bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNAs in platelet biogenesis and function
Authors: Dangwal Seema , Thum Thomas
Published: July 2012

Platelets are important to maintain primary haemostasis and play a key role in pathology of thrombotic and occlusive vascular disorders such as acute coronary syndrome or stroke. Despite of lacking a nucleus and genomic DNA, platelets possess diverse types of RNAs, ranging from protein coding messenger RNAs to small non-coding RNAs inherited from their parent megakaryocytes. Indeed, platelets are capable of using their own translational machinery to synthesise proteins upon their activation suggesting the possibility of post-transcriptional gene regulation in platelets. MicroRNAs (miRNAs) are highly conserved, tiny non-coding RNAs exhibiting a fine-tune control of protein expression by complementary sequence recognition, binding and translational repression of protein coding mRNA transcripts. Multiple functional aspects of miRNAs as well as their expression in platelets or megakaryocytes underscore a role in platelet biology. Changes in miRNA expression patterns have been noted during platelet genesis and activation. In the present review we highlight recently identified megakaryocytic/platelet miRNAs and discuss their role in platelet biogenesis and functions essential to maintain haemostasis in the body.
Effects of pioglitazone on platelet P2Y12-mediated signalling in clopidogrel-treated patients with type 2 diabetes mellitus
Authors: Suryadevara Siva , Ueno Masafumi , Tello-Montoliu Antonio , Ferreiro Jose , Desai Bhaloo , Rollini Fabiana , Box Lyndon , Zenni Martin , Guzman Luis , Bass Theodore , Angiolillo Dominick
Published: July 2012

Patients with type 2 diabetes mellitus (T2DM) have impaired clopidogrel-induced antiplatelet effects, which may be in part attributed to their reduced sensitivity to insulin and consequently, results in upregulation of the P2Y12 signalling pathway. It has been hypothesised that insulin sensitising strategies may enhance clopidogrel-mediated P2Y12 inhibitory effects. The aim of this pilot pharmacodynamics (PD) study was to assess the impact of pioglitazone on clopidogrel-mediated P2Y12 inhibitory effects in patients with T2DM. This was a prospective, randomised, double-blind, placebo-controlled, cross-over PD study. Patients with T2DM and stable coronary artery disease on maintenance aspirin and clopidogrel were randomised to receive either pioglitazone 30 mg or matching placebo daily for 14 days. PD assessments were measured at baseline, 14 days after randomisation, at the end of the wash-out period, and 14 days after cross-over. The primary endpoint measure was maximal platelet aggregation (MPA) to 20 μM adenosine diphosphate (ADP) as assessed by light transmittance aggregometry (LTA). Flow cytometric analysis of vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI), and VerifyNow P2Y12 testing were also performed. A total of 15 randomised patients completed the study. MPA to 20 μM ADP (primary endpoint) was not significantly different with pioglitazone compared with placebo (49.53 ± 4.76 vs. 52.52 ± 3.89%; p = 0.594). Similarly, other PD measures did not differ significantly between the groups. In conclusion, in patients with T2DM on maintenance aspirin and clopidogrel therapy, the adjunctive use of pioglitazone does not result in enhanced inhibition of platelet P2Y12 mediated signalling.
Familial Evaluation in Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: van der Werf Christian , Nederend Ineke , Hofman Nynke , van Geloven Nan , Ebink Corné , Frohn-Mulder Ingrid M.E. , Alings A. Marco W. , Bosker Hans A. , Bracke Frank A. , van den Heuvel Freek , Waalewijn Reinier A. , Bikker Hennie , van Tintelen J. Peter , Bhuiyan Zahurul A. , van den Berg Maarten P. , Wilde Arthur A.M.
Published: July 2012

Background—

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (
Ryr2
) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the
Ryr2
mutation is limited.

Methods and Results—

One-hundred sixteen relatives carrying the
Ryr2
mutation from 15 families who were identified by cascade screening of the
Ryr2
mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a
Ryr2
mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5–11.5;
P
=0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3–19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4–20.9 years).

Conclusions—

Relatives carrying an
Ryr2
mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low.
In Vivo Mononuclear Cell Tracking Using Superparamagnetic Particles of Iron Oxide
Authors: Richards Jennifer M.J. , Shaw Catherine A. , Lang Ninian N. , Williams Michelle C. , Semple Scott I.K. , MacGillivray Thomas J. , Gray Calum , Crawford Julie H. , Alam Shirjel R. , Atkinson Anne P.M. , Forrest Elaine K. , Bienek Carol , Mills Nicholas L. , Burdess Anne , Dhaliwal Kev , Simpson A. John , Wallace William A. , Hill Adam T. , Roddie P. Huw , McKillop Graham , Connolly Thomas A. , Feuerstein Giora Z. , Barclay G. Robin , Turner Marc L. , Newby David E.
Published: July 2012

Background—

Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies on the delivery of functional cells to their target site. Monitoring and tracking cells to ensure tissue delivery and engraftment is a critical step in establishing clinical and therapeutic efficacy. The study aims were (1) to develop a Good Manufacturing Practice–compliant method of labeling competent peripheral blood mononuclear cells with superparamagnetic particles of iron oxide (SPIO), and (2) to evaluate its potential for magnetic resonance cell tracking in humans.

Methods and Results—

Peripheral blood mononuclear cells 1–5×10
9
were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity, and pattern of cytokine release to unlabeled cells. After intramuscular administration, up to 10
8
SPIO-labeled cells were readily identifiable in vivo for at least 7 days using magnetic resonance imaging scanning. Using a phased-dosing study, we demonstrated that systemic delivery of up to 10
9
SPIO-labeled cells in humans is safe, and cells accumulating in the reticuloendothelial system were detectable on clinical magnetic resonance imaging. In a healthy volunteer model, a focus of cutaneous inflammation was induced in the thigh by intradermal injection of tuberculin. Intravenously delivered SPIO-labeled cells tracked to the inflamed skin and were detectable on magnetic resonance imaging. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin.

Conclusions—

Human peripheral blood mononuclear cells can be labeled with SPIO without affecting their viability or function. SPIO labeling for magnetic resonance cell tracking is a safe and feasible technique that has major potential for a range of cardiovascular applications including monitoring of cell therapies and tracking of inflammatory cells.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
; Unique identifier: NCT00972946, NCT01169935.
Diagnostic Accuracy of Combined Intracoronary Pressure and Flow Velocity Information During Baseline Conditions
Authors: van de Hoef Tim P. , Nolte Froukje , Damman Peter , Delewi Ronak , Bax Matthijs , Chamuleau Steven A.J. , Voskuil Michiel , Siebes Maria , Tijssen Jan G.P. , Spaan Jos A.E. , Piek Jan J. , Meuwissen Martijn
Published: July 2012

Background—

The assessment of functional coronary lesion severity using intracoronary physiological parameters such as coronary flow velocity reserve and the more widely used fractional flow reserve relies critically on the establishment of maximal hyperemia. We evaluated the diagnostic accuracy of the stenosis resistance index during nonhyperemic conditions, baseline stenosis resistance index, compared with established hyperemic intracoronary hemodynamic parameters, because achievement of hyperemia can be cumbersome in daily clinical practice.

Methods and Results—

A total of 228 patients, including 299 lesions (mean stenosis diameter 55%±11%), underwent myocardial perfusion scintigraphy for documentation of reversible perfusion defects. Distal coronary pressure and flow velocity were assessed with sensor-equipped guidewires during baseline and maximal hyperemia, induced by an intracoronary bolus of adenosine (20–40 µg). We determined stenosis resistance (SR) during baseline and hyperemic conditions as well as fractional flow reserve and coronary flow velocity reserve. The discriminative value for myocardial ischemia on myocardial perfusion scintigraphy of all parameters was compared using receiver-operating-characteristic curves. Baseline SR showed good agreement with myocardial perfusion scintigraphy. The diagnostic performance of baseline SR (area under the curve, 0.77; 95% CI, 0.71–0.83) was as accurate as fractional flow reserve and coronary flow velocity reserve (area under the curve, 0.77; 95% CI, 0.71–0.83 and area under the curve, 0.75; 95% CI, 0.68–0.81 respectively;
P
>0.05 compared with baseline SR for both). However, hyperemic SR, combining both pressure and flow velocity information during hyperemia, was superior to all other parameters (area under the curve, 0.81; 95% CI, 0.76–0.87;
P
<0.05 compared with all other parameters).

Conclusions—

Combined pressure and flow velocity measurements during baseline conditions may provide a useful tool for functional lesion severity assessment without the need for potent vasodilators.
Comparison of Risk Factor Reduction and Tolerability of a Full-Dose Polypill (With Potassium) Versus Low-Dose Polypill (Polycap) in Individuals at High Risk of Cardiovascular Diseases
Authors: Yusuf Salim , Pais Prem , Sigamani Alben , Xavier Denis , Afzal Rizwan , Gao Peggy , Teo Koon K.
Published: July 2012

Background—

A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol. We examined the incremental effects of 2 (full dose) plus K
+
supplementation versus single polycap (low dose) on risk factors and tolerability.

Methods and Results—

After a run-in period, 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were randomly assigned to a single-dose polycap or to 2 capsules of the polycap plus K
+
supplementation for 8 weeks. The effects on BP, heart rate (HR), serum lipids, serum and urinary K
+
, and tolerability were assessed using an intention-to-treat analysis. The full-dose polycap (plus K
+
supplementation) reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic, compared with that observed with the low-dose polycap (
P
=0.003;
P
=0.001), but there were no differences in HR (0.1 bpm). The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL (
P
=0.014) and 6.6 mg/dL (
P
=0.006), respectively, but there were no differences in high-density lipoprotein cholesterol or triglycerides. The rates of discontinuation of the study drug after randomization were similar in the 2 groups (6.9% low dose versus 7.8% full dose).

Conclusions—

The full-dose polycap (plus K
+
supplementation) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose, with similar tolerability. Therefore, the full-dose polycap should potentially lead to larger benefits.

Clinical Trial Registration—

URL:
http://www.ctri.nic.in
. Unique identifier: CTRI/2010/091/000054.
Prevalence of Ideal Cardiovascular Health and Its Relationship With the 4-Year Cardiovascular Events in a Northern Chinese Industrial City
Authors: Wu Shouling , Huang Zhengrong , Yang Xinchun , Zhou Yong , Wang Anxing , Chen Li , Zhao Haiyan , Ruan Chunyu , Wu Yuntao , Xin Aijun , Li Kuibao , Jin Cheng , Cai Jun
Published: July 2012

Background—

The American Heart Association Committee recently developed definitions of “ideal,” “intermediate,” and “poor” cardiovascular health based on 7 cardiovascular disease (CVD) risk factors or health behaviors. This study evaluated the prevalence of “ideal” American Heart Association cardiovascular health metrics from June 2006 to October 2007 in the Kailuan cohort (n=101 510; age 18–98 years) in northern China and its relationship with the 4-year CVD incidence.

Methods and Results—

We used Cox proportional hazards regression to calculate hazard ratios and 95% confidence intervals for baseline health behaviors and risk factor categories. The majority of participants (63 676; 69.45%) presented with ≤3 ideal cardiovascular health metrics, whereas 8342 participants (9.1%) had 5 to 7 ideal metrics. Only 93 of 91 698 participants (0.1%) had all 7 metrics in the ideal range. There was a strong relationship between the cumulative incidence of CVD events in the 4-year follow-up and the number of ideal health metrics at baseline; the 1111 participants with 6 and 7 ideal metrics had a significantly lower cumulative incidence of CVD than subjects with no or only 1 ideal health metric (0.8% versus 3.3%). Men had higher rates of CVD events than women (2.46% versus 1.18%).

Conclusions—

Few adults had ideal cardiovascular health according to the modified American Heart Association definition. We detected a strong inverse relationship between the cumulative CVD incidence and the number of ideal health metrics at baseline. Population-wide prevention, especially lifestyle improvement, is critical to increase the low-risk prevalence and thereafter decrease CVD events.

Clinical Trial Registration—

URL:
http://www.chictr.org/cn/proj/show.aspx?proj=1441
. Unique identifier: ChiCTR-TNC-11001489.
The Corpus Callosum in Monozygotic Twins Concordant and Discordant for Handedness and Language Dominance
Authors: Häberling Isabelle S. , Badzakova-Trajkov Gjurgjica , Corballis Michael C.
Published: July 2012

We used diffusion tensor imaging to assess callosal morphology in 35 pairs of monozygotic twins, of which 17 pairs were concordant for handedness and 18 pairs were discordant for handedness. Functional hemispheric language dominance was established for each twin member using fMRI, resulting in 26 twin pairs concordant and 9 twin pairs discordant for language dominance. On the basis of genetic models of handedness and language dominance, which assume one “right shift” (RS) gene with two alleles, an RS+ allele biasing toward right-handedness and left cerebral language dominance and an RS− allele leaving both asymmetries to chance, all twins were classified according to their putative genotypes, and the possible effects of the gene on callosal morphology was assessed. Whereas callosal size was under a high genetic control that was independent of handedness and language dominance, twin pairs with a high probability of carrying the putative RS+ allele showed a connectivity pattern characterized by a genetically controlled, low anisotropic diffusion over the whole corpus callosum. In contrast, the high connectivity pattern exhibited by twin pairs more likely to lack the RS+ allele was under significantly less genetic influence. The data suggest that handedness and hemispheric dominance for speech production might be at least partly dependent on genetically controlled processes of axonal pruning in the corpus callosum.
From Wunderkammern to Kinect - The Creation of Shadow Worlds
Authors: Lewis Chara , Mojsiewicz Kristin , Pettican Anneké ,   Brass Art
Published: July 2012

This paper focuses on two projects, Still Life No. 1 and Shadow Worlds | Writers' Rooms [Brontë Parsonage], to reveal the creative approaches the authors take to site, technology, and the self in their production of shadow worlds as sites of wonder. Informed by the uncanny (re-animation and the double) and an interest in the limen (thresholds in the real and virtual realms), the projects explore white light and infrared digital 3D scanning technologies as tools for capture and transformation. The authors will discuss how they suture the past with the present and ways that light slips secretly between us, revealing other realms.
Risk factors for psychological distress in Northern Ireland
Authors: Mahedy Liam , Todaro-Luck Flora , Bunting Brendan , Murphy Samuel , Kirby Karen
Published: July 2012

Background:

Stress-related mental ill health and its disorders are considered by the World Health Organization (WHO) to be the new world epidemic and their prevalence rates seem to be increasing worldwide.

Aims:

To examine and identify sub-populations at risk for psychological discomfort in Northern Ireland and map the relative impact of potential predictors.

Methods:

A sample of 4,638 respondents to the NIHSW-2001 survey was analysed with latent class analysis and latent class factorial analysis. Latent class multinomial logistic regression assessed the impact of a range of predictors on class membership.

Results:

Five sub-populations were differentiated. All subgroups at risk for anxiety and depression were characterized as being younger and female. Disability and adverse life events were strong predictors of risk. Long-standing illness and housing worries were predictors of medium and high risk membership. The effect of civil unrest was significant only for the medium-risk subgroup; marital status and income did not affect group membership.

Conclusions:

Because all five subgroups showed a different probability, but a similar profile of endorsing GHQ-12 items, it could be hypothesized that an underlying continuum dimension of anxiety and depression is present in the Northern Irish population.
The Revival of Scholastic Sacramental Theology after the Publication of Aeterni Patris
Authors: Scerri Hector
Published: July 2012

The article explores Neo-Scholasticism, a period in Catholic theology which, normally nowadays, attracts little attention. The publication of Leo XIII’s encyclical Aeterni Patris, in 1879, and its effects on theology are studied with particular reference to sacramental theology. The main exponents of the Neo-Scholastic movement (e.g. Kleutgen, Mercier) and their contributions are highlighted. The article then proceeds to an in-depth analysis of the treatise De sacramentis in genere as presented by leading theologians, such as Franzelin, Billot, and van Noort. The central issue of causality is investigated. Finally, the article reflects briefly on the positive confluence between Neo-Scholasticism and Ressourcement in the first decades of the 20th century.
Effect of interface crack on lateral buckling behavior and free vibration response of a sandwich composite beam
Authors: Toygar M Evren , Kıral Zeki , Sayman Onur , Arman Yusuf , Özen Mustafa
Published: July 2012

The aim of this study is investigation of the effect of interface crack on lateral buckling load and free vibration response of a sandwich composite beam using experimental methods and finite element solutions. The lateral buckling load and natural frequencies in a thin sandwich composite cantilever beam with crack were considered. The crack was opened between the face sheets and foam core. The length of the crack was selected, such as 100, 150, 200, and 250 mm. Lateral buckling and vibration tests were applied on these samples and then the critical lateral buckling load and natural frequencies were found using experimental and finite element method. In the experimental studies, in-house test mechanisms were used. For the numerical analysis, ANSYS finite element software was used. Close results were obtained between both two methods.
Archaeology in the Humanities
Authors: Yoffee Norman , Fowles Severin
Published: July 2012

Since archaeology is fundamentally the study of the human past, which is what the word “archaeology” connotes according to its Greek etymology, it is part of the humanities. However, archaeologists work in teams with scientists and employ quantitative techniques and comparative methods of the social sciences; archaeologists are thus an academic hybrid and are pleased to live in the interstices of many disciplines. In this article we review the history of archaeology in the humanities and explore some new directions in archaeological research. We discuss the enduring questions of origins of the antiquity of humanity, religion and art, the first agricultural villages, and the earliest cities, states, and civilizations. We also consider new agendas in archaeology: historical archaeology, landscapes in the past and present, material studies of the present, and how archaeologists are engaged in modern politics.
Effect of aqueous extract of Crocus sativus L. (saffron) stigma against subacute effect of diazinon on specific biomarkers in rats
Authors: Moallem Seyed Adel , Hariri Alireza Timcheh , Mahmoudi Mahmoud , Hosseinzadeh Hossein
Published: July 2012

In this study, the effect of aqueous extract of Crocus sativus L. (saffron) stigma was studied against subacute toxicity of diazinon (DZN) on specific biochemical markers in rats. Vitamin E (200 IU/kg) and the aqueous extract of saffron at doses 50, 100 and 200 mg/kg were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. Red blood cell (RBC) cholinesterase activity was inhibited by DZN and this effect was not affected by vitamin E or saffron plus DZN. The levels of serum tumor necrosis factor-α (inflammation marker), direct 8-iso-prostaglandin F2α (oxidative stress marker) and soluble protein-100 β (S100β, neuronal damage marker) were increased significantly by DZN. The saffron extract inhibited the effect of DZN on these biomarkers levels. However, vitamin E was able to only reduce 8-iso-prostaglandin F2α and S100β levels. This study showed that the aqueous extract of saffron prevents DZN-induced rise of several specific inflammation, oxidative stress and neuronal damage biomarkers.
Resilience and Stereotyping
Authors: Grandbois Donna M. , Sanders Gregory F.
Published: July 2012

Purpose: The lived experiences of Native American elders regarding the effects of stereotypes on resilience were examined. Method: This qualitative study emphasized culturally compatible methods of traditional storytelling and featured interpretive analysis. Results: Themes revealed were the following: (a) having the ability to successfully bridge cultures fostered resilience and inspired self-confidence, (b) a strong sense of identity was a core element of resilience, (c) being responsible and accountable inspired a sense of pride, (d) educational attainment and employment fostered resilience, and (e) cultural resilience was a key component when confronting stereotypes. Although stereotyping has had profound effects, these first Americans have taken the best of both worlds and successfully integrated them to live successful, well-adjusted lives. Discussion: These findings suggest that disparities in mental and physical health could be addressed by building on the unique foundation of cultural resilience embodied by these Native elders.
Consequences of asthma on job absenteeism and job retention
Authors: Hansen Carl Lysbeck , Baelum Jesper , Skadhauge Lars , Thomsen Gert , Omland Øyvind , Thilsing Trine , Dahl Søren , Sigsgaard Torben , Sherson David
Published: July 2012

Aims:

Various social and economic effects are associated with asthma. This quantitative study describes the effects of current asthma on work life evaluated from the number of weeks receiving transfer incomes.

Methods:

The study population comprised 7,241 persons answering the ECRHS II screening questionnaire, which was sent to a random age and gender stratified sample of 10,000 persons aged 20 to 44 years. Participants with current asthma were identified by positive answers to a set of validated questions. Transfer incomes for a five-year period were registered from a study-independent national database, which collects all public administered transfer incomes in Denmark. The numbers of weeks receiving unemployment, welfare, sick-leave and disability benefits were identified for each participant and differences between asthmatics and non-asthmatics were analyzed.

Results:

Asthmatics had significantly more annual weeks receiving welfare (36.6 vs. 20.7, p=0.00), sick leave (9.2 vs. 6.6, p=0.00) and disability (19.3 vs. 11.4, p=0.00) benefits than non-asthmatics. Adult-onset asthmatics had increased prevalence rate ratios for disability of 2.40 (95% confidence interval 1.70–3.40). Blue collar work significantly increased the probability of all public transfer incomes.

Conclusions:

Current asthma makes it harder to keep a job. Adult-onset asthmatics and blue collar workers are particularly affected.
Precariousness and discontinuous work history in association with health
Authors: Sirviö Anitta , Ek Ellen , Jokelainen Jari , Koiranen Markku , Järvikoski Timo , Taanila Anja
Published: July 2012

Aims:

Precarious type of employment may have a negative impact on health, notably on low psychological wellbeing. The basis of the former relationship is constructed by definition and operationalisation of precariousness. In this research, we first experimented with a construct of work history in the operationalisation of precariousness and second studied the relationship between precariousness and health.

Methods:

The research data originated from a large population-based birth cohort (NFBC 1966). The study sample consists of 3449 respondents to the postal questionnaire at the age of 31 and the information supplemented by the register data of the Finnish Centre for Pensions. Health was measured by self-reports of doctor-diagnosed/treated illnesses and HSCL-25 for mental symptoms.

Results:

Our operationalisation with a construct of discontinuous work history captured the precarious insecure relation to work. The precarious workers were found to have proportionally more mental symptoms in comparison with permanent workers. The perception of distress was stronger among precarious workers who perceived high job insecurity. However, there were no differences in doctor-diagnosed/treated illnesses between precarious and permanent workers.

Conclusions:

The study suggests that the construct of work history is a useful element in defining precariousness. The study also illustrates the association of precariousness, perceived job insecurity, and mental distress. The study suggests further research on disadvantages experienced by precarious workers.
Microstructure and mechanical properties of stainless maraging steel laser weldments after ageing at different temperatures
Authors: Meng Fanyan , Liu Haiyuan , Gao Xiaoxi , Wang Yuanbo , Wen Zi , Lu You , An Jian
Published: July 2012

The microstructure and mechanical properties of Fe–Cr–Ni–Mo–Ti stainless maraging steel laser weldments have been investigated after post-weld ageing treatments in a temperature range from 420 °C to 580 °C. Metallographic characterization of laser weldment revealed three zones, i.e. fusion zone, heat-affected zone and unaffected parent material zone. Martensite was the predominant phase in the three zones when the ageing temperature was lower than 500 °C whereas a large amount of reverted austenite occurred in three zones on ageing above 500 °C, leading to hardness decrease accordingly. Hardness distribution across the welds demonstrated that after all ageing treatments, the hardness in heat-affected zone was greatly increased to above 420 HV from 320 HV in as-weld condition, and hardness in three regions varied with different trends with increasing ageing temperature . The different ageing behavior in fusion zone and parent material zone has been discussed by comparison of dissolution of Ti(C, N)x inclusion within them during welding thermal cycle. The tensile properties were found satisfactory in weld subjected to ageing at 460 °C; the yield strength was increased by 14.5% as compared with as-received aged parent material. A graph was established for determination of fracture location and post-weld ageing efficiency using measured hardness values in both heat-affected zone and parent material zone.
Water impermeability of fly ash concrete composites containing silica fume and polypropylene fiber
Authors: Zhang Peng , Li Qing-Fu
Published: July 2012

A parametric experimental study has been conducted to investigate the combined effect of fly ash, silica fume and polypropylene fiber on the water impermeability of concrete composite. Four fly ash contents, four silica fume contents and five different fiber volume fractions were used. Fly ash and silica fume were mixed in concrete composites by replacing the same quantity of cement, and polypropylene fiber was mixed in concrete with the dosage of cementitious materials unchanged. Results reveal that the addition of fly ash, silica fume and polypropylene fiber can decrease the length of water permeability of the concrete composite evidently. The average length of water permeability is decreasing gradually with the increase of fly ash content, silica fume content, and fiber volume fraction, respectively. Silica fume and polypropylene fiber seem to play an important role to improve the water impermeability of concrete composites containing fly ash.
Deepwater pipelines – status, challenges and future trends
Authors: Fyrileiv Olav , Aamlid Olav , Venås Asle , Collberg Leif
Published: July 2012

The demand for energy is steadily increasing and, at least for the coming decades, the world has to rely on oil and gas to address this need. Most of the easiest accessible offshore petroleum reservoirs have been discovered and a great part developed over the last six decades. Thus, development of new oil and gas fields faces a lot of challenges as most of them are in remote areas, in deep waters and/or in areas with extreme environments like the Arctic region. One of the major trends in the offshore petroleum industry points towards deeper waters (e.g. outside West Africa, the Brazilian Pre-Salt developments and in the Gulf of Mexico). This trend also includes increased use of subsea installations instead of platforms, more subsea processing and increased use of pipelines to transport the hydrocarbons to shore or into a pipeline grid.

This paper addresses some of the challenges pipeline design, installation and operation may face in deep and ultra-deep waters. The main design challenge is related to the high external pressure that may cause collapse of the pipeline. This potential failure mode is normally dealt with by increasing the pipe wall thickness, but at ultra-deep water depths this may require a very thick walled pipe that becomes very costly, difficult to manufacture and hard to install due to its weight. One approach to overcome this is to improve some of the parameters that determine the collapse resistance by an improved manufacturing process. Other approaches are to ensure a minimum internal pressure is maintained in the pipeline during all phases, or to install a buoyant pipeline that is anchored at a moderate water depth rather that laying on the sea bed.
Ethnic heterogeneity in the activity and structure of a Black street gang
Authors: Grund Thomas U. , Densley James A.
Published: July 2012

Despite acknowledgment of ‘hybrid’ street gangs in the literature, there is little systematic research into ethnic heterogeneity within gangs. This research aims at moving beyond the broad categorization of the Black street gang. For this purpose, we examine an all-Black London-based gang in detail, using fieldwork and police arrest data, and investigate the role of ethnic heterogeneity for the workings of the gang. Our findings suggest that ethnic heterogeneity within this gang is crucial for its criminal operation. Although there is no evidence for ethnicity-related specialization of crime, the structural co-offending pattern of the gang’s activities is dominated by ethnicity. Ethnicity matters for who offends with whom.
Validation of colorectal cancer surgery data from administrative data sources
Authors: Li Xue , King Charlotte , deGara Christopher , White Jonathon , Winget Marcy
Published: July 2012

Background

Surgery is the primary treatment for colorectal cancer for both curative and palliative intent. Availability of high quality surgery data is essential for assessing many aspects of the quality of colorectal cancer care. The objective of this study was to determine the quality of different administrative data sources in identifying surgery for colorectal cancer with respect to completeness and accuracy.

Methods

All residents in Alberta, Canada who were diagnosed with invasive colorectal cancer in years 2000-2005 were identified from the Alberta Cancer Registry and included in the study. Surgery data for these patients were obtained from the Cancer Registry (which collects the date of surgery for which the primary tumor was removed) and compared to surgery data obtained from two different administrative data sources: Physician Billing and Hospital Inpatient data. Sensitivity, specificity, positive predictive value, negative predictive value and observed agreement were calculated compared to the Cancer Registry data.

Results

The Physician Billing data alone or combined with Hospital Inpatient data demonstrated equally high sensitivity (97% for both) and observed agreement with the Cancer Registry data (93% for both) for identifying surgeries. The Hospital Inpatient data, however, had the highest specificity (80%). The positive predictive value varied by disease stage and across data sources for stage IV (99% for stages I-III and 83-89% for stage IV), the specificity is better for colon cancer surgeries (72-85%) than for rectal cancer surgeries (60-73%); validation measures did not vary over time.

Conclusion

Physician Billing data identify the colorectal cancer surgery more completely than Hospital Inpatient data although both sources have a high level of completeness.
Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl2) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based in vivo model of prostate cancer
Authors: Sterenczak Katharina A , Meier Martin , Glage Silke , Meyer Matthias , Willenbrock Saskia , Wefstaedt Patrick , Dorsch Martina , Bullerdiek Jörn , Escobar Hugo Murua , Hedrich Hans , Nolte Ingo
Published: July 2012

Background

Cell lines represent a key tool in cancer research allowing the generation of neoplasias which resemble initial tumours inin-vivoanimal models. The characterisation of early tumour development is of major interest in order to evaluate the efficacy of therapeutic agents. Magnetic resonance imaging (MRI) basedin-vivocharacterisation allows visualisation and characterisation of tumour development in early stages prior to manual palpation. Contrast agents for MRI such as superparamagnetic iron oxide nanoparticles (SPIOs) and manganese chloride (MnCl2) represent powerful tools for thein-vivocharacterisation of early stage tumours. In this experimental study, we labelled prostate cancer cells with MnCl2or SPIOsin vitroand used 1 T MRI for tracing labelled cellsin-vitroand 7 T MRI for tracking in anin-vivoanimal model.

Methods

Labelling of prostate cancer cells CT1258 was establishedin-vitrowith MnCl2and SPIOs.In-vitrodetection of labelled cells in an agar phantom was carried out through 1 T MRI whilein-vivodetection was performed using 7 T MRI after subcutaneous (s.c.) injection of labelled cells into NOD-Scid mice (n = 20). The animals were scanned in regular intervals until euthanization. The respective tumour volumes were analysed and corresponding tumour masses were subjected to histologic examination.

Results

MnCl2in-vitrolabelling resulted in no significant metabolic effects on proliferation and cell vitality.In-vitrodetection-limit accounted 105cells for MnCl2as well as for SPIOs labelling.In-vivo7 T MRI scans allowed detection of 103and 104cells.In-vivoMnCl2labelled cells were detectable from days 4–16 while SPIO labelling allowed detection until 4 days after s.c. injection. MnCl2labelled cells were highly tumourigenic in NOD-Scid mice and the tumour volume development was characterised in a time dependent manner. The amount of injected cells correlated with tumour size development and disease progression. Histological analysis of the induced tumour masses demonstrated characteristic morphologies of prostate adenocarcinoma.

Conclusions

To the best of our knowledge, this is the first study reporting directin-vitroMnCl2labelling and 7 T basedin-vivoMRI tracing of cancer cells in a model of prostate cancer. MnCl2labelling was found to be suitable forin-vivotracing allowing long detection periods. The labelled cells kept their highly tumourigenic potentialin-vivo.Tumour volume development was visualised prior to manual palpation allowing tumour characterisation in early stages of the disease.
Pediatricians’ assessments of caries risk and need for a dental evaluation in preschool aged children
Authors: Long C Marshall , Quinonez Rocio B , Beil Heather A , Close Kelly , Myers Larry P , Vann William F , Rozier R Gary
Published: July 2012

Background

Risk-based prioritization of dental referrals during well-child visits might improve dental access for infants and toddlers. This study identifies pediatrician-assessed risk factors for early childhood caries (ECC) and their association with the need for a dentist’s evaluation.

Methods

A priority oral health risk assessment and referral tool (PORRT) for children<36 months was developed collaboratively by physicians and dentists and used by 10 pediatricians during well-child visits. PORRT documented behavioral, clinical, and child health risks for ECC. Pediatricians also assessed overall ECC risk on an 11-point scale and determined the need for a dental evaluation. Logistic regression models calculated the odds for evaluation need for each risk factor and according to a 3-level risk classification.

Results

In total 1,288 PORRT forms were completed; 6.8% of children were identified as needing a dentist evaluation. Behavioral risk factors were prevalent but not strong predictors of the need for an evaluation. The child’s overall caries risk was the strongest predictor of the need for an evaluation. Cavitated (OR = 17.5; 95% CI = 8.08, 37.97) and non-cavitated (OR = 6.9; 95% CI = 4.47, 10.82) lesions were the strongest predictors when the caries risk scale was excluded from the analysis. Few patients (6.3%) were classified as high risk, but their probability of needing an evaluation was only 0.36.

Conclusions

Low referral rates for children with disease and prior to disease onset but at elevated risk, indicate interventions are needed to help improve the dental referral rates of physicians.
Development of an optimized tetracycline-inducible expression system to increase the accumulation of interleukin-10 in tobacco BY-2 suspension cells
Authors: Bortesi Luisa , Rademacher Thomas , Schiermeyer Andreas , Schuster Flora , Pezzotti Mario , Schillberg Stefan
Published: July 2012

Background

Plant cell suspension cultures can be used for the production of valuable pharmaceutical and industrial proteins. When the recombinant protein is secreted into the culture medium, restricting expression to a defined growth phase can improve both the quality and quantity of the recovered product by minimizing proteolytic activity. Temporal restriction is also useful for recombinant proteins whose constitutive expression affects cell growth and viability, such as viral interleukin-10 (vIL-10).

Results

We have developed a novel, tetracycline-inducible system suitable for tobacco BY-2 suspension cells which increases the yields of vIL-10. The new system is based on a binary vector that is easier to handle than conventional vectors, contains an enhanced inducible promoter and 5′-UTR to improve yields, and incorporates a constitutively-expressed visible marker gene to allow the rapid and straightforward selection of the most promising transformed clones. Stable transformation of BY-2 cells with this vector, without extensive optimization of the induction conditions, led to a 3.5 fold increase in vIL-10 levels compared to constitutive expression in the same host.

Conclusions

We have developed an effective and straightforward molecular farming platform technology that improves both the quality and the quantity of recombinant proteins produced in plant cells, particularly those whose constitutive expression has a negative impact on plant growth and development. Although we tested the platform using vIL-10 produced in BY-2 cells, it can be applied to other host/product combinations and is also useful for basic research requiring strictly controlled transgene expression.
NF-κB p65 repression by the sesquiterpene lactone, Helenalin, contributes to the induction of autophagy cell death
Authors: Lim Chuan Bian , Fu Pan You , Ky Nung , Zhu Hong Shuang , Feng XiaoLing , Li Jinming , Srinivasan Kandhadayar Gopalan , Hamza Mohamed Sabry , Zhao Yan
Published: July 2012

Background

Numerous studies have demonstrated that autophagy plays a vital role in maintaining cellular homeostasis. Interestingly, several anticancer agents were found to exert their anticancer effects by triggering autophagy. Emerging data suggest that autophagy represents a novel mechanism that can be exploited for therapeutic benefit. Pharmacologically active natural compounds such as those from marine, terrestrial plants and animals represent a promising resource for novel anticancer drugs. There are several prominent examples from the past proving the success of natural products and derivatives exhibiting anticancer activity. Helenalin, a sesquiterpene lactone has been demonstrated to have potent anti-inflammatory and antitumor activity. Albeit previous studies demonstrating helenalin’s multi modal action on cellular proliferative and apoptosis, the mechanisms underlying its action are largely unexplained.

Methods

To deduce the mechanistic action of helenalin, cancer cells were treated with the drug at various concentrations and time intervals. Using western blot, FACS analysis, overexpression and knockdown studies, cellular signaling pathways were interrogated focusing on apoptosis and autophagy markers.

Results

We show here that helenalin induces sub-G1 arrest, apoptosis, caspase cleavage and increases the levels of the autophagic markers. Suppression of caspase cleavage by the pan caspase inhibitor, Z-VAD-fmk, suppressed induction of LC3-B and Atg12 and reduced autophagic cell death, indicating caspase activity was essential for autophagic cell death induced by helenalin. Additionally, helenalin suppressed NF-κB p65 expression in a dose and time dependent manner. Exogenous overexpression of p65 was accompanied by reduced levels of cell death whereas siRNA mediated suppression led to augmented levels of caspase cleavage, autophagic cell death markers and increased cell death.

Conclusions

Taken together, these results show that helenalin mediated autophagic cell death entails inhibition of NF-κB p65, thus providing a promising approach for the treatment of cancers with aberrant activation of the NF-κB pathway.
Enhanced photoluminescence of multilayer Ge quantum dots on Si(001) substrates by increased overgrowth temperature
Authors: Liu Zhi , Cheng Buwen , Hu Weixuan , Su Shaojian , Li Chuanbo , Wang Qiming
Published: July 2012

Four-bilayer Ge quantum dots (QDs) with Si spacers were grown on Si(001) substrates by ultrahigh vacuum chemical vapor deposition. In three samples, all Ge QDs were grown at 520 °C, while Si spacers were grown at various temperatures (520 °C, 550 °C, and 580 °C). Enhancement and redshift of room temperature photoluminescence (PL) were observed from the samples in which Si spacers were grown at a higher temperature. The enhancement of PL is explained by higher effective electrons capturing in the larger size Ge QDs. Quantum confinement of the Ge QDs is responsible for the redshift of PL spectra. The Ge QDs’ size and content were investigated by atomic force microscopy and Raman scattering measurements.
Long lasting complete molecular remission after suspending dasatinib treatment in chronic myeloid leukemia
Authors: Gadó Klára , Matolcsy András , Csomor Judit , Kicsi Dóra , Bödör Csaba , Domján Gyula
Published: July 2012

Tyrosine kinase inhibitors specific for BCR-ABL, were a major breakthrough in CML therapy. Second generation tyrosine kinase inhibitors (dasatinib, nilotinib) are indicated for imatinib resistant and intolerant patients. Present guidelines recommend continuous drug dosing for maintaining remission. There is no available data concerning the optimal duration of dasatinib therapy. We report the case of an imatinib intolerant patient who succeeded a complete molecular remission with dasatinib. Dasatinib was stopped bacause of intolerance, but complete molecular remission was sustained for one year and minor molecular remission for 27 months after discontinuation of dasatinib.
Induction of Bcl-3 by acute binge alcohol results in Toll-like receptor 4/LPS tolerance
Authors: Bala Shashi , Tang Alexander , Catalano Donna , Petrasek Jan , Taha Odette , Kodys Karen , Szabo Gyongyi
Published: July 2012

Induction of TLR4/LPS tolerance by acute binge alcohol introduces a new aspect of the complex biological effects of this commonly used substance.

Acute alcohol binge results in immunosuppression and impaired production of proinflammatory cytokines, including TNF-α. TNF-α production is induced by LPS, a TLR4 ligand, and is tightly regulated at various levels of the signaling cascade, including the NF-κB transcription factor. Here, we hypothesized that acute alcohol induces TLR4/LPS tolerance via Bcl-3, a nuclear protein and member of the NF-κB family. We found that acute alcohol pretreatment resulted in the same attenuating effect as LPS pretreatment on TLR4-induced TNF-α production in human monocytes and murine RAW 264.7 macrophages. Acute alcohol-induced Bcl-3 expression and IP studies revealed increased association of Bcl-3 with NF-κB p50 homodimers in alcohol-treated macrophages and in mice. ChIP assays revealed increased occupancy of Bcl-3 and p50 at the promoter region of TNF-α in alcohol-pretreated cells. To confirm that the Bcl-3–p50 complex regulates transcription/production of TNF-α during acute alcohol exposure, we inhibited Bcl-3 expression using a targeted siRNA. Bcl-3 knockdown prevented the alcohol-induced inhibition of TNF-α mRNA and protein production. In a mouse model of binge alcohol, an increase in Bcl-3 and a concomitant decrease in TNF-α but no change in IL-10 production were found in mice that received alcohol followed by LPS challenge. In summary, our novel data suggest that acute alcohol treatment in vitro and in vivo induces molecular signatures of TLR4/LPS tolerance through the induction of Bcl-3, a negative regulator of TNF-α transcription via its association with NF-κB p50/p50 dimers.