bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of collagen‐modified polylactide and its application in drug delivery
Authors: Li Xiao , Liu Leili , Yang Pengfei , Li Peng , Xin Jingjing , Su Ruixia
Published: February 2013

In this article, collagen modified polylactide (CPLA) was synthesized by means of graft modification, and its structure was confirmed by FTIR and FITC‐labeled fluorescence spectra. Subsequently, the performance of CPLA was characterized with hydrophilicity test and degradability test. After that, the aspirin sustained release microspheres of the synthetic copolymers were prepared via the emulsion‐solvent evaporation technique, followed with its measurements of morphology, size, and encapsulation efficiency. Finally, the controlled release properties of the obtained microspheres were investigated. The results showed that the aspirin sustained release microspheres exhibited well‐defined morphology with smooth spherical surface, with average size of 3.990 μm and encapsulation efficiency of 51.83%. Furthermore, compared with aspirin‐loaded PLA microspheres, at the initial 32 h, the drug release was faster for aspirin‐loaded CPLA microspheres favored by its increased hydrophilicity, and then the drug release was slower than that of PLA microspheres because the NH2 group on the introduced collagen inhibited acidic autocatalytic degradation. The results suggested that CPLA showed a great potential as particles for drug delivery. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Stability and Validity of an Automated Measure of Vocal Development From Day‐Long Samples in Children With and Without Autism Spectrum Disorder
Authors: Yoder Paul J. , Oller D. Kimbrough , Richards Jeffrey A. , Gray Sharmistha , Gilkerson Jill
Published: February 2013

Individual difference measures of vocal development may eventually aid our understanding of the variability in spoken language acquisition in children with autism spectrum disorder (ASD). Large samples of child vocalizations may be needed to maximize the stability of vocal development estimates. Day‐long vocal samples can now be automatically analyzed based on acoustic characteristics of speech likeness identified in theoretically driven and empirically cross‐validated quantitative models of typical vocal development. This report indicates that a single day‐long recording can produce a stable estimate for a measure of vocal development that is highly related to expressive spoken language in a group of young children with ASD and in a group that is typically developing. Autism Res 2013, 6: 103–107. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Reducing infectivity of HIV upon exposure to surfaces coated with N,N‐dodecyl, methyl‐polyethylenimine
Authors: Gerrard Stephen E. , Larson Alyssa M. , Klibanov Alexander M. , Slater Nigel K.H. , Hanson Carl V. , Abrams Barbara F. , Morris Mary K.
Published: February 2013

The infectivity of high‐titer, cell‐free HIV in culture media and human milk is rapidly reduced upon exposure to polyethylene slides painted with the linear hydrophobic polycation N,N‐dodecyl,methyl‐polyethylenimine (DMPEI). Accompanying viral p24 protein and free viral RNA analysis of solutions exposed to DMPEI‐coated surfaces suggests that virion attachment to the polycationic surface and its subsequent inactivation are the likely mechanism of this phenomenon. Biotechnol. Bioeng. 2013; 110: 2058–2062. © 2013 Wiley Periodicals, Inc.
Novel humanized anti‐CD20 antibody BM‐ca binds to a unique epitope and exerts stronger cellular activity than others
Authors: Kobayashi Hideaki , Matsunaga Yuka , Uchiyama Yumiko , Nagura Kenji , Komatsu Yasuhiko
Published: February 2013

Cellular activity of BM‐ca, a novel humanized anti‐CD20 antibody, was quantitatively compared with that of two other anti‐CD20 antibodies used for clinical practice, rituximab and ofatumumab. The results of a complement‐dependent cytotoxicity (CDC) assay revealed that the strongest antibody was ofatumumab, followed by BM‐ca, with rituximab being the weakest. Ofatumumab and BM‐ca were effective not only against rituximab‐sensitive SU‐DHL‐4 cells but also against rituximab‐resistant RC‐K8 cells. In an antibody‐dependent cell‐mediated cytotoxicity (ADCC) assay, although the effective concentrations against SU‐DHL‐4 cells were almost the same among these three antibodies, the maximum cytotoxic level was the highest for BM‐ca. In an anti‐cell proliferation assay using SU‐DHL‐4 cells, BM‐ca was the most effective and ofatumumab, the weakest. Against RC‐K8 cells, only BM‐ca was effective. When combined with each of four cancer chemotherapeutics (prednisolone, vincristine, hydroxydaunorubicin, and cisplatin), BM‐ca exerted the most effective combinatorial anti‐cell proliferation activity. To assess the in vivo effect of BM‐ca, we intravenously administered BM‐ca into cynomolgus monkeys and found that the peripheral B‐cell levels did not decrease in half of the animals. Sequencing of cDNA encoding CD20 of cynomolgus monkeys revealed that the responders and nonresponders had Leu/Pro (hetero) and Leu/Leu (homo) at amino acid (a.a.) position 160, respectively, suggesting that the epitope recognized by BM‐ca was around this a.a. By analyzing reactivity to synthetic peptides, the epitope recognized by BM‐ca was estimated to be a.a.'s 156–166, not shared with rituximab and ofatumumab. These results suggest BM‐ca to be a promising anti‐CD20 antibody having superior properties and recognizing a unique epitope.
Comparison between three‐dimensional angiographic reconstruction and intravascular ultrasound: Imaging of the left main coronary artery
Authors: Spoon Daniel B. , Rubinshtein Ronen , Psaltis Peter J. , Sandhu Gupreet S. , Lennon Ryan , Rihal Charanjit S. , Lerman Amir
Published: February 2013

Objectives

The purpose of this study was to evaluate the left main (LM) coronary artery anatomy using three‐dimensional (3D) quantitative coronary angiography (QCA) software as compared to intravascular ultrasound (IVUS).

Background

Percutaneous intervention of the LM coronary artery is becoming more common in selected patients with LM coronary artery disease (CAD). Quantification of LM CAD by conventional angiography can be difficult. IVUS is considered the gold standard to evaluate LM anatomy and severity of CAD but entails additional steps, catheters, and expertise. Our objective was to compare a novel quantitative angiographic analysis system with IVUS for LM anatomy.

Methods

Fifty five patients underwent both coronary angiography and IVUS of the LM. LM measurements were analyzed with 3D QCA (IC‐PRO, Paieon, Israel) software using IVUS as the reference standard. The measurements included proximal, middle, distal minimal luminal diameter (MLD) and area. Additionally, lesion MLD, minimal luminal area were recorded by both systems. Bland–Altman plots were used to investigate agreement between the two imaging systems.

Results

Of the 55 patients in our cohort, average age was 66 ± 11 years (25% female). By Bland‐Altman analysis there was very good agreement between 3D QCA and IVUS for measures of MLD and minimal lumen area (MLA). However, there was poor concordance in the estimation of plaque burden between the two methods.

Conclusions

Our data demonstrate that 3D QCA software has fair agreement when compared with IVUS for imaging of LM MLD and MLA. These results suggest that 3D QCA could potentially be helpful to guide intervention of the LM. © 2012 Wiley Periodicals, Inc.
Sparse models by iteratively reweighted feature scaling: a framework for wavelength and sample selection
Authors: Andries Erik
Published: February 2013

In the past decade, there has been an increase in the use of sparse multivariate calibration methods in chemometrics. Sparsity describes a parsimonious state of model complexity and can be defined in terms of a subset of samples or covariates (e.g., wavelengths) that are used to define the calibration model. With respect to their classical counterparts such as principal component regression or partial least squares, sparse models are more easily interpretable and have been shown to exhibit non‐inferior prediction performance. However, sparse methods are still not as fast as the classical methods in spite of recent numerical advances. In addition, for many chemometricians, sparse methods are still “black‐box” algorithms whose internal workings are not well understood. In this paper, we describe a simple framework whereby classical multivariate calibration methods can be iteratively used to generate sparse models. Moreover, this approach allows for either wavelength or sample sparsity. We demonstrate the effectiveness of this approach on two spectroscopic data sets. Copyright © 2013 John Wiley & Sons, Ltd.
AripiprazoleMontmorillonite: A New Organic–Inorganic Nanohybrid Material for Biomedical Applications
Authors: Oh Yeon‐Ji , Choi Goeun , Choy Young Bin , Park Je Won , Park Jung Hyun , Lee Hwa Jeong , Yoon Yeo Joon , Chang Hee Chul , Choy Jin‐Ho
Published: February 2013

Poor aqueous solubility and the unpleasant taste of aripiprazole (APZ) have been recurring problems, owing to its low bioavailability and low patient tolerance, respectively. Herein, we prepared a nanohybrid system that was based on a bentonite clay material, montmorillonite (MMT), which could both mask the taste and enhance the solubility of APZ (i.e., APZ‐MMT). To further improve the efficacy of this taste masking and drug solubility, APZ‐MMT was also coated with a cationic polymer, polyvinylacetal diethylamino acetate (AEA). In vitro dissolution tests at neutral pH showed that the amount of drug that was released from the AEA‐coated APZ‐MMT was greatly suppressed (<1 %) for the first 3 min, thus suggesting that AEA‐coated APZ‐MMT has strong potential for the taste masking of APZ. Notably, in simulated gastric juice at pH 1.2, the total percentage of APZ that was released within the first 2 h increased up to 95 % for AEA‐coated APZ‐MMT. Furthermore, this in vitro release profile was also similar to that of Abilify®, a commercially available medication. In vivo experiments by using Sprague–Dawley rats were also performed to compare the pharmacokinetics of AEA‐coated APZ‐MMT and Abilify®. AEA‐coated APZ‐MMT exhibited about 20 % higher systemic exposure of APZ and its metabolite, dehydro‐APZ, compared with Abilify®. Therefore, a new MMT‐based nanovehicle, which is coated with a cationic polymer, can act as a promising delivery system for both taste masking and for enhancing the bioavailability of APZ.
Practical Enantioselective Arylation and Heteroarylation of Aldehydes with In Situ Prepared Organotitanium Reagents Catalyzed by 3‐Aryl‐H8‐BINOL‐Derived Titanium Complexes
Authors: Uenishi Ami , Nakagawa Yuya , Osumi Hironobu , Harada Toshiro
Published: February 2013

A highly efficient and practical method for the catalytic enantioselective arylation and heteroarylation of aldehydes with organotitanium reagents, prepared in situ by the reaction of aryl‐ and heteroaryllithium reagents with ClTi(OiPr)3, is described. Titanium complexes derived from DPP‐H8‐BINOL (3 d; DPP=3,5‐diphenylphenyl) and DTBP‐H8‐BINOL (3 e; DTBP=3,5‐di‐tert‐butylphenyl) exhibit excellent catalytic activity in terms of enantioselectivity and turnover efficiency for the transformation, providing diaryl‐, aryl heteroaryl‐, and diheteroarylmethanol derivatives in high enantioselectivity at low catalyst loading (0.2–2 mol %). The reaction begins with a variety of aryl and heteroaryl bromides through their conversion into organolithium intermediates by Br/Li exchange with nBuLi, thus providing straightforward access to a range of enantioenriched alcohols from commercially available starting materials. Various 2‐thienylmethanols can be synthesized enantioselectively by using commercially available 2‐thienyllithium in THF. The reaction can be carried out on a 10 mmol scale at 0.5 mol % catalyst loading, demonstrating its preparative utility.
Precise Tuning of Surface Composition and Electron‐Transfer Properties of Graphene Oxide Films through Electroreduction
Authors: Ambrosi Adriano , Pumera Martin
Published: February 2013

Graphene materials are generally prepared from the exfoliation of graphite oxide (GO) to graphene oxide, followed by subsequent chemical or thermal reduction. These methods, although efficient in removing most of the oxygen functionalities from the GO material, lack control over the extent of the reduction process. We demonstrate here an electrochemical reduction procedure that not only allows for precise control of the reduction process to obtain a graphene material with a well‐defined C/O ratio in the range of 3 to 10, but also one that is able to tune the electrocatalytic properties of the reduced material. A method that is able to precisely control the amount and density of the oxygen functionalities on the graphene material as well as its electrochemical behaviour is very important for several applications such as electronics, bio‐composites and electrochemical devices.
Coupling Photocatalysis and Redox Biocatalysis Toward Biocatalyzed Artificial Photosynthesis
Authors: Lee Sahng Ha , Kim Jae Hong , Park Chan Beum
Published: February 2013

In green plants, solar‐energy utilization is accomplished through a cascade of photoinduced electron transfer, which remains a target model for realizing artificial photosynthesis. We introduce the concept of biocatalyzed artificial photosynthesis through coupling redox biocatalysis with photocatalysis to mimic natural photosynthesis based on visible‐light‐driven regeneration of enzyme cofactors. Key design principles for reaction components, such as electron donors, photosensitizers, and electron mediators, are described for artificial photosynthesis involving biocatalytic assemblies. Recent research outcomes that serve as a proof of the concept are summarized and current issues are discussed to provide a future perspective.
3‐Aryl‐4‐methyl‐2‐quinolones Targeting Multiresistant Staphylococcus aureus Bacteria
Authors: Doléans‐Jordheim Anne , Veron Jean‐Baptiste , Fendrich Olivier , Bergeron Emmanuelle , Montagut‐Romans Adrien , Wong Yung‐Sing , Furdui Bianca , Freney Jean , Dumontet Charles , Boumendjel Ahcène
Published: February 2013

The NorA efflux pump lowers intracellular fluoroquinolone concentrations by expelling antibiotics through the membrane of Staphylococcus aureus. We identified 3‐aryl‐4‐methyl‐2‐quinolin‐2‐ones as compounds able to restore the activity of the NorA substrate, ciprofloxacin, against resistant S. aureus strains, and acting as efflux pump inhibitors (EPI). In particular, 5‐hydroxy‐7‐methoxy‐4‐methyl‐3‐phenylquinolin‐2‐one (6 c) presents both an EPI and an antimicrobial effect. Its efficacy and safety make it a potential candidate for further investigations.
A Concise Synthesis of Pyrazole Analogues of Combretastatin A1 as Potent Anti‐Tubulin Agents
Authors: Zaninetti Roberta , Cortese Salvatore V. , Aprile Silvio , Massarotti Alberto , Canonico Pier Luigi , Sorba Giovanni , Grosa Giorgio , Genazzani Armando A. , Pirali Tracey
Published: February 2013

Combretastatin A1 (CA1) binds to the β‐subunit at the colchicine binding site of tubulin and inhibits polymerization. As such, it is both an antitumor agent and a vascular disrupting agent. It has been shown to be at least tenfold more potent than combretastatin A4 (CA4) in terms of vascular shutdown, which correlates with its metabolism to reactive ortho‐quinone species that are assumed to be directly cytotoxic in tumor cells. A series of 3,4‐diarylpyrazoles were concisely synthesized, one of which, 3‐methoxy‐6‐[4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrazol‐3‐yl]benzene‐1,2‐diol (27), proved to be a cytotoxic anti‐tubulin agent with low nanomolar potency. We also report that combretastatins, including CA1, CA4, and 27, are effective against mesothelioma cell lines and therefore have significant clinical promise. Metabolism experiments demonstrate that 27 retains the ability to form ortho‐quinone species, while the pyrazole ring shows high metabolic stability, suggesting that this compound might result in better pharmacokinetic profiles than CA1, with similar pharmacodynamic properties and clinical potential.
RET/PTC and PAX8/PPARγ chromosomal rearrangements in post‐Chernobyl thyroid cancer and their association with iodine‐131 radiation dose and other characteristics
Authors: Leeman‐Neill Rebecca J. , Brenner Alina V. , Little Mark P. , Bogdanova Tetiana I. , Hatch Maureen , Zurnadzy Liudmyla Y. , Mabuchi Kiyohiko , Tronko Mykola D. , Nikiforov Yuri E.
Published: February 2013

BACKGROUND:

Childhood exposure to iodine‐131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited.

METHODS:

Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of 131I to the thyroid. Associations between mutation types and 131I dose and other characteristics were explored.

RESULTS:

RET/PTC (ret proto‐oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator‐activated receptor gamma) rearrangement were identified. A significant negative association with 131I dose for BRAF and RAS point mutations and a significant concave association with 131I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear‐quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine‐deficient Zhytomyr region, younger age at exposure or surgery, and male sex.

CONCLUSIONS:

These results provide the first demonstration of PAX8/PPARγ rearrangements in post‐Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with 131I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and 131I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. Cancer 2013. © 2013 American Cancer Society.
Use of colonoscopy for polyp surveillance in Medicare beneficiaries
Authors: Cooper Gregory S. , Kou Tzuyung D. , Barnholtz Sloan Jill S. , Koroukian Siran M. , Schluchter Mark D.
Published: February 2013

BACKGROUND:

Professional society guidelines recommend follow‐up colonoscopy for patients with resected colonic adenomas. However, adherence to guideline recommendations in routine clinical practice has not been well characterized.

METHODS:

The authors used a population‐based sample of Medicare beneficiaries to identify all patients aged ≥70 years who had a claim for colonoscopy with polypectomy or hot biopsy during the period from 2001 to 2004. Medicare claims through 2009 identified colonoscopy within the following 5 years as well as fecal occult blood testing, sigmoidoscopy, and barium enema.

RESULTS:

In total, 12,771 patients were included. At 5 years, 45.7% of patients underwent another colonoscopy, and 32.3% of procedures included a polypectomy. The rates of fecal occult blood testing, flexible sigmoidoscopy, and barium enema at 5 years were 54%, 3.8%, and 2.9%, respectively. There was a marked decrease in repeat colonoscopy at 1 year, 3 years, and 5 years with more recent years of index procedures. Other predictors of undergoing repeat colonoscopy were younger age, African American race, and a colonoscopy before the index examination. There was no association with physician specialty. The decreasing use of colonoscopy with time was maintained in a multivariable analysis.

CONCLUSIONS:

In a sample of elderly Medicare beneficiaries, there was under use of follow‐up colonoscopy at 5 years after polypectomy, and <50% of patients received a repeat examination. In particular, the use of this procedure decreased over the 4‐year study period. Coupled with other data indicating the overuse of follow‐up colonoscopy in patients without polyps, there appeared to be significant discordance between guidelines and actual practice. Cancer 2013. © 2013 American Cancer Society.
Spiroconjugated Intramolecular Charge‐Transfer Emission in Non‐Typical Spiroconjugated Molecules: The Effect of Molecular Structure upon the Excited‐State Configuration
Authors: Zhu Linna , Zhong Cheng , Liu Cui , Liu Zhongyin , Qin Jingui , Yang Chuluo
Published: February 2013

A set of terfluorenes and terfluorene‐like molecules with different pendant substitutions or side groups were designed and synthesized, their photophysical properties and the excited‐state geometries were studied. Dual fluorescence emissions were observed in compounds with rigid pendant groups bearing electron‐donating N atoms. According to our earlier studies, in this set of terfluorenes, the blue emission is from the local π–π* transition, while the long‐wavelength emission is attributed to a spiroconjugation‐like through‐space charge‐transfer process. Herein, we probe further into how the molecular structures (referring to the side groups, the type of linkage between central fluorene and the 2,2′‐azanediyldiethanol units, and—most importantly—the amount of pendant groups), as well as the excited‐state geometries, affect the charge‐transfer process of these terfluorenes or terfluorene‐like compounds. 9‐(9,9,9′′,9′′‐tetrahexyl‐9H,9′H,9′′H‐[2,2′:7′,2′′‐terfluoren]‐9′‐yl)‐1,2,3,5,6,7‐hexahydropyrido[3,2,1‐ij]quinolone (TFPJH), with only one julolidine pendant group, was particularly synthesized, which exhibits complete “perpendicular” conformation between julolidine and the central fluorene unit in the excited state, thus typical spiroconjugation could be achieved. Notably, its photophysical behaviors resemble those of TFPJ with two pendant julolidines. This study proves that spiroconjugation does happen in these terfluorene derivatives, although their structures are not in line with the typical orthogonal π fragments. The spiroconjugation charge‐transfer emission closely relates to the electron‐donating N atoms on the pendant groups, and to the rigid connection between the central fluorene and the N atoms, whereas the amount of pendant groups and the nature of the side chromophores have little effect. These findings may shed light on the understanding of the through‐space charge‐transfer properties and the emission color tuning of fluorene derivatives.
The origin of parental care in relation to male and female life history
Authors: Klug Hope , Bonsall Michael B. , Alonzo Suzanne H.
Published: February 2013

The evolution of maternal, paternal, and bi‐parental care has been the focus of a great deal of research. Males and females vary in basic life‐history characteristics (e.g., stage‐specific mortality, maturation) in ways that are unrelated to parental investment. Surprisingly, few studies have examined the effect of this variation in male and female life history on the evolution of care. Here, we use a theoretical approach to determine the sex‐specific life‐history characteristics that give rise to the origin of paternal, maternal, or bi‐parental care from an ancestral state of no care. Females initially invest more into each egg than males. Despite this inherent difference between the sexes, paternal, maternal, and bi‐parental care are equally likely when males and females are otherwise similar. Thus, sex differences in initial zygotic investment do not explain the origin of one pattern of care over another. However, sex differences in adult mortality, egg maturation rate, and juvenile survival affect the pattern of care that will be most likely to evolve. Maternal care is more likely if female adult mortality is high, whereas paternal care is more likely if male adult mortality is high. These findings suggest that basic life‐history differences between the sexes can alone explain the origin of maternal, paternal, and bi‐parental care. As a result, the influence of life‐history characteristics should be considered as a baseline scenario in studies examining the origin of care.
Polyphenols are responsible for the proapoptotic properties of pomegranate juice on leukemia cell lines
Authors: Dahlawi Haytham , Jordan‐Mahy Nicola , Clench Malcolm , McDougall Gordon J. , Le Maitre Christine Lyn
Published: February 2013

Pomegranates have shown great promise as anti‐cancer agents in a number of cancers including clinical trials in prostate cancer. We have previously shown pomegranate juice (PGJ) induced apoptosis and preferentially alters the cell cycle in leukemia cell lines compared with nontumor control cells. However, the agents responsible have not yet been fully elucidated. Treatment of four leukemia cell lines with five fractions obtained from PGJ by solid phase extraction demonstrated that only the acetonitrile fractions decreased adenosine triphosphate (ATP) levels in all leukemia cell lines. Acetonitrile fractions also significantly activated caspase‐3 and induced nuclear morphology characteristic of apoptosis. S phase arrest was induced by acetonitrile fractions which matched S phase arrest seen previously following whole PGJ treatments. The acetonitrile fractions contained higher phenol content than whole PGJ whereas only low levels of phenols were seen in any other fraction. Liquid chromatography mass spectrometry (LC–MS) analysis demonstrated that acetonitrile fractions were enriched in ellagitannins, ellagic acid, and hydroxycinnamic acid derivatives but depleted in anthocyanins. Individual treatments with identified compounds demonstrated that the ellagitannin: punicalagin was the most active and mimicked the responses seen following acetonitrile fraction treatment. Bioactive components within pomegranate were confined to the acetonitrile fraction of PGJ. The enrichment in ellagitannins and hydroxycinnamic acids suggest these may provide the majority of the bioactivities of PGJ. Individual treatments with compounds identified demonstrated that the ellagitannin: punicalagin was the most active agent, highlighting this compound as a key bioactive agent in PGJ.
Spatiotemporal variations ofpCO2and δ13C‐DIC in subarctic streams in northern Sweden
Authors: Giesler Reiner , Mörth Carl‐Magnus , Karlsson Jan , Lundin Erik J. , Lyon Steve W. , Humborg Christoph
Published: February 2013

Current predictions of climate‐related changes in high‐latitude environments suggest major effects on the C export in streams and rivers. To what extent this will also affect the stream water CO2concentrations is poorly understood. In this study we examined the spatiotemporal variation in partial pressure of CO2(pCO2) and in stable isotopic composition of dissolved inorganic carbon (δ13C‐DIC) in subarctic streams in northern Sweden. The selected watersheds are characterized by large variations in high‐latitude boreal forest and tundra and differences in bedrock. We found that all streams generally were supersaturated inpCO2with an average concentration of 850 µatm. The variability inpCO2across streams was poorly related to vegetation cover, and carbonaceous bedrock influence was manifested in high DIC concentrations but not reflected in either streampCO2or δ13C‐DIC. Stream waterpCO2values were highest during winter base flow when we also observed the lowest δ13C‐DIC values, and this pattern is interpreted as a high contribution from CO2from soil respiration. Summer base flow δ13C‐DIC values probably are more affected by in situ stream processes such as aquatic production/respiration and degassing. A challenge for further studies will be to disentangle the origin of stream water CO2and quantify their relative importance.
Normalization of cerebral vasoreactivity using BOLD MRI after intravascular stenting
Authors: Attyé Arnaud , Villien Marjorie , Tahon Florence , Warnking Jan , Detante Olivier , Krainik Alexandre
Published: February 2013

Background and purpose: Intravascular angioplasty and stenting of intracranial arterial stenosis provided controversial results. Besides the expertise of the practitioners, the selection of the patients remains challenging. BOLD MRI of the cerebral vasoreactivity (BOLD MRI CVR) to hypercapnia provides reproducible maps of the entire brain of the vascular reserve, and could be helpful to assess the best therapeutic strategy. Case history: We report the case of a 63‐year‐old woman referred for a severe stenosis of the proximal portion of the left middle cerebral artery, revealed by a lenticulostriate and precentral infarction. Despite an aggressive medical treatment during 5 months, the occurrence of iterative transient ischemic attacks motivated intravascular stenting. Functional MRI of the vasoreactivity to hypercapnia using both Blood Oxygen Level Dependent (BOLD) and arterial spin labeling sequences showed normal basal perfusion and impaired vasoreactivity in the left middle cerebral artery territory. Three months after stenting, the BOLD MRI CVR showed vasoreactivity normalization. Since, the patient remains free of ischemic disorders one year after stenting. Conclusion: BOLD MRI of the CVR to hypercapnia may be helpful to optimize the treatment of patients with intracranial arterial stenosis, and could be performed in future therapeutic trials. Hum Brain Mapp 35:1320–1324, 2014. © 2013 Wiley Periodicals, Inc.
Macroporous structures based on biodegradable polymers—candidates for biomedical application
Authors: Simionescu Bogdan C. , Neamtu Andrei , Balhui Ciprian , Danciu Mihai , Ivanov Daniela , David Geta
Published: February 2013

New hybrid cryogels comprising natural polymers (free atelocollagen or atelocollagen mixed with a hyaluronic acid derivative) and a synthetic polyester—poly(ε‐caprolactone)—were successfully developed by a cryogenic treatment and a subsequent freeze‐drying step. Systematic studies on the effect of preparation conditions (reaction mixture composition, total concentration of the feed dispersion, and freezing regime) on cryogelation efficiency were conducted. The degree of cross‐linking and the morphology of the obtained materials were analyzed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and (environmental) scanning electron microscopy (ESEM/SEM) techniques. Considering their possible biomedical application, the developed macroporous hydrogels were also investigated in terms of swelling behavior and hemo/biocompatibility. The produced hydrogels had an uniform interconnected open porous structure with a porosity of up to 95% and pores size in the range of 83–260 μm. All obtained cryogels were elastic, mechanically stable, with a superfast swelling kinetics. In vitro hemocompatibility assay gave hemolysis ratios (HRs) lower than 0.5%, which is below the permissible limit of 5%. The in vivo tolerance tests performed by implantation of cryogel specimens into Wistar rats proved their biocompatibility. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2689–2698, 2013.
Neural regeneration in a novel nerve conduit across a large gap of the transected sciatic nerve in rats with low‐level laser phototherapy
Authors: Shen Chiung‐Chyi , Yang Yi‐Chin , Huang Tsung‐Bin , Chan Shiuh‐Chuan , Liu Bai‐Shuan
Published: February 2013

This study proposes a biodegradable nerve conduit comprising 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC) cross‐linked gelatin annexed with β‐tricalcium phosphate (β‐TCP) ceramic particles (EDC‐gelatin‐TCP, EGT). For this study, the EGT‐implant site in rats was irradiated using 660‐nm GaAlAsP laser diodes (50 mW) for trigger point therapy to investigate the use of low‐level laser (LLL) stimulation in the regeneration of a 15‐mm transected sciatic nerve. Animals were divided into three groups: a control group undergoing autologous nerve graft (autograft); a sham‐irradiated group (EGT), and an experimental group undergoing laser stimulation (EGT/LS). Two trigger points on the surgical incision along the sciatic nerve were irradiated transcutaneously for 2 min daily for 10 consecutive days. Twelve weeks after implantation, walking track analysis showed a significantly higher sciatic functional index (SFI; p < 0.05) and improved toe spreading development in the autograft and EGT/LS groups, compared to the EGT group. In the electrophysiological measurement, the mean recovery index (peak amplitude and area) of the compound muscle action potential curves in the autograft and EGT/LS groups showed significantly improved functional recovery than in the EGT group (p < 0.05). Compared with the EGT group, the autograft and EGT/LS groups showed a reduction in muscular atrophy. Histomorphometric assessments showed that the EGT/LS group had undergone more rapid nerve regeneration than the EGT group. Therefore, motor function, electrophysiological reaction, muscular reinnervation, and histomorphometric assessments demonstrate that LLL therapy can accelerate the repair of a 15‐mm transected peripheral nerve in rats after being bridged with the EGT nerve conduit. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:2763–2777, 2013.
A semimechanistic model of the time-course of release of PTH into plasma following administration of the calcilytic JTT-305/MK-5442 in humans
Authors: Cabal Antonio , Mehta Khamir , Ross David S , Shrestha Rajiv P , Comisar Wendy , Denker Andrew , Pai Sudhakar M , Ishikawa Tomohiro
Published: February 2013

JTT-305/MK-5442 is a calcium-sensing receptor (CaSR) allosteric antagonist being investigated for the treatment of osteoporosis. JTT-305/MK-5442 binds to CaSRs, thus preventing receptor activation by Ca2+. In the parathyroid gland, this results in the release of parathyroid hormone (PTH). Sharp spikes in PTH secretion followed by rapid returns to baseline are associated with bone formation, whereas sustained elevation in PTH is associated with bone resorption. We have developed a semimechanistic, nonpopulation model of the time-course relationship between JTT-305/MK-5442 and whole plasma PTH concentrations to describe both the secretion of PTH and the kinetics of its return to baseline levels. We obtained mean concentration data for JTT-305/MK-5442 and whole PTH from a multiple dose study in U.S. postmenopausal women at doses of 5, 10, 15, and 20 mg. We hypothesized that PTH is released from two separate sources: a reservoir that is released rapidly (within minutes) in response to reduction in Ca2+ binding, and a second source released more slowly following hours of reduced Ca2+ binding. We modeled the release rates of these reservoirs as maximum pharmacologic effect (Emax) functions of JTT-305/MK-5442 concentration. Our model describes both the dose-dependence of PTH time of occurrence for maximum drug concentration (Tmax) and maximum concentration of drug (Cmax), and the extent and duration of the observed nonmonotonic return of PTH to baseline levels following JTT-305/MK-5442 administration.
The treatment of nephrogenic systemic fibrosis with therapeutic plasma exchange
Authors: Poisson Jessica L. , Low Aaron , Park Yara A.
Published: February 2013

Background: Nephrogenic systemic fibrosis (NSF), also known as nephrogenic sclerosing dermopathy (NSD), is a rare progressive fibrosing disease associated with gadolinium based dyes in patients with renal disease. The exact pathophysiology is not well understood. Accepted treatments include corticosteroids, immune modulators, PUVA, rituximab and extracorporeal photopheresis (ECP). Apheresis is utilized when symptoms continue to progress. However, the paucity of centers offering ECP can be inhibitory to care. Small case reports have been published illustrating moderate treatment success with therapeutic plasma exchange (TPE). Methods: Chart review found two patients; both were African‐American women with systemic lupus erythematosus (SLE), status post renal transplant, who had biopsy documented NSF. The patients were still symptomatic, despite maximal medical management, so they underwent TPE series for symptom management. Medical therapy with immune modulators was continued in conjunction to TPE. Response to treatment was evaluated using subjective reporting to the primary care team. Results: The patients reported significant improvements in subjective pain levels after TPE. Patient 1 reported decreased skin and contracture pain after the 3rd treatment, with similar results for a second series 6 months later. Patient 2 reported drastic improvement in pain symptoms and rarely required pain medication during hospital course. No adverse reactions occurred during treatment. Conclusions: TPE is a therapy option for patients with NSF without access to ECP. TPE was well‐tolerated, easily assessable, and effective; however the etiology of the improvement following TPE is unknown. Larger studies will help further determine the efficacy of TPE for NSF. J. Clin. Apheresis 28:317–320, 2013. © 2013 Wiley Periodicals, Inc.
Accuracy of the national institute for neurological disorders and stroke/society for progressive supranuclear palsy and neuroprotection and natural history in Parkinson plus syndromes criteria for the diagnosis of progressive supranuclear palsy
Authors: Respondek Gesine , Roeber Sigrun , Kretzschmar Hans , Troakes Claire , Al‐Sarraj Safa , Gelpi Ellen , Gaig Carles , Chiu Wang Zheng , van Swieten John C. , Oertel Wolfgang H. , Höglinger Günter U.
Published: February 2013

Autopsy is the diagnostic gold standard for progressive supranuclear palsy (PSP). The National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy (NINDS‐SPSP) criteria for the clinical diagnosis of “probable” PSP are thought to possess high specificity and low sensitivity. The NINDS‐SPSP criteria for “possible” PSP are considered to increase sensitivity at the expense of specificity. The Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS) criteria are intended to improve sensitivity while maintaining high specificity. The aim of this study was to conduct a clinicopathological evaluation of the NINDS‐SPSP and NNIPPS criteria in tertiary neurological centers. Defined clinical features and their year of onset were recorded by chart review in neuropathologically diagnosed patients with PSP, Parkinsons's disease (PD), MSA parkinsonism and corticobasal degeneration from four European brain banks. Fulfilment of the clinical diagnostic criteria was verified for each year after disease onset and for the final antemortem record. We analyzed 98 PSP patients and 46 disease controls. The NINDS‐SPSP “probable” criteria yielded shorter time to diagnosis, slightly higher specificity and positive predictive value (PPV), and similar sensitivity, compared with the NNIPPS criteria. Unexpectedly, the NINDS‐SPSP “possible” criteria yielded the lowest sensitivity, specificity, and PPV. A combination of NINDS‐SPSP possible and probable criteria yielded the highest sensitivity. We suggest that the NINDS‐SPSP probable criteria might be preferred for recruitment of patients for clinical trials, where an early and specific diagnosis is important. For routine clinical care, where high sensitivity is crucial, a combination of NINDS possible and probable criteria might be preferred. © 2013 Movement Disorder Society
Computing solution spaces for robust design
Authors: Zimmermann Markus , von Hoessle Johannes Edler
Published: February 2013

In some engineering problems, tolerance to variation of design parameters is essential. In an early development phase of a distributed development process for example, the system performance should reach the design goal even under large variations of uncertain component properties. The tolerance to parameter variations may be measured by the size of a solution space on which the system is guaranteed to deliver the required performance. In order to decouple dimensions, the solution space is described as multi‐dimensional box with permissible intervals for each design parameter. An algorithm is presented that computes solution spaces for arbitrary non‐linear high‐dimensional systems. Starting from a design point with required performance, a candidate box is iteratively evaluated and modified. The evaluation is performed by Monte Carlo sampling and Bayesian statistics. The modification algorithm drives the evolution toward increasing box size. Robustness and reliability with respect to the required performance can be assessed without knowledge of the particular kind of uncertainty. Sensitivity to design parameters can be quantified by the widths of solution intervals. Designs failing to meet the performance requirement can be improved by adjusting parameter values to lie within the solution space. The approach is motivated and illustrated by automotive crash design problems. Copyright © 2012 John Wiley & Sons, Ltd.
Mifepristone for Management of Cushing's Syndrome
Authors: Morgan Farah H. , Laufgraben Marc J.
Published: February 2013

Cushing's syndrome is a debilitating endocrine disorder caused by elevated circulating glucocorticoid levels. Although uncommon, Cushing's syndrome is associated with significant morbidity necessitating rapid reversal of hypercortisolemia. Primary therapy for most patients with Cushing's syndrome is surgical, but many patients will require additional treatments with radiation or drugs. Although several options for drug therapy exist, few are readily available and all have dose‐limiting adverse effects. Mifepristone (RU 486), a first‐in‐class glucocorticoid receptor antagonist, was approved by the United States Food and Drug Administration in 2012 for use in Cushing's syndrome to control hyperglycemia in patients who are not surgical candidates or have not achieved remission from surgery. The drug is approved for oral once‐daily administration. In its pivotal trial, 60% of patients responded to mifepristone with significant improvements in glycemic control and 38% had a reduction in diastolic blood pressure. The most common adverse events were nausea, fatigue, headache, endometrial hyperplasia, and hypokalemia. Adrenal insufficiency occurred in fewer than 5% of patients. The recommended starting dosage of mifepristone is 300 mg/day. The dosage may be increased every 2–4 weeks up to a maximum of 1200 mg/day, although it should not exceed 20 mg/kg/day. Significant drug–drug interactions exist due to mifepristone's effects on a number of cytochrome P450 enzymes. Despite its limitations, mifepristone is a welcome addition and an appropriate alternative to the available drug therapy for Cushing's syndrome.
The development of a torsional braid analyser interfaced to a microprocessor and some of the factors affecting the optimisation of the technique
Authors: Sakellariou Panagiotis , White Eric F. T. , Rowe Raymond C.
Published: February 2013

This paper reports the development of a torsional braid analyser equipped with a gas lubricated bearing to minimise undesirable lateral oscillations of the sample, and its interface to a microprocessor for automatic data acquisition and reduction. The contribution of the glass braid substrate to the recorded dynamic mechanical behaviour is examined and some factors (polymer concentration in impregnating solution, braid structure) for the optimisation of the technique are discussed.
The Effect of High Pressure Processing on the Integrity of Polymeric Packaging – Analysis and Categorization of Occurring Defects
Authors: Fleckenstein Benedikt Stefan , Sterr Julia , Langowski Horst‐Christian
Published: February 2013

As high‐pressure processing is used increasingly for the treatment of packed products, different packaging has been investigated with respect to their structural behaviour and stability under high‐pressure processing. Often, failures and changes of the polymeric structure occur. Common damage symptoms of high‐pressure‐treated packaging materials are defined and classified in this review. These damage symptoms are allocated to the physico‐chemical effects that created them. The effects may be separated into direct effects induced by the action of the high‐pressure alone and indirect effects that are mediated via compressed contents of the package, i.e. filled product and gaseous headspace. The direct effects split up again in reversible and irreversible structural changes. The indirect effects are generated by compressed headspace gases, other compressed substances and the consequences of increased amounts of gases dissolved in the polymers. If applicable, current theoretical approaches have been allocated to the different categories of damage. Copyright © 2013 John Wiley & Sons, Ltd.
Raising Critical Consciousness via Creative Writing in the EFL Classroom
Authors: Stillar Scott
Published: February 2013

This study discusses a method to promote raising critical consciousness in the English as a foreign language (EFL) classroom via creative writing activities by having students write journals and/or personal letters from the perspective of individuals from outside groups that have been marginalized or vilified in the students' dominant culture. These activities are intended to encourage students to adopt new perspectives on polarizing topics while also being an enjoyable and effective means to practice English writing. Furthermore, it is recommended that these activities also be used to serve as segues to deeper critical discourse on related issues. The author incorporates several examples of implementation as well as student impressions of the activities taken from surveys in a Japanese university EFL context.
Beyond the Class Blog: Creative and Practical Uses of Blogger for the ESL Classroom
Authors: Gerich David
Published: February 2013

Using Blogger, a free Google‐powered weblog‐generating website, English as a second language (ESL) instructors can create motivating and empowering learning opportunities for students. Instructors can generate their own blogs, including not only a class blog that builds a community‐learning setting online, but also a teacher's homepage to communicate with students and a content‐specific blog that extends classroom lessons to online practice. In addition, instructors can guide ESL students in the blog‐creating process, leading them to write their own blogs, such as an online journal of their experiences in a foreign country.
Adult English Language Learners' Perceptions of Audience Response Systems (Clickers) as Communication Aides: A Q‐Methodology Study
Authors: Rodriguez Lisa Ann , Shepard Maryfriend
Published: February 2013

This study explored the perceptions of adult English language learners about audience response systems (clickers) as tools to facilitate communication. According to second language acquisition theory, learners' receptive capabilities in the early stages of second language acquisition surpass expressive capabilities, often rendering them silent in their second language. Clickers may help English language learners to communicate more effectively by enabling them to express themselves nonverbally. In this Q‐methodological study, adult English language learners enrolled in a computer skills course ranked statements about using clickers according to how closely they aligned with their perceptions about the ability of clickers to facilitate communication. Factor analysis identified commonalities and patterns in perceptions, confirming that second language acquisition theory influences how technology tools are perceived by English language learners. Results of this study may suggest more effective instructional and assessment practices for adult English language learners, and lead to further research of educational technology communication tools with English language learners of all ages.