Costs and Rewards in Priced Timed Automata

We consider Pareto analysis of reachable states of multi-priced timed automata (MPTA): timed automata equipped with multiple observers that keep track of costs (to be minimised) and rewards (to be maximised) along a computation. Each observer has a constant non-negative derivative which may depend on the location of the MPTA. We study the Pareto Domination Problem, which asks whether it is possible to reach a target location via a run in which the accumulated costs and rewards Pareto dominate a given objective vector. We show that this problem is undecidable in general, but decidable for MPTA with at most three observers. For MPTA whose observers are all costs or all rewards, we show that the Pareto Domination Problem is PSPACE-complete. We also consider an epsilon-approximate Pareto Domination Problem that is decidable without restricting the number and types of observers. We develop connections between MPTA and Diophantine equations. Undecidability of the Pareto Domination Problem is shown by reduction from Hilbert\u27s 10^{th} Problem, while decidability for three observers is shown by a translation to a fragment of arithmetic involving quadratic forms

Estimating the Impact of Understaffing on Sales and Profitability in Retail Stores

In this paper we use micro-level data on store traffic, sales and labor from 41 stores of a large retail chain to identify the extent of understaffing in retail stores and quantify its impact on sales and profitability. We show how traffic data can be leveraged in making staffing decisions through use of a structural model that captures the relationship between traffic, sales and labor. Assuming that store managers aim to maximize profits, we estimate the contribution of labor to sales and impute the cost of labor for each store in our sample. We find significant heterogeneity in the contribution of labor to sales as well as imputed cost of labor across these stores and across time. Using the estimated parameters, we establish the presence of systematic understaffing during peak hours. Aligning staffing levels with changing traffic patterns can result in a 6.15% savings in lost sales and a 5.74% improvement in profitability. We describe a pilot implementation of our approach at another large retailer where we identify periods of understaffing in their stores and document the impact on conversion rate and lost sales

SFRP4 signalling of apoptosis and angiostasis uses nitric oxide-cGMP-permeability axis of endothelium

Nitric oxide (NO) plays a critical role in endothelial functions such as cellular migration, vascular permeability and angiogenesis. Angiogenesis, the formation of new blood vessels from "pre-existing" ones is a carefully regulated process and essential during reproduction, development and wound healing. Previously our lab group reported that Secreted Frizzled-Related Protein 4 (sFRP4) could inhibit angiogenesis in both in vitro and in vivo conditions. sFRP4 belongs to a family of secreted glycoproteins that function as antagonists of the canonical Wnt signalling pathway. Although the pro-apoptotic role of sFRP4 is well discussed in literature, little is known in regards to its anti-angiogenic property. The objective of this study was to elucidate sFRP4 implications in NO biology of the endothelium. Results demonstrate that sFRP4 causes endothelial dysfunction by suppressing NO-cGMP signaling and elevating corresponding ROS levels. The imbalance between NO and ROS levels results in apoptosis and subsequent leakiness of endothelium as confirmed in vivo (Texas red/Annxin - CAM assay) and in vitro (Monolayer permeability assay) conditions. Furthermore utilizing peptides synthesized from the CRD domain of sFRP4, our results showed that while these peptides were able to cause endothelial dysfunctions, they did not cause apoptosis of the endothelial cells. Thereby confirming that sFRP4 can mediate its anti-angiogenic effect independent of its pro-apoptotic property. In conclusion, the current study reports that sFRP4-mediated anti-angiogenesis occurs as a result of impaired NO-cGMP signaling which in turn allow for elevation of redox levels and promotion of apoptosis of endothelial cells

Breast cancer nutritional chemistry cachexia oncology – A clinical trials perspective

1369-1371Breast cancer is the second largest killer disease among women globally. Annually approximately 48,000 women die of breast cancer. Breast cancer patients are at high risk of developing malnutrition from the underlying disease as well as from various drug regimen, chemotherapy and or radiotherapy interventions. As we work for personalized medicine for breast cancer, a personalized nutrition for breast cancer patients is much needed for their wellbeing both physiologically and psychologically. Most rather than all, of the treatment regimens possesses a concourse of side effects. An effective personalized nutritional therapy during and after cancer treatment leads to better quality of life for the breast cancer patients. Clinical trials are pivotal for any recommendations to be used at the commercial level upon approval of Food & Drug Administration. Several clinical trials have been carried out and many are now undertaken to come up with a significant upshot conclusion based on primary and secondary outcomes to show the after effects of particular nutrient supplements by increasing the overall survival or any other physiological upregulated / downregulated manifestation leading for a disease free survival. Docosahexaenoic acid and glutamine nutritional supplement has been reported to have beneficial effect for breast cancer patients in different clinical trials

Breast cancer nutritional chemistry cachexia oncology – A clinical trials perspective

Breast cancer is the second largest killer disease among women globally. Annually approximately 48,000 women die of breast cancer. Breast cancer patients are at high risk of developing malnutrition from the underlying disease as well as from various drug regimen, chemotherapy and or radiotherapy interventions. As we work for personalized medicine for breast cancer, a personalized nutrition for breast cancer patients is much needed for their wellbeing both physiologically and psychologically. Most rather than all, of the treatment regimens possesses a concourse of side effects. An effective personalized nutritional therapy during and after cancer treatment leads to better quality of life for the breast cancer patients. Clinical trials are pivotal for any recommendations to be used at the commercial level upon approval of Food & Drug Administration. Several clinical trials have been carried out and many are now undertaken to come up with a significant upshot conclusion based on primary and secondary outcomes to show the after effects of particular nutrient supplements by increasing the overall survival or any other physiological upregulated / downregulated manifestation leading for a disease free survival. Docosahexaenoic acid and glutamine nutritional supplement has been reported to have beneficial effect for breast cancer patients in different clinical trials

Diffusion of a soluble protein, photoactivatable GFP, through a sensory cilium

Transport of proteins to and from cilia is crucial for normal cell function and survival, and interruption of transport has been implicated in degenerative and neoplastic diseases. It has been hypothesized that the ciliary axoneme and structures adjacent to and including the basal bodies of cilia impose selective barriers to the movement of proteins into and out of the cilium. To examine this hypothesis, using confocal and multiphoton microscopy we determined the mobility of the highly soluble photoactivatable green fluorescent protein (PAGFP) in the connecting cilium (CC) of live Xenopus retinal rod photoreceptors, and in the contiguous subcellular compartments bridged by the CC, the inner segment (IS) and the outer segment (OS). The estimated axial diffusion coefficients are DCC = 2.8 ± 0.3, DIS = 5.2 ± 0.6, and DOS = 0.079 ± 0.009 µm2 s−1. The results establish that the CC does not pose a major barrier to protein diffusion within the rod cell. However, the results also reveal that axial diffusion in each of the rod’s compartments is substantially retarded relative to aqueous solution: the axial diffusion of PAGFP was retarded ∼18-, 32- and 1,000-fold in the IS, CC, and OS, respectively, with ∼20-fold of the reduction in the OS attributable to tortuosity imposed by the lamellar disc membranes. Previous investigation of PAGFP diffusion in passed, spherical Chinese hamster ovary cells yielded DCHO = 20 µm2 s−1, and estimating cytoplasmic viscosity as Daq/DCHO = 4.5, the residual 3- to 10-fold reduction in PAGFP diffusion is ascribed to sub-optical resolution structures in the IS, CC, and OS compartments

Network centrality and organizational aspirations: A behavioral interaction in the context of international strategic alliances

Whereas social network analysis has been associated with organizational aspirations, little is known on how firm's structural positioning, and particularly network centrality, affects organizational aspirations to engage in international strategic alliances (ISA). This study examines the impact of network centrality on firm's internationalization behavior within the ISA domain in response to the performance-aspiration gap. We build on social and behavioral perspectives to predict that network centrality and performance-based aspirations will be associated with the number of ISA the firm engages in. Using a sample of 7760 alliance collaborations from the top 81 global pharmaceutical firms for the period of 1991-2012, we find supporting evidence for most of our arguments

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention