bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycogen Synthase Kinase-3β Is a Prosurvival Signal for the Maintenance of Human Mast Cell Homeostasis
Authors: Rådinger Madeleine , Smrž Daniel , Metcalfe Dean D. , Gilfillan Alasdair M.
Published: October 2011

Homeostasis of mature tissue-resident mast cells is dependent on the relative activation of pro- and antiapoptotic regulators. In this study, we investigated the role of glycogen synthase kinase 3β (GSK3β) in the survival of neoplastic and nonneoplastic human mast cells. GSK3β was observed to be phosphorylated at the Y216 activating residue under resting conditions in both the neoplastic HMC1.2 cell line and in peripheral blood-derived primary human mast cells (HuMCs), suggesting constitutive activation of GSK3β in these cells. Lentiviral-transduced short hairpin RNA knockdown of GSK3β in both the HMC1.2 cells and HuMCs resulted in a significant reduction in cell survival as determined with the MTT assay. The decrease in stem cell factor (SCF)-mediated survival in the GSK3β knockdown HuMCs was reflected by enhancement of SCF withdrawal-induced apoptosis, as determined by Annexin V staining and caspase cleavage, and this was associated with a pronounced reduction in SCF-mediated phosphorylation of Src homology 2 domain-containing phosphatase 2 and ERK1/2 and reduced expression of the antiapoptotic proteins Bcl-xl and Bcl-2. These data show that GSK3β is an essential antiapoptotic factor in both neopastic and nontransformed primary human mast cells through the regulation of SCF-mediated Src homology 2 domain-containing phosphatase 2 and ERK activation. Our data suggest that targeting of GSK3β with small m.w. inhibitors such as CHIR 99021 may thus provide a mechanism for limiting mast cell survival and subsequently decreasing the intensity of the allergic inflammatory response.
α9β1 Integrin-Mediated Signaling Serves as an Intrinsic Regulator of Pathogenic Th17 Cell Generation
Authors: Kanayama Masashi , Morimoto Junko , Matsui Yutaka , Ikesue Masahiro , Danzaki Keiko , Kurotaki Daisuke , Ito Koyu , Yoshida Toshimichi , Uede Toshimitsu
Published: October 2011

The interaction between matricellular proteins such as tenascin-C (TN-C) and osteopontin (OPN) and integrins has been implicated in the pathology of rheumatoid arthritis in which Th17 cells are recognized as primary pathogenic cells. The differentiation of Th17 cells is tightly regulated by cytokines derived from APCs, receiving various signals including TLR stimuli. In this study, we used a collagen-induced arthritis model and found that increased numbers of α9 integrin-positive conventional dendritic cells and macrophage were detectable in the draining lymph node (dLN) shortly following first immunization, and these cells produced both TN-C and OPN, ligands for α9 integrin. α9 integrin-mediated signaling, induced by TN-C and OPN, promoted the production of Th17-related cytokines by conventional dendritic cells and macrophages in synergy with TLR2 and 4 signaling. This led to the Th17 cell differentiation and arthritis development. Moreover, Th17 cells generated under blocking of α9 integrin-mediated signaling showed low level of CCR6 expression and impaired migration ability toward CCL20. Thus, we have identified α9 integrin-mediated signaling by TN-C and OPN as a novel intrinsic regulator of pathogenic Th17 cell generation that contributes to the development of rheumatoid arthritis.
A p53 Defect Sensitizes Various Stages of B Cell Development to Lymphomagenesis in Mice Carrying an IgH 3′ Regulatory Region-Driven c-myc Transgene
Authors: Fiancette Rémi , Rouaud Pauline , Vincent-Fabert Christelle , Laffleur Brice , Magnone Virginie , Cogné Michel , Denizot Yves
Published: October 2011

Although c-myc is classically described as the driving oncogene in Burkitt’s lymphoma (BL), deregulation and mutations of c-myc have been reported in multiple solid tumors and in other mature B cell malignancies such as mantle cell lymphoma (MCL), myeloma, and plasma cell lymphoma (PCL). After translocation into the IgH locus, c-myc is constitutively expressed under the control of active IgH enhancers. Those located in the IgH 3′ regulatory region (3′RR) are master control elements of class switch recombination and of the transcriptional burst associated with plasma cell differentiation. c-myc-3′RR mice are prone to lymphomas with rather homogeneous, most often BL-like, phenotypes with incomplete penetrance (75% tumor incidence) and long latencies (10–12 mo). To reproduce c-myc–induced mature B cell lymphomagenesis in the context of an additional defect often observed in human lymphomas, we intercrossed c-myc-3′RR with p53+/− mice. Double transgenic c-myc-3′RR/p53+/− mice developed lymphoma with short latency (2–4 mo) and full penetrance (100% tumor incidence). The spectrum of B lymphomas occurring in c-myc-3′RR/p53+/− mice was widened, including nonactivated (CD43−) BL, activated (CD43+) BL, MCL-like lymphoma, and PCL, thus showing that 3′RR-mediated deregulation of c-myc can promote various types of B lymphoproliferation in cells that first acquired a p53 defect. c-myc/p53+/− mice closely reproduce many features of BL, MCL, and PCL and provide a novel and efficient model to dissect the molecular events leading to c-myc–induced lymphomagenesis and an important tool to test potential therapeutic agents on malignant B cells featuring various maturation stages.
Voltammetric Determination of Captopril Using Chlorpromazine as a Homogeneous Mediator
Authors: Bahramipur Hossein , Jalali Fahimeh
Published: October 2011

Chlorpromazine was used as a homogeneous electrocatalyst in the oxidation of captopril. The anodic peak current of chlorpromazine was increased substantially in the presence of low concentrations of captopril (pH 4). Cyclic voltammetry and chronoamperometry were used to study the kinetics of the catalytic electron transfer reaction. The values of electron transfer coefficient () and catalytic rate constant () were estimated to be 0.34 and , respectively. Linear sweep voltammetry was used for the determination of captopril in the presence of chlorpromazine. A linear calibration curve was obtained in the concentration range of captopril of 10.0–300.0 μM, with a limit of detection of 3.65 μM. The relative standard deviation (RSD%) for 5 replicate measurements of captopril (100 μM) was 1.96%. The method was applied to the determination of captopril in pharmaceutical formulations and blood serum samples with satisfactory results.
Models of Latent Tuberculosis: Their Salient Features, Limitations, and Development
Authors: Patel Kamlesh , Jhamb Sarbjit Singh , Singh Prati Pal
Published: October 2011

Latent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations.
Agreement of Two Different Laboratory Methods Used to Measure Electrolytes
Authors: Albert Venencia , Subramanian Arulselvi , Rangarajan Kanchana , Pandey Ravindra Mohan
Published: October 2011

Aim: The aim of our study was to do an agreement analysis of two different laboratory methods used to measure electrolytes i.e., between the ISE based Beckman Coulter Synchron CX9 PRO Biochemistry analyzer and RAL′s Ion3 Flame Photometer (Técnica para el Laboratorio, Barcelona, Spain), in serum samples.

Materials and Methods: This cross sectional study was done over a period of three months from September′09 through December′09 on routine biochemistry samples. A total of 6492 samples were received for routine biochemistry analysis from those 630 blood samples were randomly processed for this study. Two ml of sample was taken in a plain gel tube (LABTECH Disposables, Ahmedabad, India), centrifuged and further processed using both systems within one hour of the sampling to obtain the Na and K concentrations in the samples. The bias and variability of differences in measured values were analyzed according to Bland and Altman method.

Results: Flame photometry method has drawbacks such as low throughput, requires manual operation, is a time consuming procedure. Ion selective electrodes technique is a more universal method for the high throughput determination of electrolytes in physiological samples; Beckman Coulter Synchron CX9 PRO is an example of such a system. The mean difference between the two methods (standard minus test) and 95% limits of agreement for sodium in serum was -7.8±17.3 (-42.2 to 26.6) and in urine was -22±41 (-104 to 60). Similarly, the mean difference between the two methods for potassium values in serum was found to be -0.25±0.75 (-1.75 to 1.25) and in urine was -5.3±38.9 (-83.1 to 72.5). With 95% confidence interval, the value of sodium and potassium as determined by both the methods lie between the upper and lower limit showing 95% limits of agreement.

Conclusion: Good degree of agreement was seen on comparing the two methods for measuring the electrolytes; the use of Synchron CX9 in place of Flame photometer for electrolyte analysis in serum and urine is justified or use the two interchangeably.
The cytomorphologic spectrum of small-cell carcinoma and large-cell neuroendocrine carcinoma in body cavity effusions: A study of 68 cases
Authors: Khalbuss Walid E. , Yang Huaitao , Lian Qian , Elhosseiny Abdelmonem , Pantanowitz Liron , Monaco Sara E
Published: October 2011

Background:

Small-cell carcinoma (SCC) and large-cell neuroendocrine carcinoma (LCNEC) are uncommon in serous body cavity effusions. The purpose of this study is to examine the cytomorphological spectrum of SCC and LCNEC in body cavity serous fluids.

Materials and Methods:

We have 68 cases from 53 patients who had metastatic SCC or LCNEC diagnoses. All cytology slides and the available clinical data, histological follow-up, and ancillary studies were reviewed.

Results:

A total of 68 cases (60 pleural, 5 peritoneal, and 3 pericardial effusions) from 53 patients with an average age of 73 years (age range 43-92 years) were reported as diagnostic or suspicious of SCC (52 cases) or LCNEC (16 cases). The primary site was lung in 56 cases, pancreas in 6 cases, and 2 cases each from cervix, colon, and the head and neck region. Of the 68 cases, 48 cases had no history of malignancy of the same type. Ancillary studies were used in 46 cases (68%) including flow cytometric studies in 5 cases. There were three predominant cytomorphological patterns observed including small-cell clusters with prominent nuclear molding (33 cases, 49%), large-cell clusters mimicking non-small-cell carcinoma (18 cases, 26%), and single-cell pattern mimicking lymphoma (17 cases, 25%). Significant apoptosis was seen in 22 cases (33%) and marked tumor cell cannibalism was seen in 11 cases (16%). Nucleoli were prominent in 16 cases (24%). The most frequent neuroendocrine markers performed were synaptophysin and chromogranin.

Conclusions:

The most common cytomorphologic patterns seen in body cavity effusions of SCC and LCNEC were small-cell clusters with nuclear molding. However, in 51% of the cases either a predominant single-cell pattern mimicking lymphoma or large-cell clusters mimicking non-small carcinoma were noted. In our experience, effusions were the first manifestation of disease in the majority of patients diagnosed with neuroendocrine carcinoma. Therefore, familiarity with the cytomorphological spectrum of neuroendocrine carcinomas in fluid cytology may help in rapidly establishing an accurate diagnosis and in directing appropriate management.
Malignancy rate in nondominant nodules in patients with multinodular goiter: Experience with 1,606 cases evaluated by ultrasound-guided fine needle aspiration cytology
Authors: Paksoy Nadir , Yazal Kadri , Çorak Selin
Published: October 2011

Background:

Conventional medical sources recommend the use of fine needle aspiration cytology (FNAC) for single thyroid nodules and the dominant nodule in multinodular goiter (MNG). The purpose of the present study was to analyze the utility of FNAC for multiple thyroid nodules in patients with MNG and to determine the rate of malignancy in teh nondominant nodules.

Materials and Methods:

Our private practice performed ultrasound-guided FNAC on 1,606 patients between February 2001 and February 1, 2010. In the MNG cases, samples were taken from the dominant nodule and from trhee suspicious / nonsuspicious nodules larger than 1 cm on ultrasound. Ninety-four cases were diagnosed as ‘suspiciously malignant’(SUS) or ‘malignant’ (POS) based on FNAC.

Results:

The rate of an SUS / POS diagnosis was 5.7% in the dominant nodules; 2.3% of the nondominant nodules had a SUS / POS diagnosis in FNAC (p = 0.0003). Follow-up revealed malignancy in 15 (35.7%) nondominant nodules and in 27 (64.2%) dominant nodules, with 42 MNG cases undergoing surgery. X test showed a ‘p-level of 0.0003’ between the percentages of SUS / POS diagnosis in dominanat and nondominanat nodules. It was less than the significance level of 0.05. Therefore, the result was regarded to be statistically significant.

Conclusions:

Nondominant nodules could harbor malignancy. The risk of malignancy in nondominant nodules in MNG should not be underestimated. We have shown that the dominant nodule in patients with MNG was in fact about 2.5 times more likely to be malignant than a nondominant nodule. The use of FNAC for nondominant nodules could enhance the likelihood of detecting malignancy in an MNG.
Polycystic Ovary Syndrome: Update on Treatment Options and Treatment Considerations for the Future
Authors: Farrell-Turner Kristen A.
Published: October 2011

Polycystic ovary syndrome is an endocrine disorder characterized by insulin resistance, hyperandrogenemia, obesity, and inflammation, and is the most common cause of infertility. Women with PCOS are at higher risk than non-PCOS women for diabetes, cardiovascular disease, endometrial cancer, and psychiatric disorders. Because many abnormalities present in PCOS and symptoms vary considerably among PCOS women, treatment is guided by presentation and does not consist of simply one modality. Often, however, one type of medication can ameliorate more than one abnormality in PCOS. This review summarizes current research on several treatment modalities for PCOS, including drugs that are fairly well-established as efficacious and other agents that may prove efficacious in the future, with particular emphasis on the benefits and barriers of lifestyle change.
Randomized Trial of a Computer-Tailored Intervention for Patients with Depression
Authors: Levesque Deborah A. , Van Marter Deborah F. , Schneider Robert J. , Bauer Mark R. , Goldberg David N. , Prochaska James O. , Prochaska Janice M.
Published: October 2011

Purpose.

Examine the efficacy of a computer-tailored intervention (CTI) based on the transtheoretical model (TTM) for reducing depression, an increasingly important component of health promotion programs.

Design.

Pretest-posttest randomized trial.

Setting.

Participants were recruited and treated at home after being identified in two primary care clinics in Eastern Massachusetts and Chicago, Illinois.

Subjects.

A total of 350 adults experiencing at least mild symptoms of depression but not involved in or planning to seek treatment for depression.

Intervention.

A print manual and three CTI reports tailored to stage of change for using effective methods to prevent or reduce depression, other TTM variables, level of depression, and behavior.

Measures.

Pre-post changes and reliable and clinically significant change on the Beck Depression scale II and pre-post changes on the 20-item Medical Outcomes Study Short Form survey–based measure of physical functioning at 9 months' follow-up.

Analysis.

t-tests and χ2 tests. Complete-case analysis and two intention-to-treat analyses—assumption of no change and multiple imputation (MI)—are reported. Exploratory analyses examined whether the effects of the intervention on depression were moderated by five subject characteristics: baseline level of depression, baseline level of physical functioning, baseline stage of change for preventing or managing depression, age, and education.

Results.

Complete-case and intention-to-treat analyses showed that the intervention group experienced significantly greater improvements in depression (d = .220–.355); results for physical functioning were weaker (d = .150–.309) and did not reach statistical significance in the MI analysis. The effects of the intervention on reliable and clinically significant change in depression were largest among participants who were experiencing moderate depression (d = .363–.519) or severe depression (d = .603–.718) or who were in the precontemplation or contemplation stage (d = .573–.856) at baseline.
The ACTIVATE Study: Results from a Group-Randomized Controlled Trial Comparing a Traditional Worksite Health Promotion Program with an Activated Consumer Program
Authors: Terry Paul E. , Fowles Jinnet Briggs , Xi Min , Harvey Lisa
Published: October 2011

Purpose.

This study compares a traditional worksite-based health promotion program with an activated consumer program and a control program

Design.

Group randomized controlled trial with 18-month intervention.

Setting.

Two large Midwestern companies.

Subjects.

Three hundred and twenty employees (51% response).

Intervention.

The traditional health promotion intervention offered population-level campaigns on physical activity, nutrition, and stress management. The activated consumer intervention included population-level campaigns for evaluating health information, choosing a health benefits plan, and understanding the risks of not taking medications as prescribed. The personal development intervention (control group) offered information on hobbies. The interventions also offered individual-level coaching for high risk individuals in both active intervention groups.

Measures.

Health risk status, general health status, consumer activation, productivity, and the ability to evaluate health information.

Analysis.

Multivariate analyses controlled for baseline differences among the study groups.

Results.

At the population level, compared with baseline performance, the traditional health promotion intervention improved health risk status, consumer activation, and the ability to recognize reliable health websites. Compared with baseline performance, the activated consumer intervention improved consumer activation, productivity, and the ability to recognize reliable health websites. At the population level, however, only the activated consumer intervention improved any outcome more than the control group did; that outcome was consumer activation. At the individual level for high risk individuals, both traditional health coaching and activated consumer coaching positively affected health risk status and consumer activation. In addition, both coaching interventions improved participant ability to recognize a reliable health website. Consumer activation coaching also significantly improved self-reported productivity.

Conclusion.

An effective intervention can change employee health risk status and activation both at the population level and at the individual high risk level. However, program engagement at the population level was low, indicating that additional promotional strategies, such as greater use of incentives, need to be examined. Less intensive coaching can be as effective as more intensive, albeit both interventions produced modest behavior change and retention in the consumer activation arm was most difficult. Further research is needed concerning recruitment and retention methods that will enable populations to realize the full potential of activated consumerism.
Environmental Influences on Children's Physical Activity and Eating Habits in a Rural Oregon County
Authors: Findholt Nancy E. , Michael Yvonne L. , Jerofke Linda J. , Brogoitti Victoria W.
Published: October 2011

Purpose.

To identify environmental barriers and facilitators of children's physical activity and healthy eating in a rural county.

Design.

Community-based participatory research using mixed methods, primarily qualitative.

Setting.

A rural Oregon county.

Subjects.

Ninety-five adults, 6 high school students, and 41 fifth-grade students.

Measures.

In-depth interviews, focus groups, Photovoice, and structured observations using the Physical Activity Resource Assessment, System for Observing Play and Leisure Activity, Community Food Security Assessment Toolkit, and School Food and Beverage Marketing Assessment Tool.

Analysis.

Qualitative data were coded by investigators; observational data were analyzed using descriptive statistics. The findings were triangulated to produce a composite of environmental barriers and assets.

Results.

Limited recreational resources, street-related hazards, fear of strangers, inadequate physical education, and denial of recess hindered physical activity, whereas popularity of youth sports and proximity to natural areas promoted physical activity. Limited availability and high cost of healthy food, busy lifestyles, convenience stores near schools, few healthy meal choices at school, children's being permitted to bring snacks to school, candy used as incentives, and teachers' modeling unhealthy eating habits hindered healthy eating, whereas the agricultural setting and popularity of gardening promoted healthy eating.

Conclusions.

This study provides data on a neglected area of research, namely environmental determinants of rural childhood obesity, and points to the need for multifaceted and multilevel environmental change interventions.
TES ammonia retrieval strategy and global observations of the spatial and seasonal variability of ammonia
Authors: Shephard M. W. , Cady-Pereira K. E. , Luo M. , Henze D. K. , Pinder R. W. , Walker J. T. , Rinsland C. P. , Bash J. O. , Zhu L. , Payne V. H. , Clarisse L.
Published: October 2011

Abstract. Presently only limited sets of tropospheric ammonia (NH3) measurements in the Earth's atmosphere have been reported from satellite and surface station measurements, despite the well-documented negative impact of NH3 on the environment and human health. Presented here is a detailed description of the satellite retrieval strategy and analysis for the Tropospheric Emission Spectrometer (TES) using simulations and measurements. These results show that: (i) the level of detectability for a representative boundary layer TES NH3 mixing ratio value is ~0.4 ppbv, which typically corresponds to a profile that contains a maximum level value of ~1 ppbv; (ii) TES NH3 retrievals generally provide at most one degree of freedom for signal (DOFS), with peak sensitivity between 700 and 900 mbar; (iii) TES NH3 retrievals show significant spatial and seasonal variability of NH3 globally; (iv) initial comparisons of TES observations with GEOS-CHEM estimates show TES values being higher overall. Important differences and similarities between modeled and observed seasonal and spatial trends are noted, with discrepancies indicating areas where the timing and magnitude of modeled NH3 emissions from agricultural sources, and to lesser extent biomass burning sources, need further study.
A-train CALIOP and MLS observations of early winter antarctic polar stratospheric clouds and nitric acid in 2008
Authors: Lambert A. , Santee M. L. , Wu D. L. , Chae J. H.
Published: October 2011

Abstract. A-train Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) and Microwave Limb Sounder (MLS) observations are used to investigate the development of polar stratospheric clouds (PSCs) and the gas phase nitric acid distribution in the early 2008 Antarctic winter. Observational evidence of gravity-wave activity is provided by Atmospheric Infrared Sounder (AIRS) radiances and infrared spectroscopic detection of nitric acid trihydrate (NAT) in PSCs is obtained from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS). Goddard Earth Observing System Data Assimilation System (GEOS-5 DAS) analyses are used to derive Lagrangian trajectories and to determine temperature-time histories of air parcels. We use CALIOP backscatter and depolarization measurements to classify PSCs and the MLS measurements to determine the corresponding gas phase HNO3 as a function of temperature. For liquid PSCs the uptake of HNO3 follows the theoretical equilibrium curve for supercooled ternary solutions (STS), but at temperatures about 1 K lower as determined from GEOS-5. In the presence of solid phase PSCs, above the ice frost-point, the HNO3 depletion occurs over a wider range of temperatures (+2 to −7 K) distributed about the NAT equilibrium curve. Rapid gas phase HNO3 depletion is first seen by MLS from from 23–25 May 2008, consisting of a decrease in the volume mixing ratio (parts per billion by volume) from 14 ppbv to 7 ppbv on the 46–32 hPa (hectopascal) pressure levels and accompanied by a 2–3 ppbv increase by renitrification at the 68 hPa pressure level. Temperature-time histories of air parcels demonstrate that the depleted HNO3 region is more clearly correlated with prior low temperature exposure of a few kelvin above the frost-point than with either the region bounded by the NAT existence temperature threshold or the region of minimum temperatures. From the combined data we infer the presence of large-size NAT particles with effective radii >5–7 μm and low NAT number densities <1×10−3 cm−3. This denitrification event is observed close to the pole in the Antarctic vortex before synoptic temperatures first fall below the ice frost point and before the widespread occurrence of large-scale NAT PSCs at altitudes 18–26 km in a polar freezing belt. The NAT outbreak is similar to an event previously reported from MIPAS observations in mid-June 2003 and is again linked to NAT formation via ice-seeding following an episode of mountain wave activity detected by AIRS. Subsequent wave-ice formation in the rapid cooling phases over the Antarctic Peninsula and Ellsworth Mountains is detected here by CALIOP and MIPAS. The NAT clouds appear to be composed of relatively small particles with estimated effective radii of around 1 μm and high NAT number densities >0.2 cm−3.
High resolution assimilation of IASI ozone data with a global CTM
Authors: Pajot B. , Massart S. , Cariolle D. , Piacentini A. , Pannekoucke O. , Lahoz W. A. , Clerbaux C. , Coheur P. F. , Hurtmans D.
Published: October 2011

Abstract. The pixel size of the Infrared Atmospheric Sounding Interferometer (IASI) remote sensor is much smaller than the horizontal grid size of current Chemical Transport Models (CTMs). In order to assimilate the maximum of information from the IASI retrievals, we have increased the horizontal resolution of our model MOCAGE to be consistent with the IASI pixel size. Experiments are carried out with the Valentina data assimilation system using the standard and the high resolution versions of the model. Two resolutions of the horizontal Gaussian grid have been used for the model: with a T42 and a T170 triangular truncations. Our study is based on the combination of data from the IASI instrument and from the Microwave Limb Sounder (MLS), since this latter dataset allows the information to be spread through the whole atmospheric columns at a low computational cost. Two datasets of ozone super-observations have been constructed by averaging the IASI data on the two model grids. Direct model simulations without data assimilation first show that the increase of the horizontal resolution modifies the ozone smallest scale structures as well as the ozone meridional distribution. This modification results from a better representation of the vertical velocity with the T170 configuration. When the ozone assimilation is performed there is less influence of the horizontal resolution of the model. Nevertheless, in a general way, comparisons with independent data show large reductions of the ozone standard deviations when the resolution is increased. When the ozone assimilation is performed with the high resolution dataset, the high resolution model does not improve the ozone analysis compared to the one obtained with the same model resolution but with the low resolution IASI dataset. This result is due to the difficulty to combine IASI data and MLS data. For assimilating IASI data at high resolution the horizontal correlation length-scale has to be decreased to catch the small scale structures present in the dataset. By doing so the influence of the coarser resolution MLS data is decreased and part of the information brought on the vertical shape of the ozone profile is lost. It is concluded that it is essential to add information on the vertical distribution of ozone column when the IASI data is assimilated at a resolution close to the pixel size. Using IASI averaging kernels would likely improve the simulations, but the computational cost would be much higher. Alternatively, better results might be obtained by a careful tuning of the horizontal correlation length-scale.
Gas-particle partitioning of atmospheric Hg(II) and its effect on global mercury deposition
Authors: Amos H. M. , Jacob D. J. , Holmes C. D. , Fisher J. A. , Wang Q. , Yantosca R. M. , Corbitt E. S. , Galarneau E. , Rutter A. P. , Gustin M. S. , Steffen A. , Schauer J. J. , Graydon J. A. , Louis V. L. St. , Talbot R. W. , Edgerton E. S. , Sunderland E. M.
Published: October 2011

Abstract. Atmospheric deposition represents a major input of mercury to surface environments. The phase of mercury (gas or particle) has important implications for its removal from the atmosphere. We use long-term observations of reactive gaseous mercury (RGM), particle-bound mercury (PBM), fine particulate matter (PM2.5), and temperature at five sites in North America to derive an empirical gas-particle partitioning relationship log10(K-1) = (10 ± 1) − (2500 ± 300)/T where K = (PBM/PM2.5)/RGM with PBM and RGM in common mixing ratio units, PM2.5 in μg m−3, and T in Kelvin. This relationship is in the range of previous work but is based on far more extensive data from multiple sites. We implement this empirical relationship in the GEOS-Chem global 3-D Hg model to partition divalent mercury (Hg(II)). The resulting gas-phase fraction of Hg(II) ranges from over 90% in warm air with little aerosol to less than 10% in cold air with high aerosol. Hg deposition to high latitudes increases because of more efficient scavenging of particulate Hg(II) by snow. Model comparison to Hg observations at surface sites suggests that subsidence from the free troposphere (warm air, low aerosol) is a major factor driving the seasonality of RGM, while elevated PBM is mostly associated with high aerosol loads. This and other model updates, including the correction of an outstanding algorithm error, to wet deposition improve the simulation of Hg wet deposition fluxes in the US relative to the previous version of the model. The observed wintertime minimum in wet deposition fluxes is attributed to inefficient snow scavenging of gas-phase Hg(II).
Airborne formaldehyde measurements using PTR-MS: calibration, humidity dependence, inter-comparison and initial results
Authors: Warneke C. , Veres P. , Holloway J. S. , Stutz J. , Tsai C. , Alvarez S. , Rappenglueck B. , Fehsenfeld F. C. , Graus M. , Gilman J. B. , de Gouw J. A.
Published: October 2011

Abstract. We present quantitative, fast time response measurements of formaldehyde (HCHO) onboard an aircraft using a Proton-Transfer-Reaction Mass-Spectrometry (PTR-MS) instrument. The HCHO measurement by PTR-MS is strongly humidity dependent and therefore airborne measurements are difficult and have not been reported. The PTR-MS instrument was run in the standard PTR-MS operating mode (de Gouw and Warneke, 2007), where about 15 volatile organic compounds (VOCs) are measured together with HCHO onboard the NOAA WP-3 aircraft during the CalNex 2010 campaign in California. We compare the humidity dependence determined in the laboratory with in-flight calibrations of HCHO and calculate the HCHO mixing ratio during all flights using the results from both. The detection limit (S/N = 1) for HCHO was between 100 pptv in the dry free troposphere and 300 pptv in the humid marine boundary layer for a one second acquisition time every 17 s. The PTR-MS measurements are compared with HCHO measurements using a DOAS instrument and a Hantzsch monitor at a ground site in Pasadena. The PTR-MS agreed with the DOAS within the stated uncertainties and was just outside the uncertainties with the Hantzsch. We also compare HCHO enhancement ratios in the Los Angeles basin and in the free troposphere with literature values and find good agreement. The usefulness of the PTR-MS HCHO measurements in atmospheric observations is demonstrated by following an isolated anthropogenic plume. The photochemical production of HCHO can be observed simultaneously with production of acetaldehyde and the photochemical degradation of aromatic compounds using the PTR-MS. The results show that PTR-MS seems a useful instrument to measure HCHO, but more inter-comparisons are needed.
Indications for a ubiquitous dissolved pigment degradation product in subsurface waters of the global ocean
Authors: Röttgers R. , Koch B. P.
Published: October 2011

Abstract. Measurements of light absorption by chromophoric dissolved organic matter (CDOM) from sub-surface waters of the tropical Atlantic and Pacific showed a distinct absorption shoulder at 410–415 nm, indicating an underlying absorption of a pigment. A similar absorption maximum at ~410 nm was also found in the particulate fraction and is usually attributed to absorption by respiratory pigments of heterotrophic unicellular organisms. The CDOM absorption shoulder was described earlier in the Indian Ocean at 600 m depth and was related to a "deep red fluorescence" found in the same depth, i.e. in the oxygen minimum zone (Breves et al., 2003; Broenkow et al., 1983). In our study, fluorescence measurements of pre-concentrated DOM samples confirmed that the absorption at ~410 nm was related to a specific fluorescence at 650 nm. The absorption characteristic of this specific fluorophor was examined by fluorescence emission/excitation analysis and this showed a clear excitation maximum at 415 nm (in methanol) that can explain the absorption shoulder in the CDOM spectra. The spectral characteristics of the substance found in the dissolved and particulate fraction did not match with those of chlorophyll a degradation products (as found in a sample from the sea surface) but can be explained by the occurrence of respiratory pigments from heterotrophs. Combining the observations of the "deep red fluorescence" and the 410 nm-absorption shoulder suggests that there are high concentrations of a pigment degradation product (cytochrome c) in DOM of all major oceans. Most pronouncedly we found this signal in the deep chlorophyll maximum and the oxygen minimum zone of tropical regions. The origin, chemical nature, turn-over rate, and fate of this molecule is so far unknown.
Macrobenthic assemblage structure and organismal stoichiometry control faunal processing of particulate organic carbon and nitrogen in oxygen minimum zone sediments
Authors: Hunter W. R. , Levin L. A. , Kitazato H. , Witte U.
Published: October 2011

Abstract. The Arabian Sea oxygen minimum zone (OMZ) impinges on the western Indian continental margin between 150 and 1500 m, causing gradients in oxygen availability and sediment geochemistry at the sea floor. Oxygen availability and sediment geochemistry are important factors structuring macrofaunal assemblages in marine sediments. However, relationships between macrofaunal assemblage structure and sea-floor carbon and nitrogen cycling are poorly understood. We conducted in situ 13C:15N tracer experiments in the OMZ core (540 m [O2] = 0.35 μmol l−1) and lower OMZ boundary (800–1100 m, [O2] = 2.2–15.0 μmol l−1) to investigate how macrofaunal assemblage structure, affected by different oxygen levels, and C:N coupling influence the fate of particulate organic matter. No fauna were present in the OMZ core. Within the OMZ boundary, relatively high abundance and biomass resulted in the highest macrofaunal assimilation of particulate organic carbon (POC) and nitrogen (PON) at the lower oxygen 800 m stations ([O2] = 2.2–2.65 μmol l−1). At these stations the numerically dominant cirratulid polychaetes exhibited greatest POC and PON uptake. By contrast, at the higher oxygen 1100 m station ([O2] = 15.0 μmol l−1) macrofaunal C and N assimilation was lower, with POC assimilation dominated by one large solitary ascidian. Macrofaunal POC and PON assimilation were influenced by changes in oxygen availability, and significantly correlated to differences in macrofaunal assemblage structure between stations. POC and PON assimilation was characterised by carbon accumulation within the macrofauna, suggesting the importance of anaerobic metabolism at all stations. However, macrofaunal feeding responses were ultimately characterised by preferential organic nitrogen assimilation, relative to their internal C:N budgets.
Fungicide: Modes of Action and Possible Impact on Nontarget Microorganisms
Authors: Yang Chao , Hamel Chantal , Vujanovic Vladimir , Gan Yantai
Published: October 2011

Fungicides have been used widely in order to control fungal diseases and increase crop production. However, the effects of fungicides on microorganisms other than fungi remain unclear. The modes of action of fungicides were never well classified and presented, making difficult to estimate their possible nontarget effects. In this paper, the action modes and effects of fungicides targeting cell membrane components, protein synthesis, signal transduction, respiration, cell mitosis, and nucleic acid synthesis were classified, and their effects on nontarget microorganisms were reviewed. Modes of action and potential non-target effects on soil microorganisms should be considered in the selection of fungicide in order to protect the biological functions of soil and optimize the benefits derived from fungicide use in agricultural systems.
False Memory Is in the Details: Photographic Details Differentially Predict Memory Formation
Authors: Hessen‐Kayfitz Joanna K. , Scoboria Alan
Published: October 2011

Although false memory formation is a well‐documented phenomenon, the strength and rates of false memory formation vary across studies. Research indicates that the types of details provided in suggestions differentially influence memory formation, with some details enhancing and others impeding memories. This study explored the facilitation of false memories using doctored photographs, by manipulating the presence of salient familiar and unfamiliar details within photographs. Over three interviews, 82 participants viewed four photographs allegedly provided by parents. One was a doctored photograph depicting a hot‐air balloon ride, in which the presence of salient self‐relevant and unfamiliar details was varied. Participants rated the strength of their memory and associated memory characteristics for the events. Including self‐relevant details without unfamiliar details resulted in the highest memory ratings and greater increases in memory characteristic ratings. Memories were weakest when both details were provided. The theoretical implications of the findings are discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Biomimetic Titanium Alloy with Sparsely Distributed Nanotubes Could Enhance Osteoblast Functions
Authors: Mei Shenglin , Zhao Lingzhou , Wang Wei , Ma Qianli , Zhang Yumei
Published: October 2011

Designing the bone implant surface by mimicking the structure of natural tissue is an intriguing means to achieve better osseointegration. In this study, a biomimetic surface with sparsely distributed 80 nm diameter nanotubes (SNT) with a spacing of about 20–80 nm from each other, contrary to the closely distributed nanotubes on pure titanium, is fabricated by anodization of nearβtitanium alloy Ti‐5Zr‐3Sn‐5Mo‐15Nb (TLM). The structure is more similar to the cross‐section of collagen fibrils than commonly reported nanotubes on pure titanium. The SNT‐textured Ti‐alloy also shows good wettability and low elastic modulus more compatible with bone tissues. The surface bioactivity is evaluated in vitro by primary osteoblast cultures. Compared with the polished non‐textured TLM, the SNT texture exhibits satisfactory bioactivity with protein adsorption, initial cell adhesion, cell differentiation as revealed by ALP activity and osteogenesis‐related gene expression. Although cell proliferation is slightly suppressed, ECM deposition is enhanced. The enhanced cell functions are probably related to the biomimetic structure, biochemical characteristics, and mechanical properties of SNT‐textured Ti‐alloy as well as the potential fluid exchange effect among the nanotubes. The SNT texture which constitutes a bio‐interface with fluid supply from the implant surface can be tailored to enhance biological properties such as cell immigration and differentiation.
Oxygen separation through U‐shaped hollow fiber membrane using pure CO2 as sweep gas
Authors: Wei Yanying , Tang Jun , Zhou Lingyi , Xue Jian , Li Zhong , Wang Haihui
Published: October 2011

A number of U‐shaped K2NiF4‐type oxide hollow fiber membranes based on (Pr0.9La0.1)2(Ni0.74Cu0.21Ga0.05)O4+δ (PLNCG) were successfully prepared by a phase inversion spinning process. The PLNCG hollow fiber membranes were then used to investigate the effect of CO2 concentration in both the sweep gas and the feed air on the oxygen permeation flux. With pure CO2 as the sweep gas and even 10% CO2 in the feed air, a steady oxygen permeation flux of 0.9 mL/min·cm2 (STP) is obtained at 975°C during 310 h, and no decline of the oxygen permeation flux is observed. XRD, SEM and EDS characterizations show the spent membrane still maintains the intact microstructure and perfect K2NiF4‐type phase structure without carbonate, which indicates that the U‐shaped PLNCG hollow fiber membrane is a very stable membrane under CO2 atmosphere and has great potential for the practical application in oxyfuel techniques for CO2 capture and storage.©2011 American Institute of Chemical Engineers AIChE J, 2012
Mild isolated craniosynostosis due to a novel FGFR3 mutation, p.Ala334Thr
Authors: Barroso Eva , Pérez‐Carrizosa Virginia , García‐Recuero Ignacio , Glucksman Marc J. , Wilkie Andrew O. , García‐Minaur Sixto , Heath Karen E.
Published: October 2011

Craniosynostosis is the premature fusion of one or more sutures of the skull, which can be syndromic or isolated. Mutations in FGFR1, FGFR2, or FGFR3, among others, are often responsible for these syndromic cases. The associated of FGFR3 mutations with craniosynostosis has been restricted to three mutations, the common p.Pro250Arg in Muenke syndrome, p.Ala391Glu in Crouzon syndrome with acanthosis nigricans, and p.Pro250Leu identified in a family with isolated craniosynostosis. Other FGFR3 mutations result in various skeletal dysplasias: achondroplasia, hypochondroplasia, and thanatophoric dysplasia. Here, we report a novel mutation in exon 8 (IIIc) of FGFR3, p.Ala334Thr, in a young boy with mild craniosynostosis. The mutation segregated with mild craniosynostosis in the family and was absent in 188 normal controls. Alanine 334 is evolutionarily conserved in vertebrates and is located at the amino terminus of the βF loop in the FGFR3c isoform. The mutation is predicted to alter the protein tertiary structure which may impair its binding to its ligand, FGF1. The identification of a mutation in these clinically heterogeneous disorders can aid recurrence risk assessments. Although the implementation of a stepwise screening strategy is useful in diagnostics, mutations in unscreened regions of genes associated with craniosynostosis may explain a small proportion of craniosynostosis cases. © 2011 Wiley Periodicals, Inc.
Genomics really gets personal: How exome and whole genome sequencing challenge the ethical framework of human genetics research
Authors: Tabor Holly K. , Berkman Benjamin E. , Hull Sara Chandros , Bamshad Michael J.
Published: October 2011

Exome sequencing (ES) and whole genome sequencing (WGS) putatively identify all adverse functional alleles of protein‐coding genes. Accordingly, while ES/WGS are transformative new tools for gene discovery in human and medical genetics research, they also generate new manifestations of ethical issues related to the consent process, data sharing, and return of results. These manifestations have yet to be comprehensively framed, due in part to the rapidity with which new technologies for ES/WGS are being applied and because of a lack of empirical data to provide guidance. Accordingly, researchers, funding agencies, and policy makers have largely dealt with these issues intuitively. We explain how use of ES/WGS challenges: (i) models under which informed consent is typically obtained; (ii) how harms associated with data sharing are considered; and (iii) the nature of obligations surrounding unanticipated findings. We provide broad guidance about interim ways to contend with these issues and make broad recommendations for areas for novel resource and policy development. © 2011 Wiley Periodicals, Inc.
Small Molecule Inhibitors of Histone Acetyltransferases as Epigenetic Tools and Drug Candidates
Authors: Furdas Silviya D. , Kannan Srinivasaraghavan , Sippl Wolfgang , Jung Manfred
Published: October 2011

Alteration of the acetylation state of histone proteins contributes to transcriptional regulation and epigenetic inheritance. Dysregulation of these processes may lead to human diseases, especially cancer. One of the major chromatin modifications is histone acetylation and this review gives an overview of the role of histone acetyltransferases, their structural aspects, as well as of chemical modulators targeting their enzymatical activities. Inhibitors and activators of histone acetyltransferases are presented and their capability to influence histone and non‐histone protein acetylation levels is discussed. Development of small molecules as epigenetic tools that alter histone acetyltransferase activity will be helpful to better understand the consequences of histone and generally protein acetylation and potentially offer novel therapeutic approaches for the treatment of cancer and other diseases.