Alpha-1 antitrypsin deficiency: A conformational disease associated with lung and liver manifestations

Alpha-1 antitrypsin (A1AT) is a serine anti-protease produced chiefly by the liver. A1AT deficiency is a genetic disorder characterized by serum levels of less than 11 μmol/L and is associated with liver and lung manifestations. The liver disease, which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene, which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The so-called 'Z' mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of A1AT deficiency and the best clinical management protocols. © Springer Science+Business Media B.V. 2008.

Atomic layer deposition of hafnium oxide dielectrics on silicon and germanium substrates

Hafnium oxide films have been deposited at 250 °C on silicon and germanium substrates by atomic layer deposition (ALD), using tetrakis-ethylmethylamino hafnium (TEMAH) and water vapour as precursors in a modified Oxford Instruments PECVD system. Self-limiting monolayer growth has been verified, characterised by a growth rate of 0.082 nm/ cycle. Layer uniformity is approximately within ±1% of the mean value. MOS capacitors have been fabricated by evaporating aluminium electrodes. CV analysis has been used to determine the bulk and interface properties of the HfO 2, and their dependence on pre-clean schedule, deposition conditions and post-deposition annealing. The dielectric constant of the HfO 2 is typically 18. On silicon, best results are obtained when the HfO 2 is deposited on a chemically oxidised hydrophilic surface. On germanium, best results are obtained when the substrate is nitrided before HfO 2 deposition, using an in-situ nitrogen plasma treatment. © Springer Science+Business Media, LLC 2007.

Application of NMR based metabolomics for mapping metabolite variation in European wheat

In this study, we report on the use of NMR-based metabolomics to access variation in low molecular weight polar metabolites between the European wheat cultivars Apache, Charger, Claire and Orvantis. Previous unassigned resonances in the published NMR spectra of wheat extracts were identified using C NMR and two dimensional proton-carbon NMR. These included a peak for trans-aconitate (d3.43) and resonances corresponding to fructose in the crowded carbohydrate region of the spectra. Large metabolite differences were observed between two different growth stages, namely the coleoptile and two week old leaf tissue extracts which were consistent across cultivars. Two week old leaf tissue extracts had higher abundances of glutamine, glutamate, sucrose and trans-aconitate and less glucose and fructose than were observed in the coleoptile extracts. Across both growth stages the cultivars Apache and Charger showed the greatest differences in metabolite profiles. Charger had higher abundances of betaine, the single most influential metabolite in the principal component analysis, in addition to fructose and sucrose. However, Charger had lower levels of aspartate, choline and glucose than Apache. These findings demonstrate the potential for a biochemical mapping approach using NMR, across European wheat germplasm, for metabolites of known importance to functional characteristics. © Springer Science+Business Media, LLC 2009.

Stereotactic radiosurgery as a therapeutic strategy for intracranial metastatic prostate carcinoma.

Intracranial metastatic prostate carcinoma is rare. We sought to determine the clinical outcomes after Gamma Knife® stereotactic radiosurgery (GKSRS) for patients with intracranial prostate carcinoma metastases. We studied data from 10 patients who underwent radiosurgery for 15 intracranial metastases (9 dural-based and 6 parenchymal). Six patients had radiosurgery for solitary tumors and four had multiple tumors. The primary pathology was adenocarcinoma (eight patients) and small cell carcinoma (two patients). All patients received multimodality management for their primary tumor (including resection, radiation therapy, androgen deprivation therapy) and eight patients had evidence of systemic disease at time of radiosurgery. The mean tumor volume was 7.7 cm3 (range 1.1-17.2 cm3) and a median margin dose of 16 Gy was administered. Two patients had progressive intracranial disease in spite of fractionated partial brain radiation therapy (PBRT) prior to SRS. A local tumor control rate of 85% was achieved (including patients receiving boost, upfront and salvage SRS). New remote brain metastases developed in three patients (33%) and one patient had repeat SRS for tumor recurrence. The median survival after radiosurgery was 13 months and the 1-year survival rate was 60%. SRS was a well tolerated and effective therapy either alone or as a boost to fractionated radiation therapy in the management of patients with intracranial prostate carcinoma metastases. © 2009 Springer Science+Business Media, LLC.

Which Credit Unions are Acquired?

Recent years have witnessed a wave of consolidation amongst US credit unions. Through hazard function estimations, this paper identifies the determinants of acquisition for credit unions during the period 2001-06. The hazard of acquisition is inversely related to both asset size and profitability, and positively related to liquidity. Growth-constrained credit unions are less attractive acquisition targets. Institutions with low capitalization and those with small loans portfolios relative to total assets are susceptible to acquisition. The investigation presents unique empirical evidence of a link between technological capability and the hazard of acquisition. During the period 2001-06, when there was sustained growth in the use of internet technology, credit unions with no website were at the highest risk of acquisition. © Springer Science + Business Media, LLC 2009.

Information Disclosure, Market Discipline and the Management of Bank Capital: Evidence from the Chinese Financial Sector

Is there evidence that market forces effectively discipline risk management behaviour within Chinese financial institutions? This study analyses information from a comprehensive sample of Chinese banks over the 1998-2008 period. Market discipline is captured through the impact of four sets of factors namely, market concentration, interbank deposits, information disclosure, and ownership structure. We find some evidence of a market disciplining effect in that: (i) higher (lower) levels of market concentration lead banks to operate with a lower (higher) capital buffer; (ii) joint-equity banks that disclose more information to the public maintain larger capital ratios; (iii) full state ownership reduces the sensitivity of changes in a bank's capital buffer to its level of risk;(iv) banks that release more transparent financial information hold more capital against their non-performing loans. © 2010 Springer Science+Business Media, LLC.

How trophic interaction strength depends on traits

A key problem in community ecology is to understand how individual-level traits give rise to population-level trophic interactions. Here, we propose a synthetic framework based on ecological considerations to address this question systematically. We derive a general functional form for the dependence of trophic interaction coefficients on trophically relevant quantitative traits of consumers and resources. The derived expression encompasses-and thus allows a unified comparison of-several functional forms previously proposed in the literature. Furthermore, we show how a community's, potentially low-dimensional, effective trophic niche space is related to its higher-dimensional phenotypic trait space. In this manner, we give ecological meaning to the notion of the "dimensionality of trophic niche space." Our framework implies a method for directly measuring this dimensionality. We suggest a procedure for estimating the relevant parameters from empirical data and for verifying that such data matches the assumptions underlying our derivation. © Springer Science+Business Media B.V. 2009.


--------------------------------------------------------------------------------

Reaxys Database Information|

--------------------------------------------------------------------------------

Increasing incidence of Barrett's oesophagus: a population-based study

Oesophageal adenocarcinoma, a highly fatal cancer, has risen in incidence in Western societies, but it is unclear whether this is due to increasing incidence of its pre-cursor condition, Barrett's oesophagus (BO) or whether the proportion of BO patients undergoing malignant progression has increased in the face of unchanged BO incidence. Data from population-based studies of BO incidence is limited, with equivocal results to date difficult to distinguish from changes in endoscopic practices. The aim of this study was to assess population trends in Barrett's oesophagus (BO) diagnoses in relation to endoscopy and biopsy rates over a 13 year period. The Northern Ireland Barrett's oesophagus Register (NIBR) is a population-based register of all 9,329 adults diagnosed with columnar epithelium of the oesophagus in Northern Ireland between 1993 and 2005, of whom 58.3% were male. European age-standardised annual BO incidence rates were calculated per 100,000 of the population, per 100 endoscopies and per 100 endoscopies including an oesophageal biopsy. Average annual BO incidence rates rose by 159% during the study period, increasing from 23.9/100,000 during 1993-1997 to 62.0/100,000 during 2002-2005. This elevation far exceeded corresponding increases in rates of endoscopies and oesophageal biopsies being conducted. BO incidence increased most markedly in individuals aged <60 years, and most notably amongst males aged <40 years. This study points towards a true increase in the incidence of BO which would appear to be most marked in young males. These findings have significant implications for future rates of oesophageal adenocarcinoma and surveillance programmes. © 2011 Springer Science+Business Media B.V.

Increased diagnosis and detection rates of carcinoma in situ of the breast

The purpose of this study was to identify trends in the diagnosis of carcinoma in situ (CIS) of the breast in the United Kingdom (UK) and the Republic of Ireland (ROI) and to examine the impact of mammography. Data on cases of newly diagnosed CIS of the breast and mode of detection (screen detected or not) were obtained, where available, from regional cancer registries between 1990 and 2007. Age-standardised diagnosis rates for the UK and the ROI, and regional screen detected diagnosis rates were compared by calculating the annual percentage change (APC) over time. The APC of the diagnosis rate amongst women aged 50-64 years (original screening age group) showed a significant 5.9% increase in the UK (1990-2007) and 11.5% increase in the ROI (1994-2007). The rate of diagnosis (50-64 years) stabilized in the UK between 2005 and 2007 and was substantially higher than in other western populations with national screening programmes. The APC of the diagnosis rate amongst those aged 65-69 years showed a significant 12.4% increase in the UK (1990-2007) and 10.3% increase in the ROI (1994-2007). amongst women aged 50-74 years in the UK, approximately 4,300 cases of CIS (˜90% ductal carcinoma in situ) were diagnosed in 2007. Our analyses have shown that screen detected CIS contributed primarily to the increase in diagnosis of CIS of the breast. The high diagnosis rate of screen detected CIS of the breast underlines the need for further research into lesion and patient characteristics that are related to progression of CIS to invasive disease to better target treatment. © 2012 Springer Science+Business Media, LLC.

Influence of the cation on the solubility of CO2 and H 2 in ionic liquids based on the bis(trifluoromethylsulfonyl)imide anion

Experimental values for the solubility of carbon dioxide and hydrogen in three room temperature ionic liquids based on the same anion- (bistrifluoromethylsulfonyl)imide [Ntf2]-and three different cations-1-butyl-3-methylimidazolium, [C4mim], 1-ethyl-3- methylimidazolium, [C2mim] and trimethyl-butylammonium, [N 4111]-are reported between 283 and 343 K and close to atmospheric pressure. Carbon dioxide, with a mole-fraction solubility of the order of 10-2, is two orders of magnitude more soluble than hydrogen. The solubility of CO2 is very similar in the three ionic liquids although slightly lower in the presence of the [C2mim] cation. In the case of H2, noticeable differences were observed with larger mole fraction solubilities in the presence of [N4111] followed by [C 4mim]. All of the mole-fraction solubilities decrease with increasing temperature. From the variation of Henry's law constants with temperature, the thermodynamic functions of solvation were calculated. The precision of the experimental data, considered as the average absolute deviation of the Henry's law constants from appropriate smoothing equations, is always better than ±1%. © Springer Science+Business Media, LLC 2007.

From bit level systolic arrays to HDTV processor chips

The initial part of this paper reviews the early challenges (c 1980) in achieving real-time silicon implementations of DSP computations. In particular, it discusses research on application specific architectures, including bit level systolic circuits that led to important advances in achieving the DSP performance levels then required. These were many orders of magnitude greater than those achievable using programmable (including early DSP) processors, and were demonstrated through the design of commercial digital correlator and digital filter chips. As is discussed, an important challenge was the application of these concepts to recursive computations as occur, for example, in Infinite Impulse Response (IIR) filters. An important breakthrough was to show how fine grained pipelining can be used if arithmetic is performed most significant bit (msb) first. This can be achieved using redundant number systems, including carry-save arithmetic. This research and its practical benefits were again demonstrated through a number of novel IIR filter chip designs which at the time, exhibited performance much greater than previous solutions. The architectural insights gained coupled with the regular nature of many DSP and video processing computations also provided the foundation for new methods for the rapid design and synthesis of complex DSP System-on-Chip (SoC), Intellectual Property (IP) cores. This included the creation of a wide portfolio of commercial SoC video compression cores (MPEG2, MPEG4, H.264) for very high performance applications ranging from cell phones to High Definition TV (HDTV). The work provided the foundation for systematic methodologies, tools and design flows including high-level design optimizations based on "algorithmic engineering" and also led to the creation of the Abhainn tool environment for the design of complex heterogeneous DSP platforms comprising processors and multiple FPGAs. The paper concludes with a discussion of the problems faced by designers in developing complex DSP systems using current SoC technology. © 2007 Springer Science+Business Media, LLC.

Autonomy and regulation of state agencies:Reinforcement, indifference or compensation?

This paper analyses the relationships between the autonomy and regulation of state agencies in Norway, Ireland and Flanders (Belgium). The empirical basis is provided by broad surveys of public sector organizations carried out in 2002-2004. Three hypotheses on these relationships are formulated and examined, indicating different patterns. The reinforcement hypothesis, stating a negative relationship does not get any support. On the other hand, the compensation hypothesis, stating a positive relationship gets some support. In general, however, the indifference hypothesis, stating low or no correlations seems to be the most adequate. The hypotheses are also linked to prevalent administrative doctrines, and the empirical findings indicate how relevant they are. © Springer Science+Business Media, LLC 2008.

Constraint rule-based programming of norms for electronic institutions

Norms constitute a powerful coordination mechanism among heterogeneous agents. In this paper, we propose a rule language to specify and explicitly manage the normative positions of agents (permissions, prohibitions and obligations), with which distinct deontic notions and their relationships can be captured. Our rule-based formalism includes constraints for more expressiveness and precision and allows to supplement (and implement) electronic institutions with norms. We also show how some normative aspects are given computational interpretation. © 2008 Springer Science+Business Media, LLC.

Multi-Modal CTL:Completeness, Complexity, and an Application

We define a multi-modal version of Computation Tree Logic (ctl) by extending the language with path quantifiers E and A where d denotes one of finitely many dimensions, interpreted over Kripke structures with one total relation for each dimension. As expected, the logic is axiomatised by taking a copy of a ctl axiomatisation for each dimension. Completeness is proved by employing the completeness result for ctl to obtain a model along each dimension in turn. We also show that the logic is decidable and that its satisfiability problem is no harder than the corresponding problem for ctl. We then demonstrate how Normative Systems can be conceived as a natural interpretation of such a multi-dimensional ctl logic. © 2009 Springer Science+Business Media B.V.

Comparing poverty and deprivation dynamics:Issues of reliability and validity

In this paper we seek to establish if earlier findings relating to the relationship between income poverty persistence and deprivation persistence could be due to a failure to take measurement error into account. To address this question, we apply a model of dynamics incorporating structural and error components. Our analysis shows a general similarity between latent poverty and deprivation dynamics. In both cases we substantially over-estimate the probability of exiting from poverty or deprivation. We observe a striking similarity across dimensions for both observed and latent outcomes. In both cases levels of poverty and deprivation persistence are higher for the latent case. However, there is no evidence that earlier results relating to the differences in the determinants of poverty and deprivation persistence are a consequence of differential patterns of reliability. Taking measurement error into account seems more likely to accentuate rather than diminish the contrasts highlighted by earlier research. Since longitudinal differences relating to poverty and deprivation cannot be accounted for by measurement error, it seems that we must accept that we are confronted with issues relating to validity rather than reliability. Even where we measure these dimensions over reasonable periods of time and allow for measurement error, they continue to tap relatively distinct phenomenon. Thus, if measures of persistent poverty are to constitute an important component of EU social indicators, a strong case can be made for including parallel measures of deprivation persistence and continuing to explore the relationship between them. © Springer Science+Business Media, Inc. 2006.