bluuebunny/crossref_metadata_2025 huggingface dataset:
Engagement of the B cell receptor for antigen differentially affects B cell responses to Toll-like receptor-7 agonists and antagonists in BXSB mice
Authors: Layer T , Steele A , Goeken J A , Fleenor S , Lenert P
Published: January 2011

Nucleic acid sensors of the Toll-like receptor (TLR) family play a well-established role in the pathogenesis of lupus. This is particularly true for a single-stranded RNA-sensing TLR-7 receptor, as lupus mice lacking TLR-7 show ameliorated disease. Cytosine–guanosine dinucleotide (CpG)-DNA-sensing TLR-9, conversely, has a complex regulatory role in systemic lupus erythematosus (SLE). Much less is known about whether signals through the B cell receptor for antigen (BCR) may affect the ability of B cells to respond to suboptimal TLR-7 agonists and antagonists. We studied this question in prediseased BXSB male and female B cells. We found that male B cells responded more vigorously to numerous TLR-7 ligands and this responsiveness was enhanced further upon co-engagement of the BCR. This synergy was seen primarily with the interleukin (IL)-6 secretion. A number of 32-mer inhibitory oligonucleotides (INH-ODNs) with a nuclease-resistant phosphorothioate backbone were capable of blocking TLR-7, but not BCR-induced B cell activation, with an inhibitory concentration (IC)50 of approximately 100 nm. Surprisingly, while the presence of a single TGC motif at the 5′ end of an ODN did not increase its inhibitory capacity, INH-ODNs containing multiple TGC motifs had greater inhibitory potency. When BCR and TLR-7 were co-engaged, INH-ODNs showed a differential effect on B cell activation. Whereas apoptosis protection and G1-M entry completely escaped suppression, IL-6 secretion remained sensitive to inhibition, although with a 10-fold lower potency. Our results suggest that while TLR-7 antagonists may be considered as lupus therapeutics, simultaneous co-engagement of the TLR-7 and BCR might favour autoreactive B cell survival. This hypothesis needs further experimental validation.
Functional and genomic analyses of blocked protein O‐mannosylation in baker's yeast
Authors: Arroyo Javier , Hutzler Johannes , Bermejo Clara , Ragni Enrico , García‐Cantalejo Jesús , Botías Pedro , Piberger Heidi , Schott Andrea , Sanz Ana Belén , Strahl Sabine
Published: January 2011

O‐mannosylation is a crucial protein modification in eukaryotes that is initiated by the essential family of protein O‐mannosyltransferases (PMTs). Here we demonstrate that in the model yeast Saccharomyces cerevisiae rhodanine‐3‐acetic acid derivatives affect members of all PMT subfamilies. Specifically, we used OGT2468 to analyse genome‐wide transcriptional changes in response to general inhibition of O‐mannosylation in baker's yeast. PMT inhibition results in the activation of the cell wall integrity (CWI) pathway. Coinciding, the mitogen‐activated kinase Slt2p is activated in vivo and CWI pathway mutants are hypersensitive towards OGT2468. Further, induction of many target genes of the unfolded protein response (UPR) and ER‐associated protein degradation (ERAD) is observed. The interdependence of O‐mannosylation and UPR/ERAD is confirmed by genetic interactions between HAC1 and PMTs, and increased degradation of the ERAD substrate Pdr5p* in pmtΔ mutants. Transcriptome analyses further suggested that mating and filamentous growth are repressed upon PMT inhibition. Accordingly, in vivo mating efficiency and invasive growth are considerably decreased upon OGT2468 treatment. Quantitative PCR and ChIP analyses suggest that downregulation of mating genes is dependent on the transcription factor Ste12p. Finally, inhibitor studies identified a role of the Ste12p‐dependent vegetative signalling cascade in the adaptive response to inhibition of O‐mannosylation.
Functional analysis of Streptococcus pyogenes nuclease A (SpnA), a novel group A streptococcal virulence factor
Authors: Chang Ann , Khemlani Adrina , Kang HaeJoo , Proft Thomas
Published: January 2011

Streptococcus pyogenes nuclease A (SpnA) is a recently discovered DNase that plays a role in virulence as shown in a mouse infection model. SpnA is the only cell wall‐anchored DNase found in S. pyogenes thus far and shows a unique protein architecture. The C‐terminal nuclease domain contains highly conserved catalytic site and Mg2+ binding site residues. However, expression of the SpnA nuclease domain alone resulted in a soluble, but enzymatically inactive protein. We found that at least two out of three oligonucleotide/oligosaccharide‐binding fold motifs found in the N‐terminal domain are required for SpnA activity, probably contributing to substrate binding. Using a combination of a spnA deletion mutant and a Lactococcus lactis‘gain‐of‐function’ mutant, we have shown that SpnA promotes survival in whole human blood and in neutrophil killing assays and this is, at least in part, achieved by the destruction of neutrophil extracellular traps (NETs). We observed higher frequencies for anti‐SpnA antibodies in streptococcal disease patient sera (79%, n = 19) compared with sera from healthy donors (33%, n = 9) suggesting that SpnA is expressed during infection. Detection of anti‐SpnA antibodies in patient serum might be useful for the diagnostic of post‐streptococcal diseases, such as acute rheumatic fever or glomerulonephritis.
Prevalence of anger attacks in depressive and anxiety disorders: Implications for their construct?
Authors: Painuly Nitesh Prakash , Grover Sandeep , Gupta Nitin , Mattoo Surendra K.
Published: January 2011

Aims:  The present study explores anger attacks in depressive and anxiety disorders for their prevalence and some of the clinical and psychosocial correlates.

Methods:  The sample comprised of patients with ICD‐10‐diagnosed depressive and anxiety disorders (n = 328). All the subjects were given a demographic and clinical profile sheet, the Irritability Depression Anxiety Scale, World Health Organization Quality of Life – BREF Version and the Anger Attack Questionnaire. Using the Anger Attack Questionnaire they were divided into two groups – with anger attacks (n = 170) and without anger attacks (n = 158) – in order to study the differential profile of the two groups.

Results:  Anger attacks were associated with more anxiety and irritability, and poorer quality of life. Frequency of anger attacks had a positive correlation with depression, irritability and aggression, and a negative correlation with education, income, and quality of life. Panic attacks, somatic anxiety and psychological domain of quality of life predicted the categorization of subjects into those with and without anger attacks.

Conclusion:  Anger attacks are common among depressive and anxiety disorder cases and have a negative impact on quality of life. Status of anger attacks as either linked to anxiety and/or depression, or as an independent syndrome needs further study.
Effects of constraint‐induced movement therapy on neurogenesis and functional recovery after early hypoxic‐ischemic injury in mice
Authors: RHA DONG‐WOOK , KANG SEONG‐WOONG , PARK YOON‐GHIL , CHO SUNG‐RAE , LEE WON TAEK , LEE JONG EUN , NAM CHUNG MO , HAN KYUNG HWA , PARK EUN SOOK
Published: January 2011

Aim  Constraint‐induced movement therapy (CIMT) has emerged as a promising therapeutic strategy for improving affected upper limb function in children with hemiplegic cerebral palsy (CP). However, little is known about the changes in the brain that are induced by CIMT. This study was designed to investigate these changes and behavioural performance after CIMT intervention in mice with neonatal hypoxic‐ischemic brain injury.

Method  We utilized the neonatal hypoxic‐ischemic brain injury model established in mice pups. Three weeks after the injury, the mice were randomly assigned to the following three groups: the control group (n=15), the enriched‐environment group (n=17), and the CIMT with an enriched‐environment group (CIMT‐EE, n=15). 5‐bromo‐2‐deoxyuridine (BrdU) was injected daily to label proliferating cells during the 2 weeks of intervention.

Results  The CIMT‐EE group showed better fall rate in the horizontal ladder rung walking test (mean 5.4%, SD 3.6%) than either the control (mean 14.3%, SD 7.3%; p=0.001) or enriched‐environment (mean 12.4%, SD 7.7%; p=0.010) groups 2 weeks after the end of intervention. The CIMT‐EE group also showed more neurogenesis (mean 7069 cells/mm3, SD 4017 cells/mm3) than either the control group (mean 1555 cells/mm3, SD 1422 cells/mm3; p<0.001) or enriched‐environment group (mean 2994 cells/mm3, SD 3498 cells/mm3; p=0.001) in the subventricular zone. In the striatum, neurogenesis in the CIMT‐EE group (mean 534 cells/mm3, SD 441 cells/mm3) was greater than in the control group (mean 95 cells/mm3, SD 133 cells/mm3; p=0.001).

Interpretation  There was CIMT‐EE enhanced neurogenesis in the brain along with functional benefits in mice after early hypoxic‐ischemic brain injury. This is the first study to demonstrate the effects of CIMT on neurogenesis and functional recovery after experimental injury to an immature brain.
Adenosine A2A receptors control neuroinflammation and consequent hippocampal neuronal dysfunction
Authors: Rebola Nelson , Simões Ana Patrícia , Canas Paula M. , Tomé Angelo R. , Andrade Geanne M. , Barry Claire E. , Agostinho Paula M. , Lynch Marina A. , Cunha Rodrigo A.
Published: January 2011

J. Neurochem. (2011) 117, 100–111.

The blockade of adenosine A2A receptors (A2AR) affords a robust neuroprotection in different noxious brain conditions. However, the mechanisms underlying this general neuroprotection are unknown. One possible mechanism could be the control of neuroinflammation that is associated with brain damage, especially because A2AR efficiently control peripheral inflammation. Thus, we tested if the intracerebroventricular injection of a selective A2AR antagonist (SCH58261) would attenuate the changes in the hippocampus triggered by intraperitoneal administration of lipopolysaccharide (LPS) that induces neuroinflammation through microglia activation. LPS administration triggers an increase in inflammatory mediators like interleukin‐1β that causes biochemical changes (p38 and c‐jun N‐terminal kinase phosphorylation and caspase 3 activation) contributing to neuronal dysfunction typified by decreased long‐term potentiation, a form of synaptic plasticity. Long‐term potentiation, measured 30 min after the tetanus, was significantly lower in LPS‐treated rats compared with control‐treated rats, while SCH58261 attenuated the LPS‐induced change. The LPS‐induced increases in phosphorylation of c‐jun N‐terminal kinase and p38 and activation of caspase 3 were also prevented by SCH58261. Significantly, SCH58261 also prevented the LPS‐induced recruitment of activated microglial cells and the increase in interleukin‐1β concentration in the hippocampus, indicating that A2AR activation is a pivotal step in mediating the neuroinflammation triggered by LPS. These results indicate that A2AR antagonists prevent neuroinflammation and support the hypothesis that this mechanism might contribute for the ability of A2AR antagonists to control different neurodegenerative diseases known to involve neuroinflammation.
Twelve testable hypotheses on the geobiology of weathering
Authors: BRANTLEY S. L. , MEGONIGAL J. P. , SCATENA F. N. , BALOGH‐BRUNSTAD Z. , BARNES R. T. , BRUNS M. A. , VAN CAPPELLEN P. , DONTSOVA K. , HARTNETT H. E. , HARTSHORN A. S. , HEIMSATH A. , HERNDON E. , JIN L. , KELLER C. K. , LEAKE J. R. , MCDOWELL W. H. , MEINZER F. C. , MOZDZER T. J. , PETSCH S. , PETT‐RIDGE J. , PREGITZER K. S. , RAYMOND P. A. , RIEBE C. S. , SHUMAKER K. , SUTTON‐GRIER A. , WALTER R. , YOO K.
Published: January 2011

Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth’s surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar‐to‐chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant‐microbe soil networks, thereby controlling the location and extent of biological weathering. (2) Biological stoichiometry drives changes in mineral stoichiometry and distribution through weathering. (3) On landscapes experiencing little erosion, biology drives weathering during initial succession, whereas weathering drives biology over the long term.(4) In eroding landscapes, weathering‐front advance at depth is coupled to surface denudation via biotic processes.(5) Biology shapes the topography of the Critical Zone.(6) The impact of climate forcing on denudation rates in natural systems can be predicted from models incorporating biogeochemical reaction rates and geomorphological transport laws.(7) Rising global temperatures will increase carbon losses from the Critical Zone.(8) Rising atmospheric PCO2 will increase rates and extents of mineral weathering in soils.(9) Riverine solute fluxes will respond to changes in climate primarily due to changes in water fluxes and secondarily through changes in biologically mediated weathering.(10) Land use change will impact Critical Zone processes and exports more than climate change. (11) In many severely altered settings, restoration of hydrological processes is possible in decades or less, whereas restoration of biodiversity and biogeochemical processes requires longer timescales.(12) Biogeochemical properties impart thresholds or tipping points beyond which rapid and irreversible losses of ecosystem health, function, and services can occur.
Monitoring microbial redox transformations of metal and metalloid elements under high pressure using in situ X‐ray absorption spectroscopy
Authors: PICARD A. , DANIEL I. , TESTEMALE D. , KIEFFER I. , BLEUET P. , CARDON H. , OGER P. M.
Published: January 2011

X‐ray absorption spectroscopy is a well‐established method for probing local structural and electronic atomic environments in a variety of systems. We used X‐ray absorption near‐edge structure (XANES) spectroscopy for monitoring in real‐time conditions selenium reduction in situ in live cultures of Shewanella oneidensis MR‐1 under high hydrostatic pressure. High‐quality XANES data show that Shewanella oneidensis MR‐1 reduces selenite Se(IV) to red elemental selenium Se(0) up to 150 MPa without any intermediate redox state. MR‐1 reduces all selenite provided (5–10 mm) between 0.1 and 60 MPa. Above 60 MPa the selenite reduction yield decreases linearly with pressure and the activity is calculated to stop at 155 ± 5 MPa. The analysis of cultures recovered after in situ measurements showed that the decrease in activity is linked to a decrease in viability. This study emphasizes the promising potential of XANES spectroscopy for real‐time probing in situ microbial redox transformations of a broad range of metal and metalloid elements in live samples, including under high hydrostatic pressure.
Vascular responses to 8‐nitro‐cyclic GMP in non‐diabetic and diabetic mice
Authors: Tokutomi Yoshiko , Kataoka Keiichiro , Yamamoto Eiichiro , Nakamura Taishi , Fukuda Masaya , Nako Hisato , Toyama Kensuke , Dong Yi‐Fei , Ahmed Khandaker Ahtesham , Sawa Tomohiro , Akaike Takaaki , Kim‐Mitsuyama Shokei
Published: January 2011

BACKGROUND AND PURPOSE 8‐Nitroguanosine 3′,5′‐cyclic monophosphate (8‐nitro‐cGMP), formed nitric oxide (NO)‐dependently, is a physiological second messenger, yet little is known about its role in the pathophysiology of vascular diseases. To study the pharmacological activity of 8‐nitro‐cGMP in diabetic mice, we compared its effects on vascular reactivity of aortas from non‐diabetic and diabetic mice.

EXPERIMENTAL APPROACH Vascular tension recording was performed in thoracic aortic rings from wild‐type (C57BL/6), non‐diabetic db/+ and obese/diabetic db/db mice. Endothelial NO synthase (eNOS) uncoupling and superoxide were tested by Western blot and dihydroethidium fluorescence respectively.

KEY RESULTS 8‐Nitro‐cGMP, at concentrations up to 10 µM, enhanced phenylephrine‐induced contractions in aortas from C57BL/6 and db/+ mice, but not from db/db mice. This enhancement was not observed with 8‐bromo‐cGMP. Pretreatment of aortas from C57BL/6 and db/+ mice with l‐NAME (100 µM), superoxide dismutase (100 U·mL−1) or tiron (1 mM), abolished 8‐nitro‐cGMP‐induced enhancement of the phenylephrine contraction. In 8‐nitro‐cGMP (10 µM)‐treated C57BL/6 aortas, eNOS dimer/monomer ratio was significantly decreased and vascular superoxide production increased, suggesting that 8‐nitro‐cGMP‐induced superoxide production via eNOS uncoupling may mediate the enhancement of the phenylephrine contraction. At higher concentrations (>10 µM), 8‐nitro‐cGMP produced relaxation of the phenylephrine‐contracted aortas from C57BL/6, db/+ and db/db mice. The 8‐nitro‐cGMP‐induced relaxation in db/db mouse aortas was found to be resistant to a phosphodiesterase 5 inhibitor, zaprinast (1 µM).

CONCLUSIONS AND IMPLICATIONS The vasodilator effect of 8‐nitro‐cGMP may contribute to amelioration of the vascular endothelial dysfunction in diabetic mice, representing a novel pharmacological approach to prevent the complications associated with diabetes.
Rosiglitazone inhibits Kv4.3 potassium channels by open‐channel block and acceleration of closed‐state inactivation
Authors: Jeong I , Choi BH , Hahn SJ
Published: January 2011

BACKGROUND AND PURPOSERosiglitazone is a widely used oral hypoglycaemic agent, which improves insulin resistance in type 2 diabetes. Chronic rosiglitazone treatment is associated with a number of adverse cardiac events. The present study was designed to characterize the effects of rosiglitazone on cloned Kv4.3 potassium channels.

EXPERIMENTAL APPROACHThe interaction of rosiglitazone with cloned Kv4.3 channels stably expressed in Chinese hamster ovary cells was investigated using whole‐cell patch‐clamp techniques.

KEY RESULTSRosiglitazone decreased the currents carried by Kv4.3 channels and accelerated the current inactivation, concentration‐dependently, with an IC50of 24.5 µM. The association and dissociation rate constants for rosiglitazone were 1.22 µM−1·s−1and 31.30 s−1respectively. Block by rosiglitazone was voltage‐dependent, increasing in the voltage range for channel activation; however, no voltage dependence was found in the voltage range required for full activation. Rosiglitazone had no effect on either the deactivation kinetics or the steady‐state activation of Kv4.3 channels. Rosiglitazone shifted the steady‐state inactivation curves in the hyperpolarizing direction, concentration‐dependently. The Kifor the interaction between rosiglitazone and the inactivated state of Kv4.3 channels was 1.49 µM, from the concentration‐dependent shift in the steady‐state inactivation curves. Rosiglitazone also accelerated the kinetics of the closed‐state inactivation of Kv4.3 channels. Rosiglitazone did not affect either use dependence or recovery from inactivation of Kv4.3 currents.

CONCLUSION AND IMPLICATIONSOur results indicate that rosiglitazone potently inhibits currents carried by Kv4.3 channels by interacting with these channels in the open state and by accelerating the closed‐state inactivation of Kv4.3 channels.

LINKED ARTICLEThis article is commented on by Hancox, pp. 496–498 of this issue. To view this commentary visithttp://dx.doi.org/10.1111/j.1476‐5381.2011.01281.x
Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease
Authors: Rabe Klaus F.
Published: January 2011

Phosphodiesterase 4 (PDE4) is a member of the PDE enzyme superfamily that inactivates cyclic adenosine monophosphate and cyclic guanosine monophosphate, and is the main PDE isoenzyme occurring in cells involved in inflammatory airway disease such as chronic obstructive pulmonary disease (COPD). COPD is a preventable and treatable disease and is characterized by airflow obstruction that is not fully reversible. Chronic progressive symptoms, particularly dyspnoea, chronic bronchitis and impaired overall health are worse in those who have frequent, acute episodes of symptom exacerbation. Although several experimental PDE4 inhibitors are in clinical development, roflumilast, a highly selective PDE4 inhibitor, is the first in its class to be licensed, and has recently been approved in several countries for oral, once‐daily treatment of severe COPD. Clinical trials have demonstrated that roflumilast improves lung function and reduces exacerbation frequency in COPD. Furthermore, its unique mode of action may offer the potential to target the inflammatory processes underlying COPD. Roflumilast is effective when used concomitantly with all forms of bronchodilator and even in patients treated with inhaled corticosteroids. Roflumilast thus represents an important addition to current therapeutic options for COPD patients with chronic bronchitis, including those who remain symptomatic despite treatment. This article reviews the current status of PDE4 inhibitors, focusing on the pharmacokinetics, efficacy and safety of roflumilast. In particular, it provides an overview of the effects of roflumilast on lung function and exacerbations, glucose homoeostasis and weight loss, and the concomitant use of long‐acting beta2‐adrenergic receptor agonists and short‐acting muscarinic receptor antagonists.

LINKED ARTICLESThis article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visithttp://dx.doi.org/10.1111/bph.2011.163.issue‐1
Waterborne Disease‐Related Risk Perceptions in the Sonora River Basin, Mexico
Authors: Morua Agustin Robles , Halvorsen Kathleen E. , Mayer Alex S.
Published: January 2011

Waterborne disease is estimated to cause about 10% of all diseases worldwide. However, related risk perceptions are not well understood, particularly in the developing world where waterborne disease is an enormous problem. We focus on understanding risk perceptions related to these issues in a region within northern Mexico. Our findings show how waterborne disease problems and solutions are understood in eight small communities along a highly contaminated river system. We found major differences in risk perceptions between health professionals, government officials, and lay citizens. Health professionals believed that a high level of human‐waste‐related risk existed within the region. Few officials and lay citizens shared this belief. In addition, few officials and lay citizens were aware of poor wastewater‐management‐related disease outbreaks and water contamination. Finally, aside from health professionals, a few interviewees understood the importance of basic hygiene and water treatment measures that could help to prevent disease. Our results add to the literature on environmentally‐related risk perceptions in the developing world. We discuss recommendations for improving future human‐wastewater‐related risk communication within the region.
Transnational Mothers Crossing the Border and Bringing Their Health Care Needs
Authors: Sternberg Rosa Maria , Barry Charlotte
Published: January 2011

Purpose: The purpose of this study was to explore the experiences of transnational Latina mothers who immigrated to the United States without legal documentation or their children.

Design: The study used a qualitative approach to collect data from eight transnational Latina mothers from South Florida during the summer of 2009.

Methods: Data were collected using open‐ended questions in one‐on‐one, in‐depth interviews that lasted 1 to 2 hr.

Findings: A hermeneutic phenomenological analysis of the data yielded seven essential themes from the participants’ stories: living in extreme poverty, having hope, choosing to walk away from poverty, suffering through the trip to and across the border, mothering from afar, valuing family, and changing personally.

Conclusions: The results indicate that transnational Latina mothers find meaning in mothering from afar through embodied sacrifice, suffering, hoping for a better life for their children, and family reunification. These results have implications for healthcare providers, social workers, policy makers, and educators whose professional responsibility is to advocate for, and to enhance the health and social well‐being of, transnational mothers.

Clinical Relevance: Although this study focused on transnational Latina mothers in the United States, transnational motherhood is a worldwide phenomenon. Healthcare professionals play an instrumental role in providing culturally specific and evidence‐based care to women who migrate without their children.
Flash‐Sintering of Cubic Yttria‐Stabilized Zirconia at 750°C for Possible Use in SOFC Manufacturing
Authors: Cologna Marco , Prette Andre L. G. , Raj Rishi
Published: January 2011

We show that cubic 8 mol% yttria (8YSZ) can be sintered at 750°C with the application of DC electrical fields; in comparison the lowest sintering temperature for 3YSZ was 850°C. Furthermore, cubic zirconia exhibits the onset of flash sintering at 30 V/cm, whereas 3YSZ begins flash sintering at 60 V/cm. However, the volume specific power dissipation for the onset of flash sintering remains similar at ∼10 mW/mm3. The easier sintering of 8YSZ is ascribed to its higher ionic conductivity.
Prognosis of Ischaemic Stroke is Improving Similarly in Patients with Type 2 Diabetes as in Nondiabetic Patients in Finland
Authors: Winell Klas , Pääkkönen Rauni , Pietilä Arto , Reunanen Antti , Niemi Marja , Salomaa Veikko
Published: January 2011

Background

Case fatality of first ischaemic stroke has improved markedly during the past two decades.

Aims

To investigate whether stroke patients with type 2 diabetes have shared this favourable development.

Methods

Nation-wide registers were used to identify all patients with type 2 diabetes in Finland during 1988–2002. All first ischaemic strokes among them and also among all nondiabetic persons were identified from the National Hospital Discharge Register and the Causes of Death Register. Trends over time were calculated, for age-standardised case fatality of first stroke events, separately for two time periods: 0–27 and 28–364 days after the onset of stroke. These trends were compared between patients with type 2 diabetes and nondiabetic patients.

Results

Altogether, 23097 first-ever ischaemic strokes were recorded among 222 940 persons with type 2 diabetes. The 28 day case fatality was 1·1–1·3 times higher, and the one-year case fatality of 28 day survivors was 1·4–2·2 times higher in patients with type 2 diabetes compared with nondiabetic patients. A significant decline in case fatality trends was observed, but the trends did not differ between type 2 diabetes and nondiabetic patients.

Conclusions

The study revealed a positive development in survival after the first stroke event in persons with type 2 diabetes, similar to the development in nondiabetic persons. However, the level of case fatality has remained higher in patients with type 2 diabetes.
GGR Biennial Review: Key Advances in Secondary Ion Mass Spectrometry in the Geological Sciences during the Period 2008–2009
Authors: Wiedenbeck Michael
Published: January 2011

Secondary ion mass spectrometry (SIMS or ion microprobe) remains one of the most powerful techniques in the analytical geochemist’s toolkit. The key strength of SIMS is its capacity to provide trace element and isotope data at sampling sizes which are not approached by other methods. As compared with the main competing technique of laser ablation‐ICP‐MS, SIMS commonly provides a total sampling mass some 10 to 500 times smaller; this feature can be the deciding factor as to whether an analytical objective is technically achievable. Additional strengths of SIMS lie in the areas of depth profiling and trace element imaging. Though perhaps not as commonly used in the geosciences, these two operational modes represent unique capabilities of SIMS.
Development of novel microsatellite markers to identify the different invasive lineages in theCorbiculacomplex and to assess androgenesis
Authors: PIGNEUR L. ‐M. , RISTERUCCI A. ‐M. , DAUCHOT N. , LI X. , VAN DONINCK K.
Published: January 2011

Reliable markers are needed to identify the lineages in the invasive clam genusCorbicula. Previous studies have demonstrated that mitochondrial (mt) DNA poorly resolvesCorbiculaphylogeny, owing to its androgenetic reproductive mode. Moreover, hybridization and mitochondrial/nuclear mismatches occur. We developed the first eleven polymorphic markers to detect these phenomena and to investigate the nuclear identity ofCorbiculapopulations. These microsatellite loci revealed three main lineages in Western Europe. One locus allowed rapid discrimination of these three lineages on agarose gel, saving time and money. Moreover, the eleven markers were successfully cross‐amplified in the invasiveCorbiculalineages found in North America.
COI‐based DNA barcoding of Arcoida species (Bivalvia: Pteriomorphia) along the coast of China
Authors: FENG YANWEI , LI QI , KONG LINGFENG , ZHENG XIAODONG
Published: January 2011

DNA barcoding is a promising tool for the rapid and unambiguous identification of species. Some arcoid species are particularly difficult to distinguish with traditional morphological identification owing to phenotypic variation and the existence of closely related taxa. Here, we apply DNA barcoding based on mitochondrial cytochrome c oxidase I gene (COI) to arcoid species collected from the coast along China. Combining morphology with molecular data indicates the 133 specimens of Arcoida could be assigned to 24 species. Because of the deep genetic divergence within Tegillarca granosa, there was an overlap between genetic variation within species and variation between species. Nevertheless, NJ and Bayesian trees showed that all species fell into reciprocally monophyletic clades with high bootstrap values. Our results evidence that the COI marker can efficiently identify species, correct mistakes caused by morphological identification and reveal genetic differentiation among populations within species. This study provides a clear example of the usefulness of barcoding for arcoid identification. Furthermore, it also lays a foundation for other biological and ecological studies of Arcoida.
Effects of Tween 80 on volume-regulated chloride channel and cell proliferation in rat basilar artery smooth muscle cell
Authors: Du Ren-Hong , Tang Yong-Bo , Zhou Jia-Guo , Guan Yong-Yuan
Published: January 2011

Objectives

We have previously found that volume-regulated chloride current (VRCC) is involved in cell cycle progression and cell proliferation. This study was to examine the effect of Tween 80, a nonionic surfactant, on VRCC and cell proliferation in rat basilar artery smooth muscle cells (BASMCs).

Methods

VRCC was recorded using a whole-cell patch clamp. Cell proliferation and cell cycle were determined by CCK-8, cell count and flow cytometry.

Key findings

The results showed that endothelin-1 promotes cell cycle transition from the G0/G1 phase to the S phase and significantly increases VRCC in BASMCs. The effect of Tween 80 on VRCC is reversible and concentration dependent. However, this chemical has no effect on the calcium-activated chloride channel. Tween 80 also concentration-dependently inhibits BASMCs proliferation and arrests cells in the G1/S checkpoint. The antiproliferative effect is paralleled with the inhibitory effect on VRCC.

Conclutision

Our study demonstrates that the inhibitory effect of Tween 80 on VRCC contributes importantly to arrest of the cell cycle and prevention of cell proliferation.
Design and development of gliclazide-loaded chitosan microparticles for oral sustained drug delivery: in-vitro/in-vivo evaluation
Authors: Barakat Nahla S , Almurshedi Alanood S
Published: January 2011

Objectives

The objective of this study was to prepare gliclazide–chitosan microparticles with tripolyphosphate by ionic crosslinking.

Methods

Chitosan microparticles were produced by emulsification and ionotropic gelation. The effects of process variables including chitosan concentration, pH of tripolyphosphate solution, glutaraldehyde volume and release modifier agent such as pectin added to the tripolyphosphate crosslinking solution were evaluated. The microparticles were examined with scanning electron microscopy, infrared spectroscopy and differential scanning colorimetry. The serum glucose lowering effect of gliclazide microparticles was studied in streptozotocin-diabetic rabbits compared with the effect of pure gliclazide powder and gliclazide commercial tablets.

Key findings

The particle sizes of tripolyphosphate–chitosan microparticles were over the range 675–887 µm and the loading efficiency of drug was greater than 94.0%. In-vivo testing of the gliclazide–chitosan microparticles in diabetic rabbits demonstrated a significant antidiabetic effect of gliclazide–chitosan microparticles after 8 h that lasted for 18 h compared with gliclazide powder, which produced a maximum hypoglycaemic effect after 4 h.

Conclusions

The results suggests that gliclazide–chitosan microparticles are a valuable system for the sustained delivery of gliclazide.
Evaluating clinical pharmacy services on a surgical patient-care area: a nurses' satisfaction survey
Authors: Chevalier Bernadette , Neville Heather L
Published: January 2011

Objectives

To determine nurses' perceptions and expectations of clinical pharmacists prior to, and 9 months after, clinical pharmacy services were introduced on two general and gastrointestinal surgery hospital wards in Canada.

Methods

A survey tool was developed based on previous research, validated to ensure reliability and accuracy, and administered to approximately 70 nurses on the surgery wards.

Key findings

Response rates for the pre and post surveys were 75% and 67% respectively. Nurses indicated that the quality of pharmacy service improved significantly from pre to post survey (85% versus 95%; P < 0.0001). There was a statistically significant increase in positive responses to seven out of eight statements such as accessibility of pharmacists, timely responses to drug-related questions, and timely delivery of unit doses and intravenous admixtures. Almost all statements about nursing staff expectations showed increases in agreement. At least 85% of nurses indicated their expectations had been met or exceeded for all but one clinical pharmacy service. A higher proportion of nurses in the post survey felt that clinical pharmacists positively impact on their roles and responsibilities as a nurse. Comments from nurses indicated enthusiastic support for clinical pharmacy services.

Conclusions

A survey tool to assess the quality of pharmacy services in the hospital setting has been developed, validated, and distributed. A high level of nurses' satisfaction with the provision of new clinical pharmacy services on general surgery/gastrointestinal surgery wards was demonstrated. Nursing staff were more aware of the responsibilities of clinical pharmacists and how the clinical pharmacist role could assist them in their own nursing practice. The survey may be useful for other wards and other institutions to measure satisfaction with pharmacy services.
Re-examining Electron-Fermi Relaxation in Gold Films With a Nonlinear Thermoreflectance Model
Authors: Hopkins Patrick E. , Phinney Leslie M. , Serrano Justin R.
Published: January 2011

In this work, we examine Fermi relaxation in 20 nm Au films with pump-probe themoreflectance using a thin film, intraband thermoreflectance model. Our results indicate that the Fermi relaxation of a perturbed electron system occurs approximately 1.10±0.05 ps after absorption of a 785 nm, 185 fs laser pulse. This is in agreement with reported values from electron emission experiments but is higher than the Fermi relaxation time determined from previous thermoreflectance measurements. This discrepancy arises due to thermoreflectance modeling and elucidates the importance of the use of a proper thermoreflectance model for thermophysical property determination in pump-probe experiments.
Analysis of Properties of Adulterated Fuel and Its Effects on Internal Combustion Engines and the Environment: A Case Study Tema Metropolitan Assembly, Tema, Ghana
Authors: Simons A. , Gbadam E. K.
Published: January 2011

This paper seeks to investigate the sources and the level of fuel contamination in the Ghanaian market and its effects on internal combustion engines and the environment. A survey was conducted in and around the Tema Metropolitan Assembly to collect samples of fuels from different retailers without letting them know the intentions of the buyer (that these are for research). Experiments were carried out at Tema Oil Refinery (TOR), Tema, Ghana, on the two conventional fuels collected from these sources. The analysis of the results showed that fuel from the fuel tank and “Zamelama” (small scale petrol retailers) filling station had the highest level of contamination as far as the experiment on petrol (gasoline) was concerned. With the diesel fuel experiment, most of the values obtained were high but within the standard range at the refinery. Information obtained from questionnaires given to fuel tanker drivers, mechanics and sales persons at various filling stations indicated that the adulteration is done using Naphtha and Kerosene. Consequently, other experiments were carried out at TOR using different proportions of Naphtha and Kerosene and the resultant properties as a result of the adulteration were analyzed. It was observed that the adulterated fuels have undesirable properties such as High Gum Content, low Research Octane Number (RON) and Reid Vapour Pressure (RVP) values which may lead to engine damage and pollution of the environment due to increased exhaust emissions. Considering the results of the experiment, it can be concluded that Petrol adulterated with Naphtha or Kerosene should not be used in Internal Combustion Engines. This is because of its undesirable properties such as higher Gum content, lower RON and RVP values which lead to engine damage and pollution of the environment due to increased exhaust emissions.
Comparison of Filter Smoke Number and Elemental Carbon Mass From Partially Premixed Low Temperature Combustion in a Direct Injection Diesel Engine
Authors: Northrop William F. , Bohac Stanislav V. , Assanis Dennis N. , Chin Jo-Yu
Published: January 2011

Partially premixed low temperature combustion (LTC) is an established advanced engine strategy that enables the simultaneous reduction of soot and NOX emissions in diesel engines. Measuring extremely low levels of soot emissions achievable with LTC modes using a filter smoke meter requires large sample volumes and repeated measurements to achieve the desired data precision and accuracy. Even taking such measures, doubt exists as to whether filter smoke number (FSN) accurately represents the actual smoke emissions emitted from such low soot conditions. The use of alternative fuels such as biodiesel also compounds efforts to accurately report soot emissions since the reflectivity of high levels of organic matter found on the particulate matter collected may result in erroneous readings from the optical detector. Using FSN, it is desired to report mass emissions of soot using empirical correlations derived for use with petroleum diesel fuels and conventional modes of combustion. The work presented in this paper compares the experimental results of well known formulae for calculating mass of soot using FSN and elemental carbon mass using thermal optical analysis (TOA) over a range of operating conditions and fuels from a four cylinder direct injection passenger car diesel engine. The data show that the mass of soot emitted by the engine can be accurately predicted with the smoke meter method utilizing a 3000 ml sample volume over a range of FSN from 0.02 to 1.5. Soot mass exhaust concentration calculated from FSN using the best of the literature expressions and that from the TOA taken over all conditions correlated linearly with a slope of 0.99 and R2 value of 0.94. A primary implication of the work is that the level of confidence in reporting soot mass based on FSN for low soot formation regimes like LTC is improved for both petroleum diesel and biodiesel fuels.
Next-Cycle and Same-Cycle Cylinder Pressure Based Control of Internal Combustion Engines
Authors: Quillen Kristopher P. , Viele Matthew , Ciatti Stephen A.
Published: January 2011

This paper reviews next-cycle and same-cycle control techniques developed by Drivven and implemented at Argonne National Laboratory on a General Motors 1.9L common rail diesel engine. Next-cycle control involves measuring cylinder pressure engine-synchronously, performing calculations, and using the complete result in the control algorithm for the fueling event in the next engine cycle. For this control method, injection timing was manipulated to maintain a specified 50% burn location and was investigated in both single-cylinder and multi-cylinder modes. The engine was tested in steady state with step changes in input parameters such as EGR rate. Similar to next-cycle control, same-cycle control involves measuring cylinder pressure engine-synchronously, performing calculations, and making fueling decisions based on partial results within the same engine cycle. For this control method, injection pulse spacing was manipulated to optimize secondary injections by a heat-release calculated angle-by-angle. Next-cycle and same-cycle control both have the capability of enhancing production engine control while next-cycle control also has great benefits as a calibration aid.
Investigating Potential Efficiency Improvement for Light-Duty Transportation Applications Through Simulation of an Organic Rankine Cycle for Waste-Heat Recovery
Authors: Edwards K. Dean , Wagner Robert M.
Published: January 2011

Modern diesel engines used in light-duty transportation applications have peak brake thermal efficiencies in the range of 40–42% for high-load operation with substantially lower efficiencies at realistic road-load conditions. Thermodynamic energy and exergy analysis reveals that the largest losses from these engines are due to heat loss and combustion irreversibility. Substantial improvement in overall engine efficiency requires reducing or recovering these losses. Unfortunately, much of the heat transfer either occurs at relatively low temperatures resulting in large entropy generation (such as in the air-charge cooler), is transferred to low-exergy flow streams (such as the oil and engine coolant), or is radiated or convected directly to the environment. While there are significant opportunities for recovery from the exhaust and EGR cooler for heavy-duty applications, the potential benefits of such a strategy for light-duty diesel applications are unknown due to transient operation, the low thermal quality of exhaust gases at typical driving conditions, and the added mass of the system. Waste-heat recovery efforts will directly compete with NOx aftertreatment systems for the limited thermal energy in the exhaust during low-load operation. We have developed an organic Rankine cycle model using GT-Suite® to investigate the potential for efficiency improvement through waste-heat recovery from the exhaust and EGR cooler of a light-duty diesel engine. Results from steady-state and drive-cycle simulations are presented, and we discuss the operational difficulties associated with transient drive cycles and competition between waste-heat recovery systems, turbochargers, aftertreatment devices, and other systems for the limited thermal resources at typical driving conditions.
Interpreting the Lambda Sensor Output Signal to Control Emissions From Natural Gas Fueled Engines
Authors: Toema Mohamed , Chapman Kirby S.
Published: January 2011

This paper presents the work done to date on a modeling study of the Non-Selective Catalytic Reduction (NSCR) system. Several recent experimental studies indicate that the voltage signal from the heated exhaust gas oxygen sensor commonly used to control these emission reduction systems may not be interpreted correctly because of the physical nature in the way the sensor senses the exhaust gas concentration. While the current signal interpretation may be satisfactory for modest NOX and CO reduction, an improved understanding of the signal is necessary to achieve consistently low NOX and CO emission levels. The increasingly strict emission regulations may require implementing NSCR as a promising emission control technology for stationary spark ignition engines. Many recent experimental investigations that used NSCR systems for stationary natural gas fueled engines showed that NSCR systems were unable to consistently control the emissions level below the compliance limits. Modeling of NSCR components to better understand, and then exploit, the underlying physical processes that occur in the lambda sensor and the catalyst media is now considered an essential step toward improving NSCR system performance. This paper focuses only on the lambda sensor that provides feedback to the air-to-fuel ratio controller. The goals of this modeling study are: • Improve the understanding of the transport phenomena and electrochemical processes that occur within the sensor. • Investigate the cross-sensitivity of exhaust gases from natural gas fueled engines on the sensor performance. • Serve as a tool for improving NSCR control strategies. This model simulates the output from a planar switch type lambda sensor. The model consists of three modules. The first module models the multi-component mass transport through the sensor protective layer. A one dimensional mass conservation equation is used for each exhaust gas species. Diffusion fluxes are calculated using the Maxwell-Stefan equation. The second module includes all the surface catalytic reactions that take place on the sensor platinum electrodes. All kinetic reactions are modeled based on the Langmuir-Hinshelwood kinetic mechanism. The third module is responsible for simulating the reactions that occur on the electrolyte material and determining the sensor output voltage. The details of these three modules as well as a parametric study that investigates the sensitivity of the output voltage signal to various exhaust gas parameters is provided in the paper.
Particle Number and Mass Collection Efficiencies in a Close-Coupled DOC-DPF System: Experimental Analysis Supported by Soot Load Modeling
Authors: Mecocci F. , Mulone V. , Rocco V. , Perin M. , Tonetti M.
Published: January 2011

PM effects on health are believed to be more related to particle total number rather than to particle total mass. This gave rise in Europe to the forthcoming introduction of an emission standard on total particle number, that will take place for passenger cars from EURO5 (stage b) on. The behavior of the DPF is therefore under investigation, to better understand its effectiveness toward particle number reduction. Moving from that background, a study on the effect of a close coupled DOC-CDPF (Diesel Oxidation Catalyst + Catalyzed Diesel Particulate Filter) on PM emissions is proposed in this paper, with special focus on the comparison between mass and number collection efficiency. Experimental data have been gathered at the engine laboratory of the University of Rome Tor Vergata, equipped with a FIAT 2.0l EURO 5 passenger car engine. Data have been acquired with a TSI 3090 EEPS to measure particle distribution and total number, and an AVL-415 S to measure PM mass emissions. A numerical code has been also developed to represent the DPF behavior, in terms of soot load (g/l) trend, under forced regenerating operating conditions and better understand regeneration potential as a function of time. Results, acquired for three non regenerating and one forced regenerating modes, prove that mass and number efficiencies are close to 100%, with a slight decrease during the forced regeneration mode.