Evaluating Accessibility Issues in Urbana to Improve Safety at an Intersection

Details the efforts of the author to advocate for a safer pedestrian crossing at the intersection of Philo Road and Florida Avenue in Urbana, Illinois, especially for those in the community with disabilities

Seasonal cycle of precipitation variability in South America on intraseasonal timescales

The seasonal cycle of the intraseasonal (IS) variability of precipitation in South America is described through the analysis of bandpass filtered outgoing longwave radiation (OLR) anomalies. The analysis is discriminated between short (10--30 days) and long (30--90 days) intraseasonal timescales. The seasonal cycle of the 30--90-day IS variability can be well described by the activity of first leading pattern (EOF1) computed separately for the wet season (October--April) and the dry season (May--September). In agreement with previous works, the EOF1 spatial distribution during the wet season is that of a dipole with centers of actions in the South Atlantic Convergence Zone (SACZ) and southeastern South America (SESA), while during the dry season, only the last center is discernible. In both seasons, the pattern is highly influenced by the activity of the Madden--Julian Oscillation (MJO). Moreover, EOF1 is related with a tropical zonal-wavenumber-1 structure superposed with coherent wave trains extended along the South Pacific during the wet season, while during the dry season the wavenumber-1 structure is not observed. The 10--30-day IS variability of OLR in South America can be well represented by the activity of the EOF1 computed through considering all seasons together, a dipole but with the stronger center located over SESA. While the convection activity at the tropical band does not seem to influence its activity, there are evidences that the atmospheric variability at subtropical-extratropical regions might have a role. Subpolar wavetrains are observed in the Pacific throughout the year and less intense during DJF, while a path of wave energy dispersion along a subtropical wavetrain also characterizes the other seasons. Further work is needed to identify the sources of the 10--30-day-IS variability in South America

Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington's Disease Mice: Genome-Wide and Candidate Approaches

The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease HdhQ111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.HdhQ111) than on a 129 background (129.HdhQ111). Linkage mapping in (B6x129).HdhQ111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.HdhQ111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. HdhQ111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1–MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2–MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1 protein levels play an important role in driving of the efficiency of somatic expansions

Mismatch Repair Genes Mlh1 and Mlh3 Modify CAG Instability in Huntington\u27s Disease Mice: Genome-Wide and Candidate Approaches

The Huntington\u27s disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington\u27s disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111) ) than on a 129 background (129.Hdh(Q111) ). Linkage mapping in (B6x129).Hdh(Q111) F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111) mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111) somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1 protein levels play an important role in driving of the efficiency of somatic expansions

Population-based prevalence of cervical infection with human papillomavirus genotypes 16 and 18 and other high risk types in Tlaxcala, Mexico

This study was supported by the National Institute of Public Health of Mexico, the Coordinación de Investigación en Salud del Instituto Mexicano del Seguro Social, the Secretaría de Salud Tlaxcala, the Instituto Nacional de las Mujeres, and the Consejo Nacional de Ciencia y Tecnología [FOSISS 2013 202468]. Additional support has been provided by Roche Diagnostics, BD Diagnostics, DICIPA and Arbor Vita Corporation. The study sponsors did not played a role in designing the study, collecting, analyzing or interpreting the data, writing the report, or submitting this paper for publication. UC Berkeley Center for Global Public Health, Schoeneman Grant, Joint Medical Program Thesis Grant, and Cancer Research UK (C569/A10404)

Speech Communication

Contains reports on five research projects.C.J. Lebel FellowshipNational Institutes of Health (Grant 5 T32 NS07040)National Institutes of Health (Grant 5 R01 NS04332)National Science Foundation (Grant 1ST 80-17599)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0254)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0341)U.S. Navy - Naval Electronic Systems Command Contract (N00039-85-C-0290

SMAP L-Band Microwave Radiometer: Instrument Design and First Year on Orbit

The Soil Moisture Active Passive (SMAP) L-band microwave radiometer is a conical scanning instrument designed to measure soil moisture with 4 percent volumetric accuracy at 40-kilometer spatial resolution. SMAP is NASA's first Earth Systematic Mission developed in response to its first Earth science decadal survey. Here, the design is reviewed and the results of its first year on orbit are presented. Unique features of radiometer include a large 6-meter rotating reflector, fully polarimetric radiometer receiver with internal calibration, and radio-frequency interference detection and filtering hardware. The radiometer electronics are thermally controlled to achieve good radiometric stability. Analyses of on-orbit results indicate the electrical and thermal characteristics of the electronics and internal calibration sources are very stable and promote excellent gain stability. Radiometer NEdT (Noise Equivalent differential Temperature) less than 1 degree Kelvin for 17-millisecond samples. The gain spectrum exhibits low noise at frequencies greater than 1 megahertz and 1 divided by f (pink) noise rising at longer time scales fully captured by the internal calibration scheme. Results from sky observations and global swath imagery of all four Stokes antenna temperatures indicate the instrument is operating as expected

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

Fires can benefit plants by disrupting antagonistic interactions

Fire has a key role in the ecology and evolution of many ecosystems, yet its effects on plant–insect interactions are poorly understood. Because interacting species are likely to respond to fire differently, disruptions of the interactions are expected. We hypothesized that plants that regenerate after fire can benefit through the disruption of their antagonistic interactions. We expected stronger effects on interactions with specialist predators than with generalists. We studied two interactions between two Mediterranean plants (Ulex parviflorus, Asphodelus ramosus) and their specialist seed predators after large wildfires. In A. ramosus we also studied the generalist herbivores. We sampled the interactions in burned and adjacent unburned areas during 2 years by estimating seed predation, number of herbivores and fruit set. To assess the effect of the distance to unburned vegetation we sampled plots at two distance classes from the fire perimeter. Even 3 years after the fires, Ulex plants experienced lower seed damage by specialists in burned sites. The presence of herbivores on Asphodelus decreased in burned locations, and the variability in their presence was significantly related to fruit set. Generalist herbivores were unaffected. We show that plants can benefit from fire through the disruption of their antagonistic interactions with specialist seed predators for at least a few years. In environments with a long fire history, this effect might be one additional mechanism underlying the success of fire-adapted plants

The skeleton of the staghorn coral Acropora millepora: molecular and structural characterization

15 pagesInternational audienceThe scleractinian coral Acropora millepora is one of the most studied species from the Great Barrier Reef. This species has been used to understand evolutionary, immune and developmental processes in cnidarians. It has also been subject of several ecological studies in order to elucidate reef responses to environmental changes such as temperature rise and ocean acidification (OA). In these contexts, several nucleic acid resources were made available. When combined to a recent proteomic analysis of the coral skeletal organic matrix (SOM), they enabled the identification of several skeletal matrix proteins, making A. millepora into an emerging model for biomineralization studies. Here we describe the skeletal microstructure of A. millepora skeleton, together with a functional and biochemical characterization of its occluded SOM that focuses on the protein and saccharidic moieties. The skeletal matrix proteins show a large range of isoelectric points, compositional patterns and signatures. Besides secreted proteins, there are a significant number of proteins with membrane attachment sites such as transmembrane domains and GPI anchors as well as proteins with integrin binding sites. These features show that the skeletal proteins must have strong adhesion properties in order to function in the calcifying space. Moreover this data suggest a molecular connection between the calcifying epithelium and the skeletal tissue during biocalcification. In terms of sugar moieties, the enrichment of the SOM in arabinose is striking, and the monosaccharide composition exhibits the same signature as that of mucus of acroporid corals. Finally, we observe that the interaction of the acetic acid soluble SOM on the morphology of in vitro grown CaCO3 crystals is very pronounced when compared with the calcifying matrices of some mollusks. In light of these results, we wish to commend Acropora millepora as a model for biocalcification studies in scleractinians, from molecular and structural viewpoints