bluuebunny/crossref_metadata_2025 huggingface dataset:
Injury of the Spino-Thalamo-Cortical Pathway Is Necessary for Central Post-Stroke Pain
Authors: Hong Ji Heon , Bai Dai Seg , Jeong Jin Young , Choi Byung Yun , Chang Chul Hoon , Kim Seong Ho , Ahn Sang Ho , Jang Sung Ho
Published: August 2010

Objectives: We investigated the relationship between injury of the spino-thalamo-cortical pathway (STP) and central post-stroke pain (CPSP) in patients with intracerebral hemorrhage, using diffusion tensor tractography (DTT). Methods: 30 consecutive chronic patients, in whom integrity of the STP and the medial lemnisco-thalamo-cortical pathway (MLP) were spared in both hemispheres, were recruited. We classified the patients into two groups according to the presence of the CPSP. DTTs were obtained using the FMRIB Software Library. Fractional anisotropy (FA), mean diffusivity (MD), and tract volume were measured. A laterality index (LI) was used to determine asymmetry of DTT parameters between the hemispheres. Results: The LI for tract volume of the STP in the CPSP group was lower than that of the non-CPSP group (p = 0.000). However, there were no differences between the CPSP group and non-CPSP group for the LIs of FA or MD of the STP or for the LIs of FA, MD, or tract volume of the MLP (p > 0.05). Conclusions: Decrease of tract volume without changes in the STP FA or MD values in the CPSP group indicates partial injury of STP. Therefore, injury of the STP seems to be a requirement for the development of CPSP in patients with intracerebral hemorrhage.
Complex Interactions Between the Sinoatrial Node and Atrium During Reentrant Arrhythmias in the Canine Heart
Authors: Fedorov Vadim V. , Chang Roger , Glukhov Alexey V. , Kostecki Geran , Janks Deborah , Schuessler Richard B. , Efimov Igor R.
Published: August 2010

Background—

Numerous studies implicate the sinoatrial node (SAN) as a participant in atrial arrhythmias, including atrial flutter (AFL) and atrial fibrillation (AF). However, the direct role of the SAN has never been described.

Methods and Results—

The SAN was optically mapped in coronary perfused preparations from normal canine hearts (n=17). Optical action potentials were recorded during spontaneous rhythm, overdrive atrial pacing, and AF/AFL induced by acetylcholine (ACh; 0.3 to 3 μmol/L) and/or isoproterenol (Iso; 0.2 to 1 μmol/L). An optical action potential multiple component algorithm and dominant frequency analysis were used to reconstruct SAN activation and to identify specialized sinoatrial conduction pathways. Both ACh and Iso facilitated pacing-induced AF/AFL by shortening atrial repolarization. The entire SAN structure created a substrate for macroreentry with 9.6±1.7 Hz (69 episodes in all preparations). Atrial excitation waves could enter the SAN through the sinoatrial conduction pathways and overdrive suppress the node. The sinoatrial conduction pathways acted as a filter for atrial waves by slowing conduction and creating entrance block. ACh/Iso modulated filtering properties of the sinoatrial conduction pathways by increasing/decreasing the degree of the entrance block, respectively. Thus, the SAN could beat independently from AF/AFL reentrant activity during ACh (49±39%) and ACh/Iso (62±25%) (
P
=0.38). Without ACh, the AF/AFL waves captured the SAN and overdrive suppressed it. Spontaneous SAN activity could terminate or convert AFL to AF during cholinergic withdrawal.

Conclusions—

The specialized structure of the SAN can be a substrate for AF/AFL. Cholinergic stimulation not only can slow sinus rhythm and facilitate AF/AFL but also protects the intrinsic SAN function from the fast AF/AFL rhythm.
Tumor Necrosis Factor-α Antagonist Etanercept Decreases Blood Pressure and Protects the Kidney in a Mouse Model of Systemic Lupus Erythematosus
Authors: Venegas-Pont Marcia , Manigrasso Michaele B. , Grifoni Samira C. , LaMarca Babbette B. , Maric Christine , Racusen Lorraine C. , Glover Porter H. , Jones Allison V. , Drummond Heather A. , Ryan Michael J.
Published: August 2010

Chronic inflammation has been implicated in the pathology of hypertension; however, the role for specific cytokines remains unclear. We tested whether tumor necrosis factor-α blockade with etanercept (Etan) reduces mean arterial pressure in a female mouse model of systemic lupus erythematosus (SLE). SLE is a chronic inflammatory disorder with prevalent hypertension. Thirty-week–old SLE (NZBWF1) and control mice (NZW/LacJ) received Etan (0.8 mg/kg SC weekly) for 4 weeks or vehicle. Mean arterial pressure (in millimeters of mercury) was increased in SLE mice (150±5 versus 113±5 in controls;
P
<0.05) and was lower in Etan-treated SLE mice (132±3) but not controls (117±5). Albuminuria (in micrograms per milligram of creatinine) was elevated in SLE mice (28 742±9032 versus 1075±883;
P
<0.05) and was lower in Etan-treated SLE mice (8154±3899) but not control animals (783±226). Glomerulosclerosis (in percentage of glomeruli) was evident in SLE mice (2.5±1.6 versus 0.0±0.0 in controls;
P
<0.05) and was ameliorated in Etan-treated SLE mice (0.1±0.1). Renal cortex CD68
+
cell staining (in percentage of area) was elevated in SLE mice (4.75±0.80 versus 0.79±0.12 in controls;
P
<0.05) and was lower in Etan-treated SLE mice (2.28±0.32) but not controls (1.43±0.25). Renal cortex NADPH oxidase activity (relative light units per milligram of protein) was higher in SLE mice compared with controls (10 718±1276 versus 7584±229;
P
<0.05) and lowered in Etan-treated SLE mice (6645±490). Renal cortex nuclear factor κB (phosphorylated and nonphosphorylated) was increased in SLE mice compared with controls and lower in Etan-treated SLE mice. These data suggest that TNF-α mechanistically contributes to the development of hypertension in a chronic inflammatory disease through increased renal nuclear factor κB, oxidative stress, and inflammation.
Tornadoes and Tornadic Storms
Authors: Davies-Jones Robert , Trapp R. Jeffrey , Bluestein Howard B.
Published: August 2010

No Abstract available.
Convectively Driven High Wind Events
Authors: Wakimoto Roger M.
Published: August 2010

No Abstract available.
Perspectives on Fred Sanders' Research on Cold Fronts
Authors: Schultz David M.
Published: August 2010

One characteristic of Fred Sanders' research is his ability to take a topic that is believed to be well understood by the research community and show that interesting research problems still exist. Among Sanders' considerable contributions to synoptic meteorology, those concerned with surface cold fronts have been especially influential. After a brief historical review of fronts and frontal analysis, this chapter presents three stages in Sanders' career when he performed research on the structure, dynamics, and analysis of surface cold fronts. First, his 1955 paper, "An investigation of the structure and dynamics of an intense surface frontal zone," was the first study to discuss quantitatively the dynamics of a surface cold front. In the 1960s, Sanders and his students further examined the structure of cold fronts, resulting in the unpublished 1967 report to the National Science Foundation, "Frontal structure and the dynamics of frontogenesis." For a third lime in his career, Sanders published several papers (1995–2005) revisiting the structure and dynamics of cold fronts. His 1967 and 1995–2005 work raises the question of the origin and dynamics of the surface pressure trough and/or wind shift that sometimes precedes the temperature gradient (hereafter called a prefrontal trough or prefrontal wind shift, respectively). Sanders showed that the relationship between this prefrontal feature and the temperature gradient is fundamental to the strength of the front. When the wind shift is coincident with the temperature gradient, frontogenesis (strengthening of the front) results; when the wind shift lies ahead of the temperature gradient, frontolysis (weakening of the front) results. a number of proposed mechanisms for the formation of prefrontal troughs and prefrontal wind shifts exist. Consequently, much research remains to be performed on these topics.
The Application of Fred Sanders' Teaching to Current Research on Extreme Cold-Season Precipitation Events in the Saint Lawrence River Valley Region
Authors: Gyakum John R.
Published: August 2010

Fred Sanders' teaching and research contributions in the area of quasigeostrophic theory are highlighted in this paper. The application of these contributions is made to the topic of extreme cold-season precipitation events in the Saint Lawrence valley in the northeastern United States and southern Quebec.

This research focuses on analyses of Saint Lawrence valley heavy precipitation events. Synoptic- and planetary-scale circulation anomaly precursors are typically identified several days prior to these events. These precursors include transient upper-level troughs, strong moisture transports into the region, and anomalously large precipitable water amounts. The physical insight of Fred Sanders' work is used in the analysis of these composite results. Further details of this insight are provided in analyses of one case of heavy precipitation.
Back to Norway: An Essay
Authors: Emanuel Kerry
Published: August 2010

The advent of the polar front theory of cyclones in Norway early in the last century held that the development of fronts and air masses is central to understanding midlatitude weather phenomena. While work on fronts continues to this day, the concept of air masses has been largely forgotten, superseded by the idea of a continuum. The Norwegians placed equal emphasis on the thermodynamics of airmass formation and on the dynamical processes that moved air masses around; today, almost all the emphasis is on dynamics, with little published literature on diabatic processes acting on a large scale. In this essay, the author argues that a lack of understanding of large-scale diabatic processes leads to an incomplete picture of the atmosphere and contributes to systematic errors in medium- and long-range weather forecasts. At the same time, modern concepts centered around potential vorticity conservation and inversion lead one to a redefinition of the term "air mass" that may have some utility in conceptualizing atmospheric physics and in weather forecasting.
Carboxymethyl chitosan coating to block photocatalytic activity of TiO2 nanoparticles
Authors: Xianqiong Chen  , Yuyang Liu  , Haifeng Shi  , Xiaowen Wang  , Kaihong Qi  , Xiang Zhou  , Xin John H
Published: August 2010

In order to lower photocatalytic degradation of TiO2 on skin and textiles, carboxymethyl chitosan (CMCH) was used to coat TiO2 nanoparticles. The polymer (CMCH) not only acted as the blocking agent of photocatalytic activity, but also dispersed TiO2 nanoparticles better to prohibit them from congregation by anchoring them. The structure of as-prepared nanocomposites was characterized by scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM). The TiO2/CMCH nanocomposites were coated onto cotton fabrics by a dip-pad—drycure process. The treated cotton fabrics demonstrated lower photocatalytic activity in comparison to cotton fabrics treated by pure TiO2 in a typical photocatalytic test. The treated cotton showed a combination of bactericidal activity of TiO2 and CMCH, and excellent protection against UV radiation.
Is familial lupus different from sporadic lupus? Data from LUMINA (LXXIII), a multiethnic US cohort
Authors: Burgos PI , McGwin G. , Reveille JD , Vilá LM , Brown EE , Alarcon GS
Published: August 2010

The aim of this study was to characterize the clinical features of familial lupus, and determine its influence on damage accrual and survival using data from LUMINA, a longitudinal multiethnic US cohort. Familial lupus was defined as patients with a first-degree relative with systemic lupus erythematosus. Relative risks were estimated by logistic regression; odds ratios (ORs) and their 95% confidence intervals (CIs) were the measure of association for familial lupus. Hazard ratios were calculated using Cox proportional hazards adjusted for potential confounders for damage and survival. Of 644 patients, 32 had familial and 612 had sporadic lupus; both groups were of comparable age (~36 years). Patients with familial lupus were, in decreasing order of frequency, siblings, parents and children. In multivariable analyses, mucosal ulcers (OR = 1.92, 95% CI 0.65—5.70), mitral valve prolapse (OR = 1.74, 95% CI 0.50—6.10), cerebrovascular disease (OR = 4.18, 95% CI 0.98—17.76) and oral contraceptive use (ever/never; OR = 2.51, 95% CI 0.88—7.19) were more likely in familial lupus, but a history of low platelet count (<150,000/mm3; OR=0.31, 95% CI 0.08—1.17) and pulmonary disease activity (OR=0.39, 95% CI 0.14—1.20) were less likely. However, none of these associations reached statistical significance. Familial lupus was not significantly associated with a shorter time to either damage accrual or death (HR = 0.77, 95% CI 0.37—1.59, p = 0.4746 and HR = 0.20, 95% CI 0.03—1.47, p = 0.2020, respectively). We conclude that although some clinical differences were observed between patients with familial and sporadic lupus, familial lupus was not associated with a significantly greater disease burden (damage, survival) than sporadic lupus. Lupus (2010) 19, 1331—1336.
Petri Net-based Coordination Component for Collaborative Design
Authors: Huang Hong-Zhong , Xu Huan-Wei , Xu Zu
Published: August 2010

Considering the lack of efficient coordination of task interdependencies in a collaborative design system, the temporal and resource coordination mechanisms for the problems in our investigation are established based on Petri Nets. The whole system could be expanded as a Petri Net for simulation and analysis. The architecture of reusable and pluggable components is also introduced to implement such mechanisms. The proposed approach offers strong support for the performance evaluation of the collaborative design.
Functional characterization of a 13-bp deletion (c.-1522_-1510del13) in the promoter of the von Willebrand factor gene in type 1 von Willebrand disease
Authors: Othman Maha , Chirinian Yvette , Brown Christine , Notley Colleen , Hickson Nicholas , Hampshire Daniel , Buckley Suzanne , Waddington Simon , Parker Alan L. , Baker Andrew , James Paula , Lillicrap David
Published: August 2010

We have studied the effect of a 13-bp deletion in the promoter of the von Willebrand factor (VWF) gene in a patient with type 1 von Willebrand disease. The index case has a VWF:Ag of 0.49 IU/mL and is heterozygous for the deletion. The deletion is located 48 bp 5′ of the transcription start site, and in silico analysis, electrophoretic mobility shift assays, and chromatin immunoprecipitation studies all predict aberrant binding of Ets transcription factors to the site of the deletion. Transduction of reporter gene constructs into blood outgrowth endothelial cells showed a 50.5% reduction in expression with the mutant promoter (n = 16, P < .001). A similar 40% loss of transactivation was documented in transduced HepG2 cells. A similar marked reduction of transgene expression was shown in the livers of mice injected with the mutant promoter construct (n = 8, P = .003). Finally, in studies of BOEC mRNA, the index case showed a 4.6-fold reduction of expression of the VWF transcript associated with the deletion mutation. These studies show that the 13-bp deletion mutation alters the binding of Ets (and possibly GATA) proteins to the VWF promoter and significantly reduces VWF expression, thus playing a central pathogenic role in the type 1 von Willebrand disease phenotype in the index case.
When Toll-like receptor and T-cell receptor signals collide: a mechanism for enhanced CD8 T-cell effector function
Authors: Geng Degui , Zheng Liqin , Srivastava Ratika , Asprodites Nicole , Velasco-Gonzalez Cruz , Davila Eduardo
Published: August 2010

Emerging reports reveal that activating Toll-like receptor-2 (TLR2)–MyD88 signals in CD8 T lymphocytes enhances cytokine production and cytotoxicity; however, the signaling pathway remains undefined. In the present study, we examined the physiologic significance and molecular mechanisms involved in this process. We found that TLR2 engagement on T-cell receptor transgenic CD8 OT-1 T cells increased T-bet transcription factor levels consequently, augmenting effector transcript and protein levels both in vivo and in vitro. In contrast, TLR2 agonist did not costimulate TLR2−/−OT-1 or MyD88−/−OT-1 T cells. Elevated T-bet levels in TLR2-MyD88–activated T cells was a consequence of increased biosynthesis resulting from the enhanced acti- vation of the mammalian target of the rapamycin (mTOR) pathway. Inhibiting mTOR, Akt, or protein kinase C in T cells abolished the costimulatory effects of the TLR2 agonist. In vivo, activating TLR2–MyD88 signals in T cells increased effector-molecule levels and enhanced the clearance of Listeria monocytogenes-Ova. These results help define a signaling pathway linking the TLR-MyD88 and mTOR pathway in an Akt- and protein kinase C–dependent manner. These results highlight a critical role for MyD88 signaling in T-cell activation and cytotoxicity. Furthermore, these findings offer the opportunity for improving the efficacy of vaccines and T cell–based immunotherapies by targeting TLR-MyD88 signaling within T cells.
Beyond co-localization: inferring spatial interactions between sub-cellular structures from microscopy images
Authors: Helmuth Jo A , Paul Grégory , Sbalzarini Ivo F
Published: August 2010

Background

Sub-cellular structures interact in numerous direct and indirect ways in order to fulfill cellular functions. While direct molecular interactions crucially depend on spatial proximity, other interactions typically result in spatial correlations between the interacting structures. Such correlations are the target of microscopy-based co-localization analysis, which can provide hints of potential interactions. Two complementary approaches to co-localization analysis can be distinguished: intensity correlation methods capitalize on pattern discovery, whereas object-based methods emphasize detection power.

Results

We first reinvestigate the classical co-localization measure in the context of spatial point pattern analysis. This allows us to unravel the set of implicit assumptions inherent to this measure and to identify potential confounding factors commonly ignored. We generalize object-based co-localization analysis to a statistical framework involving spatial point processes. In this framework, interactions are understood as position co-dependencies in the observed localization patterns. The framework is based on a model of effective pairwise interaction potentials and the specification of a null hypothesis for the expected pattern in the absence of interaction. Inferred interaction potentials thus reflect all significant effects that are not explained by the null hypothesis. Our model enables the use of a wealth of well-known statistical methods for analyzing experimental data, as demonstrated on synthetic data and in a case study considering virus entry into live cells. We show that the classical co-localization measure typically under-exploits the information contained in our data.

Conclusions

We establish a connection between co-localization and spatial interaction of sub-cellular structures by formulating the object-based interaction analysis problem in a spatial statistics framework based on nearest-neighbor distance distributions. We provide generic procedures for inferring interaction strengths and quantifying their relative statistical significance from sets of discrete objects as provided by image analysis methods. Within our framework, an interaction potential can either refer to a phenomenological or a mechanistic model of a physico-chemical interaction process. This increased flexibility in designing and testing different hypothetical interaction models can be used to quantify the parameters of a specific interaction model or may catalyze the discovery of functional relations.
Microarray meta-analysis database (M2DB): a uniformly pre-processed, quality controlled, and manually curated human clinical microarray database
Authors: Cheng Wei-Chung , Tsai Min-Lung , Chang Cheng-Wei , Huang Ching-Lung , Chen Chaang-Ray , Shu Wun-Yi , Lee Yun-Shien , Wang Tzu-Hao , Hong Ji-Hong , Li Chia-Yang , Hsu Ian C
Published: August 2010

Background

Over the past decade, gene expression microarray studies have greatly expanded our knowledge of genetic mechanisms of human diseases. Meta-analysis of substantial amounts of accumulated data, by integrating valuable information from multiple studies, is becoming more important in microarray research. However, collecting data of special interest from public microarray repositories often present major practical problems. Moreover, including low-quality data may significantly reduce meta-analysis efficiency.

Results

M2DB is a human curated microarray database designed for easy querying, based on clinical information and for interactive retrieval of either raw or uniformly pre-processed data, along with a set of quality-control metrics. The database contains more than 10,000 previously published Affymetrix GeneChip arrays, performed using human clinical specimens. M2DB allows online querying according to a flexible combination of five clinical annotations describing disease state and sampling location. These annotations were manually curated by controlled vocabularies, based on information obtained from GEO, ArrayExpress, and published papers. For array-based assessment control, the online query provides sets of QC metrics, generated using three available QC algorithms. Arrays with poor data quality can easily be excluded from the query interface. The query provides values from two algorithms for gene-based filtering, and raw data and three kinds of pre-processed data for downloading.

Conclusion

M2DB utilizes a user-friendly interface for QC parameters, sample clinical annotations, and data formats to help users obtain clinical metadata. This database provides a lower entry threshold and an integrated process of meta-analysis. We hope that this research will promote further evolution of microarray meta-analysis.
RNA Interference inhibits Hepatitis B Virus of different genotypes in Vitro and in Vivo
Authors: Zhang Ya-Li , Cheng Tong , Cai Yi-Jun , Yuan Quan , Liu Che , Zhang Tao , Xia De-Zhen , Li Rui-Yin , Yang Lian-Wei , Wang Ying-Bin , Yeo Anthony ET , Shih James Wai-Kuo , Zhang Jun , Xia Ning-shao
Published: August 2010

Background

Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) can be a potential new tool for HBV therapy. Given the high heterogeneity of HBV strains and the sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor against the conservative site on the HBV genome is essential to ensure a therapeutic application.

Results

Forty short hairpin RNA (shRNA) expression plasmids were constructed to target conserved regions among nine HBV genotypes. HBV 1.3-fold genome plasmids carrying various genotypes were co-transfected with shRNA plasmids into either Huh7 cells or mice. The levels of various viral markers were examined to assess the anti-HBV efficacy of siRNA. Four (B245, B376, B1581 and B1789) were found with the ability to potently inhibit HBV RNA, DNA, surface antigen (HBsAg), e antigen (HBeAg) and core antigen (HBcAg) expression in HBV genotypes A, B, C, D and I (a newly identified genotype) in Huh7 cells and in mice. No unusual cytotoxicity or off-target effects were noted.

Conclusions

Such siRNA suggests an alternate way of inhibiting various HBV genotypes in vitro and in vivo, promising advances in the treatment of HBV.
The clinical Pseudomonas fluorescens MFN1032 strain exerts a cytotoxic effect on epithelial intestinal cells and induces Interleukin-8 via the AP-1 signaling pathway
Authors: Madi Amar , Lakhdari Omar , Blottière Hervé M , Guyard-Nicodème Muriel , Le Roux Karine , Groboillot Anne , Svinareff Pascal , Doré Joel , Orange Nicole , Feuilloley Marc GJ , Connil Nathalie
Published: August 2010

Background

Pseudomonas fluorescensis present in low number in the intestinal lumen and has been proposed to play a role in Crohn's disease (CD). Indeed, a highly specific antigen, I2, has been detected in CD patients and correlated to the severity of the disease. We aimed to determine whetherP. fluorescenswas able to adhere to human intestinal epithelial cells (IECs), induce cytotoxicity and activate a proinflammatory response.

Results

Behaviour of the clinical strainP. fluorescensMFN1032 was compared to that of the psychrotrophic strainP. fluorescensMF37 and the opportunistic pathogenP. aeruginosaPAO1. Both strains ofP. fluorescenswere found to adhere on Caco-2/TC7 and HT-29 cells. Their cytotoxicity towards these two cell lines determined by LDH release assays was dose-dependent and higher for the clinical strain MFN1032 than for MF37 but lower thanP. aeruginosaPAO1. The two strains ofP. fluorescensalso induced IL-8 secretion by Caco-2/TC7 and HT-29 cellsviathe AP-1 signaling pathway whereasP. aeruginosaPAO1 potentially used the NF-κB pathway.

Conclusions

The present work shows, for the first time, thatP. fluorescensMFN1032 is able to adhere to IECs, exert cytotoxic effects and induce a proinflammatory reaction. Our results are consistent with a possible contribution ofP. fluorescensin CD and could explain the presence of specific antibodies against this bacterium in the blood of patients.
When decisions of others matter to me: an electrophysiological analysis
Authors: Marco-Pallarés Josep , Krämer Ulrike M , Strehl Saskia , Schröder Andrea , Münte Thomas F
Published: August 2010

Background

Actions of others may have immediate consequences for oneself. We probed the neural responses associated with the observation of another person's action using event-related potentials in a modified gambling task. In this task a "performer" bet either a higher or lower number and could win or lose this amount. Three different groups of "observers" were also studied. The first (neutral) group simply observed the performer's action, which had no consequences for the observers. In the second (parallel) group, wins/losses of the performer were paralleled by similar wins and losses by the observer. In the third (reverse) group, wins of the performer led to a loss of the observer and vice versa.

Results

ERPs of the performers showed a mediofrontal feedback related negativity (FRN) to losses. The neutral and parallel observer groups did similarly show an FRN response to the performer's losses with a topography indistinguishable from that seen in the performers. In the reverse group, however, the FRN occurred for wins of the performer which translated to losses for the observer.

Conclusions

Taking into account previous experiments, we suggest that the FRN response in observers is driven by two evaluative processes (a) related to the benefit/loss for oneself and (b) related to the benefit/loss of another person.
Multi-agent modeling of the South Korean avian influenza epidemic
Authors: Kim Taehyong , Hwang Woochang , Zhang Aidong , Sen Surajit , Ramanathan Murali
Published: August 2010

Background

Several highly pathogenic avian influenza (AI) outbreaks have been reported over the past decade. South Korea recently faced AI outbreaks whose economic impact was estimated to be 6.3 billion dollars, equivalent to nearly 50% of the profit generated by the poultry-related industries in 2008. In addition, AI is threatening to cause a human pandemic of potentially devastating proportions. Several studies show that a stochastic simulation model can be used to plan an efficient containment strategy on an emerging influenza. Efficient control of AI outbreaks based on such simulation studies could be an important strategy in minimizing its adverse economic and public health impacts.

Methods

We constructed a spatio-temporal multi-agent model of chickens and ducks in poultry farms in South Korea. The spatial domain, comprised of 76 (37.5 km × 37.5 km) unit squares, approximated the size and scale of South Korea. In this spatial domain, we introduced 3,039 poultry flocks (corresponding to 2,231 flocks of chickens and 808 flocks of ducks) whose spatial distribution was proportional to the number of birds in each province. The model parameterizes the properties and dynamic behaviors of birds in poultry farms and quarantine plans and included infection probability, incubation period, interactions among birds, and quarantine region.

Results

We conducted sensitivity analysis for the different parameters in the model. Our study shows that the quarantine plan with well-chosen values of parameters is critical for minimize loss of poultry flocks in an AI outbreak. Specifically, the aggressive culling plan of infected poultry farms over 18.75 km radius range is unlikely to be effective, resulting in higher fractions of unnecessarily culled poultry flocks and the weak culling plan is also unlikely to be effective, resulting in higher fractions of infected poultry flocks.

Conclusions

Our results show that a prepared response with targeted quarantine protocols would have a high probability of containing the disease. The containment plan with an aggressive culling plan is not necessarily efficient, causing a higher fraction of unnecessarily culled poultry farms. Instead, it is necessary to balance culling with other important factors involved in AI spreading. Better estimations for the containment of AI spreading with this model offer the potential to reduce the loss of poultry and minimize economic impact on the poultry industry.
TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients
Authors: Wang Chao , Cao Shouqiang , Yan Ying , Ying Qiao , Jiang Tao , Xu Ke , Wu Anhua
Published: August 2010

Background

Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cellsin vitro.

Methods

RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cellsin vitrowith MTT assays and matrigel transwell assay respectively.

Results

RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients(P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasionin vitro.

Conclusions

Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy.
Prognostic significance of lymphangiogenesis in pharyngolaryngeal carcinoma patients
Authors: Garcia-Carracedo Darío , Rodrigo Juan Pablo , Astudillo Aurora , Nieto Carlos Suarez , Gonzalez Maria Victoria
Published: August 2010

Background

Lymphatic vessel spread is considered a major route for head and neck squamous cell carcinoma metastasis. Formation of new lymphatic vessels could facilitate the process, raising the malignant potential of these tumours. Recent identification of lymphatic markers allows the study of the lymphangiogenesis phenomenon. We searched for molecular events involved in the lymphangiogenic process that could have prognostic value in laryngeal/pharyngeal carcinoma patients.

Methods

104 paraffin-embedded pharyngeal/laryngeal tumour samples were studied. Immunohistochemical analysis of podoplanin and double immunofluorescence analysis of Ki-67 and D2-40 were performed. Lymph vessel density (inside the tumour mass, at its periphery or considered as a whole) and the presence of tumour emboli inside lymphatics were recorded. The proliferative state of endothelial lymphatic cells was evaluated.

Results

Lymphatic vessels were detected inside the tumour mass (75%) and in the surrounding tissue (80%); some of them in a proliferative state. Tumour emboli were detected in a high proportion of the cases (45%). Lymphatic vessel density was higher in the pharyngeal cases (p = 0.0029), in greater size (p = 0.039), more advanced stage primary tumours (p = 0.006) and in carcinomas of patients with affected nodes (p = 0.019). The presence of tumour emboli and a high global vessel density were indicators of poor prognosis (recorded as death from tumour) in the laryngeal group (p = 0.015 and p = 0.027, respectively), but notably not in the pharyngeal one. Interestingly, high global vessel density showed a negative prognostic value among pathologically staged N0 laryngeal carcinomas (p = 0.03).

Conclusions

The lymphangiogenic process correlated with aggressive tumour features (pN category, tumour size, tumour stage), but might play different roles in tumours arising from different anatomic sites.

Our results suggest that detection of tumour emboli and assessment of global vessel density using the D2-40 antibody, may be useful in the clinical practice, as predictors of reduced survival among pN0 laryngeal carcinoma patients.
Moisture-induced solid state instabilities in α-chymotrypsin and their reduction through chemical glycosylation
Authors: Flores-Fernández Giselle M , Pagán Miraida , Almenas Mariangely , Solá Ricardo J , Griebenow Kai
Published: August 2010

Background

Protein instability remains the main factor limiting the development of protein therapeutics. The fragile nature (structurally and chemically) of proteins makes them susceptible to detrimental events during processing, storage, and delivery. To overcome this, proteins are often formulated in the solid-state which combines superior stability properties with reduced operational costs. Nevertheless, solid protein pharmaceuticals can also suffer from instability problems due to moisture sorption. Chemical protein glycosylation has evolved into an important tool to overcome several instability issues associated with proteins. Herein, we employed chemical glycosylation to stabilize a solid-state protein formulation against moisture-induced deterioration in the lyophilized state.

Results

First, we investigated the consequences of moisture sorption on the stability and structural conformation of the model enzyme α-chymotrypsin (α-CT) under controlled humidity conditions. Results showed that α-CT aggregates and inactivates as a function of increased relative humidity (RH). Furthermore, α-CT loses its native secondary and tertiary structure rapidly at increasing RH. In addition, H/D exchange studies revealed that α-CT structural dynamics increased at increasing RH. The magnitude of the structural changes in tendency parallels the solid-state instability data (i.e., formation of buffer-insoluble aggregates, inactivation, and loss of native conformation upon reconstitution). To determine if these moisture-induced instability issues could be ameliorated by chemical glycosylation we proceeded to modify our model protein with chemically activated glycans of differing lengths (lactose and dextran (10 kDa)). The various glycoconjugates showed a marked decrease in aggregation and an increase in residual activity after incubation. These stabilization effects were found to be independent of the glycan size.

Conclusion

Water sorption leads to aggregation, inactivation, and structural changes of α-CT as has been similarly shown to occur for many other proteins. These instabilities correlate with an increase in protein structural dynamics as a result of moisture exposure. In this work, we present a novel methodology to stabilize proteins against structural perturbations in the solid-state since chemical glycosylation was effective in decreasing and/or preventing the traditionally observed moisture-induced aggregation and inactivation. It is suggested that the stabilization provided by these chemically attached glycans comes from the steric hindrance that the sugars conveys on the protein surface therefore preventing the interaction of the protein internal electrostatics with that of the water molecules and thus reducing the protein structural dynamics upon moisture exposure.
In silico evaluation of a control system and algorithm for automated insulin infusion in the ICU setting
Authors: Ortiz José L , Guarini Marcelo W , Borzone Gisella R , Olmos Pablo R
Published: August 2010

Background

It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions.

Methods

The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions.

Results

The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors.

Conclusions

When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.
Leukocyte oxygen radical production determines disease severity in the recurrent Guillain-Barré syndrome
Authors: Mossberg Natalia , Andersen Oluf , Nordin Magnus , Nilsson Staffan , Svedhem Åke , Bergström Tomas , Hellstrand Kristoffer , Movitz Charlotta
Published: August 2010

Background

The recurrent Guillain-Barré syndrome (RGBS) is characterized by at least two GBS episodes with intervening remission. In a previous study of monophasic GBS, we reported that the magnitude of oxygen radical production ("respiratory burst") in peripheral blood leukocytes was inversely correlated to disease severity. The present study sought to establish a similar correlation in patients with RGBS.

Methods

Oxygen radical production in leukocytes was induced by formyl-Met-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val-Met-NH2(WKYMVM), or phorbol myristate acetate (PMA) and assessed by quantifying superoxide anion formed by the leukocyte NADPH oxidase.

Results

Disease severity, assessed using the MRC score, was negatively correlated to superoxide anion production triggered by fMLF or WKYMVM (p = 0.001 and 0.002, respectively; n = 10). Superoxide anion production also was significantly lower in RGBS patients with incomplete recovery after stimulation with fMLF (p = 0.004) or WKYMVM (p = 0.003).

Conclusion

We conclude that a lower respiratory burst in leukocytes is strongly associated with a severe course of RGBS.
A novel cell-free mitochondrial fusion assay amenable for high-throughput screenings of fusion modulators
Authors: Schauss Astrid C , Huang Huiyan , Choi Seok-Yong , Xu Liqun , Soubeyrand Sébastien , Bilodeau Patricia , Zunino Rodolfo , Rippstein Peter , Frohman Michael A , McBride Heidi M
Published: August 2010

Background

Mitochondria are highly dynamic organelles whose morphology and position within the cell is tightly coupled to metabolic function. There is a limited list of essential proteins that regulate mitochondrial morphology and the mechanisms that govern mitochondrial dynamics are poorly understood. However, recent evidence indicates that the core machinery that governs mitochondrial dynamics is linked within complex intracellular signalling cascades, including apoptotic pathways, cell cycle transitions and nuclear factor kappa B activation. Given the emerging importance of mitochondrial plasticity in cell signalling pathways and metabolism, it is essential that we develop tools to quantitatively analyse the processes of fission and fusion. In terms of mitochondrial fusion, the field currently relies upon on semi-quantitative assays which, even under optimal conditions, are labour-intensive, low-throughput and require complex imaging techniques.

Results

In order to overcome these technical limitations, we have developed a new, highly quantitative cell-free assay for mitochondrial fusion in mammalian cells. This assay system has allowed us to establish the energetic requirements for mitochondrial fusion. In addition, our data reveal a dependence on active protein phosphorylation for mitochondrial fusion, confirming emerging evidence that mitochondrial fusion is tightly integrated within the global cellular response to signaling events. Indeed, we have shown that cytosol derived from cells stimulated with different triggers either enhance or inhibit the cell-free fusion reaction.

Conclusions

The adaptation of this system to high-throughput analysis will provide an unprecedented opportunity to identify and characterize novel regulatory factors. In addition, it provides a framework for a detailed mechanistic analysis of the process of mitochondrial fusion and the various axis of regulation that impinge upon this process in a wide range of cellular conditions.

See Commentary: http://www.biomedcentral.com/1741-7007/8/99
Molecular characterization of partial fusion gene and C-terminus extension length of haemagglutinin-neuraminidase gene of recently isolated Newcastle disease virus isolates in Malaysia
Authors: Berhanu Ayalew , Ideris Aini , Omar Abdul R , Bejo Mohd Hair
Published: August 2010

Background

Newcastle disease (ND), caused by Newcastle disease virus (NDV), is a highly contagious disease of birds and has been one of the major causes of economic losses in the poultry industry. Despite routine vaccination programs, sporadic cases have occasionally occurred in the country and remain a constant threat to commercial poultry. Hence, the present study was aimed to characterize NDV isolates obtained from clinical cases in various locations of Malaysia between 2004 and 2007 based on sequence and phylogenetic analysis of partial F gene and C-terminus extension length of HN gene.

Results

The coding region of eleven NDV isolates fusion (F) gene and carboxyl terminal region of haemagglutinin-neuraminidase (HN) gene including extensions were amplified by reverse transcriptase PCR and directly sequenced. All the isolates have shown to have non-synonymous to synonymous base substitution rate ranging between 0.081 - 0.264 demonstrating presence of negative selection. Analysis based on F gene showed the characterized isolates possess three different types of protease cleavage site motifs; namely 112RRQKRF117, 112RRRKRF117 and 112GRQGRL117 and appear to show maximum identities with isolates in the region such as cockatoo/14698/90 (Indonesia), Ch/2000 (China), local isolate AF2240 indicating the high similarity of isolates circulating in the South East Asian countries. Meanwhile, one of the isolates resembles commonly used lentogenic vaccine strains. On further characterization of the HN gene, Malaysian isolates had C-terminus extensions of 0, 6 and 11 amino acids. Analysis of the phylogenetic tree revealed that the existence of three genetic groups; namely, genotype II, VII and VIII.

Conclusions

The study concluded that the occurrence of three types of NDV genotypes and presence of varied carboxyl terminus extension lengths among Malaysian isolates incriminated for sporadic cases.
Anti-HCV reactive volunteer blood donors distribution character and genotypes switch in Xi'an, China
Authors: Yue Qiao-hong , Zhang Xian-qing , Shang Yu , Chen Yao-zhen , Sun Wen-li , Su Min-quan , Mu Shi-jie , Hao Xiao-ke , Hu Xing-bin
Published: August 2010

HCV is prevailed in the world as well as in China. Blood transfusion is one of the most common transmission pathways of this pathogen. Although data of HCV infection character were reported during the past years, anti-HCV reactive profile of China donors was not fully clear yet. Furthermore, infection progress was found related to the HCV genotype. Different genotype led to different efficacy when interferon was introduced into HCV therapy. Here we provided character data of HCV infection in China blood donors from the year of 2000 to 2009. The infection rate in local donors was lower than general population and descended from 0.80% to 0.40% or so in recent years. About 83% HCV strains were categorized into genotypes 1b and 2a. But 1b subtype cases climbed and 2a subtype cases decreased. The current study threw more light on HCV infection of blood donors in China, at least in the Northern region.
3D Goussev filter—a signal separation and edge detection filter applied to aeromagnetic data in the Great Australian Bight
Authors: Cameron Barrett , Goussev Serguei
Published: August 2010

A phase of image processing usually precedes the initial stages of any interpretation project. With aeromagnetic data, this image processing involves the construction of a variety of derivative grids of the total magnetic intensity data to enhance the magnetic signal and make it ready for interpretation. Routinely, the reduction-to-the-pole (RTP) transform is performed on the total magnetic intensity (TMI) data and then the first and, possibly, second vertical derivative calculations to enhance the magnetic signal. The first vertical derivative (1VD) of the RTP data is the most common derivative filter to enhance the magnetic signal to allow anomalies generated by structure and boundaries to become more evident. The tilt derivative is an excellent edge-detection filter (Miller and Singh, 1994; Fairhead et al., 2004). The Goussev filter (Goussev et al., 1998, 2003; Nabighian et al., 2005) provides high signal-to-noise ratio and high lateral resolution of magnetic anomalies from different types of structural discontinuities. These more complex filters are often applied on aeromagnetic data to produce enhanced imagery for interpretation and then compared to the RTP 1VD grid to see where they can add value to the interpretation process.
Offset VSP in a deviated well to support an OBC project
Authors: da Costa Emanuel Fonseca , Oliveira Rildo Marcio , Steagall Daniel Escobar , Corti Eduardo L. , Foster Martín
Published: August 2010

The Marlim Field consists of amalgamated Oligo-Miocene sandstones, with excellent porosity and permeability characteristics.
Sinkholes and pitfalls in urban geophysics
Authors: Dobecki Thomas L.
Published: August 2010

When does a subsurface geologic “situation” become a geohazard? Slope failures, strain release, and sinkhole collapses, for example, occur on a daily basis. When these occur in close proximity to a population center or some infrastructural component (e.g., a dam, a sports arena, a highway) and threaten the life, livelihood, or ability to conduct work or function in normal societal fashion, then these are aptly termed “geohazards.” Given these attributes, the greatest diversity and number of searches for geohazards are going to be conducted in urban settings. Application of geophysics and interpreting potential geohazards, then, does not have the luxury of study sites where the target is the only potential anomaly that will or could be observed.