Topic Similarity Networks: Visual Analytics for Large Document Sets

We investigate ways in which to improve the interpretability of LDA topic models by better analyzing and visualizing their outputs. We focus on examining what we refer to as topic similarity networks: graphs in which nodes represent latent topics in text collections and links represent similarity among topics. We describe efficient and effective approaches to both building and labeling such networks. Visualizations of topic models based on these networks are shown to be a powerful means of exploring, characterizing, and summarizing large collections of unstructured text documents. They help to "tease out" non-obvious connections among different sets of documents and provide insights into how topics form larger themes. We demonstrate the efficacy and practicality of these approaches through two case studies: 1) NSF grants for basic research spanning a 14 year period and 2) the entire English portion of Wikipedia.Comment: 9 pages; 2014 IEEE International Conference on Big Data (IEEE BigData 2014

Interference With Privacy - In What Forms Might It Be Actionable in Virginia?

Much has been written about the right of privacy since the 1890 law review article by Samuel Warren and Louis Brandeis which first proposed that such a right be recognized. In the ensuing years the tort of invasion of privacy, which is, in reality, an amalgam of four separate torts, has been widely accepted. In spite of the burgeoning recognition of various rights assembled under the rubric of right to privacy, the Supreme Court of Virginia has never decided whether private citizens are entitled to protection of their personal privacy against invasions by other private citizens. It is the intent of this article to discuss the status of the common law tort of invasion of privacy in Virginia and to consider whether the tort, if it exists in any embryonic stage, would or should be legitimatized. Because of the proliferation of articles and cases discussing various facets of the right of privacy, this article is of limited scope. It makes no attempt to discuss in detail whether particular factual situations should or should not fall within the purview of such a right, to catalogue, review or discuss the right of privacy as developed in other jurisdictions, or to deal with constitutional limitations on governments which grant or ensure a limited right of privacy. Neither does the article discuss the first amendment ramifications necessarily raised by certain branches of the tort of invasion of privacy involving publication of private facts, unauthorized appropriation of one\u27s name or likeness or portrayal of an individual in a false light

Negative magnetoresistance, negative electroresistance, and metallic behavior on the insulating side of the two-dimensional superconductor-insulator transition in granular Pb films

Granular Pb thin films on the insulating side of the two-dimensional superconductor-insulator transition are observed to exhibit a large negative magnetoresistance and electroresistance change in resistance with electric field at low temperatures. At high measurement voltages and low temperatures, the film resistances become temperature independent creating a metallic state. These phenomena are explained as manifestations of transport due to intergranular quasiparticle tunneling. This explanation might also provide insights into the similar behavior observed in other superconductors

A culture-independent approach to unravel uncultured bacteria and functional genes in a complex microbial community

Most microorganisms in nature are uncultured with unknown functionality. Sequence-based metagenomics alone answers 'who/what are there?' but not 'what are they doing and who is doing it and how?'. Function-based metagenomics reveals gene function but is usually limited by the specificity and sensitivity of screening strategies, especially the identification of clones whose functional gene expression has no distinguishable activity or phenotypes. A 'biosensor-based genetic transducer' (BGT) technique, which employs a whole-cell biosensor to quantitatively detect expression of inserted genes encoding designated functions, is able to screen for functionality of unknown genes from uncultured microorganisms. In this study, BGT was integrated with Stable isotope probing (SIP)-enabled Metagenomics to form a culture-independent SMB toolbox. The utility of this approach was demonstrated in the discovery of a novel functional gene cluster in naphthalene contaminated groundwater. Specifically, metagenomic sequencing of the (13)C-DNA fraction obtained by SIP indicated that an uncultured Acidovorax sp. was the dominant key naphthalene degrader in-situ, although three culturable Pseudomonas sp. degraders were also present in the same groundwater. BGT verified the functionality of a new nag2 operon which co-existed with two other nag and two nah operons for naphthalene biodegradation in the same microbial community. Pyrosequencing analysis showed that the nag2 operon was the key functional operon in naphthalene degradation in-situ, and shared homology with both nag operons in Ralstonia sp. U2 and Polaromonas naphthalenivorans CJ2. The SMB toolbox will be useful in providing deep insights into uncultured microorganisms and unravelling their ecological roles in natural environments

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2

Objective: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Methods: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments. Results: In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Conclusions: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile

Kloning Manusia

In the last few years, very rapid progress in the cloning technology and its development towards human cloning has become a hotly-debated issue. Cloning, which is the process of formation of a number of individuals with the same genetic structure, can be done by means of embryo-splitting method and nuclear transfer. Human cloning through the nuclear transfer method is directed towards two purposes, i.e. reproduction and therapy. The relatively new transgenic technology can be combined with the cloning technique to produce clones with new genes. However, pros and cons arise concerning the development of research on human cloning, particularly cloning for reproductive purposes. Therefore, there is need for a moratorium period before human cloning can be performed in order that solutions for all kinds of problems related to safety and ethics can be found

211 Identifying lupus patient subsets and specific pharmacodynamic changes through immune cell deconvolution of gene expression data in atacicept-treated patients in the APRIL-SLE study

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Reprogramming of Escherichia coli K-12 Metabolism during the Initial Phase of Transition from an Anaerobic to a Micro-Aerobic Environment

Background: Many bacteria undergo transitions between environments with differing O2 availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation when bacteria experience changes in O2 availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process. Methods and Findings: Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O2 sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR. Conclusion: Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O2 combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O2 sensor FNR during transition from anaerobic to micro-aerobic conditions

The effect of childhood stunting and wasting on adolescent cardiovascular diseases risk and educational achievement in rural Uganda : a retrospective cohort study

Background: Little is known about the long-term effects of early childhood undernutrition on adolescent cardiovascular disease risk and educational performance in low-income countries. We examined this in a rural Ugandan population. Objective: To investigate if stunting or wasting among children aged 2-5 years is associated with cardiovascular disease risk or educational achievement during adolescence. Methods: We conducted analyses using data from a cohort of children followed from early childhood to adolescence. Weight and height were measured in 1999-2000 when the children were 2-5 years of age and repeated in 2004/2005 and 2011. We compared cardiovascular disease risk parameters (mean blood pressure, lipids, HbA1c) and schooling years achieved in 2011 among 1054 adolescents categorised into four groups: those who experienced stunting or wasting throughout follow-up; those who recovered from stunting or wasting; those who were normal but later became stunted or wasted; and those who never experienced stunting or wasting from childhood up to adolescence. We controlled for possible confounding using multiple generalised linear regression models along with Generalised Estimating Equations to account for clustering of children within households. Results: Wasting was negatively associated with systolic blood pressure (-7.90 95%CI [-14.52,-1.28], p = 0.02) and diastolic blood pressure (-3.92, 95%CI [-7.42, -0.38], p = 0.03). Stunting had borderline negative association with systolic blood pressure (-2.90, 95%CI [-6.41, 0.61] p = 0.10). Recovery from wasting was positively associated with diastolic blood pressure (1.93, 95%CI [0.11, 3.74] p = 0.04). Stunting or wasting was associated with fewer schooling years. Conclusion: Recovery from wasting rather than just an episode in early childhood is associated with a rise in blood pressure while educational achievement is compromised regardless of whether recovery from undernutrition happens. These findings are relevant to children exposed to undernutrition in low-income settings

Mitochondrial Uncoupling Inhibits p53 Mitochondrial Translocation in TPA-Challenged Skin Epidermal JB6 Cells

The tumor suppressor p53 is known to be able to trigger apoptosis in response to DNA damage, oncogene activation, and certain chemotherapeutic drugs. In addition to its transcriptional activation, a fraction of p53 translocates to mitochondria at the very early stage of apoptosis, which eventually contributes to the loss of mitochondrial membrane potential, generation of reactive oxygen species (ROS), cytochrome c release, and caspase activation. However, the mitochondrial events that affect p53 translocation are still unclear. Since mitochondrial uncoupling has been suggested to contribute to cancer development, herein, we studied whether p53 mitochondrial translocation and subsequent apoptosis were affected by mitochondrial uncoupling using chemical protonophores, and further verified the results using a siRNA approach in murine skin epidermal JB6 cells. Our results showed that mitochondrial uncoupling blocked p53 mitochondrial translocation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA), a known tumor promoter to induce p53-mediated apoptosis in skin carcinogenesis. This blocking effect, in turn, led to preservation of mitochondrial functions, and eventually suppression of caspase activity and apoptosis. Moreover, uncoupling protein 2 (UCP2), a potential suppressor of ROS in mitochondria, is important for TPA-induced cell transformation in JB6 cells. UCP2 knock down cells showed enhanced p53 mitochondrial translocation, and were less prone to form colonies in soft agar after TPA treatment. Altogether, our data suggest that mitochondrial uncoupling may serve as an important regulator of p53 mitochondrial translocation and p53-mediated apoptosis during early tumor promotion. Therefore, targeting mitochondrial uncoupling may be considered as a novel treatment strategy for cancer