bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging the data integration gap
Authors: Bennett Travis A. , Bayrak Coskun
Published: May 2011

The integration of multiple autonomous and heterogeneous data sources (both across the web and via a company intranet) has received much attention throughout the years, particularly due to its many applications in the fields of Artificial Intelligence and medical research data sharing. Data integration systems embody this work and have come very far in the past twenty years. The problem of designing such systems is characterized by a number of issues that are interesting from a theoretical point of view: answering queries using logical views, query containment and completeness, automatic integration of existing data sources via schema mapping tools, etc. In this work we discuss these issues, compare and contrast various proposed solutions (federated database systems and data warehouses), and finally propose a novel extension of the MVC (model, view, controller) web-based framework that allows for the rapid development and implementation of data integration systems solutions suitable for use on the web.
UXSOM
Authors: Nuthakki Murali K. , Mete Mutlu , Varol Cihan , Suh Sang C.
Published: May 2011

Software developers are increasingly using Unified Modeling Language (UML) tools to automate source code generation. Therefore, nowadays calculating software metrics from UML diagrams to evaluate software quality is an important trend in the software industry. However, acquisition of software metrics from Extensible Markup Language (XML) export of UML tools has been predominantly tool dependent. Moreover, each new tool may have different specifications in XML. Despite the overall need for a process to automate XML unification, no current solution has yet been proposed. Creating a framework to automate this assessment would streamline development and increase efficiency in software industry. With the aim to overcome this deficiency, we developed a parser-based framework, named UXSOM, to calculate software metrics independently from the UML tool. Particularly UXSOM is able to generate software metrics from the XML-based outputs of the tools, ArgoUML, UMLET, MagicDraw, Sparx Systems, and ESS Model. We showed a very general case of UML class diagram, in which we extracted and compared software metrics from these five different tool.
Computing Shapley's saddles
Authors: Brandt Felix , Brill Markus , Fischer Felix , Harrenstein Paul , Hoffmann Jan
Published: May 2011

Game-theoretic solution concepts, such as Nash equilibrium, are playing an ever increasing role in the study of systems of autonomous agents. A common criticism of Nash equilibrium is that its existence relies on the possibility of
randomizing
over actions, which in many cases is deemed unsuitable, impractical, or even infeasible.
A prescriptive approach for playing games
Authors: Feldman Michal
Published: May 2011

Decision-Making lies in the foundations of fields such as Economics, Operations Research, and Artificial Intelligence. The question of what should be the action to be taken by a decision-maker when facing an uncertain environment, potentially including other decision makers, is a fundamental problem which has led to a wide variety of models and solutions. One of the only types of situations (of more than a single agent) for which this question got an agreed-upon answer is in the context of two-player zero-sum games. This setting can model any situation in which a decision-maker aims at maximizing her guaranteed payoff. When mixed strategies are allowed, such desired behavior, termed an agent's maximin (or safety level) strategy, leads to a well defined expected payoff (known as the
value
of the game). Moreover, when presented explicitly in a matrix form, the computation of a maximin strategy is polynomial (by solving a linear program).
Secretary problems and incentives via linear programming
Authors: Buchbinder Niv , Jain Kamal , Singh Mohit
Published: May 2011

In the classical secretary problem an employer would like to choose the best candidate among
n
competing candidates that arrive in a random order. Our main contribution is a new linear programming technique that we introduce as a tool for obtaining and analyzing mechanisms for the secretary problem and its variants. The linear program is formulated using judiciously chosen variables and constraints and we show a one-to-one correspondence between mechanisms for the secretary problem and feasible solutions to the linear program.
Editor's puzzle
Authors: Conitzer Vincent
Published: May 2011

Solutions should be sent to the editor at conitzer@cs.duke.edu with subject header
SIGecom Exchanges Puzzle
. The author(s) of the most elegant solution (as judged by the editor) will be allowed to publish his or her or their proof in the next issue of the Exchanges (ties broken towards earlier submissions). To make the solution accessible to a wide audience, try to minimize technical jargon in the proof. The editor will not give any feedback on submitted solutions and ignore any requests for hints,
etc
.
Editor's introduction
Authors: Conitzer Vincent
Published: May 2011

I am very happy to introduce Issue 9.1 of SIGecom Exchanges. All the contributions in this issue concern markets of various kinds. In "The Pathologies of Online Display Advertising Marketplaces," Edelman discusses various challenges faced by marketplaces for banner ads on websites (in contrast to ads displayed next to search results). In "Designing Aggregation Mechanisms for Reputation Systems in Online Marketplaces," Aperjis and Johari discuss mechanisms for aggregating ratings that a seller has received; they consider mechanisms that average over a fixed window of past transactions (and discuss how to optimize the window size), as well as a broader class of mechanisms. In "Matching, Cardinal Utility, and Social Welfare," Anshelevich and Das discuss matching markets where the participants' preferences are modeled cardinally (whereas they are often modeled ordinally in this type of market). In "Competitive Equilibria in Matching Markets with Budgets," N. Chen, Deng, and Ghosh consider the Shapley-Shubik assignment model (with general utility functions) and extend it with budget constraints; they then study how to compute a competitive equilibrium (if one still exists). In "Connections Between Markets and Learning," Y. Chen and Vaughan discuss the mathematical connections between market maker mechanisms for prediction markets, and no-regret learning, showing that any cost-function-based prediction market with bounded loss can be interpreted as a no-regret learning algorithm, and studying what the resulting no-regret learning algorithms look like. In "Competition in Mechanisms," Pai considers settings with multiple sellers that compete with each other by announcing mechanisms, and discusses some of the key issues as well as recent results. Finally, in "Approximability of Combinatorial Problems with Multi-agent Submodular Cost Functions," Goel, Karande, Tripathi, and Wang consider computational problems that come up in winner determination in combinatorial procurement auctions: a feasible set of elements must be selected, and there are multiple agents that can provide subsets of these elements. They consider the case where each agent has a submodular cost function, and establish upper and lower bounds on the approximability of these problems.
Matching, cardinal utility, and social welfare
Authors: Anshelevich Elliot , Das Sanmay
Published: May 2011

Matching markets have historically been an important topic in economics research. On the positive (descriptive) side, researchers have modeled everything ranging from marriage markets to labor markets using the framework of matching. Matching was also one of the first areas in which market design made a name for itself, perhaps most famously in the redesign of the market that matches graduating M.D.s to their first residency programs in the United States. The arrival of computer scientists to the field of market design in general can be traced to many of the reasons suggested recently by Conitzer [2010] (in a broader context than just market design) in an article in
Communications of the ACM
, including the effects of new markets that have been made possible by advances in networking and Internet technology, a more computational mindset in general, and also the ability to view problems from a different perspective. In the case of matching markets in particular, in addition to the (often) constructive nature of computational approaches, there is also the historical fact that computer scientists have studied matching from many different perspectives, perhaps because matching markets have a very natural representation in the language of graphs.
Competitive equilibria in matching markets with budgets
Authors: Chen Ning , Deng Xiaotie , Ghosh Arpita
Published: May 2011

Consider a market with
n
unit demand buyers and
m
sellers, each selling one unit of an indivisible good. The buyers specify their preferences over items via utility functions
u

ij

(
p

j

), which is the utility of buyer
i
for item
j
when its price is
p

j

. So far, this is the classic Shapley-Shubik assignment model [Shapley and Shubik 1971] which captures a variety of matching markets including housing markets and ad auctions [Edelman et al. 2007], except for the extension to general utility functions instead of the quasi-linear utilities in the original model. Shapley and Shubik show that a
competitive equilibrium
always exists in their model, and later work [Crawford and Knoer 1981, Quinnzi 1984, Gale 1984] shows that a competitive equilibrium must also exist for the model with general utility functions
u

ij

(·), provided these
u

ij

(·) are strictly decreasing and continuous everywhere.
Editor's puzzle
Authors: Conitzer Vincent
Published: May 2011

Solutions should be sent to the editor at conitzer@cs.duke.edu with subject header
SIGecom Exchanges Puzzle
. The author(s) of the most elegant solution (as judged by the editor) will be allowed to publish his or her or their proof in the next issue of the Exchanges (ties broken towards earlier submissions). To make the solution accessible to a wide audience, try to minimize technical jargon in the proof. Until the winner is chosen, the editor will not give any feedback on submitted solutions and ignore any requests for hints,
etc
.
Coordination, collaboration and the impact of computer graphics
Authors: Westman Hans
Published: May 2011

2011 marks the tenth year I've been involved with SIGGRAPH (a relative new-be) primarily as a volunteer for the newsletter. The contributions comprised of both solicited and voluntarily submissions are what make the newsletter what it is, not only an exciting and informative array of articles, but a conduit for the exchange of ideas and collaborations around a common interest - computer graphics - in all its applicable nuances.
Art + technology
Authors: Chestney-Harvey Kim
Published: May 2011

To some, the intersection between art and technology seems like an oxymoron. But to those who work with creative technology, it is the new frontier. For the past several decades, artists and technologists alike have been charting new horizons with the ever-evolving advances in both genres.
Preparing for a lunar impact
Authors: Wright Ernie
Published: May 2011

A two-ton Atlas Centaur rocket body, part of the Lunar Crater Observation and Sensing Satellite (LCROSS), struck the floor of Cabeus crater, near the south pole of the Moon, at 11:31 UT on October 9, 2009. The purpose of the crash was to create a plume of debris that could be examined for the presence of water and other chemicals in the lunar regolith. The effects of the impact were captured by sensors on board a shepherding satellite following four minutes behind the Centaur. They were also recorded by the Lunar Reconnaissance Orbiter (LRO), which passed over the crash site less than two minutes after the impact.
Effects of Surface-coated Carbon on the Chemical Selectivity for Water-Soluble Dispersants of LiFePO4
Authors: Li Chia-Chen , Wang Ya-Hui , Yang Ting-Yu
Published: May 2011

The effects of additions of dispersants, poly(4-styrene sulfonic acid) (PSSA), poly(ammonium acrylate) (PAA-NH4) and poly(acrylic acid-co-maleic acid) (PAMA), on the dispersion and electrochemical properties of carbon-coated lithium iron phosphate (LiFePO4) cathodes are studied. The influence of the addition of dispersants on the dispersion behaviors of carbon-coated LiFePO4 and conductive agents in aqueous suspensions is explored by analyses of zeta-potential and rheology. The homogeneity of the composition in the LiFePO4 cathode is assessed by scanning electron microscopy observation. The result shows that both PSSA and PAMA can interact with the carbon-coated LiFePO4 and they are efficient dispersants for LiFePO4 cathodes. PAA-NH4, however, is unfavorable to interact with carbon materials, and thus has a restricted efficiency for the dispersion of carbon-coated LiFePO4 cathodes. In addition to the dispersion property, the effect of the addition of dispersants on the rate capability of LiFePO4 cathodes is also examined. Although PSSA improves the dispersion homogeneity of the LiFePO4 electrodes, it is detrimental to the electrochemical property due to its high average molecular weight (

M

n

−

) of 70,000 g/mol. On the contrary, the PAMA used has a low

M

n

−

of 3,000 g/mol, and hence only the positive influence of the improved dispersion of the cathode in terms of an increase in rate capability is observed.
Controlling spike timing and synchrony in oscillatory neurons
Authors: Stigen Tyler , Danzl Per , Moehlis Jeff , Netoff Theoden
Published: May 2011

We describe an algorithm to control synchrony between two periodically firing neurons. The control scheme operates in real-time using a dynamic clamp platform. This algorithm is a low-impact stimulation method that brings the neurons toward the desired level of synchrony over the course of several neuron firing periods. As a proof of principle, we demonstrate the versatility of the algorithm using real-time conductance models and then show its performance with biological neurons of hippocampal region CA1 and entorhinal cortex.
Habitat Selection and Mating Success in a Mustelid
Authors: Lodé Thierry
Published: May 2011

Habitat selection remains a poorly understood ecological process, but relating mating behaviour to pattern of habitat selection constitutes a fundamental issue both in evolutionary ecology and in biological conservation. From radiotelemetry protocol, habitat-induced variations in mating success were investigated in a solitary mustelid carnivore, the European polecatMustela putorius. Selection for marshy habitat was regarded as adaptive in that mating success was found greater using marches than other habitats. Males consorted with 1.3 females, revealing a low polygyny rate. Pregnant or lactating females selectively shifted to deciduous woods. That some habitat types may favour a good reproduction forms a key factor for species conservation and environmental management. Nevertheless, such as in various vertebrates, habitat requirements seem to be based on simple broad features of habitat, suggesting that habitat avoidance rather than habitat preference can explain polecat habitat predilection.
rtMEG: A Real-Time Software Interface for Magnetoencephalography
Authors: Sudre Gustavo , Parkkonen Lauri , Bock Elizabeth , Baillet Sylvain , Wang Wei , Weber Douglas J.
Published: May 2011

To date, the majority of studies using magnetoencephalography (MEG) rely on off-line analysis of the spatiotemporal properties of brain activity. Real-time MEG feedback could potentially benefit multiple areas of basic and clinical research: brain-machine interfaces, neurofeedback rehabilitation of stroke and spinal cord injury, and new adaptive paradigm designs, among others. We have developed a software interface to stream MEG signals in real time from the 306-channel Elekta Neuromag MEG system to an external workstation. The signals can be accessed with a minimal delay (≤45 ms) when data are sampled at 1000 Hz, which is sufficient for most real-time studies. We also show here that real-time source imaging is possible by demonstrating real-time monitoring and feedback of alpha-band power fluctuations over parieto-occipital and frontal areas. The interface is made available to the academic community as an open-source resource.
Cementoblastoma Arising in the Maxilla of an 8-Year-Old Boy: A Case Report
Authors: Harada Hiroyuki , Omura Ken , Mogi Seiki , Okada Norihiko
Published: May 2011

Cementoblastoma is an uncommon disease, representing only 1–8% of all odontogenic tumours. Furthermore, this tumour is especially uncommon in children, as only five cases have been reported in this age group. Here, we describe a case of cementoblastoma arising in the maxilla of an 8-year-old boy, that was treated with a partial maxillectomy. The patient's facial appearance has remained satisfactory, and the tumour has not recurred in the 9 years after the operation.
Coping Strategies of Family Members of Hospitalized Psychiatric Patients
Authors: Eaton Phyllis M. , Davis Bertha L. , Hammond Pamela V. , Condon Esther H. , McGee Zina T.
Published: May 2011

This exploratory research paper investigated the coping strategies of families of hospitalized psychiatric patients and identified their positive and negative coping strategies. In this paper, the coping strategies of 45 family members were examined using a descriptive, correlational, mixed method research approach. Guided by the Neuman Systems Model and using the Family Crisis Oriented Personal Evaluation Scales and semistructured interviews, this paper found that these family members used more emotion-focused coping strategies than problem-focused coping strategies. The common coping strategies used by family members werecommunicating with immediate family, acceptance of their situation, passive appraisal, avoidance, and spirituality. The family members also utilized resources and support systems, such as their immediate families, mental health care professionals, and their churches.
The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications
Authors: Guerra Daniel J.
Published: May 2011

Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD.
A New Technique in Primary Repair of Congenital Esophageal Atresia Preventing Anastomotic Stricture Formation and Describing the Opening Condition of Blind Pouch: Plus (“+”) Incision
Authors: Melek Mehmet , Cobanoglu Ufuk
Published: May 2011

Anastomotic strictures are common and important problems following repair procedures of esophageal atresia. We hereby defined an anastomosis technique that could efficiently prevent this complication in 11 patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF). The proximal end of the atretic esophagus was opened with a plus (“+”)-shaped incision providing sufficient anastomosis width. Longitudinal incisions of 2 mm length were made on the anterior and posterior parts of the distal end according to the patients. The two ends were anastomosed with a primary suture at a single plain. We performed this technique on 11 patients, and in the 4-year follow-up period no dilatation proved necessary in any of our patients due to anastomotic strictures or symptomatic dysphagia. This technique that we have described provides a large zigzag anastomosis line and in this way minimizes the incidence of stricture formation. Furthermore, this technique, which we believe to have provided a new opinion on the topic of how to open the proximal end of an atretic esophagus, is quite easy and effective.
The Risk of Radiation Exposure to the Eyes of the Interventional Pain Physician
Authors: Fish David E. , Kim Andrew , Ornelas Christopher , Song Sungchan , Pangarkar Sanjog
Published: May 2011

It is widely accepted that the use of medical imaging continues to grow across the globe as does the concern for radiation safety. The danger of lens opacities and cataract formation related to radiation exposure is well documented in the medical literature. However, there continues to be controversy regarding actual dose thresholds of radiation exposure and whether these thresholds are still relevant to cataract formation. Eye safety and the risk involved for the interventional pain physician is not entirely clear. Given the available literature on measured radiation exposure to the interventionist, and the controversy regarding dose thresholds, it is our current recommendation that the interventional pain physician use shielded eyewear. As the breadth of interventional procedures continues to grow, so does the radiation risk to the interventional pain physician. In this paper, we attempt to outline the risk of cataract formation in the scope of practice of an interventional pain physician and describe techniques that may help reduce them.
The Effect of Gallium Nitrate on Arresting Blood Flow from a Wound
Authors: Goodley Paul H. , Rogosnitzky Moshe
Published: May 2011

A novel application of gallium nitrate, hitherto unreported, in reducing bleeding time from an open wound is presented. Experiments performed using simple punctures in the forearm demonstrated a very substantial reduction in bleeding time when a solution of gallium nitrate was applied relative to a control. This outcome was shown to be unaffected by the anticoagulant properties of warfarin. The mechanism for such action of gallium nitrate is unknown and merits further investigation, as do the possibilities for such an application to improve both civilian and defense trauma treatment modalities.
Intraspecific Variation in Maximum Ingested Food Size and Body Mass in Varecia rubra and Propithecus coquereli
Authors: Hartstone-Rose Adam , Perry Jonathan M. G.
Published: May 2011

In a recent study, we quantified the scaling of ingested food size (Vb
)—the maximum size at which an animal consistently ingests food whole—and found that Vb
scaled isometrically between species of captive strepsirrhines. The current study examines the relationship between Vb
and body size within species with a focus on the frugivorous Varecia rubra and the folivorous Propithecus coquereli. We found no overlap in Vb
between the species (all V. rubra ingested larger pieces of food relative to those eaten by P. coquereli), and least-squares regression of Vb
and three different measures of body mass showed no scaling relationship within each species. We believe that this lack of relationship results from the relatively narrow intraspecific body size variation and seemingly patternless individual variation in Vb
within species and take this study as further evidence that general scaling questions are best examined interspecifically rather than intraspecifically.
Heterogeneous Wireless Sensor Network for Transportation System Applications
Authors: Selvarajah K. , Shooter C. , Liotti L. , Tully A.
Published: May 2011

The important innovations in wireless and digital electronics will support many applications in the areas of safety, environmental and emissions control, driving assistance, diagnostics, and maintenance in the transport domain. The last few years have seen the emergence of many new technologies that can potentially have major impacts on transportation systems. One of these technologies is Wireless Sensor Networks. A wireless sensor device is typically composed of a processing unit, memory, and a radio chip which allows it to communicate wirelessly with other devices within range. The Embedded Middleware in Mobility Applications (EMMA) project delivers a middleware that aims to facilitate the interaction between sensing technologies in transportation systems. This paper outlines our experience in the EMMA project and provides an illustration of the important role that wireless sensor technology can play in future transportation system. The paper discusses our experience of using heterogeneous sensors to develop transportation system applications in the EMMA project and focuses on how cooperation between vehicle and infrastructure can be addressed. It also presents encouraging results obtained from the experiments in investigating the feasibility of utilising wireless sensor in vehicle and vehicle-to-infrastructure communication in real transportation applications.
Angiopoietin-2 TIEs Up Macrophages in Tumor Angiogenesis
Authors: De Palma Michele , Naldini Luigi
Published: May 2011

Angiopoietin-2 (ANG2), a ligand of the TIE2 receptor, modulates endothelial cell biology and destabilizes blood vessels to facilitate angiogenesis. Recent reports have shown that ANG2 inhibition, for example, by monoclonal antibodies, peptibodies, or CovX-Bodies, may achieve substantial antiangiogenic and antitumor responses in a variety of mouse tumor models, including spontaneous MMTV-PyMT mammary and RIP1-Tag2 pancreatic islet adenocarcinomas. There is also evidence that targeting the ANG2/TIE2 signaling pathway may inhibit the functions of TIE2-expressing macrophages (TEM), a tumor-associated macrophage subset endowed with proangiogenic activity in mouse tumor models. The clinical opportunities afforded by simultaneously targeting the effects of ANG2 on tumor angiogenesis and the proangiogenic activity of TEMs are discussed. Clin Cancer Res; 17(16); 5226–32. ©2011 AACR.
Sphingolipid Modulation of Angiogenic Factor Expression in Neuroblastoma
Authors: Li Mei-Hong , Hla Timothy , Ferrer Fernando
Published: May 2011

Metabolism of sphingolipids into downstream lipid mediators followed by signaling modulates tumor microenvironment and the cancer cells to influence tumor progression. As such, sphingolipid signaling represents a novel way to modulate tumor biology. Neuroblastoma (NB), the most common extracranial solid tumor of childhood, is highly angiogenic and often displays poor prognosis. However, the role of sphingolipid mediators is not known in NB. We found that NB expresses high levels of sphingosine kinase-2, which is essential for the formation of sphingosine-1-phosphate (S1P). S1P induced VEGF expression in SK-N-AS NB cells. The effect occurred at the transcriptional level. Hypoxia in combination with S1P had a synergistic effect on VEGF expression. Strong correlation was detected between S1P receptor-2 (S1P2) and VEGF mRNAs in 11 different cell lines and 17 NB tissues. Blockade of S1P2 with the selective antagonist JTE-013 significantly inhibited S1P-induced VEGF expression. Overexpression and knockdown of S1P2 in SK-N-AS cells increased or inhibited S1P-induced VEGF secretion, respectively. Interestingly, JTE-013 significantly inhibited tumor growth, VEGF mRNA expression, and induced apoptosis in the NB tumor xenografts. Taken together, our data suggest that enhanced formation of sphingolipid mediator S1P in NB profoundly influences tumor microenvironment by inducing VEGF expression via S1P2. Modulation of sphingolipid signaling by inhibiting S1P2 may constitute a novel strategy to control NB. Cancer Prev Res; 4(8); 1325–32. ©2011 AACR.
Influence of the Interaction between the Serotonin 1A Receptor C-1019G Polymorphism and Negative Life Stressors on the Development of Depression
Authors: Kim Ha Kyoung , Kim Seog Ju , Lee Yu Jin , Lee Heon-Jeong , Kang Seung-Gul , Choi Jung-Eun , Yun Kyu-Wol , Lim Weon-Jeong
Published: May 2011

The current study aimed to investigate the interaction between the serotonin 1A receptor gene (HTR1A) C-1019G polymorphism and recent negative life stressors on depression in a Korean community sample. The HTR1A C-1019G polymorphism was genotyped in 416 community-dwelling Koreans (156 males, 260 females; 44.37 ± 14.67 years old). Lifetime and current major depressive episodes were diagnosed using the Structured Clinical Interview for DSM-IV. The Center for Epidemiological Studies for Depression Scale (CES-D) was self-applied and face-to-face interviews investigating negative life stressors within the last 6 months were also performed. The results indicated that there were significant interactions between the C-1019G polymorphism and negative life stressors on CES-D scores (p = 0.02) as well as on current major depressive episodes (p = 0.002), but not on past major depressive episodes. G carriers alone had higher CES-D scores and more frequently experienced major depressive episodes after stressors. The interaction between the C-1019G polymorphism in HTR1A and recent negative life stressors accounted for current major depressive episodes and depressive symptoms. Our findings suggest that people with this gene variant may be more susceptible to developing depression especially after negative life stressors.
Maternal Immune Activation Impairs Reversal Learning and Increases Serum Tumor Necrosis Factor-α in Offspring
Authors: Han Xiao , Li Nanxin , Meng Qingxuan , Shao Feng , Wang Weiwen
Published: May 2011

Maternal immune activation (MIA) produces a variety of behavioral and brain abnormalities in rodent models of several neuropsychiatric disorders. However, it remains controversial whether MIA impairs reversal learning, a basic function of flexibility relevant to those diseases, in offspring. In the present study, we used the Morris water maze to investigate the effects of middle to late gestation stage poly(I:C) challenges on spatial learning and subsequent reversal learning performance in adolescent rats. Maternal poly(I:C) treatment induced deficits in reversal learning without affecting spatial acquisition abilities. In addition, the serum level of the proinflammatory cytokine tumor necrosis factor-α was increased in MIA rats. This study advances our understanding of how MIA affects adolescent behavior and brain function.
Impaired Ca2+ Regulation of CD4+CD25+ Regulatory T Cells from Pediatric Asthma
Authors: Yamamoto Yoshiki , Negoro Takaharu , Hoshi Akane , Wakagi Akiko , Shimizu Shunichi , Banham Alison H. , Ishii Masakazu , Akiyama Haruyo , Kiuchi Yuji , Sunaga Susumu , Tobe Takashi , Roncador Giovanna , Itabashi Kazuo , Nakano Yasuko
Published: May 2011

Background: CD4+CD25+ regulatory T (Treg) cells can control the allergic response to allergen, airway eosinophilia and airway hypersensitivity. We speculated that chronic inflammation persisting in asthma airways is dependent on abnormalities of these Treg cells. There are differences in the pathology of asthma in adults and children, and the airways of pediatric asthma are considered to be more naive than those of adults. Therefore, we analyzed the functionality of Treg cells in pediatric asthma and the relationship between Treg function and asthma symptoms. Methods: The anergic state, which is one of the defining properties of Treg, was analyzed by measuring intracellular Ca2+ influx following T cell receptor (TCR) stimulation. FOXP3-positive cells and FOXP3 mRNA expression were measured by flow analysis and real-time PCR with the SYBR method, respectively. Results: CD45RO+ cells make up approximately 99% of CD4+CD25high T cells and 89% of CD4+CD25low T cells in human adult blood. The proportion of CD45RO+ cells in CD4+CD25+ (high + low) T cells from pediatric asthma was much smaller (about 56%). Interestingly, our data indicated that CD45RO+ Treg cells from pediatric asthma aberrantly increased intracellular Ca2+ concentrations following TCR activation compared with pediatric nonasthma controls. Conclusion: These impaired CD45RO+ Treg cell functions were correlated with asthma symptoms. The correlation was observed in the group with a highly expressed atopic phenotype and longer duration of asthma. We suggest that chronic inflammation in pediatric asthma airways may be the result of impaired regulatory functions of CD45RO+ Treg cells.
Clinical and Laboratory Parameters of Mast Cell Activation as Basis for the Formulation of Diagnostic Criteria
Authors: Valent Peter , Horny Hans-Peter , Triggiani Massimo , Arock Michel
Published: May 2011

Mast cell (MC) activation occurs in a number of different pathologic conditions. Acute activation is commonly seen in patients with allergic reactions, with consecutive massive release of vasoactive and proinflammatory mediator substances from MCs, leading to the clinical signs and symptoms of anaphylaxis. In these patients, serum tryptase concentrations usually increase subtantially above baseline levels. Chronic MC activation is more difficult to diagnose, especially when symptoms are mild or atypical, and no underlying disease is found. In these patients, serum tryptase levels usually are normal. In a smaller group of patients, tryptase levels are constantly elevated and may point to an occult form of mastocytosis. These patients have to be examined for MC monoclonality, other criteria of a primary MC disease, non-MC hematopoietic neoplasms, and reactive disorders producing chronic MC activation or MC accumulation. In most patients in whom MC activation is found, histamine-induced symptoms can be documented and usually respond to treatment with histamine receptor antagonists or MC stabilizers. If this is not the case, alternative explanations for symptoms and differential diagnoses have to be considered.
Opipramol Improves Subjective Quality of Sleep the Night Prior to Surgery: Confirmatory Testing of a Double-Blind, Randomized Clinical Trial
Authors: Hueppe Michael , Hartge David , Stoll Klaus-Dieter , Ros Andrea , Schmucker Peter , Gerlach Klaus
Published: May 2011

Objective: Due to its pharmacological properties, opipramol may be useful in the context of evening premedication in anaesthesiology. This trial examines whether quality of sleep the night prior to surgery can be improved by opipramol and whether this effect is dose dependent. A second objective of this study is to examine whether the emotional state (in particular anxiety) is affected by opipramol. Method: 72 female patients were randomly assigned to 100 mg opipramol, 150 mg opipramol or placebo (24 patients per group) in a double-blind trial. Drug application was in the evening prior to an elective surgery. Effects were recorded the next morning by means of self-rating questionnaires regarding subjective sleep quality of the last night and patients’ current subjective state. The self-rating was done by use of the Wuerzburg Sleep Questionnaire, by use of mood inventories [BSKE (EWL) and STAI-X1] and by use of the Multidimensional Somatic Symptom List. Further dependent variables were heart rate and blood pressure. Confirmatory data analysis was conducted for subjective quality of sleep. Results: 100 mg opipramol as well as 150 mg opipramol significantly improved subjective quality of sleep (p < 0.001). The drug conditions did not differ in this effect. Opipramol marginally reduced anxiety (STAI-X1). The autonomic variables remained uninfluenced. There were no adverse events and no hints for interaction with anaesthesia. Conclusion: Opipramol may be used as a premedication in the evening prior to surgery if the primary target is an impact on the experienced quality of sleep. For this a single dosage of 100 mg opipramol is sufficient and can be recommended.
NCAM1, TACR1 and NOS Genes and Temperament: A Study on Suicide Attempters and Controls
Authors: Giegling Ina , Calati Raffaella , Porcelli Stefano , Hartmann Annette M. , Möller Hans-Jürgen , De Ronchi Diana , Rujescu Dan , Serretti Alessandro
Published: May 2011

Suicide, one of the leading causes of death among young adults, seems to be plausibly modulated by both genetic and personality factors. The aim of this study was to dissect the potential association between genetics and temperament in a sample of 111 suicide attempters and 289 healthy controls. We focused on 4 genes previously investigated in association with suicide on the same sample: the nitric oxide synthase 1 and 3 (NOS1 and NOS3), the neuronal cell adhesion molecule 1 (NCAM1), and the tachykinin receptor 1 (TACR1) genes. In particular, we investigated whether a set of genetic variants in these genes (NOS1: rs2682826, rs1353939, rs693534; NOS3: rs2070744, rs1799983, rs891512; NCAM1: rs2301228, rs1884, rs1245113, rs1369816, rs2196456, rs584427; TACR1: rs3771810, rs3771825, rs726506, rs1477157) were associated with temperamental traits at the Temperament and Character Inventory (TCI). No strong evidence was found for the association between TCI personality traits and the polymorphisms considered in the 4 genes, with the exception of an association between reward dependence trait and the rs2682826 SNP in NOS1 in the healthy sample. However, this result could be plausibly interpreted as a false-positive finding. In conclusion, our study did not support the thesis of a direct modulation of these genes on temperament; however, further studies on larger samples are clearly required in order to confirm our preliminary findings and to exclude any possible minor influence.
Sexually Dimorphic Neural Phenotypes in Golden-Collared Manakins (Manacus vitellinus)
Authors: Day Lainy B. , Fusani Leonida , Kim Carol , Schlinger Barney A.
Published: May 2011

Male golden-collared manakins (Manacus vitellinus) perform a high-speed acrobatic courtship display punctuated by loud ‘snaps’ produced by the wings. Females join males on display courts to select individuals for copulation; females follow displaying males but do not perform acrobatics or make wing snaps. Sexually dimorphic courtship displays such as those performed by manakins are the result of intense sexual selection and suggest that differences between sexes exist at neural levels as well. We examined sex differences in the volume of brain areas that might be involved in the male manakin courtship display and in the female assessment of this display. We found that males had a larger hippocampus (HP, spatial learning) and arcopallium (AP, motor and limbic areas) than females when adjusted for the size of the telencephalon (TELE) minus the target area. Females had a larger ventrolateral mesopallium (MVL) both when adjusting for the size of the remaining TELE and by direct comparison. The entopallium (E) was not sexually dimorphic. The E is part of the avian tectofugal pathway and the MVL is linked to this pathway by reciprocal connections. The MVL likely modulates visually guided behavior via descending brainstem pathways. We found no sex differences in the volume of the cerebellum or cerebellar nuclei. We speculate that the HP is important to males for cross-season site fidelity and for local spatial memory, the AP for sexually driven motor patterns that are complex in males, and that the MVL facilitates female visual processing in selecting male display traits. These results are consistent with the idea that sexual selection has acted to select sex-specific behaviors in manakins that have neural correlates in the brain.
Activation of KCNQ2/3 Potassium Channels by Novel Pyrazolo[1,5-a]pyrimidin-7(4H)-One Derivatives
Authors: Jia Caixia , Qi Jinlong , Zhang Fan , Mi Yi , Zhang Xuan , Chen Xingjuan , Liu Li , Du Xiaona , Zhang Hailin
Published: May 2011

The voltage-gated M-type potassium channel, encoded mainly by the KCNQ2/3 genes, plays an important role in the control of neuronal excitability. Mutations in the KCNQ2 gene lead to a form of neonatal epilepsy in humans termed ‘benign familial neonatal convulsions’, which is characterized by hyperexcitability of neurons. KCNQ openers or activators are expected to decrease the firing of overactive neurons and are thus conducive to the treatment of epilepsy and pain. Here, we report that four novel synthesized derivatives of pyrazolo[1,5-a]pyrimidin-7(4H)-one (PPO) named QO-26, QO-28, QO-40 and QO-41 potently augmented KCNQ2/3 channels expressed in Chinese hamster ovary cells and shifted the half-maximal activation voltage (V1/2) in the hyperpolarizing direction. The V1/2 was negatively shifted in a concentration-dependent manner. The compounds markedly slowed both KCNQ2/3 channel activation and deactivation kinetics. Structure-activity relationship studies suggest that trifluoromethyl at the C-2 position, phenyl or naphthyl at the C-3 position, and trifluoromethyl or chloromethyl at the C-5 position are essential for the activity. These results suggest the four PPO derivatives act as KCNQ2/3 channel openers, providing a new dimension for the design and development of more potent channel openers.
Assessment of the Quality of Secondary Ischemic Stroke Prevention in Selected Urban Areas of Poland and Ukraine: The ASCEP Study Results
Authors: Chwojnicki K. , Yagensky A. , Wierucki L. , Sichkaruk I. , Sydor N. , Nyka W.M. , Wyrzykowski B. , Zdrojewski T.
Published: May 2011

The aim of this study was to assess the quality of secondary ischemic stroke (IS) prevention among subjects after IS from selected urban areas of Poland (Gdynia, G) and Ukraine (Lutsk, L). Methods: The study was conducted on representative samples of post-IS patients from G and L who suffered from IS in the years 2000–2005. A questionnaire, anthropometric and blood pressure (BP) measurements and laboratory tests were performed. Results: The data of 440 patients were collected. Only 47% in G and 58% in L (p < 0.05) had visited a neurologist within 6 months before the interview. Results of the prevalence and control of consecutive IS risk factors were estimated: (1) arterial hypertension (prevalence: 88% G, 92% L, p = 0.1; BP <140/90 mm Hg: 23% G, 16% L, p = 0.02); (2) hypercholesterolemia (prevalence: 90% G, 76% L, p < 0.05; total cholesterol <175 mg/dl: 11% G, 6% L, p = 0.05); (3) self-reported diabetes or glycemia >125 mg/dl: 22% G, 17% L, p = 0.08; (4) smoking: 26% men versus 16% women in G, 33% men versus 2% women in L, p < 0.05, and (5) self-reported atrial fibrillation: 28% G, 7% L, p < 0.05. Antiplatelet drugs or oral anticoagulants were taken by 51% G versus 45.5% L (not significant). Conclusions: The quality of secondary IS prevention is insufficient, and there is a need for complex educational interventions in patients, their families and medical staff. Our data also call for organizational changes in the health service both in Poland and Ukraine.
Critical Evaluation of the Use of Extinction Paradigms for the Assessment of Opioid-Induced Conditioned Place Preference in Rats
Authors: Rutten Kris , van der Kam Elizabeth L. , De Vry Jean , Tzschentke Thomas M.
Published: May 2011

The rewarding effects of drugs of abuse are often studied by means of the conditioned place preference (CPP) paradigm. CPP is one of the most widely used models in behavioral pharmacology, yet its theoretical underpinnings are not well understood, and there are very few studies on the methodological and theoretical aspects of this model. An important drawback of the classical CPP paradigm is that it often does not show dose-dependent results. The persistence of the conditioned response, i.e. the time required until the CPP effect is extinct, may be related to the strength of conditioning, which in turn may be related to the rewarding efficacy of a drug. Resistance to extinction may therefore be a useful additional measure to quantify the rewarding effect of drugs. In the present study we examined the persistence of drug-environment associations after conditioning with morphine (1, 3 and 10 mg/kg i.p.), oxycodone (0.3, 1 and 3 mg/kg i.p.) and heroin (0.05, 0.25 and 0.5 mg/kg i.p.) by repeated retesting in the CPP apparatus (15-min sessions, 5 days/week) until the rats reached extinction (i.e. less than 55% preference over 3 consecutive sessions). Following an unbiased CPP protocol, morphine, oxycodone and heroin induced CPP with minimal effective doses of 3, 1 and 0.25 mg/kg, respectively, and with similar effect sizes for each CPP-inducing dose. The number of sessions required for extinction was positively correlated with the dose of the drug (experiment 1: 18 and 45 sessions for 3 and 10 mg/kg morphine, and 19 and 27 sessions for 1 and 3 mg/kg oxycodone; experiment 2: 12 and 24 sessions for 3 and 10 mg/kg morphine, and 10 and 14 sessions for 0.25 and 0.5 mg/kg heroin). These findings suggest that the use of an extinction paradigm can extend the quantitative assessment of the rewarding effect of drugs – however, within certain limits only. The present paradigm appears to be less suited for comparing the rewarding efficacy of different drugs due to great test-retest variability. Finally, the additional potential gain of information using this paradigm has to be weighed against the considerably large amount of additional time and effort.
Advantages and Pitfalls of Three-Dimensional Ultrasound Imaging of Carotid Bifurcation
Authors: Vicenzini E. , Galloni L. , Ricciardi M.C. , Pro S. , Sirimarco G. , Pulitano P. , Mecarelli O. , Di Piero V. , Lenzi G.L.
Published: May 2011

Objectives: Several specialists use three-dimensional (3D) ultrasound as adjuvant imaging technique in their clinical practice. It has been applied to study carotid plaque morphology, surface and volume during atherosclerosis progression. Nonetheless, no papers have so far described the use of this technique in conditions different than carotid stenosis, such as bifurcation anatomy changes of the caliber and vessel course modifications. Methods: Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. Results: Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinking) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. Conclusions: 3D ultrasound is a feasible technique. It can improve carotid axis imaging through a better presentation of caliber variations and vessel course ‘at a glance’. 3D ultrasound from the inward flow can provide imaging of the stenosis, but stenosis quantification should always take into account the assessment of plaque morphology and vessel wall.
Progression-Free Survival in Ovarian Cancer Is Reflected in Epigenetic DNA Methylation Profiles
Authors: Bauerschlag Dirk O. , Ammerpohl Ole , Bräutigam Karen , Schem Christian , Lin Qiong , Weigel Marion T. , Hilpert Felix , Arnold Norbert , Maass Nicolai , Meinhold-Heerlein Ivo , Wagner Wolfgang
Published: May 2011

Objective: Many patients with ovarian cancer disease relapse within 6 months after adjuvant chemotherapy, with a limited prognosis. Epigenetic modifications have been shown to play an important role in tumor development and formation. Therefore, global analysis of DNA methylation patterns might reveal specific CpG sites that correlate with progression-free interval (PFI) after therapy. Methods: Twenty samples of advanced ovarian cancer with a predominantly serous papillary histological subtype were subjected to DNA methylation profiling. Illumina HumanMethylation27 BeadChip technology was used for simultaneous analysis of 27,578 CpG sites in >14,000 genes. Results: Differential DNA methylation of various cytosines correlated with PFI. However, this becomes only significant by classification according to PFI with a cutoff of >28 months. Longer survival was associated with hypomethylation at specific CpG sites (e.g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e.g. TMCO5, PTPRN and GUCY2C). Gene ontology analysis revealed that differentially methylated genes were significantly overrepresented in the categories telomere organization, mesoderm development and immune regulation. Conclusion: Epigenetic modifications at specific CpG sites correlate with PFI in ovarian cancer. Therefore, such analysis might be of prognostic value.