bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing a culture of perinatal safety in a community hospital
Authors: Phelan Jeffrey P. , Korst Lisa M.
Published: July 2011

While unsafe behavior of frontline hospital staff, primarily physicians and nurses, is sometimes the proximal cause of adverse events, the critical importance of system‐wide, hospital organizational factors is now being acknowledged(1,2). These organizational factors create the “safety culture” that influences the occurrence of these proximal failures.(3) The concept of safety culture originated in high‐reliability organization theory, which was largely developed by a group of social scientists at the University of California at Berkeley who studied high‐risk organizations that have achieved very low accident and error rates, for example, aircraft carrier flight decks, nuclear power plants and air‐traffic control systems.(4–6) Safety culture refers to the enduring and shared beliefs and practices of organization members regarding the organization's willingness to detect and learn from errors.(7)
Ethics, risk, and patient‐centered care: How collaboration between clinical ethicists and risk management leads to respectful patient care
Authors: Sine David M. , Sharpe Virginia A.
Published: July 2011

Patient‐centered care is driven in part by the ethical principle of autonomy and considers patients' cultural traditions, personal preferences, values, family situations, and lifestyles. Patient decision‐making capacity, surrogate decision making with or in the absence of a patient's advance directive, and the right to refuse treatment are three patient‐care issues that are central to the work done by both the risk manager and the clinical ethicist that have strong relevance to patient‐centered care. This article discusses these three issues briefly and offers two challenging case studies involving patient‐centered care that illustrate how a clinical ethics consultation may help to avert the escalation that can lead to a tort claim.
Improving conflicting specifications of time‐modulated antenna arrays by using a multiobjective evolutionary algorithm
Authors: Chen Yikai , Yang Shiwen , Nie Zaiping
Published: July 2011

By using the time modulation technique in antenna arrays, the stringent requirements on excitation error tolerance can be relaxed. However, the sideband signals spaced at multiples of the modulation frequency need to be suppressed in some applications. Multiobjective optimization is an important tool in the design of arrays with conflicting goals, such as low sidelobe level, low sideband level, and narrow beamwidth in the time‐modulated antenna arrays. In this paper, a novel multiobjective evolutionary algorithm based on objective decomposition (MOEA/D) with differential evolution operator and objective normalization technique is employed for the time‐modulated array synthesis, which is typically a problem with disparately scaled conflicting objectives. The effectiveness of the method is demonstrated by comparing the performances obtained by MOEA/D with those of previously reported results obtained by a single‐objective differential evolution algorithm and simulated annealing technique. Copyright © 2011 John Wiley & Sons, Ltd.
Migration and remyelination by oligodendrocyte progenitor cells transplanted adjacent to focal areas of spinal cord inflammation
Authors: Wang Yanping , Piao Jing‐Hua , Larsen Eric C. , Kondo Yoichi , Duncan Ian D.
Published: July 2011

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Exogenous cell replacement in MS lesions has been proposed as a means of achieving remyelination when endogenous remyelination has failed. However, the ability of exogenous cells to remyelinate axons in the presence of inflammation remains uncertain. We have explored the remyelinating capacity of an oligodendrocyte progenitor cell line CG‐4 transduced with the GFP gene and transplanted adjacent to a zymosan‐induced focal demyelination model in the rat spinal cord. The resulting zymosan‐induced lesions were characterized by persistent macrophage/microglia activation, focal demyelination, degeneration of axons, and reactive astrogliosis. GFP+ CG‐4 cells were found to migrate preferentially toward the inflammatory lesion and survive inside the lesion. A proportion of GFP+ CG‐4 cells differentiated into mature oligodendrocytes and remyelinated axons within the lesion. These findings suggest that grafted oligodendrocyte progenitors may migrate toward areas of inflammation in the adult rat spinal cord, where they can survive and differentiate into myelinating oligodendrocytes. © 2011 Wiley‐Liss, Inc.
A six‐step approach to developing future synoptic classifications based on GCM output
Authors: Lee Cameron C. , Sheridan Scott C.
Published: July 2011

One way in which global climate model (GCM) output can be utilized to infer local impacts is through the use of synoptic climatology: creating a set of atmospheric patterns that capture the variability in the climate system, and then analyzing trends and variability in the frequency of these patterns moving into the future. In this paper, we demonstrate a new synoptic climatological technique for classifying atmospheric patterns that can be used in conjunction with GCM output data (in this case, the Community Climate System Model 3). We apply this method to 850‐hPa temperature patterns over the contiguous United States to derive daily categorizations. A total of 15 clusters are created from the data set; once the mean GCM bias is removed, historical cluster frequencies in the GCM data set are not statistically different from those of the reanalysis data set. In the future, significant changes in frequency are observed across most of the transition season clusters, as they broaden in seasonality at the expense of winter clusters, some of which nearly entirely disappear. Changes are greater moving further into the future, and greater for the more carbon‐intensive special report on emissions scenarios (SRES) scenarios (A1FI, A2) than the less‐intensive scenario tested (B1). Diagnostics test how well the mean patterns of the reanalysis data set, GCM historical data set and the future GCM data sets resemble each other. For some clusters, mean bias between the historical and future data sets grows substantially by the end of the 21st century under the more carbon‐intensive scenarios. Copyright © 2011 Royal Meteorological Society
Alkenones and coccoliths in ice‐rafted debris during the Last Glacial Maximum in the North Atlantic: implications for the use of UK37′ as a sea surface temperature proxy
Authors: Rosell‐Melé A. , Balestra B. , Kornilova O. , Mcclymont E. L. , Russell M. , Monechi S. , Troelstra S. , Ziveri P.
Published: July 2011

The UK37′ index has proven to be a robust proxy to estimate past sea surface temperatures (SSTs) over a range of time scales, but like any other proxy, it has uncertainties. For instance, in reconstructions of the Last Glacial Maximum (LGM) in the northern North Atlantic, UK37′ indicates higher temperatures than those derived from foraminiferal proxies. Here we evaluate whether such warm glacial estimates are caused by the advection of reworked alkenones in ice‐rafted debris (IRD) to deep‐sea sediments. We have quantified both coccolith assemblages and alkenones in sediments from glaciogenic debris flows in the continental margins of the northern North Atlantic, and from a deep‐sea core from the Reykjanes Ridge. Certain debris flow deposits in the North Atlantic were generated by the presence of massive ice‐sheets in the past, and their associated ice streams. Such deposits are composed of the same materials that were present in the IRD at the time they were generated. We conclude that ice rafting from some locations was a transport pathway to the deep sea floor of reworked alkenones and pre‐Quaternary coccolith species during glacial stages, but that not all of the IRD contained alkenones, even when reworked coccoliths were present. We speculate that the ratio of reworked coccoliths to alkenone concentration might be useful to infer whether significant reworked alkenone inputs from IRD did occur at a particular site in the glacial North Atlantic. We also observe that alkenones in some of the debris flows contain a colder signal than estimated for LGM sediments in the northern North Atlantic. This is also clear in the deep‐sea core studied where the warmest intervals do not correspond to the intervals with large inputs of reworked coccoliths or IRD. We conclude that any possible bias to UK37′ estimates associated with reworked alkenones is not necessarily towards higher values, and that the high SST anomalies for the LGM are unlikely to be the result of a bias caused by IRD inputs. Copyright © 2011 John Wiley & Sons, Ltd.
Synthesis and study of a molecularly imprinted polymer for specific solid‐phase extraction of vinflunine and its metabolite from biological fluids
Authors: Lopez Claire , Claude Bérengère , Morin Philippe , Pelissou Martine , Pena Richard , Max Jean‐Paul , Ribet Jean‐Paul
Published: July 2011

A molecularly imprinted polymer (MIP) was synthesized in order to specifically extract vinflunine, an anticancer agent, and its metabolite (4‐O‐deacetylvinflunine) from bovine plasma and artificial urine by solid‐phase extraction (SPE). Vinorelbine, a non‐fluorinated analogue of vinflunine, was selected as a template for MIP synthesis. The selectivity of MIP versus the template (vinorelbine) and other alkaloids (catharanthine, vinblastine, vincristine, vinflunine and 4‐O‐deacetylvinflunine) was shown by a SPE protocol carried out with non‐aqueous samples. A second protocol was developed for aqueous samples with two consecutive washing steps (AcOH–NH2OH buffer (pH 7, I=10 mM)–MeOH mixture 95:5 v/v and ACN–AcOH mixture 99:1 v/v) and an elution step (MeOH–AcOH mixture 90:10 v/v). Thus, MIP‐SPE of bovine plasma brought high recoveries, 81 and 89% for vinflunine and its metabolite, respectively. This protocol was slightly modified for artificial urine samples in order to obtain a good MIP/NIP selectivity; furthermore, elution recoveries were 73 and 81% for vinflunine and its metabolite, respectively. Repeatability was assessed in both biological matrices and RSD (%) were inferior to 4%. The MIP also showed a suitable linearity (r2 superior to 0.99), between 0.25 and 10 μg/mL for plasma, and between 1 and 5 μg/mL for artificial urine.
Using adult groups of red‐cockaded woodpeckers for translocations and population augmentation
Authors: Herbez Erin M. , Chamberlain Michael J. , Wood Douglas R.
Published: July 2011

The red‐cockaded woodpecker (Picoides borealis; hereafter RCW) was listed as federally endangered in 1973 after a population decline due primarily to habitat loss. Habitat fragmentation produces isolated populations of RCWs and managers often translocate subadult birds to augment existing populations. Although several studies have examined success of translocating subadults, detailed studies examining translocations of adults have been limited. We evaluated the feasibility and success of using adult RCWs for translocation and augmentation of existing populations in Morehouse Parish, Louisiana, 2006–2009. We translocated 41 primarily adult RCWs, consisting of 12 potential breeding groups (PBGs) and 5 single bird groups to suitable habitat at the Morehouse Parish Conservation Area (MPCA). Fifty‐nine percent of translocated RCWs remained on the MPCA and 45% became breeders. Thirty‐four percent of translocated RCWs were breeding after being on the MPCA for 2 breeding seasons, suggesting that translocated adult RCWs can augment the breeding population within 2 years of translocation. Fledglings contributed by translocated RCWs ranged from 11% to 30% of the total fledglings on the MPCA. There were 5 PBGs established on the MPCA from translocated RCWs and 20% of the fledglings had at least 1 translocated parent. Success rates for translocation of adults in our study were lower than previous studies where subadults were used. However, previous research suggested that demographically isolated groups have a high risk of abandonment and extirpation, and thus do not contribute to the recovery of the species. The success rates we observed suggest that translocating adult groups may be a useful tool in RCW recovery, and hence should be considered by managers when demographically isolated groups occur. © 2011 The Wildlife Society.
The cochleovestibular nerve identified during auditory brainstem implantation in patients with narrow internal auditory canals: Can preoperative evaluation predict cochleovestibular nerve deficiency?
Authors: Song Mee Hyun , Kim Sang Cheol , Kim Jinna , Chang Jin Woo , Lee Won‐Sang , Choi Jae Young
Published: July 2011

Objectives/Hypothesis:

To analyze the value of preoperative diagnostic tools in predicting the status of the cochleovestibular nerve (CVN) in patients with narrow internal auditory canals (IAC).

Study Design:

Retrospective case series at a tertiary hospital.

Methods:

Eight profoundly deaf patients with narrow IACs who received auditory brainstem implantation were included in this study. The results of preoperative imaging, electrophysiologic, and auditory tests were correlated with the CVN status identified during auditory brainstem implantation.

Results:

Temporal bone computed tomography (CT) findings, including the patency of the bony cochlear nerve canal and the diameter of the IAC, were limited in accurately reflecting the status of the CVN. Magnetic resonance imaging (MRI) and preoperative auditory responses to either pure tone or environmental sounds were more accurate markers for detecting the presence of a CVN than CT; however, there were limitations in cases with a very thin CVN or combined severe mental retardation. Absence of promontory or intracochlear electrically evoked auditory brainstem responses were not always indicative of an absent CVN.

Conclusions:

Visualization on MRI and detection of auditory responses suggested the presence of a CVN in patients with narrow IACs; however, the possibility of the presence of a CVN should be considered even when there is no clear evidence of a CVN on preoperative evaluations. Therefore, physicians should be prudent when determining candidacy for cochlear implantation or auditory brainstem implantation in patients with narrow IACs.
Varicella zoster virus infection of the pharynx and larynx with multiple cranial neuropathies
Authors: Lin Yuan‐Yung , Kao Chuan‐Hsiang , Wang Chih‐Hung
Published: July 2011

Varicella zoster virus (VZV) infection of the head and neck region may present with various clinical symptoms, involving different entities and different routes of viral spreading. We present a case of VZV infection of the pharynx and larynx with multiple cranial nerve (CN) neuropathies (CN VII, VIII, IX, and X) of a 52‐year‐old woman who complained of the sudden onset of hoarseness, odynophagia, dysphagia, and hearing loss in the left ear, followed by left‐side facial weakness lasting for 1 week. Endoscopic examination revealed multiple mucosal erosions over the oropharynx, with extension upward to the nasopharynx and downward to the mucosa overlying the epiglottis, arytenoid, and vocal cord. All of these lesions tended to lateralize to the left side, suggesting a VZV infection diagnosis; this was confirmed by polymerase chain reaction on eruptional exudates, as well as serologic examination.
Enhancement of Cellular Uptake and Antitumor Efficiencies of Micelles with Phosphorylcholine
Authors: Tu Song , Chen Yuan‐Wei , Qiu Yong‐Bin , Zhu Kun , Luo Xiang‐Lin
Published: July 2011

Internalization of drug delivery micelles into cancer cells is a crucial step for antitumor therapeutics. Novel amphiphilic star‐shaped copolymers with zwitterionic phosphorylcholine (PC) block, 6‐arm star poly(ε‐caprolactone)‐b‐poly(2‐methacryloyloxyethyl phosphorylcholine) (6sPCL‐b‐PMPC), have been developed for encapsulation of poorly water‐soluble drugs and enhancement of their cellular uptake. The star‐shaped copolymers were synthesized by a combination of ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The copolymers self‐assembled to form spherical micelles with low critical micelle concentration (CMC). The sizes of the micelles range from 80 to 170 nm and increase 30 ≈ 80% after paclitaxel (PTX) loading. Labeled with fluorescein isothiocyanate (FITC), the micelles were confirmed by fluorescence microscopy to have been internalized efficiently by tumor cells. Direct visualization of the micelles within tumor cells by transmission electron microscopy (TEM) confirmed that the 6sPCL‐b‐PMPC micelles were more efficiently uptaken by tumor cells compared to PCL‐b‐PEG micelles. When incorporated with PTX, the 6sPCL‐b‐PMPC micelles show much higher cytotoxicity against Hela cells than PCL‐b‐PEG micelles, in response to the higher efficiency of cellular uptake.

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In Situ Forming Physical Hydrogels for Three‐dimensional Tissue Morphogenesis
Authors: Liu Yang , Liu Bo , Riesberg Jeremiah J. , Shen Wei
Published: July 2011

In situ forming physical hydrogels are formed through a biologically benign reaction between two multi‐arm macromers, one containing terminal thiol and the other containing terminal vinyl sulfone groups. One macromer is self‐assembled through a coiled‐coil domain; and the physical junction of this macromer confers the physical nature to the whole network. Unlike covalently cross‐linked hydrogels in which material degradation is a prerequisite for three‐dimensional cell movement, these physical hydrogels have junctions that undergo reversible dissociation and re‐association, constitutively opening paths for cell movement. Epithelial cells encapsulated in these hydrogels can form hollow spherical cysts without the need for material degradation.

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In Situ Photopolymerization of Biomaterials by Thiol‐yne Click Chemistry
Authors: Lomba Miguel , Oriol Luis , Alcalá Rafael , Sánchez Carlos , Moros María , Grazú Valeria , Serrano José Luis , De la Fuente Jesús M.
Published: July 2011

The thiol‐yne click chemistry reaction has been used for the in situ photocrosslinking of an aliphatic hyperbranched polyester. The biocompatibility of the resulting networks has been studied and marked cytotoxicity was not found for HeLa (human cervical carcinoma) tumoral cells and COS7 fibroblasts. The photoinduced thiol‐yne process allows the generation of patterned structures with different geometries in films by DLW and these materials can be used as substrates for cell adhesion. The influence of the substrate geometry on cell adhesion has been studied by culturing cells onto these substrates and a preference for the photopatterned polymeric material can be seen in some of the structures by contrast phase microscopy. Actin and vinculin fluorescent staining revealed different adhesion behavior for HeLa cells and COS7 fibroblasts and this could be assigned to the different motility of cells. The thiol‐yne photoreaction has proven to be an attractive approach for the preparation of micropatterned biomaterials.

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Polysulfone/Clay Nanocomposites by in situ Photoinduced Crosslinking Polymerization
Authors: Dizman Cemil , Ates Sahin , Uyar Tamer , Tasdelen Mehmet Atilla , Torun Lokman , Yagci Yusuf
Published: July 2011

PSU/MMT nanocomposites are prepared by dispersing MMT nanolayers in a PSU matrix via in situ photoinduced crosslinking polymerization. Intercalated methacrylate‐functionalized MMT and polysulfone dimethacrylate macromonomer are synthesized independently by esterification. In situ photoinduced crosslinking of the intercalated monomer and the PSU macromonomer in the silicate layers leads to nanocomposites that are formed by individually dispersing inorganic silica nanolayers in the polymer matrix. The morphology of the nanocomposites is investigated by XRD and TEM, which suggests the random dispersion of silicate layers in the PSU matrix. TGA results confirm that the thermal stability and char yield of PSU/MMT nanocomposites increases with the increase of clay loading.

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Synthesis of Well‐defined Amphiphilic Block Copolymers by Organotellurium‐Mediated Living Radical Polymerization (TERP)
Authors: Kumar Santosh , Changez Mohammad , Murthy C. N. , Yamago Shigeru , Lee Jae‐Suk
Published: July 2011

Low‐molecular weight amphiphilic diblock copolymers, polystyrene‐block‐poly (2‐vinylpyridine) (PS‐b‐P2VP), and (P2VP‐b‐PS) with different block ratios were synthesized for the first time via organotellurium‐mediated living radical polymerization (TERP). For both the homo‐ and block copolymerizations, good agreement between the theoretical, and experimental molecular weights was found with nearly 100% yield in every case. The molecular weight distribution for all the samples ranged between 1.10 and 1.24, which is well below the theoretical lower limit of 1.50 for a conventional free radical polymerization. Furthermore, a very simple approach to producing highly dense arrays of titania nanoparticles (TiO2) is presented using a site‐selective reaction of titanium tetraisopropoxide within the P2VP domains of micellar film of P2VP‐b‐PS in toluene through the sol–gel method.

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Functional Microgels Tailored by Droplet‐Based Microfluidics
Authors: Seiffert Sebastian
Published: July 2011

Monodisperse polymer gel particles with micrometer‐scale dimensions serve for a variety of applications, including those as microcapsules for actives or as micrometer‐sized matrixes for mesoscopic additives. These particles can be produced with exquisite control through the use of droplet‐based microfluidic templating followed by subsequent droplet solidification. This can be achieved by two ways: One way is to use pre‐microgel solutions of low molecular weight monomers and to form microgels by polymerizing these monomers. Another way is to use pre‐polymerized, high molecular weight precursors and to gel them by polymer‐analogous crosslinking. Both approaches have their specific advantages, allowing microgels to be tailored and optimized for specific needs such as those as delivery systems or scaffolds for living cells. This article highlights some recent achievements in the development and use of these microfluidic techniques to fabricate functional microgel particles.

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Stem cell MicroRNAs in senescence and immortalization: novel players in cancer therapy
Authors: Leal Jose A. , Feliciano Andrea , LLeonart Matilde E.
Published: July 2011

The molecular etiology of malignancy remains one of the most challenging disease processes under scientific investigation; therefore, improved approaches for their treatment are urgently needed. MicroRNAs are highly conserved nonprotein‐coding RNAs that regulate gene expression. They are involved in important homeostatic processes, such as cellular proliferation, cell death and development, and affect many diseases, including cancer. High‐throughput screenings based on microRNAs related to senescence/immortalization are potential tools for identifying novel proliferative microRNAs that might be involved in carcinogenesis. Recently, a subgroup of highly proliferative microRNAs, which belong to a cluster expressed exclusively in embryonic stem cells and their malignant derivatives (embryonic carcinoma cells), was revealed to play a role in senescence bypass, thereby providing immortalization to human cells. This finding supports the cancer stem cell theory and the relevance of microRNAs in human tumors. This article recapitulates the role of microRNAs that are associated with stem cell properties and their possible link in common pathways related to immortalization and cancer. Ultimately, cancer therapy that is based on the induction of a senescence response is proposed to be highly associated with the loss of stemness properties. Thus, it would be possible to “kill two birds with one stone”: along with the inhibition of stemness properties in cancer stem cells, the senescence response could be induced to destroy the cancer stem cell population within a tumor. © 2011 Wiley Periodicals, Inc. Med Res Rev
Assessment of glycosaminoglycan concentration changes in the intervertebral disc via chemical exchange saturation transfer
Authors: Saar Galit , Zhang Boyang , Ling Wen , Regatte Ravinder R. , Navon Gil , Jerschow Alexej
Published: July 2011

In this study, it is shown that the chemical exchange saturation transfer (CEST) method for hydroxyl protons can be used to detect changes in glycosaminoglycan (GAG) concentration in the intervertebral disc. The method, termed gagCEST, was demonstrated ex vivo by correlating the CEST effect with the fixed charge density (FCD) of the nucleus pulposus (NP), as well as by correlating tissue CEST images with their corresponding 23Na images. Incubation of five NP samples with trypsin produced samples with varying GAG content (n = 19). A good correlation was found between the –OH CEST effect and FCD, as well as with the N‐acetyl signal amplitude. gagCEST images in vitro further illustrated the amount of detail obtainable from this contrast mechanism when compared with conventional imaging. The large concentration of GAG and the relatively long T1 of water in NP make the method sensitive, in particular, for the assessment of GAG depletion in this tissue. It is the loss of GAG in NP that indicates the early stage of disc degeneration. Copyright © 2011 John Wiley & Sons, Ltd.
The C‐terminus of Apc does not influence intestinal adenoma development or progression
Authors: Lewis Annabelle , Davis Hayley , Deheragoda Maesha , Pollard Patrick , Nye Emma , Jeffery Rosemary , Segditsas Stefania , East Philip , Poulsom Richard , Stamp Gordon , Wright Nicholas , Tomlinson Ian
Published: July 2011

Adenomatous polyposis coli (APC) mutations are found in most colorectal tumours. These mutations are almost always protein‐truncating, deleting both central domains that regulate Wnt signalling and C‐terminal domains that interact with the cytoskeleton. The importance of Wnt dysregulation for colorectal tumourigenesis is well characterized. It is, however, unclear whether loss of C‐terminal functions contributes to tumourigenesis, although this protein region has been implicated in cellular processes—including polarity, migration, mitosis, and chromosomal instability (CIN)—that have been postulated as critical for the development and progression of intestinal tumours. Since almost all APC mutations in human patients disrupt both central and C‐terminal regions, we created a mouse model to test the role of the C‐terminus of APC in intestinal tumourigenesis. This mouse (Apc$^{{\Delta}{\rm{SAMP}}}$) carries an internal deletion within Apc that dysregulates Wnt by removing the beta‐catenin‐binding and SAMP repeats, but leaves the C‐terminus intact. We compared Apc$^{{\Delta}{\rm{SAMP}}}$ mice with Apc$^{\rm{1322T}}$ animals. The latter allele represented the most commonly found human APC mutation and was identical to Apc$^{{\Delta}{\rm{SAMP}}}$ except for absence of the entire C‐terminus. Apc$^{{\Delta}{\rm{SAMP}}}$ mice developed numerous intestinal adenomas indistinguishable in number, location, and dysplasia from those seen in Apc$^{\rm{1322T}}$ mice. No carcinomas were found in Apc$^{{\Delta}{\rm{SAMP}}}$ or Apc$^{\rm{1322T}}$ animals. While similar disruption of the Wnt signalling pathway was observed in tumours from both mice, no evidence of differential C‐terminus functions (such as cell migration, CIN, or localization of APC and EB1) was seen. We conclude that the C‐terminus of APC does not influence intestinal adenoma development or progression. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Overexpression of the Flii gene increases dermal–epidermal blistering in an autoimmune ColVII mouse model of epidermolysis bullosa acquisita
Authors: Kopecki Zlatko , Arkell Ruth M , Strudwick Xanthe L , Hirose Misa , Ludwig Ralf J , Kern Johannes S , Bruckner‐Tuderman Leena , Zillikens Detlef , Murrell Dedee F , Cowin Allison J
Published: July 2011

Epidermolysis bullosa (EB) is a severe genetic skin fragility syndrome characterized by blister formation. The molecular basis of EB is still largely unknown and wound healing in patients suffering from EB remains a major challenge to their survival. Our previous studies have identified the actin remodelling protein Flightless I (Flii) as an important mediator of wound repair. Here we identify Flii as a novel target involved in skin blistering. Flii expression was significantly elevated in 30 patients with EB, most prominently in patients with recessive dystrophic EB (RDEB) who have defects in production of type VII collagen (ColVII). Using an autoimmune ColVII murine model of EB acquisita (EBA) and an immunocompetent‐ColVII‐hypomorphic genetic mouse model of RDEB together with murine Flii alleles, we investigated the contribution of Flii to EB. Overexpression of Flii produced severe blistering post‐induction of EBA, while decreased Flii reduced blister severity, elevated integrin expression, and improved ColVII production. Flii+/− blistered skin showed reduced α‐SMA, TGF‐β1, and Smad 2/3 expression, suggesting that decreasing Flii may affect fibrosis. In support of this, Flii‐deficient fibroblasts from EBA mice were less able to contract collagen gels in vitro; however, addition of TGF‐β1 restored collagen contraction, suggesting an interplay between Flii and TGF‐β1. Elevated Flii gene and protein expression was further observed in the blisters of ColVII hypomorphic mice, a murine model of RDEB, suggesting that reducing Flii in blistered skin could be a potential new approach for treating patients with EB. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
NADPH oxidase inhibition ameliorates Trypanosoma cruzi‐induced myocarditis during Chagas disease
Authors: Dhiman Monisha , Garg Nisha Jain
Published: July 2011

Trypanosoma cruzi, the aetiological agent of Chagas disease, invades nucleated mammalian cells including macrophages. In this study, we investigated the crosstalk between T. cruzi‐induced immune activation of reactive oxygen species (ROS) and pro‐inflammatory responses, and their role in myocardial pathology. Splenocytes of infected mice (C3H/HeN) responded to Tc‐antigenic stimulus by more than a two‐fold increase in NADPH oxidase (NOX) activity, ROS generation, cytokine production (IFN‐γ > IL‐4 > TNFα > IL1‐β≈ IL6), and predominant expansion of CD4+ and CD8+ T cells. Inhibition of NOX, but not of myeloperoxidase and xanthine oxidase, controlled the ROS (>98%) and cytokine (70–89%) release by Tc‐stimulated splenocytes of infected mice. Treatment of infected mice with apocynin (NOX inhibitor) in drinking water resulted in a 50–90% decline in endogenous NOX/ROS and cytokine levels, and splenic phagocytes' proliferation. The splenic percentage of T cells was maintained, though more than a 40% decline in splenic index (spleen weight/body weight) indicated decreased T‐cell proliferation in apocynin‐treated/infected mice. The blood and tissue parasite burden were significantly increased in apocynin‐treated/infected mice, yet acute myocarditis, ie inflammatory infiltrate consisting of macrophages, neutrophils, and CD8+ T cells, and tissue oxidative adducts (eg 8‐isoprostanes, 3‐nitrotyrosine, and 4‐hydroxynonenal) were diminished in apocynin‐treated/infected mice. Consequently, hypertrophy (increased cardiomyocytes' size and β‐MHC, BNP, and ANP mRNA levels) and fibrosis (increased collagen, glycosaminoglycans, and lipid contents) of the heart during the chronic phase were controlled in apocynin‐treated mice. We conclude that NOX/ROS is a critical regulator of the splenic response (phagocytes, T cells, and cytokines) to T. cruzi infection, and bystander effects of heart‐infiltrating phagocytes and CD8+ T cells resulting in cardiac remodelling in chagasic mice. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Evaluation of polymorphisms in EWSR1 and risk of Ewing sarcoma: A report from the childhood cancer survivor study
Authors: DuBois Steven G. , Goldsby Robert , Segal Mark , Woo Jonathan , Copren Kirsten , Kane John P. , Pullinger Clive R. , Matthay Katherine K. , Witte John , Lessnick Stephen L. , Robison Leslie L. , Bhatia Smita , Strong Louise C.
Published: July 2011

Background

Ewing sarcoma is a malignant bone tumor characterized by a high frequency of somatic EWSR1 translocations. Ewing sarcoma is less common in people of African or African‐American ancestry, suggesting a genetic etiology.

Procedure

Germline DNA from white patients with Ewing sarcoma (n = 135), white controls with Wilms tumor (n = 200), and African‐American controls (n = 285) was genotyped at 21 SNPs in the EWSR1 gene. Intron 7 of EWSR1, the most common site of translocation, was also sequenced in all subjects. Genetic variation between groups was evaluated statistically using exact logistic regression and Fisher exact tests.

Results

One SNP in EWSR1 (rs2857461) showed a low level of statistical association with the diagnosis of Ewing sarcoma compared to Wilms tumor. The odds ratio for having Ewing sarcoma in people with at least one copy of the minor allele of rs2857461 was 3.57 (95% confidence interval 0.79–21.7; P = 0.07). No other SNPs or variations in intron 7 of EWSR1 were associated with Ewing sarcoma. The median relative difference in minor allele frequencies between white subjects with Ewing sarcoma and African‐American controls at the evaluated EWSR1 SNPs was 45%.

Conclusions

Variations in EWSR1 at known SNPs or across intron 7 are not associated with the diagnosis of Ewing sarcoma. EWSR1 does not appear to be an Ewing sarcoma susceptibility gene. The genetic basis for this disease remains unknown. Pediatr Blood Cancer 2012; 59: 52–56. © 2011 Wiley Periodicals, Inc.
Synergistic effects of titanium dioxide with layered double hydroxides in EVA/LDH composites
Authors: Jiao Chuanmei , Chen Xilei
Published: July 2011

The synergistic effects of titanium dioxide (TiO2) with layered double hydroxides (LDH) in ethylene vinyl acetate copolymer/LDH (EVA/LDH) composites have been studied using thermogravimetric analysis (TGA), limiting oxygen index (LOI), UL‐94 tests, and cone calorimeter test (CCT). The results from the UL‐94 test show that the TiO2 can also act as flame retardant synergistic agents in the EVA/LDH composites. The CCT data indicated that the addition of TiO2 in EVA/LDH system can greatly reduce the heat release rate and the production rate of carbon monoxide. The TGA data show that the TiO2 as excellent flameretardant synergist of LDH can increase the thermal stability of the flame retardant composites at high temperature, indicating the effect of condensed phase mechanism is the main reason of the improvement of flame retardancy. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Feasibility study of thin microinjection molded components
Authors: Mahmoodi Mehdi , Park Simon S. , Rizvi Ghaus
Published: July 2011

The trend toward the miniaturization of parts has created a strong demand for the manufacturing of precision‐molded miniature polymeric components, due to their high productivity and cost‐effectiveness. The objective of this study is the investigation of the filling behavior and dimensional accuracy of thin microinjection‐molded components using chemical blowing agents and wood fibers. In order to investigate the dimensional stability of the miniature molded parts, a micromold was designed and manufactured using a precision micromilling machine. The flow pattern of the thin molded components was experimentally investigated using different materials: pure linear low‐density polyethylene (LLDPE), foamed LLDPE, and wood fiber LLDPE composite. The results indicate that viscosity significantly affects the flow patterns. Filling behavior of the molded parts was also investigated using commercial flow software. Dimensional accuracy and shrinkage of the molded parts were measured using various gauges. Controlling the cell size, cell density, and distribution of foamed parts was especially difficult for thin micro components; however, the results showed that use of chemical blowing agents can improve the flow ability of the thin components in the microinjection molding process. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers
Gender differences and social support: Mediators or moderators between peer victimization and depressive feelings?
Authors: Pouwelse Mieneke , Bolman Catherine , Lodewijkx Hein , Spaa Marguerite
Published: July 2011

Using self‐report questionnaires, a survey among 606 Dutch primary school children aged 10 to 12 years examined relationships among social support, gender, victimization, and depressive feelings. Hierarchical regression analyses confirmed that victims and bully/victims would report more depressive feelings than uninvolved children. There was no evidence that social support moderated the relationship between victimization and depressive feelings. However, social support appeared to influence the depressive feelings of victimized children, that is, pupils who were victimized received very little support and hence suffered depression. This general mediation effect could be observed in boys. In girls, the mediating effects of social support were more diffuse. For girls, the risk factor for the development of depressive feelings did not so much pertain to the type of bullying as to the subsequent lack of social support they experienced. © 2011 Wiley Periodicals, Inc.
Prediction of biological protein–protein interactions using atom‐type and amino acid properties
Authors: Aziz Md. Mominul , Maleki Mina , Rueda Luis , Raza Mohammad , Banerjee Sridip
Published: July 2011

Identification and analysis of types of biological protein–protein interactions and their interfaces to predict obligate and non‐obligate complexes is a problem that has drawn the attention of the research community in the past few years. In this paper, we propose a prediction approach to predict these two types of complexes. We use desolvation energies – amino acid and atom type – of the residues present in the interface. The prediction is performed via two state‐of‐the‐art classification techniques, namely linear dimensionality reduction (LDR) and support vector machines (SVM). The results on a newly compiled data set, namely BPPI, which is a joint and modified version of two well‐known data sets consisting of 213 obligate and 303 non‐obligate complexes, show that the best prediction is achieved with SVM (76.94% accuracy) when using desolvation energies of atom‐type features. Also, the proposed approach outperforms the previous solvent accessible area‐based approaches using SVM (75% accuracy) and LDR (73.06% accuracy). Moreover, a visual analysis of desolvation energies in obligate and non‐obligate complexes shows that a few atom‐type pairs are good descriptors for these types of complexes.
Investigation of cation–anion interaction in 1‐(2‐hydroxyethyl)‐3‐methylimidazolium‐based ion pairs by density functional theory calculations and experiments
Authors: Zhang Shiguo , Qi Xiujuan , Ma Xiangyuan , Lu Liujin , Zhang Qinghua , Deng Youquan
Published: July 2011

Gas‐phase structure, hydrogen bonding, and cation–anion interactions of a series of 1‐(2‐hydroxyethyl)‐3‐methylimidazolium ([HOEMIm]+)‐based ionic liquids (hereafter called hydroxyl ILs) with different anions (X = [NTf2]–, [PF6]–, [ClO4]–, [BF4]–, [DCA]–, [NO3]–, [AC]– and [Cl]–), as well as 1‐ethyl‐3‐methylimizolium ([EMIm]+)‐based ionic liquids (hereafter called nonhydroxyl ILs), were investigated by density functional theory calculations and experiments. Electrostatic potential surfaces and optimized structures of isolated ions, and ion pairs of all ILs have been obtained through calculations at the Becke, three‐parameter, Lee–Yang–Parr/6‐31 + G(d,p) level and their hydrogen bonding behavior was further studied by the polarity and Kamlet–Taft Parameters, and 1H‐NMR analysis. In [EMIm]+‐based nonhydroxyl ILs, hydrogen bonding preferred to be formed between anions and C2–H on the imidazolium ring, while in [HOEMIm]+‐based hydroxyl ILs, it was replaced by a much stronger one that preferably formed between anions and OH. The O–H···X hydrogen bonding is much more anion‐dependent than the C2–H···X, and it is weakened when the anion is changed from [AC]– to [NTf2]–. The different interaction between [HOEMIm]+ and variable anion involving O–H···X hydrogen bonding resulted in significant effect on their bulk phase properties such as 1H‐NMR shift, polarity and hydrogen‐bond donor ability (acidity, α). Copyright © 2011 John Wiley & Sons, Ltd.
Automated protein structure modeling in CASP9 by I‐TASSER pipeline combined with QUARK‐based ab initio folding and FG‐MD‐based structure refinement
Authors: Xu Dong , Zhang Jian , Roy Ambrish , Zhang Yang
Published: July 2011

I‐TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and fragment‐guided molecular dynamics (FG‐MD), were added to the I‐TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I‐TASSER structure assembly simulations. FG‐MD is an atomic‐level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen‐bonding networks, torsion angles, and steric clashes. Despite considerable progress in both the template‐based and template‐free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of β‐proteins are still needed to further improve the I‐TASSER pipeline. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Motivation, achievement, and advanced placement intent of high school students learning science
Authors: Bryan Robert R. , Glynn Shawn M. , Kittleson Julie M.
Published: July 2011

Within the framework of social cognitive theory, we examined the motivation of students (14–16 years old) to learn science in their introductory science courses. The students responded to a questionnaire about their intrinsic motivation, self‐efficacy, and self‐determination. The students also wrote essays about their motivation, and individual interviews were conducted with a representative sample of students. We found that the students' intrinsic motivation, self‐efficacy, self‐determination, and achievement were related. Consistent with social cognitive theory, self‐efficacy was the motivation factor most related to achievement. The Advanced Placement Program (AP) aspirants were higher than nonaspirants in intrinsic motivation, self‐efficacy, self‐determination, and achievement. Patterns in students' essays and interviews identified inspiring teachers, career interests, and collaborative‐learning activities as strong motivators. The findings suggest that science teachers should use social modeling and collaborative‐learning activities to foster students' motivation, achievement, AP intent, and interest in science careers. © 2011 Wiley Periodicals, Inc. Sci Ed 95:1049–1065, 2011
Model‐based analyses of bioequivalence crossover trials using the stochastic approximation expectation maximisation algorithm
Authors: Dubois Anne , Lavielle Marc , Gsteiger Sandro , Pigeolet Etienne , Mentré France
Published: July 2011

In this work, we develop a bioequivalence analysis using nonlinear mixed effects models (NLMEM) that mimics the standard noncompartmental analysis (NCA). We estimate NLMEM parameters, including between‐subject and within‐subject variability and treatment, period and sequence effects. We explain how to perform a Wald test on a secondary parameter, and we propose an extension of the likelihood ratio test for bioequivalence. We compare these NLMEM‐based bioequivalence tests with standard NCA‐based tests. We evaluate by simulation the NCA and NLMEM estimates and the type I error of the bioequivalence tests. For NLMEM, we use the stochastic approximation expectation maximisation (SAEM) algorithm implemented in monolix. We simulate crossover trials under H0 using different numbers of subjects and of samples per subject. We simulate with different settings for between‐subject and within‐subject variability and for the residual error variance. The simulation study illustrates the accuracy of NLMEM‐based geometric means estimated with the SAEM algorithm, whereas the NCA estimates are biased for sparse design. NCA‐based bioequivalence tests show good type I error except for high variability. For a rich design, type I errors of NLMEM‐based bioequivalence tests (Wald test and likelihood ratio test) do not differ from the nominal level of 5%. Type I errors are inflated for sparse design. We apply the bioequivalence Wald test based on NCA and NLMEM estimates to a three‐way crossover trial, showing that Omnitrope®; (Sandoz GmbH, Kundl, Austria) powder and solution are bioequivalent to Genotropin®; (Pfizer Pharma GmbH, Karlsruhe, Germany). NLMEM‐based bioequivalence tests are an alternative to standard NCA‐based tests. However, caution is needed for small sample size and highly variable drug. Copyright © 2011 John Wiley & Sons, Ltd.
Resveratrol protects against methylglyoxal‐induced apoptosis and disruption of embryonic development in mouse blastocysts
Authors: Huang Fu‐Jen , Chin Ting‐Yu , Chan Wen‐Hsiung
Published: July 2011

Methylglyoxal (MG) is a glucose metabolite. Diabetic patients have increased serum levels of MG, and MG is also implicated in tissue injury during embryonic development. In the present work, we show that MG induces apoptosis in the inner cell mass of mouse blastocysts and inhibits cell proliferation. Both effects are suppressed by resveratrol, a grape‐derived phytoalexin with known antioxidant and anti‐inflammatory properties. MG‐treated blastocysts displayed lower levels of implantation (compared to controls) when plated on culture dishes in vitro and a reduced ability to proceed to later stages of embryonic development. Pretreatment with resveratrol prevented MG‐induced disruption of embryonic development, both in vitro and in vivo. Further investigation of these processes revealed that MG directly promotes reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential (MMP), and activation of caspase‐3, whereas resveratrol effectively blocks MG‐induced ROS production and the accompanying apoptotic biochemical changes. Our results collectively imply that MG triggers the mitochondrion‐dependent apoptotic pathway via ROS generation, and the antioxidant activity of resveratrol prevents MG‐induced toxicity. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 431–441, 2013.