bluuebunny/crossref_metadata_2025_split huggingface dataset:
The GloSea4 Ensemble Prediction System for Seasonal Forecasting
Authors: Arribas Alberto , Glover M. , Maidens A. , Peterson K. , Gordon M. , MacLachlan C. , Graham R. , Fereday D. , Camp J. , Scaife A. A. , Xavier P. , McLean P. , Colman A. , Cusack S. 
Published: December 2010

Abstract
Seasonal forecasting systems, and related systems for decadal prediction, are crucial in the development of adaptation strategies to climate change. However, despite important achievements in this area in the last 10 years, significant levels of skill are only generally found over regions strongly connected with the El Niño–Southern Oscillation. With the aim of improving the skill of regional climate predictions in tropical and extratropical regions from intraseasonal to interannual time scales, a new Met Office global seasonal forecasting system (GloSea4) has been developed. This new system has been designed to be flexible and easy to upgrade so it can be fully integrated within the Met Office model development infrastructure. Overall, the analysis here shows an improvement of GloSea4 when compared to its predecessor. However, there are exceptions, such as the increased model biases that contribute to degrade the skill of Niño-3.4 SST forecasts starting in November. Global ENSO teleconnections and Madden–Julian oscillation anomalies are well represented in GloSea4. Remote forcings of the North Atlantic Oscillation by ENSO and the quasi-biennial oscillation are captured albeit the anomalies are weaker than those found in observations. Hindcast length issues and their implications for seasonal forecasting are also discussed.
Global Technology Markets
Authors: Petrusson Ulf , Rosén Henrik , Thornblad Tobias 
Published: December 2010

This article analyses Open Intellectual Property (IP) platforms—where multiple stakeholders collaborate, package and transact upon technology in systems with ‘venture-market hybrid’ characteristics. Activities on these platforms typically include collective gathering, creation and development of knowledge assets to which openness is regulated through the determined level of access, ownership and utilisation rights. We analyse how IPRs (Intellectual Property Rights) and contracts operate as a set of self-regulatory tools in the construction of platforms where technology is accessed openly but still is priced on what could be described as technology markets. A case study of the GSM (Global System for Mobile Communication) platform illustrates a transition over time as a new logic for collaborative, market-based development coalesces. To further understand the underlying building blocks and enabling legal tools that provide the foundation for open IP platforms a framework is suggested. By applying the framework to the Innovative Medicines Initiative platform the tools that govern openness and stimulate creation of new knowledge markets are made visible.
A phase 2, 24-week, randomized, placebo-controlled, double-blind study examining the efficacy and safety of an anti-interleukin-12 and -23 monoclonal antibody in patients with relapsing–remitting or secondary progressive multiple sclerosis
Authors: Vollmer Timothy L , Wynn Daniel R , Alam M Shamsul , Valdes Joaquin 
Published: December 2010

Background: Interleukins 12 and 23 (IL-12/23) have been implicated in multiple sclerosis (MS) pathogenesis. This study assessed the efficacy and safety of ABT-874, a monoclonal anti-IL-12/23 antibody, in active relapsing–remitting MS (RRMS) or secondary progressive MS (SPMS). Methods: In this 24-week study, patients with RRMS or SPMS received ABT-874 200 mg every other week (EOW), ABT-874 200 mg every week (EW), or placebo. The cumulative number of gadolinium-enhanced lesions, relapse rate, disability progression, and adverse events were measured. Results: 215 patients were randomized (ABT-874 200 mg EOW, N = 76; ABT-874 200 mg EW, N = 70; placebo, N = 69). At week 24, gadolinium-enhanced lesions were statistically significantly reduced with ABT-874 200 mg EOW vs. placebo (mean number [SD]: 5.4 [8.1] vs. 7.6 [14.4], p = 0.003), but not with ABT-874 200 mg EW (6.8 [11.3], p = 0.134). Mean relapse rate (relapses/y) was significantly lower for ABT-874 200 mg EW vs. placebo (0.1 [95% CI −0.0, 0.3] vs. 0.5 [0.2, 0.8], p = 0.007). Changes from baseline in disability scores and incidences of adverse events were not significantly different across treatment groups, although a numerically greater percentage of serious adverse events was reported for ABT-874 treatment groups. Conclusions: Although rates of adverse events were not significantly different between ABT-874 treatment groups and placebo, the magnitude of ABT-874 efficacy was less than that observed with other agents currently in development for MS treatment. Anti-IL-12/23 monotherapy does not appear to warrant further testing as monotherapy treatment for MS.
A Retrospective Clinical Study of 188 Consecutive Patients to Examine the Effectiveness of a Biologically Active Cryopreserved Human Skin Allograft (TheraSkin ®) on the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers
Authors: Landsman Adam Scott , Cook Jeremy , Cook Emily , Landsman Arnold Robert , Garrett Philip , Yoon Joonhyun , Kirkwood Alfred , Desman Eric 
Published: December 2010

A biologically active human skin allograft, currently distributed under the brand name TheraSkin®, was examined for safety and efficacy in the treatment of venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). The objective was to determine if TheraSkin could serve as a safe and effective alternative to bioengineered skin substitutes such as Apligraf® and Dermagraft®. The authors conducted a retrospective study of 214 consecutive patients seen at the Inova Wound Center (Mt Vernon, Virginia), with either a DFU or a VLU. After excluding patients who did not meet the study criteria, the final eligible cohort consisted of 188 subjects, with 134 VLUs and 54 DFUs. Multivariate logistic regression was used to evaluate the relationship between baseline wound size and the proportion of healed wounds after 12 and 20 weeks from initial allograft application. The authors found that by the 12th week, DFUs closed 60.38% of the time and VLUs closed 60.77% of the time. After 20 weeks, the number of closed DFUs increased to 74.1% and the number of VLUs increased to 74.6%. The mean wound size in the DFU group was 6.2 cm2 (±11.8) and 11.8 cm2 (±22.5) in the VLU group. The mean number of TheraSkin allografts required ranged from 1 to 8, with an average of 2.03 (±1.47) at the 12-week point and an average of 3.23 (±2.77) at the 20-week point. Multivariate logistic regression was used to calculate the odds of wound healing by week 12 and week 20 in each group. The authors also analyzed adverse events and found TheraSkin to be noncontributory to any adverse events, verifying the safety of TheraSkin in this study population. In this study, TheraSkin has been shown to be highly effective for the treatment of both VLUs and DFUs with an acceptable safety profile. Level of Evidence: Therapeutic, Level IV
Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis
Authors: Folsom James P , Richards Lee , Pitts Betsey , Roe Frank , Ehrlich Garth D , Parker Albert , Mazurie Aurélien , Stewart Philip S 
Published: December 2010

AbstractBackgroundTranscriptome analysis was applied to characterize the physiological activities ofPseudomonas aeruginosagrown for three days in drip-flow biofilm reactors. Conventional applications of transcriptional profiling often compare two paired data sets that differ in a single experimentally controlled variable. In contrast this study obtained the transcriptome of a single biofilm state, ranked transcript signals to make the priorities of the population manifest, and compared ranki ngs fora prioriidentified physiological marker genes between the biofilm and published data sets.ResultsBiofilms tolerated exposure to antibiotics, harbored steep oxygen concentration gradients, and exhibited stratified and heterogeneous spatial patterns of protein synthetic activity. Transcriptional profiling was performed and the signal intensity of each transcript was ranked to gain insight into the physiological state of the biofilm population. Similar rankings were obtained from data sets published in the GEO databasehttp://www.ncbi.nlm.nih.gov/geo. By comparing the rank of genes selected as markers for particular physiological activities between the biofilm and comparator data sets, it was possible to infer qualitative features of the physiological state of the biofilm bacteria. These biofilms appeared, from their transcriptome, to be glucose nourished, iron replete, oxygen limited, and growing slowly or exhibiting stationary phase character. Genes associated with elaboration of type IV pili were strongly expressed in the biofilm. The biofilm population did not indicate oxidative stress, homoserine lactone mediated quorum sensing, or activation of efflux pumps. Using correlations with transcript ranks, the average specific growth rate of biofilm cells was estimated to be 0.08 h-1.ConclusionsCollectively these data underscore the oxygen-limited, slow-growing nature of the biofilm population and are consistent with antimicrobial tolerance due to low metabolic activity.
Spatial distribution of suicide in Queensland, Australia
Authors: Qi Xin , Tong Shilu , Hu Wenbiao 
Published: December 2010

Abstract

Background
There has been a lack of investigation into the spatial distribution and clustering of suicide in Australia, where the population density is lower than many countries and varies dramatically among urban, rural and remote areas. This study aims to examine the spatial distribution of suicide at a Local Governmental Area (LGA) level and identify the LGAs with a high relative risk of suicide in Queensland, Australia, using geographical information system (GIS) techniques.

Methods
Data on suicide and demographic variables in each LGA between 1999 and 2003 were acquired from the Australian Bureau of Statistics. An age standardised mortality (ASM) rate for suicide was calculated at the LGA level. GIS techniques were used to examine the geographical difference of suicide across different areas.

Results
Far north and north-eastern Queensland (i.e., Cook and Mornington Shires) had the highest suicide incidence in both genders, while the south-western areas (i.e., Barcoo and Bauhinia Shires) had the lowest incidence in both genders. In different age groups (≤24 years, 25 to 44 years, 45 to 64 years, and ≥65 years), ASM rates of suicide varied with gender at the LGA level. Mornington and six other LGAs with low socioeconomic status in the upper Southeast had significant spatial clusters of high suicide risk.

Conclusions
There was a notable difference in ASM rates of suicide at the LGA level in Queensland. Some LGAs had significant spatial clusters of high suicide risk. The determinants of the geographical difference of suicide should be addressed in future research.
Mood color choice helps to predict response to hypnotherapy in patients with irritable bowel syndrome
Authors: Carruthers Helen R , Morris Julie , Tarrier Nicholas , Whorwell Peter J 
Published: December 2010

Abstract

Background
Approximately two thirds of patients with irritable bowel syndrome (IBS) respond well to hypnotherapy. However, it is time consuming as well as expensive to provide and therefore a way of predicting outcome would be extremely useful. The use of imagery and color form an integral part of the hypnotherapeutic process and we have hypothesised that investigating color and how it relates to mood might help to predict response to treatment. In order to undertake this study we have previously developed and validated a method of presenting colors to individuals for research purposes called the Manchester Color Wheel (MCW). Using this instrument we have been able to classify colors into positive, neutral and negative shades and this study aimed to assess their predictive role in hypnotherapy.

Methods
156 consecutive IBS patients (aged 14-74, mean 42.0 years, 127 (81%) females, 29 (19%) males) were studied. Before treatment, each patient was asked to relate their mood to a color on the MCW as well as completing the IBS Symptom Severity Score, the Hospital Anxiety and Depression (HAD) Scale, the Non-colonic Symptom Scale, the Quality of Life Scale and the Tellegen Absorption Scale (TAS) which is a measure of hypnotisability. Following hypnotherapy all these measures were repeated with the exception of the TAS.

Results
For patients with a positive mood color the odds of responding to hypnotherapy were nine times higher than that of those choosing either a neutral or negative color or no color at all (odds ratio: 8.889; p = 0.042). Furthermore, a high TAS score and the presence of HAD anxiety also had good predictive value (odds ratio: 4.024; p = 0.092, 3.917; p < 0.001 respectively) with these markers and a positive mood color being independent of each other. In addition, these factors could be combined to give an even stronger prediction of outcome. Twice as many responders (63, 77.8%) had a positive mood color or were anxious or had a high TAS score compared with 32 (42.7%) without these factors (p < 0.001).

Conclusion
A positive mood color, especially when combined with HAD anxiety and a high TAS score, predict a good response to hypnotherapy.
Tetra-O-methyl nordihydroguaiaretic acid (Terameprocol) inhibits the NF-κB-dependent transcription of TNF-α and MCP-1/CCL2 genes by preventing RelA from binding its cognate sites on DNA
Authors: Oyegunwa Akinbolade O , Sikes Michael L , Wilson Jason R , Scholle Frank , Laster Scott M 
Published: December 2010

Abstract

Background
Tetra-O-methyl nordihydroguaiaretic acid, also known as terameprocol (TMP), is a naturally occurring phenolic compound found in the resin of the creosote bush. We have shown previously that TMP will suppress production of certain inflammatory cytokines, chemokines and lipids from macrophages following stimulation with LPS or infection with H1N1 influenza virus. In this study our goal was to elucidate the mechanism underlying TMP-mediated suppression of cytokine and chemokine production. We focused our investigations on the response to LPS and the NF-κB protein RelA, a transcription factor whose activity is critical to LPS-responsiveness.

Methods
Reporter assays were performed with HEK293 cells overexpressing either TLR-3, -4, or -8 and a plasmid containing the luciferase gene under control of an NF-κB response element. Cells were then treated with LPS, poly(I:C), or resiquimod, and/or TMP, and lysates measured for luciferase activity.
RAW 264.7 cells treated with LPS and/or TMP were used in ChIP and EMSA assays. For ChIP assays, chromatin was prepared and complexes precipitated with anti-NF-κB RelA Ab. Cross-links were reversed, DNA purified, and sequence abundance determined by Q-PCR. For EMSA assays, nuclear extracts were incubated with radiolabeled probes, analyzed by non-denaturing PAGE and visualized by autoradiography.
RAW 264.7 cells treated with LPS and/or TMP were also used in fluorescence microscopy and western blot experiments. Translocation experiments were performed using a primary Ab to NF-κB RelA and a fluorescein-conjugated secondary Ab. Western blots were performed using Abs to IκB-α and phospho-IκB-α. Bands were visualized by chemiluminescence.

Results
In reporter assays with TLR-3, -4, and -8 over-expressing cells, TMP caused strong inhibition of NF-κB-dependent transcription.
ChIP assays showed TMP caused virtually complete inhibition of RelA binding in vivo to promoters for the genes for TNF-α, MCP-1/CCL2, and RANTES/CCL5 although the LPS-dependent synthesis of IκB-α was not inhibited. EMSA assays did not reveal an effect of TMP on the binding of RelA to naked DNA templates in vitro.
TMP did not inhibit the nuclear translocation of NF-κB RelA nor the phosphorylation of IκB-α.

Conclusion
TMP acts indirectly as an inhibitor of NF-κB-dependent transcription by preventing RelA from binding the promoters of certain key cytokine and chemokine genes.
Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of TNF and TGF-β1
Authors: Welser Jennifer V , Li Longxuan , Milner Richard 
Published: December 2010

Abstract

Background
Studies of cerebral ischemia and other neuroinflammatory states have demonstrated a strong association between new vessel formation and microglial recruitment and activation, raising the possibility that microglia may be involved in promoting angiogenesis. As endothelial cell proliferation is a fundamental early step in angiogenesis, the aim of this study was to test this hypothesis by examining the influence of microglial secreted factors on brain endothelial cell (BEC) proliferation using BrdU incorporation.

Methods
Primary cultures of mouse BEC, microglia and astrocytes were used in this study. Proliferation of BEC was examined by BrdU incorporation. ELISA was used to quantify TNF and TGF-β1 levels within cell culture supernatants.

Results
Microglia regulated BEC proliferation in a biphasic manner; microglia conditioned medium (MG-CM) from resting microglia inhibited, while that from activated microglia promoted BEC proliferation. A screen of microglial cytokines revealed that BEC proliferation was inhibited by TGF-β1, but promoted by TNF. ELISA showed that TNF and TGF-β1 were both present in MG-CM, and that while TGF-β1 dominated in resting MG-CM, TNF levels were massively increased in activated MG-CM, shifting the balance in favor of TNF. Antibody-blocking studies revealed that the influence of MG-CM to inhibit or promote BEC proliferation was largely attributable to the cytokines TGF-β1 and TNF, respectively.

Conclusion
This data suggests that microglial activation state might be an important determinant of cerebral angiogenesis; inhibiting BEC proliferation and neovascularization in the normal central nervous system (CNS), but stimulating the growth of new capillaries under neuroinflammatory conditions.
Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg) identified in HBsAg-negative blood donors
Authors: Ie Susan I , Thedja Meta D , Roni Martono , Muljono David H 
Published: December 2010

Abstract

Background
Selection of hepatitis B virus (HBV) by host immunity has been suggested to give rise to variants with amino acid substitutions at or around the 'a' determinant of the surface antigen (HBsAg), the main target of antibody neutralization and diagnostic assays. However, there have never been successful attempts to provide evidence for this hypothesis, partly because the 3 D structure of HBsAg molecules has not been determined. Tertiary structure prediction of HBsAg solely from its primary amino acid sequence may reveal the molecular energetic of the mutated proteins. We carried out this preliminary study to analyze the predicted HBsAg conformation changes of HBV variants isolated from Indonesian blood donors undetectable by HBsAg assays and its significance, compared to other previously-reported variants that were associated with diagnostic failure.

Results
Three HBV variants (T123A, M133L and T143M) and a wild type sequence were analyzed together with frequently emerged variants T123N, M133I, M133T, M133V, and T143L. Based on the Jameson-Wolf algorithm for calculating antigenic index, the first two amino acid substitutions resulted in slight changes in the antigenicity of the 'a' determinant, while all four of the comparative variants showed relatively more significant changes. In the pattern T143M, changes in antigenic index were more significant, both in its coverage and magnitude, even when compared to variant T143L. These data were also partially supported by the tertiary structure prediction, in which the pattern T143M showed larger shift in the HBsAg second loop structure compared to the others.

Conclusions
Single amino acid substitutions within or near the 'a' determinant of HBsAg may alter antigenicity properties of variant HBsAg, which can be shown by both its antigenic index and predicted 3 D conformation. Findings in this study emphasize the significance of variant T143M, the prevalent isolate with highest degree of antigenicity changes found in Indonesian blood donors. This highlights the importance of evaluating the effects of protein structure alterations on the sensitivity of screening methods being used in detection of ongoing HBV infection, as well as the use of vaccines and immunoglobulin therapy in contributing to the selection of HBV variants.
PK20, a New Opioid-Neurotensin Hybrid Peptide That Exhibits Central and Peripheral Antinociceptive Effects
Authors: Kleczkowska Patrycja , Kosson Piotr , Ballet Steven , Van den Eynde Isabelle , Tsuda Yuko , Tourwé Dirk , Lipkowski Andrzej W 
Published: December 2010

Background:The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor.Results:Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia.Conclusions:The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.