bluuebunny/crossref_metadata_2025 huggingface dataset:
Separation of recombinant antibodies from DNA using divalent cations
Authors: Satzer Peter , Tscheließnigg Anne , Sommer Ralf , Jungbauer Alois
Published: August 2014

New downstream methods for the purification of antibodies are required to meet the demands of current and future antibody applications, e.g. for mass production as cancer therapeutic. The standard chromatographic methods suffer from high material costs and mass transfer limitations. In this study, we established and characterized a method for DNA precipitation for antibody purification using divalent cations, particularly CaCl2, using four different antibodies. By implementing high‐throughput screening using a factorial design plan, we determined that CaCl2 concentration and PO43− concentration were significant factors, while temperature and pH were not significant. We detected DNA precipitation as well as host‐cell protein (HCP) reduction. Two‐dimensional difference gel electrophoresis (2D‐DIGE) revealed that improved HCP removal does not occur via an unspecific random mechanism such as the enclosure of proteins in the precipitate. CaCl2 precipitation of DNA and HCP can be combined with nonchromatographic methods such as precipitation and protein A affinity chromatography. This additional purification method not only enhances DNA removal, but also the removal of HCP and antibody multimers, which will reduce immunogenicity and increase homogeneity of the resulting drug.
Sediment connectivity: a framework for understanding sediment transfer at multiple scales
Authors: Bracken Louise J. , Turnbull Laura , Wainwright John , Bogaart Patrick
Published: August 2014

A major challenge for geomorphologists is to scale up small‐magnitude processes to produce landscape form, yet existing approaches have been found to be severely limited. New ways to scale erosion and transfer of sediment are thus needed. This paper evaluates the concept of sediment connectivity as a framework for understanding processes involved in sediment transfer across multiple scales. We propose that the concept of sediment connectivity can be used to explain the connected transfer of sediment from a source to a sink in a catchment, and movement of sediment between different zones within a catchment: over hillslopes, between hillslopes and channels, and within channels. Using fluvial systems as an example we explore four scenarios of sediment connectivity which represent end‐members of behaviour from fully linked to fully unlinked hydrological and sediment connectivity. Sediment‐travel distance – when combined with an entrainment parameter reflecting the frequency–magnitude response of the system – maps onto these end‐members, providing a coherent conceptual model for the upscaling of erosion predictions. This conceptual model could be readily expanded to other process domains to provide a more comprehensive underpinning of landscape‐evolution models. Thus, further research on the controls and dynamics of travel distances under different modes of transport is fundamental. Copyright © 2014 John Wiley & Sons, Ltd.
The effects of hydroxylated multiwalled carbon nanotubes on the toxicity of nickel to Daphnia magna under different pH levels
Authors: Wang Chao , Wei Zhongbo , Feng Mingbao , Wang Liansheng , Wang Zunyao
Published: August 2014

Hydroxylated multiwalled carbon nanotubes (OH-MWCNTs), with large amounts of hydrophilic groups attached on the nanoparticle surface, have caused considerable concern because of their inevitable release into aquatic environments. They may interact with other contaminants such as heavy metals and even influence their toxicity, fate, and transport. In the present study, the stability of OH-MWCNTs suspended in aerated Nanjing tap water (moderately hard) was evaluated using the spectrophotometric method. The toxicity of OH-MWCNTs to Daphnia magna was determined, and nontoxic concentrations were used in acute toxicity, accumulation, and sorption tests. It was found that OH-MWCNTs increased the Ni toxicity in a concentration-dependent manner under different pH levels. Nickel adsorption onto the OH-MWCNTs and the uptake of OH-MWCNTs increased the exposure of D. magna to Ni, which was verified by sorption and accumulation tests conducted under different pH levels. The lower pH level contributed to a higher overall toxicity, which could be interpreted by the increasing amount of Ni adsorption onto OH-MWCNTs with the decreasing pH levels. Environ Toxicol Chem 2014;33:2522–2528. © 2014 SETAC
Size-dependent impacts of silver nanoparticles on the lifespan, fertility, growth, and locomotion of Caenorhabditis elegans
Authors: Contreras Elizabeth Q. , Puppala Hema L. , Escalera Gabriela , Zhong Weiwei , Colvin Vicki L.
Published: August 2014

The increased bioavailability of nanoparticles engineered for good dispersion in water may have biological and environmental impacts. To examine this issue, the authors assessed the biological effects in nematodes as they relate to exposure to silver nanoparticles (AgNPs) of different sizes at low (1 mg/L Ag), medium (10 mg/L Ag), and high concentrations (100 mg/L Ag). Over multiple generations, the authors found that the smallest particle, at 2 nm, had a notable impact on nematode fertility. In contrast, the largest particle, at 10 nm, significantly reduced the lifespan of parent nematodes (P0) by 28.8% and over the span of 3 generations (F1–F3). In addition, a computer vision system automatically measured the adverse effects in body length and motility, which were not size-dependent. Environ Toxicol Chem 2014;33:2716–2723. © 2014 SETAC
Accumulation of mercury and cadmium in rice from paddy soil near a mercury mine
Authors: Li W.C. , Ouyang Y. , Ye Z.H.
Published: August 2014

Paddy soil and rice (Oryza sativa L.) in the Wanshan mining area in Guizhou Province, China, have been contaminated by toxic trace metals such as cadmium (Cd) and mercury (Hg). The present study examined correlations between the types and physicochemical parameters of the soil and the contents of trace metals and the different forms of Hg in rice. The health risks of consuming contaminated rice from the Wanshan mining area were also assessed. Sequential extraction procedures were used to investigate the chemical behavior of Hg in the soil. The results showed that Hg and Cd were the most abundant trace metals in the Wanshan mining area. The toxic methylmercury (MeHg) content was substantial in brown rice, and the total amounts of total Hg (THg), diethylenetriaminepentaacetic acid–Hg, and water-soluble Hg varied in the rhizosphere and non-rhizosphere soils. An antagonistic interaction between Mn in brown rice, straw, and husk and MeHg in brown rice was also shown. An analysis of calculated dietary intake, target hazard quotients, and hazard indexes showed a potential risk of transferring Hg, MeHg, and Cd to humans when rice from the Wanshan mining area is consumed. Therefore, it must be concluded that consuming contaminated rice near the Wanshan mining area is a potential threat to human health. Environ Toxicol Chem 2014;33:2438–2447. © 2014 SETAC
Toward a reduction of mesh imprinting
Authors: Lung T. B. , Roe P. L.
Published: August 2014

This paper is the initial investigation into a new Lagrangian cell‐centered hydrodynamic scheme that is motivated by the desire for an algorithm that resists mesh imprinting and has reduced complexity. Key attributes of the new approach include multidimensional construction, the use of flux‐corrected transport (FCT) to achieve second order accuracy, automatic determination of the mesh motion through vertex fluxes, and vorticity control. Toward this end, vorticity preserving Lax–Wendroff (VPLW) type schemes for the two‐dimensional acoustic equations were analyzed and then implemented in a FCT algorithm. Here, mesh imprinting takes the form of anisotropic dispersion relationships. If the stencil for the LW methods is limited to nine points, four free parameters exist. Two parameters were fixed by insisting that no spurious vorticity be created. Dispersion analysis was used to understand how the remaining two parameters could be chosen to increase isotropy. This led to new VPLW schemes that suffer less mesh imprinting than the rotated Richtmyer method. A multidimensional, vorticity preserving FCT implementation was then sought using the most promising VPLW scheme to address the problem of spurious extrema. A well‐behaved first order scheme and a new flux limiter were devised in the process. The flux limiter is unique in that it acts on temporal changes and does not place a priori bounds on the solution. Numerical results have demonstrated that the vorticity preserving FCT scheme has comparable performance to an unsplit MUSCL‐H algorithm at high Courant numbers but with reduced mesh imprinting and superior symmetry preservation. Copyright © 2014 John Wiley & Sons, Ltd.
The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: Final results of the START trial
Authors: Chao Yee , Chung Young‐Hwa , Han Guohong , Yoon Jung‐Hwan , Yang Jijin , Wang Jianhua , Shao Guo‐Liang , Kim Byung Ik , Lee Teng‐Yu
Published: August 2014

This phase II, investigator‐initiated, prospective single‐arm multinational study (ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin‐based transarterial chemoembolization (TACE) in patients with intermediate‐stage, unresectable hepatocellular carcinoma (HCC). Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4–7 days after TACE). TACE/sorafenib cycles were repeated every 6–8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib, and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child‐Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade ≥3 AEs were palmar‐plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median progression‐free survival and time to progression were 384 and 415 days, respectively, and the estimated 3‐year overall survival was 86.1%. This study suggests that the combination of TACE and sorafenib is well tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.
Immunomodulation of cystic fibrosis epithelial cells via NF‐κB decoy oligonucleotide‐coated polysaccharide nanoparticles
Authors: Wardwell Patricia R. , Bader Rebecca A.
Published: August 2014

Activation of the transcription factor nuclear factor‐kappa B (NF‐κB) signaling pathway is associated with enhanced secretion of pro‐inflammatory mediators and is thought to play a critical role in diseases hallmarked by inflammation, including cystic fibrosis (CF). Small nucleic acids that interfere with gene expression have been proposed as promising therapeutics for a number of diseases. However, applications have been limited by low cellular penetration and a lack of stability. Nano‐sized carrier systems have been suggested as a means of improving the effectiveness of nucleic acid‐based treatments. In this study, we successfully coated polysialic acid‐N‐trimethyl chitosan (PSA–TMC) nanoparticles with NF‐κΒ decoy oligonucleotides (ODNs). To demonstrate anti‐inflammatory activity, the decoy ODN‐coated PSA–TMC nanoparticles were administered to an in vitro model of CF generated via interleukin‐1β or P. aeruginosa lipopolysaccharides stimulation of IB3‐1 bronchial epithelial cells. While free ODN and PSA–TMC nanoparticles coated with scrambled ODNs did not have substantial impacts on the inflammatory response, the decoy ODN‐coated PSA–TMC nanoparticles were able to reduce the secretion of interleukin‐6 and interleukin‐8, pro‐inflammatory mediators of CF, by the epithelial cells, particularly at longer time points. In general, the results suggest that NF‐κB decoy ODN‐coated TMC‐PSA nanoparticles may serve as an effective method of altering the pro‐inflammatory environment associated with CF. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1622–1631, 2015.
An investigation of scavenger receptor A mediated leukocyte binding to polyanionic and uncharged polymer hydrogels
Authors: Love Ryan J. , Patenaude Mathew , Dorrington Michael , Bowdish Dawn M. E. , Hoare Todd , Jones Kim S.
Published: August 2014

Cell adhesion to biomaterials can be mediated in part by mechanisms aside from the traditionally recognized opsinization and integrin binding mechanisms. In this study, we investigated the role of scavenger receptor A (SR‐A) in leukocyte binding to a series of well‐controlled polyanionic and uncharged hydrogels based on a poly(N‐isopropylacrylamide) backbone. The hydrogels were injected in the peritoneal cavity of SR‐A knockout (KO) and wild‐type mice using a minimally invasive procedure and allowed to set in situ. After 24 h, the hydrogels were recovered and analyzed, the peritoneal cavity was lavaged, and cytokine concentrations were assessed by ELISA. The polyanionic hydrogels retrieved from the KO animals were found to be completely devoid of adherent leukocytes, which were present in other materials regardless of the mouse strain in which they were injected. Results from a subsequent in vitro cellular adhesion study with a RAW264.7 cell line failed to yield a similarly definitive role for SR‐A in the cellular binding of a polyanionic hydrogel. Taken together, the results of this study show that SR‐A mediates leukocyte adhesion to a polyanionic hydrogel in the peritoneal cavity, but other adhesion mechanisms contribute to cellular binding in vitro. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1605–1612, 2015.
Strontium exerts dual effects on calcium phosphate cement: Accelerating the degradation and enhancing the osteoconductivity both in vitro and in vivo
Authors: Kuang Guan‐Ming , Yau W. P. , Wu Jun , Yeung Kelvin W. K. , Pan Haobo , Lam W. M. , Lu W. W. , Chiu K. Y.
Published: August 2014

Calcium phosphate cements (CPCs) have long been used as osteoconductive bone substitutes in the treatment of bone defects. However, the degradation rate of CPC is typically too slow to match the new bone growth rate. It is known that strontium increases the solubility of hydroxyapatite as well as exerts both anabolic and anticatabolic effects on bone. Therefore, we hypothesized that the incorporation of strontium would accelerate the degradation rate and enhance the osteoconductivity of CPC. In this study, Three groups, CPC (0% Sr‐CPC), 5% Sr‐CPC, and 10% Sr‐CPC, were prepared, with the total molar ratio for Sr/(Sr+Ca) in the cement powder phase being 0, 5, and 10%, respectively. In the immersion test, less residual weight was observed in both 5% Sr‐CPC and 10% Sr‐CPC groups than CPC group. In addition, a higher osteoblastic cell proliferation rate and alkaline phosphatase activity were obtained in the strontium groups. In a rat femur bone defect model comparing CPC with 10% Sr‐CPC, at 2 weeks postoperation, early endochondral ossification was found in the 10% Sr‐CPC group, whereas only fibrous tissue was observed in control group; at 4–16 weeks postoperation, progressive osteoconduction toward the cement was observed in both groups. At 32 weeks, a higher peri‐cement bone area and reduced cement area were noted in the 10% Sr‐CPC group. In conclusion, in the 10% Sr‐CPC group, strontium exerts dual effects on CPC: accelerating degradation rate and enhancing osteoconductivity, as shown here both in vitro and in vivo. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1613–1621, 2015.
Polymeric nanoparticles for targeted radiosensitization of prostate cancer cells
Authors: Menon Jyothi U. , Tumati Vasu , Hsieh Jer‐Tsong , Nguyen Kytai T. , Saha Debabrata
Published: August 2014

One of the many issues of using radiosensitizers in a clinical setting is timing daily radiation treatments to coincide with peak drug concentration in target tissue. To overcome this deficit, we have synthesized a novel nanoparticle (NP) system consisting of poly (lactic‐co‐glycolic acid) (PLGA) NPs conjugated with prostate cancer cell penetrating peptide‐R11 and encapsulated with a potent radio‐sensitizer 8‐dibenzothiophen‐4‐yl‐2‐morpholin‐4‐yl‐chromen‐4‐one (NU7441) to allow prostate cancer‐specific targeting and sustained delivery over 3 weeks. Preliminary characterization studies showed that the R11‐conjugated NPs (R11‐NU7441 NPs) had an average size of about 274 ± 80 nm and were stable for up to 5 days in deionized water and serum. The NPs were cytocompatible with immortalized prostate cells (PZ‐HPV‐7). Further, the particles showed a bi‐phasic release of encapsulated NU7441 and were taken up by PC3 prostate cancer cells in a dose‐ and magnetic field‐dependent manner while not being taken up in nonprostate cancer cell lines. In addition, R11‐NU7441 NPs were effective radiation sensitizers of prostate cancer cell lines in vitro. These results thus demonstrate the potential of R11‐conjugated PLGA NPs as novel platforms for targeted radiosensitization of prostate cancer cells. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1632–1639, 2015.
MRT Letter: An extended scanning probe microscopy system for macroscopic topography imaging
Authors: Fu Ji , Li Faxin
Published: August 2014

Enlightened by the principle of scanning probe microscopy or atomic force microscope (AFM), we proposed a novel surface topography imaging system based on the scanning of a piezoelectric unimorph cantilever. The height of sample surface can be obtained by recording the cantilever's strain using an ultra‐sensitive strain gauge and the Z‐axis movement is realized by electric bending of the cantilever. This system can be operated in the way similar to the contact mode in AFM, with the practical height detection resolution better than 100 nm. Imaging of the inner surface of a steel tube and on a transparent wing of a honey bee were conducted and the obtained results showed that this proposed system is a very promising solution for in situ topography mapping. Microsc. Res. Tech. 77:749–753, 2014. © 2014 Wiley Periodicals, Inc.
Structure and anterior regeneration of musculature and nervous system inCirratuluscf.cirratus(Cirratulidae, Annelida)
Authors: Weidhase Michael , Bleidorn Christoph , Helm Conrad
Published: August 2014

Annelids provide suitable models for studying regeneration. By now, comprehensive information is restricted to only a few taxa. For many other annelids, comparative data are scarce or even missing. Here, we describe the regeneration of a member of theCirratulus cirratusspecies complex. Using phalloidin‐labeling and antibody‐stainings combined with subsequent confocal laser scanning microscopy, we provide data about the organization of body wall musculature and nervous system of intact specimens, as well as about anteriorly regenerating specimens. Our analyses show thatC. cf.cirratusexhibits a prominent longitudinal muscle layer forming a dorsal muscle plate, two ventral muscle strands and a ventral‐median muscle fiber. The circular musculature forms closed rings which are interrupted in the area of parapodia. The nervous system ofC. cf.cirratusshows a typical rope‐ladder like arrangement and the circumesophageal connectives exhibit two separate roots leading to the brain. During regeneration, the nervous system redevelops remarkably earlier than the musculature, first constituting a tripartite loop‐like structure which later become the circumesophageal connectives. Regeneration of longitudinal musculature starts with diffuse ingrowth and subsequent structuring into the blastema. In contrast, circular musculature develops independently inside the blastema. Our findings constitute the first analysis of regeneration for a member of the Cirratuliformia on a structural level. Summarizing the regeneration process inC. cf.cirratus, five main phases can be subdivided: 1) wound closure, 2) blastema formation, 3) blastema differentiation, 4) resegmentation, and 5) growth, respectively elongation. Additionally, the described tripartite loop‐like structure of the regenerating nervous system has not been reported for any other annelid taxon. In contrast, the regeneration of circular and longitudinal musculature originating from different groups of cells seems to be a general pattern in annelid regeneration. J. Morphol. 275:1418–1430, 2014. © 2014 Wiley Periodicals, Inc.
Clinical relevance of the plasma load of cytomegalovirus in patients infected with HIV—A survival analysis
Authors: Aramă Victoria , Mihăilescu Raluca , Rădulescu Mihaela , Aramă Sorin Ştefan , Streinu‐Cercel Adrian , Youle Mike ,   CMV‐HIV Study group
Published: August 2014

To investigate whether asymptomatic cytomegalovirus (CMV) viraemia impact the course of human immunodeficiency virus (HIV) infection, this study evaluated the effect of CMV replication on progression of newly‐diagnosed HIV infected individuals towards AIDS events and death. In a 3‐year prospective study on co‐infected patients, clinical, immunological, and virological tests were performed in a national reference hospital quarterly. CMV viraemia was quantified by RoboGene® HCMV DNA Quantification Kit (Analytik Jena, Germany), on ABI Prism® 7000 Sequence Detection System (Applied Biosystems, USA). One hundred and five patients were enrolled with a balanced sex distribution and a median age of 30.7 years. Median CD4+ cell count at enrollment was 164/mm3 and median HIV RNA 4.6 log10copies/ml. Detectable CMV viraemia was found in 25.7% of the patients. Kaplan–Meier analysis showed progression of HIV infection to be significantly increased in those with active CMV replication and/or low CD4+ cell count. Cox regression indicated the risk of developing new AIDS events was 2.6 times greater in patients with detectable CMV viraemia versus those without (CI95% 1–6.6; P = 0.04). Also in multivariate analysis, the overall risk of progression to AIDS events or death was 3‐fold higher in those with detectable CMV viraemia (CI95% 1.3–6.7; P = 0.008) and 2.3‐fold higher if CD4+ cell count was below 100/mm3 (CI95% 1–5.1; P = 0.04). In these young Romanian HIV‐seropositives, active CMV replication increased morbidity, even when treated with combination antiretroviral therapy. Further studies are needed to evaluate if serial quantitative CMV‐DNA levels might correlate with non‐infectious inflammation‐related risks in patients with HIV and active CMV infection. J. Med. Virol. 86:1821–1827, 2014. © 2014 Wiley Periodicals, Inc.
Prevalence and genotypic characterization of human parvovirus B19 in children with hemato‐oncological disorders in North India
Authors: Jain Parul , Jain Amita , Prakash Shantanu , Khan Danish N , Singh Desh D , Kumar Archana , Moulik Nirmalya R , Chandra Tulika
Published: August 2014

Human parvovirus B19 (B19V) has been associated with chronic anemia in immuno‐compromised patients. In the present study, the prevalence and genotype distribution of B19V in children from North India, suffering with hemato‐oncological disorders is reported. Children with aplastic anemia/leukemia/chronic hematological disorders, and healthy blood donors were enrolled in the study. Blood samples from cases and blood donors were analyzed for anti‐B19V IgM and anti‐B19V IgG antibodies by ELISA and for B19V‐DNA by PCR. B19V‐DNA positive samples were studied further for determination of viral load in samples and for B19V‐DNA sequence (VP1/VP2 overlapping region) analysis. Total 238 cases (103 leukemia, 77 aplastic anemia and 58 chronic hematological disorders) and 350 blood donors were enrolled in the study. Anti‐B19V IgM was positive in 16 (6.7%) cases, B19V‐DNA was detected in 13 (5.5%) cases and anti‐B19V IgG was positive in 127 (53.4%) cases. Total 223 (63.5%) blood donors were positive for anti‐B19V IgG, however, anti‐B19V IgM and B19V‐DNA was not detected in any blood donor. The prevalence of anti‐B19V IgG was significantly higher in children > 10 years of age. Viral load of B19V decreased with appearance of specific antibodies. Phylogenetic analysis of the VP1/VP2 overlapping region revealed that genotype 1 predominated in these patients (11/13, 84.6%), followed by genotype 3 (2/13, 15.4%). No genotype 2 was detected. All the genotype 1strains were sub‐typed as 1a, except four strains, which matched neither 1a nor 1b and formed a separate cluster. Both the genotype 3 strains were sub‐typed as 3b. J. Med. Virol. 87:303–309, 2015. © 2014 Wiley Periodicals, Inc.
Prediction of spontaneous HBeAg seroconversion in HBeAg‐positive chronic hepatitis B patients during the immune clearance phase
Authors: Song Guangjun , Rao Huiying , Feng Bo , Wei Lai
Published: August 2014

Spontaneous hepatitis B virus (HBV) e antigen (HBeAg) seroconversion is associated with reduced risk of liver‐related complications, but is poorly understood. In this study, 113 chronic hepatitis B patients in the immune active HBeAg‐positive phase were followed up for 76 weeks. Based on the outcome of liver function, HBeAg, hepatitis B viral e antibody (anti‐HBe) and HBV DNA at week 76, 18 patients were classified as spontaneous HBeAg seroconversion group (group A) and 95 patients were classified as non‐spontaneous HBeAg seroconversion group (group B). In multivariate logistic regression analysis, only week 28 HBV DNA levels were used for the logistic regression equation, and the odds ratio was 0.505 (95% confidence interval (CI): 0.366–0.697). The areas under the receiver operating characteristic curve for HBV DNA and HBeAg levels at week 28 were 0.824 (P < 0.001, 95% CI: 0.720–0.927) and 0.832 (P < 0.001, 95% CI: 0.744–0.921), respectively. Based on the maximization of Youden's index, the optimal cutoff values of HBV DNA and HBeAg levels at week 28 were 3.84 log10 IU/ml and 1.53 log10 PEI‐U/ml, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HBV DNA levels at week 28 were 50.0%, 97.9%, 81.8%, and 91.2%, respectively. The sensitivity, specificity, PPV, and NPV of HBeAg levels at week 28 were 94.4%, 60.0%, 30.9%, and 98.3%, respectively. In conclusion, the dynamic monitoring of HBV DNA and HBeAg levels predicted accurately determines spontaneous HBeAg seroconversion over the duration of 1 year. J. Med. Virol. 86:1838–1844, 2014. © 2014 Wiley Periodicals, Inc.
Immediate early gene activity‐regulated cytoskeletal‐associated protein regulates estradiol‐induced lordosis behavior in female rats
Authors: Christensen Amy , Dewing Phoebe , Micevych Pavel
Published: August 2014

Sensory feedback is an important component of any behavior, with each instance influencing subsequent activity. Female sexual receptivity is mediated both by the steroid hormone milieu and interaction with the male. We tested the influence of repeated mating on the level of sexual receptivity in ovariectomized rats treated with estradiol benzoate (EB) once every fourth day to mimic the normal phasic changes of circulating estradiol. Females were divided into two groups: naïve, which were tested for lordosis behavior once, and experienced rats, which were tested for lordosis after each EB injection. To monitor the effect of mating, the number of neurons expressing the immediate early gene activity‐regulated cytoskeleton‐associated protein (Arc) were counted in the mediobasal hypothalamus. Females were unreceptive following the first EB treatment, but the mating induced Arc expression. In naïve rats, each subsequent EB injection increased the levels of sexual receptivity. This ramping was not observed in experienced rats, which achieved only a moderate level of sexual receptivity. However, experienced females treated with EB and progesterone were maximally receptive and did not have Arc expression. To test whether the expression of Arc attenuated lordosis, Arc antisense oligodeoxynucleotides (asODN) were microinjected into experienced females' arcuate nuclei. Arc expression was attenuated, and the experienced EB‐treated females achieved maximal sexual receptivity. These results demonstrate that Arc expression in the hypothalamus might influence future sexual receptivity and provides evidence of learning in the arcuate nucleus. The loss of Arc results in unrestrained sexual receptivity. © 2014 Wiley Periodicals, Inc.
Toward an Integrative Model of Creativity and Personality: Theoretical Suggestions and Preliminary Empirical Testing
Authors: Fü rst Guillaume , Ghisletta Paolo , Lubart Todd
Published: August 2014

The present work proposes an integrative model of creativity that includes personality traits and cognitive processes. This model hypothesizes that three high‐order personality factors predict two main process factors, which in turn predict intensity and achievement of creative activities. The personality factors are: Plasticity (high openness, extraversion, energy, and inspiration), Divergence (low agreeableness and conscientiousness, high non‐conformity and impulsivity), and Convergence (high ambition, precision, persistence, and critical sense). The process factors are Generation (idea production and originality) and Selection (idea evaluation and formalization). We hypothesized and found that: (a) Plasticity and Divergence predict positively Generation, (b) Convergence predicts positively Selection, (c) Generation, Selection, and their interaction predict positively both intensity and achievement of everyday creative activities.
Exploring the Relationship between Adolescent Activities and Choice of Graduate School Discipline: Implications for Creativity Development
Authors: Hartzell Stephanie A. , Hong Eunsook
Published: August 2014

The relationship between adolescent extra‐curricular activities and choice of graduate‐education field was examined among students from three fields of study, science (n = 12), art (n = 12), and education (n = 14), using qualitative and quantitative methods. Results of profile analysis indicated that the different majors participated in stereotypically varying activities when they were adolescents. Science majors generally participated in mathematics and science activities during adolescence. Art majors generally participated in theater and music activities, and education majors tended to have participated in social leadership and educational activities. Interviews with the participants supported these findings and provided a more comprehensive discussion of these tendencies. While in high school, the participants had many influences when determining a field of study. Using personal happiness as a guide, the participants chose activities and ultimately graduate‐level majors that reflected their interests. It was concluded that adolescent extra‐curricular activities are important in the development of interest in creatively talented individuals and may lead to graduate field selection.
Structure modeling of the glenoid: Relevance to shoulder arthroplasty
Authors: Sharma Gulshan B. , McMahon Patrick J. , Robertson Douglas D.
Published: August 2014

We applied shape modeling and principal component analysis (PCA) to discover glenoid bone structural relationships relevant to improving glenoid prosthesis features, fixation, and instrumentation. Knowledge of external bone morphology guides prosthesis shape and positioning, while internal bone morphology and bone density influence fixation. CT‐based modeling defined nonarthritic glenoid subchondral bone surface and internal structure. First and second principal shape components were related to size and density. Reproducible structural parameters and glenoid feature relationships were discovered. Subchondral bone surface was approximated by a circle inferiorly and a triangle superiorly with the circle's center at a reproducible point along a superior‐inferior line. Glenoid vault's maximum depth was at the circle's center, and the highest bone density was in posterior glenoid. Glenoid subchondral bone surface version varied from superior to inferior, but not by sex or side. Male subchondral bone surfaces were larger and more retroverted. Even if subchondral bone surfaces are deformed by arthritis, glenoid morphology can be identified by extra‐articular landmarks, permitting location of the glenoid center and scapular orientation (glenoid version). Knowledge obtained from this study directs design of novel prosthesis features and instrumentation for use without pre‐op CT or computer aided surgery. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1471–1478, 2014.
Early detection of heterotopic ossification using near‐infrared optical imaging reveals dynamic turnover and progression of mineralization following Achilles tenotomy and burn injury
Authors: Perosky Joseph E. , Peterson Jonathan R. , Eboda Owulatobi N. , Morris Michael D. , Wang Stewart C. , Levi Benjamin , Kozloff Kenneth M.
Published: August 2014

Heterotopic ossification (HO) is the abnormal formation of bone in soft tissue. Current diagnostics have low sensitivity or specificity to incremental progression of mineralization, especially at early time points. Without accurate and reliable early diagnosis and intervention, HO progression often results in incapacitating conditions of limited range of motion, nerve entrapment, and pain. We hypothesized that non‐invasive near‐infrared (NIR) optical imaging can detect HO at early time points and monitor heterotopic bone turnover longitudinally. C57BL6 mice received an Achilles tenotomy on their left hind limb in combination with a dorsal burn or sham procedure. A calcium‐chelating tetracycline derivative (IRDye 680RD BoneTag) was injected bi‐weekly and imaged via NIR to measure accumulative fluorescence for 11 wk and compared to in vivo microCT images. Percent retention of fluorescence was calculated longitudinally to assess temporal bone resorption. NIR detected HO as early as five days and revealed a temporal response in HO formation and turnover. MicroCT could not detect HO until 5 wk. Confocal microscopy confirmed fluorophore localization to areas of HO. These findings demonstrate the ability of a near‐infrared optical imaging strategy to accurately and reliably detect and monitor HO in a murine model. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1416–1423, 2014.
Hip contact force in presence of aberrant bone geometry during normal and pathological gait
Authors: Bosmans Lode , Wesseling Mariska , Desloovere Kaat , Molenaers Guy , Scheys Lennart , Jonkers Ilse
Published: August 2014

Children with cerebral palsy (CP) often present aberrant hip geometry, specifically increased femoral anteversion and neck‐shaft angle. Furthermore, altered gait patterns are present within this population. We analyzed the effect of aberrant femoral geometry, as present in CP subjects, on hip contact force (HCF) during pathological and normal gait. We ran dynamic simulations of CP‐specific and normal gait using two musculoskeletal models (MSMs), one reflecting normal femoral geometry and one reflecting proximal femoral deformities. The combination of aberrant bone geometry and CP‐specific gait characteristics reduced HCF compared to normal gait on a CP subject‐specific MSM, but drastically changed the orientation of the HCF vector. The HCF was orientated more vertically and anteriorly than compared to HCF orientation during normal gait. Furthermore, subjects with more pronounced bony deformities encountered larger differences in resultant HCF and HCF orientation. When bone deformities were not accounted for in MSMs of pathologic gait, the HCF orientation was more similar to normal children. Thus, our results support a relation between aberrant femoral geometry and joint loading during pathological/normal gait and confirm a compensatory effect of altered gait kinematics on joint loading. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1406–1415, 2014.
Glucosamine protects nucleus pulposus cells and induces autophagy via the mTOR‐dependent pathway
Authors: Jiang LiBo , Jin YongLong , Wang HuiRen , Jiang YunQi , Dong Jian
Published: August 2014

Although glucosamine has been suggested to be effective in the treatment of osteoarthritis, its effect on disc degeneration remains unclear. We sought to explore whether glucosamine can activate autophagy in rat nucleus pulposus (NP) cells and protect cells treated with IL‐1β or hydrogen peroxide (H2O2). Autophagy in cells was examined by detecting for LC3, Beclin‐1, m‐TOR, and p70S6K, as well as by analyzing autophagosomes. To inhibit autophagy, 3‐methyladenine (3‐MA) was used. In the cells treated with IL‐1β, the levels of Adamts‐4, Mmp‐13, aggrecan, and Col2a1 were analyzed by real‐time PCR and immunofluorescence. Apoptosis was analyzed by TUNEL. Cell senescence under H2O2 was revealed by SA‐β‐Gal staining. Glucosamine could activate autophagy in a dose‐dependent manner within 24 h and inhibit the phosphorylation of m‐TOR and p70S6K. Autophagy in IL‐1β or H2O2‐treated cells was increased by glucosamine. Glucosamine attenuated the decrease of aggrecan and prevented the apoptosis of the NP cells induced by IL‐1β, whereas 3‐MA partly reversed these effects. The percentage of SA‐β‐Gal‐positive cells induced by H2O2 treatment was decreased by glucosamine, accompanied by the decline of p70S6K phosphorylation. Glucosamine protects NP cells and up‐regulates autophagy by inhibiting the m‐TOR pathway, which might point a potential therapeutic agent for disc degeneration. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1532–1542, 2014.
Viability of chondrocytes seeded onto a collagen I/III membrane for matrix‐induced autologous chondrocyte implantation
Authors: Hindle Paul , Hall Andrew C. , Biant Leela C
Published: August 2014

Cell viability is crucial for effective cell‐based cartilage repair. The aim of this study was to determine the effect of handling the membrane during matrix‐induced autologous chondrocyte implantation surgery on the viability of implanted chondrocytes. Images were acquired under five conditions: (i) Pre‐operative; (ii) Handled during surgery; (iii) Cut edge; (iv) Thumb pressure applied; (v) Heavily grasped with forceps. Live and dead cell stains were used. Images were obtained for cell counting and morphology. Mean cell density was 6.60 × 105 cells/cm2 (5.74–7.11 × 105) in specimens that did not have significant trauma decreasing significantly in specimens that had been grasped with forceps (p < 0.001) or cut (p = 0.004). Cell viability on delivery grade membrane was 75.1%(72.4–77.8%). This dropped to 67.4%(64.1–69.7%) after handling (p = 0.002), 56.3%(51.5–61.6%) after being thumbed (p < 0.001) and 28.8%(24.7–31.2%) after crushing with forceps (p < 0.001). When cut with scissors there was a band of cell death approximately 275 µm in width where cell viability decreased to 13.7%(10.2–18.2%, p < 0.001). Higher magnification revealed cells without the typical rounded appearance of chondrocytes. We found that confocal laser‐scanning microscope (CLSM) can be used to quantify and image the fine morphology of cells on a matrix‐induced autologous chondrocyte implantation (MACI) membrane. Careful handling of the membrane is essential to minimise chondrocyte death during surgery. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1495–1502, 2014.
Molecular markers for breast cancer diagnosis, prognosis and targeted therapy
Authors: Lang Julie E. , Wecsler Julie S. , Press Michael F. , Tripathy Debasish
Published: August 2014

Precision medicine involves understanding the molecular drivers unique to an individual patient's cancer so that specific factors may be targeted with the goal of improved patient outcomes. The purpose of this article is to review standard of care and research grade (non‐standard of care) biomarkers in breast cancer that may be useful for diagnosis, prognosis and targeted therapy. J. Surg. Oncol. 2015 111:81–90. © 2014 Wiley Periodicals, Inc.
Urine sample preparation for proteomic analysis
Authors: Olszowy Pawel , Buszewski Boguslaw
Published: August 2014

Sample preparation for both environmental and more importantly biological matrices is a bottleneck of all kinds of analytical processes. In the case of proteomic analysis this element is even more important due to the amount of cross‐reactions that should be taken into consideration. The incorporation of new post‐translational modifications, protein hydrolysis, or even its degradation is possible as side effects of proteins sample processing. If protocols are evaluated appropriately, then identification of such proteins does not bring difficulties. However, if structural changes are provided without sufficient attention then protein sequence coverage will be reduced or even identification of such proteins could be impossible. This review summarizes obstacles and achievements in protein sample preparation of urine for proteome analysis using different tools for mass spectrometry analysis. The main aim is to present comprehensively the idea of urine application as a valuable matrix. This article is dedicated to sample preparation and application of urine mainly in novel cancer biomarkers discovery.
Brachial artery perforator‐based propeller flap coverage for prevention of readhesion after ulnar nerve neurolysis
Authors: Sekiguchi Hirotake , Motomiya Makoto , Sakurai Keisuke , Matsumoto Dai , Funakoshi Tadanao , Iwasaki Norimasa
Published: August 2014

It is difficult for most plastic and orthopaedic surgeons to treat nerve dysfunction related to neural adhesion because the pathophysiology and suitable treatment have not been clarified. In the current report, we describe our experience of surgical treatment for adhesive ulnar neuropathy. A 58‐year‐old male complained of pain radiating to the ulnar nerve‐innervated area during elbow and wrist motion caused by adhesive ulnar neuropathy after complex open trauma of the elbow joint. The patient obtained a good clinical outcome by surgical neurolysis of the ulnar nerve combined with a brachial artery perforator‐based propeller flap to cover the soft tissue defect after resection of the scar tissue and to prevent readhesion of the ulnar nerve. This flap may be a useful option for ulnar nerve coverage after neurolysis without microvascular anastomosis in specific cases. © 2014 Wiley Periodicals, Inc. Microsurgery 35:158–162, 2015.
Reconstruction of a complex pelvic perineal defect with pedicled anterolateral thigh flap combined with bilateral lotus petal flap: A case report
Authors: Contedini Federico , Negosanti Luca , Pinto Valentina , Oranges Carlo Maria , Sgarzani Rossella , Lecce Ferdinando , Cola Bruno , Cipriani Riccardo
Published: August 2014

Reconstructing extensive perineal defects represents a challenge, and reconstructive choice requires a careful physical assessment of previous radiotherapy, pre‐existing scars, the presence of stomas, and the availability of donor sites. We report a case of a patient affected by an anal carcinoma who underwent a pelvic exenteration and bilateral inguinal iliac obturator lymph node dissection. We performed a pedicled anterolateral thigh flap (ALT) combined with bilateral lotus petal flaps (LPF) to reconstruct the pelvic–perineal area. The result was good, and no major post‐operative complications were reported. Bilateral LPF, combined with a pedicled ALT, may represent a valid option in pelvic–perineal reconstruction following a wide oncological resection. © 2014 Wiley Periodicals, Inc. Microsurgery 35:154–157, 2015.
Solving a partial differential equation associated with the pricing of power options with time‐dependent parameters
Authors: Okelola M. O. , Govinder K. S. , O'Hara J. G.
Published: August 2014

Previous analysis and research on the power option – one of the exotic options – have focused on the interest rate of the stock and its volatility as constant parameters throughout the run of execution. In this paper, we attempt to extend these results to the more practical and realistic case of when these parameters are time dependent. By making no ansatz or relying on ad hoc methods, we are able to achieve this via an algorithmic method – the Lie group approach – leading to exact solutions for the power option problem. Copyright © 2014 John Wiley & Sons, Ltd.
FOREIGN AID AND DECENTRALIZATION: LIMITATIONS ON IMPACT IN AUTONOMY AND RESPONSIVENESS
Authors: Dickovick J. Tyler
Published: August 2014

Donor support for decentralization comes in two main categories: policy support to increase the autonomy of subnational governments (SNGs) and project/program activities to improve the responsiveness and accountability of those SNGs. In the former, donors advocate for reforms that increase the extent or ‘quantity’ of decentralization, whereas in the latter, they aim at the ‘quality’ of decentralized governance. Drawing upon this distinction, this paper's argument is twofold. The principal argument is that donors have had modest causal impacts on the quantity of decentralization because the preexisting political incentives of central governments are sufficient to explain decisions for major reforms. Decentralization advances farthest when there are regime‐level incentives to decentralize, a moderate amount when there are government‐level incentives, and minimally when donors (or other actors outside the central state) are leading champions of decentralization. The second argument of the paper is that donor efficacy is further complicated by partially conflicting emphases that sometimes tradeoff local autonomy with accountability. Implications include support for those programming efforts that pair autonomy with responsiveness at the local level. © 2014 The Authors.Public Administration and Developmentpublished by John Wiley & Sons, Ltd.
Insights into corrosion in dye solar cells
Authors: Miettunen Kati , Etula Jarkko , Saukkonen Tapio , Jouttijärvi Sami , Halme Janne , Romu Jyrki , Lund Peter
Published: August 2014

The main issue in using low cost metals in dye solar cells is the corrosion caused by the liquid electrolyte. Contrary to typical applications of metals, the adverse effects of corrosion in dye solar cells are related to irreversible depletion of charge carriers from the electrolyte rather than consumption of the metal itself. It is calculated that the penetration rate due to corrosion should not exceed 10−4 mpy (a couple of nanometers per year) to ensure device lifetime longer than 1 year. This is 10 000 times slower rate than what is considered to be a general benchmark value for very low corrosion rate in the field of corrosion science and has a major effect on how corrosion should be investigated in the case of dye solar cells. Different methods, their applicability, and limitations to investigate corrosion in dye solar cells are evaluated here. The issue with most techniques is that they can detect metals that are clearly corroding, but they have significant limitations in proving a metal stable. Our investigation shows that the most reliable information on corrosion is obtained from complete dye solar cells that are exposed to working conditions. A combination of color analysis of the electrolyte to such measurement is proposed as a means to extrapolate future performance of the cells and estimate potential lifetimes of the dye solar cells in regards to corrosion. Copyright © 2014 John Wiley & Sons, Ltd.