bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for Autism in Mexico
Authors: Fombonne Eric , Marcin Carlos , Bruno Ruth , Tinoco Cecilia Manero , Marquez Christian Diaz
Published: May 2012

In order to conduct the screening phase of the first epidemiological survey of autism spectrum disorders (ASDs) in Mexico, we needed a screening tool to detect autistic symptomatology in a large sample of school‐age children. We used the Spanish version of the Social Responsiveness Scale (SRS). We recruited a clinical sample of 200 children (81% males; mean age: 7.4 years) with a confirmed diagnosis of ASDs and a sample of 363 control children (59.5% males; mean age: 8.5 years) without ASDs. Three‐way analyses of variance (ANOVAs) identified a main effect of clinical status (ASDs vs. controls) for both parent and teacher scales, but no gender or age effect. The mean total and subscale raw scores were significantly different between the clinical and control groups for the parent and for the teacher SRS (P < 0.001). The internal consistency of the SRS was excellent. Receiver operating characteristic (ROC) analyses showed excellent discriminant validity of the SRS in the Mexican sample (area under the curve: 0.962 for the parent, 0.960 for the teacher). ROC curves were also used to determine which cutoff would provide the best trade‐off between sensitivity and specificity. Mexican SRS scores were significantly higher than in the U.S. and German population for typically developing children but comparable for clinically referred subjects. The SRS is an acceptable screening instrument for epidemiological studies of ASDs in Mexico. Its psychometric properties are excellent and comparable to those derived from North American and other samples. Autism Res 2012, 5: 180–189. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.
Development strategies for IVIVC in an industrial environment
Authors: Cook Jack A.
Published: May 2012

Product development is typically challenging. There is a strong desire to understand critical performance factors early in order to optimize formulations for Phase III trials or marketing approval. However, over 90% of drugs entering development in humans do not make it to the market. Thus there is a tremendous risk that resources spent early in development will be wasted as candidates attrite. To overcome this apparent dilemma, a Bayesian approach is suggested. In ‘traditional’ product development, clinical study designs are typically relatively assumption free and often do not consider learning from earlier investigations. A Bayesian approach is one in which prior information is considered when interpreting the results of the current study. A candidate IVIVC can be developed at the earliest stage of clinical development. Subsequently there are multiple opportunities within a typical development program to assess the performance of the preliminary IVIVC as new formulations are introduced. With each introduction, there is an opportunity to either confirm the adequacy of the IVIVC or to identify the need for development of a more predictive dissolution test and IVIVC. Copyright © 2012 John Wiley & Sons, Ltd.
Integrating drug permeability with dissolution profile to develop IVIVC
Authors: Takano Ryusuke , Kataoka Makoto , Yamashita Shinji
Published: May 2012

In this review article, three different approaches to predict in vivo oral absorption based on the in vitro data of drug permeability, solubility and dissolution were introduced. At the drug discovery stage, the absorption potential of each candidate is most important to select better compounds for further development. The concept of maximum absorbable dose is applied widely, not only to evaluate the absorption potential but also to elucidate the rate‐limiting process of oral absorption that helps us to understand the cause of poor absorption. To integrate the permeability of the drug with its dissolution profile, two different approaches, in vitro dissolution/permeation system (D/P system) and in silico model and simulation method, are proposed. In the D/P system, by mimicking the in vivo process of drug absorption, the permeated amount of drugs, that is the total output of dissolution and permeation processes, are correlated with the fraction absorbed in human (Fa). This system is powerful for evaluating the improved absorption by various formulations and the effect of food intake. On the other hand, in the model and simulation approach, an intrinsic dissolution parameter of drug particle, z, was extracted from the small scale in vitro test and the process of intestinal absorption was re‐constructed in silico by incorporating the physiological parameters in human. The effective use of these approaches for the development of oral drug products is discussed through various case studies. Copyright © 2012 John Wiley & Sons, Ltd.
Coexpression of molecular chaperone enhances activity and export of organophosphorus hydrolase in Escherichia coli
Authors: Kang Dong Gyun , Kim Chang Sup , Seo Jeong Hyun , Kim Im Gyu , Choi Suk Soon , Ha Jeong Hyub , Nam Soo Wan , Lim Geunbae , Cha Hyung Joon
Published: May 2012

Periplasmic secretion has been used in attempts to construct an efficient whole‐cell biocatalyst with greatly reduced diffusion limitations. Previously, we developed recombinant Escherichia coli that express organophosphorus hydrolase (OPH) in the periplasmic space using the twin‐arginine translocation (Tat) pathway to degrade environmental toxic organophosphate compounds. This system has the advantage of secreting protein into the periplasm after folding in the cytoplasm. However, when OPH was expressed with a Tat signal sequence in E. coli, we found that the predominant OPH was an insoluble premature form in the cytoplasm, and thus, the whole‐cell OPH activity was significantly lower than its cell lysate activity. In this work, we, for the first time, used a molecular chaperone coexpression strategy to enhance whole‐cell OPH activity by improving the periplasmic translocation of soluble OPH. We found that the effect of GroEL‐GroES (GroEL/ES) assistance on the periplasmic localization of OPH was secretory pathway dependent. We observed a significant increase in the amount of soluble mature OPH when cytoplasmic GroEL/ES was expressed; this increase in the amount of mature OPH might be due to enhanced OPH folding in the cytoplasm. Importantly, the whole‐cell OPH activity of the chaperone–coexpressing cells was ∼5.5‐fold greater at 12 h after induction than that of cells that did not express the chaperone as a result of significant Tat‐based periplasmic translocation of OPH in the chaperone–coexpressing cells. Collectively, these data suggest that molecular chaperones significantly enhance the whole‐cell activity of periplasmic OPH‐secreting cells, yielding an effective whole‐cell biocatalyst system with highly reduced diffusion limitations. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 925–930, 2012
Optimization of a Saccharomyces cerevisiae fermentation process for production of a therapeutic recombinant protein using a multivariate bayesian approach
Authors: Fu Zhibiao , Leighton Julie , Cheng Aili , Appelbaum Edward , Aon Juan C.
Published: May 2012

Various approaches have been applied to optimize biological product fermentation processes and define design space. In this article, we present a stepwise approach to optimize a Saccharomyces cerevisiae fermentation process through risk assessment analysis, statistical design of experiments (DoE), and multivariate Bayesian predictive approach. The critical process parameters (CPPs) were first identified through a risk assessment. The response surface for each attribute was modeled using the results from the DoE study with consideration given to interactions between CPPs. A multivariate Bayesian predictive approach was then used to identify the region of process operating conditions where all attributes met their specifications simultaneously. The model prediction was verified by twelve consistency runs where all batches achieved broth titer more than 1.53 g/L of broth and quality attributes within the expected ranges. The calculated probability was used to define the reliable operating region. To our knowledge, this is the first case study to implement the multivariate Bayesian predictive approach to the process optimization for the industrial application and its corresponding verification at two different production scales. This approach can be extended to other fermentation process optimizations and reliable operating region quantitation. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 1095–1105, 2012
Enantioselective separations using chiral supported liquid crystalline membranes
Authors: Han Sangil , Rabie Feras , Marand Eva , Martin Stephen M.
Published: May 2012

Porous and nonporous supported liquid crystalline membranes were produced by impregnating porous cellulose nitrate supports with cholesteric liquid crystal (LC) materials consisting of 4‐cyano‐4′‐pentylbiphenyl (5CB) mixed with a cholesterol‐based dopant (cholesteryl oleyl carbonate [COC], cholesteryl nonanoate [CN], or cholesteryl chloride [CC]). The membranes exhibit selectivity for R‐phenylglycine and R‐1‐phenylethanol because of increased interactions between the S enantiomers and the left‐handed cholesteric phase. The selectivity of both phenylglycine and 1‐phenylethanol in 5CB/CN membranes decreases with effective pore diameter while the permeabilities increase, as expected. Phenylglycine, which is insoluble in the LC phase, exhibits no transport in the nonporous (completely filled) membranes; however, 1‐phenylethanol, which is soluble in the LC phase, exhibits transport but negligible enantioselectivity. The enantioselectivity for 1‐phenylethanol was higher (1.20 in 5CB/COC and 5CB/CN membranes) and the permeability was lower in the cholesteric phase than in the isotropic phase. Enantioselectivity was also higher in the 5CB/COC cholesteric phase than in the nematic phase of undoped 5CB (1.03). Enantioselectivity in the cholesteric phase of 5CB doped with CC (1.1), a dopant lacking hydrogen bonding groups, was lower than in the 5CB/COC phases. Finally, enantioselectivity increases with the dopant concentration up to a plateau value at approximately 17 mol%. Chirality 24:519–525, 2012. © 2012 Wiley Periodicals, Inc.
Enantioselective Degradation of Indoxacarb in Cabbage and Soil under Field Conditions
Authors: Sun Dali , Qiu Jing , Wu Yijun , Liang Hongwu , Liu Chenglan , Li Li
Published: May 2012

The enantioselective degradation of indoxacarb in cabbage and soil has been investigated in Beijing and Anhui under open conditions. Indoxacarb enantiomers in samples were extracted with acetonitrile, cleaned up by florisil SPE column, separated on high performance liquid chromatography with a cellulose‐tris‐(3, 5‐dimethylphenylcarbamate)‐based chiral stationary phase (CDMPC‐CSP), and determined by a photodiode array detector. The validation of the developed method by fortification rac‐indoxcarb in cabbage and soil showed good accuracy and precision. The results of field trials indicated that the dissipation of indoxacarb enantiomers followed pseudo‐first‐order kinetics or first‐order kinetics in cabbage and soil at two locations. The half‐lives of two enantiomers in cabbage ranged from 2.8 to 4.6 d which were shorter than those in soil ranging from 23 to 35 d. The changes of enantiomeric fraction values proved that enantioselective degradation of indoxacarb happened in cabbage and soil. The (−)‐indoxacarb showed faster degradation in the Beijing cabbage, whereas in the Anhui cabbage, (+)‐indoxacarb preferentially degraded. In soil, preferential degradation of (+)‐indoxacarb was observed at two locations. Chirality 24:628–633, 2012. © 2012 Wiley Periodicals, Inc.
Geomorphic response to an active transpressive regime: a case study along the Chaman strike‐slip fault, western Pakistan
Authors: Ul‐Hadi Shams , Khan Shuhab D. , Owen Lewis A. , Khan Abdul S.
Published: May 2012

The Chaman left‐lateral strike‐slip fault bounds the rigid Indian plate boundary at the western end of the Himalayan‐Tibetan orogen and is marked by contrasting topographic relief. Deformed landforms along the fault provide an excellent record for understanding this actively evolving intra‐continental strike‐slip fault. The geomorphic response of an active transpessional stretch of the Chaman fault was studied using digital elevation model (DEM) data integrated with Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Visible and Near Infrared/Short Wave Infrared (VNIR/SWIR) and images from GeoEye‐1. Geologic and geomorphic mapping helped in reconstructing the Late Quaternary landscape history of this transpessional strand of the Chaman strike‐slip fault and the associated Spinatizha thrust fault in western Pakistan. Topographic analysis of a part of the transpression (the thrust bounded Roghani ridge) revealed northward growth of the Spinatizha fault with the presence of three water gaps and two corresponding wind gaps. Geomorphic indices including stream length‐gradient index, mountain front sinuosity, valley floor width to valley height ratios, and entrenchment of recent alluvial fan deposits were used to define the lateral growth and direction of propagation of the Spinatizha fault. Left‐lateral displacement along Chaman fault and uplift along the Spinatizha fault was defined using topographic analysis of the Roghani ridge and geomorphic mapping of an impressive alluvial fan, the Bostankaul fan. The landforms and structures record slip partitioning along the Indian plate boundary, and account for the convergence resulting from the difference in the Chaman fault azimuth and orientation of the velocity vector of the Indian plate. Copyright © 2012 John Wiley & Sons, Ltd.
Bioavailability of pharmaceuticals in waters close to wastewater treatment plants: Use of fish bile for exposure assessment
Authors: Lahti Marja , Brozinski Jenny-Maria , Segner Helmut , Kronberg Leif , Oikari Aimo
Published: May 2012

Pharmaceuticals are ubiquitous in surface waters as a consequence of discharges from municipal wastewater treatment plants. However, few studies have assessed the bioavailability of pharmaceuticals to fish in natural waters. In the present study, passive samplers and rainbow trout were experimentally deployed next to three municipal wastewater treatment plants in Finland to evaluate the degree of animal exposure. Pharmaceuticals from several therapeutic classes (in total 15) were analyzed by liquid chromatography–tandem mass spectrometry in extracts of passive samplers and in bile and blood plasma of rainbow trout held at polluted sites for 10 d.

Each approach indicated the highest exposure near wastewater treatment plant A and the lowest near that of plant C. Diclofenac, naproxen, and ibuprofen were found in rainbow trout, and their concentrations in bile were 10 to 400 times higher than in plasma. The phase I metabolite hydroxydiclofenac was also detected in bile. Hence, bile proved to be an excellent sample matrix for the exposure assessment of fish. Most of the monitored pharmaceuticals were found in passive samplers, implying that they may overestimate the actual exposure of fish in receiving waters. Two biomarkers, hepatic vitellogenin and cytochrome P4501A, did not reveal clear effects on fish, although a small induction of vitellogenin mRNA was observed in trout caged near wastewater treatment plants B and C. Environ. Toxicol. Chem. 2012; 31: 1831–1837. © 2012 SETAC
Physical morbidity by surgical approach and tumor location in skull base surgery
Authors: de Almeida John R. , Witterick Ian J. , Gullane Patrick J. , Gentili Fred , Lohfeld Lynne , Ringash Jolie , Thoma Achilles , Vescan Allan D.
Published: May 2012

Background

Skull base tumors are associated with physical symptoms that vary depending on location and surgical approach.

Methods

Skull base surgery patients (n = 138) were retrospectively reviewed and physical symptoms were quantified. Patients were divided into 4 groups by surgical approach (open, endoscopic) and tumor location (anterior, central). Multivariate analyses determined odds for symptom development.

Results

Patients with anterior lesions presented with more nasal symptoms compared to those with central lesions (63% vs 6.8%; p < .001). Those with central lesions presented with more neurologic (41.1% vs 12.3%; p < .001) and endocrine symptoms (19.2% vs 0%; p < .001). Three of 4 groups experienced a reduction in neurologic and visual symptoms after surgery. One group (endoscopic/central) experienced a reduction in endocrine and an increase in nasal symptoms. Anterior tumors (p = .02) and endoscopic approaches (p = .002) predicted increased nasal morbidity.

Conclusion

Physical morbidity from skull base tumors may vary based on tumor location and surgical approach. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Follow‐up of parotid pleomorphic adenomas treated by extracapsular dissection
Authors: Iro Heinrich , Zenk Johannes , Koch Michael , Klintworth Nils
Published: May 2012

Background

This study was carried out to evaluate tumor recurrence following extracapsular dissection of pleomorphic adenomas of the parotid gland.

Methods

We conducted a retrospective evaluation and clinical follow‐up of the patients who underwent extracapsular dissection of a pleomorphic adenoma as primary surgery in the otolaryngologic department of the Erlangen University Clinics during the period from 2000 to 2005.

Results

In all, 601 surgical interventions on benign parotid tumors were carried out from 2000 to 2005, 219 of which were primary operations for removal of a pleomorphic adenoma. In 76 patients (34.7%), extracapsular dissection of a primary pleomorphic adenoma was carried out. Tumor recurrence has not been observed in any of these patients to date after an average monitoring period of 7.38 years (range, 5.05–10.52 years).

Conclusions

Extracapsular dissection is a conservative and safe surgical procedure for extirpation of pleomorphic adenomas that should be firmly established in the repertoire of parotid gland surgery. © 2012 Wiley Periodicals, Inc. Head Neck, 2012
Infiltration, runoff and soil loss in Andisols affected by forest fire (Canary Islands, Spain)
Authors: Neris J. , Tejedor M. , Fuentes J. , Jiménez C.
Published: May 2012

Depending on the severity of the fire, forest fires may modify infiltration and soil erosion processes. Rainfall simulations were used to determine the hydrological effects of fire on Andisols in a pine forest burned by a wildfire in 2007. Six burned zones with different fire severities were compared with unburned zones. Infiltration, runoff and soil loss were analysed on slopes of 10% and 30%. Forest floor and soil properties were evaluated. Unburned zones exhibited relatively low infiltration (23 and 16 mm h−1 on 10% and 30% slope angles, respectively) and high average runoff/rainfall ratios (43% and 50% on 10% and 30% slope angles, respectively), which were associated with the extreme water repellency of the forest floor. Nonetheless, this layer seems to provide protection against raindrop impact and soil losses were found to be low (8 and 16 g m−2 h−1 for 10% and 30% slope angles, respectively). Soil cover, soil structure and water repellency were the main properties affected by the fire. The fire reduced forest floor and soil repellency, allowing rapid infiltration. Moreover, a significant decrease was noted in soil aggregate stabilities in the burned zones, which limited the infiltration rates. Consequently, no significant differences in infiltration and runoff were found between the burned and the unburned zones. The decrease in post‐fire soil cover and soil stability resulted in order‐of‐magnitude increases in erosion. Sediment rates were 15 and 31 g m−2 h−1 on the 10% and 30% slope angles, respectively, in zones affected by light fire severity. In the moderate fire severity zones, these values reached 65 and 260 g m−2 h−1 for the 10% and 30% slope angles, respectively. Copyright © 2012 John Wiley & Sons, Ltd.
A shifting hydrological regime: a field investigation of snowmelt runoff processes and their connection to summer base flow, Sunshine Coast, British Columbia
Authors: Beaulieu M. , Schreier H. , Jost G.
Published: May 2012

The annual hydrographs of British Columbian rivers are characterized by glacial, nival, pluvial or ‘hybrid’ sources of runoff. Climate change scenarios for the 2050s indicate that snow water equivalent could diminish by 50% to 80% in low‐elevation basins of the south coastal region of British Columbia. This could trigger a shift from a hybrid to a pluvial regime for many creeks originating in the coastal mountains and could negatively affect summer low flows. However, the connection between recharge occurring in the headwaters during snowmelt and late‐summer water yield remains unclear. A mountainous creek (Stephen's Creek) was monitored in a nested design from September 2008 to November 2009. A two‐component isotopic hydrograph separation method was developed by adapting the runoff‐corrected model to a semidistributed environment to account for both the spatial and the temporal variability of the isotopic release from the snowpack in the headwater catchment. Results show that snowmelt composed most of the streamflow both at the headwater site (66% ± 19%) and at the mouth (62% ± 23%) during the peak of the freshet, and its contribution to streamflow was significantly different in July (34% ± 11% at the headwater vs 7% ± 4% at the mouth). Streamflow recession analysis suggests that a snowmelt‐recharged headwater catchment can support a steadier summer base flow compared to a much larger but rainfed‐dominated watershed. This study concluded that the large input of meltwater during the spring was sufficient to ‘overturn’ shallow subsurface reservoirs and to recharge deeper flow paths at a rate that cannot be matched by rainfed‐dominated systems. Copyright © 2012 John Wiley & Sons, Ltd.
Filtered backprojection algorithm can outperform iterative maximum likelihood expectation‐maximization algorithm
Authors: Zeng Gengsheng L.
Published: May 2012

The iterative maximum‐likelihood expectation‐maximization (ML‐EM) algorithm is an excellent algorithm for image reconstruction and usually provides better images than the filtered backprojection (FBP) algorithm. However, a windowed FBP algorithm can outperform the ML‐EM in certain occasions, when the least‐squared difference from the true image, that is, the least‐squared error (LSE), is used as the comparison criterion. Computer simulations were carried out for the two algorithms. For a given data set the best reconstruction (compared to the true image) from each algorithm was first obtained, and the two reconstructions are compared. The stopping iteration number of the ML‐EM algorithm and the parameters of the windowed FBP algorithm were determined, so that they produced an image that was closest to the true image. However, to use the LSE criterion to compare algorithms, one must know the true image. How to select the optimal parameters when the true image is unknown is a practical open problem. For noisy Poisson projections, computer simulation results indicate that the ML‐EM images are better than the regular FBP images, and the windowed FBP algorithm images are better than the ML‐EM images. For the noiseless projections, the FBP algorithms outperform the ML‐EM algorithm. The computer simulations reveal that the windowed FBP algorithm can provide a reconstruction that is closer to the true image than the ML‐EM algorithm. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 114–120, 2012
Group inference of default‐mode networks from functional magnetic resonance imaging data: comparison of random‐ and mixed‐effects group statistics
Authors: Kim Yong‐Hwan , Lee Jong‐Hwan
Published: May 2012

Default‐mode network (DMN) activity measured with functional magnetic resonance imaging (fMRI) represents dominant intrinsic neuronal activations of the human brain during rest as opposed to task periods. Previous studies have demonstrated the utility of DMNs in identifying characteristic traits such as hyperactivation and hypoactivation from group‐level fMRI data. However, these group‐level spatial patterns (SPs) were mostly based on random‐effect (RFX) statistics determined using only the intersubject variability. To reduce the potentially significant level of variability in group‐level SPs in RFX due to intrasubject variability, we were motivated to adopt a mixed‐effects (MFX) statistics that is using both intrasubject and intersubject variability. Publicly available group fMRI database during resting state was analyzed using a temporal concatenation‐based group independent component (IC) analysis, and DMN‐related ICs at the group‐level were automatically selected. The individual‐level SPs of these DMN‐related ICs were subsequently estimated using a dual‐regression approach. Using these individual‐level SPs, we evaluated the reproducibility and potential variability of the DMNs from the RFX and MFX statistics using performance measures including (1) neuronal activation levels, (2) percentages of overlap, (3) Pearson's spatial correlation coefficients, and (4) the distances between center‐of‐clusters. The resulting SPs from the MFX‐based group inference showed a significantly greater level of reproducibility than those from the RFX‐based group inference as tested in a bootstrapping framework Family‐wise error (FWE)‐corrected p < 10−10, one‐way analysis of variance (ANOVA)). The reported findings may provide a valuable supplemental option for investigating the neuropsychiatric group‐ or condition‐dependent characteristic traits implicated in DMNs. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 121–131, 2012
Morphological contrast index based on the Weber's law
Authors: Jiménez‐Sánchez Angélica R. , Santillán Israel , Resendiz Juvenal Rodriguez , Gonzalez‐Gutierrez Carlos A. , Mendiola‐Santibañez Jorge D.
Published: May 2012

In this article, a morphological contrast index based on the Weber's law is proposed to quantify the contrast in a processed image. This measure involves the contours of the image along with its background. The proposal made here is applied to detect the image with higher contrast, and also identify the enhanced image most similar to the original. Moreover, the contrast index is compared with other four indexes reported in the current literature. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 137–144, 2012
Interest points localization for brain image using landmark‐annotated atlas
Authors: Lu Huanxiang , Nolte Lutz‐Peter , Reyes Mauricio
Published: May 2012

The localization of clinically important points in brain images is crucial for many neurological studies. Conventional manual landmark annotation requires expertise and is often time‐consuming. In this work, we propose an automatic approach for interest point localization in brain image using landmark‐annotated atlas (LAA). The landmark detection procedure is formulated as a problem of finding corresponding points of the atlas. The LAA is constructed from a set of brain images with clinically relevant landmarks annotated. It provides not only the spatial information of the interest points of the brain but also the optimal features for landmark detection through a learning process. Evaluation was performed on 3D magnetic resonance (MR) data using cross‐validation. Obtained results demonstrate that the proposed method achieves the accuracy of ∼ 2 mm, which outperforms the traditional methods such as block matching technique and direct image registration. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 145–152, 2012
Charge‐conversional poly(amino acid)s derivatives as a drug delivery carrier in response to the tumor environment
Authors: Yoon Se Rim , Yang Hee‐Man , Park Chan Woo , Lim Sujin , Chung Bong Hyun , Kim Jong‐Duk
Published: May 2012

A charge‐converting and pH‐dependent nanocarrier was achieved by conjugating 2,3‐dimethylmaleic anhydride (DMMA) to the amino group of an octadecyl grafted poly (2‐hydroxyethyl aspartamide) (PHEA‐g‐C18‐NH2) backbone, thereby forming a spherical micelle. PHEA, a poly(amino acid)s derivative, was derived from poly(succinimide), which is biocompatible and biodegradable. DMMA, a detachable component at the tumor site, was added, preventing aggregation with negative blood serum and enhancing the nanocarrier's cellular uptake. The polymeric micelle was comprehensively characterized and doxorubicin was encapsulated successively. The cellular uptake and anticancer therapeutic effect were evaluated by flow cytometry, confocal laser scanning microscopy, and a MTT assay. The properties of the nanocarrier can further be exploited to develop an early detection module for cancer. The present work is also expected to advance the study of designing smart carriers for drug and gene delivery. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Effect of macrophage classical (M1) activation on implant‐adherent macrophage interactions withStaphylococcus epidermidis: A murinein vitromodel system
Authors: Park Kyung R. , Bryers James D.
Published: May 2012

A modelin vitrosystem was developed for eliciting classical (M1) activation of surface‐adherent murine macrophages, which was then used to study the interaction of the M1 macrophages withStaphylococcus epidermidis. Glass substrata were first covalently grafted with a mixture of methoxy‐ and biotin‐terminated silanated polyethylene glycol. Interferon (IFN)‐γ and/or lipopolysaccharide (LPS), ligands known to induce the highly microbicidal M1 activation state in macrophages, were biotinylated and immobilized by way of a streptavidin intermediate to the biotin‐PEG base substratum. Assessment of mouse bone marrow‐derived macrophage (BMDM) interleukin (IL)‐12(p40) and nitric oxide response to the fabricated surfaces confirmed that the model system achieved activation of adherent macrophage: IFN‐γ‐presenting surfaces primed cells for M1 activation, LPS‐presenting surfaces elicited innate activation, and surface presenting a combination of IFN‐γ and LPS induced M1 activation. The phagocytic and microbicidal capacity of activated, surface‐adherent BMDM was evaluated usingS. epidermidis, a bacterial species prevalent in implant‐associated infections. Results indicate that M1 activation of implant‐adherent macrophages trends towards diminishing their phagocytic capacity, but enhances their microbicidal capacity forS. epidermidis. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Some aspects of the host response to methacrylic acid containing beads in a mouse air pouch
Authors: Patel Riteshkumar J. , Sefton Michael V.
Published: May 2012

Exudate analysis indicated that both hydroxamated methacrylic acid‐based (HX‐MAA) and methacrylic acid‐based (MAA) beads without hydroxamation, implanted in an air pouch with gelatin discs, elicited similar biological responses, with both resulting in high cell counts and chemokine (MCP3) levels, relative to control, poly(methyl methacrylate) (PMMA) beads. HX‐MAA beads had been used elsewhere to restore homeostatic levels of extracellular matrix degrading enzymes, matrix metalloproteases, whereas the MAA beads (without hydroxamation) promoted angiogenesis in wound healing models. Furthermore, both beads appeared to activate exudate macrophages in the classical manner (high IL12/IL10 ratio) at day 4. Exudate macrophages, which were isolated by a magnetic bead protocol and analyzed by RT‐PCR, showed a mixed response: elevated levels of an alternative marker (mannose receptor C type lectin) and a classical marker (IL6) were seen, in macrophages from the HX‐MAA and MAA group compared to the PMMA group at day 4. A partial shift to an alternatively activated phenotype was seen by day 10. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Layer‐by‐layer assembly of antibacterial coating on interbonded 3D fibrous scaffolds and its cytocompatibility assessment
Authors: Tang Yanwei , Zhao Yan , Wang Hongxia , Gao Yuan , Liu Xin , Wang Xungai , Lin Tong
Published: May 2012

Bonded fibrous matrices have shown great potential in tissue engineering because of their unique 3D structures and pore characteristics. For some applications, bacterial infections must be taken into account, and antibacterial function is highly desired. In this study, an antibacterial polymer, polyhexamethylene biguanide (PHMB), was applied onto the fiber surface of a bonded poly(ε‐caprolactone) (PCL) fibrous matrix with the objective to achieve both strong antibacterial effect and good cell compatibility. The coatings were prepared by using an electrostatic layer‐by‐layer (LbL) assembly technique, which allowed the control of PHMB loading and coating uniformity on the fiber surface. The PHMB coating provided antibacterial activities, but had no toxicity on mammalian cells. This bonded PCL fibrous matrix with electrostatically self‐assembled PHMB may provide a new antiinfective tissue scaffold for various biomedical applications. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Copolymer nanoparticles composed of sulfobetaine and poly(ε‐caprolactone) as novel anticancer drug carriers
Authors: Cao Jun , Xiu Ke‐Mao , Zhu Kun , Chen Yuan‐Wei , Luo Xiang‐Lin
Published: May 2012

Novel ABA type amphiphilic copolymers (PCL‐APS‐PCL) consisting of polycaprolactone (PCL) (A) as hydrophobic block and N,N′‐bis (2‐hydroxyethyl) methylamine ammonium propane sulfonate (APS) (B) as hydrophilic segment, self‐assembled into nanoparticles (NPs) with solvent evaporation method. The sizes and size distributions of NPs were characterized by dynamic light scattering. The morphology of NPs was observed by scanning electron microscopy (SEM). The critical micelle concentration (CMC) was determined by fluorescent probe. The drug loading content (DLC) and the drug release amount were characterized by UV–visible spectrophotometer. The cytotoxicity of the NPs was measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenylte‐trazoliumbromide (MTT) assay. It was found that the NPs were spherical in shape with sizes around 100 nm. The CMCs of the copolymers were quite low (×10−4 mg/mL). The DLC decreased with lengthening of hydrophobic PCL block. In vitro drug release experiment demonstrated that the release rate of paclitaxel sped with the decrease of PCL length. MTT results showed that NPs were nontoxic to osteoblast and human epithelial carcinoma (hela) cells. After drug loading, NPs could restrain the growth of hela or even kill hela cells. Therefore, these preliminary studies suggest that the novel PCL‐APS‐PCL NPs have a great potential application as anticancer drug‐delivery carriers. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Investigating the role of substrate stiffness in the persistence of valvular interstitial cell activation
Authors: Quinlan Angela M. Throm , Billiar Kristen L.
Published: May 2012

During heart valve remodeling and in many disease states, valvular interstitial cells (VICs) shift to an activated myofibroblast phenotype characterized by enhanced synthetic and contractile activity. Pronounced alpha smooth muscle actin (αSMA)‐positive stress fibers, the hallmark of activated myofibroblasts, are also observed in VICs cultured on stiff substrates especially in the presence of transforming growth factor‐beta1 (TGF‐β1), however, the detailed relationship between stiffness and VIC phenotype has not been explored. The goal of this study was to characterize VIC activation as a function of substrate stiffness over a wide range of stiffness levels including that of diseased valves (stiff), normal valves (compliant), and hydrogels for heart valve tissue engineering (very soft). VICs obtained from porcine aortic valves were cultured on stiff tissue culture plastic to activate them, then, cultured on collagen‐coated polyacrylamide substrates of predefined stiffness in a high‐throughput culture system to assess the persistence of activation. Metrics extracted from regression analysis demonstrate that relative to a compliant substrate, stiff substrates result in higher cell numbers, more pronounced expression of αSMA‐positive stress fibers, and larger spread area which is in qualitative agreement with previous studies. Our data also indicate that VICs require a much lower substrate stiffness level to “deactivate” them than previously thought. The high sensitivity of VICs to substrate stiffness demonstrates the importance of the mechanical properties of materials used for valve repair or for engineering valve tissue. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2474–2482, 2012.
Optimal preservation of the shark retina for ultrastructural analysis: An assessment of chemical, microwave, and high‐pressure freezing fixation techniques
Authors: Harahush Blake K. , Green Kathryn , Webb Rick , Hart Nathan S. , Collin Shaun P.
Published: May 2012

Recent advances in microwave chemical fixation (MCF) and/or high pressure freezing (HPF) combined with transmission electron microscopy have resulted in superior ultrastructural detail in a variety of tissue types. To date, selachian tissue has been fixed and processed using only standard chemical fixation (CF) methods, and the resulting ultrastructure has been less than ideal. In this study, we compared the ultrastructure of the fragile retinal tissue from the brown banded bamboo shark, Chiloscyllium punctatum, obtained using CF, MCF, and HPF methods. For all fixation protocols, ultrastructural preservation was improved by keeping the tissue in oxygenated Ringer solution until the time of fixation. Both MCF and HPF produced superior retinal ultrastructure compared to conventional CF. Although HPF occasionally resulted in very high quality ultrastructure, microwave fixation was almost comparable, quicker and far more consistent. Microsc. Res. Tech. 75:1218–1228, 2012. © 2012 Wiley Periodicals, Inc.
Macroscopic and microscopic analysis of the tongue of the common opossum (Didelphis marsupialis)
Authors: Mançanares Celina A.F. , Santos Amilton C. , Piemonte Maria V. , Vasconcelos Bruno G. , Carvalho Ana F. , Miglino Maria A. , Ambrósio Carlos E. , Neto Antônio C. Assis
Published: May 2012

We performed a macroscopic and microscopic study of the tongues of common opossums, Didelphis marsupialis, from South America. We studied two males and two females. We collected morphometric data on the tongue with precision calipers. For the light microscopy and scanning electron microscopy analyses, we fixed tissue fragments in 10% formaldehyde and 2.5% glutaraldehyde, respectively. The opossum tongues averaged 5.87 ± 0.20 cm in length, 3.27 ± 0.15 cm in width at the lingual body, and 3.82 ± 0.15 cm in width at the root. The mean thickness of the lingual body was 1.8 ± 0.1 cm, and the thickness of the root was 3.82 ± 0.15 cm. Sharp filiform papillae were scattered across the entire tongue; conical filiform papillae occurred on the lingual body and tongue tip; fungiform papillae were scattered among the filiform papillae on the lingual body and tongue tip; and there were three vallate papillae at the root of the tongue. We found two strands of papillary projections in the tongue root. Despite the low variability observed in the lingual papillae, the morphological data obtained in this study may be related to the opossum's diverse food habits and the extensive geographic distribution of the species throughout America. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
Extract of white button mushroom affects skin healing and angiogenesis
Authors: Lam W.P. , Wang C.M. , Tsui T.Y. , Wai M.S , Tang H.C. , Wong Y.W. , Lam L.H. , Hui L.K. , Yew D.T.
Published: May 2012

White button mushroom extract was examined in this study on (1) its potential effect on angiogenesis in chorioallantoic culture and (2) its recovering effect on the skin after injury in the ICR mice. Methods used included TUNEL assay on apoptosis, immunohistochemistry for vascular endothelial growth factor (VEGF), proliferative cell nuclear antigen (PCNA), epidermal growth factor (EGF), transforming growth factor β (TGF‐β), and immune factor CD4 and western blotting. The results of chorioallantoic culture showed that the mushroom treatment led to significant increase in densities of VEGF sites. In the skin injury, ICR mice model increased EGF, PCNA, and collagen fibers, along with decrease of TUNEL positive apoptotic cells and limited reaction of TGF‐β and CD4 indicated that white button mushroom extract appeared to have beneficial effects on skin in regeneration and after injury. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
QUANTITATIVE ASSESSMENT OF DEGRADATION CLASSIFICATIONS for DEGRADED ALPINE MEADOWS (HEITUTAN), SANJIANGYUAN, WESTERN CHINA
Authors: Li X.‐L. , Perry G. L. W. , Brierley G. , Sun H.‐Q. , Li C.‐H. , Lu G.‐X.
Published: May 2012

Improving our understanding of abiotic and biotic thresholds that are transgressed during ecosystem degradation is vital for effective landscape‐level restoration. Establishing logical and consistent typologies of degradation is an important first‐step in this process. Areas of degraded alpine meadow in western China are referred to as Heitutan (or ‘black soil beach’) and cover vast areas. Previously, four classes of grassland degradation have been differentiated in this large area: non‐degraded alpine meadow and moderate, severe and extreme Heitutan. We evaluated existing field‐based classifications of Heitutan in the Sanjiangyuan region, and examined the criteria on which these classifications are made, by using multivariate statistical approaches. First, we asked whether existing qualitative classifications, based on vegetation cover and the abundance of impalatable plant species, adequately describe the nature of degradation at different locations. We then used a suite of vegetation and soil measures collected across 175 sites spanning a range of degradation conditions to develop a new quantitative assessment of degradation across the alpine meadows of the Qinghai‐Tibetan Plateau. Hierarchical classification highlights two broad classes of degradation: non‐degraded alpine meadow and degraded Heitutan. The non‐degraded category effectively combines the non‐degraded grassland and moderate classes, whereas the degraded Heitutan combines the severe and extreme Heitutan classes. Ordination analyses suggest that the four previously recognized classes of degradation intergrade. Of the 14 biophysical variables used to classify subsites on the basis of their degradation, bare ground area and vegetation cover are the two most useful predictors of grassland condition and associated ecological threshold conditions. Copyright © 2012 John Wiley & Sons, Ltd.
ASSESSING THE IMPACT OF THE SLOPING LAND CONVERSION PROGRAMME ON RURAL SUSTAINABILITY IN GUYUAN, WESTERN CHINA
Authors: König H. J. , Zhen L. , Helming K. , Uthes S. , Yang L. , Cao X. , Wiggering H.
Published: May 2012

The goal of China's sloping land conversion programme (SLCP) is to combat soil erosion and to reduce rural poverty. An ex‐ante assessment of possible SLCP impacts was conducted with a focus on rural sustainability, taking the drought‐prone region of Guyuan in Western China as an example. The Framework for Participatory Impact Assessment (FoPIA) was used to conduct two complementary impact assessments, one assessing SLCP impacts at regional level and a second one assessing alternative forest management options, to explore possible trade‐offs among the economic, social and environmental dimensions of sustainability. Regional stakeholders assessed the SLCP to be capable of reducing soil erosion but felt it negatively affected rural employment, and a further continuation of the Programme was advocated. Assessment of three forest management scenarios by scientists showed that an orientation towards energy forests is potentially beneficial to all three sustainability dimensions. Ecological forests had disproportionate positive impacts on environmental functions and adverse impact on the other two sustainability dimensions. Economic forests were assessed to serve primarily the economic and social sustainability dimensions, while environmental impacts were still tolerable. The FoPIA results were evaluated against the available literature on the SLCP. Overall, the assessment results appeared to be reasonable, but the results of the regional stakeholders appeared to be too optimistic compared with the more critical assessment of the scientists. The SLCP seems to have the potential to tackle soil erosion but requires integrated forest management to minimize the risk of water stress while contributing to economic and social benefits in Guyuan. Copyright © 2012 John Wiley & Sons, Ltd.
A FUZZY RULE BASE APPROACH FOR DEVELOPING A SOIL PROTECTION INDEX MAP: A CASE STUDY in the UPPER AWASH BASIN, ETHIOPIAN HIGHLANDS
Authors: Oinam B. C. , Marx W. , Scholten T. , Wieprecht S.
Published: May 2012

Land use practices and vegetation cover distribution are considered to be the most important dynamic factors that influence the land degradation or the soil erosion of a region. In this study, a Soil Protection Index (SPI) is defined as a function of land use practices and intensity of vegetation cover. This index is used to map the relative degree of protection of topsoil from being eroded by external effects such as rainfall and overland flow. A fuzzy rule‐based model integrated within ArcGIS® has been set‐up and tested with the aim to develop SPI maps. The amount of vegetation cover distribution, that is, Normalized Difference Vegetation Index as proxy parameter and Land Use–Land Cover map are chosen as fuzzy input parameters for the SPI as the desired system output. The approach was tested in the Upper Awash basin in Ethiopia. The output SPI map was qualitatively evaluated against the expert‐defined land degradation risk class, and it was found that locations that are mapped with ‘low and very low’ SPI classes at different time periods of the year have a high potential land degradation risk. Furthermore, socio‐economic data (‘population and livestock densities’) and environmental parameters (‘altitude and soil erodibility’) for the region are used to correlate with the SPI map as an indirect method of evaluation. It is found that population and livestock density explained 68 per cent of the spatial distribution pattern of predicted SPI and an adjusted R‐squared value of 0·681 (p < 0·05) was obtained. It was also found that the SPI distribution over the region for two different time periods, that is, January and July 2001, correlated positively (R2 = 0·41 and R2 = 0·51) with the soil erodibility of the region. The transferability and applicability of the model for different environmental settings or landscapes were tested by mapping the SPI of Italy. This SPI map of Italy was compared with the soil erosion map of Italy produced by the European Soil Bureau. It can be concluded that the SPI map reflects the potential land degradation risk distribution of the case‐study region. Results show that a fuzzy rule‐based model can provide useful preliminary information even without detailed and precise data information for developing appropriate strategies for land degradation assessment vital for sustainable land use management. Copyright © 2012 John Wiley & Sons, Ltd.