bluuebunny/crossref_metadata_2025 huggingface dataset:
A Journey Within a Journey
Authors: Shepherd Erin Jennifer Watt , Woodgate Roberta Lynn
Published: June 2011

Much research has been directed at childhood cancer survivors and their families to learn how to best provide care. However, little is known about parents’ experiences of transitioning to a time when their child has completed treatment for cancer when living at a distance to the tertiary cancer center. The purpose of this study was to talk to such parents about their experiences. Five Canadian parents of children who had completed treatment for cancer in the past 3 months to 5 years took part in qualitative opened-ended interviews using a phenomenological hermeneutic approach. Data analysis revealed the essence of the parents’ lived experience as a journey within a journey; 4 themes characterized the essence. Parents living a 2.5- to 5-hour drive from the cancer center expressed a willingness to travel wherever necessary in order to receive specialized care for their child. Parents emphasized the importance of having a local health care provider in whom they trusted. Assessing families’ needs, support systems, and readiness to return home are important nursing roles throughout the cancer trajectory.
Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2—3 liraglutide clinical development studies
Authors: Marso Steven P , Lindsey Jason B , Stolker Joshua M , House John A , Martinez Ravn Gabriela , Kennedy Kevin F , Jensen Troels M , Buse John B
Published: June 2011

We assessed the cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist, using existing clinical data. Patient-level results from all completed phase 2 and 3 studies from the liraglutide clinical development programme were pooled to determine rates of major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, stroke. MACE were identified by querying the study database using Medical Dictionary for Regulatory Activities (MedDRA) terms combined with serious adverse events recorded by study investigators. Broad, narrow, and custom groups of MedDRA queries were used. Candidate events from each query were independently adjudicated post hoc. In 15 studies (6638 patients; 4257 liraglutide treated), there were 114 patients with MACE identified using the broad MedDRA query. Of these, 44 were classified as serious adverse events and 39 were adjudicated as MACE. The incidence ratio for adjudicated broad/serious MACE associated with liraglutide was 0.73 (95% CI 0.38—1.41) versus all comparator drugs (metformin, glimepiride, rosiglitazone, insulin glargine, placebo), within cardiovascular safety limits defined by the United States Food & Drug Administration for diabetes therapies under current investigation.
Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification
Authors: Cornejo Melanie G. , Mabialah Vinciane , Sykes Stephen M. , Khandan Tulasi , Lo Celso Cristina , Lopez Cécile K. , Rivera-Muñoz Paola , Rameau Philippe , Tothova Zuzana , Aster Jon C. , DePinho Ronald A. , Scadden David T. , Gilliland D. Gary , Mercher Thomas
Published: June 2011

The NOTCH signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. However, the molecular basis for its role at the different steps of stem cell lineage commitment is unclear. We recently identified the NOTCH signaling pathway as a positive regulator of megakaryocyte lineage specification during hematopoiesis, but the developmental pathways that allow hematopoietic stem cell differentiation into the erythro-megakaryocytic lineages remain controversial. Here, we investigated the role of downstream mediators of NOTCH during megakaryopoiesis and report crosstalk between the NOTCH and PI3K/AKT pathways. We demonstrate the inhibitory role of phosphatase with tensin homolog and Forkhead Box class O factors on megakaryopoiesis in vivo. Finally, our data annotate developmental mechanisms in the hematopoietic system that enable a decision to be made either at the hematopoietic stem cell or the committed progenitor level to commit to the megakaryocyte lineage, supporting the existence of 2 distinct developmental pathways.
A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells
Authors: Wang Xiuli , Chang Wen-Chung , Wong ChingLam W. , Colcher David , Sherman Mark , Ostberg Julie R. , Forman Stephen J. , Riddell Stanley R. , Jensen Michael C.
Published: June 2011

An unmet need in cell engineering is the availability of a single transgene encoded, functionally inert, human polypeptide that can serve multiple purposes, including ex vivo cell selection, in vivo cell tracking, and as a target for in vivo cell ablation. Here we describe a truncated human EGFR polypeptide (huEGFRt) that is devoid of extracellular N-terminal ligand binding domains and intracellular receptor tyrosine kinase activity but retains the native amino acid sequence, type I transmembrane cell surface localization, and a conformationally intact binding epitope for pharmaceutical-grade anti-EGFR monoclonal antibody, cetuximab (Erbitux). After lentiviral transduction of human T cells with vectors that coordinately express tumor-specific chimeric antigen receptors and huEGFRt, we show that huEGFRt serves as a highly efficient selection epitope for chimeric antigen receptor+ T cells using biotinylated cetuximab in conjunction with current good manufacturing practices (cGMP)-grade anti-biotin immunomagnetic microbeads. Moreover, huEGFRt provides a cell surface marker for in vivo tracking of adoptively transferred T cells using both flow cytometry and immunohistochemistry, and a target for cetuximab-mediated antibody-dependent cellular cytotoxicity and in vivo elimination. The versatility of huEGFRt and the availability of pharmaceutical-grade reagents for its clinical application denote huEGFRt as a significant new tool for cellular engineering.
Cellular transcriptional profiling in human lung epithelial cells infected by different subtypes of influenza A viruses reveals an overall down-regulation of the host p53 pathway
Authors: Terrier Olivier , Josset Laurence , Textoris Julien , Marcel Virginie , Cartet Gaëlle , Ferraris Olivier , N'Guyen Catherine , Lina Bruno , Diaz Jean-Jacques , Bourdon Jean-Christophe , Rosa-Calatrava Manuel
Published: June 2011

Background

Influenza viruses can modulate and hijack several cellular signalling pathways to efficiently support their replication. We recently investigated and compared the cellular gene expression profiles of human lung A549 cells infected by five different subtypes of human and avian influenza viruses (Jossetet al.Plos One 2010). Using these transcriptomic data, we have focused our analysis on the modulation of the p53 pathway in response to influenza infection.

Results

Our results were supported by both RT-qPCR and western blot analyses and reveal multiple alterations of the p53 pathway during infection. A down-regulation of mRNA expression was observed for the main regulators of p53 protein stability during infection by the complete set of viruses tested, and a significant decrease in p53 mRNA expression was also observed in H5N1 infected cells. In addition, several p53 target genes were also down-regulated by these influenza viruses and the expression of their product reduced.

Conclusions

Our data reveal that influenza viruses cause an overall down-regulation of the host p53 pathway and highlight this pathway and p53 protein itself as important viral targets in the altering of apoptotic processes and in cell-cycle regulation.
Levosimendan and mortality after coronary revascularisation: a meta-analysis of randomised controlled trials
Authors: Maharaj Ritesh , Metaxa Victoria
Published: June 2011

Introduction

Patients undergoing coronary revascularization often require inotropic support that has been associated with an increased risk for death and morbidity. The purpose of this study was to evaluate the effect of levosimendan versus control on survival after coronary revascularization.

Methods

A systemic review and meta-analysis of the literature was carried out on published randomized controlled clinical trials that investigated the efficacy of levosimendan compared to other therapy in patients having coronary revascularisaion. The databases searched were Pubmed, EMBASE, the Cochrane Registry of Clinical Trials and the metaRegister of Controlled Trials. Studies that compared levosimendan to any other therapy for coronary revascularisation in adult humans and reported at least one outcome of interest were considered for inclusion. Both percutaneous coronary intervention and cardiac surgery were included. Data extraction was performed independently by two reviewers using predefined criteria. Relevant outcomes included mortality, cardiac index, cardiac enzymes, length of stay and post-procedural atrial fibrillation.

Results

The meta-analysis included 729 patients from 17 studies. Levosimendan was associated with a mortality reduction after coronary revascularization, (19/386 in the levosimendan group vs 39/343 in the control arm) odds ratio (OR) 0.40 (95% confidence interval (CI) 0.21 to 0.76, P for overall effect 0.005, P for heterogeneity = 0.33, I2 = 12% with a total of 729 patients. Levosimendan also had a favourable effect on cardiac index (standardised mean difference 1.63, 95% CI 1.43 to 1.83, P for overall effect < 0.00001), length of intensive care stay (random effects model, mean difference - 26.18 hours 95% CI 46.20 to 6.16, P for heterogeneity < 0.00001, I2 = 95%, P for overall effect P = 0.01), reductions in the rate of atrial fibrillation (OR 0.54, 95% CI 0.36 to 0.82, P for effect = 0.004, P for heterogeneity 0.84, I2 = 0% for 465 patients) and troponin I levels group (mean difference -1.59, 95% CI 1.78 to 1.40, P for overall effect < 0.00001, P for heterogeneity < 0.00001, I2 = 95%). Limitations of this analysis are discussed.

Conclusions

Levosimendan is associated with a significant improvement in mortality after coronary revascularization. There are also improvements in several secondary endpoints. A suitably powered randomised controlled trial is required to confirm these findings and to address the unresolved questions about the timing and dosing of levosimendan.
Prevalence of dementia in African–Caribbean compared with
UK-born White older people: two-stage cross-sectional study
Authors: Adelman Simon , Blanchard Martin , Rait Greta , Leavey Gerard , Livingston Gill
Published: June 2011

Background

Preliminary studies in the UK, all using screening instruments of unknown
cultural validity, indicate that there may be an increased prevalence of
dementia in African–Caribbean people, possibly related to vascular risk
factors and potentially amenable to preventative measures.

Aims

To determine the prevalence of dementia in older people of
African–Caribbean country of birth compared with their White UK-born
counterparts.

Method

A total of 218 people of African–Caribbean country of birth and 218 White
UK-born people aged ⩾60 years were recruited from five general practices
in North London. Those who screened positive for cognitive impairment
using a culturally valid instrument were offered a standardised
diagnostic interview. Two independent assessors diagnosed dementia
according to standard operationalised criteria.

Results

African–Caribbean participants were 2 years younger, and those with
dementia nearly 8 years younger than their White counterparts. The
prevalence of dementia was significantly higher in the African–Caribbean
(9.6%) than the White group (6.9%) after adjustment for the confounders
age and socioeconomic status (odds ratio (OR) = 3.1, 95%CI 1.3–7.3,
P = 0.012).

Conclusions

There is an increased prevalence of dementia in older people of
African–Caribbean country of birth in the UK and at younger ages than in
the indigenous White population. These findings have implications for
service provision and preventive interventions. Further research is
needed to explore the role of vascular risk factors and social adversity
in the excess of dementia in this population.
Increased serum and bone matrix levels of transforming growth factor β1 in patients with GH deficiency in response to GH treatment
Authors: Ueland Thor , Lekva Tove , Otterdal Kari , Dahl Tuva B , Olarescu Nicoleta Cristina , Jørgensen Anders P , Fougner Kristian J , Brixen Kim , Aukrust Pål , Bollerslev J
Published: June 2011

Objective

Patients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor β1 (TGFβ1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1in vivoandin vitro.

Design and methods

The effects of GH substitution (9–12 months, placebo controlled) on circulating and cortical bone matrix contents of TGFβ1 were investigated in patients with aoGHD. The effects of GH/IGF1 on TGFβ1 secretion in osteoblasts (hFOB), adipocytes, and THP-1 macrophages as well as the effects on release from platelets were investigatedin vitro.

Results

In vivoGH substitution increased TGFβ1 protein levels in cortical bone and serum.In vitro, GH/IGF1 stimulation induced a significant increase in TGFβ1 secretion in hFOB. In contrast, no major effect of GH/IGF1 on TGFβ1 was found in adipocytes and THP-1 macrophages. Finally, a minor modifying effect on SFLLRN-stimulated platelet release of TGFβ1 was observed in the presence of IGF1.

Conclusion

GH substitution increases TGFβ1in vivoandin vitro, and this effect could contribute to improved bone metabolism during such therapy, potentially reflecting direct effect of GH/IGF1 on bone cells.
Intersections and Translocations: New Paradigms for Thinking about Cultural Diversity and Social Identities
Authors: Anthias Floya
Published: June 2011

This article reflects on the concepts of cultural diversity, belonging and identity which inform important debates for managing ‘difference’ in contemporary European societies. These address issues relating to transnational migration, ethnic diversity and racialisation in a range of social contexts. The article also reflects on the concept of intersectionality as a means of developing a more integrated analysis of social divisions and identities relating particularly to gender, ethnicity and class. It is clear that once we focus on the intersectionality of social divisions and identities, we can move away from essentialised notions of culture, difference and belonging. However, the complexity of social divisions and their inter-relations, both as analytical categories and as categories of practice, asks us to rethink the terms that we use for understanding both identity formations and forms of inequality. This article considers the utility of a more intersectional framing and the notion of translocational positionality in understanding the articulation of social identities.
Voice Conversion Using Pitch Shifting Algorithm by Time Stretching with PSOLA and Re-Sampling
Authors: Mousa Allam
Published: June 2011

Voice Conversion Using Pitch Shifting Algorithm by Time Stretching with PSOLA and Re-Sampling

Voice changing has many applications in the industry and commercial filed. This paper emphasizes voice conversion using a pitch shifting method which depends on detecting the pitch of the signal (fundamental frequency) using Simplified Inverse Filter Tracking (SIFT) and changing it according to the target pitch period using time stretching with Pitch Synchronous Over Lap Add Algorithm (PSOLA), then resampling the signal in order to have the same play rate. The same study was performed to see the effect of voice conversion when some Arabic speech signal is considered. Treatment of certain Arabic voiced vowels and the conversion between male and female speech has shown some expansion or compression in the resulting speech. Comparison in terms of pitch shifting is presented here. Analysis was performed for a single frame and a full segmentation of speech.
A Simple Robust PID Controller Design Method Based on Sine Wave Identification of the Uncertain Plant
Authors: Bucz Štefan , Marič Ladislav , Harsányi Ladislav , Veselý Vojtech
Published: June 2011

A Simple Robust PID Controller Design Method Based on Sine Wave Identification of the Uncertain Plant

The paper deals with the development and application of a new simple empirical approach to the design of robust PID controllers for technological processes in industrial practice. The main advantage of the proposed approach is the possibility to specify the required performance before the design algorithm implementation. Identification of characteristic data of the black-box type plant with varying parameters is carried out using the sine wave excitation signal, thus allowing to design the controller without necessarily knowing the mathematical model of the plant. The proposed approach has been verified on a real-world physical process.
Detection and Recording of Partial Discharges Below the Inception Voltage with a Point-Plane Electrode Arrangement in Air: Experimental Data and Definitions
Authors: Danikas Michael
Published: June 2011

Detection and Recording of Partial Discharges Below the Inception Voltage with a Point-Plane Electrode Arrangement in Air: Experimental Data and Definitions

The problem of insulation damage from partial discharges below the inception voltage has not yet attracted much attention. Indications of possible damage exist from previous research. In this paper, the possibility of existence of such phenomena is investigated with small air gaps and point-plane electrode arrangements. It is shown that random discharges below inception voltage may exist. Such discharges are registered and their waveforms are discussed. Experimental evidence is offered that discharges change from the pulse-type to a pulseless-type as the air gap becomes larger. Phenomena affecting in some way the insulating systems below inception may help us to better understand the mechanism of small current flow at relatively low voltages and may contribute to a better formulation of dielectric materials. Furthermore, besides the experimental results, the problem of definitions regarding these phenomena is discussed and commented upon.
Hybrid Evolutionary-Heuristic Algorithm for Capacitor Banks Allocation
Authors: Barukčić Marinko , Nikolovski Srete , Jović Franjo
Published: June 2011

Hybrid Evolutionary-Heuristic Algorithm for Capacitor Banks Allocation

The issue of optimal allocation of capacitor banks concerning power losses minimization in distribution networks are considered in this paper. This optimization problem has been recently tackled by application of contemporary soft computing methods such as: genetic algorithms, neural networks, fuzzy logic, simulated annealing, ant colony methods, and hybrid methods. An evolutionaryheuristic method has been proposed for optimal capacitor allocation in radial distribution networks. An evolutionary method based on genetic algorithm is developed. The proposed method has a reduced number of parameters compared to the usual genetic algorithm. A heuristic stage is used for improving the optimal solution given by the evolutionary stage. A new cost-voltage node index is used in the heuristic stage in order to improve the quality of solution. The efficiency of the proposed two-stage method has been tested on different test networks. The quality of solution has been verified by comparison tests with other methods on the same test networks. The proposed method has given significantly better solutions for time dependent load in the 69-bus network than found in references.
Prevalence of Frozen Shoulder among Patients Undergoing Cardiothoracic Surgery
Authors: Uddin Md Jamal , Ahmed MSA Mansur , Moniruzzaman M , Rahman Md Habibur , Uddin Md Jalal , Siraj Masoom
Published: June 2011

Keywords: Frozen shoulder; cardiothoracic surgery; physiotherapy; treatment complianceIbrahim Card Med J 2011; 1(1):14-16
Regulation of Autophagy by Kinases
Authors: Sridharan Savitha , Jain Kirti , Basu Alakananda
Published: June 2011

Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.
Microwave Accelerated Transglycosylation of Rutin by Cyclodextrin Glucanotransferase from Bacillus sp. SK13.002
Authors: Sun Tao , Jiang Bo , Pan Beilei
Published: June 2011

Rutin was subjected to intermolecular transglycosylation assisted with microwave irradiation using cyclodextrin glucanotransferase (CGTase) produced from Bacillus sp. SK13.002. Compared with the conventional enzymatic method for rutin transglycosylation (without microwave irradiation), microwave-assisted reaction (MAR) was much faster and thus more efficient. While the conventional reaction took dozens of hours to reach the highest conversion rate of rutin and yield of transglycosylated rutin, MAR of rutin transglycosylation completed within only 6 min providing almost the same conversion rate of rutin and yield of products consisting of mono-, di-, tri-, tetra-, penta-glucosylated rutins. The optimum transglycosylation conditions for microwave irradiation were 40 °C and 60 W with the reaction system consisting mainly of the mixture of 0.3 g rutin (0.49 mmol) pre-dissolved in 15 mL methanol, 1.8 g maltodextrin in 15 mL of 0.2 M sodium acetate buffer (pH 5.5) and CGTase (900 U). Results from this study indicated that MAR could be a potentially useful and economical technique for a faster and more efficient transglycosylation of rutin.
Canadian Initiatives for Locally Advanced Breast Cancer Research and Treatment: Inaugural Meeting of the Canadian Consortium for LABC
Authors: Brackstone M. , Robidoux A. , Chia S. , Mackey J. , Dent R. , Boileau J.F. , Clemons M.
Published: June 2011

The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11–12, 2010. The meeting focused on current and future directions in labc treatment and research, the specific benefits of labc as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in labc research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference.
Introduction
Authors:   The Editors
Published: June 2011

Future directions are often shaped by quirks of necessity or chance: the groundbreaking iconoclast that is Moebius’s Garage hermétique, with its rejection of conventional narrative or character coherence, came as a result of the author having forgotten previous scripts from one week to the next; Rodolphe Töpffer, so often credited for having invented the modern comic strip, initially saw himself as producing no more than scribblings for the entertainment of his pupils; one of the earliest of text/image forms, the emblem, may well be the result of Augsburg printer, Heinrich Steiner, adding images in 1531 to Andrea Alciato’s epigrams, a far cry from the composed intertwining of Francesco Colonna’s Hypnerotomachia Poliphili of 1499. Mirroring such processes in our own way, European Comic Art is embarking on a new direction, as we turn to issues that can reflect the diversity of comic art rather than being necessarily united by a single theme. It is a logical direction, but also one shaped by chance and necessity, that of the diversity of high-quality submissions that we have been delighted to receive.
A Creative Culture Where It Is Hard to Make a Living
Authors: Lefèvre Pascal , Di Salvia Morgan
Published: June 2011

On the initiative of the research office of the non-profit SMartBe Professional Association for Creative Professions, an exploratory survey into the current socio-economic circumstances of comics authors and illustrators in Belgium has been undertaken for the first time. The replies of 191 French-speaking and 72 Dutch-speaking artists to the online questionnaire have given an idea of the profile of comics authors and illustrators in Belgium (in terms of gender, age, place of residence, educational background), their professional activities and the type of publications in which their work appears, and their employment status and income. The results show that, in general, their monthly income falls below the Belgian median, and that many artists, particularly in the younger age range, are reliant on supplementing their earnings from other sources. A number of differences emerged between the situation of French-speaking and Dutch-speaking artists. The role of creative grants (especially subsidies from the government) is shown to be crucial.
Book Reviews
Authors: Gazzola Giuseppe , Leader Karen J.
Published: June 2011

Simone Castaldi, Drawn and Dangerous: Italian Comics of the 1970s and 1980s
Giuseppe Gazzola

Joel E. Vessels, Drawing France: French Comics and the Republic
Karen J. Leader
Targeting FcαRI on Polymorphonuclear Cells Induces Tumor Cell Killing through Autophagy
Authors: Bakema Jantine E. , Ganzevles Sonja H. , Fluitsma Donna M. , Schilham Marco W. , Beelen Robert H. J. , Valerius Thomas , Lohse Stefan , Glennie Martin J. , Medema Jan Paul , van Egmond Marjolein
Published: June 2011

Neutrophils are the most abundant circulating FcR-expressing WBCs with potent cytotoxic ability. Currently, they are recognized as promising effector cells for Ab-mediated immunotherapy of cancer, because their capacity to kill tumor cells is greatly enhanced by tumor Ag-specific mAbs. The FcαRI represents the most potent FcR on neutrophils for induction of Ab-mediated tumor cell killing. However, the mechanisms of cell death that are induced are poorly understood. Because these mechanisms can be used for modulation of anticancer treatment, we investigated the tumor cell death induced by neutrophil-mediated Ab-dependent killing via FcαRI. Human mammary carcinoma cells were efficiently killed when incubated with human neutrophils and tumor-specific FcαRI bispecific or IgA Abs. Interestingly, we observed characteristics of autophagy such as autophagic structures by electron microscopy and LC3B+ autophagosomes in different human epithelial carcinoma cells, which resulted in tumor cell death. To a lesser extent, necrotic features, such as cellular membrane breakdown and spillage of intracellular content, were found. By contrast, apoptotic features including fragmented nuclei, Annexin V-positivity, and presence of cleaved caspase-3 were not observed. These findings indicate that neutrophils mainly facilitate autophagy to induce tumor cell death rather than the more commonly recognized apoptotic cell death mechanisms induced by NK cells or cytotoxic T cells. This knowledge not only reveals the type of tumor cell death induced in neutrophil-mediated, Ab-dependent cellular cytotoxicity, but importantly opens up additional perspectives for modulation of anticancer therapy in, for example, apoptosis-resistant tumor cells.
Gab2, via PI-3K, Regulates ARF1 in FcεRI-Mediated Granule Translocation and Mast Cell Degranulation
Authors: Nishida Keigo , Yamasaki Satoru , Hasegawa Aiko , Iwamatsu Akihiro , Koseki Haruhiko , Hirano Toshio
Published: June 2011

Mast cells are major players in allergic responses. IgE-dependent activation through FcεR leads to degranulation and cytokine production, both of which require Gab2. To clarify how the signals diverge at Gab2, we established Gab2 knock-in mice that express Gab2 mutated at either the PI3K or SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) binding sites. Examination of these mutants showed that both binding sites were required for the degranulation and anaphylaxis response but not for cytokine production or contact hypersensitivity. Furthermore, the PI3K, but not the SHP2, binding site was important for granule translocation during degranulation. We also identified a small GTPase, ADP-ribosylation factor (ARF)1, as the downstream target of PI3K that regulates granule translocation. FcεRI stimulation induced ARF1 activation, and this response was dependent on Fyn and the PI3K binding site of Gab2. ARF1 activity was required for FcεRI-mediated granule translocation. These data indicated that Fyn/Gab2/PI3K/ARF1-mediated signaling is specifically involved in granule translocation and the anaphylaxis response.
Bayesian statistical modeling of spatially correlated error structure in atmospheric tracer inverse analysis
Authors: Mukherjee C. , Kasibhatla P. S. , West M.
Published: June 2011

Abstract. We present and discuss the use of Bayesian modeling and computational methods for atmospheric chemistry inverse analyses that incorporate evaluation of spatial structure in model-data residuals. Motivated by problems of refining bottom-up estimates of source/sink fluxes of trace gas and aerosols based on satellite retrievals of atmospheric chemical concentrations, we address the need for formal modeling of spatial residual error structure in global scale inversion models. We do this using analytically and computationally tractable conditional autoregressive (CAR) spatial models as components of a global inversion framework. We develop Markov chain Monte Carlo methods to explore and fit these spatial structures in an overall statistical framework that simultaneously estimates source fluxes. Additional aspects of the study extend the statistical framework to utilize priors on source fluxes in a physically realistic manner, and to formally address and deal with missing data in satellite retrievals. We demonstrate the analysis in the context of inferring carbon monoxide (CO) sources constrained by satellite retrievals of column CO from the Measurement of Pollution in the Troposphere (MOPITT) instrument on the TERRA satellite, paying special attention to evaluating performance of the inverse approach using various statistical diagnostic metrics. This is developed using synthetic data generated to resemble MOPITT data to define a proof-of-concept and model assessment, and then in analysis of real MOPITT data. These studies demonstrate the ability of these simple spatial models to substantially improve over standard non-spatial models in terms of statistical fit, ability to recover sources in synthetic examples, and predictive match with real data.
Source brightness fluctuation correction of solar absorption fourier transform mid infrared spectra
Authors: Ridder T. , Warneke T. , Notholt J.
Published: June 2011

Abstract. The precision and accuracy of trace gas observations using solar absorption Fourier Transform infrared spectrometry depend on the stability of the light source. Fluctuations in the source brightness, however, cannot always be avoided. Current correction schemes, which calculate a corrected interferogram as the ratio of the raw DC interferogram and a smoothed DC interferogram, are applicable only to near infrared measurements. Spectra in the mid infrared spectral region below 2000 cm−1 are generally considered uncorrectable, if they are measured with a MCT detector. Such measurements introduce an unknown offset to MCT interferograms, which prevents the established source brightness fluctuation correction. This problem can be overcome by a determination of the offset using the modulation efficiency of the instrument. With known modulation efficiency the offset can be calculated, and the source brightness correction can be performed on the basis of offset-corrected interferograms. We present a source brightness fluctuation correction method which performs the smoothing of the raw DC interferogram in the interferogram domain by an application of a running mean instead of high-pass filtering the corresponding spectrum after Fourier transformation of the raw DC interferogram. This smoothing can be performed with the onboard software of commercial instruments. The improvement of MCT spectra and subsequent ozone profile and total column retrievals is demonstrated. Application to InSb interferograms in the near infrared spectral region proves the equivalence with the established correction scheme.
The effect of resource history on the functioning of soil microbial communities is maintained across time
Authors: Keiser A. D. , Strickland M. S. , Fierer N. , Bradford M. A.
Published: June 2011

Abstract. Historical resource conditions appear to influence microbial community function. With time, historical influences might diminish as populations respond to the contemporary environment. Alternatively, they may persist given factors such as contrasting genetic potentials for adaptation to a new environment. Using experimental microcosms, we test competing hypotheses that function of distinct soil microbial communities in common environments (H1a) converge or (H1b) remain dissimilar over time. Using a 6 × 2 (soil community inoculum × litter environment) full-factorial design, we compare decomposition rates in experimental microcosms containing grass or hardwood litter environments. After 100 days, communities that develop are inoculated into fresh litters and decomposition followed for another 100 days. We repeat this for a third, 100-day period. In each successive, 100-day period, we find higher decomposition rates (i.e. functioning) suggesting communities function better when they have an experimental history of the contemporary environment. Despite these functional gains, differences in decomposition rates among initially distinct communities persist, supporting the hypothesis that dissimilarity is maintained across time. In contrast to function, community composition is more similar following a common, experimental history. We also find that "specialization" on one experimental environment incurs a cost, with loss of function in the alternate environment. For example, experimental history of a grass-litter environment reduced decomposition when communities were inoculated into a hardwood-litter environment. Our work demonstrates experimentally that despite expectations of fast growth rates, physiological flexibility and rapid evolution, initial functional differences between microbial communities are maintained across time. These findings question whether microbial dynamics can be omitted from models of ecosystem processes if we are to predict reliably global change effects on biogeochemical cycles.
Transport and fate of hexachlorocyclohexanes in the oceanic air and surface seawater
Authors: Xie Z. , Koch B. P. , Möller A. , Sturm R. , Ebinghaus R.
Published: June 2011

Abstract. Hexachlorocyclohexanes (HCHs) are ubiquitous organic pollutants derived from pesticide application. They are subject to long-range transport, persistent in the environment, and capable of accumulation in biota. Shipboard measurements of HCH isomers (α-, γ- and β-HCH) in surface seawater and boundary layer atmospheric samples were conducted in the Atlantic and the Southern Ocean in October to December of 2008. ΣHCHs concentrations (the sum of α-, γ- and β-HCH) in the lower atmosphere ranged from 11.8 to 36.9 pg m−3 (mean: 26.6 ± 11.0 pg m−3) in the Northern Hemisphere (NH), and from 1.5 to 4.0 pg m−3 (mean: 2.8 ± 1.1 pg m−3) in the Southern Hemisphere (SH), respectively. Water concentrations were: α-HCH 0.33–46.8 pg l−1, γ-HCH 0.02–33.2 pg l−1 and β-HCH 0.11–2 pg l−1. HCH concentrations decreased from the North Atlantic to the Southern Ocean, indicating historical use of HCHs in the NH. Spatial distribution showed increasing concentrations from the equator towards North and South latitudes illustrating the concept of cold condensation and less interhemispheric mixing process. In comparison to concentrations measured in 1987–1999/2000, gaseous HCHs were slightly lower, while dissolved HCHs decreased by factor of 2–3 orders of magnitude. Air-water exchange gradients suggested net deposition for α-HCH (mean: 3759 pg m−2 day−1) and γ-HCH (mean: 1987 pg m−2 day−1), whereas β-HCH varied between equilibrium (volatilization: <0–12 pg m−2 day−1) and net deposition (range: 6–687 pg m−2 day−1), indicating a multi-hopper transport behavior. Climate change may significantly accelerate the releasing process of "old" HCHs from continental storage (e.g. soil, vegetation and high mountains) and drive long-range transport from sources to deposition in the open oceans. Biological productivities may interfere with the air-water exchange process as well. Consequently, further investigation is necessary to elucidate the long term trends and the biogeochemical turnover of HCHs in the oceanic environment.
Reply to Henriksson et al.'s comment on "Using multiple observationally-based constraints to estimate climate sensitivity" by Annan and Hargreaves (2010)
Authors: Annan J. D. , Hargreaves J. C.
Published: June 2011

Abstract. Henriksson et al. (2010), hereafter HALTL10, criticize Annan and Hargreaves (2006a) (AH06) primarily on the grounds that we assumed that different sources of data were conditionally independent given the climate sensitivity. While we consider this approximation to have been a reasonable one under the circumstances (and provided arguments to justify this approach), we also acknowledged its importance in our original paper and performed several sensitivity analyses. The alternative calculations presented by HALTL10 appear to strengthen rather than contradict our conclusion. HALTL10 additionally criticize Annan and Hargreaves (2009) (AH09) for proposing a Cauchy type prior (as an alternative to the use of a uniform prior, which was widespread up to that time) "without sufficient support", and further claim that anticipated economic damages were used as a means of selecting the prior. We are surprised by these claims, especially considering that the proposed prior was justified at some length both on the basis of both the "Charney report" (National Research Council, 1979) and basic physical arguments, and also in light of our elementary demonstration of the pathological failings of the most commonly-used alternative. Thus, these claims are factually incorrect.
Active gesture-changeable underactuated finger for humanoid robot hand based on multiple tendons
Authors: Che D. , Zhang W.
Published: June 2011

Abstract. The concept called gesture-changeable under-actuated (GCUA) function is utilized to improve the dexterities of traditional under-actuated hands and reduce the control difficulties of dexterous hands. Based on GCUA function, a novel mechanical finger by multiple tendons: GCUA-T finger, is designed. The finger uses tendon mechanisms to achieve GCUA function which includes traditional underactuated (UA) grasping motion and special pre-bending (PB, or pre-shaping) motion before UA grasping. Operation principles and force analyses of the fingers are given, and the effect of GCUA function on the movements of a hand is discussed. The finger can satisfy the requirements of grasping and operating with low dependence on control system and low cost on manufacturing expenses, which develops a new way between dexterous hand and traditional under-actuated hand. This paper was presented at the IFToMM/ASME International Workshop on Underactuated Grasping (UG2010), 19 August 2010, Montréal, Canada.
Stabilization of switching Takagi–Sugeno systems by switched Lyapunov function
Authors: Benzaouia Abdellah , Hajjaji Ahmed El , Tadeo Fernando
Published: June 2011

This paper presents sufficient conditions for the stabilization of switching T‐S fuzzy discrete‐time linear systems. These conditions are obtained when state feedback control laws are used. The obtained results are formulated in terms of LMIs. A numerical example illustrates the technique. Copyright © 2011 John Wiley & Sons, Ltd.
Strain‐Promoted Alkyne–Azide Cycloadditions (SPAAC) Reveal New Features of Glycoconjugate Biosynthesis
Authors: Mbua Ngalle Eric , Guo Jun , Wolfert Margreet A. , Steet Richard , Boons Geert‐Jan
Published: June 2011

We have shown that 4‐dibenzocyclooctynol (DIBO), which can easily be obtained by a streamlined synthesis approach, reacts exceptionally fast in the absence of a CuI catalyst with azido‐containing compounds to give stable triazoles. Chemical modifications of DIBO, such as oxidation of the alcohol to a ketone, increased the rate of strain promoted azide–alkyne cycloadditions (SPAAC). Installment of a ketone or oxime in the cyclooctyne ring resulted in fluorescent active compounds whereas this property was absent in the corresponding cycloaddition adducts; this provides the first example of a metal‐free alkyne–azide fluoro‐switch click reaction. The alcohol or ketone functions of the cyclooctynes offer a chemical handle to install a variety of different tags, and thereby facilitate biological studies. It was found that DIBO modified with biotin combined with metabolic labeling with an azido‐containing monosaccharide can determine relative quantities of sialic acid of living cells that have defects in glycosylation (Lec CHO cells). A combined use of metabolic labeling/SPAAC and lectin staining of cells that have defects in the conserved oligomeric Golgi (COG) complex revealed that such defects have a greater impact on O‐glycan sialylation than galactosylation, whereas sialylation and galactosylation of N‐glycans was similarly impacted. These results highlight the fact that the fidelity of Golgi trafficking is a critical parameter for the types of oligosaccharides being biosynthesized by a cell. Furthermore, by modulating the quantity of biosynthesized sugar nucleotide, cells might have a means to selectively alter specific glycan structures of glycoproteins.
Protoberberine Alkaloids and Cancer Chemopreventive Properties of Compounds from Alangium salviifolium
Authors: Pailee Phanruethai , Prachyawarakorn Vilailak , Mahidol Chulabhorn , Ruchirawat Somsak , Kittakoop Prasat
Published: June 2011

New protoberberine alkaloids, namely alangiumkaloids A (1) and B (2), 27‐O‐trans‐caffeoylcylicodiscic acid (3), and β‐D‐glucopyranos‐1‐yl N‐methylpyrrole‐2‐carboxylate (5) together with myriceric acid B (4), isoalangiside (6), alangiside (7), 3‐O‐demethyl‐2‐O‐methylalangiside (8), and demethylalangiside (9) have been isolated from Alangium salviifolium. The cancer chemopreventive properties and cytotoxic activities of the isolated compounds were evaluated. Compounds 3, 4, and 9 scavenged DPPH free radicals with IC50 values of 21.4, 21.8, and 24.0 μM, respectively. Alangisides 7 and 9 inhibited superoxide anion radical formation in the xanthine/xanthine oxidase (XXO) assay with IC50 values of 19.4 and 5.3 μM, respectively. Compounds 6–9 showed excellent antioxidant activity in the oxygen radical absorbance capacity (ORAC) assay with 12.8–24.9 ORAC units. Compounds 3 and 4 inhibited aromatase activity with IC50 values of 4.7 and 6.8 μM, respectively. Although the isolated compounds showed only weak cytotoxicity or were inactive, compounds 3 and 4 exhibited cytotoxic activity towards the MOLT‐3 cell line with IC50 values of 5.6 and 3.9 μM, respectively, and compound 8 selectively inhibited the growth of the HepG2 cancer cell line with an IC50 value of 7.1 μM.
A synthetic hydrologic‐response dataset
Authors: Mirus Benjamin B. , Loague Keith , Cristea Nicoleta C. , Burges Stephen J. , Kampf Stephanie K.
Published: June 2011

Synthetic data have long been employed in hydrology for model development and testing. The objective of this study was to generate a synthetic dataset of hydrologic response with higher spatial and temporal resolution than could presently be obtained in the field, spanning a longer period than the typical duration of monitoring campaigns in experimental catchments. The synthetic dataset was generated for a rangeland catchment with the Integrated Hydrology Model (InHM), and is presented for future use by the community. The InHM boundary‐value problem is based upon the previously reported hypothetical reality of Tarrawarra‐like hydrologic response. Whereas the emphasis in developing the hypothetical reality was on parameterising InHM to reproduce observations from the Tarrawarra catchment, the emphasis in generating the synthetic dataset is on developing an internally valid hydrologic‐response dataset that extends well beyond the period of observations at Tarrawarra. The synthetic dataset spans 11 years of continuous forcing and response data (e.g. integrated response, distributed fluxes, state variable dynamics). The dataset should be useful for a wide range of problems including evaluation of simple rainfall runoff modelling techniques, design of measurement networks, development of data‐assimilation algorithms, and studies on information theory. The dataset is available at: ftp://pangea.stanford.edu/pub/loague/. Copyright © 2011 John Wiley & Sons, Ltd.
Analysis of Aspergillus nidulans germination, initial growth and carbon source response by flow cytometry
Authors: Pereira de Souza Camila Cristina , Moreira Prado Giselda , da Conceição Freitas Roberta Cristina , Silva Santos Guimarães Patrícia , Calegário de Oliveira Leida , Eustáquio Alvim Brito‐Melo Gustavo , de Figueiredo Conte Vanzela Ana Paula
Published: June 2011

In this work, flow cytometry was utilized to analyze the initial vegetative growth of the model fungus Aspergillus nidulans as measured by the number of events increasing size and internal complexity. It was established the ideal parameters for the analysis of conidial populations, whose growth was followed after germination in glucose or sucrose. While glucose in culture increased growth several magnitudes in comparison to control cultures in saline, growth was less intense in cultures amended with sucrose. Results indicated that flow cytometry could be a useful tool to study fungal germination and initial growth since it allowed rapid identification of different populations by means of their increasing in size and granularity with good reproducibility and without the need for direct observation and count of individual cells. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)