63 research outputs found
Machine Translation for Accessible Multi-Language Text Analysis
English is the international standard of social research, but scholars are
increasingly conscious of their responsibility to meet the need for scholarly
insight into communication processes globally. This tension is as true in
computational methods as any other area, with revolutionary advances in the
tools for English language texts leaving most other languages far behind. In
this paper, we aim to leverage those very advances to demonstrate that
multi-language analysis is currently accessible to all computational scholars.
We show that English-trained measures computed after translation to English
have adequate-to-excellent accuracy compared to source-language measures
computed on original texts. We show this for three major analytics -- sentiment
analysis, topic analysis, and word embeddings -- over 16 languages, including
Spanish, Chinese, Hindi, and Arabic. We validate this claim by comparing
predictions on original language tweets and their backtranslations: double
translations from their source language to English and back to the source
language. Overall, our results suggest that Google Translate, a simple and
widely accessible tool, is effective in preserving semantic content across
languages and methods. Modern machine translation can thus help computational
scholars make more inclusive and general claims about human communication.Comment: 5000 words, 6 figure
Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism That Increases Risk of Docetaxel-Induced Neuropathy
Purpose Discovery of single nucleotide polymorphisms (SNPs) that predict a patient\u27s risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy. Experimental Design A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy. Results 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. A SNP in VAC14 (rs875858) surpassed genome-wide significance (p=2.12×10-8 adjusted p=5.88×10-7). siRNA knockdown of VAC14 in stem cell derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (p=0.0015) and branches (p\u3c0.0001). Prior to docetaxel treatment VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (p=0.001). Conclusions VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization
High content live cell imaging for the discovery of new antimalarial marine natural products
<p>Abstract</p> <p>Background</p> <p>The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, <it>Plasmodium falciparum</it>.</p> <p>Methods</p> <p>A high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown <it>in vitro </it>in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope.</p> <p>Results</p> <p>Image analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasite's phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts.</p> <p>Conclusion</p> <p>Collectively, our results show that high-content live cell-imaging (HCLCI) can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials.</p
Analysis of the putative role of CR1 in Alzheimer’s disease: Genetic association, expression and function
Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer's disease (AD). Recent large genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the C3b/C4b receptor (CR1 or CD35) that are associated with late onset AD. Here, anti-CR1 antibodies (Abs) directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1) regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved
Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats
In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security
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NASA DEEP SPACE NETWORK OPERATIONS CONTROL
International Telemetering Conference Proceedings / September 28-30, 1982 / Sheraton Harbor Island Hotel and Convention Center, San Diego, CaliforniaOverall direction, coordination and control of the real-time activities of the NASA Deep Space Network (DSN) is the responsibility of the Network Operations Control Team located at the Operations Control Center at JPL in Pasadena. Real-time operation of the DSN is a complex task, requiring efficient interaction among operations personnel, hardware, software, communications and mechanical systems. Control is maintained by the team at JPL through allocation of responsibility for specific operational facilities to specific team members. The Network Operations Control Team is comprised of an Operations Chief, a Track Chief, and one or more Deep Space Station (DSS) Controllers. The Operations Chief is responsible for overall performance of the Operations Control Center, and provides a single point of interface with the Control Center to end user organizations. The Track Chief is responsible for overall performance of the DSN as a facility, while the Station controllers are assigned responsibility for monitoring and coordinating the operational activities at individual Deep Space Stations.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection
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Thallium Poisoning from Maliciously Contaminated Food
Abstract
Four young adults presented two days after one of them had received marzipan balls packaged in a box from an expensive candy manufacturer. Two ate one candy ball, while two others shared a third. The next day, variable gastrointestinal symptoms developed. On the third day, two patients developed painful paresthesiae of the hands and feet, an early but nonspecific clinical marker of thallium poisoning. A tentative diagnosis of thallium poisoning was made based on symptoms, and treatment was initiated. The remaining candies were radiographed. Metallic densities in the candies supported the diagnosis, and atomic absorption spectroscopy was used to quantitate thallium content. Each candy contained a potentially fatal dose. Five to seven days later, hypertension and tachycardia developed in the two patients who had ingested an entire candy. All patients developed alopecia but recovered without overt neurologic or other sequelae. While the diagnosis of thallium poisoning is often delayed until alopecia develops, an early diagnosis favors an effective treatment strategy
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