Targeting determinants of dosage compensation in Drosophila

The dosage compensation complex (DCC) in Drosophila melanogaster is responsible for up-regulating transcription from the single male X chromosome to equal the transcription from the two X chromosomes in females. Visualization of the DCC, a large ribonucleoprotein complex, on male larval polytene chromosomes reveals that the complex binds selectively to many interbands on the X chromosome. The targeting of the DCC is thought to be in part determined by DNA sequences that are enriched on the X. So far, lack of knowledge about DCC binding sites has prevented the identification of sequence determinants. Only three binding sites have been identified to date, but analysis of their DNA sequence did not allow the prediction of further binding sites. We have used chromatin immunoprecipitation to identify a number of new DCC binding fragments and characterized them in vivo by visualizing DCC binding to autosomal insertions of these fragments, and we have demonstrated that they possess a wide range of potential to recruit the DCC. By varying the in vivo concentration of the DCC, we provide evidence that this range of recruitment potential is due to differences in affinity of the complex to these sites. We were also able to establish that DCC binding to ectopic high-affinity sites can allow nearby low-affinity sites to recruit the complex. Using the sequences of the newly identified and previously characterized binding fragments, we have uncovered a number of short sequence motifs, which in combination may contribute to DCC recruitment. Our findings suggest that the DCC is recruited to the X via a number of binding sites of decreasing affinities, and that the presence of high-and moderate-affinity sites on the X may ensure that lower-affinity sites are occupied in a context-dependent manner. Our bioinformatics analysis suggests that DCC binding sites may be composed of variable combinations of degenerate motifs

Emergency ambulance service involvement with residential care homes in the support of older people with dementia : an observational study

© 2014 Amador et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Older people resident in care homes have a limited life expectancy and approximately two-thirds have limited mental capacity. Despite initiatives to reduce unplanned hospital admissions for this population, little is known about the involvement of emergency services in supporting residents in these settings.METHODS: This paper reports on a longitudinal study that tracked the involvement of emergency ambulance personnel in the support of older people with dementia, resident in care homes with no on-site nursing providing personal care only. 133 residents with dementia across 6 care homes in the East of England were tracked for a year. The paper examines the frequency and reasons for emergency ambulance call-outs, outcomes and factors associated with emergency ambulance service use. RESULTS: 56% of residents used ambulance services. Less than half (43%) of all call-outs resulted in an unscheduled admission to hospital. In addition to trauma following a following a fall in the home, results suggest that at least a reasonable proportion of ambulance contacts are for ambulatory care sensitive conditions. An emergency ambulance is not likely to be called for older rather than younger residents or for women more than men. Length of residence does not influence use of emergency ambulance services among older people with dementia. Contact with primary care services and admission route into the care home were both significantly associated with emergency ambulance service use. The odds of using emergency ambulance services for residents admitted from a relative's home were 90% lower than the odds of using emergency ambulance services for residents admitted from their own home. CONCLUSIONS: Emergency service involvement with this vulnerable population merits further examination. Future research on emergency ambulance service use by older people with dementia in care homes, should account for important contextual factors, namely, presence or absence of on-site nursing, GP involvement, and access to residents' family, alongside resident health characteristics.Peer reviewedFinal Published versio

ifo Konjunkturprognose 2006/2007: Aufschwung setzt sich fort

Die Weltwirtschaft ist in einem robusten Aufschwung. Das vom ifo Institut erhobene Weltwirtschaftsklima hat sich im Frühjahr 2006 zum dritten Mal in Folge verbessert; und liegt deutlich über dem langfristigen Durchschnitt. Die Expansion der Weltwirtschaft wird im Prognosezeitraum schwungvoll bleiben, sich jedoch schrittweise etwas abflachen. Die Konjunktur in Deutschland zeigt sich zur Jahresmitte 2006 gut in Form. Das hervorragende ifo Geschäftsklima indiziert, dass der Aufschwung der deutschen Wirtschaft beträchtlich an Breite gewonnen hat. Neben dem mit hoher Drehzahl laufenden Exportmotor ist nun auch die Binnenkonjunktur in Schwung gekommen. Die Investitionen in Ausrüstungen haben Tritt gefasst; die neuesten Zahlen des ifo Konjunkturtests signalisieren, dass nicht nur die im Sog des Exportbooms stehenden Unternehmen investieren, sondern nun auch die eher binnenwirtschaftlich orientierten Unternehmen. Selbst der private Konsum hat, nach dem Rückgang im Jahresendquartal 2005, zugelegt; zusätzliche Impulse werden in der zweiten Jahreshälfte von vorgezogenen Käufen ausgehen, mit denen die ab Januar kommenden Jahres geltende höhere Mehrwertsteuer kurzfristig noch eingespart werden kann. Ingesamt wird das reale Bruttoinlandsprodukt im laufenden Jahr um 1,8% expandieren; nach Ausschaltung der im Vergleich zu 2005 geringeren Zahl an Arbeitstagen um 2%. Im kommenden Jahr wird die Konjunktur durch die massive Erhöhung von Steuern und Abgaben zwar beträchtlich gedämpft; gleichwohl wird sich aber der Aufschwung fortsetzen. Diese Einschätzung stützt sich zu einem großen Teil auf die endogene Konjunkturdynamik der deutschen Wirtschaft. Nach einem "klassischen" Abschwung in den ersten Jahren dieses Jahrzehnts, der von einem Rückgang der Trendwachstumsrate begleitet war, wurde sowohl bei der gesamtwirtschaftlichen Produktion als auch bei den Ausrüstungsinvestitionen im Laufe des Jahres 2004 der untere Wendepunkt erreicht.Weltkonjunktur, Konjunkturprognose, Wirtschaftslage, Wirtschaftswachstum, Geschäftsklima, Deutschland, Welt

Nutzung öffentlichen Raums am Beispiel Freiburg: Forschungsfokus auf Adressat*innen Sozialer Arbeit der Sucht- und Straffälligenhilfe

In diesem Forschungsprojekt wir versucht herauszufinden, welche Menschen sich an welchen Orten im öffentlichen Raum aufhalten, wozu sie den öffentlichen Raum nutzen und wie sie sich dort verhalten. Daraus könnten sich Rückschlüsse für die Bedeutung des öffentlichen Raums bei unterschiedlichen Menschen ziehen lassen, so die Annahme. Diese Schlüsse und Vermutungen könnten dabei helfen die Lebenssituation der Menschen vor Ort besser zu verstehen. Die Bedeutung für Soziale Arbeit ergibt sich aus den Erkenntnissen, der Nutzung und Bedeutungszuschreibung des öffentlichen Raums durch Adressat*innen Sozialer Arbeit. Hierzu wurden von der Seminargruppe zunächst Handlungsfeld spezifische Personengruppen bzw. Adressat*innen ausgewählt, die im Laufe des Seminars durch Beobachtungsmethoden genauer "unter die Lupe genommen" werden sollten. Als Beobachtungsfeld und Gegenstand der Untersuchung öffentlichen Raums, wurde mit dem "Platz an der alten Synagoge" ein zent-raler Platz in der Freiburger Innenstadt ausgewählt. Das Lernziel des Lehrforschungsprojektes war, den Einsatz von Beobachtungsmethoden kennen und exemplarisch anwenden zu lernen, um diese auch für die empirische Arbeit in ihrer Abschlussarbeit einsetzen zu können

Draft Genome Sequencing of Three Glutaraldehyde-Tolerant Bacteria from Produced Water from Hydraulic Fracturing

Here, we report the draft genome sequence of three glutaraldehyde-resistant isolates from produced water from hydraulic fracturing operations. The three strains were identified as sp. strain G11, sp. strain G15, and sp. strain G16. The genome sequences of these isolates will provide insights into biocide resistance in hydraulic fracturing operations

Neutrino Interactions at Ultrahigh Energies

We report new calculations of the cross sections for deeply inelastic neutrino-nucleon scattering at neutrino energies between 10^{9}\ev and 10^{21}\ev. We compare with results in the literature and assess the reliability of our predictions. For completeness, we briefly review the cross sections for neutrino interactions with atomic electrons, emphasizing the role of the $W$-boson resonance in $\bar{\nu}_{e}e$ interactions for neutrino energies in the neighborhood of 6.3\pev. Adopting model predictions for extraterrestrial neutrino fluxes from active galactic nuclei, gamma-ray bursters, and the collapse of topological defects, we estimate event rates in large-volume water \v{C}erenkov detectors and large-area ground arrays.Comment: 32 pages, 11 figures, uses RevTeX and boxedep

Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: A systematic review and meta-analysis of randomized clinical trials

Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto\ue2\u80\u99s method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up