bluuebunny/crossref_metadata_2025 huggingface dataset:
DOC:NO3− ratios and NO3− uptake in forested headwater streams
Authors: Rodríguez‐Cardona Bianca , Wymore Adam S. , McDowell William H.
Published: December 2015

The underlying mechanisms driving the coupled interactions between inorganic nitrogen uptake and dissolved organic matter are not well understood, particularly in surface waters. To determine the relationship between dissolved organic carbon (DOC) quantity and nitrate (NO3−) uptake kinetics in streams, we performed a series of NO3− Tracer Additions for Spiraling Curve Characterization experiments in four streams within the Lamprey River Watershed, New Hampshire, across a range in background DOC concentrations (1–8 mg C/L). Experiments were performed throughout the 2013 and 2014 growing seasons. Across streams and experimental dates, ambient uptake velocity (Vf) correlated positively with increasing DOC concentrations and DOC:NO3− ratios but was only weakly negatively associated with NO3− concentrations. Ambient NO3− Vf was unrelated to pH, light, temperature, dissolved oxygen, and Specific Ultraviolet Absorbance at 254 nm. Although there were general tendencies across the entire Lamprey River Watershed, individual sites behaved differently in their uptake kinetics. NO3− uptake dynamics in the Lamprey River Watershed are most strongly influenced by DOC concentrations rather than NO3− concentrations or physicochemical parameters, which have been identified as regional‐ to continental‐scale drivers in previous research. Understanding the fundamental relationships between dissolved organic matter and inorganic nutrients will be important as global and climatic changes influence the delivery and production of DOC and NO3− in aquatic ecosystems.
Potential predictability of Indian summer monsoon rainfall in NCEP CFSv2
Authors: Saha Subodh Kumar , Pokhrel Samir , Salunke Kiran , Dhakate Ashish , Chaudhari Hemantkumar S. , Rahaman Hasibur , Sujith K. , Hazra Anupam , Sikka D. R.
Published: December 2015

The potential predictability of the Indian summer monsoon rainfall (ISMR), soil moisture, and sea surface temperature (SST) is explored in the latest version of the NCEP Climate Forecast System (CFSv2) retrospective forecast at five different lead times. The focus of this study is to find out the sensitivity of the potential predictability of the ISMR to the initial condition through analysis of variance technique (ANOVA), information‐based measure, including relative entropy (RE), mutual information (MI), and classical perfect model correlation. In general, the all methods show an increase in potential predictability with a decrease in lead time. Predictability is large over the Pacific Ocean basin as compared to that of the Indian Ocean basin. However, over the Indian land region the potential predictability increases from lead‐4 to lead‐2 and then decreases at lead‐1 followed by again increase at lead‐0. While the actual ISMR prediction skill is highest at lead‐3 forecast (second highest at lead‐1), the potential predictability is highest at lead‐2. It is found that highest and second highest actual prediction skill of the ISMR in CFSv2 is due to the combined effects of initial Eurasian snow and SST over Indian, west Pacific and eastern equatorial Pacific Ocean region. While the teleconnection between the ISMR and El Niño‐Southern Oscillation is too strong, the ISMR and Indian Ocean dipole have completely out of phase relation in the model as compared to the observation. Furthermore, the actual prediction skill of the ISMR is now very close to the potential predictability limit. Therefore, in order to improve the ISMR prediction skill further, development of model physics as well as improvements in the initial conditions is required.
Impacts of parameterized orographic drag on the Northern Hemisphere winter circulation
Authors: Sandu Irina , Bechtold Peter , Beljaars Anton , Bozzo Alessio , Pithan Felix , Shepherd Theodore G. , Zadra Ayrton
Published: December 2015

A recent intercomparison exercise proposed by the Working Group for Numerical Experimentation (WGNE) revealed that the parameterized, or unresolved, surface stress in weather forecast models is highly model‐dependent, especially over orography. Models of comparable resolution differ over land by as much as 20% in zonal mean total subgrid surface stress (τtot). The way τtot is partitioned between the different parameterizations is also model‐dependent. In this study, we simulated in a particular model an increase in τtot comparable with the spread found in the WGNE intercomparison. This increase was simulated in two ways, namely by increasing independently the contributions to τtot of the turbulent orographic form drag scheme (TOFD) and of the orographic low‐level blocking scheme (BLOCK). Increasing the parameterized orographic drag leads to significant changes in surface pressure, zonal wind and temperature in the Northern Hemisphere during winter both in 10 day weather forecasts and in seasonal integrations. However, the magnitude of these changes in circulation strongly depends on which scheme is modified. In 10 day forecasts, stronger changes are found when the TOFD stress is increased, while on seasonal time scales the effects are of comparable magnitude, although different in detail. At these time scales, the BLOCK scheme affects the lower stratosphere winds through changes in the resolved planetary waves which are associated with surface impacts, while the TOFD effects are mostly limited to the lower troposphere. The partitioning of τtot between the two schemes appears to play an important role at all time scales.
Mixture design using derivative‐free optimization in the space of individual component properties
Authors: Austin Nick D. , Samudra Apurva P. , Sahinidis Nikolaos V. , Trahan Daniel W.
Published: December 2015

In this work, we propose a new methodology for mixture design. By projecting the problem on the space of individual component properties, the methodology exploits a natural problem decomposition and capitalizes on fast methods for pure compound design and mixture fraction design. We demonstrate the proposed methodology through application to two illustrative examples and then to two problems from the mixture design literature concerning the purification of ibuprofen. In all cases, the proposed approach finds optimal solutions while exploring a small number of feasible molecular structures. © 2016 American Institute of Chemical Engineers AIChE J, 62: 1514–1530, 2016
Oxygenation cascade analysis in conversion of n‐octane catalyzed by cytochrome P450 CYP102A3 mutants at the P331 site
Authors: Wang Songhe , Liu Zhibin
Published: December 2015

To improve the hydroxylation efficiency of cytochrome P450 CYP102A3 to substrate n‐octane, a previously reported triple‐mutant F88V/S188Q/A330V with altered regioselectivity was selected and site‐saturation mutagenesis was performed at its P331 site, which is adjacent to one of the active sites A330. Using whole‐cell biotransformations to analyze the created mutants, four better mutants P331A, P331T, P331S, and P331V were achieved and exhibited significantly improved conversion rates toward n‐octane, which are 33%, 33%, 22% and 28%, respectively, whereas the activity of P331R was greatly reduced and P331K gave almost zero conversion of n‐octane. Besides the main product octanols, different octanones and 1,7‐octanediol were also detected for some of the mutants. The above results demonstrated that the P331 site of CYP102A3 also plays an important role in the n‐octane oxidation and CYP102A3 is a functionally flexible biocatalyst that can be optimized for a variety of industrial applications.
Association between maternal aluminum exposure and the risk of congenital heart defects in offspring
Authors: Liu Zhen , Lin Yuan , Tian Xiaoxian , Li Jun , Chen Xinlin , Yang Jiaxiang , Li Xiaohong , Deng Ying , Li Nana , Liang Juan , Li Shengli , Zhu Jun
Published: December 2015

Background

Aluminum (Al) is the third most common element in the earth' s crust and has been reported to be teratogenic. However, there is lack of understanding about the association between maternal aluminum exposure and the risks of birth defects such as congenital heart defects (CHDs).

Methods

A multi‐center, hospital‐based case–control study was performed at four maternal and child tertiary hospitals in China. A total of 223 cases with CHDs and 223 controls without any abnormalities were recruited according to the inclusion and matching criteria. Hair samples were prepared and measured by inductively coupled plasma mass spectrometry (ICP‐MS). The correlation between CHDs and maternal aluminum concentrations was estimated by a 1:1 conditional logistic regression.

Results

The geometric mean and median of hair aluminum levels in isolated or multiple CHD cases was significantly higher than in controls (p < 0.05). A significant association was found between increased hair aluminum concentrations and the risk of total CHDs in offspring (adjusted odds ration [aOR], 2.32; 95% confidence interval [CI], 1.72–3.13), especially in some subtypes of CHDs, such as septal defects (aOR, 2.17; 95% CI, 1.15–4.10), conotruncal defects (aOR, 5.42; 95%CI, 2.43–12.10), and right ventricular outflow track obstruction (aOR, 2.43; 95% CI, 1.08–5.44). However, there was no statistically significant association with left ventricular outflow track obstruction (aOR, 1.66; 95% CI, 0.95–2.88).

Conclusion

A high maternal aluminum concentration may significantly increase the risk of delivering a child with a CHD, such as a septal defect, conotruncal heart defect and right‐side obstruction. Birth Defects Research (Part A) 106:95–103, 2016. © 2015 Wiley Periodicals, Inc.
Consequences of ccmR deletion on respiration, fermentation and H2 metabolism in cyanobacterium Synechococcus sp. PCC 7002
Authors: Krishnan Anagha , Zhang Shuyi , Liu Yang , Tadmori Kinan A. , Bryant Donald A. , Dismukes Charles G.
Published: December 2015

CcmR, a LysR‐type transcriptional regulator, represses the genes encoding components of the high‐affinity carbon concentration mechanism in cyanobacteria. Unexpectedly, deletion of the ccmR gene was found to alter the expression of the terminal oxidase and fermentative genes, especially the hydrogenase operon in the cyanobacterium Synechococcus sp. PCC 7002. Consistent with the transcriptomic data, the deletion strain exhibits flux increases (30–50%) in both aerobic O2 respiration and anaerobic H2 evolution. To understand how CcmR influences anaerobic metabolism, the kinetics of autofermentation were investigated following photoautotrophic growth. The autofermentative H2 yield increased by 50% in the CcmR deletion strain compared to the wild‐type strain, and increased to 160% (within 20 h) upon continuous removal of H2 from the medium (“milking”) to suppress H2 uptake. Consistent with this greater reductant flux to H2, the mutant excreted less lactate during autofermentation (NAD(P)H consuming pathway). To enhance the rate of NADH production during anaerobic metabolism, the ccmR mutant was engineered to introduce GAPDH overexpression (more NADH production) and LDH deletion (less NADH consumption). The triple mutant (ccmR deletion + GAPDH overexpression + LDH deletion) showed 6–8‐fold greater H2 yield than the WT strain, achieving conversion rates of 17 nmol 108 cells−1 h−1 and yield of 0.87 H2 per glucose equivalent (8.9% theoretical maximum). Simultaneous monitoring of the intracellular NAD(P)H concentration and H2 production rate by these mutants reveals an inverse correspondence between these variables indicating hydrogenase‐dependent H2 production as a major sink for consuming NAD(P)H in preference to excretion of reduced carbon as lactate during fermentation. Biotechnol. Bioeng. 2016;113: 1448–1459. © 2015 Wiley Periodicals, Inc.
Itaconic acid production from glycerol using Escherichia coli harboring a random synonymous codon‐substituted 5′‐coding region variant of the cadA gene
Authors: Jeon Ho‐Geun , Cheong Dae‐Eun , Han Yunjon , Song Jae Jun , Choi Jong Hyun
Published: December 2015

Aspergillus terreus cadA, encoding cis‐aconitate decarboxylase, is an essential gene for itaconic acid (IA) biosynthesis, but it is primarily expressed as insoluble aggregates in most industrial hosts. This has been a hurdle for the development of recombinant strategies for IA production. Here, we created a library of synonymous codon variants (scv) of the cadA gene containing synonymous codons in the first 10 codons (except ATG) and screened it in Escherichia coli. Among positive clones, E. coli scvCadA_No8 showed more than 95% of expressed CadA in the soluble fraction, and in production runs, produced threefold more IA than wild‐type E. coli in Luria‐Bertani broth supplemented with 0.5% glucose. In M9 minimal media containing 0.85 g/L citrate and 1% glycerol, E. coli scvCadA_No8 produced 985.6 ± 33.4 mg/L IA during a 72‐h culture after induction with isopropyl β‐D‐1‐thiogalactopyranoside. In a 2‐L fed‐batch fermentation consisting of two stages (growth and nitrogen limitation conditions), we obtained 7.2 g/L IA by using E. coli by introducing only the scv_cadA gene and optimizing culture conditions for IA production. These results could be combined with metabolic engineering and generate an E. coli strain as an industrial IA producer. Biotechnol. Bioeng. 2016;113: 1504–1510. © 2015 Wiley Periodicals, Inc.
Modification of gellan gum with nanocrystalline hydroxyapatite facilitates cell expansion and spontaneous osteogenesis
Authors: Jamshidi Parastoo , Chouhan Gurpreet , Williams Richard L. , Cox Sophie C. , Grover Liam M.
Published: December 2015

Nanocomposites composed of hydrogels and calcium phosphates are of great interest in the development of bone graft replacements since they may have a structural and compositional resemblance to bone. Culture beads formed from such materials could be used in stirred tank culture and thereby enable cell expansion in a sufficiently efficient manner to allow for the generation of enough large number of cells for large‐scale bone reconstruction. Although combinations of materials such as alginate, collagens, and various calcium phosphates have been investigated as culture beads, these materials are unsuitable for application since they have been shown to rapidly degrade in physiological conditions and enable relatively little tailoring of mechanical properties. In this study, gellan gum‐nano sized hydroxyapatite (nHA) composites, which have been shown to be resistant to degradation and easily modified with respect to modulus, were formulated and characterized as regards their ability to enable cell attachment and proliferation. It was shown that the addition of 5 wt% of nHA to the culture beads enabled cell attachment and that an increase in nHA concentration to up to 25 wt% enhanced the rate of cell proliferation. Most importantly, it was demonstrated that the addition of nHA to the cell culture beads enabled the formation of nodules in culture of MC3T3‐E1 cells and strikingly stimulated the osteogenic differentiation of bone marrow stromal cells in the absence of osteogenic media when compared with tissue culture plastic (TCP) with the same condition. Biotechnol. Bioeng. 2016;113: 1568–1576. © 2016 Wiley Periodicals, Inc.
Droplet digital PCR‐aided screening and characterization of Pichia pastoris multiple gene copy strains
Authors: Cámara Elena , Albiol Joan , Ferrer Pau
Published: December 2015

Pichia (syn. Komagataella) pastoris is a widely used yeast platform for heterologous protein production. Expression cassettes are usually stably integrated into the genome of this host via homologous recombination. Although increasing gene dosage is a powerful strategy to improve recombinant protein production, an excess in the number of gene copies often leads to decreased product yields and increased metabolic burden, particularly for secreted proteins. We have constructed a series of strains harboring different copy numbers of a Rhizopus oryzae lipase gene (ROL), aiming to find the optimum gene dosage for secreted Rol production. In order to accurately determine ROL gene dosage, we implemented a novel protocol based on droplet digital PCR (ddPCR), and cross validated it with conventional real‐time PCR. Gene copy number determination based on ddPCR allowed for an accurate ranking of transformants according to their ROL gene dosage. Results indicated that ddPCR was particularly superior at lower gene dosages (one to five copies) over quantitative real‐time PCR (qPCR). This facilitated the determination of the optimal ROL gene dosage as low as two copies. The ranking of ROL gene dosage versus Rol yield was consistent at both small scale and bioreactor chemostat cultures, thereby easing clone characterization in terms of gene dosage dependent physiological effects, which could be discriminated even among strains differing by only one ROL copy. A selected two‐copy strain showed twofold increase in Rol specific production in a chemostat culture over the single copy strain. Conversely, strains harboring more than two copies of the ROL gene showed decreased product and biomass yields, as well as altered substrate consumption specific rates, compared to the reference (one‐copy) strain. Biotechnol. Bioeng. 2016;113: 1542–1551. © 2015 Wiley Periodicals, Inc.
Kinetics of tRNAPyl‐mediated amber suppression in Escherichia coli translation reveals unexpected limiting steps and competing reactions
Authors: Wang Jinfan , Kwiatkowski Marek , Forster Anthony C.
Published: December 2015

The utility of ribosomal incorporation of unnatural amino acids (AAs) in vivo is generally restricted by low efficiencies, even with the most widely used suppressor tRNAPyl. Because of the difficulties of studying incorporation in vivo, almost nothing is known about the limiting steps after tRNA charging. Here, we measured the kinetics of all subsequent steps using a purified Escherichia coli translation system. Dipeptide formation from initiator fMet‐tRNAfMet and tRNAPyl charged with allylglycine or methylserine displayed unexpectedly sluggish biphasic kinetics, ∼30‐fold slower than for native substrates. The amplitude of the fast phases increased with increasing EF‐Tu concentration, allowing measurement of Kd values of EF‐Tu binding, both of which were ∼25‐fold weaker than normal. However, binding could be increased ∼30‐fold by lowering temperature. The fast phase rates were limited by the surprisingly ∼10‐fold less efficient binding of EF‐Tu:GTP:AA‐tRNAPyl ternary complex to the ribosomes, not GTP hydrolysis or peptide bond formation. Furthermore, processivity was unexpectedly impaired as ∼40% of the dipeptidyl‐tRNAPyl could not be elongated to tripeptide. Dipeptide formation was slow enough that termination due to misreading the UAG codon by non‐cognate RF2 became very significant. This new understanding provides a framework for improving unnatural AA incorporation by amber suppression. Biotechnol. Bioeng. 2016;113: 1552–1559. © 2015 Wiley Periodicals, Inc.
The effect of PVDF‐TrFE scaffolds on stem cell derived cardiovascular cells
Authors: Hitscherich Pamela , Wu Siliang , Gordan Richard , Xie Lai‐Hua , Arinzeh Treena , Lee Eun Jung
Published: December 2015

Recently, electrospun polyvinylidene fluoride (PVDF) and polyvinylidene fluoride‐trifluoroethylene (PVDF‐TrFE) scaffolds have been developed for tissue engineering applications. These materials have piezoelectric activity, wherein they can generate electric charge with minute mechanical deformations. Since the myocardium is an electroactive tissue, the unique feature of a piezoelectric scaffold is attractive for cardiovascular tissue engineering applications. In this study, we examined the cytocompatibility and function of pluripotent stem cell derived cardiovascular cells including mouse embryonic stem cell‐derived cardiomyocytes (mES‐CM) and endothelial cells (mES‐EC) on PVDF‐TrFE scaffolds. MES‐CM and mES‐EC adhered well to PVDF‐TrFE and became highly aligned along the fibers. When cultured on scaffolds, mES‐CM spontaneously contracted, exhibited well‐registered sarcomeres and expressed classic cardiac specific markers such as myosin heavy chain, cardiac troponin T, and connexin43. Moreover, mES‐CM cultured on PVDF‐TrFE scaffolds responded to exogenous electrical pacing and exhibited intracellular calcium handling behavior similar to that of mES‐CM cultured in 2D. Similar to cardiomyocytes, mES‐EC also demonstrated high viability and maintained a mature phenotype through uptake of low‐density lipoprotein and expression of classic endothelial cell markers including platelet endothelial cell adhesion molecule, endothelial nitric oxide synthase, and the arterial specific marker, Notch‐1. This study demonstrates the feasibility of PVDF‐TrFE scaffold as a candidate material for developing engineered cardiovascular tissues utilizing stem cell‐derived cells. Biotechnol. Bioeng. 2016;113: 1577–1585. © 2015 Wiley Periodicals, Inc.
Combining 3D human in vitro methods for a 3Rs evaluation of novel titanium surfaces in orthopaedic applications
Authors: Stevenson G. , Rehman S. , Draper E. , Hernández‐Nava E. , Hunt J. , Haycock J.W.
Published: December 2015

In this study, we report on a group of complementary human osteoblast in vitro test methods for the preclinical evaluation of 3D porous titanium surfaces. The surfaces were prepared by additive manufacturing (electron beam melting [EBM]) and plasma spraying, allowing the creation of complex lattice surface geometries. Physical properties of the surfaces were characterized by SEM and profilometry and 3D in vitro cell culture using human osteoblasts. Primary human osteoblast cells were found to elicit greater differences between titanium sample surfaces than an MG63 osteoblast‐like cell line, particularly in terms of cell survival. Surface morphology was associated with higher osteoblast metabolic activity and mineralization on rougher titanium plasma spray coated surfaces than smoother surfaces. Differences in osteoblast survival and metabolic activity on titanium lattice structures were also found, despite analogous surface morphology at the cellular level. 3D confocal microscopy identified osteoblast organization within complex titanium surface geometries, adhesion, spreading, and alignment to the biomaterial strut geometries. Mineralized nodule formation throughout the lattice structures was also observed, and indicative of early markers of bone in‐growth on such materials. Testing methods such as those presented are not traditionally considered by medical device manufacturers, but we suggest have value as an increasingly vital tool in efficiently translating pre‐clinical studies, especially in balance with current regulatory practice, commercial demands, the 3Rs, and the relative merits of in vitro and in vivo studies. Biotechnol. Bioeng. 2016;113: 1586–1599. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
TAP‐mediated processing of exoerythrocytic antigens is essential for protection induced with radiation‐attenuated Plasmodium sporozoites
Authors: Pichugin Alexander , Steers Nick , De La Vega Patricia , Zarling Stasya , Chalom Isaac , Krzych Urszula
Published: December 2015

MHC class I dependent CD8+ T cells are essential for protection induced by radiation‐attenuated Plasmodium sporozoites (RAS) in murine malaria models. Apart from the mechanism of activation of CD8+ T cells specific for the circumsporozoite protein, the major sporozoite antigen (Ag), CD8+ T cells specific for other exoerythrocytic Ags that have been shown to mediate protection have not been thoroughly investigated. Specifically, mechanisms of processing and presentation of exoerythrocytic Ags, which includes liver stage (LS) Ags, remain poorly understood. We hypothesize that as exogenous proteins, LS Ags are processed by mechanisms involving either the TAP‐dependent phagosomal‐to‐cytosol or TAP‐independent vacuolar pathway of cross‐presentation. We used TAP‐deficient mice to investigate whether LS Ag mediated induction of naïve CD8+ T cells and their recall during sporozoite challenge occur by the TAP‐dependent or TAP‐independent pathways. On the basis of functional attributes, CD8+ T cells were activated via the TAP‐independent pathway during immunizations with Plasmodium berghei RAS; however, IFN‐γ+CD8+ T cells previously induced by P. berghei RAS in TAP‐deficient mice failed to be recalled against sporozoite challenge and the mice became parasitemic. On the basis of these observations, we propose that TAP‐associated Ag processing is indispensable for sterile protection induced with P. berghei RAS.
Picomolar detection of carcinoembryonic antigen in whole blood using microfluidics and surface‐enhanced Raman spectroscopy
Authors: Zou Kun , Gao Zhigang , Deng Quanfeng , Luo Yong , Zou Lijuan , Lu Yao , Zhao Weijie , Lin Bingcheng
Published: December 2015

Carcinoembryonic antigen (CEA) is a wide‐spectrum biomarker. Clinically, we generally use serum sample to detect CEA, which needs to be centrifuged to pretreat the raw blood sample. In this study, we realized direct CEA detection in raw blood samples exploiting microfluidics. The LOD was as low as 10−12 M.
A stabilized Nitsche‐type extended embedding mesh approach for 3D low‐ and high‐Reynolds‐number flows
Authors: Schott B. , Shahmiri S. , Kruse R. , Wall W.A.
Published: December 2015

This paper presents a stabilized extended finite element method (XFEM) based fluid formulation to embed arbitrary fluid patches into a fixed background fluid mesh. The new approach is highly beneficial when it comes to computational grid generation for complex domains, as it allows locally increased resolutions independent from size and structure of the background mesh. Motivating applications for such a domain decomposition technique are complex fluid‐structure interaction problems, where an additional boundary layer mesh is used to accurately capture the flow around the structure. The objective of this work is to provide an accurate and robust XFEM‐based coupling for low‐ as well as high‐Reynolds‐number flows. Our formulation is built from the following essential ingredients: Coupling conditions on the embedded interface are imposed weakly using Nitsche's method supported by extra terms to guarantee mass conservation and to control the convective mass transport across the interface for transient viscous‐dominated and convection‐dominated flows. Residual‐based fluid stabilizations in the interior of the fluid subdomains and accompanying face‐oriented fluid and ghost‐penalty stabilizations in the interface zone stabilize the formulation in the entire fluid domain. A detailed numerical study of our stabilized embedded fluid formulation, including an investigation of variants of Nitsche's method for viscous flows, shows optimal error convergence for viscous‐dominated and convection‐dominated flow problems independent of the interface position. Challenging two‐dimensional and three‐dimensional numerical examples highlight the robustness of our approach in all flow regimes: benchmark computations for laminar flow around a cylinder, a turbulent driven cavity flow at Re = 10000 and the flow interacting with a three‐dimensional flexible wall. Copyright © 2016 John Wiley & Sons, Ltd.
Dynamic thalamus parcellation from resting‐state fMRI data
Authors: Ji Bing , Li Zhihao , Li Kaiming , Li Longchuan , Langley Jason , Shen Hui , Nie Shengdong , Zhang Renjie , Hu Xiaoping
Published: December 2015

The thalamus is a relay center between various subcortical brain areas and the cerebral cortex with delineation of its constituent nuclei being of particular interest in many applications. While previous studies have demonstrated efficacy of connectivity‐based thalamus segmentation, they used approaches that do not consider the dynamic nature of thalamo‐cortical interactions. In this study, we explicitly exploited the dynamic variation of thalamo‐cortical connections to identify different states of functional connectivity and performed state‐specific thalamus parcellation. With normalized spectral clustering successively applied in temporal and spatial domains, nine thalamo‐cortical connectivity states were identified and the dynamic thalamus parcellation revealed finer thalamic structures with improved atlas correspondence. The present results extend our understanding of thalamo‐cortical connectivity and provide a more comprehensive view of the thalamo‐cortical interaction. Hum Brain Mapp 37:954–967, 2016. © 2015 Wiley Periodicals, Inc.
Intensity‐modulated radiotherapy for head and neck surgeons
Authors: Gutiontov Stanley I. , Shin Edward J. , Lok Benjamin , Lee Nancy Y. , Cabanillas Ruben
Published: December 2015

The development of intensity‐modulated radiotherapy (IMRT) has played a major role in improving outcomes and decreasing morbidity in patients with head and neck cancer. This review addresses this vital modality with a focus on the important role of the head and neck surgeon. The technique as well as its benefits and points of caution are outlined, the definitions of tumor and treatment volumes are discussed, and the dose and fractionation are detailed. Following this are several sections dedicated to the role of the head and neck surgeon in the planning of both definitive and postoperative radiotherapy to the primary site and neck. There is a focus throughout on anatomic and surgical considerations; commonly encountered situations are illustrated. With a deeper understanding of this technique and their own pivotal contribution to target delineation, head and neck surgeons will be poised to expand their role and improve cancer care for their patients. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2368–E2373, 2016
Intensity‐modulated proton therapy for nasopharyngeal carcinoma: Decreased radiation dose to normal structures and encouraging clinical outcomes
Authors: Lewis Gary D. , Holliday Emma B. , Kocak–Uzel Esengul , Hernandez Mike , Garden Adam S. , Rosenthal David I. , Frank Steven J.
Published: December 2015

Background

Intensity‐modulated proton therapy (IMPT) has the potential to spare dose to organs at risk (OAR) when compared to intensity‐modulated radiotherapy (IMRT) while maintaining excellent clinical outcomes.

Methods

Ten patients with nasopharyngeal carcinoma (NPC) were identified for whom IMPT was planned; 9 patients also had a comparison photon‐based IMRT plan generated. Dosimetric comparison of mean radiation dose to 29 adjacent OAR was performed. Disease control, survival, and toxicity outcomes were collected from the medical records.

Results

There were significant differences in mean doses in 15 of the 29 OAR; 13 OAR received lower mean dose with proton‐based plans. Median follow‐up was 24.5 months (range, 19–32 months). Two‐year locoregional control was 100% and the 2‐year overall survival was 88.9%.

Conclusion

We observed dosimetric advantages conferred by IMPT compared to IMRT. Further study is needed to determine if these translate into reduced toxicity and/or improved disease control. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1886–E1895, 2016
Learning history and cholinergic modulation in the dorsal hippocampus are necessary for rats to infer the status of a hidden event
Authors: Fast Cynthia D. , Flesher M. Melissa , Nocera Nathanial A. , Fanselow Michael S. , Blaisdell Aaron P.
Published: December 2015

Identifying statistical patterns between environmental stimuli enables organisms to respond adaptively when cues are later observed. However, stimuli are often obscured from detection, necessitating behavior under conditions of ambiguity. Considerable evidence indicates decisions under ambiguity rely on inference processes that draw on past experiences to generate predictions under novel conditions. Despite the high demand for this process and the observation that it deteriorates disproportionately with age, the underlying mechanisms remain unknown. We developed a rodent model of decision‐making during ambiguity to examine features of experience that contribute to inference. Rats learned either a simple (positive patterning) or complex (negative patterning) instrumental discrimination between the illumination of one or two lights. During test, only one light was lit while the other relevant light was blocked from physical detection (covered by an opaque shield, rendering its status ambiguous). We found experience with the complex negative patterning discrimination was necessary for rats to behave sensitively to the ambiguous test situation. These rats behaved as if they inferred the presence of the hidden light, responding differently than when the light was explicitly absent (uncovered and unlit). Differential expression profiles of the immediate early gene cFos indicated hippocampal involvement in the inference process while localized microinfusions of the muscarinic antagonist, scopolamine, into the dorsal hippocampus caused rats to behave as if only one light was present. That is, blocking cholinergic modulation prevented the rat from inferring the presence of the hidden light. Collectively, these results suggest cholinergic modulation mediates recruitment of hippocampal processes related to past experiences and transfer of these processes to make decisions during ambiguous situations. Our results correspond with correlations observed between human brain function and inference abilities, suggesting our experiments may inform interventions to alleviate or prevent cognitive dysfunction. © 2015 Wiley Periodicals, Inc.
Association of Serum Asymmetric Dimethylarginine With Muscle Strength and Gait Speed: A Cross-Sectional Study of the HEIJO-KYO Cohort
Authors: Obayashi Kenji , Saeki Keigo , Maegawa Taeko , Sakai Takahide , Kitagawa Maiko , Otaki Naoto , Kataoka Hiroshi , Kurumatani Norio
Published: December 2015

Muscle strength and gait speed are related with functional limitations and disabilities and also predict cardiovascular and all-cause mortality. Nitric oxide (NO) plays an important role in regulating physiological process in skeletal muscles; however, the association between serum asymmetric dimethylarginine (ADMA) level, an endogenous competitive inhibitor of NO synthesis, and physical performance has not yet been studied. We investigated the associations of serum ADMA level with muscle strength and usual gait speed in a cross-sectional study of 550 elderly individuals (mean age, 71.2 ± 6.6 years). Mean ADMA level was 0.45 ± 0.06 µmol/L; mean grip and quadriceps strengths were 27.7 ± 8.4 kg and 165.1 ± 81.6 Nm, respectively; and mean gait speed was 1.37 ± 0.30 m/s. In multivariate linear regression analysis adjusted for potential confounding factors (age, gender, body weight, smoking and drinking status, household income, hypertension, diabetes, renal function, and physical activity), higher serum ADMA level was significantly associated with lower grip and quadriceps strengths and slower gait speed (grip strength: β, –1.257; 95% confidence interval [CI], –1.990 to –0.525; p = 0.001; quadriceps strength: β, –11.730; 95% CI, –20.924 to –2.536; p = 0.012; gait speed: β, –0.065; 95% CI, –0.108 to –0.022; p = 0.003). Our findings indicate the significant association between serum ADMA level and physical performance among elderly individuals, which was independent of the important potential confounders. © 2015 American Society for Bone and Mineral Research.
Ursodeoxycholic acid after bile duct stone removal and risk factors for recurrence: a randomized trial
Authors: Yamamoto Ryuichi , Tazuma Susumu , Kanno Keishi , Igarashi Yoshinori , Inui Kazuo , Ohara Hirotaka , Tsuyuguchi Toshio , Ryozawa Shomei
Published: December 2015

Background

Currently, no established pharmacologic treatment exists for the prevention of recurrent common bile duct (CBD) stones.

Methods

Here, we present a multi‐center randomized trial that compared the CBD recurrence rate after bile duct stone removal between patients given ursodeoxycholic acid (UDCA) and the untreated group. A total of 36 patients were randomly assigned to either the UDCA (n = 15) or the untreated group (n = 21). The primary end‐point was the recurrence rate of CBD stones.

Results

The recurrence rate of CBD stones was 6.6% in the UDCA group and 18.6% in the untreated group (P = 0.171). A multivariate analysis found that not receiving UDCA was an independent risk factor for stone recurrence. The recurrence rates of CBD stones did not differ by sex, past history of cholecystectomy, or the presence of gallstones.

Conclusions

Our findings indicate that UDCA may be a novel treatment strategy to prevent the recurrence of CBD stones. However, further evaluation of UDCA in a larger number of subjects will be required to confirm the applicability of these results.
Epidemiologic study of human parvovirus B19 infection in East China
Authors: Zhang Lahong , Cai Chengsong , Pan Feng , Hong Liquan , Luo Xian , Hu Sha , Xu Jiali , Chen Zhaojun
Published: December 2015

Human parvovirus B19 (B19V) infection causes a number of diseases in humans, and, in some circumstances, can be life threatening. To understand the epidemiology of B19V infection in the greater metropolitan area of Hangzhou, East China, we performed surveys of IgM and IgG antibodies against B19V and quantification of B19V DNA, by using enzyme‐linked immunosorbent assay and quantitative PCR, respectively, in plasma samples from diverse groups. These groups included anemia patients, Mycoplasma pneumonia‐ and Treponema pallidum‐infected patients, HIV‐positive individuals, and healthy blood donor volunteers. Our results demonstrated a low level of B19V IgG antibody presence, ranging from 21.9% to 41.8% in all the groups tested, suggesting a low prevalence of B19V infection in the area. Of note, we found that two healthy blood donors and one Mycoplasma pneumonia‐infected patient had B19V IgM antibody among 1,290 plasma samples tested. The Mycoplasma pneumonia‐infected patient had viremia with viral genome copies of 2.86 × 106 per ml of plasma. We detected a high rate of B19V DNA (7.1%) in HIV‐positive injection drug users. Importantly, an amino acid mutation of P558S in the large non‐structural protein NS1 was identified to be conserved among 14 B19V isolates from the HIV‐positive group but not in the B19V isolate of the Mycoplasma pneumonia‐infected patient, representing a hallmark of B19V isolates that circulate in HIV1‐positive patients in the greater metropolitan area of Hangzhou, East China. J. Med. Virol. 88:1113–1119, 2016. © 2015 Wiley Periodicals, Inc.
Usefulness of Dried Blood Spots (DBS) to perform hepatitis C virus genotyping in drug users in Senegal
Authors: Ndiaye O. , Gozlan J. , Diop‐Ndiaye H. , Sall A.S. , Chapelain S. , Leprêtre A. , Maynart M. , Gueye M. , Lo G , Thiam M. , Ba I. , Lacombe K. , Girard P.M. , Mboup S. , Kane C.T.
Published: December 2015

The aim of this pilot study was to analyze the Hepatitis C Virus (HCV) genotypes circulating in Senegal among Drug User (DUs), using Dried Blood Spots (DBS) as RNA source for molecular assays. Heroin and/or cocaine users (n = 506) were recruited in Dakar from April to July 2011, using a Respondent Driven Sampling (RDS) method. DBS preparation consisted of five drops of whole blood from finger applied to a Whatman paper card. HCV infection was screened by the detection of anti‐HCV antibodies, using a rapid immune‐chromatographic test. HCV RNA was quantified on anti‐HCV positive DBS, using the Abbott RealTime HCV® Genotyping was performed on DBS with detectable viral load with Versant® HCV Genotype 2.0 Assay (LiPA) and Abbott RealTime HCV Genotype II assay®. Among the 506 participants, 120 were tested as positive for anti‐HCV antibodies and their samples were analyzed for HCV RNA viral load and genotype. Out of the 120 DBS tested, HCV RNA was detected on 25 (20.8%). The median viral load was 15,058 IU/ml (ranging from 710 to 766,740 IU/ml). All positive DBS were suitable for the genotyping assay, that showed a predominance of genotype 1 (21/25) including 16 genotypes 1a and 5 genotypes 1b. HCV genotype 1 prevails in a DU population in Dakar. DBS could be useful for HCV RNA genotyping, but optimal storage conditions should required avoiding RNA impairment. Acknowledging this limitation, DBS could be a great interest for detecting and genotyping HCV viremic patients. J. Med. Virol. 89:484–488, 2017. © 2015 Wiley Periodicals, Inc.
Multiplex‐PCR for the detection of viruses in the CSF of infants and young children
Authors: Walls Tony , McSweeney Alice , Anderson Trevor , Jennings Lance C.
Published: December 2015

We aimed to establish the utility of the Fast‐track diagnostics Viral meningitis multiplex PCR kit for the diagnosis of central nervous system infection in infants. The multiplex assay had reduced sensitivity for the detection of enterovirus, the predominant pathogen in young infants, when compared to our in‐house singleplex PCR. In our infant population, multiple singleplex PCR assays perform better than a multiplex assay for the detection of CSF viruses. J. Med. Virol. 89:559–561, 2017. © 2016 Wiley Periodicals, Inc.
Computational characterization of fracture healing under reduced gravity loading conditions
Authors: Gadomski Benjamin C. , Lerner Zachary F. , Browning Raymond C. , Easley Jeremiah T. , Palmer Ross H. , Puttlitz Christian M.
Published: December 2015

The literature is deficient with regard to how the localized mechanical environment of skeletal tissue is altered during reduced gravitational loading and how these alterations affect fracture healing. Thus, a finite element model of the ovine hindlimb was created to characterize the local mechanical environment responsible for the inhibited fracture healing observed under experimental simulated hypogravity conditions. Following convergence and verification studies, hydrostatic pressure and strain within a diaphyseal fracture of the metatarsus were evaluated for models under both 1 and 0.25 g loading environments and compared to results of a related in vivo study. Results of the study suggest that reductions in hydrostatic pressure and strain of the healing fracture for animals exposed to reduced gravitational loading conditions contributed to an inhibited healing process, with animals exposed to the simulated hypogravity environment subsequently initiating an intramembranous bone formation process rather than the typical endochondral ossification healing process experienced by animals healing in a 1 g gravitational environment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1206–1215, 2016.
Development of Passive Immunotherapies for Synucleinopathies
Authors: Bergström Ann‐Louise , Kallunki Pekka , Fog Karina
Published: December 2015

Immunotherapy using antibodies targeting alpha‐synuclein has proven to be an effective strategy for ameliorating pathological and behavioral deficits induced by excess pathogenic alpha‐synuclein in various animal and/or cellular models. However, the process of selecting the anti‐alpha‐synuclein antibody with the best potential to treat synucleinopathies in humans is not trivial. Critical to this process is a better understanding of the pathological processes involved in the synucleinopathies and how antibodies are able to influence these. We will give an overview of the first proof‐of‐concept studies in rodent disease models and discuss challenges associated with developing antibodies against alpha‐synuclein resulting from the distribution and structural characteristics of the protein. We will also provide a status on the passive immunization approaches targeting alpha‐synuclein that have entered, or are expected to enter, clinical evaluation. © 2015 Movement Disorder Society
Fully coupled linear modelling of incompressible free‐surface flow, compressible air and flexible structures
Authors: Toth F. , Kaltenbacher M.
Published: December 2015

Incompressible free‐surface flow is a common assumption for the modelling of water waves. Connected with the aim to develop very large floating platforms, air chamber supported floating structures have attracted considerable research interest in the past. Such structures are carried by air entrapped in chambers formed by stiff, vertical walls. In order to model these types of structures, the interactions between surface gravity waves and compressible air must be taken into account. If the payload requirements for air chamber supported structures are low enough, the air chambers may be formed by flexible membrane cylinders. In such systems, pressure variations can lead to considerable changes in chamber volume. Therefore, the flexibility of the bounding structures must be taken into account. We present a modelling strategy to tackle the fully coupled problem of compressible gas in a flexible chamber and incompressible free‐surface flow in an unbounded domain. The governing equations and boundary conditions are described and solved by the finite element method. A perfectly matched layer is used to obtain a solution for an unbounded domain. Finally, the numerical implementation is validated by various test cases. Copyright © 2015 John Wiley & Sons, Ltd.
Formulation and implementation of stress‐driven and/or strain‐driven computational homogenization for finite strain
Authors: van Dijk N. P.
Published: December 2015

In this paper, we present a homogenization approach that can be used in the geometrically nonlinear regime for stress‐driven and strain‐driven homogenization and even a combination of both. Special attention is paid to the straightforward implementation in combination with the finite‐element method. The formulation follows directly from the principle of virtual work, the periodic boundary conditions, and the Hill–Mandel principle of macro‐homogeneity. The periodic boundary conditions are implemented using the Lagrange multiplier method to link macroscopic strain to the boundary displacements of the computational model of a representative volume element. We include the macroscopic strain as a set of additional degrees of freedom in the formulation. Via the Lagrange multipliers, the macroscopic stress naturally arises as the associated ‘forces’ that are conjugate to the macroscopic strain ‘displacements’. In contrast to most homogenization schemes, the second Piola–Kirchhoff stress and Green–Lagrange strain have been chosen for the macroscopic stress and strain measures in this formulation. The usage of other stress and strain measures such as the first Piola–Kirchhoff stress and the deformation gradient is discussed in the Appendix. Copyright © 2015 John Wiley & Sons, Ltd.
Relationship between actigraphy‐assessed sleep quality and fat mass in college students
Authors: Kahlhöfer Julia , Karschin Judith , Breusing Nicolle , Bosy‐Westphal Anja
Published: December 2015

Objective

Only a few studies have used objective measurements to investigate the relationship between sleep quality and obesity. These studies showed controversial results.

Methods

Sleep efficiency was measured by Actiwatch 2 in 132 healthy students (age 23.3 ± 3.7 years, BMI 23.1 ± 4.1 kg/m2) for 12 ± 3 nights, differentiating between work and free days. Physical activity, dietary habits, and autonomic function (heart rate variability, HRV) were analyzed as potential determinants of sleep quality and its relationship with body composition.

Results

Sleep efficiency was 87.0% in women and 84.9% in men (P < 0.05) and was higher at free days when compared to work days in women (P < 0.05). Lower sleep efficiency was associated with a higher fat mass. This was true for sleep efficiency on work days in women [fat mass index (FMI): r = −0.35, P < 0.01] and for free days in men (FMI: r = −0.37, P < 0.05). Poor sleep efficiency was associated with less physical activity (r = 0.29, P < 0.05) and impaired HRV in women (r = 0.60, P < 0.05) and with a higher fat intake in men (r = −0.39, P < 0.05).

Conclusions

Poor sleep efficiency was associated with higher fat mass. The relationship between sleep quality and fat mass differs between work and free days and may be explained by physical activity and autonomic function in women and dietary habits in men.