bluuebunny/crossref_metadata_2025 huggingface dataset:
IFN-γ Attenuates Hypoxia-Inducible Factor (HIF) Activity in Intestinal Epithelial Cells through Transcriptional Repression of HIF-1β
Authors: Glover Louise E. , Irizarry Karina , Scully Melanie , Campbell Eric L. , Bowers Brittelle E. , Aherne Carol M. , Kominsky Douglas J. , MacManus Christopher F. , Colgan Sean P.
Published: January 2011

Numerous studies have revealed that hypoxia and inflammation occur coincidentally in mucosal disorders, such as inflammatory bowel disease. During inflammation, epithelial-expressed hypoxia-inducible factor (HIF) serves an endogenously protective function. In this study, we sought to explore how mucosal immune responses influence HIF-dependent end points. Guided by a screen of relevant inflammatory mediators, we identified IFN-γ as a potent repressor of HIF-dependent transcription in human intestinal epithelial cells. Analysis of HIF levels revealed that HIF-1β, but not HIF-1α, is selectively repressed by IFN-γ in a JAK-dependent manner. Cloning and functional analysis of the HIF-1β promoter identified a prominent region for IFN-γ–dependent repression. Further studies revealed that colonic IFN-γ and HIF-1β levels were inversely correlated in a murine colitis model. Taken together, these studies demonstrated that intestinal epithelial HIF is attenuated by IFN-γ through transcriptional repression of HIF-1β. These observations are relevant to the pathophysiology of colitis (i.e., that loss of HIF signaling during active inflammation may exacerbate disease pathogenesis).
NLRP4 Negatively Regulates Autophagic Processes through an Association with Beclin1
Authors: Jounai Nao , Kobiyama Kouji , Shiina Masaaki , Ogata Kazuhiro , Ishii Ken J. , Takeshita Fumihiko
Published: January 2011

Although more than 20 putative members have been assigned to the nucleotide-binding and oligomerization domain-like receptor (NLR) family, their physiological and biological roles, with the exception of the inflammasome, are not fully understood. In this article, we show that NLR members, such as NLRC4, NLRP3, NLRP4, and NLRP10 interact with Beclin1, an important regulator of autophagy, through their neuronal apoptosis inhibitory protein, MHC class II transcription activator, incompatibility locus protein from Podospora anserina, and telomerase-associated protein domain. Among such NLRs, NLRP4 had a strong affinity to the Beclin1 evolutionally conserved domain. Compromising NLRP4 via RNA interference resulted in upregulation of the autophagic process under physiological conditions and upon invasive bacterial infections, leading to enhancement of the autophagic bactericidal process of group A streptococcus. NLRP4 recruited to the subplasma membrane phagosomes containing group A streptococcus and transiently dissociated from Beclin1, suggesting that NLRP4 senses bacterial infection and permits the initiation of Beclin1-mediated autophagic responses. In addition to a role as a negative regulator of the autophagic process, NLRP4 physically associates with the class C vacuolar protein-sorting complex, thereby negatively regulating maturation of the autophagosome and endosome. Collectively, these results provide novel evidence that NLRP4, and possibly other members of the NLR family, plays a crucial role in biogenesis of the autophagosome and its maturation by the association with regulatory molecules, such as Beclin1 and the class C vacuolar protein-sorting complex.
IL-1β Is Overexpressed and Aberrantly Regulated in Corticosteroid Nonresponders with Autoimmune Inner Ear Disease
Authors: Pathak Shresh , Goldofsky Elliot , Vivas Esther X. , Bonagura Vincent R. , Vambutas Andrea
Published: January 2011

Autoimmune inner ear disease is an enigmatic disorder characterized by recurring episodes of sudden or progressive sensorineural hearing loss. Hearing loss can be improved by timely corticosteroid administration, but only half of those treated respond, and for many responders, that response is lost over time. The mechanisms that control corticosteroid responsiveness in this disorder are largely uncharacterized. We have previously identified that the induction by dexamethasone of IL-1R type II (IL-1R2) expression in PBMC predicts corticosteroid responsiveness in this disorder. In this study, we asked whether IL-1β was overexpressed, and whether clinical corticosteroid responders differentially regulated IL-1β expression or release in response to dexamethasone, as compared with nonresponders. IL-1β has been reported to induce matrix metalloproteinase-9 (MMP-9) expression. Given that metalloproteinases can cleave IL-1R2, we also asked whether MMP-9 expression was altered in this disorder. In this study, we demonstrate that corticosteroid nonresponders have elevated plasma levels of IL-1β and MMP-9 as compared with clinically responsive patients (p = 0.0008 and p = 0.037, respectively). Increasing MMP-9 expression correlated with increasing IL-1β concentration, suggesting that IL-1β expression regulates MMP-9 expression. As expected, monocytes were the predominant producers of IL-1β. In vitro exposure of PBMC to dexamethasone from clinical corticosteroid responders suppressed IL-1β release. PBMC of corticosteroid nonresponders have substantially higher release of IL-1β into the conditioned media, and when exposed to dexamethasone, failed to repress IL-1β release (p = 0.05). Treatment of PBMC from clinical corticosteroid nonresponders with anakinra resulted in repression of IL-1β release, suggesting that IL-1β blockade may be a viable therapy for these patients.
The Melanocortin 3 Receptor: A Novel Mediator of Exercise-Induced Inflammation Reduction in Postmenopausal Women?
Authors: Henagan Tara M. , Phillips Melody D. , Cheek Dennis J. , Kirk K. Michelle , Barbee James J. , Stewart Laura K.
Published: January 2011

The purpose of this study was to determine whether resistance exercise training-induced reductions in inflammation are mediated via melanocortin 3 receptor expression in obese (BMI ) women ( yrs) randomized to either a control () or resistance training group (). The resistance trained group performed resistance training 3 days/week for 12 weeks. Resting blood samples were collected before and after the training intervention in both resistance trained and control groups. Resistance training upregulated melanocortin 3 receptor mRNA by 16-fold () and decreased monocyte count, without changing leukocyte number, body composition, or body weight. Resistance trained individuals exhibited increased sensitivity to inflammatory stimuli, whereas control individuals exhibited no change. While there was no change in whole blood tumor necrosis factor alpha mRNA between the groups, whole blood interleukin 10 mRNA was higher in the resistance trained group following the intervention period. In summary, it appears that resistance training may modulate melanocortin 3 receptor expression, providing a possible mechanism for the anti-inflammatory effects of exercise training.
A Prospective Study of Acute Diarrhea in a Cohort of United States Military Personnel on Deployment to the Multinational Force and Observers, Sinai, Egypt
Authors: Riddle Mark S. , Rockabrand David M. , Schlett Carey , Monteville Marshall R. , Frenck Robert W. , Romine Marcy , Ahmed Salwa F. , Sanders John W.
Published: January 2011

To better understand the epidemiology of diarrhea in deployed personnel to the Middle East, a prospective cohort study of travelers' diarrhea (TD) was conducted between May 2004 and January 2005 at the Multinational Force and Observers (MFO) camp in the southern Sinai. A baseline entry questionnaire and stool specimen was provided on study entry, and volunteers were followed every 6 weeks. Of 211 volunteers, 145 (68.7%) completed one or more follow-up visits. In total, 416 follow-up surveys were completed, which described an overall incidence of 25.2 episodes per 100 person months (95% confidence interval = 21.2–30.0). Additionally, stools were collected in 72 of 77 diarrhea-associated clinic visits, with bacterial pathogens most commonly isolated (enterotoxigenic Escherichia coli in 30 [42%] samples and Campylobacter jejuni in 7 [10%] samples) Despite modern preventive methods, diarrhea is still a common problem for deployed US military personnel in Egypt, frequently resulting in diminished ability to work.
The Immune Response to Schistosome Antigens in Formerly Infected Travelers
Authors: Soonawala Darius , Geerts Jan-Willem H. J. , de Mos Marissa , Yazdanbakhsh Maria , Visser Leo G.
Published: January 2011

We investigated the type and strength of the immune response to schistosome antigens in a group of 20 Dutch travelers who had been infected with Schistosoma spp. during a group visit to Mali in 1991 and 8 non-infected controls. At the time, 9 had Katayama syndrome (KS), and 11 remained asymptomatic. All had been treated with praziquantel. Eight years later, serology remained positive in all 20 formerly infected travelers. The lymphocyte proliferative responses and cytokine responses (interleukin 13 [IL-13], IL-10, and interferon [IFN-γ] responses to soluble egg antigens and the IL-13, IL-10, and IL-5 response to adult worm antigen) were stronger in the travelers than in the controls and tended to be stronger in those with KS compared with those who had remained asymptomatic. In conclusion, Schistosoma infection induced a memory immune response, and people who experienced KS tended to have a stronger immune response to schistosome antigens than their asymptomatic counterparts.
Field Efficacy of New Larvicide Products for Control of Multi-Resistant Aedes aegypti Populations in Martinique (French West Indies)
Authors: Marcombe Sébastien , Darriet Frédéric , Agnew Philip , Etienne Manuel , Yp-Tcha Marie-Michelle , Yébakima André , Corbel Vincent
Published: January 2011

World-wide dengue vector control is hampered by the spread of insecticide resistance in Aedes aegypti. We report the resistance status of a wild Ae. aegypti population from Martinique (Vauclin) to conventional larvicides (Bacillus thuringiensis var israeliensis [Bti] and temephos) and potential alternatives (spinosad, diflubenzuron, and pyriproxyfen). The efficacy and residual activity of these insecticides were evaluated under simulated and field conditions. The Vauclin strain exhibited a high level of resistance to temephos, a tolerance to insect growth regulators, and full susceptibility to spinosad and Bti. In simulated trials, pyriproxyfen and Bti showed long residual activities in permanent breeding containers (28 and 37 weeks), whereas under field conditions they failed to curtail Ae. aegypti populations after four weeks. Conversely, diflubenzuron and spinosad showed a residual efficacy of 16 weeks, suggesting that these chemicals may be promising alternatives to Bti and temephos for controlling insecticide-resistant Ae. aegypti populations.
Evaluation of Human Enteric Viruses in Surface Water and Drinking Water Resources in Southern Ghana
Authors: Gibson Kristen E. , Opryszko Melissa C. , Schissler James T. , Guo Yayi , Schwab Kellogg J.
Published: January 2011

An estimated 884 million people worldwide do not have access to an improved drinking water source, and the microbial quality of these sources is often unknown. In this study, a combined tangential flow, hollow fiber ultrafiltration (UF), and real-time PCR method was applied to large volume (100 L) groundwater (N = 4), surface water (N = 9), and finished (i.e., receiving treatment) drinking water (N = 6) samples for the evaluation of human enteric viruses and bacterial indicators. Human enteric viruses including norovirus GI and GII, adenovirus, and polyomavirus were detected in five different samples including one groundwater, three surface water, and one drinking water sample. Total coliforms and Escherichia coli assessed for each sample before and after UF revealed a lack of correlation between bacterial indicators and the presence of human enteric viruses.
Integrated Implementation of Programs Targeting Neglected Tropical Diseases through Preventive Chemotherapy: Proving the Feasibility at National Scale
Authors: Linehan Mary , Hanson Christy , Weaver Angela , Baker Margaret , Kabore Achille , Zoerhoff Kathryn L. , Sankara Dieudonne , Torres Scott , Ottesen Eric A.
Published: January 2011

In 2006, the United States Agency for International Development established the Neglected Tropical Disease (NTD) Control Program to facilitate integration of national programs targeting elimination or control of lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and blinding trachoma. By the end of year 3, 12 countries were supported by this program that focused first on disease mapping where needed, and then on initiating or expanding disease-specific programs in a coordinated/integrated fashion. The number of persons reached each year increased progressively, with a cumulative total during the first three years of 98 million persons receiving 222 million treatments with donated drugs valued at more than $1.4 billion. Geographic coverage increased substantially for all these infections, and the program has supported training of more than 220,000 persons to implement the programs. This current experience of the NTD Control Program demonstrates clearly that an integrated approach to control or eliminate these five neglected diseases can be effective at full national scale.
Quantification of Plasmodium falciparum Gametocytes by Magnetic Fractionation
Authors: Karl Stephan , Davis Timothy M. E. , St. Pierre Tim G.
Published: January 2011

A method of gametocyte quantitation in human blood was developed based on magnetic fractionation using commercially available magnetic fractionation columns (MFCs) and exploiting the magnetic susceptibility of mature Plasmodium falciparum gametocytes. The technique uses magnetic microspheres as a calibration standard. Microspheres are added to each blood sample to a known concentration. When exposed to a magnetic field, gametocytes and magnetic microspheres are preferentially captured inside MFCs. After removal of the magnetizing field, the magnetically captured material can be eluted, placed on a microscope slide that is stained, and counted by using conventional methods. The limits of quantitation for P. falciparum gametocytes were determined from serial dilutions of blood samples with known gametocyte density. The upper limit was 1,000 gametocytes/μL. Quantitative analysis above this threshold is difficult because of an over-abundance of gametocytes. The lower limit was 0.1 gametocytes/μL, and there is a significant probability of a false-negative result below this level.
Wealth and Its Associations with Enteric Parasitic Infections in a Low-Income Community in Peru: Use of Principal Component Analysis
Authors: Nundy Shantanu , Gilman Robert H. , Xiao Lihua , Cabrera Lilia , Cama Rosa , Ortega Ynes R. , Kahn Geoffrey , Cama Vitaliano A.
Published: January 2011

The association of wealth and infections with Giardia, Cryptosporidium, Cyclospora, and microsporidia were examined in a longitudinal cohort conducted in Peru from 2001 to 2006. Data from 492 participants were daily clinical manifestations, weekly copro-parasitological diagnosis, and housing characteristics and assets owned (48 variables), and these data were used to construct a global wealth index using principal component analysis. Data were analyzed using continuous and categorical (wealth tertiles) models. Participant's mean age was 3.43 years (range = 0–12 years), with average follow-up of 993 days. Univariate and multivariate analyses identified significant associations between wealth and infections with Giardia and microsporidia. Participants with greater wealth indexes were associated with protection against Giardia (P < 0.001) and persistent Giardia infections (> 14 days). For microsporidia, greater wealth was protective (P = 0.066 continuous and P = 0.042 by tertiles). Contrarily, infections with Cryptosporidium and Cyclospora were independent of wealth. Thus, subtle differences in wealth may affect the frequency of specific parasitic infections within low-income communities.
Epidemiological Factors Associated with Dengue Shock Syndrome and Mortality in Hospitalized Dengue Patients in Ho Chi Minh City, Vietnam
Authors: Anders Katherine L. , Nguyet Nguyen Minh , Van Vinh Chau Nguyen , Hung Nguyen Thanh , Thuy Tran Thi , Lien Le Bich , Farrar Jeremy , Wills Bridget , Hien Tran Tinh , Simmons Cameron P.
Published: January 2011

Understanding trends in dengue disease burden and risk factors for severe disease can inform health service allocation, clinical management, and planning for vaccines and therapeutics. Dengue admissions at three tertiary hospitals in Ho Chi Minh City, Vietnam, increased between 1996 and 2009, peaking at 22,860 in 2008. Children aged 6–10 years had highest risk of dengue shock syndrome (DSS); however, mortality was highest in younger children and decreased with increasing age (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36–0.75 in 6- to 10- year-old children and OR = 0.27, 95% CI = 0.16–0.44 in 11- to 15-year-old children compared with 1- to 5-year-old children). Males were overrepresented among dengue cases; however, girls had higher risk of DSS (OR = 1.19, 95% CI = 1.14–1.24) and death (OR = 1.57, 95% CI = 1.14–2.17). Young children with dengue had greatest risk of death and should be targeted in dengue vaccine and drug trials. The increased risk of severe outcomes in girls warrants further attention in studies of pathogenesis, health-seeking behavior, and clinical care.
Post-Arrival Screening for Malaria in Asymptomatic Refugees Using Real-Time PCR
Authors: Matisz Chelsea E. , Naidu Prenilla , Shokoples Sandra E. , Grice Diane , Krinke Valerie , Brown Stuart Z. , Kowalewska-Grochowska Kinga , Houston Stan , Yanow Stephanie K.
Published: January 2011

Malaria is a significant health risk to refugee populations originating from endemic areas, but there is little consensus on screening and/or treatment approaches for malaria in this population. Furthermore, detection of malaria in semi-immune asymptomatic refugees is limited by the sensitivity of diagnostic tests used for screening. We determined the prevalence of malaria by microscopy and real-time polymerase chain reaction (PCR) in a consecutive population of 324 asymptomatic refugees examined in Edmonton, Canada, during 2009–2010. Although all thick and thin blood smear results were negative, 10 subjects (3.1%) tested PCR positive for Plasmodium DNA. Interestingly, 6 of 10 PCR positive subjects are at risk of malaria relapse by P. vivax or P. ovale infections. These results suggest that appropriate guidelines for malaria screening should consider the risk of relapsing infections, and they highlight the potential usefulness of real-time PCR in the diagnosis of asymptomatic malaria.
Computer-Based Rhythm and Timing Training in Severe, Stroke-Induced Arm Hemiparesis
Authors: Beckelhimer Sarah C. , Dalton Ann E. , Richter Charissa A. , Hermann Valerie , Page Stephen J.
Published: January 2011

OBJECTIVE. We pilot tested the efficacy of computer-based training implementing rhythm and timing in chronic, severe, stroke-induced hemiparesis.

METHOD. Two chronic stroke patients were administered the upper-extremity section of the Fugl-Meyer Impairment Scale (FM), the Arm Motor Ability Test (AMAT), Stroke Impact Scale (SIS), and Canadian Occupational Performance Measure (COPM). We then administered the computer-based intervention for 60 min, 3 days/wk for 4 wk. One week after intervention, we administered the FM, AMAT, COPM, and SIS.

RESULTS. After intervention, participants exhibited reduced arm impairment (indicated by FM scores of +2.0 and +4.0) and increases in average functional ability (+0.85 and +1.1 points on the AMAT), perceived quality of life (+2.0 and +32.0 points on the SIS), and perception of overall recovery (+10.0 points for each participant on the SIS).

CONCLUSION. This study provides preliminary evidence suggesting efficacy of computer-based rhythm and timing in chronic stroke.
Methodology for the Systematic Reviews on Occupational Therapy for Individuals With Work-Related Injuries and Illnesses
Authors: Arbesman Marian , Lieberman Deborah , Thomas V. Judith
Published: January 2011

Systematic reviews of literature relevant to individuals with work-related injuries and illnesses are important to the practice of occupational therapy. This article describes the four questions that served as the focus for the systematic reviews of the effectiveness of occupational therapy interventions for individuals with work-related injuries and illnesses of the low back; hand, wrist, and forearm; elbow; and shoulder. The article includes the background for the reviews; the process followed for each question, including search terms and search strategy; the databases searched; and the methods used to summarize and critically appraise the literature. The final number of articles included in each systematic review; a summary of the results; the strengths and limitations of the findings; and the implications for practice, education, and research are presented.
Effectiveness of Sensory Integration Interventions in Children With Autism Spectrum Disorders: A Pilot Study
Authors: Pfeiffer Beth A. , Koenig Kristie , Kinnealey Moya , Sheppard Megan , Henderson Lorrie
Published: January 2011

The purpose of this pilot study was to establish a model for randomized controlled trial research, identify appropriate outcome measures, and address the effectiveness of sensory integration (SI) interventions in children with autism spectrum disorders (ASD). Children ages 6–12 with ASD were randomly assigned to a fine motor or SI treatment group. Pretests and posttests measured social responsiveness, sensory processing, functional motor skills, and social–emotional factors. Results identified significant positive changes in Goal Attainment Scaling scores for both groups; more significant changes occurred in the SI group, and a significant decrease in autistic mannerisms occurred in the SI group. No other results were significant. The study discusses considerations for designing future outcome studies for children with ASD.
Possibilities of Enacting and Researching Epistemic Communities
Authors: Lorenz-Meyer Dagmar
Published: January 2011

This article explores what the concept of epistemic community can contribute to studies of science and technology and to existing analytical frames of epistemic cultures, technosocial network and community of practice. Reviewing conceptions of epistemic community in political science, organisational studies and feminist epistemologies I suggest that heuristic dimensions include a focus on historical contingencies and timings; on particular epistemic projects and technologies that work as boundary objects; and on epistemic responsibilities and stratifications. These dimensions are further explored in two research vignettes. The first vignette follows the mobilisation and expectations of the Czech synchrotron user community at a funding event as a focal point for examining epistemic responsibilities and the genderings of community. The second vignette follows a biographical narrative about being and becoming a member of an epistemic community and amplifies the importance of different configurations of community. I argue that the contours, distributions and textures of an epistemic community cannot be studied at a single analytical site such as the laboratory and conclude by outlining what can be gained by using a refined concept of epistemic communities and sketching some strategies for further research.
From Communities of Practice to Epistemic Communities: Health Mobilizations on the Internet
Authors: Akrich Madeleine
Published: January 2011

This paper describes the emergence of new activist groups in the health sector, spinning off from internet discussion groups. In the first part, it shows how self-help discussion groups can be considered as communities of practice in which, partly thanks to the Internet media, collective learning activities result in the constitution of experiencial knowledge, the appropriation of exogenous sources of knowledge, including medical knoweldge and the articulation of these different sources of knowledge in some lay expertise. In the second part, it describes how activist groups might emerge from these discussion groups and develop specific modes of action drawing upon the forms of expertise constituted through the Internet groups. Activists groups together with self-help groups might form epistemic communities ( HAAS 1992 ), i.e. groups of experts engaged in a policy enterprise in which knowledge plays a major role : in the confrontation of health activists with professionals, the capacity to translate political claims into the langage of science appears as a condition to be (even) heard and be taken into consideration.
Governing through Standards: Networks, Failure and Auditing
Authors: Spencer Dale
Published: January 2011

This article seeks to understand network governance within the context of the North American automotive industry. Within this industry, original equipment manufacturers (lead firms) have outsourced a substantial portion of parts production over the last 30 years. This paper argues that in an aim to govern their supplier relations, North American lead firms imposed quality assurance standards upon their suppliers. In addition, this paper considers how nodes situated in the network are called upon to pre-emptively manage failures. Utilizing the quality assurance standards themselves, and 15 in-depth interviews with quality assurance managers at different part supplier plants, this article explores the technologies of performance used to manage failures. The focus of this paper is on the creation of part narratives, and particularly, the quality audit and its role in governing the conduct of part suppliers at-a-distance. Lastly, this paper focuses on the network prudential subject who is called upon to pre-emptively manage failures on behalf of the network.
Second-generation products contribute substantially to the particle-phase organic material produced by β-caryophyllene ozonolysis
Authors: Li Y. J. , Chen Q. , Guzman M. I. , Chan C. K. , Martin S. T.
Published: January 2011

Abstract. The production of secondary organic aerosol (SOA) by the dark ozonolysis of gas-phase β-caryophyllene was studied. The experiments were conducted in a continuous-flow environmental chamber for organic particle mass concentrations of 0.5 to 30 μg m−3 and with ozone in excess, thereby allowing the study of second-generation particle-phase products under atmospherically relevant conditions. The particle-phase products were characterized by an ultra-performance liquid chromatograph equipped with an electrospray ionization time-of-flight mass spectrometer (UPLC-ESI-ToF-MS). Fragmentation mass spectra were used for the structural elucidation of each product, and the structures were confirmed as consistent with the accurate m/z values of the parent ions. In total, fifteen products were identified. Of these, three are reported for the first time. The structures showed that 9 out of 15 particle-phase products were second generation, including all three of the new products. The relative abundance of the second-generation products was approximately 90% by mass among the 15 observed products. The O:C and H:C elemental ratios of the 15 products ranged from 0.13 to 0.50 and from 1.43 to 1.60, respectively. Fourteen of the products contained 3 to 5 oxygen atoms. A singular product, which was one of the three newly identified ones, had 7 oxygen atoms, including 1 carboxylic group, 2 carbonyl groups, and 3 hydroxyl groups. It was identified as 2, 3-dihydroxy-4-[2-(4-hydroxy-3-oxobutyl)-3, 3-dimethylcyclobutyl]-4-oxobutanoic acid (C14H22O7). The estimated saturation vapor pressure of this product is 3.3×10−13 Pa, making this product a candidate contributor to new particle formation in the atmosphere.
Regional scale effects of the aerosol cloud interaction simulated with an online coupled comprehensive chemistry model
Authors: Bangert M. , Kottmeier C. , Vogel B. , Vogel H.
Published: January 2011

Abstract. We have extended the coupled mesoscale atmosphere and chemistry model COSMO-ART to account for the transformation of aerosol particles into cloud condensation nuclei and to quantify their interaction with warm cloud microphysics on the regional scale. The new model system aims to fill the gap between cloud resolving models and global scale models. It represents the very complex microscale aerosol and cloud physics as detailed as possible, whereas the continental domain size and efficient codes will allow for both studying weather and regional climate. The model system is applied in a first extended case study for Europe for a cloudy five day period in August 2005. The model results show that the mean cloud droplet number concentration of clouds is correlated with the structure of the terrain, and we present a terrain slope parameter TS to classify this dependency. We propose to use this relationship to parameterise the PDF of subgrid-scale cloud updraft velocity in the activation parameterisations of climate models. The simulations show that the presence of CCN and clouds are closely related spatially. We find high aerosol and CCN number concentrations in the vicinity of clouds at high altitudes. The nucleation of secondary particles is enhanced above the clouds. This is caused by an efficient formation of gaseous aerosol precursors above the cloud due to more available radiation, transport of gases in clean air above the cloud, and humid conditions. Therefore the treatment of complex photochemistry is crucial in atmospheric models to simulate the distribution of CCN. The mean cloud droplet number concentration and droplet diameter showed a close link to the change in the aerosol. To quantify the net impact of an aerosol change on the precipitation we calculated the precipitation susceptibility β for the whole model domain over a period of two days with an hourly resolution. The distribution function of β is slightly skewed to positive values and has a mean of 0.23. Clouds with a liquid water path LWP of approximately 0.85 kg m−2 are on average most susceptible to aerosol changes in our simulations with an absolute value of β of 1. The average β for LWP between 0.5 kg m−2 and 1 kg m−2 is approximately 0.4.
Distribution of hydrogen peroxide, methyl hydroperoxide and formaldehyde over central Europe during the HOOVER project
Authors: Klippel T. , Fischer H. , Bozem H. , Lawrence M. G. , Butler T. , Jöckel P. , Tost H. , Martinez M. , Harder H. , Regelin E. , Sander R. , Schiller C. L. , Stickler A. , Lelieveld J.
Published: January 2011

Abstract. In this study we report measurements of hydrogen peroxide (H2O2), methyl hydroperoxide (CH3OOH) and formaldehyde (HCHO) from the HOx OVer EuRope (HOOVER) project (HOx=OH+HO2). HOOVER included two airborne field campaigns, in October 2006 and July 2007. Measurement flights were conducted from the base of operation Hohn (Germany, 54° N, 9° E) towards the Mediterranean and to the subpolar regions over Norway. We find negative concentration gradients with increasing latitude throughout the troposphere for H2O2 and CH3OOH. In contrast, observed HCHO is almost homogeneously distributed over Central and Northern Europe and is elevated over the Mediterranean. In general, the measured gradients tend to be steepest entering the Mediterranean region, where we also find the highest abundances of the 3 species. Mixing ratios of these tracers generally decrease with altitude. H2O2 and CH3OOH show maxima above the boundary layer at 2–5 km, being more distinct over Southern than over Northern Europe. We also present a comparison of our data with simulations by two global 3-D-models, MATCH-MPIC and EMAC, and with the box model CAABA. The models realistically represent altitude and latitude gradients for both HCHO and hydroperoxides (ROOH). In contrast, the models have problems reproducing the absolute mixing ratios, in particular of H2O2. Large uncertainties about retention coefficients and cloud microphysical parameters suggest that cloud scavenging might be a large source of error for the simulation of H2O2. A sensitivity study with EMAC shows a strong influence of cloud and precipitation scavenging on the budget of H2O2 as simulations improve significantly with this effect switched off.
Optimizing global CO emissions using a four-dimensional variational data assimilation system and surface network observations
Authors: Hooghiemstra P. B. , Krol M. C. , Meirink J. F. , Bergamaschi P. , van der Werf G. R. , Novelli P. C. , Aben I. , Röckmann T.
Published: January 2011

Abstract. We apply a four-dimensional variational (4D-VAR) data assimilation system to optimize carbon monoxide (CO) emissions for 2003 and 2004 and to reduce the uncertainty of emission estimates from individual sources using the chemistry transport model TM5. The system is designed to assimilate large (satellite) datasets, but in the current study only a limited amount of surface network observations from the National Oceanic and Atmospheric Administration Earth System Research Laboratory (NOAA/ESRL) Global Monitoring Division (GMD) is used to test the 4D-VAR system. By design, the system is capable to adjust the emissions in such a way that the posterior simulation reproduces background CO mixing ratios and large-scale pollution events at background stations. Uncertainty reduction up to 60% in yearly emissions is observed over well-constrained regions and the inferred emissions compare well with recent studies. However, with the limited amount of data from the surface network, the system becomes data sparse. This results in a large solution space and the 4D-VAR system has difficulties in separating anthropogenic and biogenic sources in particular. In addition we show that uncertainties in the model such as biomass burning injection height and the OH distribution largely influence the inversion results. The inferred emissions are validated with NOAA aircraft data over North America and the agreement is significantly improved from prior to posterior simulation. Validation with the Measurements Of Pollution In The Troposphere (MOPITT) instrument version 4 (V4) shows only a slight improved agreement over the well-constrained Northern Hemisphere. However, the model with optimized emissions underestimates MOPITT CO total columns on the remote Southern Hemisphere (SH) by about 40%. This is caused by a reduction in SH CO sources mainly due to surface stations on the high southern latitudes.
Organic condensation – a vital link connecting aerosol formation to climate forcing
Authors: Riipinen I. , Pierce J. R. , Yli-Juuti T. , Nieminen T. , Häkkinen S. , Ehn M. , Junninen H. , Lehtipalo K. , Petäjä T. , Slowik J. , Chang R. , Shantz N. C. , Abbatt J. , Leaitch W. R. , Kerminen V.-M. , Worsnop D. R. , Pandis S. N. , Donahue N. M. , Kulmala M.
Published: January 2011

Abstract. Atmospheric aerosol particles influence global climate as well as impair air quality through their effects on atmospheric visibility and human health. Ultrafine (<100 nm) particles often dominate aerosol numbers, and nucleation of atmospheric vapors is an important source of these particles. To have climatic relevance, however, the freshly-nucleated particles need to grow in size. We combine observations from two continental sites (Egbert, Canada and Hyytiälä, Finland) to show that condensation of organic vapors is a crucial factor governing the lifetimes and climatic importance of the smallest atmospheric particles. We demonstrate that state-of-the-science organic gas-particle partitioning models fail to reproduce the observations, and propose a modeling approach that is consistent with the measurements. We demonstrate the large sensitivity of climatic forcing of atmospheric aerosols to these interactions between organic vapors and the smallest atmospheric nanoparticles – highlighting the need for representing this process in global climate models.
Tropopause height at 78° N 16° E: average seasonal variation 2007–2010
Authors: Hall C. M. , Hansen G. , Sigernes F. , Kuyeng Ruiz K. M.
Published: January 2011

Abstract. We present a seasonal climatology of tropopause altitude for 78° N 16° E derived from observations 2007–2010 by the SOUSY VHF radar on Svalbard. The spring minimum occurs one month later than that of surface air temperature and instead coincides with the maximum in ozone column density. This confirms similar studies based on radiosonde measurements in the arctic and demonstrates downward control by the stratosphere. If one is to exploit the potential of tropopause height as a metric for climate change at high latitude and elsewhere, it is imperative to observe and understand the processes which establish the tropopause – an understanding to which this study contributes.
Sq field characteristics at Phu Thuy, Vietnam, during solar cycle 23: comparisons with Sq field in other longitude sectors
Authors: Pham Thi Thu H. , Amory-Mazaudier C. , Le Huy M.
Published: January 2011

Abstract. Quiet days variations in the Earth's magnetic field (the Sq current system) are compared and contrasted for the Asian, African and American sectors using a new dataset from Vietnam. This is the first presentation of the variation of the Earth's magnetic field (Sq), during the solar cycle 23, at Phu Thuy, Vietnam (geographic latitudes 21.03° N and longitude: 105.95° E). Phu Thuy observatory is located below the crest of the equatorial fountain in the Asian longitude sector of the Northern Hemisphere. The morphology of the Sq daily variation is presented as a function of solar cycle and seasons. The diurnal variation of Phu Thuy is compared to those obtained in different magnetic observatories over the world to highlight the characteristics of the Phu Thuy observations. In other longitude sectors we find different patterns. At Phu Thuy the solar cycle variation of the amplitude of the daily variation of the X component is correlated to the F.10.7 cm solar radiation (~0.74). This correlation factor is greater than the correlation factor obtained in two observatories located at the same magnetic latitudes in other longitude sectors: at Tamanrasset in the African sector (~0.42, geographic latitude ~22.79) and San Juan in the American sector (~0.03, geographic latitude ~18.38). At Phu Thuy, the Sq field exhibits an equinoctial and a diurnal asymmetry: – The seasonal variation of the monthly mean of X component exhibits the well known semiannual pattern with 2 equinox maxima, but the X component is larger in spring than in autumn. Depending of the phase of the sunspot cycle, the maximum amplitude of the X component varies in spring from 30 nT to 75 nT and in autumn from 20 nT to 60 nT. The maximum amplitude of the X component exhibits roughly the same variation in both solstices, varying from about ~20 nT to 50 nT, depending on the position into the solar cycle. – In all seasons, the mean equinoctial diurnal Y component has a morning maximum Larger than the afternoon minimum i.e. the equivalent current flow over a day is more southward than northward. During winter, the asymmetry is maximum, it erases the afternoon minimum. At the Gnangara observatory, in Asian Southern Hemisphere, the diurnal Y pattern is opposite and the current flow is more northward. It seems that in the Asian sector, the northern and southern Sq current cells both contribute strongly to the equatorial electrojet. The pattern is different in the African and American sectors where the northern Sq current cell contribution to the equatorial electrojet is smaller than the southern one. These observations can explain the unexpected maximum of amplitude of the equatorial electrojet observed in the Asian sector where the internal field is very large. During winter the Y component flow presents an anomaly, it is always southward during the whole day and there is no afternoon northward circulation.
Carbon isotope discrimination during litter decomposition can be explained by selective use of substrate with differing δ13C
Authors: Ngao J. , Cotrufo M. F.
Published: January 2011

Abstract. Temporal dynamics of C isotopic composition (δ13C) of CO2 and leaf litter was monitored during a litter decomposition experiment using Arbutus unedo L., as a slow decomposing model substrate. This allowed us (1) to quantify isotopic discrimination variation during litter decomposition, and (2) to test whether selective substrate use or kinetic fractionation could explain the observed isotopic discrimination. Total cumulative CO2-C loss (CL) comprised 27% of initial litter C. Temporal evolution of CL was simulated following a three-C-pool model. Isotopic composition of respired CO2 (δRL) was higher with respect to that of the bulk litter. The isotopic discrimination Δ(L/R) varied from −2‰ to 0‰ and it is mostly attributed to the variations of δRL. A three-pool model, with the three pools differing in their δ13C, described well the dynamic of Δ(L/R), in the intermediate stage of the process. This suggests that the observed isotopic discrimination between respired CO2 and bulk litter is in good agreement with the hypothesis of successive consumption of C compounds differing in δ13C during decomposition. However, to explain also 13C-CO2 dynamics at the beginning and end of the incubation the model had to be modified, with discrimination factors ranging from −1‰ to −4.6‰ attributed to the labile and the recalcitrance pool, respectively. We propose that this discrimination is also the result of further selective use of specific substrates within the two pools, likely being both the labile and recalcitrant pool of composite nature. In fact, the 2‰ 13C enrichment of the α-cellulose observed by the end of the experiment, and potentially attributable to kinetic fractionation, could not explain the measured Δ(L/R) dynamics.
Methane variations on orbital timescales: a transient modeling experiment
Authors: Konijnendijk T. Y. M. , Weber S. L. , Tuenter E. , van Weele M.
Published: January 2011

Abstract. Methane (CH4) variations on orbital timescales are often associated with variations in wetland coverage, most notably in the summer monsoon areas of the Northern Hemisphere. Here we test this assumption by simulating orbitally forced variations in global wetland emissions, using a simple wetland distribution and CH4 emissions model that was coupled off-line to a climate model containing atmosphere, ocean and vegetation components. The transient climate modeling simulation extends over the last 650 000 yrs and includes variations in land-ice distribution and greenhouse gases. Tropical temperature and global vegetation are found to be the dominant controls for global CH4 emissions and thus atmospheric concentrations. The relative importance of wetland coverage, vegetation coverage, and emission temperatures depends on the specific climatic zone (boreal, tropics and Indian/Asian monsoon area) and timescale (precession, obliquity and glacial-interglacial timescales). Simulated variations in emissions agree well with those in measured concentrations, both in their time series and spectra. The simulated lags with respect to the orbital forcing also show close agreement with those found in measured data, both on the precession and obliquity timescale. We only find covariance between monsoon precipitation and CH4 concentrations, however we find causal links between atmospheric concentrations and tropical temperatures and global vegetation. The primary importance of these two factors explains the lags found in the CH4 record from ice cores.
Clinical and Neuroimaging Assessments for Research Studies (Including Drug Trials) in Multiple Sclerosis
Authors: Apperson Michelle L. , Agius Mark A.
Published: January 2011

Multiple sclerosis (MS) is an immune‐mediated disorder causing inflammation and demyelination in the central nervous system. As the onset of multiple sclerosis is at a young age, it is one of the leading neurological causes of disability. Disease activity and disability can be measured by neurological assessments and by magnetic resonance imaging. The development of standardized assessments has been a very important step in clinical research in MS. Clinical research in MS has led to a better understanding of the disease itself and has resulted in exciting new therapies. The protocols provided in this unit are four basic clinical and neuroimaging assessments commonly used as outcome measures in clinical research studies of MS subjects. These step‐by‐step instructions may be used by researchers and neurologists in clinical practice to obtain objective measures of MS disease progression and response to treatments. Curr. Protoc. Neurosci. 54:10.4.1‐10.4.16. © 2011 by John Wiley & Sons, Inc.
Fluorescent Cell Barcoding for Multiplex Flow Cytometry
Authors: Krutzik Peter O. , Clutter Matthew R. , Trejo Angelica , Nolan Garry P.
Published: January 2011

Fluorescent cell barcoding (FCB) enables high throughput, high content flow cytometry by multiplexing samples prior to staining and acquisition on the cytometer. Individual cell samples are barcoded, or labeled, with unique signatures of fluorescent dyes so that they can be mixed together, stained, and analyzed as a single sample. By mixing samples prior to staining, antibody consumption is typically reduced 10‐ to 100‐fold. In addition, data robustness is increased through the combination of control and treated samples, which minimizes pipetting error, staining variation, and the need for normalization. Finally, speed of acquisition is enhanced, enabling large profiling experiments to be run with standard cytometer hardware. In this unit, we outline the steps necessary to apply the FCB method to cell lines, as well as primary peripheral blood samples. Important technical considerations, such as choice of barcoding dyes, concentrations, labeling buffers, compensation, and software analysis, are discussed. Curr. Protoc. Cytom. 55:6.31.1‐6.31.15. © 2011 by John Wiley & Sons, Inc.
High‐Resolution Multiparameter DNA Flow Cytometry for the Detection and Sorting of Tumor and Stromal Subpopulations from Paraffin‐Embedded Tissues
Authors: Corver Willem E. , ter Haar Natalja T.
Published: January 2011

This unit contains a detailed protocol for the simultaneous flow cytometric measurement of tumor cells, stromal cells, and DNA content of formalin‐fixed, paraffin‐embedded (FFPE) tissues. The vimentin‐positive stromal cell fraction can be used as an internal reference for DNA content assessments. This allows clear detection of keratin‐positive tumor cells with a DNA index lower than 1.0 and of keratin‐positive tumor cells with a DNA close to 1.0 in overall DNA aneuploid samples, thus improved DNA ploidy assessment in FFPE carcinomas. Furthermore, the protocol is useful for studying molecular genetic alterations and intratumor heterogeneity in archival FFPE samples. Keratin‐positive tumor cell fractions can be flow‐sorted for further molecular genetic analysis, while DNA from the sorted vimentin‐positive stromal cells can serve as a reference when normal tissue of the patient is not available. Curr. Protoc. Cytom. 55:7.37.1‐7.37.21. © 2010 by John Wiley & Sons, Inc.
Dual‐Pulse Labeling Using 5‐Ethynyl‐2′‐Deoxyuridine (EdU) and 5‐Bromo‐2′‐Deoxyuridine (BrdU) in Flow Cytometry
Authors: Bradford Jolene A. , Clarke Scott T.
Published: January 2011

Changes in DNA replication during S‐phase can give insights into mechanisms of cell growth, cell cycle kinetics, and cytotoxicity. A common method for detection of cell proliferation utilizes the incorporation of a thymidine analog during DNA synthesis. Incorporation of multiple analogs at different time points can further define cell cycle kinetics. Traditionally, the dual‐pulse method has been done by combining 5‐bromo‐2′‐deoxyuridine (BrdU) with iododeoxyuridine or chlorodeoxyuridine, with detection using multiple cross‐reacting BrdU antibodies. This unit presents a dual‐pulse method using the thymidine analog 5‐ethyl‐2′‐deoxyuridine (EdU), detected by click chemistry, combined with BrdU labeling and detection. No cross reactivity with incorporated EdU is observed using the BrdU antibody clone MoBU‐1. EdU detection using click chemistry does not cross‐react with incorporated BrdU. Cells are first pulsed with EdU, and then pulsed with BrdU; sequential pulses of EdU, followed by BrdU, are done without removing or washing out EdU. Curr. Protoc. Cytom. 55:7.38.1‐7.38.15. © 2011 by John Wiley & Sons, Inc.