Circadian rhythm and cell population growth

Molecular circadian clocks, that are found in all nucleated cells of mammals, are known to dictate rhythms of approximately 24 hours (circa diem) to many physiological processes. This includes metabolism (e.g., temperature, hormonal blood levels) and cell proliferation. It has been observed in tumor-bearing laboratory rodents that a severe disruption of these physiological rhythms results in accelerated tumor growth. The question of accurately representing the control exerted by circadian clocks on healthy and tumour tissue proliferation to explain this phenomenon has given rise to mathematical developments, which we review. The main goal of these previous works was to examine the influence of a periodic control on the cell division cycle in physiologically structured cell populations, comparing the effects of periodic control with no control, and of different periodic controls between them. We state here a general convexity result that may give a theoretical justification to the concept of cancer chronotherapeutics. Our result also leads us to hypothesize that the above mentioned effect of disruption of circadian rhythms on tumor growth enhancement is indirect, that, is this enhancement is likely to result from the weakening of healthy tissue that are at work fighting tumor growth

MODELLING THE DISTRIBUTIONAL IMPACTS OF AGRICULTURAL POLICIES IN DEVELOPING COUNTRIES: THE DEVELOPMENT POLICY EVALUATION MODEL (DEVPEM)

The purpose of the Development Policy Evaluation Model (DEVPEM) is to provide an appropriate modelling structure for analysing the welfare and distributional implications of alternative agricultural policies in developing countries. The aim of the model is to provide illustrative results that show how structural diversity among developing countries, and systemic differences from developed OECD countries, can affect the outcomes of alternative policy interventions. The model is relatively stylised, seeking to capture, as simply as possible, four critical aspects of rural economies in developing countries that are important when evaluating the impacts of agricultural and trade policies. These are: (1). The role of the household as both a producer and a consumer of food crops. (2). High transaction costs of participating in markets, resulting in a subsistence sector that often is important in terms of the number of households and the amount of food production it encompasses. (3). Market linkages that can transmit impacts of policy and market shocks among heterogeneous rural producers and consumers, particularly via factor markets (for labour, land or capital, when those markets exist). (4). The imperfect convertibility of land from one use to another.International Relations/Trade,

The Best of Times, the Worst of Times: Understanding Pro-cyclical Mortality

A growing literature documents cyclical movements in mortality and health. We examine this pattern more closely and attempt to identify the mechanisms behind it. Specifically, we distinguish between mechanisms that rely on fluctuations in own employment or time use and those involving factors that are external to the individual. Our investigation suggests that changes in individuals’ own behavior contribute very little to pro-cyclical mortality. Looking across broad age and gender groups, we find that own-group employment rates are not systematically related to own-group mortality. In addition, we find that most of the additional deaths that occur during times of economic growth are among the elderly, particularly elderly women, who have limited labor force attachment. Focusing on mortality among the elderly, we show that cyclicality is especially strong for deaths occurring in nursing homes, and is stronger in states where a higher fraction of the elderly reside in nursing homes. We also demonstrate that staffing in skilled nursing facilities moves counter-cyclically. Taken together, these findings suggest that cyclical fluctuations in the mortality rate may be largely driven by fluctuations in the quality of health care.

Commissioning the UPM satellite simulator facility platform

The purpose of this paper is to test and validate the UPM Satellite Simulator Facility (SSF) platform. The work relates to satellite testing and qualification experiments. The satellite Attitude Determination and Control System (ADCS) consist of flight-proven equipment from Canada, Germany and America. The flight hardware check has to be performed for the SSF qualification. Therefore, dedicated test procedures in order to test and verify the satellite control mode (i.e., Idle mode, Detumble mode, Coarse Pointing mode and Fine Pointing mode) has to be implemented. The results of these experiments are discussed to qualify the health of the satellite itself and the ADCS equipment. The UPM SSF responded very well to all the conducted tests and therefore, its performances are validated

Clock gene Per2 as a controller of liver carcinogenesis

Environmental disruption of molecular clocks promoted liver carcinogenesis and accelerated cancer progression in rodents. We investigated the specific role of clock gene Period 2 (Per2) for liver carcinogenesis and clock-controlled cellular proliferation, genomic instability and inflammation. We assessed liver histopathology, and determined molecular and physiology circadian patterns in mice on chronic diethylnitrosamine (DEN) exposure according to constitutive Per2 mutation. First, we found that Per2m/m liver displayed profound alterations in proliferation gene expression, including c-Myc derepression, phase-advanced Wee1, and arrhythmic Ccnb1 and K-ras mRNA expressions, as well as deregulated inflammation, through arrhythmic liver IL-6 protein concentration, in the absence of any DEN exposure. These changes could then make Per2m/m mice more prone to subsequently develop liver cancers on DEN. Indeed, primary liver cancers were nearly fourfold as frequent in Per2m/m mice as compared to wild-type (WT), 4 months after DEN exposure. The liver molecular clock was severely disrupted throughout the whole carcinogenesis process, including the initiation stage, i.e. within the initial 17 days on DEN. Per2m/m further exhibited increased c-Myc and Ccnb1 mean 24h expressions, lack of P53 response, and arrhythmic ATM, Wee1 and Ccnb1 expressions. DEN-induced tumor related inflammation was further promoted through increased protein concentrations of liver IL-6 and TNF-α as compared to WT during carcinogenesis initiation. Per2 mutation severely deregulated liver gene or protein expressions related to three cancer hallmarks, including uncontrolled proliferation, genomic instability, and tumor promoting inflammation, and accelerated liver carcinogenesis several-fold. Clock gene Per2 acted here as a liver tumor suppressor from initiation to progression

Making health insurance pro-poor: evidence from a household panel in rural China

BACKGROUND: In 2002, China launched the largest public health insurance scheme in the world, the New Cooperative Medical Scheme (NCMS). It is intended to enable rural populations to access health care services, and to curb medical impoverishment. Whether the scheme can reach its equity goals depends on how it is used, and by whom. Our goal is to shed light on whether and how income levels affect the ability of members to reap insurance benefits. METHODS: We exploit primary panel data consisting of a complete census (over 3500 individuals) in three villages in Puding County, Guizhou province, collected in 2004, 2006, 2009 and 2011. Data was collected during in-person interviews with household member(s). The data include yearly gross and net medical expenses for all individuals, and socio-economic information. We apply probit, ordinary least squares, and tobit multivariate regression analyses to the three waves in which NCMS was active (2006, 2009 and 2011). Explained variables include obtainment, levels and rates of NCMS reimbursement. Household income is the main explanatory variable, with household- and individual-level controls. We restrict samples to rule out self-selection, and exploit the 2009 NCMS reform to highlight equity-enhancing features of insurance. RESULTS: Prior to 2009 reforms, higher income in our sample was statistically significantly related to higher probability of obtaining reimbursement, as well as higher levels and rates of reimbursement. These relations all disappear after the reform, suggesting lower-income households were better able to reap insurance benefits after the scheme was reformed. Regression results suggest this is partly explained by reimbursement for chronic diseases. CONCLUSIONS: The post-reform NCMS distributed benefits more equitably in our study area. Making health insurance pro-poor may require a focus on outpatient costs, credit constraints and chronic diseases, rather than catastrophic illnesses

Design and implementation of a modified fourier analysis harmonic current computation technique for power active filters using DSPs

The design and implementation of a harmonic current computation technique based on a modified Fourier analysis, suitable for active power filters incorporating DSPs is presented. The proposed technique is suitable for the monitoring and control of load current harmonics for real-time applications. The derivation of the basic equations based on the proposed technique and the system implementation using the Analogue Devices SHARC processor are presented. The steady state and dynamic performance of the system are evaluated for a range of loading conditions

Large-scale Oscillation of Structure-Related DNA Sequence Features in Human Chromosome 21

Human chromosome 21 is the only chromosome in human genome that exhibits oscillation of (G+C)-content of cycle length of hundreds kilobases (500 kb near the right telomere). We aim at establishing the existence of similar periodicity in structure-related sequence features in order to relate this (G+C)% oscillation to other biological phenomena. The following quantities are shown to oscillate with the same 500kb periodicity in human chromosome 21: binding energy calculated by two sets of dinucleotide-based thermodynamic parameters, AA/TT and AAA/TTT bi-/tri-nucleotide density, 5'-TA-3' dinucleotide density, and signal for 10/11-base periodicity of AA/TT or AAA/TTT. These intrinsic quantities are related to structural features of the double helix of DNA molecules, such as base-pair binding, untwisting/unwinding, stiffness, and a putative tendency for nucleosome formation.Comment: submitted to Physical Review

Critical cholangiocarcinogenesis control by cryptochrome clock genes

A coordinated network of molecular circadian clocks in individual cells generates 24-hour rhythms in liver metabolism and proliferation. Circadian disruption through chronic jet lag or Per2 clock gene mutation was shown to accelerate hepatocarcinoma development in mice. Since divergent effects were reported for clock genes Per and Cry regarding xenobiotic toxicity, we questioned the role of Cry1 and Cry2 in liver carcinogenesis. Male WT and Cry1-/-Cry2-/- mice (C57Bl/6 background) were chronically exposed to diethylnitrosamine (DEN) at ZT11. Rest-activity and body temperature rhythms were monitored using an implanted radiotransmitter. Serum aspartate and alanine aminotransferases (AST, ALT) were determined on four occasions during the progression stage. After 7 months, serum alkaline phosphatases (ALP) were determined, and livers were sampled for microscopic tumor nodule counting and histopathology. Five months after initiation of DEN treatment, we found that Cry1-/-Cry2-/- mice developed severe liver dysplasia, as evident from the increased AST, ALT and ALP levels, as compared to WT mice. DEN exposure induced primary liver cancers in nearly fivefold as many Cry1-/-Cry2-/- mice as compared to WT mice (p= 0.01). Microscopic study revealed no difference in the average number of hepatocarcinomas and a nearly 8-fold increase in the average number of cholangiocarcinomas in Cry1-/-Cry2-/- mice, as compared to WT mice. The study validated the hypothesis that molecular circadian clock disruption dramatically increased chemically-induced liver carcinogenesis. In addition, the pronounced shift towards cholangiocarcinoma in DEN exposed Cry1-/-Cry2-/- mice revealed a critical role of the Cry clock genes in bile duct carcinogenesis. This article is protected by copyright. All rights reserved