bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and clinical implications of cyclin D1 expression in diffuse large B‐cell lymphoma (DLBCL) treated with immunochemotherapy: A report from the International DLBCL Rituximab‐CHOP Consortium Program
Authors: Ok Chi Young , Xu‐Monette Zijun Y. , Tzankov Alexandar , O'Malley Dennis P. , Montes‐Moreno Santiago , Visco Carlo , Møller Michael B. , Dybkær Karen , Orazi Attilio , Zu Youli , Bhagat Govind , Richards Kristy L. , Hsi Eric D. , Han van Krieken J. , Ponzoni Maurilio , Farnen John P. , Piris Miguel A. , Winter Jane N. , Medeiros L. Jeffrey , Young Ken H.
Published: March 2014

BACKGROUND

Cyclin D1 expression has been reported in a subset of patients with diffuse large B‐cell leukemia (DLBCL), but studies have been few and generally small, and they have demonstrated no obvious clinical implications attributable to cyclin D1 expression.

METHODS

The authors reviewed 1435 patients who were diagnosed with DLBCL as part of the International DLBCL rituximab with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R‐CHOP) Consortium Program and performed clinical, immunohistochemical, and genetic analyses with a focus on cyclin D1. All patients who were cyclin D1‐positive according to immunohistochemistry were also assessed for rearrangements of the cyclin D1 gene (CCND1) using fluorescence in situ hybridization. Gene expression profiling was performed to compare patients who had DLBCL with and without cyclin D1 expression.

RESULTS

In total, 30 patients (2.1%) who had DLBCL that expressed cyclin D1 and lacked CCND1 gene rearrangements were identified. Patients with cyclin D1‐positive DLBCL had a median age of 57 years (range, 16.0‐82.6 years). There were 23 males and 7 females. Twelve patients (40%) had bulky disease. None of them expressed CD5. Two patients expressed cyclin D2. Gene expression profiling indicated that 17 tumors were of the germinal center type, and 13 were of the activated B‐cell type. Genetic aberrations of B‐cell leukemia/lymphoma 2 (BCL2), BCL6, v‐myc avian myelocytomatosis viral oncogene homolog (MYC), mouse double minute 2 oncogene E3 ubiquitin protein ligase (MDM2), MDM4, and tumor protein 53 (TP53) were rare or absent. Gene expression profiling did not reveal any striking differences with respect to cyclin D1 in DLBCL.

CONCLUSIONS

Compared with patients who had cyclin D1‐negative DLBCL, men were more commonly affected with cyclin D1‐positive DLBCL, and they were significantly younger. There were no other significant differences in clinical presentation, pathologic features, overall survival, or progression‐free survival between these two subgroups of patients with DLBCL. Cancer 2014;120:1818–1829. © 2014 American Cancer Society.
Self‐Assembly of Nanocellulose and Indomethacin into Hierarchically Ordered Structures with High Encapsulation Efficiency for Sustained Release Applications
Authors: Gao Jiali , Li Qing , Chen Wenshuai , Liu Yixing , Yu Haipeng
Published: March 2014

Cellulose nanofibers (CNFs) were isolated from poplar wood by using a mild chemical pretreatment combined with a high‐intensity ultrasonication method. The as‐prepared CNFs were used as a template to load indomethacin (IMC). With the nucleation and growth of IMC on the surfaces of CNFs and CNF clusters, CNF/IMC composite fibers were eventually fabricated. The effects of solvent and processing method on the structures of the composite fibers were analyzed in terms of morphology, surface charge, and crystal form. Drug‐release characteristics of the composite fibers were evaluated by dissolution tests, in which the drug‐releasing curves of the composite fibers were fitted to a mathematical model describing the releasing kinetics. The experimental results demonstrated that the composite fibers possessed an encapsulation efficiency of up to 97 %, and a sustained drug‐release period of over 30 days.
Common Factor Mechanisms in Clinical Practice and Their Relationship with Outcome
Authors: Gaitan‐Sierra Carolina , Hyland Michael E.
Published: March 2014

This study investigates three common factor mechanisms that could affect outcome in clinical practice: response expectancy, the affective expectation model and motivational concordance. Clients attending a gestalt therapy clinic (30 clients), a sophrology (therapeutic technique) clinic (33 clients) and a homeopathy clinic (31 clients) completed measures of expectancy and the Positive Affect and Negative Affect Schedule (PANAS) before their first session. After 1 month, they completed PANAS and measures of intrinsic motivation, perceived effort and empowerment. Expectancy was not associated with better outcome and was no different between treatments. Although some of the 54 clients who endorsed highest expectations showed substantial improvement, others did not: 19 had no change or deteriorated in positive affect, and 18 had the same result for negative affect. Intrinsic motivation independently predicted changes in negative affect (β = −0.23). Intrinsic motivation (β = 0.24), effort (β = 0.23) and empowerment (β = 0.20) independently predicted positive affect change. Expectancy (β = −0.17) negatively affected changes in positive affect. Clients found gestalt and sophrology to be more intrinsically motivating, empowering and effortful compared with homeopathy. Greater improvement in mood was found for sophrology and gestalt than for homeopathy clients. These findings are inconsistent with response expectancy as a common factor mechanism in clinical practice. The results support motivational concordance (outcome influenced by the intrinsic enjoyment of the therapy) and the affective expectation model (high expectations can lead for some clients to worse outcome). When expectancy correlates with outcome in some other studies, this may be due to confound between expectancy and intrinsic enjoyment. Copyright © 2014 John Wiley & Sons, Ltd.

Key Practitioner Message

Common factors play an important role in outcome.

Intrinsic enjoyment of a therapeutic treatment is associated with better outcome.

Active engagement with a therapeutic treatment improves outcome.

Unrealistic expectations about a therapeutic treatment can have a negative impact on outcome.
Regulation of the tolerogenic function of steady‐state DCs
Authors: Probst Hans Christian , Muth Sabine , Schild Hansjörg
Published: March 2014

Dendritic cells (DCs) are master regulators of T‐cell responses. After sensing pathogen‐derived molecular patterns (PAMPs), or signals of inflammation and cellular stress, DCs differentiate into potent activators of naïve CD4+ and CD8+ T cells through a process that is termed DC maturation. By contrast, DCs induce and maintain peripheral T‐cell tolerance in the steady state, that is in the absence of overt infection or inflammation. However, the immunological steady state is not devoid of DC‐activating stimuli, such as commensal microorganisms, subclinical infections, or basal levels of proinflammatory mediators. In the presence of these activating stimuli, DC maturation must be calibrated to ensure self‐tolerance yet allow for adequate T‐cell responses to infections. Here, we review the factors that are known to control DC maturation in the steady state and discuss their effect on the tolerogenic function of steady‐state DCs.
Self‐Assembly Properties of NCN Pincer Palladium(II) Complexes Bearing a Uracil Moiety
Authors: Moriuchi Toshiyuki , Ohata Ryohei , Sakamoto Yuki , Hirao Toshikazu
Published: March 2014

NCN pincer palladium(II) complexes bearing a 6‐ethynyl‐1‐octyluracil moiety were designed by the combination of an NCN pincer palladium(II) complexes as an organometallic compound and a uracil derivative as a nucleobase to afford bioorganometallic compounds. The reaction of the NCN pincer ligand with Pd(dba)2 (dba = dibenzylideneacetone) led to the formation of the NCN pincer palladium(II) complex Pd‐Br. The crystal structure of the cationic complex Pd‐MeCN, which was prepared by the treatment of Pd‐Br with AgOTf (OTf = trifluoromethanesulfonate) in acetonitrile, revealed that a dimeric structure formed through intermolecular hydrogen bonds between the uracil moieties of two independent molecules. The self‐assembly properties of the NCN pincer palladium(II) complexes were found to depend on the ancillary ligands. Each hydrogen‐bonded dimer was connected through an intermolecular hydrogen‐bonding bridge between the coordinated water molecule and the triflate anion in the cationic complex Pd‐H2O. Intermolecular hydrogen bonding between the uracil moiety and the triflate anion bound to the palladium center was observed in the NCN pincer palladium(II) complex Pd‐OTf, although a dimeric structure between the uracil moieties was formed in the NCN pincer palladium(II) complex Pd‐O2CCF3, which was obtained by the abstraction of the bromide ion from Pd‐Br with AgO2CCF3.
Total protein quantitation using the bicinchoninic acid assay and gradient elution moving boundary electrophoresis
Authors: Kralj Jason G. , Munson Matthew S. , Ross David
Published: March 2014

We investigated the ability of gradient elution moving boundary electrophoresis (GEMBE) with capacitively coupled contactless conductivity detection (C4D) to assay total protein concentration using the bicinchoninic acid (BCA) reaction. We chose this format because GEMBE‐C4D behaves as a concentration dependent detection system, unlike optical methods that also rely on pathlength (due to Beer's law). This system tolerates proteins well compared with other capillary electrophoretic methods, allowing the capillary to be reused without coatings or additional hydroxide wash steps. The typical reaction protocol was modified by reducing the pH slightly from 11.25 to 9.4, which enabled elimination of tartrate from the reagents. We estimated that copper (I) could be detected at approximately 3.0 μmol/L, which agrees with similar GEMBE and CZE systems utilizing C4D. Under conditions similar to the BCA “micro method” assay, we determined the LOD for three common proteins (insulin, BSA, and bovine gamma globulin) and found that they agree well with the existing spectroscopic detection methods. Further, we investigated how long reaction times impact the LOD and found that the conversion was proportional to log(time). This indicated that little sensitivity is gained by extending the reaction past 1 h. Hence, GEMBE provides an alternative platform for total protein assays while maintaining the excellent sensitivity of the optical‐based methods.
The free solution mobility of DNA and other analytes varies as the logarithm of the fractional negative charge
Authors: Stellwagen Nancy C. , Peters Justin P. , Dong Qian , Maher L. James , Stellwagen Earle
Published: March 2014

The free solution mobilities of ssDNA and dsDNA molecules with variable charge densities have been measured by CE. DNA charge density was modified either by appending positively or negatively charged groups to the thymine residues in a 98 bp DNA molecule, or by replacing some of the negatively charged phosphate internucleoside linkers in small ssDNA or dsDNA oligomers with positively charged phosphoramidate linkers. Mobility ratios were calculated for each dataset by dividing the mobility of a charge variant by the mobility of its unmodified parent DNA. Mobility ratios essentially eliminate the effect of the BGE on the observed mobility, making it possible to compare analytes measured under different experimental conditions. Neutral moieties attached to the thymine residues in the 98‐bp DNA molecule had little or no effect on the mobility ratios, indicating that bulky substituents in the DNA major groove do not affect the mobility significantly. The mobility ratios observed for the thymine‐modified and linker‐modified DNA charge variants increased approximately linearly with the logarithm of the fractional negative charge of the DNA. Mobility ratios calculated from previous studies of linker‐modified DNA charge variants and small multicharged organic molecules also increased approximately linearly with the logarithm of the fractional negative charge of the analyte. The results do not agree with the Debye–Hückel–Onsager theory of electrophoresis, which predicts that the mobility of an analyte should depend linearly on analyte charge, not the logarithm of the charge, when the frictional coefficient is held constant.
Antipsychotic medication use in nursing homes: a proposed measure of quality
Authors: Lucas Judith A. , Chakravarty Sujoy , Bowblis John R. , Gerhard Tobias , Kalay Ece , Paek Eun Kwang , Crystal Stephen
Published: March 2014

Objective

The potential misuse of antipsychotic medications (APMs) is an ongoing quality concern in nursing homes (NHs), especially given recent black box warnings and other evidence regarding the risk of APMs when used in NH populations. One mechanism regulators could use is public reporting of APM use by NHs; however, there is currently no agreed‐upon measure of guideline‐inconsistent APM use. In this paper, we describe a proposed measure of quality of APM use that is based on Centers for Medicare and Medicaid Services (CMS) Interpretive Guidelines, Food and Drug Administration (FDA) indications for APMs, and severity of behavioral symptoms.

Methods

The proposed measure identifies NH residents who receive an APM but do not have an approved indication for APM use. We demonstrate the feasibility of this measure using data from Medicaid‐eligible long‐stay residents aged 65 years and older in seven states. Using multivariable logistic regressions, we compare it to the current CMS Nursing Home Compare quality measure.

Results

We find that nearly 52% of residents receiving an APM lack indications approved by CMS/FDA guidelines compared with 85% for the current CMS quality measure. APM guideline‐inconsistent use rates vary significantly across resident and facility characteristics, and states. Only our measure correlates with another quality indicator in that facilities with higher deficiencies have significantly higher odds of APM use. Predictors of inappropriate use are found to be consistent with other measures of NH quality, supporting the validity of our proposed measure.

Conclusion

The proposed measure provides an important foundation to improve APM prescribing practices without penalizing NHs when there are limited alternative treatments available. Copyright © 2014 John Wiley & Sons, Ltd.
Trend analyses with river sediment rating curves
Authors: Warrick Jonathan A.
Published: March 2014

Sediment rating curves, which are fitted relationships between river discharge (Q) and suspended‐sediment concentration (C), are commonly used to assess patterns and trends in river water quality. In many of these studies, it is assumed that rating curves have a power‐law form (i.e.C = aQb, whereaandbare fitted parameters). Two fundamental questions about the utility of these techniques are assessed in this paper: (i) how well to the parameters,aandb, characterize trends in the data, and (ii) are trends in rating curves diagnostic of changes to river water or sediment discharge? As noted in previous research, the offset parameter,a, is not an independent variable for most rivers but rather strongly dependent onbandQ. Here, it is shown thatais a poor metric for trends in the vertical offset of a rating curve, and a new parameter,â, as determined by the discharge‐normalized power function [C = â(Q/QGM)b], whereQGMis the geometric mean of theQ‐values sampled, provides a better characterization of trends. However, these techniques must be applied carefully, because curvature in the relationship between log(Q) and log(C), which exists for many rivers, can produce false trends inâandb. Also, it is shown that trends inâandbare not uniquely diagnostic of river water or sediment supply conditions. For example, an increase inâcan be caused by an increase in sediment supply, a decrease in water supply or a combination of these conditions. Large changes in water and sediment supplies can occur without any change in the parameters,âandb. Thus, trend analyses using sediment rating curves must include additional assessments of the time‐dependent rates and trends of river water, sediment concentrations and sediment discharge. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.Hydrological Processespublished by John Wiley & Sons Ltd.
Exposure to parabens at the concentration of maximal proliferative response increases migratory and invasive activity of human breast cancer cells in vitro
Authors: Khanna Sugandha , Dash Philip R. , Darbre Philippa D.
Published: March 2014

Alkyl esters of p–hydroxybenzoic acid (parabens) are widely used as preservatives in personal care products, foods and pharmaceuticals. Their oestrogenic activity, their measurement in human breast tissue and their ability to drive proliferation of oestrogen‐responsive human breast cancer cells has opened a debate on their potential to influence breast cancer development. As proliferation is not the only hallmark of cancer cells, we have investigated the effects of exposure to parabens at concentrations of maximal proliferative response on migratory and invasive properties using three oestrogen‐responsive human breast cancer cell lines (MCF‐7, T‐47‐D, ZR‐75‐1). Cells were maintained short‐term (1 week) or long‐term (20 ± 2 weeks) in phenol‐red‐free medium containing 5% charcoal‐stripped serum with no addition, 10–8 M 17β‐oestradiol, 1–5 × 10–4 M methylparaben, 10‐5 M n‐propylparaben or 10–5 M n‐butylparaben. Long‐term exposure (20 ± 2 weeks) of MCF‐7 cells to methylparaben, n‐propylparaben or n‐butylparaben increased migration as measured using a scratch assay, time‐lapse microscopy and xCELLigence technology: invasive properties were found to increase in matrix degradation assays and migration through matrigel on xCELLigence. Western immunoblotting showed an associated downregulation of E‐cadherin and β‐catenin in the long‐term paraben‐exposed cells which could be consistent with a mechanism involving epithelial to mesenchymal transition. Increased migratory activity was demonstrated also in long‐term paraben‐exposed T‐47‐D and ZR‐75‐1 cells using a scratch assay and time‐lapse microscopy. This is the first report that in vitro, parabens can influence not only proliferation but also migratory and invasive properties of human breast cancer cells. Copyright © 2014 John Wiley & Sons, Ltd.
Teneurin‐4, a transmembrane protein, is a novel regulator that suppresses chondrogenic differentiation
Authors: Suzuki Nobuharu , Mizuniwa Chihiro , Ishii Kana , Nakagawa Yusuke , Tsuji Kunikazu , Muneta Takeshi , Sekiya Ichiro , Akazawa Chihiro
Published: March 2014

Teneurin‐4 (Ten‐4), a transmembrane protein, is expressed in the nervous systems and the mesenchymal tissues, including the cartilage. However, the Ten‐4 function in cartilage development remains unknown. Here, we showed that Ten‐4 is a novel regulator of chondrogenesis. In situ hybridization analysis revealed that Ten‐4 was highly expressed in the mesenchymal condensation area of the mouse femur at embryonic day (E) 13.5, while its expression was decreased in the growth plate of the femur at E18.5. Using the cartilage‐like pellet culture of human synovial mesenchymal cells, Ten‐4 expression was induced and peaked 7 days after induction of differentiation, while a production of type II and X collagens was increased after Day 14. In the cartilage‐like pellet, Ten‐4 was highly expressed in the less differentiated region. In the chondrogenic cell line ATDC5, knockdown of Ten‐4 expression significantly increased the alcian blue staining and expression levels of aggrecan and type II and X collagens. Further, an elevated expression of Sox6, Sox9, and Runx2 and an attenuation of the ERK activation were observed in the Ten‐4‐knockdown ATDC5 cells. These results suggested that Ten‐4 suppresses chondrogenic differentiation and regulates the expression and activation of the key molecules for chondrogenesis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:915–922, 2014.
Inferior long-term outcomes of liver-kidney transplantation using donation after cardiac death donors: Single-center and organ procurement and transplantation network analyses
Authors: Wadei Hani M. , Bulatao Ilynn G. , Gonwa Thomas A. , Mai Martin L. , Prendergast Mary , Keaveny Andrew P. , Rosser Barry G. , Taner Burcin C.
Published: March 2014

Limited data are available for outcomes of simultaneous liver-kidney (SLK) transplantation using donation after cardiac death (DCD) donors. The outcomes of 12 DCD-SLK transplants and 54 SLK transplants using donation after brain death (DBD) donors were retrospectively compared. The baseline demographics were similar for the DCD-SLK and DBD-SLK groups except for the higher liver donor risk index for the DCD-SLK group (1.8 ± 0.4 versus 1.3 ± 0.4, P = 0.001). The rates of surgical complications and graft rejections within 1 year were comparable for the DCD-SLK and DBD-SLK groups. Delayed renal graft function was twice as common in the DCD-SLK group. At 1 year, the serum creatinine levels and the iothalamate glomerular filtration rates were similar for the groups. The patient, liver graft, and kidney graft survival rates at 1 year were comparable for the groups (83.3%, 75.0%, and 82.5% for the DCD-SLK group and 92.4%, 92.4%, and 92.6% for the DBD-SLK group, P = 0.3 for all). The DCD-SLK group had worse patient, liver graft, and kidney graft survival at 3 years (62.5%, 62.5%, and 58.9% versus 90.5%, 90.5%, and 90.6%, P = 0.03 for all) and at 5 years (62.5%, 62.5%, and 58.9% versus 87.4%, 87.4%, and 87.7%, P < 0.05 for all). An analysis of the Organ Procurement and Transplantation Network database showed inferior 1- and 5-year patient and graft survival rates for DCD-SLK patients versus DBD-SLK patients. In conclusion, despite comparable rates of surgical and medical complications and comparable kidney function at 1 year, DCD-SLK transplantation was associated with inferior long-term survival in comparison with DBD-SLK transplantation. Liver Transpl 20:728-735, 2014. © 2014 AASLD.
MicroRNAs in the bile of patients with biliary strictures after liver transplantation
Authors: Lankisch Tim O. , Voigtländer Torsten , Manns Michael P. , Holzmann Angelika , Dangwal Seema , Thum Thomas
Published: March 2014

Biliary complications after liver transplantation remain a major cause of morbidity and reduced graft survival. Ischemic-type biliary lesions (ITBLs) are common and difficult to treat. The pathophysiology of ITBLs remains unclear, and diagnostic markers are still missing. The analysis of microRNA (miRNA) profiles is an evolving field in hepatology. Our aim was to identify specific miRNA patterns in the bile of patients with ITBLs after liver transplantation. Liver transplant patients with biliary complications were included in a cross-sectional study. Patients with ITBLs (n = 37), anastomotic strictures (ASs; n = 39), and bile duct stones (BDSs; n = 12) were compared. Patients with ITBLs were categorized by disease severity. The miRNA concentrations in bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction–mediated validation. The concentrations of microRNA 517a (miR-517a), miR-892a, and miR-106a* in bile were increased for patients with ITBLs versus patients with ASs or BDSs (P < 0.05). Categorization by ITBL severity showed higher median concentrations in patients with intrahepatic and extrahepatic strictures (P > 0.05). miR-210, miR-337-5p, miR-577, and miR-329 displayed no statistical differences. In conclusion, miR-517a, miR-892a, and miR-106a* are increased in the bile fluid of patients with ITBLs versus patients with ASs or BDSs. An analysis of miRNA profiles may be useful in the diagnosis and management of patients with ITBLs. Future studies are needed to prove the potential prognostic value of these miRNAs. Liver Transpl 20:673-678, 2014. © 2014 AASLD.
Analytical layer element solutions for deformations of transversely isotropic multilayered elastic media under nonaxisymmetric loading
Authors: Ai Zhi Yong , Feng Dong Liang , Cang Nai Rui
Published: March 2014

This paper presents the analytical layer element solutions for deformations of transversely isotropic elastic media subjected to nonaxisymmetric loading at an arbitrary depth. The state vectors for the nonaxisymmetric problem are deduced through the substitution of the Hu Hai‐chang solutions into the basic equations for the transversely isotropic elastic media. From the state vectors, the analytical layer element of a single layer is obtained in the Hankel transformed domain. The analytical layer element is an exact and symmetric stiffness matrix whose elements are without positive exponential functions, which can not only simplify the calculation but also improve the stability of computation. On the basis of the continuity conditions between adjacent layers, the global stiffness matrix is obtained by assembling the interrelated layer elements. The solutions for the multilayered elastic media in the transformed domain are obtained by solving the algebraic equation of the global stiffness matrix, which satisfies the boundary conditions. The actual solutions in the physical domain are further obtained by inverting the Hankel transform. Finally, some cases are analyzed to verify the solutions and evaluate the influences of the transversely isotropic character and stratified character of the media on the load–displacement responses. The numerical results show that the variations of the elastic properties between layers have a great effect on the displacements of the multilayered media. Copyright © 2014 John Wiley & Sons, Ltd.
High aspect ratio electrodeposited Ni/Au contacts for GaAs‐based III–V concentrator solar cells
Authors: Ward J. Scott , Duda Anna , Friedman Daniel J. , Geisz John , McMahon William , Young Michelle
Published: March 2014

We report on a photolithographic and electro‐deposition process that results in an optimized front grid structure for high efficiency multi‐junction III–V concentrator solar cells operating under flux concentrations up to 1000 suns. Two different thick photoresists were investigated to achieve a 6 µm wide grid line with an aspect ratio of 1:1. A positive photoresist, SPR220 manufactured by Rohm and Haas was compared with a negative photoresist, nXT15 manufactured by AZ. A gold sulfite electrolyte was employed to prevent underplating as well as for environmental and safety considerations. An initial layer of nickel was discovered to be necessary to prevent delamination of the fingers during the removal of the contact layer. When deposited on a purpose grown, heavily doped GaAs contact layer, this Ni/Au contact exhibits an acceptable specific contact resistance in the low 10−4 to mid 10−5 Ohm cm2 range along with excellent adhesion without sintering. Copyright © 2014 John Wiley & Sons, Ltd.
Intestinal proteomics in pig models of necrotising enterocolitis, short bowel syndrome and intrauterine growth restriction
Authors: Jiang Pingping , Sangild Per Torp
Published: March 2014

Necrotising enterocolitis (NEC), short bowel syndrome (SBS) and intrauterine growth restriction (IUGR) are three conditions associated with intestinal dysfunction in newborn infants, particularly those born preterm. Piglet (Sus scrofa) models have recently been developed for NEC, SBS and IUGR, and tissue proteomic analyses have identified unknown pathways and new prognostic disease markers. Intestinal HSPs, iron metabolism proteins and proteins related to amino acid (e.g. arginine) and glucose metabolism are consistently affected by NEC progression and some of these proteins are also affected by SBS and IUGR. Parallel changes in some plasma and urinary proteins (e.g. haptoglobin, globulins, complement proteins, fatty acid binding proteins) may mirror the intestinal responses and pave the way to biomarker discovery. Explorative non‐targeted proteomics provides ideas about the cellular pathways involved in intestinal adaptation during the critical neonatal period. Proteomics, combined with other ‐omic techniques, helps to get a more holistic picture of intestinal adaptation during NEC, SBS and IUGR. Explorative ‐omic research methods also have limitations and cannot replace, but only supplement, classical hypothesis‐driven research that investigate disease mechanisms using a single or few endpoints.
Role of growth parameters in equalizing simultaneous growth of N‐ and Ga‐polar GaN by MOCVD
Authors: Hite Jennifer K. , Zoll Rachel , Mastro Michael A. , Eddy Charles R.
Published: March 2014

In preparing periodically‐oriented gallium nitride (PO GaN) samples for optical applications, smooth surfaces are essential. Although post‐growth processing of these surfaces is possible, it is challenged by significantly different reactivity of the two polar surfaces. To this end, it would be highly desirable to grow PO GaN structures with smooth surfaces. In this paper, the influence of growth parameters on the morphology of PO GaN structures is investigated. The three primary parameters investigated include the V/III ratio of the gas phase precursors, the nature of the carrier gas, and the geometry of the structure. The V/III ratio was varied from 1100 to 5500. Substitution of N2 for the standard H2 carrier gas is investigated. Finally, the effects of changing the structure periodicity from 2 to 100 mm are studied. Smoother structures (resulting from more equal growth rates of the two polarities) are achieved with increases in V/III ratio, substitution of H2 with N2, and by reducing the stripe width. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Characterization of a‐plane GaN templates grown by HVPE and high efficiency deep UV emitting AlGaN/AlN MQWs grown by MBE on such templates
Authors: Moldawer Adam , Bhattacharyya Anirban , Zhou Lin , Smith David J. , Moustakas Theodore D.
Published: March 2014

Thick GaN templates (>50 µm) were grown by hydride‐vapor‐phase epitaxy (HVPE) on the r‐plane of sapphire. While X‐ray diffraction indicates that the GaN grows with its a‐plane parallel to the r‐plane of sapphire, the surface has a triangular morphology of 120º, which is the result of the faster growth rate of the a‐plane compared to the m‐plane. Electron microscopy studies indicate that these GaN templates have a high concentration of threading defects (>1010 cm–2) and basal plane stacking faults (7x105 cm–1). Several identical deep‐UV emitting Al0.7Ga0.3N/AlN multiple quantum wells (MQWs) were grown on such GaN templates by molecular‐beam epitaxy (MBE). The wells were grown under more gallium than required by stoichiometry, which changes the growth mode from physical vapor deposition to liquid phase epitaxy. This growth mode leads to deep band structure potential fluctuations. The structure and microstructure of these MQWs were evaluated by transmission electron microscopy (TEM) and found to have even higher density of threading defects than the GaN template. In spite of this, the internal quantum efficiency (IQE) of these MQWs was estimated from the temperature dependence of the cathodoluminescence spectra to be 87%. This remarkable result was attributed to the deep band structure potential fluctuations introduced by the liquid‐phase epitaxy growth mode as well as the high concentration of basal plane stacking faults. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Conditional Monte Carlo randomization tests for regression models
Authors: Parhat Parwen , Rosenberger William F. , Diao Guoqing
Published: March 2014

We discuss the computation of randomization tests for clinical trials of two treatments when the primary outcome is based on a regression model. We begin by revisiting the seminal paper of Gail, Tan, and Piantadosi (1988), and then describe a method based on Monte Carlo generation of randomization sequences. The tests based on this Monte Carlo procedure are design based, in that they incorporate the particular randomization procedure used. We discuss permuted block designs, complete randomization, and biased coin designs. We also use a new technique by Plamadeala and Rosenberger (2012) for simple computation of conditional randomization tests. Like Gail, Tan, and Piantadosi, we focus on residuals from generalized linear models and martingale residuals from survival models. Such techniques do not apply to longitudinal data analysis, and we introduce a method for computation of randomization tests based on the predicted rate of change from a generalized linear mixed model when outcomes are longitudinal. We show, by simulation, that these randomization tests preserve the size and power well under model misspecification. Copyright © 2014 John Wiley & Sons, Ltd.
Modulation of symmetry for discrete variables and some extensions
Authors: Azzalini Adelchi , Regoli Giuliana
Published: March 2014

Substantial work has been dedicated in recent years to the construction of families of continuous distributions obtained by applying a modulation factor to a base symmetric density so as to obtain non‐symmetric variant forms, often denoted skew‐symmetric distributions. All this development has dealt with the case of continuous variables, while here we extend the formulation to the discrete case; moreover, some of the statements are of general validity. The results are illustrated with an application to the distribution of the score difference in sport matches. Copyright © 2014 John Wiley & Sons, Ltd
Connexins in respiratory and gastrointestinal mucosal immunity
Authors: Bou Saab Joanna , Losa Davide , Chanson Marc , Ruez Richard
Published: March 2014

The mucosal lining forms the physical and chemical barrier that protects against pathogens and hostile particles and harbors its own population of bacteria, fungi and archea, known as the microbiota. The immune system controls tolerance of this population of microorganisms that have proven to be beneficial for its host. Keeping its physical integrity and a correct balance with the microbiota, the mucosa preserves its homeostasis and its protective function and maintains host's health. However, in some conditions, pathogens may succeed in breaching mucosal homeostasis and successfully infecting the host. In this review we will discuss the role the mucosa plays in the defense against bacterial pathogens by considering the gap junction protein connexins. We will detail their implication in mucosal homeostasis and upon infection with bacteria in the respiratory and the gastrointestinal tracts.
A new angle on blood–CNS interfaces: A role for connexins?
Authors: De Bock Marijke , Vandenbroucke Roosmarijn E. , Decrock Elke , Culot Maxime , Cecchelli Romeo , Leybaert Luc
Published: March 2014

Neuronal signaling in the CNS depends on the microenvironment around synapses and axons. To prevent fluctuations in blood composition affecting the interstitial fluid and CSF, two barriers, the blood–brain barrier (BBB) and blood–CSF barrier (BCSFB), are interposed between the blood and the brain/CSF compartment. Brain capillary endothelial cells (ECs) constitute the BBB whereas choroid plexus epithelial (CPE) cells form the BCSFB. The anatomical basis of these barriers is located at the level of an intercellular junctional complex that impedes paracellular diffusion. Tight and adherens junctions are known as the principal constituents of this junctional complex. Transmembrane connexins (Cxs) are the prime building blocks of plasma membrane hemichannels that combine to form intercellular gap junctions (GJ). Although Cxs co‐exist within the junctional complex, their influence on tight/adherens junctions and their role in barrier function of BBB ECs and CPE has been mostly ignored. Here, we review current knowledge on the role of Cxs in the BBB, BCSFB and other interfaces that subside within the CNS. We conclude that Cxs are a rather unexplored but promising target for influencing CNS barrier function.
Detection and quantification of alternative splice sites in Arabidopsis genes AtDCL2 and AtPTB2 with highly sensitive surface enhanced Raman spectroscopy (SERS) and gold nanoprobes
Authors: Kadam Ulhas S. , Schulz Burkhard , lrudayaraj Joseph
Published: March 2014

Alternative splicing (AS) increases the size of the transcriptome and proteome to enhance the physiological capacity of cells. We demonstrate surface enhanced Raman spectroscopy (SERS) in combination with a DNA hybridization analytical platform to identify and quantify AS genes in plants. AS in AtDCL2 and AtPTB2 were investigated using non‐fluorescent Raman probes using a ‘sandwich assay’. Utilizing Raman probes conjugated to gold nanoparticles we demonstrate the recognition of RNA sequences specific to AtDCL2 and AtPTB2 splice junction variants with detection sensitivity of up to 0.1 fM.
GDSL lipase 1 regulates ethylene signaling and ethylene‐associated systemic immunity in Arabidopsis
Authors: Kim Hye Gi , Kwon Sun Jae , Jang Young Jin , Chung Joo Hee , Nam Myung Hee , Park Ohkmae K.
Published: March 2014

Arabidopsis GDSL lipase 1 (GLIP1) has been shown to modulate systemic immunity through the regulation of ethylene signaling components. Here we demonstrate that the constitutive triple response mutant ctr1‐1 requires GLIP1 for the ethylene response, gene expression, and pathogen resistance. The glip1‐1 mutant was defective in induced resistance following primary inoculation of necrotrophic pathogens, whereas GLIP1‐overexpressing plants showed resistance to multiple pathogens. Necrotrophic infection triggered the downregulation of EIN3 and the activation of ERF1 and SID2 in a GLIP1‐dependent manner. These results suggest that GLIP1 positively and negatively regulates ethylene signaling, resulting in an ethylene‐associated, necrotroph‐induced immune response.
The two common polymorphic forms of human NRH‐quinone oxidoreductase 2 (NQO2) have different biochemical properties
Authors: Megarity Clare F. , Gill James R.E. , Clare Caraher M. , Stratford Ian J. , Nolan Karen A. , Timson David J.
Published: March 2014

There are two common forms of NRH‐quinone oxidoreductase 2 (NQO2) in the human population resulting from SNP rs1143684. One has phenylalanine at position 47 (NQO2‐F47) and the other leucine (NQO2‐L47). Using recombinant proteins, we show that these variants have similar steady state kinetic parameters, although NQO2‐L47 has a slightly lower specificity constant. NQO2‐L47 is less stable towards proteolytic digestion and thermal denaturation than NQO2‐F47. Both forms are inhibited by resveratrol, but NQO2‐F47 shows negative cooperativity with this inhibitor. Thus these data demonstrate, for the first time, clear biochemical differences between the variants which help explain previous biomedical and epidemiological findings.
Hunting for connexin hemichannels
Authors: Sáez Juan C. , Leybaert Luc
Published: March 2014

Connexin hemichannels (connexons) are building blocks of gap junctions but also function as free unapposed channels, which has become an active field of research. Defining functions of hemichannels and their involvement in any biological event requires ruling out possible participation of other channels that share biophysical and regulatory properties, for example pannexins, CALHM1 and P2X receptors. The lack of specific inhibitors for these channels has become an obstacle in elucidating the role of connexin hemichannels. Several experimental approaches are now available to identify hemichannels at the cell surface and to characterize their electrophysiological, permeability and regulatory properties. The use of connexin knockout/knockdown, and the development of peptides that target intracellular connexin domains and specific antibodies directed to extracellular domains have helped to dissect the role of hemichannels in endogenously expressing systems. Moreover, studies of connexin mutants in exogenous expression systems have provided convincing evidence on hemichannels in the pathogenesis of several human genetic diseases. We here present a brief overview of connexin hemichannels as functional channels and itemize a list of aspects to consider when concluding on their involvement.
Recent findings in evolution and function of insect innexins
Authors: Hasegawa Daniel K. , Turnbull Matthew W.
Published: March 2014

The past decade has seen significant advances in the field of innexin biology, particularly in the model invertebrate organisms, the nematode Caenorhabditis elegans and the fly Drosophila melanogaster. However, advances in genomics and functional techniques during this same period are ushering in a period of comparative innexin biology. Insects are the most diverse metazoan taxa in terms of species number, as well as in developmental, physiological, and morphological processes. Combined with genomics data, the study of innexins should rapidly advance. In this review, we consider the current state of knowledge regarding innexins in insects, focusing on innexin diversity, both evolutionary and functional. We also consider an unusual set of innexins, known as vinnexins, that have been isolated from mutualistic viruses of some parasitoid wasps. We conclude with a call to study insect innexins from a broader, evolutionary perspective. Knowledge derived from such comparative studies will offer significant insight into developmental and evolutionary physiology, as well as specific functional processes in a taxon that has huge biomedical and ecological impact on humans.
Models, monitoring, and the mind: Comments on Wansink and Chandon's “Slim by Design”
Authors: Herman C. Peter , Polivy Janet
Published: March 2014

Wansink and Chandon have examined the “mindlessness” that is often evident in everyday food intake. In this commentary, we focus on four issues raised by Wansink and Chandon's paper: (1) the distinction between food choice and food intake; (2) their model of food intake (and how it compares and contrasts with our own model of food intake); (3) the role of monitoring in the control of food intake; and (4) the meaning of “mindless” eating. In each case we find value in Wansink and Chandon's proposals but also an opportunity for further analysis and refinement.
Evaluation of efficacy of chemiluminescence for diagnosis of leukoplakia
Authors: Chaudhry Astha , Manjunath M
Published: March 2014

Objective: Leukoplakia is the most common potentially malignant disorder preceding oral cancer. Chemiluminescence has been developed as an adjunct to conventional examination for the diagnosis of these potentially malignant disorders. This study was conducted to assess the efficacy of chemiluminescence in the diagnosis of leukoplakia and to compare the results with histopathological examination.

Study design: A total of 50 patients with leukoplakia were included from the outpatients attending the Department of Oral Medicine and Radiology, Dental Hospital, Bengaluru, Karnataka, India. These patients were subjected to conventional oral examination followed by chemiluminescent examination with Vizilite (Zila, Fort Collins, CO, USA) and biopsy for histopathological confirmation.

Results: The sensitivity, specificity, positive predictive value, and negative predictive value of chemiluminescence were 93.75%, 55.56%, 78.95%, and 83.3%, respectively. The overall accuracy of chemiluminescence was 80%. A statistically significant association was observed between histopathology results and chemiluminescence results.

Conclusion: Although it is an easy, safe, minimal time consuming, and noninvasive technique, it has only adjunctive utility and it does not replace biopsy for the diagnosis of leukoplakia.
On the way to language: event segmentation in homesign and gesture
Authors: ÖZYÜREK ASLI , FURMAN REYHAN , GOLDIN-MEADOW SUSAN
Published: March 2014

Languages typically express semantic components of motion events such as manner (roll) and path (down) in separate lexical items. We explore how these combinatorial possibilities of language arise by focusing on (i) gestures produced by deaf children who lack access to input from a conventional language (homesign); (ii) gestures produced by hearing adults and children while speaking; and (iii) gestures used by hearing adults without speech when asked to do so in elicited descriptions of motion events with simultaneous manner and path. Homesigners tended to conflate manner and path in one gesture, but also used a mixed form, adding a manner and/or path gesture to the conflated form sequentially. Hearing speakers, with or without speech, used the conflated form, gestured manner, or path, but rarely used the mixed form. Mixed form may serve as an intermediate structure on the way to the discrete and sequenced forms found in natural languages.
On the ‘bang-bang’ principle for a class of fractional semilinear evolution inclusions
Authors: Liu Xiaoyou , Liu Zhenhai
Published: March 2014

In this paper, we study the problem of the existence of solutions for a class of fractional semilinear evolution inclusions with non-convex right-hand side. We mainly focus on the existence of the extreme solution and the relationship of the solution sets between the original problem and the convexified problem. An example is provided to illustrate the application of the obtained theory.
Prehospital Use of Aspirin Rarely Is Associated with Adverse Events
Authors: Quan Dan , LoVecchio Frank , Clark Bryan , Gallagher John V.
Published: March 2014

Introduction:

Aspirin is commonly administered for acute coronary syndromes in the prehospital setting. Few studies have addressed the incidence of adverse effects associated with prehospital administration of aspirin. Objective: To determine the incidence of adverse events following the administration of aspirin by prehospital personnel.

Methods:

Multi-center, retrospective, case series that involved all patients who received aspirin in the prehospital setting from (01 August 1999–31 January 2000). Patient encounter forms of the emergency medical services (EMS) of a metropolitan fire department were reviewed. All patients who had a potential cardiac syndrome (i.e., chest pain, dyspnea) as documented on the EMS forms were included in the review. Exclusion criteria included failure to meet inclusion criteria, and chest pain secondary to apparent noncardiac causes (i.e., trauma). Hospital charts were reviewed from a subset of patients at the participating hospitals. The major outcome was an adverse event following prehospital administration of aspirin. This outcome was evaluated during the EMS encounter, at emergency department discharge, or at six and 24-hours post-aspirin ingestion. An adverse event secondary to aspirin ingestion was defined as anaphylaxis or allergic reactions, such as rash or respiratory changes.

Results:

A total of 25,600 EMS encounter forms were reviewed, yielding 2,399 patients with a potential cardiac syndrome. Prior to EMS arrival, 585 patients had received aspirin, and 893 were administered aspirin by EMS personnel. No patients had an adverse event during the EMS encounter. Of these patients, 229 were transported to participating hospitals and 219 medical records were available for review with no adverse reactions recorded during their hospital course.

Conclusion:

Aspirin is rarely associated with adverse events when administered by prehospital personnel for presumed coronary syndromes.