Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth

One classical feature of cancer cells is their metabolic acquisition of a highly glycolytic phenotype. Carbon monoxide (CO), one of the products of the cytoprotective molecule heme oxygenase-1 (HO-1) in cancer cells, has been implicated in carcinogenesis and therapeutic resistance. However, the functional contributions of CO and HO-1 to these processes are poorly defined. In human prostate cancers, we found that HO-1 was nuclear localized in malignant cells, with low enzymatic activity in moderately differentiated tumors correlating with relatively worse clinical outcomes. Exposure to CO sensitized prostate cancer cells but not normal cells to chemotherapy, with growth arrest and apoptosis induced in vivo in part throughmitotic catastrophe. CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption, free radical generation, and mitochondrial collapse. Collectively, our findings indicated that CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell bioenergetics, ultimately resulting in metabolic exhaustion. ©2013 AACR.

Abusive supervision and contextual performance:The mediating role of emotional exhaustion and the moderating role of work unit structure

This study examined the processes linking abusive supervision to employee contextual performance by focusing on the mediating influence of emotional exhaustion and the moderating influence of work unit structure. Data were obtained from 285 subordinate-supervisor dyads from three manufacturing companies in north-eastern China. The results revealed that: (i) emotional exhaustion mediated the relationships between abusive supervision and the contextual performance dimensions of interpersonal facilitation and job dedication; and (ii) work unit structure moderated these relationships such that the relationships were stronger in mechanistic than in organic work unit structures. © 2008 Blackwell Publishing Ltd.

Uneasy lies the head that bears the trust:the effects of feeling trusted on emotional exhaustion

The construct of feeling trusted reflects the perception that another party is willing to accept vulnerability to one's actions. Although this construct has received far less attention than trusting, the consensus is that believing their supervisors trust them has benefits for employees' job performance. Our study challenges that consensus by arguing that feeling trusted can be exhausting for employees. Drawing on Stevan Hobfoll's conservation of resources theory, we develop a model in which feeling trusted fills an employee with pride a benefit for exhaustion and performance while also increasing perceived workload and concerns about reputation maintenance burdens for exhaustion and performance. We test our model in a field study using a sample of public transit bus drivers in London, England. Our results suggest that feeling trusted is a double-edged sword for job performance, bringing with it both benefits and burdens. Given that recommendations for managers generally encourage placing trust in employees, these results have important practical implications.

Design of improved membrane protein production experiments:quantitation of the host response

Eukaryotic membrane proteins cannot be produced in a reliable manner for structural analysis. Consequently, researchers still rely on trial-and-error approaches, which most often yield insufficient amounts. This means that membrane protein production is recognized by biologists as the primary bottleneck in contemporary structural genomics programs. Here, we describe a study to examine the reasons for successes and failures in recombinant membrane protein production in yeast, at the level of the host cell, by systematically quantifying cultures in high-performance bioreactors under tightlydefined growth regimes. Our data show that the most rapid growth conditions of those chosen are not the optimal production conditions. Furthermore, the growth phase at which the cells are harvested is critical: We show that it is crucial to grow cells under tightly-controlled conditions and to harvest them prior to glucose exhaustion, just before the diauxic shift. The differences in membrane protein yields that we observe under different culture conditions are not reflected in corresponding changes in mRNA levels of FPS1, but rather can be related to the differential expression of genes involved in membrane protein secretion and yeast cellular physiology. Copyright © 2005 The Protein Society.

The effects of changes in recycling patterns on United Kingdom resource consumption

Recycling, substitution and product life extension are identified as significant factors contributing to an extension of the time to exhaustion of industrially Dnportant materials. A quantitative assessment of the significance of virtually all materials to the U.K. is made. Copper is identified as one of the most important materials deserving of further investigation into potential resource savings through increased recycling. The other factors listed above are accounted for in the modelling technique employed. United Kingdom copper flows are qualitatively and statistically described for the years 1949 - 1976. Less accurate statistics are developed for 1922 - 1948. Adaptive expectations type causal models of total, unalloyed, and alloyed copper demand are successfully constructed and are used to generate future scenarios. Evidence is demonstrated for a break in the historical link between U.K. copper demand and industrial production. Simple causal models of potential copper scrap supply are constructed and a comparison made with actual old scrap withdrawals. Accurate adaptive expectations type models of total scrap demand are developed, but no conclusion is reached about the price elasticity of scrap demand. Various scenarios of copper goods demand are forecast and their effect on copper scrap demand. The potential to recover up to an extra 100.000 tonnes/year of generally lower grade old scrap is identified. Policy options are examined and the following recommendations made: 1) A total investment of up to £67 million in secondary refining capacity by the year 2000 is needed. 2) The copper scrap content of copper bearing goods should be specified to aid recovery. 3) A U.K. copper scrap buffer stock scheme would be advantageous for the secondary copper industry. Finally the methodology used is summarised for potential application to other materials.

Sales manager problem resolution styles:measure development and an examination of their salesperson-related consequences

Personal selling and sales management play a critical role in the short and long term success of the firm, and have thus received substantial academic interest since the 1970s. Sales research has examined the role of the sales manager in some depth, defining a number of key technical and interpersonal roles which sales managers have in influencing sales force effectiveness. However, one aspect of sales management which appears to remain unexplored is that of their resolution of salesperson-related problems. This study represents the first attempt to address this gap by reporting on the conceptual and empirical development of an instrument designed to measure sales managers' problem resolution styles. A comprehensive literature review and qualitative research study identified three key constructs relating to sales managers' problem resolution styles. The three constructs identified were termed; sales manager willingness to respond, sales manager caring, and sales manager aggressiveness. Building on this, existing literature was used to develop a conceptual model of salesperson-specific consequences of the three problem resolution style constructs. The quantitative phase of the study consisted of a mail survey of UK salespeople, achieving a total sample of 140 fully usable responses. Rigorous statistical assessment of the sales manager problem resolution style measures was undertaken, and construct validity examined. Following this, the conceptual model was tested using latent variable path analysis. The results for the model were encouraging overall, and also with regard to the individual hypotheses. Sales manager problem resolution styles were found individually to have significant impacts on the salesperson-specific variables of role ambiguity, emotional exhaustion, job satisfaction, organisational commitment and organisational citizenship behaviours. The findings, theoretical and managerial implications, limitations and directions for future research are discussed.

Work-related stressors and psychological strain in the sales force:the role of intrinsic and extrinsic motivation

The contemporary workplace appears rife with psychological strain, which can have considerable deleterious outcomes to the firm and the individual. However, research on strain in the sales force is underdeveloped. This paper reports the results of a study of the antecedents and consequences of psychological strain in the sales force, with particular attention to the roles of role ambiguity, emotional exhaustion, and intrinsic and extrinsic motivation. Emotional exhaustion is found to increase strain. Intrinsic motivation reduces strain under conditions of relatively high role ambiguity, but leads to more strain under conditions of low role ambiguity. Strain is found to have a J-shaped relationship with turnover intentions, and is linearly related to lower job satisfaction and lower job performance.

Gesundheitsrisiken bei Unternehmern

An einer Studie zum Zusammenhang zwischen der Gesundheit von Unternehmern, deren Arbeitsmerkmalen und deren Erfolg nahmen 53 klein- und mittelständische Unternehmer teil. Erfasste Arbeitsmerkmale waren: Handlungs-/Entscheidungsspielraum, Arbeitsintensität, Arbeitszeit, Konkurrenzdruck und Prognose über die Auftragsentwicklung. Der Unternehmenserfolg wurde über das Mitarbeiterwachstum, die Möglichkeit des Unternehmers, von seiner Firma abwesend zu sein (Urlaubstage), und dem erlebten Unternehmenserfolg operationalisiert. Gesundheitsindikatoren waren Depression, Angst, vitale Erschöpfung, Schlafstörungen und Bluthochdruck. Im Vergleich zur Gesamtbevölkerung wiesen die Unternehmer in allen untersuchten Gesundheitsvariablen häufiger Beeinträchtigungen auf. Regressionsanalysen ergaben, dass lange Arbeitszeiten und Konkurrenzdruck mit einer verzögerten Rückstellung des systolischen Blutdrucks (SBD) in der Freizeit und Nacht einhergingen. Alle untersuchten Erfolgsmerkmale waren für die Gesundheit prädiktiv. So war Mitarbeiterwachstum negativ mit dem SBD während der Arbeit sowie Schlafstörungen assoziiert. Je mehr Unternehmenserfolg erlebt wurde, desto geringer waren die Werte für vitale Erschöpfung und Depression. Die Urlaubsdauer war negativ mit Angst und vitaler Erschöpfung korreliert. Insgesamt hatte von den Arbeitsmerkmalen nur die Dauer der Arbeitszeit einen Effekt auf die Gesundheit von Unternehmern. Daneben existieren aber offensichtlich weitere Faktoren, die mit der Unternehmergesundheit in Beziehung stehen. Dies sind neben dem Konkurrenzdruck am Markt insbesondere Indikatoren des Unternehmenserfolgs. The relationship between health and workload as well as entrepreneurial success was analyzed in 53 entrepreneurs. Workload data (decision latitude, job demand, working time, competition, market development) were determined by using structured interviews and Karasek's job content questionnaire. Firm success was operationalized by employee growth, the possibility of absence from the company (days of holiday), and perceived success. Health was measured by questionnaires for sleep disturbances, vital exhaustion, depression, and anxiety, and by 24 hour ambulatory blood pressure monitoring. Regression analyses showed that working time and strength of competition within the market were predictive for systolic blood pressure (SBP) during leisure time and night, but not during work. All variables measuring entrepreneurial success were predictive for health. Employee growth was related to decreasing SBP during work and to fewer sleep disturbances. The duration of holidays was negatively related to vital exhaustion and anxiety. Perceived company success was negatively related to depression and vital exhaustion. In conclusion, only the relationship between working time and bad health conformed to findings reported for the relationship between work and health in employees. However, there were additional indicators, especially indicators of competition and entrepreneurial success, that affected the health of entrepreneurs.

Ensuring efficiency and robustness in MANET

This paper introduces a joint load balancing and hotspot mitigation protocol for mobile ad-hoc network (MANET) termed by us as 'load_energy balance + hotspot mitigation protocol (LEB+HM)'. We argue that although ad-hoc wireless networks have limited network resources - bandwidth and power, prone to frequent link/node failures and have high security risk; existing ad hoc routing protocols do not put emphasis on maintaining robust link/node, efficient use of network resources and on maintaining the security of the network. Typical route selection metrics used by existing ad hoc routing protocols are shortest hop, shortest delay, and loop avoidance. These routing philosophy have the tendency to cause traffic concentration on certain regions or nodes, leading to heavy contention, congestion and resource exhaustion which in turn may result in increased end-to-end delay, packet loss and faster battery power depletion, degrading the overall performance of the network. Also in most existing on-demand ad hoc routing protocols intermediate nodes are allowed to send route reply RREP to source in response to a route request RREQ. In such situation a malicious node can send a false optimal route to the source so that data packets sent will be directed to or through it, and tamper with them as wish. It is therefore desirable to adopt routing schemes which can dynamically disperse traffic load, able to detect and remove any possible bottlenecks and provide some form of security to the network. In this paper we propose a combine adaptive load_energy balancing and hotspot mitigation scheme that aims at evenly distributing network traffic load and energy, mitigate against any possible occurrence of hotspot and provide some form of security to the network. This combine approach is expected to yield high reliability, availability and robustness, that best suits any dynamic and scalable ad hoc network environment. Dynamic source routing (DSR) was use as our underlying protocol for the implementation of our algorithm. Simulation comparison of our protocol to that of original DSR shows that our protocol has reduced node/link failure, even distribution of battery energy, and better network service efficiency.

Stress, burnout and coping strategies in the emergency and intensive care hospital departments

Doctors and nurses working at the accident and emergency (A&E), and intensive care departments are at risk of burnout. They often spend substantial time in intense interactions with other people, centered on patients? health problems (physical, psychological and social) that may lead to feelings of anger, anxiety and frustration, and eventually to burnout. Burnout is a syndrome of emotional exhaustion, depersonalization and reduced personal accomplishment (Maslach & Jackson, 1981) The purpose of this chapter is to assess work stressors, burnout and stress-coping mechanisms among doctors and nurses at the A&E and intensive care departments. A quantitative design using the survey approach was used to collect data from a sample of 200 participants with a response rate of 71% (n=154) Work stressors were associated with burnout in both doctors and nurses. Workload was the most salient work stressor in the sample. Nurses experienced more stress (M=1.5, SD=0.4) than doctors (M=1.2, SD=0.4) in all the work stressor variables examined. The A&E department was reported as more stressful than the intensive care department. Avoidance-oriented and task-oriented coping were the most and the least frequently reported coping strategies respectively. Additionally, only emotion-oriented coping strategy was significantly different between doctors and nurses, and this strategy was also significantly positively correlated with all the variables in the adapted nursing stress scale, and the three burnout variables. Death and dying was most strongly correlated with emotion-oriented coping. This chapter provides an assessment of stress, burnout and coping experienced by both doctors and nurses within the A&E and intensive care departments. Methods that may mitigate stress in these environments may be adequate staffing, supportive management, stress management programs, as well as improvement in communication strategies between doctors and nurses.

The relationship between perceived training and development and employee retention:the mediating role of work attitudes

This paper considers how utilizing a model of job-related affect can be used to explain the processes through which perceived training and development influence employee retention. We applied Russell’s model of core affect to categorize four different forms of work attitude, and positioned these as mediators of the relationship between perceived training and development and intention to stay. Using data from 1,191 employees across seven organizations, multilevel analyses found that job satisfaction, employee engagement, and change-related anxiety were significantly associated with intention to stay, and fully mediated the relationship between perceived training and development and intention to stay. Contrary to our hypotheses, emotional exhaustion was not significantly associated with intention to stay nor acted as a mediator when the other attitudes were included. These findings show the usefulness of Russell’s model of core affect in explaining the link between training and development and employee retention. Moreover, the findings collectively suggest that studies examining employee retention should include a wider range of work attitudes that highlight pleasant forms of affect.