PPARγ Loss Leads to Reduced Fertility

The peroxisome proliferation-activated receptor gamma (PPARγ) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B- and T-cells. PPARγ has an anti-proliferative effect in pre-adipocytes and mammary epithelial cells, and treatment with its ligands reduced the progression of carcinogen-induced mammary tumors in mice. Because PPARγ-null mice die in utero it has not been possible to study its role in development and tumorigenesis in vivo. To investigate whether PPARγ is required for the establishment and physiology of different cell types, a cell-specific deletion of the gene was carried out in mice using the Cre-loxP recombination system. We deleted the PPARγ gene in mammary epithelium using WAP-Cre transgenic mice and in epithelial cells, B- and T-cells, and ovary cells using MMTV-Cre mice. The presence of PPARγ was not required for functional development of the mammary gland during pregnancy and for the establishment of B- and T-cells. In addition, no increase in mammary tumors was observed. However, loss of the PPARγ gene in oocytes and granulosa cells resulted in impaired fertility. These mice have normal populations of follicles, they ovulate and develop corpora lutea. Although progesterone levels are decreased and implantation rates are reduced, the exact cause of the impaired fertility remains to be determined

ASSESSMENT OF CROP YIELDS IN MODERN AGRICULTURE ON THE BASIS OF GIS-TECHNOLOGIES - Langfasssung

The uneven distribution of natural properties- for example, soil quality, topography, microclimate - on the territory of any size determined a different degree of their suitability for growing different groups of crops. Information-analytical system of ensuring agricultural technologies was developed on the base of several GIS and models of crop yield. The system included creation of maps of potential yield (function of the natural factors) and possible (function of the real level of the field fertility) yield of various crops. These dates were received in the field experiments with fertilizers and in available modern bases of agro-chemical, landscape, climatic parameters

Effective organic matter stock management in agricultural practices: modeling and observation - Langfassung

RothC soil carbon dynamic model was used for simulation SOC stocks in 6 Russian long-term fertilization experiments for estimation which agricultural practices lead to soil C accumulation. For all the treatments tested above ground NPP input is sufficient for maintaining constant SOM stocks and additional C gain

Soil Quality and Crop Yield Potential of Sites in North and Central Asian

Science and technology may help to find solutions for sustainable use of soils. The awareness about limited and degrading natural resources have fired the energy and creativity of responsible and innovative people to develop and install monitoring systems and countermeasures. However, the access to modern monitoring systems and agri-environmental technologies is different over regions of Eurasia. Some regions of Central Asia and Asian Russia require modern monitoring systems for their land and water resources in order to avoid their accelerating degradation and maintain their productivity function and ecosystem services for the populatio

Estimation of input costs for a Markov model in a German health economic evaluation of newer antidepressants

Background: Estimating input costs for Markov models in health economic evaluations requires health state-specific costing. This is a challenge in mental illnesses such as depression, as interventions are not clearly related to health states. We present a hybrid approach to health state-specific cost estimation for a German health economic evaluation of antidepressants. Methods: Costs were determined from the perspective of the community of persons insured by statutory health insurance (“SHI insuree perspective”) and included costs for outpatient care, inpatient care, drugs, and psychotherapy. In an additional step, costs for rehabilitation and productivity losses were calculated from the societal perspective. We collected resource use data in a stepwise hierarchical approach using SHI claims data, where available, followed by data from clinical guidelines and expert surveys. Bottom-up and top-down costing approaches were combined. Results: Depending on the drug strategy and health state, the average input costs varied per patient per 8-week Markov cycle. The highest costs occurred for agomelatine in the health state first-line treatment (FT) (“FT relapse”) with €506 from the SHI insuree perspective and €724 from the societal perspective. From both perspectives, the lowest costs (excluding placebo) were €55 for selective serotonin reuptake inhibitors in the health state “FT remission.” Conclusion: To estimate costs in health economic evaluations of treatments for depression, it can be necessary to link different data sources and costing approaches systematically to meet the requirements of the decision-analytic model. As this can increase complexity, the corresponding calculations should be presented transparently. The approach presented could provide useful input for future models

A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents

Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 days in co-culture has been established at a minute but standardized microsystem scale. Preformed human intestine and skin models have been integrated into the four-organ-chip on standard cell culture inserts at a size 100000-fold smaller than their human counterpart organs. A 3D-based spheroid, equivalent to ten liver lobules, mimics liver function. Finally, a barrier segregating the media flow through the organs from fluids excreted by the kidney has been generated by a polymeric membrane covered by a monolayer of human proximal tubule epithelial cells. A peristaltic on-chip micropump ensures pulsatile media flow interconnecting the four tissue culture compartments through microfluidic channels. A second microfluidic circuit ensures drainage of the fluid excreted through the kidney epithelial cell layer. This four-organ-chip system assures near to physiological fluid-to-tissue ratios. In-depth metabolic and gene analysis revealed the establishment of reproducible homeostasis among the co-cultures within two to four days, sustainable over at least 28 days independent of the individual human cell line or tissue donor background used for each organ equivalent. Lastly, 3D imaging two-photon microscopy visualised details of spatiotemporal segregation of the two microfluidic flows by proximal tubule epithelia. To our knowledge, this study is the first approach to establish a system for in vitro microfluidic ADME profiling and repeated dose systemic toxicity testing of drug candidates over 28 days.BMBF, 0315569, GO-Bio 3: Multi-Organ-Bioreaktoren für die prädiktive Substanztestung im Chipforma

MHD alpha^2-dynamo, Squire equation and PT-symmetric interpolation between square well and harmonic oscillator

It is shown that the alpha^2-dynamo of Magnetohydrodynamics, the hydrodynamic Squire equation as well as an interpolation model of PT-symmetric Quantum Mechanics are closely related as spectral problems in Krein spaces. For the alpha^2-dynamo and the PT-symmetric model the strong similarities are demonstrated with the help of a 2x2 operator matrix representation, whereas the Squire equation is re-interpreted as a rescaled and Wick-rotated PT-symmetric problem. Based on recent results on the Squire equation the spectrum of the PT-symmetric interpolation model is analyzed in detail and the Herbst limit is described as spectral singularity.Comment: 21 pages, LaTeX2e, 10 figures, minor improvements, references added, to appear in J. Math. Phy