TOWARDS A STOCHASTIC TWO-COMPARTMENT MODEL IN TUMOR GROWTH

The cells of organisms as diverse as bacteria and humans can enter stable, nonproliferating quiescent states. Quiescent cells of eukaryotic and prokaryotic microorganisms can survive for long periods without nutrients. This alternative state of cells is still poorly understood, yet much benefit is to be gained by understanding it both scientifically and with reference to human health. Here, we review our knowledge of one "model" quiescent cell population, in cultures of yeast grown to stationary phase in rich media. We outline the importance of understanding quiescence, summarize the properties of quiescent yeast cells, and clarify some definitions of the state. We propose that the processes by which a cell enters into, maintains viability in, and exits from quiescence are best viewed as an environmentally triggered cycle: the cell quiescence cycle. We synthesize what is known about the mechanisms by which yeast cells enter into quiescence, including the possible roles of the protein kinase A, TOR, protein kinase C, and Snf1p pathways. We also discuss selected mechanisms by which quiescent cells maintain viability, including metabolism, protein modification, and redox homeostasis. Finally, we outline what is known about the process by which cells exit from quiescence when nutrients again become available.

Microenvironment-regulated lncRNA-HAL is able to promote stemness in breast cancer cells

This study aims to examine the effect of the type of district/city government, total population, and area size on changes to district/city government budgets in Aceh in 2020 and 2021. The data used is secondary data from local government financial reports audited by the BPK RI (Badan Pemeriksa Keuangan Republik Indonesia), reports on changes to the budget obtained from BPKA (Badan Pengelola Keuangan Aceh), total population data from BPS (Badan Pusat Statistik), and area size data from the Directorate General of Population and Civil Registry of the Ministry of Home Affairs. The data analysis method used is the Multiple Linear Regression Test. The results showed that the area size and total population had a significant effect on budget changes, the type of district/city government did not affect changes to district/city government budgets in Aceh during the Covid-19, while the three independent variables simultaneously affected dependent variables. The Coefficient of Determination analysis result is 0.279, which means that the variable type of district/city government, total population, and area size can explain 27.9% of changes in district/city government budgets during the pandemic.

APC mutation/s resulting in aberrant Wnt signaling, initiates intestinal polyposis and drives adenoma to carcinoma progression in human colon. This represents a target for specific therapeutic intervention and has generated extreme interest among the scientific community. However, it is becoming increasingly apparent that though Wnt signaling may cause robust proliferation, it is the quiescent cell population, defined by stem-ness related gene signatures, that evades chemo-radio therapy targeted at rapidly dividing cells, and perpetuates self-renewal ultimately causing relapse at local site and/or recurrence as distant metastases. We report that SOX2, an embryonic stem cell transcription factor, counteracts Wnt driven tumor cell proliferation and maintains quiescence in colo-rectal cancers (CRC). SOX2 expression increases with progressive staging of colon cancer patients. Using colon cancer cell lines transduced with Wnt reporter constructs, we identified distinct sub-populations with varying degrees of Wnt activity and found that SOX2 expression and Wnt activity are mutually exclusive in SW480 primary CRC cell line, but co-expressed in the isogenic SW620 metastatic CRC cell line. Knockdown of SOX2 in SW620 cell increased anchorage independence in vitro and tumor growth in xenograft models. This was accompanied by an increase of cells in S-phase and increased Ki67 index in IHC of xenograft tissue. Over-expression of SOX2 in SW480 cells resulted in decreased colony formation in soft agar and primary tumor growth in mice. Over-expression also caused increased fraction of cells in G0-G1 phase and decreased Ki67 staining in tumor tissue. In SW620 cell line, SOX2 knockdown not only increased basal Wnt activity, but also caused acquisition of Wnt activity in hitherto Wnt negative cells. Intriguingly, over-expression of SOX2 in SW480 cells, reversed the enhanced Wnt activity gained by loss-of-function APC mutation. Experiments conducted with both SOX2 silenced and over-expressed cell lines revealed that SOX2 inhibits phosphorylation of β-catenin at Serine 552 and 675 thereby decreasing its nuclear sequestration and activation. Screening with protein kinase and phosphatase inhibitors identified PHLPP and PHLPPL as candidate genes that are controlled by SOX2 and are responsible for its effects on β-catenin. Western Blot and qPCR analyses showed that SOX2 enhances PHLPP/L expression. Reporter assays demonstrated that SOX2 controls PHLPP/L promoter activity while ChIP assays confirmed binding of SOX2 to various regions of the respective promoters. IHC of SOX2 silenced xenograft tissue showed decreased PHLPP/L and increased pβ-catenin staining while SOX2 over-expression showed reciprocal changes. Our findings delineate the mechanism by which CRC cells suppress Wnt activity thereby maintaining a pool of quiescent cancer cells, and lay the basis for further research to identify and target these cells. Citation Format: Debasish Boral, Man-Tzu Wang, Daotai Nie. SOX2 inhibits Wnt driven colon cancer cell proliferation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5006. doi:10.1158/1538-7445.AM2013-5006

With the overall-two-child policy been fully opened, as the important influence factor of economic development and social life, population structure is more worthy of study. In order to get the more intuitive result of the policy for relief the China's ageing population, this paper uses the Leslie model to predict the future population and the age structure change. Based on census data of Henan province, this paper divided the people's fertility wishes into high, medium and low, proposed four kinds of fertility strategies, and qualitative analysis the total fertility rate and birth population sex ratio of three different fertility wishes. Firstly, this paper predicts the total population size and the age structure under different fertility strategies during 2011-2050. Secondly, based on the total population, the elderly population coefficient and the total population dependency ratio, this paper analyzed the optimal fertility strategy under different fertility wishes. Finally, the conclusion is as follows, when the fertility wishes is low, medium and high respectively, the fertility strategies should be chosen as IV, III and II respectively, that is to say, in the early period, a woman had less than two children and later each woman had 2.1 children, which fully accords with the concept of population sustainable development.

Occupation time theorems for one-dimensional random walks and diffusion processes in random environments

Modelling tumour cell proliferation from vascular structure using tissue decomposition into avascular elements

Resistance of Quiescent Cells to T Cell Attack Determines Both the Efficacy and Specificity of Adoptive T Cell Therapy.

ObjectivesThis study was conducted to examine modification in heat-related mortality in the Netherlands by sociodemographic and geographical factors including socioeconomic position and population density (PD).DesignThis observational study applied time series...

Southern elephant seals (Mirounga leonina) play a pivotal role in the Southern Ocean as wide-ranging marine predators and major prey consumers within Southern Ocean marine ecosystems. Due to their circumpolar distribution and the remoteness of their habitat, large uncertainties remain about their total population sizes. This is especially true for elephant seal populations in the French Southern Territories in the southern Indian Ocean (i.e. Crozet and Kerguelen Archipelagos) as many breeding sites are inaccessible for ground censuses. Here, we present a simple and efficient approach for estimating the total elephant seal populations of the Kerguelen and Crozet Archipelagos by using very high-resolution satellite imagery (<1m resolution). Twenty-eight satellite images taken during the breeding season to count female elephant seals in inaccessible areas were used and complemented the traditional annual ground counts in accessible areas. For Kerguelen Island sectors likely to host colonies and where no satellite images were available for the breeding season, a statistical predictive model was built to estimate the most likely number of breeding females to be present on a given beach according to its physiographic characteristics. Our results show the reliability of using very high-resolution satellite images, a relatively low-cost platform, to count pinniped populations and provide the first estimation of the total southern elephant seal population for both the Kerguelen 347,995 (s e = 4,950) and Crozet 13,065 (s e = 169) Archipelagos. The combined total represents over 35% of the global elephant seal population with the Kerguelen stock being numerically equivalent to the South Georgia stock. In addition, we re-examined the population trends since the last mid-century for Kerguelen and over the last five decades for Crozet. The demographic trends of the southern Indian Ocean populations show marked growth over the last decade (5.1% and 1.6% annual growth rate for Crozet and Kerguelen respectively), particularly on Crozet where the elephant seal population has more than tripled.

Systemic Cancer Gene Therapy Using Adeno-associated Virus Type 1 Vector Expressing MDA-7/IL24

We investigate the critical behavior of a one-dimensional diffusive epidemic propagation process by means of a Monte Carlo procedure. In the model, healthy (A) and sick (B) individuals diffuse on a lattice with diffusion constants D(A) and D(B), respectively. According to a Wilson renormalization calculation, the system presents a second-order phase transition between a steady reactive state and a vacuum state, with distinct universality classes for the cases D(A)=D(B) and D(A)<D(B). A first-order transition has been conjectured for D(A)>D(B). In this work we perform a finite size scaling analysis of order parameter data at the vicinity of the critical point in dimension d=1. Our results show no signature of a first-order transition in the case of D(A)>D(B). A finite size scaling typical of second-order phase transitions fits well the data from all three regimes. We found that the correlation exponent nu=2 as predicted by field-theoretical arguments. Estimates for beta/nu are given for all relevant regimes.

DNA-PK inhibitor AZD7648 is a more portent radiosensitizer than PARP inhibitor Olaparib in BRCA1/2 deficient tumors

Nineteen per cent of world’s children live in India. Of all the children in the world, one in five is an Indian. India is home to more than one billion people, of which 42 per cent are children, defined as persons under 18 years of age. Women and children constitute seventy two percent of the population of India. The women and children homogenous whole. A great deal of heterogeneity exist. The form of marginalize and vulnerable group of sc, st, obc, and other religious minorities suffer multiple challenge. Women from these group and even more disadvantages as they are subject to additional discrimination on account of societal construct of gender and the consequently adverse power balance. The main problem with the minorities is that no proper database of these have been done. The Integrated Child Development Services (ICDS) Scheme since 1975 for delivery of an integrated package of services relating to health, nutrition and non-formal education to children in the age group 0-6 years, pregnant women and nursing mothers. This package is aimed at improvement in the nutritional and health status of children in this age group, reduction in the incidence of mortality, morbidity, malnutrition and school drop-out rates, and enhancement of the capability of the mother to look after the health and nutritional needs of the child through proper nutrition and health education In short, these objectives which envisage the laying of the foundation for the proper psychological, physical and social development of the child, with appropriate support from the mother, aim at the ultimate goal of human resource development, in its broadest sense. The twin objective of this strategy being comprehensive child development and family welfare, effective coordination in the states, between the departments and agencies that are responsible for the major inputs in the program Wherever this convergence of the maternal and child health services and the ICDS program have been achieved Early childhood period (0-6 years) deserves special attention. It is due to the fact of accumulated scientific evidences that powerfully demonstrates in instituting either family and or centre based early childhood interventions so as to nurture (i) psycho - social development (cognition, motor, social, emotional and language) through maturation and interaction in an properly designed appropriate environment suiting to the child and (ii) generating long term social, economic and educational benefits in terms of lower rates of grades repetition; increased earning potential; reduction in juvenile delinquency; increased social mobilization; reduced social and economic inequalities; psycho - social readiness for school; reduction of drop out rate ; expanding universalization of elementary education ; improved parent - child interaction and finally reducing high developmental costs at later stage of life due to inadequate care. Numerically also, children less than 6 years of age constitute about 15 % of the total population. Of the total child population, 2.07 crore (6 per cent) are infants who are below 1 year; 4.17 crore (12 per cent) are toddlers in the age group of 1-2 years; and 7.73 crores (22.2 per cent) are pre scholars in the age group of 3-5 years. Thus one of the salient demographic features of our country is that it has a sizeable proportion of young population. India is not only home to 21 per cent of developing world’s young children but its young child population size is larger than the total population size of many countries. In 2016, about 25 million infants were immunization services and their mothers will require maternal health services. Similarly, pre school education services will need to be provided for 72 million children in 2016. No other nation in the world including China is likely to enjoy the benefits of such a large young population. This was done with the help of ICDS Programe. By using group work Today, social workers are not only the bridge linking clients to other helpers, they also provide their clients with hope, and encourage their first steps towards a new life. Social workers usually stand in the front line, and reach out to the clients soon after problems occur. They provide an initial assessment of the situation and mobilize other needed services. Social work uses a team approach and is multi-disciplined. Its goal is to provide a service to those who need help.

Two approaches are described for estimating the prevalence of a disease that may have developed in a previous restricted age interval among persons of a given age at a particular calendar time. The prevalence for all those who ever developed disease is treated as a special case. The counting method (CM) obtains estimates of prevalence by dividing the estimated number of diseased persons by the total population size, taking loss to follow-up into account. The transition rate method (TRM) uses estimates of transition rates and competing risk calculations to estimate prevalence. Variance calculations are described for CM and TRM as well as for a variant of CM, called counting method times 10 (CM10), that is designed to yield more precise estimates than CM. We compare these three estimators in terms of precision and in terms of the underlying assumptions required to justify the methods. CM makes fewer assumptions but is typically ess precise than TRM or CM10. For common diseases such as breast cancer, CM may be preferred because its precision is excellent even though not as high as for TRM or CM10. For less common diseases, such as brain cancer, however, TRM or CM10 and other methods that make stabilizing assumptions may be preferred to CM.