bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies for capacity building for health research in Bangladesh: Role of core funding and a common monitoring and evaluation framework
Authors: Mahmood Shakeel , Hort Krishna , Ahmed Shakil , Salam Mohammed , Cravioto Alejandro
Published: July 2011

Background

There is increasing interest in building the capacity of researchers in low and middle income countries (LMIC) to address their national priority health and health policy problems. However, the number and variety of partnerships and funding arrangements can create management problems for LMIC research institutes. This paper aims to identify problems faced by a health research institute in Bangladesh, describe two strategies developed to address these problems, and identify the results after three years of implementation.

Methods

This paper uses a mixture of quantitative and qualitative data collected during independent annual reviews of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) between 2006 and 2010. Quantitative data includes the number of research activities according to strategic priority areas, revenues collected and expenditure. Qualitative data includes interviews of researchers and management of ICDDR,B, and of research users and key donors. Data in a Monitoring and Evaluation Framework (MEF) were assessed against agreed indicators.

Results

The key problems faced by ICDDR,B in 2006 were insufficient core funds to build research capacity and supporting infrastructure, and an inability to direct research funds towards the identified research priorities in its strategic plan. Two strategies were developed to address these problems: a group of donors agreed to provide unearmarked pooled core funding, and accept a single common report based on an agreed MEF. On review after three years, there had been significant increases in total revenue, and the ability to allocate greater amounts of money on capacity building and infrastructure. The MEF demonstrated progress against strategic objectives, and better alignment of research against strategic priorities. There had also been changes in the sense of ownership and collaboration between ICDDR,B's management and its core donors.

Conclusions

The changes made to funding relationships supported and monitored by an effective MEF enabled the organisation to better align funding with research priorities and to invest in capacity building. This paper identified key issues for capacity building for health research in low and middle income countries. The findings have relevance to other research institutes in similar contexts to advocate and support research capacity strengthening efforts.
The impact of tensioning device mal-positioning on strand tension during Anterior Cruciate Ligament reconstruction
Authors: Maharjan Rajesh , Costi John J , Stanley Richard M , Martin David , Hearn Trevor C , Field John R
Published: July 2011

Background

In order to confer optimal strength and stiffness to the graft in Anterior Cruciate Ligament (ACL) reconstruction, the maintenance of equal strand tension prior to fixation, is desired; positioning of the tensioning device can significantly affect strand tension This study aimed to determine the effect of tensioning device mal-positioning on individual strand tension in simulated cadaveric ACL reconstructions.

Methods

Twenty cadaveric specimens, comprising bovine tibia and tendon harvested from sheep, were used to simulate ACL reconstruction with a looped four-strand tendon graft. A proprietary tensioning device was used to tension the graft during tibial component fixation with graft tension recorded using load cells. The effects of the tensioning device at extreme angles, and in various locking states, was evaluated.

Results

Strand tension varied significantly when the tensioning device was held at extreme angles (p < 0.001) or in 'locked' configurations of the tensioning device (p < 0.046). Tendon position also produced significant effects (p < 0.016) on the resultant strand tension.

Conclusion

An even distribution of tension among individual graft strands is obtained by maintaining the tensioning device in an unlocked state, aligned with the longitudinal axis of the tibial tunnel. If the maintenance of equal strand tension during tibial fixation of grafts is important, close attention must be paid to positioning of the tensioning device in order to optimize the resultant graft tension and, by implication, the strength and stiffness of the graft and ultimately, surgical outcome.
Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control study
Authors: Carrasquillo Minerva M , Belbin Olivia , Hunter Talisha A , Ma Li , Bisceglio Gina D , Zou Fanggeng , Crook Julia E , Pankratz V Shane , Sando Sigrid B , Aasly Jan O , Barcikowska Maria , Wszolek Zbigniew K , Dickson Dennis W , Graff-Radford Neill R , Petersen Ronald C , Passmore Peter , Morgan Kevin ,   for the Alzheimer's Research UK (ARUK) consortium, Younkin Steven G
Published: July 2011

Background

A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near MS4A4A, CD2AP, EPHA1 and CD33. Meta-analyses of this and a previously published GWAS revealed significant association at ABCA7 and MS4A, independent evidence for association of CD2AP, CD33 and EPHA1 and an opposing yet significant association of a variant near ARID5B. In this study, we genotyped five variants (in or near CD2AP, EPHA1, ARID5B, and CD33) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE ε4 dosage.

Results

We found no significant evidence of series heterogeneity. Associations with LOAD were successfully replicated for EPHA1 (rs11767557; OR = 0.87, p = 5 × 10-4) and CD33 (rs3865444; OR = 0.92, p = 0.049), with odds ratios comparable to those previously reported. Although the two ARID5B variants (rs2588969 and rs494288) showed significant association with LOAD in meta-analysis of our dataset (p = 0.046 and 0.008, respectively), the associations did not survive adjustment for covariates (p = 0.30 and 0.11, respectively). We had insufficient evidence in our data to support the association of the CD2AP variant (rs9349407, p = 0.56).

Conclusions

Our data overwhelmingly support the association of EPHA1 and CD33 variants with LOAD risk: addition of our data to the results previously reported (total n > 42,000) increased the strength of evidence for these variants, providing impressive p-values of 2.1 × 10-15 (EPHA1) and 1.8 × 10-13 (CD33).
Bilateral herpetic keratitis presenting with unilateral neurotrophic keratitis in pemphigus foliaceus: a case report
Authors: Yang Hee K , Han Young K , Wee Won R , Lee Jin H , Kwon Ji W
Published: July 2011

Introduction

We report a case of bilateral herpetic keratitis developing after rapid oral corticosteroid tapering in a patient with pemphigus foliaceus, which was followed by unilateral neurotrophic keratitis that was treated with amniotic membrane transplantation.

Case presentation

A 71-year-old Korean man developed bilateral herpetic keratitis one week after rapid tapering of systemic corticosteroid. He had been on high-dose oral corticosteroid and azathioprine therapy for six months for treatment of pemphigus foliaceus. Topical acyclovir ointment was prescribed. A week later, our patient's right eye had healed, but his left eye showed increased stromal edema with enlarged epithelial defects. He was prescribed oral acyclovir with topical broad-spectrum antibiotics applied to his left eye. The stromal edema cleared within a week but the epithelial defect remained unchanged. An amniotic membrane transplantation was performed on our patient's left eye, and his epithelial defect had totally healed three weeks later.

Conclusions

Patients with autoimmune disease or who are on immunosuppressive therapy have a higher chance of developing bilateral herpetic keratitis. Although rare, the condition may be followed by unilateral neurotrophic keratitis. Rapid corticosteroid tapering may act as a triggering factor for viral infection or reactivation of herpes.
Periodontal disease in a patient with Prader-Willi syndrome: a case report
Authors: Yanagita Manabu , Hirano Hiroyuki , Kobashi Mariko , Nozaki Takenori , Yamada Satoru , Kitamura Masahiro , Murakami Shinya
Published: July 2011

Introduction

Prader-Willi syndrome is a complex genetic disease caused by lack of expression of paternally inherited genes on chromosome 15q11-q13. The prevalence of Prader-Willi syndrome is estimated to be one in 10,000 to 25,000. However, descriptions of the oral and dental phenotype are rare.

Case presentation

We describe the clinical presentation and periodontal findings in a 20-year-old Japanese man with previously diagnosed Prader-Willi syndrome. Clinical and radiographic findings confirmed the diagnosis of periodontitis. The most striking oral findings were anterior open bite, and crowding and attrition of the lower first molars. Periodontal treatment consisted of tooth-brushing instruction and scaling. Home care involved recommended use of adjunctive chlorhexidine gel for tooth brushing twice a week and chlorhexidine mouthwash twice daily. Gingival swelling improved, but further treatment will be required and our patient's oral hygiene remains poor. The present treatment of tooth-brushing instruction and scaling every three weeks therefore only represents a temporary solution.

Conclusions

Rather than being a direct result of genetic defects, periodontal diseases in Prader-Willi syndrome may largely result from a loss of cuspid guidance leading to traumatic occlusion, which in turn leads to the development of periodontal diseases and dental plaque because of poor oral hygiene. These could be avoided by early interventions to improve occlusion and regular follow-up to monitor oral hygiene. This report emphasizes the importance of long-term follow-up of oral health care by dental practitioners, especially pediatric dentists, to prevent periodontal disease and dental caries in patients with Prader-Willi syndrome, who appear to have problems maintaining their own oral health.
Sinonasal neuroendocrine carcinoma: impact of differentiation status on response and outcome
Authors: Likhacheva Anna , Rosenthal David I , Hanna Ehab , Kupferman Michael , DeMonte Franco , El-Naggar Adel K
Published: July 2011

Background

The impact of tumor differentiation on the behavior and response of sinonasal neuroendocrine carcinoma is unknown.

Methods

We performed a retrospective review of the patients treated for neuroendocrine carcinoma (NEC) of the nasal cavity or paranasal sinuses from 1992 to 2008 at MDACC.

Results

The results of our study suggest that pathologic differentiation may not be a critical factor in the clinical management of patients with NEC of the sinonasal tract. This is in contrast to laryngeal and lung NEC for which pathological differentiation has traditionally guided clinical management.

Conclusion

Mutlimodality approach should be the cornerstone of treating sinonasal NEC regardless of their differentiation. Specifically, RT may provide durable local control for patients with moderately differentiated NEC if resection is not feasible or desirable, while surgical resection can benefit patients with chemo-resistant or radio-resistant disease.
'Score to Door Time', a benchmarking tool for rapid response systems: a pilot multi-centre service evaluation
Authors: Oglesby Kieran J , Durham Lesley , Welch John , Subbe Christian P
Published: July 2011

Introduction

Rapid Response Systems were created to minimise delays in recognition and treatment of deteriorating patients on general wards. Physiological 'track and trigger' systems are used to alert a team with critical care skills to stabilise patients and expedite admission to intensive care units. No benchmarking tool exists to facilitate comparison for quality assurance. This study was designed to create and test a tool to analyse the efficiency of intensive care admission processes.

Methods

We conducted a pilot multicentre service evaluation of patients admitted to 17 intensive care units from the United Kingdom, Ireland, Denmark, United States of America and Australia. Physiological abnormalities were recorded via a standardised track and trigger score (VitalPAC™ Early Warning Score). The period between the time of initial physiological abnormality (Score) and admission to intensive care (Door) was recorded as 'Score to Door Time'. Participants subsequently suggested causes for admission delays.

Results

Score to Door Time for 177 admissions was a median of 4:10 hours (interquartile range (IQR) 1:49 to 9:10). Time from physiological trigger to activation of a Rapid Response System was a median 0:47 hours (IQR 0:00 to 2:15). Time from call-out to intensive care admission was a median of 2:45 hours (IQR 1:19 to 6:32). A total of 127 (71%) admissions were deemed to have been delayed. Stepwise linear regression analysis yielded three significant predictors of longer Score to Door Time: being treated in a British centre, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and increasing age. Binary regression analysis demonstrated a significant association (P < 0.045) of APACHE II scores >20 with Score to Door Times greater than the median 4:10 hours.

Conclusions

Score to Door Time seemed to be largely independent of illness severity and, when combined with qualitative feedback from centres, suggests that admission delays could be due to organisational issues, rather than patient factors. Score to Door Time could act as a suitable benchmarking tool for Rapid Response Systems and helps to delineate avoidable organisational delays in the care of patients at risk of catastrophic deterioration.
The late phase of sepsis is characterized by an increased microbiological burden and death rate
Authors: Otto Gordon P , Sossdorf Maik , Claus Ralf A , Rödel Jürgen , Menge Katja , Reinhart Konrad , Bauer Michael , Riedemann Niels C
Published: July 2011

Introduction

Recent models capturing the pathophysiology of sepsis and ex-vivo data from patients are speculating about immunosuppression in the so-called late phase of sepsis. Clinical data regarding survival and microbiological burden are missing. The aim of this study was to determine the clinical significance of the 'late phase' of sepsis with respect to overall survival and occurrence of microbiological findings.

Methods

In a retrospective trial, 16,041 patient charts from a university intensive care unit were screened, and 999 patients with severe sepsis or septic shock were identified. Three phases were established according to the mortality peaks which were separated by two distinct nadirs: phase I (days 1 to 5), phase II (days 6 to 15) and phase III (days 16 to 150). Patients were analyzed for outcome, SOFA scores, procalcitonin levels, antimicrobial treatment, dialysis, mechanical ventilation and results of blood cultures during their hospital stay.

Results

Out of 999 enrolled patients, 308 died during the course of sepsis presenting a characteristic mortality rate (30.8%) with three distinct mortality peaks (at days 2, 7 and 17). Overall 36.7% of all deaths occurred in the early phase (phase I) and 63.3% during the later phases (phase II + III). In total 2,117 blood cultures were drawn. In phase I, 882 blood cultures were drawn, representing a sampling rate of 88% with a positive rate of 14.9%. In phase II, 461 samples were taken, indicating a sampling rate of 52% and a positive rate of 11.3%. Within phase III, 524 samples were obtained representing a sampling rate of 66% with a positive rate of 15.3%, which was significantly higher compared to the positive rate of phase II and similar to phase I. In particular, the rate of typically opportunistic bacteria increased significantly from 9% in phase I up to 18% in phase III. The same is true for Candida spp. (phase I 13%, phase III 30%).

Conclusions

The later phase of sepsis is associated with a significant re-increase of positive blood culture results, especially regarding opportunistic bacteria and fungi. These observations warrant further studies focusing on the underlying mechanisms resulting in this outcome burden in the later phase of sepsis.
MTCH2 in Human White Adipose Tissue and Obesity
Authors: Kulyté Agné , Rydén Mikael , Mejhert Niklas , Dungner Elisabeth , Sjölin Eva , Arner Peter , Dahlman Ingrid
Published: July 2011

Context:

Genome-wide association studies have identified single-nucleotide polymorphisms in approximately 40 loci associated with obesity-related traits. How these loci regulate obesity is largely unknown. One obesity-associated single-nucleotide polymorphism is close to the MTCH2 gene (mitochondrial carrier homolog 2).

Objective:

The objective of the study was to assess the expression of genes in obesity-associated loci in abdominal sc white adipose tissue (scWAT) in relation to obesity. A more comprehensive expression study was performed on MTCH2.

Design:

mRNA levels of 66 genes from 40 loci were determined by microarray in scWAT from lean and obese women (n = 30). MTCH2 mRNA was measured by quantitative RT-PCR in lean and obese before and after weight loss in intact adipose pieces and isolated adipocytes, paired samples of scWAT and omental WAT, and primary adipocyte cultures (n = 191 subjects in total). MTCH2 genotypes were compared with mRNA expression in 96 women. MTCH2 protein was examined in scWAT of 38 individuals.

Results:

Adipose expression of eight genes was significantly associated with obesity; of these, MTCH2 displayed the highest absolute signal. MTCH2 mRNA and protein expression was significantly increased in obese women but was not affected by weight loss. MTCH2 was enriched in isolated fat cells and increased during adipocyte differentiation. There was no cis influence of MTCH2 genotypes on mRNA levels.

Conclusion:

MTCH2 is highly expressed in human WAT and adipocytes with increased levels in obese women. These results suggest that MTCH2 may play a role in cellular processes underlying obesity.
“The Universal Alliance of All Peoples”: Romantic Socialists, the Human Family, and the Defense of Empire during the July Monarchy, 1830–1848
Authors: Andrews Naomi J.
Published: July 2011

This article documents the procolonial rhetoric among romantic socialists in France during the July Monarchy (1830–48), demonstrating its pervasiveness. It argues that these years must be highlighted as key to the transition from eighteenth-century universalist ideas of humanity toward taxonomies of national, racial, and sexual difference that underpinned the rationale of empire in the second half of the nineteenth century. It explores the views on colonialism espoused by socialists such as Etienne Cabet, Pierre Leroux, Constantin Pecqueur, and Jean Reynaud; situates them in the broad socialist consensus on empire; and demonstrates the relationship between these men's socialism and their colonialism. Further, it contextualizes their advocacy for colonialism in relation to contemporary debates about the abolition of slavery and free trade. Finally, it demonstrates the coexistence of universalist and particularist language in romantic socialist discourse on colonial expansion and its importance to the developing logic of the mission civilisatrice.

Cet article décrit la rhétorique procoloniale parmi les socialistes romantiques durant la Monarchie de Juillet en France, démontrant à quel point elle était omniprésente. Il soutient que cette époque doit être considérée comme primordiale pour la transition des idées universalistes de l'humanité aux taxonomies des différences entre nations, races et sexes qui étaient à la base des justifications de l'empire pendant la deuxième moitié du dixneuvième siècle. Il sonde les opinions sur le colonialisme partagées par les socialistes tels que Etienne Cabet, Pierre Leroux, Constantin Pecqueur et Jean Reynaud, et les situe dans le consensus des socialistes, démontrant la relation entre leur socialisme et leur colonialisme. Enfin, il démontre la coexistence des langues universalistes et « particularistes » dans le discours socialiste romantique sur l'expansion coloniale et son importance pour la rhétorique de la mission civilisatrice en pleine expansion à cette époque.
Differential adhesion and actomyosin cable collaborate to drive Echinoid-mediated cell sorting
Authors: Chang Li-Hsun , Chen Peilong , Lien Mong-Ting , Ho Yu-Huei , Lin Chiao-Ming , Pan Yi-Ting , Wei Shu-Yi , Hsu Jui-Chou
Published: July 2011

Cell sorting involves the segregation of two cell populations into `immiscible' adjacent tissues with smooth borders. Echinoid (Ed), a nectin ortholog, is an adherens junction protein in Drosophila, and cells mutant for ed sort out from the surrounding wild-type cells. However, it remains unknown which factors trigger cell sorting. Here, we dissect the sequence of this process and find that cell sorting occurs when differential expression of Ed triggers the assembly of actomyosin cable. Conversely, Ed-mediated cell sorting can be rescued by recruitment of Ed, via homophilic or heterophilic interactions, to the wild-type cell side of the clonal interface, even when differential Ed expression persists. We found, unexpectedly, that when actomyosin cable was largely absent, differential adhesion was sufficient to cause limited cell segregation but with a jagged tissue border (imperfect sorting). We propose that Ed-mediated cell sorting is driven both by differential Ed adhesion that induces cell segregation with a jagged border and by actomyosin cable assembly at the interface that smoothens this border.
A critical balance between Cyclin B synthesis and Myt1 activity controls meiosis entry inXenopusoocytes
Authors: Gaffré Melina , Martoriati Alain , Belhachemi Naima , Chambon Jean-Philippe , Houliston Evelyn , Jessus Catherine , Karaiskou Anthi
Published: July 2011

In fully grown oocytes, meiosis is arrested at first prophase until species-specific initiation signals trigger maturation. Meiotic resumption universally involves early activation of M phase-promoting factor (Cdc2 kinase-Cyclin B complex, MPF) by dephosphorylation of the inhibitory Thr14/Tyr15 sites of Cdc2. However, underlying mechanisms vary. In Xenopus oocytes, deciphering the intervening chain of events has been hampered by a sensitive amplification loop involving Cdc2-Cyclin B, the inhibitory kinase Myt1 and the activating phosphatase Cdc25. In this study we provide evidence that the critical event in meiotic resumption is a change in the balance between inhibitory Myt1 activity and Cyclin B neosynthesis. First, we show that in fully grown oocytes Myt1 is essential for maintaining prophase I arrest. Second, we demonstrate that, upon upregulation of Cyclin B synthesis in response to progesterone, rapid inactivating phosphorylation of Myt1 occurs, mediated by Cdc2 and without any significant contribution of Mos/MAPK or Plx1. We propose a model in which the appearance of active MPF complexes following increased Cyclin B synthesis causes Myt1 inhibition, upstream of the MPF/Cdc25 amplification loop.
Kif7 promotes hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu
Authors: Hsu Shu-Hsuan C. , Zhang Xiaoyun , Yu Chunying , Li Zhu Juan , Wunder Jay S. , Hui Chi-Chung , Alman Benjamin A.
Published: July 2011

Proper regulation of Indian hedgehog (Ihh) signaling is vital for chondrocyte proliferation and differentiation in the growth plate. Its dysregulation causes skeletal dysplasia, osteoarthritis or cartilaginous neoplasia. Here, we show that Suppressor of fused (Sufu) and Kif7 are essential regulators of Ihh signaling. While Sufu acts as a negative regulator of Gli transcription factors, Kif7 functions both positively and negatively in chondrocytes. Kif7 plays a role in the turnover of Sufu and the exclusion of Sufu-Gli complexes from the primary cilium. Importantly, halving the dose of Sufu restores normal hedgehog pathway activity and chondrocyte development in Kif7-null mice, demonstrating that the positive role of Kif7 is to restrict the inhibitory activity of Sufu. Furthermore, Kif7 also inhibits Gli transcriptional activity in the chondrocytes when Sufu function is absent. Therefore, Kif7 regulates the activity of Gli transcription factors through both Sufu-dependent and -independent mechanisms.
The role of SmpB and the ribosomal decoding center in licensing tmRNA entry into stalled ribosomes
Authors: Miller Mickey R. , Liu Zhu , Cazier DeAnna J. , Gebhard Grant M. , Herron Steven R. , Zaher Hani S. , Green Rachel , Buskirk Allen R.
Published: July 2011

In bacteria, stalled ribosomes are recycled by a hybrid transfer–messenger RNA (tmRNA). Like tRNA, tmRNA is aminoacylated with alanine and is delivered to the ribosome by EF-Tu, where it reacts with the growing polypeptide chain. tmRNA entry into stalled ribosomes poses a challenge to our understanding of ribosome function because it occurs in the absence of a codon–anticodon interaction. Instead, tmRNA entry is licensed by the binding of its protein partner, SmpB, to the ribosomal decoding center. We analyzed a series of SmpB mutants and found that its C-terminal tail is essential for tmRNA accommodation but not for EF-Tu activation. We obtained evidence that the tail likely functions as a helix on the ribosome to promote accommodation and identified key residues in the tail essential for this step. In addition, our mutational analysis points to a role for the conserved K131GKK tail residues in trans-translation after peptidyl transfer to tmRNA, presumably EF-G-mediated translocation or translation of the tmRNA template. Surprisingly, analysis of A1492, A1493, and G530 mutants reveals that while these ribosomal nucleotides are essential for normal tRNA selection, they play little to no role in peptidyl transfer to tmRNA. These studies clarify how SmpB interacts with the ribosomal decoding center to license tmRNA entry into stalled ribosomes.
How Does Status Affect Performance? Status as an Asset vs. Status as a Liability in the PGA and NASCAR
Authors: Bothner Matthew S. , Kim Young-Kyu , Smith Edward Bishop
Published: July 2011

Two competing predictions about the effect of status on performance appear in the organizational theory and sociological literatures. On one hand, various researchers have asserted that status improves performance. This line of work emphasizes tangible and intangible resources that accrue to occupants of high-status positions and therefore pictures status as an asset. On the other hand, a second stream of research argues that status instead diminishes performance. This alternative line of work emphasizes complacency and distraction as deleterious processes that plague occupants of high-status positions and thus portrays status as a liability. Which of these two perspectives best characterizes the actual performance of individuals in a competitive setting? And are they in any way reconcilable? In this paper, we summarize these two perspectives and test them in two empirical settings: the Professional Golf Association (PGA) and the National Association for Stock Car Auto Racing (NASCAR). Using panel data on the PGA Tour, we model golfers' strokes from par in each competition as a function of their status in the sport. Using similar data on NASCAR's Winston Cup Series, we model drivers' speed in the qualifying round as a function of their status in the sport. We find curvilinear effects of status in both contexts. Performance improves with status until a very high level of status is reached, after which performance wanes. This result not only concurs with the view that status brings tangible and intangible resources but also provides empirical support for the contention that status fosters dispositions and behaviors that ultimately erode performance.
Trefoil factor family peptides are increased in the saliva of children with mucositis
Authors: Verey Fran , Nexo Ebba , Greenwood Rosemary , Berry Monica , Corfield Anthony P.
Published: July 2011

Mucositis is a painful ulcerative condition of the oral cavity and gastrointestinal tract, occurring in association with chemotherapy and radiotherapy regimes. Trefoil factor family peptides (TFF, trefoil peptides), present in saliva, contribute to epithelial restitution and repair and are therefore potentially important in the healing phase of mucositis. This study aimed to assess any changes in the levels of trefoil peptides in oncology patients with and without mucositis.

Saliva was collected from healthy children, pre-treatment oncology patients, neutropenic patients on treatment with no oral disease and mucositic patients. TFF1, 2 and 3 were quantified using ELISA.

In healthy children TFF2 and 3 were positively correlated with age (ρ=0.454, p=0.01 for TFF2; ρ=0.410, p=0.05 for TFF3 Spearman rank correlation). TFF3 was higher in mucositis compared to all other groups. A linear regression prediction model indicated that TFF3, but not TFF1 and TFF2, was significantly different in mucositic and healthy controls, suggesting an altered pattern of trefoil peptide secretion (p=0.021).

This study is the first to focus on trefoil peptides in paediatric saliva. It shows the correlation between TFF2, TFF3 and age in healthy children. Paediatric mucositis disease occurs in the presence of increased concentrations and an altered pattern of trefoil peptides.
Methylenetetrahydrofolate reductase C677T polymorphism and congenital heart disease: a meta-analysis
Authors: Nie Yu , Gu Haiyong , Gong Jie , Wang Jue , Gong Dingxu , Cong Xiangfeng , Chen Xi , Hu Shengshou
Published: July 2011

As a key enzyme in folate metabolism, 5,10-methylenetetrahydrofolate reductase (MTHFR) regulates the homeostasis between DNA synthesis and methylation. Data on the association between the

To assess the relationship between the

The

Our meta-analysis suggests that genotypes for the
Characterization of the human SLC30A8 promoter and intronic enhancer
Authors: Pound Lynley D , Sarkar Suparna A , Cauchi Stéphane , Wang Yingda , Oeser James K , Lee Catherine E , Froguel Philippe , Hutton John C , O'Brien Richard M
Published: July 2011

Genome-wide association studies have shown that a polymorphic variant inSLC30A8, which encodes zinc transporter-8, is associated with altered susceptibility to type 2 diabetes (T2D). This association is consistent with the observation that glucose-stimulated insulin secretion is decreased in islets isolated fromSlc30a8knockout mice. In this study, immunohistochemical staining was first used to show thatSLC30A8is expressed specifically in pancreatic islets. Fusion gene studies were then used to examine the molecular basis for the islet-specific expression ofSLC30A8. The analysis ofSLC30A8-luciferase expression in βTC-3 cells revealed that the proximal promoter region, located between −6154 and −1, relative to the translation start site, was only active in stable but not transient transfections. VISTA analyses identified three regions in theSLC30A8promoter and a region inSLC30A8intron 2 that are conserved in the mouseSlc30a8gene. Additional fusion gene experiments demonstrated that none of theseSlc30a8promoter regions exhibited enhancer activity when ligated to a heterologous promoter whereas the conserved region inSLC30A8intron 2 conferred elevated reporter gene expression selectively in βTC-3 but not in αTC-6 cells. Finally, the functional effects of a single nucleotide polymorphism (SNP), rs62510556, in this conserved intron 2 enhancer were investigated. Gel retardation studies showed that rs62510556 affects the binding of an unknown transcription factor and fusion gene analyses showed that it modulates enhancer activity. However, genetic analyses suggest that this SNP is not a causal variant that contributes to the association betweenSLC30A8and T2D, at least in Europeans.
Processing of proglucagon to GLP-1 in pancreatic α-cells: is this a paracrine mechanism enabling GLP-1 to act on β-cells?
Authors: Whalley N M , Pritchard L E , Smith D M , White A
Published: July 2011

Proglucagon is cleaved to glucagon by prohormone convertase 2 (PC2) in pancreatic α-cells, but is cleaved to glucagon-like peptide-1 (GLP-1) by PC1 in intestinal L-cells. The aim of this study was to identify mechanisms which switch processing of proglucagon to generate GLP-1 in the pancreas, given that GLP-1 can increase insulin secretion and β-cell mass. The α-cell line, αTC1-6, expressed PC1 at low levels and GLP-1 was detected in cells and in culture media. GLP-1 was also found in isolated human islets and in rat islets cultured for 7 days. High glucose concentrations increasedPc1gene expression and PC1 protein in rat islets. High glucose (25 mM) also increased GLP-1 but decreased glucagon secretion from αTC1-6 cells suggesting a switch in processing to favour GLP-1. Three G protein-coupled receptors, GPR120, TGR5 and GPR119, implicated in the release of GLP-1 from L-cells are expressed in αTC1-6 cells. Incubation of these cells with an agonist of TGR5 increased PC1 promoter activity and GLP-1 secretion suggesting that this is a mechanism for switching processing to GLP-1 in the pancreas. Treatment of isolated rat islets with streptozotocin caused β-cell toxicity as evidenced by decreased glucose-stimulated insulin secretion. This increased GLP-1 but not glucagon in the islets. In summary, proglucagon can be processed to GLP-1 in pancreatic cells. This process is upregulated by elevated glucose, activation of TGR5 and β-cell destruction. Understanding this phenomenon may lead to advances in therapies to protect β-cell mass, and thereby slow progression from insulin resistance to type 2 diabetes.
The influence of the BRAF V600E mutation in thyroid cancer cell lines on the anticancer effects of 5-aminoimidazole-4-carboxamide-ribonucleoside
Authors: Choi Hyun-Jeung , Kim Tae Yong , Chung Namhyun , Yim Ji Hye , Kim Won Gu , Kim Jin A , Kim Won Bae , Shong Young Kee
Published: July 2011

5-Aminoimidazole-4-carboxamide-ribonucleoside (AICAR) is an activator of 5′-AMP-activated protein kinase (AMPK), which plays a role in the maintenance of cellular energy homeostasis. Activated AMPK inhibits the protein kinase mechanistic target of rapamycin, thereby reducing the extent of protein translation and suppressing both cell growth and cell cycle entry. Recent reports indicate that AMPK-mediated growth inhibition is achieved via an action of the RAF–MEK–ERK mitogen-activated protein kinase pathway in melanoma cells harboring the V600E mutant form of the BRAF oncogene. In this study, we investigated the anti-cancer efficacy of AICAR by measuring its effects on proliferation, apoptosis, and cell cycle progression of BRAF wild-type and V600E-mutant thyroid cancer cell lines. We also explored the mechanism underlying these effects. AICAR inhibited the proliferation of BRAF V600E-mutant thyroid cancer cell lines more strongly than was the case with wild-type cell lines. The suppressive effect of AICAR on cell proliferation was associated with increased S-phase cell cycle arrest and apoptosis. Interestingly, AICAR suppressed phosphorylation of ERK and p70S6K in BRAF V600E-mutant thyroid cancer cells, but rather increased phosphorylation in wild-type cells. Together, the results indicate that AICAR-induced AMPK activation in BRAF V600E-mutant thyroid cancer cell lines resulted in increases in apoptosis and S-phase arrest via downregulation of ERK and p70S6K activity. Thus, regulation of AMPK activity may be potentially useful as a therapy for thyroid cancer if the cancer harbors a BRAF V600E mutation.
Bovine blastocysts with developmental competence to term share similar expression of developmentally important genes although derived from different culture environments
Authors: Ghanem N , Salilew-Wondim D , Gad A , Tesfaye D , Phatsara C , Tholen E , Looft C , Schellander K , Hoelker M
Published: July 2011

This study was conducted to investigate the gene expression profile of in vivo-derived bovine embryo biopsies based on pregnancy outcomes after transferring to recipients. For this, biopsies of 30–40% embryos were taken from grade I blastocysts (International Embryo Transfer Society Manual) and the remaining 60–70% of the intact embryos were transferred to recipients. Frozen biopsies were pooled into three distinct groups based on the pregnancy outcome after transferring the corresponding parts, namely those resulting in no pregnancy (NP), pregnancy loss (PL), and calf delivery (CD). Array analysis revealed a total of 41 and 43 genes to be differentially expressed between biopsies derived from blastocysts resulting in NP versus CD and PL versus CD respectively. Genes regulating placental development and embryo maternal interaction (PLAC8) were found to be upregulated in embryo biopsies that ended up with CD. Embryo biopsies that failed to induce pregnancy were enriched with mitochondrial transcripts (Fl405) and stress-related genes (HSPD1). Overall, gene expression profiles of blastocysts resulting in NP and CD shared similar expression profiles with respect to genes playing significant roles in preimplantation development of embryo. Finally, comparing the transcript signatures of in vivo- and in vitro-derived embryos with developmental competence to term revealed a similarity in the relative abundance of 18 genes. Therefore, we were able to present a genetic signature associated with term developmental competence independent of the environmental origin of the transferred blastocysts.
Interval Annealing During Alternating Pulse Deposition
Authors: Conley J.F. , Tweet D.J. , Ono Y. , Stecker G.
Published: July 2011

Thin films deposited via atomic layer deposition at low temperature tend to be less dense than bulk material and typically require high temperature post deposition annealing for densification and removal of unreacted precursor ligands. We have found that improved film densification can be achieved by interval annealing, in which in-situ moderate temperature (∼420°C) rapid thermal anneals are performed after every n deposition cycles. HfO2 film density and refractive index were found to increase with decreasing anneal interval (more frequent annealing). The highest density films could be achieved only by every-cycle annealing and could not be achieved by post deposition annealing. The densified every cycle annealed films have been shown to have improved equivalent thickness and leakage and decreased interfacial layer thickness.
Dielectric breakdown Characteristics of poly-Si/HfAlOx/SiON gate stack
Authors: Torii Kazuyoshi , Ohji Hiroshi , Mutoh Akiyoshi , Kawahara Takaaki , Mitsuhashi Riichiro , Horiuchi Atsushi , Miyazaki S. , Kitajima Hiroshi
Published: July 2011

The dielectric breakdown behavior of poly-Si gate CMOSFETs with HfAlOx/SiON gate dielectric fabricated using mass production worthy 300 mm process was investigated. If SiO2 is used as an interfacial layer (IL), the IL reduction and the intermixing between the HfAlOx layer and the IL occurred, which causes extrinsic breakdown. By using the SiON of [N]=18% as an IL and setting the maximum temperature after the HfAlOx deposition to be 1000°C, the interfacial reaction was suppressed and the extrinsic breakdown component was eliminated. In the case of the n-capacitor accumulation, an abrupt increase of gate leakage was observed, which is believed to correspond to the IL breakdown. The mean time to failure (MTTF for 0.1cm2 at 125°C) is long enough. On the other hand, gate current initially decreases and then starts to increase in the case of p-capacitor accumulation. If we define the time to breakdown at the onset of current increase, the MTTF would be only 3.7 years if it obeys the V-plot (MTTF predicted by 1/V-plot was 1.6×107 years).
Reduction of CV Hysteresis in Metal/High-k MISFETs Using Flash Lamp Post Deposition Annealing
Authors: Matsuki Takeo , Akasaka Yasushi , Hayashi Kiyoshi , Noguchi Masataka , Yamashita Koji , Syoji Hideyuki , Torii Kazuyoshi , Kasai Naoki , Arikado Tsunetoshi
Published: July 2011

A Xe flash lamp (FL) heating technique was applied to the post deposition annealing process (PDA) for HfAlOx/SiO2 gate insulator with poly-Si or W/TiN gate electrode in a gate last based process. In the case of W/TiN/HfAlOx/SiO2, CV hysteresis with less than 10mV was achieved using the FL-PDA. However, the FL-PDA increased hysteresis width up to over 100 mV when poly-Si was used as a gate electrode. That occurred also with low temperature (700 °C) rapid thermal PDA process. The lower thermal budget achieved by the flash lamp annealing and the metal gate is effective to suppress the interfacial reaction which causes the traps responsible for the hysteresis. Charge trapping in the W/TiN/HfAlOx/SiO2 was evaluated using CV hysteresis characteristics in the MISFETs and the MIS capacitors. Electron was major trapped charge of the HfAlOx.
Analysis of Ferroelectric Microcapacitors by Scanning Probe Microscope
Authors: Kin Nobuhiro , Honda Koichiro
Published: July 2011

To develop higher density FRAM requires reducing cell size. Therefore, the size effects resulting from device processing and the material's physical properties must be measured. Therefore, analyzing the electric characteristics of a single bit cell capacitor has become important. Two known characteristics of ferroelectric material are that the Vc increases at low temperatures, and the Pr falls at high temperatures. To further evaluate the impact of temperature on ferroelectrics, we constructed a new evaluation system based on a scanning probe microscope, that can measure the electric characteristics of a single bit cell capacitor. This system can be used in the temperature range from −120 degrees to 300 degrees C. We accomplished this by circulating liquid nitrogen around a SPM stage and by using an electrical heater. We measured the electrical properties of ferroelectric microcapacitors by using a sample with IrOx/PZT/Pt structure. Our measurements revealed that 2Pr really increases at low temperatures, and Pr decreases at high temperatures. That is, we have shown that Vc increases 30% at low temperatures and Pr decreases 10% also in an actual FRAM single bit cell capacitor.
Effect of different annealing procedures on the microstructure and the electrical properties of CSD derived (Ba,Sr)TiO3 thin films.
Authors: Halder Sandip , Schneller Theodor , Waser Rainer
Published: July 2011

Processing of BST thin films is becoming more and more important for microwave electronics and for its probable incorporation in future high density DRAM's. A co-relation between processing and final device characteristics is of utmost importance. Differences in microstructure and electrical properties were observed when chemical solution deposited thin films were annealed using a conventional diffusion furnace, rapid thermal annealing furnace with different heating ramps, and a hot plate for pyrolysis prior crystallization. The solution was made with the propionate route and then deposited on Pt coated silicon wafers. Cross-sectional SEM's were performed on the different films. It was found that the microstructure depended on the annealing method of the film. The electrical properties of the films were also found to vary considerably. Frequency dependence of the dielectric constant was studied. The leakage study on different films was performed at different temperatures.
A Study of APCVD-Deposited TiO2Characteristics in the Structure of a Tunneling Transistor
Authors: Behnam A. , Hekmatshoar B. , Mohajerzadeh S. , Arvan B. , Karbassian F. , Khakifirooz A.
Published: July 2011

TiO2 and nickel-silicide layers are consequently deposited and micro machined to compose a mesa-structured tunneling transistor. The depositions are done with the RF-sputtering method and the electrical and physical characteristics of the products are investigated. Transistors show an amplification coefficient of about 20. To improve the quality and coverage of the TiO2 layer, the oxide deposition is made by means of an APCVD reactor. The grown oxide shows a dielectric coefficient between 19 and 21 and its breakdown field is about 107 V/cm.
Investigations of Metal Gate Electrodes on HfO2 Gate Dielectrics
Authors: Schaeffer Jamie , Samavedam Sri , Fonseca Leonardo , Capasso Cristiano , Adetutu Olubunmi , Gilmer David , Hobbs Chris , Luckowski Eric , Gregory Rich , Jiang Zhi-Xiong , Liang Yong , Moore Karen , Roan Darrell , Nguyen Bich-Yen , Tobin Phil , White Bruce
Published: July 2011

As traditional poly-silicon gated MOSFET devices scale, the additional series capacitance due to poly-silicon depletion becomes an increasingly large fraction of the total gate capacitance, excessive boron penetration causes threshold voltage shifts, and the gate resistance is elevated. To solve these problems and continue aggressive device scaling we are studying metal electrodes with suitable work-functions and sufficient physical and electrical stability. Our studies of metal gates on HfO2 indicate that excessive inter-diffusion, inadequate phase stability, and interfacial reactions are mechanisms of failure at source drain activation temperatures that must be considered during the electrode selection process. Understanding the physical properties of the metal gate – HfO2 interface is critical to understanding the electrical behavior of MOS devices. Of particular interest is Fermi level pinning, a phenomenon that occurs at metal – dielectric interfaces which causes undesirable shifts in the effective metal work function. The magnitude of Fermi level pinning on HfO2 electrodes is studied with Pt and LaB6 electrodes. In addition, the intrinsic and extrinsic contributions to Fermi level pinning of platinum electrodes on HfO2 gate dielectrics are investigated by examining the impact of oxygen and forming gas anneals on the work function of platinum-HfO2-silicon capacitors. The presence of interfacial oxygen vacancies or Pt-Hf bonds is believed to be responsible for a degree of pinning that is stronger than predicted from the MIGS model alone. Interface chemistry and defects influence the effective metal work function.
Retarded Growth of Sputtered HfO2 Films on Germanium
Authors: Kita Koji , Sasagawa Masashi , Toyama Masahiro , Kyuno Kentaro , Toriumi Akira
Published: July 2011

HfO2 films were deposited by reactive sputtering on Ge and Si substrates simultaneously, and we found not only the interface layer but the HfO2 film was thinner on Ge substrate compared with that on Si substrate. A metallic Hf layer has a crucial role for the thickness differences of both interface layer and HfO2 film, since those thickness differences were observed only when an ultrathin metallic Hf layer was predeposited before HfO2 film deposition. The role of metallic Hf is understandable by assuming a formation of volatile Hf-Ge-O ternary compounds at the early stage of film growth. These results show an advantage of HfO2/Ge over HfO2/Si systems from the viewpoint of further scaling of electrical equivalent thickness of the gate oxide films.
Electrical modeling and simulation of nanoscale MOS devices with a high-permittivity dielectric gate stack
Authors: Autran J.L. , Munteanu D. , Houssa M. , Bescond M. , Garros X. , Leroux C.
Published: July 2011

The electrical behavior of decananometer MOS transistors with high-k dielectric gate stack has been investigated using 2D numerical simulation. Two important electrostatic limitations of high-k materials have been analyzed and discussed in this work: i) the gate-fringing field effects which compromise short-channel performance when simultaneously increasing the dielectric constant and its physical thickness and ii) the presence of discrete fixed charges in the gate stack, suspected to be at the origin of the stretch-out of C-V characteristics, that induces 2D potential fluctuations in the structure. In both cases, the resulting degradation of transistor operation and performance is evaluated with a two-dimensional quantum simulation code.