bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient Intracellular siRNA Delivery by Ethyleneimine‐Modified Amphiphilic Macromolecules
Authors: Sparks Sarah M. , Waite Carolyn L. , Harmon Alexander M. , Nusblat Leora M. , Roth Charles M. , Uhrich Kathryn E. 
Published: July 2011

AbstractNew materials that can bind and deliver oligonucleotides such as short interfering RNA (siRNA) without toxicity are greatly needed to fulfill the promise of therapeutic gene silencing. Amphiphilic macromolecules (AMs) were functionalized with linear ethyleneimines to create cationic AMs capable of complexing with siRNA. Structurally, the parent AM is formed from a mucic acid backbone whose tetra‐hydroxy groups are alkylated with 12‐carbon aliphatic chains to form the hydrophobic component of the macromolecule. This alkylated mucic acid is then mono‐functionalized with poly(ethylene glycol) (PEG) as a hydrophilic component. The resulting AM contains a free carboxylic acid within the hydrophobic domain. In this work, linear ethyleneimines were conjugated to the free carboxylic acid to produce an AM with one primary amine (1N) or one primary amine and four secondary amines (5N). Further, an AM with amine substitution both to the free carboxylic acid in the hydrophobic domain and also to the adjacent PEG was synthesized to produce a polymer with one primary amine and eight secondary amines (9N), four located on each side of the AM hydrophobic domain. All amine‐functionalized AMs formed nanoscale micelles but only the 5N and 9N AMs had cationic zeta potentials, which increased with increasing number of amines. All AMs exhibited less inherent cytotoxicity than linear polyethyleneimine (L‐PEI) at concentrations of 10 µM and above. By increasing the length of the cationic ethyleneimine chain and the total number of amines, successful siRNA complexation and cellular siRNA delivery was achieved in a malignant glioma cell line. In addition, siRNA‐induced silencing of firefly luciferase was observed using complexes of siRNA with the 9N AM and comparable to L‐PEI, yet showed better cell viability at higher concentrations (above 10 µM). This work highlights the promise of cationic AMs as safe and efficient synthetic vectors for siRNA delivery. Specifically, a novel polymer (9N) was identified for efficient siRNA delivery to cancer cells and will be further evaluated.magnified image
Biodegradable Bicomponent Fibers from Renewable Sources: Melt‐Spinning of Poly(lactic acid) and Poly[(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)]
Authors: Hufenus Rudolf , Reifler Felix A. , Maniura‐Weber Katharina , Spierings Adriaan , Zinn Manfred 
Published: July 2011

AbstractPHBV is produced by bacteria as intracellular carbon storage. It is advantageous concerning biocompatibility and biodegradability, but its low crystallization rate hinders the melt‐processing of fibers. This problem can be overcome by combining PHBV with PLA in a core/sheath configuration and introducing a new spin pack concept. The resulting PHBV/PLA bicomponent fibers show an ultimate tensile stress of up to 0.34 GPa and an E‐modulus of up to 7.1 GPa. XRD reveals that PLA alone is responsible for tensile strength. In vitro biocompatibility studies with human fibroblasts reveal good cytocompatibility, making these fibers promising candidates for medical therapeutic approaches.magnified image
A Phase Field Crystal Approach for Particles in a Flowing Solvent
Authors: Praetorius Simon , Voigt Axel 
Published: July 2011

AbstractA number of dynamic density functional theories (dDFTs) have been developed to describe the dynamics of the one‐particle density of atomic fluids. We review an approach that accounts for particle advection by a flowing solvent, and make further approximations using a locally advected phase‐field‐crystal model which in turn is coupled with a Navier–Stokes equation. In particular we apply the approach to Brownian particles (e.g., coarse grained polymer coils) in a solvent flowing around various obstacles (e.g., colloidal particles). We compare the bow wave in the density distribution of particles in front of the obstacles as well as the wake behind it. The results qualitatively agree with full dDFT results and simulations based on the underlying Brownian dynamics. The much lower computational cost of the phase field crystal approach provides an efficient way to couple fluid flow around macroscopic fixed or moving particle with interactions of particles in the solvent.magnified image
Immune tolerance induction therapy for patients with hemophilia A and FVIII inhibitors particularly using low‐dose regimens
Authors: Lin Pei‐Chin , Liao Yu‐Mei , Tsai Shih‐Pien , Chang Tai‐Tsung 
Published: July 2011

AbstractBackgroundInhibitory antibodies against infused clotting factor VIII concentrates (FVIII) developed in 20–30% of patients with hemophilia A. Bypass therapy may control the bleeds in patients with FVIII inhibitors, however, immune tolerance induction (ITI) therapy is the only proven modality for eradicating FVIII inhibitors. Since the cost of high‐dose (200 IU/kg) ITI is extremely expansive, we conducted this study to identify whether low‐dose ITI can be an alternative strategy besides high‐dose ITI or bypass therapy.ProcedurePatients with hemophilia A and FVIII inhibitors treated by ITI in Kaohsiung Medical University Hospital from January 2000 to January 2010 were enrolled. Regimens of ITI therapy included high‐dose (100 IU/kg) and low‐dose (30–50 IU/kg).ResultsHigh‐dose ITI therapy for two high responders (HRs) and low‐dose ITI therapy for three HRs and all low responders (LRs) were performed. Complete tolerance was achieved in 2 HRs with high‐dose regimen, and in one HR and 19 LRs with low‐dose regimens. We administered low‐dose ITI combined with immune suppressants treatment for one of the patient with extremely high FVIII inhibitor titers and the inhibitor level markedly declined and no spontaneous bleeding episode was noticed during the treatment period.ConclusionsThe outcome of ITI in our study was satisfactory without clinically significant complications. Low‐dose ITI regimens can effectively treat patients with high responder inhibitors, including one patient with extremely high inhibitor levels over 700 BU. Low‐dose ITI may be an alternative modality for FVIII inhibitors management, especially in countries with limited resources. Pediatr Blood Cancer 2011; 57: 1029–1033. © 2011 Wiley‐Liss, Inc.
Extensional rheology of raw natural rubber from new clones of Hevea brasiliensis
Authors: Lotti Cybele , Moreno Rogério M.B. , Gonçalves Paulo de S. , Bhattacharya Satinath , Mattoso Luiz H.C. 
Published: July 2011

AbstractNatural rubber (NR) is a biopolymer whose properties depend on the molecular structure of the 1,4‐cis polyisoprene chains, nonrubber constituents, environmental conditions, etc. NR has been characterized by Mooney viscosity, Wallace plasticity, nitrogen content (%N). However, these cannot effectively account for clone's differences. The aim of this work is to use extensional rheology to characterize and differentiate NR samples as for clone type and the season of the year in comparison to the traditional characterizations. Three IAC 300 series and RRIM 600 clones of Hevea brasiliensis tapped between October 2006 (Oct_06) and August 2008 (Aug_08) were investigated. IAC 329 clones showed the least susceptibility to seasonal changes, whereas RRIM 600 was the most influenced. An opposite trend between extensional viscosity (ηE) and %N was established. The former was very sensitive to changes in the molecular structure of NR, being fundamental for monitoring purposes and strategic development of new rubber tree clones. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers
Fibril elongation mechanisms of HET‐s prion‐forming domain: Topological evidence for growth polarity
Authors: Baiesi Marco , Seno Flavio , Trovato Antonio 
Published: July 2011

AbstractThe prion‐forming C‐terminal domain of the fungal prion HET‐s forms infectious amyloid fibrils at physiological pH. The conformational switch from the nonprion soluble form to the prion fibrillar form is believed to have a functional role, as HET‐s in its prion form participates in a recognition process of different fungal strains. On the basis of the knowledge of the high‐resolution structure of the prion forming domain HET‐s(218‐289) in its fibrillar form, we here present a numerical simulation of the fibril growth process, which emphasizes the role of the topological properties of the fibrillar structure. An accurate thermodynamic analysis of the way an intervening HET‐s chain is recruited to the tip of the growing fibril suggests that elongation proceeds through a dock and lock mechanism. First, the chain docks onto the fibril by forming the longest β‐strands. Then, the re‐arrangement in the fibrillar form of all the rest of the molecule takes place. Interestingly, we also predict that one side of the HET‐s fibril is more suitable for sustaining its growth with respect to the other. The resulting strong polarity of fibril growth is a consequence of the complex topology of HET‐s fibrillar structure, as the central loop of the intervening chain plays a crucially different role in favoring or not the attachment of the C‐terminus tail to the fibril, depending on the growth side. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Evaluating change during pharmaceutical product development and manufacture—comparability and equivalence
Authors: Chatfield Marion J. , Borman Phil J. , Damjanov Ivana 
Published: July 2011

AbstractIn the pharmaceutical industry it is necessary to manage changes to processes or analytical methods to ensure that the quality of drug products is maintained. This often includes an assessment of similarity using data. Scientists may be asked to show that output before and after a change is or will be ‘equivalent’, without clarity on what exactly is required. In the area of analytical methods, the authors have found it useful to promote the differentiation between equivalence and a wider set of comparability approaches. This paper discusses equivalence and comparability, when such approaches should be applied and provides examples of applications to analytical methods. The discussion is then widened to other application areas such as processes including the appropriateness of the approaches and aspects to be considered when designing equivalence studies. Change management, the design of studies and appropriate statistical analysis can be challenging. However, use of the terminology and methodology exemplified here has enabled scientific project teams to focus on appropriate goals and the means to achieve them with great benefits. Copyright © 2011 John Wiley & Sons, Ltd.
Systematic assessment on aqueous pKa and pKb of an amino acid base on RISM‐SCF‐SEDD method: Toward first principles calculations
Authors: Kido Kentaro , Sato Hirofumi , Sakaki Shigeyoshi 
Published: July 2011

AbstractToward accurate computations of pKa and pKb from the first principles, a systematic assessment based on accurate evaluation of free energy is presented. Because the process is essentially bond formation and dissociation in aqueous solution, both of highly sophisticated quantum chemistry and an accurate evaluation of solvation‐free energy are necessary to appropriately compute pKa and pKb. In this study, the proton dissociation of carboxyl and amino groups in glycine molecule in aqueous solution was examined. A hybrid approach called reference interaction site model self consistent field with spatial electron density distribution (RISM‐SCF‐SEDD) was used, in which HF, DFT, and CCSD(T) were combined with statistical mechanical theory for molecular liquid. We found that a spatial extension of electronic distribution of the carboxyl group was essential to correctly evaluate pKa and pKb. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012
Piezoelectric actuator design for MR elastography: implementation and vibration issues
Authors: Tse Zion Tsz Ho , Chan Yum Ji , Janssen Henning , Hamed Abbi , Young Ian , Lamperth Michael 
Published: July 2011

AbstractBackgroundMR elastography (MRE) is an emerging technique for tumor diagnosis. MRE actuation devices require precise mechanical design and radiofrequency engineering to achieve the required mechanical vibration performance and MR compatibility.MethodA method of designing a general‐purpose, compact and inexpensive MRE actuator is presented. It comprises piezoelectric bimorphs arranged in a resonant structure designed to operate at its resonant frequency for maximum vibration amplitude. An analytical model was established to understand the device vibration characteristics.ResultsThe model‐predicted performance was validated in experiments, showing its accuracy in predicting the actuator resonant frequency with an error < 4%. The device MRI compatibility was shown to cause minimal interference to a 1.5 tesla MRI scanner, with maximum signal‐to‐noise ratio reduction of 7.8% and generated artefact of 7.9 mm in MR images.ConclusionsA piezoelectric MRE actuator is proposed, and its implementation, vibration issues and future work are discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Inclusions and metal composition of ancient copper‐based artefacts: a diachronic view by micro‐EDXRF and SEM‐EDS
Authors: Figueiredo Elin , Valério Pedro , Araújo M. Fátima , Silva Rui J. C. , Monge Soares António M. 
Published: July 2011

AbstractA diachronic view of the metallurgy in the Portuguese territory during the first three millennia after its appearance in the Iberian Peninsula is presented based on the current state of the art. Results of micro‐energy dispersive X‐ray fluorescence (micro‐EDXRF) analyses made on metal artefacts to determine their composition and scanning electron microscopy with energy dispersive analysis (SEM‐EDS) analyses to study microstructural features as inclusions are shown to illustrate trends and specificities of each chronological period. Generally, in early periods, namely during the Copper Age and first stages of the Bronze Age, unalloyed copper and arsenical copper were at use, and only by the Late Bronze Age (LBA) did tin bronze substitute almost completely the previous role of copper. In the Early Iron Age, during the Orientalising period, a general decrease in the average tin content in bronzes seems to happen. Regarding the inclusions observed in the metal matrix, these seem to suffer a diversification with the appearance of tin bronzes. By the Copper Age, only CuO and CuAsO inclusions are observed, while by the LBA CuS inclusions become regular, besides others less frequent, as SnO, CuSFe and Pb globules. Overall, with the present analytical study, the complementary character of micro‐EDXRF and SEM‐EDS in the study of ancient metals is demonstrated, providing a first general overview of the ancient metallurgy at the Portuguese territory which is of key importance to specific investigations of the future. Copyright © 2011 John Wiley & Sons, Ltd.
Elemental depth profiling with a wire in microbeam X‐ray fluorescence analysis
Authors: Iida Atsuo 
Published: July 2011

AbstractThis study proposes simple techniques involving the use of a thin wire set close to the sample surface to measure the elemental depth distribution in microbeam X‐ray fluorescence analysis. One is the X‐ray fluorescence detection in energy‐dispersive mode using a solid‐state detector in combination with the sample movement, and the other is in projection mode using an X‐ray charge‐coupled device camera. The minimum depth resolution (spatial resolution) obtained with a thin Mo wire is about 15 µm. Compared with a confocal depth‐profiling method, wire depth‐profile analysis is easy to implement, flexible, and has reasonable sensitivity. Copyright © 2011 John Wiley & Sons, Ltd.
Prevalence of asymptomatic vasogenic edema in pretreatment Alzheimer's disease study cohorts from phase 3 trials of semagacestat and solanezumab
Authors: Carlson Christopher , Estergard Wahiba , Oh Joonmi , Suhy Joyce , Jack Clifford R. , Siemers Eric , Barakos Jerome 
Published: July 2011

BackgroundCerebral vasogenic edema (VE) has been reported to occur during antiamyloid immunotherapy. VE may be associated with central nervous system pathology with blood–brain barrier disruptions; however, less is known about the prevalence of naturally occurring VE in patients with Alzheimer's disease (AD).MethodsFluid‐attenuated inversion recovery imaging sequences were obtained from four ongoing multicenter, randomized, double‐blind, placebo‐controlled, phase 3 trials in patients with mild‐to‐moderate AD. The first set of baseline scans was from patients in volumetric magnetic resonance imaging addenda in the Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of Amyloid PaThologY (IDENTITY) studies examining semagacestat, a γ‐secretase inhibitor (cohort 1, n = 621). The second set of baseline scans was from the EXPanding Alzheimer's Disease InvestigaTIONs (EXPEDITION) studies examining solanezumab, an anti‐Aβ monoclonal antibody (cohort 2, n = 2141). Readers were blinded to patient‐identifying information and future treatment. A third set of baseline scans was from the first 700 patients who underwent protocol‐specified magnetic resonance imaging before randomization in the EXPEDITION studies (cohort 3). The analysis used three neuroradiologists: two performed independent primary interpretations and the third was the adjudicator. Readers were blinded to patient information, treatment, protocol, and time point.ResultsFour cases of asymptomatic VE were detected at baseline/screening. Two VE cases were due to underlying extra‐axial mass lesions. The third VE case was associated with numerous microhemorrhages in keeping with cerebral amyloid angiopathy‐related inflammation or Aβ‐related angiitis. The final VE case demonstrated localized sulcal fluid‐attenuated inversion recovery imaging hyperintensity. No VE was detected in cohort 3 by readers blinded to patient baseline status.ConclusionsVE seems to be rare at baseline in patients with AD in clinical trials, 2 of 2762 associated with AD. Additional cohorts should be evaluated to support these findings.
The anti-metastatic efficacy of β-ionone and the possible mechanisms of action in human hepatocarcinoma SK-Hep-1 cells
Authors: Huang Chin-Shiu , Lyu Shih-Chieh , Chen Jen-Yin , Hu Miao-Lin 
Published: July 2011

β-Ionone (BI), a precursor for carotenoids, is widely distributed in fruit and vegetables. Recent in vitro studies have demonstrated the potential anti-metastatic effects of BI, but the mechanisms underlying such actions are not clear. Because liver cancer is the most endemic cancer in Taiwan and in a large region of the world, we hereby investigate the anti-metastatic effects of BI and its mechanisms of actions in a highly metastatic human hepatocarcinoma SK-Hep-1 cells. We show that incubation of cells with BI (1–50 μm) for 24 and 48 h significantly inhibited cell invasion, migration and adhesion. Mechanistically, incubation of cells with BI (1–50 μm) for 24 h resulted in the following: (1) significant inhibition of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator activities, (2) up-regulation of protein expression of the tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and plasminogen activator inhibitor-1, (3) down-regulation of the expression of migration-related proteins, including focal adhesion kinase (FAK), phosphorylated form of FAK, Rho, Rac1 and Cdc42 and (4) up-regulation of the expression of nm23-H1 protein (P < 0·05). Overall, the results show that BI effectively inhibits the metastasis of SK-Hep-1 cells, and this effect involves the regulation of gene expression and signal pathways related to invasion and migration.
SNP may modify the effect of vitamin A supplementation at birth on cytokine production in a whole blood culture assay
Authors: Jørgensen Mathias Jul , Fisker Ane Bærent , Erikstrup Christian , Claesson Mogens H. , Benn Christine Stabell 
Published: July 2011

Within a neonatal vitamin A supplementation (VAS) trial, we investigated the effect of VAS on TNF-α, IL-10, IL-5 and IL-13 production after lipopolysaccharide, purified protein derivative (PPD) of Mycobacterium tuberculosis and phytohaemagglutinin stimulation using a whole blood culture protocol. We found that VAS recipients had lower unstimulated TNF-α concentrations than placebo recipients. In the present paper, we investigated whether the SNP TNF-α − 308, TNF-α − 238, IL-10 − 592, IL-10 − 1082 and toll-like receptor 4 (TLR4)+896 modified the effect of VAS on cytokine production. DNA and cytokine concentrations were available from 291 children. We found a significant interaction between TNF-α − 308 genotype and VAS for the unstimulated TNF-α production (Pinteraction = 0·04); among G homozygotes, TNF-α concentrations were significantly lower after VAS compared with placebo, whereas for A carriers, VAS did not appear to have any effect. For TNF-α − 238, there was a tendency towards an increase in PPD-stimulated TNF-α production after VAS for the G homozygotes, but the opposite tendency for A allele carriers (Pinteraction = 0·07). Stratification by sex revealed a significant VAS–genotype interaction for boys for TNF-α − 238. There was a borderline-significant three-way interaction (P = 0·05) between sex, VAS and TLR4+896 genotype. Although the present study had very limited representation of the genetic variation with potential for modification of the response to VAS, it adds to the efforts of untangling the diverse effects and impact of VAS.
Effects of yeast cell walls on performance and immune responses of cyclosporine A-treated, immunosuppressed broiler chickens
Authors: Zhang Shaojin , Liao Bingling , Li Xiao , Li Lei , Ma Libao , Yan Xianghua 
Published: July 2011

The present study was conducted to investigate the effects of dietary yeast (Saccharomyces cerevisiae) cell walls (YCW) from the yeast extract industry on performance and immune function of cyclosporine A (CSA)-treated, immunosuppressed broiler chickens. A total of 240 day-old male broilers were allocated randomly into four treatments: (1) non-challenged control; (2) non-challenged control+0·3 % YCW; (3) CSA-challenged group; (4) CSA-challenged+0·3 % YCW. On days 1–4 and 22–25 of age, broilers were subcutaneously injected with CSA or sterile saline. The results showed that supplementation of YCW significantly improved daily weight gain (DWG) during the starter (days 1–21,P < 0·01), finisher (days 22–42,P < 0·01) and overall (days 1–42,P < 0·05) periods compared with the control birds, but had no effect on feed conversion ratio (FCR,P>0·05). Compared with the CSA-treated birds, YCW alleviated the decrease of DWG (P < 0·01) and increase of FCR (P < 0·05) caused by CSA challenge at different periods and cumulatively. On days 21 and 42, YCW mitigated the CSA-induced decrease of peripheral blood lymphocyte blastogenic response (P < 0·01). In addition, YCW improved the relative weights of the bursa of Fabricius (P < 0·01) and thymus (P < 0·01) and up-regulated the splenic expression of pro-inflammatory cytokines IL-1β (P < 0·01) and IL-6 (P < 0·01) on day 42 compared with the CSA-treated birds. These results indicate that YCW supplementation has beneficial effects in attenuating the immunosuppressive effects of CSA challenge, therefore improving growth performance of broiler chickens.