bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent microdeletion 2q21.1: Report on a new patient with neurological disorders
Authors: Gimelli Stefania , Stathaki Elisavet , Béna Frédérique , Leoni Massimiliano , Di Rocco Maja , Cuoco Cristina , Tassano Elisa
Published: December 2013

Whole genome profiling such as array comparative genomic hybridization has identified novel genomic imbalances. Copy number studies led to an explosion of the discoveries of new segmental duplication‐mediated deletions and duplications. These rearrangements are mostly the result of non‐allelic homologous recombination (NAHR) between low‐copy repeats or segmental duplications. We have identified an individual with a small, rare deletion on chromosome 2q21.1 with psychomotor delay, hyperactivity, and aggressive behavior. The rearranged region is flanked by large complex low‐copy repeats and includes only five genes: GPR148, FAM123C (AMER3), ARHGEF4, FAM168B, and PLEKHB2. The comparison between our patient and the cases previously reported in the literature contributes to a better definition of genotype–phenotype correlation of 2q21.1 microdeletions. © 2013 Wiley Periodicals, Inc.
In multiple sclerosis, oligoclonal bands connect to peripheral B‐cell responses
Authors: Bankoti Jaishree , Apeltsin Leonard , Hauser Stephen L. , Allen Simon , Albertolle Matthew E. , Witkowska H. Ewa , von Büdingen H.‐Christian
Published: December 2013

Objective

To determine to what extent oligoclonal band (OCB) specificities are clonally interrelated and to what degree they are associated with corresponding B‐cell responses in the peripheral blood (PB) of multiple sclerosis (MS) patients.

Methods

Mass‐spectrometric proteomic analysis of isoelectric focused (IEF) cerebrospinal fluid (CSF) immunoglobulin G (IgG) was used in combination with next‐generation deep‐immune repertoire sequencing of PB and CSF IgG heavy chain variable regions from MS patients.

Results

We find evidence for ongoing stimulation and maturation to antibody‐expressing B cells to occur primarily inside the central nervous system (CNS) compartment. B cells participating in OCB production can also be identified in PB; these cells appear to migrate across the blood–brain barrier and may also undergo further antigen stimulation in the periphery. In individual patients, different bands comprising OCBs are clonally related.

Interpretation

Our data provide a high‐resolution molecular analysis of OCBs and strongly support the concept that OCBs are not merely the terminal result of a targeted immune response in MS but represent a component of active B cell immunity that is dynamically supported on both sides of the blood‐brain barrier. Ann Neurol 2014;75:266–276
Capillary study on geometrical dependence of shear viscosity of polymer melts
Authors: Lin Xiang , Kelly Adrian , Woodhead Mike , Ren Dongyun , Wang Kuisheng , Coates Phil
Published: December 2013

Geometrical dependence of viscosity of polymethylmethacrylate (PMMA) and high density polyethylene (HDPE) are studied by means of a twin‐bore capillary rheometer based on power‐law model. Contrary geometrical dependences of shear viscosity are observed for PMMA between 210 and 255°C, but similar geometrical dependences are revealed for HDPE between 190 and 260°C. The fact that wall slip can not successfully explain the irregular geometrical dependence of PMMA viscosity is found in this work. Then, pressure effect and dependence of fraction of free volume (FFV) on both pressure and temperature are proposed to be responsible for the geometrical dependence of capillary viscosity of polymers. The dependence of shear viscosity on applied pressure is first investigated based on the Barus equation. By introducing a shift factor, shear viscosity curves of PMMA measured under different pressures can be shifted onto a set of parallel plots by correcting the pressure effect and the less shear‐thinning then disappears, especially at high pressure. Meanwhile, the FFV and combining strength among molecular chains are evaluated for both samples based on molecular dynamics simulation, which implies that the irregular geometrical dependence of PMMA viscosity can not be attributed to the wall slip behavior. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39982.
Safe amine based zinc dithiocarbamates for the vulcanization of carbon black reinforced natural rubber
Authors: Alam Md. Najib , Mandal Swapan Kumar , Roy Kumarjyoti , Debnath Subhas Chandra
Published: December 2013

Binary combination of three safe amine based synthesized zinc dithiocarbamates (ZDC), namely zinc (N‐benzyl piperazino) dithiocarbamate (ZBPDC), zinc (N‐ethyl piperazino) dithiocarbamate (ZEPDC), and zinc (N‐phenyl piperazino) dithiocarbamate (ZPPDC) with mercapto benzothiazole disulfide (MBTS) as an effective accelerator system for the vulcanization of carbon black (N330, N550, and N774) filled natural rubber (NR) composites are studied. A comparison between the safe amine based zinc dithiocarbamates with the unsafe zinc dimethyl dithiocarbamate (ZDMC) in the light of mechanical and aging resistance behavior, introduces the non carcinogenic rubber additives in the filled vulcanization of rubber. Both accelerator and filler have the major importance for improving the mechanical as well as aging resistance behavior of the resultant vulcanizate. Variation in the filler and also filler to oil ratio are done to optimize the mechanical properties. SEM studies of different types of filler with different amounts show that N330 at 30 phr loading composites forms more homogeneity and less aggregated structures. Natural rubber systems with N330 carbon black show the best results with respect to tensile strength, but after the aging N774 carbon black filled system indicates better retention in the tensile strength. ZPPDC‐MBTS accelerated vulcanizate shows the better age resistance behavior than ZDMC‐MBTS accelerated vulcanizate. From both the points of age resistance and mechanical properties, ZBPDC‐MBTS accelerator system is the suitable substitute for ZDMC‐MBTS accelerated system in the filled vulcanization of natural rubber composites. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39988.
Enhancement of stain‐induced crystallization in polylactide via thermal preannealing
Authors: Na Bing , Zhu Jie , Lv Ruihua , Zhang Peng , Liu Qingxian
Published: December 2013

Stretching of amorphous polylactide above glass transition temperature can lead to strain‐induced crystallization, which is mainly determined by stretching rate and temperature. This study demonstrates that thermal annealing prior to stretching is alternative to enhance strain‐induced crystallization of a given polylactide at the identical stretching conditions. The local order generated during thermal annealing acts as physical crosslinks to effectively alleviate molecular relaxation and thus facilitates the advent of strain‐induced crystallization. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39993.
Oxidation of γ‐irradiated microbial cellulose results in bioresorbable, highly conformable biomaterial
Authors: Czaja Wojciech , Kyryliouk Dmytro , DePaula C. Alex , Buechter Douglas D.
Published: December 2013

Conformability to tissues and adequate mechanical strength are clinically useful properties of resorbable biomaterials used in soft tissue repair. Microbially derived cellulose is attractive as a high strength, highly conformable, and biocompatible material for tissue repair, but is not naturally resorbable. Here we show that controlled oxidation of microbial cellulose sheets that have been pre‐irradiated with γ‐radiation results in a resorbable and fully conformable membrane that can be rapidly rehydrated in aqueous fluids. In vitro studies showed that degradation of the resorbable membranes occurs in two major phases: (1) initial rapid degradation of about 70–80% of the entire sample followed by (2) slower degradation of an additional 5–10% which eventually levels off leaving a small amount of nonresorbable material. In vivo, prototype materials showed marked degradation at all time points, with the most rapid degradation occurring in the first 2–4 weeks. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39995.
Silk‐inspired polyurethane containing glyalaglyala tetrapeptide. III. morphological, thermal, and mechanical features of electrosprayed and electrospun deposition
Authors: Liu Hongtao , Zhou Jiangang , Zuo Danying , Liu Xiuying , Gu Shaojin , Xu Weilin
Published: December 2013

Morphological, thermal, and mechanical features of electrosprayed and electrospun deposition of the silk‐inspired polyurethane (PU) containing GlycineAlanineGlycineAlanine (GlyAlaGlyAla, the featured peptide sequence of silkworm silk fibroin) tetrapeptide, which was synthesized by the traditional liquid‐phase peptide synthesis method and the classical two‐step polymerization method using Boc‐protected amino acids and diisocyanates as starting materials, were characterized. The results show that the synthesized silk‐inspired PU dissolved in tetrahydrofuran (THF) can be easily electrosprayed or electrospun into the film form, although its molecular weight ranging from 13,000 to 15,000 is quite low. Elastomeric fibrous membranes with surface morphologies of “droplets,” “bead‐on‐string,” and “nonwoven fibers” have been obtained by electrospraying and electrospinning the silk‐inspired PU/THF solution of varying concentrations. The thermograms confirm high thermostability of the silk‐inspired PU between 350 and 400°C due to the polar peptide linkages. The tanδ peak of dynamic mechanical analysis curve corresponding to its glass transition temperatures is detected at −34.3°C. Its elongation at break is about 140–150%, and the breaking tensile strength ranges from 22 to 27 MPa, which is consistent with the data of other PUs containing l‐alanine residue. Information provided by this study can be used to better understand the correlation between the natural and man‐made silk polymers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40245.
Crystallinity evolution of soft segments during the synthesis of polyester‐based waterborne polyurethane
Authors: Cao Gaohua , Xia Zhengbin , Lei Liang , Zhang Yanhong , Xing Junheng
Published: December 2013

Polyester‐based waterborne polyurethane (WPU) dispersions having poly(ethylene glycol) adipate diol, isophorone diisocyanate, and hexamethylene diisocyanate as the main raw materials were synthesized by an acetone process. In each step of the synthesis process, the intermediate products were collected, and the crystallization morphologies and relative crystallinity (X) of the soft segments (SSs) in their films were investigated by means of polarizing optical microscopy, differential scanning calorimetry, and X‐ray diffraction. The fracture surfaces and thermostability of the intermediate films were also investigated by scanning electron microscopy (SEM) and TGA, respectively. The results show that the crystalline dimensions of the SSs decreased substantially during the synthesis process of WPU. X of the SSs decreased after the prepolymerization reaction and increased after the hydrophilic chain‐extending reaction, then decreased after emulsification, and finally increased after the secondary chain‐extending reaction. Moreover, The SEM photos indicate that with decreasing crystalline dimensions, the fracture mechanisms of the intermediate films varied gradually from brittle failure to ductile fracture. The thermostability of the intermediates obtained in each step of the synthesis process was in accordance with the variation tendency of the X of the SSs. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40270.
Interactive radiological anatomy eLearning solution for first year medical students: Development, integration, and impact on learning
Authors: Webb Alexandra Louise , Choi Sunhea
Published: December 2013

A technology enhanced learning and teaching (TELT) solution, radiological anatomy (RA) eLearning, composed of a range of identification‐based and guided learning activities related to normal and pathological X‐ray images, was devised for the Year 1 nervous and locomotor course at the Faculty of Medicine, University of Southampton. Its effectiveness was evaluated using a questionnaire, pre‐ and post‐tests, focus groups, summative assessment, and tracking data. Since introduced in 2009, a total of 781 students have used RA eLearning, and among them 167 Year 1 students in 2011, of whom 116 participated in the evaluation study. Students enjoyed learning (77%) with RA eLearning, found it was easy to use (81%) and actively engaged them in their learning (75%), all of which were associated to the usability, learning design of the TELT solution and its integration in the curriculum; 80% of students reported RA eLearning helped their revision of anatomy and 69% stated that it facilitated their application of anatomy in a clinical context, both of which were associated with the benefits offered by the learning and activities design. At the end of course summative assessment, student knowledge of RA eLearning relevant topics (mean 80%; SD ±16) was significantly better as compared to topics not relevant to RA eLearning (mean 63%; SD ±15) (mean difference 18%; 95% CI 15% to 20%; P < 0.001). A well designed and integrated TELT solution can be an efficient method for facilitating the application, integration, and contextualization of anatomy and radiology to create a blended learning environment. Anat Sci Educ 7: 350–360. © 2013 American Association of Anatomists.
Type 2 lysophosphatidic acid receptor in gastric surface mucous cells: Possible implication of prostaglandin E2 production
Authors: Tanaka Tamotsu , Ohmoto Mayumi , Morito Katsuya , Kondo Hiroki , Urikura Mai , Satouchi Kiyoshi , Tokumura Akira
Published: December 2013

Lysophosphatidic acid (LPA) is a lipid mediator that induces various cell responses via its specific receptors. Recently, we found that orally administered LPA and phosphatidic acid (PA) ameliorate stress‐ or aspirin‐induced stomach injury. However, the mechanisms underlying these effects have not been elucidated yet. In this study, we examined effect of LPA on prostaglandin (PG) E2 production in MKN74 cells, a gastric cell‐line expressing type 2 LPA receptor (LPA2). When the cells were treated with LPA, the level of mRNA of COX‐2 but not COX‐1 was upregulated. The LPA effect was abolished when the cells were pretreated with pertussis toxin (PTX), suggesting the involvement of receptor(s) coupled with Gi. Pretreatment of MKN74 cells with LPA enhanced the PGE2 production triggered by calcium ionophore A23187. Again, PTX abolished the LPA effect. Fluorescent immunohistochemistry using an antibody against LPA2 showed that surface mucous cells (pit cells) in gastric mucosa of mice express LPA2 on the apical side of the plasma membrane. These results suggest that LPA in the diet or its digestion may contribute to the epithelial integrity of stomach mucosa by enhancement of PGE2 production via activation of LPA2. © 2013 BioFactors, 40(3):355–361, 2014
Rho GTPases and cancer
Authors: Li Hui , Peyrollier Karine , Kilic Gülcan , Brakebusch Cord
Published: December 2013

Rho GTPases are a family of small GTPases, which play an important role in the regulation of the actin cytoskeleton. Not surprisingly, Rho GTPases are crucial for cell migration and therefore highly important for cancer cell invasion and the formation of metastases. In addition, Rho GTPases are involved in growth and survival of tumor cells, in the interaction of tumor cells with their environment, and they are vital for the cancer supporting functions of the tumor stroma. Recent research has significantly improved our understanding of the regulation of Rho GTPase activity, the specificity of Rho GTPases, and their function in tumor stem cells and tumor stroma. This review summarizes these novel findings and tries to define challenging questions for future research. © 2013 BioFactors, 40(2):226–235, 2014
Homology modeling and molecular docking for the science curriculum
Authors: McDougal Owen M. , Cornia Nic , Sambasivarao S. V. , Remm Andrew , Mallory Chris , Oxford Julia Thom , Maupin C. Mark , Andersen Tim
Published: December 2013

DockoMatic 2.0 is a powerful open source software program (downloadable from sourceforge.net) that allows users to utilize a readily accessible computational tool to explore biomolecules and their interactions. This manuscript describes a practical tutorial for use in the undergraduate curriculum that introduces students to macromolecular structure creation, ligand binding calculations, and visualization of docking results. A student procedure is provided that illustrates the use of DockoMatic to create a homology model for the amino propeptide region (223 amino acids with two disulfide bonds) of collagen α1 (XI), followed by molecular docking of the commercial drug Arixtra® to the homology model of α1 (XI), and finally, analysis of the results of the docking experiment. The activities and Supporting Information described are intended to educate students in the use of computational tools to create and investigate homology models for other systems of interest and to train students to perform and analyze molecular docking studies. The tutorial also serves as a foundation for investigators seeking to explore the viability of using computational biochemistry to study their receptor–ligand binding motifs. © 2013 by The International Union of Biochemistry and Molecular Biology, 42(2):179–182, 2014.
An inquiry‐based biochemistry laboratory structure emphasizing competency in the scientific process: A guided approach with an electronic notebook format
Authors: L. Hall Mona , Vardar‐Ulu Didem
Published: December 2013

The laboratory setting is an exciting and gratifying place to teach because you can actively engage the students in the learning process through hands‐on activities; it is a dynamic environment amenable to collaborative work, critical thinking, problem‐solving and discovery. The guided inquiry‐based approach described here guides the students through their laboratory work at a steady pace that encourages them to focus on quality observations, careful data collection and thought processes surrounding the chemistry involved. It motivates students to work in a collaborative manner with frequent opportunities for feedback, reflection, and modification of their ideas. Each laboratory activity has four stages to keep the students' efforts on track: pre‐lab work, an in‐lab discussion, in‐lab work, and a post‐lab assignment. Students are guided at each stage by an instructor created template that directs their learning while giving them the opportunity and flexibility to explore new information, ideas, and questions. These templates are easily transferred into an electronic journal (termed the E‐notebook) and form the basic structural framework of the final lab reports the students submit electronically, via a learning management system. The guided‐inquiry based approach presented here uses a single laboratory activity for undergraduate Introductory Biochemistry as an example. After implementation of this guided learning approach student surveys reported a higher level of course satisfaction and there was a statistically significant improvement in the quality of the student work. Therefore we firmly believe the described format to be highly effective in promoting student learning and engagement. © 2013 by The International Union of Biochemistry and Molecular Biology, 42(1):58–67, 2014.
Validated LC‐MS/MS method for the simultaneous determination of hyperoside and 2′′–O‐galloylhyperin in rat plasma: application to a pharmacokinetic study in rats
Authors: Zhou Donghui , Jin Yuanzhe , Yao Fengchen , Duan Zhiying , Wang Qi , Liu Jing
Published: December 2013

An LC‐MS/MS method was developed for the first time to simultaneously determine hyperoside and 2′′–O‐galloylhyperin, two major components in Pyrola calliantha extract, in rat plasma. Following extraction by one‐step protein precipitation with methanol, the analytes were separated on a Venusil MP‐C18 column within 2 min, using methanol–water–formic acid (50:50:0.1, v/v/v) as the mobile phase at a flow rate of 0.4 mL/min. Detection was performed on electrospray negative ionization mass spectrometry by multiple‐reaction monitoring of the transitions of 2′′–O‐galloylhyperin at m/z 615.1 → 301.0, of hyperoside at m/z 463.1 → 300.1, and of internal standard at m/z 415.1 → 295.1. The limits of quantification were 2 ng/mL for both hyperoside and 2′′–O‐galloylhyperin. The precisions were <13.1%, and the accuracies were between −9.1 and 5.5% for both compounds. The method was successfully applied in pharmacokinetic studies following intravenous administration of the total flavonoids of P. calliantha extract in rats. Copyright © 2013 John Wiley & Sons, Ltd.
Online integrity monitoring in the Protein A step of mAb Production Processes—increasing reliability and process robustness
Authors: Bork Christopher , Holdridge Sarah , Walter Mark , Fallon Eric , Pohlscheidt Michael
Published: December 2013

The purification of recombinant proteins and antibodies using large packed‐bed columns is a key component in most biotechnology purification processes. Because of its efficiency and established practice in the industry, column chromatography is a state of the art technology with a proven capability for removal of impurities, viral clearance, and process efficiency. In general, the validation and monitoring of chromatographic operations—especially of critical process parameters—is required to ensure robust product quality and compliance with health authority expectations. One key aspect of chromatography that needs to be monitored is the integrity of the packed bed, since this is often critical to achieving sufficient separation of protein species. Identification of potential column integrity issues before they occur is important for both product quality and economic efficiency. In this article, we examine how transition analysis techniques can be utilized to monitor column integrity. A case study on the application of this method during a large scale Protein A capture step in an antibody purification process shows how it can assist with improving process knowledge and increasing the efficiency of manufacturing operations. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:383–390, 2014
Advanced online monitoring of cell culture off‐gas using proton transfer reaction mass spectrometry
Authors: Schmidberger Timo , Gutmann Rene , Bayer Karl , Kronthaler Jennifer , Huber Robert
Published: December 2013

Mass spectrometry has been frequently applied to monitor the O2 and CO2 content in the off‐gas of animal cell culture fermentations. In contrast to classical mass spectrometry the proton transfer reaction mass spectrometry (PTR‐MS) provides additional information of volatile organic compounds by application of a soft ionization technology. Hence, the spectra show less fragments and can more accurately assigned to particular compounds. In order to discriminate between compounds of non‐metabolic and metabolic origin cell free experiments and fed‐batch cultivations with a recombinant CHO cell line were conducted. As a result, in total eight volatiles showing high relevance to individual cultivation or cultivation conditions could be identified. Among the detected compounds methanethiol, with a mass‐to‐charge ratio of 49, qualifies as a key candidate in process monitoring due to its strong connectivity to lactate formation. Moreover, the versatile and complex data sets acquired by PTR MS provide a valuable resource for statistical modeling to predict non direct measurable parameters. Hence, partial least square regression was applied to the complete spectra of volatiles measured and important cell culture parameters such as viable cell density estimated (R2 = 0.86). As a whole, the results of this study clearly show that PTR‐MS provides a powerful tool to improve bioprocess‐monitoring for mammalian cell culture. Thus, specific volatiles emitted by cells and measured online by the PTR‐MS and complex variables gained through statistical modeling will contribute to a deeper process understanding in the future and open promising perspectives to bioprocess control. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:496–504, 2014
Pathway analysis of Pichia pastoris to elucidate methanol metabolism and its regulation for production of recombinant proteins
Authors: Unrean Pornkamol
Published: December 2013

This research rationally analyzes metabolic pathways of Pichia pastoris to study the metabolic flux responses of this yeast under methanol metabolism. A metabolic model of P. pastoris was constructed and analyzed by elementary mode analysis (EMA). EMA was used to comprehensively identify the cell's metabolic flux profiles and its underlying regulation mechanisms for the production of recombinant proteins from methanol. Change in phenotypes and flux profiles during methanol adaptation with varying feed mixture of glycerol and methanol was examined. EMA identified increasing and decreasing fluxes during the glycerol–methanol metabolic shift, which well agreed with experimental observations supporting the validity of the metabolic network model. Analysis of all the identified pathways also led to the determination of the metabolic capacities as well as the optimum metabolic pathways for recombinant protein synthesis during methanol induction. The network sensitivity analysis revealed that the production of proteins can be improved by manipulating the flux ratios at the pyruvate branch point. In addition, EMA suggested that protein synthesis is optimum under hypoxic culture conditions. The metabolic modeling and analysis presented in this study could potentially form a valuable knowledge base for future research on rational design and optimization of P. pastoris by determining target genes, pathways, and culture conditions for enhanced recombinant protein synthesis. The metabolic pathway analysis is also of considerable value for production of therapeutic proteins by P. pastoris in biopharmaceutical applications. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:28–37, 2014
Postmortem circulation: A new model for testing endovascular devices and training clinicians in their use
Authors: Chevallier Christine , Willaert Wouter , Kawa Emilia , Centola Marcos , Steger Beat , Dirnhofer Richard , Mangin Patrice , Grabherr Silke
Published: December 2013

The development of new medical devices, such as aortic valves, requires numerous preliminary studies on animals and training of personnel on cadavers before the devices can be used in patients. Postmortem circulation, a technique used for postmortem angiography, allows the vascular system to be reperfused in a way similar to that in living persons. This technique is used for postmortem investigations to visualize the human vascular system and to make vascular diagnoses. Specific material for reperfusing a human body was developed recently. Our aim was to investigate whether postmortem circulation that imitates in vivo conditions allows for the testing of medical materials on cadavers. We did this by delivering an aortic valve using minimally invasive methods. Postmortem circulation was established in eight corpses to recreate an environment as close as possible to in vivo conditions. Mobile fluoroscopy and a percutaneous catheterization technique were used to deliver the material to the correct place. Once the valve was implanted, the heart and primary vessels were extracted to confirm its position. Postmortem circulation proved to be essential in several of the cadavers because it helped the clinicians to deliver the material and improve their implantation techniques. Due to the intravascular circulation, sites with substantial arteriosclerotic stenosis could be bypassed, which would have been impossible without perfusion. Although originally developed for postmortem investigations, this reperfusion technique could be useful for testing new medical devices intended for living patients. Clin. Anat. 556–562, 2014. © 2013 Wiley Periodicals, Inc.
Effective Polynomial Ballisticity Conditions for Random Walk in Random Environment
Authors: Berger Noam , Drewitz Alexander , Ramírez Alejandro F.
Published: December 2013

The conditions (T)γ, γ ∊ (0,1), which were introduced by Sznitman in 2002, have had a significant impact on research in random walk in a random environment. Among others, these conditions entail a ballistic behavior as well as an invariance principle. They require the stretched exponential decay of certain slab exit probabilities for the random walk under the averaged measure and are asymptotic in nature.

The main goal of this paper is to show that in all relevant dimensions (i.e., d ≥ 2), in order to establish the conditions (T)γ, it is actually enough to check a corresponding condition (𝒫) of polynomial type. In addition to only requiring an a priori weaker decay of the corresponding slab exit probabilities than (T)γ, another advantage of the condition (𝒫) is that it is effective in the sense that it can be checked on finite boxes.

In particular, this extends the conjectured equivalence of the conditions (T)γ, γ ∊ (0,1), to all relevant dimensions. © 2014 Wiley Periodicals, Inc.
Cytological evaluation using liquid‐based cytology in the male urogenital tract infected with human papillomavirus
Authors: Shigehara Kazuyoshi , Sasagawa Toshiyuki , Kawaguchi Shohei , Nakashima Kazufumi , Nakashima Takao , Shimamura Masayoshi , Furubayashi Keiichi , Namiki Mikio
Published: December 2013

This study was performed to determine the associations between human papillomavirus (HPV) infection and cytological changes in the male glans and urethral samples. Two rubbed samples of the glans and distal urethra were collected from 160 patients with urethritis, and the collected cells were placed into preservative solution for liquid‐based cytology. DNA was extracted from all samples, and β‐globin gene amplification, HPV‐DNA test, and HPV genotyping were performed. After papanicolaou staining of each sample, cytological findings were assessed based on nine non‐classic signs, and compared with the results of HPV‐DNA test. Among the β‐globin positive samples, HPV (any type) was detected in 33 and 25% of the glans and urethra samples, respectively. High‐risk HPV‐DNA was detected in 25 and 15% of the glans and urethra samples, respectively. In the glans samples, cytological signs of HPV infection were observed in 17% of low‐risk HPV‐positive samples and in 58% of high‐risk HPV‐positive samples. Cytological atypia suspected to indicate penile intraepithelial neoplasia were observed in 17 and 33%, respectively. On the other hand, abnormal cells were observed in 29% of low‐risk HPV‐positive and 83% of high‐risk HPV‐positive urethral samples. Cytological atypia suspected to be urethral intraepithelial neoplasia was observed in 29 and 65%, respectively. In situ hybridization demonstrated the presence of HPV‐DNA in the morphologically abnormal cells in 31 and 35% of high‐risk HPV‐positive glans and urethral samples, respectively. Cytological changes similar to cervical intraepithelial neoplasia in females could be detected in the HPV‐positive glans and urethral samples. Diagn. Cytopathol. 2014;42:491–497. © 2013 Wiley Periodicals, Inc.
Assessment of Her‐2/neu status using immunocytochemistry and fluorescence in situ hybridization on fine‐needle aspiration cytology smears: Experience from a tertiary care centre in India
Authors: Durgapal Prashant , Mathur Sandeep R. , Kalamuddin Md. , Datta Gupta Siddhartha , Parshad Rajinder , Julka Pramod K. , Panda S. K.
Published: December 2013

Breast carcinoma shows amplification/overexpression of Her‐2/neu in ∼20–30% of cases. The determination of Her‐2/neu expression accurately is vital in clinical practice as it has significant predictive value and eligibility for anti Her‐2/neu therapy. Amplification and overexpression of Her‐2/neu gene is traditionally identified by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) on tissue sections; only a few studies have evaluated feasibility of these techniques on cytological smears.

One hundred cases of breast cancer with fine‐needle aspiration cytology (FNAC) samples and corresponding surgically resected specimen were selected. Immunocytochemistry (ICC) and FISH for Her‐2/neu was done on FNA smears, whereas IHC was performed on corresponding tissue sections.

Diagnostic accuracy of ICC was 99% when compared with IHC. Comparison of FISH results with IHC showed 100% concordance.

Unlike many centers in West, FNAC is still routinely performed in developing countries like India where vast majority of breast cancer cases present as palpable lumps. The high rates of accuracy of ICC and FISH for Her‐2/neu detection can make FNAC a relevant first line of investigation as a cost effective model with a rapid turn‐around time, providing complete information necessary for initial management of breast cancer patients. Diagn. Cytopathol. 2014;42:726–731. © 2013 Wiley Periodicals, Inc.
Patterning of sexually dimorphic neurogenesis in the Caenorhabditis elegans ventral cord by Hox and TALE homeodomain transcription factors
Authors: Kalis Andrea K. , Kissiov Djem U. , Kolenbrander Emily S. , Palchick Zachary , Raghavan Shraddha , Tetreault Breanna J. , Williams Erin , Loer Curtis M. , Wolff Jennifer Ross
Published: December 2013

COVER PHOTOGRAPH: Pseudocolored array of C. elegans L1 larvae overexpressing the midbody Hox reporter, lin‐39::lacZ. From Patterning of sexually dimorphic neurogenesis in the Caenorhabditis elegans ventral cord by Hox and TALE homeodomain transcription factors; Kalis, et al, Developmental Dynamics 243:159–171.
Evolution of aging through reduced demographic stochasticity – an extension of the pleiotropy theory to finite populations
Authors: Giaimo Stefano
Published: December 2013

In finite populations, there is selection against demographic stochasticity. In this study, it is shown that an increase in the rate of aging, here defined as an increase in early‐life survival at the expense of later survival, may reduce this form of stochasticity. In particular, a trade‐off between juvenile and adult survival is highly efficient in reducing demographic stochasticity. Therefore, aging may evolve as a response to selective pressure for reduced demographic stochasticity.
ERK1/2 signaling is essential for the chemoattraction exerted by human FGF2 and human anosmin‐1 on newborn rat and mouse OPCs via FGFR1
Authors: Murcia‐Belmonte Verónica , Medina‐Rodríguez Eva M. , Bribián Ana , de Castro Fernando , Esteban Pedro F.
Published: December 2013

Signaling through fibroblast growth factor receptors (FGFRs) is essential for many cellular processes including proliferation and migration, as well as differentiation events such as myelination. Anosmin‐1 is an extracellular matrix (ECM) glycoprotein that interacts with the fibroblast growth factor receptor 1 (FGFR1) to exert its biological actions through this receptor, although the intracellular pathways underlying anosmin‐1 signaling remain largely unknown. This protein is defective in the X‐linked form of Kallmann syndrome (KS) and has a prominent role in the migration of neuronal and oligodendroglial precursors. We have shown that anosmin‐1 exerts a chemotactic effect via FGFR1 on neuronal precursors from the subventricular zone (SVZ) and the essential role of the ERK1/2 signaling. We report here the positive chemotactic effect of FGF2 and anosmin‐1 on rat and mouse postnatal OPCs via FGFR1. The same effect was observed with the truncated N‐terminal region of anosmin‐1 (A1Nt). The introduction in anosmin‐1 of the missense mutation F517L found in patients suffering from KS annulled the chemotactic activity; however, the mutant form carrying the disease‐causing mutation E514K also found in KS patients, behaved as the wild‐type protein. The chemoattraction exhibited by FGF2 and anosmin‐1 on OPCs was blocked by the mitogen‐activated protein kinase (MAPK) inhibitor U0126, suggesting that the activation of the ERK1/2 MAPK signaling pathway following interaction with the FGFR1 is necessary for FGF2 and anosmin‐1 to exert their chemotactic effect. In fact, both proteins were able to induce the phosphorylation of the ERK1/2 kinases after the activation of the FGFR1 receptor. GLIA 2014;62:374–386
Structural and functional underconnectivity as a negative predictor for language in autism
Authors: Verly Marjolein , Verhoeven Judith , Zink Inge , Mantini Dante , Oudenhove Lukas Van , Lagae Lieven , Sunaert Stefan , Rommel Nathalie
Published: December 2013

The development of language, social interaction, and communicative skills are remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the interplay between their brain connectivity and language performance remains largely understudied. Using diffusion tensor imaging tractography and resting‐state fMRI, the authors explored the structural and functional connectivity of the language network and its relation to the language profile in a group of healthy control subjects (N = 25) and a group of children with ASD (N = 17). The authors hypothesized that in children with ASD, a neural connectivity deficit of the language network can be related to the observed abnormal language function. They found an absence of the right‐hemispheric arcuate fascicle (AF) in 28% (7/25) of the healthy control children and in 59% (10/17) of the children with ASD. In contrast to healthy control children, the absence of the right‐hemispheric AF in children with autism was related to a lower language performance as indicated by a lower verbal IQ, lower scores on the Peabody Picture Vocabulary Test, and lower language scores on the Dutch version of the Clinical Evaluation of Language Fundamentals (CELF‐4NL). In addition, through iterative fMRI data analyses, the language impairment of children with ASD could be linked to a marked loss of intrahemispheric functional connectivity between inferior frontal and superior temporal regions, known as the cortical language network. Both structural and functional underconnectivity patterns coincide and are related to an abnormal language function in children with ASD. Hum Brain Mapp 35:3602–3615, 2014. © 2013 Wiley Periodicals, Inc.
“Well I Got a Few of My Own”: Therapists' Reactions to Attraction, Sex, and Love in Psychotherapy
Authors: Hayes Jeffrey A.
Published: December 2013

This article serves as an introduction to this issue of the journal on sex, love, intimacy, and attraction in psychotherapy, with a particular emphasis on therapists’ reactions to these subjects. A common theme throughout this special issue is that such topics are natural, common, challenging, and potentially dangerous. I call attention to a few of the highlights of each of the articles in the issue, and I offer suggestions on how therapists might effectively manage their own reactions to these challenging topics.
Sexual Feelings and Behaviors in the Psychotherapy Relationship: An Ethics Perspective
Authors: Barnett Jeffrey E.
Published: December 2013

Sexual intimacies with clients are inappropriate behaviors under all circumstances. Yet, psychologists who adhere to rigid rules about boundaries and multiple relationships in an ill‐guided effort to avoid such occurrences may find that they actually harm clients by acting in ways that are inconsistent with clients’ treatment needs and goals. Boundaries and multiple relationships are discussed and strategies for negotiating them effectively are presented. A thoughtful and deliberative process is described for responding to the inevitable feelings of attraction toward clients that at times arise, and steps for addressing psychotherapists’ vulnerabilities are presented. Ethics principles and standards as well as decision‐making considerations are presented so that psychologists will be better prepared for addressing these important issues in psychotherapy.
Fast Tracking of Co‐Localization of Multiple Markers by Using the Nanozoomer Slide Scanner and NDPViewer
Authors: Zheng Ping‐Pin , van der Weiden Marcel , Kros Johan M.
Published: December 2013

The detection of co‐localization of immunohistochemical markers in tissues or cells requires the application of the confocal laser scanning microscope (CLSM) to multiple immunofluorescence (MIF) stainings. CLSM is operationally sophisticated but requires time‐consuming procedures of imaging and reconstruction, and a professional operator is required for manipulation of the microscopic system. Therefore, this technique is less suitable for the examination of many samples in a short time. Moreover, the technique only allows imaging of selected areas of a sample at one time and is not practical for fast panoramic mapping and tracking of whole tissue sections. Here we show a powerful high‐throughput and operationally simple histological approach using the Hamamatsu NDP slide scanner (Hamamatsu Nanozoomer 2.0HT) and its viewing platform (NDP.Viewer). The approach not only enables fast mapping and tracking of overlapping spots or regions stained with multiple markers, but also offers panoramic screening of whole tissue sections with fully electronic manipulation for the visualization and analysis of any individual regions. J. Cell. Physiol. 229: 967–973, 2014. © 2013 Wiley Periodicals, Inc.
New Advances of microRNAs in Glioma Stem Cells, With Special Emphasis on Aberrant Methylation of microRNAs
Authors: Zhao Bing , Bian Er‐Bao , Li Jia , Li Jun
Published: December 2013

Malignant brain tumors are thought to be originate from a small population of cells that display stem cell properties, including the capacity of self‐renewal, multipotent differentiation, initiation of tumor tissues. Cancer stem cells (CSCs) have been identified in gliomas in which they are named as glioma stem cells (GSCs). GSCs, sharing some characteristics with normal neural stem cells (NSCs), contribute to the cellular origin for primary gliomas and the recurrence of malignant gliomas after current conventional therapy. Recently, increasing evidences have showed that miRNAs play a central role in GSCs. In this review we focus on the role of GSCs in gliomas and in the abnomal expression of miRNAs in GSCs. Furthermore, we also discuss epigenetic dysregulation of tumor‐suppressor miRNAs by promoter DNA methylation is involved in the regulation of GSCs biology. Recent advances in understanding dysregulated expression of miRNAs and methylation of tumor‐suppressor miRNAs in GSCs and their possible use as new therapeutic targets of gliomas. J. Cell. Physiol. 229: 1141–1147, 2014. © 2013 Wiley Periodicals, Inc.
Effects of an acceptance/defusion intervention on experimentally induced generalized avoidance: A laboratory demonstration
Authors: Luciano Carmen , Valdivia‐Salas Sonsoles , Ruiz Francisco J. , Rodríguez‐Valverde Miguel , Barnes‐Holmes Dermot , Dougher Michael J. , López‐López Juan C. , Barnes‐Holmes Yvonne , Gutierrez‐Martínez Olga
Published: December 2013

This study tests the effectiveness of an acceptance/defusion intervention in reducing experimentally induced generalized avoidance. After the formation of two 6‐member equivalence classes, 23 participants underwent differential conditioning with two elements from each class: A1 and B1 were paired with mild electric shock, whereas A2 and B2 were paired with earning points. Participants learned to produce avoidance and approach responses to these respective stimuli and subsequently showed transfer of functions to non‐directly conditioned equivalent stimuli from Class 1 (i.e., D1 and F1 evoked avoidance responses) and Class 2 (i.e., D2 and F2 evoked approach responses). Participants were then randomly assigned to either a motivational protocol (MOT) in which approaching previously avoided stimuli was given a general value, or to a defusion protocol (DEF) in which defusion (a component of Acceptance and Commitment Therapy) was trained while approaching previously avoided stimuli was connected to personally meaningful examples. A post‐hoc control group (CMOT) was conducted with 16 participants to control for differences in protocol length between the former two groups. All participants in the DEF group showed a complete suppression of avoidance responding in the presence of Class 1 stimuli (A1–F1 and additional novel stimuli in relation to them), as compared to 40% of participants in the MOT condition and 20% in the CMOT condition. The acceptance/defusion protocol eliminated experimentally induced avoidance responding even for stimuli that elicited autonomic fear responses.
Nanoscale intracortical iron injection induces chronic epilepsy in rodent
Authors: Jo Areum , Heo Chaejeong , Schwartz Theodore H. , Suh Minah
Published: December 2013

We studied the electrophysiological, hemodynamic, and cytomorphological consequences of microhemorrhagic brain injury induced by a nanoscale iron injection. Of particular interest were the etiology, development, and treatment of epilepsy associated with this injury. We developed an animal model of chronic epilepsy using nanoscale injection into the adult mouse cortex. Although injection of nanoamounts of iron did not cause clear cell death or damage in the cortex, it elicited varying degrees of spontaneous epileptiform events that could be recorded under anesthesia 3 months postinjection. The influence of these chronic epileptiform events on neurovascular coupling was probed by directly stimulating the cortex ipsilateral to the epileptic focus and by measuring cerebral blood volume simultaneously in both hemispheres using intrinsic signal optical imaging. The ipsilateral hemodynamic response was dramatically lower in animals that exhibited longer, more frequent epileptiform events, but it was unchanged in animals displaying infrequent, short events. In contrast, the contralateral hemodynamic response was augmented in all iron‐injected animals compared with the control group. These abnormal hemodynamic responses in chronically epileptic animals were correlated with the degree of reduction in the number of GABAergic interneurons. Therefore, nanoscale iron injection, which mimics some aspects of microhemorrhagic brain injury, generated chronic, yet varying, degrees of spontaneous epileptiform events. Moreover, the severity of the epileptiform events corresponded to the degree of reduction in GABAergic interneurons in the iron‐injected hemisphere and the level of autoregulatory dysfunction of cerebral blood flow. © 2013 Wiley Periodicals, Inc.
DFT study on the influence of electric field on surface‐enhanced Raman scattering from pyridine–metal complex
Authors: Zhao Xiuming , Chen Maodu
Published: December 2013

The influence of a static external electric field on surface‐enhanced Raman scattering is investigated by calculating the Raman spectra and excited state properties of pyridine–Au20 complex with the density functional theory and time‐dependent density functional theory method. The external electric field with orientation parallel (positive) or antiparallel (negative) to the permanent dipole moment is respectively applied on the complex. This field slightly changes the equilibrium geometry and polarizabilities, which results in shifted vibration frequencies and selectively enhanced Raman intensities. The changes of charge transfer (CT) excited states in response to the electric field are visualized by employing the charge difference densities. Further, the energy of charge transfer transition is tuned by electric field to be resonant or not with the incident light, leading to the Raman intensities are enhanced or not enhanced. At the same time, the intensities of vibration modes are sensitive to the orientation of the field. The positive electric field enhances the totally symmetric ring breathing mode (~1009 cm−1) but suppresses the trigonal ring breathing mode (~1051 cm−1). On the contrary, the mode at 1051 cm−1 is more enhanced than the mode at 1009 cm−1 when the negative electric field is applied on the complex. The Raman spectra could be modulated by tuning the strength and direction of the electric field. Copyright © 2013 John Wiley & Sons, Ltd.