61 research outputs found
From Vertices to Vortices in magnetic nanoislands
Recent studies in magnetic nanolithography show that a variety of complex
magnetic states emerge as a function of a single magnetic island's aspect
ratio. We propose a model which, in addition to fitting experiments, predicts
magnetic states with continuous symmetry at particular aspect ratios and
reveals a duality between vortex and vertex states. Our model then opens new
means of engineering novel types of artificial spin systems, and their
application to complex magnetic textures in devices and computing.Comment: 3 pages + epsilon + 18 supplementary materia
Bennett Public School Principal Induction Program
Thesis advisor: Irwin BlumerEnsuring equity in education and academic success for all students requires a highly skilled principal engages others in continually improving the instructional program in order to meet the needs of students. Over the past few years, a number of reports have indicated that the role of principal is becoming more challenging. School districts are having trouble attracting and retaining highly qualified principals, and principal candidates and current principals are not prepared or supported enough for managing the various demands of the job. In 2010, according to the district, 49 of the 129 active principals had been in their role for three years or fewer. The Bennett Public Schools are designing a leadership development program for aspiring and new principals. This study is designed to support the Bennett Public Schools in its efforts to develop effective school leaders and is focused on answering two research questions: What does the literature say about skills that are required to be an effective urban principal? Based on the literature review and interviews with principals in Bennett Public Schools, what should be the components of an induction program to support principals in their first three years in the district? Twelve novice Bennett Public Schools principals were interviewed using a semi-structured interview protocol. The pool of interviewees reflects the diversity of the population in characteristics including gender, racial diversity, elementary and secondary schools, as well as the various structures of schools in the district: traditional, pilot, innovation and in-district charter. A synthesis of literature and interviews reinforces the importance of the Bennett Public Schools establishing an induction program with a clear set of competencies, or a competency framework, aligned with the 2011 standards for effective school leadership from the Massachusetts Department of Elementary and Secondary Education. This program should include five components: recruitment and selection strategy, year-long site-based internship, mentoring and coaching, relevant professional development and evaluation of the program and participants.Thesis (EdD) — Boston College, 2012.Submitted to: Boston College. Lynch School of Education.Discipline: Educational Leadership and Higher Education
Complex structural rearrangements are present in high-grade dysplastic Barrett\u27s oesophagus samples
Background: Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett’s oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the early identification of at-risk individuals.
Methods: In this study, we assessed the genomic features of 16 BE samples using whole-genome sequencing. These included non-dysplastic samples collected at two time-points from two BE patients who had not progressed to EAC over several years. Seven other non-dysplastic samples and five dysplastic BE samples with high-grade dysplasia were also examined. We compared the genome profiles of these 16 BE samples with 22 EAC samples.
Results: We observed that samples from the two non-progressor individuals had low numbers of somatic single nucleotide variants, indels and structural variation events compared to dysplastic and the remaining non-dysplastic BE. EAC had the highest level of somatic genomic variations. Mutational signature 17, which is common in EAC, was also present in non-dysplastic and dysplastic BE, but was not present in the non-progressors. Many dysplastic samples had mutations in genes previously reported in EAC, whereas only mutations in CDKN2A or in the fragile site genes appeared common in non-dysplastic samples. Rearrangement signatures were used to identify a signature associated with localised complex events such as chromothripsis and breakage fusion-bridge that are characteristic of EACs. Two dysplastic BE samples had a high contribution of this signature and contained evidence of localised rearrangements. Two other dysplastic samples also had regions of localised structural rearrangements. There was no evidence for complex events in non-dysplastic samples.
Conclusions: The presence of complex localised rearrangements in dysplastic samples indicates a need for further investigations into the role such events play in the progression from BE to EAC
Recommended from our members
POT1 mutations predispose to familial melanoma
Deleterious germline variants in CDKN2A account for around 40% of familial melanoma cases, and rare variants in CDK4, BRCA2, BAP1 and the promoter of TERT have also been linked to the disease. Here we set out to identify new high-penetrance susceptibility genes by sequencing 184 melanoma cases from 105 pedigrees recruited in the UK, The Netherlands and Australia that were negative for variants in known predisposition genes. We identified families where melanoma cosegregates with loss-of-function variants in the protection of telomeres 1 gene (POT1), with a proportion of family members presenting with an early age of onset and multiple primary tumors. We show that these variants either affect POT1 mRNA splicing or alter key residues in the highly conserved oligonucleotide/oligosaccharide-binding (OB) domains of POT1, disrupting protein-telomere binding and leading to increased telomere length. These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres.D.J.A., C.D.R.-E., Z.D., J.Z.L., J.C.T., M.P. and T.M.K. were supported by Cancer Research UK and the Wellcome Trust (WT098051). C.D.R.-E. was also supported by the Consejo Nacional de Ciencia y Tecnología of Mexico. K.A.P. and A.M.D. were supported by Cancer Research UK (grants C1287/A9540 and C8197/A10123) and by the Isaac Newton Trust. N.K.H. was supported by a fellowship from the National Health and Medical Research Council of Australia (NHMRC). L.G.A. was supported by an Australia and New Zealand Banking Group Limited Trustees PhD scholarship. A.L.P. is supported by Cure Cancer Australia. The work was funded in part by the NHMRC and Cancer Council Queensland. The work of N.A.G. was in part supported by the Dutch Cancer Society (UL 2012-5489). M.H., J.A.N.-B. and D.T.B. were supported by Cancer Research UK (programme awards C588/A4994 and C588/A10589 and the Genomics Initiative). C.L.-O., A.J.R. and V.Q. are funded by the Spanish Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III (ISCIII), the Red Temática de Investigación del Cáncer (RTICC) del ISCIII and the Consolider-Ingenio RNAREG Consortium. C.L.-O. is an investigator with the Botín Foundation.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.294
Il sito web dell'Osservatorio Vesuviano
L'Osservatorio Vesuviano ha di recente realizzato una radicale ristrutturazione del
proprio sito Web, attivo dalla seconda metà del 1997, al fine di adeguarlo alla sua
nuova configurazione giuridica. Infatti, dal 10 gennaio 2001 è entrato a far parte
dell'Istituto Nazionale di Geofisica e Vulcanologia (INGV), un ente nazionale di
nuova formazione in cui sono confluiti i maggiori enti ed istituzioni di ricerca
operanti nel campo della geofisica e della vulcanologia in Italia. Con la nascita
dell'INGV si è posta un'esigenza di coordinamento tra i siti web di dette istituzioni,
che si configurano attualmente come sezioni del nuovo ente nazionale. Inoltre, è
sorta la necessità di creare delle pagine comuni, relative all'ente nella sua totalità, che
introducessero i visitatori alle pagine delle singole sezioni ed eventualmente a
specifici tematismi riguardanti le attività dell'ente. A tal fine, è stato istituito un
gruppo di Coordinamento Nazionale per il Web che comprende personale afferente
alle diverse sezioni. Parallelamente sono stati istituiti gruppi di lavoro locali per la
ristrutturazione dei siti delle sezioni. Nell'ambito di questa riorganizzazione, presso
l'Osservatorio Vesuviano, con Decreto Direttoriale N. 6, del 30 gennaio 2002, è stato
istituito un gruppo di lavoro con il compito di curare la progettazione e lo sviluppo
del nuovo sito web della sezione. Nello svolgimento di questa attività il gruppo di
lavoro si è posto come obbiettivi prioritari l'usabilità e l'accessibilità del sito, in
ottemperanza alle indicazioni espresse dalla più recente normativa apparsa in
materia. Per perseguire a pieno questi obbiettivi e garantire la massima fruibilità
delle informazioni è stata prevista, fin dalla fase progettuale, la realizzazione del sito
anche in versione inglese, che attualmente è in allestimento.
Il nuovo sito web dell'Osservatorio Vesuviano è stato messo in linea il 22 maggio
2002 ed è visitabile all'indirizzo http://www.ov.ingv.it. Nel seguito del presente
rapporto sono introdotte sinteticamente le finalità istituzionali e le principali attività
dell'Osservatorio Vesuviano e sono descritte le fasi di progettazione e sviluppo del
sito, con particolare dettaglio sulla strutturazione dei contenuti, definita nell'ambito
delle linee dettate dal decreto di istituzione del gruppo di lavoro, e sulle scelte
tecnologiche adottate
Complex structural rearrangements are present in high-grade dysplastic Barrett’s oesophagus samples
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract
Background
Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett’s oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the early identification of at-risk individuals.
Methods
In this study, we assessed the genomic features of 16 BE samples using whole-genome sequencing. These included non-dysplastic samples collected at two time-points from two BE patients who had not progressed to EAC over several years. Seven other non-dysplastic samples and five dysplastic BE samples with high-grade dysplasia were also examined. We compared the genome profiles of these 16 BE samples with 22 EAC samples.
Results
We observed that samples from the two non-progressor individuals had low numbers of somatic single nucleotide variants, indels and structural variation events compared to dysplastic and the remaining non-dysplastic BE. EAC had the highest level of somatic genomic variations. Mutational signature 17, which is common in EAC, was also present in non-dysplastic and dysplastic BE, but was not present in the non-progressors. Many dysplastic samples had mutations in genes previously reported in EAC, whereas only mutations in CDKN2A or in the fragile site genes appeared common in non-dysplastic samples. Rearrangement signatures were used to identify a signature associated with localised complex events such as chromothripsis and breakage fusion-bridge that are characteristic of EACs. Two dysplastic BE samples had a high contribution of this signature and contained evidence of localised rearrangements. Two other dysplastic samples also had regions of localised structural rearrangements. There was no evidence for complex events in non-dysplastic samples.
Conclusions
The presence of complex localised rearrangements in dysplastic samples indicates a need for further investigations into the role such events play in the progression from BE to EAC
3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings
RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of ongoing debate. OBJECTIVE: The present paper reviews four specific issues related to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on monoamine neurons, (2) the use of “interspecies scaling” to adjust MDMA doses across species, (3) the effects of MDMA on established markers of neuronal damage, and (4) functional impairments associated with MDMA-induced 5-HT depletions. RESULTS: MDMA is a substrate for monoamine transporters, and stimulated release of 5-HT, NE, and DA mediates effects of the drug. MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1–2 mg/kg), suggesting that there is no reason to adjust doses between these species. Typical doses of MDMA causing long-term 5-HT depletions in rats (e.g., 10–20 mg/kg) do not reliably increase markers of neurotoxic damage such as cell death, silver staining, or reactive gliosis. MDMA-induced 5-HT depletions are accompanied by a number of functional consequences including reductions in evoked 5-HT release and changes in hormone secretion. Perhaps more importantly, administration of MDMA to rats induces persistent anxiety-like behaviors in the absence of measurable 5-HT deficits. CONCLUSIONS: MDMA-induced 5-HT depletions are not necessarily synonymous with neurotoxic damage. However, doses of MDMA which do not cause long-term 5-HT depletions can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks
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