bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon stocks and accumulation rates in Pacific Northwest forests: role of stand age, plant community, and productivity
Authors: Gray Andrew N. , Whittier Thomas R. , Harmon Mark E.
Published: February 2016

Forest ecosystems are removing significant amounts of carbon from the atmosphere. Both abiotic resource availability and biotic interactions during forest succession affect C accumulation rates and maximum C stocks. However, the timing and controls on the peak and decline in C accumulation rates as stands age, trees increase in size, and canopy gaps become prevalent are not well‐understood. Our study examines measured change in live and dead woody C pools from 8767 inventory plots on 9.1 million ha of Pacific Northwest National Forest lands to determine how the balance of tree growth, mortality, and dead wood decomposition varied by stand age, plant community type, and site productivity; and to compare the contribution of different tree sizes to C accumulation. Maximum non‐mineral soil C for old‐growth stands varied significantly by productivity class within plant community types, but on average stands accumulated 75% of maximum stocks by age 127 ± 35 yr. We did not see a decline in net primary production of wood (NPPw) with age in moderate and low‐productivity classes, but found a 33% reduction in high‐productivity classes. Mortality increased with stand age such that net change in live tree biomass, and change in total woody C, was not significantly different from zero in old‐growth stands over age 400 (0.15 ± 0.64 Mg C·ha−1·yr−1for woody C). However, significant though modest C accumulation was found in forests 200–400 yr old (0.34–0.70 Mg C·ha−1·yr−1, depending on age class). Mortality of trees >100 cm diameter exceeded or equaled NPPw, but trees were growing into the larger sizes at a high‐enough rate that a net increase in large tree C was seen across the region. Although large trees accumulated C at a faster rate than small trees on an individual basis, their contribution to C accumulation rates was smaller on an area basis, and their importance relative to small trees declined in older stands compared to younger stands. In contrast to recent syntheses, our results suggest that old‐growth and large trees are important C stocks, but they play a minor role in additional C accumulation.
Aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist eplerenone in patients with systolic heart failure and mild symptoms: an analysis of the EMPHASIS‐HF study
Authors: Chin Ken Lee , Collier Timothy J. , Pitt Bertram , McMurray John J.V. , Swedberg Karl , van Veldhuisen Dirk J. , Pocock Stuart J. , Vincent John , Turgonyi Eva , Zannad Faiez , Krum Henry ,   for the EMPHASIS‐HF Study Investigators
Published: February 2016

Aims

It is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for heart failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), and serum potassium >5.5 mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS‐HF).

Methods and results

Patients with chronic heart failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS‐HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P‐values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46–0.75) or treated (adjusted HR 0.71, 95% CI 0.59–0.87) with aspirin at baseline (interaction P‐value = 0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful.

Conclusion

Aspirin use in patients with chronic systolic heart failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors.
Mitochondria‐Targeting Iron(III) Catecholates for Photoactivated Anticancer Activity under Red Light
Authors: Basu Uttara , Pant Ila , Kondaiah Paturu , Chakravarty Akhil R.
Published: February 2016

Iron(III) catecholates [Fe(R′‐bpa)(R‐dopa)Cl] (1, 2) with a triphenylphosphonium (TPP) moiety, where R′‐bpa is 2‐(TPP‐N,N‐bis((pyridin‐2‐yl)methyl)ethanamine) chloride (TPPbpa) and R‐dopa is 4‐{2‐[(anthracen‐9‐yl)methylamino]ethyl}benzene‐1,2‐diol (andopa, 1) or 4‐{2‐[(pyren‐1‐yl)‐methylamino]ethyl}benzene‐1,2‐diol (pydopa, 2), were synthesized and their photocytotoxicity studied. Complexes 3 and 4 with [phenyl‐N,N‐bis(pyridin‐2‐yl)methyl]methanamine (phbpa) were used as controls. The catecholate complexes showed an absorption band near 720 nm. The 5e– paramagnetic complexes showed a FeIII/FeII irreversible response near –0.45 V and a quasi‐reversible catechol/semiquinone couple near 0.5 V versus saturated calomel electrode (SCE) in DMF/0.1 M tetrabutylammonium perchlorate. They showed photocytotoxicity in red/visible light in HeLa, HaCaT, MCF‐7, and A549 cells. Complexes 1 and 2 displayed mitochondrial localization, reactive oxygen species (ROS) generation under red light, and apoptotic cell death. Control complexes 3 and 4 exhibited uniform distribution throughout the cell. The complexes showed DNA photocleavage under red light (785 nm), forming hydroxyl radicals as the ROS.
The influence of methyl jasmonate, cholesterol and l‐arginine on solasodine production in hairy root culture of Solanum mammosum
Authors: Ooi Chai Theam , Syahida Ahmad , Stanslas Johnson , Maziah Mahmood
Published: February 2016

The increasing demand of diosgenin for high‐revenue synthesis of steroid hormones by the pharmaceutical industries has driven researchers to look for other alternatives. Solasodine which was reported to be present in Solanum mammosum is known to be a potential source. The present study highlighted that added methyl jasmonate, cholesterol and l‐arginine into the modified liquid full‐strength Murashige and Skoog (MS) medium (with ammonium to nitrate ratio 10.3 mM: 39.4 mM, and 4% (w/v) sucrose) could influence the solasodine production in the hairy roots of S. mammosum. The findings showed that both hairy root line‐ATCC31798 and line‐A4 (which were separately induced by Agrobacterium rhizogenes strain ATCC31798 and A4) acquired solasodine productivity of 4.5 mg/g dry weight roots with average dry biomass of 190 mg after 32 days culture, when using 50 mg fresh weight roots as initial inoculum size, with 100 mM cholesterol, 1000 μM l‐arginine and 300 μM methyl jasmonate added simultaneously into the culture medium on day 20 of culture. The amount of solasodine obtained was five times higher than those without both the elicitor and precursor treatment. The improved solasodine production with a high‐biomass growth could reduce the production cost of steroid synthesis in the long run.
Use of Descurainia sophia L. As a natural coagulant for the treatment of dye‐containing wastewater
Authors: Ahmadi Neda , Chaibakhsh Naz , Zanjanchi Mohammad Ali
Published: February 2016

In this study, Descurainia sophia L. has been introduced as a potential source of natural coagulant for the treatment of dye‐containing wastewater. Response surface methodology (RSM) based on a three‐variable, three‐level Box–Behnken design (BBD) was used to analyze the decolorization of a model textile wastewater containing neutral red dye. The effect of three parameters including contact time, pH, and the coagulant dose on the color removal was investigated. A second‐order polynomial equation could accurately model the process with a R2 of 0.96. The pH was found to be the most significant parameter affecting the color removal. High color (90.2%) removal efficiency was obtained at the optimal conditions of 6.5 min, pH 5.6, and 102.6 mg/L of coagulant. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 996–1001, 2016
Planform dynamics of the Iquitos anabranching structure in the Peruvian Upper Amazon River
Authors: Mendoza Alejandro , Abad Jorge D. , Frias Christian E. , Ortals Collin , Paredes Jorge , Montoro Hugo , Vizcarra Jorge , Simon Cesar , Soto‐Cortés Gabriel
Published: February 2016

The upper reach of the Amazon River has a very dynamic morphology, with the highest rates of migration observed in the entire Amazon River. It has an anabranching channel pattern which alternates between a condition of single channel and anabranching structures; in particular, the anabranching structure near Iquitos City shows an interesting channel behavior. Its channels migrate at different rates, where there are processes of narrowing and widening, and also collision and development of new channels. The temporal evolution of the Iquitos anabranching structure is described during the period from 1985 to 2014. The study is carried out by using satellite images to track the migration patterns, which are contrasted to the underlying geological units in the valley. Bathymetry of the structure and several velocity transects were obtained during a field campaign prior to the 2012 historic flood event. This information allowed for numerical modeling in order to compute the hydrodynamic flow field that complements the temporal analysis, aiming to understand the planform migration patterns after the 2012 flood event. It is observed that the geological units play an important role in modulating the migration rates and planform development of the channels. The channels in the structure are in contention to be the main channel, which become the secondary channel after migration. This causes the channels to experience a rise in bed elevation and narrowing of the channel itself; if this trend continues for several more years, these channels will detach from the Iquitos anabranching structure, thus forming paleo‐channels. This geomorphic process is important for horizontal and vertical soil heterogeneity along the floodplain. In general, the analysis shows a complex interaction between the underlying geological units, flow structure, morphology of the bed and planform migration. Copyright © 2016 John Wiley & Sons, Ltd.
Determination of silicone rubber and low-density polyethylene diffusion and polymer/water partition coefficients for emerging contaminants
Authors: Pintado-Herrera Marina G. , Lara-Martín Pablo A. , González-Mazo Eduardo , Allan Ian J.
Published: February 2016

There is a growing interest in assessing the concentration and distribution of new nonregulated organic compounds (emerging contaminants) in the environment. The measurement of freely dissolved concentrations using conventional approaches is challenging because of the low concentrations that may be encountered and their temporally variable emissions. Absorption-based passive sampling enables the estimation of freely dissolved concentrations of hydrophobic contaminants of emerging concern in water. In the present study, calibration was undertaken for 2 polymers, low-density polyethylene (LDPE) and silicone rubber for 11 fragrances, 5 endocrine-disrupting compounds, 7 ultraviolet (UV) filters, and 8 organophosphate flame retardant compounds. Batch experiments were performed to estimate contaminant diffusion coefficients in the polymers (Dp), which in general decreased with increasing molecular weight. The values for fragrances, endocrine-disrupting compounds, and UV filters were in ranges similar to those previously reported for polycyclic aromatic hydrocarbons, but were 1 order of magnitude lower for organophosphate flame retardant compounds. Silicone rubber had higher Dp values than LDPE and was therefore selected for further experiments to calculate polymer/water partition coefficients (KPW). The authors observed a positive correlation between log KPW and log octanol/water partition coefficient values. Field testing of silicone rubber passive samplers was undertaken though exposure in the River Alna (Norway) for an exposure time of 21 d to estimate freely dissolved concentration. Some fragrances and UV filters were predominant over other emerging and regulated contaminants, at levels up to 1600 ng L−1 for galaxolide and 448 ng L−1 for octocrylene. Environ Toxicol Chem 2016;35:2162–2172. © 2016 SETAC
Dilation‐based shock capturing for high‐order methods
Authors: Moro David , Nguyen Ngoc Cuong , Peraire Jaime
Published: February 2016

In this paper, we introduce a shock‐capturing artificial viscosity technique for high‐order unstructured mesh methods. This artificial viscosity model is based on a non‐dimensional form of the divergence of the velocity. The technique is an extension and improvement of the dilation‐based artificial viscosity methods introduced in Premasuthan et al., and further extended in Nguyen and Peraire . The approach presented has a number attractive properties including non‐dimensional analytical form, sub‐cell resolution, and robustness for complex shock flows on anisotropic meshes. We present extensive numerical results to demonstrate the performance of the proposed approach. Copyright © 2016 John Wiley & Sons, Ltd.
Structural MRI correlates of cognitive impairment in patients with multiple sclerosis
Authors: Preziosa Paolo , Rocca Maria A. , Pagani Elisabetta , Stromillo Maria Laura , Enzinger Christian , Gallo Antonio , Hulst Hanneke E. , Atzori Matteo , Pareto Deborah , Riccitelli Gianna C. , Copetti Massimiliano , De Stefano Nicola , Fazekas Franz , Bisecco Alvino , Barkhof Frederik , Yousry Tarek A. , Arévalo Maria J. , Filippi Massimo ,   and the MAGNIMS Study Group
Published: February 2016

In a multicenter setting, we applied voxel‐based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal‐appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing‐remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel‐wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty‐three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive‐relevant WM tracts followed by atrophy of cognitive‐relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel‐wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. Hum Brain Mapp 37:1627‐1644, 2016. © 2016 Wiley Periodicals, Inc.
Human epidermal growth factor receptor 3 in head and neck squamous cell carcinomas
Authors: Rysman Bénédicte , Mouawad François , Gros Abigaëlle , Lansiaux Amélie , Chevalier Dominique , Meignan Samuel
Published: February 2016

Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptor (HER) family. The main characteristic of HER3 is that it does not possess tyrosine kinase activity, unlike other HERs. The role of HER3 in tumorigenesis has now been recognized, particularly in head and neck squamous cell carcinomas (HNSCCs). Despite conflicting studies, HER3 was found to be overexpressed in HNSCC samples, and correlates with disease progression and poor survival, especially when it is coexpressed with other HERs. HER3 is a significant factor in HNSCC treatment resistance. Indeed, HER3 is a major mechanism described for cetuximab resistance because of modification of epidermal growth factor receptor (EGFR) internalization and by phosphotidylinositol‐3‐kinase (PI3K)/AKT signaling pathway activation. HER3 also affects resistance to tyrosine kinase inhibitors (TKIs) and thereby promotes treatment escape and radiotherapy resistance by activation of the survival signaling pathway. To counteract this, pharmacologic inhibitors of HER3 are currently in development and could significantly improve HNSCC treatment. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2412–E2418, 2016
Abducens ocular neuromyotonia as a delayed complication of oropharyngeal carcinoma treated with radiation
Authors: Sychev Yevgeniy V. , McInnis Colin P. , Francis Courtney E.
Published: February 2016

Background

Ocular neuromyotonia (ONM) is a disorder characterized by periodic involuntary extraocular muscle contraction that occurs almost exclusively in the setting of prior radiation to the sella or skull base. We present the first case of abducens neuromyotonia associated with oropharyngeal carcinoma.

Methods and Results

We report a case of a 63‐year‐old patient with abducens ONM occurring 16 years after radiation treatment for oropharyngeal squamous cell carcinoma. A literature review was performed using Medline and PubMed databases to search for all documented cases of abducens neuromyotonia. Our review found 20 cases of abducens neuromyotonia but none after radiotherapy (RT) to the oropharynx.

Conclusion

Abducens ONM can occur because of disease at anatomic locations remote from the course of the sixth cranial nerve, most likely because of the irradiated area exceeding the intended field. Our case also supports the fact that RT can significantly precede symptom onset. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2428–E2431, 2016
A low‐cost, user‐friendly electroencephalographic recording system for the assessment of hepatic encephalopathy
Authors: Schiff Sami , Casa Mariella , Di Caro Valeria , Aprile Daniele , Spinelli Giuseppe , De Rui Michele , Angeli Paolo , Amodio Piero , Montagnese Sara
Published: February 2016

Electroencephalography (EEG) is useful to objectively diagnose/grade hepatic encephalopathy (HE) across its spectrum of severity. However, it requires expensive equipment, and hepatogastroenterologists are generally unfamiliar with its acquisition/interpretation. Recent technological advances have led to the development of low‐cost, user‐friendly EEG systems, allowing EEG acquisition also in settings with limited neurophysiological experience. The aim of this study was to assess the relationship between EEG parameters obtained from a standard‐EEG system and from a commercial, low‐cost wireless headset (light‐EEG) in patients with cirrhosis and varying degrees of HE. Seventy‐two patients (58 males, 61 ± 9 years) underwent clinical evaluation, the Psychometric Hepatic Encephalopathy Score (PHES), and EEG recording with both systems. Automated EEG parameters were calculated on two derivations. Strong correlations were observed between automated parameters obtained from the two EEG systems. Bland and Altman analysis indicated that the two systems provided comparable automated parameters, and agreement between classifications (normal versus abnormal EEG) based on standard‐EEG and light‐EEG was good (0.6 < κ < 0.8). Automated parameters such as the mean dominant frequency obtained from the light‐EEG correlated significantly with the Model for End‐Stage Liver Disease score (r = −0.39, P < 0.05), fasting venous ammonia levels (r = −0.41, P < 0.01), and PHES (r = −0.49, P < 0.001). Finally, significant differences in light‐EEG parameters were observed in patients with varying degrees of HE. Conclusion: Reliable EEG parameters for HE diagnosing/grading can be obtained from a cheap, commercial, wireless headset; this may lead to more widespread use of this patient‐independent tool both in routine liver practice and in the research setting. (Hepatology 2016;63:1651‐1659)
Urban base flow with low impact development
Authors: Bhaskar Aditi S. , Hogan Dianna M. , Archfield Stacey A.
Published: February 2016

A novel form of urbanization, low impact development (LID), aims to engineer systems that replicate natural hydrologic functioning, in part by infiltrating stormwater close to the impervious surfaces that generate it. We sought to statistically evaluate changes in a base flow regime because of urbanization with LID, specifically changes in base flow magnitude, seasonality, and rate of change. We used a case study watershed in Clarksburg, Maryland, in which streamflow was monitored during whole‐watershed urbanization from forest and agricultural to suburban residential development using LID. The 1.11‐km2 watershed contains 73 infiltration‐focused stormwater facilities, including bioretention facilities, dry wells, and dry swales. We examined annual and monthly flow during and after urbanization (2004–2014) and compared alterations to nearby forested and urban control watersheds. We show that total streamflow and base flow increased in the LID watershed during urbanization as compared with control watersheds. The LID watershed had more gradual storm recessions after urbanization and attenuated seasonality in base flow. These flow regime changes may be because of a reduction in evapotranspiration because of the overall decrease in vegetative cover with urbanization and the increase in point sources of recharge. Precipitation that may once have infiltrated soil, been stored in soil moisture to be eventually transpired in a forested landscape, may now be recharged and become base flow. The transfer of evapotranspiration to base flow is an unintended consequence to the water balance of LID. © 2016 The Authors Hydrological Processes Published by John Wiley & Sons Ltd.
Lycopene, tomato products and prostate cancer‐specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort
Authors: Wang Ying , Jacobs Eric J. , Newton Christina C. , McCullough Marjorie L.
Published: February 2016

While dietary lycopene and tomato products have been inversely associated with prostate cancer incidence, there is limited evidence for an association between consumption of lycopene and tomato products and prostate‐cancer specific mortality (PCSM). We examined the associations of prediagnosis and postdiagnosis dietary lycopene and tomato product intake with PCSM in a large prospective cohort. This analysis included men diagnosed with nonmetastatic prostate cancer between enrollment in the Cancer Prevention Study II Nutrition Cohort in 1992 or 1993 and June 2011. Prediagnosis dietary data, collected at baseline, were available for 8,898 men, of whom 526 died of prostate cancer through 2012. Postdiagnosis dietary data, collected on follow‐up surveys in 1999 and/or 2003, were available for 5,643 men, of whom 363 died of prostate cancer through 2012. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for PCSM. Neither prediagnosis nor postdiagnosis dietary lycopene intake was associated with PCSM (fourth vs. first quartile HR = 1.00, 95% CI 0.78–1.28; HR = 1.22, 95% CI 0.91–1.64, respectively). Similarly, neither prediagnosis nor postdiagnosis consumption of tomato products was associated with PCSM. Among men with high‐risk cancers (T3–T4 or Gleason score 8–10, or nodal involvement), consistently reporting lycopene intake ≥ median on both postdiagnosis surveys was associated with lower PCSM (HR = 0.41, 95% CI 0.17–0.99, based on ten PCSM cases consistently ≥ median intake) compared to consistently reporting intake < median. Future studies are needed to confirm the potential inverse association of consistently high lycopene intake with PCSM among men with high‐risk prostate cancers.
Polyampholyte‐ and nanosilicate‐based soft bionanocomposites with tailorable mechanical and cell adhesion properties
Authors: Jain Minkle , Matsumura Kazuaki
Published: February 2016

Engineered tissues are excellent substitutes for treating organ failure associated with disease, injury, and degeneration. Designing new biomaterials with controlled release profiles, good mechanical properties, and cell adhesion characteristics can be useful for the formation of specific functional tissues. Here, we report the formulation of nanocomposite hydrogels based on carboxylated poly‐l‐lysine and synthetic clay laponite XLG in which four‐arm polyethylene glycol with N‐hydroxy succinimide ester (PEG‐NHS) was used as the chemical crosslinker. Interestingly, the degradation of this gel could be adjusted from a few days to a few months. Incorporation of laponite XLG resulted in the formation of mechanically tough hydrogels and conferred cytocompatibility. The mechanical properties of the nanocomposite could be modulated by changing the crosslinking density and laponite concentration. The feasibility of using this system for cellular therapies was investigated by evaluating cell adhesion on the nanocomposite surface. Thus, these nanocomposites can serve as scaffolds with tunable mechanical and degradation properties that also provide structural integrity to tissue constructs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1379–1386, 2016.
Layer‐by‐layer coating of textile with two oppositely charged cyclodextrin polyelectrolytes for extended drug delivery
Authors: Junthip Jatupol , Tabary Nicolas , Chai Feng , Leclercq Laurent , Maton Mickael , Cazaux Frederic , Neut Christel , Paccou Laurent , Guinet Yannick , Staelens Jean‐Noel , Bria Marc , Landy David , Hédoux Alain , Blanchemain Nicolas , Martel Bernard
Published: February 2016

The coating of a nonwoven textile by polyelectrolyte multilayer film (PEM) issued from cationic and anionic β‐cyclodextrin (βCD) polyelectrolytes according to the layer‐by‐layer (LbL) technique was successfully attempted. The tert‐butyl benzoic acid (TBBA) was used as drug model to evaluate the loading capacity and sustained release properties of this PEM system. The build‐up of the multilayer assembly was monitored in situ by optical waveguide lightmode spectroscopy (OWLS) on the one hand, and was assessed by gravimetry on the other hand when applied onto the textile substrate. In parallel, the complexation study of TBBA with both CD polyelectrolytes was also investigated by nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC). The influence of thermal crosslinking of the multilayered coating on its stability and on TBBA release kinetics in phosphate buffered saline (PBS) at 37°C was studied. Finally, biological and microbiological tests were performed to investigate the cytocompatibility and the intrisic antibacterial activity of multilayer assemblies. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1408–1424, 2016.
Structures and energetics of complexation of metal ions with ammonia, water, and benzene: A computational study
Authors: Sharma Bhaskar , Neela Y. Indra , Narahari Sastry G.
Published: February 2016

Quantum chemical calculations have been performed at CCSD(T)/def2‐TZVP level to investigate the strength and nature of interactions of ammonia (NH3), water (H2O), and benzene (C6H6) with various metal ions and validated with the available experimental results. For all the considered metal ions, a preference for C6H6 is observed for dicationic ions whereas the monocationic ions prefer to bind with NH3. Density Functional Theory–Symmetry Adapted Perturbation Theory (DFT‐SAPT) analysis has been employed at PBE0AC/def2‐TZVP level on these complexes (closed shell), to understand the various energy terms contributing to binding energy (BE). The DFT‐SAPT result shows that for the metal ion complexes with H2O electrostatic component is the major contributor to the BE whereas, for C6H6 complexes polarization component is dominant, except in the case of alkali metal ion complexes. However, in case of NH3 complexes, electrostatic component is dominant for s‐block metal ions, whereas, for the d and p‐block metal ion complexes both electrostatic and polarization components are important. The geometry (M+–N and M+–O distance for NH3 and H2O complexes respectively, and cation–π distance for C6H6 complexes) for the alkali and alkaline earth metal ion complexes increases down the group. Natural population analysis performed on NH3, H2O, and C6H6 complexes shows that the charge transfer to metal ions is higher in case of C6H6 complexes. © 2016 Wiley Periodicals, Inc.
Fast search algorithms for computational protein design
Authors: Traoré Seydou , Roberts Kyle E. , Allouche David , Donald Bruce R. , André Isabelle , Schiex Thomas , Barbe Sophie
Published: February 2016

One of the main challenges in computational protein design (CPD) is the huge size of the protein sequence and conformational space that has to be computationally explored. Recently, we showed that state‐of‐the‐art combinatorial optimization technologies based on Cost Function Network (CFN) processing allow speeding up provable rigid backbone protein design methods by several orders of magnitudes. Building up on this, we improved and injected CFN technology into the well‐established CPD package Osprey to allow all Osprey CPD algorithms to benefit from associated speedups. Because Osprey fundamentally relies on the ability of
to produce conformations in increasing order of energy, we defined new
strategies combining CFN lower bounds, with new side‐chain positioning‐based branching scheme. Beyond the speedups obtained in the new
‐CFN combination, this novel branching scheme enables a much faster enumeration of suboptimal sequences, far beyond what is reachable without it. Together with the immediate and important speedups provided by CFN technology, these developments directly benefit to all the algorithms that previously relied on the DEE/
combination inside Osprey* and make it possible to solve larger CPD problems with provable algorithms. © 2016 Wiley Periodicals, Inc.
The catalytic effect of the NH3 base on the chemical events in the caryolene‐forming carbocation cascade
Authors: Ortega Daniela E. , Nguyen Quynh Nhu N. , Tantillo Dean J. , Toro‐Labbé Alejandro
Published: February 2016

Caryolene formation occur asynchronously in a concerted way through carbocationic rearrangements involving the generation of a secondary or a tertiary carbocation whether the reaction proceeds in the absence or in the presence of NH3, respectively. Both caryolene formation mechanisms are analyzed within the general framework of the reaction force; the reaction force constant is used to gain insights into the synchronicity of the mechanisms and the reaction electronic flux helps to characterize the electronic activity taking place during the reaction. DFT calculations at the B3LYP/6‐31+G(d,p) level show a clear difference in the mechanisms of the base promoted or base free caryolene formation reactions. © 2016 Wiley Periodicals, Inc.
Sequence‐based prediction of protein–peptide binding sites using support vector machine
Authors: Taherzadeh Ghazaleh , Yang Yuedong , Zhang Tuo , Liew Alan Wee‐Chung , Zhou Yaoqi
Published: February 2016

Protein–peptide interactions are essential for all cellular processes including DNA repair, replication, gene‐expression, and metabolism. As most protein–peptide interactions are uncharacterized, it is cost effective to investigate them computationally as the first step. All existing approaches for predicting protein–peptide binding sites, however, are based on protein structures despite the fact that the structures for most proteins are not yet solved. This article proposes the first machine‐learning method called SPRINT to make Sequence‐based prediction of Protein–peptide Residue‐level Interactions. SPRINT yields a robust and consistent performance for 10‐fold cross validations and independent test. The most important feature is evolution‐generated sequence profiles. For the test set (1056 binding and non‐binding residues), it yields a Matthews’ Correlation Coefficient of 0.326 with a sensitivity of 64% and a specificity of 68%. This sequence‐based technique shows comparable or more accurate than structure‐based methods for peptide‐binding site prediction. SPRINT is available as an online server at: http://sparks-lab.org/. © 2016 Wiley Periodicals, Inc.
A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis
Authors: Plavina Tatiana , Fox Edward J. , Lucas Nisha , Muralidharan Kumar Kandadi , Mikol Daniel
Published: February 2016

The study's primary objective was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of single subcutaneous (SC) or intramuscular (IM) 300‐mg doses of natalizumab with IV 300‐mg doses of natalizumab in patients with multiple sclerosis (MS). Secondary objectives included investigation of the safety, tolerability, and immunogenicity of repeated SC and IM natalizumab doses. DELIVER was a 32‐week, open‐label, multicenter study of natalizumab‐naive patients with relapsing‐remitting MS (RRMS) or secondary progressive MS (SPMS) randomized to receive 300 mg natalizumab by SC injection, IM injection, or IV infusion. PK and PD were evaluated over 8 weeks after the first natalizumab treatment (Part 1) and over 24 weeks with repeated dosing every 4 weeks, beginning at week 8 (Part 2). Seventy‐six patients (24 with RRMS and 52 with SPMS) were enrolled in DELIVER. Following SC or IM administration of natalizumab, peak serum concentrations were approximately 40% of those observed with IV administration and showed no major differences in elimination characteristics. Mean bioavailability relative to IV administration was 57.1% to 71.3% with SC administration and 48.7% with IM administration; mean trough serum concentrations were similar with SC or IV administration and lower with IM administration. Following single or multiple doses of natalizumab, PD response was comparable across administration routes and disease stages. No meaningful differences were observed across administration groups in the incidence or nature of overall adverse events, serious adverse events, administration site reactions, hypersensitivity reactions, or antinatalizumab antibodies. These findings support the comparability of PD measures of natalizumab administered IV, SC, or IM.
Detailed evaluation of different 68Ge/68Ga generators: an attempt toward achieving efficient 68Ga radiopharmacy
Authors: Chakravarty Rubel , Chakraborty Sudipta , Ram Ramu , Vatsa Rakhee , Bhusari Priya , Shukla Jaya , Mittal B. R. , Dash Ashutosh
Published: February 2016

The present study is aimed at carrying out a comparative performance evaluation of different types of 68Ge/68Ga generators to identify the best choice for use in 68Ga‐radiopharmacy. Over the 1 year period of evaluation, the elution yields from the CeO2‐based and SiO2‐based 68Ge/68Ga generators remained almost consistent, in contrast to the sharp decrease observed in the elution yields from TiO2 and SnO2‐based generators. The level of 68Ge impurity in 68Ga eluates from the CeO2 and SiO2‐based 68Ge/68Ga generator was always <10−3%, while this level increased from 10−3% to 10−1% in case of TiO2 and SnO2‐based generators. The level of chemical impurities in 68Ga eluates from CeO2 and SiO2‐based 68Ge/68Ga generators was negligibly low (<0.1 ppm) in contrast to the significantly higher level (1–20 ppm) of such impurities in eluates from other two generators. As demonstrated by radiolabeling studies carried out using DOTA‐coupled dimeric cyclic RGD peptide derivative (DOTA‐RGD2), CeO2‐PAN and SiO2‐based generators are directly amenable for radiopharmaceutical preparation, whereas the other generators can be only used after post‐elution purification of 68Ga eluates. Clinically relevant dose of 68Ga‐DOTA‐RGD2 was prepared in a hospital radiopharmacy for non‐invasive visualization of tumors in breast cancer patients using positron emission tomography.
The effect of low‐intensity pulsed ultrasound on bone‐tendon junction healing: Initiating after inflammation stage
Authors: Lu Hongbin , Liu Feifei , Chen Huabin , Chen Can , Qu Jin , Xu Daqi , Zhang Tao , Zhou Jingyong , Hu Jianzhong
Published: February 2016

The purpose of this study was to explore the effect of low‐intensity pulsed ultrasound (LIPUS) treatment initiating after inflammation stage on the process of bone‐tendon junction (BTJ) healing in a rabbit model. Thirty‐six rabbits undergoing partial patellectomy were randomly divided into two groups: control and LIPUS. The period of initial inflammatory stage is 2 weeks. So LIPUS treatment was initiated at postoperative week 2 and continued until the patella‐patellar tendon (PPT) complexes were harvested at postoperative weeks 4, 8, and 16. At each time point, the PPT complexes were harvested for qRT‐PCR, histology, radiographs, synchroton radiation micro computed tomography (SR‐µCT), and biomechanical testing. The qRT‐PCR results showed that LIPUS treatment beginning at postoperative week 2 played an anti‐inflammatory role in BTJ healing. Histologically, the LIPUS group showed more advanced remodeling of the lamellar bone and marrow cavity than the control group. The area and length of the new bone in the LIPUS group were significantly greater than the control group at postoperative weeks 8 and 16. SR‐µCT demonstrated that new bone formation and remodeling in the LIPUS group were more advanced than the control group. Biomechanical test results demonstrated that the failure load, ultimate strength and energy at failure were significantly higher than those of the control group. In conclusion, LIPUS treatment beginning at postoperative week 2 was able to accelerate bone formation during the bone‐tendon junction healing process and significantly improved the healing quality of BTJ injury. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society.
Indirect enantioseparation of fluoxetine in mouse serum by derivatization with 1R‐(–)‐menthyl chloroformate followed by ultra high performance liquid chromatography and quadrupole time‐of‐flight mass spectrometry
Authors: Zhao Jing , Jin Yan , Shin Yujin , Jeong Kyung Min , Lee Jeongmi
Published: February 2016

Here we describe a simple and sensitive analytical method for the enantioselective quantification of fluoxetine in mouse serum using ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry. The sample preparation method included a simple deproteinization with acetonitrile in 50 μL of serum, followed by derivatization of the extracts in 50 μL of 2 mM 1R‐(–)‐menthyl chloroformate at 45ºC for 55 min. These conditions were statistically optimized through response surface methodology using a central composite design. Under the optimized conditions, neither racemization nor kinetic resolution occurred. The derivatized diastereomers were readily resolved on a conventional sub‐2 μm C18 column under a simple gradient elution of aqueous methanol containing 0.1% formic acid. The established method was validated and found to be linear, precise, and accurate over the concentration range of 5.0–1000.0 ng/mL for both R and S enantiomers (r2 > 0.993). Stability tests of the prepared samples at three different concentration levels showed that the R‐ and S‐fluoxetine derivatives were relatively stable for 48 h. No significant matrix effects were observed. Last, the developed method was successfully used for enantiomeric analysis of real serum samples collected at a number of time points from mice administered with racemic fluoxetine.
Analysis of lignans in Magnoliae Flos by turbulent flow chromatography with online solid‐phase extraction and high‐performance liquid chromatography with tandem mass spectrometry
Authors: Zhou Xuan , Chen Cen , Ye Xiaolan , Song Fenyun , Fan Guorong , Wu Fuhai
Published: February 2016

In this study, a method coupling turbulent flow chromatography with online solid‐phase extraction and high‐performance liquid chromatography with tandem mass spectrometry was developed for analyzing the lignans in Magnoliae Flos. By the online pretreatment of turbulent flow chromatography solid‐phase extraction, the impurities removal and analytes concentration were automatically processed, and the lignans were separated rapidly and well. Seven lignans of Magnoliae Flos including epieudesmin, magnolin, 1‐irioresinol‐B‐dimethyl ether, epi‐magnolin, fargesin aschantin, and demethoxyaschantin were identified by comparing their retention behavior, UV spectra, and mass spectra with those of reference substances or literature data. The developed method was validated, and the good results showed that the method was not only automatic and rapid, but also accurate and reliable. The turbulent flow chromatography with online solid‐phase extraction and high‐performance liquid chromatography with tandem mass spectrometry method holds a high potential to become an effective method for the quality control of lignans in Magnoliae Flos and a useful tool for the analysis of other complex mixtures.
Rapid determination of the volatile components in tobacco by ultrasound‐microwave synergistic extraction coupled to headspace solid‐phase microextraction with gas chromatography‐mass spectrometry
Authors: Yang Yanqin , Chu Guohai , Zhou Guojun , Jiang Jian , Yuan Kailong , Pan Yuanjiang , Song Zhiyu , Li Zuguang , Xia Qian , Lu Xinbo , Xiao Weiqiang
Published: February 2016

An ultrasound‐microwave synergistic extraction coupled to headspace solid‐phase microextraction was first employed to determine the volatile components in tobacco samples. The method combined the advantages of ultrasound, microwave, and headspace solid‐phase microextraction. The extraction, separation, and enrichment were performed in a single step, which could greatly simplify the operation and reduce the whole pretreatment time. In the developed method, several experimental parameters, such as fiber type, ultrasound power, and irradiation time, were optimized to improve sampling efficiency. Under the optimal conditions, there were 37, 36, 34, and 36 components identified in tobacco from Guizhou, Hunan, Yunnan, and Zimbabwe, respectively, including esters, heterocycles, alkanes, ketones, terpenoids, acids, phenols, and alcohols. The compound types were roughly the same while the contents were varied from different origins due to the disparity of their growing conditions, such as soil, water, and climate. In addition, the ultrasound‐microwave synergistic extraction coupled to headspace solid‐phase microextraction method was compared with the microwave‐assisted extraction coupled to headspace solid‐phase microextraction and headspace solid‐phase microextraction methods. More types of volatile components were obtained by using the ultrasound‐microwave synergistic extraction coupled to headspace solid‐phase microextraction method, moreover, the contents were high. The results indicated that the ultrasound‐microwave synergistic extraction coupled to headspace solid‐phase microextraction technique was a simple, time‐saving and highly efficient approach, which was especially suitable for analysis of the volatile components in tobacco.
Evolution of Chain Microstructure and Kinetics of Reaching Equilibrium in Living Reversible Copolymerization
Authors: Szymanski Ryszard , Sosnowski Stanislaw , Cypryk Marek
Published: February 2016

Theoretical considerations and Monte Carlo simulations have proved that the microstructure of copolymer chains in living reversible copolymerization can be effectively described by the first‐order Markov chain process only when the system space of this process reaches chain lengths above the number‐average degree of polymerization (DPn). The time scale of equilibration depends mostly on DPn of the product, rate constants of depropagation, as well as on the equilibrium microstructure of copolymer. During the process, evolution encompasses, besides the chain‐length distribution like in homopolymerization, also the chain microstructure. The kinetically determined microstructure (gradient, alternate, etc.) observed in the first stage of copolymerization is related to reactivity ratios. It evolves into the equilibrium microstructure, determined exclusively by the equilibrium constants and initial conditions. Discussion of this evolution together with the statistical description of the reversible binary copolymerization systems at various stages of equilibration is given.

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Advanced Monte Carlo Modeling Using Weight‐Based Selection of Arborescent Polyisobutylene Molecules in a Batch Reactor
Authors: Zhao Yutian R. , McAuley Kimberley B. , Iedema Piet D. , Puskas Judit E.
Published: February 2016

An advanced Monte Carlo (MC) method is developed, using weight‐based selection of polymer chains, to predict the molecular weight distribution (MWD) and branching level for arborescent polyisobutylene (arbPIB) at the end of a batch reaction. This new weight‐based MC method uses differential equations and random numbers to determine the detailed structure of arbPIB molecules. Results agree with those from an advanced number‐based MC method. The proposed weight‐based algorithm requires approximately twice the computation time of the number‐based method, but produces more accurate results in the high‐molecular‐weight portion of the MWD when the same number of polymer chains is assembled.

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Universality in Branching Frequencies and Molecular Dimensions during Hyperbranched Polymer Formation: 2. Step Polymerization of AB2 Type Monomer with Different Reactivity for the Second B Group
Authors: Tobita Hidetaka
Published: February 2016

Hyperbranched polymer formation during step polymerization of AB2 type monomer with different reactivity for the second B group is investigated to find the following universal characteristics that are invariant during the whole course of polymerization: (1) The degree of branching (DB) at large degree of polymerization (P) limit, , and (2) the mean square radius of gyration for the unperturbed chains having the same P. The value of and the universal curve for change with the reactivity ratio of two B groups; however, the universal power law holds for large polymers, irrespective of the magnitude of reactivity ratio. The exponent, 0.5, is the same as that for the random branched polymers. Similarities and differences in comparison with random branched polymer formation are discussed.

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