bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation between Tropical Easterly Waves, Convection, and Tropical Cyclogenesis: A Lagrangian Perspective
Authors: Leppert Kenneth D. , Cecil Daniel J. , Petersen Walter A.
Published: January 2013

In this study, a wave-following Lagrangian framework was used to examine the evolution of tropical easterly wave structure, circulation, and convection in the days leading up to and including tropical cyclogenesis in the Atlantic and east Pacific basins. After easterly waves were separated into northerly, southerly, trough, and ridge phases using the National Centers for Environmental Prediction–National Center for Atmospheric Research reanalysis 700-hPa meridional wind, waves that developed a tropical cyclone [developing waves (DWs)] and waves that never developed a cyclone [nondeveloping waves (NDWs)] were identified. Day zero (D0) was defined as the day on which a tropical depression was identified for DWs or the day the waves achieved maximum 850-hPa vorticity for NDWs. Both waves types were then traced from five days prior to D0 (D − 5) through one day after D0. Results suggest that as genesis is approached for DWs, the coverage by convection and cold cloudiness (e.g., fractional coverage by infrared brightness temperatures ≤240 K) increases, while convective intensity (e.g., lightning flash rate) decreases. Therefore, the coverage by convection appears to be more important than the intensity of convection for tropical cyclogenesis. In contrast, convective coverage and intensity both increase from D − 5 to D0 for NDWs. Compared to NDWs, DWs are associated with significantly greater coverage by cold cloudiness, large-scale moisture throughout a deep layer, and large-scale, upper-level (~200 hPa) divergence, especially within the trough and southerly phases, suggesting that these parameters are most important for cyclogenesis and for distinguishing DWs from NDWs.
Introduction: The State of Democracy 20 Years on
Authors: Rupnik Jacques , Zielonka Jan
Published: January 2013

The countries of East-Central Europe (ECE) embarked on a democratic transition in 1989 were proclaimed consolidated democracies when they joined the European Union (EU) in 2004. Today most of the new democracies are experiencing “democratic fatigue” and some seem vulnerable to an authoritarian turn. The EU, seen as the guarantor of the post-1989 democratic changes, is experiencing an unprecedented economic, financial, and democratic crisis with the combined challenges of technocracy and populism. The article explores the different approaches to the study of democracies in ECE, their specific features and vulnerabilities, and tries to provide an interpretation of the premature crisis of democracy in ECE in a broader transeuropean context.
The Effect of Reliance on International Funding on Banking Fragility: Evidence from East Asia
Authors: Hamid Fazelina Sahul
Published: January 2013

The East Asian crisis highlights the importance of liquidity for smooth functioning of the banking system. It also shows the vulnerabilities that arise as a result of high dependence on international liquidity. This article empirically analyses the influx of liquidity before the crisis and illiquidity during the crisis in finding out whether banks in East Asia held ‘too little’ or ‘too much’ liquidity before and during a crisis and how their vulnerabilities to failure changed as a result of that. Instrumental Variable estimation is used to dissociate the effect of international illiquidity on banks’ liquidity risk during a crisis year. The study finds that the effect of liquidity on the probability of bank failure varies before and during a crisis. The findings also highlight the vulnerabilities of banks to failure as a result of international illiquidity and high reliance on external funding. These findings bring forward the case for stronger regulation of banks’ liquidity, which can be brought forward by better liquidity management.
Monetary integration in crisis: how well do existing theories explain the predicament of EMU?
Authors: Schelkle Waltraud
Published: January 2013

Three theories or rationales can be invoked to explain the formation of the monetary union as well as its policy architecture. One sees its rationale as forming an optimal currency area, another as making macroeconomic policies credibly stability-oriented and a last one as overcoming collective action problems of mutually beneficial policy coordination. Each theory also implies an explanation for why the euro area is in crisis now. The article contains a critical assessment of these theories, with a view to how they have informed crisis management of the euro area but have also failed so far to stabilize the monetary union effectively.
The animals went in two by two: Heteronormativity in television wildlife documentaries
Authors: Mills Brett
Published: January 2013

This article examines British television wildlife documentaries in order to outline the ways in which limited representations of animal behaviour recur. It focuses on representations of animal sexuality, monogamy and parenthood, and suggests that how such activities are repeatedly represented draw on normalised human notions of such behaviour. This is demonstrated through comparison of these representations with literature from zoology and ethology, which shows that a considerably wider variety of animal behaviour has been documented. The article suggests that the discourses of sexuality, monogamy and parenthood are interrelated and interdependent, with the validity of each supported by the existence of the others. It is argued that how animals are represented in such documentaries matters, partly because normalised discourses must be drawn on in order for programmes to make sense of the behaviour they present, but mainly because animal behaviour is commonly used as evidence for ‘natural’ forms of human behaviour.
Locating anxiety in the social: The cultural mediation of food fears
Authors: Jackson Peter , Watson Matthew , Piper Nicholas
Published: January 2013

Drawing on current research about food-related anxieties, this article argues for an expanded understanding of the presence and location of anxiety in the social. It contends that anxiety is usefully conceptualised as collective and distributed, rather than solely as a property or experience of the individual. Focusing on anxiety as a social condition, the article explores how anxieties become embedded and embodied within routinised practices, technologies and institutions. It draws out and demonstrates the processes and practices through which anxieties are socially constituted and culturally mediated, and through which they travel across spaces and scales. This is exemplified through the case of Jamie’s Ministry of Food (a 2008 television series and media campaign featuring the British celebrity chef Jamie Oliver). The article shows how food serves as a vehicle for the circulation of a variety of related concerns, including anxieties about class and gender relations, notions of place identity and regional stereotyping.
Entertainment-education for the media-saturated: Audience perspectives on social issues in entertainment programming
Authors: Klein Bethany
Published: January 2013

The representation of social issues in entertainment television challenges the assumed and nominal function of such programming to simply entertain its audience. Drawing on focus groups with television viewers in the UK, this article explores the ways in which audiences engage with and use entertainment television in discussions of social issues that conventionally have been framed narrowly across news and entertainment media: crimes against children, immigration and disability. Entertainment television that includes alternative perspectives on these issues offers the possibility of broadening resources and encouraging deliberation, although assumptions about the role of entertainment television are reflected in audience scepticism about the appropriateness of using such programming as a basis for considering the social world.
IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice
Authors: Kurimoto Etsuko , Miyahara Nobuaki , Kanehiro Arihiko , Waseda Koichi , Taniguchi Akihiko , Ikeda Genyo , Koga Hikari , Nishimori Hisakazu , Tanimoto Yasushi , Kataoka Mikio , Iwakura Yoichiro , Gelfand Erwin W , Tanimoto Mitsune
Published: January 2013

Background

Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it’s role in the inflammatory response of elastase-induced emphysema remains unclear.

Methods

In a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid.

Results

Wild-type mice developed emphysematous changes in the lung tissue on day 21 after elastase treatment, whereas emphysematous changes were decreased in IL-17A-deficient mice compared to wild-type mice. Neutrophilia in BAL fluid, seen in elastase-treated wild-type mice, was reduced in elastase-treated IL-17A-deficient mice on day 4, associated with decreased levels of KC, MIP-2 and IL-1 beta. Elastase-treated wild-type mice showed increased IL-17A levels as well as increased numbers of IL-17A+ CD4 T cells in the lung in the initial period following elastase treatment.

Conclusions

These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression.
Predicting PDZ domain mediated protein interactions from structure
Authors: Hui Shirley , Xing Xiang , Bader Gary D
Published: January 2013

Background

PDZ domains are structural protein domains that recognize simple linear amino acid motifs, often at protein C-termini, and mediate protein-protein interactions (PPIs) in important biological processes, such as ion channel regulation, cell polarity and neural development. PDZ domain-peptide interaction predictors have been developed based on domain and peptide sequence information. Since domain structure is known to influence binding specificity, we hypothesized that structural information could be used to predict new interactions compared to sequence-based predictors.

Results

We developed a novel computational predictor of PDZ domain and C-terminal peptide interactions using a support vector machine trained with PDZ domain structure and peptide sequence information. Performance was estimated using extensive cross validation testing. We used the structure-based predictor to scan the human proteome for ligands of 218 PDZ domains and show that the predictions correspond to known PDZ domain-peptide interactions and PPIs in curated databases. The structure-based predictor is complementary to the sequence-based predictor, finding unique known and novel PPIs, and is less dependent on training-testing domain sequence similarity. We used a functional enrichment analysis of our hits to create a predicted map of PDZ domain biology. This map highlights PDZ domain involvement in diverse biological processes, some only found by the structure-based predictor. Based on this analysis, we predict novel PDZ domain involvement in xenobiotic metabolism and suggest new interactions for other processes including wound healing and Wnt signalling.

Conclusions

We built a structure-based predictor of PDZ domain-peptide interactions, which can be used to scan C-terminal proteomes for PDZ interactions. We also show that the structure-based predictor finds many known PDZ mediated PPIs in human that were not found by our previous sequence-based predictor and is less dependent on training-testing domain sequence similarity. Using both predictors, we defined a functional map of human PDZ domain biology and predict novel PDZ domain function. Users may access our structure-based and previous sequence-based predictors athttp://webservice.baderlab.org/domains/POW.
Inferring homologous protein-protein interactions through pair position specific scoring matrix
Authors: Lin Chun-Yu , Chen Yung-Chiang , Lo Yu-Shu , Yang Jinn-Moon
Published: January 2013

Background

The protein-protein interaction (PPI) is one of the most important features to understand biological processes. For a PPI, the physical domain-domain interaction (DDI) plays the key role for biology functions. In the post-genomic era, to rapidly identify homologous PPIs for analyzing the contact residue pairs of their interfaces within DDIs on a genomic scale is essential to determine PPI networks and the PPI interface evolution across multiple species.

Results

In this study, we proposed "pair P osition S pecific S coring M atrix (pair PSSM)" to identify homologous PPIs. The pair PSSM can successfully distinguish the true protein complexes from unreasonable protein pairs with about 90% accuracy. For the test set including 1,122 representative heterodimers and 2,708,746 non-interacting protein pairs, the mean average precision and mean false positive rate of pair PSSM were 0.42 and 0.31, respectively. Moreover, we applied pair PSSM to identify ~450,000 homologous PPIs with their interacting domains and residues in seven common organisms (e.g. Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Escherichia coli).

Conclusions

Our pair PSSM is able to provide statistical significance of residue pairs using evolutionary profiles and a scoring system for inferring homologous PPIs. According to our best knowledge, the pair PSSM is the first method for searching homologous PPIs across multiple species using pair position specific scoring matrix and a 3D dimer as the template to map interacting domain pairs of these PPIs. We believe that pair PSSM is able to provide valuable insights for the PPI evolution and networks across multiple species.
A practical O(n log2 n) time algorithm for computing the triplet distance on binary trees
Authors: Sand Andreas , Brodal Gerth Stølting , Fagerberg Rolf , Pedersen Christian NS , Mailund Thomas
Published: January 2013

The triplet distance is a distance measure that compares two rooted trees on the same set of leaves by enumerating all sub-sets of three leaves and counting how often the induced topologies of the tree are equal or different. We present an algorithm that computes the triplet distance between two rooted binary trees in time O (n log2
n). The algorithm is related to an algorithm for computing the quartet distance between two unrooted binary trees in time O (n log n). While the quartet distance algorithm has a very severe overhead in the asymptotic time complexity that makes it impractical compared to O (n
2) time algorithms, we show through experiments that the triplet distance algorithm can be implemented to give a competitive wall-time running time.
Building Markov state models with solvent dynamics
Authors: Gu Chen , Chang Huang-Wei , Maibaum Lutz , Pande Vijay S , Carlsson Gunnar E , Guibas Leonidas J
Published: January 2013

Background

Markov state models have been widely used to study conformational changes of biological macromolecules. These models are built from short timescale simulations and then propagated to extract long timescale dynamics. However, the solvent information in molecular simulations are often ignored in current methods, because of the large number of solvent molecules in a system and the indistinguishability of solvent molecules upon their exchange.

Methods

We present a solvent signature that compactly summarizes the solvent distribution in the high-dimensional data, and then define a distance metric between different configurations using this signature. We next incorporate the solvent information into the construction of Markov state models and present a fast geometric clustering algorithm which combines both the solute-based and solvent-based distances.

Results

We have tested our method on several different molecular dynamical systems, including alanine dipeptide, carbon nanotube, and benzene rings. With the new solvent-based signatures, we are able to identify different solvent distributions near the solute. Furthermore, when the solute has a concave shape, we can also capture the water number inside the solute structure. Finally we have compared the performances of different Markov state models. The experiment results show that our approach improves the existing methods both in the computational running time and the metastability.

Conclusions

In this paper we have initiated an study to build Markov state models for molecular dynamical systems with solvent degrees of freedom. The methods we described should also be broadly applicable to a wide range of biomolecular simulation analyses.
Expanding the boundaries of local similarity analysis
Authors: Durno W Evan , Hanson Niels W , Konwar Kishori M , Hallam Steven J
Published: January 2013

Background

Pairwise comparison of time series data for both local and time-lagged relationships is a computationally challenging problem relevant to many fields of inquiry. The Local Similarity Analysis (LSA) statistic identifies the existence of local and lagged relationships, but determining significance through a p-value has been algorithmically cumbersome due to an intensive permutation test, shuffling rows and columns and repeatedly calculating the statistic. Furthermore, this p-value is calculated with the assumption of normality -- a statistical luxury dissociated from most real world datasets.

Results

To improve the performance of LSA on big datasets, an asymptotic upper bound on the p-value calculation was derived without the assumption of normality. This change in the bound calculation markedly improved computational speed from O(pm
2
n) to O(m
2
n), where p is the number of permutations in a permutation test, m is the number of time series, and n is the length of each time series. The bounding process is implemented as a computationally efficient software package, FAST LSA, written in C and optimized for threading on multi-core computers, improving its practical computation time. We computationally compare our approach to previous implementations of LSA, demonstrate broad applicability by analyzing time series data from public health, microbial ecology, and social media, and visualize resulting networks using the Cytoscape software.

Conclusions

The FAST LSA software package expands the boundaries of LSA allowing analysis on datasets with millions of co-varying time series. Mapping metadata onto force-directed graphs derived from FAST LSA allows investigators to view correlated cliques and explore previously unrecognized network relationships. The software is freely available for download at: http://www.cmde.science.ubc.ca/hallam/fastLSA/.
Disease resistance is related to inherent swimming performance in Atlantic salmon
Authors: Castro Vicente , Grisdale-Helland Barbara , Jørgensen Sven M , Helgerud Jan , Claireaux Guy , Farrell Anthony P , Krasnov Aleksei , Helland Ståle J , Takle Harald
Published: January 2013

Background

Like humans, fish can be classified according to their athletic performance. Sustained exercise training of fish can improve growth and physical capacity, and recent results have documented improved disease resistance in exercised Atlantic salmon. In this study we investigated the effects of inherent swimming performance and exercise training on disease resistance in Atlantic salmon.

Atlantic salmon were first classified as either poor or good according to their swimming performance in a screening test and then exercise trained for 10 weeks using one of two constant-velocity or two interval-velocity training regimes for comparison against control trained fish (low speed continuously). Disease resistance was assessed by a viral disease challenge test (infectious pancreatic necrosis) and gene expression analyses of the host response in selected organs.

Results

An inherently good swimming performance was associated with improved disease resistance, as good swimmers showed significantly better survival compared to poor swimmers in the viral challenge test. Differences in mortalities between poor and good swimmers were correlated with cardiac mRNA expression of virus responsive genes reflecting the infection status. Although not significant, fish trained at constant-velocity showed a trend towards higher survival than fish trained at either short or long intervals. Finally, only constant training at high intensity had a significant positive effect on fish growth compared to control trained fish.

Conclusions

This is the first evidence suggesting that inherent swimming performance is associated with disease resistance in fish.
Mobile technology supporting trainee doctors’ workplace learning and patient care: an evaluation
Authors: Hardyman Wendy , Bullock Alison , Brown Alice , Carter-Ingram Sophie , Stacey Mark
Published: January 2013

Background

The amount of information needed by doctors has exploded. The nature of knowledge (explicit and tacit) and processes of knowledge acquisition and participation are complex. Aiming to assist workplace learning, Wales Deanery funded “iDoc”, a project offering trainee doctors a Smartphone library of medical textbooks.

Methods

Data on trainee doctors’ (Foundation Year 2) workplace information seeking practice was collected by questionnaire in 2011 (n = 260). iDoc baseline questionnaires (n = 193) collected data on Smartphone usage alongside other workplace information sources. Case reports (n = 117) detail specific instances of Smartphone use.

Results

Most frequently (daily) used information sources in the workplace: senior medical staff (80% F2 survey; 79% iDoc baseline); peers (70%; 58%); and other medical/nursing team staff (53% both datasets). Smartphones were used more frequently by males (p < 0.01). Foundation Year 1 (newly qualified) was judged the most useful time to have a Smartphone library because of increased responsibility and lack of knowledge/experience.

Preferred information source varied by question type: hard copy texts for information-based questions; varied resources for skills queries; and seniors for more complex problems. Case reports showed mobile technology used for simple (information-based), complex (problem-based) clinical questions and clinical procedures (skills-based scenarios). From thematic analysis, the Smartphone library assisted: teaching and learning from observation; transition from medical student to new doctor; trainee doctors’ discussions with seniors; independent practice; patient care; and this ‘just-in-time’ access to reliable information supported confident and efficient decision-making.

Conclusion

A variety of information sources are used regularly in the workplace. Colleagues are used daily but seniors are not always available. During transitions, constant access to the electronic library was valued. It helped prepare trainee doctors for discussions with their seniors, assisting the interchange between explicit and tacit knowledge.

By supporting accurate prescribing and treatment planning, the electronic library contributed to enhanced patient care. Trainees were more rapidly able to medicate patients to reduce pain and more quickly call for specific assessments. However, clinical decision-making often requires dialogue: what Smartphone technology can do is augment, not replace, discussion with their colleagues in the community of practice.
Microstructure and optical properties of Pr3+-doped hafnium silicate films
Authors: An YongTao , Labbé Christophe , Khomenkova Larysa , Morales Magali , Portier Xavier , Gourbilleau Fabrice
Published: January 2013

In this study, we report on the evolution of the microstructure and photoluminescence properties of Pr3+-doped hafnium silicate thin films as a function of annealing temperature (T
A). The composition and microstructure of the films were characterized by means of Rutherford backscattering spectrometry, spectroscopic ellipsometry, Fourier transform infrared absorption, and X-ray diffraction, while the emission properties have been studied by means of photoluminescence (PL) and PL excitation (PLE) spectroscopies. It was observed that a post-annealing treatment favors the phase separation in hafnium silicate matrix being more evident at 950°C. The HfO2 phase demonstrates a pronounced crystallization in tetragonal phase upon 950°C annealing. Pr3+ emission appeared at T
A = 950°C, and the highest efficiency of Pr3+ ion emission was detected upon a thermal treatment at 1,000°C. Analysis of the PLE spectra reveals an efficient energy transfer from matrix defects towards Pr3+ ions. It is considered that oxygen vacancies act as effective Pr3+ sensitizer. Finally, a PL study of undoped HfO2 and HfSiO
x
matrices is performed to evidence the energy transfer.
On the transcendence of some power series
Authors: Karadeniz Gözeri Gül , Pekin Ayten , Kılıçman Adem
Published: January 2013

In this study, we consider some power series with rational coefficients and investigate transcendence of the values of these series for Liouville number arguments. It is proved that these values are either a Liouville number or a rational number under certain conditions.

AMS Subject Classification:11J81, 11J17.
Drug-likeness analysis of traditional Chinese medicines: 2. Characterization of scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines
Authors: Tian Sheng , Li Youyong , Wang Junmei , Xu Xiaojie , Xu Lei , Wang Xiaohong , Chen Lei , Hou Tingjun
Published: January 2013

Background

In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared.

Results

First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets.

Conclusion

The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and de novo drug design.
One cell, multiple roles: contribution of mesenchymal stem cells to tumor development in tumor microenvironment
Authors: Yang Xue , Hou Jing , Han Zhipeng , Wang Ying , Hao Chong , Wei Lixin , Shi Yufang
Published: January 2013

The discovery of tissue reparative and immunosuppressive abilities of mesenchymal stem cells (MSCs) has drawn more attention to tumor microenvironment and its role in providing the soil for the tumor cell growth. MSCs are recruited to tumor which is referred as the never healing wound and altered by the inflammation environment, thereby helping to construct the tumor microenvironment. The environment orchestrated by MSCs and other factors can be associated with angiogenesis, immunosuppression, inhibition of apoptosis, epithelial-mesenchymal transition (EMT), survival of cancer stem cells, which all contribute to tumor growth and progression. In this review, we will discuss how MSCs are recruited to the tumor microenvironment and what effects they have on tumor progression.
Ruptured left ventricular pseudoaneurysm in the mediastinum following acute myocardial infarction: a case report
Authors: Si Daoyuan , Shi Kaiyao , Gao Dongmei , Yang Ping
Published: January 2013

Left ventricular pseudoaneurysm is an uncommon complication after transmural acute myocardial infarction (AMI). Here we describe the case of a 43-year-old man who presented with AMI and chest distress despite the normal appearance of his coronary artery during coronary angiography. Timely thrombolytic therapy was administered. Echocardiography, and cardiac computed tomography showed a ventricular pseudoaneurysm, and direct visualization at the time of surgery showed that it had ruptured in the mediastinum instead of the pericardium. The survival rate of patients with ventricular pseudoaneurysm rupture is low. The rupture of ventricular pseudoaneurysm in the mediastinum is rare; therefore, this case is noteworthy.
Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy
Authors: Atri Alireza , Molinuevo José L , Lemming Ole , Wirth Yvonne , Pulte Irena , Wilkinson David
Published: January 2013

Introduction

Memantine and cholinesterase inhibitors potentially offer additional benefits in Alzheimer's disease (AD) when used together. This study assessed the efficacy and safety of combination treatment with memantine added to stable donepezil in patients with moderate to severe AD, and in a subset with moderate AD.

Methods

Post hoc meta-analyses of data combined from two 24-week, randomised, double-blind, placebo-controlled trials of memantine 20 mg/day versus placebo, added to a stable cholinesterase inhibitor, were conducted. Data were included for all patients receiving donepezil 10 mg/day with Mini-Mental State Examination (MMSE) scores < 20 (n = 510). Efficacy was assessed using measures of cognition, function, and global status. Furthermore, marked clinical worsening, defined as concurrent deterioration from baseline in the three main efficacy domains, and safety, measured by treatment-emergent adverse events, were assessed. Analyses were performed for patients with moderate to severe AD (MMSE 5-19; MOD-SEV subgroup), and also for patients with moderate AD (MMSE 10-19; MOD subgroup; n = 367).

Results

At week 24, in the MOD-SEV subgroup, patients receiving memantine added to donepezil significantly outperformed those receiving placebo added to donepezil in measures of cognition (P < 0.0001), function (P = 0.02), and global status (P = 0.010), with standardised mean differences (SMDs) of 0.36, 0.21, and 0.23, respectively (all last observation carried forward). Similarly, in the MOD subgroup, significant benefits were observed for cognition (P = 0.008), function (P = 0.04) and global status (P = 0.008), with SMDs of 0.28, 0.21, and 0.28, respectively. Significantly fewer patients receiving memantine added to donepezil showed marked clinical worsening than those receiving placebo added to donepezil, in both subgroups (MOD-SEV: 8.7% versus 20.4%, P = 0.0002; MOD: 5.9% versus 15.0%, P = 0.006). The incidence of adverse events was similar between treatment groups.

Conclusions

These results support and extend previous evidence that combination treatment with memantine added to stable donepezil in patients with moderate AD, and in those with moderate to severe AD, is associated with significant benefits in reducing 24-week decline in cognition, function and global status. Combination treatment produces substantially reduced rates of marked clinical worsening, has good safety and tolerability, and generates effect sizes that are both statistically significant and clinically meaningful.
The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer
Authors: Peurala Emmi , Koivunen Peppi , Haapasaari Kirsi-Maria , Bloigu Risto , Jukkola-Vuorinen Arja
Published: January 2013

Introduction

Loss of the retinoblastoma protein tumor suppressor gene (RB) coding for a nuclear phosphoprotein that regulates the cell cycle is found in many human cancers and probably leads to disruption of the p16-cyclin D1-CDK4/6-RB pathway. Cyclin D1 is known to activate CDK4, which then phosphorylates the RB protein, leading to cell cycle progression. p16 inhibits CDK4, keeping RB hypophosphorylated and preventing cell cycle progression. The significance of these three markers, cyclin D1, CDK4 and p16, for breast cancer and carcinogenesis is nevertheless still controversial.

Methods

The material consisted of 102 formalin-fixed human breast cancer samples, in which cyclin D1, CDK4 and p16 expression was evaluated immunohistochemically. The amounts of cyclin D1 mRNA present were analyzed by quantitative real time PCR.

Results

High cyclin D1 expression statistically significantly correlated with lower tumor grade, estrogen and progesterone receptor positivity and lower proliferation activity in breast tumors and increased breast cancer-specific survival and overall survival. Tumors with high cyclin D1 protein had 1.8 times higher expression of cyclin D1 mRNA. CDK4 expression did not correlate with cyclin D1 expression or the survival data. p16 expression was associated with Human Epidermal Growth Factor Receptor 2 (HER2) negativity and increased breast cancer-specific survival and disease-free survival. No statistical correlations between cyclin D1, CDK4 and p16 were found.

Conclusions

Cyclin D1 was associated with a good breast cancer prognosis but functioned independently of CDK4. High cyclin D1 expression may be partially due to increased CCND1 transcription. p16 correlated with a better prognosis and may function without CDK4. In conclusion, it appears that cyclin D1, CDK4 and p16 function independently in human breast cancer.
Prognostic consequences of borderline dysnatremia: pay attention to minimal serum sodium change
Authors: Darmon Michael , Diconne Eric , Souweine Bertrand , Ruckly Stéphane , Adrie Christophe , Azoulay Elie , Clec'h Christophe , Garrouste-Orgeas Maïté , Schwebel Carole , Goldgran-Toledano Dany , Khallel Hatem , Dumenil Anne-Sylvie , Jamali Samir , Cheval Christine , Allaouchiche Bernard , Zeni Fabrice , Timsit Jean-François
Published: January 2013

Introduction

To assess the prevalence of dysnatremia, including borderline changes in serum sodium concentration, and to estimate the impact of these dysnatremia on mortality after adjustment for confounders.

Methods

Observational study on a prospective database fed by 13 intensive care units (ICUs). Unselected patients with ICU stay longer than 48 h were enrolled over a 14-year period were included in this study. Mild to severe hyponatremia were defined as serum sodium concentration < 135, < 130, and < 125 mmol/L respectively. Mild to severe hypernatremia were defined as serum sodium concentration > 145, > 150, and > 155 mmol/L respectively. Borderline hyponatremia and hypernatremia were defined as serum sodium concentration between 135 and 137 mmol/L or 143 and 145 respectively.

Results

A total of 11,125 patients were included in this study. Among these patients, 3,047 (27.4%) had mild to severe hyponatremia at ICU admission, 2,258 (20.3%) had borderline hyponatremia at ICU admission, 1,078 (9.7%) had borderline hypernatremia and 877 (7.9%) had mild to severe hypernatremia. After adjustment for confounder, both moderate and severe hyponatremia (subdistribution hazard ratio (sHR) 1.82, 95% CI 1.002 to 1.395 and 1.27, 95% CI 1.01 to 1.60 respectively) were associated with day-30 mortality. Similarly, mild, moderate and severe hypernatremia (sHR 1.34, 95% CI 1.14 to 1.57; 1.51, 95% CI 1.15 to 1.99; and 2.64, 95% CI 2.00 to 3.81 respectively) were independently associated with day-30 mortality.

Conclusions

One-third of critically ill patients had a mild to moderate dysnatremia at ICU admission. Dysnatremia, including mild changes in serum sodium concentration, is an independent risk factor for hospital mortality and should not be neglected.
Cognitive Theories of Genre: The Prototype Effect and Early Modern Spanish Tragedy
Authors: Simerka Barbara
Published: January 2013

This essay analyzes recent developments in the field of genre-oriented theories of tragedy, such as the materialist and postmodern approaches offered in Terry Eagleton’s Sweet Violence and Rita Felski’s Rethinking Tragedy . It also incorporates recent advances in the cognitive sciences about taxonomical activity, such as the prototype effect, that can inform genre theory. Prototype theories of categorization provide insights into both the history and current status of tragedy theory, illuminating such diverse aspects as the enduring legacy of Aristotelian approaches, how the canon of prized tragedies changes over time, and the status of hybrid dramatic forms. The anthology Hacia la tragedia áurea: Lecturas para un nuevo milenio (2007) serves as a point of departure for exploring the nexus of early modern Hispanism and genre theory as a literary and cognitive endeavor.
Warrior Women, Unmanly Men: Mira de Amescua’s El clavo de Jael
Authors: Campbell Gwyn E.
Published: January 2013

Antonio Mira de Amescua bases his Old Testament play on the brief story (Judg. 4 and 5) of two powerful women—a Judith-like Kenite and a prophetess—who deliver premonarchic Israel from the Canaanite oppression of King Jabín and Sísara. Mira remains faithful to the sexually charged biblical sources, while he supplements the epic with the characters and intrigue to befit a comedia . Mira doubles the couples of Judges (here, Eber Fineo/Jael and the juridical military dyad of Débora/ Barac) with an enamoured gracioso (Simaneo) and maid (Tamar), and with, more importantly, the pairing of Sísara and the emblematic Sofonisa, Jabín’s sister. The dramatist establishes a symmetrical schematic, including the axis of an economy of recompense among other literary mechanisms, which allows for the male characters to reflect one another. Mira juxtaposes the two warrior women with the four male characters who are “disarmed”—literally or symbolically—in one form or another, and who share a fate of shame in varying degrees. Furthermore, in the dramatist’s own paradigmatic supersession of this biblical tale about love, (dis) honour, and Faith, Jael is an Israelite, thus representative of the Christian thematic lessons of the play. Her hapless husband, however, remains a Kenite. In this manner, he represents the “other,” even the Jewish converso , who must suffer the consequences of failing to believe, and/or believing the dishonour that he thought his wife brought upon his name, much to an audience’s delight.
The Biblical Ruth as Dama Principal: Tirso’s La mejor espigadera
Authors: Stroud Matthew D.
Published: January 2013

The comedia mined a variety of source texts for its plots—Italian novelle, Spanish history, Greek and Roman mythology, and, of course, the Bible—but always managed to adapt plot, setting, and characters to the conventions of the Spanish national theater. This process offered great benefits, such as audience familiarity, as well as challenges, including inherent and unavoidable limitations on artistic freedom. One of the more interesting adaptations is Tirso de Molina’s reworking of the Biblical story of Ruth in La mejor espigadera , primarily because of the lack of dramatic potential offered by the original: there are no villains, no obstacles that appear to be insurmountable, no internal conflicts that any of the principal characters must resolve. Indeed, the Biblical characters are for the most part rather one-dimensional and exceedingly virtuous. This study focuses on the central figure of Ruth and her transformation from young, simple Moabite to a leading lady with much in common with other damas principales . Tirso’s techniques—elevating Ruth to nobility, describing her in conventional poetic terms, creation of a love triangle, even recasting her as a strong-willed, intelligent, and competent woman who does not submit meekly to the wishes of others—not only provide the audience with a different interpretation of this righteous woman of the Hebrew Bible, but also reveal a great deal about seventeenth-century Spanish views of women and the art of comedia dramaturgy as well. In the end, Tirso does not just demonstrate the Baroque aspiration to imitate its models with the goal of surpassing them, he makes the case that the comedia as a genre should take second place to nothing, not even to the Holy Bible.
Tirso de Molina and His Nephew: The Case for the Real Existence of Francisco Lucas de Ávila
Authors: Sullivan Henry Wells , Monteiro Luciana da Cunha
Published: January 2013

Gabriel Téllez’s autobiography offers fascinating questions for scholars. The present essay brings new material to light and speculates on Tirso de Molina’s family. We argue that a particular nephew of Tirso existed in reality (despite some twentiethcentury critical myths), because otherwise there would be no viable theory for the transmission of the playwright’s texts from manuscript to printed Parte , specifically the Partes II-V. The essay also treats Tirso’s direct knowledge of Luis de Camões and the probable origin of the Téllez family in Portugal. We suggest that Tirso had a younger sister who was the mother of Francisco Lucas de Ávila, and that the father of the controversial nephew was the Madrid-born Francisco de Ávila, an editor and compiler of villancicos and Partes of comedias. It is our contention that these two similar-sounding men were confused by both Cayetano Alberto de la Barrera y Leirado in 1860 and by Alan Paterson as recently as 1966.
Violent Masculinity Onstage and Off: A Rereading of Ana Caro’s Valor, agravio y mujer through the Memoir of Catalina de Erauso
Authors: Seagraves Rosie
Published: January 2013

Scholars have interpreted the feminist quality of Ana Caro’s Valor, agravio y mujer , and its protagonist Leonor, through various paradigms, as part of what Robert Bayliss terms “the post- dramaturga era.” Many interpretations of Caro’s play, however, ignore an essential element of Leonor’s plot as the avenging mujer varonil so as to reconcile her essentially deviant cross-dressing, skillful manipulations, and courage with the conventional marriage at the end of the work, interpreting the marriage arrangement as Leonor’s desired conclusion, or goal. This study aims to underscore Leonor’s wish to murder, and not marry, Don Juan, and the way in which this violent intention reveals her innovative position that eludes the female/male dichotomy. Given that she has shifted the female/male divide, Leonor can use tools from one side of her identity to remedy the other. In an episode of the memoir of another crossdressed figure of the time, Catalina de Erauso, violence as a masculine device works against masculine advantage, similarly highlighting woman’s disadvantaged position as related to the honor code. By comparing the two figures, we may better comprehend an overall discursive imagination of female cross-dressing in seventeenth-century Spain and reconsider the nature of Leonor’s plight in Caro’s play.
From the Beautiful to the Sublime in Calderón’s El pintor de su deshonra
Authors: García-Bryce Ariadna
Published: January 2013

This article analyzes Calderón de la Barca’s El pintor de su deshonra in the framework of the sublime, with sustained attention to the comedia ’s reflection on painting. Diverging from the notion that the sublime emerges in eighteenth-century Northern Europe, this study approaches the sublime as an ongoing development from antiquity through modernity, Calderonian drama being an illustrative example of its tension-ridden aesthetic function. Specifically, the sublime is formulated in the play’s articulation of a shift from Renaissance conceptions of beauty as a harmonious integration of senses and intellect to a Baroque disencounter between corporeal and conceptual perception. Echoing Longinus’s and Kant’s definitions of the sublime as differing from Platonic beauty, the Calderonian sublime subverts civic forms of aesthetic pleasure. Replicating the physical and conceptual density of the mise-en-abîme common in seventeenth-century painting, the work combines a self-reflexive skepticism of appearances with the implication that specular representation, although desultory, is an essential epistemological tool. In the dynamic ocular movement that it elicits, it maintains a productive, albeit disturbing, oscillation between analytic and sensorial fruition.
El periplo artístico de la escenificación de un clásico: La moza de cántaro de Lope de Vega
Authors: Fernández Esther
Published: January 2013

La moza de cántaro (1625) de Lope de Vega no pertenece al corpus de comedias canónicas del auto; sin embargo, su diversa trayectoria escénica desde el siglo XIX la ha convertido en un referente dentro de la historia de la representación del repertorio clásico español. La obra fue refundida por Cándido María Trigueros y Tomás Luceño en 1803 y 1903, respectivamente; transformada en coro (1843) y en zarzuela (1943); puesta en escena en tres ocasiones desde 1883 hasta 1950; adaptada al cine (1953) y a la televisión (1981); y, finalmente, representada en el 2010 por la Joven Compañía Nacional de Teatro Clásico (CNTC). Dentro de este ajetreado periplo escénico, el presente artículo se propone estudiar la evolución de dicha comedia a través de tres paradas claves en su andadura artística—la adaptación cinematográfica de Florián Rey en la década de los cincuenta, la filmación televisiva en los ochenta para Estudios 1 y el reciente montaje de la Joven CNTC dirigido por Eduardo Vasco—y calibrar lo que estas tres adaptaciones a medios espectaculares muy distintos y separadas entre ellas por un intervalo temporal de treinta años han podido significar para la historia de la representación de un texto clásico y de su consecuente recepción socio-cultural.
DARE —: On Beyond Zydeco
Authors: Goebel George H.
Published: January 2013

The fifth volume of the Dictionary of American Regional English , ending with zydeco , was finished last year and published this spring. Since then the project has been working on preparing material for a sixth volume of supplemental materials (geographical and social maps, an index to the entries, and lists of responses to selected questions in the DARE questionnaire), which is to appear early next year, and for a corrected and enhanced online edition of the whole work, to be launched late next year. Plans are already being made for periodic updates and revisions of the online edition, which will take advantage not only of the thousands of new citations that have already been collected, but also of the many Web resources that have become available since the first three volumes were written. Future plans include a pilot project to test the feasibility of using modern methods—Web-based questionnaires and telephone interviews—to achieve the same sort of results as the original DARE fieldwork, and a project to make the sound recordings from the original fieldwork—along with a database containing detailed content listings—available on the Web.