Antiproliferative effects of carbon monoxide on pancreatic cancer

Background - Carbon monoxide, the gaseous product of heme oxygenase, is a signalling molecule with a broad spectrum of biological activities. The aim of this study was to investigate the effects of carbon monoxide on proliferation of human pancreatic cancer. Methods - In vitro studies were performed on human pancreatic cancer cells (CAPAN-2, BxPc3, and PaTu-8902) treated with a carbon monoxide-releasing molecule or its inactive counterpart, or exposed to carbon monoxide gas (500 ppm/24 h). For in vivo studies, pancreatic cancer cells (CAPAN-2/PaTu-8902) were xenotransplanted subcutaneously into athymic mice, subsequently treated with carbon monoxide-releasing molecule (35 mg/kg b.w. i.p./day), or exposed to safe doses of carbon monoxide (500 ppm 1 h/day; n = 6 in each group). Results - Both carbon monoxide-releasing molecule and carbon monoxide exposure significantly inhibited proliferation of human pancreatic cancer cells (p < 0.05). A substantial decrease in Akt phosphorylation was observed in carbon monoxide-releasing molecule compared with inactive carbon monoxide-releasing molecule treated cancer cells (by 30–50%, p < 0.05). Simultaneously, carbon monoxide-releasing molecule and carbon monoxide exposure inhibited tumour proliferation and microvascular density of xenotransplanted tumours (p < 0.01), and doubled the survival rates (p < 0.005). Exposure of mice to carbon monoxide led to an almost 3-fold increase in carbon monoxide content in tumour tissues (p = 0.006). Conclusion - These data suggest a new biological function for carbon monoxide in carcinogenesis, and point to the potential chemotherapeutic/chemoadjuvant use of carbon monoxide in pancreatic cancer.

Antiproliferative effects of carbon monoxide on pancreatic cancer

Background: Carbon monoxide, the gaseous product of heme oxygenase, is a signalling molecule with a broad spectrum of biological activities. The aim of this study was to investigate the effects of carbon monoxide on proliferation of human pancreatic cancer. Methods: In vitro studies were performed on human pancreatic cancer cells (CAPAN-2, BxPc3, and PaTu-8902) treated with a carbon monoxide-releasing molecule or its inactive counterpart, or exposed to carbon monoxide gas (500. ppm/24. h). For in vivo studies, pancreatic cancer cells (CAPAN-2/PaTu-8902) were xenotransplanted subcutaneously into athymic mice, subsequently treated with carbon monoxide-releasing molecule (35. mg/kg b.w. i.p./day), or exposed to safe doses of carbon monoxide (500. ppm 1. h/day; n=. 6 in each group). Results: Both carbon monoxide-releasing molecule and carbon monoxide exposure significantly inhibited proliferation of human pancreatic cancer cells (p<0.05). A substantial decrease in Akt phosphorylation was observed in carbon monoxide-releasing molecule compared with inactive carbon monoxide-releasing molecule treated cancer cells (by 30-50%, p<. 0.05). Simultaneously, carbon monoxide-releasing molecule and carbon monoxide exposure inhibited tumour proliferation and microvascular density of xenotransplanted tumours (p<0.01), and doubled the survival rates (p<0.005). Exposure of mice to carbon monoxide led to an almost 3-fold increase in carbon monoxide content in tumour tissues (p=0.006). Conclusion: These data suggest a new biological function for carbon monoxide in carcinogenesis, and point to the potential chemotherapeutic/chemoadjuvant use of carbon monoxide in pancreatic cancer. © 2013 Editrice Gastroenterologica Italiana S.r.l.

Diagnosing autism spectrum disorder:who will get a DSM-5 diagnosis?

Background Introduction of proposed criteria for DSM-5 Autism Spectrum Disorder (ASD) has raised concerns that some individuals currently meeting diagnostic criteria for Pervasive Developmental Disorder (PDD; DSM-IV-TR/ICD-10) will not qualify for a diagnosis under the proposed changes. To date, reports of sensitivity and specificity of the new criteria have been inconsistent across studies. No study has yet considered how changes at the 'sub domain' level might affect overall sensitivity and specificity, and few have included individuals of different ages and ability levels. Methods A set of DSM-5 ASD algorithms were developed using items from the Diagnostic Interview for Social and Communication Disorders (DISCO). The number of items required for each DSM-5 subdomain was defined either according to criteria specified by DSM-5 (Initial Algorithm), a statistical approach (Youden J Algorithm), or to minimise the number of false positives while maximising sensitivity (Modified Algorithm). The algorithms were designed, tested and compared in two independent samples (Sample 1, N = 82; Sample 2, N = 115), while sensitivity was assessed across age and ability levels in an additional dataset of individuals with an ICD-10 PDD diagnosis (Sample 3, N = 190). Results Sensitivity was highest in the Initial Algorithm, which had the poorest specificity. Although Youden J had excellent specificity, sensitivity was significantly lower than in the Modified Algorithm, which had both good sensitivity and specificity. Relaxing the domain A rules improved sensitivity of the Youden J Algorithm, but it remained less sensitive than the Modified Algorithm. Moreover, this was the only algorithm with variable sensitivity across age. All versions of the algorithm performed well across ability level. Conclusions This study demonstrates that good levels of both sensitivity and specificity can be achieved for a diagnostic algorithm adhering to the DSM-5 criteria that is suitable across age and ability level. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

A Super-Dimension Approach in ROLAP Environments

Often the designer of ROLAP applications follows up with the question “can I create a little joiner table with just the two dimension keys and then connect that table to the fact table?” In a classic dimensional model there are two options - (a) both dimensions are modeled independently or (b) two dimensions are combined into a super-dimension with a single key. The second approach is not widely used in ROLAP environments but it is an important sparsity handling method in MOLAP systems. In ROLAP this design technique can also bring storage and performance benefits, although the model becomes more complicated. The dependency between dimensions is a key factor that the designers have to consider when choosing between the two options. In this paper we present the results of our storage and performance experiments over a real life data cubes in reference to these design approaches. Some conclusions are drawn.

DSM-5 Autism Spectrum Disorder:in search of essential behaviours for diagnosis

The objective of this study was to identify a set of 'essential' behaviours sufficient for diagnosis of DSM-5 Autism Spectrum Disorder (ASD). Highly discriminating, 'essential' behaviours were identified from the published DSM-5 algorithm developed for the Diagnostic Interview for Social and Communication Disorders (DISCO). Study 1 identified a reduced item set (48 items) with good predictive validity (as measured using receiver operating characteristic curves) that represented all symptom sub-domains described in the DSM-5 ASD criteria but lacked sensitivity for individuals with higher ability. An adjusted essential item set (54 items; Study 2) had good sensitivity when applied to individuals with higher ability and performance was comparable to the published full DISCO DSM-5 algorithm. Investigation at the item level revealed that the most highly discriminating items predominantly measured social-communication behaviours. This work represents a first attempt to derive a reduced set of behaviours for DSM-5 directly from an existing standardised ASD developmental history interview and has implications for the use of DSM-5 criteria for clinical and research practice. © 2014 The Authors.

Signposting for diagnosis of Autism Spectrum Disorder using the Diagnostic Interview for Social and Communication Disorders (DISCO)

Recent research has investigated the capability of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) descriptions to identify individuals who should receive a diagnosis of Autism Spectrum Disorder (ASD) using standardised diagnostic instruments. Building on previous research investigating behaviours essential for the diagnosis of DSM-5 ASD, the current study investigated the sensitivity and specificity of a set of 14 items derived from the Diagnostic Interview for Social and Communication Disorders (DISCO Signposting set) that have potential for signposting the diagnosis of autism according to both the new DSM-5 criteria for ASD and ICD-10 criteria for Childhood Autism. An algorithm threshold for the Signposting set was calculated in Sample 1 (n = 67), tested in an independent validation sample (Sample 2; n = 78), and applied across age and ability sub-groups in Sample 3 (n = 190). The algorithm had excellent predictive validity according to best estimate clinical diagnosis (Samples 1 and 2) and excellent agreement with established algorithms for both DSM-5 and ICD-10 (all samples). The signposting set has potential to inform our understanding of the profile of ASD in relation to other neurodevelopmental disorders and to form the basis of a Signposting Interview for use in clinical practice.

Gait Measurements and Motor Recovery after Stroke

2000 Mathematics Subject Classification: 62P10, 92C20

Multiple Dipole Source Models for Scalp-Recorded Event-Related Potentials: Example from Complex Visual Processing in the Human Brain

2000 Mathematics Subject Classification: 62P10, 92C20

Model Mining and Efficient Verification of Software Product Lines

Software product line modeling aims at capturing a set of software products in an economic yet meaningful way. We introduce a class of variability models that capture the sharing between the software artifacts forming the products of a software product line (SPL) in a hierarchical fashion, in terms of commonalities and orthogonalities. Such models are useful when analyzing and verifying all products of an SPL, since they provide a scheme for divide-and-conquer-style decomposition of the analysis or verification problem at hand. We define an abstract class of SPLs for which variability models can be constructed that are optimal w.r.t. the chosen representation of sharing. We show how the constructed models can be fed into a previously developed algorithmic technique for compositional verification of control-flow temporal safety properties, so that the properties to be verified are iteratively decomposed into simpler ones over orthogonal parts of the SPL, and are not re-verified over the shared parts. We provide tool support for our technique, and evaluate our tool on a small but realistic SPL of cash desks.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Ó Sheán Clárach Mac Domhnaill go dtí Nioclás Tóibín: traidisiún na hamhránaíochta ins na Déise

Féachann an tráchtas seo le solas a chaitheamh ar an amhránaíocht mar a chleachtaítí agus mar a chleactaítear fós i gcontae Phort Láirge í. Ardaítear ann ceisteanna a bhaineann le seachadadh agus le sealbhú na n-amhrán I measc an phobail i gceantar na nDéise sa tréimhse c.1750-1960, ó aimsir Sheáin Chláraigh go dtí an ré sin ina raibh Nioclás Tóibín, ‘rí-amhránaí Éireann’, ar bhuaic a réime. Cuirtear spéis anseo i bhfás agus i dteacht chun cinn an Rómánsachais agus (a leathchúpla) an náisiúnachais ar Mhór-roinn na hEorpa in earr an 18ú haois agus amach san 19ú haois; ar thionchar na ngluaiseachtaí sin i bhfad ó bhaile ar Éirinn i gcoitinne san aimsir úd; orthu sin a raibh díolamaí amhrán á gcur in eagar acu in Éirinn san 19ú agus amach san 20ú haois; agus, ar deireadh, ar an stór amhrán mar atá le clos inniu I measc na ndaoine i nGaeltacht na Déise.

Saothair Oideachais an Ghúim 1926-46

Ceann de phrionsabail bhunaidh An Ghúim téacsleabhair agus leabhair ghinearálta a sholáthar do dhaltaí scoile is do lucht léitheoireachta na Gaeilge. Ábhair a bhaineann le curaclam na scoile, cuir i gcás, eolaíocht is tíos, oideachas, saoránaíocht, spórt, na teangacha Clasaiceacha, tíreolaíocht, taisteal agus an nádúr, creideamh is stair, a roghnaítear don taighde seo. Tugtar Aguisín (921 lch) le bheith ina threoir do phríomh-bhunachar sonraí na dochtúireachta seo (an chiall ghinearálta mar bhailiúchán eolais atá i gceist le “bunachar” sa tráchtas seo in ionad brí theicniúil ar leith). Trí phríomhchuid atá sa staidéar: “buneolas”, “anailís” is “toradh”. Sa “Bhuneolas”, tugtar cuntas beathaisnéiseach ar na bunúdair, soláthraítear achoimre ar na foilseacháin faoi staidéar, mar aon le faisnéis bhibleagrafaíochta i dtaobh na n- aistritheoirí, agus eolas faoi na comhlachtaí foilsitheoireachta a bhí páirteach sna tograí. Pléann “Anailís” brainsí de chuid an státchórais mar an Roinn Oideachais agus an Roinn Airgeadais i gcúrsaí maoinithe, nó gníomhairí lasmuigh de, cosúil le lucht deartha is clóchuradóireachta; moladh is coimisiúnú na saothar; sonraí cóipchirt na bhfoilseachán; roghnú, monatóireacht is díolaíocht na n-aistritheoirí, mar aon le breithniú inmheánach is seachtrach. Sa chuid dheireanach, féachtar le “Toradh” na hiarrachta a mheas, ag tagairt den líon cóipeanna de na leabhair a díoladh. Faightear eolas ar fhiosrú léitheoirí; praghas na leabhar; a ndíolachán is a n- athchló. Tugtar léirmheasanna a scríobhadh ar na haistriúcháin Ghaeilge agus na cúiseanna nár tháinig tograí ar leith chun críche. Is é aidhm na hoibre thar aon ní eile gné lárnach chasta d’eisint An Ghúim atá ligthe i ndíchuimhne a thabhairt ar ais chugainn go beo beathaíoch faoi mar a bhí lena ré saoil féin.

Age, body mass, mass change and dispersal distance of suckling and weaned grey seal (Halichoerus grypus) pups

Grey seal, Halichoerus grypus, pups in the breeding colony at Froan, Norway, have a bimodal pattern of early aquatic behaviour. About 40% of the pups spend their time ashore to save energy, which can be allocated to growth or deposition of energy-rich adipose tissue. The other 60% of the pups enter the sea during suckling and the early postweaning period, and disperse to other locations within the breeding colony. Pups may swim distances up to 12 km. Neonatal aquatic dispersal behaviour may lead to increased energy expenditure for thermoregulation and swimming, and thus lead to a low rate of body mass gain during suckling and a high rate of body mass loss after weaning. Thus, we examined relationships between natal aquatic dispersal behaviour and change in body mass (DeltaBM) in suckling and weaned pups. Suckling pups that had dispersed >2000 m had a significantly lower DBM than suckling pups that dispersed <2000 m or that did not disperse. In weaned pups, there were no effects of aquatic dispersal behaviour on DBM. We suggest that the bimodal natal aquatic dispersal behaviour in grey seals at the study site reflects two different strategies for postweaning survival: to stay ashore and get fat, or to take a swim and acquire diving and feeding skills.

DIGITAL HISTORY: DESIGNING VIRTUAL ENVIRONMENTS THAT SUPPORT CRITICAL THINKING AND IDEA EXCHANGE, MOTIVATE AND ENGAGE USERS

In my thesis I argue for the use of system designs that: a) open access to a variety of users and allow for collaboration and idea exchange, while at the same time, b) are designed to motivate and engage users. To exemplify my proposed systems design, I created an interactive and open digital history project focused on Romanian culture and identity during Communism, from 1947, when the Communist Party took power by forcing the King to abdicate, until the revolution in 1989, which marked the end of Communism in Romania (Gilberg, 1990, Boia, 2014). In my project, I present the possibility to recreate Habermas’ notion of public sphere and “the unforced force of the better argument” (Habermas, 1989) and Dewey’s (2004) understanding of democracy as a mode of associated living imbued of the spirit of inquiry within contemporary digital history projects. Second, I outline system designs that motivate and engage users, by satisfying the basic psychological needs outlined in Ryan and Deci’s (2000) self-determination theory: autonomy, competence, and relatedness. Two more concepts are included to complete the proposed digital history project design: presence (Ryan, Rigby, & Przybylski, 2006) and learner hero (Rigby & Przybylski, 2009).