<i>P. berghei</i> telomerase subunit TERT is essential for parasite survival

Telomeres define the ends of chromosomes protecting eukaryotic cells from chromosome instability and eventual cell death. The complex regulation of telomeres involves various proteins including telomerase, which is a specialized ribonucleoprotein responsible for telomere maintenance. Telomeres of chromosomes of malaria parasites are kept at a constant length during blood stage proliferation. The 7-bp telomere repeat sequence is universal across different Plasmodium species (GGGTTT/CA), though the average telomere length varies. The catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), is present in all sequenced Plasmodium species and is approximately three times larger than other eukaryotic TERTs. The Plasmodium RNA component of TERT has recently been identified in silico. A strategy to delete the gene encoding TERT via double cross-over (DXO) homologous recombination was undertaken to study the telomerase function in P. berghei. Expression of both TERT and the RNA component (TR) in P. berghei blood stages was analysed by Western blotting and Northern analysis. Average telomere length was measured in several Plasmodium species using Telomere Restriction Fragment (TRF) analysis. TERT and TR were detected in blood stages and an average telomere length of ~950 bp established. Deletion of the tert gene was performed using standard transfection methodologies and we show the presence of tert− mutants in the transfected parasite populations. Cloning of tert- mutants has been attempted multiple times without success. Thorough analysis of the transfected parasite populations and the parasite obtained from extensive parasite cloning from these populations provide evidence for a so called delayed death phenotype as observed in different organisms lacking TERT. The findings indicate that TERT is essential for P. berghei cell survival. The study extends our current knowledge on telomere biology in malaria parasites and validates further investigations to identify telomerase inhibitors to induce parasite cell death

Terra Incognita: On First Reading ‘L’Invitation au Voyage’

Autumn term, 1962, a South London (Boys’) Grammar School: the Cuban Missile Crisis had just come to an end, but Planet Earth had not, which meant that I would, after all, be taking my A-levels in English, German, and French. C’est la vie. French O-level had been taught – or rather, enforced – by an elderly irascible Scot, who kept a cane in his drawer, and never gave the slightest hint that French words could be combined to make French poems, which could in their turn be delicious, haunting – or even seductive. Grammar, dictation, and repetition were all. Whereas Mr. B – our A-level master, much younger but nevertheless somewhat meticulous, and a little desiccated and ascetic in manner (he would have made a credible monk), revelled in his sonorous readings of Verlaine and Baudelaire – ‘de la musique avant toute chose’

Pancreatic Cysts Identification Using Unstructured Information Management Architecture

poster abstractPancreatic cancer is one of the deadliest cancers, mostly diagnosed at late stages. Patients with pancreatic cysts are at higher risk of developing cancer and surveillance of these patients can help with early diagnosis. Much information about pancreatic cysts can be found in free text format in various medical narratives. In this retrospective study, a corpus of 1064 records from 44 patients at Indiana University Hospital from 1990 to 2012 was collected. A natural language processing system was developed and used to identify patients with pancreatic cysts. The input goes through series of tasks within the Unstructured Information Management Architecture (UIMA) framework consisting of report separation, metadata detection, sentence detection, concept annotation and writing into the database. Metadata such as medical record number (MRN), report id, report name, report date, report body were extracted from each report. Sentences were detected and concepts within each sentence were extracted using regular expression. Regular expression is a pattern of characters matching specific string of text. Our medical team assembled concepts that are used to identify pancreatic cysts in medical reports and additional keywords were added by searching through literature and Unified Medical Language System (UMLS) knowledge base. The Negex Algorithm was used to find out negation status of concepts. The 1064 reports were divided into sets of train and test sets. Two pancreatic-cyst surgeons created the gold standard data (Inter annotator agreement K=88%). The training set was analyzed to modify the regular expression. The concept identification using the NegEx algorithm resulted in precision and recall of 98.9% and 89% respectively. In order to improve the performance of negation detection, Stanford Dependency parser (SDP) was used. SDP finds out how words are related to each other in a sentence. SDP based negation algorithm improved the recall to 95.7%

Zonisamide, Topiramate, and Levetiracetam: Efficacy and Neuropsychological Effects in Alcohol Use Disorders

Abstract The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing

The Pan-STARRS Moving Object Processing System

We describe the Pan-STARRS Moving Object Processing System (MOPS), a modern software package that produces automatic asteroid discoveries and identifications from catalogs of transient detections from next-generation astronomical survey telescopes. MOPS achieves > 99.5% efficiency in producing orbits from a synthetic but realistic population of asteroids whose measurements were simulated for a Pan-STARRS4-class telescope. Additionally, using a non-physical grid population, we demonstrate that MOPS can detect populations of currently unknown objects such as interstellar asteroids. MOPS has been adapted successfully to the prototype Pan-STARRS1 telescope despite differences in expected false detection rates, fill-factor loss and relatively sparse observing cadence compared to a hypothetical Pan-STARRS4 telescope and survey. MOPS remains >99.5% efficient at detecting objects on a single night but drops to 80% efficiency at producing orbits for objects detected on multiple nights. This loss is primarily due to configurable MOPS processing limits that are not yet tuned for the Pan-STARRS1 mission. The core MOPS software package is the product of more than 15 person-years of software development and incorporates countless additional years of effort in third-party software to perform lower-level functions such as spatial searching or orbit determination. We describe the high-level design of MOPS and essential subcomponents, the suitability of MOPS for other survey programs, and suggest a road map for future MOPS development.Comment: 57 Pages, 26 Figures, 13 Table

Volunteering for INSPIRE : the AGI experience.

The Association for Geographic Information (AGI) is the UK volunteer membership body for everyone with an interest in geographic information. It serves members from all sectors including public, private, the third sector, academia, students and individuals. This paper describes how a voluntary organisation with very limited funds, and representing a wide cross section of the industry, has made – and is continuing to make – a significant contribution to the development of the INSPIRE Directive. It includes a summary of how AGI has supported the Directive, documenting the validity, the experience and the lessons learnt. Both AGI and INSPIRE seek to ‘maximise the use of geographic information for the benefit of the citizen, good governance and commerce.' AGI has been actively engaged from the first stages of the INSPIRE programme. It has responded to all consultations from the EC as well as those from the UK. This has been achieved by volunteers from across the UK and particularly those in the Devolved Administrations such as Scotland. AGI set up an Action Working Group in 2007 which tracked the Transposition stage and is now ensuring that AGI contributes to the Implementation phase. The AGI’s Scottish committee prepared a report to encourage the Scottish Government to act. This led to the publication of ‘One Scotland - One Geography’ in 2005 which is regarded as a model for other countries to follow. AGI is represented by its Director on the UK Location Council – responsible for the UK Location Strategy and oversight of the UK Location Programme – where it provides a focus for commercial, academic and third sector organisations. AGI has provided direct help for awareness events and technical workshops as well as organising an annual conference that always has INSPIRE or Location Programme ‘streams’

“All Sorts and Any Quantity of Outlandish Recreations”: History, Sociology, and the Study of Leisure in England, 1820 to 1870

L'étude des loisirs populaires en Angleterre durant la période victorienne jouit présentement d'une grande faveur. Cependant, de nombreux problèmes se posent au chercheur qui s'y adonne. En effet, le sujet est non seulement complexe en lui-même mais il est aussi perçu différemment par les uns ou les autres. Par exemple, certains historiens abordent le problème comme s'il se rattachait aux traditions populaires plus anciennes, d'autres y voient plutôt l'émergence du phénomène de la « culture de masse » alors que d'aucuns l'approchent d'une façon tout à fait élitiste en concentrant leurs efforts sur l'étude de la réforme des loisirs tout en ignorant les réactions populaires aux mesures de réforme. En fait, la question est d'autant plus compliquée qu'on lui associe habituellement le concept de contrôle social.L'auteur suggère ici des approches différentes qui auraient avantage à être utilisées. Ainsi, il fait valoir tout le profit que l'on pourrait tirer de l'examen des modes d'invention et de diffusion des activités de loisir, de l'étude du contenu spécifique de ces activités et de la préparation d'études de communautés particulières où l'on ferait une large place aux rapports qui s'établissent entre l'occupation, les aspirations et les choix individuels qui se font, compte tenu de la gamme des activités récréatives qui sont offertes dans un temps et un espace donnés

‘Reflection is embedded in my brain forever now!’: personal development as a core module on an Executive MBA

Professional progression and skills development are the main expectations of mid-career managers when enrolling on an Executive MBA (EMBA), yet it can be personal development (PD) that turns out to be the unexpected benefit of management education. Joining a growing number of voices making a case for personal development and self-awareness in management education, and calling for schools to incorporate it in the curriculum, this paper advances the case for personal development as a core Executive MBA module. The paper sets out the holistic rationale and philosophic principles used to design and deliver a course underpinned by curiosity and self-reflection on an EMBA in the United Kingdom, and presents empirical findings from a survey conducted among 230 students and alumni. These suggest that the focus on reflective practice and integration of PD promotes a richer and deeper appreciation of the value of reflection for lasting and sometimes unexpected personal growth. In addition, the raising of awareness of self also brings awareness of others, and develops critical thinking in application of the MBA at work. The paper concludes with a discussion re-evaluating the subject of tacit knowledge in reflective practice