California\u27s War Over the Bay-Delta: Historic Failures and Current Battles

California has one highly-coveted possession: the Bay-Delta, which is the second largest estuary in the United States. Today, tensions are higher than ever as Southern California continues to grow and demand water from the Delta, agriculture suffers from drought and less-than-promised water allocations, and aquatic life diminishes due to environmentally damaging processes like pumping and exporting of water elsewhere. This paper will examine the historic policies that have shaped how the Delta has been managed, their successes and failures, and current plans in discussion for continuing improvement of the Delta. The Bay-Delta Conservation Plan and the Sacramento-San Joaquin Valley Water Reliability Act (HR 1837) are the specific current plans presented and analyzed for potential effectiveness. Despite some of the promising suggestions in HR 1837 and the Bay-Delta Conservation Plan, the Delta will remain a problem in the 21st century until stakeholders from all perspectives compromise enough to enact a single, clear-cut solution

Effects of solute concentrations on kinetic pathways in Ni-Al-Cr alloys

The kinetic pathways resulting from the formation of coherent L12-ordered y'-precipitates in the g-matrix (f.c.c.) of Ni-7.5 Al-8.5 Cr at.% and Ni-5.2 Al-14.2 Cr at.% alloys, aged at 873 K, are investigated by atom-probe tomography (APT) over a range of aging times from 1/6 to 1024 hours; these alloys have approximately the same volume fraction of the y'-precipitate phase. Quantification of the phase decomposition within the framework of classical nucleation theory reveals that the y-matrix solid-solution solute supersaturations of both alloys provide the chemical driving force, which acts as the primary determinant of the nucleation behavior. In the coarsening regime, the temporal evolution of the y'-precipitate average radii and the y-matrix supersaturations follow the predictions of classical coarsening models, while the temporal evolution of the y'-precipitate number densities of both alloys do not. APT results are compared to equilibrium calculations of the pertinent solvus lines determined by employing both Thermo-Calc and Grand-Canonical Monte Carlo simulation.Comment: Submitted to Acta Materialia, June, 200

Overcoming the challenges of cancer drug resistance through bacterial-mediated therapy.

Despite tremendous efforts to fight cancer, it remains a major public health problem and a leading cause of death worldwide. With increased knowledge of cancer pathways and improved technological platforms, precision therapeutics that specifically target aberrant cancer pathways have improved patient outcomes. Nevertheless, a primary cause of unsuccessful cancer therapy remains cancer drug resistance. In this review, we summarize the broad classes of resistance to cancer therapy, particularly pharmacokinetics, the tumor microenvironment, and drug resistance mechanisms. Furthermore, we describe how bacterial-mediated cancer therapy, a bygone mode of treatment, has been revitalized by synthetic biology and is uniquely suited to address the primary resistance mechanisms that confound traditional therapies. Through genetic engineering, we discuss how bacteria can be potent anticancer agents given their tumor targeting potential, anti-tumor activity, safety, and coordinated delivery of anti-cancer drugs

The Insidious Effects of Smiles on Social Judgments

We propose that broad smiles increase perceptions of warmth but decrease perceptions of competence. These effects influence consumers' behavioral intentions and actual behaviors, and are moderated by level of consumption risk. Three studies, including one using data from Kickstarter.com, support these hypotheses

Manipulations of antibody galactosylation in a fed-batch adapted perfusion process

Perfusion processes have demonstrated significantly higher volumetric productivity while maintaining consistent product quality attributes (PQAs) throughout an extended harvest period. With this, a drastic decrease of the bioreactor footprint in future commercial plants can be achieved. Therefore, there are significant efforts in biopharmaceutical industry focused on developing high productivity perfusion process for both future biologics, as well as on developing new generation processes for legacy fed-batch processes. In this presentation, we will report the adaptation of an established 14-day fed-batch process for a therapeutic monoclonal antibody to a 30-day perfusion process using alternating tangential flow (ATF) technology. In the proof-of-concept perfusion process, a 6-fold viable cell density (VCD) was reached and maintained compared to the peak VCD in the fed-batch process. The productivity increased 3.5-fold as compared to the original fed-batch process after normalization to cell culture duration. The major PQAs from this perfusion process were consistent throughout the harvest period. Most of the PQAs from the perfusion process showed no significant differences from the original fed-batch process. However, significantly higher galactosylation level was observed in the perfusion process as compared to its fed-batch version. In the presentation, we will also detail the perfusion medium and process parameter optimization, which enabled the matching of the galactosylation profile of the last version perfusion process to the established fed-batch process without compromising target VCD, productivities, and other PQA profiles

Sex tourism among Chinese men who have sex with men: a cross-sectional observational study.

BACKGROUND: Sex tourism among men who have sex with men (MSM) may exacerbate transmission of HIV and other sexually transmitted infections (STIs). Sex tourism is defined as purchasing sex with gifts or money outside of one's hometown. Our objective was to characterize the frequency, socio-demographic characteristics, and sexual risk behaviors among Chinese MSM sex tourists. METHODS: An online, cross-sectional survey for high-risk MSM throughout China was conducted in November 2015 covering sociodemographic characteristics, sexual risk behaviors, and sex tourism. Univariate and multivariable logistic regressions were performed to identify correlates of sex tourism. The mean MSM HIV prevalence of sex tourism journey origins and destinations were compared. RESULTS: Of 1189 MSM who completed the survey, 62 (5%) men identified as sex tourists; among these sex tourists, twenty (32%) traveled primarily to purchase sex and the remainder purchased sex while traveling for another purpose. There was minimal socio-demographic and behavioral difference between the two groups. In multivariable analyses, adjusting for age and income, sex tourism was correlated with high-risk sexual behaviors, higher income (aOR 4.44, 95%CI 1.77-11.18) and living with HIV (aOR 2.79, 95%CI 1.03-7.55). Sex tourism was more often from locations with lower to higher MSM HIV prevalence (mean = 4.47, SD = 2.01 versus mean = 6.86, SD = 5.24). CONCLUSION: MSM sex tourists were more likely to have risky sexual behaviors and travel to locations with a higher HIV prevalence. MSM sex tourists may be part of core groups that are disproportionately responsible for MSM HIV transmission. Enhanced surveillance and interventions tailored to MSM sex tourists should be considered

Transcriptomics-Based Network Medicine Approach Identifies Metformin as a Repurposable Drug for Atrial Fibrillation

Effective drugs for atrial fibrillation (AF) are lacking, resulting in significant morbidity and mortality. This study demonstrates that network proximity analysis of differentially expressed genes from atrial tissue to drug tar-gets can help prioritize repurposed drugs for AF. Using enrichment analysis of drug-gene signatures and functional testing in human inducible pluripotent stem cell (iPSC)-derived atrial-like cardiomyocytes, we identify metformin as a top repurposed drug candidate for AF. Using the active compactor, a new design analysis of large-scale longitudinal electronic health record (EHR) data, we determine that metformin use is significantly associated with a reduced risk of AF (odds ratio = 0.48, 95%, confidence interval [CI] 0.36- 0.64, p \u3c 0.001) compared with standard treatments for diabetes. This study utilizes network medicine meth-odologies to identify repurposed drugs for AF treatment and identifies metformin as a candidate drug

Sequence divergence of Mus spretus and Mus musculus across a skin cancer susceptibility locus

<p>Abstract</p> <p>Background</p> <p><it>Mus spretus </it>diverged from <it>Mus musculus </it>over one million years ago. These mice are genetically and phenotypically divergent. Despite the value of utilizing <it>M. musculus </it>and <it>M. spretus </it>for quantitative trait locus (QTL) mapping, relatively little genomic information on <it>M. spretus </it>exists, and most of the available sequence and polymorphic data is for one strain of <it>M. spretus</it>, Spret/Ei. In previous work, we mapped fifteen loci for skin cancer susceptibility using four different <it>M. spretus </it>by <it>M. musculus </it>F1 backcrosses. One locus, <it>skin tumor susceptibility 5 </it>(<it>Skts5</it>) on chromosome 12, shows strong linkage in one cross.</p> <p>Results</p> <p>To identify potential candidate genes for <it>Skts5</it>, we sequenced 65 named and unnamed genes and coding elements mapping to the peak linkage area in outbred <it>spretus</it>, Spret/EiJ, FVB/NJ, and NIH/Ola. We identified polymorphisms in 62 of 65 genes including 122 amino acid substitutions. To look for polymorphisms consistent with the linkage data, we sequenced exons with amino acid polymorphisms in two additional <it>M. spretus </it>strains and one additional <it>M. musculus </it>strain generating 40.1 kb of sequence data. Eight candidate variants were identified that fit with the linkage data. To determine the degree of variation across <it>M. spretus</it>, we conducted phylogenetic analyses. The relatedness of the <it>M. spretus </it>strains at this locus is consistent with the proximity of region of ascertainment of the ancestral mice.</p> <p>Conclusion</p> <p>Our analyses suggest that, if <it>Skts5 </it>on chromosome 12 is representative of other regions in the genome, then published genomic data for Spret/EiJ are likely to be of high utility for genomic studies in other <it>M. spretus </it>strains.</p

Transepithelial Anti-Neuroblastoma Response to Kale among Four Vegetable Juices Using In Vitro Model Co-Culture System

Juicing vegetables is thought to be an anticancer treatment. Support exists for a rank order of anticancer greens (kale \u3e dandelion \u3e lettuce \u3e spinach) based on degrees of bioavailability of different phytochemicals, also offset by some noxious molecules (i.e., calcium-oxalate). We developed a new in vitro transepithelial anti-neuroblastoma model system. The juices were diluted as predicted once in the small intestine. They were applied to apical Caco-2Bbe1 cells atop dividing SH-SY5Y neuroblastoma cells, and changes in transepithelial electrical resistance (TEER) and cell growth were considered with juice spectroscopies. Studied first in monoculture, kale and dandelion were the most cytostatic juices on SH-SY5Ys, lettuce showed no effect, and high (4.2%) spinach was cytotoxic. In co-culture, high (4.2%) kale was quickest (three days) to inhibit neuroblastoma growth. By five days, dandelion and kale were equally robust. Lettuce showed small anti-proliferative effects at five days and spinach remained cytotoxic. Spinach’s cytotoxicity corresponded with major infrared bands indicative of oxalate. Kale juice uniquely induced reactive oxygen species and S-phase cell cycle arrest in SH-SY5Y. The superiority of kale and dandelion was also apparent on the epithelium, because raising TEER levels is considered healthy. Kale’s unique features corresponded with a major fluorescent peak that co-eluted with kaempferol during high performance liquid chromatography. Because the anticancer rank order was upheld, the model appears validated for screening anticancer juices