What is wrong with consumerism

Contemporary consumerism is frequently the target of criticisms by intellectuals, academics, religious spokesmen and commentators. Five of the more common of these criticisms are selected for analysis and examination; these being (a) the need criticism (b) the materialism criticism (c) the addiction criticism (d) the selfishness criticism, and (e) the irrationality criticism. Each is then shown either to be misconceived or to lack empirical support

HDAC inhibitors increase NRF2-signaling in tumour cells and blunt the efficacy of co-adminstered cytotoxic agents

The NRF2 signalling cascade provides a primary response against electrophilic chemicals and oxidative stress. The activation of NRF2-signaling is anticipated to have adverse clinical consequences; NRF2 is activated in a number of cancers and, additionally, its pharmacological activation by one compound can reduce the toxicity or efficiency of a second agent administered concomitantly. In this work, we have analysed systematically the ability of 152 research, pre-clinical or clinically used drugs to induce an NRF2 response using the MCF7-AREc32 NRF2 reporter. Ten percent of the tested drugs induced an NRF2 response. The NRF2 activators were not restricted to classical cytotoxic alkylating agents but also included a number of emerging anticancer drugs, including an IGF1-R inhibitor (NVP-AEW541), a PIM-1 kinase inhibitor (Pim1 inhibitor 2), a PLK1 inhibitor (BI 2536) and most strikingly seven of nine tested HDAC inhibitors. These findings were further confirmed by demonstrating NRF2-dependent induction of endogenous AKR genes, biomarkers of NRF2 activity. The ability of HDAC inhibitors to stimulate NRF2-signalling did not diminish their own potency as antitumour agents. However, when used to pre-treat cells, they did reduce the efficacy of acrolein. Taken together, our data suggest that the ability of drugs to stimulate NRF2 activity is common and should be investigated as part of the drug-development process

Solar sail formation flying for deep-space remote sensing

In this paper we consider how 'near' term solar sails can be used in formation above the ecliptic plane to provide platforms for accurate and continuous remote sensing of the polar regions of the Earth. The dynamics of the solar sail elliptical restricted three-body problem (ERTBP) are exploited for formation flying by identifying a family of periodic orbits above the ecliptic plane. Moreover, we find a family of 1 year periodic orbits where each orbit corresponds to a unique solar sail orientation using a numerical continuation method. It is found through a number of example numerical simulations that this family of orbits can be used for solar sail formation flying. Furthermore, it is illustrated numerically that Solar Sails can provide stable formation keeping platforms that are robust to injection errors. In addition practical trajectories that pass close to the Earth and wind onto these periodic orbits above the ecliptic are identified

Biochip sensors for the rapid and sensitive detection of viral disease

Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. The advantages of the multi-parameter microarray technologies could be combined with the speed and sensitivity of cell-based systems to give 'cell-omic' sensors

Evaluation of a tumor microenvironment-based prognostic score in primary operable colorectal cancer

Purpose: The tumor microenvironment is recognized as an important determinant of progression and outcome in colorectal cancer. The aim of the present study was to evaluate a novel tumor microenvironment–based prognostic score, based on histopathologic assessment of the tumor inflammatory cell infiltrate and tumor stroma, in patients with primary operable colorectal cancer. Experimental Design: Using routine pathologic sections, the tumor inflammatory cell infiltrate and stroma were assessed using Klintrup–Mäkinen (KM) grade and tumor stroma percentage (TSP), respectively, in 307 patients who had undergone elective resection for stage I–III colorectal cancer. The clinical utility of a cumulative score based on these characteristics was examined. Results: On univariate analysis, both weak KM grade and high TSP were associated with reduced survival (HR, 2.42; P = 0.001 and HR, 2.05; P = 0.001, respectively). A cumulative score based on these characteristics, the Glasgow Microenvironment Score (GMS), was associated with survival (HR, 1.93; 95% confidence interval, 1.36–2.73; P < 0.001), independent of TNM stage and venous invasion (both P < 0.05). GMS stratified patients in to three prognostic groups: strong KM (GMS = 0), weak KM/low TSP (GMS = 1), and weak KM/high TSP (GMS = 2), with 5-year survival of 89%, 75%, and 51%, respectively (P < 0.001). Furthermore, GMS in combination with node involvement, venous invasion, and mismatch repair status further stratified 5-year survival (92% to 37%, 93% to 27%, and 100% to 37%, respectively). Conclusions: The present study further confirms the clinical utility of assessment of the tumor microenvironment in colorectal cancer and introduces a simple, routinely available prognostic score for the risk stratification of patients with primary operable colorectal cancer

Application of the Todd-Coxeter coset enumeration algorithm

This thesis is concerned with a topic in combinatorial group theory and, in particular, with a study of some groups with finite presentations. After preliminary definitions and theorems we describe the Todd-Coxeter coset enumeration algorithm and the modified Todd-Coxeter algorithm which shows that, given a finitely generated subgroup H of finite index in a finitely presented group G, we can find a presentation for H. We then give elementary examples illustrating the algorithms and include a discussion on the computer programmes that are to be used. In the main part of the thesis we investigate two classes of cyclically presented groups. Supposewhere w1 = w is a word in a1,a2,...,an, and wi+1 is obtained from wi by applying the permutation (1 2 ... n) to the suffices of the a's. The first class we investigate are the groups that is the groups G(l,m,n) are groups of type G2 (w). Secondly we investigate the Fibonacci-type groups H(r,n,k,s,h) obtained when, for some integers r,s,h > 1, k > O, the word w is given by Fibonacci groups being the special case given by k = s = h = 1. For both classes we begin by giving some homomorphisms and isomorphisms that may be obtained. We show, using the Todd-Coxeter algorithm when appropriate, that the six groups G(2,2,3), G(2,2,-3), G(-l,-l,4), G(2,3,-2), G(-2,2,-1) and G(-2,3,l) are finite non-metacyclic groups of deficiency zero, having orders 215.33, 28.33, 29.3.5, 23.33.7, 23.3.5.11 amd 23.36 respectively. We also show that the groups G(1-n, 6, n) where n = 1 mod 5 give an infinite series of non-metacyclic groups. We consider the structure of the non-metacyclic groups H(3,6,1,1,1) and H(3,6,5,l,2) both of order 1512, showing that neither is isomorphic to G(2, 3, -2) another non-metacyclic group of order 1512. In a paper on the Fibonacci groups D.L. Johnson, J.W. Wamsley and D. Wright pose two questions relating to the Fibonacci groups for the case r = 1 mod n, namely to find 2-generator 2-relation presentations for them and also their orders. We answer these questions and generalise the results to the class H(r,n,k,s,1) where it is shown that H(r,n,k,s,1) is metacyclic if (i) r = s mod n, (ii) (r,n) = 1, (iii) (r + k - 1, n) - 1, and a 2-generator 2-relation presentation is found for these groups. Further if (iv) (r,s) = 1, then we show that H(r,n,k,s,1) is a finite metacyclic group of order rn - sn. A possible generalisation to the groups H(r,n,k,s,h) is considered. Finally the metacyclic groups H(r,4,1,2,1), r odd are discussed

Boolean Networks as Predictive Models of Emergent Biological Behaviors

Interacting biological systems at all organizational levels display emergent behavior. Modeling these systems is made challenging by the number and variety of biological components and interactions (from molecules in gene regulatory networks to species in ecological networks) and the often-incomplete state of system knowledge (e.g., the unknown values of kinetic parameters for biochemical reactions). Boolean networks have emerged as a powerful tool for modeling these systems. We provide a methodological overview of Boolean network models of biological systems. After a brief introduction, we describe the process of building, analyzing, and validating a Boolean model. We then present the use of the model to make predictions about the system's response to perturbations and about how to control (or at least influence) its behavior. We emphasize the interplay between structural and dynamical properties of Boolean networks and illustrate them in three case studies from disparate levels of biological organization.Comment: Review, to appear in the Cambridge Elements serie

Next-Generation Evaporative Cooling Systems for the Advanced Extravehicular Mobility Unit Portable Life Support System

The development of the Advanced Extravehicular Mobility Unit (AEMU) Portable Life Support System (PLSS) is currently underway at NASA Johnson Space Center. The AEMU PLSS features two new evaporative cooling systems, the Reduced Volume Prototype Spacesuit Water Membrane Evaporator (RVP SWME), and the Auxiliary Cooling Loop (ACL). The RVP SWME is the third generation of hollow fiber SWME hardware, and like its predecessors, RVP SWME provides nominal crewmember and electronics cooling by flowing water through porous hollow fibers. Water vapor escapes through the hollow fiber pores, thereby cooling the liquid water that remains inside of the fibers. This cooled water is then recirculated to remove heat from the crewmember and PLSS electronics. Major design improvements, including a 36% reduction in volume, reduced weight, and more flight like back-pressure valve, facilitate the packaging of RVP SWME in the AEMU PLSS envelope. In addition to the RVP SWME, the Auxiliary Cooling Loop (ACL), was developed for contingency crewmember cooling. The ACL is a completely redundant, independent cooling system that consists of a small evaporative cooler--the Mini Membrane Evaporator (Mini-ME), independent pump, independent feed-water assembly and independent Liquid Cooling Garment (LCG). The Mini-ME utilizes the same hollow fiber technology featured in the RVP SWME, but is only 25% of the size of RVP SWME, providing only the necessary crewmember cooling in a contingency situation. The ACL provides a number of benefits when compared with the current EMU PLSS contingency cooling technology; contingency crewmember cooling can be provided for a longer period of time, more contingency situations can be accounted for, no reliance on a Secondary Oxygen Vessel (SOV) for contingency cooling--thereby allowing a SOV reduction in size and pressure, and the ACL can be recharged-allowing the AEMU PLSS to be reused, even after a contingency event. The development of these evaporative cooling systems will contribute to a more robust and comprehensive AEMU PLSS

Reduced Volume Prototype Spacesuit Water Membrane Evaporator; A Next-Generation Evaporative Cooling System for the Advanced Extravehicular Mobility Unit Portable Life Support System

Development of the Advanced Extravehicular Mobility Unit (AEMU) portable life support subsystem (PLSS) is currently under way at NASA Johnson Space Center. The AEMU PLSS features a new evaporative cooling system, the reduced volume prototype (RVP) spacesuit water membrane evaporator (SWME). The RVP SWME is the third generation of hollow fiber SWME hardware. Like its predecessors, RVP SWME provides nominal crew member and electronics cooling by flowing water through porous hollow fibers. Water vapor escapes through the hollow fiber pores, thereby cooling the liquid water that remains inside of the fibers. This cooled water is then recirculated to remove heat from the crew member and PLSS electronics. Major design improvements, including a 36% reduction in volume, reduced weight, and a more flight-like backpressure valve, facilitate the packaging of RVP SWME in the AEMU PLSS envelope. The development of these evaporative cooling systems will contribute to a more robust and comprehensive AEMU PLSS

Design and Evaluation of a Water Recirculation Loop Maintenance Device for the Advanced Spacesuit Water Membrane Evaporator

A dual-bed device to maintain the water quality of the Advanced Spacesuit Water Membrane Evaporation (SWME) water recirculation loop has been designed and is undergoing testing. The SWME is a heat rejection device under development at the NASA Johnson Space Center to perform thermal control for advanced spacesuits. One advantage to this technology is the potential for a significantly greater degree of tolerance to contamination when compared to the existing Sublimator technology. The driver for the development of a water recirculation maintenance device is to further enhance this advantage through the leveraging of fluid loop management lessons-learned from the International Space Station (ISS). A bed design that was developed for a Hamilton Sundstrand military application, and considered for a potential ISS application with the Urine Processor Assembly, provides a low pressure drop means for water maintenance in a recirculation loop. The bed design is coupled with high capacity ion exchange resins, organic adsorbents, and a cyclic methodology developed for the Extravehicular Mobility Unit (EMU) Transport Water loop. The bed design further leverages a sorbent developed for ISS that introduces a biocide in a microgravity-compatible manner for the Internal Active Thermal Control System (IATCS). The leveraging of these water maintenance technologies to the SWME recirculation loop is a clear demonstration of applying the valuable lessons learned on the ISS to the next generation of manned spaceflight Environmental Control and Life Support System (ECLSS) hardware