bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptosis, senescence, and autophagy in rat nucleus pulposus cells: Implications for diabetic intervertebral disc degeneration
Authors: Jiang Libo , Zhang Xiaolei , Zheng Xuhao , Ru Ao , Ni Xiao , Wu Yaosen , Tian Naifeng , Huang Yixing , Xue Enxing , Wang Xiangyang , Xu Huazi
Published: December 2012

This research was aimed to study the mechanisms by which diabetes aggravates intervertebral disc degeneration (IDD) and to discuss the relationship between autophagy and IDD in nucleus pulposus (NP) cells. Sixteen weeks after injecting streptozotocin (STZ), the intervertebral discs (IVDs) were studied by histology, Alcian blue, 1,9‐dimethylmethylene blue (DMMB), immunohistochemistry, and RT‐PCR to explore the IDD. The apoptosis and senescence of NP cells was investigated by terminal deoxyribonucleotidyl transferase (TDT)‐mediated dUTP‐digoxigenin nick end labeling (TUNEL) assay, immunohistochemistry, and Western blot for caspase3, caspase8, caspase9, and p16lnk4A (increased in cellular senescence). The level of autophagy in NP cells was detected by Western blot, immunohistochemistry, and transmission electron microscopy (TEM). The proteoglycan and collagen II in the extracellular matrix and the aggrecan and collagen II mRNA expression in NP cells of diabetic rats were decreased compared with the control group. Diabetes increased apoptosis of NP cells and led to activations of initiators of intrinsic (caspases‐9) and extrinsic (caspase‐8) pathways as well as their common executioner (caspase‐3). Cellular senescence was increased about twofold in NP of diabetic rats. In addition, the Western blot, immunohistochemistry, and TEM demonstrated higher level of autophagy in NP cells of diabetic rats than control rats to a statistically significant extent. These findings support that diabetes induced by STZ can cause IDD by accelerating the apoptosis and senescence of NP cells excluding the overweight influence. And the results suggest that the autophagy may be a response mechanism to the change of NP cells in diabetic rats. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 692–702, 2013
Fractal Structuring in Polymer Processing
Authors: Neerincx Peter E. , Meijer Han E. H.
Published: December 2012

For a multitude of high‐end applications such as photovoltaics and membranes for fuel cells or gas separation, creating large internal surfaces via fractal structuring during polymer processing can result in unique possibilities for enhancing performance. Structuring is possible even in processing techniques like injection molding. Inspired by microfluidic practice, an optimized splitting and recombining static mixer is realized on the parting surface of a mold. Different geometries are used to multiply, rotate, and add stratified structures. After the obvious structuring of a number of parallel layers, attention is focused on layers perpendicular to the product surface. A combination of the two allows complex hierarchical fractal structures to be obtained. A first demonstration of its feasibility is reported.
Disulfide Cross‐Linked Polypeptide Nanogel Conjugated with a Fluorescent Probe as a Potential Image‐Guided Drug‐Delivery Agent
Authors: Xing Tao , Lai Bin , Yan Lifeng
Published: December 2012

A disulfide cross‐linked PEGylated polypeptide nanogel with a near infrared fluorescence (NIRF) group has been synthesized. At first, a NIRF nanogel precursor is prepared by a ring‐opening polymerization of L‐cystine‐N‐carboxy anhydride with azide‐functionalized poly(ethylene glycol) methyl ether. Alkyne cyanine is then conjugated to the nanogel by a click chemical reaction. The formation of the targeted nanogel is confirmed by a series of characterizations. The anticancer drug doxorubicin can be loaded into the NIRF nanogel by physical encapsulation, and the obtained drug‐loaded NIRF nanoparticle shows reduction‐promoted drug‐release behavior in the presence of 10 mM glutathione. The as‐prepared drug‐loaded NIRF nanoparticle has potential applications in the real‐time imaging of drug delivery in vivo.
Enantioselective Enzymatic Modification of Chiral Block Copolymers
Authors: Yeniad Bahar , Naik Hemantkumar , Koning Cor E. , Heise Andreas
Published: December 2012

Block copolymers comprising blocks with pendant hydroxy groups of opposite chirality are synthesized by RAFT polymerization of (R)‐ and (S)‐1‐(4‐vinylphenyl)ethanol (1R and 1S) as monomers. Initially, poly(styrene) macro‐RAFT agents are chain‐extended with both enantiomeric monomers to obtain poly(styrene‐b‐1R) and poly(styrene‐b‐1S) with controlled molecular weight and low polydispersities. Enantioselective esterification with vinyl acetate by Candida Antarctica Lipase B (CALB) is only possible on the 1R‐containing block copolymer. This concept is extended to a series of chiral block copolymers poly(1R‐b‐1S) which, apart from their optical rotation, all behave like very similar homopolymers. By enzymatic enantioselective esterification on the 1R‐block, block copolymer structures were obtained.
Solvent‐Annealing‐Induced Nanowetting in Templates: Towards Tailored Polymer Nanostructures
Authors: Chen Jiun‐Tai , Lee Chih‐Wei , Chi Mu‐Huan , Yao I‐Chun
Published: December 2012

We study the solvent‐annealing‐induced nanowetting in templates using porous anodic aluminum oxide membranes. The morphology of polystyrene and poly(methyl methacrylate) nanostructures can be controlled, depending on whether the swollen polymers are in the partial or complete wetting regimes, which are characterized by the spreading coefficient. When the swollen polymers are in the partial wetting regime, polymers wet the nanopores by capillary action, resulting in the formation of polymer nanorods. When the swollen polymers are in the complete wetting regime, polymers form wetting layers in the nanopores, resulting in the formation of polymer nanotubes. The solubility parameters of polymers and solvents are also used to predict the wetting behavior of swollen polymers in cylindrical geometry.
Extracellular proteases are key mediators of Staphylococcus aureus virulence via the global modulation of virulence‐determinant stability
Authors: Kolar Stacey L. , Antonio Ibarra J. , Rivera Frances E. , Mootz Joe M. , Davenport Jessica E. , Stevens Stanley M. , Horswill Alexander R. , Shaw Lindsey N.
Published: December 2012

Staphylococcus aureus is a highly virulent and successful pathogen that causes a diverse array of diseases. Recently, an increase of severe infections in healthy subjects has been observed, caused by community‐associated methicillin‐resistant S. aureus (CA‐MRSA). The reason for enhanced CA‐MRSA virulence is unclear; however, work suggests that it results from hypersecretion of agr‐regulated toxins, including secreted proteases. In this study, we explore the contribution of exo‐proteases to CA‐MRSA pathogenesis using a mutant lacking all 10 enzymes. We show that they are required for growth in peptide‐rich environments, serum, in the presence of antimicrobial peptides (AMPs), and in human blood. We also reveal that extracellular proteases are important for resisting phagocytosis by human leukocytes. Using murine infection models, we reveal contrasting roles for the proteases in morbidity and mortality. Upon exo‐protease deletion, we observed decreases in abscess formation, and impairment during organ invasion. In contrast, we observed hypervirulence of the protease‐null strain in the context of mortality. This dichotomy is explained by proteomic analyses, which demonstrates exo‐proteases to be key mediators of virulence‐determinant stability. Specifically, increased abundance of both secreted (e.g. α‐toxin, Psms, LukAB, LukE, PVL, Sbi, γ‐hemolysin) and surface‐associated (e.g. ClfA+B, FnbA+B, IsdA, Spa) proteins was observed upon protease deletion. Collectively, our findings provide a unique insight into the progression of CA‐MRSA infections, and the role of secreted proteolytic enzymes.
Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)
Authors: Sánchez‐Ferro Álvaro , Benito‐León Julián , Louis Elan D. , Mitchell Alex J. , Molina‐Arjona José Antonio , Trincado Rocío , Villarejo Alberto , Bermejo‐Pareja Félix
Published: December 2012

Previous research has documented cognitive impairment in the early stages of Parkinson's disease (PD). It is not known when this decline starts or if decline progresses at an accelerated rate during the premotor period of the disorder. In this population‐based prospective study of older people (≥65 years) from the Neurological Disorders in Central Spain (NEDICES) cohort, we compared the rates of cognitive decline in 3 groups: (1) non‐PD elderly controls; (2) prevalent PD patients (those diagnosed with the disease at baseline, 1994–95); and (3) premotor PD subjects (those diagnosed with the disease at follow up, 1997–98, but not at baseline). A 37‐item version of the Mini–Mental State Examination (37‐MMSE) was administered in the 2 visits of the study. From 2487 participants (age, 72.8 ± 6.0 years), including 2429 controls, we recruited 21 premotor PD cases, and 37 prevalent PD cases. At baseline, the mean 37‐MMSE score was 28.5 ± 4.7 in prevalent cases, 28.1 ± 4.6 in premotor cases, and 29.9 ± 5.0 in controls (P = .046). During the 3‐year follow‐up period, there was a significant score decline of 2.4 ± 4.6 points in prevalent cases versus 0.2 ± 4.1 points in premotor cases and 0.3 ± 4.0 points in controls (Kruskal–Wallis test, P = .03). In the NEDICES cohort, cognitive test scores of prevalent PD cases declined at a rate above and beyond that observed in premotor PD cases and in controls. The rate of cognitive decline in premotor PD and controls was similar. Our data suggest that a decline in global cognitive function does not occur in premotor PD. © 2012 Movement Disorder Society
Identification and migration of primordial germ cells in Atlantic salmon, Salmo salar: Characterization of Vasa, Dead End, and Lymphocyte antigen 75 genes
Authors: Nagasawa Kazue , Fernandes Jorge M.O. , Yoshizaki Goro , Miwa Misako , Babiak Igor
Published: December 2012

No information exists on the identification of primordial germ cells (PGCs) in the super‐order Protacanthopterygii, which includes the Salmonidae family and Atlantic salmon (Salmo salar L.), one of the most commercially important aquatic animals worldwide. In order to identify salmon PGCs, we cloned the full‐length cDNA of vasa, dead end (dnd), and lymphocyte antigen 75 (ly75/CD205) genes as germ cell marker candidates, and analyzed their expression patterns in both adult and embryonic stages of Atlantic salmon. Semi‐quantitative RT‐PCR results showed that salmon vasa and dnd were specifically expressed in testis and ovary, and vasa, dnd, and ly75 mRNA were maternally deposited in the egg. vasa mRNA was consistently detected throughout embryogenesis while dnd and ly75 mRNA were gradually degraded during cleavages. In situ analysis revealed the localization of vasa and dnd mRNA and Ly75 protein in PGCs of hatched larvae. Whole‐mount in situ hybridization detected vasa mRNA during embryogenesis, showing a distribution pattern somewhat different to that of zebrafish; specifically, at mid‐blastula stage, vasa‐expressing cells were randomly distributed at the central part of blastodisc, and then they migrated to the presumptive region of embryonic shield. Therefore, the typical vasa localization pattern of four clusters during blastulation, as found in zebrafish, was not present in Atlantic salmon. In addition, salmon PGCs could be specifically labeled with a green fluorescence protein (GFP) using gfp‐rt‐vasa 3′‐UTR RNA microinjection for further applications. These findings may assist in understanding PGC development not only in Atlantic salmon but also in other salmonids. Mol. Reprod. Dev. © 2013 Wiley Periodicals, Inc.
AA Amyloidosis: Mount Sinai Experience, 1997–2012
Authors: Bunker Daniel , Gorevic Peter
Published: December 2012

Background: AA amyloidosis is a systemic disease characterized by the extracellular deposition of amyloid fibrils derived from the acute‐phase reactant serum amyloid A protein. It is typically a consequence of chronic inflammatory conditions like rheumatoid arthritis or Crohn's disease, although more patients are being identified who have more unusual causes or no known inflammatory stimulus.

Methods: We performed a retrospective chart review of all patients with AA amyloidosis seen at Mount Sinai during the period of 1997–2012. Particular attention was paid to the patients' underlying diseases, extent of organ involvement, levels of inflammatory markers and proinflammatory cytokines, presence of pyrin gene mutations, and outcomes.

Results: Forty‐three patients were seen at Mount Sinai with AA amyloidosis during this period. The most common underlying diseases were rheumatoid arthritis (21%) and Crohn's disease (16%), though 21% of patients were considered to have idiopathic AA amyloid after an extensive search found no underlying inflammatory disease. Almost all patients (95%) had renal involvement based on biopsy or clinical criteria, with 19 patients (44%) eventually requiring dialysis and 5 (12%) undergoing renal transplantation. Inflammatory markers were elevated in most patients; however, interleukin‐6 was the only consistently elevated cytokine. Three patients (of 9 tested) were found to be positive for the E148Q pyrin gene mutation.

Conclusions: Our study confirms the increasing number of patients being seen with idiopathic AA amyloidosis. More research is needed to determine if these patients have an underlying genetic susceptibility encoded in pyrin or other genes. Our study also confirms the dominance of renal disease in this population. The elevated levels of interleukin‐6, in comparison with other cytokines, could represent a therapeutic target. Mt Sinai J Med 79:749–756, 2012. © 2012 Mount Sinai School of Medicine
Minority Undergraduate Programs Intended to Increase Participation in Biomedical Careers
Authors: MacLachlan Anne J.
Published: December 2012

This article reviews a selection of undergraduate programs intended to increase successful minority participation in science, technology, engineering, and mathematics majors, potentially leading to biomedical careers. The object is to examine their structure, consider how well they address the issues of the target population, and assess the extent to which they have met/meet their goals. As a means of conducting this review, the first step is to examine the concepts used as the building blocks for program design. These concepts are found in a shared, yet often undefined, vocabulary used in most undergraduate programs for minority students. The hypothesis is that a shared vocabulary obscures a broad range of meaning and interpretation that has serious ramifications affecting student success. How these building blocks are understood and implemented strongly reflects the institution where the program is housed. The discussion further considers the nature of a number of programs created by the National Science Foundation and the National Institutes of Health specifically for underrepresented minority students and examines one program in detail, the University of California Berkeley's National Science Foundation Research Experience for Undergraduates Program in Molecular, Cell, and Evolutionary Biology. The characteristics of federally organized programs and the Research Experience for Undergraduates are contrasted with 2 very successful student‐centered local programs based on a different conceptual model. Mt Sinai J Med 79:769–781, 2012. © 2012 Mount Sinai School of Medicine
Maximizing Therapeutic Envelope for Prevention of Cardiovascular Disease: Role of Polypill
Authors: Sanz Ginés , Fuster Valentin
Published: December 2012

Cardiovascular‐disease prevention is often inadequate due to several factors. Lack of professional adherence to guidelines, unaffordable medication, and lack of patients' adherence to treatment are the most important. It has been suggested that an affordable, fixed‐dose combination drug containing evidence‐based active compounds could improve cardiovascular prevention by improving patients' adherence to treatment. The available evidence suggests that the polypill strategy can achieve this objective and it will gain a place in the therapeutic armamentarium for the prevention of cardiovascular events in patients at high risk. Mt Sinai J Med 79:683–688, 2012. © 2012 Mount Sinai School of Medicine
Elimination disorders in persons with Prader–Willi and Fragile‐X syndromes
Authors: Equit Monika , Piro‐Hussong Aline , Niemczyk Justine , Curfs Leopold , von Gontard Alexander
Published: December 2012

Aims

Elimination disorders are common in typically developing children. Only few studies have addressed elimination disorders in persons with intellectual disability (ID)—and even fewer studies in those with specific syndromes. The aim of the study was to investigate the rates of elimination disorders and behavioral symptoms in persons with Prader–Willi (PWS) and Fragile‐X syndromes (FXS) in a large sample.

Methods

Three hundred fifty‐seven persons with PWS or FXS were recruited through parent self‐help groups. A questionnaire regarding elimination symptoms, as well as the child behavior checklist (CBCL)/young adult behavior checklist (YABCL) were filled out by parents or caregivers.

Results

The sample included 191 persons with PWS (54.5% male) with a mean age of 20.0 years and 166 persons with FXS (92.2% male) with a mean age of 15.4 years. Persons with FXS were significantly more often affected by elimination disorders. 29.3% of persons with PWS and 48.8% of persons with FXS had at least one elimination disorder. Persons with FXS also had more often DUI (29.5% vs. 12.0%) and FI (28.9% vs. 12.6%). Rates of NE were similar in both groups (22.0% in PWS vs. 28.9% in FXS). Young adults with PWS had more behavioral symptoms in the clinical range (70.8% vs. 48.3%). Incontinence and behavioral symptoms were significantly associated in persons with FXS.

Conclusions

NE, DUI, and FI are very common in persons with FXS and PWS and are associated with other behavioral symptoms in persons with FXS. They persist into adulthood. Early assessment and treatment are recommended. Neurourol. Urodynam. 32: 986–992, 2013. © 2012 Wiley Periodicals, Inc.
Influence of shape and surface modification of nanoparticle on the rheological and dynamic‐mechanical properties of polyamide 6 nanocomposites
Authors: Marini Juliano , Bretas Rosario Elida Suman
Published: December 2012

Nanocomposites of polyamide 6 (PA6) with different concentrations of silane‐treated, organic‐treated, and nontreated nanoparticles of halloysite (HNT) and montmorillonite (MMT) had their microstructure and melt and solid state rheological behavior analyzed. The microstructure analysis was done using transmission electron microscopy (TEM) and wide angle X‐ray diffraction (WAXD); the effectiveness of the silanization was studied by thermogravimetric analysis (TGA) and Fourier transform infrared. It was found that exfoliation occurred in the organic‐treated MMT, but not in the silane‐treated MMT and that silanization was small in the HNT nanoparticles (due to its low amount of surface hydroxyls groups). Steady state shear, small amplitude oscillatory, and transient tests also indicated that: (i) only the nanocomposites with organic‐treated MMT, at concentrations above the theoretical percolation threshold developed a percolated network; (ii) the silane treatment increased the shear elastic modulus (G) of the PA6/HNT nanocomposites in the solid state, but not of the PA6/MMT; (iii) the organic‐treated MMT formed composites with the highest G, as expected. Thus, it was concluded that the HNT nanoparticles had a high potential as nanofiller for PA6, but further research on more efficient compatibilizers for HNT is still needed. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers.
Microstructure, thermal, physico–mechanical and tribological characteristics of molybdenum disulphide‐filled polyamide 66/carbon black composites
Authors: Basavaraj E. , Ramaraj B. , Lee Joong‐Hee , Siddaramaiah
Published: December 2012

With an objective to investigate the influence of molybdenum disulphide (MoS2) on physico–mechanical and tribological properties of polyamide 66 (PA 66), was compounded with MoS2 in the presence of carbon black (CB). The compounded material was injection molded to make test specimens to evaluate physico–mechanical, thermal, and tribological (wear, friction, and laser etching) characteristics. It was found that tensile strength, percentage elongation at break, and tensile modulus of PA 66/CB/MoS2 composite increased linearly with increase in MoS2 content. The impact strength of the PA 66 matrix increased from 37.2 to 43.2 J/m with an increase in MoS2 content. The wear behavior of PA 66/CB/MoS2 composites have been investigated under dry sliding conditions at different normal loads, sliding distances, and sliding velocities at room temperature. It was found that the introduction of MoS2 in the presence of CB has certainly reduced the friction, wear behavior of PA 66 with improvement in laser etching resistance. MoS2 could increase the adhesion between the transfer film and the counterface surface. The ability of the synergistic fillers in helping the formation of thin, uniform, and continuous transfer film would contribute to enhance the wear resistance of PA 66 composites. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers
A new smart coating of polyaniline–SiO2 composite for protection of mild steel against corrosion in strong acidic medium
Authors: Kumar S Anoop , Bhandari Hema , Sharma Chandrica , Khatoon Fehmeeda , Dhawan Sundeep K
Published: December 2012

Organic coating approaches for corrosion protection with inherently conducting polymers have become important because of restriction on the use of heavy metals and chromates in coatings due to their environmental problems. The present work is directed towards the synthesis of polyaniline (PANI) and polyaniline–SiO2 composites (PSCs) by chemical oxidation polymerization in the presence of phosphoric acid and evaluation of synthesized PANI and PSCs for protection of mild steel from corrosion in a strong aggressive medium (i.e. 1.0 mol L–1 HCl). A suitable coating with PSC was formed on mild steel using epoxy resin by the powder coating technique. A comparative study of the corrosion protection efficiency of mild steel coated with PANI and PSC in 1.0 mol L–1 HCl solution was evaluated using the Tafel extrapolation, chrono‐amperometry and weight loss methods. The PSC coating showed that a significant reduction in the corrosion current density reflects the better protection of mild steel in an acidic environment. Higher protection efficiency up to 99% was achieved by using PSC‐coated mild steel at 6.0 wt% loading of PSC in epoxy resin. The coating performance and corrosion rate of mild steel were investigated by using immersion of polymer‐coated mild steel in 1.0 mol L–1 HCl for 60 days and indicated that PSC‐coated mild steel showed better performance from corrosion than PANI in an acidic medium.© 2012 Society of Chemical Industry
Clustering and overlapping modules detection in PPI network based on IBFO
Authors: Lei Xiujuan , Wu Shuang , Ge Liang , Zhang Aidong
Published: December 2012

As is known to all, traditional clustering algorithms do not work well due to the topological features of protein–protein interaction networks. An improved clustering method based on bacteria foraging optimization (BFO) mechanism and intuitionistic fuzzy set, short for improved BFO, is proposed in this paper, in which the trigonometric function is used to define the membership degrees and the indeterminacy degree is introduced to detect the overlapping modules. In chemotactic operation of BFO, the algorithm initializes a cluster center according to comprehensive network feature value of node and eliminates the isolated point in accordance with edge‐clustering coefficient. In the reproduction operation of BFO, the nodes possessing high membership degrees are merged into the cluster that the cluster center belongs to and labeled as visited nodes. Meanwhile, the nodes that also have high indeterminacy degrees are visited again when generating another cluster. The procedure of elimination–dispersal operation is equivalent to the selection of the next cluster center. Finally, the algorithm merges the clusters having high similarity. The results show that the algorithm not only determines the cluster number automatically, improves the f‐measure value of cluster results, but also identify the overlaps in protein–protein interaction network successfully.
Predicting positive and negative impacts of cancer among long‐term endometrial cancer survivors
Authors: Rowlands Ingrid J. , Lee Christina , Janda Monika , Nagle Christina M. , Obermair Andreas , Webb Penelope M. ,   Australian National Endometrial Cancer Study Group
Published: December 2012

Objective

Although the survival outcomes among women diagnosed with endometrial cancer are very favorable, little is known about the long‐term impact of their cancer experience. This study identifies the extent of positive and negative impacts of cancer and factors associated with this, amongst long‐term survivors of endometrial cancer.

Methods

Australian women diagnosed with endometrial cancer (N = 632) were sent questionnaires at the time of diagnosis and 3–5 years later. Hierarchical multiple regression models were used to examine whether a range of variables at diagnosis/treatment predicted subsequent scores on the Impact of Cancer Scale, which examines positive (e.g. health awareness) and negative (e.g. appearance concerns) impacts amongst cancer survivors.

Results

Overall, women had a higher mean score for the positive than negative impact scales (M = 3.5 versus M = 2.5, respectively). An intermediate grade of endometrial cancer, a prior diagnosis of cancer and lower levels of education were significant, but weak, predictors of higher scores on the positive impact scale. Higher scores on the negative impact scale were predicted by a higher grade of cancer, poor physical and mental health, a younger age, being single or having lower levels of education.

Conclusions

The study demonstrates that factors that predict positive impact in cancer survivors differ to those that predict negative impact, suggesting that interventions to optimize cancer survivors' quality of life will need to be multi‐dimensional, and this supports the need for tailored intervention. Copyright © 2012 John Wiley & Sons, Ltd.
Critical multiple angiogenic factors secreted by glioblastoma stem‐like cells underline the need for combinatorial anti‐angiogenic therapeutic strategies
Authors: Thirant Cécile , Gavard Julie , Junier Marie‐Pierre , Chneiweiss Hervé
Published: December 2012

Glioblastomas are the most frequent adult primary brain tumors that still remain fatal despite major clinical efforts. As in other solid tumors, populations of glioblastoma stem‐like cells (GSCs) endowed with tumor initiating and therapeutic resistance properties have been identified. Glioblastomas are highly vascularized tumors resulting in a rich dialog between GSCs and endothelial cells. In one direction, endothelial cells and their secreted proteins are able to sustain GSC properties while, in turn, GSCs can promote neoangiogenesis, modulate endothelial cell functions and may even transdifferentiate into endothelial cells. Accordingly, targeting tumor vasculature seems a promising issue despite incomplete and transient results obtained from anti‐vascular endothelial growth factor therapeutic trials. Recent findings of novel GSC‐secreted molecules with pro‐angiogenic properties (Semaphorin 3A, hepatoma‐derived growth factor) open the path to the design of a concerted attack of glioblastoma vasculature that could overcome the development of resistance to single‐targeted therapies while keeping away the toxicity of the treatments.
Chronic constipation: current assessment and management
Authors: Lee Lennard , Blaker Paul , Wilkinson Mark
Published: December 2012

A wide choice of treatments is available for chronic constipation but supporting clinical evidence is often lacking. Our Drug review considers the aetiology and assessment of chronic constipation and discusses the efficacy and safety of the available treatment options.
Renal anaemia services: current provision and future developments
Authors: Macdougall Iain , Ashley Caroline , Dring Belinda
Published: December 2012

In this Expert Panel Discussion, three healthcare professionals discuss renal anaemia services, providing examples of their own experiences. Clinical Commissioning Groups (CCGs) are considering moving some of these services from secondary to primary care, and the panel reflects on how this might affect services and patients in the future, particularly at the community level.
Boceprevir and telaprevir: new treatments for chronic hepatitis C
Authors: Chaplin Steve , Dusheiko Geoffrey
Published: December 2012

Boceprevir and telaprevir are new antiviral drugs indicated for the treatment of chronic hepatitis C genotype 1 infection. In our New products review, Steve Chaplin presents the clinical data relating to their efficacy and adverse effects and Professor Geoffrey Dusheiko discusses their place in treatment.
Cu2MnAl thin films grown onto sapphire and MgO substrates: Exchange stiffness and magnetic anisotropy
Authors: Belmeguenai M. , Tuzcuoglu H. , Chérif S. M. , Westerholt K. , Chauveau T. , Mazaleyrat F. , Moch P.
Published: December 2012

Cu2MnAl films of different thicknesses (50, 70, and 100 nm) were grown by UHV RF‐sputtering on a‐plane sapphire or on MgO (100) substrates. Their structural and static magnetic properties have been studied by X‐rays diffraction (XRD) and by vibrating sample magnetometry (VSM), respectively. The Cu2MnAl films exhibit a (100) and (110)‐texture when grown on MgO and sapphire substrates, respectively. The best growth quality and the higher magnetization at saturation were obtained for the films grown on MgO. Dynamic magnetic properties were investigated using micro‐strip line ferromagnetic resonance (MS‐FMR). From the resonance measurements varying the direction and the amplitude of the in‐plane and out‐of‐plane applied magnetic fields we derive the effective magnetization, the Landé g‐factor (g = 2.11), the exchange constant (Aex = 0.34 µerg cm−1) and the magnetic anisotropy terms. The in‐plane anisotropy can be described as a superposition of two terms showing a small twofold and a dominant fourfold symmetry.
Interactions between components of SrTi0.98Nb0.02O3−δ–YSZ and SrTi0.98Nb0.02O3−δ–CeO2 composites
Authors: Bochentyn Beata , Karczewski Jakub , Gazda Maria , Jasiński Piotr , Kusz Bogusław
Published: December 2012

Composites consisting of SrTiO3‐based perovskite and either yttria‐stabilized zirconia or ceria were investigated. The mechanical compatibility and possible inter‐diffusion between phases were characterized by scanning electron microscopy, X‐ray diffraction, and energy‐dispersive X‐ray spectroscopy. A gradual disappearance of Ce‐containing phases with an increase in the temperature of reduction in hydrogen was noticed. Moreover, a diffusion of Sr, Ti, and Ce was observed between the composites and the yttria‐stabilized zirconia electrolyte support in the conditions of high temperature (1300–1400 °C) reduction in H2.
Effects of interface geometry on the thermoelectric properties of laterally microstructured ZnO‐based thin films
Authors: Homm G. , Gather F. , Kronenberger A. , Petznick S. , Henning T. , Eickhoff M. , Meyer B. K. , Heiliger C. , Klar P. J.
Published: December 2012

A series of samples consisting of alternating stripes of ZnO grown by molecular‐beam epitaxy (MBE) and radio‐frequency (rf) sputtered Ga‐doped ZnO stripes was laterally microstructured with a self‐aligned pattern transfer method. We measured as a function of temperature the Seebeck coefficient S and the electrical resistivity ρ in‐plane of the samples with the transport direction perpendicular to the stripe direction. Throughout the series the bar width and hence the number of interfaces was kept constant, but the interface profile was varied yielding different interface lengths and geometries. The dependence of S, ρ and the power factor S2/ρ on the interface length at room temperature were simulated using an empirical network model and it was demonstrated that the macroscopic transport coefficients are very sensitive to the interface region and that even this rather simple modelling yields useful information about the interface region.
Strain profiles and radii of semiconductor rolled‐up tubes made by a single material
Authors: Laniel Dominique , Shtinkov Nikolay
Published: December 2012

Single‐material rolled‐up microtubes provide an opportunity to study the processes of strain relaxation and defect formation near the interface of strained‐layer semiconductor heterostructures. We study theoretically tubes formed by a single strained Si layer grown beyond the critical thickness on a Ge substrate. The residual strain accumulated in the Si layer causes the layer to roll after it is released from the substrate by etching. Computer simulations are carried out using Keating's valence force field method, with uniform and non‐uniform residual (initial) strain profiles and different strained layer widths. We show that the radius of the tubes is affected by a combination of these two factors and thus by the total elastic deformation present before rolling, a larger total deformation resulting in a smaller tube radius. However, uniform and non‐uniform residual strain profiles can be easily distinguished by analyzing the final profiles of the azimuthal and the radial strain components.
Evidence for giant spin entropy contribution in thermoelectric Ca3Co4O9+δ
Authors: Tang Guodong , Xu Feng , He Yun , Wang Liaoyu , Qiu Li , Wang Zhihe
Published: December 2012

We report magnetic field dependence of both in‐plane and out‐of plane thermopower in Ca3Co4O9+δ single crystal. Strong field dependence of both in‐plane and out‐of plane thermopower evinces giant spin entropy contribution to the thermopower in the thermoelectric material. These discovered effects indicate that spin entropy dominates the enhancement of thermopower in misfit‐layered cobalt oxides materials. An obvious suppression of thermopower is stronger by an out‐of‐plane magnetic field than by an in‐plane field.
Lattice dynamics and structure of GeTe, SnTe and PbTe
Authors: Bauer Pereira Paula , Sergueev Ilya , Gorsse Stéphane , Dadda Jayaram , Müller Eckhard , Hermann Raphaël P.
Published: December 2012

The lattice dynamics in the IV–VI compounds GeTe, SnTe and PbTe were studied by 125Te and 119Sn nuclear inelastic scattering and the obtained partial density of phonon states were compared with published theoretical calculations. The phase purity and structure were characterized by high energy X‐ray diffraction. The effect of the atomic arrangement, rhombohedral for GeTe and cubic for SnTe and PbTe, is visible in the density of phonon states. Vibrational properties are found to be in good agreement with available calculated data and the softer character of the NaCl‐type structures in comparison with the rhombohedral GeTe is confirmed.
Lipid profiling for early diagnosis and progression of colorectal cancer using direct‐infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry
Authors: Li Fang , Qin Xuzhen , Chen Haiquan , Qiu Ling , Guo Yumei , Liu Hui , Chen Guoqiang , Song Gaoguang , Wang Xiaodong , Li Fenjie , Guo Shuai , Wang Baohua , Li Zhili
Published: December 2012

RATIONALE

Colorectal cancer (CRC) has attracted increasing attention due to its common occurrence and worldwide distribution.

METHODS

Direct‐infusion positive and negative ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (DI‐ESI(±)‐FTICR MS) was applied to analyze the serum metabolites from 52 CRC patients and 52 healthy controls. Metabolites whose inter‐group intensities were determined to be statistically significant by univariate and multivariate statistical analyses were further identified by a combination of the Human Metabolome Database, accurate mass measurement, isotopic abundance distribution simulation, and tandem mass spectrometry. Orthogonal partial least square discriminant analysis (OPLS‐DA), based on the data from DI‐ESI(±)‐FTICR MS, revealed a remarkable discrimination among early stage patients, late stage patients, and healthy controls.

RESULTS

A total of 15 differentially expressed metabolites were identified and categorized into four lipid classes. Each lipid class demonstrated specific changing trends in CRC progression. Biomarker panel 1 containing palmitic amide, oleamide, hexadecanedioic acid, octadecanoic acid, eicosatrienoic acid, LPC(18:2), LPC(20:4), LPC(22:6), myristic acid and LPC(16:0) achieved excellent diagnostic accuracy with area under the ROC curve (AUC) of 0.991, a sensitivity of 0.981 and a specificity of 1.000 for differentiating early stage patients from healthy controls, which was better than the carcinoembryonic antigen biomarker.

CONCLUSIONS

Our study revealed that the consideration of CRC stages would be necessary in diagnostic biomarker discovery, as well as that attention should be paid to the facile loss of methyl chloride from the [M + Cl]– form of LPC(16:0) in its tandem mass spectrum. Copyright © 2012 John Wiley & Sons, Ltd.
The determination of flavonoids in Wikstroemia indica C. A. Mey. by liquid chromatography with photo‐diode array detection and negative electrospray ionization tandem mass spectrometry
Authors: Ko Yen‐Chen , Feng Hai‐Tung , Lee Ren‐Jye , Lee Maw‐Rong
Published: December 2012

RATIONALE

Flavonoids in the medicinal plant Wikstroemia indica C. A. Mey. are present in trace amounts and found in complex matrices. An efficient and sensitive method is necessary for the rapid identification of such biomolecules.

METHODS

Flavonoids were extracted with methanol via ultrasonic‐assisted extraction and analyzed by liquid chromatography with photo‐diode array detection and tandem mass spectrometry. The extract was analyzed and compounds were identified using negative electrospray ionization data‐dependent tandem mass spectrometry.

RESULTS

The results confirmed the presence of three flavonoid compounds, seven biflavonoid compounds, and one coumarin‐like compound, daphnoretin, in the extracts of different plant parts of W. indica. The method detection limit was evaluated down to 5 µg/g using kaempfol as a reference standard.

CONCLUSIONS

The proposed method offers a rapid and reliable analysis for the determination of flavonoids in medicinal plants. Copyright © 2012 John Wiley & Sons, Ltd.
Electron transfer followed by collision‐induced dissociation (NET‐CID) for generating sequence information from backbone‐modified oligonucleotide anions
Authors: Gao Yang , McLuckey Scott A.
Published: December 2012

RATIONALE

Oligonucleotides with 2'‐modifications and/or phosphorothioate (PS) backbones are prone to undergo limited backbone fragmentation upon ion trap collision‐induced dissociation (CID). For better identification and characterization of chemically modified oligonucleotides, a more universal fragmentation method is desirable.

METHODS

Gas‐phase dissociation of various 2'‐position‐modified oligonucleotides and mixed‐backbone oligonucleotides (MBOs) has been studied by ion trap CID of the radical anion species formed via electron transfer ion/ion reactions.

RESULTS

For 2'‐modified mix‐mer radical anions, complete sequence information was generated with non‐complementary d/w‐ion series, while a/z‐ions were observed randomly with relatively low intensity. The 2'‐position modification, which has been observed to affect CID patterns of oligonucleotide anions, did not exhibit any observable influence on the dissociation patterns of oligonucleotide radical anions. For MBOs comprised of DNA nucleotides, ion trap CID of even‐electron species generated complementary a‐B/w‐type ions and multiple fragment types at the phosphorothioate (PS) linkages. For MBOs comprised of 2'‐OMe‐modified nucleotides, only PS bond cleavage was observed for ion trap CID of doubly deprotonated precursor ions. Negative electron transfer reaction with or without supplemental activation of MBOs gave rise to a/d/w‐type fragments similar to those of the 2'‐modified mix‐mers. PS bonds were observed to be more fragile under the electron detachment process, and phosphodiester (PO) bond cleavages were noted upon further collisional activation.

CONCLUSIONS

NET‐CID proved to be an efficient method of generating full sequence information for 2'‐modifications and/or mixed‐backbone oligonucleotides. Copyright © 2012 John Wiley & Sons, Ltd.
5‐Amino‐1‐naphthol, a novel 1,5‐naphthalene derivative matrix suitable for matrix‐assisted laser desorption/ionization in‐source decay of phosphorylated peptides
Authors: Osaka Issey , Sakai Mami , Takayama Mitsuo
Published: December 2012

RATIONALE

Although matrix‐assisted laser desorption/ionization in‐source decay (MALDI‐ISD) is an important method for post‐translational modification (PTM) analysis, the conventional matrices, 2,5‐dihydroxybenzoic acid (2,5‐DHB) and 1,5‐diaminonaphthalene (1,5‐DAN), are poor in terms of the fragment ion yields of the phosphorylated peptides. The use of 5‐amino‐1‐naphthol (5,1‐ANL) as a novel matrix for ISD of phosphorylated peptides in MALDI time‐of‐flight mass spectrometry (TOFMS) is described here.

METHODS

We have evaluated the ion yields of ISD fragments obtained from phosphorylated peptides using three 1,5‐naphthalene derivatives as MALDI‐ISD matrices, i.e., 5,1‐ANL, 1,5‐DAN and 1,5‐dihydroxynaphthalene (1,5‐DHN). The signal‐to‐noise ratio (S/N) of c'‐series ions obtained from these matrices was used to estimate their suitability for MALDI‐ISD of non‐modified and phosphorylated peptides.

RESULTS

The order of the S/N values of the ISD fragments for non‐modified and phosphorylated peptides were 1,5‐DAN > 5,1‐ANL > 1,5‐DHN and 5,1‐ANL > 1,5‐DHN > 1,5‐DAN, respectively.

CONCLUSIONS

The newly introduced matrix 5,1‐ANL gave highest ion yields of ISD fragments from mono‐, di‐, and tetraphosphorylated peptides, while 1,5‐DAN was poor in the ISD ion yields for phosphorylated peptides. Copyright © 2012 John Wiley & Sons, Ltd.
Novel laser spectroscopic technique for continuous analysis of N2O isotopomers – application and intercomparison with isotope ratio mass spectrometry
Authors: Köster Jan Reent , Well Reinhard , Tuzson Béla , Bol Roland , Dittert Klaus , Giesemann Anette , Emmenegger Lukas , Manninen Albert , Cárdenas Laura , Mohn Joachim
Published: December 2012

RATIONALE

Nitrous oxide (N2O), a highly climate‐relevant trace gas, is mainly derived from microbial denitrification and nitrification processes in soils. Apportioning N2O to these source processes is a challenging task, but better understanding of the processes is required to improve mitigation strategies. The N2O site‐specific 15 N signatures from denitrification and nitrification have been shown to be clearly different, making this signature a potential tool for N2O source identification. We have applied for the first time quantum cascade laser absorption spectroscopy (QCLAS) for the continuous analysis of the intramolecular 15 N distribution of soil‐derived N2O and compared this with state‐of‐the‐art isotope ratio mass spectrometry (IRMS).

METHODS

Soil was amended with nitrate and sucrose and incubated in a laboratory setup. The N2O release was quantified by FTIR spectroscopy, while the N2O intramolecular 15 N distribution was continuously analyzed by online QCLAS at 1 Hz resolution. The QCLAS results on time‐integrating flask samples were compared with those from the IRMS analysis.

RESULTS

The analytical precision (2σ) of QCLAS was around 0.3 ‰ for the δ15Nbulk and the 15 N site preference (SP) for 1‐min average values. Comparing the two techniques on flask samples, excellent agreement (R2 = 0.99; offset of 1.2 ‰) was observed for the δ15Nbulk values while for the SP values the correlation was less good (R2 = 0.76; offset of 0.9 ‰), presumably due to the lower precision of the IRMS SP measurements.

CONCLUSIONS

These findings validate QCLAS as a viable alternative technique with even higher precision than state‐of‐the‐art IRMS. Thus, laser spectroscopy has the potential to contribute significantly to a better understanding of N turnover in soils, which is crucial for advancing strategies to mitigate emissions of this efficient greenhouse gas. Copyright © 2012 John Wiley & Sons, Ltd.
Comparison of the LTQ‐Orbitrap Velos and the Q‐Exactive for proteomic analysis of 1–1000 ng RAW 264.7 cell lysate digests
Authors: Sun Liangliang , Zhu Guijie , Dovichi Norman J.
Published: December 2012

RATIONALE

There is interest in extending bottom‐up proteomics to the smallest possible sample size. We investigated the performance of two modern mass spectrometers for the analysis of samples ranging from 1 ng to 1 µg of RAW 264.7 cell lysate digests.

METHODS

An ultra‐performance liquid chromatography (UPLC) system coupled with either an LTQ‐Orbitrap Velos or a Q‐Exactive mass spectrometer was used for peptide separation and identification.

RESULTS

For 1–1000 ng RAW 264.7 cell lysate digests, the Q‐Exactive generated 10–83% more protein groups and 11–109% more peptides than the LTQ‐Orbitrap Velos (higher‐energy collisional dissociation, HCD) with MASCOT database searching, due to its faster scan rate and higher resolution. In addition, HCD and collision‐induced dissociation (CID) modes of the LTQ‐Orbitrap Velos were compared. HCD produced higher peptide and protein group IDs than CID for 1–1000 ng RAW 264.7 cell lysate digests with MASCOT database searching. Database searching results from SEQUEST and MASCOT were also compared and comparable protein group IDs were obtained from the two search engines.

CONCLUSIONS

The Q‐Exactive outperformed the LTQ‐Orbitrap Velos for shotgun proteomics analysis of 1 to 1000 ng RAW 264.7 cell lysate digests in terms of obtained peptide and protein group IDs. Copyright © 2012 John Wiley & Sons, Ltd.
Analysis and quantification of vitamin D metabolites in serum by ultra‐performance liquid chromatography coupled to tandem mass spectrometry and high‐resolution mass spectrometry – a method comparison and validation
Authors: Bruce Stephen J. , Rochat Bertrand , Béguin Alexandre , Pesse Benoît , Guessous Idris , Boulat Olivier , Henry Hugues
Published: December 2012

RATIONALE

The aim of the work was to develop and validate a method for the quantification of vitamin D metabolites in serum using ultra‐high‐pressure liquid chromatography coupled to mass spectrometry (LC/MS), and to validate a high‐resolution mass spectrometry (LC/HRMS) approach against a tandem mass spectrometry (LC/MS/MS) approach using a large clinical sample set.

METHODS

A fast, accurate and reliable method for the quantification of the vitamin D metabolites, 25‐hydroxyvitamin D2 (25OH‐D2) and 25‐hydroxyvitamin D3 (25OH‐D3), in human serum was developed and validated. The C3 epimer of 25OH‐D3 (3‐epi‐25OH‐D3) was also separated from 25OH‐D3. The samples were rapidly prepared via a protein precipitation step followed by solid‐phase extraction (SPE) using an HLB μelution plate. Quantification was performed using both LC/MS/MS and LC/HRMS systems.

RESULTS

Recovery, matrix effect, inter‐ and intra‐day reproducibility were assessed. Lower limits of quantification (LLOQs) were determined for both 25OH‐D2 and 25OH‐D3 for the LC/MS/MS approach (6.2 and 3.4 µg/L, respectively) and the LC/HRMS approach (2.1 and 1.7 µg/L, respectively). A Passing & Bablok fit was determined between both approaches for 25OH‐D3 on 662 clinical samples (1.11 + 1.06x). It was also shown that results can be affected by the inclusion of the isomer 3‐epi‐25OH‐D3.

CONCLUSIONS

Quantification of the relevant vitamin D metabolites was successfully developed and validated here. It was shown that LC/HRMS is an accurate, powerful and easy to use approach for quantification within clinical laboratories. Finally, the results here suggest that it is important to separate 3‐epi‐25OH‐D3 from 25OH‐D3. Copyright © 2012 John Wiley & Sons, Ltd.