bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of renewable poly(amidoamine)/hemicellulose hydrogels for heavy metal adsorption
Authors: Ferrari Elena , Ranucci Elisabetta , Edlund Ulrica , Albertsson Ann‐Christine
Published: November 2014

Renewable poly(amidoamine)/hemicellulose hydrogels were prepared from O‐acetylated galactoglucomannan (AcGGM)‐rich biomass and shown to display a significantly high adsorption capacity for Cu2+, Cd2+, Pb2+, Zn2+, Ni2+, Co2+, and
. Two different acrylamido end‐capped poly(amidoamine) oligomers (PAA) were prepared and covalently immobilized onto an in situ formed polysaccharide network via water‐based free radical graft copolymerization and cross‐linking. The synthetic approach was shown to be viable when using a highly purified AcGGM or a crude spruce hydrolysate, an AcGGM and lignin containing biomass fraction as a reactant. Homogeneous reaction mixtures were obtained in both cases with polysaccharide contents up to 20% by weight. Oscillatory shear measurements indicated a predominantly solid‐like behavior of the hydrogels with an increase in shear storage modulus with increasing cross‐link density. The mechanical integrity of the PAA/hemicellulose hydrogels showed higher water swelling capacity and less fragility than the parent PAA hydrogels and they retained the heavy metal ion absorption ability of the PAA component, even in the presence of the least purified hemicellulose fraction. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41695.
A changing role for university professors? Professorial academic leadership as it is perceived by ‘the led’
Authors: Evans Linda
Published: November 2014

This article examines the academic leadership role of university professors in the UK (a grade title which in that national context generally refers only to the most distinguished, senior academics, who equate to the North American full professor). Drawing on theoretical interpretations of professionalism and applying these to professors, it analyses selected preliminary findings from a funded study that explored the nature of professorial academic leadership by gathering data from academics, teachers and researchers who are not themselves professors and who thus constitute ‘the led’. The findings revealed an unclearly defined professorial academic leadership role that seems to reflect expectations that professors should be all things to all people, and within which three key features of professorial practice were highlighted: distinction, knowledge, and relationality. The article considers the extent to which this represents a changed or changing role for professors in the UK, and concludes that the notion of the UK‐based professor—in the singular—is very elusive.
Osmoprotective polymer additives attenuate the membrane pore‐forming activity of antimicrobial peptoids
Authors: Smith Peter T. , Huang Mia L. , Kirshenbaum Kent
Published: November 2014

Antimicrobial peptides (AMPs) are critical components of the innate immune system and exhibit bactericidal activity against a broad spectrum of bacteria. We investigated the use of N‐substituted glycine peptoid oligomers as AMP mimics with potent antimicrobial activity. The antimicrobial mechanism of action varies among different AMPs, but many of these peptides can penetrate bacterial cell membranes, causing cell lysis. We previously hypothesized that amphiphilic cyclic peptoids may act through a similar pore formation mechanism against methicillin‐resistant Staphylococcus aureus (MRSA). Peptoid‐induced membrane disruption is observed by scanning electron microscopy and results in a loss of membrane integrity. We demonstrate that the antimicrobial activity of the peptoids is attenuated with the addition of polyethylene glycol osmoprotectants, signifying protection from a loss of osmotic balance. This decrease in antimicrobial activity is more significant with larger osmoprotectants, indicating that peptoids form pores with initial diameters of ∼2.0–3.8 nm. The initial membrane pores formed by cyclic peptoid hexamers are comparable in diameter to those formed by larger and structurally distinct AMPs. After 24 h, the membrane pores expand to >200 nm in diameter. Together, these results indicate that cyclic peptoids exhibit a mechanism of action that includes effects manifested at the cell membrane of MRSA. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 227–236, 2015.
Thermal‐ and urea‐induced unfolding processes of glutathione S‐transferase by molecular dynamics simulation
Authors: Li Jiahuang , Chen Yuan , Yang Jie , Hua Zichun
Published: November 2014

The Schistosoma juponicum 26 kDa glutathione S‐transferase (sj26GST) consists of the N‐terminal domain (N‐domain), containing three alpha‐helices (named H1‐H3) and four anti‐parallel beta‐strands (S1‐S4), and the C‐terminal domain (C‐domain), comprising five alpha‐helices (named H4‐H8). In present work, molecular dynamics simulations and fluorescence spectroscopic were used to gain insights into the unfolding process of sj26GST. The molecular dynamics simulations on sj26GST subunit both in water and in 8 M urea were carried out at 300 K, 400 K and 500 K, respectively. Spectroscopic measurements were employed to monitor structural changes. Molecular dynamics simulations of sj26GST subunit induced by urea and temperature showed that the initial unfolding step of sj26GST both in water and urea occurred on N‐domain, involving the disruption of helices H2, H3 and strands S3 and S4, whereas H6 was the last region exposed to solution and was the last helix to unfold. Moreover, simulations analyses combining with fluorescence and circular dichroism spectra indicated that N‐domain could not fold independent, suggesting that correct folding of N‐domain depended on its interactions with C‐domain. We further proposed that the folding of GSTs could begin with the hydrophobic collapse of C‐domain whose H4, H5, H6 and H7 could move close to each other and form a hydrophobic core, especially H6 wrapped in the hydrophobic center and beginning spontaneous formation of the helix. S3, S4, H3, and H2 could form in the wake of the interaction between C‐domain and N‐domain. The paper can offer insights into the molecular mechanism of GSTs unfolding. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 247–259, 2015.
A Green and Sustainable Approach: Celebrating the 30th Anniversary of the Asymmetricl‐Menthol Process
Authors: Emura Makoto , Matsuda Hiroyuki
Published: November 2014

Takasagohas been devoted to producingl‐menthol since 1954, and our long history of manufacturing this important aroma chemical is reviewed here. The current asymmetric catalytic process had its 30th anniversary in 2013. Ourl‐menthol process is considered carbon‐neutral, and, therefore, ‘green’ and sustainable. It uses renewable myrcene obtained from gum rosin as a starting material. In addition, the Rh‐BINAP (=2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl) catalytic system is highly efficient. This pathway not only leadsl‐menthol, but a variety of 100% biobased aroma chemical products as well. By measuring the14C levels in a material, one can determine the percentage of carbon that is biobased. This biobased assay, described as the ratio plant‐derived C/fossil‐derived C, can clarify how renewable a product really is. This will be highlighted for several ofTakasago's key aroma chemicals.
Robust, Efficient, and Recyclable Catalysts from the Impregnation of Preformed Dendrimers Containing Palladium Nanoparticles on a Magnetic Support
Authors: Deraedt Christophe , Wang Dong , Salmon Lionel , Etienne Laetitia , Labrugère Christine , Ruiz Jaime , Astruc Didier
Published: November 2014

The simple impregnation of γ‐Fe2O3(core)/SiO2(shell) magnetic nanoparticles with a dendrimer that contains stabilized Pd nanoparticles is presented as a new method to produce highly efficient heterogeneous catalysts. This technique provides much better stability, recyclability, and activity in CC cross‐coupling reactions and selective oxidation of benzyl alcohol to benzaldehyde in water than unsupported Pd nanoparticles.
The Small Deborah Number Limit of the Doi‐Onsager Equation to the Ericksen‐Leslie Equation
Authors: Wang Wei , Zhang Pingwen , Zhang Zhifei
Published: November 2014

We present a rigorous derivation of the Ericksen‐Leslie equation starting from the Doi‐Onsager equation by the Hilbert expansion method. The existence of the Hilbert expansion is related to an open question of whether the energy of the Ericksen‐Leslie equation is dissipated. On this point, we show that the energy is dissipated for the Ericksen‐Leslie equation derived from the Doi‐Onsager equation. The most difficult step is to prove a uniform bound for the remainder of the Hilbert expansion. This step is connected to the spectral stability of the linearized Doi‐Onsager operator around a critical point and the lower bound estimate for a bilinear form associated with the linearized operator. By introducing two important auxiliary operators, we can obtain the detailed spectral information for the linearized operator around all the critical points. We establish a precise lower bound of the bilinear form by introducing a five‐dimensional space called the Maier‐Saupe space.© 2015 Wiley Periodicals, Inc.
The Generation Effect: Cavity Accessibility in Dense‐Shell Polyphenylene Dendrimers
Authors: Brutschy Malte , Stangenberg René , Beer Cornelia , Lubczyk Daniel , Baumgarten Martin , Müllen Klaus , Waldvogel Siegfried R.
Published: November 2014

Size exclusion is a widespread phenomenon in supra‐ and macromolecular chemistry. Herein, the size exclusion properties of polyphenylene dendrimers on the surface of high fundamental frequency quartz crystal microbalances are reported. For this purpose, a new dense fifth‐generation polyphenylene dendrimer, which was previously not possible owing to the high steric demand of the dendron arms, was synthesized. By increasing the volume and size of subjected analytes an affinity shift from smaller to larger dendrimers can be obtained.
Survey study and experimental investigation on the local behavior of pedestrian groups
Authors: Wei Xiaoge , Lv Wei , Song Weiguo , Li Xiaolian
Published: November 2014

Current research on pedestrian dynamics mainly focuses on the interactions among isolated individuals, the impact of the presence of groups is not fully considered. In recent 5 years, researchers have started to investigate pedestrian group movement. The aim of this work is to explore the local behavior of pedestrian groups by questionnaires and field observation. Survey study focused on pedestrians' psychology when walking in groups, which included five parts: group size, interpersonal distance, spatial relationship among group members, speed adjustment of group members, information transmission, and acid action among group members. Meantime a field observation was carried out to study group movement characteristics, which contained speed, step frequency, offset angle and interpersonal distance. The survey results show that group members have a closer interpersonal distance, faster information transmission and plenty of acid action. Conversely, group walking has a negative influence on pedestrian's speed, step frequency by comparing with the way isolated pedestrian walks. In addition, it is found that for a certain group, the group members are able to keep movement consistent. Also there exists obvious movement diversity among different group types (male dyads, female dyads, couple groups, and ordinary‐friend groups) because of different gender and social relationship. Ultimately the results will be more promising for helping to model the movement of pedestrian groups. © 2014 Wiley Periodicals, Inc. Complexity 20: 87–97, 2015
NLRC5 interacts with RIG‐I to induce a robust antiviral response against influenza virus infection
Authors: Ranjan Priya , Singh Neetu , Kumar Amrita , Neerincx Andreas , Kremmer Elisabeth , Cao Weiping , Davis William G. , Katz Jacqueline M. , Gangappa Shivaprakash , Lin Rongtuan , Kufer Thomas A. , Sambhara Suryaprakash
Published: November 2014

The NLR protein, NLRC5 is an important regulator of MHC class I gene expression, however, the role of NLRC5 in other innate immune responses is less well defined. In the present study, we report that NLRC5 binds RIG‐I and that this interaction is critical for robust antiviral responses against influenza virus. Overexpression of NLRC5 in the human lung epithelial cell line, A549, and normal human bronchial epithelial cells resulted in impaired replication of influenza virus A/Puerto Rico/8/34 virus (PR8) and enhanced IFN‐β expression. Influenza virus leads to induction of IFN‐β that drives RIG‐I and NLRC5 expression in host cells. Our results suggest that NLRC5 extends and stabilizes influenza virus induced RIG‐I expression and delays expression of the viral inhibitor protein NS1. We show that NS1 binds to NLRC5 to suppress its function. Interaction domain mapping revealed that NLRC5 interacts with RIG‐I via its N‐terminal death domain and that NLRC5 enhanced antiviral activity in an leucine‐rich repeat domain independent manner. Taken together, our findings identify a novel role for NLRC5 in RIG‐I‐mediated antiviral host responses against influenza virus infection, distinguished from the role of NLRC5 in MHC class I gene regulation.
TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition
Authors: Tougaard Peter , Skov S. , Pedersen A. E. , Krych L. , Nielsen D. S. , Bahl M. I. , Christensen E. G. , Licht T. R. , Poulsen S. S. , Metzdorff S. B. , Hansen A. K. , Hansen C. H. F.
Published: November 2014

TL1A is a proinflammatory cytokine, which is prevalent in the gut. High TL1A concentrations are present in patients with inflammatory bowel disease (IBD) and in IBD mouse models. However, the role of TL1A during steady‐state conditions is relatively unknown. Here, we used TL1A knockout (KO) mice to analyse the impact of TL1A on the intestinal immune system and gut microbiota. The TL1A KO mice showed reduced amounts of small intestinal intraepithelial TCRγδ+ and CD8+ T cells, and reduced expression of the activating receptor NKG2D. Moreover, the TL1A KO mice had significantly reduced body weight and visceral adipose tissue deposits, as well as lower levels of leptin and CXCL1, compared with wild‐type mice. Analysis of the gut microbial composition of TL1A KO mice revealed a reduction of caecal Clostridial cluster IV, a change in the Firmicutes/Bacteroidetes ratio in caecum and less Lactobacillus spp. in the mucosal ileum. Our results show that TL1A deficiency impacts on the gut microbial composition and the mucosal immune system, especially the intraepithelial TCRγδ+ T‐cell subset, and that TL1A is involved in the establishment of adipose tissue. This research contributes to a broader understanding of TL1A inhibition, which is increasingly considered for treatment of IBD.
A stromal cell free culture system generates mouse pro‐T cells that can reconstitute T‐cell compartments in vivo
Authors: Gehre Nadine , Nusser Anja , von Muenchow Lilly , Tussiwand Roxane , Engdahl Corinne , Capoferri Giuseppina , Bosco Nabil , Ceredig Rhodri , Rolink Antonius G.
Published: November 2014

T‐cell lymphopenia following BM transplantation or diseases such as AIDS result in immunodeficiency. Novel approaches to ameliorate this situation are urgently required. Herein, we describe a novel stromal cell free culture system in which Lineage−Sca1+c‐kit+ BM hematopoietic progenitors very efficiently differentiate into pro‐T cells. This culture system consists of plate‐bound Delta‐like 4 Notch ligand and the cytokines SCF and IL‐7. The pro‐T cells developing in these cultures express CD25, CD117, and partially CD44; express cytoplasmic CD3ε; and have their TCRβ locus partially D–J rearranged. They could be expanded for over 3 months and used to reconstitute the T‐cell compartments of sublethally irradiated T‐cell‐deficient CD3ε−/− mice or lethally irradiated WT mice. Pro‐T cells generated in this system could partially correct the T‐cell lymphopenia of pre‐Tα−/− mice. However, reconstituted CD3ε−/− mice suffered from a wasting disease that was prevented by co‐injection of purified CD4+ CD25high WT Treg cells. In a T‐cell‐sufficient or T‐lymphopenic setting, the development of disease was not observed. Thus, this in vitro culture system represents a powerful tool to generate large numbers of pro‐T cells for transplantation and possibly with clinical applications.
Dendritic cell specific targeting of MyD88 signalling pathways in vivo
Authors: Arnold‐Schrauf Catharina , Berod Luciana , Sparwasser Tim
Published: November 2014

Dendritic cells (DCs) are key regulators of both innate and adaptive immunity. During infection, DCs recognise pathogen‐associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs) including the Toll‐like receptor (TLR) family. TLRs mainly signal via the adaptor protein MyD88. This signalling pathway is required for immune protection during many infections, which are lethal in the absence of MyD88. However, the cell type specific importance of this pathway during both innate and adaptive immune responses against pathogens in vivo remains ill‐defined. We discuss recent findings from conditional KO or gain‐of‐function mouse models targeting TLR/MyD88 signalling pathways in DCs and other myeloid cells during infection. While the general assumption that MyD88‐dependent recognition by DCs is essential for inducing protective immunity holds true in some instances, the results surprisingly indicate a much more complex context‐dependent requirement for this pathway in DCs and other myeloid or lymphoid cell‐types in vivo. Furthermore, we highlight the advantages of Cre‐mediated DC targeting approaches and their possible limitations. We also present future perspectives on the development of new genetic mouse models to target distinct DC subsets in vivo. Such models will serve to understand the functional heterogeneity of DCs in vivo.
Lipase‐catalyzed synthesis of glucose‐6‐O‐hexanoate in deep eutectic solvents
Authors: Pöhnlein Martin , Ulrich Jonas , Kirschhöfer Frank , Nusser Michael , Muhle‐Goll Claudia , Kannengiesser Bastian , Brenner‐Weiß Gerald , Luy Burkhard , Liese Andreas , Syldatk Christoph , Hausmann Rudolf
Published: November 2014

Enzymatic synthesis of sugar fatty acid esters in organic solvents is a well‐described procedure to synthesize glycolipids. This study aims at replacing these solvents with deep eutectic solvents (DES), a group of solvents that gained more and more interest during the last years, since they can be easily produced from non‐toxic resources. Enzymatic glycolipid synthesis in deep eutectic solvents was investigated, employing Candida antarctica lipase B (Novozyme 435) in various deep eutectic solvents. A successful lipase‐catalyzed synthesis of glucose fatty acid esters gave proof of this concept, while using the two deep eutectic solvents consisting of choline chloride and urea (CC : U) and choline chloride and glucose (CC : Glc). Additionally the DES consisting of choline chloride and glucose was observed to act as solvent and substrate for the synthesis at the same time.

Practical applications

Glycolipids find applications in many everyday products like cosmetic and pharmaceutical formulations, food and classic cleaning products, utilizing their good detergent or emulsification properties. Glycolipids can, among other routes, be synthesized via lipase‐catalyzed reactions, which are often carried out in organic solvents. By replacing these organic solvents with more ecologically friendly solvents like deep eutectic solvents, the reaction might be improved and the amount of waste produced could be reduced.

The lipase‐catalyzed synthesis of glucose‐6‐O‐hexanoate employing glucose and vinyl hexanoate in different deep eutectic solvents was demonstrated within the manuscript.
Enantioselective Epoxidation of Dihydroquinolines by Using Iminium Salt Organocatalysts
Authors: Bulman Page Philip C. , Day David P. , Chan Yohan
Published: November 2014

The first examples of asymmetric epoxidation of dihydroquinoline substrates using iminium salt organocatalysts are reported. The 3,4‐epoxytetrahydroquinoline products are obtained in good yields and with moderate to good enantioselectivities.
Conducting polymer‐based flexible supercapacitor
Authors: Shown Indrajit , Ganguly Abhijit , Chen Li‐Chyong , Chen Kuei‐Hsien
Published: November 2014

Flexible supercapacitors, a state‐of‐the‐art material, have emerged with the potential to enable major advances in for cutting‐edge electronic applications. Flexible supercapacitors are governed by the fundamentals standard for the conventional capacitors but provide high flexibility, high charge storage and low resistance of electro active materials to achieve high capacitance performance. Conducting polymers (CPs) are among the most potential pseudocapacitor materials for the foundation of flexible supercapacitors, motivating the existing energy storage devices toward the future advanced flexible electronic applications due to their high redox active‐specific capacitance and inherent elastic polymeric nature. This review focuses on different types of CPs‐based supercapacitor, the relevant fabrication methods and designing concepts. It describes recent developments and remaining challenges in this field, and its impact on the future direction of flexible supercapacitor materials and relevant device fabrications.
Phenolic Metabolites from the Stems and Leaves of Sophora flavescens
Authors: Zhang Chi , Wang Yan‐Min , Zhao Feng‐Chun , Chen Liang‐Mian , Zhang Qi‐Wei , Gao Hui‐Min , Wang Zhi‐Min
Published: November 2014

Two new compounds, (−)‐(6aR,11aR)‐4‐methoxy‐8,9‐(methylenedioxy)pterocarpan 3‐O‐β‐D‐glucopyranoside (1) and 5‐hydroxy‐7‐methoxyisoflavone 4′‐O‐β‐D‐xylopyranosyl‐(1→6)‐β‐D‐glucopyranoside (2), were isolated, together with 30 known compounds from the stems and leaves of Sophora flavescens Aition. Their structures were elucidated by extensive spectroscopic analysis, including HR‐ESI‐MS data. A preliminary comparison of phenolic metabolite profiles, based on the qualitative HPLC analysis, indicated that the composition of the roots and the aerial parts were significantly different.
Terminology Related to the Phenomenon ‘Self‐Disproportionation of Enantiomers’ (SDE)
Authors: Soloshonok Vadim A. , Klika Karel D.
Published: November 2014

Terms related to the phenomenon self‐disproportion of enantiomers (SDE) are discussed, particularly with respect to recently suggested alternative terms. Of the numerous terms proffered to describe this phenomenon, it is recommended that the acronym SDE be retained based on its qualities and the fact that its perceived shortcomings are invalid. The term can be readily applied to any process that exhibits the phenomenon of transforming a scalemic sample into fractions containing different enantiomeric compositions in comparison to the enantiomeric composition of the starting sample, and is not restricted solely to chromatographic occurrences. Chromatographic observations, though, can be specifically described by the term enantiomer self‐disproportionation over achiral chromatography (ESDAC). Use of the term homochiral in concert with its intended original meaning is also advocated.
25‐Hydroxyvitamin D2/D3 levels and factors associated with systemic inflammation and melanoma survival in the Leeds Melanoma Cohort
Authors: Newton‐Bishop Julia A. , Davies John R. , Latheef Faheem , Randerson‐Moor Juliette , Chan May , Gascoyne Jo , Waseem Saila , Haynes Susan , O'Donovan Charles , Bishop D. Timothy
Published: November 2014

Lower 25‐hydroxyvitamin D2/D3 levels at melanoma diagnosis are associated with thicker primaries and poorer survival. We postulated that this might relate to the deleterious effect of systemic inflammation as 25‐hydroxyvitamin D2/D3 levels are inversely associated with levels of C‐reactive protein. 2,182 participants in the Leeds Melanoma Cohort (median follow‐up 7.98 years) provided data on drug exposure, comorbidities and a serum 25‐hydroxyvitamin D2/D3 level at recruitment. Factors reported to modify systemic inflammation (low vitamin D levels, high body mass index, use of aspirin or nonsteroidal anti‐inflammatory drugs or smoking were tested as predictors of microscopic ulceration (in which primary tumors are inflamed) and melanoma‐specific survival (MSS). Ulceration was independently associated with lower 25‐hydroxyvitamin D2/D3 levels (odds ratio (OR) = 0.94 per 10 nmol/L, 95% CI 0.88–1.00, p = 0.05) and smoking at diagnosis (OR = 1.47, 95% CI 1.00–2.15, p = 0.04). In analyses adjusted for age and sex, a protective effect was seen of 25‐hydroxyvitamin D2/D3 levels at diagnosis on melanoma death (OR = 0.89 per 10 nmol/L, 95% CI 0.83–0.95, p < 0.001) and smoking increased the risk of death (OR = 1.13 per 10 years, 95% CI 1.05–1.22, p = 0.001). In multivariable analyses (adjusted for tumor thickness) the associations with death from melanoma were low 25‐hydroxyvitamin D2/D3 level at recruitment (<20 nmol/L vs. 20–60 nmol/L, hazard ratio (HR) = 1.52, 95% CI 0.97–2.40, p = 0.07) and smoking duration at diagnosis (HR = 1.11, 95% CI 1.03–1.20, p = 0.009). The study shows evidence that lower vitamin D levels and smoking are associated with ulceration of primary melanomas and poorer MSS. Further analyses are necessary to understand any biological mechanisms that underlie these findings.
Human papillomavirus testing 2007–2012: Co‐testing and triage utilization and impact on subsequent clinical management
Authors: Cuzick Jack , Myers Orrin , Hunt William C. , Saslow Debbie , Castle Philip E. , Kinney Walter , Waxman Alan , Robertson Michael , Wheeler Cosette M. ,   on behalf of the New Mexico HPV Pap Registry Steering Committee
Published: November 2014

In the United States, high‐risk human papillomavirus (HPV) testing is recommended for women with atypical squamous cells of unknown significance (ASC‐US) cytology, and co‐testing with cytology and HPV is a recommended option for screening women aged ≥30 years. No population‐based data are available to examine utilization of HPV testing in the United States. Using the New Mexico HPV Pap Registry data resource, we describe population trends (2007–2012) in utilization and positivity rates for HPV testing as a routine co‐testing screening procedure and for triage of ASC‐US and other cytologic outcomes. For women aged 30–65 years co‐testing increased from 5.2% in 2007 to 19.1% in 2012 (p < 0.001). Overall 82% of women with ASC‐US cytology who did not receive co‐testing also had an HPV test. HPV positivity was age and cytology result dependent but did not show time trends. For women with negative cytology, 64% received an additional screening test within 3 years if no co‐test was done or if it was positive, but this was reduced to 47% with a negative co‐test. Reflex HPV testing for ASC‐US cytology is well established and occurs in most women. Evidence for reflex testing is also observed following other abnormal cytology outcomes. Co‐testing in women aged 30–65 years has more than tripled from 2007 to 2012, but was still only used in 19.1% of women aged 30–65 years attending for screening in 2012. Women receiving co‐testing had longer repeat screening intervals, but rescreening within 3 years is still very common even with co‐testing.
Dietary acrylamide and cancer risk: An updated meta‐analysis
Authors: Pelucchi Claudio , Bosetti Cristina , Galeone Carlotta , La Vecchia Carlo
Published: November 2014

The debate on the potential carcinogenic effect of dietary acrylamide is open. In consideration of the recent findings from large prospective investigations, we conducted an updated meta‐analysis on acrylamide intake and the risk of cancer at several sites. Up to July 2014, we identified 32 publications. We performed meta‐analyses to calculate the summary relative risk (RR) of each cancer site for the highest versus lowest level of intake and for an increment of 10 µg/day of dietary acrylamide, through fixed‐effects or random‐effects models, depending on the heterogeneity test. Fourteen cancer sites could be examined. No meaningful associations were found for most cancers considered. The summary RRs for high versus low acrylamide intake were 0.87 for oral and pharyngeal, 1.14 for esophageal, 1.03 for stomach, 0.94 for colorectal, 0.93 for pancreatic, 1.10 for laryngeal, 0.88 for lung, 0.96 for breast, 1.06 for endometrial, 1.12 for ovarian, 1.00 for prostate, 0.93 for bladder and 1.13 for lymphoid malignancies. The RR was of borderline significance only for kidney cancer (RR = 1.20; 95% confidence interval, CI, 1.00–1.45). All the corresponding continuous estimates ranged between 0.95 and 1.03, and none of them was significant. Among never‐smokers, borderline associations with dietary acrylamide emerged for endometrial (RR = 1.23; 95% CI, 1.00–1.51) and ovarian (RR = 1.39; 95% CI, 0.97–2.00) cancers. This systematic review and meta‐analysis of epidemiological studies indicates that dietary acrylamide is not related to the risk of most common cancers. A modest association for kidney cancer, and for endometrial and ovarian cancers in never smokers only, cannot be excluded.
Spatially defined microsatellite analysis reveals extensive genetic mosaicism and clonal complexity in intestinal metaplastic glands
Authors: Guo Yan , Zhou Juan , Huang Ayuan , Li Jianfang , Yan Min , Zhu Zhenggang , Zhao Xiaodong , Gu Jianren , Liu Bingya , Shao Zhifeng
Published: November 2014

Intestinal metaplasia (IM) has been recognized as the first irreversible precancerous stage of intestinal‐type gastric cancer at which genetic instabilities, such as microsatellite (MS) instability and loss of heterozygosity, can already be detected. However, the extent and clonal relationship of these genetic lesions in the precancerous tissues are not fully appreciated. In this work, we have used well established MS markers to analyze the relatedness of spatially separated individual metaplastic glands as well as subsegments within single glands from the same patients. We found that individual IM glands frequently show different marker lengths even for closely apposed IM glands, suggesting that these tissues have already gained the ability to independently evolve their genome regardless of whether or not they share a common origin. Furthermore, within individual IM glands, there is also significant intra‐gland diversity in the MS markers. Since most of these cells are not dividing and only have a limited lifespan, this result indicates that in each IM gland, a single dominant clone is rare and new clones are constantly created by either progenitor cells or stem cells. This greatly enhanced ability to create de novo genetic alterations may underlie the importance of this stage in the eventual progression toward cancer. Given the widely observed phenotype switch in the early stages of many solid tumors, whether this associated genetic stability is also an intrinsic property of metaplastic transformation should be extensively characterized to further our understanding of cancer initiation.
Effects of altered expression and activity levels of CK1δ and ɛ on tumor growth and survival of colorectal cancer patients
Authors: Richter Julia , Ullah Kalim , Xu Pengfei , Alscher Vanessa , Blatz Annette , Peifer Christian , Halekotte Jakob , Leban Johann , Vitt Daniel , Holzmann Karlheinz , Bakulev Vasiliy , Pinna Lorenzo A. , Henne‐Bruns Doris , Hillenbrand Andreas , Kornmann Marko , Leithäuser Frank , Bischof Joachim , Knippschild Uwe
Published: November 2014

Colorectal cancer (CRC) is the fourth leading cause of cancer related death worldwide due to high apoptotic resistance and metastatic potential. Because mutations as well as deregulation of CK1 isoforms contribute to tumor development and tumor progression, CK1 has become an interesting drug target. In this study we show that CK1 isoforms are differently expressed in colon tumor cell lines and that growth of these cell lines can be inhibited by CK1‐specific inhibitors. Furthermore, expression of CK1δ and ɛ is changed in colorectal tumors compared to normal bowel epithelium, and high CK1ɛ expression levels significantly correlate with prolonged patients' survival. In addition to changes in CK1δ and ɛ expression, mutations within exon 3 of CK1δ were detected in colorectal tumors. These mutations influence ATP binding resulting in changes in kinetic parameters of CK1δ. Overexpression of these mutants in HT29 cells alters their ability to grow anchorage independently. Consistent with these results, these CK1δ mutants lead to differences in proliferation rate and tumor size in xenografts due to changes in gene expression, especially in genes involved in regulation of cell proliferation, cell cycle, and apoptosis. In summary, our results provide evidence that changes in the expression levels of CK1 isoforms in colorectal tumors correlate with patients' survival. Furthermore, CK1 mutants affect growth and proliferation of tumor cells and induce tumor growth in xenografts, leading to the assumption that CK1 isoforms provide interesting targets for the development of novel effective therapeutic concepts to treat colorectal cancer.
Attenuating noise from computed tomography medical images using a coefficients‐driven total variation denoising algorithm
Authors: Al‐Ameen Zohair , Sulong Ghazali
Published: November 2014

The aim of image denoising is to recover a visually accepted image from its noisy observation with as much detail as possible. The noise exists in computed tomography images due to hardware errors, software faults and/or low radiation dose. Because of noise, the analysis and extraction of accurate medical information is a challenging task for specialists. Therefore, a novel modification on the total variational denoising algorithm is proposed in this article to attenuate the noise from CT images and provide a better visual quality. The newly developed algorithm can properly detect noise from the other image components using four new noise distinguishing coefficients and reduce it using a novel minimization function. Moreover, the proposed algorithm has a fast computation speed, a simple structure, a relatively low computational cost and preserves the small image details while reducing the noise efficiently. Evaluating the performance of the proposed algorithm is achieved through the use of synthetic and real noisy images. Likewise, the synthetic images are appraised by three advanced accuracy methods –Gradient Magnitude Similarity Deviation (GMSD), Structural Similarity (SSIM) and Weighted Signal‐to‐Noise Ratio (WSNR). The empirical results exhibited significant improvement not only in noise reduction but also in preserving the minor image details. Finally, the proposed algorithm provided satisfying results that outperformed all the comparative methods.
Improved resolution of 3D printed scaffolds by shrinking
Authors: Chia Helena N. , Wu Benjamin M.
Published: November 2014

Three‐dimensional printing (3DP) uses inkjet printheads to selectively deposit liquid binder to adjoin powder particles in a layer‐by‐layer fashion to create a computer‐modeled 3D object. Two general approaches for 3DP have been described for biomedical applications (direct and indirect 3DP). The two approaches offer competing advantages, and both are limited by print resolution. This study describes a materials processing strategy to enhance 3DP resolution by controlled shrinking net‐shape scaffolds. Briefly, porogen preforms are printed and infused with the desired monomer or polymer solution. After solidification or polymerization, the porogen is leached and the polymer is allowed to shrink by controlled drying. Heat treatment is performed to retain the dimensions against swelling forces. The main objective of this study is to determine the effects of polymer content and post‐processing on dimension, microstructure, and thermomechanical properties of the scaffold. For polyethylene glycol diacrylate (PEG‐DA), reducing polymer content corresponded with greater shrinkage with maximum shrinkage of ∼80 vol% at 20% vol% PEG‐DA. The secondary heat treatment retains the microarchitecture and new dimensions of the scaffolds, even when the heat‐treated scaffolds are immersed into water. To demonstrate shrinkage predictability, 3D components with interlocking positive and negative features were printed, processed, and fitted. This material processing strategy provides an alternative method to enhance the resolution of 3D scaffolds, for a wide range of polymers, without optimizing the binder‐powder interaction physics to print each material combination. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1415–1423, 2015.
Anti-Sclerostin Antibody Treatment in a Rat Model of Progressive Renal Osteodystrophy
Authors: Moe Sharon M , Chen Neal X , Newman Christopher L , Organ Jason M , Kneissel Michaela , Kramer Ina , Gattone Vincent H , Allen Matthew R
Published: November 2014

Chronic kidney disease (CKD) is associated with abnormalities in bone quantity and quality, leading to increased fractures. Recent studies suggest abnormalities of Wnt signaling in animal models of CKD and elevated sclerostin levels in patients with CKD. The goal of this study was to evaluate the effectiveness of anti-sclerostin antibody treatment in an animal model of progressive CKD with low and high parathyroid hormone (PTH) levels. Cy/+ male rats (CKD) were treated without or with calcium in the drinking water at 25 weeks of age to stratify the animals into high PTH and low PTH groups, respectively, by 30 weeks. Animals were then treated with anti-sclerostin antibody at 100 mg/kg i.v. weekly for 5 doses, a single 20-µg/kg subcutaneous dose of zoledronic acid, or no treatment, and were then euthanized at 35 weeks. As a positive control, the efficacy of anti-sclerostin antibody treatment was also evaluated in normal littermates. The results demonstrated that the CKD animals with high PTH had lower calcium, higher phosphorus, and lower FGF23 compared to the CKD animals with low PTH. Treatment with anti-sclerostin antibody had no effect on any of the biochemistries, whereas zoledronic acid lowered dkk-1 levels. The anti-sclerostin antibody increased trabecular bone volume/total volume (BV/TV) and trabecular mineralization surface in animals with low PTH, but not in animals with high PTH. Neither anti-sclerostin antibody nor zoledronic acid improved biomechanical properties in the animals. Cortical porosity was severe in high-PTH animals and was unaffected by either treatment. In contrast, in normal animals treated with anti-sclerostin antibody, there was an improvement in bone volume, cortical geometry, and biomechanical properties. In summary, this is the first study to test the efficacy of anti-sclerostin antibody treatment on animals with advanced CKD. We found efficacy in improving bone properties only when the PTH levels were low. © 2014 American Society for Bone and Mineral Research
Bisphosphonates for the Prevention of Fractures in Osteogenesis Imperfecta: Meta-Analysis of Placebo-Controlled Trials
Authors: Hald Jannie D , Evangelou Evangelos , Langdahl Bente L , Ralston Stuart H
Published: November 2014

Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69–1.01], p = 0.06) with no heterogeneity between studies (I2 = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52–0.96], p = 0.02), but with considerable heterogeneity (I2 = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61–1.02], p = 0.07, I2 = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition. © 2014 American Society for Bone and Mineral Research.
MiR-497∼195 Cluster MicroRNAs Regulate Osteoblast Differentiation by Targeting BMP Signaling
Authors: Grünhagen Johannes , Bhushan Raghu , Degenkolbe Elisa , Jäger Marten , Knaus Petra , Mundlos Stefan , Robinson Peter N , Ott Claus-Eric
Published: November 2014

MicroRNAs play important roles during cell reprogramming and differentiation. In this study, we identified the miR-497∼195 cluster, a member of the miR-15 family, as strongly upregulated with age of postnatal bone development in vivo and late differentiation stages of primary osteoblasts cultured in vitro. Early expression of miR-195–5p inhibits differentiation and mineralization. Microarray analyses along with quantitative PCR demonstrate that miR-195–5p alters the gene regulatory network of osteoblast differentiation and impairs the induction of bone morphogenetic protein (BMP) responsive genes. Applying reporter gene and Western blot assays, we show that miR-195–5p interferes with the BMP/Smad-pathway in a dose-dependent manner. Systematically comparing the changes in mRNA levels in response to miR-195–5p overexpression with the changes observed in the natural course of osteoblast differentiation, we demonstrate that microRNAs of the miR-15 family affect several target genes involved in BMP signaling. Predicted targets including Furin, a protease that cleaves pro-forms, genes encoding receptors such as Acvr2a, Bmp1a, Dies1, and Tgfbr3, molecules within the cascade like Smad5, transcriptional regulators like Ski and Zfp423 as well as Mapk3 and Smurf1 were validated by quantitative PCR. Taken together, our data strongly suggest that miR-497∼195 cluster microRNAs act as intracellular antagonists of BMP signaling in bone cells. © 2014 American Society for Bone and Mineral Research.
Permanents and Determinants of Latin Squares
Authors: Donovan Diane , Johnson Kenneth , Wanless Ian M.
Published: November 2014

Let L be a latin square of indeterminates. We explore the determinant and permanent of L and show that a number of properties of L can be recovered from the polynomials and per(L). For example, it is possible to tell how many transversals L has from per(L), and the number of 2 × 2 latin subsquares in L can be determined from both and per(L). More generally, we can diagnose from or per(L) the lengths of all symbol cycles. These cycle lengths provide a formula for the coefficient of each monomial in and per(L) that involves only two different indeterminates. Latin squares A and B are trisotopic if B can be obtained from A by permuting rows, permuting columns, permuting symbols, and/or transposing. We show that nontrisotopic latin squares with equal permanents and equal determinants exist for all orders that are divisible by 3. We also show that the permanent, together with knowledge of the identity element, distinguishes Cayley tables of finite groups from each other. A similar result for determinants was already known.
Soil moisture variability in Iowa
Authors: Khong Angela , Wang Jessica K. , Quiring Steven M. , Ford Trent W.
Published: November 2014

Thirty years (1954–1983) of soil moisture data from 60 sites in Iowa are used to identify the dominant modes of spatial and temporal variability. Both soil moisture and precipitation exhibit a northwest to southeast gradient across Iowa, with wetter conditions in the southeast and drier conditions in the northwest. Climate and soil characteristics are responsible for the spatial variations in soil moisture. There is a pronounced annual soil moisture cycle that has three distinct phases: a moist phase (April–June), a drying phase (June–September), and a recharge phase (September–November). Spring soil moisture is strongly controlled by the amount of recharge during the previous fall. There is no evidence of a long‐term trend in soil moisture; however there is significant interannual variability and about 20% of the variance is attributable to El Niño‐Southern Oscillation (ENSO). The warm (cold) phase of ENSO is associated with above (below) average soil moisture in Iowa. The multi‐decadal soil moisture record is used to analyse drought frequency and magnitude in Iowa, and to place the 2012 Midwest drought in historical context. In general, Iowa drought is more common during the latter part of the warm season (August through November), but tends to be more severe during the early part of the warm season (April–July). We find that the 2012 drought was unusual because it persisted and intensified throughout the growing season.
Changing temperature and precipitation extremes in the Hindu Kush‐Himalayan region: an analysis of CMIP3 and CMIP5 simulations and projections
Authors: Panday Prajjwal K. , Thibeault Jeanne , Frey Karen E.
Published: November 2014

The Hindu Kush‐Himalayan (HKH) region epitomizes a geographic region where cryospheric processes coupled with hydrological regimes are under threat owing to a warming climate and shifts in climate extremes. In this study, we analyse global climate models in the Coupled Model Intercomparison Project phase 3 (CMIP3) and phase 5 (CMIP5) archives to investigate the qualitative aspects of change and trends in temperature and precipitation indices. Specifically, we examine and evaluate multi‐model, multi‐scenario climate change projections and seven extreme temperature and precipitation indices over the eastern Himalaya (EH) and western Himalaya‐Karakoram (WH) regions for the 21st century. Density distribution plots of observed climate indices for meteorological stations and gridded indices are also analysed, which indicate significant negative trends in the annual number of frost days and significant increasing trends in warm nights in the EH region over the 1960–2000 period. Multi‐model average (MMA) projections additionally indicate continued trends towards more extreme conditions consistent with a warmer, wetter climate. Precipitation projections indicate increased mean precipitation with more frequent extreme rainfall during monsoon season in the EH region, and a wetter cold season in the WH region. Time series of all MMA precipitation indices exhibit significant increasing trends over the 1901–2099 period. By comparison, time series of temperature indices show decreases in the intra‐annual extreme temperature range and total number of frost days, as well as increases in warm nights. In general, these future projections point towards increases in summertime temperatures and modifications in precipitation across both regions.
Structural phase transitions in loparite‐(Ce): evidences from Raman light scattering
Authors: Popova E. A. , Yakovenchuk V. N. , Lushnikov S. G. , Krivovichev S. V.
Published: November 2014

Raman spectroscopic studies of loparite‐(Ce), a mineral of the perovskite family, are presented. Polarized Raman spectra were obtained in the temperature range of 50–300 K. As analysis of the behavior of Raman modes showed, the temperature dependences of wavenumber, damping and intensity of the optical modes exhibited anomalies near 220 and 150 K. Softening of the low‐wavenumber modes observed in the vicinity of 150 K is interpreted as an evidence of a ferroelectric phase transition. An anisotropic quasielastic light scattering in the low‐wavenumber region of the Raman spectra was observed from 300 to 150 K. As the data suggest, loparite‐(Ce) has two structural phase transitions, one of which (at 150 K) is a ferroelectric transition of the order–disorder type. Copyright © 2014 John Wiley & Sons, Ltd.