bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostics analysis for log‐Birnbaum–Saunders regression models with censored data
Authors: Qu Hao , Xie Feng‐Chang
Published: June 2010

This article develops influence diagnostics for log‐Birnbaum–Saunders (LBS) regression models with censored data based on case‐deletion model (CDM). The one‐step approximations of the estimates in CDM are given and case‐deletion measures are obtained. Meanwhile, it is shown that CDM is equivalent to mean shift outlier model (MSOM) in LBS regression models and an outlier test is presented based on MSOM. Furthermore, we discuss a score test for homogeneity of shape parameter in LBS regression models. Two numerical examples are given to illustrate our methodology and the properties of score test statistic are investigated through Monte Carlo simulations under different censoring percentages.
Using the SDIlightApproach in Teaching a Geoinformatics Master
Authors: Köbben Barend , De By Rolf , Foerster Theodor , Huisman Otto , Lemmens Rob , Morales Javier
Published: June 2010

ITC, the Faculty of Geo–Information Science and Earth Observation of the University of Twente, is an institute that aims at capacity building and institutional development, specifically in developing countries. In our Geoinformatics curriculum, we emphasise two principles. The first addresses the systematics of purposeful spatial data production and uptake into computerised systems; the second addresses the methodical construction of these computerised systems, applying principles of model – driven architecture, formal specification and transformational design of SDI nodes. The term Spatial Data Infrastructure (SDI) usually denotes large, complex systems, but its principles can also be applied in simple and cost–effective ways. This approach we have calledSDIlightand it is of particular interest to our students that come from developing countries. We work with and build a software stack consisting of free and open source components. To achieve interoperability, we emphasise the use of open standards from the Open Geospatial Consortium and others. In this paper, we explain how our students apply the SDIlightapproach in the GeoinformaticsMaster degree course. An important part of that course is a Case Study Application Building & Programming, in which students apply their knowledge in a ‘real–world’ project, with a focus on geo–information engineering skills. We conclude with a section that evaluates the effectiveness of using the SDIlightconcept in teaching our Geoinformatics Master, and on the more general applicability of the methodology.
Moving Code in Spatial Data Infrastructures – Web Service Based Deployment of Geoprocessing Algorithms
Authors: Müller Matthias , Bernard Lars , Brauner Johannes
Published: June 2010

This article proposes a concept for offering complex geoprocessing functionality in service‐based Spatial Data Infrastructures (SDI). Today, geoprocessing in SDI is typically realized in a data driven manner. Applying the suggested “moving code” approach in a case study in the field of Spatial Decision Support proves its applicability. The proposed solution is analyzed and assessed in terms of gained efficiency, performance behavior and support for distributed development of geoprocessing functionality. In data and computation intensive SDI applications the deployment of moving code proves to be beneficial.
Improving Geocode Accuracy with Candidate Selection Criteria
Authors: Goldberg Daniel W. , Cockburn Myles G.
Published: June 2010

Geocoding systems typically use more than one geographic reference dataset to improve match rates and spatial accuracy, resulting in multiple candidate geocodes from which the single “best” result must be selected. Little scientific evidence exists for formalizing this selection process or comparing one strategy to another, leading to the approach used in existing systems which we term the hierarchy‐based criterion: place the available reference data layers into qualitative, static, and in many cases, arbitrary hierarchies and attempt a match in each layer, in order. The first non‐ambiguous match with suitable confidence is selected and returned as output. This approach assumes global relationships of relative accuracy between reference data layers, ignoring local variations that could be exploited to return more precise geocodes. We propose a formalization of the selection criteria and present three alternative strategies which we term the uncertainty‐, gravitationally‐, and topologically‐based strategies. The performance of each method is evaluated against two ground truth datasets of nationwide GPS points to determine any resulting spatial improvements. We find that any of the three new methods improves on current practice in the majority of cases. The gravitationally‐ and topologically‐based approaches offer improvement over a simple uncertainty‐based approach in cases with specific characteristics.
CAUSTA: Clifford Algebra‐based Unified Spatio‐Temporal Analysis
Authors: Yuan Linwang , Yu Zhaoyuan , Chen Shaofei , Luo Wen , Wang Yongjun , Lü Guonian
Published: June 2010

Introducing Clifford algebra as the mathematical foundation, a unified spatio‐temporal data model and hierarchical spatio‐temporal index are constructed by linking basic data objects, like pointclouds and Spatio‐Temporal Hyper Cubes of different dimensions, within the multivector structure of Clifford algebra. The transformation from geographic space into homogeneous and conformal space means that geometric, metric and many other kinds of operators of Clifford algebra can be implemented and we then design the shortest path, high‐dimensional Voronoi and unified spatial‐temporal process analyses with spacetime algebra. Tests with real world data suggest these traditional GIS analysis algorithms can be extended and constructed under Clifford Algebra framework, which can accommodate multiple dimensions. The prototype software system CAUSTA (Clifford Algebra based Unified Spatial‐Temporal Analysis) provides a useful tool for investigating and modeling the distribution characteristics and dynamic process of complex geographical phenomena under the unified spatio‐temporal structure.
Using the Newly‐created ILE DBMS to Better Represent Temporal and Historical GIS Data
Authors: Kantabutra Vitit , Owens J. B. “Jack” , Ames Daniel P. , Burns Charles N. , Stephenson Barbara
Published: June 2010

This article introduces a type of DBMS called the Intentionally‐Linked Entities (ILE) DBMS for use as the basis for temporal and historical Geographical Information Systems. ILE represents each entity in a database only once, thereby mostly eliminating redundancy and fragmentation, two major problems in Relational and other database systems. These advantages of ILE are realized by using relationship objects and pointers to implement all of the relationships among data entities in a native fashion using dynamically‐allocated linked data structures. ILE can be considered to be a modern and extended implementation of the E/R data model. ILE also facilitates storage of things that are more faithful to the historical records, such as gazetteer entries of places with imprecisely known or unknown locations. This is difficult in Relational database systems but is a routine task using ILE because ILE is implemented using modern memory allocation techniques. We use the China Historical GIS (CHGIS) and other databases to illustrate the advantages of ILE. This is accomplished by modeling these databases in ILE and comparing them to the existing Relational implementations.
Graphical Models for Marked Point Processes Based on Local Independence
Authors: Didelez Vanessa
Published: June 2010

A new class of graphical models capturing the dependence structure of events that occur in time is proposed. The graphs represent so-called local independences, meaning that the intensities of certain types of events are independent of some (but not necessarilly all) events in the past. This dynamic concept of independence is asymmetric, similar to Granger non-causality, so the corresponding local independence graphs differ considerably from classical graphical models. Hence a new notion of graph separation, which is called δ-separation, is introduced and implications for the underlying model as well as for likelihood inference are explored. Benefits regarding facilitation of reasoning about and understanding of dynamic dependences as well as computational simplifications are discussed.
Development of axonal pathways in the human fetal fronto‐limbic brain: histochemical characterization and diffusion tensor imaging
Authors: Vasung Lana , Huang Hao , Jovanov‐Milošević Nataša , Pletikos Mihovil , Mori Susumu , Kostović Ivica
Published: June 2010

The development of cortical axonal pathways in the human brain begins during the transition between the embryonic and fetal period, happens in a series of sequential events, and leads to the establishment of major long trajectories by the neonatal period. We have correlated histochemical markers (acetylcholinesterase (AChE) histochemistry, antibody against synaptic protein SNAP‐25 (SNAP‐25‐immunoreactivity) and neurofilament 200) with the diffusion tensor imaging (DTI) database in order to make a reconstruction of the origin, growth pattern and termination of the pathways in the period between 8 and 34 postconceptual weeks (PCW). Histological sections revealed that the initial outgrowth and formation of joined trajectories of subcortico‐frontal pathways (external capsule, cerebral stalk–internal capsule) and limbic bundles (fornix, stria terminalis, amygdaloid radiation) occur by 10 PCW. As early as 11 PCW, major afferent fibers invade the corticostriatal junction. At 13–14 PCW, axonal pathways from the thalamus and basal forebrain approach the deep moiety of the cortical plate, causing the first lamination. The period between 15 and 18 PCW is dominated by elaboration of the periventricular crossroads, sagittal strata and spread of fibers in the subplate and marginal zone. Tracing of fibers in the subplate with DTI is unsuccessful due to the isotropy of this zone. Penetration of the cortical plate occurs after 24–26 PCW. In conclusion, frontal axonal pathways form the periventricular crossroads, sagittal strata and ‘waiting’ compartments during the path‐finding and penetration of the cortical plate. Histochemistry is advantageous in the demonstration of a growth pattern, whereas DTI is unique for demonstrating axonal trajectories. The complexity of fibers is the biological substrate of selective vulnerability of the fetal white matter.
Exact solution of emerging quadratic assignment problems
Authors: Hahn Peter M. , Zhu Yi‐Rong , Guignard Monique , Smith J. MacGregor
Published: June 2010

We report on a growing class of assignment problems that are increasingly of interest and very challenging in terms of the difficulty they pose to attempts at exact solution. These problems address economic issues in the location and design of factories, hospitals, depots, transportation hubs and military bases. Others involve improvements in communication network design. In this article we survey the latest and best methods available for solving exactly these difficult problems and suggest a taxonomy that provides a framework for combining existing solution methods and sets of computer tools that can be modified and extended to make inroads in solving this growing class of optimization problems.
Opting for Opting‐In? An Evaluation of the European Commission's Proposals for Reforming VAT on Financial Services*
Authors: De La Feria Rita , Lockwood Ben
Published: June 2010

This paper provides a legal and economic analysis of the European Commission's recent proposals for reforming the application of VAT to financial services, with particular focus on their ‘third pillar’, under which firms would be allowed to opt in to taxation on exempt insurance and financial services. From a legal perspective, we show that the proposals’‘first and second pillars’ would give rise to considerable interpretative and qualification problems, resulting in as much complexity and legal uncertainty as the current regime. Equally, an option to tax could potentially follow significantly different legal designs, which would give rise to discrepancies in the application of the option amongst Member States of the European Union (EU). On the economic side, we show that quite generally, when firms cannot coordinate their behaviour, they have an individual incentive to opt in on business‐to‐business (B2B) transactions, but not on business‐to‐consumer (B2C) transactions. We also show that opting‐in eliminates the cost disadvantage that EU financial services firms face in competing with foreign firms for B2B sales. But these results donothold if firms can coordinate their behaviour. An estimate of the upper bound on the amount of tax revenue that might be lost from allowing opting‐in is provided for a number of EU countries.
The anti‐aggregating effect of BAY 41‐2272, a stimulator of soluble guanylyl cyclase, requires the presence of nitric oxide
Authors: Roger Séverine , Badier‐Commander Cécile , Paysant Jérôme , Cordi Alex , Verbeuren Tony J , Félétou Michel
Published: June 2010

BACKGROUND AND PURPOSEThe purpose of the present study was to determine whether a stimulator of soluble guanylyl cyclase, BAY 41‐2272, inhibits platelet aggregation and to clarify its interaction with nitric oxide (NO).

EXPERIMENTAL APPROACHBlood was collected from anaesthetized Wistar Kyoto rats. The aggregation of washed platelets was measured and the production of cAMP and cGMP was determined.

KEY RESULTSIn adenosine 5′‐diphosphate (ADP)‐induced platelet aggregation, the anti‐aggregating effects of BAY 41‐2272, nitroglycerin, sodium nitroprusside and DEA‐NONOate were associated with increased levels of cGMP while that of beraprost, a prostacyclin analogue, was correlated with an increase in cAMP. 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) prevented the effects of BAY 41‐2272 and that of nitroglycerin and sodium nitroprusside, but only inhibited the increase in cGMP produced by of DEA‐NONOate. Hydroxocobalamin, an NO scavenger, inhibited the effects of the three NO donors and BAY 41‐2272 but did not affect those of beraprost. ADP‐induced aggregation and the effects of BAY 41‐2272 were not affected by L‐nitroarginine. A positive interaction was observed between BAY 41‐2272 and the three NO donors. BAY 41‐2272 potentiated also the anti‐aggregating effects of beraprost, and again this potentiation was inhibited by hydroxocobalamin.

CONCLUSIONS AND IMPLICATIONSInhibition of platelet aggregation by BAY 41‐2272 requires the reduced form of soluble guanylyl cyclase and the presence of NO. The positive interaction observed between BAY 41‐2272 and various NO donors is qualitatively similar whatever the mechanism involved in NO release. Furthermore, a potent synergism is observed between BAY 41‐2272 and a prostacyclin analogue, but only in the presence of NO.
Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid
Authors: Chen Limin , Borozan Ivan , Milkiewicz Piotr , Sun Jing , Meng Xiangbin , Coltescu Catalina , Edwards Aled M. , Ostrowski Mario A. , Guindi Maha , Heathcote Elizabeth J. , McGilvray Ian D.
Published: June 2010

Objectives: Primary biliary cirrhosis (PBC) is a poorly understood disease, both in terms of its pathogenesis and the mechanism of action of its most common treatment, ursodeoxycholic acid (UDCA). We used gene expression profiling to compare liver tissue from treatment‐naïve and UDCA‐treated patients in order to outline some of the molecular changes associated with PBC and its treatment.

Patients and Experimental Design: Liver biopsy specimens from non‐cirrhotic, treatment‐naïve (n=11) patients were compared with biopsies from UDCA‐treated patients (n=20) and with 10 normal, healthy female controls. Gene expression was determined using a 19K cDNA microarray. In order to determine whether the observed changes in gene expression levels were specific to PBC or generic to liver damage overall, PBC samples were also compared with chronically diseased [48 hepatitis C virus (HCV), 18 hepatitis B virus (HBV)] and acutely stressed liver tissue (25 liver biopsies taken after reperfusion of liver transplant grafts).

Results: We found a gene signature specific to PBC (P≤0.012), containing biologically plausible genes (221 genes with adjusted P≤0.05). Differences in the expression of selected genes were confirmed using real‐time polymerase chain reaction. When gene expression from non‐cirrhotic UDCA‐treated (n=20) and UDCA‐naïve liver tissue was compared, we found a striking downregulation of a number of genes involved in protein biosynthetic pathways.

Conclusions: These studies highlight the genes associated with both treatment‐naïve and UDCA‐treated PBC, and suggest that the effects of UDCA are mediated, at least in part, via a modulation of protein biosynthesic pathways.
Semiautomatic Quantification of Left Ventricular Function by Two‐Dimensional Feature Tracking Imaging Echocardiography. A Comparison Study with Cardiac Magnetic Resonance Imaging
Authors: Di Bella Gianluca , Zito Concetta , Gaeta Michele , Cusmà Piccione Maurizio , Minutoli Fabio , Donato Rocco , Recupero Antonino , Madaffari Antonio , Coglitore Sebastiano , Carerj Scipione
Published: June 2010

Objective: To evaluate the accuracy of a semiautomatic quantification of left ventricular (LV) volumes and ejection fraction (EF) using two‐dimensional (2D) feature tracking imaging (FTI). Methods: Thirty‐four consecutive subjects (11 patients with dilated cardiomyopathy, 13 with hypertrophic cardiomyopathy, and 10 subjects with no cardiac disease) underwent, on the same day, trans‐thoracic echocardiography (TTE) examination, FTI, and cardiac magnetic resonance imaging (MRI), as gold standard, in order to quantify LV volumes and EF. The echocardiographic quantification of LV volumes and EF was determined from four‐ and two‐chamber views using both standard TTE Biplane Simpson's method and a semiautomatic border detection based on FTI. Furthermore, the time for data analysis for each method was measured. Results: The time required for semiautomatic analysis of volumes and EF was significantly lower (P < 0.0001) by FTI (71 seconds) in comparison with standard biplane Simpson's method (93 seconds). LV volumes obtained by FTI were significant underestimated (P < 0.001) in comparison with MRI. Bland‐Altman analysis of EDV and ESV using FTI and cardiac MRI showed a low level of agreement for EDV (mean difference = 40.8; SD = 39) and ESV (mean difference = 38.1; SD = 42). On the contrary, no significant difference between FTI and MRI in assessing the LVEF was found; furthermore, a very low bias (2 ± 12) by Bland‐Altman analysis was found between FTI and cardiac MRI for the quantification of EF. Conclusion: Semiautomatic quantification of LV volumes using FTI allows an accurate, rapid, easy and reliable assessment of LV EF and a rough estimation of LV volumes. (Echocardiography 2010;27:791‐797)
Elastophagocytosis in extragenital lichen sclerosus
Authors: Abbas Ossama , Chatrath Vandana , Goldberg Lynne J.
Published: June 2010

Background: Elastophagocytosis, or elastic fiber phagocytosis by multinucleate macrophages, has been observed in different skin conditions that may or may not occur on sun‐exposed skin. Although loss of elastic fibers has been well documented in the homogenized papillary dermal zone in lichen sclerosus (LS), elastophagocytosis, to the best of our knowledge, has never been observed.

Methods: We encountered striking elastophagocytosis in a case of extragenital LS which prompted us to review all cases of LS diagnosed at the Skin Pathology Laboratory at Boston University over a 2‐year period to assess for the presence of elastophagocytosis.

Results: In 7 of 35 patients diagnosed with LS (20%), we found prominent elastophagocytosis to be present either immediately below or at the junction of the homogenized collagen and the normal underlying reticular dermis. Interestingly, all the cases in which elastophagocytosis was observed were in extragenital locations.

Conclusion: Elastophagocytosis was observed in 20% of LS cases, all of which were extragenital. We hypothesize that elastophagocytosis in LS, especially in extragenital sites, may not be an epiphenomenon but rather represents a contributing factor to elastic fiber loss in the hyalinized papillary dermal collagen that typifies this disease.

Abbas O, Chatrath V, Goldberg LJ. Elastophagocytosis in lichen sclerosus.
Increased versican content is associated with tendinosis pathology in the patellar tendon of athletes with jumper's knee
Authors: Scott A. , Lian Ø. , Roberts C. R. , Cook J. L. , Handley C. J. , Bahr R. , Samiric T. , Ilic M. Z. , Parkinson J. , Hart D. A. , Duronio V. , Khan K. M.
Published: June 2010

Expansion of the extracellular matrix is a prominent but poorly characterized feature of tendinosis. The present study aimed to characterize the extent and distribution of the large aggregating proteoglycan versican in patients with patellar tendinosis. We obtained tendon from tendinopathy patients undergoing debridement of the patellar tendon and from controls undergoing intramedullary tibial nailing. Versican content was investigated by Western blotting and immunohistochemistry. Microvessel thickness and density were determined using computer‐assisted image analysis. Markers for smooth muscle actin, endothelial cells (CD31) and proliferating cells (Ki67) were examined immunohistochemically. Western blot analysis and immunohistochemical staining revealed elevated versican content in the proximal patellar tendon of tendinosis patients (P=0.042). Versican content was enriched in regions of fibrocartilage metaplasia and fibroblast proliferation, as well as in the perivascular matrix of proliferating microvessels and within the media and intima of arterioles. Microvessel density was higher in tendinosis tissue compared with control tissue. Versican deposition is a prominent feature of patellar tendinosis. Because this molecule is not only a component of normal fibrocartilagenous matrices but also implicated in a variety of soft tissue pathologies, future studies should further detail both pathological and adaptive roles of versican in tendons.
Relationship between growth retardation and impaired glucose tolerance in hypothyroidal growth‐retarded (grt) mice
Authors: Tasaki Yoshie , Taguchi Yusuke , Machida Takeo , Kobayashi Tetsuya
Published: June 2010

Growth‐retarded (grt) mice exhibit congenital hypothyroidism and a characteristic growth pause followed by delayed onset of pubertal growth. This pattern of growth has never been reported in any other animal model exhibiting hypothyroidism; therefore, the growth retardation observed ingrtmice is unlikely to be explained completely by the low plasma thyroid hormone levels. As growth is closely related to nutrient metabolism, we investigated the relationship between the appearance of growth retardation and glucose utilization, which is the main component of nutrient metabolism, in the peripubertal stage ofgrtmice. The relative weights of the organs involved in nutrient digestion and absorption were abnormal ingrtmice. The intraperitoneal glucose tolerance test (IGTT) showed impaired glucose tolerance ingrtmice. Moreover, this symptom appeared in parallel with the progression of growth retardation ingrtmice. The impaired blood glucose levels on the IGTT ingrtmice were considered to be attributable to decreased plasma insulin levels rather than to impaired insulin sensitivity. The pattern of anti‐insulin antibody staining on sections of pancreatic islets fromgrtmice was almost the same as that in the corresponding sections from normal mice. Insulin treatment accelerated the growth of peripubertalgrtmice. These findings suggest that the appearance of growth retardation ingrtmice might be partially attributable to a reduction in glucose metabolism and impairment of insulin secretion during the early period of growth.
Co‐Administration of Dextromethorphan and Morphine: Reduction of Post‐Operative Pain and Lack of Influence on Morphine Metabolism
Authors: Suski Maciej , Bujak‐Gizycka Beata , Madej Jozef , Kacka Katarzyna , Dobrogowski Jan , Woron Jaroslaw , Olszanecki Rafal , Korbut Ryszard
Published: June 2010

Abstract: We investigated co‐analgesic effect of dextromethorphan in adolescent post‐operative patients with idiopathic scoliosis. In a double‐blind study, 60 patients with ASA physical status I–II were randomised into two groups. Group dextromethorphan (n = 30; age: 15.9 ± 2.4 years) was given oral dextromethorphan 30 or 45 mg 1 hr before surgery and 8, 20 and 32 hr after operation. Group placebo (n = 30; age: 16.5 ± 2.7 years) received placebo at identical times. Post‐operative analgesic requirements were assessed using nurse‐controlled analgesia system. Pain was assessed using numeric rating scale before first administration of morphine and at 2, 3, 4, 6, 24 and 48 hr after operation. Blood samples were taken 20 min. after the first use of morphine (within 1 hr after operation). The total use of analgesics during surgery was lower in the dextromethorphan group. The dose of morphine providing relief immediately after surgery, as well as total analgesic requirements in the first and second day after surgery did not differ between groups. Subjectively evaluated pain intensity score (numeric rating scale) was lower for the dextromethorphan patients in the first 4 hr, but not later after surgery. Plasma levels of morphine, morphine‐6‐glucuronide and morphine‐3‐glucuronide did not differ between groups. Dextromethorphan did not influence morphine glucuronidation, in terms of promotion of formation of any morphine glucuronides. In conclusion, in young patients subjected to spine surgery, addition of dextromethorphan to morphine reduced pain only in early post‐operative period. In such patients, co‐analgesic action of dextromethorphan was not associated with significant changes in plasma levels of morphine metabolites.
RING CHARACTERIZATION OF QUALITY INDICES IN BUTTERHEAD LETTUCE CULTIVATED UNDER MULCH AND BARE SOIL
Authors: GOÑI MARÍA G. , AGÜERO MARÍA V. , MOREIRA MARÍA DEL R. , PONCE ALEJANDRA , ROURA SARA I.
Published: June 2010

Butterhead lettuce was characterized by physical, microbiological and nutritional quality indices as a function of plant zoning and soil management (bare soil and mulch). Quality indices were measured in all the rings from the external toward the internal ratio. Assayed indices were: relative water content, water content, free and bound water, and the ratio between free water and total water, leaf area and color, total microbial counts (TMC) and ascorbic acid content (AA). The lettuce characterization by rings showed a remarkable plant zoning as a function of leaf age and development; also, some initial indices were affected by the soil management employed. Plastic mulches affect the microclimate around the plant, resulting in better plant water status. However, the use of black plastic covers could absorb sunlight therefore increasing soil temperature and causing lower AA and higher TMC in lettuce tissue.

PRACTICAL APPLICATIONS

During lettuce development, each leaf had a different level of exposure to environmental conditions, such as light, humidity, nutrients absorption and temperature affecting the quality indices of the raw material and introducing a source of variability in the physico‐chemical, biochemical, nutritional and microbiological indices within the plant. In this way, the location of the leaf within the whole plant is an important factor to be considered. Moreover, during lettuce heads trading, it is a common practice to remove the external leaves as storage advances. These leaves are more perishable than middle and internal ones because of their direct exposure to environmental conditions. Understanding the way in which physical, microbiological and nutritional indices were distributed in the whole lettuce plant could be of interest, to know the value of the losses of regular green grocers' practices, from a nutritional and a safety point of view.
Fruit and Vegetable Distribution Program Versus a Multicomponent Program to Increase Fruit and Vegetable Consumption: Which Should Be Recommended for Implementation?
Authors: Reinaerts Evelien B.M. , De Nooijer Jascha , De Vries Nanne K.
Published: June 2010

Background:  Two primary school–based interventions were implemented, aimed at increasing fruit and vegetable (F&V) consumption by children, both with proven effectiveness: (1) a free daily F&V distribution scheme for all primary school children and (2) a multicomponent, age‐specific program consisting of a classroom curriculum, parental involvement, and an environmental component. This article describes and compares the implementation, evaluation, and potential for adoption of the 2 interventions.

Methods:  A total of 48 teachers who worked with either of these programs filled out a questionnaire at the end of the intervention period. Additionally, 24 of the teachers who worked with the multicomponent program filled out periodic monitoring reports during the intervention.

Results:  Compared to the F&V distribution, the multicomponent program was less fully implemented and that implementation of activities decreased over time. Both programs were evaluated favorably, and about half of the teachers indicated that they were willing to use the program again in the following school year. Teachers who used the multicomponent program experienced more social pressure to implement the program. They rated the program they had used as more complex and risky than the other group rated the distribution program.

Conclusions:  The free distribution program has the greatest potential for being adopted by schoolteachers, but that efforts must be made to acquire funding for it. Until these resources are available, the multicomponent program seems to be a good alternative if improved as suggested.
Design, Synthesis, Docking and Antitumor Activity of Quinazolino [3, 4‐a] thieno [3, 2‐d] pyrimidin‐8‐one Derivatives
Authors: Zheng Youguang , Wu Xiaoqing , Xue Bai , Li Mingdong , Ji Min
Published: June 2010

Several novel quinazolino [3, 4‐a] thieno [3, 2‐d] pyrimidin‐8‐one derivatives were synthesized. All of the compounds were determined against MiaPaCa2 and DU145 cells in vitro, and the crystal structures of analog 8 and 20 in the active site of the EGFR complexes were presented. The entire compounds had been identified by 1HNMR, 13CNMR, IR, MS and EA.
Lenses from Brown‐Norway pigmented rats are more tolerant to in vitro ultraviolet irradiation than lenses from Fischer‐344 albino rats
Authors: Löfgren Stefan
Published: June 2010

Purpose:  To investigate if the previously shown difference in in vivo‐induced ultraviolet B radiation (UVR‐B) cataractogenesis between pigmented and albino rats can be seen also with in vitro irradiation. The shielding effect of the iris and UVR absorption in the anterior segment is nullified, and inherent differences in lenticular UVR‐B sensitivity between the strains may be revealed.

Methods:  Lenses from albino (Fischer‐344) and pigmented (Brown‐Norway) rats were irradiated in vitro with 1.8 kJ/m2 UVR‐B. The lenses were cultured in standard environment in a culture incubator. Cataract was quantified daily by measuring the amount of lens forward light scattering over a period of 1 week. All lenses were photographed during the week.

Results:  Two days after exposure, both strains developed significant cataract compared to control lenses, and the light scattering increased exponentially to the last day. From day 4, exposed Fischer lenses scattered more light than Brown‐Norway lenses. This difference increased towards the end of the week. The type of cataract (anterior subcapsular, equatorial, and posterior cortical cataract) was similar in both strains. No anterior polar or nuclear cataract was observed.

Conclusions:  Lenses from albino Fischer rats are more sensitive to in vitro UVR‐B than lenses from pigmented Brown‐Norway rats. Ultraviolet B radiation cataract type induced in vitro differs from in vivo cataract in pigmented rats, but not from albino rats. In vitro UVR‐B exposure induces more cataract than corresponding lenticular UVR‐B in vivo exposures, for both albino and pigmented rat.
Inactivation of AHLs by Ochrobactrum sp. A44 depends on the activity of a novel class of AHL acylase
Authors: Czajkowski Robert , Krzyżanowska Dorota , Karczewska Joanna , Atkinson Steve , Przysowa Joanna , Lojkowska Ewa , Williams Paul , Jafra Sylwia
Published: June 2010

The soil isolate Ochrobactrum sp. A44 inactivates N‐acyl homoserine lactone (AHL) quorum sensing signal molecules and is capable of quenching the AHL‐dependent virulence of Pectobacterium carotovorum in planta. To characterize this AHL inactivating activity, Ochrobactrum cell extracts were prepared and their capacity to degrade a broad range of AHLs was determined. AHLs with acyl chains ranging from C4 to C14 with or without 3‐oxo or 3‐hydroxy substituents were all inactivated to varying extents; long chain AHLs were generally more susceptible than short chain compounds irrespective of the three position substituent. HPLC and LC‐tandem mass spectrometry of the AHL degradation products revealed that the AHL inactivating activity present in the Ochrobactrum cell extract cleaved the AHL amide bond. To identify the gene(s) responsible for AHL degradation, Ochrobactrum sp. A44 was subjected to random transposon (Tn) mutagenesis and the resulting mutants screened for the loss of AHL acylase activity. The Tn insertion in mutant A6731 was mapped to a gene termed aiiO, the translated product of which belongs to the α/β hydrolase superfamily which constitutes a novel type of AHL acylase.
Molecular identification of reproductive cells released from Cypassis irregularis Nigrini (Radiolaria)
Authors: Kimoto Katsunori , Yuasa Tomoko , Takahashi Osamu
Published: June 2010

The mechanisms of the extensive distribution of radiolarian‐affiliated sequences from clone libraries of marine picoeukaryotes from deeper water remain poorly understood. Here, we describe an event that could explain this phenomenon. A polycystine radiolarian species, Cypassis irregularis Nigrini, released a large number of pico‐size cells under culture conditions. The diameters of the cells averaged ∼3 µm and the 18S rDNA sequences fell within those of typical radiolarian families. This finding suggests that the radiolarian sequences found in the picoeukaryote size fraction from deep water are from swarmers or gametes released for reproduction. Thus, the deep ocean is expected to aid in the widespread dispersal of the genetic material of eukaryotes.
Origins and Diversification of a Complex Signal Transduction System in Prokaryotes
Authors: Wuichet Kristin , Zhulin Igor B.
Published: June 2010

The bacterial chemotaxis system evolved from simpler regulatory proteins that primarily control transcription.
Evolution of the TSC1/TSC2-TOR Signaling Pathway
Authors: Serfontein Jaco , Nisbet R. Ellen R. , Howe Christopher J. , de Vries Petrus J.
Published: June 2010

The TSC1/TSC2-TOR signaling pathway evolved from a primitive signaling pathway linking adenosine monophosphate abundance to cell growth.
G Protein Signaling Is Not a Done Deal
Authors: Ray L. Bryan
Published: June 2010

A screen in yeast uncovers new signaling components in the pheromone response pathway.
Aggregator of the Regulator
Authors: Wong Wei
Published: June 2010

In addition to oxidative stress, the transcription factor Nrf2 can also be activated by impaired autophagy.
Bacterial (Interferon)ce
Authors: Hurtley Stella M.
Published: June 2010

Within the host cell, a small secondary signaling molecule from a pathogen triggers a pathway of innate immunity.
Science Signaling
Podcast: 29 June 2010
Authors: Howe Christopher J. , VanHook Annalisa M.
Published: June 2010

Analysis of TOR signaling pathway evolution may shed light on the early divergence of eukaryotic lineages.
Cloning and Occurrence of
czrC
, a Gene Conferring Cadmium and Zinc Resistance in Methicillin-Resistant
Staphylococcus aureus
CC398 Isolates
Authors: Cavaco L. M. , Hasman H. , Stegger M. , Andersen P. S. , Skov R. , Fluit A. C. , Ito T. , Aarestrup F. M.
Published: June 2010

We recently reported a phenotypic association between reduced susceptibility to zinc and methicillin resistance in
Staphylococcus aureus
CC398 isolates from Danish swine (F. M. Aarestrup, L. M. Cavaco, and H. Hasman, Vet. Microbiol.
142:
455-457, 2009). The aim of this study was to identify the genetic determinant causing zinc resistance in CC398 and examine its prevalence in isolates of animal and human origin. Based on the sequence of the staphylococcal cassette chromosome
mec
(SCC
mec
) element from methicillin-resistant
S. aureus
(MRSA) CC398 strain SO385, a putative metal resistance gene was identified in strain 171 and cloned in
S. aureus
RN4220. Furthermore, 81 MRSA and 48 methicillin-susceptible
S. aureus
(MSSA) strains, isolated from pigs (31 and 28) and from humans (50 and 20) in Denmark, were tested for susceptibility to zinc chloride and for the presence of a putative resistance determinant,
czrC
, by PCR. The cloning of
czrC
confirmed that the zinc chloride and cadmium acetate MICs for isogenic constructs carrying this gene were increased compared to those for
S. aureus
RN4220. No difference in susceptibility to sodium arsenate, copper sulfate, or silver nitrate was observed. Seventy-four percent (
n
= 23) of the animal isolates and 48% (
n
= 24) of the human MRSA isolates of CC398 were resistant to zinc chloride and positive for
czrC
. All 48 MSSA strains from both human and pig origins were found to be susceptible to zinc chloride and negative for
czrC
. Our findings showed that
czrC
is encoding zinc and cadmium resistance in CC398 MRSA isolates, and that it is widespread both in humans and animals. Thus, resistance to heavy metals such as zinc and cadmium may play a role in the coselection of methicillin resistance in
S. aureus
.
Association of the Extended-Spectrum β-Lactamase Gene
bla
TLA-1
with a Novel IS
CR
Element, IS
CR20
Authors: Berçot Beatrice , Poirel Laurent , Silva-Sanchez Jesus , Nordmann Patrice
Published: June 2010

The
bla
TLA-1
gene encoding an extended-spectrum β-lactamase was identified in 11 enterobacterial isolates from Mexico City, Mexico. This gene was located on different plasmids and plasmid types with different sizes and incompatibility groups. It was associated with a novel insertion sequence, IS
CR20
, encoding a putative transposase that shared only 20% amino acid identity with the most closely related transposase of IS
CR1
. The IS
CR20
element provided specific promoter sequences for expression of the
bla
TLA-1
gene.
Small-Molecule Screening Using a Whole-Cell Viral Replication Reporter Gene Assay Identifies 2-{[2-(Benzoylamino)Benzoyl]Amino}-Benzoic Acid as a Novel Antiadenoviral Compound
Authors: Andersson Emma K. , Strand Mårten , Edlund Karin , Lindman Kristina , Enquist Per-Anders , Spjut Sara , Allard Annika , Elofsson Mikael , Mei Ya-Fang , Wadell Göran
Published: June 2010

Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their antiadenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential antiadenoviral compounds. The assay is unique in that it is based on a replication-competent adenovirus type 11p green fluorescent protein (GFP)-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expressionin vitroby ≥80%, but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.
Impact of Multidrug-Resistant
Pseudomonas aeruginosa
Bacteremia on Patient Outcomes
Authors: Tam Vincent H. , Rogers Cary A. , Chang Kai-Tai , Weston Jaye S. , Caeiro Juan-Pablo , Garey Kevin W.
Published: June 2010

Trends of rising rates of resistance in
Pseudomonas aeruginosa
make selection of appropriate empirical therapy increasingly difficult, but whether multidrug-resistant (MDR)
P. aeruginosa
is associated with worse clinical outcomes is not well established. The objective of this study was to determine the impact of MDR (resistance to three or more classes of antipseudomonal agents)
P. aeruginosa
bacteremia on patient outcomes. We performed a retrospective cohort study of adult patients with
P. aeruginosa
bacteremia from 2005 to 2008. Patients were identified by the microbiology laboratory database, and pertinent clinical data were collected. Logistic regression was used to explore independent risk factors for 30-day mortality. Classification and regression tree analysis was used to determine threshold breakpoints for continuous variables. Kaplan-Meier survival analysis was used to compare time to mortality, after normalization of the patients' underlying risks by propensity scoring. A total of 109 bacteremia episodes were identified; 25 episodes (22.9%) were caused by MDR
P. aeruginosa
. Patients with MDR
P. aeruginosa
bacteremia were more likely to receive inappropriate empirical therapy (44.0% and 6.0%, respectively;
P
< 0.001) and had longer prior hospital stays (32.6 ± 37.3 and 14.4 ± 43.6 days, respectively;
P
= 0.046). Multivariate regression revealed that 30-day mortality was associated with multidrug resistance (odds ratio [OR], 6.8; 95% confidence interval [CI], 1.9 to 24.0), immunosuppression (OR, 5.0; 95% CI, 1.4 to 17.5), and an APACHE II score of ≥22 (OR, 29.0; 95% CI, 5.0 to 168.2). Time to mortality was also shorter in the MDR cohort (
P
= 0.011). Multidrug resistance is a significant risk factor for 30-day mortality in patients with
P. aeruginosa
bacteremia; efforts to curb the spread of MDR
P. aeruginosa
could be beneficial.
Easy Strategy To Protect Antimicrobial Peptides from Fast Degradation in Serum
Authors: Knappe Daniel , Henklein Petra , Hoffmann Ralf , Hilpert Kai
Published: June 2010

Antimicrobial peptides are promising novel peptide leads, but their low serum stability often limits their further consideration in drug development programs. Here, we describe a generally applicable strategy to stabilize peptides against serum proteases by replacing arginine residues with α-amino-3-guanidino-propionic acid (Agp). Peptide NH
2
-RRWRIVVIRVRR-CONH
2
was nearby totally degraded after 8 h in mouse serum, whereas the variant with Agp substituted was degraded less than 20%. The antimicrobial activity was not affected.
Emergence of Resistance among USA300 Methicillin-Resistant
Staphylococcus aureus
Isolates Causing Invasive Disease in the United States
Authors: McDougal Linda K. , Fosheim Gregory E. , Nicholson Ainsley , Bulens Sandra N. , Limbago Brandi M. , Shearer Julia E. S. , Summers Anne O. , Patel Jean B.
Published: June 2010

USA300 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates are usually resistant only to oxacillin, erythromycin, and, increasingly, levofloxacin. Of these, oxacillin and levofloxacin resistances are chromosomally encoded. Plasmid-mediated clindamycin, mupirocin, and/or tetracycline resistance has been observed among USA300 isolates, but these descriptions were limited to specific patient populations or isolated occurrences. We examined the antimicrobial susceptibilities of invasive MRSA isolates from a national surveillance population in order to identify USA300 isolates with unusual, possibly emerging, plasmid-mediated antimicrobial resistance. DNA from these isolates was assayed for the presence of resistance determinants and the presence of a pSK41-like conjugative plasmid. Of 823 USA300 isolates, 72 (9%) were tetracycline resistant; 69 of these were doxycycline susceptible and
tet
K
positive, and 3 were doxycycline resistant and
tet
M
positive. Fifty-one (6.2%) isolates were clindamycin resistant and
erm
C
positive; 22 (2.7%) isolates were high-level mupirocin resistant (
mup
A
positive); 5 (0.6%) isolates were trimethoprim-sulfamethoxazole (TMP-SMZ) resistant, of which 4 were
dfr
A
positive; and 7 (0.9%) isolates were gentamicin resistant and
aac
6
′-
aph
2
″ positive. Isolates with pSK41-like plasmids (
n
= 24) were positive for
mup
A
(
n
= 19),
dfr
A
(
n
= 6),
aac
6
′-
aph
2
″ (
n
= 6),
tet
M
(
n
= 2), and
erm
C
(
n
= 8); 20 pSK41-positive isolates were positive for two or more resistance genes. Conjugative transfer of resistance was demonstrated between four gentamicin- and mupirocin-resistant and three gentamicin- and TMP-SMZ-resistant USA300 isolates; transconjugants harbored a single pSK41-like plasmid, which was PCR positive for
aac
6
′-
aph
2
″ and either
mup
A
and/or
dfr
A
. USA300 and USA100 isolates from the same state with identical resistance profiles contained pSK41-like plasmids with indistinguishable restriction and Southern blot profiles, suggesting horizontal plasmid transfer between USA100 and USA300 isolates.
In Vitro
Activity of the New Multivalent Glycopeptide-Cephalosporin Antibiotic TD-1792 against Vancomycin-Nonsusceptible
Staphylococcus
Isolates
Authors: Leuthner Kimberly D. , Vidaillac Celine , Cheung Chrissy M. , Rybak Michael J.
Published: June 2010

TD-1792 is a glycopeptide-cephalosporin heterodimer antibiotic with activity against a broad spectrum of Gram-positive pathogens that includes methicillin-susceptible and -resistant
Staphylococcus aureus
. The objective of the present study was to evaluate the
in vitro
activity of TD-1792 against a collection of clinical isolates of vancomycin-intermediate
Staphylococcus
spp. (VISS), heteroresistant VISS (hVISS), and vancomycin-resistant
S. aureus
(VRSA). The TD-1792, vancomycin, daptomycin, linezolid, and quinupristin-dalfopristin MICs and minimum bactericidal concentrations (MBCs) were determined for 50 VISS/hVISS isolates and 3 VRSA isolates. Time-kill experiments (TKs) were then performed over 24 h with two vancomycin-intermediate
S. aureus
strains and two VRSA strains, using each agent at multiples of the MIC. TD-1792 and daptomycin were also evaluated in the presence and absence of 50% human serum to determine the effects of the proteins on their activities. Most of the VISS/hVISS isolates were susceptible to all agents except vancomycin. TD-1792 exhibited the lowest MIC values (MIC
90
= 0.125 μg/ml), followed by quinupristin-dalfopristin and daptomycin (MIC
90
= 1 μg/ml) and then linezolid (MIC
90
= 2 μg/ml). The presence of serum resulted in a 2- to 8-fold increase in the TD-1792 and daptomycin MIC values. In TKs, QD demonstrated bactericidal activity at multiples of the MIC that simulated therapeutic levels, whereas linezolid was only bacteriostatic. Both TD-1792 and daptomycin demonstrated rapid bactericidal activities against all isolates tested. The presence of proteins had only a minimal impact on the activity of TD-1792 in TKs. TD-1792 exhibited significant
in vitro
activity against multidrug-resistant
Staphylococcus
isolates and represents a promising candidate for the treatment of infections caused by Gram-positive organisms.