bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual therapy versus monotherapy of trandolapril and telmisartan on diabetic nephropathy in experimentally induced type 2 diabetes mellitus rats
Authors: Rao Ravi P , Jain AK , Srinivasan BP
Published: March 2011

Objective: To investigate the combination of telmisartan with trandolapril therapy versus monotherapy of trandolapril and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats.

Material and methods: Neonatal rats (2 days old) were used for inducing type 2 diabetes mellitus. Streptozotocin at a dose of 90 mg/kg, in freshly prepared citrate buffer (0.1M, pH 4.5), was injected intraperitoneally. There were five groups: (1) normal control, (2) diabetic control, (3) diabetic treated with telmisartan, (4) diabetic treated with trandolapril and (5) diabetic treated with telmisartan and trandolapril. Albumin excretion rate, total protein excretion rate, plasma fibronectin, transforming growth factor beta 1(TGF-β1), tumour necrosis factor-α (TNF-α) concentration and renal structural changes were measured.

Results: Albumin excretion rate, total protein excretion rate, plasma fibronectin, TGF-β1, TNF-α concentration and renal structural changes increased significantly in untreated diabetic rats compared with normal control rats. Administration of telmisartan, trandolapril, or both decreased these changes.

Conclusions: Addition of the telmisartan to trandolapril was more effective in reducing renal structural changes and improvement of renal function than monotherapy with either drug, possibly due to dual inhibitory effect on the renin— angiotensin system, and thus suppression of TGF-β1, TNF-α.
Renin–angiotensin–aldosterone system genotypes and haplotypes affect the susceptibility to nephropathy in type 2 diabetes patients
Authors: Mtiraoui Nabil , Ezzidi Intissar , Turki Amira , Chaieb Molka , Mahjoub Touhami , Almawi Wassim Y
Published: March 2011

Background: The association between renin C-4063T and angiotensinogen (AGT) T174M, M235T, and A-6G polymorphisms with diabetic nephropathy (DN) was investigated in Tunisian type 2 diabetes (T2DM) patients.

Methods: Study subjects comprised 917 T2DM patients (405 normoalbuminuric, 329 microalbuminuric and 185 macroalbuminuric). Genotyping was done by PCR-RFLP.

Results: Renin C-4063T allele and genotype frequencies were comparable between DN cases and normoalbuminuric controls. Although AGT 235T and -6G allele, and 235T/T and -6G/G genotype frequencies were higher in DN compared to normoalbuminuric patients, they were comparable between microalbuminuric or macroalbuminuric patients. Three-locus AGT haplotype analysis (A-6G/T174M/M235T) identified DN-protective (ATM, AMM, GTM) and DN-susceptible (GTM, ATT, GMT and AMT) haplotypes, and demonstrated enrichment of GTT haplotype in macroalbuminuric compared to microalbuminuric or normoalbuminuric patients. Regression analysis confirmed negative (AMM) and positive (GTM, ATT, GMT, AMT) association of AGT haplotypes with microalbuminuria, and negative (AMM) and positive (GTM and ATT) association of AGT haplotypes with macroalbuminuria. None of the AGT haplotypes was associated with DN severity.

Conclusions: Genetic variation at the AGT gene influences the risk of nephropathy in T2DM patients but not extent of DN severity, and thus represents a potential DN genetic susceptibility locus worthy of replication.
Study of the mechanisms of aldosterone prothrombotic effect in rats
Authors: Gromotowicz Anna , Szemraj Janusz , Stankiewicz Adrian , Zakrzeska Agnieszka , Mantur Maria , Jaroszewicz Ewa , Rogowski Franciszek , Chabielska Ewa
Published: March 2011

Introduction: We investigated the role of primary haemostasis, fibrinolysis, nitric oxide (NO) and oxidative stress as well as mineralocorticoid receptors (MR) in acute aldosterone prothrombotic action.

Materials and methods: Venous thrombosis was induced by stasis in Wistar rats. Aldosterone (ALDO; 10, 30, 100 µg/kg/h) was infused for 1 h. Eplerenone (EPL; 100 mg/kg, p.o.), a selective MR antagonist, was administered before ALDO infusion. Bleeding time (BT) and platelet adhesion to collagen were evaluated. The expression of nitric oxide synthase (NOS), NADPH oxidase, superoxide dismutase (SOD) and plasminogen activator inhibitor (PAI-1) was measured. NO, malonyl dialdehyde (MDA) and hydrogen peroxide (H2O2) plasma levels were assayed.

Results: Significant enhancement of venous thrombosis was observed after ALDO infusion. ALDO shortened BT and increased platelet adhesion. Marked increases were observed in PAI-1, NADPH oxidase and SOD mRNA levels. MDA and H2O2 levels were augmented in ALDO-treated groups, and NOS expression and NO level were decreased. EPL reduced ALDO effects on thrombus formation, primary haemostasis, PAI-1 expression and MDA level.

Conclusion: Short-term ALDO infusion enhances experimental venous thrombosis in the mechanism involving primary haemostasis, fibrinolysis, NO and oxidative stress-dependent pathways. The MR antagonist only partially diminished the ALDO effects, suggesting the involvement of additional mechanisms.
Role of the AT2 receptor in modulating the angiotensin II contractile response of the uterine artery at mid-gestation
Authors: Pulgar Victor M , Yamashiro Henry , Rose James C , Moore Lorna G
Published: March 2011

Introduction: During human pregnancy, circulating concentrations of components of the renin—angiotensin system increase, but pressor refractoriness to angiotensin II (Ang-II) is observed. Given the importance of the Ang-II pressor response in deciding susceptibility to preeclampsia and of the Ang-II system for controlling uterine vasoreactivity, we sought to address the effects of pregnancy on the reactivity of the isolated uterine artery (UA) in mice.

Materials and methods : Blood pressure was measured throughout pregnancy in awake C57BL/6J mice. UA segments were isolated from three groups of animals (non-pregnant, mid [day 12—13] and late [day 18—19] gestation) and studied by wire myography.

Results: UA diameters, KCl-mediated responses, and acetylcholine-dependent vasorelaxation were greater at mid and late gestation than in non-pregnant animals. Ang-II responses were also greater during pregnancy, with an increased contraction in response to AT2 receptor blockade at mid-gestation. AT1 receptor blockade abolished the Ang-II response in all groups.

Conclusions: Study findings are consistent with the possibility that AT2 receptor-mediated vasodilatation plays a role in modulating Ang-II contractile responses in pregnancy.
Attenuation of angiotensin converting enzyme inhibitor induced cough by iron supplementation: role of nitric oxide
Authors: Bhalla Payal , Singh Narinder Pal , Ravi Krishnan
Published: March 2011

The present study examined whether (1) the cough associated with angiotensin converting enzyme inhibitor therapy is attenuated by oral intake of iron and anti-oxidants, and (2) nitric oxide (NO) has any role in this attenuation. Of the 100 patients under investigation, cough occurred in 28 of them with preponderance in females. All the 28 patients were followed up for six weeks: the first two weeks were the observation period and the remaining four weeks the experimentation period. After the observation period, 11 patients received a single oral dose of ferrous sulphate (200 mg), eight received vitamin E (200 mg, o.d.) and vitamin C (150 mg, o.d.) and nine were given placebo during the experimentation period. Cough scoring, serum NO and malondialdehyde (MDA) levels were determined during both the periods. While there were significant decreases in cough scores, NO and MDA levels between these two periods in the iron group, cough scores and MDA level decreased significantly in the anti-oxidant group. None of these parameters changed in the control group. NO level was found to be increased significantly in patients who developed cough ( n = 28) compared with those who did not cough ( n = 72). These results suggest that iron supplementation suppresses cough in patients on ACE-I therapy through its effect on NO generation.
When to shut students up: Civility, silencing, and free speech
Authors: Callan Eamonn
Published: March 2011

Teachers sometimes shut students up for the sake of civility. My question is whether silencing for the sake of civility can be morally justified when a student derogates fellow students as members of some widely stigmatized group, and the offending speech is not for any further reason to be deplored, for example, as a personally targeted insult. Exploring possible answers to that question sheds light on a bigger issue: the proper character of ‘civility regimes’ in educational institutions whenever group stigmatization persists in the social background and impinges seriously on some students’ lives. A plausible argument for silencing under the conditions specified is derived from respect for students’ equal dignity and the protection of fair educational opportunity. That argument is nonetheless defeated by considerations about the rightful place of intellectual candor in a culture of free speech and the centrality of educational institutions in supporting candor’s development.
Translating Research to Practice
Authors: Austin Glenn , Bell Tanya , Caperchione Cristina , Mummery W. Kerry
Published: March 2011

Although there has been an increase in the availability of effective, evidence-based physical activity interventions in school settings during the past decade, there is a paucity of published research focusing on the translation of these effective interventions into real-world practice. The purpose of this research was to examine the translatability of an existing school-based physical activity intervention. More specifically, this research sought to identify the barriers and facilitators in adopting, implementing, and maintaining a school-based physical activity intervention using RE-AIM as a theoretical evaluation framework. It was concluded that interventions that consider issues around complexity and compatibility with the school setting are more likely to be adopted, implemented, and maintained. It was recommended that future evaluations of physical activity interventions should not be limited to testing internal validity, but should consider external validity and ecological aspects, relevant to increasing dissemination in real-world settings.
Kin-to-Be: Betrothal, Legal Documents, and Reconfiguring Relational Obligations in Egypt
Authors: Hegel-Cantarella Christine
Published: March 2011

Through an examination of a case from Port Said, Egypt, this article is concerned with betrothal as a perilous social and legal status in contemporary Egypt and with women’s strategies for counteracting the risks it poses. Analysis of the way litigants mobilize specific legal documents (a commercial receipt, a police report, and a marriage contract) suggests that although Egyptian women use legal action to protect their interests their claims may be embedded in complex strategies that marshal both legal and moral power. By redirecting law’s gaze, women reconfigure their rights and obligations and leverage outcomes that are traditionally non-enforceable. This article draws on theoretical engagements with legal documents and documentation as social practice to contribute to debates on gendered legal subjectivity, citizenship, and marriage politics in the Middle East.
God, Justice and Law: Reflections on Christian Legal Thought
Authors: Brewbaker William S.
Published: March 2011

Rowan Williams once asserted that “all that can be said by the Christian about justice rests on a doctrine of God.” This article uses Williams’ argument in support of that statement as a vehicle for examining the challenges facing those who would construct explicitly theological accounts of law as well as the potential contributions of theologically informed legal scholarship. An important focus of the article is on theological particularity.
Foucault, Government and Acts of Obedience
Authors: Ganguly Amitava
Published: March 2011

Conventional political writings influenced by Foucault emphasize how various kinds of coercive measures are hidden behind the veil of a justified government. Their investigations tell us what makes it possible for the sovereign to exercise power over its subjects, and how, subject as we are to such constraints, we may still evolve ways and means to ensure our political liberties. In their endorsement of Foucault, they, however, lean in favor of political liberalism and find common theoretical grounds with his rivals. Instead we use Foucault to examine the nature and character of governance in Europe since the late medieval period focusing on the relationship between the framing of sovereignty and the application of pastoral power. This takes us on a journey from Aquinas to the literature on ‘‘advice-to-prince’’ and finally Kant. The idea is to capture what their theoretical preoccupations with governance suggest when we read them with Foucault’s principles.
Standing in Barack Obama’s Shoes: Judging the President’s Jurisprudence of Empathy by James Wilson’s Jurisprudence of Common Sense
Authors: Rollert John Paul
Published: March 2011

What did President Barack Obama mean when he called empathy an “essential ingredient” in judicial decision making and, thus, the outstanding quality he would look for in his Supreme Court nominees? This article attempts to answer that question by an analysis of Obama’s public statements and published writing. It also provides a comparative study of Obama’s jurisprudence of empathy with Founding Era Justice James Wilson’s jurisprudence of common sense in order to illustrate the dangers of a judge deciding difficult cases with recourse to unconventional, extra-legal tools.
Rifaximin treatment for reduction of risk of overt hepatic encephalopathy recurrence
Authors: Flamm Steven L.
Published: March 2011

Hepatic encephalopathy (HE) is a common problem in patients with chronic liver disease and is characterized by diminished mentation and neuromuscular abnormalities. Symptoms range from subtle cognitive changes to coma and death. Gut-derived toxins such as ammonia are thought to play a central role in the pathogenesis of HE. Treatment strategies are directed at increased elimination or reduction of gut-derived ammonia in addition to correction of dynamic conditions that provoke bouts of HE. The standard of care for treatment of acute HE is lactulose, a nonabsorbable disaccharide that is thought to increase elimination and reduce absorption of ammonia. Although lactulose seems to work in the acute setting, the rate of recurrent HE on maintenance lactulose is high. Medications have been sought that reduce the rate of recurrent HE in patients at high risk for HE but none have been identified. Rifaximin is a poorly absorbed antibiotic that is thought to reduce ammonia production by eliminating ammonia-producing colonic bacteria. Many small studies have suggested that rifaximin is effective in treating acute HE and is extremely well tolerated. This led to a randomized, placebo-controlled, multicenter, multinational trial investigating the efficacy of rifaximin over a 6-month period in reducing the risk of recurrent HE in patients at baseline, but with a history of at least two bouts of acute HE in the previous 6 months prior to enrollment. Lactulose could be administered at the discretion of the investigator. A total of 299 patients were randomized to receive rifaximin or placebo; 91% of patients in each group received lactulose. Compared with placebo, patients at high risk for recurrent HE in the rifaximin group had highly statistically significant reductions in bouts of acute HE (58%) and reductions in hospitalizations related to HE (50%) over a 6-month period. The medication was well tolerated with a side-effect profile comparable to placebo. This led to the approval of rifaximin for reduction of risk of recurrent HE by the US Food and Drug Administration in March 2010. It is recommended that patients with a history of recurrent acute HE should be maintained on rifaximin with or without lactulose to reduce the risk of recurrent HE and related hospitalization.
The role of insulin-sensitizing agents in the treatment of nonalcoholic steatohepatitis
Authors: Van Wagner Lisa B. , Rinella Mary E.
Published: March 2011

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, which includes dyslipidemia, central obesity, hypertension, and insulin resistance. These diseases collectively and individually increase the risk of cardiovascular disease. Nonalcoholic steatohepatitis (NASH) is a subset of NAFLD that can progress to cirrhosis in up to 30% of patients and lead to decompensated liver disease requiring liver transplantation in many patients. Insulin resistance is the pathophysiological hallmark of NASH and addressing insulin resistance is an important aspect of NASH management. Lifestyle modifications with diet and exercise improve insulin sensitivity and are the cornerstone of therapy, but are often difficult to maintain long term. Not surprisingly, insulin-sensitizing agents have been a focus of pharmacologic investigation in NASH. Insulin sensitizers such as the thiazolidinediones, biguanides, glucagon-like peptide-1 receptor agonists, and the dipeptidyl peptidase IV inhibitors, also known as incretins, will be discussed with respect to their mechanism of action and how these drugs might target aspects of NASH pathophysiology. Finally, we will summarize the available clinical data and review both the risks and benefits of insulin sensitizers in the treatment of NASH.
Symptomatic therapy in multiple sclerosis
Authors: Frohman Teresa C. , Castro Wanda , Shah Anjali , Courtney Ardith , Ortstadt Jeffrey , Davis Scott L. , Logan Diana , Abraham Thomas , Abraham Jaspreet , Remington Gina , Treadaway Katherine , Graves Donna , Hart John , Stuve Olaf , Lemack Gary , Greenberg Benjamin , Frohman Elliot M.
Published: March 2011

Multiple sclerosis is the most common disabling neurological disease of young adults. The ability to impact the quality of life of patients with multiple sclerosis should not only incorporate therapies that are disease modifying, but should also include a course of action for the global multidisciplinary management focused on quality of life and functional capabilities.
A major outbreak of Norovirus in an acute NHS hospital in 2010: a practical management approach
Authors: Cooper Tracey , Atta Mustafa , Mackay Andrew , Roberts Honor , Clement Amanda
Published: March 2011

This article describes a major outbreak of Norovirus that occurred in February 2010 in an acute hospi-T tal in London, including a summary of the epidemiology, control measures, and impact on the organisation. Due to the scale of this outbreak, the design of the site, and multiple patient safety priorities, outbreak management strictly in accordance with national guidelines proved to be difficult. Large-scale cohorting measures were implemented and appeared to be helpful in terminating the outbreak, supporting the delivery of safe patient care for emergency admissions, and minimising impact on the trust’s achievement of performance targets. With current demands on NHS resources, adoption of more flexible approaches to the isolation and cohorting of patients with diarrhoea and vomiting due to Norovirus may be required.
Norovirus - a serious threat to business continuity for hospitals
Authors: Colville Alaric
Published: March 2011

Norovirus is a small RNA virus which causes the majority of outbreaks of infectious diarrhoea and vomiting. Outbreaks can occur in many settings including schools, military camps, cruise ships, hotels and hospitals. In the winter 2009-2010 surveillance in the UK revealed an increase in hospital outbreaks. Such outbreaks cause distress and discomfort to patients, and have the potential to cause serious disruption to the normal working of hospitals. This article describes some of the ways in which norovirus can disrupt a hospital’s normal business, and the consequences of such disruption. The case for investing in norovirus control is compelling.
Predictors of lithium response in bipolar disorder
Authors: Tighe Sarah K. , Mahon Pamela B. , Potash James B.
Published: March 2011

While lithium is generally regarded as the first-line agent for patients with bipolar disorder, it does not work for everyone, which raises the question: can we predict who will be most likely to respond? In this paper, we review the most compelling clinical, biologic, and genetic predictors of lithium response in bipolar disorder. Among clinical factors, the strongest predictors of good response are fewer hospitalizations preceding treatment, an episodic course characterized by an illness pattern of mania followed by depression, and a later age at onset of bipolar disorder. While several biologic predictors have been studied, the results are preliminary and require replication with studies of larger patient samples over longer observation periods. Neuroimaging is a particularly promising method given that it might concurrently illuminate pathophysiologic underpinnings of bipolar disorder, the mechanism of action of lithium, and potential predictors of lithium response. The first genome-wide association study of lithium response was recently completed. No definitive results emerged, perhaps because the study was underpowered. With major new initiatives in progress aiming to identify genes and genetic variations associated with lithium response, there is much reason to be hopeful that clinically useful information might be generated within the next several years. This could ultimately translate into tests that could guide the choice of mood-stabilizing medication for patients. In addition, it might facilitate pharmacologic research aimed at developing newer, more effective medications that might act more quickly and yield fewer side effects.
Effects of carbon capture on the performance of an advanced coal-based integrated gasification fuel cell system
Authors: Li M , Rao A D , Brouwer J , Samuelsen G S
Published: March 2011

Integrated gasification fuel cell (IGFC) power plants combining gasification and solid oxide fuel cell (SOFC) technologies are very promising for highly efficient and environmentally friendly power generation from coal. IGFC plant amenability to carbon capture for sequestration makes the technology more attractive given the increasing concern over global climate change caused by greenhouse gas emissions. With the support of the US Department of Energy and the National Energy Technology Laboratory, the Advanced Power and Energy Program has conducted a study to identify promising conceptual designs for IGFC plants. The most promising IGFC concept identified so far is a system with catalytic hydro-gasification, a pressurized (operating pressure of 10 bar) SOFC followed by a turbo-expander and a steam cycle. The design requirement for recycling de-carbonized anode exhaust back to the gasifier for hydro-gasification not only produces a synergistic integration of SOFC and gasification subsystems, but also makes carbon separation a natural result. The current analyses of this system show an efficiency of 58.4 per cent (coal higher heating value basis) while capturing 94 per cent of the CO2. Using this system as a baseline case, this work investigates the sensitivity of IGFC system performance on the extent of carbon capture. It is shown that the proposed IGFC system can achieve ultra-high carbon capture (>99 per cent) at small system efficiency expense while reducing carbon capture to below 90 per cent actually diminishes the system efficiency because less fuel is converted in the SOFC.
Design and development of a self-supported polymer electrolyte fuel cell system with anodic dead-end operation
Authors: Manokaran A , Jalajakshi A , Sahu A K , Sridhar P , Pitchumani S , Shukla A K
Published: March 2011

Design and operational details for a self-supported polymer electrolyte fuel cell (PEFC) system with anodic dead-end fuel supply and internally humidified cathodic oxidant flow are described. During the PEFC operation, nitrogen and water back diffuse across the Nafion membrane from the cathode to the anode and accumulate in the anode flow channels affecting stack performance. The accumulated inert species are flushed from the stack by purging the fuel cell stack with a timer-activated purge valve to address the aforesaid problem. To minimize the system complexity, stack is designed in such a way that all the inert species accumulate in only one cell called the purge cell. A pulsed purge sequence comprises opening the valve for purge duration followed by purge-valve closing for the hold period and repeating the sequence in cycles. Since self-humidification is inadequate to keep the membrane wet, the anodic dead-end-operated PEFC stack with composite membrane comprising perflourosulphonic acid (Nafion) and silica is employed for keeping the membrane humidified even while operating the stack with dry hydrogen and internally humidified air.
Characterization and application of anion exchange polymer membranes with non-platinum group metals for fuel cells
Authors: Mamlouk M , Wang X , Scott K , Horsfall J A , Williams C
Published: March 2011

An investigation of the carbon-supported iron phthalocyanine (Fe-Pc) catalyst for oxygen reduction reaction (ORR) in alkaline media and in hydrogen fuel cells is described. The non-noble metal Fe-Pc catalyst is shown to be a promising alternative to platinum for ORR in alkaline media, with onset potentials of ca. 15 mV higher and double the mass activity than that of Pt. The catalyst also showed lower peroxide generation at lower voltages than Pt when tested at a rotating ring disc electrode.

The effect of various parameters such as catalyst loading, catalyst layer thickness, fabrication technique, and ionomer on a hydrogen fuel cell performance using an alkaline electrolyte membrane made by radiation grafting is described. Peak power densities of the fuel cell with Pt/C oxygen reduction catalysts were greater than 100 mW/cm at 60 °C using air. The performance of the fuel cell with the Fe-Pc catalyst was inferior to that with the Pt catalyst giving approximately half the peak power density initially due to the thicker catalyst layer and instability in the quaternary ammonium environment. However, the performance of the Fe-Pc catalyst under fuel cell conditions was found to fall with time due to an interaction of the catalyst with the ion-exchange group of the membrane and the ionomer used in the catalyst layer.
Effective transport properties of the porous electrodes in solid oxide fuel cells
Authors: Choi H-W , Berson A , Pharoah J G , Beale S B
Published: March 2011

This article presents a numerical framework for the computation of the effective transport properties of solid oxide fuel cells (SOFCs) porous electrodes from three-dimensional (3D) constructions of the microstructure. Realistic models of the 3D microstructure of porous electrodes are first constructed from measured parameters such as porosity and particle size distribution. Then each phase in the model geometries is tessellated with a computational grid. Three different types of grids are considered: Cartesian, octree, and body-fitted/cut-cell with successive levels of surface refinement. Finally, a finite volume method is used to compute the effective transport properties in the three phases (pore, electron, and ion) of the electrode. To validate the numerical approach, results obtained with the finite volume method are compared to those calculated with a random walk simulation for the case of a body-centred cubic lattice of spheres. Then, the influence of the sample size is investigated for random geometries with monosized particle distributions. Finally, effective transport properties are calculated for model geometries with polydisperse particle size distributions similar to those observed in actual SOFC electrodes.
Role of fuel cell based micro-cogeneration in low carbon heating
Authors: Hawkes A D , Brett D J L , Brandon N P
Published: March 2011

Micro-cogeneration, otherwise known as micro-combined heat and power (micro-CHP), is an emerging class of technologies designed to replace conventional home space heating and hot water systems. In addition to meeting thermal needs, they also provide electricity for on-site consumption or sale. The prime mover in a micro-CHP system can be based on a number of technologies: Stirling engine, internal combustion engine, Rankine cycle, or fuel cells. This article is concerned with the technology, techno-economics, and environmental credentials of the fuel cell-based systems, notably polymer electrolyte fuel cells and solid oxide fuel cells. It is demonstrated that these systems have a distinct advantage over their engine-based counterparts in that they have a low heat-to-power ratio, allowing them to operate more consistently over the year and thus achieve higher utilization. It is also shown that they could form an important part of a future portfolio of low carbon heating technologies. The challenge now lies with fuel cell developers and integrators to demonstrate their durability and to reduce capital costs.
Earth's energy “Golden Zone”: a synthesis from mineralogical research
Authors: Nadeau P. H.
Published: March 2011

The impact of diagenetic processes on petroleum entrapment and recovery efficiency has focused the vast majority of the world's conventional oil and gas resources into relatively narrow thermal intervals, which we call Earth's energy “Golden Zone”. Two key mineralogical research breakthroughs, mainly from the North Sea, underpinned this discovery. The first is the fundamental particle theory of clay mineralogy, which showed the importance of dissolution/precipitation mechanisms in the formation of diagenetic illitic clays with increasing depth and temperature. The second is the surface area precipitation-rate-controlled models for the formation of diagenetic cements, primarily quartz, in reservoirs. Understanding the impacts of these geological processes on permeability evolution, porosity loss, overpressure development, and fluid migration in the subsurface, lead to the realization that exploration and production risks are exponential functions of reservoir temperature. Global compilations of oil/gas reserves relative to reservoir temperature, including the US Gulf Coast, have verified the “Golden Zone” concept, as well as stimulated further research to determine in greater detail the geological/mineralogical controls on petroleum migration and entrapment efficiency within the Earth's sedimentary basins.
Late Cretaceous—Palaeocene mid-latitude climates: inferences from clay mineralogy of continental-coastal sequences (Tremp-Graus area, southern Pyrenees, N Spain)
Authors: Arostegi J. , Baceta J. I. , Pujalte V. , Carracedo M.
Published: March 2011

The origin and distribution of late Maastrichtian–early Palaeocene clay mineral associations were investigated in the Tremp-Graus basin (South Pyrenees, Spain) to assess palaeoclimate changes during that period. The studied succession is made up of expanded continental and transitional terrigeneous and carbonate deposits accumulated in a coastal plain setting. X-ray diffraction, SEM-EDX and TEM-AEM analysis reveal that the main clay components are illite and smectite, but kaolinite, chlorite and illite-smectite mixed layers are present, although irregularly distributed, all of them showing a platy morphology typical of a detrital origin. Persistence of the chemical features of the Al-dioctahedral smectites throughout the whole succession demonstrates the persistence of the same source area during the interval studied. Palygorskite occurs in the late Danian and Selandian, within carbonate tidal flats as sabkha-like facies. In SEM images, the palygorskite displays straight fibre morphologies, both coating and branched curling out, a clear proof of authigenic origin.

Physical or chemical weathering (PhW/ChW) determined as illite + chlorite/smectite + kaolinite ratio, smectite/kaolinite ratio and palygorskite distribution have been used as clay proxies for palaeoclimate reconstructions. Such data suggest a shift from temperate subhumid (perennial) conditions in late Maastrichtian times to a warm seasonal climate during early Palaeocene times. This trend, however, was dramatically altered during the late Danian–Selandian interval, when prevailing warm and semi-arid to arid climatic conditions caused intense evaporation and the development of an alkaline environment in which the palygorskite authigenesis took place.

The proposed climatic trend partly concurs with that established for earliest Danian time by Domingoet al.(2007), also in the Tremp-Graus basin, from isotopic and geochemical proxies, as well as with the reconstruction of Cojan & Moreau (2006), in which a semiarid Danian phase for the near continental basin of Aix-en-Provence is postulated. However, it is at odds with the notion of a humid Danian state in the Pyrenees, as inferred by Gawendaet al.(1999) from clay mineral proxies of deep marine successions.
Effect of Pakistani bentonite on properties of mortar and concrete
Authors: Ahmad S. , Barbhuiya S. A. , Elahi A. , Iqbal J.
Published: March 2011

Bentonite is composed primarily of montmorillonite and is useful in a wide range of applications. This paper presents the results of an experimental investigation carried out to evaluate the possibility of using a Pakistani bentonite (from Jehangira, Swabi District) as a cement replacement material in mortar and concrete. The cement in mortar and concrete was replaced with the bentonite at 0%, 20%, 30%, 40% and 50% by cement mass. The strength activity index of bentonite was determined ‘as received’ (20ºC) and ‘heated’ (treatment at 500ºC and 900ºC). The test results indicated that the strength activity index of bentonite conformed to the ASTM Standard C618 specifications, except for the ‘900ºC heated’ bentonite. The water absorption decreased for mortar containing up to 30% bentonite and then steadily increased at higher bentonite loadings. When immersed in 5% Na2SO4 and 2% MgSO4 solution, the greatest compressive strength was observed for mortar containing 30% bentonite. The water demand of concrete increased with increasing bentonite content. Although the compressive strength of concrete decreased progressively as the substitution level of bentonite was increased, the compressive strength of concrete containing 30% ‘as received’ bentonite was found to be 70% of the control concrete, whereas for concrete containing 30% ‘500ºC heated’ bentonite, the strength was found to be 79% of the control concrete. It can be concluded that this Pakistani bentonite can be used to replace up to 30% of cement to produce concrete with sufficient compressive strength for low-cost construction resistant to sulphate attack.
Clonal B cells in patients with hepatitis C virus–associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset
Authors: Charles Edgar D. , Brunetti Claudia , Marukian Svetlana , Ritola Kimberly D. , Talal Andrew H. , Marks Kristen , Jacobson Ira M. , Rice Charles M. , Dustin Lynn B.
Published: March 2011

Hepatitis C virus (HCV) is associated with the B-cell lymphoproliferative disorders mixed cryoglobulinemia (MC) and non-Hodgkin lymphoma. We have previously reported that HCV+MC+ patients have clonal expansions of hypermutated, rheumatoid factor–bearing marginal zone-like IgM+CD27+ peripheral B cells using the VH1-69 gene. Here we coupled transcriptional profiling with immunophenotypic and functional studies to ascertain these cells' role in MC pathogenesis. Despite their fundamental role in MC disease, these B cells have overall transcriptional features of anergy and apoptosis instead of neoplastic transformation. Highly up-regulated genes include SOX5, CD11C, galectin-1, and FGR, similar to a previously described FCRL4+ memory B-cell subset and to an “exhausted,” anergic CD21low memory B-cell subset in HIV+ patients. Moreover, HCV+MC+ patients' clonal peripheral B cells are enriched with CD21low, CD11c+, FCRL4high, IL-4Rlow memory B cells. In contrast to the functional, rheumatoid factor–secreting CD27+CD21high subset, the CD27+CD21low subpopulation exhibits decreased calcium mobilization and does not efficiently differentiate into rheumatoid factor–secreting plasmablasts, suggesting that a large proportion of HCV+MC+ patients' clonally expanded peripheral B cells is prone to anergy and/or apoptosis. Down-regulation of multiple activation pathways may represent a homeostatic mechanism attenuating otherwise uncontrolled stimulation of circulating HCV-containing immune complexes. This study was registered at www.clinicaltrials.gov as #NCT00435201.
Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment
Authors: Singbrant Sofie , Russell Megan R. , Jovic Tanja , Liddicoat Brian , Izon David J. , Purton Louise E. , Sims Natalie A. , Martin T. John , Sankaran Vijay G. , Walkley Carl R.
Published: March 2011

Erythropoietin (Epo) has been used in the treatment of anemia resulting from numerous etiologies, including renal disease and cancer. However, its effects are controversial and the expression pattern of the Epo receptor (Epo-R) is debated. Using in vivo lineage tracing, we document that within the hematopoietic and mesenchymal lineage, expression of Epo-R is essentially restricted to erythroid lineage cells. As expected, adult mice treated with a clinically relevant dose of Epo had expanded erythropoiesis because of amplification of committed erythroid precursors. Surprisingly, we also found that Epo induced a rapid 26% loss of the trabecular bone volume and impaired B-lymphopoiesis within the bone marrow microenvironment. Despite the loss of trabecular bone, hematopoietic stem cell populations were unaffected. Inhibition of the osteoclast activity with bisphosphonate therapy blocked the Epo-induced bone loss. Intriguingly, bisphosphonate treatment also reduced the magnitude of the erythroid response to Epo. These data demonstrate a previously unrecognized in vivo regulatory network coordinating erythropoiesis, B-lymphopoiesis, and skeletal homeostasis. Importantly, these findings may be relevant to the clinical application of Epo.
Evolution of the donor T-cell repertoire in recipients in the second decade after allogeneic stem cell transplantation
Authors: Le Robert Quan , Melenhorst J. Joseph , Battiwalla Minoo , Hill Brenna , Memon Sarfraz , Savani Bipin N. , Shenoy Aarthi , Hensel Nancy F. , Koklanaris Eleftheria K. , Keyvanfar Keyvan , Hakim Frances T. , Douek Daniel C. , Barrett A. John
Published: March 2011

After allogeneic stem cell transplantation (SCT), T lymphocyte function is reestablished from the donor's postthymic T cells and through thymic T-cell neogenesis. The immune repertoire and its relation to that of the donor have not been characterized in detail in long-term adult SCT survivors. We studied 21 healthy patients in their second decade after a myeloablative SCT for hematologic malignancy (median follow-up, 12 years). Immune profiles were compared with donor samples cryopreserved at transplant and beyond 10 years from SCT. Only one recipient was on continuing immunosuppression. Compared with the donor at transplant, there was no significant difference in CD4, CD8, natural killer, and B-cell blood counts. However, compared with donors, recipients had significantly fewer naive T cells, lower T-cell receptor excision circle levels, fewer CD4 central memory cells, more effector CD8+ cells, and more regulatory T cells. TCR repertoire analysis showed no significant difference in complexity of TCRVβ spectratype between recipients and donors, although spectratype profiles had diverged with both gain and loss of donor repertoire peaks in the recipient. In conclusion, long-term allogeneic SCT survivors have subtle defects in their immune profile consistent with defective thymic function but compatible with normal health. This study is registered at http://www.clinicaltrials.gov as NCT00106925.
An ENU-induced mouse mutant of SHIP1 reveals a critical role of the stem cell isoform for suppression of macrophage activation
Authors: Nguyen Nhu-Y. N. , Maxwell Mhairi J. , Ooms Lisa M. , Davies Elizabeth M. , Hilton Adrienne A. , Collinge Janelle E. , Hilton Douglas J. , Kile Benjamin T. , Mitchell Christina A. , Hibbs Margaret L. , Jane Stephen M. , Curtis David J.
Published: March 2011

In a recessive ENU mutagenesis screen for embryonic lethality, we identified a mouse pedigree with a missense mutation of SHIP1 (SHIP1el20) leading to an amino acid substitution I641T in the inositol-5′-phosphatase domain that represses phosphatidylinositol-3-kinase signaling. Despite detectable expression of functional SHIP1 protein, the phenotype of homozygous SHIP1el20/el20 mice was more severe than gene-targeted SHIP1-null (SHIP1−/−) mice. Compared with age-matched SHIP1−/− mice, 5-week-old SHIP1el20/el20 mice had increased myeloid cells, serum IL-6 levels, marked reductions in lymphoid cells, and died by 7 weeks of age with infiltration of the lungs by activated macrophages. Bone marrow transplantation demonstrated that these defects were hematopoietic-cell-autonomous. We show that the el20 mutation reduces expression in SHIP1el20/el20 macrophages of both SHIP1 and s-SHIP, an isoform of SHIP1 generated by an internal promoter. In contrast, SHIP1−/− macrophages express normal levels of s-SHIP. Compound heterozygous mice (SHIP1−/el20) had the same phenotype as SHIP1−/− mice, thus providing genetic proof that the more severe phenotype of SHIP1el20/el20 mice is probably the result of concomitant loss of SHIP1 and s-SHIP. Our results suggest that s-SHIP synergizes with SHIP1 for suppression of macrophage activation, thus providing the first evidence for a role of s-SHIP in adult hematopoiesis.
Molecular evolution of a gene cluster of serine proteases expressed in the Anopheles gambiae female reproductive tract
Authors: Mancini Emiliano , Tammaro Federica , Baldini Francesco , Via Allegra , Raimondo Domenico , George Phillip , Audisio Paolo , Sharakhov Igor V , Tramontano Anna , Catteruccia Flaminia , Torre Alessandra della
Published: March 2011

Background

Genes involved in post-mating processes of multiple mating organisms are known to evolve rapidly due to coevolution driven by sexual conflict among male-female interacting proteins. In the malaria mosquitoAnopheles gambiae- a monandrous species in which sexual conflict is expected to be absent or minimal - recent data strongly suggest that proteolytic enzymes specifically expressed in the female lower reproductive tissues are involved in the processing of male products transferred to females during mating. In order to better understand the role of selective forces underlying the evolution of proteins involved in post-mating responses, we analysed a cluster of genes encoding for three serine proteases that are down-regulated after mating, two of which specifically expressed in the atrium and one in the spermatheca ofA. gambiaefemales.

Results

The analysis of polymorphisms and divergence of these female-expressed proteases in closely related species of theA. gambiaecomplex revealed a high level of replacement polymorphisms consistent with relaxed evolutionary constraints of duplicated genes, allowing to rapidly fix novel replacements to perform new or more specific functions. Adaptive evolution was detected in several codons of the 3 genes and hints of episodic selection were also found. In addition, the structural modelling of these proteases highlighted some important differences in their substrate specificity, and provided evidence that a number of sites evolving under selective pressures lie relatively close to the catalytic triad and/or on the edge of the specificity pocket, known to be involved in substrate recognition or binding. The observed patterns suggest that these proteases may interact with factors transferred by males during mating (e.g. substrates, inhibitors or pathogens) and that they may have differently evolved in independentA. gambiaelineages.

Conclusions

Our results - also examined in light of constraints in the application of selection-inference methods to the closely related species of theA. gambiaecomplex - reveal an unexpectedly intricate evolutionary scenario. Further experimental analyses are needed to investigate the biological functions of these genes in order to better interpret their molecular evolution and to assess whether they represent possible targets for limiting the fertility ofAnophelesmosquitoes in malaria vector control strategies.
Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia
Authors: Al-Khateeb Alyaa , Zahri Mohd K , Mohamed Mohd S , Sasongko Teguh H , Ibrahim Suhairi , Yusof Zurkurnai , Zilfalil Bin A
Published: March 2011

Background

Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.

We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.

Results

A total of 29 gene sequence variants were reported in 117(76.0%) of the studied subjects. Eight different mutations (1 large rearrangement, 1 short deletion, 5 missense mutations, and 1 splice site mutation), and 21 variants. Eight gene sequence variants were reported for the first time and they were noticed in familial hypercholesterolemic patients, but not in controls (p.Asp100Asp, p.Asp139His, p.Arg471Gly, c.1705+117 T>G, c.1186+41T>A, 1705+112C>G, Dup exon 12 and p.Trp666ProfsX45). The incidence of the p.Arg471Gly variant was 11%. Patients with pathogenic mutations were younger, had significantly higher incidences of cardiovascular disease, xanthomas, and family history of hyperlipidemia, together with significantly higher total cholesterol and low density lipoprotein levels than patients with non-pathogenic variants.

Conclusions

Twenty-nine gene sequence variants occurred among FH patients; those with predicted pathogenicity were associated with higher incidences of cardiovascular diseases, tendon xanthomas, and higher total and low density lipoprotein levels compared to the rest. These results provide preliminary information on the mutation spectrum of this gene among patients with FH in Malaysia.
Resveratrol protects leukemic cells against cytotoxicity induced by proteasome inhibitors via induction of FOXO1 and p27Kip1
Authors: Niu Xiao-Fang , Liu Bao-Qin , Du Zhen-Xian , Gao Yan-Yan , Li Chao , Li Ning , Guan Yifu , Wang Hua-Qin
Published: March 2011

Background

It was reported recently that resveratrol could sensitize a number of cancer cells to the antitumoral effects of some conventional chemotherapy drugs. The current study was designed to investigate whether resveratrol could sensitize leukemic cells to proteasome inhibitors.

Methods

Leukemic cells were treated with MG132 alone or in combination with resveratrol. Cell viability was investigated using MTT assay, and induction of apoptosis and cell cycle distribution was measured using flow cytometry. Western blot and real-time RT-PCR were used to investigate the expression of FOXO1 and p27Kip1. CHIP was performed to investigate the binding of FOXO1 to the p27 Kip1 promoter.

Results

Resveratrol strongly reduced cytotoxic activities of proteasome inhibitors against leukemic cells. MG132 in combination with resveratrol caused cell cycle blockade at G1/S transition via p27Kip1 accumulation. Knockdown of p27Kip1 using siRNA dramatically attenuated the protective effects of resveratrol on cytotoxic actions of proteasome inhibitors against leukemic cells. Resveratrol induced FOXO1 expression at the transcriptional level, while MG132 increased nuclear distribution of FOXO1. MG132 in combination with resveratrol caused synergistic induction of p27Kip1 through increased recruitment of FOXO1 on the p27Kip1 promoter.

Conclusions

Resveratrol may have the potential to negate the cytotoxic effects of proteasome inhibitors via regulation of FOXO1 transcriptional activity and accumulation of p27Kip1.