bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding affinity of surface functionalized gold nanoparticles to hydroxyapatite
Authors: Ross Ryan D. , Roeder Ryan K.
Published: July 2011

Gold nanoparticles (Au NPs) have been investigated for a number of biomedical applications, including drug and gene delivery vehicles, thermal ablation therapy, diagnostic sensors, and imaging contrast agents. Surface functionalization with molecular groups exhibiting calcium affinity can enable targeted delivery of Au NPs to calcified tissue, including damaged bone tissue. Therefore, the objective of this study was to investigate the binding affinity of functionalized Au NPs for targeted delivery to bone mineral, using hydroxyapatite (HA) crystals as a synthetic analog in vitro. Au NPs were synthesized to a mean particle size of 10–15 nm and surface functionalized with either L‐glutamic acid, 2‐aminoethylphosphonic acid, or alendronate, which exhibit a primary amine for binding gold opposite carboxylate, phosphonate, or bisphosphonate groups, respectively, for targeting calcium. Bisphosphonate functionalized Au NPs exhibited the most rapid binding kinetics and greatest binding affinity to HA, followed by glutamic acid and phosphonic acid. All functional groups reached complete binding after 24 h. Equilibrium binding constants in de‐ionized water, determined by nonlinear regression of Langmuir isotherms, were 3.40, 0.69, and 0.25 mg/L for bisphosphonate, carboxylate, and phosphonate functionalized Au NPs, respectively. Functionalized Au NPs exhibited lower overall binding in fetal bovine serum compared to de‐ionized water, but relative differences between functional groups were similar. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 58–66, 2011.
Many‐body exchange‐repulsion in polarizable molecular mechanics. I. orbital‐based approximations and applications to hydrated metal cation complexes
Authors: Chaudret Robin , Gresh Nohad , Parisel Olivier , Piquemal Jean‐Philip
Published: July 2011

We have quantified the extent of the nonadditivity of the short‐range exchange‐repulsion energy, Eexch‐rep, in several polycoordinated complexes of alkali, alkaline‐earth, transition, and metal cations. This was done by performing ab initio energy decomposition analyses of interaction energies in these complexes. The magnitude of Eexch‐rep(n‐body, n > 2) was found to be strongly cation‐dependent, ranging from close to zero for some alkali metal complexes to about 6 kcal/mol for the hexahydrated Zn2+ complex. In all cases, the cation–water molecules, Eexch‐rep(three‐body), has been found to be the dominant contribution to many‐body exchange‐repulsion effects, higher order terms being negligible. As the physical basis of this effect is discussed, a three‐center exponential term was introduced in the SIBFA (Sum of Interactions Between Fragments Ab initio computed) polarizable molecular mechanics procedure to model such effects. The three‐body correction is added to the two‐center (two‐body) overlap‐like formulation of the short‐range repulsion contribution, Erep, which is grounded on simplified integrals obtained from localized molecular orbital theory. The present term is computed on using mostly precomputed two‐body terms and, therefore, does not increase significantly the computational cost of the method. It was shown to match closely Ethree‐body in a series of test cases bearing on the complexes of Ca2+, Zn2+, and Hg2+. For example, its introduction enabled to restore the correct tetrahedral versus square planar preference found from quantum chemistry calculations on the tetrahydrate of Hg2+ and [Hg(H2O)4]2+. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Comparison between self‐guided Langevin dynamics and molecular dynamics simulations for structure refinement of protein loop conformations
Authors: Olson Mark A. , Chaudhury Sidhartha , Lee Michael S.
Published: July 2011

This article presents a comparative analysis of two replica‐exchange simulation methods for the structure refinement of protein loop conformations, starting from low‐resolution predictions. The methods are self‐guided Langevin dynamics (SGLD) and molecular dynamics (MD) with a Nosé–Hoover thermostat. We investigated a small dataset of 8‐ and 12‐residue loops, with the shorter loops placed initially from a coarse‐grained lattice model and the longer loops from an enumeration assembly method (the Loopy program). The CHARMM22 + CMAP force field with a generalized Born implicit solvent model (molecular‐surface parameterized GBSW2) was used to explore conformational space. We also assessed two empirical scoring methods to detect nativelike conformations from decoys: the all‐atom distance‐scaled ideal‐gas reference state (DFIRE‐AA) statistical potential and the Rosetta energy function. Among the eight‐residue loop targets, SGLD out performed MD in all cases, with a median of 0.48 Å reduction in global root‐mean‐square deviation (RMSD) of the loop backbone coordinates from the native structure. Among the more challenging 12‐residue loop targets, SGLD improved the prediction accuracy over MD by a median of 1.31 Å, representing a substantial improvement. The overall median RMSD for SGLD simulations of 12‐residue loops was 0.91 Å, yielding refinement of a median 2.70 Å from initial loop placement. Results from DFIRE‐AA and the Rosetta model applied to rescoring conformations failed to improve the overall detection calculated from the CHARMM force field. We illustrate the advantage of SGLD over the MD simulation model by presenting potential‐energy landscapes for several loop predictions. Our results demonstrate that SGLD significantly outperforms traditional MD in the generation and populating of nativelike loop conformations and that the CHARMM force field performs comparably to other empirical force fields in identifying these conformations from the resulting ensembles. Published 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Extracellular matrix deposited by synovium‐derived stem cells delays replicative senescent chondrocyte dedifferentiation and enhances redifferentiation
Authors: Pei Ming , He Fan
Published: July 2011

The aim of this study was to assess the effect of extracellular matrix (ECM) deposited by synovium‐derived stem cells (SDSCs) on articular chondrocyte expansion and maintenance of differentiation status and redifferentiation capacity. Passage 0 (P0) pig articular chondrocytes were expanded for six passages on plastic flasks (Plastic), SDSC‐derived ECM (ECM), or substrate switching from either Plastic to ECM (PtoE) or ECM to Plastic (EtoP). Cell morphology, gene expression profiles, and immunophenotypes at each passage were used to characterize differentiation status of expanded cells. Chondrocytes at P0, P2, and P6 were assessed for redifferentiation capacity in a pellet culture system treated with either TGF‐β1‐ or serum‐containing medium for 14 days, using histology, immunohistochemistry, biochemistry, Western blot, and real‐time PCR. We found that ECM not only greatly enhanced chondrocyte expansion but also delayed dedifferentiation of expanded chondrocytes. Intriguingly, compared to a dramatic decrease in CD90+/CD105+ cells and CD90+ cells, CD105+ cells dramatically increased when chondrocytes were plated on Plastic; on the contrary, ECM expansion dramatically increased CD90+ cells and delayed the decrease of CD90+/CD105+ cells. Interestingly, expanded chondrocytes on ECM also acquired a strong redifferentiation capacity, particularly in the pellets treated with TGF‐β1. In conclusion, the ratio of CD90 to CD105 may serve as a marker indicative of proliferation and redifferentiation capacity of dedifferentiated chondrocytes. ECM deposited by SDSCs provides a tissue‐specific three‐dimensional microenvironment for ex vivo expansion of articular chondrocytes while retaining redifferentiation capacity, suggesting that ECM may provide a novel approach for autologous chondrocyte‐based cartilage repair. J. Cell. Physiol. 227: 2163–2174, 2012. © 2011 Wiley Periodicals, Inc.
The inflammatory response of keratinocytes and its modulation by vitamin D: The role of MAPK signaling pathways
Authors: Miodovnik Mor , Koren Ruth , Ziv Esther , Ravid Amiram
Published: July 2011

The hormonal form of vitamin D, calcitriol, and its analogs are known for their beneficial effect in the treatment of inflammatory skin disorders. Keratinocytes play a role in epidermal inflammatory responses invoked by breeching of the epidermal barrier, by infectious agents and by infiltrating immune cells. We studied the role of calcitriol in the initiation of keratinocyte inflammatory response by the viral and injury mimic polyinosinic‐polycytidylic acid (poly(I:C)) and in its maintenance by tumor‐necrosis‐factor α (TNFα) and investigated the role of the mitogen‐activated protein kinase cascades in these processes and their regulation by calcitriol. The inflammatory response of human HaCaT keratinocytes to poly(I:C) or TNFα was assessed by measuring mRNA levels of 13 inflammation‐related molecules by real‐time PCR microarray and by in‐depth investigation of the regulation of interleukin 8, intercellular‐adhesion‐molecule 1, and TNFα expression. We found that while calcitriol had only a minor effect on the keratinocyte response to poly(I:C) and a modest effect on the early response (2 h) to TNFα, it markedly attenuated the later response (16–24 h) to TNFα. The expression of CYP27B1, the enzyme responsible for calcitriol production, was marginally increased by poly(I:C) and markedly by TNFα treatment. This pattern suggests that while allowing the initial keratinocyte inflammatory response to proceed, calcitriol contributes to its timely resolution. Using pharmacological inhibitors we found that while the p38 MAPK and the extracellular signal‐regulated kinase have only a minor role, c‐Jun N‐terminal kinase plays a pivotal role in the induction of the pro‐inflammatory genes and its modulation by calcitriol. J. Cell. Physiol. 227: 2175–2183, 2012. © 2011 Wiley Periodicals, Inc.
The novel insights into spatiotemporal cell biology and its schematic frame, triple W
Authors: Hou Yingchun , Hou Yang , He Siyu , Xing Ruihuan
Published: July 2011

Numerous research results have suggested that the events occurred in a selected cell target and the fates of the cells are spatiotemporally regulated. It has been paying much attention to study the cell events with spatiotemporal proposal designation and analysis. We have been tracking and thinking the new scientific area for many years. Spatiotemporal cell biology and its schematic frame, triple W (when, where, which), are systemically introduced in this study. The triple W under pathological conditions is also discussed. J. Cell. Physiol. 227: 1787–1790, 2012. © 2011 Wiley Periodicals, Inc.
Blood derived stem cells: An ameliorative therapy in veterinary ophthalmology
Authors: Marfe Gabriella , Massaro‐Giordano Mina , Ranalli Marco , Cozzoli Eliana , Di Stefano Carla , Malafoglia Valentina , Polettini Marco , Gambacurta Alessandra
Published: July 2011

Stem cell technology has evoked considerable excitement among people interested in the welfare of animals, as it has suggested the potential availability of new tools for several pathologies, including eye disease, which in many cases is considered incurable. One such example is ulcerative keratitis, which is very frequent in horses. Because some of these corneal ulcers can be very severe, progress rapidly and, therefore, can be a possible cause of vision loss, it is important to diagnose them at an early stage and administer an appropriate treatment, which can be medical, surgical, or a combination of both. The therapeutic strategy should eradicate the infection in order to reduce or stop destruction of the cornea. In addition, it should support the corneal structures and control the uveal reaction, and the pain associated with it, in order to minimize scarring. In this study, we address how stem cells derived from peripheral blood can be used also in ophthalmological pathologies. Our results demonstrate that this treatment protocol improved eye disease in four horse cases, including corneal ulcers and one case of retinal detachment. In all cases, we detected a decrease in the intense inflammatory reaction as well as the restoration of the epithelial surface of the central cornea. J. Cell. Physiol. 227: 1250–1256, 2012. © 2011 Wiley Periodicals, Inc.
Galectin‐3 is a new MerTK‐specific eat‐me signal
Authors: Caberoy Nora B. , Alvarado Gabriela , Bigcas Jo‐Lawrence , Li Wei
Published: July 2011

Phagocytosis of apoptotic cells and cellular debris is a critical process of maintaining tissue and immune homeostasis. Defects in the phagocytosis process cause autoimmunity and degenerative diseases. Phagocytosis ligands or “eat‐me” signals control the initiation of the process by linking apoptotic cells to receptors on phagocyte surface and triggering signaling cascades for cargo engulfment. Eat‐me signals are traditionally identified on a case‐by‐case basis with challenges, and the identification of their cognate receptors is equally daunting. Here, we identified galectin‐3 (Gal‐3) as a new MerTK ligand by an advanced dual functional cloning strategy, in which phagocytosis‐based functional cloning is combined with receptor‐based affinity cloning to directly identify receptor‐specific eat‐me signal. Gal‐3 interaction with MerTK was independently verified by co‐immunoprecipitation. Functional analyses showed that Gal‐3 stimulated the phagocytosis of apoptotic cells and cellular debris by macrophages and retinal pigment epithelial cells with MerTK activation and autophosphorylation. The Gal‐3‐mediated phagocytosis was blocked by excessive soluble MerTK extracellular domain and lactose. These results suggest that Gal‐3 is a legitimate MerTK‐specific eat‐me signal. The strategy of dual functional cloning with applicability to other phagocytic receptors will facilitate unbiased identification of their unknown ligands and improve our capacity for therapeutic modulation of phagocytic activity and innate immune response. J. Cell. Physiol. 227: 401–407, 2012. © 2011 Wiley Periodicals, Inc.
The challenge of change
Authors: Kicklighter Leilani , Miller Vivian B.
Published: July 2011

This article provides the Risk Manager with a framework for dealing with today's challenging times and how much uncertainty an organization is willing to accept. The frame work is ERM: Enterprise Risk Management. An argument is made that by applying an established ERM decision‐making framework, Risk Managers can integrate governance, risk management, compliance, quality performance, and technology which allows organizations to explore, evaluate, predict, mitigate, and even prevent adverse events from occurring in the first place.
Maximising Opportunities to Detect Verbal Deception: Training Police Officers to Interview Tactically
Authors: Dando Coral J. , Bull Ray
Published: July 2011

The purpose of this research was to investigate the efficacy of a novel information gathering technique for detecting truthful and deceptive verbal accounts in interview settings. Five police officers were trained to use each of the three interview techniques, namely tactical, strategic and early. Post‐training, each interviewed 30 mock suspects (five truth tellers and five liars in each interview condition) who had taken part in an immersive interactive computer game, competing as either a terrorist (deceiver) or a builder (truth tellers). Post‐interview, officers completed a questionnaire designed to collect veracity judgments, confidence levels and the type of interviewee behaviour that had influenced their veracity decision. Results revealed a significant advantage for detecting both deceivers and truth tellers using our new tactical procedure (67% and 74% accuracy, respectively) versus the strategic (54% and 42%) and early (53% and 47%) interviews. Additionally, when interviewing tactically, not only were interviewers more confident in their judgments but they also reported using verbal behaviour more to inform their judgments. We introduce the new tactical approach to interviewing and discuss our findings, suggesting why tactical interviewing is effective for detecting verbal deception. Copyright © 2011 John Wiley & Sons, Ltd.
Chrono‐stratigraphy of the Upper Pleistocene and Holocene archaeological sequence in Cova Gran (south‐eastern Pre‐Pyrenees, Iberian Peninsula)
Authors: Mora R. , Benito‐Calvo A. , Martínez‐Moreno J. , Marcen P. González , De La Torre I.
Published: July 2011

The Cova Gran de Santa Linya (Lleida, Spain) is a recently discovered site, with a broad chrono‐cultural sequence that contains archaeological levels dating to the Middle Palaeolithic, Early Upper Palaeolithic, Late Upper Palaeolithic, Neolithic and Early Bronze Age. We present the chronometric and stratigraphic context of these occupations, which were dated using 14C accelerator mass spectrometry and thermoluminescence. The sequence provides important indicators that aid in the reconstruction of the history of human occupation on the southern slopes of the Spanish Pyrenees over the past 50,000 years. Copyright © 2011 John Wiley & Sons, Ltd.
Non‐synchronous deposition of North Atlantic Ash Zone II in Greenland ice cores, and North Atlantic and Norwegian Sea sediments: an example of complex glacial‐stage tephra transport
Authors: Brendryen Jo , Haflidason Haflidi , Sejrup Hans Petter
Published: July 2011

Tephra provides regional chronostratigraphical marker horizons that can link different climate archives with highly needed accuracy and precision. The results presented in this work exemplify, however, that the intermittent storage of tephra in ice sheets and during its subsequent iceberg transport, especially during glacial stages, constitutes a potential source of serious error for the application of tephrochronology to Nordic Seas and North Atlantic sediment archives. The peak shard concentration of the rhyolitic component of the North Atlantic Ash Zone II (NAAZ‐II) tephra complex, often used to correlate marine and ice core records in Marine Isotope Stage (MIS) 3, is shown to lag the eruption event by ca. 100–400 years in some North Atlantic and Norwegian Sea cores. While still allowing for a correlation of archives on millennial timescales, this time delay in deposition is a major obstacle when addressing the lead–lag relationship on short timescales (years to centuries). A precise and accurate determination of lead–lag relationships between archives recording different parts of the climate system is crucial in order to test hypotheses about the processes leading to abrupt climate change and to evaluate results from climate models. Copyright © 2011 John Wiley & Sons, Ltd.
Speleothem‐derived Asian summer monsoon variations in Central China, 54–46 ka
Authors: Zhou Houyun , Zhao Jianxin , Qing Wang , Feng Yuexing , Tang Jing
Published: July 2011

The oxygen isotope signature (δ18O) of stalagmite SI3 collected from Shizi Cave in north‐east Sichuan Province provides an Asian Summer Monsoon (ASM) record in Central China for the period 54–46 ka. The SI3 δ18O record clearly shows a negative δ18O excursion centred around 49.4 ka, which was reported in Hulu Cave in East China but not identified in the speleothem records from South‐west China. As a whole, this record displays a higher coherence with the two Hulu records from East China than with the speleothem δ18O records from South‐west China, suggesting that at 54–46 ka, Central China was influenced more by the East Asian Summer Monsoon than by the Indian Summer Monsoon. It also displays a significant negative δ18O excursion at 47.5–46.6 ka, which is not clearly documented in two other speleothem δ18O records previously reported from South‐west China. This suggests that details of the Greenland interstadial 12 warrant further investigations in future in monsoonal China. The SI3 δ18O record displays more significant centennial‐scale variations than the other four speleothem δ18O records from East and South‐west China, which may be due to the fact that the study site is closer to the north‐west boundary of the ASM and more sensitive to variations of the ASM than East and South‐west China. Copyright © 2011 John Wiley & Sons, Ltd.
Variation in life history and demography of the American black bear
Authors: Beston Julie A.
Published: July 2011

Variation in life history and demography across a species' range informs researchers about regional adaptations and affects whether managers can borrow information from other populations in decision‐making. The American black bear (Ursus americanus) is a long‐lived game species whose continued persistence depends on management of harvest and removal of habituated bears that come into conflict with humans. Understanding the demography of black bears guides efforts at management and conservation, yet detailed knowledge of many populations is typically lacking. I performed a hierarchical Bayesian meta‐analysis of black bear demographic studies across the geographic range of the species to explore how vital rates vary across the range, what information they give us about population growth, and whether managers can justify borrowing information from other studies to inform management decisions. Cub, yearling, and adult survival and fecundity varied between eastern and western North America, whereas subadult survival did not show geographic structuring. Adult survival and fecundity appeared to trade off, with higher survival in the western portions of bears' range and higher fecundity in the east. Although adult survival had the highest elasticity, differences in reproduction drove differences in population growth rate. Mean population growth rate was higher in the east (0.99; 95% credible interval [CrI]: 0.96, 1.03) than the west (0.97; 95%CrI: 0.93, 1.01). Despite declining trends in the west, 34% of the distribution of population growth rate was >1, compared to 55% in the east. Further work needs to be done to address the cause of the apparent trade‐off between adult survival and fecundity and explore how the estimated growth rates are likely to affect population status of black bears. Because population growth rates are close to 1 and small deviations could impact whether a population is considered increasing or decreasing, managers need to employ caution in borrowing vital rates from other populations. © 2011 The Wildlife Society.
The laryngeal mask airway and otorhinolaryngology head and neck surgery
Authors: Jefferson Niall , Riffat Faruque , McGuinness John , Johnstone Charlotte
Published: July 2011

Objectives/Hypothesis:

To review the use of the laryngeal mask airway (LMA) in otorhinolaryngology, as well as the advantages and disadvantages across the range of procedures typically performed.

Study Design:

Contemporary review.

Methods:

Published articles identified through PubMed, Medline, and conference proceedings were reviewed.

Results:

With only minimal stimulation of the oropharyngeal airway at the time of insertion and removal, the LMA provides safe, hands‐free airway maintenance and is ideally suited to many of the procedures performed in otorhinolaryngology.

Conclusions:

The relationship between surgeon and anesthetist is particularly strong in otorhinolaryngology. The impact of airway management on the surgical field and perioperative conditions requires the surgeon to be aware of contemporary tools and techniques available. The LMA has been shown to be safe and efficacious by both the literature and clinical practice. Its use in selected patients should be encouraged.
Tracheocele—a case report
Authors: Nerurkar Nupur , Patil Prakash , Tampi Shyamsunder , Yadav Karan , Jain Shraddha
Published: July 2011

A tracheocele is a rarely encountered entity that may be congenital or acquired. This tracheal lesion is characterized by the presence of a single cystic pouch filled with air or a mixture of liquid and air. We recently managed a case of a large voluminous acquired tracheocele originating from the right posterolateral tracheal wall. A 39‐year‐old male patient presented with chronic cough and breathy voice. Rigid laryngoscopy revealed a right immobile vocal fold. Computed tomography scan revealed a tracheocele that was excised externally with recurrent laryngeal nerve preservation.
Association of common variants, not rare mutations, in IRF6 With nonsyndromic clefts in a honduran population
Authors: Larrabee Yuna C. , Birkeland Andrew C. , Kent David T. , Flores Carlos , Su Gloria H. , Lee Joseph H. , Haddad Joseph
Published: July 2011

Objectives/Hypothesis:

Cleft lip with or without cleft palate (CL/P) is a common birth defect throughout the world. Linkage studies have shown interferon regulatory factor 6 (IRF6) to be associated with CL/P in multiple populations, including one in Honduras. It is unknown, however, whether rare sporadic mutations or common variants are the cause of this association, and reports exist supporting both hypotheses. Thus, it is important to determine the cause for this association in a Honduran population.

Study Design:

Case‐control and family‐based association studies.

Methods:

Families with two or more members affected by CL/P were identified. We collected DNA from affected and unaffected family members (608 total), and from 100 gender‐matched controls from Honduras. We sequenced the exons of IRF6 for mutations in probands and controls. All patients were genotyped for single nucleotide polymorphisms (SNPs) rs642961 and rs2235371, which are proposed to have potential biological significance to IRF6 expression and function.

Results:

We found no mutations in IRF6 in our CL/P probands. We found a risk association with the G allele of rs2235371 in both case‐control (P = .01) and family‐based association (P = .01) studies. We found no association with either allele of rs642961.

Conclusions:

This study suggests that common variants, rather than rare mutations, are the cause for association between IRF6 and nonsyndromic CL/P. rs2235371, but not rs642961, shows association with CL/P, suggesting a functional role for this polymorphism in our Honduran population. rs642961 has been previously reported to have an effect in other populations, suggesting that different populations may be affected by different polymorphisms.
A new method of nasal dermoplasty (MW grafting method) in patients with large septal perforation
Authors: Ichimura Keiichi , Kikuchi Hisashi , Imayoshi Shoichiro
Published: July 2011

Nasal dermoplasty is effective in controlling epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). Skin graft take failure occurs mostly in cases of large septal perforation. The MW method was developed as a modification of nasal dermoplasty designed for patients with HHT having a large septal perforation. It seems to be a safe and effective approach and should be tried for recurrent bleeders with septal perforation.
The mitochondrial A3243G mutation involves the peripheral vestibule as well as the cochlea
Authors: Iwasaki Shinichi , Egami Naoya , Fujimoto Chisato , Chihara Yasuhiro , Ushio Munetaka , Kashio Akinori , Yamasoba Tatsuya
Published: July 2011

Objectives/Hypothesis:

To evaluate vestibular function in patients with the mitochondrial A3243G mutation.

Study Design:

Data from patients with the A3243G mutation attending an academic tertiary referral center were prospectively recorded.

Methods:

The clinical histories of 13 unrelated patients with the mitochondrial A3243G mutation (six mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes; and seven maternally inherited diabetes and deafness) were recorded, in particular their history of vestibular symptoms. Vestibular examinations including caloric testing and vestibular evoked myogenic potentials in response to air‐conducted sound (ACS‐VEMPs) were performed. In seven patients who showed abnormal ACS‐VEMP, VEMP in response to galvanic stimuli (galvanic‐VEMP) were also recorded.

Results:

Eleven of the 13 patients had vestibular symptoms. The age of onset of vestibular symptoms was significantly later than the ages of onset of hearing loss and diabetes mellitus (P < .05). Ten of the 13 patients showed abnormal caloric responses, whereas 12 patients showed abnormal ACS‐VEMPs on one or both sides. All of the seven patients who underwent galvanic‐VEMP testing showed normal responses.

Conclusions:

The A3243G mutation is associated with vestibular dysfunction involving both the superior and inferior vestibular nerve systems. Furthermore, our results from galvanic‐VEMP testing suggests that a labyrinthine lesion is primarily responsible for the symptoms of vestibular dysfunction.
How to Integrate Biological Motors towards Bio‐Actuators Fueled by ATP
Authors: Kabir Arif Md. Rashedul , Kakugo Akira , Gong Jian Ping , Osada Yoshihito
Published: July 2011

Biological motors, driven by the conversion of chemical energy into mechanical energy, are much more efficient than man‐made machines. The development of such efficient biomimetic motor systems in vitro is currently a vital need. However, great difficulty lies in how to integrate the sophisticated functions of the constituent components to obtain a performance as in the case of natural living systems. Based on ‘active’ and ‘passive’ self‐organization principles, it has been demonstrated that the functions of motor protein systems can be integrated to obtain complex hierarchical structures that can work as actuators. Most of the works discussed here concern two‐dimensional behavior, and recent works aim to explore the three‐dimensional features of such artificial bio‐mechanical systems.

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Poly(Vinyl Alcohol) Physical Hydrogels: New Vista on a Long Serving Biomaterial
Authors: Alves Marie‐Helene , Jensen Bettina E. B. , Smith Anton A. A. , Zelikin Alexander N.
Published: July 2011

Poly(vinyl alcohol), PVA, and physical hydrogels derived thereof have an excellent safety profile and a successful history of biomedical applications. However, these materials are hardly in the focus of biomedical research, largely due to poor opportunities in nano‐ and micro‐scale design associated with PVA hydrogels in their current form. In this review we aim to demonstrate that with PVA, a (sub)molecular control over polymer chemistry translates into fine‐tuned supramolecular association of chains and this, in turn, defines macroscopic properties of the material. This nano‐ to micro‐ to macro‐ translation of control is unique for PVA and can now be accomplished using modern tools of macromolecular design. We believe that this strategy affords functionalized PVA physical hydrogels which meet the demands of modern nanobiotechnology and have a potential to become an indispensable tool in the design of biomaterials.

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Non‐oxidative Thermal Degradation of Poly(glycidol), Poly(glycidol)‐g‐L‐lactide, and Poly(glycidol)‐g‐glycolide
Authors: Atkinson Jeffrey L. , Vyazovkin Sergey
Published: July 2011

Three polymers of pharmaceutical/medical relevance are synthesized: poly(glycidol) (PG), poly(glycidol)‐g‐L‐lactide (PG‐g‐La), and poly(glycidol)‐g‐glycolide (PG‐g‐Gly). Because the thermal stability of these polymers is an essential factor of their processing and practical application, the study focuses on kinetic and mechanistic aspects of non‐oxidative thermal degradation. The study is conducted by combining thermogravimetry, Fourier transform infrared spectroscopy, and isoconversional kinetic analysis. It is found that PG degrades in a single mass loss step, whereas, PG‐g‐La and PG‐g‐Gly in two. It is demonstrated that the first step in degradation of PG‐g‐La and PG‐g‐Gly is associated with decomposition of the pendant groups and the second is due to degradation of the PG backbone.

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Photodynamic therapy based on 5‐aminolevulinic acid and its use as an antimicrobial Agent
Authors: Harris Frederick , Pierpoint Lynne
Published: July 2011

Exogenous 5‐aminolevulinic acid (ALA) is taken up directly by bacteria, yeasts, fungi, and some parasites, which then induces the accumulation of protoporphyrin IX (PPIX). Subsequent light irradiation of PPIX leads to the inactivation of these organisms via photodamage to their cellular structures. ALA uptake and light irradiation of PPIX produced by host cells leads to the inactivation of other parasites, along with some viruses, via the induction of an immune response. ALA‐mediated PPIX production by host cells and light irradiation result in the inactivation of other viruses via either the induction of a host cell response or direct photodynamic attack on viral particles. This ALA‐mediated production of light‐activated PPIX has been extensively used as a form of photodynamic therapy (PDT) and has shown varying levels of efficacy in treating conditions that are associated with microbial infection, ranging from acne and verrucae to leishmaniasis and onychomycosis. However, for the treatment of some of these conditions by ALA‐based PDT, the role of an antimicrobial effect has been disputed and in general, the mechanisms by which the technique inactivates microbes are not well understood. In this study, we review current understanding of the antimicrobial mechanisms used by ALA‐based PDT and its role in the treatment of microbial infections along with its potential medical and nonmedical applications.
Relating discrete element method parameters to rock properties using classical and micropolar elasticity theories
Authors: Alassi Haitham Tayseer , Holt Rune
Published: July 2011

Micro–macro relations for discrete element method (DEM) media are derived using both classical and micropolar elasticity theories. The DEM media are classified into two main categories: dense packing, and loose packing. For both categories, relations for Young modulus (E), Poisson's ratio (ν) to represent static behaviors, and wave velocities (P‐wave and S‐wave) to represent dynamic behaviors are derived using the internal DEM parameters (kn, ks) and compared with values obtained from static and dynamic numerical tests. Whereas the dynamic behaviors for the two categories and the static behaviors for the dense packing match the analytical relations, the static behavior for the loose packing does not. Micropolar elasticity theory is also used to study the behaviors of the DEM media, where it is shown that if element rotation is included, DEM media behave according to linear elasticity theory. However, if element rotation is constrained, asymmetrical stresses arise in the DEM media, and a new expression is derived for the S‐wave, which allows it, under certain conditions, to travel faster than the P‐wave. Copyright © 2011 John Wiley & Sons, Ltd.
Model order reduction based on proper generalized decomposition for the propagation of uncertainties in structural dynamics
Authors: Chevreuil Mathilde , Nouy Anthony
Published: July 2011

A priori model reduction methods based on separated representations are introduced for the prediction of the low frequency response of uncertain structures within a parametric stochastic framework. The proper generalized decomposition method is used to construct a quasi‐optimal separated representation of the random solution at some frequency samples. At each frequency, an accurate representation of the solution is obtained on reduced bases of spatial functions and stochastic functions. An extraction of the deterministic bases allows for the generation of a global reduced basis yielding a reduced order model of the uncertain structure, which appears to be accurate on the whole frequency band under study and for all values of input random parameters. This strategy can be seen as an alternative to traditional constructions of reduced order models in structural dynamics in the presence of parametric uncertainties. This reduced order model can then be used for further analyses such as the computation of the response at unresolved frequencies or the computation of more accurate stochastic approximations at some frequencies of interest. Because the dynamic response is highly nonlinear with respect to the input random parameters, a second level of separation of variables is introduced for the representation of functions of multiple random parameters, thus allowing the introduction of very fine approximations in each parametric dimension even when dealing with high parametric dimension. Copyright © 2011 John Wiley & Sons, Ltd.
Solid‐phase synthesis of aromatic polyamide dendrons
Authors: Tsushima Hiroyuki , Matsumoto Kazuya , Jikei Mitsutoshi
Published: July 2011

Dendrimer syntheses usually require time‐consuming and tedious procedures, especially for high‐generation dendrimers. Solid‐phase synthesis using insoluble supports allows the easy separation of growing molecules on the resin and other chemicals in solution. In this study, aromatic polyamide dendrons were prepared on a glycine‐modified Wang resin. 3,5‐Bis(4‐(9‐fluorenylmethyloxycarbonyl)aminophenoxy)benzoic acid and (2,3‐dihydro‐2‐thioxo‐3‐benzoxazolyl)phosphonic acid diphenyl ester were used as a building block and a condensation agent, respectively. The colorimetric test using the Disperse Red 1 p‐nitrophenyl ester (NF31) was carried out to ensure complete consumption of the aromatic amino group in each coupling reaction. The isolated yields of the G2, G3, G4, and G5 dendrons were 81%, 71%, 60%, and 67%, respectively. The good yield of the generation 5 dendron suggests that the solid‐phase synthesis combined with appropriate colorimetric test has a potential to simplify conventional dendrimer syntheses in solution. Copyright © 2011 John Wiley & Sons, Ltd.
Formation of cyclophosphamide specific DNA adducts in hematological diseases
Authors: Johnson L'Aurelle A. , Malayappan Bhaskar , Tretyakova Natalia , Campbell Colin , MacMillan Margaret L. , Wagner John E. , Jacobson Pamala A.
Published: July 2011

Background

Fanconi anemia (FA) patients are hypersensitive to DNA alkylating agents and require lower doses than non‐FA patients to minimize serious toxicity. The mechanism by which hypersensitivity occurs is thought to be due to the inability of these individuals to effectively repair drug‐induced interstrand DNA–DNA crosslinks. We recently developed a highly sensitive assay for cyclophosphamide specific interstrand DNA–DNA crosslinks (G‐NOR‐G) and are able to quantify and compare formation of these adducts in the blood of patients. Therefore we sought to determine whether FA patients have higher in vivo exposure to the cyclophosphamide specific interstrand DNA crosslink, G‐NOR‐G, relative to patients without FA.

Procedure

Cyclophosphamide interstrand DNA crosslinks were measured with the first dose of cyclophosphamide in FA and non‐FA patients receiving a cyclophosphamide based preparative regimen prior to hematopoietic cell transplantation (HCT). FA patients received a lower cyclophosphamide dose than the non‐FA patients (5–10 mg/kg/day vs. 50–60 mg/kg/day).

Results

Despite the lower cyclophosphamide dose and lower plasma concentrations in FA patients, they had G‐NOR‐G amounts similar to the non‐FA patients (area under the curve (AUC)0–∞, 99.8 vs. 144.9 G‐NOR‐G adducts/106 nucleotides hour, respectively, P = 0.47). When G‐NOR‐G AUC was normalized for cyclophosphamide plasma concentrations, FA study subjects produced 15‐fold higher adducts than non‐FA patients (P = 0.05).

Conclusions

FA patients are hypersensitive to DNA alkylating agents possibly as a result of greater formation of cyclophosphamide specific interstrand DNA crosslinks and/or diminished capacity for DNA repair. Identification and quantification of these adducts may be important determinant of cyclophosphamide related toxicity. Pediatr Blood Cancer 2012; 58: 708–714. © 2011 Wiley Periodicals, Inc.
Nonisothermal crystallization behavior of biodegradable poly(butylene terephthalate‐co‐butylene adipate‐co‐ethylene terephthalate‐co‐ethylene adipate) copolyester
Authors: Wang Xiaohui , Shi Jun , Chen Ying , Shi Yan , Fu Zhifeng
Published: July 2011

A series of biodegradable aliphatic‐aromatic copolyester, poly(butylene terephthalate‐co‐butylene adipate‐co‐ethylene terephthalate‐co‐ethylene adipate) (PBATE), were synthesized from terephthalic acid (PTA), adipic acid (AA), 1,4‐butanediol (BG) and ethylene glycol (EG) by direct esterification and polycondensation. The nonisothermal crystallization behavior of PBATE copolyesters was studied by the means of differential scanning calorimeter, and the nonisothermal crystallization kinetics were analyzed via the Avrami equation modified by Jeziorny, Ozawa analysis and Z.S. Mo method, respectively. The results show that the crystallization peak temperature of PBATE copolyesters shifted to lower temperature at higher cooling rate. The modified Avrami equation could describe the primary stage of nonisothermal crystallization of PBATE copolyesters. The value of the crystallization half‐time (t1/2) and the crystallization parameter (Zc) indicates that the crystallization rate of PBATE copolyesters with more PTA content was higher than that with less PTA at a given cooling rate. Ozawa analysis was not suitable to study the nonisothermal crystallization process of PBATE copolyesters, but Z.S. Mo method was successful in treatingthis process. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Limiting photovoltaic efficiency under new ASTM International G173‐based reference spectra
Authors: Green Martin A.
Published: July 2011

Efficiency limits upon photovoltaic energy conversion are re‐evaluated under the new ASTM International G173‐based reference spectra. Peak terrestrial efficiency for a single‐junction device increases to 33.8% under the new air mass 1.5G spectrum, whereas overall and time‐symmetric limits increase to 74.0% and 68.0%, respectively. Copyright © 2011 John Wiley & Sons, Ltd.
Patterns and changes in psychopathic interpersonal behaviour in forensic inpatient treatment
Authors: Draycott Simon , Askari Roxanna , Kirkpatrick Tim
Published: July 2011

Psychopathy is a vital construct in the treatment of mentally disordered offenders, and it is arguable that at the heart of psychopathy is a deviant interpersonal style. The present study analysed the changes in perceived dominance and warmth (as rated by staff using the Chart of Interpersonal Reactions in Closed Living Environments) of 34 male psychopathic patients admitted to the Dangerous and Severe Personality Disorder Service of a high‐security hospital in the UK. Results showed that the level and direction of change in dominance and warmth were dependent on the level of psychopathy; patients with a higher level of psychopathy increased significantly in dominance but did not decrease in warmth, whereas patients with a lower level of psychopathy decreased significantly in warmth but did not increase in dominance. These results are discussed in terms of possible implications for the treatment and management of patients with varying levels of psychopathy. Copyright © 2011 John Wiley & Sons, Ltd.
Progress in super long loop prediction
Authors: Zhao Suwen , Zhu Kai , Li Jianing , Friesner Richard A.
Published: July 2011

Sampling errors are very common in super long loop (referring here to loops that have more than thirteen residues) prediction, simply because the sampling space is vast. We have developed a dipeptide segment sampling algorithm to solve this problem. As a first step in evaluating the performance of this algorithm, it was applied to the problem of reconstructing loops in native protein structures. With a newly constructed test set of 89 loops ranging from 14 to 17 residues, this method obtains average/median global backbone root‐mean‐square deviations (RMSDs) to the native structure (superimposing the body of the protein, not the loop itself) of 1.46/0.68 Å. Specifically, results for loops of various lengths are 1.19/0.67 Å for 36 fourteen‐residue loops, 1.55/0.75 Å for 30 fifteen‐residue loops, 1.43/0.80 Å for 14 sixteen‐residue loops, and 2.30/1.92 Å for nine seventeen‐residue loops. In the vast majority of cases, the method locates energy minima that are lower than or equal to that of the minimized native loop, thus indicating that the new sampling method is successful and rarely limits prediction accuracy. Median RMSDs are substantially lower than the averages because of a small number of outliers. The causes of these failures are examined in some detail, and some can be attributed to flaws in the energy function, such as π–π interactions are not accurately accounted for by the OPLS‐AA force field we employed in this study. By introducing a new energy model which has a superior description of π–π interactions, significantly better results were achieved for quite a few former outliers. Crystal packing is explicitly included in order to provide a fair comparison with crystal structures. Proteins 2011;. © 2011 Wiley‐Liss, Inc.
Energetics of charge–charge interactions between residues adjacent in sequence
Authors: Loladze Vakhtang V. , Makhatadze George I.
Published: July 2011

Statistical analysis of the residue separation between a pair of ionizable side chains within 4 Å of each other was performed on a set of 1560 non‐homologous PDB structures. We found that the frequency of pairs of like charges (i.e., pairs consisting of acidic residues Asp and Glu or pairs consisting of basic residues Arg and Lys) is two orders of magnitude lower than the pairs of oppositely charged residues (salt‐bridges). We also found that for pairs of like charges the distribution is skewed dramatically towards short residue separation (<3). On the basis of these observations, we hypothesize that at short residue separation the repulsion between charges does not contribute much to the protein stability and the effects are largely dominated by the long range charge–charge interactions with other ionizable groups in the protein molecule. To test this hypothesis, we incorporated various pairs of charged residues at position 63 and 64 of ubiquitin and compared the stabilities of these variants. We also performed calculations of the expected changes in the charge–charge interactions. A very good correlation between experimental changes in the stability of ubiquitin variants, and changes in the energy of charge–charge interactions provides support for the hypothesis that a pair of ionizable residues next to each other in sequence modulates protein stability via long range charge–charge interactions with the rest of the protein. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Ensemble predictability of an isolated mountain thunderstorm in a high‐resolution model
Authors: Hanley K. E. , Kirshbaum D. J. , Belcher S. E. , Roberts N. M. , Leoncini G.
Published: July 2011

Convective‐scale ensemble simulations with perturbed initial conditions are performed to investigate the physical mechanisms, sensitivities and predictability of convective precipitation for a well‐observed event from the Convective and Orographically induced Precipitation Study (COPS). On this day an isolated thunderstorm developed over the Black Forest mountains in southwest Germany that was initiated by thermally driven low‐level convergence. With the default ensemble configuration, none of the members simulated any deep convection. A soil moisture and atmospheric moisture deficiency was found to be responsible for a lack of boundary layer moisture in the analysis. Correction of this moisture bias yielded an ensemble in which some members produced a realistic convective storm. In contrast, other members only produced shallow convection. A robust feature of the members that simulated the storm was that an impinging upper‐level disturbance to the west had progressed further east towards the COPS region. This led to increased westerly winds aloft, which when mixed down into the boundary layer acted to feed a deeper layer of moist valley air into the convergent mountain circulation. The simulations reveal a very strong sensitivity to uncertainties in the large‐scale flow as well as the boundary layer structure and stability. Copyright © 2011 Royal Meteorological Society and British Crown Copyright, the Met Office