bluuebunny/crossref_metadata_2025 huggingface dataset:
Glial fibrillary acidic protein promoter determines transgene expression in satellite glial cells following intraganglionic adeno‐associated virus delivery in adult rats
Authors: Xiang Hongfei , Xu Hao , Fan Fan , Shin Seung‐Min , Hogan Quinn H. , Yu Hongwei
Published: September 2017

Recombinant adeno‐associated viral (AAV)‐mediated therapeutic gene transfer to dorsal root ganglia (DRG) is an effective and safe tool for treating chronic pain. However, AAV with various constitutively active promoters leads to transgene expression predominantly to neurons, while glial cells are refractory to AAV transduction in the peripheral nervous system. The present study evaluated whether in vivo satellite glial cell (SGC) transduction in the DRG can be enhanced by the SGC‐specific GFAP promoter and by using shH10 and shH19, which are engineered capsid variants with Müller glia‐prone transduction. Titer‐matched AAV6 (as control), AAVshH10, and AAVshH19, all encoding the EGFP driven by the constitutively active CMV promoter, as well as AAV6‐EGFP and AAVshH10‐EGFP driven by a GFAP promoter (AAV6‐GFAP‐EGFP and AAVshH10‐GFAP‐EGFP), were injected into DRG of adult male rats. Neurotropism of gene expression was determined and compared by immunohistochemistry. Results showed that injection of AAV6‐ and AAVshH10‐GFAP‐EGFP induces robust EGFP expression selectively in SGCs, whereas injection of either AAVshH10‐CMV‐EGFP or AAVshH19‐CMV‐EGFP into DRG resulted in a similar in vivo transduction profile to AAV6‐CMV‐EGFP, all showing efficient transduction of sensory neurons without significant transduction of glial cell populations. Coinjection of AAV6‐CMV‐mCherry and AAV6‐GFAP‐EGFP induces transgene expression in neurons and SGCs separately. This report, together with our prior studies, demonstrates that the GFAP promoter rather than capsid tropism determines selective gene expression in SGCs following intraganglionic AAV delivery in adult rats. A dual AAV system, one with GFAP promoter and the other with CMV promoter, can efficiently express transgenes selectively in neurons versus SGCs.
Lipolysis and aroma generation as mechanisms involved in masking boar taint in sodium reduced fermented sausages inoculated with Debaryomyces hansenii yeast
Authors: Corral Sara , Belloch Carmela , López‐Díez José J , Flores Mónica
Published: September 2017

BACKGROUND

The use of boar back fat for processing of fermented sausages may cause the presence of abnormal odours. In dry‐cured products, ripening time is essential to develop the sensory characteristics. Yeast has been proposed as an alternative to mask boar taint odour through its metabolic activity but it is necessary to elucidate which mechanisms are involved. The aim is to study the effect of Debaryomyces hansenii inoculation on the lipolysis process and generation of aroma compounds in fermented sausages manufactured with boar back fat at two different ripening times.

RESULTS

D. hansenii inoculated sausages had a higher degree of lipolysis as demonstrated by higher content of free fatty acids, ester compounds and branched aldehydes which contribute the fruity odour. The increase in lipolysis produced by D. hansenii inoculation was not followed by an increase in oxidation during processing possibly due to the metabolic activity of yeast. The effect of back fat type was scarcely appreciated whereas ripening time had a stronger effect on sausage. Boar sausages were characterised by a lower polyunsaturated fatty acid profile and lesser lipolysis than gilt sausages.

CONCLUSION

Yeast inoculation with D. hansenii and long ripening time were appropriate strategies to limit the perception of boar taint in dry fermented sausages. © 2017 Society of Chemical Industry
Modeling and predicting the solute polarity parameter in reversed‐phase liquid chromatography using quantitative structure–property relationship approaches
Authors: Golmohammadi Hassan , Dashtbozorgi Zahra , Khooshechin Sajad
Published: September 2017

A prediction of quantitative structure–property relationships is developed to model the polarity parameter of a set of 146 organic compounds in acetonitrile in reversed‐phase liquid chromatography. Enhanced replacement method and support vector machine regressions were employed to build prediction models based on molecular descriptors calculated from the structure alone. The correlation coefficients between experimental and predicted values of polarity parameter for the test set by enhanced replacement method and support vector machine were 0.970 and 0.993, respectively. The obtained results demonstrated that the support vector machine model is more reliable and has a better prediction performance than the enhanced replacement method.
Multivariate optimization of dispersive liquid–liquid microextraction for the determination of paclobutrazol and triflumizole in water by GC–MS
Authors: Chormey Dotse Selali , Karakuş Yeşim , Karayaka Sena , Özsöyler Çağla , Bozdoğan Abdürrezzak Emin , Bakırdere Sezgin
Published: September 2017

A new analytical method based on dispersive liquid–liquid microextraction with gas chromatography mass spectrometry has been optimized for the simultaneous determination of paclobutrazol and triflumizole in tap water and wastewater samples. A two‐level, full‐factorial design that allowed the study of main effects and factor interactions was applied to analyze the influence on microextraction process by chloroform, ethanol, potassium iodide and hand shaking period. The extraction conditions selected were 200 μL of chloroform, 3.0 mL of ethanol, 2.0 g of potassium iodide and 15 s of hand shaking. The limits of detection obtained for triflumizole and paclobutrazol under optimum conditions were 0.97 and 0.29 ng/mL, respectively. Calibration plots of both analytes were linear over a wide concentration range, and good precision was observed for replicate measurements. Applicability and accuracy of the method were determined by performing spiked recovery tests. Appreciable recovery results were obtained for municipal wastewater and matrix matching was used to obtain close to 100% recovery for tap water.
The maternal uniparental disomy of chromosome 6 (upd(6)mat) “phenotype”: result of placental trisomy 6 mosaicism?
Authors: Eggermann Thomas , Oehl‐Jaschkowitz Barbara , Dicks Severin , Thomas Wolfgang , Kanber Deniz , Albrecht Beate , Begemann Matthias , Kurth Ingo , Beygo Jasmin , Buiting Karin
Published: September 2017

Background

Maternal uniparental disomy of chromosome 6 (upd(6)mat) is a rare finding and its clinical relevance is currently unclear. Based on clinical data from two new cases and patients from the literature, the pathogenetic significance of upd(6)mat is delineated.

Methods

Own cases were molecularly characterized for isodisomic uniparental regions on chromosome 6. For further cases with upd(6)mat, a literature search was conducted and genetic and clinical data were ascertained.

Results

Comparison of isodisomic regions between the new upd(6)mat cases and those from four reports did not reveal any common isodisomic region. Among the patients with available cytogenetic data, five had a normal karyotype in lymphocytes, whereas a trisomy 6 (mosaicism) was detected prenatally in four cases. A common clinical picture was not obvious in upd(6)mat, but intrauterine growth restriction (IUGR) and preterm delivery were frequent.

Conclusion

A common upd(6)mat phenotype is not obvious, but placental dysfunction due to trisomy 6 mosaicism probably contributes to IUGR and preterm delivery. In fact, other clinical features observed in upd(6)mat patients might be caused by homozygosity of recessive mutations or by an undetected trisomy 6 cell line. Upd(6)mat itself is not associated with clinical features, and can rather be regarded as a biomarker. In case upd(6)mat is detected, the cause for the phenotype is identified indirectly, but the UPD is not the basic cause.
Rapid compressed sensing reconstruction of 3D non‐Cartesian MRI
Authors: Baron Corey A. , Dwork Nicholas , Pauly John M. , Nishimura Dwight G.
Published: September 2017

Purpose

Conventional non‐Cartesian compressed sensing requires multiple nonuniform Fourier transforms every iteration, which is computationally expensive. Accordingly, time‐consuming reconstructions have slowed the adoption of undersampled 3D non‐Cartesian acquisitions into clinical protocols. In this work we investigate several approaches to minimize reconstruction times without sacrificing accuracy.

Methods

The reconstruction problem can be reformatted to exploit the Toeplitz structure of matrices that are evaluated every iteration, but it requires larger oversampling than what is strictly required by nonuniform Fourier transforms. Accordingly, we investigate relative speeds of the two approaches for various nonuniform Fourier transform kernel sizes and oversampling for both GPU and CPU implementations. Second, we introduce a method to minimize matrix sizes by estimating the image support. Finally, density compensation weights have been used as a preconditioning matrix to improve convergence, but this increases noise. We propose a more general approach to preconditioning that allows a trade‐off between accuracy and convergence speed.

Results

When using a GPU, the Toeplitz approach was faster for all practical parameters. Second, it was found that properly accounting for image support can prevent aliasing errors with minimal impact on reconstruction time. Third, the proposed preconditioning scheme improved convergence rates by an order of magnitude with negligible impact on noise.

Conclusion

With the proposed methods, 3D non‐Cartesian compressed sensing with clinically relevant reconstruction times (<2 min) is feasible using practical computer resources. Magn Reson Med 79:2685–2692, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Phase correction for three‐dimensional (3D) diffusion‐weighted interleaved EPI using 3D multiplexed sensitivity encoding and reconstruction (3D‐MUSER)
Authors: Chang Hing‐Chiu , Hui Edward S. , Chiu Pui‐Wai , Liu Xiaoxi , Chen Nan‐kuei
Published: September 2017

Purpose

Three‐dimensional (3D) multiplexed sensitivity encoding and reconstruction (3D‐MUSER) algorithm is proposed to reduce aliasing artifacts and signal corruption caused by inter‐shot 3D phase variations in 3D diffusion‐weighted echo planar imaging (DW‐EPI).

Theory and Methods

3D‐MUSER extends the original framework of multiplexed sensitivity encoding (MUSE) to a hybrid k‐space‐based reconstruction, thereby enabling the correction of inter‐shot 3D phase variations. A 3D single‐shot EPI navigator echo was used to measure inter‐shot 3D phase variations. The performance of 3D‐MUSER was evaluated by analyses of point‐spread function (PSF), signal‐to‐noise ratio (SNR), and artifact levels. The efficacy of phase correction using 3D‐MUSER for different slab thicknesses and b‐values were investigated.

Results

Simulations showed that 3D‐MUSER could eliminate artifacts because of through‐slab phase variation and reduce noise amplification because of SENSE reconstruction. All aliasing artifacts and signal corruption in 3D interleaved DW‐EPI acquired with different slab thicknesses and b‐values were reduced by our new algorithm. A near‐whole brain single‐slab 3D DTI with 1.3‐mm isotropic voxel acquired at 1.5T was successfully demonstrated.

Conclusion

3D phase correction for 3D interleaved DW‐EPI data is made possible by 3D‐MUSER, thereby improving feasible slab thickness and maximum feasible b‐value. Magn Reson Med 79:2702–2712, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
A phase II study of radioimmunotherapy with intraventricular 131I‐3F8 for medulloblastoma
Authors: Kramer Kim , Pandit‐Taskar Neeta , Humm John L. , Zanzonico Pat B. , Haque Sofia , Dunkel Ira J. , Wolden Suzanne L. , Donzelli Maria , Goldman Debra A. , Lewis Jason S. , Lyashchenko Serge K. , Khakoo Yasmin , Carrasquillo Jorge A. , Souweidane Mark M. , Greenfield Jeffrey P. , Lyden David , De Braganca Kevin D. , Gilheeney Stephen W. , Larson Steven M. , Cheung Nai‐Kong V.
Published: September 2017

Background

High‐risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell‐surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular 131I‐labeled 3F8 in patients with MB on a phase II clinical trial.

Methods

Patients with histopathologically confirmed high‐risk or recurrent MB were eligible for cRIT. After determining adequate cerebrospinal fluid (CSF) flow, patients received 2 mCi (where Ci is Curie) 124I‐3F8 or 131I‐3F8 with nuclear imaging for dosimetry, followed by up to four therapeutic (10 mCi/dose) 131I‐3F8 injections. Dosimetry estimates were based on serial CSF and blood samplings over 48 hr plus region‐of‐interest analyses on serial imaging scans. Disease evaluation included pre‐ and posttherapy brain/spine magnetic resonance imaging approximately every 3 months for the first year after treatment, and every 6–12 months thereafter.

Results

Forty‐three patients received a total of 167 injections; 42 patients were evaluable for outcome. No treatment‐related deaths occurred. Toxicities related to drug administration included acute bradycardia with somnolence, headache, fatigue, and CSF pleocytosis consistent with chemical meningitis and dystonic reaction. Total CSF absorbed dose was 1,453 cGy (where Gy is Gray; 350.0–2,784). Median overall survival from first dose of cRIT was 24.9 months (95% confidence interval [CI]:16.3–55.8). Patients treated in radiographic and cytologic remission were at a lower risk of death compared to patients with radiographically measurable disease (hazard ratio: 0.40, 95% CI: 0.18–0.88, P = 0.024).

Conclusions

cRIT with 131I‐3F8 is safe, has favorable dosimetry to CSF, and when added to salvage therapy using conventional modalities, may have clinical utility in maintaining remission in high‐risk or recurrent MB.
Recruiting primary care physicians to qualitative research: Experiences and recommendations from a childhood cancer survivorship study
Authors: Signorelli Christina , Wakefield Claire E. , Fardell Joanna E. , Thornton‐Benko Elysia , Emery Jon , McLoone Jordana K. , Cohn Richard J. ,   On Behalf of the ANZCHOG Survivorship Study Group
Published: September 2017

Background

Primary care physicians (PCPs) are essential for healthcare delivery but can be difficult to recruit to health research. Low response rates may impact the quality and value of data collected. This paper outlines participant and study design factors associated with increased response rates among PCPs invited to participate in a qualitative study at Sydney Children's Hospital, Australia.

Procedure

We invited 160 PCPs by post, who were nominated by their childhood cancer patients in a survey study. We followed‐up by telephone, email, or fax 2 weeks later.

Results

Without any follow‐up, 32 PCPs opted in to the study. With follow‐up, a further 42 PCPs opted in, with email appearing to be the most effective method, yielding a total of 74 PCPs opting in (46.3%). We reached data saturation after 51 interviews. On average, it took 34.6 days from mail‐out to interview completion. Nonrespondents were more likely to be male (P = 0.013). No survivor‐related factors significantly influenced PCPs’ likelihood of participating. Almost double the number of interviews were successfully completed if scheduled via email versus phone. Those requiring no follow‐up did not differ significantly to late respondents in demographic/survivor‐related characteristics.

Conclusion

PCP factors associated with higher opt in rates, and early responses, may be of interest to others considering engaging PCPs and/or their patients in cancer‐related research, particularly qualitative or mixed‐methods studies. Study resources may be best allocated to email follow‐up, incentives, and personalization of study documents linking PCPs to patients. These efforts may improve PCP participation and the representativeness of study findings.
Paraffin/wood flour/high‐density polyethylene composites for thermal energy storage material in buildings: A morphology, thermal performance, and mechanical property study
Authors: Guo Xi , Zhang Liangliang , Cao Jinzhen , Peng Yao
Published: September 2017

Thermal energy storage composites were fabricated using paraffin as phase change material (PCM) and wood flour/high‐density polyethylene (WF/HDPE) as the composite matrix. Expanded graphite (EG) was added to modify the thermal conductivity. The prepared paraffin/WF/HDPE composites were examined by scanning electron microscopy (SEM), X‐ray diffractometer (XRD), differential scanning calorimetry (DSC), thermogravimetry (TG), infrared thermography, and laserflash thermal analysis. Physical and mechanical properties of the composites were also investigated. The results showed that: (1) the composite was the integration of paraffin, EG, WF, and HDPE with no new diffraction peaks were found in the XRD pattern; (2) thermal tests indicated that the paraffin/WF/HDPE composites had satisfying temperature conditioning ability, and the thermal conductivity of the composites was improved with the addition of EG; (3) incorporation of paraffin and EG into composites benefited their impact strength, but negatively affected the flexural properties; and (4) mechanical properties of the composites can be acceptable as building materials where mechanical strength are less important. POLYM. COMPOS., 39:E1643–E1652, 2018. © 2017 Society of Plastics Engineers
β‐Crystallization and mechanical properties of aluminum hydroxide‐filled polypropylene composites
Authors: Li Mei , Zhang Zishou , Wu Lijun , Zhang Yangfan , Mai Kancheng
Published: September 2017

In order to provide aluminum hydroxide with β‐nucleating surface (β‐ATH) for PP crystallization, the calcium pimelate supported on the surface of ATH was prepared through chemical reaction between calcified ATH and pimelic acid in our lab. The β‐ATH particles were characterized by Fourier transform infrared spectrometry, X‐ray photoelectron spectroscopy and scanning electron microscopy. Effect of ATH, calcified ATH, and β‐ATH on crystallization and crystalline modification of PP was investigated by differential scanning calorimetry. The results indicated that the prepared β‐ATH has higher heterogeneous nucleation than ATH and calcified ATH for PP crystallization. Addition of ATH and calcified ATH has no influence on the crystalline modification of PP. The β‐ATH can induce the formation of β‐crystal in the ATH‐filled PP composites with β‐crystal content of above 90%. The transformation of surface nucleation mechanism of ATH from α‐nucleation into β‐nucleation was investigated. The effects of β‐ATH content, mass ratio of calcified ATH/pimelic acid and concentration of calcium acetate solution in the preparation of calcified ATH on the heterogeneous nucleation and β‐crystal content of β‐ATH‐filled PP composites were discussed. The mechanical performance of the prepared β‐ATH‐filled PP composites were also characterized. POLYM. COMPOS., 40:E194–E201, 2019. © 2017 Society of Plastics Engineers
Mechanisms of Drug Resistance in Cancer: The Role of Extracellular Vesicles
Authors: Samuel Priya , Fabbri Muller , Carter David Raul Francisco
Published: September 2017

Drug resistance remains a major barrier to the successful treatment of cancer. The mechanisms by which therapeutic resistance arises are multifactorial. Recent evidence has shown that extracellular vesicles (EVs) play a role in mediating drug resistance. EVs are small vesicles carrying a variety of macromolecular cargo released by cells into the extracellular space and can be taken up into recipient cells, resulting in transfer of cellular material. EVs can mediate drug resistance by several mechanisms. They can serve as a pathway for sequestration of cytotoxic drugs, reducing the effective concentration at target sites. They can act as decoys carrying membrane proteins and capturing monoclonal antibodies intended to target receptors at the cell surface. EVs from resistant tumor cells can deliver mRNA, miRNA, long noncoding RNA, and protein inducing resistance in sensitive cells. This provides a new model for how resistance that arises can then spread through a heterogeneous tumor. EVs also mediate cross‐talk between cancer cells and stromal cells in the tumor microenvironment, leading to tumor progression and acquisition of therapeutic resistance. In this review, we will describe what is known about how EVs can induce drug resistance, and discuss the ways in which EVs could be used as therapeutic targets or diagnostic markers for managing cancer treatment. While further characterization of the vesiculome and the mechanisms of EV function are still required, EVs offer an exciting opportunity in the fight against cancer.
Discovery of Antimicrobial Peptides in Cervical‐Vaginal Fluid from Healthy Nonpregnant Women via an Integrated Proteome and Peptidome Analysis
Authors: Muytjens Carla M. J. , Yu Yijing , Diamandis Eleftherios P.
Published: September 2017

Cervical‐vaginal fluid (CVF) covers the lower part of the female reproductive system and functions in the homeostasis and immunity of the surrounding tissues. In contrast to the CVF proteome of both nonpregnant and pregnant women, the CVF peptidome has not been reported to date. In the current study, we identified 1087 proteins in CVF, of which 801 proteins were not previously identified in CVF proteomes. The presence of the tissue‐specific proteins oviductal glycoprotein 1 and tubulin polymerization–promoting protein family member 3 strongly suggests that the tissues of the upper female reproductive tract contribute to the protein composition of CVF. The tremendous catalytic potential of CVF was highlighted by the identification of 85 proteases and the detection of pH‐dependent trypsin‐like proteolytic activity. Over 1000 endogenous peptides were detected in the CVF peptidome, and 39 peptides are predicted to have antimicrobial activity. The detailed proteomic and peptidomic analysis of CVF will further aid in the delineation of pathways related to reproduction, immunity and host defense, and assist in developing new biomarkers for malignant and other diseases of the female reproductive tract. Data are available via ProteomeXchange with identifiers PXD004450 (CVF peptidome) and PDX004363 (CVF proteome).
The human protein atlas: A spatial map of the human proteome
Authors: Thul Peter J. , Lindskog Cecilia
Published: September 2017

The correct spatial distribution of proteins is vital for their function and often mis‐localization or ectopic expression leads to diseases. For more than a decade, the Human Protein Atlas (HPA) has constituted a valuable tool for researchers studying protein localization and expression in human tissues and cells. The centerpiece of the HPA is its unique antibody collection for mapping the entire human proteome by immunohistochemistry and immunocytochemistry. By these approaches, more than 10 million images showing protein expression patterns at a single‐cell level were generated and are publicly available at www.proteinatlas.org. The antibody‐based approach is combined with transcriptomics data for an overview of global expression profiles. The present article comprehensively describes the HPA database functions and how users can utilize it for their own research as well as discusses the future path of spatial proteomics.
Development and relative fitness of Cry1C resistance in Chilo suppressalis
Authors: Tang Hui , Chen Geng , Chen Fajun , Han Lanzhi , Peng Yufang
Published: September 2017

BACKGROUND

Chilo suppressalis is an important lepidopteran rice pest in the rice‐growing areas of China, and the development of transgenic rice expressing the Cry1C insecticidal protein has provided a useful strategy for controlling this pest. However, insect resistance is a major threat to the durability of cry1C rice. Thus, evaluation of the risk of insect resistance before the commercial use of cry1C rice is crucial.

RESULTS

This study investigated the development of C. suppressalis resistance to Cry1C protein and the relative fitness of Cry1C‐resistant and ‐susceptible strains on different Bt rice lines. The LC50 value of the Cry1C‐resistant strain increased 42.6‐fold after 41 generations of selection, and the estimated realized heritability (h2) of Cry1C resistance was 0.096 in C. suppressalis. Moreover, the Cry1C‐resistant strain displayed high fitness on the cry1C line, but not on the cry1Ab and cry1Ab + cry1C lines and was not cross‐resistant to Cry1Ab.

CONCLUSIONS

These findings suggest that C. suppressalis has the potential to develop resistance to Cry1C, although the rate of evolution is low. The pyramiding of the cry1A and cry1C genes in Bt rice is an effective strategy for delaying the evolution of resistance in C. suppressalis and sustainably maintaining the utility of Bt rice. © 2017 Society of Chemical Industry
Complexes between cyclopentene and cyclopentyne derivatives with HCu and FCu: The importance of cyclization effects
Authors: Arslancan Serra , Lamsabhi Al Mokhtar , Mó Otilia , Yáñez Manuel
Published: September 2017

B3LYP/6‐311+G(3df,2p)//B3LYP/6‐31+G(d,p) density functional theory calculations show that cyclopentene and cyclopentyne derivatives yield very strong π‐type complexes with HCu and FCu molecules. This interaction is so strong in the case of cyclopentyne derivatives that the complexes formed can be considered as a new kind of metallocycles. These complexes resemble those reported before in the literature for ethylene and acetylene, though whereas the interaction energies between cyclopentene and HCu and FCu are smaller than those reported for ethylene, those involving cyclopentyne are larger than the ones calculated for acetylene. This very different behavior is due to the dramatic change in the local environment of the two carbon atoms of cyclopentyne with respect to acetylene, which does not occur on going from ethylene to cyclopentene. The introduction of heteroatoms in the five‐membered rings opens the possibility of forming other isomers in which the CuX (X = H, F) is attached to the heteroatom rather than to the unsaturated CC bond. This arrangement is precisely the most favorable one for cyclopentene derivatives, though for cyclopentyne ones the π‐type complexes are still the global minima.
Understanding the synergistic effects, optical and electronic properties of ternary Fe/C/S‐doped TiO2 anatase within the DFT + U approach
Authors: Opoku Francis , Govender Krishna Kuben , van Sittert Cornelia Gertina Catharina Elizabeth , Govender Penny Poomani
Published: September 2017

Although TiO2 is an efficient photocatalyst, its large band gap limits its photocatalytic activity only to the ultraviolet region. An experimentally synthesized ternary Fe/C/S‐doped TiO2 anatase showed improved visible light photocatalytic activity. However, a theoretical study of the underlying mechanism of the enhanced photocatalytic activity and the interaction of ternary Fe/C/S‐doped TiO2 has not yet been investigated. In this study, the defect formation energy, electronic structure and optical property of TiO2 doped with Fe, C, and S are investigated in detail using the density functional theory + U method. The calculated band gap (3.21 eV) of TiO2 anatase agree well with the experimental band gap (3.20 eV). The defect formation energy shows that the co‐ and ternary‐doped systems are thermodynamically favorable under oxygen‐rich condition. Compared to the undoped TiO2, the absorption edge of the mono‐, co‐, and ternary‐doped TiO2 is significantly enhanced in the visible light region. We have shown that ternary doping with C, S, and Fe induces a clean band structure without any impurity states. Moreover, the ternary Fe/C/S‐doped TiO2 exhibit an enhanced photocatalytic activity, a smaller band gap and negative formation energy compared to the mono‐ and co‐doped systems. Moreover, the band edges of Fe/C/S‐doped TiO2 align well with the redox potentials of water, which shows that the ternary Fe/C/S‐doped TiO2 is promising photocatalysts to split water into hydrogen and oxygen. These findings rationalize the available experimental results and can assist the design of TiO2‐based photocatalyst materials.
Solubilized Amnion Membrane Hyaluronic Acid Hydrogel Accelerates Full-Thickness Wound Healing
Authors: Murphy Sean V. , Skardal Aleksander , Song Lujie , Sutton Khiry , Haug Rebecca , Mack David L. , Jackson John , Soker Shay , Atala Anthony
Published: September 2017

The early and effective treatment of wounds is vital to ensure proper wound closure and healing with appropriate functional and cosmetic outcomes. The use of human amnion membranes for wound care has been shown to be safe and effective. However, the difficulty in handling and placing thin sheets of membrane, and the high costs associated with the use of living cellularized tissue has limited the clinical application of amniotic membrane wound healing products. Here, we describe a novel amnion membrane-derived product, processed to result in a cell-free solution, while maintaining high concentrations of cell-derived cytokines and growth factors. The solubilized amnion membrane (SAM) combined with the carrier hyaluronic acid (HA) hydrogel (HA-SAM) is easy to produce, store, and apply to wounds. We demonstrated the efficacy of HA-SAM as a wound treatment using a full-thickness murine wound model. HA-SAM significantly accelerated wound closure through re-epithelialization and prevented wound contraction. HA-SAM-treated wounds had thicker regenerated skin, increased total number of blood vessels, and greater numbers of proliferating keratinocytes within the epidermis. Overall, this study confirms the efficacy of the amnion membrane as a wound treatment/dressing, and overcomes many of the limitations associated with using fresh, cryopreserved, or dehydrated tissue by providing a hydrogel delivery system for SAM.
Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke
Authors: Doeppner Thorsten R. , Bähr Mathias , Hermann Dirk M. , Giebel Bernd
Published: September 2017

Despite recent advances in stroke therapy, current therapeutic concepts are still limited. Thus, additional therapeutic strategies are in order. In this sense, the transplantation of stem cells has appeared to be an attractive adjuvant tool to help boost the endogenous regenerative capacities of the brain. Although transplantation of stem cells is known to induce beneficial outcome in (preclinical) stroke research, grafted cells do not replace lost tissue directly. Rather, these transplanted cells like neural progenitor cells or mesenchymal stem cells act in an indirect manner, among which the secretion of extracellular vesicles (EVs) appears to be one key factor. Indeed, the application of EVs in preclinical stroke studies suggests a therapeutic role, which appears to be noninferior in comparison to the transplantation of stem cells themselves. In this short review, we highlight some of the recent advances in the field of EVs as a therapeutic means to counter stroke.
Stromal Cell-Derived Factor-1 Mediates Cardiac Allograft Tolerance Induced by Human Endometrial Regenerative Cell-Based Therapy
Authors: Lan Xu , Wang Grace , Xu Xiaoxi , Lu Shanzheng , Li Xiang , Zhang Baoren , Shi Ganggang , Zhao Yiming , Du Caigan , Wang Hao
Published: September 2017

Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells, and their therapeutic potential has been tested in the prevention of renal ischemic reperfusion injury, acute liver injury, ulcerative colitis, and immunosuppression. However, their potential in the induction of transplant tolerance has not been investigated. The present study was undertaken to investigate the efficacy of ERCs in inducing cardiac allograft tolerance and the function of stromal cell-derived factor-1 (SDF-1) in the ERC-mediated immunoregulation. The inhibitory efficacy of human ERCs in the presence or absence of rapamycin was examined in both mouse cardiac allograft models between BALB/c (H-2d) donors and C57BL/6 (H-2b) recipients and in vitro cocultured splenocytes. AMD3100 was used to inhibit the function of SDF-1. Intragraft antibody (IgG and IgM) deposition and immune cell (CD4+ and CD8+) infiltration were measured by immunohistochemical staining, and splenocyte phenotypes were determined by fluorescence-activated cell sorting analysis. The results showed that ERC-based therapy induced donor-specific allograft tolerance, and functionally inhibiting SDF-1 resulted in severe allograft rejection. The negative effects of inhibiting SDF-1 on allograft survival were correlated with increased levels of intragraft antibodies and infiltrating immune cells, and also with reduced levels of regulatory immune cells including MHC class IIlowCD86lowCD40lowdendritic cells, CD68+CD206+macrophages, CD4+CD25+Foxp3+T cells, and CD1dhighCD5highCD83lowIL-10highB cells both in vivo and in vitro. These data showed that human ERC-based therapy induces cardiac allograft tolerance in mice, which is associated with SDF-1 activity, suggesting that SDF-1 mediates the immunosuppression of ERC-based therapy for the induction of transplant tolerance.
Ghrelin receptor antagonism of hyperlocomotion in cocaine‐sensitized mice requires βarrestin‐2
Authors: Toth Krisztian , Slosky Lauren M. , Pack Thomas F. , Urs Nikhil M. , Boone Peter , Mao Lan , Abraham Dennis , Caron Marc G. , Barak Lawrence S.
Published: September 2017

The “brain‐gut” peptide ghrelin, which mediates food‐seeking behaviors, is recognized as a very strong endogenous modulator of dopamine (DA) signaling. Ghrelin binds the G protein‐coupled receptor GHSR1a, and administration of ghrelin increases the rewarding properties of psychostimulants while ghrelin receptor antagonists decrease them. In addition, the GHSR1a signals through βarrestin‐2 to regulate actin/stress fiber rearrangement, suggesting βarrestin‐2 participation in the regulation of actin‐mediated synaptic plasticity for addictive substances like cocaine. The effects of ghrelin receptor ligands on reward strongly suggest that modulation of ghrelin signaling could provide an effective strategy to ameliorate undesirable behaviors arising from addiction. To investigate this possibility, we tested the effects of ghrelin receptor antagonism in a cocaine behavioral sensitization paradigm using DA neuron‐specific βarrestin‐2 KO mice. Our results show that these mice sensitize to cocaine as well as wild‐type littermates. The βarrestin‐2 KO mice, however, no longer respond to the locomotor attenuating effects of the GHSR1a antagonist YIL781. The data presented here suggest that the separate stages of addictive behavior differ in their requirements for βarrestin‐2 and show that pharmacological inhibition of βarrestin‐2 function through GHSR1a antagonism is not equivalent to the loss of βarrestin‐2 function achieved by genetic ablation. These data support targeting GHSR1a signaling in addiction therapy but indicate that using signaling biased compounds that modulate βarrestin‐2 activity differentially from G protein activity may be required.
Ten‐Year Follow‐Up of a Randomized Clinical Trial of Total Thyroidectomy Versus Dunhill Operation Versus Bilateral Subtotal Thyroidectomy for Multinodular Non‐toxic Goiter
Authors: Barczyński Marcin , Konturek Aleksander , Hubalewska‐Dydejczyk Alicja , Gołkowski Filip , Nowak Wojciech
Published: September 2017

Background

The aim of this study was to validate in a 10‐year follow‐up the initial outcomes of various thyroid resection methods for multinodular non‐toxic goiter (MNG) reported in World J Surg 2010;34:1203–13.

Materials and methods

Six hundred consenting patients with MNG were randomized to three groups of 200 patients each: total thyroidectomy (TT), Dunhill operation (DO), bilateral subtotal thyroidectomy (BST). Obligatory follow‐up period of 60 months was extended up to 120 months for all the consenting patients. The primary outcome measure was the prevalence of recurrent goiter and need for revision thyroid surgery. The secondary outcome measure was the cumulative postoperative and post‐revision morbidity rate.

Results

The primary outcomes were twice as inferior at 10 years when compared to 5‐year results for DO and BST, but not for TT. Recurrent goiter was found at 10 years in 1 (0.6%) TT versus 15 (8.6%) DO versus 39 (22.4%) BST (p < 0.001), and revision thyroidectomy was necessary in 1 (0.6%) TT versus 5 (2.8%) DO versus 14 (8.0%) BST patients (p < 0.001). Any permanent morbidity at 10 years was present in 5 (2.8%) TT patients following initial surgery versus 7 (4.0%) DO and 10 (5.7%) BST patients following initial and revision thyroidectomy (nonsignificant differences). At 10 years, 23 (11.5%) TT versus 25 (12.5%) DO versus 26 (13.0%) BST patients were lost to follow‐up.

Conclusions

Total thyroidectomy can be considered the preferred surgical approach for patients with MNG, as it abolishes the risk of goiter recurrence and need for future revision thyroidectomy when compared to more limited thyroid resections, whereas the prevalence of permanent morbidity is not increased at experienced hands.

Registration number:

NCT00946894 (http://www.clinicaltrials.gov).
Berberine Inhibits Oxygen Consumption Rate Independent of Alteration in Cardiolipin Levels in H9c2 Cells
Authors: Chang Wenguang , Zhang Ming , Chen Li , Hatch Grant M.
Published: September 2017

Small clinical studies have shown that oral treatment with the plant alkaloid berberine (BBR) reduces blood glucose levels similar to that of metformin and have promoted its use as a novel anti‐diabetic therapy. However, in vitro studies have shown that high concentrations of BBR potently inhibit cell proliferation through inhibition of mitochondrial function. Cardiolipin (Ptd2Gro) is a key phospholipid required for regulating mitochondrial bioenergetic function. We examined if BBR inhibited oxygen consumption rate in H9c2 cardiac myocytes through alteration in Ptd2Gro metabolism. Treatment of H9c2 cells with BBR resulted in a rapid (within minutes) concentration‐dependent decrease in the oxygen consumption rate (OCR) as determined using a Seahorse XF24 analyzer. Concentrations of BBR as low as 1 µM were effective in inhibiting OCR. In addition, all concentrations of BBR inhibited the fatty acid‐mediated increase in OCR that was observed in untreated cells. Treatment of H9c2 cells with up to 25 µM BBR for 24 h markedly reduced [3H]thymidine incorporation into cells but did not alter the pool size of Ptd2Gro. In contrast, 12.5 µM BBR increased [1‐14C]palmitate incorporation into Ptd2Gro and 12.5 µM and 25 µM BBR reduced [1‐14C]oleate incorporation into Ptd2Gro. Protein kinase C delta (PKCδ) activation through its increased membrane association is known to alter Ptd2Gro distribution within mitochondria. BBR treatment resulted in a decrease in membrane‐associated PKCδ and attenuated the palmitate‐mediated increase in PKCδ membrane‐association. Thus, BBR treatment of H9c2 cardiac myocytes inhibits cellular OCR independent of alteration in Ptd2Gro levels.
Bonus versus penalty: How robust are the effects of contract framing?
Authors: de Quidt Jonathan , Fallucchi Francesco , Kölle Felix , Nosenzo Daniele , Quercia Simone
Published: September 2017

We study the relative effectiveness of contracts that are framed either in terms of bonuses or penalties. In one set of treatments, subjects know at the time of effort provision whether they have achieved the bonus/avoided the penalty. In another set of treatments, subjects only learn the success of their performance at the end of the task. We fail to observe a contract framing effect in either condition: effort provision is statistically indistinguishable under bonus and penalty contracts.
Olfactory identification in subjective cognitive decline and mild cognitive impairment: Association with tau but not amyloid positron emission tomography
Authors: Risacher Shannon L. , Tallman Eileen F. , West John D. , Yoder Karmen K. , Hutchins Gary D. , Fletcher James W. , Gao Sujuan , Kareken David A. , Farlow Martin R. , Apostolova Liana G. , Saykin Andrew J.
Published: September 2017

Introduction

We investigated the association between olfactory identification and Alzheimer's disease biomarkers, including amyloid, tau, and neurodegeneration.

Methods

Thirty‐four older adults, including 19 cognitively normal (CN), 10 subjective cognitive decline (SCD), and 5 mild cognitive impairment, underwent amyloid positron emission tomography, magnetic resonance imaging, and the University of Pennsylvania Smell Identification Test (UPSIT). Twenty‐six also underwent tau positron emission tomography. Associations between the UPSIT and regionally sampled amyloid, tau, and temporal atrophy were evaluated. Voxel‐wise regression models were also utilized. Analyses were conducted with the full sample and only CN/SCD.

Results

Lower UPSIT scores were associated with increased temporal and parietal tau burden in regional and voxel‐wise analyses in the full sample and in CN and SCD only. Temporal lobe atrophy was associated with lower UPSIT score. Amyloid was not associated with the UPSIT.

Discussion

Impairment on the UPSIT may be a good marker for tau and neurodegeneration in preclinical or prodromal Alzheimer's disease.
Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs
Authors: Parcon Paul A. , Balasubramaniam Meenakshisundaram , Ayyadevara Srinivas , Jones Richard A. , Liu Ling , Shmookler Reis Robert J. , Barger Steven W. , Mrak Robert E. , Griffin W. Sue T.
Published: September 2017

Introduction

Alzheimer apolipoprotein E (APOE) ɛ4/ɛ4 carriers have earlier disease onset and more protein aggregates than patients with other APOE genotypes. Autophagy opposes aggregation, and important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to “coordinated lysosomal expression and regulation” (CLEAR) DNA motifs.

Methods

Autophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by APOE genotype and in a glioblastoma cell line expressing either apoE3 or apoE4. Computational modeling assessed interactions between apoE and mutated apoE with CLEAR or modified DNA.

Results

Three TFEB‐regulated mRNA transcripts—SQSTM, MAP1LC3B, and LAMP2—were lower in AD ɛ4/ɛ4 than in AD ɛ3/ɛ3 brains. Computational modeling predicted avid specific binding of apoE4 to CLEAR motifs. ApoE was found in cellular nuclei, and in vitro binding assays suggest competition between apoE4 and TFEB at CLEAR sites.

Conclusion

ApoE4‐CLEAR interactions may account for suppressed autophagy in APOE ɛ4/ɛ4 carriers and, in this way, contribute to earlier AD onset.
Proton pump inhibitors and the risk of severe cognitive impairment: The role of posttraumatic stress disorder
Authors: Clouston Sean A.P. , Shapira Oren , Kotov Roman , Lei Lan , Waszczuk Monika , Bromet Evelyn J. , Luft Benjamin J.
Published: September 2017

Introduction

Proton pump inhibitors (PPIs), a common treatment for gastroesophageal reflux disease (GERD), were recently associated with increased risk of dementia. However, severe or chronic stress including, for example, posttraumatic stress disorder (PTSD) was not accounted for. This study examined whether PPI use was associated with severe cognitive impairment (SCI) and whether PTSD explained this association in a cohort of World Trade Center (WTC) responders.

Method

A prospective cohort study of 3779 WTC responders attending a university‐based monitoring and treatment program. Prescriptions for PPIs and SCI determined using the Montreal Cognitive Assessment were the focus of the analysis.

Results

Overall, 1451 (38.4%) responders were dispensed PPIs, and 83 (2.2%) had SCI. Bivariable analyses revealed significant associations between being‐dispensed PPIs in relation to SCI. After adjusting for PTSD, major depressive disorder, WTC exposures, age, and sex, being‐dispensed PPIs were significantly associated with odds of SCI (adjusted odds ratio = 1.67 95% confidence interval = 1.054–2.643).

Conclusions

Being‐dispensed PPIs were associated with SCI in this analysis of WTC responders. Results suggest that clinicians treating GERD seek to both understand patients' mental health history and monitor cognitive functioning when designing treatment routines. Overall, results confirmed that this is an important area of investigation with potential direct clinical implications.
Electrochemical determination of the gallium-nitride photocorrosion potential in acidic media
Authors: Baker D. R. , Lundgren C. A.
Published: September 2017

The surface of GaN shows corrosion when under illumination and the applied potential is above the photocorrosion potential in low pH aqueous media.
Tetraphenylethylene tetracylhydrazine macrocycle with capability for discrimination of n-propanol from i-propanol and highly sensitive/selective detection of nitrobenzene
Authors: Xie Wen-Zhao , Zhang Hong-Chao , Zheng Yan-Song
Published: September 2017

Tetraphenylethylene tetracylhydrazine macrocycle could discriminate n-propanol from i-propanol, detect nitrobenzene in water at 3.99 μg L−1, sense nitrobenzene vapour at 1.01 femtogram per mL of air.
Oxidative stress and endoplasmic reticulum (ER) stress in the development of neonatal hypoxic–ischaemic brain injury
Authors: Thornton Claire , Baburamani Ana A. , Kichev Anton , Hagberg Henrik
Published: September 2017

Birth asphyxia in term neonates affects 1–2/1000 live births and results in the development of hypoxic–ischaemic encephalopathy with devastating life-long consequences. The majority of neuronal cell death occurs with a delay, providing the potential of a treatment window within which to act. Currently, treatment options are limited to therapeutic hypothermia which is not universally successful. To identify new interventions, we need to understand the molecular mechanisms underlying the injury. Here, we provide an overview of the contribution of both oxidative stress and endoplasmic reticulum stress in the development of neonatal brain injury and identify current preclinical therapeutic strategies.
Active Canny: edge detection and recovery with open active contour models
Authors: Baştan Muhammet , Bukhari Syed Saqib , Breuel Thomas
Published: September 2017

The authors introduce an edge detection and recovery framework based on open active contour models (snakelets) to mitigate the problem of noisy or broken edges produced by classical edge detection algorithms, like Canny. The idea is to utilise the local continuity and smoothness cues provided by strong edges and grow them to recover the missing edges. This way, the strong edges are used to recover weak or missing edges by considering the local edge structures, instead of blindly linking edge pixels based on a threshold. The authors initialise short snakelets on the gradient magnitudes or binary edges automatically and then deform and grow them under the influence of gradient vector flow. The output snakelets are able to recover most of the breaks or weak edges and provide a smooth edge representation of the image; they can also be used for higher‐level analysis, like contour segmentation.