bluuebunny/crossref_metadata_2025 huggingface dataset:
Early intervention and long‐term outcome with cardiac resynchronization therapy in patients without a history of advanced heart failure symptoms
Authors: Herscovici Romana , Kutyifa Valentina , Barsheshet Alon , Solomon Scott , McNitt Scott , Polonsky Bronislava , Lee Andy Y. , Zareba Wojciech , Moss Arthur J. , Goldenberg Ilan
Published: April 2015

Aims

MADIT‐CRT showed that cardiac resynchronization therapy with a defibrillator (CRT‐D) improves long‐term outcomes in currently mildly symptomatic heart failure (HF) patients with LBBB regardless of the presence of prior advanced HF symptoms. We aimed to evaluate the long‐term benefit of CRT‐D in patients who never experienced advanced HF symptoms prior to device implantation.

Methods and results

Interaction term analysis was used to compare the clinical and echocardiographic benefit of CRT‐D vs. implantable cardioverter defibrillator (ICD)‐only therapy during long‐term follow‐up (median 5.6 years) between LBBB patients with or without a history of advanced HF [defined as NYHA class ≥ III or past hospitalization for worsening HF >3 months prior to enrolment in MADIT‐CRT (n = 529 and 752, respectively)]. Multivariable analysis showed that treatment with CRT‐D was associated with a significant reduction in the risk of HF or death during long‐term follow‐up regardless of the presence of prior advanced HF symptoms [hazard ratio 0.53 (P < 0.001) and 0.47 (P < 0.001) in the respective groups of patients with and without prior advanced HF; interaction P for the difference = 0.58]. Echocardiographic response to CRT at 1 year was also similar between the two groups (P > 0.10 for all comparisons).

Conclusion

Our findings suggest that treatment with CRT‐D is associated with pronounced echocardiographic and long‐term clinical benefit in patients with LV dysfunction and LBBB who never experienced advanced HF symptoms. These data further emphasize the benefit of early intervention with CRT in this population.
Semiconducting BiOCuSe Thermoelectrics and Its Metallic Derivative Bi2YO4Cu2Se2
Authors: Chou Ta‐Lei , Tewari Girish C. , Chan Ting‐Shan , Hsu Ying‐Ya , Chen Jin‐Ming , Yamauchi Hisao , Karppinen Maarit
Published: April 2015

ZrCuSiAs‐type mixed‐anion oxychalcogenides and oxypnictides form a massive family of functional materials readily tailored to host diverse transport properties. Here we investigate semiconducting BiOCuSe, which has been considered as a promising candidate for intermediate‐temperature thermoelectric applications, and its intergrowth derivative Bi2YO4Cu2Se2, by using X‐ray absorption spectroscopy. Stronger anisotropy and bond covalency are revealed for the latter phase, and in contrast to the simple charge‐balance scenario of [Bi3+O2–]+[Cu+Se2–]– in the former phase, mixed‐valence Cu+/Cu2+ with a single coordination sphere is seen in the selenide block of Bi2YO4Cu2Se2, which gives rise to a metallic electrical conductivity.
Model Studies on Peroxidic Glutathione Transferase (GST) Inhibitors: C5‐Methylated 1,2,4‐Trioxanes with C6‐Acrylate Side Chains
Authors: Griesbeck Axel G. , Maaßen Andreas , Bräutigam Maria , Pietsch Markus
Published: April 2015

The 1,2‐hydroxy hydroperoxide 7 was obtained with high threo diastereoselectivity from the ester‐conjugated allylic alcohol 6 through a porphyrin‐sensitized singlet oxygen ene reaction. Compound 7 was used as substrate for peroxy(trans)acetalization with aldehydes, orthoesters, and acetals, catalyzed by boron and indium Lewis acids, as well as by PPTS as a Brønsted acid catalyst (for trioxane 10). The 1,2,4‐trioxane 8 was formed with high diasteroselectivity with all‐equatorially positioned substitutents at C‐3, C‐5, and C‐6. Additionally, perorthoester 9 was obtained by indium(III)‐catalyzed condensation of an orthoester with the hydroperoxide 7. The new compounds 8 and 9 exhibited moderate inhibition of human placental glutathione transferase (GST), comparable to that shown by the 5‐unsubstituted model trioxane 11.
Mild Oxidative Cleavage of 9‐BBN‐Protected Amino Acid Derivatives
Authors: Ankner Tobias , Norberg Thomas , Kihlberg Jan
Published: April 2015

Protection of the amino acid moiety using 9‐BBN is an effective method to enable side chain manipulations in synthesis of complex amino acids. We investigated the standard, mild method for deprotection of the 9‐BBN group in methanolic chloroform, and found that it relies on a slow oxidation mediated by molecular oxygen. Building on this insight, we have developed a method that allows for a fast and selective deprotection using simple peroxy acid reagents. After Fmoc protection, products were isolated in >90 % yield for a series of amino acid derivatives, including a galactosylated derivative of hydroxylysine.
Choice of Reference Electrode is Critical for Potentiometric Whole Cell‐based Sensor
Authors: Kolli Ramya , Kaivosoja Emilia , Levon Kalle
Published: April 2015

Cells have a net negative outer charge which gives rise to a potential difference in a potentiometric set up. Here, Triton X‐100 was used as a model toxin and the cell death was monitored by the potential change, noticed as decrease in negativity. Hence, cytotoxicity can be tested in vitro and real‐time using potentiometry. However, silver ions (Ag+) and/or silver chloride ions (AgCl2)−1 lead to cell death when we used the standard Ag/AgCl reference electrode with 3 M NaCl as filling solution. Our further experimentation showed that PBS as filling solution was biocompatible and also gave stable potentiometric profiles.
Model‐based development of an assay for the rapid detection of biotin‐blocked binding sites of streptavidin
Authors: Müller Jakob M. , Risse Joe M. , Friehs Karl , Flaschel Erwin
Published: April 2015

The protein streptavidin (SAV) is applied in a large variety of molecular methods due to an extraordinarily strong binding to the vitamin biotin (BIO). The protein structure is homotetrameric, characterized by one binding site for BIO per subunit. Therefore, one of the major criteria to determine the quality of SAV isolates is the proportion of BIO‐blocked binding sites per tetramer. A rapid analysis of BIO‐free binding sites is achieved by fluorescence quenching of biotin‐4‐fluorescein (B4F). However, BIO‐blocked binding sites can only be determined by costly and laborious procedures such as ELISA‐based methods or radioactive labeling. This study describes the systematic, model‐supported development of a method for the quick and simple detection of BIO‐blocked binding sites, based on a short‐term heat incubation of the sample in the presence of B4F. Kinetic modeling and parameter estimation yielded dissociation constants of 1.22 ± 0.27 × 10−11 M for the complex SAV–BIO and 5.16 ± 0.70 × 10−13 M for SAV–B4F at 70°C, allowing a displacement of SAV‐bound BIO by B4F. This method allows the rapid monitoring of BIO‐blocked binding sites in fermentation processes, independent from the chain length of SAV and the concentration of contaminating proteins, e.g. when optimizing the BIO concentration in cultivation media.
Endogenous neural stem cell responses to stroke and spinal cord injury
Authors: Grégoire Catherine‐Alexandra , Goldenstein Brianna L. , Floriddia Elisa M. , Barnabé‐Heider Fanie , Fernandes Karl J. L.
Published: April 2015

Stroke and spinal cord injury (SCI) are among the most frequent causes of central nervous system (CNS) dysfunction, affecting millions of people worldwide each year. The personal and financial costs for affected individuals, their families, and the broader communities are enormous. Although the mammalian CNS exhibits little spontaneous regeneration and self‐repair, recent discoveries have revealed that subpopulations of glial cells in the adult forebrain subventricular zone and the spinal cord ependymal zone possess neural stem cell properties. These endogenous neural stem cells react to stroke and SCI by contributing a significant number of new neural cells to formation of the glial scar. These findings have raised hopes that new therapeutic strategies can be designed based on appropriate modulation of endogenous neural stem cell responses to CNS injury. Here, we review the responses of forebrain and spinal cord neural stem cells to stroke and SCI, the role of these responses in restricting injury‐induced tissue loss, and the possibility of directing these responses to promote anatomical and functional repair of the CNS. GLIA 2015;63:1469–1482
Peripheral T‐cell lymphoma with unusual clinical presentation of rhabdomyolysis
Authors: Liu Zhiyu , Medeiros L. Jeffrey , Young Ken H.
Published: April 2015

Primary extranodal lymphoma is known to occur in nose, gastrointestinal tract, skin, bone, and central nervous system. However, it is extremely rare for primary lymphoma to arise in skeletal muscle. We report a case of a 32‐year‐old man who presented initially with fever and fatigue. He had a history of alcohol abuse. Laboratory studies and computerized tomography scan showed results consistent with rhabdomyolysis, but the cause of the rhabdomyolysis was undetermined. After biopsy of abdominal skeletal muscle with histologic examination and T‐cell receptor gamma chain gene rearrangement analysis, the diagnosis of peripheral T‐cell lymphoma was established. After two cycles of the cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide regimen, the patient's symptoms greatly improved. This is the third reported case of peripheral T‐cell lymphoma arising in skeletal muscle reported in the literature and which presented clinically with rhabdomyolysis. The alcohol abuse during the clinical course likely worsens the pathologic process of the rhabdomyolysis. Copyright © 2015 John Wiley & Sons, Ltd.
A dual‐specific anti‐IGF‐1/IGF‐2 human monoclonal antibody alone and in combination with temsirolimus for therapy of neuroblastoma
Authors: Zhao Qi , Tran Hoa , Dimitrov Dimiter S. , Cheung Nai‐Kong V.
Published: April 2015

The insulin‐like growth factors (IGFs), IGF‐1 and IGF‐2, have been implicated in the growth, survival and metastasis of a broad range of malignancies including pediatric tumors. They bind to the IGF receptor type 1 (IGF‐1R) and the insulin receptor (IR) which are overexpressed in many types of solid malignancies. Activation of the IR by IGF‐2 results in increased survival of tumor cells. We have previously identified a novel human monoclonal antibody, m708.5, which binds with high (pM) affinity to both human IGF‐1 and IGF‐2, and potently inhibits phosphorylation of the IGF‐1R and the IR in tumor cells. m708.5 exhibited strong antitumor activity as a single agent against most cell lines derived from neuroblastoma, Ewing family of tumor, rhabdomyosarcoma and osteosarcoma. When tested in neuroblastoma cell lines, it showed strong synergy with temsirolimus and synergy with chemotherapeutic agents in vitro. In xenograft models, the combination of m708.5 and temsirolimus significantly inhibited neuroblastoma growth and prolonged mouse survival. Taken together, these results support the clinical development of m708.5 for pediatric solid tumors with potential for synergy with chemotherapy and mTOR inhibitors.
Chemistry of 4,4′‐(arylmethylene)‐bis(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐ol)s
Authors: Gouda Moustafa A.
Published: April 2015

This review presents a systematic and comprehensive survey of the method of preparation and the chemical reactivity of 4,4′‐(arylmethylene)‐bis(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐ol)s. The target compounds are important intermediates for the synthesis of a variety of synthetically useful and novel heterocyclic systems.
Enhancement impedance transforming ratios of coupled line impedance transformer with wide out‐of‐band suppression characteristics
Authors: Kim Phirun , Chaudhary Girdhari , Jeong Yongchae
Published: April 2015

This article presents the design of an impedance transformer (IT) with wide out‐of‐band suppression characteristics. The wide out‐of‐band suppression characteristics can be obtained by loading several transmission zeros in the lower and upper out‐of‐bands. For experimental validation, a 50‐to‐10 Ω IT was implemented at a center frequency (f0) of 2.6 GHz for the long term evolution signal. The measured results are in good agreement with the simulations, showing a return loss higher than 20 dB over a passband bandwidth of 0.35 GHz (2.35–2.7 GHz) and out‐of‐band suppression better than 18 dB from DC to 1.78 GHz and from 3.45 to 6.97 GHz. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:1600–1603, 2015
Design and development of implantable CPW fed monopole U slot antenna at 2.45 GHz ISM band for biomedical applications
Authors: Kumar S. Ashok , Shanmuganantham T. , Sasikala G.
Published: April 2015

In this chapter, an implantable coplanar waveguide (CPW) fed monopole U Slot antenna at industrial scientific and medical (ISM) band for biomedical applications is proposed. The proposed antenna has a overall dimensions of 29 mm × 29 mm × 0.5 mm at the ISM band (2.4–2.48 GHz). The proposed antenna placed on human tissues like skin, fat, and muscle. The designed antenna is made compatible for implantation by embedding it on RT Duroid substrate and the 10 dB return loss bandwidth is 5.24% ranging from 2.35 to 2.5 GHz. Implantable CPW fed monopole slot antennas are being significantly used into implantable medical devices and RF, because of its merits like conformability, flexibility in design and shape and also it has biocompatibility, patient safety, miniaturization, power consumption etc. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:1604–1608, 2015
Isolation enhancement of a wideband MIMO antenna using floating parasitic elements
Authors: Khan Muhammad Saeed , Capobianco Antonio‐Daniele , Shafique Muhammad Farhan , Ijaz Bilal , Naqvi Aftab , Braaten Benjamin D.
Published: April 2015

A Multiple‐input multiple‐output antenna array with two radiating elements having a wide bandwidth is reported in this work. Spatial diversity has been introduced to achieve the diversity gain and the array was kept compact by introducing five parasitic decoupling elements on the bottom of the substrate; each having a length equal to λ/2 at a specific frequency. Each resonant element offers a resonant bandwidth of 1 GHz starting from 3 GHz to 8.5 GHz. Good agreement between the measured and simulated results shows that the antenna system performs very well over the frequency range 3 GHz to 8.5 GHz. In addition, an isolation of more than 15 dB is achieved with the help of the parasitic elements, while keeping an edge‐to‐edge and center‐to‐center separation of 4 mm and 19 mm, respectively. The proposed antenna measures 26 × 40.5 mm2, and it is suitable for handheld devices, personal digital assistants, next generation home entertainment systems, and robots. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:1677–1682, 2015
Modified calculation for input impedance of probe‐fed and inset‐fed rectangular microstrip antennas
Authors: Günel Tayfun
Published: April 2015

An approach to the modified calculation for input impedance of inset‐fed rectangular microstrip antenna and probe‐fed rectangular microstrip antenna with variable air gap and varying aspect ratio is presented. To modify the expressions for the input impedances of the antennas, continuous parameter genetic algorithm (CPGA) has been used. The results obtained by CPGA for different antenna dimensions are compared with the experimental and theoretical results given in the literature. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:1650–1652, 2015
Novel dual‐band matching network for concurrent dual‐band power amplifier applications
Authors: Cheng Qian‐Fu , Fu Hai‐Peng , Zhu Shou‐Kui , Ma Jian‐Guo
Published: April 2015

This article presents a novel and simple dual‐band (DB) matching network (MN) consisting of a traditional single‐band MN with a DB stub‐loaded line‐based network in cascade. Design equations are presented, and design procedures are elaborated. The fabricated DB power amplifier achieves peak power added efficiency of 72 and 71.5% with output power of 41 and 40.1 dBm at 1.8 and 2.4 GHz, respectively. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:1597–1600, 2015
Activation treatment of recipient oocytes affects the subsequent development and ploidy of bovine parthenogenetic and somatic cell nuclear transfer (SCNT) embryos
Authors: Felmer R. , Arias M. E.
Published: April 2015

We evaluated the potential effect of anisomycin, an antibiotic produced by Streptomyces griseolus, on the parthenogenetic activation of bovine oocytes and reconstructed somatic‐cell nuclear transfer (SCNT) embryos. A higher cleavage and blastocyst rate were achieved with anisomycin (70.3% and 27.8%) and 6‐dimethylaminopurine (DMAP) (73.3% and 30.2%), relative to oocytes parthenogenetically activated with cycloheximide (CHX) (54.1% and 20.2%). In reconstructed SCNT embryos, a greater proportion of embryos reached the blastocyst stage after anisomycin (32.2%) compared to DMAP (22.3%) and CHX (23.5%) treatment. Furthermore, the quality of embryos—assessed by the total number of cells and the inner cell mass‐to‐total‐cell ratio—was higher with anisomycin (166.2 ± 6.9 and 26.9 ± 1.9) compared to DMAP (135.0 ± 8.7 and 39.4 ± 3.5) and CHX (149.1 ± 8.4 and 36.3 ± 2.5), while a lower percentage of chromosomal abnormalities was observed with anisomycin compared to DMAP and CHX treatments, both in parthenotes (though not significant) and in SCNT embryos (P < 0.05). Therefore, anisomycin can enhance the in vitro developmental potential in parthenotes and reconstructed SCNT embryos, specifically improving the quality of SCNT embryos and decreasing the abnormal ploidy of parthenotes and SCNT embryos compared to the traditional protocols of chemical activation with DMAP and CHX. These results may have important implications for the success of reproductive technologies, including SCNT and intracytoplasmic sperm injection, in different mammalian species. Mol. Reprod. Dev. 82: 441–449, 2015. © 2015 Wiley Periodicals, Inc.
Suppression of skeletal muscle signal using a crusher coil: A human cardiac 31p‐MR spectroscopy study at 7 tesla
Authors: Schaller Benoit , Clarke William T. , Neubauer Stefan , Robson Matthew D. , Rodgers Christopher T.
Published: April 2015

Purpose

The translation of sophisticated phosphorus MR spectroscopy (31P‐MRS) protocols to 7 Tesla (T) is particularly challenged by the issue of radiofrequency (RF) heating. Legal limits on RF heating make it hard to reliably suppress signals from skeletal muscle that can contaminate human cardiac 31P spectra at 7T. We introduce the first surface‐spoiling crusher coil for human cardiac 31P‐MRS at 7T.

Methods

A planar crusher coil design was optimized with simulations and its performance was validated in phantoms. Crusher gradient pulses (100 μs) were then applied during human cardiac 31P‐MRS at 7T.

Results

In a phantom, residual signals were 50 ± 10% with BISTRO (B1‐insensitive train to obliterate signal), and 34 ± 8% with the crusher coil. In vivo, residual signals in skeletal muscle were 49 ± 4% using BISTRO, and 24 ± 5% using the crusher coil. Meanwhile, in the interventricular septum, spectral quality and metabolite quantification did not differ significantly between BISTRO (phosphocreatine/adenosine triphosphate [PCr/ATP] = 2.1 ± 0.4) and the crusher coil (PCr/ATP = 1.8 ± 0.4). However, the specific absorption rate (SAR) decreased from 96 ± 1% of the limit (BISTRO) to 16 ± 1% (crusher coil).

Conclusion

A crusher coil is an SAR‐efficient alternative for selectively suppressing skeletal muscle during cardiac 31P‐MRS at 7T. A crusher coil allows the use of sequence modules that would have been SAR‐prohibitive, without compromising skeletal muscle suppression. Magn Reson Med 75:962–972, 2016. © 2015 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance.
Pricing and inventory management during new product introduction when shortage creates hype
Authors: Chintapalli Prashant , Hazra Jishnu
Published: April 2015

In this study, we analyze the joint pricing and inventory management during new product introduction when product shortage creates additional demand due to hype. We develop a two‐period model in which a firm launches its product at the beginning of the first period, before it observes sales in the two periods. The product is successful with an exogenous probability, or unsuccessful with the complementary probability. The hype in the second period is observed only when the product is successful. The firm learns the actual status of the product only after observing the first‐period demand. The firm must decide the stocking level and price of the product jointly at the beginning of each of the two periods. In this article, we derive some structural properties of the optimal prices and inventory levels, and show that (i) firms do not always exploit hype, (ii) firms do not always increase the price of a successful product in the second period, (iii) firms may price out an unsuccessful product in the first period if the success probability is above a threshold, and (iv) such a threshold probability is decreasing in the first‐period market potential of the successful product. © 2015 Wiley Periodicals, Inc. Naval Research Logistics 62: 304–320, 2015
Large‐scale identification of secretome glycoproteins recognized by Wisteria floribunda agglutinin: A glycoproteomic approach to biomarker discovery
Authors: Sugahara Daisuke , Tomioka Azusa , Sato Takashi , Narimatsu Hisashi , Kaji Hiroyuki
Published: April 2015

One of the promising approaches to the development of cancer diagnostic systems is quantification of a specific protein carrying cancerous glycans. Potential utility of Wisteria floribunda agglutinin (WFA) for such assays has been suggested for several cancer types. To develop such diagnostic systems, identification of WFA‐recognized glycoproteins is essential. Here, we successfully identified 504 WFA‐recognized glycoproteins from the secretome of HEK293T cells. Most of the identified proteins were likely soluble or single‐pass transmembrane proteins, which may serve as specific proteins for the diagnosis using biological fluids. Our method may help to discover marker glycoproteins for various cancers generating WFA‐recognized glycans.
FunRich: An open access standalone functional enrichment and interaction network analysis tool
Authors: Pathan Mohashin , Keerthikumar Shivakumar , Ang Ching‐Seng , Gangoda Lahiru , Quek Camelia Y.J. , Williamson Nicholas A. , Mouradov Dmitri , Sieber Oliver M. , Simpson Richard J. , Salim Agus , Bacic Antony , Hill Andrew F. , Stroud David A. , Ryan Michael T. , Agbinya Johnson I. , Mariadason John M. , Burgess Antony W. , Mathivanan Suresh
Published: April 2015

As high‐throughput techniques including proteomics become more accessible to individual laboratories, there is an urgent need for a user‐friendly bioinformatics analysis system. Here, we describe FunRich, an open access, standalone functional enrichment and network analysis tool. FunRich is designed to be used by biologists with minimal or no support from computational and database experts. Using FunRich, users can perform functional enrichment analysis on background databases that are integrated from heterogeneous genomic and proteomic resources (>1.5 million annotations). Besides default human specific FunRich database, users can download data from the UniProt database, which currently supports 20 different taxonomies against which enrichment analysis can be performed. Moreover, the users can build their own custom databases and perform the enrichment analysis irrespective of organism. In addition to proteomics datasets, the custom database allows for the tool to be used for genomics, lipidomics and metabolomics datasets. Thus, FunRich allows for complete database customization and thereby permits for the tool to be exploited as a skeleton for enrichment analysis irrespective of the data type or organism used. FunRich (http://www.funrich.org) is user‐friendly and provides graphical representation (Venn, pie charts, bar graphs, column, heatmap and doughnuts) of the data with customizable font, scale and color (publication quality).
Bioreducible hyperbranched polyglycerols with disulfide linkages: Synthesis and biocompatibility evaluation
Authors: Shenoi Rajesh A. , Chafeeva Irina , Lai Benjamin F. L. , Horte Sonja , Kizhakkedathu Jayachandran N.
Published: April 2015

In this article, we describe the development of multifunctional, water‐soluble hyperbranched polyglycerols containing redox‐sensitive disulfide linkages as a new class of biodegradable polymers. The polymers were synthesized by the anionic ring opening multibranching (co)polymerization of glycidol with an epoxide monomer bearing disulfide groups, 2‐((2‐oxiran‐2‐ylmethoxy)ethyl)disulfanyl) ethan‐1‐ol. Polymerizations were optimized at 65 °C unlike the homopolymerization of glycidol. Both low (5–10 kDa) and high (100 kDa) molecular weight polymers were synthesized in a controlled manner with low polydispersity. The polymers underwent degradation in presence of reducing agents such as tris(2‐carboxyethyl)phosphine, dithiothreitol, and glutathione resulting in low molecular weight fragments with thiol groups. Blood compatibility analysis using coagulation, platelet activation, complement activation and red blood cell lysis assays as well as cell toxicity analysis using MTS assay revealed the excellent biocompatibility of these newly synthesized polymer architectures. All these features make these polymers suitable for intracellular delivery of therapeutic molecules. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2104–2115
Urinary proteomics in renal pathophysiology: Impact of proteinuria
Authors: Sancho‐Martínez Sandra M. , Prieto‐García Laura , Blanco‐Gozalo Víctor , Fontecha‐Barriuso Miguel , López‐Novoa José M. , López‐Hernández Francisco J.
Published: April 2015

Urinary differential proteomics is used to study renal pathophysiological mechanisms, find novel markers of biological processes and renal diseases, and stratify patients according to proteomic profiles. The proteomic procedure determines the pathophysiological meaning and clinical relevance of results. Urine samples for differential proteomic studies are usually normalized by protein content, regardless of its pathophysiological characteristics. In the field of nephrology, this approach translates into the comparison of a different fraction of the total daily urine output between proteinuric and nonproteinuric samples. Accordingly, alterations in the level of specific proteins found by this method reflect the relative presence of individual proteins in the urine; but they do not necessarily show alterations in their daily excretion, which is a key parameter for the understanding of the pathophysiological meaning of urinary components. For renal pathophysiology studies and clinical biomarker identification or determination, an alternative proteomic concept providing complementary information is based on sample normalization by daily urine output, which directly informs on changes in the daily excretion of individual proteins. This is clinically important because daily excretion (rather than absolute or relative concentration) is the only self‐normalized way to evaluate the real meaning of urinary parameters, which is also independent of urine concentration.
The protein interactome of collapsin response mediator protein‐2 (CRMP2/DPYSL2) reveals novel partner proteins in brain tissue
Authors: Martins‐de‐Souza Daniel , Cassoli Juliana S. , Nascimento Juliana M. , Hensley Kenneth , Guest Paul C. , Pinzon‐Velasco Andres M. , Turck Christoph W.
Published: April 2015

Purpose

Collapsin response mediator protein‐2 (CRMP2) is a CNS protein involved in neuronal development, axonal and neuronal growth, cell migration, and protein trafficking. Recent studies have linked perturbations in CRMP2 function to neurodegenerative disorders such as Alzheimer's disease, neuropathic pain, and Batten disease, and to psychiatric disorders such as schizophrenia. Like most proteins, CRMP2 functions though interactions with a molecular network of proteins and other molecules.

Experimental design

Here, we have attempted to identify additional proteins of the CRMP2 interactome to provide further leads about its roles in neurological functions. We used a combined co‐immunoprecipitation and shotgun proteomic approach in order to identify CRMP2 protein partners.

Results

We identified 78 CRMP2 protein partners not previously reported in public protein interaction databases. These were involved in seven biological processes, which included cell signaling, growth, metabolism, trafficking, and immune function, according to Gene Ontology classifications. Furthermore, 32 different molecular functions were found to be associated with these proteins, such as RNA binding, ribosomal functions, transporter activity, receptor activity, serine/threonine phosphatase activity, cell adhesion, cytoskeletal protein binding and catalytic activity. In silico pathway interactome construction revealed a highly connected network with the most overrepresented functions corresponding to semaphorin interactions, along with axon guidance and WNT5A signaling.

Conclusions and clinical relevance

Taken together, these findings suggest that the CRMP2 pathway is critical for regulating neuronal and synaptic architecture. Further studies along these lines might uncover novel biomarkers and drug targets for use in drug discovery.
Elastic anisotropy and thermodynamic properties of chromium tetraboride from first‐principles calculations
Authors: Xu Chao , Liu Chunmei , Duan Manyi , Wang Haikuo
Published: April 2015

First‐principles calculations are performed to investigate the elastic anisotropy, and thermodynamic properties of chromium tetraboride (CrB4) under extreme P–T conditions. The calculated equilibrium lattice and the normalized crystal parameters as a function of pressure are in good agreement with the available experimental and theoretical data. Elastic constants Cij are calculated in the pressure range of 0–50 GPa, and the bulk modulus B, shear modulus G, and Young's modulus E are also obtained according to the Voigt–Reuss–Hill (VRH) approximation. Anisotropic indexes are employed to characterize the mechanical anisotropy. The bulk modulus and Young's modulus as a function of crystal orientations are also investigated. The obtained results suggest that CrB4 exhibits a pronounced elastic anisotropy. It is strongest along the b‐axis in response to compression loading, and the {100} and {001} shear planes might be the cleavage planes. The elastic anisotropy of CrB4 may possibly limit its applications. Using the quasiharmonic Debye model, thermodynamic properties like Debye temperature, Grüneisen parameter, heat capacity, and expansion coefficient are also systematically explored under extreme P–T conditions.
Comparisons between S‐, C‐ and X‐band polarimetric radar observations and convective‐scale simulations of the HyMeX first special observing period
Authors: Augros C. , Caumont O. , Ducrocq V. , Gaussiat N. , Tabary P.
Published: April 2015

This article describes a forward observation operator for polarimetric radar variables, developed within the research mesoscale non‐hydrostatic model Meso‐NH. The forward operator enables direct comparisons of atmospheric simulations with polarimetric radar observations and constitutes a first step towards the assimilation of polarimetric radar data. The parameters of the polarimetric forward operator were defined in order to be consistent (whenever possible) with the model microphysical parametrization. Subjective and quantitative comparisons between observations and simulations are analyzed for S‐, C‐ and X‐band radars for two convective cases that were observed in autumn 2012 in southeastern France during the first observing period (SOP1) of the Hydrological cycle in the Mediterranean Experiment (HyMeX) campaign. The good consistency between the medians of the observed and simulated distributions of Zdr and Kdp as a function of Zhh, in rain and in dry snow, enables the validation of the parametrization of the polarimetric forward operator. However, the higher spread in observed Zdr and Kdp (due to noise and microphysical variability) reveals a need for careful data quality control and pre‐processing for use in assimilation. Comparisons between observed and simulated vertical profiles of Zhh, Kdp and Zdr in convective areas also show generally good agreement. Some differences between observations and simulations are attributed to model limitations, in particular its one‐moment microphysics scheme and coarser resolution.
A high‐order vertical discretization method for a semi‐implicit mass‐based non‐hydrostatic kernel
Authors: Yang Jinhui , Song Junqiang , Wu Jianping , Ren KaiJun , Leng Hongze
Published: April 2015

Applying finite‐element vertical discretization to a mass‐based non‐hydrostatic kernel has proved difficult due to the constraints of vertical operators. This article proposes a novel hybrid finite‐element vertical discretization method for a semi‐implicit mass‐based non‐hydrostatic kernel, which integrates a finite‐differential scheme and a finite‐element scheme. In the hybrid method, the finite‐differential scheme which satisfies the set of constraints is applied to the linear part, while a cubic finite‐element scheme with high‐order accuracy is applied to the non‐linear part. Furthermore, to improve the accuracy of the linear part, an enlarged set of vertical levels is applied to the differential scheme. This set of vertical levels is only used to solve semi‐implicit equations, and has no impact on the grid point calculation and spectral transformations. A series of 2D idealized test cases are conducted to verify the stability and the accuracy of our new method.
Photosensitizer‐Conjugated Albumin−Polypyrrole Nanoparticles for Imaging‐Guided In Vivo Photodynamic/Photothermal Therapy
Authors: Song Xuejiao , Liang Chao , Gong Hua , Chen Qian , Wang Chao , Liu Zhuang
Published: April 2015

Conjugated polymers with strong absorbance in the near‐infrared (NIR) region have been widely explored as photothermal therapy agents due to their excellent photostability and high photothermal conversion efficiency. Herein, polypyrrole (PPy) nanoparticles are fabricated by using bovine serum albumin (BSA) as the stabilizing agent, which if preconjugated with photosensitizer chlorin e6 (Ce6) could offer additional functionalities in both imaging and therapy. The obtained PPy@BSA‐Ce6 nanoparticles exhibit little dark toxicity to cells, and are able to trigger both photodynamic therapy (PDT) and photothermal therapy (PTT). As a fluorescent molecule that in the meantime could form chelate complex with Gd3+, Ce6 in PPy@BSA‐Ce6 nanoparticles after being labeled with Gd3+ enables dual‐modal fluorescence and magnetic resonance (MR) imaging, which illustrate strong tumor uptake of those nanoparticles after intravenous injection into tumor‐bearing mice. In vivo combined PDT and PTT treatment is then carried out after systemic administration of PPy@BSA‐Ce6, achieving a remarkably improved synergistic therapeutic effect compared to PDT or PTT alone. Hence, a rather simple one‐step approach to fabricate multifunctional nanoparticles based on conjugated polymers, which appear to be promising in cancer imaging and combination therapy, is presented.
Building blocks of the cerebral cortex: from development to the dish
Authors: Harris James , Tomassy Giulio Srubek , Arlotta Paola
Published: April 2015

Since Ramon y Cajal's examination of the cellular makeup of the cerebral cortex, it has been appreciated that this tissue exhibits some of the greatest degrees of cellular heterogeneity in the entire nervous system. This intricate structure emerges during a well‐choreographed developmental process. Here, we review current classifications of the cellular constituents of the cerebral cortex and examine how these building blocks are forged during development. We also look at how basic developmental features underlying cortex formation in vivo have been applied to protocols aimed at generating cortical tissue in vitro. WIREs Dev Biol 2015, 4:529–544. doi: 10.1002/wdev.192

This article is categorized under:

Nervous System Development > Vertebrates: Regional Development

Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion
Analysis of the Reasons for Non‐Uptake of Predictive Testing for Huntington's Disease in Spain: A Qualitative Study
Authors: Rivera‐Navarro Jesús , Cubo Esther , Mariscal Natividad
Published: April 2015

Children of persons affected by Huntington's disease (HD) have a 50% chance of inheriting the disease. Genetic testing in Spain is offered to individuals (presymptomatic test) or mothers of fetuses (prenatal) who run the risk of suffering from HD. The objective of this study is to analyze the factors that influence the decisions of adult children of persons affected with HD regarding predictive testing. A qualitative research methodology was used involving 4 focus groups (FGs) made up of adult children of persons with HD in different cities in Spain. The results of the study showed that over half of the focus group participants were inclined to decline genetic testing. The main explanatory determinants for taking or not taking the predictive test are: Maturity of the individual at risk, which was directly related to age; Ability to cope with a positive test result; Experience of living with HD sufferers; Information about testing and psychological support; Attitude of the family; Social visibility of genetic testing; Personality and temperament of each subject at risk of HD. These results imply that these factors should be analyzed in more detail in quantitative studies in order to help the Spanish Department of Health understand why some children of parents with HD decline genetic testing, so that they may and apply these data when creating specific policy regarding this issue.
Profile Likelihood-Based Confidence Intervals and Regions for Structural Equation Models
Authors: Pek Jolynn , Wu Hao
Published: April 2015

Structural equation models (SEM) are widely used for modeling complex multivariate relationships among measured and latent variables. Although several analytical approaches to interval estimation in SEM have been developed, there lacks a comprehensive review of these methods. We review the popular Wald-type and lesser known likelihood-based methods in linear SEM, emphasizing profile likelihood-based confidence intervals (CIs). Existing algorithms for computing profile likelihood-based CIs are described, including two newer algorithms which are extended to construct profile likelihood-based confidence regions (CRs). Finally, we illustrate the use of these CIs and CRs with two empirical examples, and provide practical recommendations on when to use Wald-type CIs and CRs versus profile likelihood-based CIs and CRs. OpenMx example code is provided in an Online Appendix for constructing profile likelihood-based CIs and CRs for SEM.
What Factors are Associated with a Second Opioid Prescription after Treatment of Distal Radius Fractures with a Volar Locking Plate?
Authors: Teunis Teun , Stoop Nicky , Park Christine J. , Ring David
Published: April 2015

Purpose

Knowledge of factors associated with patient's requests for a second opioid prescription after volar plate fixation of a fracture of the distal radius might inform better pain management protocols and encourage decreased and safer use of opioids. This study tested the primary null hypothesis that there is no difference in demographics, prior opioid prescriptions, injury characteristics, and psychological factors between patients that do and do not receive a second opioid prescription following treatment volar locking plate after distal radius fracture.

Patients and Methods

We used data on 206 patients enrolled in one of two prospective studies. Their mean age was 53 years±SD 15, and 60 (30 %) were men. Forty-seven (23 %) patients received a second opioid prescription. We recorded additional demographics, AO fracture type, American Society for Anesthesiologists (ASA) classification, radiographic parameters at the time of injury prior to reduction and after surgery, and catastrophic thinking.

Results

Male sex (odds ratio [OR] 2.2, 95 % confidence interval [CI] 1.0–4.6, partial pseudo R2=0.018, p=0.044) and greater dorsal angulation of the articular surface on the lateral post injury radiograph (OR 0.98, 95 % CI 0.96 to 1.0, partial pseudo R2=0.033, p=0.040) were associated with a second opioid prescription after surgery (pseudo R2 0.12, p=0.0071). Conclusions One measure of fracture severity (dorsal displacement) was independently associated with a second opioid prescription, but alone it accounted for 3.3 % of the variation. Other factors such as the patient's expectation prior to surgery, in particular the realization that injury and surgery hurt, might be addressed in future research.

Level of Evidence

Prognostic II
Development of Al-B-C Master Alloy Under External Fields
Authors: Joshi Utsavi , VadakkeMadam Sreekumar , Eskin Dmitry G. , Nadendla Hari Babu
Published: April 2015

This study investigates the application of external fields in the development of an Al-B-C alloy, with the aim of synthesizing in situ Al3BC particles. A combination of ultrasonic cavitation and distributive mixing was applied for uniform dispersion of insoluble graphite particles in the Al melt, improving their wettability and its subsequent incorporation into the Al matrix. Lower operating temperatures facilitated the reduction in the amount of large clusters of reaction phases, with Al3BC being identified as the main phase in XRD analysis. The distribution of Al3BC particles was quantitatively evaluated. Grain refinement experiments reveal that Al-B-C alloy can act as a master alloy for Al-4Cu and AZ91D alloys, with average grain size reduction around 50 pct each at 1 wt pctAl-1.5B-2C additions.
A direct numerical simulation study of interface propagation in homogeneous turbulence
Authors: Yu R. , Bai X.-S. , Lipatnikov A. N.
Published: April 2015

A 3D direct numerical simulation (DNS) study of the evolution of a self-propagating interface in forced constant-density statistically stationary homogeneous isotropic turbulence was performed by solving Navier–Stokes and level-set equations under a wide range of conditions that cover various (from 0.1 to 2.0) ratios of the interface speed $S_{L}$ to the r.m.s. turbulent velocity $U^{\prime }$ and various (50, 100 and 200) turbulent Reynolds numbers$\mathit{Re}$. By analysing computed data, the following issues were addressed: (i) dependence of the speed and thickness of the fully developed statistically planar mean front that envelops the interface on$U^{\prime }/S_{L}$and$\mathit{Re}$, (ii) dependence of the fully developed mean turbulent flux of a scalar$c$that characterizes the state of the fluid ($c=0$and 1 ahead and behind the interface respectively) on$U^{\prime }/S_{L}$and$\mathit{Re}$, (iii) evolution of the mean front speed, its thickness, and the mean scalar flux during the front development after embedding a planar interface into the forced turbulence and (iv) relation between canonical and conditioned moments of the velocity, velocity gradient and pressure gradient fields.
Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet
Authors: Xu Li , Huang Danping , Hu Qiaolin , Wu Jing , Wang Yizhen , Feng Jie
Published: April 2015

To assess the effects of betaine on hepatic lipid accumulation and investigate the underlying mechanism, thirty-two male Sprague–Dawley rats weighing 100 (sd2·50) g were divided into four groups, and started on one of four treatments: basal diet, basal diet with betaine administration, high-fat diet and high-fat diet with betaine administration. The results showed that no significant difference of body weight was found among experimental groups. Compared with high-fat diet-fed rats, a betaine supplementation decreased (P< 0·05) hepatic TAG accumulation induced by high-fat diet, which was also supported by hepatic histology results. Additionally, hepatic betaine–homocysteine methyltransferase activity as well as its mRNA abundance and lecithin level were found increased (P< 0·05) by betaine supplementation in both basal diet-fed rats and high-fat diet-fed rats. Betaine administration in high-fat diet-fed rats exhibited a higher (P< 0·05) activity of hepatic carnitine palmitoyltransferase 1 (CPT1) compared with high-fat diet-fed rats. High-fat diet inhibited (P< 0·05) the gene expression of hepaticPPARαandCPT1. However, betaine administration in high-fat diet-fed rats elevated (P< 0·05) the gene expression ofPPARαandCPT1. Moreover, concentration, gene and protein expressions of hepatic fibroblast growth factor 21 (FGF21) were increased (P< 0·05) in response to betaine administration in high-fat diet group; meanwhile the gene expression of hepatic AMP-activated protein kinase was increased (P< 0·05) as well. The results suggest that betaine administration enhanced hepatic lipid export and fatty acid oxidation in high-fat diet-fed rats, thus effectively alleviating fat accumulation in the liver.
Comparison of fermentation characteristics and bacterial diversity in the rumen of sheep and in batch cultures of rumen microorganisms
Authors: MATEOS I. , RANILLA M. J. , SARO C. , CARRO M. D.
Published: April 2015

The objective of the current study was to assess how closely batch cultures (BC) of rumen microorganisms can mimic the dietary differences in fermentation characteristics found in the rumen, and to analyse changes in bacterial diversity over the in vitro incubation period. Four ruminally and duodenally cannulated sheep were fed four diets having forage : concentrate ratios (FCR) of 70 : 30 or 30 : 70, with either alfalfa hay or grass hay as forage. Rumen fluid from each sheep was used to inoculate BC containing the same diet fed to the donor sheep, and the main rumen fermentation parameters were determined after 24 h of incubation. There were differences between BC and sheep in the magnitude of most measured parameters, but BC detected differences among diets due to forage type similar to those found in sheep. In contrast, BC did not reproduce the dietary differences due to FCR found in sheep for pH, degradability of neutral detergent fibre and total volatile fatty acid (VFA) concentrations. There were differences between systems in the magnitude of most determined parameters and BC showed higher pH values and NH3–N concentrations, but lower fibre degradability and VFA and lactate concentrations compared with sheep. There were significant relationships between in vivo and in vitro values for molar proportions of acetate, propionate and butyrate, and the acetate : propionate ratio. The automated ribosomal intergenic spacer analysis (ARISA) of 16S ribosomal deoxyribonucleic acid showed that FCR had no effect on bacterial diversity either in the sheep rumen fluid used as inoculum (IN) or in BC samples. In contrast, bacterial diversity was greater with alfalfa hay diets than those with grass hay in the IN, but was unaffected by forage type in the BC. Similarity index between the bacterial communities in the inocula and those in the BC ranged from 67·2 to 74·7%, and was unaffected by diet characteristics. Bacterial diversity was lower in BC than in the inocula with 14 peaks out of a total of 181 detected in the ARISA electropherograms never appearing in BC samples, which suggests that incubation conditions in the BC may have caused a selection of some bacterial strains. However, each BC sample showed the highest similarity index with its corresponding rumen IN, which highlights the importance of using rumen fluid from donors fed a diet similar to that being incubated in BC when conducting in vitro experiments.