bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of biotin to demonstrate immunohistochemistry, western blotting, and dot blots in university practical classes
Authors: Millar Thomas James , Knighton Ronald , Chuck Jo‐Anne
Published: April 2012

Immunological detection of proteins is an essential method to demonstrate to undergraduate biology students, however, is often difficult in resource and time poor student laboratory sessions. This method describes a failsafe method to rapidly and economically demonstrate this technique using biotinylated proteins or biotin itself as targets for detection. This negates the need for a specific primary antibody, saving cost and time. In addition, the easily available and safe reagents allow the methods to be readily adopted without specialist technical expertise. As a result, staff can confidently transfer ownership of the task to the student so as to also develop scientific inquiry skills which promotes student motivation and engagement.
Changing the Regioselectivity of a P450 from C15 to C11 Hydroxylation of Progesterone
Authors: Nguyen Kim Thoa , Virus Cornelia , Günnewich Nils , Hannemann Frank , Bernhardt Rita
Published: April 2012

CYP106A2 is known as a 15β‐hydroxylase, but also shows minor 11α‐hydroxylase activity for progesterone. 11α‐Hydroxyprogesterone is an important pharmaceutical compound with anti‐androgenic and blood‐pressure‐regulating activity. This work therefore focused on directing the regioselectivity of the enzyme towards hydroxylation at position 11 in the C ring of the steroid through a combination of saturation mutagenesis and rational site‐directed mutagenesis. With the aid of data from a homology model of CYP106A2 containing docked progesterone, together with site‐directed mutagenesis of active‐site residues (Lisurek et al. ChemBioChem 2008, 9, 1439–1449), a saturation mutagenesis library at positions A395 and G397 was created. Screening of the library identified the mutants A395I and A395W/G397K as having 11α‐hydroxylase activities 8.9 and 11.5 times higher than that of the wild type (WT). In the next step, additional mutations were integrated by a rational site‐directed mutagenesis approach to increase the catalytic efficiency. Of the 40 candidates analyzed, the mutants A106T/A395I, A106T/A395I/R409L, and T89N/A395I turned out to display increased 11α‐hydroxylase selectivities and activities relative to the WT (14.3‐, 12.6‐, and 11.8‐fold increases in selectivity and 39.3‐, 108‐, and 24.4‐ in kcat/Km). In the last step of the study, the best mutants were applied in a whole‐cell biotransformation. In these experiments the production (percentage) of 15β‐hydroxyprogesterone decreased from 50.4 % (wild type) to 4.8 % (mutant T89N/A395I), whereas that of 11α‐hydroxyprogesterone increased from 27.7 to 80.9 %, thus demonstrating an impressive regioselectivity.
A Native Chemical Ligation Approach for Combinatorial Assembly of Affibody Molecules
Authors: Lindgren Joel , Ekblad Caroline , Abrahmsén Lars , Eriksson Karlström Amelie
Published: April 2012

Affinity molecules labeled with different reporter groups, such as fluorophores or radionuclides, are valuable research tools used in a variety of applications. One class of engineered affinity proteins is Affibody molecules, which are small (6.5 kDa) proteins that can be produced by solid phase peptide synthesis (SPPS), thereby allowing site‐specific incorporation of reporter groups during synthesis. The Affibody molecules are triple‐helix proteins composed of a variable part, which gives the protein its binding specificity, and a constant part, which is identical for all Affibody molecules. In the present study, native chemical ligation (NCL) has been applied for combinatorial assembly of Affibody molecules from peptide fragments produced by Fmoc SPPS. The concept is demonstrated for the synthesis of three different Affibody molecules. The cysteine residue introduced at the site of ligation can be used for directed immobilization and does not interfere with the function of the investigated proteins. This strategy combines a high‐yield production method with facilitated preparation of proteins with different C‐terminal modifications.
Asymmetric Cyclization Reactions of Allenoates with Imines or α,β‐Unsaturated Ketones Catalyzed by Organocatalysts Derived from Cinchona Alkaloids
Authors: Pei Cheng‐Kui , Shi Min
Published: April 2012

Lewis base‐catalyzed cyclization reactions of allenoates with electron‐deficient olefins and imines have been demonstrated by the preparation of biologically active natural products and pharmaceutically interesting substances and have emerged as powerful synthetic tools in the rapid construction of cyclic molecular complexity. In contrast to phosphine‐containing Lewis bases, nitrogen‐containing Lewis base amines display markedly different reaction profiles; however, this area is not well‐developed. Herein we summarize the recent progress in this emerging field and outline the challenges ahead.
Sustainable Heck–Matsuda Reaction with Catalytic Amounts of Diazonium Salts: An Experimental and Theoretical Study
Authors: Susperregui Nicolas , Miqueu Karinne , Sotiropoulos Jean‐Marc , Le Callonnec François , Fouquet Eric , Felpin François‐Xavier
Published: April 2012

The palladium‐catalyzed Heck–Matsuda reaction with a catalytic amount of an in‐situ‐generated diazonium salt proceeded under mild and sustainable conditions. The reaction proceeded at room temperature, under base‐free conditions, and only generated tBuOH, H2O, and N2 as by‐products. Ortho‐substituted diazonium salts were more‐efficiently coupled to methyl acrylate than their corresponding para isomers, which required the addition of anisole as an additive. In support of these experimental data, we carried out theoretical studies to gain a deeper understanding of these reaction outcomes.
Efficiency Enhancement of Reductants Use in the Blast Furnace to Reduce CO2 Emissions and Costs
Authors: Schott Robin , Malek Christian , Schott Hans‐Klaus
Published: April 2012

Das Hochofenverfahren ist das wichtigste Verfahren zur Roheisenerzeugung. Dabei wird die Prozessenergie hauptsächlich über Koks gedeckt. Die Koks‐Herstellung ist jedoch mit CO2‐Frachten und hohen Kosten verbunden. Eine wichtige Maßnahme zur Reduzierung des Kokssatzes und damit der CO2‐Emissionen sowie Kosten ist das Einblasen von Kohlenstaub über die Blasformen in den Hochofen. Weitere Verbesserungen können durch die Oxycoal+ Technologie erreicht werden. Anhand vereinfachter Energiebilanzen werden die Wirtschaftlichkeit sowie die Minderung der CO2‐Emissionen für den Nur‐Koks‐Betrieb des Hochofens, den Betrieb beim Einblasen von Kohlenstaub und den Betrieb bei Anwendung der Oxycoal+ Technologie einander gegenüber gestellt und bewertet.
The Effect of Particulate Matter Components on the Acidity of Rain in Upper Silesia (Poland)
Authors: Hlawiczka Stanislaw , Korszun Katarzyna
Published: April 2012

Analysis of data characterizing the chemical composition of atmospheric precipitation was presented, with an emphasis on components responsible for neutralization of rain acidity. For this purpose, chemometric methods were applied. Based on a principal component analysis (PCA) a strong correlation between precipitation pH and potassium and ammonium ions in the heating period (October–March) and potassium and sodium ions in the non‐heating period (April–September) was observed. Additionally, a classification of eight variables, i.e., Na+, K+, Mg2+, Ca2+, ${\rm SO}_{4}^{2- } $, ${\rm NO}_{3}^{- } $, Cl−, and ${\rm NH}_{4}^{ + } $ according to their similarities was made using a cluster analysis. Based on this study, two ions, potassium and ammonium, together with the pH value were classified into one group (cluster) in the heating period while in the non‐heating period ions of potassium and sodium were clustered together with the pH. The results of the cluster analysis indicated that the selected ions contributed the most to the neutralization of the atmospheric precipitation acidity. This relationship was confirmed by a discriminant analysis in which potassium and ammonium ions were selected as components of the highest potential for precipitation classification according to its acidity degree. The relationship between the precipitation pH and the number of non‐precipitation days preceding the precipitation was also analyzed. It was found that although the observed an increase of the pH value was not very high, nevertheless, the effect of the duration of the period preceding the precipitation on the pH value recorded on the day of the precipitation occurrence was quite evident.
Kinase Inhibitor Scaffolds against Neurodegenerative Diseases from a Southern Australian Ascidian, Didemnum sp.
Authors: Plisson Fabien , Conte Melissa , Khalil Zeinab , Huang Xiao‐Cong , Piggott Andrew M. , Capon Robert J.
Published: April 2012

Screening a library of Southern Australian and Antarctic marine invertebrates and algae for inhibitors of neurodegenerative disease kinase targets casein kinase 1 (CK1δ), cyclin‐dependent kinase 5 (CDK5) and glycogen synthase kinase 3β (GSK3β) identified a Western Australian Didemnum species (CMB‐02127) as a high‐priority specimen. Chemical fractionation returned the known aromatic alkaloids ningalins B–D as the major metabolites, together with six minor metabolites, the new ningalins E–G and the known hexacyclic pyrrole alkaloids lamellarins Z, G and A6. All structures were assigned by detailed spectroscopic analysis and literature comparisons, and the structural assignments were supported by biosynthetic considerations. The ningalins showed potent and broad inhibition across the three kinases, while the lamellarins were generally more selective for CDK5. Docking studies using published X‐ray crystal structures of CDK5 revealed both scaffolds target the ATP binding pocket.
Grothendieck‐Type Inequalities in Combinatorial Optimization
Authors: Khot Subhash , Naor Assaf
Published: April 2012

We survey connections of the Grothendieck inequality and its variants to combinatorial optimization and computational complexity. © 2011 Wiley Periodicals, Inc.
Studies in the Dynamics of a Plasma
Authors: Weitzner Harold
Published: April 2012

No abstracrt.
Universal vaccine against influenza virus: Linking TLR signaling to anti‐viral protection
Authors: Schmitz Nicole , Beerli Roger R. , Bauer Monika , Jegerlehner Andrea , Dietmeier Klaus , Maudrich Melanie , Pumpens Paul , Saudan Philippe , Bachmann Martin F.
Published: April 2012

A vaccine protecting against all influenza strains is a long‐sought goal, particularly for emerging pandemics. As previously shown, vaccines based on the highly conserved extracellular domain of M2 (M2e) may protect against all influenza A strains. Here, we demonstrate that M2e‐specific monoclonal antibodies (mAbs) protect mice from a lethal influenza infection. To be protective, antibodies had to be able to bind to Fc receptors and fix complement. Furthermore, mAbs of IgG2c isotype were protective in mice, while antibodies of identical specificity, but of the IgG1 isotype, failed to prevent disease. These findings readily translated into vaccine design. A vaccine targeting M2 in the absence of a toll‐like receptor (TLR) 7 ligand primarily induced IgG1, whilst the same vaccine linked to a TLR7 ligand yielded high levels of IgG2c antibodies. Although both vaccines protected mice from a lethal challenge, mice treated with the vaccine containing a TLR7 ligand showed significantly lower morbidity. In accordance with these findings, vaccination of TLR7–/– mice with a vaccine containing a TLR7 ligand did not result in protection from a lethal challenge. Hence, the innate immune system is required to direct isotype switching toward the more protective IgG2a/c antibodies.
NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans
Authors: Juárez Esmeralda , Carranza Claudia , Hernández‐Sánchez Fernando , León‐Contreras Juan C. , Hernández‐Pando Rogelio , Escobedo Dante , Torres Martha , Sada Eduardo
Published: April 2012

A role for the nucleotide‐binding oligomerization domain 2 (NOD2) receptor in pulmonary innate immune responses has recently been explored. In the present study, we investigated the role that NOD2 plays in human alveolar macrophage innate responses and determined its involvement in the response to infection with virulent Mycobacterium tuberculosis. Our results showed that NOD2 was expressed in human alveolar macrophages, and significant amounts of IL‐1β, IL‐6, and TNF‐α were produced upon ligand recognition with muramyldipeptide (MDP). NOD2 ligation induced the transcription and protein expression of the antimicrobial peptide LL37 and the autophagy enzyme IRGM in alveolar macrophages, demonstrating a novel function for this receptor in these cells. MDP treatment of alveolar macrophages improved the intracellular growth control of virulent M. tuberculosis; this was associated with a significant release of TNF‐α and IL‐6 and overexpression of bactericidal LL37. In addition, the autophagy proteins IRGM, LC3 and ATG16L1 were recruited to the bacteria‐containing autophagosome after treatment with MDP. In conclusion, our results suggest that NOD2 can modulate the innate immune response of alveolar macrophages and play a role in the initial control of respiratory M. tuberculosis infections.
Complement, Candida, and cytokines: The role of C5a in host response to fungi
Authors: Zipfel Peter F. , Skerka Christine
Published: April 2012

Complement is the central host defense system that clears invading microbes and balances homeostasis. Pathogenic microbes such as Candida albicans have to breach this efficient and important immune defense layer in order to propagate within the host and to establish an infection. Knowing exactly how the activated complement cascade responds to and attacks microbial invaders is central to understanding the immune battle and the infection process. This also allows a better understanding of how Candida counteracts the individual steps of host innate immunity. Ultimately this knowledge will allow the design of appropriate therapeutic molecules. In this issue Cheng et al. [Eur. J. Immunol. 2012. 42: 993‐1004] identify a new cellular effect of the activated human complement system in the defense against the fungal pathogen C. albicans. The authors show that the complement activation fragment C5a, which is formed in response to Candida infection, induces the cellular release of the inflammatory cytokines IL‐6 and IL‐1β.
Isolated Silver Intermediate of Gold Precatalyst Activation
Authors: Weber Simone G. , Rominger Frank , Straub Bernd F.
Published: April 2012

The silver chloride and gold chloride complex of the extremely sterically shielding N‐heterocyclic carbene ligand IPr** have been synthesized and characterized. Formally, eight methyl groups of IPr have been replaced by 4‐tert‐butylphenyl substituents, and two para‐methyl groups have been added. The world record for the ligand's buried volume (55.4 % for IPr**AuCl, and 56.7 % for IPr**AgCl) has been determined by single‐crystal X‐ray analyses. Reaction of IPr**AuCl with AgSbF6 in toluene yields AgCl and a cationic gold complex with toluene coordination. The same reaction in 1,2‐dichloroethane leads to precipitation of AgCl and an equilibrium of [IPr**Au]SbF6 and [IPr**AuClAg]SbF6. Single crystals of the latter were suitable for an X‐ray structure analysis, which reveal an Au–Cl–Ag triangle with an almost undisturbed IPr**–Au–Cl fragment and the coordination of two IPr** arenes to a silver cation. The structural parameters emphasize the role of NHC‐Au cations as highly electrophilic “soft protons”.
Oxysterol‐binding proteins–emerging roles in cell regulation
Authors: Olkkonen Vesa M. , Zhou You , Yan Daoguang , Vihervaara Terhi
Published: April 2012

Cytoplasmic oxysterol‐binding protein homologues, designated OSBP‐like (OSBPL) or OSBP‐related (ORP) proteins, constitute a family of lipid binding/transfer proteins present in a wide spectrum of eukaryotes. In mammals these proteins are encoded by 12 genes expressed ubiquitously but at different quantities in different tissue and cell types. Their unifying feature is a β‐barrel‐like ligand‐binding domain that has been shown to accommodate sterol ligands: oxysterols, cholesterol, or both, while a recent report shows that also phospholipid can be bound. Certain family members have the capacity to mediate or facilitate intracellular sterol transport or lipid exchange, while others are implicated as sterol sensors involved in cell regulation: lipid homeostatic control, signal transduction, organelle motility, or vesicle transport. Several ORPs have been localized to membrane contact sites, at which endoplasmic reticulum membranes are closely apposed with other organelles—indicating functions in the non‐vesicular transport of ions or small molecules, or in regulation of enzymatic components active at the contact sites. OSBPL gene polymorphisms are associated with cardiovascular risk factors, and altered ORP expression levels occur in certain cancers, providing the first indications of ORP involvement in human disease. In this review we summarize and analyze the latest findings concerning the function of OSBPL/ORP proteins.
Label‐free indicator‐free nucleic acid biosensors using carbon nanotubes
Authors: Balasubramanian Kannan
Published: April 2012

Carbon nanotubes (CNTs) are promising components for electrical biosensors due to their high surface‐to‐volume ratio and improved electron transfer properties. This review surveys CNT‐based label‐free indicator‐free biosensing strategies that have been demonstrated for the sensitive detection of nucleic acids. After an introduction to CNTs, the fabrication of biosensors and techniques for the immobilization of probe nucleic acids are outlined. Subsequently, two major label‐free strategies namely electrochemical transduction and field‐effect detection are presented. The focus is on direct detection methods that avoid labels, indicators, intercalating agents, mediators, and even secondary receptors. The review concludes with a comparison between the various biosensors and presents ways of engineering them so that they can be deployed in realistic diagnostic applications.
Performance of two laboratory‐scale horizontal wetlands under varying influent loads treating artificial sewage
Authors: Wu Shubiao , Wiessner Arndt , Dong Renjie , Pang Changle , Kuschk Peter
Published: April 2012

The performance of two laboratory‐scale horizontal subsurface‐flow constructed wetlands(CWs) treating artificial sewage in response to varying influent components and loads was investigated. Acidification with a pH of 3.0 was detected under an organic carbon load of 100 mg/day, which further inhibited the activity of the denitrification process. With an increase in the carbon load to 240 mg/day, the pH was significantly elevated to 6.0. However, a negative effect of sulphide as a product of sulphate reduction was observed on the removal of ammonium, the plants (Juncus effusus), and the organic carbon degradation. With a produced sulphide concentration of about 3.5 mg/L, the ammonium removal decreased from 100% to 30% under an inflow load of 100 mg/day, and the number of healthy stalks of J. effuses was reduced from about 14 000/m2 to less than 6000/m2. The removal of organic carbon decreased from 94% to 68% under an influent load of 240 mg/day, when the sulphide concentrations reached up to about 8–10 mg/L. The production of sulphide was not immediately controlled by stopping the inflow sulphate load to remove the negative effect of the sulphide toxicity, thus indicating an immobilization of the deposited reduced sulphur compounds. Moreover, the effect of a nitrate dosage on the sulphide control was also examined, but was shown to be only evident under the conditions of a low organic carbon input.
A Comparative Study of Head‐Mounted and Table‐Mounted Augmented Vision Systems for Assembly Error Detection
Authors: Odenthal Barbara , Mayer Marcel Ph. , Kabuß Wolfgang , Schlick Christopher M.
Published: April 2012

Within the Cluster of Excellence “Integrative Production Technology for High‐Wage Countries,” a research project has been initiated to study self‐optimizing assembly cells and to design innovative ergonomic human–machine interfaces of the cell's numerical control. An experimental assembly cell was designed in which two robots carry out a certain repertoire of coordinated pick‐and‐place operations with small workpieces. To support the human operator while monitoring the operations and intervening in the case of assembly errors, an Augmented Vision System (AVS) has been designed and developed. The study described in this article deals with the ergonomic presentation of assembly information by the AVS to support the human operator in detecting assembly errors in small workpieces. Two laboratory experiments were carried out to compare two visual display types and to investigate different variations of presenting assembly information. Forty‐eight subjects participated in the experiments. The statistical analysis shows that the use of a head‐mounted display instead of a common table‐mounted display for the AVS increases the accuracy of assembly error detection significantly (α = 0.05). In contrast, a trend toward a longer detection time was found. © 2012 Wiley Periodicals, Inc.
Steady flow to a partially penetrating blind‐wall well in a confined aquifer
Authors: Behrooz‐Koohenjani Saivash , Samani Nozar , Kompani‐Zare Mazda
Published: April 2012

Wells in aquifers of loose collapsible sediment are cased so that they have a blind wall and gain water only from the bottom. The hydraulic gradient established at the bottom of these wells during pumping brings the aquifer materials in a quicksand state, which may cause abrasion of pipes and pumps and even the destruction of well structure. To examine the quicksand occurrence, an analytical solution for the steady flow to a partially penetrating blind‐wall well in a confined aquifer is developed. The validity of the proposed solution is evaluated numerically. The sensitivity of maximum vertical gradient along the well bottom in response to aquifer and well parameters is examined. The solution is presented in the form of dimensionless‐type curves and equations that can be easily used to design the safe pumping rate and optimum well geometry to protect the well against sand production. The solution incorporates the anisotropy of aquifer materials and can also be used to determine the hydraulic conductivity of the aquifer. Copyright © 2012 John Wiley & Sons, Ltd.
What we talked about at the pediatrician's office: Exploring differences between healthy steps and traditional pediatric primary care visits
Authors: Buchholz Melissa , Talmi Ayelet
Published: April 2012

Healthy Steps for Young Children (HS) is a program designed to enhance pediatric primary care experiences for children birth to 3 years and their families by pairing a developmental specialist with a pediatric provider during well‐child visits. This study examined the impact of HS on content discussed during well‐child visits by providers, HS Specialists, and families. The impact of HS on pediatric outcomes, including timeliness of well‐child visits and immunizations, also was examined. Using retrospective medical review, records of 40 children enrolled in HS were compared with records of 36 demographically matched controls. A developmental topics checklist was used to analyze content of well‐child visits. Attendance at well‐child visits, receipt of immunizations, and healthcare utilization also was evaluated. Important developmental topics were discussed more often during well‐child visits of children enrolled in HS than for children who were not enrolled. Children enrolled in HS received timelier well‐child visits and immunizations. No differences between groups were found in the number of sick or emergency room visits. Integrating HS Specialists into pediatric primary care well‐child visits allows for discussion of important developmental topics while also impacting pediatric health outcomes.
Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: The HORIZON-Pivotal Fracture Trial (PFT)
Authors: Jacques Richard M , Boonen Steven , Cosman Felicia , Reid Ian R , Bauer Douglas C , Black Dennis M , Eastell Richard
Published: April 2012

Measurements of change in bone mineral density (BMD) are thought to be weak predictors of treatment effect on the reduction of fracture risk. In this study we report an alternative year-on-year approach for the estimation of treatment effect explained by BMD in which we examine the relationship between fracture risk and the most recent change in BMD. We studied 7736 postmenopausal women (ages 65 to 89 years) who were participants in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly–Pivotal Fracture Trial (HORIZON-PFT) and were randomized to either intravenous administration of zoledronic acid or placebo. The percentage of treatment effect explained by change in total hip BMD was estimated using the alternative year-on-year approach and the standard approach of looking at change over 3 years. We also studied a subset of 1132 women in whom procollagen type 1 amino-terminal propeptide (PINP) was measured at baseline and 12 months, to estimate the percentage of treatment effect explained by change in PINP. Regardless of the method used, the change in total hip BMD explained a large percentage of the effect of zoledronic acid in reducing new vertebral fracture risk (40%; 95% CI, 30% to 54%; for the 3-year analysis). The treatment effects for nonvertebral fracture were not statistically significant for the year-on-year analysis but 3-year change in BMD explained 61% (95% CI, 24% to 156%) of treatment effect. Change in PINP explained 58% (95% CI, 15% to 222%) of the effect of zoledronic acid in reducing new vertebral fracture risk. We conclude that our estimates of the percentage of treatment effect explained may be higher than in previous studies because of high compliance with zoledronic acid (due to its once-yearly intravenous administration). Previous studies may have underestimated the relationship between BMD change and the effect of treatment on fracture risk. © 2012 American Society for Bone and Mineral Research.
Plasma exchange for renal disease: Evidence and use 2011
Authors: Clark W.F.
Published: April 2012

Over the past 37 year the role of plasma exchange in the treatment of patients with renal disease has undergone several changes. The majority of the changes for the use of plasma exchange relied on randomized control trials and delineations of mechanisms that potentially would benefit from the use of plasma exchange. Over the past 11 years plasma exchange indications for renal disease, the absolute numbers have been relatively unchanged but the indications are quite different. The Canadian Apheresis Group indicated in 2010 that TTP/HUS is still the number 1 indication at 63% of the total plasma exchange activity for renal disease but P and C ANCA Vasculitis had risen to 14% followed by renal transplant at 10%, Goodpasture's Syndrome at 6% and transplant FSGS at 5% with Cryoglobulinemia 2% and Myeloma Nephropathy had dropped dramatically to less than 1% with no cases of SLE reported. This report describes the most common indications for plasma exchange in patient's with renal disease and the evidence that supports it's use in 2011. J. Clin. Apheresis 2012. © 2012 Wiley Periodicals, Inc.
Intrathyroidal thymic tissue mimicking a thyroid nodule in a 4‐year‐old child
Authors: Patel Manish N. , Komlos Marcia , Racadio Judy M.
Published: April 2012

A 4 year‐old girl was referred for CT of her neck for suspected submental lymphadenopathy and was found to have an incidental low‐attenuation thyroid mass. Subsequent thyroid ultrasound showed a heterogeneous thyroid mass with punctate areas of increased echogenicity. Cytologic examination was consistent with ectopic intrathyroidal thymic nodule. We review the presentation of ectopic thymic tissue, especially in the thyroid gland. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 41:319–320, 2013
Interpreting “Mind‐Cure”: William James and the “Chief Task…of the Science of Human Nature”
Authors: SUTTON EMMA KATE
Published: April 2012

The private papers of the philosopher‐psychologist, William James, indicate that he frequented several mental healers during his life, undertaking 100–200 therapeutic sessions concerning a range of symptoms from angina to insomnia. The success of the mind‐cure movement constituted for James both a corroboration, and an extension, of the new research into the subconscious self and the psychogenesis of disease. Epistemologically, the experiences of those converts to the “mind‐cure religion” exemplified his conviction that positivistic scientific enquiry can only reveal only one part of a wider reality. Metaphysically their reports comprised a powerful body of support for the existence of a “higher consciousness,” a supernatural world of some description. The positing of such a source of “supernormal” healing power was, for James, the best way to reconcile the accounts of those who had been regenerated, via their faith, despite having exhausted all natural reserves of energy and will.
The Construction of Mind, Self, and Society: The Social Process Behind G. H. Mead'S Social Psychology
Authors: HUEBNER DANIEL R.
Published: April 2012

Mind, Self, and Society, the posthumously published volume by which George Herbert Mead is primarily known, poses acute problems of interpretation so long as scholarship does not consider the actual process of its construction. This paper utilizes extensive archival correspondence and notes in order to analyze this process in depth. The analysis demonstrates that the published form of the book is the result of a consequential interpretive process in which social actors manipulated textual documents within given practical constraints over a course of time. The paper contributes to scholarship on Mead by indicating how this process made possible certain understandings of his social psychology and by relocating the materials that make up the single published text within the disparate contexts from which they were originally drawn.
Multiparametric 3T endorectal mri after external beam radiation therapy for prostate cancer
Authors: Westphalen Antonio C. , Reed Galen D. , Vinh Phillip P. , Sotto Christopher , Vigneron Daniel B. , Kurhanewicz John
Published: April 2012

Purpose:

To determine the best combination of magnetic resonance imaging (MRI) parameters for the detection of locally recurrent prostate cancer after external beam radiation therapy.

Materials and Methods:

Our Institutional Review Board approved this study with a waiver of informed consent. Twenty‐six patients with suspected recurrence due to biochemical failure were part of this research. The MR protocol included T2‐weighted, MR spectroscopy, and diffusion‐weighted MRI. Transrectal ultrasound‐guided biopsy was the standard of reference. We used logistic regression to model the probability of a positive outcome and generalized estimating equations to account for clustering. The diagnostic performance of imaging was described using receiver operating characteristic (ROC) curves.

Results:

The area under the ROC curve of MR spectroscopic imaging (MRSI) was 83.0% (95% confidence interval [CI] = 75.5–89.1). The combination of all MR techniques did not significantly improve the performance of imaging beyond the accuracy of MRSI alone, but a trend toward improved discrimination was noted (86.9%; 95% CI = 77.6–93.4; P = 0.09).

Conclusion:

Incorporation of MRSI to T2‐weighted and/or diffusion‐weighted MRI significantly improves the assessment of patients with suspected recurrence after radiotherapy and a combined approach with all three modalities may have the best diagnostic performance. J. Magn. Reson. Imaging 2012;36:430–437. ©2012 Wiley Periodicals, Inc.
Histological differentiation grade and microvascular invasion of hepatocellular carcinoma predicted by dynamic contrast‐enhanced MRI
Authors: Witjes Caroline D.M. , Willemssen François E.J.A. , Verheij Joanne , van der Veer Sacha J. , Hansen Bettina E. , Verhoef Cornelis , de Man Robert A. , IJzermans Jan N.M.
Published: April 2012

Purpose:

To explore the potential use of magnetic resonance imaging (MRI) in predicting the outcome for patients with hepatocellular carcinoma (HCC), imaging characteristics were correlated with pathological findings and clinical outcome.

Materials and Methods:

With permission from the Ethical Board, clinical data and tissues of resected HCC patients were collected, including the preoperative MRI. The role of MRI characteristics on recurrence and survival were evaluated with univariate and multivariate analyses.

Results:

Between January 2000 and December 2008, 87 patients with 104 HCCs were operated on. Microvascular invasion was present in 55 lesions (53%). HCC was characterized as well differentiated in 15 lesions (14%), as moderate in 50 lesions (48%), and as poorly differentiated in 34 lesions (33%). Due to preoperative treatment in five lesions (5%) no vital tumor was left. In 85 lesions (88%) washout of contrast was noted. Of the 87 patients, 28 (32%) with 37 lesions developed HCC recurrence; these patients had microvascular invasion significantly more often and a moderate or poorly differentiated tumor (P < 0.001 and P = 0.025, respectively). MRI more often showed washout when HCC was moderately or poorly differentiated (P < 0.001) or microvascular invasion was present (P = 0.032).

Conclusion:

Differentiation grade and microvascular invasion are significantly associated with the presence of washout demonstrated on dynamic contrast‐enhanced MRI. J. Magn. Reson. Imaging 2012;36:641–647. © 2012 Wiley Periodicals, Inc.
Subclinical Cushing's syndrome
Authors: Tsinberg Michael , Liu Chienying , Duh Quan‐Yang
Published: April 2012

Subclinical Cushing's syndrome (SCS) refers to subtle autonomous cortisol hypersecretion that is insufficient to generate the typical, clinically recognizable overt syndrome. Diagnosis of SCS is challenging. The combination of 1 mg overnight dexamethasone suppression test, serum ACTH level, and urinary cortisol level are used to diagnose SCS. Laparoscopic adrenalectomy is the treatment of choice for SCS. Patients with adrenal incidentalomas and SCS should be treated with perioperative steroids to prevent post‐operative hypocortisolism. J. Surg. Oncol. 2012; 106:572–574. © 2012 Wiley Periodicals, Inc.
Argon‐Plasma‐Induced Ultrathin Thermal Grafting of Thermoresponsive pNIPAm Coating for Contractile Patterned Human SMC Sheet Engineering
Authors: Rayatpisheh Shahrzad , Li Peng , Chan‐Park Mary B.
Published: April 2012

A new method for ultrathin grafting of pNIPAm on PDMS surfaces is introduced that employs plasma activation of the surface followed by thermal polymerization. This method is optimized for human primary SMC attachment and subsequent intact cell sheet detachment by lowering the temperature. The contractile gene expression of the cells showed that the contractile phenotype of the SMCs which is induced by aligning the cells through micropatterning is more preserved after thermoresponsive cell sheet detachment in contrast with enzymatic detachment. Given its simplicity and low cost, this thermoresponsive grafting method can be utilized for engineering patterned cell sheets for future bottom‐up tissue engineering techniques.

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A nonlinear elliptic problem with terms concentrating in the boundary
Authors: Aragão Gleiciane S. , Pereira Antônio L. , Pereira Marcone C.
Published: April 2012

In this paper, we investigate the behavior of a family of steady‐state solutions of a nonlinear reaction diffusion equation when some reaction and potential terms are concentrated in aε‐neighborhood of a portion Γ of the boundary. We assume that thisε‐neighborhood shrinks to Γ as the small parameterεgoes to zero. Also, we suppose the upper boundary of thisε‐strip presents a highly oscillatory behavior. Our main goal here was to show that this family of solutions converges to the solutions of a limit problem, a nonlinear elliptic equation that captures the oscillatory behavior. Indeed, the reaction term and concentrating potential are transformed into a flux condition and a potential on Γ, which depends on the oscillating neighborhood. Copyright © 2012 John Wiley & Sons, Ltd.
International children's continence society's recommendations for initial diagnostic evaluation and follow‐up in congenital neuropathic bladder and bowel dysfunction in children
Authors: Bauer Stuart B. , Austin Paul F. , Rawashdeh Yazan F. , de Jong Tom P. , Franco Israel , Siggard Charlotte , Jorgensen Troels Munch
Published: April 2012

Purpose

The objective of this ICCS standardization document is to report the initial diagnostic evaluation and subsequent work‐up of children with neuropathic bladder dysfunction.

Materials and Methods

Due to a paucity of level I or level II, “levels of evidence” publications, these recommendations are actually a compilation of best practices because they seem to be effective and reliable, although not with any control.

Results

Throughout the document, the emphasis is on promoting early, comprehensive evaluation of lower urinary tract function that is thorough but with a minimum of unnecessary testing. This includes what tests to order, when to order them and what to do with the results. Some of the recommendations may not be practical in various worldwide locations but the suggested testing should be considered the ideal approach to completely diagnosing and then promulgating treatments based on the full knowledge of the condition and its effect on urinary tract function. Once the findings are delineated, those lower urinary tract patterns of dysfunction that put the kidneys at risk for deterioration, that are barriers to attaining eventual continence, and that have long‐term consequence to the lower urinary track can be obviated by specific management recommendations. The indications and timing of investigations to achieve these objectives are clearly defined in each diagnostic category and during follow‐up.

Recommendations

This document should be used as a basis for appropriate evaluation and timely surveillance of the various neuro‐urologic conditions that affect children. Neurourol. Urodynam. 31:610–614, 2012. © 2012 Wiley Periodicals, Inc.
Double incontinence in a cohort of nulliparous pregnant women
Authors: Espuña‐Pons Montserrat , Solans‐Domènech Maite , Sánchez Emília ,   On Behalf of the Pelvic Floor Research Group (Grup de Recerca del Sòl Pelvià, GRESP)
Published: April 2012

Aims

To estimate the frequency of double incontinence, and to identify associated risk factors during pregnancy and postpartum in previously continent nulliparous women.

Methods

A cohort study in healthy, nulliparous, continent pregnant women, attending the public healthcare system of Catalonia (Spain) was designed. The field work was conducted during the control visits of pregnancy, at the time of delivery, and in the postpartum. Double incontinence was defined as a situation in which participants reported simultaneously urinary incontinence (UI) and anal incontinence with the help of a self‐administered questionnaire. Prevalence rates, and their corresponding confidence intervals (95% CI), were calculated, as well as the impact on daily life. Multivariable logistic regressions in pregnancy and postpartum were estimated to assess the association of potential risk factors.

Results

The prevalence rate of double incontinence during pregnancy was 8.6% (95% CI: 7.0–10.3). Age over 35 years, and family history of UI were associated to a higher risk of double incontinence. After delivery, the prevalence rate decreased to 3.5% (95% CI: 2.4–4.6); only 6.7% of women with double incontinence in pregnancy had a persistency of their symptoms in early postpartum. Instrumental vaginal deliveries carried 2.2 times more risk of double incontinence than spontaneous ones. Episiotomy implied a higher risk for double incontinence.

Conclusions

Symptoms of double incontinence are prevalent during first pregnancy; age and other intrinsic factors may favor the occurrence of double incontinence throughout gestation, while instrumental delivery and episiotomy increase the risk of double incontinence in the postpartum period. Neurourol. Urodynam. 31:1236–1241, 2012. © 2012 Wiley Periodicals, Inc.
Detection of fluoroquinolone‐induced tendon disorders using a hospital database in Japan
Authors: Hori Katsuhito , Yamakawa Kasumi , Yoshida Naoko , Ohnishi Kazunori , Kawakami Junichi
Published: April 2012

Purpose

Tendinitis and tendon rupture are well‐known side effects of fluoroquinolones (FQs) in Western countries. In Japan, some case reports have been reported; however, the incidence of FQ‐induced tendon disorders has not been investigated. The aims of this study were to measure the occurrence of tendon disorders associated with FQs in Japanese patients and to compare the observed risk with that of previous reports. Moreover, the observed risk in FQ‐prescribed patients was compared with that in cephalosporin‐prescribed patients.

Methods

The Hamamatsu University Hospital database was examined to determine the risk of tendon disorders that occurred in all inpatients and outpatients between the first day of prescription of an oral FQ or cephalosporins to the calculated end date plus 30 days. The risk of tendon disorders, the risk ratio, and their 95% confidence intervals (CIs) were evaluated.

Results

From April 1996 to December 2009, FQs were prescribed to 17 147 patients, 14 of whom had tendon disorders (risk: 0.082%, 95%CI: 0.049–0.137). The risk of a tendon disorder in FQ‐prescribed patients was significantly higher than that in cephalosporin‐prescribed patients (five tendon disorders in 38 517 patients, risk: 0.013%, 95%CI: 0.006–0.030, and p < 0.001). The risk ratio of a tendon disorder in FQ‐prescribed patients in relation to cephalosporin‐prescribed patients was 6.29 (95%CI: 2.27–17.46). A large discrepancy in the risk of tendon disorders was not observed between our findings and previous reports.

Conclusion

A hospital database search revealed that the risk of tendon disorders in Japanese patients administered with FQs was higher than in those administered with cephalosporins. Copyright © 2012 John Wiley & Sons, Ltd.
Modulation of spin‐transport and spin‐minibands in a magnetic superlattice
Authors: Kim Jinwoo , Kim Heesang , Kim Nammee
Published: April 2012

We study the spin miniband structure and the ballistic spin‐polarized transport of a magnetic superlattice (MSL), formed by inhomogeneous magnetic field in a semiconductor nanowire. Based on the transfer matrix theory and Bloch's theorem, we calculate the energy dispersion having spin‐minibands and spin‐minigaps due to Bloch periodicity and spin‐dependent ballistic conductance for various geometrical and physical parameters. Results show that full spin‐polarization in the ballistic conductance of the system occurs clearly for each spin, and that the fully spin‐polarized range for each spin can be enhanced by modulation of geometrical and physical parameters.

magnified image

Schematic diagram of a MSL constructed by superconducting gridded mask on the top of a quantum wire formed by the split gate technique in two‐dimensional electron gas system. Transverse modes in Q1DEG serve as transmission channels.
Simulation of massive public health data by power polynomials
Authors: Demirtas Hakan , Hedeker Donald , Mermelstein Robin J.
Published: April 2012

Situations in which multiple outcomes and predictors of different distributional types are collected are becoming increasingly common in public health practice, and joint modeling of mixed types has been gaining popularity in recent years. Evaluation of various statistical techniques that have been developed for mixed data in simulated environments necessarily requires joint generation of multiple variables. Most massive public health data sets include different types of variables. For instance, in clustered or longitudinal designs, often multiple variables are measured or observed for each individual or at each occasion. This work is motivated by a need to jointly generate binary and possibly non‐normal continuous variables. We illustrate the use of power polynomials to simulate multivariate mixed data on the basis of a real adolescent smoking study. We believe that our proposed technique for simulating such intensive data has the potential to be a handy methodological addition to public health researchers’ toolkit. Copyright © 2012 John Wiley & Sons, Ltd.
Balancing continuous and categorical baseline covariates in sequential clinical trials using the area between empirical cumulative distribution functions
Authors: Lin Yunzhi , Su Zheng
Published: April 2012

Covariate adaptive allocation is often adopted in sequential clinical trials to maintain the balance of baseline covariates that could potentially confound the outcome of a trial. Several allocation methods exist in the literature that can handle both continuous and categorical covariates. We propose a minimization approach to maintaining the balance of multiple continuous and categorical covariates in sequential clinical trials, which uses the area between the empirical cumulative distribution functions of the observed covariate values as the imbalance metric. Numerical results based on extensive simulation studies and a real dataset show that the proposed approach produces more accurate estimates of the treatment effect and leads to more powerful trials than the existing approaches for trials with binary, continuous, and time‐to‐event outcomes. Copyright © 2012 John Wiley & Sons, Ltd.
A new partition testing strategy for multiple endpoints
Authors: Wang Bushi , Cui Xinping
Published: April 2012

To evaluate efficacy in multiple endpoints in confirmatory clinical trials is a challenging problem in multiple hypotheses testing. The difficulty comes from the different importance of each endpoint and their underlying correlation. Current approaches to this problem, which test the efficacy in certain dose–endpoint combinations and collate the results, are based on closed testing or partition testing. Despite their different formulations, all current approaches test their dose–endpoint combinations as intersection hypotheses and apply various union‐intersection tests. Likelihood ratio test is seldom used owing to the extensive computation and lack of consistent inferences.

In this article, we first generalize the formulation of multiple endpoints problem to include the cases of alternative primary endpoints and co‐primary endpoints. Then we propose a new partition testing approach that is based on consonance‐adjusted likelihood ratio test. The new procedure provides consistent inferences, and yet, it is still conservative and does not rely on the estimation of endpoint correlation or independence assumptions that might be challenged by regulatory agencies. Copyright © 2012 John Wiley & Sons, Ltd.
A survey of dynamic software updating
Authors: Seifzadeh Habib , Abolhassani Hassan , Moshkenani Mohsen Sadighi
Published: April 2012

Application update at run‐time remains a challenging issue in software engineering. There are many techniques with different evaluation metrics, resulting in different behaviours in the application being updated. In this paper, we provide an extensive review of research work on dynamic software updating. A framework for the evaluation of dynamic updating features is developed, and the articles are categorized and discussed based on the provided framework. Areas of online software maintenance requiring further research are also identified and highlighted. This information is deemed to not only assist practitioners in selecting appropriate dynamic updating techniques for their systems, but also to facilitate the ongoing and continuous research in the field of dynamic software updating. Copyright © 2012 John Wiley & Sons, Ltd.