Optimal Configuration of Regional Water Supply Systems (WASOPT2)

Any water supply system can be conceptualized as consisting of three componenets--source development facilities (including treatment), transmission facilities, and a distribution network. The scope of this report is limited to the first two--the source related facilities upstream from the distribution network. In the mathematical modeling of regional rural systems, the number of variables, and hence the size of the model, increases rapidly as the number of system componenets and their alternative designs increase. Regardless of the method of solution, manual preparation of large models is cumbersome and is vulnerable to human error both in the computations of the matrix coefficients as well as in the format requirements. This research is aimed at developing a flexible matrix generator for the general rural water supply problem and alternative solution methods that can be used for especially large problems. The Mixed Integer Programming (MIP) method is particularly expensive to use for large problems and is not practical if the number of variables approaches a hundred or so, while the laternative solution methods can handle hundreds of variables. A real-world application problem is solved using the MIP and the three alternative methods developed during this research. These include the continuous, the nonlinear discrete, and the objective bounding methods. The solutions are compared and conclusions drawn as to the conditions under which the different methods are recommended

Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis

Background: High throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh human surgical tissue are logistically difficult, preclude histopathological triage of samples, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets and increase experimental costs. Although tissue preservation methods have been previously explored to address such issues, it is yet to be examined on complex human tissues, such as solid cancers and on high throughput scRNA-Seq platforms. Methods: Using the Chromium 10X platform, we sequenced a total of ~ 120,000 cells from fresh and cryopreserved replicates across three primary breast cancers, two primary prostate cancers and a cutaneous melanoma. We performed detailed analyses between cells from each condition to assess the effects of cryopreservation on cellular heterogeneity, cell quality, clustering and the identification of gene ontologies. In addition, we performed single-cell immunophenotyping using CITE-Seq on a single breast cancer sample cryopreserved as solid tissue fragments. Results: Tumour heterogeneity identified from fresh tissues was largely conserved in cryopreserved replicates. We show that sequencing of single cells prepared from cryopreserved tissue fragments or from cryopreserved cell suspensions is comparable to sequenced cells prepared from fresh tissue, with cryopreserved cell suspensions displaying higher correlations with fresh tissue in gene expression. We showed that cryopreservation had minimal impacts on the results of downstream analyses such as biological pathway enrichment. For some tumours, cryopreservation modestly increased cell stress signatures compared to freshly analysed tissue. Further, we demonstrate the advantage of cryopreserving whole-cells for detecting cell-surface proteins using CITE-Seq, which is impossible using other preservation methods such as single nuclei-sequencing. Conclusions: We show that the viable cryopreservation of human cancers provides high-quality single-cells for multiomics analysis. Our study guides new experimental designs for tissue biobanking for future clinical single-cell RNA sequencing studies

STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological NKG2Dhi CD8+T cell dysregulation and accumulation

The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co -exist-ing autoimmunity. To investigate whether these mutations are the cause or consequence of CD8+ T cell clonal expansions and autoimmunity, we analyzed patients and mice with germline STAT3 GOF mutations. STAT3 GOF mutations drove the accumulation of effector CD8+ T cell clones highly expressing NKG2D, the receptor for stress-induced MHC-class-I-related molecules. This subset also expressed genes for granzymes, perforin, interferon-y, and Ccl5/Rantes and required NKG2D and the IL-15/IL-2 receptor IL2RB for maximal accumula-tion. Leukocyte-restricted STAT3 GOF was sufficient and CD8+ T cells were essential for lethal pathology in mice. These results demonstrate that STAT3 GOF mutations cause effector CD8+ T cell oligoclonal accumu-lation and that these rogue cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease.Peer reviewe

Entomological aspects and the role of human behaviour in malaria transmission in a highland region of the Republic of Yemen

© 2016 Al-Eryani et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Hydrology and ground water potential of the Tihama-Yemen Arab Republic

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Hydrology and ground water potential of the Tihama-Yemen Arab Republic

Tihama is Yemen's coastal strip of land bordering the Red Sea. It occupies an area of about 20,000 km² and represents the country's most promising agronomic resource. With a total median annual volume of about 1,000 MCM (million cubic meters), surface water enters the Tihama plain through seven major wadis that drain the mountainous catchments to the east. The Tihama's Quaternary section constitutes the region's only known ground water aquifer. It consists of a thick sequence of alluvial sediments. Ground water occurs under water table conditions, and is annually replenished primarily by seepage of surface runoff. Using the technique of flow net analysis, it was found that annual natural ground water discharge through the Tihama aquifer to the Red Sea amounts to about 300 MCM. A confirmation of this magnitude of discharge was possible by computing two water balances at two of the major wadis. Results of the discharge computations can be applied in the planning of future salvage of this non-beneficial loss. Given that the current system of surface and ground water irrigation in the Tihama supports an area of about 150,000 hectares, a recovery of as little as 50 percent of this loss can increase the irrigated area by an additional 15,000 hectares.hydrology collectio