5 T was 1,025 s/mm(2)

Deregulation of CRAD-controlled cytoskeleton initiates mucinous colorectal cancer via β-catenin

Epithelial integrity is maintained by the cytoskeleton and through cell adhesion. However, it is not yet known how a deregulated cytoskeleton is associated with cancer. We identified cancer-related regulator of actin dynamics (CRAD) as frequently mutated or transcriptionally downregulated in colorectal cancer. We found that CRAD stabilizes the cadherin-catenin-actin complex via capping protein inhibition. The loss of CRAD inhibits F-actin polymerization and subsequently disrupts the cadherin-catenin-actin complex, which leads to β-catenin release and Wnt signalling hyperactivation. In mice, CRAD knockout induces epithelial cell integrity loss and Wnt signalling activation, resulting in the development of intestinal mucinous adenoma. With APC mutation, CRAD knockout initiates and accelerates mucinous and invasive adenoma development in the colorectum. These results define CRAD as a tumour suppressor, the inactivation of which deregulates the cytoskeleton and hyperactivates Wnt signalling thus initiating mucinous colorectal cancer. Our study reveals the unexpected roles of an actin cytoskeletal regulator in maintaining epithelial cell integrity and suppressing tumorigenesis

The genetic basis of flowering responses to seasonal cues

Plants respond to the changing seasons to initiate developmental programmes precisely at particular times of year. Flowering is the best characterized of these seasonal responses, and in temperate climates it often occurs in spring. Genetic approaches in Arabidopsis thaliana have shown how the underlying responses to changes in day length (photoperiod) or winter temperature (vernalization) are conferred and how these converge to create a robust seasonal response. Recent advances in plant genome analysis have demonstrated the diversity in these regulatory systems in many plant species, including several crops and perennials, such as poplar trees. Here, we report progress in defining the diverse genetic mechanisms that enable plants to recognize winter, spring and autumn to initiate flower development

Down’s syndrome, neuroinflammation, and Alzheimer neuropathogenesis

Down syndrome (DS) is the result of triplication of chromosome 21 (trisomy 21) and is the prevailing cause of mental retardation. In addition to the mental deficiencies and physical anomalies noted at birth, triplication of chromosome 21 gene products results in the neuropathological and cognitive changes of Alzheimer’s disease (AD). Mapping of the gene that encodes the precursor protein (APP) of the β-amyloid (Aβ) present in the Aβ plaques in both AD and DS to chromosome 21 was strong evidence that this chromosome 21 gene product was a principal neuropathogenic culprit in AD as well as DS. The discovery of neuroinflammatory changes, including dramatic proliferation of activated glia overexpressing a chromosome 2 gene product - the pluripotent immune cytokine interleukin-1 (IL-1) - and a chromosome 21 gene product - S100B - in the brains of fetuses, neonates, and children with DS opened the possibility that early events in Alzheimer pathogenesis were driven by cytokines. The specific chromosome 21 gene products and the complexity of the mechanisms they engender that give rise to the neuroinflammatory responses noted in fetal development of the DS brain and their potential as accelerators of Alzheimer neuropathogenesis in DS are topics of this review, particularly as they relate to development and propagation of neuroinflammation, the consequences of which are recognized clinically and neuropathologically as Alzheimer’s disease