bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of HIF‐1α by gene therapy enhances angiogenesis and osteogenesis in alveolar bone defect regeneration
Authors: Zhang Yang , Huang Jiao , Wang Chao , Zhang Yan , Hu Changhong , Li Guangyue , Xu Ling
Published: March 2016

Background

A successful clinical outcome for implanted tissue‐engineered bone is dependent on the establishment of a functional vascular network. Gene‐enhanced tissue engineering represents a promising approach for vascularization and osteogenesis. In the present study, we tested the angiogenesis and osteogenesis efficacy of gelatin as the scaffold carrier in combination with a virus encoding the HIF‐1α gene in a rat alveolar bone defect model.

Methods

Three groups of 10 rats each were either left untreated, treated with adenovirus encoding hypoxia‐inducible factor‐1α (AdHIF‐1α)/gelatin sponge or treated with gelatin sponge with adenovirus encoding red fluorescence protein, respectively. At 4 weeks, all samples were determined by micro‐computed tomography, histological analyses and immunohistochemical studies.

Results

Scaffolds loaded with AdHIF‐1α were able to sustain the release of AdHIF‐1α for up to 21 days and alveolar bone defects treated with scaffolds containing AdHIF‐1α significantly induced new bone and new vessel formation in vivo.

Conclusions

Overexpression of HIF‐1α by gene therapy may be a useful method for enhancing alveolar bone defect osteogenesis and angiogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
Speciation of phosphorus in temperate zone forest soils as assessed by combined wet‐chemical fractionation and XANES spectroscopy
Authors: Prietzel Jörg , Klysubun Wantana , Werner Florian
Published: March 2016

Phosphorus availability in terrestrial ecosystems is strongly dependent on soil P speciation. Here we present information on the P speciation of 10 forest soils in Germany developed from different parent materials as assessed by combined wet‐chemical P fractionation and synchrotron‐based X‐ray absorption near‐edge structure (XANES) spectroscopy. Soil P speciation showed clear differences among different parent materials and changed systematically with soil depth. In soils formed from silicate bedrock or loess, Fe‐bound P species (FePO4, organic and inorganic phosphate adsorbed to Fe oxyhydroxides) and Al‐bound P species (AlPO4, organic and inorganic phosphate adsorbed to Al oxyhydroxides, Al‐saturated clay minerals and Al‐saturated soil organic matter) were most dominant. In contrast, the P speciation of soils formed from calcareous bedrock was dominated (40–70% of total P) by Ca‐bound organic P, which most likely primarily is inositol hexakisphosphate (IHP) precipitated as Ca3‐IHP. The second largest portion of total P in all calcareous soils was organic P not bound to Ca, Al, or Fe. The relevance of this P form decreased with soil depth. Additionally, apatite (relevance increasing with depth) and Al‐bound P were present. The most relevant soil properties governing the P speciation of the investigated soils were soil stocks of Fe oxyhydroxides, organic matter, and carbonate. Different types of P speciation in soils on silicate and calcareous parent material suggest different ecosystem P nutrition strategies and biogeochemical P cycling patterns in the respective ecosystems. Our study demonstrates that combined wet‐chemical soil P fractionation and synchrotron‐based XANES spectroscopy provides substantial novel information on the P speciation of forest soils.
Crystalline, thermal and swelling properties of starches from single‐segment substitution lines with different Wx alleles in rice (Oryza sativa L.)
Authors: Teng Bin , Zhang Ying , Du Shiyun , Wu Jingde , Li Zefu , Luo Zhixiang , Yang Jianbo
Published: March 2016

BACKGROUND

In rice, five common Wx alleles, wx, Wxt, Wxg1, Wxg2 and Wxg3, have been identified according to their apparent amylose content (AAC) phenotypes. Previous studies revealed that this Wx allelic variation may also affect other starch properties. However, so far, to what extent the five Wx alleles influence the crystalline structure, thermal and swelling properties of rice starch is still unclear. For this purpose, a set of single‐segment substitution lines (SSSLs) harboring five different Wx alleles, varying widely in AAC, was used for comparative studies.

RESULTS

The crystalline structure, thermal properties and swelling behavior of starches from the SSSLs varied widely depending on Wx genotype. Effects of different Wx alleles on relative crystallinity followed the order wx > Wxt > Wxg1 = Wxg2 > Wxg3. The glutinous and Wxt genotype starches showed higher gelatinization temperatures and enthalpy compared with other Wx genotypes. The order for swelling power was wx > Wxt > Wxg1 > Wxg2 > Wxg3, while the order for degree of solubility was Wxg3 > Wxg1 > Wxg2 > Wxt = wx. Correlation analysis indicated that AAC was significantly and negatively correlated with relative crystallinity (r = −0.996, P < 0.01) and swelling power (r = −0.982, P < 0.01).

CONCLUSION

The present results provide new knowledge about the influence of different Wx alleles on the structural and physicochemical properties of rice starch. © 2016 Society of Chemical Industry
A comparison between field and laboratory pH measurements for seawater on the East China Sea shelf
Authors: Chou Wen‐Chen , Gong Gwo‐Ching , Yang Chin‐Yo , Chuang Kai‐Yuan
Published: March 2016

To evaluate the effect of sample storage on pH analysis, a comparison experiment between field and laboratory pH measurements was conducted on a total of 88 seawater samples collected on the East China Sea shelf during 16 July 2014–29 July 2014. The results show that although pH directly measured onboard was statistically higher than the pH later measured onshore with an average residual of 0.0052 ± 0.0057, after correcting for the perturbation caused by the addition of the HgCl2 solution, the observed difference was within the uncertainty in pH measurement. Therefore, our result suggests that, similar to total alkalinity and dissolved inorganic carbon determinations, seawater samples can be stored for pH analysis with a precision that is comparable to the uncertainty of onboard measurement for a period of at least 20 d.
Non‐centrosymmetric plasmonic crystals for second‐harmonic generation with controlled anisotropy and enhancement
Authors: Kolkowski Radoslaw , Szeszko Justyna , Dwir Benjamin , Kapon Eli , Zyss Joseph
Published: March 2016

Rectangular arrays of pyramidal recesses coated by silver film are investigated by means of polarization‐resolved nonlinear microscopy at 900 nm fundamental wavelength, demonstrating strong dependence of the dipole‐allowed SHG upon the lattice parameters. The plasmonic band gap causes nearly complete SHG suppression in arrays of 650 nm periodicity, whereas a sharp resonance at 550 nm periodicity is observed due to excitation of band edge Bloch states at fundamental frequency, accompanied by symmetry‐constrained interactions with similar modes at the second‐harmonic frequency. Additionally, coupling with modes at the bottom side of the silver film may lead to extraordinary optical transmission, opening a channel for SHG from the highly nonlinear GaAs substrate. Changing the lattice geometry enables SHG intensity modulation over three orders of magnitude, while the effective nonlinear anisotropy can be continuously switched between the two lattice directions, reaching values as high as ±0.96.

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Preferential accumulation of T helper cells but not cytotoxic T cells characterizes benign subclinical rejection of human liver allografts
Authors: Baumann Anna K. , Schlue Jerome , Noyan Fatih , Hardtke‐Wolenski Matthias , Lehner Frank , Barg‐Hock Hannelore , Klempnauer Juergen , Manns Michael P. , Taubert Richard , Jaeckel Elmar
Published: March 2016

Subclinical rejection (SCR) is a common event in protocol biopsies after liver transplantation (LT). So far the interpretation of the underlying histological changes and clinical significance is limited. Previous studies were restricted to SCR manifestations within the first weeks after transplantation with limited follow‐up. We analyzed clinical data from our prospective protocol biopsy program and found late SCR (at least 3 months after transplantation) to be a common event (41/94 patients). SCR manifested much later than acute cellular rejection (ACR). In the second year after transplantation, the SCR incidence in protocol biopsies reached a plateau of approximately 25% and remained at this level until the latest observed manifestations more than 5 years after transplantation. During a median follow‐up of 32 months after SCR, no acute or chronic rejection, relevant graft fibrosis, graft loss, or liver‐related death occurred even without specific therapy for SCR. Immunophenotyping of liver biopsies during SCR showed that similar to ACR, the composition of intrahepatic T cells depended on the severity of histological rejection. However, SCR showed a different pattern of infiltrating T cells with a stronger accumulation of CD4+ cells, an increasing CD4+/CD8+ ratio, and an increasing CD4+ forkhead box P3 (FOXP3)+ regulatory T cell (Treg)/CD8+ ratio, which was not seen in ACR. These intrahepatic T cell patterns were not reflected in the peripheral blood. In conclusion, late SCR after LT has a good clinical prognosis, and it seems safe to leave it untreated. This benign clinical course compared to ACR is associated with intrahepatic T cell infiltration patterns showing less cytotoxic T cells and more CD4+FOXP3+ Tregs. Liver Transplantation 22 943–955 2016 AASLD
Synthesis of Hydrophobic Polymeric Cryogels with Supermacroporous Structure
Authors: Chen Xilu , Sui Weiwei , Ren Dayong , Ding Yuanyuan , Zhu Xiaoli , Chen Zhiyong
Published: March 2016

A versatile approach to synthesis of hydrophobic polymeric cryogels is proposed using acetic acid crystals instead of ice crystals as porogen through cryo‐polymerization. In the range of 60 to 90 vol% of acetic acid, polymerization at ambient temperature gives rise to particulate polymers in beaded or amorphous shape, while polymerization at 4 °C, lower than the melting point of acetic acid (16.6 °C), leads to the formation of cryogel‐like monoliths with supermacroporous structure, which is mainly ascribed to cryo‐concentration effect. According to the measurements by scanning electron microscopy and mercury intrusion porosimetry, the dried samples are supermacroporous with pore size mainly ranging from several micrometers to several hundred micrometers, which can be feasible for rapid mass transfer. The forming cryogels display a superfast responsiveness to organic solvents, possibly stemming from their supermacroporosity and distinctive hydrophobicity.

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Large time asymptotics of Feynman–Kac functionals for symmetric stable processes
Authors: Takeda Masayoshi , Wada Masaki
Published: March 2016

Let μ be a positive Kato measure on associated with the Green kernel of the transient symmetric α‐stable process, the Markov process with generator (). Let be the positive continuous additive functional in the Revuz correspondence with μ. If, in addition, μ is of compact support, we give exact large time asymptotics of the expectation of the Feynman–Kac functional, .
Long‐term Thalamic Deep Brain Stimulation for Essential Tremor: Clinical Outcome and Stimulation Parameters
Authors: Rodríguez Cruz Pedro M. , Vargas Antonio , Fernández‐Carballal Carlos , Garbizu Jose , De La Casa‐Fages Beatriz , Grandas Francisco
Published: March 2016

Background

The reasons underlying the loss of efficacy of deep brain stimulation (DBS) of the thalamic nucleus ventralis intermedius (VIM‐DBS) over time in patients with essential tremor are not well understood.

Methods

Long‐term clinical outcome and stimulation parameters were evaluated in 14 patients with essential tremor who underwent VIM‐DBS. The mean ± standard deviation postoperative follow‐up was 7.7 ± 3.8 years. At each visit (every 3–6 months), tremor was assessed using the Fahn‐Tolosa‐Marin tremor rating scale (FTM‐TRS) and stimulation parameters were recorded (contacts, voltage, frequency, pulse width, and total electrical energy delivered by the internal generator [TEED1sec]).

Results

The mean reduction in FTM‐TRS score was 73.4% at 6 months after VIM‐DBS surgery (P < 0.001) and 50.1% at the last visit (P < 0.001). The gradual worsening of FTM‐TRS scores over time fit a linear regression model (coefficient of determination [R2] = 0.887; P < 0.001). Stimulation adjustments to optimize tremor control required a statistically significant increase in voltage (P = 0.01), pulse width (P = 0.01), frequency (P = 0.02), and TEED1sec (P = 0.008). TEED1sec fit a third‐order polynomial curve model throughout the follow‐up period (R2 = 0.966; P < 0.001). The initial exponential increase (first 4 years of VIM‐DBS) was followed by a plateau and a further increase from the seventh year onward.

Conclusions

The current findings suggest that the waning effect of VIM‐DBS over time in patients with essential tremor may be the consequence of a combination of factors. Superimposed on the progression of the disease, tolerance can occur during the early years of stimulation.
Existence and nonexistence of ground states for a class of quasilinear Schrödinger equations
Authors: Zhang Hui , Zhang Fubao , Xu Junxiang
Published: March 2016

For a class of asymptotically periodic quasilinear Schrödinger equations with three times growth, the existence and nonexistence of ground states are established. The method used here is based on the method of Nehari manifold and concentration compactness principle. Copyright © 2016 John Wiley & Sons, Ltd.
Error behaviour in explicit integration algorithms with automatic substepping
Authors: Lloret‐Cabot Martí , Sloan Scott W. , Sheng Daichao , Abbo Andrew J.
Published: March 2016

This paper studies the behaviour of the error incurred when numerically integrating the elasto‐plastic mechanical relationships of a constitutive model for soils using an explicit substepping formulation with automatic error control. The correct update of all the variables involved in the numerical integration of the incremental stress–strain relationships is central to the computational performance of the integration scheme, and, although often missed in the literature, all variables (including specific volume) should be explicitly considered in the algorithmic formulation. This is demonstrated in the paper by studying, in the context of the Cam clay formulations for saturated soils, the influence that the updating of the specific volume has on the accuracy of the numerical solution. The fact that the variation of the local error with the size of the integrated strain depends on the order of local accuracy of the numerical method is also used in the paper to propose a simple and powerful strategy to verify the correctness of the implemented mathematical formulation. Copyright © 2016 John Wiley & Sons, Ltd.
Increasing obesity rates in school children in United Arab Emirates
Authors: AlBlooshi A. , Shaban S. , AlTunaiji M. , Fares N. , AlShehhi L. , AlShehhi H. , AlMazrouei A. , Souid A. ‐K.
Published: March 2016

Background

The remarkable socioeconomic changes in United Arab Emirates (UAE) necessitate regular monitoring of obesity in our population. This study explored the epidemiology of obesity in a large cohort of UAE students.

Methods

This population‐based study investigated the prevalence of obesity in 44,942 students attending governmental schools in Ras Al‐Khaimah. Body‐mass‐index (BMI) was calculated in 15,532 children (4–12 y) in 2013–2014, and in 29,410 children (3–18 y) in 2014–2015. The International Obesity Task Force, World Health Organization, and Centers for Disease Control (CDC) reference methods were used to identify overweight, obesity, and extremely‐obesity.

Results

Using CDC interpretation of BMI, from 11 to 14 y, the prevalence of BMI ≥85th percentile was 41.2%, BMI ≥95th percentile 24.3% and BMI ≥99th percentile 5.7%. Obesity increased linearly from 3 to 12 y (R2 ≥ 0.979); each year an additional 2.36% of the students became obese and 0.28% became extremely obese. The rate of extreme‐obesity was 9.6‐fold higher in boys than girls (0.58% vs. 0.06%). From 15 to 18 y, 10.3% of boys were extremely obese and 3.0% of girls were extremely obese.

Conclusions

These results confirm a steady rise in obesity in children 3–18 y. The rising rate of extreme obesity is also alarming, especially among boys.
Investigating the Experiences of Childhood Cancer Patients and Parents Participating in Optional Nontherapeutic Clinical Research Studies in the UK
Authors: Errington Julie , Malik Ghada , Evans Julie , Baston Jenny , Parry Annie , Price Lisa , Johnstone Hina , Peters Selena , Oram Victoria , Howe Karen , Whiteley Emma , Tunnacliffe Jane , Veal Gareth J.
Published: March 2016

Background

While the majority of childhood cancer clinical trials are treatment related, additional optional research investigations may be carried out that do not directly impact on treatment. It is essential that these studies are conducted ethically and that the experiences of families participating in these studies are as positive as possible.

Methods

A questionnaire study was carried out to investigate the key factors that influence why families choose to participate in optional nontherapeutic research studies, the level of understanding of the trials involved, and the experiences of participation.

Results

A total of 100 participants from six UK centers were studied; 77 parents, 10 patients >16 years, and 13 patients aged 8–15 years. Ninety‐seven percent of parents and 90% of patients felt that information provided prior to study consent was of the right length, with 52% of parents and 65% of patients fully understanding the information provided. Seventy‐four percent of parents participated in research studies in order to “do something important”, while 74% of patients participated “to help medical staff”. Encouragingly, <5% of participants felt that their clinical care would be negatively affected if they did not participate. Positive aspects of participation included a perception of increased attention from medical staff. Negative aspects included spending longer periods in hospital and the requirement for additional blood samples. Ninety‐six percent of parents and 87% of patients would participate in future studies.

Conclusions

The study provides an insight into the views of childhood cancer patients and their parents participating in nontherapeutic clinical research studies. Overwhelmingly, the findings suggest that participation is seen as a positive experience.
Mammalian Target of Rapamycin Inhibitor Induced Complete Remission of a Recurrent Subependymal Giant Cell Astrocytoma in a Patient Without Features of Tuberous Sclerosis Complex
Authors: Appalla Deepika , Depalma Andres , Calderwood Stanley
Published: March 2016

The majority of patients with subependymal giant cell astrocytoma (SEGA) have tuberous sclerosis complex (TSC). In such patients, the mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to induce responses. Isolated SEGA have been reported in patients without clinical or genetic features of TSC. The treatment of these patients with everolimus has not previously been reported. We treated a patient with a recurrent isolated SEGA with an mTOR inhibitor. The patient tolerated therapy well and had a sustained complete remission. MTOR inhibitors may be useful for the treatment of isolated SEGA. Further study is warranted.
The synergistic flame‐retardant behaviors of pentaerythritol phosphate and expandable graphite in rigid polyurethane foams
Authors: Wang Shijun , Qian Lijun , Xin Fei
Published: March 2016

The flame‐retardant rigid polyurethane foams (RPUFs) containing pentaerythritol phosphate (PEPA) and expandable graphite (EG) were prepared by box‐foaming. The flame retardancy of RPUFs was characterized using the limiting oxygen index (LOI) and cone calorimeter. The results show that the PEPA/EG system can effectively enhance the LOI values and reduce the peak release rate of RPUFs comparing with the foams only containing PEPA or EG although the flame retardants in all the samples are same proportion. The two results imply that the PEPA/EG system form flame‐retardant synergistic effect. The micromorphology and chemical structure of residues of RPUFs were also investigated by scanning electron microscope and Fourier transform‐infrared instruments. During combustion, the polyphosphates and their related analogues generated by PEPA can combine with the surfaces of expanded graphite, thereby resulting in the formation of the improved char layer. The layer possessed increased barrier effect and thereby imposing the better flame retardancy to RPUFs. POLYM. COMPOS., 39:329–336, 2018. © 2016 Society of Plastics Engineers
Eiskalt gegen Kurzschluss
Authors: Schmidt Wolfgang , Krämer Hans‐Peter , Schacherer Christian
Published: March 2016

Kurzschlüsse in Stromnetzen sind unangenehm für Netzbetreiber und Verbraucher. Mit Supraleitern ließe sich das Problem entschärfen, hierfür ist ihr nichtlineares Widerstandsverhalten ideal. Im Normalbetrieb ist ihr Widerstand nahezu Null bis auf geringe Wechselstromverluste. Bei Kurzschluss werden sie normalleitend und begrenzen so den Kurzschlussstrom. In Pilotprojekten werden verschiedene Bauformen getestet. Grundsätzlich unterscheidet man zwischen resistiven und induktiven supraleitenden Strombegrenzern. Letztere nutzen das Transformatorprinzip, unter anderem um den Kühlaufwand für die supraleitende Sekundärwicklung zu reduzieren. Die meisten Pilotprojekte basieren bislang aber auf den weniger aufwendig aufgebauten resistiven Strombegrenzern. Sie werden vor allem in den Verteilnetzen erprobt. In China laufen erste Tests bei höheren Spannungen im Übertragungsnetz.
Stehaufkreisel – a never ending story
Authors: Vollmer Michael , Mölmann Klaus‐Peter
Published: March 2016

Stehaufkreisel sind faszinierende physikalische Spielzeuge, die scheinbar die Schwerkraft auszutricksen vermögen: Nach anfänglicher Rotation drehen sie sich so um, dass sie schließlich auf der früheren Spitze rotieren. Hochgeschwindigkeits‐Videos ermöglichen es, die komplizierten mathematischen Lösungen ihrer Bewegung experimentell zu überprüfen.
Cooper‐Paare tunneln durch einen Quantenpunkt
Authors: Baumgartner Andreas , Gramich Jörg , Schönenberger Christian
Published: March 2016

Elektronische Bauteile aus Supraleitern und Quantenpunkten zeigen eine Vielzahl von neuen und fundamentalen physikalischen Eigenschaften und stellen neue quantentechnologische Anwendungen in Aussicht. Kürzlich ist es gelungen, den wohl grundlegendsten Transportprozess in einer solchen Struktur in Experimenten zu identifizieren, nämlich den direkten Transport von Elektronen aus einem Supraleiter durch einen Quantenpunkt, das sogenannte Andreev‐Tunneln. Das Verständnis dieses Prozesses liefert die Grundlage für zukünftige Anwendungen, die quantenmechanische Phänomene in elektronischen Bauteilen ausnutzen werden.
Apps, die beim Lüften helfen
Authors: Wilhelm Thomas , Kuhn Jochen
Published: March 2016

Mit verschiedenen Apps lässt sich die relative Luftfeuchtigkeit anzeigen, die ein Sensor in einem Smartphone misst. Andere Apps berechnen, wie sich die Luftfeuchtigkeit zum Beispiel durch das Lüften einer Wohnung verändern würde.
Programmable protein arrays for immunoprofiling HPV‐associated cancers
Authors: Ewaisha Radwa , Meshay Ian , Resnik Jack , Katchman Benjamin A. , Anderson Karen S.
Published: March 2016

Over 600 000 cancers each year are attributed to the human papillomavirus (HPV), including cervical, anogenital and oropharyngeal cancers (OPC). A key challenge in understanding HPV immunobiology is the diversity of oncogenic HPV types and the need for multiplexed display of HPV antigens to measure antibody responses. We have generated custom HPV protein microarrays displaying 98 proteins as C‐terminal GST fusion proteins, representing eight antigens of two low‐risk HPV types (HPV6 and 11) and ten oncogenic high‐risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52 and 58). We demonstrate robust and reproducible protein expression of 96/98 of the antigens using a human cell lysate expression system. The target epitopes and specificities of four monoclonal antibodies were identified. Using sera from ten patients with newly diagnosed OPC and ten controls, we demonstrate specific IgG seroreactivity to HPV16 E1, E2, and E7 (a fold increase of 1.52, 2.19 and 1.35 in cases vs. controls, respectively, all p < 0.005), confirming our prior data on an ELISA platform. We also detect HPV52 E7 Abs in serum from a patient with cervical cancer. The HPV protein array has potential for rapid identification of serologic responses to 12 HPV types.
Detection of molecular signatures of oral squamous cell carcinoma and normal epithelium – application of a novel methodology for unsupervised segmentation of imaging mass spectrometry data
Authors: Widlak Piotr , Mrukwa Grzegorz , Kalinowska Magdalena , Pietrowska Monika , Chekan Mykola , Wierzgon Janusz , Gawin Marta , Drazek Grzegorz , Polanska Joanna
Published: March 2016

Intra‐tumor heterogeneity is a vivid problem of molecular oncology that could be addressed by imaging mass spectrometry. Here we aimed to assess molecular heterogeneity of oral squamous cell carcinoma and to detect signatures discriminating normal and cancerous epithelium. Tryptic peptides were analyzed by MALDI‐IMS in tissue specimens from five patients with oral cancer. Novel algorithm of IMS data analysis was developed and implemented, which included Gaussian mixture modeling for detection of spectral components and iterative k‐means algorithm for unsupervised spectra clustering performed in domain reduced to a subset of the most dispersed components. About 4% of the detected peptides showed significantly different abundances between normal epithelium and tumor, and could be considered as a molecular signature of oral cancer. Moreover, unsupervised clustering revealed two major sub‐regions within expert‐defined tumor areas. One of them showed molecular similarity with histologically normal epithelium. The other one showed similarity with connective tissue, yet was markedly different from normal epithelium. Pathologist's re‐inspection of tissue specimens confirmed distinct features in both tumor sub‐regions: foci of actual cancer cells or cancer microenvironment‐related cells prevailed in corresponding areas. Hence, molecular differences detected during automated segmentation of IMS data had an apparent reflection in real structures present in tumor.
Chiral recognition in amyloid fiber growth
Authors: Torbeev Vladimir , Grogg Marcel , Ruiz Jérémy , Boehringer Régis , Schirer Alicia , Hellwig Petra , Jeschke Gunnar , Hilvert Donald
Published: March 2016

Insoluble amyloid fibers represent a pathological signature of many human diseases. To treat such diseases, inhibition of amyloid formation has been proposed as a possible therapeutic strategy. d‐Peptides, which possess high proteolytic stability and lessened immunogenicity, are attractive candidates in this context. However, a molecular understanding of chiral recognition phenomena for d‐peptides and l‐amyloids is currently incomplete. Here we report experiments on amyloid growth of individual enantiomers and their mixtures for two distinct polypeptide systems of different length and structural organization: a 44‐residue covalently‐linked dimer derived from a peptide corresponding to the [20–41]‐fragment of human β2‐microglobulin (β2m) and the 99‐residue full‐length protein. For the dimeric [20–41]β2m construct, a combination of electron paramagnetic resonance of nitroxide‐labeled constructs and 13C‐isotope edited FT‐IR spectroscopy of 13C‐labeled preparations was used to show that racemic mixtures precipitate as intact homochiral fibers, i.e. undergo spontaneous Pasteur‐like resolution into a mixture of left‐ and right‐handed amyloids. In the case of full‐length β2m, the presence of the mirror‐image d‐protein affords morphologically distinct amyloids that are composed largely of enantiopure domains. Removal of the l‐component from hybrid amyloids by proteolytic digestion results in their rapid transformation into characteristic long straight d‐β2m amyloids. Furthermore, the full‐length d‐enantiomer of β2m was found to be an efficient inhibitor of l‐β2m amyloid growth. This observation highlights the potential of longer d‐polypeptides for future development into inhibitors of amyloid propagation. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
A Six‐Stage Workflow for Robust Application of Systems Pharmacology
Authors: Gadkar K , Kirouac DC , Mager DE , van der Graaf PH , Ramanujan S
Published: March 2016

Quantitative and systems pharmacology (QSP) is increasingly being applied in pharmaceutical research and development. One factor critical to the ultimate success of QSP is the establishment of commonly accepted language, technical criteria, and workflows. We propose an integrated workflow that bridges conceptual objectives with underlying technical detail to support the execution, communication, and evaluation of QSP projects.
Antioxidant and Physicochemical Properties of Hydrogen Peroxide‐Treated Sugar Beet Dietary Fibre
Authors: Mišan Aleksandra , Sakač Marijana , Medić Đorđe , Tadić Vanja , Marković Goran , Gyura Julliana , Pagano Ester , Izzo Angelo A. , Borrelli Francesca , Šarić Bojana , Milovanović Ivan , Milić Nataša
Published: March 2016

The aim of the present work was to examine if hydrogen peroxide treatment of sugar beet fibre that aimed at improving its physicochemical properties would impair its antioxidant potential. Three different sugar beet fibres were obtained from sugar beet – non‐treated fibre (NTF) from sugar beet cossettes extracted with sulphurous acid, treated fibre (TF) from NTF treated with hydrogen peroxide in alkaline solution and commercially available Fibrex®. The antioxidant activity of extractable and non‐extractable fibre fractions in ethanol/water mixture (80:20, v/v) of three fibre samples was estimated. Non‐extractable fractions obtained after alkaline treatment of investigated fibres were much higher in phenolic compounds and possessed higher antioxidant potential than extractable fractions. Ferulic acid was proven to be the dominant phenolic acid. Regarding both extractable and non‐extractable fractions, Fibrex® had the highest antioxidant activity in chemical tests, while NTF was superior in comparison with TF. Based on the results of Caco‐2 cells‐based test, all non‐extractable fractions possessed potential for reactive oxygen species inhibition. Regarding the extractable fractions, only the TF manifested this effect.Copyright © 2016 John Wiley & Sons, Ltd.
Optimal Upgrade Policy for Used Products Sold with Two‐dimensional Warranty
Authors: Su Chun , Wang Xiaolin
Published: March 2016

In this paper, a pre‐sale upgrade model is developed for repairable used products sold with two‐dimensional warranty policies. Two kinds of two‐dimensional warranty regions are considered, that is, rectangular and L‐shaped regions. The marginal approach is used to describe the effect of age and usage on product reliability by treating usage as a random function of age. The optimal upgrade policy is determined to minimize the dealer's total expected servicing cost which is the sum of upgrade cost and warranty servicing cost. Analytical properties of the optimal solutions are also investigated. Furthermore, a five‐step approach is presented to design flexible warranty contracts with optimized upgrade policies for used products, which allow customers to choose the most suitable warranty plans among the available options offered by the dealer. Numerical example and sensitivity analysis are provided to demonstrate the proposed models. This study provides the dealers of used products with useful guidelines on designing flexible and optimized warranty contracts. Copyright © 2016 John Wiley & Sons, Ltd.
A new organic reference material, l‐glutamic acid, USGS41a, for δ13C and δ15N measurements − a replacement for USGS41
Authors: Qi Haiping , Coplen Tyler B. , Mroczkowski Stanley J. , Brand Willi A. , Brandes Lauren , Geilmann Heike , Schimmelmann Arndt
Published: March 2016

Rationale

The widely used l‐glutamic acid isotopic reference material USGS41, enriched in both 13C and 15N, is nearly exhausted. A new material, USGS41a, has been prepared as a replacement for USGS41.

Methods

USGS41a was prepared by dissolving analytical grade l‐glutamic acid enriched in 13C and 15N together with l‐glutamic acid of normal isotopic composition. The δ13C and δ15N values of USGS41a were directly or indirectly normalized with the international reference materials NBS 19 calcium carbonate (δ13CVPDB = +1.95 mUr, where milliurey = 0.001 = 1 ‰), LSVEC lithium carbonate (δ13CVPDB = −46.6 mUr), and IAEA‐N‐1 ammonium sulfate (δ15NAir = +0.43 mUr) and USGS32 potassium nitrate (δ15N = +180 mUr exactly) by on‐line combustion, continuous‐flow isotope‐ratio mass spectrometry, and off‐line dual‐inlet isotope‐ratio mass spectrometry.

Results

USGS41a is isotopically homogeneous; the reproducibility of δ13C and δ15N is better than 0.07 mUr and 0.09 mUr, respectively, in 200‐μg amounts. It has a δ13C value of +36.55 mUr relative to VPDB and a δ15N value of +47.55 mUr relative to N2 in air. USGS41 was found to be hydroscopic, probably due to the presence of pyroglutamic acid. Experimental results indicate that the chemical purity of USGS41a is substantially better than that of USGS41.

Conclusions

The new isotopic reference material USGS41a can be used with USGS40 (having a δ13CVPDB value of −26.39 mUr and a δ15NAir value of −4.52 mUr) for (i) analyzing local laboratory isotopic reference materials, and (ii) quantifying drift with time, mass‐dependent isotopic fractionation, and isotope‐ratio‐scale contraction for isotopic analysis of biological and organic materials. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.
Investigation of the selective androgen receptor modulators S1, S4 and S22 and their metabolites in equine plasma using high‐resolution mass spectrometry
Authors: Hansson Annelie , Knych Heather , Stanley Scott , Thevis Mario , Bondesson Ulf , Hedeland Mikael
Published: March 2016

Rationale

Selective androgen receptor modulators (SARMs) are prohibited in sports due to their performance enhancing ability. It is important to investigate the metabolism to determine appropriate targets for doping control. This is the first study where the equine metabolites of SARMs S1, S4 (Andarine) and S22 (Ostarine) have been studied in plasma.

Methods

Each SARM was administered to three horses as an intravenous bolus dose and plasma samples were collected. The samples were pretreated with protein precipitation using cold acetonitrile before separation by liquid chromatography. The mass spectrometric analysis was performed using negative electrospray, quadrupole time‐of‐flight mass spectrometry operated in MSE mode and triple‐quadrupole mass spectrometry operated in selected reaction monitoring mode. For the quantification of SARM S1, a deuterated analogue was used as internal standard.

Results

The numbers of observed metabolites were eight, nine and four for the SARMs S1, S4 and S22, respectively. The major metabolite was formed by the same metabolic reactions for all three SARMs, namely amide hydrolysis, hydroxylation and sulfonation. The values of the determined maximum plasma concentrations were in the range of 97–170 ng/mL for SARM S1, 95–115 ng/mL for SARM S4 and 92–147 ng/mL for SARM S22 and the compounds could be detected for 96 h, 12 h and 18 h, respectively.

Conclusions

The maximum plasma concentration of SARMs S1, S4 and S22 was measured in the first sample (5 min) after administration and they were eliminated fast from plasma. The proposed targets to be used in equine doping control are the parent compounds for all three SARMs, but with the metabolite yielding the highest response as a complementary target. Copyright © 2016 John Wiley & Sons, Ltd.
A zero phase adaptive fuzzy Kalman filter for physiological tremor suppression in robotically assisted minimally invasive surgery
Authors: Sang Hongqiang , Yang Chenghao , Liu Fen , Yun Jintian , Jin Guoguang , Chen Fa
Published: March 2016

Background

Hand physiological tremor of surgeons can cause vibration at the surgical instrument tip, which may make it difficult for the surgeon to perform fine manipulations of tissue, needles, and sutures.

Methods

A zero phase adaptive fuzzy Kalman filter (ZPAFKF) is proposed to suppress hand tremor and vibration of a robotic surgical system. The involuntary motion can be reduced by adding a compensating signal that has the same magnitude and frequency but opposite phase with the tremor signal.

Results

Simulations and experiments using different filters were performed. Results show that the proposed filter can avoid the loss of useful motion information and time delay, and better suppress minor and varying tremor.

Conclusions

The ZPAFKF can provide less error, preferred accuracy, better tremor estimation, and more desirable compensation performance, to suppress hand tremor and decrease vibration at the surgical instrument tip. Copyright © 2016 John Wiley & Sons, Ltd.
Performance, cost analysis, and ground segment design of ultra high throughput multi‐spot beam satellite networks applying different capacity enhancing techniques
Authors: Katona Zoltán , Clazzer Federico , Shortt Kevin , Watts Simon , Lexow Hans Peter , Winduratna Ratna
Published: March 2016

There is an ever present demand for increasingly higher data rates in multi‐spot beam satellite networks. This can be enabled, by shifting carrier frequencies to higher bands, such as the Q/V‐band, where more bandwidth is available. Furthermore, the available bandwidth has to be used as efficiently as possible, which requires efficient capacity enhancing techniques. The present paper identifies and analyzes ground segment capacity enhancing techniques for ultra high throughput multi‐spot beam satellite networks operating in Q/V‐band in the feeder link and in Ka‐band in the user link. The impact of several capacity enhancing techniques on system performance is analyzed using a realistic time step‐based system simulator. Their impact on the ground segment costs is also analyzed. The examined capacity enhancing techniques are as follows: (i) reduced carrier spacing with adjacent channel interference cancellation; (ii) full frequency reuse with co‐channel interference cancellation and scheduling; (iii) four different smart gateway diversity techniques and; (iv) employing optical feeder links as an alternative to radio frequency feeder links. The paper shows that these techniques are capable of improving system performance at the expense of an increase in cost related to the complexity and maturity of the applied capacity‐increasing technique. Copyright © 2016 John Wiley & Sons, Ltd.
Implementation of adaptive methods in early‐phase clinical trials
Authors: Petroni Gina R. , Wages Nolan A. , Paux Gautier , Dubois Frédéric
Published: March 2016

There has been constant development of novel statistical methods in the design of early‐phase clinical trials since the introduction of model‐based designs, yet the traditional or modified 3+3 algorithmic design remains the most widely used approach in dose‐finding studies. Research has shown the limitations of this traditional design compared with more innovative approaches yet the use of these model‐based designs remains infrequent. This can be attributed to several causes including a poor understanding from clinicians and reviewers into how the designs work, and how best to evaluate the appropriateness of a proposed design. These barriers are likely to be enhanced in the coming years as the recent paradigm of drug development involves a shift to more complex dose‐finding problems. This article reviews relevant information that should be included in clinical trial protocols to aid in the acceptance and approval of novel methods. We provide practical guidance for implementing these efficient designs with the aim of augmenting a broader transition from algorithmic to adaptive model‐guided designs. In addition we highlight issues to consider in the actual implementation of a trial once approval is obtained. Copyright © 2016 John Wiley & Sons, Ltd.
Multiparametric Biomechanical and Biochemical Phenotypic Profiling of Single Cancer Cells Using an Elasticity Microcytometer
Authors: Hu Shuhuan , Liu Guangyu , Chen Weiqiang , Li Xiang , Lu Wei , Lam Raymond H. W. , Fu Jianping
Published: March 2016

Deep phenotyping of single cancer cells is of critical importance in the era of precision medicine to advance understanding of relationships between gene mutation and cell phenotype and to elucidate the biological nature of tumor heterogeneity. Existing microfluidic single‐cell phenotyping tools, however, are limited to phenotypic measurements of 1–2 selected morphological and physiological features of single cells. Herein a microfluidic elasticity microcytometer is reported for multiparametric biomechanical and biochemical phenotypic profiling of free‐floating, live single cancer cells for quantitative, simultaneous characterizations of cell size, cell deformability/stiffness, and surface receptors. The elasticity microcytometer is implemented for measurements and comparisons of four human cell lines with distinct metastatic potentials and derived from different human tissues. An analytical model is developed from first principles for the first time to convert cell deformation and adhesion information of single cancer cells encapsulated inside the elasticity microcytometer to cell deformability/stiffness and surface protein expression. Together, the elasticity microcytometer holds great promise for comprehensive molecular, cellular, and biomechanical phenotypic profiling of live cancer cells at the single cell level, critical for studying intratumor cellular and molecular heterogeneity using low‐abundance, clinically relevant human cancer cells.
Oxygen Evolution Assisted Fabrication of Highly Loaded Carbon Nanotube/MnO2 Hybrid Films for High‐Performance Flexible Pseudosupercapacitors
Authors: Chen Hongyuan , Zeng Sha , Chen Minghai , Zhang Yongyi , Zheng Lianxi , Li Qingwen
Published: March 2016

To date, it has been a great challenge to design high‐performance flexible energy storage devices for sufficient loading of redox species in the electrode assemblies, with well‐maintained mechanical robustness and enhanced electron/ionic transport during charge/discharge cycles. An electrochemical activation strategy is demonstrated for the facile regeneration of carbon nanotube (CNT) film prepared via floating catalyst chemical vapor deposition strategy into a flexible, robust, and highly conductive hydrogel‐like film, which is promising as electrode matrix for efficient loading of redox species and the fabrication of high‐performance flexible pseudosupercapacitors. The strong and conductive CNT films can be effectively expanded and activated by electrochemical anodic oxygen evolution reaction, presenting greatly enhanced internal space and surface wettability with well‐maintained strength, flexibility, and conductivity. The as‐formed hydrogel‐like film is quite favorable for electrochemical deposition of manganese dioxide (MnO2) with loading mass up to 93 wt% and electrode capacitance kept around 300 F g−1 (areal capacitance of 1.2 F cm−2). This hybrid film was further used to assemble a flexible symmetric pseudosupercapacitor without using any other current collectors and conductive additives. The assembled flexible supercapacitors exhibited good rate performance, with the areal capacitance of more than 300 mF cm−2, much superior to other reported MnO2 based flexible thin‐film supercapacitors.
Layered MoS2 Hollow Spheres for Highly‐Efficient Photothermal Therapy of Rabbit Liver Orthotopic Transplantation Tumors
Authors: Tan Longfei , Wang Shengping , Xu Ke , Liu Tianlong , Liang Ping , Niu Meng , Fu Changhui , Shao Haibo , Yu Jie , Ma Tengchuang , Ren Xiangling , Li Hong , Dou Jianping , Ren Jun , Meng Xianwei
Published: March 2016

Combining photothermal therapy (PTT) with clinical technology to kill cancer via overcoming the low tumor targeting and poor therapy efficiency has great potential in basic and clinical researches. A brand‐new MoS2 nanostructure is designed and fabricated, i.e., layered MoS2 hollow spheres (LMHSs) with strong absorption in near‐infrared region (NIR) and high photothermal conversion efficiency via a simple and fast chemical aerosol flow method. Owing to curving layered hollow spherical structure, the as‐prepared LMHSs exhibit unique electronic properties comparing with MoS2 nanosheets. In vitro and in vivo studies demonstrate their high photothermal ablation of cell and tumor elimination rate by single NIR light irradiation. Systematic acute toxicity study indicates that these LMHSs have negligible toxic effects to normal tissues and blood. Remarkably, minimally invasive interventional techniques are introduced to improve tumor targeting of PTT agents for the first time. To explore PTT efficiency on orthotopic transplantation tumors, New Zealand white rabbits with VX2 tumor in liver are used as animal models. The effective elimination of tumors is successfully realized by PTT under the guidance of digital subtraction angiography, computed tomography, and thermal imaging, which provides a new way for tumor‐targeting delivery and cancer theranostic application.
Quantification of seismic performance factors for self‐centering controlled rocking special concentrically braced frame
Authors: Rahgozar Navid , Moghadam Abdolreza S. , Aziminejad Armin
Published: March 2016

Modern self‐centering controlled rocking special concentrically braced frame (SC‐CR SCBF) is capable of reducing structural damage compared with conventional buildings following an earthquake. This investigation quantifies three seismic performance factors, including over‐strength factor (Ω0), period‐based ductility (μT) and response modification coefficient (R), for low‐ and mid‐rise SC‐CR SCBFs. Nonlinear static analysis is conducted to derive Ω0 and μT factors for 12 SC‐CR archetypes. Validity of trial R coefficient is also evaluated using a collapse‐based assessment procedure by comparing adjusted collapse margin ratios with the established acceptance criteria. Results indicate that the Ω0 and μT factors are in the range of 1.39 to 2.29 and 12.25 to 29.0, respectively, and R of 8 is proposed for design of SC‐CR archetypes. A reliability study is also performed to examine the effects of modeling and ground motion parameters on the safety margin of designed SC‐CR archetypes with the proposed R value. Results indicate that the design of mid‐rise space archetypes in high‐seismicity regions with the R coefficient of 8 is more reliable than that of the low‐rise perimeter ones in low‐seismicity regions. Copyright © 2016 John Wiley & Sons, Ltd.
Strategic Talent Management in Emerging Markets and Its Impact on Employee Retention: Evidence from Brazilian MNCs
Authors: Ambrosius Judith
Published: March 2016

Previous literature highlights that employee turnover is one of the biggest challenges for multinational corporations (MNCs) stemming from emerging markets. This study analyzes the relationship between different strategic talent management practices and employees’ intention to leave Brazilian multinational corporations. Drawing on the resource‐based view, eight research hypotheses are developed and tested using a sample of 61 employees from Brazilian MNCs. Linear regression modeling reveals that organizational support and perceived career opportunity are negatively related to Brazilian employees’ intention to leave, while training and development is positively related. Furthermore, it is found that perceived career opportunity moderates these relationships. This study derives important implications for strategic talent management in Brazilian MNCs and contributes to the more general literature on human resource management in emerging‐market multinationals. © 2016 Wiley Periodicals, Inc.