Manifolds with large isotropy groups

We classify all simply connected Riemannian manifolds whose isotropy groups act with cohomogeneity less than or equal to two.Comment: 21 page

Clifford algebras and new singular Riemannian foliations in spheres

Using representations of Clifford algebras we construct indecomposable singular Riemannian foliations on round spheres, most of which are non-homogeneous. This generalizes the construction of non-homogeneous isoparametric hypersurfaces due to by Ferus, Karcher and Munzner.Comment: 21 pages. Construction of foliations in the Cayley plane added. Proofs simplified and presentation improved, according to referee's suggestions. To appear in Geom. Funct. Ana

DNA binding kinetics of two response regulators, PlnC and PlnD, from the bacteriocin regulon of Lactobacillus plantarum C11

<p>Abstract</p> <p>Background</p> <p>Bacteriocin production in the lactic acid bacterium <it>Lactobacillus plantarum </it>C11 is regulated through a quorum sensing based pathway involving two highly homologous response regulators (59% identity and 76% similarity), PlnC as a transcriptional activator and PlnD as a repressor. Previous <it>in vitro </it>studies have shown that both regulators bind, as homodimers, to the same DNA regulatory repeats to exert their regulatory functions. As the genes for these two proteins are located on the same auto-regulatory operon, hence being co-expressed upon gene activation, it is plausible that their opposite functions must somehow be differentially regulated, either in terms of timing and/or binding kinetics, so that their activities do not impair each other in an uncontrolled manner. To understand the nature behind this potential differentiation, we have studied the binding kinetics of the two regulators on five target promoters (P_{<it>plnA</it>}, P_{<it>plnM</it>}, P_{<it>plnJ</it>}, P_{<it>plnE </it>}and P_{<it>plnG</it>}) from the bacteriocin regulon of <it>L. plantarum </it>C11.</p> <p>Results</p> <p>By using surface plasmon resonance spectroscopy we obtained parameters such as association rates, dissociation rates and dissociation constants, showing that the two regulators indeed differ greatly from each other in terms of cooperative binding and binding strength to the different promoters. For instance, cooperativity is very strong for PlnC binding to the promoter of the regulatory operon (P_{<it>plnA</it>}), but not to the promoter of the transport operon (P_{<it>plnG</it>}), while the opposite is seen for PlnD binding to these two promoters. The estimated affinity constants indicate that PlnC can bind to P_{<it>plnA </it>}to activate transcription of the key regulatory operon <it>plnABCD </it>without much interference from PlnD, and that the repressive function of PlnD might act through a different mechanism than repression of the regulatory operon.</p> <p>Conclusion</p> <p>We have characterised the DNA binding kinetics of the two regulators PlnC and PlnD from the bacteriocin locus in <it>L. plantarum </it>C11. Our data show that PlnC and PlnD, despite their strong homology to each other, differ greatly from each other in terms of binding affinity and cooperativity to the different promoters of the <it>pln </it>regulon.</p

Characterization of the RaD-X Mission Instruments

The NASA Radiation Dosimetry Experiment (RaD-X) stratospheric balloon flight mission, launched on 25 September 2015, provided dosimetric measurements above the Pfotzer maximum. The goal of taking these measurements is to improve aviation radiation models by providing a characterization of cosmic ray primaries, which are the source of radiation exposure at aviation altitudes. The RaD-X science payload consists of four instruments. The main science instrument is a tissue-equivalent proportional counter (TEPC). The other instruments consisted of three solid state silicon dosimeters: Liulin, Teledyne total ionizing dose (TID) and RaySure detectors. To properly interpret the measurements, it is necessary to evaluate how the payload affects the radiation environment of the detectors. In addition, it is necessary to evaluate how the detectors react to the different particles impacting them. We present the results of the Geant-4 simulations of the interaction of the different radiations with the payload and the instruments. We show how it affect the measurements, and which instruments are better suited for future mission

Genome-Wide Expression Analysis in Drosophila Reveals Genes Controlling Circadian Behavior

In Drosophila, a number of key processes such as emergence from the pupal case, locomotor activity, feeding, olfaction, and aspects of mating behavior are under circadian regulation. Although we have a basic understanding of how the molecular oscillations take place, a clear link between gene regulation and downstream biological processes is still missing. To identify clock-controlled output genes, we have used an oligonucleotide-based high-density array that interrogates gene expression changes on a whole genome level. We found genes regulating various physiological processes to be under circadian transcriptional regulation, ranging from protein stability and degradation, signal transduction, heme metabolism, detoxification, and immunity. By comparing rhythmically expressed genes in the fly head and body, we found that the clock has adapted its output functions to the needs of each particular tissue, implying that tissue-specific regulation is superimposed on clock control of gene expression. Finally, taking full advantage of the fly as a model system, we have identified and characterized a cycling potassium channel protein as a key step in linking the transcriptional feedback loop to rhythmic locomotor behavior.Fil: Ceriani, Maria Fernanda. The Scripps Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Hogenesch, John B.. Genomics Institute of the Novartis Research Foundation; Estados UnidosFil: Yanovsky, Marcelo Javier. The Scripps Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Panda, Satchidananda. Genomics Institute of the Novartis Research Foundation; Estados Unidos. The Scripps Research Institute; Estados UnidosFil: Straume, Martin. University Of Virginia; Estados UnidosFil: Kay, Steve A.. Genomics Institute of the Novartis Research Foundation; Estados Unidos. The Scripps Research Institute; Estados Unido

Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock

AbstractIn mammals, circadian control of physiology and behavior is driven by a master pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed ∼650 cycling transcripts and showed that the majority of these were specific to either the SCN or the liver. Genetic and genomic analysis suggests that a relatively small number of output genes are directly regulated by core oscillator components. Major processes regulated by the SCN and liver were found to be under circadian regulation. Importantly, rate-limiting steps in these various pathways were key sites of circadian control, highlighting the fundamental role that circadian clocks play in cellular and organismal physiology

A systematic review of strategies to recruit and retain primary care doctors

Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established