Current and future water balance for coupled human-natural systems – Insights from a glacierized catchment in Peru

Study region Santa River basin, Peru. Study focus In the Andes of Peru, climate change and socio-economic development are expected to jeopardize future water availability. However, little is known about the interplay of multiple climatic and non-climatic stressors and related processes driving water resource changes. We developed an integrated model that analyzes different trajectories of water availability including hydro-climatic (water supply) and socio-economic (water demand) variables with consistent multi-descriptor future scenarios until 2050. New hydrological insights for the region At the lower-basin outflow of Condorcerro, mean annual water availability is projected to increase by 10% ± 12% by 2050. This gain is mainly driven by an increase in annual precipitation amounts of about 14% (RCP2.6) and 18% (RCP8.5), respectively, which was computed using a global climate multi-model ensemble. In contrast, mean dry-season water availability is projected to substantially decrease by 33% and 36% ( ± 24%) by 2050, for RCP2.6 and RCP8.5, respectively. This decline is driven by a combination of diminishing glacier discharge and increasing water demand both of which adopt a major role in the absence of considerable precipitation inputs. These seasonal differences highlight the need to adequately consider spatiotemporal scales within multi-scenario water balance models to support local decision-making. Our results elucidate the need for improvements in water management and infrastructure to counteract diminishing dry-season water availability and to reduce future risks of water scarcity

Reliable, Economic, Efficient CO2 Heat Pump Water Heater for North America

Adoption of heat pump water heating technology for commercial hot water could save up to 0.4 quads of energy and 5 million metric tons of CO2 production annually in North America, but industry perception is that this technology does not offer adequate performance or reliability and comes at too high of a cost. Development and demonstration of a CO2 heat pump water heater is proposed to reduce these barriers to adoption. Three major themes are addressed: market analysis to understand barriers to adoption, use of advanced reliability models to design optimum qualification test plans, and field testing of two phases of water heater prototypes. Market experts claim that beyond good performance, market adoption requires 'drop and forget' system reliability and a six month payback of first costs. Performance, reliability and cost targets are determined and reliability models are developed to evaluate the minimum testing required to meet reliability targets. Three phase 1 prototypes are designed and installed in the field. Based on results from these trials a product specification is developed and a second phase of five field trial units are built and installed. These eight units accumulate 11 unit-years of service including 15,650 hours and 25,242 cycles of compressor operation. Performance targets can be met. An availability of 60% is achieved and the capability to achieve >90% is demonstrated, but overall reliability is below target, with an average of 3.6 failures/unit-year on the phase 2 demonstration. Most reliability issues are shown to be common to new HVAC products, giving high confidence in mature product reliability, but the need for further work to minimize leaks and ensure reliability of the electronic expansion valve is clear. First cost is projected to be above target, leading to an expectation of 8-24 month payback when substituted for an electric water heater. Despite not meeting all targets, arguments are made that an industry leader could sufficiently develop this technology to impact the water heater market in the near term

Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer?

Immunotherapy has been studied for many years in lung cancer without significant results, making the majority of oncologists quite skeptical about its possible application for non-small cell lung cancer treatment. However, the recent knowledge about immune escape and subsequent 'cancer immunoediting' has yielded the development of new strategies of cancer immunotherapy, heralding a new era of lung cancer treatment. Cancer vaccines, including both whole-cell and peptide vaccines have been tested both in early and advanced stages of non-small cell lung cancer. New immunomodulatory agents, including anti-CTLA4, anti-PD1/PDL1 monoclonal antibodies, have been investigated as monotherapy in metastatic lung cancer. To date, these treatments have shown impressive results of efficacy and tolerability in early clinical trials, leading to testing in several large, randomized Phase III trials. As these results will be confirmed, these drugs will be available in the near future, offering new exciting therapeutic options for lung cancer treatment

Characterization of gastric adenocarcinoma cell lines established from CEA424/SV40 T antigen-transgenic mice with or without a human CEA transgene

BACKGROUND: Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new therapies, like immunotherapy for the treatment of gastric cancer is of utmost importance. Since the usability of existing preclinical models for the evaluation of immunotherapies for gastric adenocarcinomas is limited, the goal of the present study was to establish murine in vivo models which allow the stepwise improvement of immunotherapies for gastric cancer. METHODS: Since no murine gastric adenocarcinoma cell lines are available we established four cell lines (424GC, mGC3, mGC5, mGC8) from spontaneously developing tumors of CEA424/SV40 T antigen (CEA424/Tag) mice and three cell lines derived from double-transgenic offsprings of CEA424/Tag mice mated with human carcinoembryonic antigen (CEA)-transgenic (CEA424/Tag-CEA) mice (mGC2(CEA), mGC4(CEA), mGC11(CEA)). CEA424/Tag is a transgenic C57BL/6 mouse strain harboring the Tag under the control of a -424/-8 bp CEA gene promoter which leads to the development of invasive adenocarcinoma in the glandular stomach. Tumor cell lines established from CEA424/Tag-CEA mice express the well defined tumor antigen CEA under the control of its natural regulatory elements. RESULTS: The epithelial origin of the tumor cells was proven by morphological criteria including the presence of mucin within the cells and the expression of the cell adhesion molecules EpCAM and CEACAM1. All cell lines consistently express the transgenes CEA and/or Tag and MHC class I molecules leading to their susceptibility to lysis by Tag-specific CTL in vitro. Despite the presentation of CTL-epitopes derived from the transgene products the tumor cell lines were tumorigenic when grafted into C57BL/6, CEA424/Tag or CEA424/Tag-CEA-transgenic hosts and no significant differences in tumor take and tumor growth were observed in the different hosts. Although no spontaneous tumor rejection was observed, vaccination of C57BL/6 mice with lysates from gastric carcinoma cell lines protected C57BL/6 mice from tumor challenge, demonstrating the tumorigenicity of the tumor cell lines in nontransgenic mice of the H-2(b )haplotype. CONCLUSION: These tumor cell lines grafted in different syngeneic hosts should prove to be very useful to optimize immunotherapy regimens to be finally tested in transgenic animals developing primary gastric carcinomas

Design by Search

Consider a world in which computers are infinetely fast. How would you do design with such computers? One of the possibilities is an on-line search in a space of free design parameters. The bottlenecks are the the man-machine interfaces, in particular keyboard input to the computer and interpretation of displays showing attributes like performance of a control system to be designed. This paper deals with the question: Is it possible to do design by search in sensomotoric interaction between designer and design machine? For design of a robust controller for a simple two mass system with two uncertain parameters the answer is "yes"

PARADISE User's Manual

This manual describes the Parametric Robustness Analysis and Design Interactive Software Environment (PARADISE) Toolbox. Toolbox based on Matlab. It is a flexible and efficient tool for the design and analysis of robust control systems: Parametric models can be specified using Simulink. A closed loop symbolic representation of the control system will be generated automatically using symbolic computation. The parameter space approach can be applied to this parametric model. Graphical user interfaces guide you through design and analysis