bluuebunny/crossref_metadata_2025 huggingface dataset:
Using a Strategic Environmental Assessment framework to quantify the environmental impact of bioenergy plans
Authors: Finnan John , Styles David , Fitzgerald Joanne , Connolly John , Donnelly Alison
Published: December 2011

Renewable energy and greenhouse gas (GHG) reduction targets are driving an acceleration in the use of bioenergy resources. The environmental impact of national and regional development plans must be assessed in compliance with the EU Strategic Environmental Assessment (SEA) Directive (2001/42/EC). Here, we quantify the environmental impact of an Irish Government bioenergy plan to replace 30% of peat used in three peat‐burning power stations, located within the midlands region, with biomass. Four plan alternatives for supplying biomass to the power plant were considered in this study: (1) importation of palm kernel shell from south‐east Asia, (2) importation of olive cake pellets from Spain and (3) growing either willow or (4) Miscanthus in the vicinity of the power stations. The impact of each alternative on each of the environmental receptors proposed in the SEA Directive was first quantified before the data were normalized on either an Irish, regional or global scale. Positive environmental impacts were very small compared to the negative environmental impacts for each of the plan alternatives considered. Comparison of normalized indicator values confirmed that the adverse environmental consequences of each plan alternative are concentrated at the location where the biomass is produced. The analysis showed that the adverse environmental consequences of biomass importation are substantially greater than those associated with the use of willow and Miscanthus grown on former grassland. The use of olive cake pellets had a greater adverse environmental effect compared to the use of peat whereas replacement of peat with either willow or Miscanthus feedstocks led to a substantial reduction in environmental pressure. The proposed assessment framework combines the scope of SEA with the quantitative benefits of life cycle assessment and can be used to evaluate the environmental consequences of bioenergy plans.
Patient‐related risk factors for implant therapy. A critique of pertinent literature
Authors: Liddelow G , Klineberg I
Published: December 2011

Background:  Treatment planning for dental implants involves the assessment of patient‐related risk factors prior to formulation of a treatment plan. The aim of this review was to assess relevant literature and provide evidence‐based information on the successful surgical placement of dental implants.

Methods:  An electronic search of Medline, PubMed and the Cochrane Databases of Systematic Reviews was undertaken using a combination of MeSH terms and keywords. A handsearch was also performed and cross‐referenced with articles cited in papers selected. The primary study parameter was implant failure.

Results:  Forty‐three studies were selected based on specific inclusion criteria. Many studies contain confounding variables, numbers in subcategories are often too small for meaningful statistical analysis, and follow‐up times vary and are often short‐term.

Conclusions:  There are many risk factors which the clinician is required to know and understand to advise patients, and consider in planning and treatment provision. Consistent evidence exists to show an increased failure rate with smokers, a history of radiotherapy and local bone quality and quantity. Weaker evidence exists to show a higher incidence of peri‐implant disease in patients with a history of periodontitis‐related tooth loss. Lack of evidence precludes definitive guidelines for patients with autoimmune disorders where expert opinion recommends caution. Osteoporotic patients show acceptable survival rates; however patients on oral bisphosphonates show a small incidence but high morbidity from osteonecrosis of the jaw. Emerging evidence suggests that there is a correlation between genetic traits and disruption of osseointegration.
Travel patterns for government emergency dental care in Australia: a new approach using GIS tools
Authors: McGuire S , Kruger E , Tennant M
Published: December 2011

Background:  Government subsidized dental care is provided as a community safety‐net to complement the private dental sector. The aim of this study was to detail the geographic catchment characteristics of three outer metropolitan government dental clinics.

Methods:  Three outer metropolitan dental clinics with the greatest number of geocoded triage patients were selected for the study. In total these three facilities had 5742 patients over the 12‐week period with 2010 at clinic A, 1278 at clinic B and 2454 at clinic C. Cumulative proportions of patients’ residential address locations at distances were calculated; there was close correlation between the three clinics. A best fit curve with a correlation coefficient of 0.998 was developed.

Results:  In summary, approximately 50% of patients were within 6 km of the clinic and 75% were within 10 km.

Conclusions:  This study has critical outcomes for the planning of future services in developing a network model for care. The data presented will assist in the development of more evidence‐based approaches to planning new service network structures.
Structure, composition, and location of organic matter in the enstatite chondrite Sahara 97096 (EH3)
Authors: PIANI Laurette , ROBERT François , BEYSSAC Olivier , BINET Laurent , BOUROT‐DENISE Michèle , DERENNE Sylvie , LE GUILLOU Corentin , MARROCCHI Yves , MOSTEFAOUI Smail , ROUZAUD Jean‐Noël , THOMEN Aurélien
Published: December 2011

Abstract– The insoluble organic matter (IOM) of an unequilibrated enstatite chondrite Sahara (SAH) 97096 has been investigated using a battery of analytical techniques. As the enstatite chondrites are thought to have formed in a reduced environment at higher temperatures than carbonaceous chondrites, they constitute an interesting comparative material to test the heterogeneities of the IOM in the solar system and to constrain the processes that could affect IOM during solar system evolution. The SAH 97096 IOM is found in situ: as submicrometer grains in the network of fine‐grained matrix occurring mostly around chondrules and as inclusions in metallic nodules, where the carbonaceous matter appears to be more graphitized. IOM in these two settings has very similar δ15N and δ13C; this supports the idea that graphitized inclusions in metal could be formed by metal catalytic graphitization of matrix IOM. A detailed comparison between the IOM extracted from a fresh part and a terrestrially weathered part of SAH 97096 shows the similarity between both IOM samples in spite of the high degree of mineral alteration in the latter. The isolated IOM exhibits a heterogeneous polyaromatic macromolecular structure, sometimes highly graphitized, without any detectable free radicals and deuterium‐heterogeneity and having mean H‐ and N‐isotopic compositions in the range of values observed for carbonaceous chondrites. It contains some submicrometer‐sized areas highly enriched in 15N (δ15N up to 1600‰). These observations reinforce the idea that the IOM found in carbonaceous chondrites is a common component widespread in the solar system. Most of the features of SAH 97096 IOM could be explained by the thermal modification of this main component.
Solution of Inverse Convection Heat Transfer Problem Using an Enhanced Particle Swarm Optimization Algorithm
Authors: Ding Peng
Published: December 2011

The main objective of this paper is to solve the inverse convection heat transfer problems with particle swarm optimization method. An enhanced particle swarm optimization (EPSO) algorithm is proposed to overcome the shortcoming of earlier convergence of standard PSO algorithms. The performance of EPSO is tested by some benchmark functions; it is shown that EPSO has a strong antilocal trap capability especially for high dimensional multimodal optimization problems. At last, EPSO is used to identify the unknown boundary heat flux in a channel flow. According to the computational results of four test problems, it is clear that the proposed EPSO algorithm is able to estimate the unknown heat flux accurately even when the input data contain measurement error.
Newest Developments on the Manufacture of Helical Profiles by Hot Extrusion
Authors: Khalifa Nooman Ben , Tekkaya A. Erman
Published: December 2011

A new innovative direct extrusion process, helical profile extrusion (HPE) is presented, which increases the flexibility of aluminum profile manufacturing processes. The application fields of such profiles can be seen in screw rotors for compressors and pumps. The investigations concentrate on experimental and numerical analyses by 3D-FEM simulations to analyze the influence of friction and the material flow on the twisting angle and contour accuracy. By means of finite-element method (FEM), the profile shape could be improved by modifying the die design. The numerical results were validated by experiments. For these investigations, a common aluminum alloy AA6060 was used. Mainly, the friction in the die influences the twist angle and the shape of the helical profile. Two die coatings were analyzed, but the friction was not substantially decreased in any of these cases. Although there is no efficient practical solution for reducing the friction in extrusion dies using tested die coatings, the required profile contour could be achieved by new die designing and by modifying the material flow. However, increasing the twist angle is limited due to geometrical aspects of this technology, namely, by the ratio of the volume to the contact area with the die for the displaced metal.
Skin Sees the Light with Rhodopsin
Authors: Gough Nancy R.
Published: December 2011

Rhodopsin present in melanocytes contributes to a retinal-dependent rapid pigmentation response to ultraviolet light.
Primed for Death
Authors: Kiberstis Paula A.
Published: December 2011

The mitochondrial state of a tumor cell prior to chemotherapy may help determine how well it responds to drug treatment.
Autofluorescent fused-pyrimidine nucleosides: Synthesis and evaluation as permeants and inhibitors of human nucleoside transporters
Authors: Nowak Ireneusz , Damaraju Vijaya L. , Cass Carol E. , Young James D. , Robins Morris J.
Published: December 2011

Nucleosides with an aromatic five-membered ring heterocycle (N, O, or S) fused at C4–C5 of pyrimidin-2-one were prepared by ring closures with 5-(alkyn-1-yl)pyrimidin-2-one intermediates, heterocyclic atom replacements, and ring closure with a 5-aminocytidine derivative. Ultraviolet absorption and emission properties of the autofluorescent products enabled studies on permeation and inhibition of the trans-cellular trafficking effected by human equilibrative nucleoside transporters (hENTs). Some of the autofluorescent nucleosides were shown to be potent and selective inhibitors of human concentrative nucleoside transporters (hCNTs) in a companion study reported elsewhere.
Transcriptional implications of ultradian glucocorticoid secretion in homeostasis and in the acute stress response
Authors: Scheff Jeremy D. , Calvano Steve E. , Lowry Stephen F. , Androulakis Ioannis P.
Published: December 2011

Endogenous glucocorticoids are secreted by the hypothalamic-pituitary-adrenal (HPA) axis in response to a wide range of stressors. Glucocorticoids exert significant downstream effects, including the regulation of many inflammatory genes. The HPA axis functions such that glucocorticoids are released in a pulsatile manner, producing ultradian rhythms in plasma glucocorticoid levels. It is becoming increasingly evident that this ultradian pulsatility is important in maintaining proper homeostatic regulation and responsiveness to stress. This is particularly interesting from a clinical perspective given that pathological dysfunctions of the HPA axis produce altered ultradian patterns. Modeling this system facilitates the understanding of how glucocorticoid pulsatility arises, how it can be lost, and the transcriptional implications of ultradian rhythms. To approach these questions, we developed a mathematical model that integrates the cyclic production of glucocorticoids by the HPA axis and their downstream effects by integrating existing models of the HPA axis and glucocorticoid pharmacodynamics. This combined model allowed us to evaluate the implications of pulsatility in homeostasis as well as in response to acute stress. The presence of ultradian rhythms allows the system to maintain a lower response to homeostatic levels of glucocorticoids, but diminished feedback within the HPA axis leads to a loss of glucocorticoid rhythmicity. Furthermore, the loss of HPA pulsatility in homeostasis correlates with a decrease in the peak output in response to an acute stressor. These results are important in understanding how cyclic glucocorticoid secretion helps maintain the responsiveness of the HPA axis.
A Pain in the Buttock
Authors: Landman Zachary C. , Beres Shannon , Cabana Michael D.
Published: December 2011

Spondylolysis, a fracture of the pars interarticularis, is a common source back pain in children and adolescents. While the incidence is significantly higher in Asian and Inuit populations, it is never seen in nonambulatory children and is most commonly associated with athletic activities that involve extension or rotational deformity about the spine suggesting a functional component. Given that the associated pain is typically insidious in onset, lacks preceding trauma, and is accompanied by muscular spasm, prompt diagnosis requires a high index of suspicion, familiarity with provocative testing, and knowledge of the appropriate radiographic evaluation. Treatment requires cessation of athletic activity, bracing, and rest for a minimum of four to six weeks, or until symptomatic and radiographic resolution.
Generation and Analysis of Large-Scale Data-Driven Mycobacterium tuberculosis Functional Networks for Drug Target Identification
Authors: Mazandu Gaston K. , Mulder Nicola J.
Published: December 2011

Technological developments in large-scale biological experiments, coupled with bioinformatics tools, have opened the doors to computational approaches for the global analysis of whole genomes. This has provided the opportunity to look at genes within their context in the cell. The integration of vast
amounts of data generated by these technologies provides a strategy for identifying potential drug targets
within microbial pathogens, the causative agents of infectious diseases. As proteins are druggable targets,
functional interaction networks between proteins are used to identify proteins essential to the survival,
growth, and virulence of these microbial pathogens. Here we have integrated functional genomics data to
generate functional interaction networks between Mycobacterium tuberculosis proteins and carried out computational analyses to dissect the functional interaction network produced for identifying drug targets
using network topological properties. This study has provided the opportunity to expand the range of potential drug targets and to move towards optimal target-based strategies.
Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia
Authors: Perluigi Marzia , Butterfield D. Allan
Published: December 2011

Down syndrome (DS) is one of the most frequent genetic abnormalities characterized by multiple pathological phenotypes. Indeed, currently life expectancy and quality of life for DS patients have improved, although with increasing age pathological dysfunctions are exacerbated and intellectual disability may lead to the development of Alzheimer's type dementia (AD). The neuropathology of DS is complex and includes the development of AD by middle age, altered free radical metabolism, and impaired mitochondrial function, both of which contribute to neuronal degeneration. Understanding the molecular basis that drives the development of AD is an intense field of research. Our laboratories are interested in understanding the role of oxidative stress as link between DS and AD. This review examines the current literature that showed oxidative damage in DS by identifying putative molecular pathways that play a central role in the neurodegenerative processes. In addition, considering the role of mitochondrial dysfunction in neurodegenerative phenomena, results demonstrating the involvement of impaired mitochondria in DS pathology could contribute a direct link between normal aging and development of AD-like dementia in DS patients.
VTX-2337 Is a Novel TLR8 Agonist That Activates NK Cells and Augments ADCC
Authors: Lu Hailing , Dietsch Gregory N. , Matthews Maura-Ann H. , Yang Yi , Ghanekar Smita , Inokuma Margaret , Suni Maria , Maino Vernon C. , Henderson Katherine E. , Howbert James Jeffry , Disis Mary L. , Hershberg Robert M.
Published: December 2011

Purpose: We aim to characterize VTX-2337, a novel Toll-like receptor (TLR) 8 agonist in clinical development, and investigate its potential to improve monoclonal antibody–based immunotherapy that includes the activation of natural killer (NK) cells.

Experimental Design: HEK-TLR transfectants were used to compare the selectivity and potency of VTX-2337, imiquimod, CpG ODN2006, and CL075. The ability of VTX-2337 to induce cytokine and chemokine production from human peripheral blood mononuclear cells (PBMC) and activation of specific immune cell subsets was examined. The potential for VTX-2337 to activate NK cell activity through direct and indirect mechanisms was also investigated. Finally, we tested the potential for VTX-2337 to augment antibody-dependent cell-mediated cytotoxicity (ADCC), especially in individuals with low-affinity FcγR3A single-nucleotide polymorphism (SNP).

Results: VTX-2337 selectively activates TLR8 with an EC50 of about 100 nmol/L and stimulates production of TNFα and interleukin (IL)-12 from monocytes and myeloid dendritic cells (mDC). VTX-2337 stimulates IFNγ production from NK cells and increases the cytotoxicity of NK cells against K562 and ADCC by rituximab and trastuzumab. Effects of VTX-2337 on NK cells were, in part, from direct activation as increased IFNγ production and cytotoxic activity were seen with purified NK cells. Finally, VTX-2337 augments ADCC by rituximab in PBMCs with different FcγR3A genotypes (V/V, V/F, and F/F at position 158).

Conclusions: VTX-2337 is a novel small-molecule TLR8 agonist that activates monocytes, DCs, and NK cells. Through the activation of NK cells, it has the potential to augment the effectiveness of monoclonal antibody treatments where a polymorphism in FcγR3A limits clinical efficacy. Clin Cancer Res; 18(2); 499–509. ©2011 AACR.
Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene Is Associated with Poor Prognosis in Resected Pancreatic Cancer
Authors: Lee Jih-Hsiang , Giovannetti Elisa , Hwang Jin-Hyeok , Petrini Iacopo , Wang Qiuyan , Voortman Johannes , Wang Yonghong , Steinberg Seth M. , Funel Niccola , Meltzer Paul S. , Wang Yisong , Giaccone Giuseppe
Published: December 2011

Purposes: Pancreatic cancer is the fourth leading cause of cancer-related death, and studies on the clinical relevance of its genomic imbalances are warranted.

Experimental Design: Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens. Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent validation cohort of 61 resected pancreatic cancers. The functions of gene identified were evaluated by proliferation, cell cycle, and migration assays in pancreatic cancer cells.

Results: We showed recurrent copy number gains and losses in the first cohort. Loss of 18q22.3 was significantly associated with short-term overall survival in the first cohort (P = 0.019). This cytoband includes the carboxypeptidase of glutamate-like (CPGL) gene. CPGL gene deletion was associated with shorter overall survival in the validation cohort (P = 0.003). CPGL deletion and mutations of TP53 or Kras seem to be independent events. A Cox model analysis of the two cohorts combined showed that loss of 18q22.3/deletion of the CPGL gene was an independent poor prognostic factor for overall survival (HR = 2.72, P = 0.0007). Reconstitution of CPGL or its splicing variant CPGL-B into CPGL-negative pancreatic cancer cells attenuated cell growth, migration, and induced G1 accumulation.

Conclusion: Loss of 18q22.3/deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer. Clin Cancer Res; 18(2); 524–33. ©2011 AACR.
Genome-Wide Association and Fine Mapping of Genetic Loci Predisposing to Colon Carcinogenesis in Mice
Authors: Liu Pengyuan , Lu Yan , Liu Hongbo , Wen Weidong , Jia Dongmei , Wang Yian , You Ming
Published: December 2011

To identify the genetic determinants of colon tumorigenesis, 268 male mice from 33 inbred strains derived from different genealogies were treated with azoxymethane (AOM; 10 mg/kg) once a week for six weeks to induce colon tumors. Tumors were localized exclusively within the distal colon in each of the strains examined. Inbred mouse strains exhibit a large variability in genetic susceptibility to AOM-induced colon tumorigenesis. The mean colon tumor multiplicity ranged from 0 to 38.6 (mean = 6.5 ± 8.6) and tumor volume ranged from 0 to 706.5 mm3 (mean = 87.4 ± 181.9) at 24 weeks after the first dose of AOM. AOM-induced colon tumor phenotypes are highly heritable in inbred mice, and 68.8% and 71.3% of total phenotypic variation in colon tumor multiplicity and tumor volume, respectively, are attributable to strain-dependent genetic background. Using 97,854 single-nucleotide polymorphisms, we carried out a genome-wide association study (GWAS) of AOM-induced colon tumorigenesis and identified a novel susceptibility locus on chromosome 15 (rs32359607, P = 6.31 × 10–6). Subsequent fine mapping confirmed five (Scc3, Scc2, Scc12, Scc8, and Ccs1) of 16 linkage regions previously found to be associated with colon tumor susceptibility. These five loci were refined to less than 1 Mb genomic regions of interest. Major candidates in these loci are Sema5a, Fmn2, Grem2, Fap, Gsg1l, Xpo6, Rabep2, Eif3c, Unc5d, and Gpr65. In particular, the refined Scc3 locus shows high concordance with the human GWAS locus that underlies hereditary mixed polyposis syndrome. These findings increase our understanding of the complex genetics of colon tumorigenesis, and provide important insights into the pathways of colorectal cancer development and might ultimately lead to more effective individually targeted cancer prevention strategies. Mol Cancer Res; 10(1); 66–74. ©2011 AACR.
Fragile X Syndrome: The GABAergic System and Circuit Dysfunction
Authors: Paluszkiewicz Scott M. , Martin Brandon S. , Huntsman Molly M.
Published: December 2011

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disability, sensory hypersensitivity, and high incidences of autism spectrum disorders and epilepsy. These phenotypes are suggestive of defects in neural circuit development and imbalances in excitatory glutamatergic and inhibitory GABAergic neurotransmission. While alterations in excitatory synapse function and plasticity are well-established in Fmr1 knockout (KO) mouse models of FXS, a number of recent electrophysiological and molecular studies now identify prominent defects in inhibitory GABAergic transmission in behaviorally relevant forebrain regions such as the amygdala, cortex, and hippocampus. In this review, we summarize evidence for GABAergic system dysfunction in FXS patients and Fmr1 KO mouse models alike. We then discuss some of the known developmental roles of GABAergic signaling, as well as the development and refinement of GABAergic synapses as a framework for understanding potential causes of mature circuit dysfunction. Finally, we highlight the GABAergic system as a relevant target for the treatment of FXS.
Safety of Low-Frequency Transcranial Ultrasound in Permanent Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats
Authors: Wang Zuojun , Fukuda Takahiro , Azuma Takashi , Furuhata Hiroshi
Published: December 2011

Background: Some studies suggest that low-frequency transcranial ultrasound (LFTUS) can enhance thrombolysis, but other studies suggest that it may have adverse effects on intracranial tissues. We previously reported that LFTUS with appropriate parameters was effective and safe in a normotensive rat model of thromboembolic middle cerebral artery occlusion (MCAO) stroke. The goal of this study was to test the safety of this strategy in a spontaneously hypertensive rat (SHR) model of permanent MCAO. Methods: Right MCAO was achieved in male SHRs using intraluminal nylon sutures. Rats exhibiting left hemiparesis were randomly assigned to one of four different groups: (1) normal saline (NS) group (n = 8), intravenous administration of NS as placebo at 3 h after MCAO; (2) NS+LFTUS group (n = 10), NS administration with simultaneous application of LFTUS (480.4 kHz, continuous wave, at an intensity of 0.3 W/cm2) for 1 h; (3) tissue plasminogen activator (tPA) group (n = 11), intravenous administration of alteplase (10 mg/kg body weight) over 1 h instead of NS; or (4) tPA+LFTUS group (n = 11), tPA administration and application of LFTUS. Twenty-four hours after treatment, neurological change was evaluated, and brains were removed and examined histologically. Results: There was no significant difference (p > 0.09) when comparing changes in neurologic status and body weight, infarct ratio, edema ratio, or hemorrhagic transformation among the four groups. Conclusions: Our findings suggest that sonothrombolytic treatment with LFTUS with appropriate parameters is safe when used for the treatment of ischemic stroke in hypertensive rats under the undesired permanent MCAO condition.
Risk Factors Associated with Cardiovascular Morbidity and Mortality in Spanish Incident Hemodialysis Patients: Two-Year Results from the ANSWER Study
Authors: Cuevas Xavier , García Fernando , Martín-Malo Alejandro , Fort Joan , Lladós Fina , Lozano Javier , Pérez-García Rafael ,   on behalf of all investigators from the ANSWER study
Published: December 2011

Aims: To identify factors associated with cardiovascular (CV) disease in hemodialysis. Methods: Multicenter, prospective, 2-year, observational study in 2,310 incident patients (3,496 patient-years). Multivariate Cox models determined baseline characteristics associated with CV disease. Results: Main factors associated with CV deaths (6.3/100 patient-years) were: high Charlson score (hazard ratio (HR) 3.6; 95% confidence interval (CI) 1.7–7.5 for ≧9 vs. ≤4); low Karnofsky score (KS; HR 2.2; 95% CI 1.5–3.3 for KS ≤50 vs. >70); female gender (HR 1.4; 95% CI 1.1–1.9); catheter access (HR 1.4; 95% CI 1.0–1.9); low (<3.5 g/dl) albumin (HR 2.5; 95% CI 1.8–3.3); ferritin deficiency (HR 1.6; 95% CI 1.2–2.2 for <100 vs. ≧100–500 ng/ml) and low body mass index (BMI; HR 1.9; 95% CI 1.2–3.0 for <20 vs. 20–25). A BMI of ≧30 was a protective factor (HR 0.6; 95% CI 0.4–0.9). Conclusions: There is a high CV risk, especially in older patients with high comorbidity, low BMI, low albumin or iron deficiency. Catheter access increases the CV death risk.
Children's Morning and Evening Salivary Cortisol: Pattern, Instruction Compliance and Sampling Confounders
Authors: Michels N. , Sioen I. , De Vriendt T. , Huybrechts I. , Vanaelst B. , De Henauw S.
Published: December 2011

Background/Aims: Salivary cortisol has been widely used to assess childhood stress. Yet, there is no consensus on reference concentrations, awakening response, guideline compliance and contribution of sampling factors to the variation in children's salivary cortisol levels. Methods: Samples were collected from 444 Belgian children participating in the ChiBS study (5-11 years old) on two consecutive weekdays at four moments: awakening, 30 min later, 60 min later and in the evening. A checklist requested awakening time, collection hours and guideline compliance. Results: Reference values were determined. Mixed model analyses revealed that age, time compliance and awakening time contributed significantly to the variance in cortisol levels. In only 52.5% of the children a cortisol morning increase was observed. Participants with no morning increase showed higher awakening but lower post-awakening concentrations on that day, and the morning response showed a small negative correlation with the time lag between first and second sampling. Conclusion: This study emphasizes the importance of excluding extreme time deviation and correcting for age and awakening time. Appearance of a cortisol morning increase was only found in approximately half of the children, suggesting the absence of the cortisol awakening response as a general characteristic. Also, this could partially be explained by poor time compliance.
Phase II Study of Bolus 5-Fluorouracil and Leucovorin Combined with Weekly Paclitaxel as First-Line Therapy for Advanced Gastric Cancer
Authors: Matsubara Junichi , Shimada Yasuhiro , Kato Ken , Nagai Yushi , Iwasa Satoru , Nakajima Takako E. , Hamaguchi Tetsuya , Yamada Yasuhide , Takagi Seiichi , Kobayashi Kazuma , Yoshioka Akira , Nakayama Norisuke , Tsuji Akihito
Published: December 2011

Objective: We evaluated the efficacy and safety of bolus 5-fluorouracil (5-FU) and leucovorin combined with weekly paclitaxel (FLTAX) in advanced gastric cancer (GC) patients. Methods: Patients with untreated stage IV GC received paclitaxel 80 mg/m2 as a 1-hour infusion, followed by 5-FU 600 mg/m2 as a bolus infusion and L-leucovorin 250 mg/m2 as a 2-hour infusion on days 1, 8 and 15. Treatment cycles were repeated every 28 days. The primary endpoint was response rate. Results: Thirty-five patients were enrolled. The median age was 62 years (range 34–75). Twenty-one patients (60%) had diffuse-type cancer and 11 had peritoneal metastasis. The confirmed response rate was 43% (95% CI 26–61) with 15 partial responses. Stable disease was observed in 16 (46%) patients. Median progression-free survival and overall survival were 6.8 months (95% CI 5.8–7.4) and 16.2 months (95% CI 10.0–22.8), respectively. Grade 3–4 adverse events were: neutropenia (54%), febrile neutropenia (3%), diarrhea (6%) and sensory neuropathy (11%). Conclusion: FLTAX showed a desirable safety profile, and the efficacy against advanced GC was encouraging. FLTAX may be a good option for GC patients with deteriorated general condition, and a randomized clinical trial in such patients is currently underway.
Clopidogrel Pharmacodynamics and Pharmacokinetics in the Fed and Fasted State: A Randomized Crossover Study of Healthy Men
Authors: Hurbin Fabrice , Boulenc Xavier , Daskalakis Nikki , Farenc Christine , Taylor Theresa , Bonneau Damien , LaCreta Frank , Cheng Sue , Sultan Eric
Published: December 2011

Clopidogrel requires CYP450‐mediated hepatic metabolism to form its active metabolite (clopi‐H4). This randomized, placebo‐controlled, crossover study was designed to characterize the effect of a high‐fat or standard breakfast on adenosine diphosphate (ADP)—induced platelet aggregation and exposure to unchanged clopidogrel and clopi‐H4 following clopidogrel (300‐mg loading dose, 75 mg/d for 4 days) in 72 healthy men. At day 5 and as assessed by liquid chromatography—tandem mass spectrometry, unchanged clopidogrel area under the concentration‐time curve from 0 to 24 hours (AUC0–24) increased 3.32‐fold (90% confidence interval [CI], 2.88–3.84), and clopi‐H4 AUC0–24 decreased nonsignificantly by 12% (90% CI, 0.82–0.94) upon administration of clopidogrel with a standard breakfast. The estimated treatment difference in maximum platelet aggregation (MPA) induced by ADP 5 μM and assessed by light transmission aggregometry was 4.7%, with the 90% CI (0.9%–8.5%) contained within the prespecified equipotency range of ±15%. The mean ± standard deviation of day 5 inhibition of platelet aggregation was 49.7% ± 17.2% and 54.0% ± 13.3% in the fed and fasted states, respectively. Despite increased unchanged clopidogrel and slightly decreased clopi‐H4 exposure following clopidogrel administration, the numerical increase in MPA in the fed versus fasted state was small and within the prespecified limit of equipotency. These findings confirm that clopidogrel can be taken with or without food.
‘It’s Not Like We’re Going to Jump Them’: How Transgressing Heteronormativity Shapes Police Interactions with LGBT Young People
Authors: Dwyer Angela
Published: December 2011

This paper explores how visibly transgressing heteronormativity shapes police interactions with LGBT young people. While research provides evidence about how sexually and gender diverse bodies can be abused in schools, policing is overlooked. Interviews with 35 LGBT young people demonstrate how bodies transgressing heteronormativity (that is, non-heteronormative bodies) mediate their policing experiences in Queensland, Australia. Drawing on Foucault, Butler, and others, this article suggests police interactions and use of discretion with LGBT young people was informed by non-heteronormative bodies discursively performing queerness in ways read by police. The article concludes noting tensions produced for youthful LGBT bodies in public spaces.
Calcium- and integrin-binding protein 1 regulates megakaryocyte ploidy, adhesion, and migration
Authors: Kostyak John C. , Naik Meghna U. , Naik Ulhas P.
Published: December 2011

Megakaryocytes are large, polyploid cells that produce platelets. We have previously reported that calcium- and integrin-binding protein 1 (CIB1) regulates endomitosis in Dami cells. To further characterize the role of CIB1 in megakaryopoiesis, we used a Cib1−/− mouse model. Cib1−/− mice have more platelets and BM megakaryocytes than wild-type (WT) controls (P < .05). Furthermore, subsequent analysis of megakaryocyte-CFU production revealed an increase with Cib1 deletion compared with WT (P < .05). In addition, BM from Cib1−/− mice, cultured with thrombopoietin (TPO) for 24 hours, produced more highly polyploid megakaryocytes than WT BM (P < .05). Subsequent analysis of TPO signaling revealed enhanced Akt and ERK1/2 phosphorylation, whereas FAKY925 phosphorylation was reduced in Cib1−/− megakaryocytes treated with TPO. Conversely, platelet recovery in Cib1−/− mice after platelet depletion was attenuated compared with WT (P < .05). This could be the result of impaired adhesion and migration, as adhesion to fibrinogen and fibronectin and migration toward an SDF-1α gradient were reduced in Cib1−/− megakaryocytes compared with WT (P < .05). In addition, Cib1−/− megakaryocytes formed fewer proplatelets compared with WT (P < .05), when plated on fibrinogen. These data suggest that CIB1 plays a dual role in megakaryopoiesis, initially by negatively regulating TPO signaling and later by augmenting proplatelet production.
Novel tree-based method to generate markers from rare variant data
Authors: Jiang Yuan , Brennan Jennifer S , Calixte Rose , He Yunxiao , Nyirabahizi Epiphanie , Zhang Heping
Published: December 2011

Existing methods for analyzing rare variant data focus on collapsing a group of rare variants into a single common variant; collapsing is based on an intuitive function of the rare variant genotype information, such as an indicator function or a weighted sum. It is more natural, however, to take into account the single-nucleotide polymorphism (SNP) interactions informed directly by the data. We propose a novel tree-based method that automatically detects SNP interactions and generates candidate markers from the original pool of rare variants. In addition, we utilize the advantage of having 200 phenotype replications in the Genetic Analysis Workshop 17 data to assess the candidate markers by means of repeated logistic regressions. This new approach shows potential in the rare variant analysis. We correctly identify the association between gene FLT1 and phenotype Affect, although there exist other false positives in our results. Our analyses are performed without knowledge of the underlying simulating model.
Evaluation of pooled association tests for rare variant identification
Authors: Lin Wan-Yu , Zhang Boshao , Yi Nengjun , Gao Guimin , Liu Nianjun
Published: December 2011

Genome-wide association studies have successfully identified many common variants associated with complex human diseases. However, a large portion of the remaining heritability cannot be explained by these common variants. Exploring rare variants associated with diseases is now catching more attention. Several methods have been recently proposed for identification of rare variants. Among them, the fixed-threshold, weighted-sum, and variable-threshold methods are effective in combining the information of multiple variants into a functional unit; these approaches are commonly used. We evaluate the performance of these three methods. Based on our analyses of the Genetic Analysis Workshop 17 data, we find that no method is universally better than the others. Furthermore, adjusting for potential covariates can not only increase the true-positive proportions but also reduce the false-positive proportions. Our study concludes that there is no uniformly most powerful test among the three methods we compared (the fixed-threshold, weighted-sum, and variable-threshold methods), and their performances depend on the underlying genetic architecture of a disease.
Disassociation between Preprandial Gut Peptide Release and Food-Anticipatory Activity
Authors: Dailey Megan J. , Stingl Katherine C. , Moran Timothy H.
Published: December 2011

Animals learn to anticipate a meal as evidenced by increases in premeal activity. This learned response appears to be independent of the nutrient status of an animal because food-anticipatory activity (FAA) can be seen after entrainment by a highly palatable food when rats remain ad libitum on chow. Mealtime feeding not only induces an increase in activity but also appears to entrain the secretion of various peptides prior to a meal including insulin, ghrelin, and glucagon-like peptide-1 (GLP-1). It is not clear whether these meal-anticipatory changes in peptides are causally associated with FAA. To assess whether FAA and preprandial peptide changes co-occur with meal entrainment using different diets, rats were conditioned to receive a 6-h chow meal, 6-h high-fat meal, or 2 h access of chocolate while ad libitum on chow in the middle of the light cycle. FAA was measured for 4 h prior to mealtime. Rats were then killed at 90, 60, and 30 min prior to mealtime and plasma was collected. Although the chocolate-entrained rats showed comparable FAA with the nonchocolate-entrained animals, they did not show anticipatory increases in the ghrelin or GLP-1. All entrainment conditions induced a decrease in insulin and an increase in glucose prior to mealtime. These data suggest that separate mechanisms may underlie the preprandial increases in ghrelin and GLP-1 and changes in FAA, insulin, and glucose.
Circadian Regulation of Cortisol Release in Behaviorally Split Golden Hamsters
Authors: Lilley Travis R. , Wotus Cheryl , Taylor Daniel , Lee Jennifer M. , de la Iglesia Horacio O.
Published: December 2011

The master circadian clock located within the hypothalamic suprachiasmatic nucleus (SCN) is necessary for the circadian rhythm of glucocorticoid (GC) release. The pathways by which the SCN sustains rhythmic GC release remain unclear. We studied the circadian regulation of cortisol release in the behaviorally split golden hamster, in which the single bout of circadian locomotor activity splits into two bouts approximately12 h apart after exposing the animals to constant light conditions. We show that unsplit control hamsters present a single peak of cortisol release that is concomitant with a single peak of ACTH release. In contrast, split hamsters show two peaks of cortisol release that are approximately12 h appart and are appropriately phased to each locomotor activity bout but surprisingly do not rely on rhythmic release of ACTH. Our results are consistent with a model in which the circadian pacemaker within the SCN regulates the circadian release of GC via input to the hypothalamo-pituitary-adrenal axis and via a second regulatory pathway, which likely involves sympathetic innervation of the adrenal and can operate even in the absence of ACTH circadian rhythmic release. Furthermore, we show that although the overall 24-h cortisol output in split hamsters is lower than in unsplit controls, split hamsters release constant low levels of ACTH. This result suggests that the timing, rather than the absolute amount, of cortisol release is more critical for the induction of negative feedback effects that regulate the hypothalamo-pituitary-adrenal axis.
Effect of pH on lignin analysis by Raman spectroscopy
Authors: Warsta Elina , Lähdetie Anni , Jääskeläinen Anna-Stiina , Vuorinen Tapani
Published: December 2011

Ultraviolet resonance Raman (UVRR) spectroscopy is a powerful tool for structural lignin analysis in situ: modification or isolation of lignin from biomass is not necessary. UVRR spectroscopy is equally applicable for samples with high lignin content and those with very low lignin content. Monomeric phenolic lignin model compounds and wood pulp samples have been studied at neutral and alkaline pH with UVRR spectroscopy. Concentration of guaiacol correlated well with the relative Raman band intensity, which indicates that lignin-containing solutions can be quantitatively measured with UVRR spectroscopy. A change in pH induced a recordable shift in the aromatic band position in the spectra, which was 25–35 cm-1 with phenolic model compounds without para substitution, 8–12 cm-1 with phenolic model compounds with para substitution, and about 2–7 cm-1 with pulp samples. No shift was detected with a non-phenolic model compound. Increasing the amount of phenolic hydroxyl groups increased the UVRR band shift in pulp samples. Additionally, increasing the pH enhanced the relative aromatic band intensity in the UVRR spectra in solution of the phenolic model compound. Accordingly, pH adjustment is relevant prior to any lignin analysis with Raman spectroscopy.
FEM Analysis of a DCP Implant on a Human Femoral Bone With a Fracture Gap
Authors: Fongsamootr T. , Bernard S.
Published: December 2011

Our research aims to determine the optimal screw configuration of a dynamic compressive plate (DCP) implant on a human femoral bone. The number of screws and the positioning are sensitive parameters of DCP implant stress repartition. Several previous studies have assessed the influence of thescrew configuration of a DCP implant. Using a realistic geometry of a human left femur and the finite element method (FEM), the calculations in those papers were based on a safe femoral bone. This study evaluates the influence of the application of a simulated fracture gap in the diaphyseal part on the stress repartition of the bone, plate, and screws. The main purpose is to complete the existing studies in order to provide surgeons with information on an optimal prosthesis screw configuration. The plate and screws were modeled and assembled on a cracked femoral bone. The hip region of the femur was loaded with vertical and horizontal forces. The femoral bone was cut into two parts because of the gap: the top part, close to thehip, and the bottom part, close to the knee. The FEM analysis shows that the stresses in screws located in the top part of the femoral bone had significantly increased, whereas the stresses on the plate and the bone had been reduced.
Attempt at Quantification of Surface Degradation and Evaluation of Relationship between Outdoor and Accelerated Exposure of Construction Sealants
Authors: Enomoto Noriyoshi , Ito Akihiko , Tanaka Kyoji
Published: December 2011

The weatherability of construction sealants is a highly important performance criterion for the prediction of their service lives. Currently, the evaluation of a sealant’s surface weatherability is carried out mainly via qualitative visual judgment. One objective of this paper is to establish a quantitative method for the assessment of surface degradation. A further objective is the evaluation of the relationship between outdoor and accelerated exposure with regard to surface degradation. The understanding of this relationship is important for the shortening of the development cycle and the prediction of a sealant’s service life. The paper presents information on the weatherability of construction sealants based on a recently developed test specimen design that allows simultaneous exposure of the sealant to forced compression and extension movement in a single specimen with cyclic movement and weathering carried out simultaneously. A quantitative method for the assessment of surface cracks is employed, and the relationship between outdoor and accelerated weathering exposure is evaluated by using metrics that indicate the degree of surface cracking as a new semi-quantitative criterion of surface degradation.
Von modellbasierten Storyboards zu kontextsensitiven Interaction-Cases
Authors: Kühn Romina , Keller Christine , Schlegel Thomas
Published: December 2011

Storyboarding als Analyseinstrument und Prototyping-Methode für das ”User-Centered Design“ etabliert sich aufgrund der Einfachheit, bildliche Darstellungen zu erstellen und zu verstehen. Da in ubiquitären Umgebungen oftmals sehr komplexe Interaktionen stattfinden, die zusätzlich stark vom Kontext beeinflusst werden, stellen modellgestützte Storyboards eine gute Möglichkeit dar, ubiquitäre interaktive Systeme zu modellieren. Detaillierte Interaktionsabläufe können mit Hilfe von Interaction-Cases aus den Storyboards abgeleitet werden. In dieser Arbeit wird eine Methode vorgestellt, wie anhand von Storyboards Kontext für kontextsensitive ubiquitäre Systeme identifiziert und in kontextadaptive Interaction-Cases überführt werden kann. Dazu werden Ergebnisse einer Benutzerbefragung herangezogen.
Ein UML-basierter Ansatz für die modellgetriebene Generierung grafischer Benutzungsschnittstellen
Authors: Honold Frank , Schüssel Felix , Weber Michael
Published: December 2011

Die Erstellung der Benutzungsschnittstelle nimmt mittlerweile einen großen Teil im Entwicklungsprozess ein. Je komplexer Anwendungen werden, desto zeit- und kostenintensiver wird es, geeignete Oberflächen zu erstellen. Eine automatisierte Lösung könnte hier Abhilfe schaffen. Vorhandene Techniken bieten maximal eine Teilautomatisierung und sind zudem nicht in den Arbeitsprozess der Entwickler ohne Störungen einzubinden, da sie oftmals eigene Modellierungssprachen voraussetzen. Der hier vorgestellte Ansatz basiert auf dem Cameleon Reference Framework und verwendet als Ausgangsbasis für die Generierung die UML. So kann das Verfahren ohne aufwendiges Einarbeiten angewendet werden. GUIs für unterschiedliche Zielplattformen können automatisch aus UML-Diagrammen erzeugt werden. Durch den Einsatz von Beautifications ist es zudem möglich, wiederverwendbare Anpassungen der Oberflächen zu erstellen und so Expertenwissen bezüglich Interaktion und Gestaltung einzubringen.
Automatiserte Generierung von WIMP-UIs basierend auf Kommunikationsmodellen
Authors: Falb Jürgen , Kaindl Hermann , Popp Roman , Raneburger David
Published: December 2011

Manuelles Erstellen von User Interfaces (UIs) ist teuer und zeitaufwändig, insbesondere für UIs, die auf mehreren Endgeräten mit verschiedenen Eigenschaften (z.B. Größe bzw. Auflösung des Bildschirms) ablaufen sollen. Etwa sind Webseiten, die für PCs konzipiert wurden, oft nur schlecht auf einem Smartphone zu bedienen. Daher wird es im Allgemeinen für gute Bedienbarkeit nötig sein, verschiedene UIs für verschiedene Geräte zu erstellen. Eine Möglichkeit zur Verbesserung ist die automatisierte Generierung von UIs aus Modellen mit hoher Abstraktion. Dies sind meist Task-basierte Modelle. Wir definieren hingegen Kommunikationsmodelle zur Spezifikation kommunikativer Interaktion durch Diskurse im Sinne von (Klassen von) Dialogen. Ähnlich wie bei einigen Task-basierten Ansätzen verwenden auch wir automatisierte Modell-Transformationen in immer konkretere Modelle und letztlich Code für die UIs. Unser Ansatz zeichnet sich allerdings durch Optimierungen aus, die automatisch für gegebene Geräte-Spezifikationen erfolgen. Konkret ergeben sich dadurch sogar spezielle Anpassungen für verschiedene Smartphones (iPhone vs. Android-basierte Geräte).