bluuebunny/crossref_metadata_2025 huggingface dataset:
Decrease in phosphatidylinositol 4,5‐bisphosphate levels mediates desensitization of the cold sensor TRPM8 channels
Authors: Yudin Yevgen , Lukacs Viktor , Cao Chike , Rohacs Tibor
Published: October 2011

Non‐technical summary  The transient receptor potential melastatin 8 (TRPM8) ion channel is a physiological sensor of environmental cold temperatures. This channel is also activated by menthol, which is responsible for the cooling sensation evoked by this compound. It is well known that we adapt to moderately cold temperatures, i.e. the same temperature feels less cold over time, and the cooling effects of menthol also wear off with time, presumably due to the calcium‐dependent desensitization of TRPM8 activity. The membrane phospholipid phosphatidylinositol 4,5‐bisphosphate (PIP2) is known to be required for TRPM8 activity. Our data support a model for desensitization, in which calcium influx through TRPM8 activates a phospholipase C enzyme, which breaks down PIP2, leading to decreased channel activity.
A Markov Perspective on Development Interdependencies in Networks of Systems
Authors: Mane Muharrem , DeLaurentis Daniel , Frazho Arthur
Published: October 2011

The development and acquisition of complex systems remain a challenge, especially in the aerospace/defense sector, due to complexities in both program management and engineering design that often are a result of interdependencies. The interdependencies between constituent systems form networks that, while enabling capabilities that are beyond those of individual systems, also increase risk since disruptions in the development of one system may propagate to other directly or indirectly dependent systems. This paper demonstrates an approach to aggregate the network interdependency characteristics and compare alternatives with respect to the time required to arrest the propagation of development delays in a network. Delay propagation is modeled as a Markov chain, where the states are defined as the constituent systems and the transition probabilities as the dependency strengths between systems. A proof-of-concept application shows the approach can distinguish between alternate networks and indicates its applicability for managing risk in design and development of systems with significant interdependencies.
Fabrication of nanogaps by a progressive electromigration technique using wires of various thicknesses
Authors: Saha Swatilekha , Qian Guoguang , Lewis Kim M.
Published: October 2011

The authors report the fabrication of nanogaps formed by electromigration from gold wires of various widths (25–80 nm). This technique is a reliable and consistent method to create quality gaps without the need of very thin gold wires. The gaps are fabricated at room temperature and ambient atmosphere in contrast to the method of performing electromigration at liquid helium temperatures and in high vacuum environments. The authors observed that every nanogap formed using this technique was free of residual particles left over from the electromigration process.
La0.6Sr0.4Fe0.6Co0.2Cu0.2O3-δ Powders by XPS
Authors: Natile Marta Maria , Poletto Fabio , Galenda Alessandro , Glisenti Antonella
Published: October 2011

In recent years, the growing interest in hydrogen energy has caused particularly large demand for catalysts used in the production of hydrogen and hydrogen-containing gases by the conversion of natural hydrocarbons. Perovskite oxides having the general formula of ABO3, where B usually designates a transition metal cation surrounded by six oxygen ions in octahedral coordination, and A is a cation of rare-earth metal coordinated by 12 oxygen ions are very promising for this application. The present work focuses on the XPS analysis of a new perovskite material: La0.6Sr0.4Fe0.6Co0.2Cu0.2O3-δ powder. This powder was obtained by citrate gel process. The surface proprieties are investigated by means of XPS. Besides the wide scan spectrum, detailed spectra for the La 3d, Sr 3d, Fe 2p, Co 2p, Cu 2p, Cu LMM, O 1s and C 1s regions and related data are presented and discussed.
Determination of surface tension from the measurement of internal pressure of mini soap bubbles
Authors: Behroozi F. , Behroozi P. S.
Published: October 2011

We review the elementary theory that gives the internal pressure of a soap bubble in terms of its radius and surface tension. The theory is generalized to relate the pressure difference across any element of a soap film to its local curvature. This result is used to introduce the concept of the mean curvature of a surface element and is applied to a double soap bubble to obtain the relation between the three radii that characterize its geometry. We also describe a simple setup, suitable for the undergraduate laboratory, to produce mini bubbles and to obtain the surface tension of the soap solution by measuring the radius and internal pressure of the bubbles.
Poynting vector flow in a circular circuit
Authors: S. Davis Basil , Kaplan Lev
Published: October 2011

A circuit is considered in the shape of a ring, with a battery of negligible size and a wire of uniform resistance. A linear charge distribution along the wire maintains an electrostatic field and a steady current, which produces a constant magnetic field. Earlier studies of the Poynting vector and the rate of flow of energy considered only idealized geometries in which the Poynting vector was confined to the space within the circuit. But in more realistic cases, the Poynting vector is nonzero outside as well as inside the circuit. An expression is obtained for the Poynting vector in terms of products of integrals, which are evaluated numerically to show the energy flow. Limiting expressions are obtained analytically. It is shown that the total power generated by the battery equals the energy flowing into the wire per unit time
Resistance Analysis and Characterization of a Thiazole Analogue, BP008, as a Potent Hepatitis C Virus NS5A Inhibitor
Authors: Lin Hui-Mei , Wang Jing-Chyi , Hu Han-Shu , Wu Pei-Shan , Yang Chi-Chen , Wu Chung-Pu , Pu Szu-Yuan , Hsu Tsu-An , Jiaang Weir-Torn , Chao Yu-Sheng , Chern Jyh-Haur , Yeh Teng-Kuang , Yueh Andrew
Published: October 2011

Hepatitis C virus (HCV) is a global health problem, affecting approximately 3% of the world's population. The standard treatment for HCV infection is often poorly tolerated and ineffective. Therefore, the development of novel or more effective treatment strategies to treat chronic HCV infection is urgently needed. In this report, BP008, a potent small-molecule inhibitor of HCV replication, was developed from a class of compounds with thiazol core structures by means of utilizing a cell-based HCV replicon system. The compound reduced the reporter expression of the HCV1b replicon with a 50% effective concentration (EC50) and selective index value of 4.1 ± 0.7 nM and >12,195, respectively. Sequencing analyses of several individual clones derived from BP008-resistant RNAs purified from cells harboring HCV1b replicon revealed that amino acid substitutions mainly within the N-terminal region (domain I) of NS5A were associated with decreased inhibitor susceptibility. Q24L, P58S, and Y93H are the key substitutions for resistance selection; F149L and V153M play the compensatory role in the replication and drug resistance processes. Moreover, BP008 displayed synergistic effects with alpha interferon (IFN-α), NS3 protease inhibitor, and NS5B polymerase inhibitor, as well as good oral bioavailability in SD rats and favorable exposure in rat liver. In summary, our results pointed to an effective small-molecule inhibitor, BP008, that potentially targets HCV NS5A. BP008 can be considered a part of a more effective therapeutic strategy for HCV in the future.
Nosocomial Outbreak of VIM-1-Producing Klebsiella pneumoniae Isolates of Multilocus Sequence Type 15: Molecular Basis, Clinical Risk Factors, and Outcome
Authors: Sánchez-Romero Isabel , Asensio Ángel , Oteo Jesús , Muñoz-Algarra María , Isidoro Beatriz , Vindel Ana , Álvarez-Avello José , Balandín-Moreno Bárbara , Cuevas Oscar , Fernández-Romero Sara , Azañedo Luisa , Sáez David , Campos José
Published: October 2011

We study the epidemiology, molecular basis, clinical risk factors, and outcome involved in the clonal dissemination of VIM-1-producing
Klebsiella pneumoniae
isolates in the hospital setting. All patients infected/colonized by carbapenem-nonsusceptible
K. pneumoniae
(CNSKP) in 2009 were included. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Antibiotic resistance genes were analyzed by PCR and sequencing. Plasmids were studied by PFGE with S1 nuclease digestion and for incompatibility group by a PCR-based replicon typing scheme. Risk factors associated with CNSKP colonization/infection were assessed by an observational case-control study. All 55 patients studied were infected (
n
= 28) or colonized (
n
= 27) by VIM-1-producing
K. pneumoniae
. All but one acquired isolates of a single clone (PFGE cluster 1 [C1], sequence type 15 [ST15]), while another clone (PFGE C2, ST340) was detected in four patients. C1 isolates also produced the new extended-spectrum β-lactamase SHV-134.
bla
VIM-1
was carried in a class 1 integron and an untypeable plasmid of ∼50 bp. The number of days that the patient received mechanical ventilation, the use of parenteral nutrition, previous treatment with linezolid, and treatment with extended-spectrum cephalosporins for more than 7 days were detected to be independent risk factors for CNSKP acquisition. The VIM-1-producing
K. pneumoniae
ST15 clone has a high capacity to spread among intensive care unit patients with severe underlying conditions. A high rate of associated mortality and great difficulty in controlling the spread of this clone, without permanent behavioral changes in the personnel, were observed.
A nationwide prospective cohort study on return to gainful occupation after stroke in Denmark 1996–2006
Authors: Hannerz Harald , Holbæk Pedersen Betina , Poulsen Otto M , Humle Frank , Andersen Lars L
Published: October 2011

Background

Return to work is an important outcome factor for working-age patients poststroke. Previous epidemiological studies on this topic have been small (on average 125 patients per study). Their estimated effects are therefore associated with a tremendous statistical uncertainty. The present study estimates the effect of various predictors on the odds of returning to work after stroke in the total population of 20–57-year-old previously employed hospital treated patients with stroke in Denmark 1996–2006 (N=19 985).

Methods and results

The patients were followed through national registers; 62% were gainfully occupied 2 years after stroke. The odds of returning to work were higher among people with intracerebral infarction, OR 1.0 (the reference group), than they were among people with subarachnoid haemorrhage, OR 0.79 (95% CI 0.71 to 0.88), and intracerebral haemorrhage, OR 0.39 (0.35 to 0.43). The odds of returning to work were lower among workers in elementary occupations OR 1.0 (reference group) than they were among workers in occupations that require skills at a basic level, OR 1.50 (1.38 to 1.64), technicians and associate professionals, OR 2.33 (2.05 to 2.65) and professionals, OR 3.04 (2.70 to 3.43). Patients in municipalities with a brain-injury rehabilitation centre did not have a better prognosis than patients in other municipalities, OR 0.91 (0.78 to 1.06). Being a woman, OR 0.79 (0.74 to 0.84), self-employed, OR 0.87 (0.78 to 0.96), or ≥50 years, OR 0.61 (0.57 to 0.65), was associated with an adverse prognosis.

Conclusion

Further research is needed to explain the gender inequality, which suggests either a potential to improve return-to-work rates among the females or a tendency among the males to return too early.
Factors that affect software systems development project outcomes
Authors: McLeod Laurie , MacDonell Stephen G.
Published: October 2011

Determining the factors that have an influence on software systems development and deployment project outcomes has been the focus of extensive and ongoing research for more than 30 years. We provide here a survey of the research literature that has addressed this topic in the period 1996–2006, with a particular focus on empirical analyses. On the basis of this survey we present a new classification framework that represents an abstracted and synthesized view of the types of factors that have been asserted as influencing project outcomes.
XML data clustering
Authors: Algergawy Alsayed , Mesiti Marco , Nayak Richi , Saake Gunter
Published: October 2011

In the last few years we have observed a proliferation of approaches for clustering XML documents and schemas based on their structure and content. The presence of such a huge amount of approaches is due to the different applications requiring the clustering of XML data. These applications need data in the form of similar contents, tags, paths, structures, and semantics. In this article, we first outline the application contexts in which clustering is useful, then we survey approaches so far proposed relying on the abstract representation of data (instances or schema), on the identified similarity measure, and on the clustering algorithm. In this presentation, we aim to draw a taxonomy in which the current approaches can be classified and compared. We aim at introducing an integrated view that is useful when comparing XML data clustering approaches, when developing a new clustering algorithm, and when implementing an XML clustering component. Finally, the article moves into the description of future trends and research issues that still need to be faced.
Geometric distortion measurement for shape coding
Authors: Sohel Ferdous A. , Karmakar Gour C. , Dooley Laurence S. , Bennamoun Mohammed
Published: October 2011

Geometric distortion measurement and the associated metrics involved are integral to the Rate Distortion (RD) shape coding framework, with importantly the efficacy of the metrics being strongly influenced by the underlying measurement strategy. This has been the catalyst for many different techniques with this article presenting a comprehensive review of geometric distortion measurement, the diverse metrics applied, and their impact on shape coding. The respective performance of these measuring strategies is analyzed from both a RD and complexity perspective, with a recent distortion measurement technique based on arc-length-parameterization being comparatively evaluated. Some contemporary research challenges are also investigated, including schemes to effectively quantify shape deformation.
Progress in autonomous fault recovery of field programmable gate arrays
Authors: Parris Matthew G. , Sharma Carthik A. , Demara Ronald F.
Published: October 2011

The capabilities of current fault-handling techniques for Field Programmable Gate Arrays (FPGAs) develop a descriptive classification ranging from simple passive techniques to robust dynamic methods. Fault-handling methods not requiring modification of the FPGA device architecture or user intervention to recover from faults are examined and evaluated against overhead-based and sustainability-based performance metrics such as additional resource requirements, throughput reduction, fault capacity, and fault coverage. This classification alongside these performance metrics forms a standard for confident comparisons.
Coverage problems in sensor networks
Authors: Wang Bang
Published: October 2011

Sensor networks, which consist of sensor nodes each capable of sensing environment and transmitting data, have lots of applications in battlefield surveillance, environmental monitoring, industrial diagnostics, etc. Coverage which is one of the most important performance metrics for sensor networks reflects how well a sensor field is monitored. Individual sensor coverage models are dependent on the sensing functions of different types of sensors, while network-wide sensing coverage is a collective performance measure for geographically distributed sensor nodes. This article surveys research progress made to address various coverage problems in sensor networks. We first provide discussions on sensor coverage models and design issues. The coverage problems in sensor networks can be classified into three categories according to the subject to be covered. We state the basic coverage problems in each category, and review representative solution approaches in the literature. We also provide comments and discussions on some extensions and variants of these basic coverage problems.
Hybrid analytical modeling of pending cache hits, data prefetching, and MSHRs
Authors: Chen Xi E. , Aamodt Tor M.
Published: October 2011

This article proposes techniques to predict the performance impact of pending cache hits, hardware prefetching, and miss status holding register resources on superscalar microprocessors using hybrid analytical models. The proposed models focus on timeliness of pending hits and prefetches and account for a limited number of MSHRs. They improve modeling accuracy of pending hits by 3.9× and when modeling data prefetching, a limited number of MSHRs, or both, these techniques result in average errors of 9.5% to 17.8%. The impact of non-uniform DRAM memory latency is shown to be approximated well by using a moving average of memory access latency.
Vague regions in Geographic Information Retrieval
Authors: Schockaert Steven
Published: October 2011

Vagueness abounds in natural language descriptions of geographical space. We frequently refer to place names for which no universally agreed boundaries exist (e.g. the Alps, Central London, Southern Europe) and describe spatial configurations using phrases that cannot indisputably be translated to hard constraints (e.g. within walking distance, north of, adjacent to).
Challenges for indexing in GIR
Authors: Leveling Johannes
Published: October 2011

Geographic information retrieval (GIR) has been evaluated in campaigns such as GeoCLEF, GikiP, and GikiCLEF [8, 12, 11]. Surprisingly, most results from these evaluations showed that adding more geographic knowledge typically had little or no effect on performance of GIR systems or that it even decreases performance compared to traditional (textual) information retrieval baselines (see e.g. [4]). In this position paper, current challenges of how to further improve the creation, structure and access to geographic resources (for simplicity, called the geographic index in the rest of this note) are discussed. The major challenges for indexing in GIR discussed in this note are applying methods beyond named entity recognition to identify geographic references, integrating additional, proven methods from related research areas such as question answering for semantic indexing, and aiming for better index support to interpret geographic relations. After summarizing the state of the art in indexing for GIR as it has evolved from GIR evaluation campaigns, research challenges and directions for future research are presented.
Evaluating GIR
Authors: Mandl Thomas
Published: October 2011

Geographic terms appear very often in user queries. Many geographic references are present in query log-files. Examples found in different log files [6] include question answering style queries such as "What time is it in
West Samoa
?", terms within book titles like "Death in
Venice
", detailed street addresses and single term city names.
Geographic information from georeferenced social media data
Authors: Naaman Mor
Published: October 2011

In the last few years, we are witnessing an emerging class of communication and information platforms some call social awareness streams (SAS) [15]. Available from social media services such as Facebook, Twitter, FourSquare, Flickr, and others, these hugely popular platforms allow participants to post streams of lightweight content items, from short status messages to links, pictures, and videos, in a highly connected social environment. Many of these items are associated with location coordinates in the form of latitude and longitude, or with a business or venue that is in turn associated with a precise location. The number of "geotagged" items is likely to grow with the number of people using geo-enabled devices to access and produce SAS data. The vast amounts of SAS data offer unique opportunities for understanding local communities and people's attitudes, attention, and interest in them. Robust methods for learning from SAS data about geographies and local communities, using methods from Artificial Intelligence, Information Retrieval and Natural Language Processing, can greatly improve the state of geographic information retrieval. Such contributions, from better modelling of geographic areas, to improved knowledge about these areas and how they are used by individuals and communities, have begun to surface in the last few years, and are summarized in this article. The structure of this work borrows from Lynch [13], who referred to five elements that make up an individual's perception of city: districts, landmarks, paths, nodes, and edges. This article borrows from Lynch in the context of social media and SAS, proposing the four elements that make up the geographic information that can be derived from social media about a city or area: districts, landmarks, paths, and activities. This article presents a simple model for geographic SAS data, and then considers the four social media elements, or main types of applications of SAS data to geographic information systems. These applications include boundary definition and detection (district); computation of attractions (landmarks); derivation and recommendation of paths; and evaluation of activities, interests and temporal trends.
Your mileage may vary
Authors: Murdock Vanessa
Published: October 2011

We lead a double life. We have relationships that enrich our lives, events we participate in, and places we go that become a part of who we are. We also have online friendships, which enrich our lives and make up part of who we are. There are points of intersection between our two lives: events we arrange online that take place offline, places that we have been (offline) that we photograph, tag, and share with our online social community. The amount of data being generated by people online, who share information about their offline lives, is unprecedented and growing. We are a lucky few. We are the "technorati": the people who have access to technology, and the knowledge to use it. We are wealthy, well-travelled, well-educated, and proud owners of a plethora of gadgets that allow us to weave a seamless tapestry between our online and offline lives. We are not most people. The data we generate does not represent most people.
The dimensions of context and its role in mobile information retrieval
Authors: Mountain David
Published: October 2011

Mobile information retrieval is a sub discipline that has been the focus of much research over the last 10-15 years. Drivers of this interest include the emergence of enabling technology, particularly position determining hardware and mobile communications. A second driver has been the increased availability of georeferenced information objects, including points of interest databases and conventions for adding geographic information to documents in a structured way using mark-up languages such as GML, KML, GeoRSS and GeoJSON. In many cases this associated geographic information is a simplistic spatial representation (such as a point), but increasingly commercial implementations are giving consideration to both an object's physical location and its sphere of influence: Google Places, for example. Such georeferenced information objects have the capacity to satisfy the diverse "where", "what" and "when" aspects of queries. As well as the development of enabling technology, there has been widespread acceptance that whilst information needs are ubiquitous, so long as information searches can only be conducted in a small number of static settings, then needs will frequently go unsatisfied [1].
Primary Malignant Fibrous Histiocytoma: A Rare Case
Authors: Katsourakis Anastasios , Noussios George , Hadjis Iosif , Evangelou Neofitos , Chatzitheoklitos Efthimios
Published: October 2011

Malignant fibrous histiocytoma (MFH) of the small intestine is an extremely rare condition. It occurs most commonly in the extremities and the trunk. We report a case of a 67-year-old woman who admitted with fever, myalgia, and altered status. After thorough investigation, a tumor of the jejunum was found. The patient underwent complete surgical removal of the tumor. A diagnosis of MFN (undifferentiated high-grade pleomorphic sarcoma) was made. The patient received adjuvant chemotherapy with Gemcitabine. Two years after the operation, the patient died due to recurrence of the disease. MFH of the small intestine is an extremely rare neoplasm with an aggressive biological behaviour. In this paper, pathogenesis, natural history, and treatment are reviewed.
Constructing Dynamic Multiple‐Input Multiple‐Output Logic Gates
Authors: Peng Haipeng , Hu Gang , Li Lixiang , Yang Yixian , Xiao Jinghua
Published: October 2011

Investigation of computing devices with dynamic architecture which makes devices
have reconfigurable ability is an interesting research direction for designing the next
generation of computer chip. In this paper, we present a window threshold method to
construct such dynamic logic architecture. Here, dynamic multiple‐input multiple‐output (MIMO) logic gates are proposed, analyzed, and implemented. By using a
curve‐intersections‐based graphic method, we illustrate the relationships among the
threshold, the control parameter, and the functions of logic gates. A noise analysis
on all the parameters is also given. The chips based on the proposed schemes can
be transformed into different arrangements of logic gates within a single clock cycle.
With these schemes in hand, it is conceivable to build more flexible, robust, cost
effective, yet general‐purpose computing devices.
On Second‐Order Duality for Minimax Fractional Programming Problems with Generalized Convexity
Authors: Ahmad Izhar
Published: October 2011

We focus our study on a discussion of duality relationships of a minimax fractional programming problem with its two types of second‐order dual models under the second‐order generalized convexity type assumptions. Results obtained in this paper naturally unify and extend some previously known results on minimax fractional programming in the literature.
Mixed-Effects Tobit Joint Models for Longitudinal Data with Skewness, Detection Limits, and Measurement Errors
Authors: Dagne Getachew A. , Huang Yangxin
Published: October 2011

Complex longitudinal data are commonly analyzed using nonlinear mixed-effects (NLME) models with a normal distribution. However, a departure from normality may lead to invalid inference and unreasonable parameter estimates. Some covariates may be measured with substantial errors, and the response observations may also be subjected to left-censoring due to a detection limit. Inferential procedures can be complicated dramatically when such data with asymmetric characteristics, left censoring, and measurement errors are analyzed. There is relatively little work concerning all of the three features simultaneously. In this paper, we jointly investigate a skew-tNLME Tobit model for response (with left censoring) process and a skew-tnonparametric mixed-effects model for covariate (with measurement errors) process under a Bayesian framework. A real data example is used to illustrate the proposed methods.
Do Motion Controllers Make Action Video Games Less Sedentary? A Randomized Experiment
Authors: Lyons Elizabeth J. , Tate Deborah F. , Ward Dianne S. , Ribisl Kurt M. , Bowling J. Michael , Kalyanaraman Sriram
Published: October 2011

Sports- and fitness-themed video games using motion controllers have been found to produce physical activity. It is possible that motion controllers may also enhance energy expenditure when applied to more sedentary games such as action games. Young adults (N= 100) were randomized to play three games using either motion-based or traditional controllers. No main effect was found for controller or game pair (P> .12). An interaction was found such that in one pair, motion control (mean [SD] 0.96 [0.20] kcal ⋅ kg-1⋅ hr-1) produced 0.10 kcal ⋅ kg-1⋅ hr-1(95% confidence interval 0.03 to 0.17) greater energy expenditure than traditional control (0.86 [0.17] kcal ⋅ kg-1⋅ hr-1,P= .048). All games were sedentary. As currently implemented, motion control is unlikely to produce moderate intensity physical activity in action games. However, some games produce small but significant increases in energy expenditure, which may benefit health by decreasing sedentary behavior.
Hypoxia Induces Escape from Innate Immunity in Cancer Cells via Increased Expression of ADAM10: Role of Nitric Oxide
Authors: Barsoum Ivraym B. , Hamilton Thomas K. , Li Xin , Cotechini Tiziana , Miles Ellen A. , Siemens D. Robert , Graham Charles H.
Published: October 2011

One key to malignant progression is the acquired ability of tumor cells to escape immune-mediated lysis. Whereas tumor hypoxia is known to play a causal role in cancer metastasis and resistance to therapy, the link between hypoxia and immune escape in cancer remains poorly understood. Here, we show that hypoxia induces tumor cell resistance to lysis mediated by immune effectors and that this resistance to lysis occurs via a hypoxia-inducible factor-1 (HIF-1)–dependent pathway linked to increased expression of the metalloproteinase ADAM10. This enzyme is required for the hypoxia-induced shedding of MHC class I chain–related molecule A (MICA), a ligand that triggers the cytolytic action of immune effectors, from the surface of tumor cells. Indeed, our findings show a mechanistic link between hypoxia-induced accumulation of the α-subunit of HIF-1 (HIF-1α), increased expression of ADAM10, and decreased surface MICA levels leading to tumor cell resistance to lysis mediated by innate immune effectors. Nitric oxide mimetic agents interfered with the hypoxia-induced accumulation of HIF-1α and with the hypoxia-induced upregulation of ADAM10 expression required for decreased surface MICA expression and resistance to lysis. Furthermore, treatment of tumor-bearing mice with nitroglycerin, a nitric oxide mimetic, attenuated tumor growth by a mechanism that relied upon innate immune effector cells. Together, these findings reveal a novel mechanism by which the hypoxic tumor microenvironment contributes to immune escape in cancer, lending support to potential immunotherapeutic strategies involving the use of nitric oxide mimetics. Cancer Res; 71(24); 7433–41. ©2011 AACR.
Temporal and Spatial Cooperation of Snail1 and Twist1 during Epithelial–Mesenchymal Transition Predicts for Human Breast Cancer Recurrence
Authors: Tran David D. , Corsa Callie Ann S. , Biswas Hirak , Aft Rebecca L. , Longmore Gregory D.
Published: October 2011

Epithelial–mesenchymal transition (EMT) is a normal developmental program that is considered to also play an important role in cancer metastasis. Ultimate inducers of EMT are transcriptional repressors that individually can induce experimental EMT, yet in many cells, particularly cancer cells, multiple inducers are expressed simultaneously. Why, and if, and how they interact to regulate EMT is unanswered. Using RNA interference technology to affect protein knockdown and avoid potential overexpression artifact coupled with transient TGFβ treatment to better mimic in vivo conditions we show, in both nontumorigenic and tumorigenic epithelial cancer cells, that Snail1 is uniquely required for EMT initiation, whereas Twist1 is required to maintain late EMT. Twist1, present in resting epithelial cells, is dispensable for EMT initiation. Mechanistically, in response to transient TGFβ treatment, transient Snail1 expression represses Twist1 transcription directly, which is subsequently upregulated, as Snail1 levels decrease, to sustain E-cadherin downregulation and growth arrest of EMT. Persistent Twist1 expression is associated with a p38 and extracellular signal–regulated kinase signal feedback loop that sustains growth-inhibitory signals characteristic of quiescent micrometastatic tumors. This Snail1–Twist1 temporal and spatial cooperation was also observed in vivo during human breast cancer progression to metastasis. Twist1 level, but not Snail1 level, and Twist1:Snail1 ratio in disseminated micrometastatic bone marrow tumor cells was found to correlate with survival and treatment resistance and is highly predictive of metastatic or recurrent disease. Mol Cancer Res; 9(12); 1644–57. ©2011 AACR.
Population Pharmacokinetics and Penetration into Prostatic, Seminal, and Vaginal Fluid for Ciprofloxacin, Levofloxacin, and Their Combination
Authors: Bulitta Jurgen B. , Kinzig Martina , Naber Christoph K. , Wagenlehner Florian M.E. , Sauber Christian , Landersdorfer Cornelia B. , Sörgel Fritz , Naber Kurt G.
Published: October 2011

Background: Our objectives were to assess the pharmacokinetic interaction and body fluid penetration of ciprofloxacin and levofloxacin. Methods: This study was a single-dose open randomized three-way crossover in 15 healthy volunteers receiving 500 mg oral levofloxacin, 500 mg oral ciprofloxacin, or 250 mg levofloxacin and 250 mg ciprofloxacin co-administered. Serum, urine, and body fluid concentrations were determined by high-performance liquid chromatography and analyzed via population pharmacokinetic modeling. Results: Modeling indicated that ciprofloxacin inhibited the renal reabsorption of levofloxacin. Ciprofloxacin increased the net renal clearance of levofloxacin by 13%, as its estimated affinity for a putative tubular reabsorption transporter was 12-fold higher (Km: 568 µM) compared to levofloxacin (Km: 6,830 µM). Levofloxacin increased the bioavailability of ciprofloxacin by 12% and achieved significantly (p < 0.05) higher concentrations at 3 h in ejaculate, prostatic, seminal, and vaginal fluid compared to ciprofloxacin. Conclusion: Modeling suggested that ciprofloxacin inhibited the tubular reabsorption of levofloxacin due to a 12-fold higher affinity for a putative tubular reabsorption transporter compared to levofloxacin. This pharmacokinetic interaction was not clinically relevant.
Decompressive Hemicraniectomy for Pediatric Traumatic Brain Injury: Long-Term Outcome Based on Quality of Life
Authors: Jacob Arun T. , Heuer Gregory G. , Grant Ryan , Georgoff Patrick , Danish Shabbar F. , Storm Phillip B. , Stein Sherman C.
Published: October 2011

Aims: The impact of decompressive hemicraniectomy (DCH) on the overall outcome of pediatric brain injury patients has not been fully determined. In this paper, the authors performed a systematic review of patient outcome based on quality of life following DCH in a pediatric population. Methods: We describe our experience with decompressive craniectomy in pediatric patients and perform a literature review and pooled outcomes analysis to supplement these findings. A total of 13 children underwent DCH for intractable intracranial pressure in our institution from 2000 to 2008. Follow-up was available in 11 patients with 1 death (9%) and 7 survivors (70%) obtaining a favorable outcome (Glasgow Outcome Scale, GOS, scores = 4–5). Results: A literature review to determine the usefulness of DCH identified 17 articles that, when combined with our series, resulted in 186 pediatric DCH cases. Pooled outcomes found 42 deaths and 112 patients who had favorable outcomes at 6 months. The average 6-month mortality was 21.1%, and the pooled mean quality of life among survivors 0.75 (0.68–0.82), midway between moderate disability and good outcome. Conclusions: Based on our findings, DCH results in a majority of pediatric patients having a good outcome based on the GOS score.
Progressive Osteolytic Calvarial Lesions in Children after Minor Head Injury
Authors: Hermann Elvis J. , Hong Bujung , Brandis Almuth , Krauss Joachim K.
Published: October 2011

Objective: Osteolytic lesions of the skull in children have a broad differential diagnosis including congenital, inflammatory and neoplastic lesions. Progressive osteolysis of the skull secondary to head trauma is rare and has been poorly characterized. Methods: The pediatric database at our hospital was screened for children with osteolytic lesions who had a previous mild head injury without fracture or dural tears. We identified 2 children with circumscribed progressive cranial osteolysis after minor head trauma detected by CT and MRI scans. Three additional cases were found in a review of the published literature. Results: Ten children with an osteolytic skull lesion treated between January 1998 and February 2008 were identified in our pediatric database. In 2 children there was evidence of previous mild head injury without a skull fracture. Trauma had occurred 7 and 2 months prior to presentation, respectively. The inner table of the skull was intact in both cases. In 1 case, surgery was performed, and in the other case, a wait-and-see strategy was adopted. Pathological examination in case 1 revealed an organized hemorrhage with focal papillary endothelial hyperplasia. Conclusions: Progressive osteolytic calvarial lesions may occur in both infants and adolescents after mild head injury. They involve either only the diploe and outer table of the skull or both the inner and outer tables. These lesions might be due to intradiploic or subgaleal hematomas triggering an inflammatory process. While surgical resection can be considered to confirm a histopathological diagnosis and to exclude other diagnoses, spontaneous reossification is possible.
Ventriculosubgaleal Shunting – A Strategy to Reduce the Incidence of Shunt Revisions and Slit Ventricles: An Institutional Experience and Review of the Literature
Authors: Petraglia Anthony L. , Moravan Michael J. , Dimopoulos Vassilios G. , Silberstein Howard J.
Published: October 2011

Background/Aims: Slit ventricles and multiple episodes of shunt failure are problematic in many infants and preterm neonates shunted for hydrocephalus. We utilized ventriculosubgaleal (VSG) shunting as the initial neurosurgical intervention in neonates with hydrocephalus associated with intraventricular hemorrhage and infants with myelomeningocele. Methods: We conducted a chart review of 21 children initially treated with a VSG shunt between November 2002 and July 2009. Patient records and imaging studies were reviewed. Demographics, case data and clinical outcome were collected. Results: Five patients (27.8%) required a revision after conversion to a ventriculoperitoneal (VP) shunt. There were 9 cases of radiographic slit ventricles (45%). Average follow-up was 59.5 months (range 12–97 months). Average time interval to shunt conversion was 81.5 days. Two patients have not required conversion to a VP shunt (one with an 8-year follow-up). To date, none of these patients has required a subtemporal window or cranial vault expansion. Conclusion: Based on our results, initial management of selected hydrocephalic infants with a VSG shunt may prove to be advantageous in the long run for these children as the number of shunt revisions and the incidence of slit ventricles are significantly less than those reported in the literature.
Meningioangiomatosis in a 5-Year-Old Boy Presenting with Intractable Seizures
Authors: Alexiou George A. , Moschovi Maria , Stefanaki Kalliopi , Siozos George , Hatzigiorgi Christiana , Prodromou Neofytos
Published: October 2011

A 5-year-old boy with a history of epilepsy underwent brain magnetic resonance imaging (MRI) because of an increase in seizure frequency. Brain MRI demonstrated a left frontal lesion. The patient was operated upon, and gross total excision was performed. The histological diagnosis was meningioangiomatosis. On follow-up examination 10 years later, the patient was free of seizures and without any evidence of tumor recurrence. Meningioangiomatosis is a rare benign hamartomatous lesion that is associated with seizures. Complete excision is associated with favorable long-term outcome. The novelty of the present case is the young age of the child at presentation and the curative role of surgery considering the long-term follow-up.
Initial Observations of Combination Barbiturate Coma and Decompressive Craniectomy for the Management of Severe Pediatric Traumatic Brain Injury
Authors: Glick Roberta P. , Ksendzovsky Alexander , Greesh John , Raksin Patti
Published: October 2011

Objective: In the pediatric population, treatment of severely injured children presenting with low Glasgow Coma Score (GCS) and fixed and dilated pupils is controversial. The combination of barbiturate coma and decompressive craniectomy as an aggressive means of controlling intracranial pressure is limited to few studies. In the present series, we report our experience with aggressive combination therapy resulting in good outcomes in pediatric patients with severe traumatic brain injury (TBI). Patients and Methods: Six TBI patients, aged <18 years, either presented with or deteriorated to a GCS <5 with fixed and dilated pupils and CT evidence of surgical lesions with brain edema. Despite hyperventilation, anesthesia, and mannitol, intracranial pressures remained elevated and all patients underwent decompressive craniectomy and external ventricular drainage and were subsequently placed into barbiturate coma for 72 h. Results: One patient died and 1 patient remained vegetative. Two patients had excellent recoveries (GOS 5/Rankin 1 or 0, no cognitive deficits) and 2 patients had good recoveries (GOS 4/Rankin 1, mild cognitive deficits). Conclusions: Combination of barbiturate coma with decompressive craniectomy and external ventricular drainage led to good outcomes in a small group of pediatric patients with severe TBI. Based on this series we recommend further investigation into aggressive combination management.
Protective Therapy with Novel Chromone Derivative against Leishmania donovani Infection Induces Th1 Response in vivo
Authors: Mallick Suvadip , Dutta Aritri , Ghosh Joydip , Maiti Sourav , Mandal Ajay Kumar , Banerjee Rajat , Bandyopadhyay Chandrakanta , Pal Chiranjib
Published: October 2011

Background: Visceral leishmaniasis is a chronic protozoan disease caused by Leishmania donovani, an obligatory intracellular parasite that resides and multiplies within macrophages of the reticuloendothelial system. The aim of this study was to evaluate the efficacy of nine novel synthetic chromone derivatives as antileishmanial molecules in experimental murine visceral leishmaniasis. Methods: In vitro activity of the molecules (2, 5 and 10 µg/ml) was assessed against promastigotes of both pentavalent antimonial-responsive strain AG83 and pentavalent antimonial-resistant strain GE1F8R at days 2 (48 h), 4 (96 h) and 6 (144 h). The efficacy of the most efficient chromone derivative [C-(6-Methyl-4-oxo-4H-1-benzopyran-3-yl)-N-(p-tolyl) nitrone], designated here as NP1, was also tested against intracellular amastigotes in vitro and in vivo. Results: NP1, 5 µg/ml, inhibited the growth of AG83 and GE1F8R promastigotes by 98.57% (day 4) and 75.75% (day 6), respectively, and also inhibited the growth of intracellular amastigotes by 85% (day 3), compared to DMSO control. Treatment of L. donovani-infected mice with NP1 resulted in a 70% significant decrease in parasite load in the spleen in the 7th week after infection (5 mice in each group), with associated induction of interferon-γ synthesis by dose 2 (37.5 mg/kg body weight) compared to DMSO control. Dose 2 was found efficient over dose 1 (25 mg/kg body weight). Conclusions: The novel synthetic chromone derivative is effective in the treatment of visceral leishmaniasis and induces the synthesis of interferon-γ in rodent models.
Circulation: Cardiovascular Genetics
Editors' Picks
Authors:   The Editors
Published: October 2011

The following articles are being highlighted as part of
Circulation: Cardiovascular Genetics'
Topic Review series. This series will summarize the most important articles, as selected by the editors, published in
Circulation: Cardiovascular Genetics
and the rest of the
Circulation
portfolio. The articles included in this report represent the most read genome-wide and candidate gene association studies published in 2009 and 2010.
Circulation: Cardiovascular Interventions
Editors' Picks
Authors:   The Editors
Published: October 2011

The following are highlights from the series,
Circulation: Cardiovascular Interventions
Topic Review. This series summarizes the most important manuscripts, as selected by the editors, that have published in the
Circulation
portfolio. The studies included in this article represent the most noteworthy research in the area of antiplatelet therapy.
Impact of Onsite or Dispatched Automated External Defibrillator Use on Survival After Out-of-Hospital Cardiac Arrest
Authors: Berdowski Jocelyn , Blom Marieke T. , Bardai Abdennasser , Tan Hanno L. , Tijssen Jan G.P. , Koster Rudolph W.
Published: October 2011

Background—

There have been few studies on the effectiveness of bystander automated external defibrillator (AED) use in out-of-hospital cardiac arrest. The objective of this study was to determine whether actual use of onsite or dispatched AED reduces the time to first shock compared with no AED use and thereby improves survival.

Methods and Results—

We performed a population-based cohort study of 2833 consecutive patients with a nontraumatic out-of-hospital cardiac arrest before emergency medical system arrival between 2006 and 2009. The primary outcome, neurologically intact survival to discharge, was compared by use of multivariable logistic regression analysis. An onsite AED had been applied in 128 of the 2833 cases, a dispatched AED in 478, and no AED in 2227. Onsite AED use reduced the time to first shock from 11 to 4.1 minute. Neurologically intact survival was 49.6% for patients treated with an onsite AED compared with 14.3% without an AED (unadjusted odds ratio, 5.63; 95% confidence interval, 3.91–8.10). The odds ratio remained statistically significant after adjustment for confounding (odds ratio, 2.72; 95% confidence interval, 1.77–4.18). Dispatched AED use reduced the time from call to first shock to 8.5 minutes. Neurologically intact survival was 17.2% for patients treated with a dispatched AED (unadjusted odds ratio, 1.07; 95% confidence interval, 0.82–1.39). Every year, onsite AEDs saved 3.6 lives per 1 million inhabitants; dispatched AEDs saved 1.2 lives.

Conclusions—

The use of an onsite AED leads to a doubling of neurologically intact survival. In our system, the survival benefit of dispatched AED use was much smaller than that of onsite AED use.