bluuebunny/crossref_metadata_2025 huggingface dataset:
Delamination and wear in drilling of carbon-fiber reinforced plastic composites using multilayer TiAlN/TiN PVD-coated tungsten carbide tools
Authors: Isbilir Ozden , Ghassemieh Elaheh
Published: June 2012

This study aims to investigate drilling process in carbon-fiber reinforced plastic (CFRP) composites with multilayer TiAlN/TiN PVD-coated tungsten carbide drill. The effect of process parameters have been investigated in drilling of Hexcel M21-T700GC. Thrust force and torque were measured online throughout the drilling experiments. Delamination were observed using optical microscope and analyzed via a developed algorithm based on digital image processing technique. Surface roughness of each hole was measured using a surface profilometer. In addition, the progression of tool wear in various surfaces of drill was observed using tool microscope and measured using image software. Our results indicate that the thrust force and torque increased with the increasing cutting speed and feed rate. Delamination and average surface roughness that rose with the increase in feed rate, however, decreased with the increasing cutting speed. The average surface roughness tended to increase with the increase in feed rate and decrease with the increasing cutting speed in drilling of carbon-fiber reinforced plastic (CFRP). Feed rate was found as the predominant factor on the drilling outputs. Abrasive wear was observed on both flank and relief surfaces, which created edge wear on cutting edges. No sign of chipping or plastic deformation has been observed on the surfaces of drills.
Epoxy-layered silicate nanocomposites: effect of cross-linking amines and fillers on curing, morphology and oxygen permeation
Authors: Mittal Vikas
Published: June 2012

Epoxy-layered silicate nanocomposites were achieved by solution casting method using different amine hardeners as well as different filler surface modifications and their microstructure and oxygen permeation performance have been analyzed. The optimization of the curing conditions was achieved by differential scanning calorimetric analysis and the amount of the amine used to cure the epoxy resin was adjusted according to the number of cross-linking sites present in its structure. Apart from that, the presence of filler was also observed to have catalytic effect on the curing of the polymer. Different amines led to different extents of cross-link density of the epoxy network structure and the oxygen permeation was accordingly affected. The chemical architecture of the surface modifications also affected the morphology and the oxygen permeation through the nanocomposite films. When the interface between the filler and the polymer was optimally designed, the filler was observed to have exfoliation in the polymer matrix which also led to subsequent enhancement in the permeation resistance. On the other hand, when polarity mismatch existed between the filler surface modification and the polymer chains, minimal filler exfoliation and intercalation was observed. The enhanced permeation resistance in the already high barrier epoxy matrix did not affect the adhesive properties of the polymer, thus, confirming their potential for use as barrier as well as adhesive layer in packaging laminates.
Damage-tolerant design optimization of laminated composite structures using dispersion of ply angles by genetic algorithm
Authors: Gyan Sonali , Ganguli Ranjan , Naik G Narayana
Published: June 2012

This article aims to obtain damage-tolerant designs with minimum weight for a laminated composite structure using genetic algorithm. Damage tolerance due to impacts in a laminated composite structure is enhanced by dispersing the plies such that too many adjacent plies do not have the same angle. Weight of the structure is minimized and the Tsai–Wu failure criterion is considered for the safe design. Design variables considered are the number of plies and ply orientation. The influence of dispersed ply angles on the weight of the structure for a given loading conditions is studied by varying the angles in the range of 0°–45°, 0°–60° and 0°–90° at intervals of 5° and by using specific ply angles tailored to loading conditions. A comparison study is carried out between the conventional stacking sequence and the stacking sequence with dispersed ply angles for damage-tolerant weight minimization and some useful designs are obtained. Unconventional stacking sequence is more damage tolerant than the conventional stacking sequence is demonstrated by performing a finite element analysis under both tensile as well as compressive loading conditions. Moreover, a new mathematical function called the dispersion function is proposed to measure the dispersion of ply angles in a laminate. The approach for dispersing ply angles to achieve damage tolerance is especially suited for composite material design space which has multiple local minima.
Analytical model of one flexible link system with nonlinear kinematics
Authors: Saad Mohamad , Akhrif Ouassima , Saydy Lahcen
Published: June 2012

The dynamical model of a flexible Euler–Bernoulli link system subject to high-speed motions is developed. Nonlinear kinematics are considered to take into account the foreshortening effect of the link. A continuous model with boundary conditions is derived using Hamilton's principle and spatially discretized dynamical equations are derived using Lagrange's equation based on the expression of the kinetic and potential energies of the flexible link system. The effect of the links foreshortening on the dynamical response is shown for a sinusoidal torque input at the links hub. The simulation results showed that for small torque amplitudes the difference between linear and nonlinear kinematics is small. However, for large amplitudes, this difference is prominent.
Using Read-Alouds of Grade-Level Biographies and Systematic Prompting to Promote Comprehension for Students With Moderate and Severe Developmental Disabilities
Authors: Mims Pamela J. , Hudson Melissa E. , Browder Diane M.
Published: June 2012

The purpose of this study was to investigate the effects of a modified system of least intrusive prompts on text-dependent listening comprehension for four middle-school-aged students with intellectual disability and autism during read-alouds of adapted grade-level biographies. A system of least intrusive prompts was modified by inserting a rule for answering “Wh” questions and an opportunity to hear sections of the biography again. The procedure was evaluated via a multiple probe design across students. Outcomes indicate that all students improved listening comprehension after intervention and all students maintained high levels of correct responding 2 weeks after intervention. In addition, three students generalized skills to new biographies. The need for future research and implications for practice are discussed.
‘If I learn do we learn?’: The link between executive coaching and organizational learning
Authors: Swart Juani , Harcup Joy
Published: June 2012

This article contributes to the organizational learning literature by providing empirical evidence of how coaching enables the translation from individual learning into collective learning, i.e. enacting behaviours, enacting a coaching approach and embedding collective learning processes. It draws on interview data gathered in two law firms wherein learning was the result of executive coaching interventions to pinpoint the mechanisms by which individual and collective learning is interconnected, thereby heeding a call for a more detailed understanding of the mechanisms of learning presented in Management Learning (Bapuji and Crossan, 2004). This enables us to understand the role that coaching plays in the translation from individual to collective learning.
Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression
Authors: Teunissen CE , Sombekke M , van Winsen L , Killestein J , Barkhof F , Polman CH , Dijkstra CD , Blankenstein MA , Pratico D
Published: June 2012

Background:

Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression.

Objective:

To study whether plasma isoprostane levels were related to disease progression in MS.

Methods:

Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters.

Results:

Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS).

Conclusion:

These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.
Carotid intima–media thickness and the prediction of vascular events
Authors: Robertson Christine M , Gerry F , Fowkes R , Price Jacqueline F
Published: June 2012

Carotid intima–media thickness (cIMT) has received interest as a predictor of cardiovascular events in recent years. Use of cIMT in a clinical setting is limited by the variability in measurement and the lack of evidence for its use in clinical risk prediction. This review examines the major studies that have assessed the relationship between cIMT and cardiovascular event risk and discusses the current role of IMT in cardiovascular risk prediction.
Narrative health research: Exploring big and small stories as analytical tools
Authors: Sools Anneke
Published: June 2012

In qualitative health research many researchers use a narrative approach to study lay health concepts and experiences. In this article, I explore the theoretical linkages between the concepts narrative and health, which are used in a variety of ways. The article builds on previous work that conceptualizes health as a multidimensional, positive, dynamic and morally dilemmatic yet meaningful practice. I compare big and small stories as analytical tools to explore what narrative has to offer to address, nuance and complicate five challenges in narrative health research: (1) the interplay between health and other life issues; (2) the taken-for-granted yet rare character of the experience of good health; (3) coherence or incoherence as norms for good health; (4) temporal issues; (5) health as moral practice. In this article, I do not present research findings per se; rather, I use two interview excerpts for methodological and theoretical reflections. These interview excerpts are derived from a health promotion study in the Netherlands, which was partly based on peer-to-peer interviews. I conclude with a proposal to advance narrative health research by sensitizing researchers to different usages of both narrative and health, and the interrelationship(s) between the two.
Global Nollywood: The Nigerian movie industry and alternative global networks in production and distribution
Authors: Miller Jade
Published: June 2012

While Nollywood, Nigeria’s video industry, is largely separate from dominant global cultural industry networks of production inputs and distribution, it is an industry that is still globally linked in a number of ways. In this article, I investigate the nature and layout of these connections via interviews with those populating these networks, from key Nollywood producers to shop owners thousands of miles from Lagos. I conclude that, instead of the formal links of dominant cultural industry networks, these links are mostly via alternative global networks, forged on the flipside of – or the gaps between – the connections that link the Network Society. Some formal international institutions have a presence, but these are largely mediated through Nollywood’s situation in global cultural industry networks. I argue that this renders Nollywood as situated in an alternative media capital, central to alternative networks, while too informal to integrate into dominant networks, and it is from this position that we can best understand Nollywood’s position in global media flows.
Reconsidering the role of participatory media in nursing research and knowledge dissemination
Authors: Haigh Carol , Costa Cristina
Published: June 2012

This theoretically focused and discursive paper explores the role that participatory media can play in the field of nursing research and subsequent knowledge dissemination. Being able to gather information, sieve through it, access the latest developments in the field, and produce new information is a core part of the academic researcher’s role. Moreover, it could even be argued that for centuries it has been knowledge workers’ main tangible work currency. Indeed, the information age is not exclusive of the networked society. Haigh (2010) has noted that the information gathering and sharing opportunities, referred to as participatory media, offered by the second generation of web design that allow for information sharing – known as web 2.0 – have expanded our horizons beyond academia to the whole of the global research and education community. If we accept the premise that the use of social networks in the development of ideas is one that has a long and distinguished pedigree, then it can be seen that the role of participatory media is the latest iteration in its evolution. What makes this development such a challenge for nursing research in particular is that whilst nursing academia generally remains suspicious of the advantages offered by technology, this paper argues that the next 10–15 years will see an increase in the chasm between the existing research community and the next generation of researchers. This has been attributed to the difference between the two groups in their approach and attitude to technology.
Analysis of loading curve characteristics on the production of brain deformation metrics
Authors: Post Andrew , Walsh Evan S , Hoshizaki T Blaine , Gilchrist Michael D
Published: June 2012

Traumatic and mild traumatic brain injuries are incurred as a result of the complex motions of the head after an impact. These motions can be quantified in terms of linear and rotational accelerations which cause the injurious levels of brain deformation. Currently, it is unclear what aspects of the linear and rotational acceleration loading curves influence injurious brain deformation. This research uses the University College Dublin Brain Trauma Model to analyse the loading curve shapes from a series of centric and non-centric impacts to a Hybrid III headform fitted with different hockey helmets. The results found that peak resultant linear acceleration did not always correlate with brain deformation measures. The results also indicated that, due to the complex nature of the interaction between loading curve characteristic and tissue parameters, there was no commonality in curve shape which produced large magnitudes of brain deformation. However, the discriminant function did show that angular acceleration loading curve characteristics would predict brain deformation more reliably than linear acceleration loading curves.
Comparative analysis of two phenotypically-similar but genomically-distinct Burkholderia cenocepacia-specific bacteriophages
Authors: Lynch Karlene H , Stothard Paul , Dennis Jonathan J
Published: June 2012

Background

Genomic analysis of bacteriophages infecting the Burkholderia cepacia complex (BCC) is an important preliminary step in the development of a phage therapy protocol for these opportunistic pathogens. The objective of this study was to characterize KL1 (vB_BceS_KL1) and AH2 (vB_BceS_AH2), two novel Burkholderia cenocepacia-specific siphoviruses isolated from environmental samples.

Results

KL1 and AH2 exhibit several unique phenotypic similarities: they infect the same B. cenocepacia strains, they require prolonged incubation at 30°C for the formation of plaques at low titres, and they do not form plaques at similar titres following incubation at 37°C. However, despite these similarities, we have determined using whole-genome pyrosequencing that these phages show minimal relatedness to one another. The KL1 genome is 42,832 base pairs (bp) in length and is most closely related to Pseudomonas phage 73 (PA73). In contrast, the AH2 genome is 58,065 bp in length and is most closely related to Burkholderia phage BcepNazgul. Using both BLASTP and HHpred analysis, we have identified and analyzed the putative virion morphogenesis, lysis, DNA binding, and MazG proteins of these two phages. Notably, MazG homologs identified in cyanophages have been predicted to facilitate infection of stationary phase cells and may contribute to the unique plaque phenotype of KL1 and AH2.

Conclusions

The nearly indistinguishable phenotypes but distinct genomes of KL1 and AH2 provide further evidence of both vast diversity and convergent evolution in the BCC-specific phage population.
Mutagenesis of RpoE-like sigma factor genes in Bdellovibrio reveals differential control of groEL and two groES genes
Authors: Lambert Carey , Till Rob , Hobley Laura , Sockett R Elizabeth
Published: June 2012

Background

Bdellovibrio bacteriovorus HD100 must regulate genes in response to a variety of environmental conditions as it enters, preys upon and leaves other bacteria, or grows axenically without prey. In addition to “housekeeping” sigma factors, its genome encodes several alternate sigma factors, including 2 Group IV-RpoE-like proteins, which may be involved in the complex regulation of its predatory lifestyle.

Results

We find that one sigma factor gene, bd3314, cannot be deleted from Bdellovibrio in either predatory or prey-independent growth states, and is therefore possibly essential, likely being an alternate sigma 70. Deletion of one of two Group IV-like sigma factor genes, bd0881, affects flagellar gene regulation and results in less efficient predation, although not due to motility changes; deletion of the second, bd0743, showed that it normally represses chaperone gene expression and intriguingly we find an alternative groES gene is expressed at timepoints in the predatory cycle where intensive protein synthesis at Bdellovibrio septation, prior to prey lysis, will be occurring.

Conclusions

We have taken the first step in understanding how alternate sigma factors regulate different processes in the predatory lifecycle of Bdellovibrio and discovered that alternate chaperones regulated by one of them are expressed at different stages of the lifecycle.
Interactions of an Arabidopsis RanBPM homologue with LisH-CTLH domain proteins revealed high conservation of CTLH complexes in eukaryotes
Authors: Tomaštíková Eva , Cenklová Věra , Kohoutová Lucie , Petrovská Beáta , Váchová Lenka , Halada Petr , Kočárová Gabriela , Binarová Pavla
Published: June 2012

Background

RanBPM (Ran-binding protein in the microtubule-organizing centre) was originally reported as a centrosome-associated protein in human cells. However, RanBPM protein containing highly conserved SPRY, LisH, CTLH and CRA domains is currently considered as a scaffolding protein with multiple cellular functions. A plant homologue of RanBPM has not yet been characterized.

Results

Based on sequence similarity, we identified a homologue of the human RanBPM inArabidopsis thaliana.AtRanBPM protein has highly conserved SPRY, LisH, CTLH and CRA domains. Cell fractionation showed that endogenous AtRanBPM or expressed GFP-AtRanBPM are mainly cytoplasmic proteins with only a minor portion detectable in microsomal fractions. AtRanBPM was identified predominantly in the form of soluble cytoplasmic complexes ~230 – 500 kDa in size. Immunopurification of AtRanBPM followed by mass spectrometric analysis identified proteins containing LisH and CRA domains; LisH, CRA, RING-U-box domains and a transducin/WD40 repeats in a complex with AtRanBPM. Homologues of identified proteins are known to be components of the C-terminal to the LisH motif (CTLH) complexes in humans and budding yeast. Microscopic analysis of GFP-AtRanBPMin vivoand immunofluorescence localization of endogenous AtRanBPM protein in cultured cells and seedlings ofArabidopsisshowed mainly cytoplasmic and nuclear localization. Absence of colocalization with γ-tubulin was consistent with the biochemical data and suggests another than a centrosomal role of the AtRanBPM protein.

Conclusion

We showed that as yet uncharacterizedArabidopsisRanBPM protein physically interacts with LisH-CTLH domain-containing proteins. The newly identified high molecular weight cytoplasmic protein complexes of AtRanBPM showed homology with CTLH types of complexes described in mammals and budding yeast. Although the exact functions of the CTLH complexes in scaffolding of protein degradation, in protein interactions and in signalling from the periphery to the cell centre are not yet fully understood, structural conservation of the complexes across eukaryotes suggests their important biological role.
Endoscopic surgery versus conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage (ECMOH): study protocol for a randomized controlled trial
Authors: Zan Xin , Li Hao , Liu Wenke , Fang Yuan , Ma Junpeng , Lan Zhigang , Li Xi , Liu Xin , You Chao
Published: June 2012

Background

Spontaneous intracerebral hemorrhage is a disease with high morbidity, high disability rate, high mortality, and high economic burden. Whether patients can benefit from surgical evacuation of hematomas is still controversial, especially for those with moderate-volume hematomas in the basal ganglia. This study is designed to compare the efficacy of endoscopic surgery and conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage.

Methods

Patients meet the criteria will be randomized into the endoscopic surgery group (endoscopic surgery for hematoma evacuation and the best medical treatment) or the conservative treatment group (the best medical treatment). Patients will be followed up at 1, 3, and 6 months after initial treatment. The primary outcomes include the Extended Glasgow Outcome Scale and the Modified Rankin Scale. The secondary outcomes consist of the National Institutes of Health Stroke Scale and the mortality. The Barthel Index(BI) will also be evaluated. The sample size is 100 patients.

Discussion

The ECMOH trial is a randomized controlled trial designed to evaluate if endoscopic surgery is better than conservative treatment for patients with moderate-volume hematomas in the basal ganglia.

Trial registration

Chinese Clinical Trial Registry: ChiCTR-TRC-11001614

(http://www.chictr.org/en/proj/show.aspx?proj=1618)
A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection
Authors: Van Neste Leander , Bigley Joseph , Toll Adam , Otto Gaëtan , Clark James , Delrée Paul , Van Criekinge Wim , Epstein Jonathan I
Published: June 2012

Background

PSA-directed prostate cancer screening leads to a high rate of false positive identifications and an unnecessary biopsy burden. Epigenetic biomarkers have proven useful, exhibiting frequent and abundant inactivation of tumor suppressor genes through such mechanisms. An epigenetic, multiplex PCR test for prostate cancer diagnosis could provide physicians with better tools to help their patients. Biomarkers like GSTP1, APC and RASSF1 have demonstrated involvement with prostate cancer, with the latter two genes playing prominent roles in the field effect. The epigenetic states of these genes can be used to assess the likelihood of cancer presence or absence.

Results

An initial test cohort of 30 prostate cancer-positive samples and 12 cancer-negative samples was used as basis for the development and optimization of an epigenetic multiplex assay based on the GSTP1, APC and RASSF1 genes, using methylation specific PCR (MSP). The effect of prostate needle core biopsy sample volume and age of formalin-fixed paraffin-embedded (FFPE) samples was evaluated on an independent follow-up cohort of 51 cancer-positive patients. Multiplexing affects copy number calculations in a consistent way per assay. Methylation ratios are therefore altered compared to the respective singleplex assays, but the correlation with patient outcome remains equivalent. In addition, tissue-biopsy samples as small as 20 μm can be used to detect methylation in a reliable manner. The age of FFPE-samples does have a negative impact on DNA quality and quantity.

Conclusions

The developed multiplex assay appears functionally similar to individual singleplex assays, with the benefit of lower tissue requirements, lower cost and decreased signal variation. This assay can be applied to small biopsy specimens, down to 20 microns, widening clinical applicability. Increasing the sample volume can compensate the loss of DNA quality and quantity in older samples.
Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides (GOS): double-blind, randomized, controlled trial
Authors: Ashley Claude , Johnston William H , Harris Cheryl L , Stolz Suzanne I , Wampler Jennifer L , Berseth Carol Lynn
Published: June 2012

Background

To ensure the suitability of an infant formula as the sole source of nutrition or provide benefits similar to outcomes in breastfed infants, advancements in formula composition are warranted as more research detailing the nutrient composition of human milk becomes available. This study was designed to evaluate growth and tolerance in healthy infants who received one of two investigational cow’s milk-based formulas with adjustments in carbohydrate, fat, and calcium content and supplemented with a prebiotic blend of polydextrose (PDX) and galactooligosaccharides (GOS) or GOS alone.

Methods

In this multi-center, double-blind, parallel-designed, gender-stratified prospective study 419 infants were randomized and consumed either a marketed routine cow’s milk-based infant formula (Control; Enfamil® LIPIL®, Mead Johnson Nutrition, Evansville, IN) (n = 142) or one of two investigational formulas from 14 to 120 days of age. Investigational formulas were supplemented with 4 g/L (1:1 ratio) of a prebiotic blend of PDX and GOS (PDX/GOS; n = 139) or 4 g/L of GOS alone (GOS; n = 138). Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age. Daily recall of formula intake, tolerance, and stool characteristics was collected during study weeks 1 and 2 and 24-h recall was collected at 60, 90, and 120 days of age. Medically-confirmed adverse events were recorded throughout the study.

Results

There were no group differences in growth rate from 14 to 120 days of age. Discontinuation rates were not significantly different among study groups. No differences in formula intake or infant fussiness or gassiness were observed. During study weeks 1 and 2 and at 60 days of age stool consistency ratings were higher (i.e. softer stools) for infants in the PDX/GOS and GOS groups versus Control and remained higher at 120 days for the PDX/GOS group (allP < 0.05). The overall incidence of medically-confirmed adverse events was similar among groups.

Conclusions

Investigational routine infant formulas supplemented with 4 g/L of either a prebiotic blend of PDX and GOS or GOS alone were well-tolerated and supported normal growth. Compared to infants who received the unsupplemented control formula, infants who received prebiotic supplementation experienced a softer stooling pattern similar to that reported in breastfed infants.

Trial registration

ClinicalTrials.gov Identifier: NCT00712608
Removal from the plasma of the free and esterified forms of cholesterol and transfer of lipids to HDL in type 2 diabetes mellitus patients
Authors: Oliveira Carolina P , Maranhão Raul C , Bertato Marina P , Wajchenberg Bernardo L , Lerario Antonio C
Published: June 2012

Background

The aim was to investigate new markers for type 2 diabetes (T2DM) dyslipidemia related with LDL and HDL metabolism. Removal from plasma of free and esterified cholesterol transported in LDL and the transfer of lipids to HDL are important aspects of the lipoprotein intravascular metabolism. The plasma kinetics (fractional clearance rate, FCR) and transfers of lipids to HDL were explored in T2DM patients and controls, using as tool a nanoemulsion that mimics LDL lipid structure (LDE).

Results

14C- cholesteryl ester FCR of the nanoemulsion was greater in T2DM than in controls (0.07 ± 0.02 vs. 0.05 ± 0.01 h-1, p = 0.02) indicating that LDE was removed faster, but FCR 3 H- cholesterol was equal in both groups. Esterification rates of LDE free-cholesterol were equal. Cholesteryl ester and triglyceride transfer from LDE to HDL was greater in T2DM (4.2 ± 0.8 vs. 3.5 ± 0.7%, p = 0.03 and 6.8 ± 1.6% vs. 5.0 ± 1.1, p = 0.03, respectively). Phospholipid and free cholesterol transfers were not different.

Conclusions

The kinetics of free and esterified cholesterol tended to be independent in T2DM patients and the lipid transfers to HDL were also disturbed. These novel findings may be related with pathophysiological mechanisms of diabetic macrovascular disease.
Fatty acids-stress attenuates gluconeogenesis induction and glucose production in primary hepatocytes
Authors: Budick-Harmelin Noga , Anavi Sarit , Madar Zecharia , Tirosh Oren
Published: June 2012

Background

Hepatic gluconeogenesis tightly controls blood glucose levels in healthy individuals, yet disorders of fatty acids (FAs) oxidation are characterized by hypoglycemia. We studied the ability of free-FAs to directly inhibit gluconeogenesis, as a novel mechanism that elucidates the hypoglycemic effect of FAs oxidation defects.

Methods

Primary rat hepatocytes were pre-treated with FAs prior to gluconeogenic stimuli with glucagon or dexamethasone and cAMP.

Results

Pre-treatment with 1 mM FAs (mixture of 2:1 oleate:palmitate) for 1 hour prior to gluconeogenic induction, significantly decreases the induced expression of the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6pase) as well as the induced glucose production by the cells. The inhibitory effect of FAs upon gluconeogenesis is abolished when pre-treatment is elongated to 18 hours, allowing clearance of FAs into triglycerides by the cells. Replacement of palmitate with the non-metabolic fatty acid 2-bromopalmitate inhibits esterification of FAs into triglycerides. Accordingly, the increased exposure to unesterified-FAs allows their inhibitory effect to be extended even when pre-treatment is elongated to 18 hours. Similar changes were caused by FAs to the induction of peroxisome-proliferator-activated receptor-γ coactivator 1α (PGC1α) expression, indicating this transcriptional coactivator as the mediating link of the effect. This inhibitory effect of FAs upon gluconeogenic induction is shown to involve reduced activation of cAMP response element-binding (CREB) transcription factor.

Conclusions

The present results demonstrate that free-FAs directly inhibit the induced gluconeogenic response in hepatocytes. Hence, high levels of free-FAs may attenuate hepatic gluconeogenesis, and liver glucose output.
Dietary whey protein lessens several risk factors for metabolic diseases: a review
Authors: Sousa Gabriela TD , Lira Fábio S , Rosa José C , de Oliveira Erick P , Oyama Lila M , Santos Ronaldo V , Pimentel Gustavo D
Published: June 2012

Obesity and type 2 diabetes mellitus (DM) have grown in prevalence around the world, and recently, related diseases have been considered epidemic. Given the high cost of treatment of obesity/DM-associated diseases, strategies such as dietary manipulation have been widely studied; among them, the whey protein diet has reached popularity because it has been suggested as a strategy for the prevention and treatment of obesity and DM in both humans and animals. Among its main actions, the following activities stand out: reduction of serum glucose in healthy individuals, impaired glucose tolerance in DM and obese patients; reduction in body weight; maintenance of muscle mass; increases in the release of anorectic hormones such as cholecystokinin, leptin, and glucagon like-peptide 1 (GLP-1); and a decrease in the orexigenic hormone ghrelin. Furthermore, studies have shown that whey protein can also lead to reductions in blood pressure, inflammation, and oxidative stress.
Emergence of biopharmaceutical innovators in China, India, Brazil, and South Africa as global competitors and collaborators
Authors: Rezaie Rahim , McGahan Anita M , Frew Sarah E , Daar Abdallah S , Singer Peter A
Published: June 2012

Biopharmaceutical innovation has had a profound health and economic impact globally. Developed countries have traditionally been the source of most innovations as well as the destination for the resulting economic and health benefits. As a result, most prior research on this sector has focused on developed countries. This paper seeks to fill the gap in research on emerging markets by analyzing factors that influence innovative activity in the indigenous biopharmaceutical sectors of China, India, Brazil, and South Africa. Using qualitative research methodologies, this paper a) shows how biopharmaceutical innovation is taking place within the entrepreneurial sectors of these emerging markets, b) identifies common challenges that indigenous entrepreneurs face, c) highlights the key role played by the state, and d) reveals that the transition to innovation by companies in the emerging markets is characterized by increased global integration. It suggests that biopharmaceutical innovators in emerging markets are capitalizing on opportunities to participate in the drug development value chain and thus developing capabilities and relationships for competing globally both with and against established companies headquartered in developed countries.
The adapter protein ADAP is required for selected dendritic cell functions
Authors: Togni Mauro , Engelmann Swen , Reinhold Dirk , Schraven Burkhart , Reinhold Annegret
Published: June 2012

Background

The cytosolic adaptor protein ADAP (adhesion and degranulation promoting adapter protein) is expressed by T cells, natural killer cells, myeloid cells and platelets. ADAP is involved in T-cell-receptor-mediated inside-out signaling, which leads to integrin activation, adhesion and reorganization of the actin cytoskeleton. However, little is known about the role of ADAP in myeloid cells. In the present study, we analyzed the function of ADAP in bone-marrow-derived dendritic cells (BMDCs) from ADAP-deficient mice.

Results

ADAP-deficient BMDCs showed almost normal levels of antigen uptake, adhesion, maturation, migration from the periphery to the draining lymph nodes, antigen-specific T-cell activation, and production of the proinflammatory cytokines IL-6 and TNF-∝. Furthermore, we provide evidence that the activation of signaling pathways after lipopolysaccharide (LPS) stimulation are not affected by the loss of ADAP. In contrast, ADAP-deficient BMDCs showed defects in CD11c-mediated cellular responses, with significantly diminished production of IL-6, TNF-∝ and IL-10. Actin polymerization was enhanced after CD11c integrin stimulation.

Conclusions

In summary, we propose that the adapter molecule ADAP is critical for selected CD11c integrin-mediated functions of dendritic cells.
An improved ITU-R rain attenuation prediction model over terrestrial microwave links in tropical region
Authors: Islam Rafiqul MD , Abdulrahman Yusuf A , Rahman Tharek A
Published: June 2012

An improved approach of predicting rain attenuation cumulative distribution (CD) over terrestrial microwave links operating in tropical regions is presented in this article. The proposed method offers a better extrapolation approach for determining the values of rain attenuation at different exceedance probability from the measured attenuation at 0.01% of the time. The experimental data consist of measured rainfall rates and rain attenuation over six geographically spread DIGI MINI-LINKs operating at 15 GHz in Malaysia. A new set of numerical coefficients was derived for improved rain attenuation CD predictions in the Malaysian tropical climate. In order to test the applicability of the proposed extrapolation method, a validation was performed using rain rate and rain attenuation measurements from five Brazilian and seven Nigerian tropical locations. When tested against measurements, the proposed method seems to provide a significant improvement over the current extrapolation method adopted by ITU-R Recommendations P.530-14, for the prediction of rain attenuation CD over tropical regions.
Predictive value of IgE/IgG4 antibody ratio in children with egg allergy
Authors: Okamoto Shindou , Taniuchi Shoichiro , Sudo Kyoko , Hatano Yasuko , Nakano Keiji , Shimo Tomohiko , Kaneko Kazunari
Published: June 2012

Background

The aim of this study was to investigate the role of specific IgG4 antibodies to hen’s egg white and determine their utility as a marker for the outcome of oral challenge test in children sensitized to hen’s egg

Methods

The hen’s egg oral food challenge test was performed in 105 sensitized children without atopic dermatitis, and the titers of egg white-specific immunoglobulin G4 (IgG4) and immunoglobulin E (IgE) antibodies were measured. To set the cut-off values of IgG4, IgE, and the IgE/IgG4 ratio for predicting positive results in oral challenges, receiver operating characteristic curves were plotted and the area under the curves (AUC) were calculated.

Results

Sixty-four of 105 oral challenges with whole eggs were assessed as positive. The AUC for IgE, IgG4, and IgE/IgG4 for the prediction of positive results were 0.609, 0.724, and 0.847, respectively. Thus, the IgE/IgG4 ratio generated significantly higher specificity, sensitivity, positive predictive value (%), and negative predictive value (%) than the individual IgE and IgG4. The negative predictive value of the IgE/IgG4 ratio was 90% at a value of 1.

Conclusions

We have demonstrated that the egg white-specific serum IgE/IgG4 ratio is important for predicting reactivity to egg during food challenges.
Immunodominant fragments of myelin basic protein initiate T cell-dependent pain
Authors: Liu Huaqing , Shiryaev Sergey A , Chernov Andrei V , Kim Youngsoon , Shubayev Igor , Remacle Albert G , Baranovskaya Svetlana , Golubkov Vladislav S , Strongin Alex Y , Shubayev Veronica I
Published: June 2012

Background

The myelin sheath provides electrical insulation of mechanosensory Aβ-afferent fibers. Myelin-degrading matrix metalloproteinases (MMPs) damage the myelin sheath. The resulting electrical instability of Aβ-fibers is believed to activate the nociceptive circuitry in Aβ-fibers and initiate pain from innocuous tactile stimulation (mechanical allodynia). The precise molecular mechanisms, responsible for the development of this neuropathic pain state after nerve injury (for example, chronic constriction injury, CCI), are not well understood.

Methods and results

Using mass spectrometry of the whole sciatic nerve proteome followed by bioinformatics analyses, we determined that the pathways, which are classified as the Infectious Disease and T-helper cell signaling, are readily activated in the nerves post-CCI. Inhibition of MMP-9/MMP-2 suppressed CCI-induced mechanical allodynia and concomitant TNF-α and IL-17A expression in nerves. MMP-9 proteolysis of myelin basic protein (MBP) generated the MBP84-104 and MBP68-86 digest peptides, which are prominent immunogenic epitopes. In agreement, the endogenous MBP69-86 epitope co-localized with MHCII and MMP-9 in Schwann cells and along the nodes of Ranvier. Administration of either the MBP84-104 or MBP68-86 peptides into the naïve nerve rapidly produced robust mechanical allodynia with a concomitant increase in T cells and MHCII-reactive cell populations at the injection site. As shown by the genome-wide expression profiling, a single intraneural MBP84-104 injection stimulated the inflammatory, immune cell trafficking, and antigen presentation pathways in the injected naïve nerves and the associated spinal cords. Both MBP84-104-induced mechanical allodynia and characteristic pathway activation were remarkably less prominent in the T cell-deficient athymic nude rats.

Conclusions

These data implicate MBP as a novel mediator of pain. Furthermore, the action of MMPs expressed within 1 day post-injury is critical to the generation of tactile allodynia, neuroinflammation, and the immunodominant MBP digest peptides in nerve. These MBP peptides initiate mechanical allodynia in both a T cell-dependent and -independent manner. In the course of Wallerian degeneration, the repeated exposure of the cryptic MBP epitopes, which are normally sheltered from immunosurveillance, may induce the MBP-specific T cell clones and a self-sustaining immune reaction, which may together contribute to the transition of acute pain into a chronic neuropathic pain state.
Anti-Hyperalgesic Effects of Calcitonin on Neuropathic Pain Interacting with its Peripheral Receptors
Authors: Ito Akitoshi , Takeda Mineko , Yoshimura Takeshi , Komatsu Takayuki , Ohno Takeshi , Kuriyama Hiroshi , Matsuda Akio , Yoshimura Megumu
Published: June 2012

Background:

The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats.

Results:

Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI). Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX)-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG), which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of 125I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions.

Conclusions:

These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.
Genetic alterations in a primary medullary thyroid carcinoma and its lymph node metastasis in a patient with 15 years follow-up
Authors: González-Yebra Beatriz , Peralta Raúl , González Ana Lilia , Ayala-Garcia Marco Antonio , de Zarate María E Medrano Ortiz , Salcedo Mauricio
Published: June 2012

Background

Association between DNA alterations and clinical parameters as recurrence, survival or prognosis has been found in a variety of tumors. A clear association between Medullary Thyroid Carcinoma (MTC) and RET oncogene mutation has been accepted. Specifically M918T RET mutation represents the main genetic event in most cases of sporadic MTC (SMTC) and limited chromosomal alterations analyses have been performed.

Methods

In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918T RET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations. We studied a patient with 15 years of follow-up and persistence of disease, confirmed by periodical elevated serum calcitonin (CT) levels.

Results

Only 3 chromosomal imbalances were identified in the primary tumor, gain of 18p, and loss of 6p and 16p region, whereas 25 chromosomal imbalances were identified in the metastasis (9 gains and 16 losses).

Conclusion

The chromosomal changes 6p-, 16p-, 18p + could determine in part the oncogenic phenotype in the primary M918T RET positive tumor and probably related to persistence of high serum CT levels in this patient. The additional chromosomal changes observed could be related to the metastasis phenotype. We suggest that some genes mapped at 6p, 16p and 18p chromosomal regions, could act as genes associated to cancer and could be related to persistent SMTC and good prognosis.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720753793691097
Relation between smoking history and gene expression profiles in lung adenocarcinomas
Authors: Staaf Johan , Jönsson Göran , Jönsson Mats , Karlsson Anna , Isaksson Sofi , Salomonsson Annette , Pettersson Helen M , Soller Maria , Ewers Sven-Börje , Johansson Leif , Jönsson Per , Planck Maria
Published: June 2012

Background

Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers’ lung carcinomas remain to a large extent unclear.

Methods

Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets.

Results

Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking.

Conclusions

Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.