bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal microbial single‐cell analysis using a high‐throughput microfluidics cultivation platform
Authors: Grünberger Alexander , Probst Christopher , Helfrich Stefan , Nanda Arun , Stute Birgit , Wiechert Wolfgang , von Lieres Eric , Nöh Katharina , Frunzke Julia , Kohlheyer Dietrich
Published: September 2015

Cell‐to‐cell heterogeneity typically evolves due to a manifold of biological and environmental factors and special phenotypes are often relevant for the fate of the whole population but challenging to detect during conventional analysis. We demonstrate a microfluidic single‐cell cultivation platform that incorporates several hundred growth chambers, in which isogenic bacteria microcolonies growing in cell monolayers are tracked by automated time‐lapse microscopy with spatiotemporal resolution. The device was not explicitly developed for a specific organism, but has a very generic configuration suitable for various different microbial organisms. In the present study, we analyzed Corynebacterium glutamicum microcolonies, thereby generating complete lineage trees and detailed single‐cell data on division behavior and morphology in order to demonstrate the platform's overall capabilities. Furthermore, the occurrence of spontaneously induced stress in individual C. glutamicum cells was investigated by analyzing strains with genetically encoded reporter systems and optically visualizing SOS response. The experiments revealed spontaneous SOS induction in the absence of any external trigger comparable to results obtained by flow cytometry (FC) analyzing cell samples from conventional shake flask cultivation. Our microfluidic setup delivers detailed single‐cell data with spatial and temporal resolution; complementary information to conventional FC results. © 2015 International Society for Advancement of Cytometry
Intracellular flow cytometry may be combined with good quality and high sensitivity RT‐qPCR analysis
Authors: Sandstedt Mikael , Jonsson Marianne , Asp Julia , Dellgren Göran , Lindahl Anders , Jeppsson Anders , Sandstedt Joakim
Published: September 2015

Flow cytometry (FCM) has become a well‐established method for analysis of both intracellular and cell‐surface proteins, while quantitative RT‐PCR (RT‐qPCR) is used to determine gene expression with high sensitivity and specificity. Combining these two methods would be of great value. The effects of intracellular staining on RNA integrity and RT‐qPCR sensitivity and quality have not, however, been fully examined. We, therefore, intended to assess these effects further. Cells from the human lung cancer cell line A549 were fixed, permeabilized and sorted by FCM. Sorted cells were analyzed using RT‐qPCR. RNA integrity was determined by RNA quality indicator analysis. A549 cells were then mixed with cells of the mouse cardiomyocyte cell line HL‐1. A549 cells were identified by the cell surface marker ABCG2, while HL‐1 cells were identified by intracellular cTnT. Cells were sorted and analyzed by RT‐qPCR. Finally, cell cultures from human atrial biopsies were used to evaluate the effects of fixation and permeabilization on RT‐qPCR analysis of nonimmortalized cells stored prior to analysis by FCM. A large amount of RNA could be extracted even when cells had been fixed and permeabilized. Permeabilization resulted in increased RNA degradation and a moderate decrease in RT‐qPCR sensitivity. Gene expression levels were also affected to a moderate extent. Sorted populations from the mixed A549 and HL‐1 cell samples showed gene expression patterns that corresponded to FCM data. When samples were stored before FCM sorting, the RT‐qPCR analysis could still be performed with high sensitivity and quality. In summary, our results show that intracellular FCM may be performed with only minor impairment of the RT‐qPCR sensitivity and quality when analyzing sorted cells; however, these effects should be considered when comparing RT‐qPCR data of not fixed samples with those of fixed and permeabilized samples. © 2015 International Society for Advancement of Cytometry
Data Location Optimization for Improvement of Tiered Storage Performance
Authors: HAYASHI SHINICHI , KOMODA NORIHISA
Published: September 2015

We propose a new method for tiered storage and evaluate its characteristics. In this method, the fast tier is divided into two areas and the data in each area are managed on the basis of two I/O (input/output) measurement periods. When I/Os to these areas increase, the proposed method allocates the frequently accessed areas to a fast tier in advance, thereby improving storage I/O performance. We evaluate the proposed method by simulating storage I/Os and data migration between tiers. When I/O locality is high or frequently accessed areas rarely move, the proposed method is more effective and improves storage I/O performance by up to 44%.
Calculation of Whole‐Body Average SARs in Pregnant Woman and Child Simultaneously Exposed to Multiple Radio‐Frequency Waves in Real Environment
Authors: ASAYAMA RYOTA , WANG JIANQING , FUJIWARA OSAMU
Published: September 2015

There are few published papers on the whole‐body average specific absorption rates (WBA‐SARs) in humans for simultaneous exposure to multiple radio frequencies (RFs). In order to evaluate human safety of radiowaves in real environments, in this paper we calculate the WBA‐SARs in models of a pregnant woman and 3‐year‐old child for multiple RF exposure, using measured results on electric field intensities from multiple base station antennas installed for cellular phones with four different radiowave frequencies in an underground shopping mall and with five radiowave frequencies in the neighborhood of an elementary school. The Japan Ministry of Internal Affairs and Communications officially reported these data in 2008. Statistical analyses show that the squared sum ratio of the measured electric field to the corresponding Japanese guideline for the general public is smaller than one‐hundredth and one‐thousand at most in the underground shopping mall and elementary school areas, respectively. As a result, we found that the WBA‐SARs in the pregnant woman and 3‐year‐old child models calculated at each of the frequencies for base station antennas in both areas are significantly lower than the The International Commission on Non‐Ionizing Radiation Protection (ICNIRP) basic restriction (0.08 W/kg) for the general public, and that the sum of the WBA‐SARs never exceeds one‐hundredth of 0.08 W/kg for simultaneous exposure to multiple RF.
Analysis of Offshore Software Development by Process Growth Visualization
Authors: ICHINOTSUBO TAKEO , NAKAMURA YU , SAGA RYOSUKE , TSUJI HIROSHI
Published: September 2015

To create criteria for the activities involved in offshore software development, this paper proposes a method to visualize the status of an organization. The basic premises in this research are that there are 12 capabilities and each capability has five levels. First, this paper introduces a knowledge management system called SPICE, which has a visualization function. The function includes the growth path of an individual, the growth path of a group, and a dependency structure. Then, to explain the use of method in the realm of offshore software development, this paper describes an experimental analysis and the accompanying visualization. The future possibilities of the method are also examined in detail.
Analysis of TV Viewing Modes Based on Stress Coping Style
Authors: WATANUKI TAKUYA , NOZAWA AKIO
Published: September 2015

In this research, based on the stress coping style as expressed by hemodynamic parameters, we evaluated the modes of television viewing with the aim of estimating different modes of watching television. The central nervous system was assessed by means of electroencephalograms (EEG). The autonomic nervous system was assessed using the nasal skin temperature (NST) and the heart rate variability (HRV) with spectral analysis. In the spectral analysis of the HRV, the high‐frequency components (HF) were evaluated. The cardiovascular system was assessed using the mean pressure (MP), the heart rate (HR), the stroke volume (SV), the cardiac output (CO), and the total peripheral resistance (TPR). The multiple mood scale (MMS) and visual analog scale (VAS) were administered to evaluate psychological status. It was found that modes of television viewing could not be distinguished using only the television content preference. It became clear that the modes of television viewing could be distinguished on the basis of the stress coping style using hemodynamic parameters.
[NaCu(2,4‐HPdc)(2,4‐Pdc)] Mixed Metal–Organic Framework as a Heterogeneous Catalyst
Authors: Larrea Edurne S. , Fernández de Luis Roberto , Orive Joseba , Iglesias Marta , Arriortua María I.
Published: September 2015

The synthesis of a new mixed metal–organic framework (M′MOF) has been accomplished by the metalloligand approach. [NaCu(2,4‐HPdc)(2,4‐Pdc)] (2,4‐H2Pdc = pyridine‐2,4‐dicarboxylic acid) has been obtained from the hydrothermal reaction of the metalloligand [Cu(2,4‐HPdc)2(H2O)2] NaOH, and a transition metal salt. [NaCu(2,4‐HPdc)(2,4‐Pdc)] is isostructural to [CuMn(2,4‐Pdc)2] and crystallizes in the triclinic space group P$\bar {1}$. The 3D structure is built up from [Cu(2,4‐HPdc)2(H2O)2] metalloligands and [NaO6] octahedra in a pcu α‐Po‐like uninodal six‐connected net. The compound is stable to 290 °C, and its crystal structure undergoes a 3 % volume expansion between room temperature and thermal decomposition. The unsaturated CuII centers at the surface act as a heterogeneous Lewis acid catalyst for the cyanosilylation of aldehydes and Knoevenagel C–C bond‐forming reactions. The catalytic activity has been compared with those of other copper(II) porous metal–organic frameworks such as HKUST‐1 and MOF‐74.
Mechanism of CO2 Fixation by IrI–X Bonds (X = OH, OR, N, C)
Authors: Vummaleti Sai Vikrama Chaitanya , Talarico Giovanni , Nolan Steven P. , Cavallo Luigi , Poater Albert
Published: September 2015

Density functional theory calculations have been used to investigate the CO2 fixation mechanism proposed by Nolan et al. for the IrI complex [Ir(cod)(IiPr)(OH)] (1; cod = 1,5‐cyclooctadiene; IiPr = 1,3‐diisopropylimidazol‐2‐ylidene) and its derivatives. For 1, our results suggest that CO2 insertion is the rate‐limiting step rather than the dimerization step. Additionally, in agreement with the experimental results, our results show that CO2 insertion into the Ir–OR1 (R1 = H, methyl, and phenyl) and Ir–N bonds is kinetically facile, and the calculated activation energies span a range of only 12.0–23.0 kcal/mol. Substantially higher values (35.0–50.0 kcal/mol) are reported for analogous Ir–C bonds.
High‐throughput techniques to evaluate the effect of ligand density for impurity separations with multimodal cation exchange resins
Authors: Welsh John P. , Bao Haiying , Barlow Kenneth , Pollard Jennifer M. , Brekkan Eggert , Lacki Karol M. , Linden Thomas O. , Roush David J.
Published: September 2015

Scale‐down, high‐throughput screening techniques are well on their way to becoming a commodity in downstream bioprocess development, especially for the rapid development of chromatography process steps. This work used both resin slurry plate and miniature column high‐throughput screening methodologies to identify the best resin properties for mAb separations utilizing a multimodal chromatography ligand interaction. A ligand with both cation exchange and hydrophobic interaction properties was studied at several ligand densities and compared to a commercially available multimodal resin with a larger particle size at high ligand density. The resins were screened with mAbs containing distinct process impurities (aggregates and a hydrophobic variant), and optimized conditions provided more than a log of clearance of both types of impurities for the different resins screened. These studies reveal that while a smaller particle size is generally preferable, optimal ligand densities can be different depending on the properties of both the mAb and impurity studied.
Self‐poled Efficient Flexible “Ferroelectretic” Nanogenerator: A New Class of Piezoelectric Energy Harvester
Authors: Ghosh Sujoy Kumar , Sinha Tridib Kumar , Mahanty Biswajit , Mandal Dipankar
Published: September 2015

Superior ferro‐ and piezo‐electret properties in a self‐poled, porous hybrid ferroelectretic polymer nanocomposite film for next‐generation device paradigms is introduced by in situ generation of platinum (Pt) nanoparticles (NPs) embedded in poly(vinylidenefluoride‐co‐hexafluoropropylene) P(VDF–HFP). The cooperative functionality between the self‐polarized β‐phase and the micropores as charge trapping sites is realized by using a simple solvent evaporation method. As a consequence, the resulting film exhibits extraordinary ferroelectretic behavior, as demonstrated by the superior electrical square‐shaped hysteresis loop with large remnant polarization (Pr≈61.7 μC cm−2), piezoelectric charge coefficient (d33∼−686 pC N−1), and ultrahigh dielectric properties (εr=2678, tan δ=0.79 at 1 kHz). A new type of ferroelectretic nanogenerator (FTNG) is fabricated using a flexible hybrid nanocomposite film that effectively converts the applied mechanical energy into electrical energy upon compressive normal stress (e.g., by actuating with a human finger). The 18 V of the open‐circuit output voltage with expected 17.7 μA short‐circuit current are generated from the FTNG under 4 MPa of normal stress amplitude. The high piezoelectric energy conversion efficiency (ηpiezo≈0.2 %) of the FTNG shows that the hybrid polymer nanocomposite film is well suited for the next generation of piezoelectric‐based energy harvesters. The operation of more than 50 blue LEDs, 25 green LEDs, and several capacitors without any subsidiary batteries is demonstrated using the FTNG.
Diagnosed Anxiety Disorders and the Risk of Subsequent Anorexia Nervosa: A Danish Population Register Study
Authors: Meier Sandra M. , Bulik Cynthia M. , Thornton Laura M. , Mattheisen Manuel , Mortensen Preben B. , Petersen Liselotte
Published: September 2015

Anxiety disorders and anorexia nervosa are frequently acknowledged to be highly comorbid conditions, but still, little is known about the clinical and aetiological cohesion of specific anxiety diagnoses and anorexia nervosa. Using the comprehensive Danish population registers, we aimed to determine the risk of anorexia nervosa in patients with register‐detected severe anxiety disorders. We also explored whether parental psychopathology was associated with offspring's anorexia nervosa. Anxiety disorders increased the risk of subsequent anorexia nervosa, with the highest risk observed in obsessive–compulsive disorder. Especially, male anxiety patients were at an increased risk for anorexia nervosa. Furthermore, an increased risk was observed in offspring of fathers with panic disorder. A diagnosis of an anxiety disorder, specifically obsessive–compulsive disorder, constitutes a risk factor for subsequent diagnosis of anorexia nervosa. These observations support the notion that anxiety disorders and anorexia nervosa share etiological mechanisms and/or that anxiety represents one developmental pathway to anorexia nervosa. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.
How do hydrologic modeling decisions affect the portrayal of climate change impacts?
Authors: Mendoza Pablo A. , Clark Martyn P. , Mizukami Naoki , Gutmann Ethan D. , Arnold Jeffrey R. , Brekke Levi D. , Rajagopalan Balaji
Published: September 2015

End users face a range of subjective decisions when evaluating climate change impacts on hydrology, but the importance of these decisions is rarely assessed. In this paper, we evaluate the implications of hydrologic modelling choices on projected changes in the annual water balance, monthly simulated processes, and signature measures (i.e. metrics that quantify characteristics of the hydrologic catchment response) under a future climate scenario. To this end, we compare hydrologic changes computed with four different model structures – whose parameters have been obtained using a common calibration strategy – with hydrologic changes computed with a single model structure and parameter sets from multiple options for different calibration decisions (objective function, local optima, and calibration forcing dataset). Results show that both model structure selection and the parameter estimation strategy affect the direction and magnitude of projected changes in the annual water balance, and that the relative effects of these decisions are basin dependent. The analysis of monthly changes illustrates that parameter estimation strategies can provide similar or larger uncertainties in simulations of some hydrologic processes when compared with uncertainties coming from model choice. We found that the relative effects of modelling decisions on projected changes in catchment behaviour depend on the signature measure analysed. Furthermore, parameter sets with similar performance, but located in different regions of the parameter space, provide very different projections for future catchment behaviour. More generally, the results obtained in this study prompt the need to incorporate parametric uncertainty in multi‐model frameworks to avoid an over‐confident portrayal of climate change impacts. Copyright © 2015 John Wiley & Sons, Ltd.
Remodeling ofECMpatch into functional myocardium in an ovine model: A pilot study
Authors: Scully Brandi B. , Fan Christopher , Grigoryan Bagrat , Jacot Jeffrey G. , Vick G. W. , Kim Jeffrey J. , Fraser Charles D. , Grande‐Allen K. J. , Morales David L. S.
Published: September 2015

Background

Previous studies have demonstrated that surgical patches comprised of small intestinal submucosa‐derived extracellular matrix (ECM) have biological remodeling potential. This pilot study investigated histological, mechanical, and bioelectrical properties of an ECM patch implanted in the ovine right‐ventricular outflow tract (RVOT).

Materials and Methods

ECM patches (2 × 2 cm2) were implanted in four Western Range sheep (wether males, 37–49 kg, age <1 year) and explanted at 5 months (n = 2) and 8 months (n = 2).In vivoanalysis included epicardial echocardiography and contact electrical mapping. Optical mapping was used to map electrical activity of two hearts on a Langendorff preparation. Mechanical testing quantified stiffness. Histological stains characterized structure, neovascularization, and calcification; immunohistochemistry (IHC) assessed cell phenotype.

Results

In vivoanalysis showed that ECM patch tissue was contractile by M‐mode and two‐dimensional echocardiographic evaluation.In vivoelectrical mapping, and optical mapping confirmed that ECM conducted an organized electrical signal. Mechanical testing of native and ECM patched RVOT tissue showed an elastic modulus of the implanted patch comparable to native tissue stiffness.

Conclusions

At 5 and 8 months, the ECM had undergone extracellular matrix remodeling and neovascularization without calcification. The ECM was populated with locally aligned muscle cells positive for sarcomeric alpha‐actinin, CD45, and troponin I and T. In sheep, the ECM patch appears to have the potential of remodeling to resemble native, functional ventricular tissue as evidenced by histological, mechanical, and electrical properties. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1713–1720, 2016.
Uniform and electrically conductive biopolymer‐doped polypyrrole coating for fibrousPLA
Authors: Hiltunen M. , Pelto J. , Ellä V. , Kellomäki M.
Published: September 2015

Three‐dimensional, fibrous scaffolds can be easily fabricated from polylactide (PLA) using melt spinning and textile techniques. However, the surface properties of PLA scaffolds are not ideal for tissue engineering purposes. Furthermore, electrically conducting scaffolds are required to deliver electrical stimulation to cells. In this study, uniform, electrically conducting polypyrrole (PPy) coatings were fabricated on biodegradable PLA fibers. Biopolymer dopants—hyaluronic acid (HA) and chondroitin sulfate (CS)—were compared, and a PPy/CS composition was analyzed further. The effect of the oxidative polymerization conditions on the PLA fibers and CS counterion was studied. Furthermore, the initial molecular weight of CS and its degree of polymerization were determined. Our experiments showed that the molecular weight of CS decreases under oxidizing conditions but that the decay is not significant with the short polymerization process we used. The coating process was transferred to nonwoven PLA fabrics, and the stability of PPy/CS coating was studied duringin vitroincubation in phosphate buffer solution at physiological temperature. The conductivity and surface roughness of the coating decayed during the 20‐day incubation. The mechanical strength, however, remained at the initial level. Thus, the fabricated structures are suitable for short‐term electrical stimulation adequate to promote cell functions in specific cases. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1721–1729, 2016.
Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases
Authors: Gregson Celia L , Wheeler Lawrie , Hardcastle Sarah A , Appleton Louise H , Addison Kathryn A , Brugmans Marieke , Clark Graeme R , Ward Kate A , Paggiosi Margaret , Stone Mike , Thomas Joegi , Agarwal Rohan , Poole Kenneth ES , McCloskey Eugene , Fraser William D , Williams Eleanor , Bullock Alex N , Davey Smith George , Brown Matthew A , Tobias Jon H , Duncan Emma L
Published: September 2015

High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52-kb intronic deletion 3′). Family members were assessed for HBM segregation with identified variants. Three-dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM (∼prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non-LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5-HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST-LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z-scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z-scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only account for a very small proportion (∼3%) of HBM individuals, suggesting the great majority are explained by either unknown monogenic causes or polygenic inheritance. © 2015 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
New Pyrimidine‐2‐thiones from Reactions of Amidrazonethiols with 2‐Amino‐1,1,2‐ethenetricarbonitrile and Investigation of Their Antitumor Activity
Authors: Elkanzi N. A. A. , Morsy Nesrin M. , Aly Ashraf A. , Brown Alan B. , Ramadan Mohamed
Published: September 2015

Reactions of thiosemicarbazones with 2‐amino‐1,1,2‐ethenetricarbonitrile were reported. The reaction occurred in the amidrazonyl site, and new pyrimidine‐2‐thiones were obtained. The reaction mechanism was discussed. The structure of products was elucidated by MS, IR, and NMR spectra together with elemental analyses. The antitumor activity was evaluated against one tumor cell line. Using a standard MTT assay, the effect of the samples on the growth of HepG2 cells was investigated. Half of these compounds showed no cytotoxic effect on HepG2 cells, while the others result in decreasing in the HepG2 cell viability.
Design, Multicomponent Synthesis and Characterization of Diversely Substituted Pyrazolo[1,5‐a] Pyrimidine Derivatives
Authors: Ghelani Satish M. , Naliapara Yogesh T.
Published: September 2015

The synthesis of various heterocyclic compounds using acetoacetanilide[AAA], we have demonstrated that acetoactanilide are versatile intermediate for the synthesis of pyrazolopyrimidine derivatives. Thus, to explore further, we sought that the reaction of various acetoactanilide, an appropriate aldehyde and 5‐amino‐N‐cyclohexyl‐3‐(methylthio)‐1H‐pyrazole‐4‐carboxamide in the presence of base in isopropyl alcohol could be an effective strategy to furnish the novel pyrazolopyrimidine derivatives. Here we describe the novel synthetic methodology for the fused pyrazolopyrimidines.
HIV migration between blood plasma and cellular subsets before and after HIV therapy
Authors: Choi Jun Yong , Chaillon Antoine , Oh Jin Ok , Ahn Jin Young , Ann Hae Won , Jung In Young , Ahn Mi‐Young , Jeon Yong Duk , Ku Nam Su , Smith Davey M. , Kim June Myung
Published: September 2015

The cellular source of HIV RNA circulating in blood plasma remains unclear. Here, we investigated whether sequence analysis of HIV RNA populations circulating before combination antiretroviral therapy (cART) and HIV DNA populations in cellular subsets (CS) after cART could identify the cellular sources of circulating HIV RNA. Blood was collected from five subjects at cART initiation and again 6 months later. Naïve CD4+ T cells, resting central memory and effector memory CD4+ T cells, activated CD4+ T cells, monocytes, and natural killer cells were sorted using a fluorescence‐activated cell sorter. HIV‐1 env C2V3 sequences from HIV RNA in blood plasma and HIV DNA in CSs were generated using single genome sequencing. Sequences were evaluated for viral compartmentalization (Fst test) and migration events (MEs; Slatkin Maddison and cladistic measures) between blood plasma and each CS. Viral compartmentalization was observed in 88% of all cellular subset comparisons (range: 77–100% for each subject). Most observed MEs were directed from blood plasma to CSs (52 MEs, 85.2%). In particular, there was only viral movement from plasma to NK cells (15 MEs), monocytes (seven MEs), and naïve cells (five ME). We observed a total of nine MEs from activated CD4 cells (2/9 MEs), central memory T cells (3/9 MEs), and effector memory T cells (4/9 MEs) to blood plasma. Our results revealed that the HIV RNA population in blood plasma plays an important role in seeding various cellular reservoirs and that the cellular source of the HIV RNA population is activated central memory and effector memory T cells. J. Med. Virol. 88:606–613, 2016. © 2015 Wiley Periodicals, Inc.
Early‐stage development of human induced pluripotent stem cell‐derived neurons
Authors: Ohara Yuki , Koganezawa Noriko , Yamazaki Hiroyuki , Roppongi Reiko T. , Sato Kaoru , Sekino Yuko , Shirao Tomoaki
Published: September 2015

Recent advances in human induced pluripotent stem cells (hiPSCs) offer new possibilities for biomedical research and clinical applications. Differentiated neurons from hiPSCs are expected to be useful for developing novel methods of treatment for various neurological diseases. However, the detailed process of functional maturation of hiPSC‐derived neurons (hiPS neurons) remains poorly understood. This study analyzes development of hiPS neurons, focusing specifically on early developmental stages through 48 hr after cell seeding; development was compared with that of primary cultured neurons derived from the rat hippocampus. At 5 hr after cell seeding, neurite formation occurs in a similar manner in both neuronal populations. However, very few neurons with axonal polarization were observed in the hiPS neurons even after 48 hr, indicating that hiPS neurons differentiate more slowly than rat neurons. We further investigated the elongation speed of axons and found that hiPS neuronal axons were slower. In addition, we characterized the growth cones. The localization patterns of skeletal proteins F‐actin, microtubule, and drebrin were similar to those of rat neurons, and actin depolymerization by cytochalasin D induced similar changes in cytoskeletal distribution in the growth cones between hiPS neurons and rat neurons. These results indicate that, during the very early developmental stage, hiPS neurons develop comparably to rat hippocampal neurons with regard to axonal differentiation, but the growth of axons is slower. © 2015 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
Breast reconstruction and adjuvant therapy: A systematic review of surgical outcomes
Authors: El‐Sabawi Bassim , Sosin Michael , Carey Joseph N. , Nahabedian Maurice Y. , Patel Ketan M.
Published: September 2015

Background and Objectives: The impact of adjuvant therapy on the surgical outcomes following breast reconstruction is poorly understood. The purpose of this systematic review was to evaluate surgical outcomes following autologous and prosthetic reconstruction in the setting of post‐mastectomy radiation therapy (PMRT) and adjuvant chemotherapy.

Methods: A systematic review of the English literature published from 2000 to 2015 in the Pubmed/MEDLINE database was performed to identify all manuscripts reporting outcome of breast reconstruction in patients receiving PMRT and/or adjuvant chemotherapy.

Results: Sixty‐two manuscripts met the criteria for inclusion. This included 56 manuscripts (5437 patients) evaluating patients treated with PMRT and 11 manuscripts (820 patients) evaluating patients treated with chemotherapy. Pooled analysis of the PMRT cohort revealed significantly higher weighted incidences of re‐operation (P < 0.0001), total complications (P < 0.0001), and reconstructive failure (P < 0.0001) in prosthetic reconstruction compared to autologous. There was little evidence to suggest that postoperative chemotherapy is associated with poorer overall outcomes.

Conclusions: PMRT was associated with an increased incidence of adverse events when compared to chemotherapy. There was little evidence to suggest that adverse events following breast reconstruction were related to adjuvant chemotherapy. Manipulating the method and timing of reconstruction may mitigate some of the undesirable outcomes associated with PMRT. J. Surg. Oncol. 2015; 112:458–464. © 2015 Wiley Periodicals, Inc.
Histogram analysis of quantitative T1 and MT maps from ultrahigh field MRI in clinically isolated syndrome and relapsing–remitting multiple sclerosis
Authors: Al‐Radaideh Ali , Mougin Olivier E. , Lim Su‐Yin , Chou I‐Jun , Constantinescu Cris S. , Gowland Penny
Published: September 2015

This study used quantitative MRI to study normal appearing white matter (NAWM) in patients with clinically isolated syndromes suggestive of multiple sclerosis and relapsing–remitting multiple sclerosis (RRMS). This was done at ultrahigh field (7 T) for greater spatial resolution and sensitivity. 17 CIS patients, 11 RRMS patients, and 20 age‐matched healthy controls were recruited. They were scanned using a 3D inversion recovery turbo field echo sequence to measure the longitudinal relaxation time (T1). A 3D magnetization transfer prepared turbo field echo (MT‐TFE) sequence was also acquired, first without a presaturation pulse and then with the MT presaturation pulse applied at −1.05 kHz and +1.05 kHz off resonance from water to produce two magnetization transfer ratio maps (MTR(−) and MTR(+)). Histogram analysis was performed on the signal from the voxels in the NAWM mask. The upper quartile cut‐off of the T1 histogram was significantly higher in RRMS patients than in controls (p < 0.05), but there was no difference in CIS. In contrast, MTR was significantly different between CIS or RRMS patients and controls (p < 0.05) for most histogram measures considered. The difference between MTR(+) and MTR(−) signals showed that NOE contributions dominated the changes found. There was a weak negative correlation (r = −0.46, p < 0.05) between the mode of T1 distributions and healthy controls' age; this was not significant for MTR(+) (r = −0.34, p > 0.05) or MTR(−) (r = 0.13, p > 0.05). There was no significant correlation between the median of T1, MTR(−), or MTR(+) and the age of healthy controls. Furthermore, no significant correlation was observed between EDSS or disease duration and T1, MTR(−), or MTR(+) for either CIS or RRMS patients. In conclusion, MTR was found to be more sensitive to early changes in MS disease than T1. Copyright © 2015 John Wiley & Sons, Ltd.
The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation
Authors: Favennec Marie , Hennart Benjamin , Caiazzo Robert , Leloire Audrey , Yengo Loïc , Verbanck Marie , Arredouani Abdelilah , Marre Michel , Pigeyre Marie , Bessede Alban , Guillemin Gilles J. , Chinetti Giulia , Staels Bart , Pattou François , Balkau Beverley , Allorge Delphine , Froguel Philippe , Poulain‐Godefroy Odile
Published: September 2015

Objective

This study characterized the kynurenine pathway (KP) in human obesity by evaluating circulating levels of kynurenines and the expression of KP enzymes in adipose tissue.

Methods

Tryptophan and KP metabolite levels were measured in serum of individuals from the D.E.S.I.R. cohort (case–cohort study: 212 diabetic, 836 randomly sampled) and in women with obesity, diabetic or normoglycemic, from the ABOS cohort (n = 100). KP enzyme gene expressions were analyzed in omental and subcutaneous adipose tissue of women from the ABOS cohort, in human primary adipocytes and in monocyte‐derived macrophages.

Results

In the D.E.S.I.R. cohort, kynurenine levels were positively associated with body mass index (BMI) (P = 4.68 × 10−19) and with a higher HOMA2‐IR insulin resistance index (P = 6.23 × 10−4). The levels of kynurenine, kynurenic acid, and quinolinic acid were associated with higher BMI (P < 0.05). The expression of several KP enzyme genes (indoleamine 2,3‐dioxygenase 1 [IDO1], kynureninase [KYNU], kynurenine 3‐monooxygenase [KMO], and kynurenine aminotransferase III [CCBL2]) was increased in the omental adipose tissue of women with obesity compared to lean (P < 0.05), and their expression was induced by proinflammatory cytokines in human primary adipocytes (P < 0.05), except for KMO that is not expressed in these cells. The expressions of IDO1, KYNU, KMO, and CCBL2 were higher in proinflammatory than in anti‐inflammatory macrophages (P < 0.05).

Conclusions

In the context of obesity, the presence of macrophages in adipose tissue may contribute to diverting KP toward KMO activation.
The Play Experiences of Preschool Children from a Low‐socio‐economic Rural Community in Worcester, South Africa
Authors: Bartie Michelle , Dunnell Alex , Kaplan Jesse , Oosthuizen Dianka , Smit Danielle , van Dyk Anchen , Cloete Lizahn , Duvenage Mia
Published: September 2015

Occupational therapists believe that play is a child's main occupation and is considered essential for healthy motor, cognitive and emotional development. However, play spaces and activities in low socio‐economic areas are often different to those provided in structured occupational therapy treatment environments. The main objective was to determine play opportunities, activities, equipment, toys and the play environment for 5‐ to 6‐year‐olds living in a low‐socio‐economic community outside a small town in South Africa, in order to understand the nature of play in this environment better. Participant observation together with an adapted photovoice method to capture the play experience was used. Data was analysed using inductive content analysis. Two global themes emerged from the results: “neighbourhood children find ways to play” and “context influences play”. Children were given ample opportunity to play and participated in extensive outdoor play. Their games were highly social and involved the imaginative use of found items as toys. Play was also used to make sense of social hazards. An understanding of play in a low‐income context has implications for the development of future play assessments and the provision of play therapy in these communities. Copyright © 2015 John Wiley & Sons, Ltd.
Magnetic mechanism investigations on the ferromagnetism of (Sr,Na)(Zn,Mn)As with decoupled charge and spin doping
Authors: Yang Jun‐Tao , Luo Shi‐Jun , Xiong Yong‐Chen
Published: September 2015

The electronic structure and the magnetic properties of a new diluted magnetic semiconductor have been investigated, using first‐principles calculations within the Perdew–Burke–Ernzerhof generalized gradient approximation. Compound is a ‐type structure semiconductor with a direct bandgap of 0.57 eV at the point. With spins doped via isovalent (Zn, Mn) substitutions, the system prefers the antiferromagnetic ground state, resulting from the Mn–Mn superexchange interactions. Via off‐stoichiometry (Sr, Na) substitutions, holes are introduced into the system, resulting in the ferromagnetic spin responses for Mn–Mn pairs, except for the nearest‐neighboring Mn–Mn pair. Based on our calculations, the ferromagnetism in the II–II–V‐based diluted magnetic semiconductor originates from Zener's p–d exchange interactions between localized Mn spins and itinerant holes mediated by As atoms.
Advanced techniques for spectrally efficient DVB‐S2X systems
Authors: Ugolini Alessandro , Modenini Andrea , Colavolpe Giulio , Mignone Vittoria , Morello Alberto
Published: September 2015

We investigate different techniques to improve the spectral efficiency of systems based on the DVB‐S2 standard, when the transmitted signal bandwidth cannot be increased because it has already been optimized to the maximum value allowed by transponder filters. We will investigate and compare several techniques involving different sections of the transceiver scheme. The techniques that will be considered include the use of advanced detection algorithms, the adoption of time packing, and the optimization of the constellation and shaping pulses. The low‐density parity‐check codes recently proposed for the evolution of the DVB‐S2 standard will be considered, as well as the adoption of iterative detection and decoding. Information‐theoretical analysis will be followed by the study of practical modulation and coding schemes. Copyright © 2015 John Wiley & Sons, Ltd.
A Gathering of Native American Healers: Exploring the Interface of Indigenous Tradition and Professional Practice
Authors: Moorehead Virgil D. , Gone Joseph P. , December Damia
Published: September 2015

This article reports insights from a 4‐day Gathering of Native American Healers at the University of Michigan in October of 2010. This event convened 18 traditional healers, clinically trained service providers, and cross‐cultural mental health researchers for a structured group dialogue to advance professional knowledge about the integration of Indigenous healing practices and conventional mental health treatments in community‐based mental health services for Native Americans. Our thematic analysis of transcripts from five Roundtable sessions afforded several key insights and understandings pertaining to the integration of Indigenous healing and conventional mental health services. First, with reference to traditional healing, the importance of a rampant relationality, various personal qualities, Indigenous spirituality, and maintenance of traditional life and culture were accentuated by Roundtable participants. Second, for traditional healers to practice effectively, Roundtable participants posited that these individuals must maintain personal wellness, cultivate profound knowledge of healing practices, recognize the intrinsic healing potential within all human beings, and work for the community rather than themselves. In speaking to the possibilities and challenges of collaboration between Indigenous and conventional biomedical therapeutic approaches, Roundtable participants recommended the implementation of cultural programming, the observance of mutuality and respect, the importance of clear and honest communication, and the need for awareness of cultural differences as unique challenges that must be collaboratively overcome.
Management options and fertility‐preserving therapy for premenopausal endometrial hyperplasia and early‐stage endometrial cancer
Authors: Gressel Gregory M. , Parkash Vinita , Pal Lubna
Published: September 2015

Background

Definitive management with hysterectomy could be appropriate for some patients with endometrial cancer and its precursor lesions, but poses challenges for those desiring future fertility.

Objectives

To review risk factors for endometrial hyperplasia/cancer among premenopausal women and discuss management options for fertility preservation.

Search strategy

A literature search through the PubMed, Ovid, and Cochrane databases was conducted using the terms “endometrial hyperplasia” and “endometrial cancer,” cross‐referenced with “fertility preservation.”

Selection criteria

All articles published in English between January 1, 2000, and January 1, 2015, were considered if they were readily available online.

Data collection and analysis

Articles were analyzed and information was synthesized into a comprehensive review.

Main results

Chronic anovulation, obesity, polycystic ovarian syndrome, metabolic syndrome, insulin resistance, and type 2 diabetes mellitus must be appreciated as risk factors for endometrial pathology. Providers must exert vigilance in identifying patients at risk and in initiating pre‐emptive strategies. Risk reduction with lifestyle modification, weight loss, and glycemic control can improve regression and overall health. Fertility outcomes for these patients are promising, especially with assisted reproductive technology.

Conclusions

Conservative management could be appropriate for carefully selected women with complex atypical endometrial hyperplasia or early‐stage endometrial cancer who desire future fertility.
Incident pregnancy and pregnancy outcomes among HIV‐infected women in Uganda and Zimbabwe
Authors: Lancaster Kathryn E. , Kwok Cynthia , Rinaldi Anne , Byamugisha Josaphat , Magwali Tulani , Nyamapfeni Prisca , Salata Robert A. , Morrison Charles S.
Published: September 2015

Objective

To describe pregnancy outcomes among HIV‐infected women and examine factors associated with live birth among those receiving and not receiving combination antiretroviral therapy (cART).

Methods

The present analysis included women with HIV from Uganda and Zimbabwe who participated in a prospective cohort study during 2001–2009. Incident pregnancies and pregnancy outcomes were recorded quarterly. The Kaplan–Meier method was used to estimate incident pregnancy probabilities; factors associated with live birth were evaluated by Poisson regression with generalized estimating equations.

Results

Among 306 HIV‐infected women, there were 160 incident pregnancies (10.1 per 100 women‐years). The pregnancy rate was higher among cART‐naïve women than among those receiving cART (10.7 vs 5.5 per 100 women‐years; P = 0.047), and it was higher in Uganda than in Zimbabwe (14.4 vs 7.7 per 100 women‐years; P < 0.001). Significant associations were noted between a live birth and prenatal care (relative risk 3.9; 95% confidence interval 2.2–6.9) and illness during pregnancy (relative risk 0.8; 95% confidence interval 0.7–1.0).

Conclusion

Women not receiving cART have higher pregnancy rates than do those receiving cART, but cART use might not affect the risk of adverse pregnancy outcomes. Timely prenatal care and monitoring of illnesses during pregnancy should be incorporated into treatment services for HIV‐infected women.
Interleukin‐33 predicts poor prognosis and promotes ovarian cancer cell growth and metastasis through regulating ERK and JNK signaling pathways
Authors: Tong Xiaoguang , Barbour Mark , Hou Kezuo , Gao Chao , Cao Shuang , Zheng Jingli , Zhao Yang , Mu Rong , Jiang Hui-Rong
Published: September 2015

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, it remains a huge challenge to understand the cellular and molecular mechanisms of the aggressive behavior of EOC cells. Here we investigated the role of an immunomodulatory cytokine IL‐33 and its receptor ST2 in mediating the growth and metastasis of EOC. Our data show that both IL‐33 and ST2 were highly up‐regulated in EOC tumors compared with normal ovary and ovarian benign tumors, and the expression levels were further increased in tumor tissues at the metastatic site. The expression levels of IL‐33 and ST2 were positively correlated with the Ki‐67 expression, and negatively correlated with the patient survival time. Using EOC cell lines, we observed that cells knocked down of IL‐33 gene by siRNA had reduced migratory and invasive potential, while full length human IL‐33 (fl‐hIL‐33) promoted the invasive, migratory and proliferative capacity of EOC cells and this process could be inhibited by IL‐33 decoy receptor sST2. Signaling pathway analysis suggested that IL‐33 increased the phosphorylation of ERK and JNK which was blocked by sST2. Fl‐hIL‐33‐induced increases in EOC cell migration, invasive potential and proliferation were specifically abrogated by treatment with the ERK inhibitor U0126 while JNK inhibitor SP600125 only disrupted IL‐33‐induced enhancement of cell viability. Taken together, our data suggest that IL‐33/ST2 axis closely associates with poor prognosis of EOC patients, and it promotes ovarian cancer growth and metastasis through regulating ERK and JNK signaling pathways. Thus IL‐33/ST2 might be potential prognosis markers and therapeutic targets for EOC patients.
Subjective well-being in older adults: folate and vitamin B12independently predict positive affect
Authors: Edney Laura C. , Burns Nicholas R. , Danthiir Vanessa
Published: September 2015

Vitamin B12, folate and homocysteine have long been implicated in mental illness, and growing evidence suggests that they may play a role in positive mental health. Elucidation of these relationships is confounded due to the dependence of homocysteine on available levels of vitamin B12and folate. Cross-sectional and longitudinal relationships between vitamin B12, folate, homocysteine and subjective well-being were assessed in a sample of 391 older, community-living adults without clinically diagnosed depression. Levels of vitamin B12, but not folate, influenced homocysteine levels 18 months later. Vitamin B12, folate and their interaction significantly predicted levels of positive affect (PA) 18 months later, but had no impact on the levels of negative affect or life satisfaction. Cross-sectional relationships between homocysteine and PA were completely attenuated in the longitudinal analyses, suggesting that the cross-sectional relationship is driven by the dependence of homocysteine on vitamin B12and folate. This is the first study to offer some evidence of a causal link between levels of folate and vitamin B12on PA in a large, non-clinical population.