bluuebunny/crossref_metadata_2025 huggingface dataset:
Gasoline partially premixed combustion, the future of internal combustion engines?
Authors: Manente V , Johansson B , Cannella W
Published: June 2011

Gasoline partially premixed combustion showed the potential of very high efficiency, emissions of nitrogen oxides (NO x) and soot below future emission regulations, and acceptable acoustic noise from idle up to 26 bar gross indicated mean effective pressure. For instance, gross indicated efficiencies in the range of 53 to 55 per cent were achieved in the whole load range keeping NO x below 0.30 g/kWh, soot below 0.30 filter smoke number (FSN), and relative maximum pressure rise rate below 8 bar/crank angle degree. The goal was achieved by developing an appropriate EGR–λ (exhaust gas recirculation/relative excess of air) combination and an advanced injection strategy, and by making minor modifications to the engine layout.

The current paper presents a summary of the advantages of using gasoline-type fuels (research octane number (RON) from 80 to 69) in a heavy-duty compression ignition engine. Low-octane-number gasoline fuels were chosen because they can run from idle to maximum load without any major modification to the engine layout and because low-load operations are achievable even when the engine is cold and the inlet temperature is low. Experiments were carried out in two single-cylinder engines, Scania D12 and Scania D13, using a total of three different engine setups. The influence of different types of gasoline (RON from 99 to 69) on this novel combustion concept was analysed. A comparison between gasoline and diesel fuels is presented and the viability of reaching 50 per cent brake efficiency while keeping low emissions of NO x and soot is shown.
Cooled exhaust-gas recirculation for fuel economy and emissions improvement in gasoline engines
Authors: Alger T , Gingrich J , Roberts C , Mangold B
Published: June 2011

Modern gasoline engines face fuel-efficiency challenges due to inherent limitations including knock, pumping losses, and fuel enrichment. The addition of exhaust-gas recirculation (EGR) has been shown to improve the fuel consumption of gasoline engines, either port fuel injected or direct injected, by reducing pumping losses and knock and eliminating the enrichment region. In addition, the use of EGR has been shown to substantially reduce emissions of nitrogen oxides (NO x) and CO. A 2.4-litre multi-point injection engine and a 1.6-litre gasoline direct injection engine were run with high levels of both cooled and uncooled EGR. Unlike numerous previous publications, these engines included a modified ignition system that allows extension of the cooled EGR limit of the engine to greater than 25 per cent and improves combustion at lower EGR levels. The results showed that an improvement of between 5 and 30 per cent in fuel consumption is possible, with the largest improvement occurring in the typical enrichment region. In addition, the results showed that EGR can reduce knock, resulting in an improvement in combustion phasing. Finally, the high levels of EGR reduced the emissions of CO by 30 per cent and of NO x by up to 80 per cent. A detailed effort has been made to quantify the sources of improvement throughout the engine cycle and to demonstrate an EGR strategy (cooled EGR at high loads, internal EGR at low loads) that will maximize fuel consumption improvements. The results presented here indicate that the use of EGR in gasoline engines has the potential to reduce fuel consumption and emissions in a very cost-effective manner.
The effect of fuel properties on thermal efficiency of advanced spark-ignition engines
Authors: Nakata K , Sasaki N , Ota A , Kawatake K
Published: June 2011

Owing to issues of global warming and energy security, improving engine thermal efficiency has become increasingly important today. This paper investigates the impact of high-research-octane-number (RON) fuels on engine thermal efficiency. It is shown that the lean boosted engine has higher potential to increase engine thermal efficiency than naturally aspirated (NA) engines and the combination of lean boosted engine and high-RON fuels gives around 44 per cent engine thermal efficiency. The engine thermal efficiency exceeds a diesel engine’s thermal efficiency. Therefore, the combination is expected to be an effective way to reduce CO2 emissions in the future. In this paper, the high-RON fuels are blended with gasoline components or bio-components. This paper also describes the combustion characteristics of ethanol and butanol. These fuels have good combustion features after the engine has warmed up. However, it is found that butanol gives more severe combustion characteristics under cold conditions.
Model-based comparative study of Euro 6 diesel aftertreatment concepts, focusing on fuel consumption
Authors: Tourlonias P , Koltsakis G
Published: June 2011

A model-based study is used to assess various Euro 6 diesel PM/NO x aftertreatment concepts for one specific engine and vehicle combination. The assessment focuses on fuel consumption/carbon dioxide (CO2) emissions considering the fuel penalties resulting from both a periodically regenerating system as well as a catalyst heat-up strategy. The modelling work is carried out with a complete platform for simulating transient thermal and chemical phenomena of all exhaust aftertreatment components.

It is shown that, in all cases, the selective catalytic reduction (SCR) system requires a heat-up strategy to satisfy Euro 6 NO x emissions limits, making configurations with an SCR located upstream of the particulate filter more favourable. On the other hand, it is verified that these configurations suffer owing to the lack of passive regeneration that, in turn, increases the active regeneration frequency. The use of a catalyzed particulate filter upstream of the SCR allows for an increase in NO x conversion efficiency. The use of an heat-up strategy for SCR light-off promotes the passive regeneration effect. The benefit of using a fuel-borne catalyst (FBC) system for active regeneration is confirmed. Finally, all these aspects are quantified and the overall fuel penalty results are presented and discussed.
Home, children and moral standpoints
Authors: Helavirta Susanna
Published: June 2011

Contemporary adult discussions often set up strong, even unchallenged norms of what things in the home promote children’s well-being and what constitutes a threat to it. This article examines children’s own descriptions of their homes and their standpoints on what is a good and proper life at home. The analysis focuses on the interview talk of child clients of Finnish child welfare. Children’s talk of home is characterized by positiveness, the presence of mother and scarcity of words. Home talk was not tinged with worry and problems. The study shows that children also have personal moral standpoints related to their homes. The children regard their homes as places of reciprocal obligations and responsibilities. Just as the adults have a moral obligation to look after the daily life at home, the children and the livelihood, the children also must look after the adults in situations where the adults have not enough energy, time or capability. The results argue for the need to rethink ‘adultist’ and professional norms of homes as a platform to promote the good life of children.
What does the Q mean? Including queer voices in qualitative research
Authors: Levy Denise L. , Johnson Corey W.
Published: June 2011

Despite much of the fear and ambiguity over the use of the term queer in professional and academic settings, we recommend researchers include the language and the population in the study of sexual identity. During our own recent research endeavors, where we both recruited and focused on Queer participants, we learned some important lessons. Based on these experiences we explore the existing methodological literature about accessing and including Queer participants, provide an overview of two studies that both invited Queer participation and examined the population’s experience, discuss the benefits and challenges of incorporating people who identify as Queer, and finally present recommendations for future research.
Being wholesome: The paradox of methamphetamine addiction and recovery – A hermeneutical phenomenological interpretation within an interdisciplinary, transmethodological study
Authors: Vandermause Roxanne K.
Published: June 2011

This article presents a Heideggerian hermeneutic interpretation of findings from an interdisciplinary, transmethodological study addressing the questions, ‘What does it mean to experience methamphetamine addiction? What does it mean to recover?’ Study aims, to: (1) uncover the meaning of addiction and recovery via case intensive analysis, and (2) generate an interdisciplinary, transmethodology for understanding complex healthcare problems, were intended to stimulate a deeper understanding of the experience of addiction and recovery through an innovative methodological approach. Scholars from Nursing, English, Teaching and Learning, and Fine Arts contributed to the analysis. This article presents the hermeneutic interpretation of the transmethodological study.
An acoustic emission energy index for damage evaluation of reinforced concrete slabs under seismic loads
Authors: Benavent-Climent Amadeo , Gallego Antolino , Vico Juan M
Published: June 2011

This article presents the results and analysis of Acoustic Emission (AE) as recorded in a reinforced concrete (RC) slab supported by four steel columns and subjected to earthquake-type dynamic loading on a shake table. Fifteen seismic simulations were conducted using an accelerogram registered during the Campano-Lucano earthquake (Italy, 1980). The peak acceleration applied to the shake table was increased until the slab reinforcement was on the brink of yielding and slippage of the bars within the concrete occurred. This limit state is commonly associated with low-to-moderate intensity earthquakes in earthquake-prone regions. The evolution of damage to the slab was monitored in terms of AE energy and the history of plastic strain energy was calculated from the acceleration and displacement measurements. A good correlation was found between the energy dissipated by the concrete through plastic deformations and the AE energy associated with concrete cracking and friction. On this basis, a tentative formula is proposed for predicting the level of damage to RC slabs, based on the AE energy recorded by sensors located near the region of expected damage concentration under lateral loads.
Increased heart rate variability during nondirective meditation
Authors: Nesvold Anders , Fagerland Morten W , Davanger Svend , Ellingsen Øyvind , Solberg Erik E , Holen Are , Sevre Knut , Atar Dan
Published: June 2011

Purpose: Meditation practices are in use for relaxation and stress reduction. Some studies indicate beneficial cardiovascular health effects of meditation. The effects on the autonomous nervous system seem to vary among techniques. The purpose of the present study was to identify autonomic nerve activity changes during nondirective meditation.

Materials and methods: Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) were monitored in 27 middle-aged healthy participants of both genders, first during 20 min regular rest with eyes closed, thereafter practising Acem meditation for 20 min. Haemodynamic and autonomic data were collected continuously (beat-to-beat) and non-invasively. HRV and BPV parameters were estimated by power spectral analyses, computed by an autoregressive model. Spontaneous activity of baroreceptors were determined by the sequence method. Primary outcomes were changes in HRV, BPV, and BRS between rest and meditation.

Results: HRV increased in the low-frequency (LF) and high-frequency (HF) bands during meditation, compared with rest ( p = 0.014, 0.013, respectively). Power spectral density of the RR-intervals increased as well ( p = 0.012). LF/HF ratio decreased non-significantly, and a reduction of LF-BPV power was observed during meditation ( p < 0.001). There was no significant difference in BRS. Respiration and heart rates remained unchanged. Blood pressure increased slightly during meditation.

Conclusion: There is an increased parasympathetic and reduced sympathetic nerve activity and increased overall HRV, while practising the technique. Hence, nondirective meditation by the middle aged may contribute towards a reduction of cardiovascular risk.
Primary Care Physician Reports of Amount of Time Spent with Male Patients in Prostate Cancer Screening Discussions
Authors: Hall Ingrid J. , Ross Louie E. , Taylor Yhenneko J. , Richardson Lisa C.
Published: June 2011

Background: Major health organizations recommend that physicians discuss the risks and benefits of prostate cancer screening with men before ordering tests. The length of time that health care providers spend discussing prostate cancer screening-related issues with patients has been given little attention. The purpose of this study was to determine the amount of time that primary care physicians (PCP) in the United States reported spending in discussions about prostate cancer screening with patients by selected PCP individual, practice-related, and screening-related factors. Methods: Data were obtained from the 2007-2008 National Survey of Primary Care Physician Practices Regarding Prostate Cancer Screening. We determined whether PCP characteristics were associated with amount of time spent with patients. Results: Results showed that female, African American or other race, and older PCP spend more time (above the median) with patients compared to their referents. Also, more time spent with male patients was more often associated with PCP having practices in urban inner city areas as well as when the screening decision was shared between the PCP and the patient/family. Conclusion: Results from this study offer some insight into the amount of time that PCP report spending with patients in discussing prostate cancer screening-related issues specifically, and confirms the involvement of individual as well as practice-level factors.
Agammaglobulinemia associated with BCR− B cells and enhanced expression of CD19
Authors: Dobbs A. Kerry , Bosompem Amma , Coustan-Smith Elaine , Tyerman Gayle , Saulsbury Frank T. , Conley Mary Ellen
Published: June 2011

Expression of a BCR is critical for B-cell development and survival. We have identified 4 patients with agammaglobulinemia and markedly reduced but detectable B cells in the peripheral circulation. These B cells have an unusual phenotype characterized by increased expression of CD19 but no BCR. The cells are positive for CD20, CD22, and CD38, but not for Annexin 5 or activation markers, including CD69, CD83, or CD86. EBV lines derived from these B cells lack functionally rearranged immunoglobulin heavy-chain transcripts, as shown by PCR–rapid amplification of cDNA ends (PCR-RACE). Analysis of BM from 2 of the patients showed a severe reduction in the number of pro-B cells as well as pre-B cells. Functionally rearranged heavy-chain transcripts were identified, indicating that machinery to rearrange immunoglobulin genes was intact. Flow cytometry of B-lineage cells suggested accelerated acquisition of maturation markers in early B-cell precursors and increased phosphorylation of signal transduction molecules. Further, expression of TdT, a molecule that is normally down-regulated by a functional pre-BCR complex, was decreased. We hypothesize that the accelerated maturation, increased expression of CD19, and lack of a BCR were due to the constitutive activation of the BCR signal transduction pathway in these patients.
Dynamic reorganization of flotillins in chemokine-stimulated human T-lymphocytes
Authors: Affentranger Sarah , Martinelli Sibylla , Hahn Jonas , Rossy Jérémie , Niggli Verena
Published: June 2011

Background

Different types of membrane microdomains (rafts) have been postulated to be present in the rear and front of polarized migrating T-lymphocytes. Disruption of rafts by cholesterol sequestration prevents T-cell polarization and migration. Reggie/flotillin-1 and -2 are two highly homologous proteins that are thought to shape membrane microdomains. We have previously demonstrated the enrichment of flotillins in the uropod of human neutrophils. We have now investigated mechanisms involved in chemokine-induced flotillin reorganization in human T-lymphocytes, and possible roles of flotillins in lymphocyte polarization.

Results

We studied flotillin reorganization and lateral mobility at the plasma membrane using immunofluorescence staining and FRAP (fluorescence recovery after photobleaching). We show that flotillins redistribute early upon chemokine stimulation, and form very stable caps in the uropods of human peripheral blood T-lymphocytes, colocalizing with the adhesion molecule PSGL-1 and activated ezrin/radixin/moesin (ERM) proteins. Chemokine-induced formation of stable flotillin caps requires integrity and dynamics of the actin cytoskeleton, but is not abolished by inhibitors suppressing Rho-kinase or myosin II activity. Tagged flotillin-2 and flotillin-1 coexpressed in T-lymphocytes, but not singly expressed proteins, colocalize in stable caps at the tips of uropods. Lateral mobility of coexpressed flotillins at the plasma membrane is already partially restricted in the absence of chemokine. Incubation with chemokine results in almost complete immobilization of flotillins. Capping is abolished when wild-type flotillin-1 is coexpressed with a mutant of flotillin-2 (G2A) that is unable to interact with the plasma membrane, or with a deletion mutant of flotillin-2 that lacks a putative actin-binding domain. Wild-type flotillin-2 in contrast forms caps when coexpressed with a mutant of flotillin-1 unable to interact with membranes. Transfection of T-lymphocytes with flotillin-2-G2A reduces cell polarization and uropod recruitment of endogenous flotillin-1 and PSGL-1.

Conclusions

Our data suggest that stable flotillin cap formation in the rear of polarized T-lymphocytes requires flotillin heterooligomer formation, as well as direct F-actin interactions of flotillin-2 and raft/membrane association of flotillin-2, but not -1. Our data also implicate flotillin-rich actin-dependent membrane microdomains in T-lymphocyte uropod formation.
Live in vivo imaging of Egr-1 promoter activity during neonatal development, liver regeneration and wound healing
Authors: Dussmann Philipp , Pagel Judith I , Vogel Sabina , Magnusson Terese , Zimmermann Rene , Wagner Ernst , Schaper Wolfgang , Ogris Manfred , Deindl Elisabeth
Published: June 2011

Background

The zinc finger transcription factor Egr-1 (Early growth response 1) is central to several growth factors and represents an important activator of target genes not only involved in physiological processes like embryogenesis and neonatal development, but also in a variety of pathophysiological processes, for example atherosclerosis or cancer. Current options to investigate its transcription and activation in vivo are end-point measurements that do not provide insights into dynamic changes in the living organism.

Results

We developed a transgenic mouse (Egr-1-luc) in which the luciferase reporter gene is under the control of the murine Egr-1 promoter providing a versatile tool to study the time course of Egr-1 activation in vivo. In neonatal mice, bioluminescence imaging revealed a high Egr-1 promoter activity reaching basal levels three weeks after birth with activity at snout, ears and paws. Using a model of partial hepatectomy we could show that Egr-1 promoter activity and Egr-1 mRNA levels were increased in the regenerating liver. In a model of wound healing, we demonstrated that Egr-1 promoter activity was upregulated at the site of injury.

Conclusion

Taken together, we have developed a transgenic mouse model that allows real time in vivo imaging of the Egr-1 promoter activity. The ability to monitor and quantify Egr-1 activity in the living organism may facilitate a better understanding of Egr-1 function in vivo.
Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFcchimeric protein targeting tissue factor
Authors: Cocco Emiliano , Varughese Joyce , Buza Natalia , Bellone Stefania , Glasgow Michelle , Bellone Marta , Todeschini Paola , Carrara Luisa , Silasi Dan-Arin , Azodi Masoud , Schwartz Peter E , Rutherford Thomas J , Pecorelli Sergio , Lockwood Charles J , Santin Alessandro D
Published: June 2011

Background

Cervical cancer continues to be an important worldwide health problem for women. Up to 35% of patients who are diagnosed with and appropriately treated for cervical cancer will recur and treatment results are poor for recurrent disease. Given these sobering statistics, development of novel therapies for cervical cancer remains a high priority. We evaluated the expression of Tissue Factor (TF) in cervical cancer and the potential of hI-con1, an antibody-like-molecule targeted against TF, as a novel form of immunotherapy against multiple primary cervical carcinoma cell lines with squamous- and adenocarcinoma histology.

Methods

Because TF is a transmembrane receptor for coagulation factor VII/VIIa (fVII), in this study we evaluated thein vitroexpression of TF in cervical carcinoma cell lines by immunohistochemistry (IHC), real time-PCR (qRT-PCR) and flow cytometry. Sensitivity to hI-con1-dependent cell-mediated-cytotoxicity (IDCC) was evaluated in 5-hrs-51chromium-release-assays against cervical cancer cell linesin vitro.

Results

Cytoplasmic and/or membrane TF expression was observed in 8 out of 8 (100%) of the tumor tissues tested by IHC and in 100% (11 out of 11) of the cervical carcinoma cell lines tested by real-time-PCR and flow cytometry but not in normal cervical keratinocytes (p= 0.0023 qRT-PCR;p= 0.0042 flow cytometry). All primary cervical cancer cell lines tested overexpressing TF, regardless of their histology, were highly sensitive to IDCC (mean killing ± SD, 56.2% ± 15.9%, range, 32.4%-76.9%,p< 0.001), while negligible cytotoxicity was seen in the absence of hI-con1 or in the presence of rituximab-control-antibody. Low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (p= 0.025) while human serum did not significantly decrease IDCC against cervical cancer cell lines (p= 0.597).

Conclusions

TF is highly expressed in squamous and adenocarcinoma of the uterine cervix. hI-con1 induces strong cytotoxicity against primary cervical cancer cell lines overexpressing TF and may represent a novel therapeutic agent for the treatment of cervical cancer refractory to standard treatment modalities.
Prevalence of non-communicable diseases in Brazilian children: follow-up at school age of two Brazilian birth cohorts of the 1990's
Authors: Silva Antônio A , Barbieri Marco A , Cardoso Viviane C , Batista Rosângela F , Simões Vanda M , Vianna Elcio O , Gutierrez Manoel R , Figueiredo Maria L , Silva Nathalia A , Pereira Thaís S , Rodriguez Juliana D , Loureiro Sônia R , Ribeiro Valdinar S , Bettiol Heloisa
Published: June 2011

Background

Few cohort studies have been conducted in low and middle-income countries to investigate non-communicable diseases among school-aged children. This article aims to describe the methodology of two birth cohorts, started in 1994 in Ribeirão Preto (RP), a more developed city, and in 1997/98 in São Luís (SL), a less developed town.

Methods

Prevalences of some non-communicable diseases during the first follow-up of these cohorts were estimated and compared. Data on singleton live births were obtained at birth (2858 in RP and 2443 in SL). The follow-up at school age was conducted in RP in 2004/05, when the children were 9-11 years old and in SL in 2005/06, when the children were 7-9 years old. Follow-up rates were 68.7% in RP (790 included) and 72.7% in SL (673 participants). The groups of low (<2500 g) and high (≥ 4250 g) birthweight were oversampled and estimates were corrected by weighting.

Results

In the more developed city there was a higher percentage of non-nutritive sucking habits (69.1% vs 47.9%), lifetime bottle use (89.6% vs 68.3%), higher prevalence of primary headache in the last 15 days (27.9% vs 13.0%), higher positive skin tests for allergens (44.3% vs 25.3%) and higher prevalence of overweight (18.2% vs 3.6%), obesity (9.5% vs 1.8%) and hypertension (10.9% vs 4.6%). In the less developed city there was a larger percentage of children with below average cognitive function (28.9% vs 12.2%), mental health problems (47.4% vs 38.4%), depression (21.6% vs 6.0%) and underweight (5.8% vs 3.6%). There was no difference in the prevalence of bruxism, recurrent abdominal pain, asthma and bronchial hyperresponsiveness between cities.

Conclusions

Some non-communicable diseases were highly prevalent, especially in the more developed city. Some high rates suggest that the burden of non-communicable diseases will be high in the future, especially mental health problems.
Alcohol use behaviors and risk of metabolic syndrome in South Korean middle-aged men
Authors: Kim Jinhee , Chu Su-Kyung , Kim Kyungjoo , Moon Ju-Ryoung
Published: June 2011

Background

It is thought that small volumes of alcohol may have positive effects on health. However, excessive drinking results in serious health problems. An accurate method to determine individual alcohol use behaviors are needed to assess objectively the extent to which drinking affects health. This study investigated the association between risk of metabolic syndrome (MetS) and alcohol use behaviors in middle-aged South Korean men using the Alcohol Use Disorders Identification Test.

Methods

This study used data from the South Korea National Health and Nutrition Examination (KNHANES) IV (2008), which extracted the standard survey household by using the proportional systematic sampling method. Data of 714 participants from KNHANES IV, 2008 were analyzed using Surveyfreq and Surveylogistic regression to investigate the association between MetS and alcohol use behaviors in middle-aged South Korean men.

Results

After adjustment for education, smoking, and physical activity, alcohol use behaviors were significantly associated with an increased risk of hypertension [odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.5-4.06 in the hazardous group; OR = 2.99, 95% CI = 1.84-4.92 in the problem group]; impaired fasting glucose (OR = 2.15, 95% CI = 1.16-3.99 in the hazardous group; OR = 2.48, 95% CI = 1.42-4.33 in the problem group); dyslipidemia (OR = 2.19, 95% CI = 1.38-3.47 in the problem group); abdominal obesity (OR = 1.93, 95% CI = 1.17-3.19 in the hazardous group; OR = 1.85, 95% CI = 1.17-2.92 in the problem group); and MetS (OR = 2.16, 95% CI = 1.24-3.77 in the hazardous group; OR = 2.54, 95% CI = 1.41-4.58 in problem group).

Conclusions

This study found that excessive alcohol use behaviors increased the risk of hypertension, diabetes, dyslipidemia, abdominal obesity, and MetS. Considering the rising rate of alcohol consumption and heavy drinking at single sittings, a culture of less risky alcohol consumption must be established to promote health among middle-aged men.
Efficacy of vitamin D3-fortified-yogurt drink on anthropometric, metabolic, inflammatory and oxidative stress biomarkers according to vitamin D receptor gene polymorphisms in type 2 diabetic patients: a study protocol for a randomized controlled clinical trial
Authors: Shab-Bidar Sakineh , Neyestani Tirang R , Djazayery Abolghassem
Published: June 2011

Background

Development of type 2 diabetes mellitus (T2DM) is determined by the interactions of genetic and environmental factors. This study was designed to evaluate the possible role of VDR single nucleotide polymorphisms (SNPs) on different aspects of diabetic host response (anthropometric, metabolic, oxidative stress and inflammatory) to daily intake of vitamin D through fortified yogurt drink for 12 weeks.

Methods/Design

This study comprises two parts: (i) a case-control study; and (ii) an intervention trial. In the first part, VDR polymorphisms(Taq1,FokI,Apa1,Bsm1, andCdx2)are determined in 350 T2DM patients and 350 non-diabetic subjects. In the second part, the possible effects of daily intake of two servings of vitamin D3-fortified yogurt drink (FYD; 500 IU vitamin D/250 mL) on some selected metabolic (including insulin resistance), inflammatory and oxidative stress biomarkers in 135 T2DM patients are assessed. To relate the resulted changes in the biomarkers to vitamin D replenishment, another group of diabetic patients (n = 45) are also included in the study who receive 2 servings of plain yogurt drink (PYD) a day. The primary outcome is serum level of 25(OH) D, which it is expected to be elevated only in FYD group. Secondary outcomes include improvements in glycemic, metabolic, inflammatory and oxidative stress biomarkers in FYD group compared to PYD group. Three VDRFokIpolymorphisms are determined only in FYD group followed by comparison of changes in the biomarkers among these genotypic variants.

Discussion

The present study, at least in part, elucidates the discrepancies in the results of different vitamin D-diabetes studies pertaining to the genetic variations of the population. If VDR polymorphisms are found to influence the response to our intervention, then knowing distribution of VDR polymorphisms in both diabetic and non-diabetic populations can give a picture of the proportion of the community in whom up to 1000 IU/d vitamin D may not be effective enough to improve insulin resistance and related morbidities. Therefore, they should ideally receive further nutritional support according to their genotype.

Trial Registration

ClinicalTrials.gov:NCT01236846
Drug safety of rosiglitazone and pioglitazone in France: a study using the French PharmacoVigilance database
Authors: Berthet Stephanie , Olivier Pascale , Montastruc Jean-Louis , Lapeyre-Mestre Maryse
Published: June 2011

Background

Thiazolidinediones (TZDs), rosiglitazone (RGZ) and pioglitazone (PGZ) are widely used as hypoglycemic drugs in patients with type 2 diabetes mellitus. The aim of our study was to investigate the profile of adverse drug reactions (ADRs) related to TZDs and to investigate potential risk factors of these ADRs.

Methods

Type 2 diabetic patients were identified from the French Database of PharmacoVigilance (FPVD) between 2002 and 2006. We investigated ADR related to TZD, focusing on 4 ADR: edema, heart failure, myocardial infarction and hepatitis corresponding to specific WHO-ART terms.

Results

Among a total of 99,284 adult patients in the FPVD, 2295 reports concerned type 2 diabetic patients (2.3% of the whole database), with 161 (7%) exposed to TZDs. The frequency of edema and cardiac failure was significantly higher with TZDs than in other patients (18% and 7.4% versus 0.8% and 0.1% respectively, p < 0.001) whereas the frequency of hepatitis was similar (5.9% versus 4%, NS). A multiple logistic regression model taking into account potential confounding factors (age, gender, drug exposure and co-morbidities) found that TZD exposure remained associated with heart failure and edema, but not with hepatitis or myocardial infarction.

Conclusions

Thiazolidinediones exposure is associated with an increased risk of edema and heart failure in patients with type 2 diabetes even when recommendations for use are respected. In contrast, the risk of hepatic reactions and myocardial infarction with this class of drugs seems to be similar to other hypoglycemic agents.
Quantitative transcript analysis of the inducible expression system pSIP: comparison of the overexpression of Lactobacillus spp. β-galactosidases in Lactobacillus plantarum
Authors: Nguyen Tien-Thanh , Nguyen Thu-Ha , Maischberger Thomas , Schmelzer Philipp , Mathiesen Geir , Eijsink Vincent GH , Haltrich Dietmar , Peterbauer Clemens K
Published: June 2011

Background

Two sets of overlapping genes, lacLMReu and lacLMAci, encoding heterodimeric β-galactosidases from Lactobacillus reuteri and Lactobacillus acidophilus, respectively, have previously been cloned and expressed using the pSIP vector system and Lactobacillus plantarum WCSF1 as host. Despite the high similarity between these lacLM genes and the use of identical cloning and expression strategies, strains harboring lacLMReu produced about twenty-fold more β-galactosidase than strains containing lacLMAci.

Results

In this study, the plasmid copy numbers (PCN) of expression vectors pEH9R (lacLMReu) and pEH9A (lacLMAci) as well as the transcription levels of both lacLM genes were compared using quantitative PCR methods. Analyses of parallel fermentations of L. plantarum harboring either pEH9R or pEH9A showed that the expression plasmids were present in similar copy numbers. However, transcript levels of lacLM from L. reuteri (pEH9R) were up to 18 times higher than those of lacLM from L. acidophilus (pEH9A). As a control, it was shown that the expression levels of regulatory genes involved in pheromone-induced promoter activation were similar in both strains.

Conclusion

The use of identical expression strategies for highly similar genes led to very different mRNA levels. The data indicate that this difference is primarily caused by translational effects that are likely to affect both mRNA synthesis rates and mRNA stability. These translational effects thus seem to be a dominant determinant for the success of gene expression efforts in lactobacilli.
Aromatase inhibitors in post-menopausal endometriosis
Authors: Polyzos Nikolaos P , Fatemi Human M , Zavos Apostolos , Grimbizis Grigoris , Kyrou Dimitra , Velasco Juan-Garcia , Devroey Paul , Tarlatzis Basil , Papanikolaou Evangelos G
Published: June 2011

Postmenopausal endometriosis is a rare clinical condition. The diagnosis and treatment of an endometriotic lesion in postmenopausal women is complicated. First line treatment choice should be surgical, given that there is a potential risk of malignancy. Medical treatment may be considered as second line or as an alternate first line treatment whenever surgery is contradicted and aims to alter the hormonal pathway leading to endometriosis progress. Different hormonal regimens have been administered to these patients, with conflicting however results. Aromatase inhibitors (AIs) represent one of the most recently used drugs for postmenopausal endometriosis. Clinical data for the use of (AIs) in postmenopausal patients is scarce. Up to date only 5 case reports are available regarding the use of these agents in postmenopausal women. Although definite conclusions may be premature, AIs appear to considerably improve patients' symptoms and reduce endometriotic lesions size. Nonetheless the subsequent induced reduction in estrogen production, leads to certain short-term and long-term adverse effects. Despite the limited available data, AIs appear to represent a new promising method which may improve symptoms and treat these patients, either as first line treatment, when surgery is contraindicated or as a second line for recurrences following surgical treatment. However, careful monitoring of patients' risk profile and further research regarding long-term effects and side-effects of these agents is essential prior implementing them in everyday clinical practice.
Composite iterative schemes for maximal monotone operators in reflexive Banach spaces
Authors: Cholamjiak Prasit , Cho Yeol Je , Suantai Suthep
Published: June 2011

In this article, we introduce composite iterative schemes for finding a zero point of a finite family of maximal monotone operators in a reflexive Banach space. Then, we prove strong convergence theorems by using a shrinking projection method. Moreover, we also apply our results to a system of convex minimization problems in reflexive Banach spaces.

AMS Subject Classification: 47H09, 47H10
Effects of naturally-arising HIV Nef mutations on cytotoxic T lymphocyte recognition and Nef's functionality in primary macrophages
Authors: Mwimanzi Philip , Hasan Zafrul , Hassan Ranya , Suzu Shinya , Takiguchi Masafumi , Ueno Takamasa
Published: June 2011

Background

Although HIV can infect several cellular subsets, such as CD4+ T lymphocytes and macrophages, it remains unclear whether an HIV infection in macrophages supports cytotoxic T lymphocyte (CTL) escape. Here, we tested two naturally-arising mutations located in the well-conserved polyproline region of Nef for their effects on CTL recognition, Nef's functionality, and viral replication capacity in macrophages. These mutations were selected because they are known to cause CTL escape in the context of T lymphocytes.

Findings

Monocyte-derived macrophages (MDMs) infected with the wild-type virus, but not with variant viruses, were efficiently killed by CTL clones targeting Nef epitopes, VY8 (VPLRPMTY) and RY11 (RPQVPLRPMTY). The CTL-escape mutation, Arg75Thr, or Arg75Thr/Tyr85Phe double mutation, reduced the HLA class I down-regulation activity and, interestingly, increased the susceptibility of virus-infected MDMs to recognition by CTLs targeting a different epitope. The same mutations reduced the CCR5, but not CD4, down-regulation activity. Moreover, the Nef variants were impaired for Hck activation and enhancement of viral replication in MDMs.

Conclusions

These results suggest that HIV-infected MDMs are killed by CTLs targeting Nef epitopes, contributing to selection and adaptation of CTL-escape viral variants.
High level soluble expression, one-step purification and characterization of HIV-1 p24 protein
Authors: Zhang Baozhong , Liu Dabin , Bao Zuoyi , Chen Bin , Li Cun , Jiang Huanhuan , Wang Xiaona , Mi Zhiqiang , An Xiaoping , Lu Jun , Tong Yigang
Published: June 2011

Background

P24 protein is the major core protein of HIV virus particle and has been suggested as a specific target for antiviral strategies. Recombinant p24 protein with natural antigenic activity would be useful for various studies, such as diagnostic reagents and multi-component HIV vaccine development. The aim of this study was to express and purify the p24 protein in soluble form in E.coli.

Results

According to the sequence of the p24 gene, a pair of primers was designed, and the target sequence of 700 bp was amplified using PCR. The PCR product was cloned into pQE30 vector, generating the recombinant plasmid pQE30-p24. SDS-PAGE analysis showed that the His-tagged recombinant p24 protein was highly expressed in soluble form after induction in E. coli strain BL21. The recombinant protein was purified by nickel affinity chromatography and used to react with HIV infected sera. The results showed that the recombinant p24 protein could specifically react with the HIV infected sera. To study the immunogenicity of this soluble recombinant p24 protein, it was used to immunize mice for the preparation of polyclonal antibody. Subsequent ELISA and Western-Blot analysis demonstrated that the p24 protein had proper immunogenicity in inducing mice to produce HIV p24 specific antibodies.

Conclusion

In this work, we report the high level soluble expression of HIV-1 p24 protein in E. coli. This soluble recombinant p24 protein specifically react with HIV infected sera and elicit HIV p24 specific antibodies in mice, indicating this soluble recombinant p24 protein could be a promising reagent for HIV diagnosis.
MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival
Authors: Chi Jianxiang , Ballabio Erica , Chen Xiao-He , Kušec Rajko , Taylor Steve , Hay Deborah , Tramonti Daniela , Saunders Nigel J , Littlewood Timothy , Pezzella Francesco , Boultwood Jacqueline , Wainscoat James S , Hatton Christian SR , Lawrie Charles H
Published: June 2011

Background

MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0) of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 controls.

Results

Unsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+cells. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis.

Conclusions

In summary, this work has identified aberrantly expressed microRNAs associated with the diagnosis, pathogenesis and prognosis of MM, data which will prove an invaluable resource for understanding the role of microRNAs in this devastating disease.

Reviewers

This article was reviewed by Prof. Neil Smalheiser, Prof. Yuriy Gusev, and an unknown reviewer.
Henoch Schönlein purpura associated with pulmonary adenocarcinoma
Authors: Mifune Daiki , Watanabe Satoshi , Kondo Rie , Wada Yoko , Moriyama Hiroshi , Kagamu Hiroshi , Yoshizawa Hirohisa , Tetsuka Takafumi , Matsuyama Asako , Ito Kaoru , Narita Ichiei
Published: June 2011

Introduction

Henoch-Schönlein purpura is a common immunoglobulin A-mediated vasculitis syndrome in children. Henoch-Schönlein purpura can also affect adults and is probably related to malignancy.

Case presentation

We report the case of a 61-year-old Japanese man who presented for examination after an abnormal shadow was detected by chest radiography. He received a diagnosis of pulmonary adenocarcinoma, stage IV. Purpura on the legs, abdominal pain, diarrhea, hematuria and proteinuria developed at this time. Henoch-Schönlein purpura was diagnosed, base on the clinical symptoms and histological findings of biopsy specimens of the skin, which showed vasculitis with immunoglobulin A deposits. Our patient received chemotherapy with gemcitabine after successful steroid therapy for the Henoch-Schönlein purpura.

Conclusion

Although hematological malignancies are well-known causes of vasculitides, cases of Henoch-Schönlein purpura associated with lung adenocarcinoma are rare. Our patient was treated with corticosteroid therapy, which cleared the purpura and cytotoxic chemotherapy for the non-small cell lung cancer. However, he died from heart failure due to cardiac tamponade.
The microbiological profile and presence of bloodstream infection influence mortality rates in necrotizing fasciitis
Authors: Chen I-Chuan , Li Wen-Cheng , Hong Yu-Cheng , Shie Shian-Sen , Fann Wen-Chih , Hsiao Cheng-Ting
Published: June 2011

Introduction

Necrotizing fasciitis (NF) is a life threatening infectious disease with a high mortality rate. We carried out a microbiological characterization of the causative pathogens. We investigated the correlation of mortality in NF with bloodstream infection and with the presence of co-morbidities.

Methods

In this retrospective study, we analyzed 323 patients who presented with necrotizing fasciitis at two different institutions. Bloodstream infection (BSI) was defined as a positive blood culture result. The patients were categorized as survivors and non-survivors. Eleven clinically important variables which were statistically significant by univariate analysis were selected for multivariate regression analysis and a stepwise logistic regression model was developed to determine the association between BSI and mortality.

Results

Univariate logistic regression analysis showed that patients with hypotension, heart disease, liver disease, presence of Vibrio spp. in wound cultures, presence of fungus in wound cultures, and presence of Streptococcus group A, Aeromonas spp. or Vibrio spp. in blood cultures, had a significantly higher risk of in-hospital mortality. Our multivariate logistic regression analysis showed a higher risk of mortality in patients with pre-existing conditions like hypotension, heart disease, and liver disease. Multivariate logistic regression analysis also showed that presence of Vibrio spp in wound cultures, and presence of Streptococcus Group A in blood cultures were associated with a high risk of mortality while debridement > = 3 was associated with improved survival.

Conclusions

Mortality in patients with necrotizing fasciitis was significantly associated with the presence of Vibrio in wound cultures and Streptococcus group A in blood cultures.
Peripheral and Central GLP-1 Receptor Populations Mediate the Anorectic Effects of Peripherally Administered GLP-1 Receptor Agonists, Liraglutide and Exendin-4
Authors: Kanoski Scott E. , Fortin Samantha M. , Arnold Myrtha , Grill Harvey J. , Hayes Matthew R.
Published: June 2011

The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists, exendin-4 and liraglutide, suppress food intake and body weight. The mediating site(s) of action for the anorectic effects produced by peripheral administration of these GLP-1R agonists are not known. Experiments addressed whether food intake suppression after ip delivery of exendin-4 and liraglutide is mediated exclusively by peripheral GLP-1R or also involves direct central nervous system (CNS) GLP-1R activation. Results showed that CNS delivery [third intracerebroventricular (3rd ICV)] of the GLP-1R antagonist exendin-(9–39) (100 μg), attenuated the intake suppression by ip liraglutide (10 μg) and exendin-4 (3 μg), particularly at 6 h and 24 h. Control experiments show that these findings appear to be based neither on the GLP-1R antagonist acting as a nonspecific competing orexigenic signal nor on blockade of peripheral GLP-1R via efflux of exendin-(9–39) to the periphery. To assess the contribution of GLP-1R expressed on subdiaphragmatic vagal afferents to the anorectic effects of liraglutide and exendin-4, food intake was compared in rats with complete subdiaphragmatic vagal deafferentation and surgical controls after ip delivery of the agonists. Both liraglutide and exendin-4 suppressed food intake at 3 h, 6 h, and 24 h for controls; for subdiaphragmatic vagal deafferentation rats higher doses of the GLP-1R agonists were needed for significant food intake suppression, which was observed at 6 h and 24 h after liraglutide and at 24 h after exendin-4. Conclusion: Food intake suppression after peripheral administration of exendin-4 and liraglutide is mediated by activation of GLP-1R expressed on vagal afferents as well as direct CNS GLP-1R activation.