Development of new host-specific Bacteroides qPCRs for the identification of fecal contamination sources in water

Bacteroides spp. have been proposed as indicators of fecal contamination in microbial source tracking (MST) methodologies. The aim of this study was to develop new qPCR assays that target host-specific Bacteroidal 16S ribosomal RNA genes, to determine the source of fecal contamination in water. Denaturing gradient gel electrophoresis (DGGE) was used to select for host-specific bands of Bacteroides associated with a fecal pollution source and later to design four qPCR host-specific assays. A set of common primers for Bacteroides spp., four different Bacteroides spp. host-associated hydrolysis probes (human, cattle, pig, and poultry), and one hydrolysis probe for the Bacteroides genus were designed. This set of qPCR assays together with other previously developed Bacteroidetes MST targets were used to analyze water samples with fecal contamination from the four sources studied. The host-specific Bacteroides qPCRs designed for human (HMprobeBac), pig (PGprobeBac), and poultry (PLprobeBac) were highly specific for its sources (1.0, 0.97, and 1.0, respectively) although its sensitivity was lower (0.45, 0.50, and 0.73, respectively). The cattle-specific qPCR was totally unspecific and was discarded for future experiments. When compared to previously designed assays, the human and pig qPCRs showed better accuracies (0.86 and 0.84) than their counterparts HF183 and Pig-2-Bac (0.38 and 0.65). Thus, the newly designed human, pig, and poultry qPCR assays outperform other methods developed until date and may be useful for source tracking purpose

How Far Are Current Advisory Speeds from being Optimal? An Analysis Based on Safety Performance

Posting advisory speed signs at sharp horizontal curves to provide the driving public with a safe speed is a practice well established in the United States. The operational effectiveness of these signs has long been questioned in the current literature. The authors of this paper recently developed a function to model the expected safety effect of these signs. The function stems from a statistical analysis on crash data from 2-lane rural highways in the state of Oregon. In general, that research effort found that advisory speed signs tend to enhance safety. However, the authors also determined that advisory speed signs may not be displaying the value with the greatest potential safety benefit. Since the derived function proved meaningful from the engineering and human factors perspectives, these authors then extend the use of this function to compute and recommend the theoretically “optimal” advisory speed. A new posting procedure resulted from this effort. The authors compared the expected performance of advisory speeds from the proposed procedure to the speeds derived from current posting guidelines. A comparable performance suggests that current guidelines are close to the hypothetically “optimal” advisory speed. In general, both the current and new computational methods performed better than speeds determined by the ball bank indicator method. This paper also presents a field validation analysis of the engine function of the new posting method. The results confirmed the meaningfulness of the function, and therefore, of the potential benefit for determining safety-based advisory speeds with the method proposed in this paper.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Transportation Research Board of the National Academies (TRB) and can be found at: http://www.trb.org/Main/Blurbs/154702.aspx.Keywords: Advisory speed, Optimal advisory speed, Side Friction Demand, ASCF, Safet

Negativity of the Wigner function as an indicator of nonclassicality

A measure of nonclassicality of quantum states based on the volume of the negative part of the Wigner function is proposed. We analyze this quantity for Fock states, squeezed displaced Fock states and cat-like states defined as coherent superposition of two Gaussian wave packets.Comment: 10 pages, 7 figure

Laboratório móvel para monitoramento, avaliação e gerência de atributos de sistemas de produção agrícola.

bitstream/CNPMS/18890/1/Doc_49.pd

A multidimensional systems biology analysis of cellular senescence in aging and disease.

BACKGROUND: Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. RESULTS: We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. CONCLUSIONS: Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins

Heavy genealogy: mapping the currents, contraflows and conflicts of the emergent field of metal studies, 1978-2010

What is metal studies? How can we define and characterize it? How has it emerged as a body of academic enquiry? What are its dominant disciplinary strands, theoretical concepts and preferred methodologies? Which studies have claimed most attention, defined the goals of scholarship, typical research strategies and values? How has the claim for the legitimacy or symbolic value of metal scholarship been achieved (if it has): over time and through gradual acceptance or through conflict and contestation? How can this process of formation, or strategy of legitimation, be mapped, examined and interrogated and which methods of historical, institutional and cultural analysis are best suited to this task? Working with the most complete bibliography to date of published research on heavy metal, music and culture (the MSBD), this article employs Foucault’s archaeological “method” to examine the institutional, cultural and political contexts and conflicts that inform the genealogy of this scholarship. Such analysis reveals a formative, largely negative account of heavy metal to be found in the “sociology of rock”; a large volume of psychology work, examining heavy metal music preference as an indicator of youth risk, deviance and delinquency; sociological work on youth and deviancy critical of the values of this research and its links to social policy and politics; culminating in the work of Weinstein and Walser, who advocate a perspective sympathetic to the values of heavy metal fans themselves. Following Bourdieu, I interpret such symbolic strategies as claims for expertise within the academic field that are high or low in symbolic capital to the extent they can attain disciplinary autonomy. I then go on to examine the most recent strands of research, within cultural studies and ethnomusicology, concerned with the global metal music diaspora, and consider to what extent such work is constitutive of a coherent subfield of metal studies that can be distinguished from earlier work and what the implications of this might be