bluuebunny/crossref_metadata_2025 huggingface dataset:
Neodymium isotope analyses after combined extraction of actinide and lanthanide elements from seawater and deep‐sea coral aragonite
Authors: Struve Torben , van de Flierdt Tina , Robinson Laura F. , Bradtmiller Louisa I. , Hines Sophia K. , Adkins Jess F. , Lambelet Myriam , Crocket Kirsty C. , Kreissig Katharina , Coles Barry , Auro Maureen E.
Published: December 2015

Isotopes of the actinide elements protactinium (Pa), thorium (Th), and uranium (U), and the lanthanide element neodymium (Nd) are often used as complementary tracers of modern and past oceanic processes. The extraction of such elements from low abundance matrices, such as seawater and carbonate, is however labor‐intensive and requires significant amounts of sample material. We here present a combined method for the extraction of Pa, Th, and Nd from 5 to 10 L seawater samples, and of U, Th, and Nd from <1 g carbonate samples. Neodymium is collected in the respective wash fractions of Pa‐Th and U‐Th anion exchange chromatographies. Regardless of the original sample matrix, Nd is extracted during a two‐stage ion chromatography, followed by thermal ionization mass spectrometry (TIMS) analysis as NdO+. Using this combined procedure, we obtained results for Nd isotopic compositions on two GEOTRACES consensus samples from Bermuda Atlantic Time Series (BATS), which are within error identical to results for separately sampled and processed dedicated Nd samples (εNd = −9.20 ± 0.21 and −13.11 ± 0.21 for 15 and 2000 m water depths, respectively; intercalibration results from 14 laboratories: εNd = −9.19 ± 0.57 and −13.14 ± 0.57). Furthermore, Nd isotope results for an in‐house coral reference material are identical within analytical uncertainty for dedicated Nd chemistry and after collection of Nd from U‐Th anion exchange chromatography. Our procedure does not require major adaptations to independently used ion exchange chromatographies for U‐Pa‐Th and Nd, and can hence be readily implemented for a wide range of applications.
Do split and displacement sudden stratospheric warmings have different annular mode signatures?
Authors: Maycock Amanda C. , Hitchcock Peter
Published: December 2015

Sudden stratospheric warmings (SSWs) contribute to intraseasonal tropospheric forecasting skill due to their surface impacts. Recent studies suggest these impacts depend upon whether the polar vortex splits or is displaced during the SSW. We analyze the annular mode signatures of SSWs in a 1000 year IPSL‐CM5A‐LR simulation. Although small differences in the mean surface Northern Annular Mode (NAM) index following splits and displacements are found, the sign is not consistent for two independent SSW algorithms, and over 50 events are required to distinguish the responses. We use the wintertime correlation between extratropical lower stratospheric wind anomalies and the surface NAM index as a metric for two‐way stratosphere‐troposphere coupling and find that the differences between splits and displacements, and between classification methodologies, can be simply understood in terms of their mean stratospheric wind anomalies. Predictability studies should therefore focus on understanding the factors that determine the persistence of these anomalies following SSWs.
Derivation of the specific optical properties of suspended mineral particles and their contribution to the attenuation of solar irradiance in offshore waters by ocean color remote sensing
Authors: Mitchell Catherine , Cunningham Alex , McKee David
Published: December 2015

Two independently derived algorithms which had previously been validated against in situ data were applied to 8 years of MODIS observations of the Irish Sea to obtain (i) concentrations of lithogenic mineral particles (MSSl) in surface waters and (ii) the specific backscattering and absorption coefficients for these particles in the 488 nm waveband (the values obtained were a*MSSl488 = 0.031 m2 g−1 and bb*MSSl488 = 0.010 m2 g−1). This information was used to calculate the mean attenuation coefficient for downward irradiance
in the surface mixed layer, and the fraction of this coefficient that was attributable to suspended mineral particles. Mineral particles at relatively low concentrations (<5 g m−3) were the major determinant of
values throughout the region in winter, and in the central Irish Sea this influence persisted for much of the spring/autumn primary production period. In the north and south, however, marked short‐term increases in
due to phytoplankton blooms occurred during periods when MSSl values were relatively low. Seasonally averaged maps of the fractional contribution of MSSl to
show strong links to vertical mixing, with sharp contrasts developing in spring at the boundaries between mixed and stratified waters. We conclude that the ocean color processing sequence presented here can reveal spatial and seasonal patterns in the dynamics of lithogenic mineral particles which have potentially valuable applications in ecosystem status assessment, environmental impact monitoring, and the tuning and validation of numerical models of shelf sea ecosystems.
Toward a new parameterization of hydraulic conductivity in climate models: Simulation of rapid groundwater fluctuations in Northern California
Authors: Vrettas Michail D. , Fung Inez Y.
Published: December 2015

Preferential flow through weathered bedrock leads to rapid rise of the water table after the first rainstorms and significant water storage (also known as “rock moisture”) in the fractures. We present a new parameterization of hydraulic conductivity that captures the preferential flow and is easy to implement in global climate models. To mimic the naturally varying heterogeneity with depth in the subsurface, the model represents the hydraulic conductivity as a product of the effective saturation and a background hydraulic conductivity Kbkg, drawn from a lognormal distribution. The mean of the background Kbkg decreases monotonically with depth, while its variance reduces with the effective saturation. Model parameters are derived by assimilating into Richards’ equation 6 years of 30 min observations of precipitation (mm) and water table depths (m), from seven wells along a steep hillslope in the Eel River watershed in Northern California. The results show that the observed rapid penetration of precipitation and the fast rise of the water table from the well locations, after the first winter rains, are well captured with the new stochastic approach in contrast to the standard van Genuchten model of hydraulic conductivity, which requires significantly higher levels of saturated soils to produce the same results. “Rock moisture,” the moisture between the soil mantle and the water table, comprises 30% of the moisture because of the great depth of the weathered bedrock layer and could be a potential source of moisture to sustain trees through extended dry periods. Furthermore, storage of moisture in the soil mantle is smaller, implying less surface runoff and less evaporation, with the proposed new model.
Utilization of Ambulatory Physician Encounters, Emergency Room Visits, and Hospitalizations by Systemic Lupus Erythematosus Patients: A 13‐Year Population Health Study
Authors: Hanly John G. , Thompson Kara , Skedgel Chris
Published: December 2015

Objective

To determine total physician encounters, emergency room (ER) visits, and hospitalizations in an incident cohort of systemic lupus erythematosus (SLE) cases and matched control patients over 13 years.

Methods

A retrospective cohort study was performed utilizing administrative health care data from approximately 1 million people with access to universal health care. Using International Classification of Diseases, Ninth and Tenth Revisions diagnostic codes, 7 SLE case definitions were used. Each case was matched by age and sex to 4 randomly selected controls. Data included physician billings, ER visits, and hospital discharges over 13 years.

Results

The number of incident SLE cases varied from 564 to 4,494 depending on the case definition used. The mean age varied from 47.7 to 50.6 years and the proportion of females from 78.0% to 85.1%. SLE utilization of physicians was highest in the index year, and declined significantly thereafter for all case definitions. By the fourth year, encounters with subspecialty physicians fell by 60% (rheumatologists), 50% (internists), and 31% (other physicians). In contrast, visits to family physicians fell by only 9%. Visits to the ER and hospital admissions for SLE cases were also more frequent early in the disease course and fell significantly over the study for both ER visits (all case definitions) and hospitalizations (2 of 7 case definitions).

Conclusion

In SLE patients, health care utilization is highest in the first few years following the diagnosis, which is also the time of maximal involvement by rheumatologists. Utilization declines over time, and encounters with patients’ family physicians predominate over those of other physician groups.
Toward a Standardized Reporting of Outcomes in Hand Osteoarthritis: Developing a Common Metric of Outcome Measures Commonly Used to Assess Functioning
Authors: Prodinger Birgit , Stamm Tanja , Peterson Diana , Stucki Gerold , Tennant Alan ,   on behalf of the International Classification of Functioning, Disability, and Health Info Network
Published: December 2015

Objective

Functioning is an important outcome in hand osteoarthritis (OA). The heterogeneity of patient‐reported outcome measures (PROMs) available challenges the direct comparability of information collected by these instruments. This study aimed to examine whether it is possible to achieve metric equivalence of PROMs commonly used to measure functioning in people with hand OA.

Methods

A secondary analysis of data from 253 persons who participated in the Vienna Hand Osteoarthritis Cohort Study was conducted applying the Rasch measurement model. Participants completed the Health Assessment Questionnaire, the Australian/Canadian Index for Hand Osteoarthritis, the Functional Index for Hand Osteoarthritis (FIHOA), and the Cochin Scale. The assumptions of stochastic ordering, local independence, unidimensionality, and invariance were tested for each scale independently before the scales were co‐calibrated onto a common metric.

Results

Except for the FIHOA, all measures indicated issues of local dependency in the initial analyses. After accommodating those with testlets, all scales satisfied the assumptions of the Rasch model (χ2 > 0.05). Marginal misfit in 2 items was found in the FIHOA, but this did not disturb person estimates. As the 4 scales form a common metric that satisfies the assumptions of the Rasch model, the scores can be equated.

Conclusion

The scores of the 4 hand function measures can be transformed to a common 0–100 metric, such that scores can be interchanged. A user‐friendly transformation table enables clinicians and researchers to have access to the common metric by simply adding up the total score for each instrument and identifying the corresponding transformed score on the common metric.
Contradictory Role of CD97 in Basal and Tumor Necrosis Factor–Induced Osteoclastogenesis In Vivo
Authors: Won Hee Yeon , Mun Se Hwan , Shin Bongjin , Lee Sun‐Kyeong
Published: December 2015

Objective

CD97, a member of the 7‐transmembrane epidermal growth factor family of adhesion G protein–coupled receptors, is expressed on various cell types. This study was undertaken to elucidate the functions of CD97 in bone and inflammation in an experimental mouse model, by examining the effect of CD97 on osteoclastogenesis in vitro, characterizing the skeletal phenotype of CD97‐deficient (CD97‐knockout [KO]) mice, and assessing the responses to tumor necrosis factor (TNF) treatment.

Methods

Femoral tissue and bone marrow (BM)–derived cells from CD97‐KO and wild‐type (WT) mice were assessed using histomorphometric analyses, in vitro cultures, and reverse transcription–polymerase chain reaction. Serum cytokine and chemokine levels in the presence or absence of TNF challenge were analyzed by multiplex assay.

Results

In cultures of mouse BM‐derived macrophages in vitro, RANKL induced the expression of CD97. In vivo, the trabecular bone volume of the femurs of female CD97‐KO mice was increased, and this was associated with a decrease in the number of osteoclasts. Compared to WT mice, CD97‐KO mice had a reduced potential to form osteoclast‐like cells in vitro. Furthermore, TNF treatment augmented the formation of osteoclasts in the calvaria of CD97‐KO mice in vivo, by increasing the production of RANKL and other cytokines and chemokines and by reducing the production of osteoprotegerin by calvarial cells.

Conclusion

These findings demonstrate that CD97 is a positive regulator of osteoclast‐like cell differentiation, a mechanism that influences bone homeostasis. However, the presence of CD97 may be essential to suppress the initial osteoclastogenesis that occurs in response to acute and local inflammatory stimuli.
Brief Report: Influence of HLA–DRB1 Susceptibility Alleles on the Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans
Authors: Bang So‐Young , Choi Ji‐Young , Park Songree , Choi Jeongim , Hong Seung‐Jae , Lee Hye‐Soon , Choi Chan‐Bum , Bae Sang‐Cheol
Published: December 2015

Objective

To investigate the association between HLA–DRB1 alleles and systemic lupus erythematosus (SLE) susceptibility and features of SLE, such as clinical manifestations and autoantibody profiles, in a Korean population.

Methods

We tested the genetic associations between HLA–DRB1 alleles and SLE susceptibility and clinical subphenotypes in 1,089 patients with SLE and 2,161 control subjects, including a discovery set (475 patients and 1,119 controls) and a replication set (614 patients and 1,042 controls). We used a relative predispositional effects (RPEs) method to examine the independent effect of each allele associated with SLE or its subphenotypes.

Results

We identified 4 HLA–DRB1 alleles that were associated with increased susceptibility to SLE, 2 of which had been detected previously (*15:01; P for RPE = 1.11 × 10−13, odds ratio [OR] 1.88) and *09:01 (P for RPE = 1.59 × 10−5, OR 1.46), and 2 of which were novel alleles (*08:03 [P for RPE = 8.80 × 10−8, OR 1.62]) and *07:01 (P for RPE = 1.14 × 10−6, OR 1.57)]. In addition, protective effects on the development of SLE were observed for 2 novel alleles (HLA–DRB1*12:02 [P for RPE = 6.35 × 10−4, OR 0.49]) and *11:01 [P for RPE = 1.24 × 10−3, OR 0.59]). The SLE risk alleles had an additive genetic effect, as demonstrated by the finding that double copies of these alleles (OR 3.38) had larger risk effects size compared with single copies (OR 1.95) and no copy (OR 1 [reference]). In a subphenotype analysis, various HLA–DRB1 alleles (including SLE risk alleles) were observed to have significant predispositional effects on diverse clinical manifestations. In particular, HLA–DRB1*15:01 (OR 2.30), *09:01 (OR 2.46), *07:01 (OR 2.61), and *08:03 (OR 2.97) were strongly associated with the risk of anti‐Sm antibody production.

Conclusion

We detected 6 HLA–DRB1 alleles that were associated with SLE in Koreans. The SLE risk alleles promoted the production of autoantibodies, including anti‐Sm, and diverse clinical manifestations.
Thigh Muscle Strength Predicts Knee Replacement Risk Independent of Radiographic Disease and Pain in Women: Data From the Osteoarthritis Initiative
Authors: Culvenor Adam G. , Wirth Wolfgang , Ruhdorfer Anja , Eckstein Felix
Published: December 2015

Objective

To determine whether thigh muscle strength predicts the risk of undergoing knee replacement surgery, independent of radiographic severity of osteoarthritis and pain.

Methods

Participants in the Osteoarthritis Initiative study who had received a knee replacement between the 12‐month and 60‐month follow‐up visits (cases) were each matched with 1 control subject (who did not receive a knee replacement over 60 months) for age, sex, height, body mass index, baseline radiographic stage, and location of joint space narrowing. Isometric knee extensor and flexor strength was recorded biennially. The strength examination prior to knee replacement (≤2 years) was termed time 0, that 2 years prior to time 0 was termed time −2, and that 4 years prior to time 0 was termed time −4. Muscle strength in patients and controls was compared using paired t‐tests and conditional logistic regression analysis adjusted for pain.

Results. One hundred thirty‐six participants (60% women, mean ± SD age 65 ± 9 years, body mass index 29 ± 4 kg/m2) received a knee replacement during follow‐up, had strength data for at least time 0, and had a matched control. Knee extensor strength at time 0 (primary outcome measure) was significantly lower in female patients compared with controls (P < 0.001, pain‐adjusted odds ratio [ORadj] 1.72, 95% confidence interval 1.16–2.56), but no significant difference was observed in men. Results were similar for knee flexor strength at time 0 and for longitudinal change in extensor and flexor strength between time −2 and time 0. Thigh muscle strength at time −2 or time −4, or change between time −4 and time −2, did not predict the risk of undergoing knee replacement surgery in men or women.

Conclusion

Thigh muscle strength predicted the risk of undergoing knee replacement surgery in women, but not in men. The results of this study may identify a window during which the risk of undergoing knee replacement surgery in women can be modified.
Identification of Cyclin‐Dependent Kinase 1 as a Novel Regulator of Type I Interferon Signaling in Systemic Lupus Erythematosus
Authors: Wu Lingling , Qin Yuting , Xia Shiwei , Dai Min , Han Xiao , Wu Yanfang , Zhang Xiaoyan , Ma Jianyang , Wang Yan , Tang Yuanjia , Liu Zheng , Zhu Wei , Jallal Bahija , Yao Yihong , Qu Bo , Shen Nan
Published: December 2015

Objective

Type I interferon (IFN) signaling is regarded as a central pathogenic pathway in systemic lupus erythematosus (SLE). Specific inhibition of this pathway is a core area for the development of new therapies for SLE. This study was undertaken to clarify the pathogenic mechanism involved and to identify new therapeutic targets, using a high‐throughput screening platform to determine novel regulators that contribute to the overactivation of the type I IFN signaling pathway in SLE.

Methods

A high‐throughput IFN‐stimulated response element (ISRE)–luciferase assay was used to screen for candidate genes that regulate the IFN signaling pathway. Western blotting was used to confirm the regulatory function of CDK1. SYBR Green quantitative reverse transcriptase–polymerase chain reaction was used to detect the expression of individual IFN‐stimulated genes (ISGs). The differential expression of CDK1 and ISGs in SLE patients and healthy controls was analyzed using RNA sequencing data and a microarray.

Results

The high‐throughput ISRE‐luciferase assay revealed that CDK1 enhanced type I IFN signaling. Consistent with this finding, CDK1 promoted the type I IFN–induced phosphorylation of STAT‐1 and the up‐regulated expression of ISGs. CDK1 expression was elevated in peripheral blood mononuclear cells (PBMCs) and kidney biopsy specimens from SLE patients and correlated positively with their IFN scores. A CDK1 inhibitor reduced the expression of ISGs in PBMCs from SLE patients and in renal cells from mice with lupus.

Conclusion

Our findings indicate that CDK1 is a positive regulator of the IFN signaling pathway. The overexpression of CDK1 might contribute to the abnormally amplified type I IFN signaling in SLE, and the inhibition of CDK1 could be used to down‐regulate type I IFN signaling in SLE.
Whole Exome Sequencing Identifies Rare Protein‐Coding Variants in Behçet's Disease
Authors: Ognenovski Mikhail , Renauer Paul , Gensterblum Elizabeth , Kötter Ina , Xenitidis Theodoros , Henes Jörg C. , Casali Bruno , Salvarani Carlo , Direskeneli Haner , Kaufman Kenneth M. , Sawalha Amr H.
Published: December 2015

Objective

Behçet's disease (BD) is a systemic inflammatory disease with an incompletely understood etiology. Despite the identification of multiple common genetic variants associated with BD, rare genetic variants have been less explored. We undertook this study to investigate the role of rare variants in BD by performing whole exome sequencing in BD patients of European descent.

Methods

Whole exome sequencing was performed in a discovery set comprising 14 German BD patients of European descent. For replication and validation, Sanger sequencing and Sequenom genotyping were performed in the discovery set and in 2 additional independent sets of 49 German BD patients and 129 Italian BD patients of European descent. Genetic association analysis was then performed in BD patients and 503 controls of European descent. Functional effects of associated genetic variants were assessed using bioinformatic approaches.

Results

Using whole exome sequencing, we identified 77 rare variants (in 74 genes) with predicted protein‐damaging effects in BD. These variants were genotyped in 2 additional patient sets and then analyzed to reveal significant associations with BD at 2 genetic variants detected in all 3 patient sets that remained significant after Bonferroni correction. We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and between BD and NEIL1 (rs5745908), involved in base excision DNA repair (P = 3.22 × 10−4 and P = 5.16 × 10−4, respectively). The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis (Bonferroni‐corrected P = 5.63 × 10−14, P = 7.29 × 10−6, P = 1.15 × 10−5, and P = 6.40 × 10−3, respectively). The genetic association in NEIL1 is a predicted splice donor variant that may introduce a deleterious intron retention and result in a noncoding transcript variant.

Conclusion

We used whole exome sequencing in BD for the first time and identified 2 rare putative protein‐damaging genetic variants associated with this disease. These genetic variants might influence cytoskeletal regulation and DNA repair mechanisms in BD and might provide further insight into increased leukocyte tissue infiltration and the role of oxidative stress in BD.
Adaptation of CHO cells in serum‐free conditions for erythropoietin production: Application of EVOP technique for process optimization
Authors: Jukić Suzana , Bubenik Dijana , Pavlović Nediljko , Tušek Ana Jurinjak , Srček Višnja Gaurina
Published: December 2015

Mammalian cell cultures are the preferred expression systems for the production of biopharmaceuticals requiring posttranslational processing. Usually, cell cultures are cultivated in medium supplemented with serum, which supports cell proliferation, viability, and productivity. However, due to scientific and regulatory concerns, serum‐free conditions are required in recombinant protein production. Cell lines that are intended for commercial recombinant protein production have to adapt to serum‐ or protein‐free conditions early in their development. This is a labor‐ and time‐consuming process because of the specific cell requirements related to their adaptation in new microenvironment. In the present study, a Chinese hamster ovary (CHO) cell line producing glycosylated recombinant human erythropoietin (rhEPO) was adapted for growth and rhEPO production in serum‐ and protein‐free conditions. The physiology, growth parameters, and morphology of the CHO cells and rhEPO biosynthesis and structure were closely monitored during the adaptation process to avoid unwanted selection of cell subpopulations. The results showed that the CHO cells were successfully adapted to suspension growth and rhEPO production in the protein‐free conditions and that the structure of rhEPO remained nearly unchanged. In addition, during rhEPO production in the protein‐free suspension conditions, the agitation rate seem to be significant for optimal process performance in contrast to the initial cell concentration, evaluated through evolutionary operation method.
Functionalization of poly(amidoamine) dendrimer‐based nano‐architectures using a naphthalimide derivative and their fluorescent, dyeing and antimicrobial properties on wool fibers
Authors: Sadeghi‐Kiakhani Mousa , Safapour Siyamak
Published: December 2015

Novel naphthalimide–poly(amidoamine) dendrimer fluorescent dyes were synthesized, and their structures were identified and confirmed using different characterization methods such as Fourier transform infrared, 1H NMR, 13C NMR, differential scanning calorimetry, elemental analysis and UV–vis spectroscopy. The spectrophotometric studies demonstrated absorption maxima (λmax) and extinction coefficient (εmax) values in the ranges of 429–438 nm and 25,635–88,618 L/mol/cm, respectively. The dyeing, fastness and antimicrobial properties of dyed wool fibers were examined. Colorimetric measurements demonstrated a greenish‐yellow hue with remarkable fluorescence intensity on dyed wool. Although the fastness properties of naphthalimide dye on wool fibers were poor/moderate, color fastness was appreciably improved through modification of the dye using dendrimers. The results revealed that the newly synthesized dyes are potent antimicrobial agents on wool fibers. Overall, it was deduced that poly(amidoamine) (PAMAM) dendrimers could be exploited as a promising tool in tailoring the different properties of naphthalimide dyes, being suitable for dyeing and antimicrobial finishing agents for wool fibers. Copyright © 2015 John Wiley & Sons, Ltd.
Beyond Asian Biotechnology: Collaboration between Asia and Europe
Authors: Kim Hyun Jung
Published: December 2015

Asian Federation of Biotechnology (AFOB) has built a strong network of scientists, researchers, enterprisers, etc. of Asian biotechnology through scientific symposiums, congresses and other various activities.
Randomized clinical trial of 940- versus 1470-nm endovenous laser ablation for great saphenous vein incompetence
Authors: Malskat W S J , Giang J , De Maeseneer M G R , Nijsten T E C , van den Bos R R
Published: December 2015

Background

The independent effect of wavelength used for endovenous laser ablation (EVLA) on patient-reported outcomes, health-related quality of life (HRQoL), treatment success and complications has not yet been established in a randomized clinical trial. The aim was to compare two different wavelengths, with identical energy level and laser fibres, in patients undergoing EVLA.

Methods

Patients with great saphenous vein incompetence were randomized to receive 940- or 1470-nm EVLA. The primary outcome was pain at 1 week. Secondary outcomes were: patient satisfaction, duration of analgesia use and time without normal activities assessed at 1 week; HRQoL after 12 weeks; treatment success after 12 and 52 weeks; change in Venous Clinical Severity Score (VCSS) after 12 weeks; and adverse events at 1 and 12 weeks.

Results

A total of 142 legs were randomized (940-nm EVLA, 70; 1470-nm EVLA, 72). Patients in the 1470-nm laser group reported significantly less pain on a visual analogue scale than those in the 940-nm laser group: median (i.q.r.) score 3 (2–7) versus 6 (3–8) (P = 0·004). Duration of analgesia use was significantly shorter after 1470-nm EVLA: median (i.q.r.) 1 (0–3) versus 2 (0–5) days (P = 0·037). HRQoL and VCSS improved equally in both groups. There was no difference in treatment success rates. Complications were comparable in both groups, except for more superficial vein thrombosis 1 week after 1470-nm EVLA.

Conclusion

EVLA using a 1470-nm wavelength fibre was associated with improved postoperative pain and a reduction in analgesia use in the first week after surgery compared with use of a 940-nm fibre. Treatment success and adverse event rates were similar. Registration number: NCT01637181 (http://www.clinicaltrials.gov).
Problems and solutions in delivering global surgery in the 21st century
Authors: McDermott F D , Kelly M E , Warwick A , Arulampalam T , Brooks A J , Gaarder T , Cotton B A , Winter D C
Published: December 2015

Background

Surgery has had low priority in global health planning, so the delivery of surgical care in low- and middle-income countries is often poorly resourced. A recent Lancet Commission on Global Surgery has highlighted the need for change.

Methods

A consensus view of the problems and solutions was identified by individual surgeons from high-income countries, familiar with surgical care in remote and poorer environments, based on recent publications related to global surgery.

Results

The major issues identified were: the perceived unimportance of surgery, shortage of personnel, lack of appropriate training and failure to establish surgical standards, failure to appreciate local needs and poor coordination of service delivery.

Conclusion

Surgery deserves a higher priority in global health resource allocation. Lessons learned from participation in humanitarian crises should be considered in surgical developments.
No‐Regret Solutions – Modular Production Concepts for Times of Complexity and Uncertainty
Authors: Mothes Helmut
Published: December 2015

Global competition, shorter product cycles, individualized products, and faster technology innovation lead to more complex production systems. For the product life cycle, forecast of product demand, resource availability, and technology chances becomes a mission impossible. Applying a modularization strategy, future production systems are designed as no‐regret‐solutions that add risk minimization to profit maximization. Additive manufacturing and the Internet of Things will significantly improve economics of modular designs for the chemical‐pharmaceutical Industry.
Chemical Programming of the Domain of Existence of Liquid Crystals
Authors: Dutronc Thibault , Terazzi Emmanuel , Guénée Laure , Buchwalder Kerry‐Lee , Floquet Sébastien , Piguet Claude
Published: December 2015

This work illustrates how enthalpy and entropy changes responsible for successive phase transitions of cyanobiphenyl‐based liquid crystals can be combined to give cohesive free energy densities. These new parameters are able to rationalize and quantify the demixing of the melting and clearing processes that occur in thermotropic liquid crystals. Minor structural variations at the molecular level can be understood as pressure increments that alter either the melting or clearing temperatures in a predictable way. This assessment of microsegregation operating in amphiphilic molecules paves the way for the chemical programming of the domain of existence of liquid‐crystalline phases.
On the Orthogonality of Two Thiol‐Based Modular Ligations
Authors: Turgut Hatice , Delaittre Guillaume
Published: December 2015

The chemoselectivity of two thiol‐based modular ligations operating under mild conditions is assessed. For this purpose, a macromolecular scaffold possessing allyl and pentafluorophenyl groups in two distinct parts is employed, which enables facile characterization by NMR spectroscopy (1H and 19F) and size‐exclusion chromatography. By using appropriate triggers (introduction of a base or light irradiation), it is possible to direct thiols to an arbitrarily chosen part of the scaffold, without any change to the other part and with no involvement of protecting group chemistry. Dual functionalization experiments are achieved by applying these triggers consecutively with no consideration of the reaction sequence order, evidencing full bidirectionality. A set of one‐pot, purification‐free procedures that enable near‐quantitative to full dual functionalization in (very) short reaction times (17–180 min) is also presented.
Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART‐1) trial design
Authors: Bartunek Jozef , Davison Beth , Sherman Warren , Povsic Thomas , Henry Timothy D. , Gersh Bernard , Metra Marco , Filippatos Gerasimos , Hajjar Roger , Behfar Atta , Homsy Christian , Cotter Gad , Wijns William , Tendera Michal , Terzic Andre
Published: December 2015

Aims

Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient‐derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART‐1 is designed as a large randomized, sham‐controlled multicentre study aimed to validate cardiopoietic stem cell therapy.

Methods

Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (<35%), and at high risk for recurrent HF‐related events, despite optimal medical therapy, will be randomized 1:1 to receive 600 × 106 bone marrow‐derived and lineage‐directed autologous cardiopoietic stem cells administered via a retention‐enhanced intramyocardial injection catheter or a sham procedure. The primary efficacy endpoint is a hierarchical composite of mortality, worsening HF, Minnesota Living with Heart Failure Questionnaire score, 6 min walk test, LV end‐systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months.

Conclusion

The CHART‐1 clinical trial is powered to examine the therapeutic impact of lineage‐directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART‐1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF.

Trial registration: NCT01768702
Electronic Structure Evaluation of an Oxidized Tris(methoxy)‐Substituted Ni Salen Complex
Authors: Chiang Linus , Clarke Ryan M. , Herasymchuk Khrystyna , Sutherland Mathew , Prosser Kathleen E. , Shimazaki Yuichi , Storr Tim
Published: December 2015

The Ni salen complex N,N′‐bis(2,3,4‐trimethoxysalicylidene)‐1,2‐cyclohexane‐(1R,2R)‐diamine nickel(II) (1), containing ortho‐, meta‐, and para‐methoxy‐substituted phenolate moieties, was prepared. Electrochemical studies revealed that the first oxidation of 1 occurs at a similar potential to a previously reported Ni salen complex NiSaltBu,OMe, employing an ortho‐tBu and para‐methoxy substitution pattern (M. Orio et al., Angew. Chem. Int. Ed. 2010, 49, 4989), demonstrating the counteracting effects of the methoxy substituent depending on ring location (ortho/para vs. meta). The second oxidation occurred at a much lower potential (E1/22 – E1/21 = 0.11 V) for 1, in comparison to NiSaltBu,OMe, suggesting significant localization of the ligand radical. The one‐electron oxidized form was prepared and studied using a number of experimental and theoretical methods. A localized ligand radical electronic structure was confirmed by the shape and intensity of the NIR bands, which was further verified by the presence of both phenolate and phenoxyl signatures in the resonance Raman spectrum. Theoretical calculations provided insight into the degree of ligand radical localization, and the nature of the low energy bands observed in the Vis/NIR experiment. Overall, the oxidation of 1 results in a localized ligand radical complex, with further oxidation processes easily accessible due to resonance stabilization afforded by the methoxy substituents.
Full‐duplex OFDMA multi‐user cellular systems: resource allocation and user pairing
Authors: Jiang Yunxiang , Chen He (Henry) , Lau Francis C.M. , Wang Peng , Li Yonghui
Published: December 2015

In this paper, we consider an orthogonal frequency division multiple access multi‐user cellular system with one full‐duplex base station communicating with multiple half‐duplex users in a bidirectional way. The uplink and downlink transmissions are coupled together because of the existence of the self‐interference at the base station and the inter‐user interference (IUI) from the uplink users to the downlink users. We aim to maximize the system sum‐rate of uplink and downlink transmissions by optimally pairing the uplink and downlink users and allocating the subcarriers and powers to these users. We formulate the problem as a mixed integer nonlinear programming problem. A two‐layer iterative solution based on the dual method and the sequential parametric convex approximation (SPCA) method is proposed. It is referred to as the dual–SPCA algorithm. The dual–SPCA algorithm requires the IUI channel state information to be available at the base station, and hence, a significant overhead is generated. To reduce the amount of overhead required, we assume that the IUI channel model is known at the base station, and we design a location‐aware resource allocation algorithm with limited channel state information that maximizes the system sum‐rate. Simulation results show that when self‐interference is low, uplink and downlink user‐pairing can provide significant improvement on the system sum‐rate compared with the conventional unidirectional half‐duplex transmission. In addition, by considering two different network deployments, such as urban macro cell scenario and small cell scenario, we show that the improvement of full‐duplex transmission over half‐duplex transmission highly depends on the channel parameters. Copyright © 2015 John Wiley & Sons, Ltd.
Significance of visual hallucinations and cerebral hypometabolism in the risk of dementia in Parkinson's disease patients with mild cognitive impairment
Authors: Gasca‐Salas Carmen , Clavero Pedro , García‐García David , Obeso José A. , Rodríguez‐Oroz María C.
Published: December 2015

Introduction

Mild cognitive impairment (MCI) and visual hallucinations (VH) are common co‐morbidities and risk factors for dementia in Parkinson's disease (PD). The relative value of each of them in the progression to dementia is unknown. We investigated cognitive impairment and cerebral hypometabolism in PD‐MCI patients with VH (VH‐positive) and without (VH‐negative).

Methods

Twenty‐one PD‐MCI patients (12 VH‐negative, nine VH‐positive) and 19 controls were studied using a comprehensive neuropsychological battery and [18F]‐Fluorodeoxyglucose positron emission tomography (FDG‐PET). The neuropsychological assessment was repeated after 30 months. Regional FDG uptake was analyzed using statistical parametric mapping.

Results

VH‐positive patients had lower FDG uptake bilaterally in the occipital, and parietal cortex, right temporal lobe and in the left cingulum compared with VH‐negative patients. The two groups showed no significant differences in clinical characteristics and cognitive status at baseline. After 30 months of follow‐up, three (25%) and four (50%) of the VH‐negative and VH‐positive patients, respectively, had progressed to dementia.

Conclusion

Even in the absence of significant cognitive differences, PD‐MCI patients with VH exhibit more severe cerebral hypometabolism and had a higher rate of progression to dementia than VH‐negative patients, supporting the importance of VH and cerebral hypometabolism in establishing the risk of dementia in PD‐MCI. Hum Brain Mapp 37:968–977, 2016. © 2015 Wiley Periodicals, Inc.
Coprisin exerts antibacterial effects by inducing apoptosis‐like death in Escherichia coli
Authors: Choi Hyemin , Hwang Jae‐Sam , Lee Dong Gun
Published: December 2015

Apoptosis commonly occurs in eukaryotes to eliminate unwanted cells. In this study, we demonstrated that coprisin‐treated bacteria undergo cell death that is mechanistically and morphologically similar to apoptosis in eukaryotes. Time‐kill kinetic assay against Escherichia coli indicated that coprisin exerted bactericidal activity. The bactericidal mechanism was studied by terminal deoxynucleotidyl transferase dUTP nick end labeling analysis, followed by Western blotting. We confirmed coprisin‐induced DNA fragmentation and activation of the RecA protein as a SOS response. Furthermore, FITC‐VAD‐FMK, FITC‐Annexin V, and bis‐(1,3‐dibutylbarbituric acid) trimethineoxonol [DiBAC4(3)] staining showed that caspase‐like protein(s), such as RecA, were activated, and membrane alterations such as phosphatidylserine externalization and cytoplasmic depolarization were induced. Finally, 3′‐(p‐hydroxyphenyl) fluorescein assay indicated that depolarization of membrane potential leads to hydroxyl radicals (•OH) formation. Based on these results, we conclude that coprisin exerts bactericidal activity against E. coli by causing severe DNA damage, which induces apoptosis‐like death. © 2015 IUBMB Life, 68(1):72–78, 2016
Foxc1 Expression in Early Osteogenic Differentiation Is Regulated by BMP4‐SMAD Activity
Authors: Hopkins Alexander , Mirzayans Freda , Berry Fred
Published: December 2015

FOXC1 is an important regulator of the initial steps in intramembranous and endochondral ossification processes. As BMP signalling is a key initiator of these processes, we sought to determine whether Foxc1 expression is regulated by such signalling factors. BMP4 treatment of C2C12 cells resulted in an induction in Foxc1 mRNA levels. Chromatin immunoprecipitation assays demonstrated that SMAD proteins interacted with the mouse Foxc1 promoter approximately 300 bp upstream of the transcription start site. This ChIP positive region was cloned into a luciferase reporter and demonstrated to be responsive to BMP4 stimulation. Reduction of Foxc1 levels in C2C12 cells though siRNA impaired BMP4 osteogenic differentiation. In contrast, BMP4 treatment repressed Foxc1 expression in 10T1/2 or D1‐ORL mesenchymal cells and MC3T3 preosteoblasts. Finally, siRNA knock‐down of Foxc1 in MC3T3 cells resulted in an induction of markers of osteoblast differentiation and an accelerated mineralization. These data indicate that Foxc1 expression is regulated by BMP4 and FOXC1 functions in the commitment of progenitor cells to the osteoblast fate and its expression is reduced when differentiation proceeds. J. Cell. Biochem. 117: 1707–1717, 2016. © 2015 Wiley Periodicals, Inc.
A hybrid adaptive sampling algorithm for obtaining reduced order models for systems with frequency dependent state‐space matrices
Authors: Samuel Elizabeth Rita , Ferranti Francesco , Knockaert Luc , Dhaene Tom
Published: December 2015

This paper proposes a hybrid adaptive sampling algorithm to automate the generation of reduced order models for systems described by large‐scale frequency dependent state‐space models. The evaluation of the frequency dependent state‐space model for each frequency sample can be computationally expensive. The distribution of frequency samples must be optimized to avoid oversampling and undersampling. In order to have an optimum number of frequency samples, the proposed algorithm uses the reflective exploration technique for the adaptive selection of samples, and the sampling is further refined using a binary search to validate the frequency dependent reduced order models. Projection‐based model order reduction techniques are used for obtaining the reduced order model. The projection matrix for each frequency sample is merged to obtain a common projection matrix for all samples. However, in certain cases when the number of sample points increases, the merged projection matrix also increases in dimension and might fail to provide a satisfactory reduction in model size. Thus, the merged projection matrix is truncated based on its singular values to obtain a compact common projection matrix. Then, the reduced order state‐space matrices per frequency are interpolated over the frequency range of interest to obtain the system response. Pertinent examples validate the proposed hybrid adaptive sampling algorithm. Copyright © 2015 John Wiley & Sons, Ltd.
Monitoring of the microstructure of ion‐irradiated nuclear ceramics by in situ Raman spectroscopy
Authors: Miro S. , Bordas E. , Thomé L. , Costantini J.‐M. , Leprêtre F. , Trocellier P. , Serruys Y. , Beck L. , Gosset D. , Verlet R. , Huguet‐Garcia J. , Tupin M. , Belleil M.
Published: December 2015

Raman spectroscopy is an efficient technique for studying the evolution of microstructure of materials under irradiation. For that purpose, a Raman spectrometer has been recently installed at the JANNUS‐Saclay platform. In this paper, we describe the new setup for in situ experiments. These in situ experiments allowed following the microstructural evolution of different materials (SiC, ZrO2 and B4C) as a function of ion fluence on a single sample (either single crystal or polycrystalline ceramics) under the same irradiation conditions. Our results show that Raman spectroscopy is a versatile non‐contact technique for studying on‐line crystalline phase changes or amorphization of irradiated iono‐covalent solids. A detailed analysis of Raman spectra is provided for the three materials (SiC, ZrO2 and B4C) investigated in this study, revealing quite different behaviors upon irradiation. Basically, Raman spectroscopy gives insight on these evolutions at the level of bonds given by specific phonon modes, in good agreement with Rutherford backscattering channeling (RBS/C), X‐ray diffraction (XRD) or transmission electron microscopy (TEM) data, which provide information at a long‐range scale. Copyright © 2015 John Wiley & Sons, Ltd.
Activity of α‐Chymotrypsin in Cationic and Nonionic Micellar Media: Ultraviolet and Fluorescence Spectroscopic Approach
Authors: Verma Santosh K. , Ghosh Kallol K. , Verma Rameshwari , Verma Shekhar , N. Girish H. , Zhao Xiujian
Published: December 2015

α‐Chymotrypsin (α‐CT) activity was measured in aqueous buffer with the following alkyltriphenylphosphonium bromide surfactants in the series cetyl, tetradecyl, and dodecyl as a tail length. For the sake of comparison with mixed micellar investigation on activity of α‐CT, cationic cetyltriphenylphosphonium bromide (CTPB) and nonionic surfactant Triton X‐100, Brij‐56, Brij‐35, Tween 20, and Igepal Co‐210 have been used. The p‐nitrophenyl acetate (PNPA) hydrolysis rate was determined at the surfactant concentration of both cationic and mixed micellar systems by a UV–vis spectrophotometer. The catalytic reaction follows the Michaelis–Menten mechanism, and the catalytic efficiency (kcat/KM) was evaluated for both homogeneous and mixed‐micellar media. The maximum catalytic efficiency was observed at 5 mM concentration of CTPB, but the highest catalytic efficiency, 572 M−1 s−1, was measured in the presence of mixed micellar (7.5 mM CTPB + 2.5 mM Tween‐20). The fluorescence (FL) spectra showed the differences of α‐CT conformations in the presence of cationic surfactants. The FL results suggest that the influence of cationic surfactant on proteolysis arises from the interaction with the α‐CT. The binding constant, ksv, of α‐CT with cationic aggregates was determined in the buffer using the Stern–Volmer equation by the fluorescence spectroscopic approach.