bluuebunny/crossref_metadata_2025 huggingface dataset:
ITPA gene polymorphism (94C>A) effects on ribavirin‐induced anemia during therapy in Egyptian patients with chronic hepatitis C
Authors: El Raziky Maissa , Zayed Naglaa A. , Abdel Baki Amin , Mansour Shimaa A. , Shahin Rasha M. H.
Published: May 2017

Inosine triphosphatase (ITPA) gene variants can protect against ribavirin (RBV)‐induced anemia in patients treated for chronic hepatitis C. The aim of this study was to determine the relationship between genetic variants of ITPA polymorphism, anemia, RBV dose reduction, and treatment response in hepatitis C virus (HCV)‐infected patients. This study was conducted on 97 Egyptian chronic HCV patients who were scheduled for pegylated‐interferon (PEG‐INF) /RBV therapy. ITPA genotypes rs1127354 were determined by Real Time PCR melting curve analysis. Effects of ITPA polymorphism on hemoglobin (Hb) levels, RBV dose reduction and treatment response were analyzed. The homozygous wild genotype (CC) was associated with Hb reduction at week 4 (P = 0.004). The minor allele protected against Hb reduction. No association with sustained virological response was observed (P = 0.492). Female gender; lower baseline Hb and higher baseline WBC were associated with week 4 anemia (P = 0.04; P = 0.023; 0.033, respectively). The ITPA gene polymorphism rs1127354 heterozygous genotype (CA) may influence Hb levels and protect against hemolytic anemia during RBV‐containing regimens for HCV. However, such findings were not significantly related to treatment outcomes. Patients with wild ITPA genotype (CC) experienced a more Hb drop and RBV dose reductions more frequently.
Adequacy assessment of a 2 area system with renewable integration
Authors: Nayak Ashwini Kumar , Mohanty Kanungo Barada , Kommukuri Vinaya Sagar
Published: May 2017

In this paper, impacts of renewable sources on the adequacy of a 2 area system are presented. Integration of popular renewable sources like photovoltaic (PV) and wind is forcing the operational planner to operate differently. Here, an effort has been made to propose some planning scenarios for 2 area system on the basis of renewable sources integration, and reliability is evaluated corresponding to each scenario. Loss of load expectation is popular method for adequacy assessment following 2 state principle (available or unavailable) of conventional sources. Photovoltaic and wind system never follow 2 state principle unlike conventional. Existing PV module configuration determine the unavailability rate of PV plant considering component failure. Random wind speed is simulated using time series auto regressive moving average model. Wind turbine characteristics and simulated wind speed create multistate wind energy conversion system and reduced by apportioning method to predict unavailability rate. A simple 2 area system is considered to validate the efficacy of proposed theme.
An exercise in brain genoarchitectonics: Analysis of AZIN2‐Lacz expressing neuronal populations in the mouse hindbrain
Authors: Martinez‐de‐la‐Torre Margaret , Lambertos Ana , Peñafiel Rafael , Puelles Luis
Published: May 2017

We examined in detail the distribution of AZIN2 (antizyme inhibitor 2) expression in the adult mouse hindbrain and neighboring spinal cord. AZIN2, similar to previously known AZIN1, is a recently‐discovered, a functional paralog of ornithine decarboxylase (ODC). Due to their structural similarity to ODC, both AZIN1 and AZIN2 counteract the inhibitory action of 3 known antizymes (AZ1‐3) on the ODC synthesis of polyamines, thus increasing intracytoplasmic levels of polyamines. AZIN2 is strongly, but heterogeneously, expressed in the brain. Our study uses a mouse line carrying an AZIN2‐LacZ construct, and, in our topographic analysis of AZIN2‐positive structures, we intend to share new knowledge about the rhombomeric segmentation of the hindbrain (a function of Hox paralogs and other genes). The observed labeled cell populations predominantly coincide with known cholinergic and glutamatergic cells, but occasionally also correspond to GABAergic, and possibly glycinergic cells. Some imperfectly known hindbrain populations stood out in unprecedented detail, and some axonal tracts were also differentially stained. © 2017 Wiley Periodicals, Inc.
Multiple sclerosis: Presence of serum antibodies to lipids and predominance of cholesterol recognition
Authors: Jurewicz Anna , Domowicz Malgorzata , Galazka Grazyna , Raine Cedric S. , Selmaj Krzysztof
Published: May 2017

A lot of available data on lipid immunology in multiple sclerosis (MS) have been derived from studies using synthetic lipids, therefore the role of lipids in the immunopathogenesis of MS remains poorly defined. The present study on the lipid response in MS was performed on native lipids from autopsied brain tissue. For this, lipid fractions (n = 9) were prepared from MS (n = 3) and control (n = 2) white matter according to the Folch procedure and were characterized depending on their solubility in chloroform/methanol. TLC showed that, in brain from MS cases, neutral lipids were rich in cholesterol and cholesterol esters while lipids from control brains displayed a predominance of phospholipids. MS serum IgG and IgM were found to bind to MS brain lipid fractions with a higher efficacy (p < 0.05) than the control serum. F(ab)2 fractionation revealed that MS serum IgG binding depended on a specific antibody‐type of recognition. Pre‐adsorption of serum with cholesterol, galactocerebrosides, sulfitides, and phosphatidylinositol prior to ELISA with MS brain lipids, showed that cholesterol diminished IgG and IgM binding up to 70%. Experiments with synthetic lipids confirmed the predominance of cholesterol binding by MS serum. Our results demonstrate that IgG and IgM fractions from MS serum specifically and predominantly recognize native cholesterol and cholesterol esters isolated from the brain tissue of patients with MS. © 2017 Wiley Periodicals, Inc.
Repair of the musculocutaneous nerve using the vagus nerve as donor by helicoid end‐to‐side technique: an experimental study in rats
Authors: Yan Ji‐Geng , Shen Feng‐Yi , Thayer Jacob , Yan Yuhui , LoGiudice John , Matloub Hani , Sanger James , Zhang Lin‐Ling , Havlik Robert
Published: May 2017

Although several donor nerves can be chosen to repair avulsed brachial plexus nerve injury, available nerves are still limited. The purpose of this study is to validate whether the vagus nerve (VN) can be used as a donor. Eighteen Sprague‐Dawley male rats were divided into three groups (n = 6). The right musculocutaneous nerve (McN) was transected with differing subsequent repair. (1) HS‐VN group: a saphenous nerve (SN) graft‐end was helicoidally wrapped round the VN side (epi‐and perineurium was opened) with a 30 ° angle, distal SN end was coapted to the McN with end‐to‐end repair. (2) EE‐PN group: a SN was interpositionally grafted between the transected phrenic nerve (PN) and the McN by end‐to‐end coaptation. (3) Sham control group: McN was transected and not repaired and postoperative vital signs were checked daily. At three months, electrophysiology, tetanic force, wet biceps muscle weight, and histology were evaluated. Every tested mean value in HS‐VN group was significantly greater than the EE‐PN or the sham control groups (p < 0.05 or p < 0.005). The mean recovery ratio of regenerated nerve fibers was 96% and, in HS‐VN group, the mean recovery ratio of CMAP was 79%. No vital signs changed in any group. There was no statistical difference (p > 0.5) between the mean VN nerve‐fiber numbers of the segments proximal (2237 ± 134) and distal (2150 ± 156) to the VN graft‐attachment site. Histological analysis revealed no axon injury or intraneural scarring at any point along the VN. This study demonstrated that VN is a practical and reliable donor nerve for end‐to‐side nerve transfer. © 2017 Wiley Periodicals, Inc.
Activation of ryanodine receptors is required for PKA‐mediated downregulation of A‐type K+ channels in rat hippocampal neurons
Authors: Yang Yoon‐Sil , Jeon Sang‐Chan , Kang Moon‐Suk , Kim Seon‐Hee , Eun Su‐Yong , Jin Soo‐Hee , Jung Sung‐Cherl
Published: May 2017

A‐type K+ channels (IA channels) contribute to learning and memory mechanisms by regulating neuronal excitabilities in the CNS, and their expression level is targeted by Ca2+ influx via synaptic NMDA receptors (NMDARs) during long‐term potentiation (LTP). However, it is not clear how local synaptic Ca2+ changes induce IA downregulation throughout the neuron, extending from the active synapse to the soma. In this study, we tested if two major receptors of endoplasmic reticulum (ER), ryanodine (RyRs), and IP3 (IP3R) receptors, are involved in Ca2+‐mediated IA downregulation in cultured hippocampal neurons of rats. The downregulation of IA channels was induced by doubling the Ca2+ concentration in culture media (3.6 mM for 24 hrs) or treating with glycine (200 μM for 3 min) to induce chemical LTP (cLTP), and the changes in IA peaks were measured electrophysiologically by a whole‐cell patch. We confirmed that Ca2+ or glycine treatment significantly reduced IA peaks and that their effects were abolished by blocking NMDARs or voltage‐dependent Ca2+ channels (VDCCs). In this cellular processing, blocking RyRs (by ryanodine, 10 μM) but not IP3Rs (by 2APB, 100 μM) completely abolished IA downregulation, and the LTP observed in hippocampal slices was more diminished by ryanodine rather than 2APB. Furthermore, blocking RyRs also reduced Ca2+‐mediated PKA activation, indicating that sequential signaling cascades, including the ER and PKA, are involved in regulating IA downregulation. These results strongly suggest a possibility that RyR contribution and mediated IA downregulation are required to regulate membrane excitability as well as synaptic plasticity in CA3‐CA1 connections of the hippocampus. © 2017 Wiley Periodicals, Inc.
Further inquiry into characteristics of MJO in boreal winter
Authors: Chen Xiong , Li Chongyin , Tan Yanke
Published: May 2017

The characteristics of Madden–Julian Oscillation (MJO), especially over the equatorial western Pacific, during the boreal winter (November to March) have got a further investigation based on the reanalysis data. The MJO activity prevails over the equatorial Indian Ocean and western Pacific and its main active centres are in the Southern Hemisphere. The MJO also has the highest percentage in the atmospheric variability and strong interannual variability here. The MJO over the equatorial western Pacific shows a prominent interannual variability with a period of 2–8 years and an interdecadal variability with a period of 12–16 years. These variabilities of MJO are closely related to the intensity and duration of strong discrete MJO events over there. During the equatorial western Pacific MJO activity strong winter, the MJO is intensified throughout the tropics and its eastward propagation is more continuous, more coherent, and further east. Anomalous ascending motion and moisture convergence over the equatorial western Pacific could enhance the Walker circulation over the equatorial Pacific and favour the activity of MJO over the equatorial western Pacific. The further eastward propagation of MJO in strong MJO activity winter is mainly due to the strong moistening at the lower troposphere to the east of the MJO convection centre. This moistening is dominated by the vertical advection of moisture. In weak MJO activity winter, the above characteristics are reversed. Furthermore, the MJO activity over the Indian Ocean and Pacific has undergone several interdecadal changes in both of its intensity and propagation during the past 150 years.
Bamboo biochar does not affect paddy soil N2O emissions or source following slurry or mineral fertilizer amendment—a15N tracer study
Authors: Case Sean D. C. , Uno Hikaru , Nakajima Yasuhiro , Stoumann Jensen Lars , Akiyama Hiroko
Published: May 2017

Nitrogen (N)‐containing fertilizers, such as slurry and ammonium nitrate (NH4NO3), can significantly increase soil nitrous oxide (N2O) emissions following addition to agricultural soil. Biochar amendment to soil has been observed to suppress N2O emissions in a number of studies. However, the effect varies depending on many factors, including when biochar is added to soil concurrently with organic or mineral fertilizers. An incubation was conducted in which bamboo biochar (created at 800°C) was added to an ex‐rice paddy soil (1% rate) concurrently with dairy cattle slurry or NH4NO3(100 mg N kg−1). At three time points, following biochar amendment,15N‐labelled NH4NO3(50 mg N kg−1) was added to the soil to determine the N2O emissions derived from nitrification and denitrification in the 24 h that followed (at 70% water filled pore space; days 0, 7, and 28). Nitrous oxide emissions from slurry‐amended soils were much greater than those from NH4NO3‐amended soils, as well as the proportion of soil N2O emissions derived from denitrification. Biochar amendment did not significantly affect soil N2O emissions or consistently affect the percentage of soil N2O emissions derived from nitrification in slurry or NH4NO3‐amended treatments. The lack of N2O‐emission suppression with biochar amendment may have been due to the relatively‐low addition rate of a biochar that had a low content of volatile organic carbons and redox‐reactive organic/inorganic compounds, and did not greatly increase the pH of the acidic soil (pH 5). These results suggest that bamboo biochar produced at such a high temperature may not be suitable for mitigation of soil N2O emissions.
Sonography for an Imperforate Anus: Approach, Timing of the Examination, and Evaluation of the Type of Imperforate Anus and Associated Anomalies
Authors: Hosokawa Takahiro , Yamada Yoshitake , Tanami Yutaka , Hattori Shinya , Sato Yumiko , Tanaka Yujiro , Kawashima Hiroshi , Hsokawa Mayumi , Oguma Eiji
Published: May 2017

This systematic review outlines the role of sonography in an imperforate anus. The diagnostic performance for type of imperforate anus is superior on the day after birth than that on the day of birth by using the pouch‐perineum distance. Three approaches can be used (suprapubic, infracoccygeal, and perineal). The pouch‐perineum distance, fistula location, and relationship between the puborectalis muscle and distal rectal pouch are useful for classifying the type of imperforate anus. However, the pouch‐perineum distance measured has an overlap between the low and high/intermediate types of imperforate anus. Sonography can be useful for some of the associated anomalies and helpful for surgeons in some cases.
Invasive invertebrate predator, Bythotrephes longimanus, reverses trophic cascade in a north‐temperate lake
Authors: Walsh Jake R. , Lathrop Richard C. , Vander Zanden M. Jake
Published: May 2017

Trophic cascades can determine the structure of aquatic food webs, a role often used to manage water quality in lakes. However, trophic cascades are subject to multiple interacting drivers of environmental change. For example, invasive species can dramatically alter food webs, though we know less about invasive species effects on managed trophic cascades. Here, we investigate the changing food web dynamics of Lake Mendota (Wisconsin, U.S.A.) over a 40‐yr time period. Piscivore stocking (biomanipulation) beginning in 1988 coupled with a 1987 die‐off of cisco (the dominant zooplanktivore) led to decreased zooplanktivory that cascaded to increases in the large‐bodied herbivorous zooplankton Daphnia pulicaria and greater water clarity. In 2009, the invasive spiny water flea Bythotrephes longimanus was first detected in Lake Mendota and soon reached record densities. As a result of this invasive invertebrate predator, zooplanktivory increased to 47% of the earlier cisco period. Concomitant with the spiny water flea population explosion were declines in D. pulicaria and water clarity as both exhibited a strong negative relationship to zooplanktivory across the 40‐yr time series. We argue that the trophic cascade of 1987–1988 created an environment of high food resources and low fish planktivory that promoted the proliferation of Bythotrephes as it functionally replaced cisco in Lake Mendota's food web. Our results highlight how a manipulated, eutrophic lake was vulnerable to adverse impacts by invasive species, calling attention to the importance of understanding interactions among drivers of environmental change.
Determination of glycolic acid in natural seawater by liquid chromatography coupled with triple quadrupole mass spectrometry
Authors: Hong Haizheng , Li Weiying , Li Xiaolin , Huang Bangqin , Shi Dalin
Published: May 2017

Glycolic acid, which is produced during photorespiration, is one of the major components of dissolved organic matter released by phytoplankton, comprising up to 40% of their daily primary productivity. However, the sensitivity of existing methods does not allow for accurate measurement of glycolic acid levels in oligotrophic seawater. In this study, we present a straightforward, robust, and sensitive liquid chromatography‐mass spectrometry (LC‐MS) method to quantify glycolic acid in natural seawater following liquid‐liquid extraction, requiring only a small sample size (25 mL seawater). The method has a highly sensitive detection limit of 9 nM, at least fivefold lower than existing methods. This approach was successfully applied to the analysis of seawater samples collected from both eutrophic and oligotrophic marine environments. The results showed that glycolic acid concentrations in natural seawater are positively correlated with chlorophyll a concentrations, indicating that phytoplankton contribute significantly to glycolic acid production in marine environments. As glycolic acid is an important carbon and energy source for marine bacteria, the method developed within this study allows further investigation into the rates of its release and uptake by phytoplankton and heterotrophic bacteria, respectively, as well as the role it plays in phytoplankton–bacteria interactions.
Self‐Healing Gelatin Hydrogels Cross‐Linked by Combining Multiple Hydrogen Bonding and Ionic Coordination
Authors: Zhang Guangzhao , Lv Lei , Deng Yonghong , Wang Chaoyang
Published: May 2017

Self‐healing hydrogels have been studied by many researchers via multiple cross‐linking approaches including physical and chemical interactions. It is an interesting project in multifunctional hydrogel exploration that a water soluble polymer matrix is cross‐linked by combining the ionic coordination and the multiple hydrogen bonds to fabricate self‐healing hydrogels with injectable property. This study introduces a general procedure of preparing the hydrogels (termed gelatin‐UPy‐Fe) cross‐linked by both ionic coordination of Fe3+ and carboxyl group from the gelatin and the quadruple hydrogen bonding interaction from the ureido‐pyrimidinone (UPy) dimers. The gelatin‐UPy‐Fe hydrogels possess an excellent self‐healing property. The effects of the ionic coordination of Fe3+ and quadruple hydrogen bonding of UPy on the formation and mechanical behavior of the prepared hydrogels are investigated. In vitro drug release of the gelatin‐UPy‐Fe hydrogels is also observed, giving an intriguing glimpse into possible biological applications.

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Apurinic/apyrimidinic endonuclease 1 (APE1/Ref‐1) overexpression is an independent prognostic marker in prostate cancer without TMPRSS2:ERG fusion
Authors: Juhnke Manuela , Heumann Asmus , Chirico Viktoria , Höflmayer Doris , Menz Anne , Hinsch Andrea , Hube‐Magg Claudia , Kluth Martina , Lang Dagmar S. , Möller‐Koop Christina , Sauter Guido , Simon Ronald , Beyer Burkhard , Pompe Raisa , Thederan Imke , Schlomm Thorsten , Luebke Andreas M.
Published: May 2017

Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9763 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data. The comparison with normal prostate tissue revealed an upregulation of APE1 in cancer samples. APE1 immunostaining was considered weak in 20.2%, moderate in 36.7%, and strong in 33.4% of cancers. Strong APE1 expression was markedly more frequent in prostate cancers harboring the TMPRSS2:ERG fusion (52.9%) than in ERG‐negative cancers (19.1%, P < 0.0001). Significant associations with Gleason grade, tumor stage, tumor grade, and early biochemical recurrence (P < 0.0001 each) were largely limited to ERG‐negative tumors. Multivariable analysis revealed that the prognostic value of APE1 upregulation in ERG‐negative prostate cancers was independent from established histopathological and clinical parameters. In conclusion, the results of our study demonstrate that APE1 overexpression is an independent prognostic marker, but exclusively in ERG‐negative prostate cancers.
Development of Safe Drugs: The hERG Challenge
Authors: Kalyaanamoorthy Subha , Barakat Khaled H.
Published: May 2017

Drug‐induced blockade of human ether‐a‐go‐go‐related gene (hERG) remains a major impediment in delivering safe drugs to the market. Several drugs have been withdrawn from the market due to their severe cardiotoxic side effects triggered by their off‐target interactions with hERG. Thus, identifying the potential hERG blockers at early stages of lead discovery is fast evolving as a standard in drug design and development. A number of in silico structure‐based models of hERG have been developed as a low‐cost solution to evaluate drugs for hERG liability, and it is now agreed that the hERG blockers bind at the large central cavity of the channel. Nevertheless, there is no clear convergence on the appropriate drug binding modes against the channel. The proposed binding modes differ in their orientations and interpretations on the role of key residues in the channel. Such ambiguities in the modes of binding remain to be a significant challenge in achieving efficient computational predictive models and in saving many important already Food and Drug Administration approved drugs. In this review, we discuss the spectrum of reported binding modes for hERG blockers, the various in silico models developed for predicting a drug's affinity to hERG, and the known successful optimization strategies to avoid off‐target interactions with hERG.
A new analysis for fractional model of regularized long‐wave equation arising in ion acoustic plasma waves
Authors: Kumar Devendra , Singh Jagdev , Baleanu Dumitru
Published: May 2017

The key purpose of the present work is to constitute a numerical scheme based on q‐homotopy analysis transform method to examine the fractional model of regularized long‐wave equation. The regularized long‐wave equation explains the shallow water waves and ion acoustic waves in plasma. The proposed technique is a mixture of q‐homotopy analysis method, Laplace transform, and homotopy polynomials. The convergence analysis of the suggested scheme is verified. The scheme provides
and n‐curves, which show that the range convergence of series solution is not a local point effects and elucidate that it is superior to homotopy analysis method and other analytical approaches. Copyright © 2017 John Wiley & Sons, Ltd.
Numerical and asymptotic study of non‐axisymmetric magnetohydrodynamic boundary layer stagnation‐point flows
Authors: Kudenatti Ramesh B. , Kirsur Shreenivas R.
Published: May 2017

Both numerical and asymptotic analyses are performed to study the similarity solutions of three‐dimensional boundary‐layer viscous stagnation point flow in the presence of a uniform magnetic field. The three‐dimensional boundary‐layer is analyzed in a non‐axisymmetric stagnation point flow, in which the flow is developed because of influence of both applied magnetic field and external mainstream flow. Two approaches for the governing equations are employed: the Keller‐box numerical simulations solving full nonlinear coupled system and a corresponding linearized system that is obtained under a far‐field behavior and in the limit of large shear‐to‐strain‐rate parameter (λ). From these two approaches, the flow phenomena reveals a rich structure of new family of solutions for various values of the magnetic number and λ. The various results for the wall stresses and the displacement thicknesses are presented along with some velocity profiles in both directions. The analysis discovered that the flow separation occurs in the secondary flow direction in the absence of magnetic field, and the flow separation disappears when the applied magnetic field is increased. The flow field is divided into a near‐field (due to viscous forces) and far‐field (due to mainstream flows), and the velocity profiles form because of an interaction between two regions. The magnetic field plays an important role in reducing the thickness of the boundary‐layer. A physical explanation for all observed phenomena is discussed. Copyright © 2017 John Wiley & Sons, Ltd.
Efficient experimental designs for isotropic generalized diffusion tensor MRI (IGDTI)
Authors: Avram Alexandru V. , Sarlls Joelle E. , Hutchinson Elizabeth , Basser Peter J.
Published: May 2017

Purpose

We propose a new generalized diffusion tensor imaging (GDTI) experimental design and analysis framework for efficiently measuring orientationally averaged diffusion‐weighted images (DWIs), which remove bulk signal modulations attributed to diffusion anisotropy and quantify isotropic higher‐order diffusion tensors (HOT). We illustrate how this framework accelerates the clinical measurement of rotation‐invariant tissue microstructural parameters derived from HOT, such as the HOT‐Trace and the mean t‐kurtosis.

Theory and Methods

For a large range of b‐values, we compare orientationally averaged DWIs measured with high angular resolution diffusion imaging to those obtained with the proposed isotropic GDTI (IGDTI) experimental design. We compare rotation‐invariant microstructural parameters measured with IGDTI to those derived from HOTs measured explicitly with GDTI.

Results

In both fixed‐brain microimaging and in vivo clinical experiments, IGDTI accurately quantifies mean apparent diffusion coefficient (mADC)‐weighted DWIs over a wide range of b‐values and allows efficient computation of HOT‐derived scalar tissue parameters from a small number of DWIs.

Conclusions

IGDTI provides direct and accurate estimates of orientationally averaged tissue water mobilities over a wide range of b‐values. This efficient method may enable new, sensitive, and quantitative assessments for clinical applications in which changes in mADC can be observe,d such as detecting and characterizing stroke, cancers, and neurodegenerative diseases. Magn Reson Med 79:180–194, 2018. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Quantification and tracking of genetically engineered dendritic cells for studying immunotherapy
Authors: Bar‐Shir Amnon , Alon Lina , Korrer Michael J. , Lim Hong Seo , Yadav Nirbhay N. , Kato Yoshinori , Pathak Arvind P. , Bulte Jeff W.M. , Gilad Assaf A.
Published: May 2017

Purpose

Genetically encoded reporters can assist in visualizing biological processes in live organisms and have been proposed for longitudinal and noninvasive tracking of therapeutic cells in deep tissue. Cells can be labeled in situ or ex vivo and followed in live subjects over time. Nevertheless, a major challenge for reporter systems is to identify the cell population that actually expresses an active reporter.

Methods

We have used a nucleoside analog, pyrrolo‐2′‐deoxycytidine, as an imaging probe for the putative reporter gene, Drosophila melanogaster 2′‐deoxynucleoside kinase. Bioengineered cells were imaged in vivo in animal models of brain tumor and immunotherapy using chemical exchange saturation transfer MRI. The number of transduced cells was quantified by flow cytometry based on the optical properties of the probe.

Results

We performed a comparative analysis of six different cell lines and demonstrate utility in a mouse model of immunotherapy. The proposed technology can be used to quantify the number of labeled cells in a given region, and moreover is sensitive enough to detect less than 10,000 cells.

Conclusion

This unique technology that enables efficient selection of labeled cells followed by in vivo monitoring with both optical and MRI. Magn Reson Med 79:1010–1019, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Accelerated noncontrast‐enhanced 4‐dimensional intracranial MR angiography using golden‐angle stack‐of‐stars trajectory and compressed sensing with magnitude subtraction
Authors: Zhou Ziwu , Han Fei , Yu Songlin , Yu Dandan , Rapacchi Stanislas , Song Hee Kwon , Wang Danny J.J. , Hu Peng , Yan Lirong
Published: May 2017

Purpose

To evaluate the feasibility and performance of compressed sensing (CS) with magnitude subtraction regularization in accelerating non–contrast‐enhanced dynamic intracranial MR angiography (NCE‐dMRA).

Methods

A CS algorithm was introduced in NCE‐dMRA by exploiting the sparsity of the magnitude difference of the control and label images. The NCE‐dMRA data were acquired using golden‐angle stack‐of‐stars trajectory on six healthy volunteers and one patient with arteriovenous fistula. Images were reconstructed using (i) the proposed magnitude‐subtraction CS (MS‐CS); (ii) complex‐subtraction CS; (iii) independent CS; and (iv) view‐sharing with k‐space weighted image contrast (KWIC). The dMRA image quality was compared across the four reconstruction strategies. The proposed MS‐CS method was further compared with KWIC for temporal fidelity of depicting dynamic flow.

Results

The proposed MS‐CS method was able to reconstruct NCE‐dMRA images with detailed vascular structures and clean background. It provided better subjective image quality than the other two CS strategies (P < 0.05). Compared with KWIC, MS‐CS showed similar image quality, but reduced temporal blurring in delineating the fine distal arteries.

Conclusions

The MS‐CS method is a promising CS technique for accelerating NCE‐dMRA acquisition without compromising image quality and temporal fidelity. Magn Reson Med 79:867–878, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
The conventional tuning fork as a quantitative tool for vibration threshold
Authors: Alanazy Mohammed H. , Alfurayh Nuha A. , Almweisheer Shaza N. , Aljafen Bandar N. , Muayqil Taim
Published: May 2017

Introduction: This study was undertaken to describe a method for quantifying vibration when using a conventional tuning fork (CTF) in comparison to a Rydel‐Seiffer tuning fork (RSTF) and to provide reference values. Methods: Vibration thresholds at index finger and big toe were obtained in 281 participants. Spearman's correlations were performed. Age, weight, and height were analyzed for their covariate effects on vibration threshold. Reference values at the fifth percentile were obtained by quantile regression. Results: The correlation coefficients between CTF and RSTF values at finger/toe were 0.59/0.64 (P = 0.001 for both). Among covariates, only age had a significant effect on vibration threshold. Reference values for CTF at finger/toe for the age groups 20–39 and 40–60 years were 7.4/4.9 and 5.8/4.6 s, respectively. Reference values for RSTF at finger/toe for the age groups 20–39 and 40–60 years were 6.9/5.5 and 6.2/4.7, respectively. Discussion: CTF provides quantitative values that are as good as those provided by RSTF. Age‐stratified reference data are provided. Muscle Nerve 57: 49–53, 2018
Clinical comparison of intravesical hyaluronic acid and chondroitin sulfate therapies in the treatment of bladder pain syndrome/interstitial cystitis
Authors: Gülpınar Ömer , Esen Barış , Kayış Aytaç , Gökçe Mehmet İlker , Süer Evren
Published: May 2017

Introduction

Intravesical glucosaminoglycan (GAG) replacement therapies are commonly used in the treatment of bladder pain syndrome (BPS)/interstitial cystitis (IC). Different intravesical glucosaminoglycan products are currently available. In this prospective study, clinical efficacy of chondroitin sulfate and hyaluronic acid are compared in patients with BPS/IC.

Methods

Patients were randomized to CS and HA groups. All patients were evaluated for visual analogue pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), voiding diary for frequency/nocturia, and mean urine volume per void at the beginning of the therapy and after 6 months. All patients had a potassium sensitivity test (PST) initially. Wilcoxon and Mann‐Whitney U tests were used for statistical analysis.

Results

There were 21 patients in both groups. Mean age of patients in CS and HA groups were 47.10 and 48.90, respectively(P > 0.05). Before treatment, Parson's test was positive in 64.3% of patients (27/42) with no difference between groups. VAS of pain, ICSI, ICPI, frequency at 24 h and nocturia results have improved significantly at both treatment arms. Intravesical CS was also found superior to intravesical HA in terms of 24 h frequency, nocturia and ICPI (P < 0.05). No severe adverse effects were reported.

Conclusions

Data comparing clinical efficiencies of different GAG therapies are very limited. In this study, intravesical CS was found superior to intravesical HA in terms of 24 h frequency, nocturia and ICPI in patients with BPS/IC in short term follow‐up. To provide a definitive conclusion on superiority of one GAG therapy to others, further evaluation with long term follow up is required.
Rheological and thermal properties of exfoliated graphite nanoplatelets‐filled impact modified polypropylene nanocomposites
Authors: Erbas Kiziltas Esra , Duguay Alex J. , Kiziltas Alper , Nazari Behzad , Nader Jacques W. , Gardner Douglas J. , Rushing Todd S.
Published: May 2017

The objective of this research was to investigate the influence of exfoliated graphite nanoplatelets (xGnP) particle diameter, filler loading, and the addition of coupling agents on the rheological and thermal properties of xGnP‐filled impact modified polypropylene (IMPP) nanocomposites. xGnP‐filled IMPP composites were manufactured via melt mixing with and without the addition of polypropylene‐graft‐maleic anhydride (PP‐g‐MA). Particle diameter of xGnP had no significant effect on the melting (Tm) and crystallization (Tc) temperatures as well as degradation behavior of the composites. Storage modulus (E′) of the composites increased with increasing xGnP percent at high filler loadings and the incorporation of xGnP did not significantly affect the glass transition temperature, but filler loading does have a significant effect on the magnitude of the tan delta max peak values. The shear storage modulus (G′) of the composites with smaller diameter xGnP particles was lower than those of the composites with big diameter particle xGnP at lower frequencies. The higher the xGnP content of the composite, the higher the shear viscosity and the smaller particle diameter of xGnP results in lower viscosity values. Addition of a coupling agent decreased the melt viscosity of the xGnP‐filled nanocomposites and caused a slight reduction in the shear‐thinning behavior. POLYM. COMPOS., 39:E1512–E1519, 2018. © 2017 Society of Plastics Engineers
Refining estimates of prescription durations by using observed covariates in pharmacoepidemiological databases: an application of the reverse waiting time distribution
Authors: Støvring Henrik , Pottegård Anton , Hallas Jesper
Published: May 2017

Purpose

The study aimed to develop an automated method to estimate prescription durations in pharmacoepidemiological studies that may depend on patient and redemption characteristics.

Methods

We developed an estimation algorithm based on maximum likelihood estimation for the reverse waiting time distribution (WTD), which is the distribution of time from the last prescription of each patient within a time window to the end of the time window. The reverse WTD consists of two distinctly different components: one component for prevalent users and one for patients stopping treatment. We extended the model to allow parameters of the reverse WTD to depend on linear combinations of covariates to obtain estimates and confidence intervals for percentiles of the inter‐arrival density (time from one prescription to the subsequent). We applied the method to redemptions of warfarin, using the amount of drug filled, patient sex and patient age as covariates.

Results

The estimated prescription durations increased with redeemed amount and age. Women generally had longer prescription durations, which increased more with age than men. For 70‐year‐old women redeeming 300+ pills, we predicted a 95th percentile of the inter‐arrival density of 225 (95%CI: 201, 249) days. For 50‐year‐old men redeeming 100 pills, the corresponding prediction was 97 (88, 106) days.

Conclusions

The algorithm allows estimation of prescription durations based on the reverse WTD, which can depend upon observed covariates. Statistical uncertainty intervals and tests allow statistical inference on the influence of observed patient and prescription characteristics. The method may replace ad hoc decision rules. Copyright © 2017 John Wiley & Sons, Ltd.
Cellulose nanofibril‐reinforced polypropylene composites for material extrusion: Rheological properties
Authors: Wang Lu , Gardner Douglas J. , Bousfield Douglas W.
Published: May 2017

Polypropylene (PP) is not typically utilized in 3D printing material extrusion because PP shrinks and warps during the printing process. Cellulose nanofibrils (CNF) have the potential to make PP 3D printer processable and also enhance mechanical properties of PP printed parts. The rheological behavior of CNF‐PP composites during material extrusion requires study because it is different from injection molding and compression molding processes. This study revealed the effects of CNF contents (3 and 10 wt%) and maleic anhydride polypropylene (MAPP) coupling agent on the rheological properties of CNF–PP composites. Morphological analysis showed that CNF agglomerated during spray drying and a spherical structure was formed. Rheological tests showed that the elastic modulus, complex viscosity, viscosity, and transient flow shear stress of PP were increased by the addition of 10 wt% CNF, while the creep strain of PP was reduced. The damping factor and stress relaxation time remained the same when 10 wt% CNF was added to the PP. Incorporation of MAPP into the CNF–PP composites impacted the rheological properties of the CNF–PP composites. Flexural strength and modulus of PP were improved by 5.9% and 26.8% by adding 10 wt% CNF compared to the control. POLYM. ENG. SCI., 2017. © 2017 Society of Plastics Engineers
Cover Image, Volume 66, Issue 6
Authors: Purnama Aloisius R , Hennessy Matthew G , Vitale Alessandra , Cabral João T
Published: May 2017

The cover image, by Aloisius R Purnama et al., is based on the Research Article Coarse‐grained models for frontal photopolymerization with evolving conversion profile, DOI: 10.1002/pi.5344.

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EMPIRICAL SYNTHESIS OF THE EFFECT OF STANDARD ERROR OF MEASUREMENT ON DECISIONS MADE WITHIN BRIEF EXPERIMENTAL ANALYSES OF READING FLUENCY
Authors: Burns Matthew K. , Taylor Crystal N. , Warmbold‐Brann Kristy L. , Preast June L. , Hosp John L. , Ford Jeremy W.
Published: May 2017

Intervention researchers often use curriculum‐based measurement of reading fluency (CBM‐R) with a brief experimental analysis (BEA) to identify an effective intervention for individual students. The current study synthesized data from 22 studies that used CBM‐R data within a BEA by computing the standard error of measure (SEM) for the median data point from the baseline and intervention data. The median CBM‐R score from the intervention that the authors of each study identified as most effective fell within the SEM (68% confidence interval) of the baseline data approximately 30% of the time, but the ranges for the two author‐identified most effective interventions overlapped over 75% of the time. Extended analyses were consistent with the BEA results for approximately three‐fourths of the instances after considering the SEM of the baseline and intervention phases. Using matched passages did not improve the overlap of the ranges, but there was less overlap when the study used three data points per condition. Results emphasize the importance of considering SEM of CBM‐R data when comparing interventions within a BEA. Further implications for practice and future research are included.
Refolding the unfoldable: A systematic approach for renaturation ofBacillus circulansxylanase
Authors: Kötzler Miriam P. , McIntosh Lawrence P. , Withers Stephen G.
Published: May 2017

Xylanases are important polysaccharide‐cleaving catalysts for the pulp and paper, animal feeds and biofuels industries. They have also proved to be valuable model systems for understanding enzymatic catalysis, with one of the best studied being the GH11 xylanase fromBacillus circulans(Bcx). However, proteins from this class are very recalcitrant to refoldingin vitro. This both limits their high level expression in heterologous hosts, and prevents experimental approaches, such as peptide ligation or chemical modifications, to probe and engineer their stability and function. To solve this problem, a systematic screening approach was employed to identify suitable buffer conditions for renaturing Bcxin vitro. The fractional factorial screen employed identified starting conditions for refolding, which were then refined and developed into a generic protocol for renaturing preparative amounts of active Bcx in a 50–60% yield from inclusion bodies. The method is robust and proved equally proficient at refolding circularly permuted versions that carry cysteine mutations. This general approach should be applicable to related GH11 xylanases, as well as proteins adopting a similar β‐jellyroll fold, that are otherwise recalcitrant to refoldingin vitro.
Carbohydrate recognition by the rhamnose‐binding lectin SUL‐I with a novel three‐domain structure isolated from the venom of globiferous pedicellariae of the flower sea urchin Toxopneustes pileolus
Authors: Hatakeyama Tomomitsu , Ichise Ayaka , Unno Hideaki , Goda Shuichiro , Oda Tatsuya , Tateno Hiroaki , Hirabayashi Jun , Sakai Hitomi , Nakagawa Hideyuki
Published: May 2017

The globiferous pedicellariae of the venomous sea urchin Toxopneustes pileolus contains several biologically active proteins. We have cloned the cDNA of one of the toxin components, SUL‐I, which is a rhamnose‐binding lectin (RBL) that acts as a mitogen through binding to carbohydrate chains on target cells. Recombinant SUL‐I (rSUL‐I) was produced in Escherichia coli cells, and its carbohydrate‐binding specificity was examined with the glycoconjugate microarray analysis, which suggested that potential target carbohydrate structures are galactose‐terminated N‐glycans. rSUL‐I exhibited mitogenic activity for murine splenocyte cells and toxicity against Vero cells. The three‐dimensional structure of the rSUL‐I/l‐rhamnose complex was determined by X‐ray crystallographic analysis at a 1.8 Å resolution. The overall structure of rSUL‐I is composed of three distinctive domains with a folding structure similar to those of CSL3, a RBL from chum salmon (Oncorhynchus keta) eggs. The bound l‐rhamnose molecules are mainly recognized by rSUL‐I through hydrogen bonds between its 2‐, 3‐, and 4‐hydroxy groups and Asp, Asn, and Glu residues in the binding sites, while Tyr and Ser residues participate in the recognition mechanism. It was also inferred that SUL‐I may form a dimer in solution based on the molecular size estimated via dynamic light scattering as well as possible contact regions in its crystal structure.
Stationary D = 4 black holes in supergravity: The issue of real nilpotent orbits
Authors: Ruggeri Daniele , Trigiante Mario
Published: May 2017

The complete classification of the nilpotent orbits of SO(2,2)2 in the representation (2,2,2,2), achieved in , is applied to the study of multi‐center, asymptotically flat, extremal black hole solutions to the STU model. These real orbits provide an intrinsic characterization of regular single‐center solutions, which is invariant with respect to the action of the global symmetry group SO(4,4), underlying the stationary solutions of the model, and provide stringent regularity constraints on multi‐centered solutions. The known almost‐BPS and composite non‐BPS solutions are revisited in this setting. We systematically provide, for the relevant SO(2,2)2‐nilpotent orbits of the global Noether charge matrix, regular representatives thereof. This analysis unveils a composition law of the orbits according to which those containing regular multi‐centered solutions can be obtained as combinations of specific single‐center orbits defining the constituent black holes. Some of the SO(2,2)2‐orbits of the total Noether charge matrix are characterized as “intrinsically singular” in that they cannot contain any regular solution.
Profile of cell proliferation and apoptosis activated by the intrinsic and extrinsic pathways in the prostate of aging rats
Authors: Gonzaga Amanda C.R. , Campolina‐Silva Gabriel H. , Werneck‐Gomes Hipácia , Moura‐Cordeiro Júnia D. , Santos Letícia C. , Mahecha Germán A.B. , Morais‐Santos Mônica , Oliveira Cleida A.
Published: May 2017

BACKGROUND

Estrogens acting through the receptors ERα and ERβ participate in prostate normal growth and cancer. ERβ is highly expressed in the prostate epithelium, playing pro‐apoptotic, anti‐proliferative, and pro‐differentiation roles. Apoptosis is activated by the intrinsic pathway after castration and by the extrinsic pathway after ERβ agonist treatment. This differential activation of apoptotic pathways is important since a major problem in the treatment of prostate cancer is the recurrence of tumors after androgen withdrawal. However, a comprehensive study about the pattern of apoptosis in the aging prostate is lacking, a knowledge gap that we aimed to address herein.

METHODS

Cellular age‐related proliferative and apoptotic profiles of prostate tissue obtained from aging Wistar rats were evaluated. Cell death (caspase‐3, ‐8, ‐9, TNFα) was assessed by immunohistochemistry, immunofluorescence, and TUNEL. Cell proliferation (MCM7) and cell survival factors (ERK1/2, p‐ERK1/2, p‐Akt, and NF‐κB) were determined by immunohistochemistry.

RESULTS

As the rats aged, the number of proliferating cells gradually reduced in the normal epithelium of all prostate lobes, while increasing in focal areas of intraepithelial proliferation. Interestingly, in areas of intraepithelial proliferation, we observed a reduction in the number of cells positive for caspase‐3, ‐8, and ‐9. Regardless the animal's age, few prostate epithelial cells were positive for caspase‐3, caspase‐9, and TUNEL. In contrast, a progressive increase was seen in the positivity for caspase‐8, especially in the atrophic epithelium of ventral prostate, which coincided with a reduction in TNFα immunoreaction. However, morphology of most caspase‐8 positive cells suggests that they were not apoptotic. We also found reduced ERβ expression in the same areas. Possibly, low levels of the pro‐apoptotic inductors TNFα and ERβ direct caspase‐8 activity to an alternative pro‐survival role in the atrophic epithelium. This hypothesis is supported by the increased expression of the key survival factors (ERK1/2, p‐ERK1/2, p‐Akt, and NF‐κB) in these areas.

CONCLUSIONS

Our findings reveal that, as the animals age, there is an increase of proliferation in restricted areas of the prostate epithelium, and a concomitant reduction of the apoptosis rate with an increase in cell survival induced by caspase‐8, indicating a focused and spontaneous disruption of tissue homeostasis.