bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational model of matrix remodeling and entrenchment in the free‐floating fibroblast‐populated collagen lattice
Authors: Simon D. D. , Murtada S.‐I. , Humphrey J. D.
Published: September 2014

Tissue equivalents represent excellent model systems for elucidating principles of mechanobiology and for exploring methods to improve the functionality of tissue‐engineered constructs. The simplest tissue equivalent is the free‐floating fibroblast‐populated collagen lattice. Although introduced over 30 years ago, the associated mechanics of the cell‐mediated compaction of this lattice was only recently analyzed in detail. The goal of this paper was to build on this recent stress analysis by developing a computational model of the evolving geometry, regionally varying material properties and cell stresses, and overall residual stress fields during the first two days of compaction. Baseline results were found to agree well with most experimental observations, namely evolving changes in radius, thickness, and material symmetry, yet hypothesis testing revealed aspects of the mechanobiology that require more experimental attention. Given the generality of the proposed framework, we submit that modifications and refinements can be used to study many similar systems and thereby help guide future experiments. Copyright © 2014 John Wiley & Sons, Ltd.
A Multifrequency Virtual Spectrometer for Complex Bio‐Organic Systems: Vibronic and Environmental Effects on the UV/Vis Spectrum of Chlorophyll a
Authors: Barone Vincenzo , Biczysko Malgorzata , Borkowska‐Panek Monika , Bloino Julien
Published: September 2014

The subtle interplay of several different effects means that the interpretation and analysis of experimental spectra in terms of structural and dynamic characteristics is a challenging task. In this context, theoretical studies can be helpful, and as such, computational spectroscopy is rapidly evolving from a highly specialized research field toward a versatile and widespread tool. However, in the case of electronic spectra (e.g. UV/Vis, circular dichroism, photoelectron, and X‐ray spectra), the most commonly used methods still rely on the computation of vertical excitation energies, which are further convoluted to simulate line shapes. Such treatment completely neglects the influence of nuclear motions, despite the well‐recognized notion that a proper account of vibronic effects is often mandatory to correctly interpret experimental findings. Development and validation of improved models rooted into density functional theory (DFT) and its time‐dependent extension (TD‐DFT) is of course instrumental for the optimal balance between reliability and favorable scaling with the number of electrons. However, the implementation of easy‐to‐use and effective procedures to simulate vibrationally resolved electronic spectra, and their availability to a wide community of users, is at least equally important for reliable simulations of spectral line shapes for compounds of biological and technological interest. Here, such an approach has been applied to the study of the UV/Vis spectra of chlorophyll a. The results show that properly tailored approaches are feasible for state‐of‐the‐art computational spectroscopy studies, and allow, with affordable computational resources, vibrational and environmental effects on the spectral line shapes to be taken into account for large systems.
Abundance, diversity, and feeding behavior of coral reef butterflyfishes at Lord Howe Island
Authors: Pratchett Morgan S. , Hoey Andrew S. , Cvitanovic Christopher , Hobbs Jean‐Paul A. , Fulton Christopher J.
Published: September 2014

Endemic species are assumed to have a high risk of extinction because their restricted geographic range is often associated with low abundance and high ecological specialization. This study examines the abundance of Chaetodon butterflyfishes at Lord Howe Island in the south‐west Pacific, and compares interspecific differences in local abundance to the feeding behavior and geographic range of these species. Contrary to expected correlations between abundance and geographic range, the single most abundant species of butterflyfish was Chaetodon tricinctus, which is endemic to Lord Howe Island and adjacent reefs; densities of C. tricinctus (14.1 ± 2.1 SE fish per 200m2) were >3 times higher than the next most abundant butterflyfish (Chaetodon melannotus), and even more abundant than many other geographically widespread species. Dietary breadth for the five dominant butterflyfishes at Lord Howe Island was weakly and generally negative correlated with abundance. The endemic C. tricinctus was a distinct outlier in this relationship, though our extensive feeding observations suggest some issues with the measurements of dietary breadth for this species. Field observations revealed that all bites taken on benthic substrates by C. tricinctus were from scleractinian corals, but adults rarely, if ever, took bites from the benthos, suggesting that they may be feeding nocturnally and/or using mid‐water prey, such as plankton. Alternatively, the energetic demands of C. tricinctus may be fundamentally different to other coral‐feeding butterflyfishes. Neither dietary specialization nor geographic range accounts for interspecific variation in abundance of coral reef butterflyfishes at Lord Howe Island, while much more work on the foraging behavior and population dynamics of C. tricinctus will be required to understand its’ abundance at this location.
Impedance Analysis of Single Melanoma Cells in Microfluidic Devices
Authors: Chiang Yang , Jang Ling‐Sheng , Tsai Sung‐Lin , Chen Ming‐Kun , Wang Min‐Haw
Published: September 2014

The electrical impedance analysis of single cells can provide information on cells’ pathological condition in various environments. Cell electrical properties are affected by factors such as the location, adhesion, and size of the cell. The proposed microfluidic device captures a single cell, maintains growth conditions, and allows single‐melanoma‐cell impedance to be measured using an impedance analyzer and a function generator. The rate of impedance variation (ROIV) can be used to determine cell growth conditions. Cellular apoptosis affects cell size and membrane surface area, and thus the electrical properties of cells. At 24 h without Antrodia cinnamomea (AC) addition, ROIV was 15.23 %, 17.04 %, and 12.60 % at temperatures of 34 °C, 37 °C, and 40 °C, respectively. At 24 h and 37 °C, ROIV was 17.04 %, 40.37 %, and 45.02 % for AC concentrations of 0, 20, and 40 µL/mL, respectively. The results show that the cell impedance variation of cells cultured without AC is much lower than that of cells cultured with AC. Regarding cellular morphology, with AC addition, the cells shrank obviously after 24 h, whereas they barely shrank without AC addition.
Sensitive Voltammetric Sensor Based on Boron‐Doped Diamond Electrode for Determination of the Chemotherapeutic Drug Methotrexate in Pharmaceutical and Biological Samples
Authors: Šelešovská Renáta , Janíková‐Bandžuchová Lenka , Chýlková Jaromíra
Published: September 2014

A novel sensitive voltammetric method for the determination of an important chemotherapeutic drug, methotrexate, was designed using a bare boron‐doped diamond electrode in connection with differential pulse voltammetry. Methotrexate provided one well developed oxidation peak suitable for analytical purposes at about +1000 mV (vs. Ag/AgCl electrode) in an acidic medium. The voltammetric behavior of methotrexate in dependence of pH of the supporting electrolyte and scan rate has been investigated using cyclic voltammetry and DC voltammetry, respectively, to select the suitable experimental parameters. The optimum conditions for its determination using differential pulse voltammetry have been found to be 0.05 mol L−1 H2SO4 with a limit of detection of 1.0×10−8 mol L−1 and a linear dynamic range from 5×10−8 to 2×10−5 mol L−1. Calculated values of relative standard deviations of repeated determinations (n≥5) in various concentration levels of methotrexate did not exceed 4 %. The influence of possible interfering agents was studied as well. Finally, practical applicability of the newly proposed method was verified by analysis of real drug preparations and spiked human urine. The calculated recovery values ranged from 99.2 to 101.4 %.
Comparing Computational Methods for Identification of Allele‐Specific Expression based on Next Generation Sequencing Data
Authors: Liu Zhi , Yang Jing , Xu Huayong , Li Chao , Wang Zhen , Li Yuanyuan , Dong Xiao , Li Yixue
Published: September 2014

Allele‐specific expression (ASE) studies have wide‐ranging implications for genome biology and medicine. Whole transcriptome RNA sequencing (RNA‐Seq) has emerged as a genome‐wide tool for identifying ASE, but suffers from mapping bias favoring reference alleles. Two categories of methods are adopted nowadays, to reduce the effect of mapping bias on ASE identification—normalizing RNA allelic ratio with the parallel genomic allelic ratio (pDNAar) and modifying reference genome to make reads carrying both alleles with the same chance to be mapped (mREF). We compared the sensitivity and specificity of both methods with simulated data, and demonstrated that the pDNAar, though ideally practical, was lower in sensitivity, because of its lower mapping rate of reads carrying nonreference (alternative) alleles, although mREF achieved higher sensitivity and specificity for its efficiency in mapping reads carrying both alleles. Application of these two methods in real sequencing data showed that mREF were able to identify more ASE loci because of its higher mapping efficiency, and able to correcting some seemly incorrect ASE loci identified by pDNAar due to the inefficiency in mapping reads carrying alternative alleles of pDNAar. Our study provides useful information for RNA sequencing data processing in the identification of ASE.
Palladium‐Catalyzed Decarbonylative Rearrangement of N‐Allenyl Seleno‐ and Tellurocarbamates
Authors: Shiro Daisuke , Nagai Hiroyuki , Fujiwara Shin‐ichi , Tsuda Susumu , Iwasaki Takanori , Kuniyasu Hitoshi , Kambe Nobuaki
Published: September 2014

Decarbonylative rearrangement of seleno‐ and tellurocarbamates carrying an allenyl group on the nitrogen was found to proceed in the presence of a palladium catalyst to afford 3‐chalcogeno‐1‐azadienes. This transformation may involve oxidative addition of Pd to a carbon–chalcogen bond, decarbonylation from a carbamoylpalladium unit (R2N‐C(O)‐PdChPh: Ch = Se or Te), Pd shift, and reductive elimination.
Adhesive interface and bond strength of endodontic sealers to root canal dentine after immersion in phosphate‐buffered saline
Authors: Tedesco Maybell , Felippe Mara Cristina Santos , Felippe Wilson Tadeu , Alves Ana Maria Hecke , Bortoluzzi Eduardo Antunes , Teixeira Cleonice Silveira
Published: September 2014

This study evaluated the bond strength (BS) and the adhesive interface of four endodontic sealers to root canal dentine, before, and after immersion in phosphate buffered saline (PBS) to simulate an in vivo environment. Eighty roots were instrumented using ProTaper rotatory files, under irrigation with 17% EDTA and 1% NaOCl. Posteriorly were divided into four groups (n = 20) according to the sealer used: Endofill, AH Plus, Sealapex, and MTA Fillapex. Each group was divided into two subgroups (n = 10) and stored at 37°C immersed in water for 7 days and in PBS for 60 days. From each subgroup, 1 mm thick sections were obtained. One section of each region (coronal, middle, and apical) was submitted to the push‐out test and failures were observed. Twelve sections of each subgroup (four from each region) were evaluated under SEM. Three‐way ANOVA evaluation for BS showed significant differences between groups and regions (P < 0.0001), but not between subgroups (P > 0.05). AH Plus had significantly higher BS than the others sealers, regardless of the analyzed subgroup (Tukey's test, P < 0.5). The most common failures were adhesive to dentine and cohesive of the sealer. The SEM evaluation (Kruskal–Wallis, Mann–Whitney) showed homogeneous adhesive interface formed and sealer tags in all groups with significant statistical differences with AH Plus, regardless of PBS immersion. AH Plus was superior to the other sealers for both BS and quality of interface formation. Immersion in PBS did not interfere on BS or adhesive interface of the sealers tested. Microsc. Res. Tech. 77:1015–1022, 2014. © 2014 Wiley Periodicals, Inc.
Pathogenesis and classification of intrahepatic cholangiocarcinoma: different characters of perihilar large duct type versus peripheral small duct type
Authors: Aishima Shinichi , Oda Yoshinao
Published: September 2014

Intrahepatic cholangiocarcinomas (ICCs) are made up of heterogenous carcinomas arising from different anatomical sites of the liver. Two types of candidate stem/progenitor cells of the biliary tree are postulated to exist at the peribiliary glands for large bile ducts and at the canals of Hering for small ducts and hepatocytes. According to the recent observations, ICCs can be subclassified into two types: tumors involving the large bile ducts comparable in size to the intrahepatic second branches and composed of a tubular or papillary component with tall columnar epithelium, and tumors involving the smaller duct than segmental branches and composed of small tubules with cuboidal epithelium. Perihilar large duct type ICCs can be interpreted as arising from large bile duct type ICCs, and peripheral small duct type ICCs may arise from small bile duct type or ductular type ICCs. Chronic biliary inflammation induces neoplastic change of the large bile ducts and thereby progression to the perihilar large duct type ICC, which can be grossly classified into periductal filtrating type ICC and intraductal growth type ICC, while chronic hepatitis or cirrhosis induces mass‐forming peripheral small duct type ICC. The different morphological and molecular features, including stromal components and tumor vasculature, support the hypothesis that perihilar large duct type ICCs and peripheral small duct type ICCs arise from different backgrounds, have different carcinogenetic pathways, and exhibit different biologic behaviors.
Eating with a saw for a jaw: Functional morphology of the jaws and tooth‐whorl inHelicoprion davisii
Authors: Ramsay Jason B. , Wilga Cheryl D. , Tapanila Leif , Pruitt Jesse , Pradel Alan , Schlader Robert , Didier Dominique A.
Published: September 2014

The recent reexamination of a tooth‐whorl fossil ofHelicoprioncontaining intact jaws shows that the symphyseal tooth‐whorl occupies the entire length of Meckel's cartilage. Here, we use the morphology of the jaws and tooth‐whorl to reconstruct the jaw musculature and develop a biomechanical model of the feeding mechanism in these early Permian predators. The jaw muscles may have generated large bite‐forces; however, the mechanics of the jaws and whorl suggest thatHelicoprionwas better equipped for feeding on soft‐bodied prey. Hard shelled prey would tend to slip anteriorly from the closing jaws due to the curvature of the tooth‐whorl, lack of cuspate teeth on the palatoquadrate (PQ), and resistance of the prey. When feeding on soft‐bodied prey, deformation of the prey traps prey tissue between the two halves of the PQ and the whorl. The curvature of the tooth‐whorl and position of the exposed teeth relative to the jaw joint results in multiple tooth functions from anterior to posterior tooth that aid in feeding on soft‐bodied prey. Posterior teeth cut and push prey deeper into the oral cavity, while middle teeth pierce and cut, and anterior teeth hook and drag more of the prey into the mouth. Furthermore, the anterior‐posterior edges of the teeth facilitate prey cutting with jaw closure and jaw depression. The paths traveled by each tooth during jaw depression are reminiscent of curved pathways used with slashing weaponry such as swords and knifes. Thus, the jaws and tooth‐whorl may have formed a multifunctional tool for capturing, processing, and transporting prey by cyclic opening and closing of the lower jaw in a sawing fashion. J. Morphol. 276:47–64, 2015. © 2014 Wiley Periodicals, Inc.
The politics of employment liability
Authors: Munyon Timothy P. , Kane‐Frieder Rachel E.
Published: September 2014

Employment liability is an important check and balance against employee harm at work. In practice, however, an inadvertent consequence of employment liability is a potential shift in power from organizations to employees that affects subsequent managerial decision making. In this Incubator, we discuss behavioral and attitudinal ramifications of employment liability at work. Copyright © 2014 John Wiley & Sons, Ltd.
Operative utilization of balloon versus traditional endoscopic sinus surgery
Authors: Ference Elisabeth H. , Graber Madeline , Conley David , Chandra Rakesh K. , Tan Bruce K. , Evans Charlesnika , Pynnonen Melissa , Smith Stephanie S.
Published: September 2014

Objectives/Hypothesis

To study the utilization of balloon catheter dilation (BCD) compared to traditional endoscopic sinus surgery (ESS)

Study Design

Cross‐sectional analysis

Methods

Cases identified by Current Procedural Terminology codes as BCD (2,717) or traditional ESS (31,059) were extracted from the State Ambulatory Surgery Databases 2011 for California, Florida, Maryland, and New York. Patient demographics, surgical center and surgeon volume, mean charge, and operating room (OR) time were compared.

Results

There were 33,776 patients who underwent sinus surgery in the included states in 2011. Of these, 4.6% of maxillary, 5.6% of sphenoid, and 13.9% of frontal procedures were performed using BCD. Adjusted analyses found increased use of BCD in patients with chronic diseases(P < .001). Patients who had limited sinus surgery were less likely to have BCD compared to patients who had all four sinuses instrumented (P < .001). Surgeons who performed a medium (odds ratio 1.38 [1.14–1.65]) or high (odds ratio 1.71 [1.42–2.07]) volume of ESSs were more likely to use BCD compared to those who performed a low volume (P < .001). However, among surgeons who utilized BCD, there was a minimal relationship between the percentage of surgeries performed with BCD and the surgeon's total number of cases (R2 = 0.055). Compared to traditional ESS, the median charges for maxillary/ethmoid procedures (mini‐ESS) involving BCD were approximately $4,500 (P < .001) and maxillary/ethmoid/sphenoid/frontal procedures (pan‐ESS) were approximately $2,950 (P = .003) greater, whereas the median OR time involving BCD was 8 minutes less for mini‐ESS procedures(P = .01) but not statistically different for pan‐ESS procedures (P = .58).

Conclusions

In the study sample, balloon technology was used in 8.0% of ESS cases in 2011. Procedures using BCD were on average more expensive compared to traditional ESS procedures, with minimal decrease in OR time.

Level of Evidence

2c Laryngoscope, 125:49–56, 2015
Early Allograft Dysfunction in Liver Transplantation With Donation After Cardiac Death Donors Results in Inferior Survival
Authors: Lee David D. , Singh Amandeep , Burns Justin M. , Perry Dana K. , Nguyen Justin H. , Taner Burcin C.
Published: September 2014

Donation after cardiac death (DCD) liver allografts have been associated with increased morbidity from primary nonfunction, biliary complications, early allograft failure, cost, and mortality. Early allograft dysfunction (EAD) after liver transplantation has been found to be associated with inferior patient and graft survival. In a cohort of 205 consecutive liver-only transplant patients with allografts from DCD donors at a single center, the incidence of EAD was found to be 39.5%. The patient survival rates for those with no EAD and those with EAD at 1, 3, and 5 years were 97% and 89%, 79% and 79%, and 61% and 54%, respectively (P = 0.009). Allograft survival rates for recipients with no EAD and those with EAD at 1, 3, and 5 years were 90% and 75%, 72% and 64%, and 53% and 43%, respectively (P = 0.003). A multivariate analysis demonstrated a significant association between the development of EAD and the cold ischemia time [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.01–1.56, P = 0.037] and hepatocellular cancer as a secondary diagnosis in recipients (OR = 2.26, 95% CI = 1.11–4.58, P = 0.025). There was no correlation between EAD and the development of ischemic cholangiopathy. In conclusion, EAD results in inferior patient and graft survival in recipients of DCD liver allografts. Understanding the events that cause EAD and developing preventive or early therapeutic approaches should be the focus of future investigations. Liver Transpl 20:1447–1453, 2014. © 2014 AASLD.
Detection of aneuploidy from single fetal nucleated red blood cells using whole genome sequencing
Authors: Hua Rui , Barrett Angela N. , Tan Tuan Zea , Huang Zhouwei , Mahyuddin Aniza Puteri , Ponnusamy Sukumar , Sandhu Jaspal Singh , Ho Sherry S. Y. , Chan Jerry K. Y. , Chong Samuel , Quan Song , Choolani Mahesh
Published: September 2014

Objective

The objective of the study was to detect aneuploidy in single fetal nucleated red blood cells (FNRBCs) from placental villi using whole genome amplification (WGA) and next generation sequencing.

Methods

Three single FNRBCs per sample were manually picked from villi collected from ten women undergoing elective first‐trimester termination of pregnancy, and one or two cells were picked from each of four aneuploid chorionic villus samples. Following WGA and addition of adaptor and index sequences, samples were sequenced on the Illumina MiSeq. Leading and trailing 15 bases were trimmed, and reads were aligned to the human reference genome. Z‐scores were calculated to determine deviation of the mean of the test from reference samples, with a score of 3 used as the threshold for classification of a particular chromosome as trisomic.

Results

We successfully made correct diagnoses from ten single cells isolated from villi from two cases of trisomy 21 (one case from a single cell and one from two cells), two cases of trisomy 18 (two cells each), and a case of trisomy 15 (three cells).

Conclusion

With their faithful representation of fetal genome, diagnosis using single FNRBCs provides a definitive result compared with non‐invasive prenatal testing using cell‐free fetal DNA, and is a safer alternative to invasive amniocentesis. © 2014 John Wiley & Sons, Ltd.
Isobenzofuranone derivatives exhibit antileishmanial effect by inhibiting type II DNA topoisomerase and inducing host response
Authors: Mishra Amartya , Vinayagam Jayaraman , Saha Sourav , Chowdhury Sayan , Roychowdhury Somenath , Jaisankar Parasuraman , Majumder Hemanta K.
Published: September 2014

Leishmania, a protozoan parasite, causes a wide range of human diseases ranging from the localized self‐healing cutaneous lesions to fatal visceral leishmaniasis. Toxicity of traditional first line drugs and emergence of drug‐resistant strains have worsened the situation. DNA topoisomerase II in kinetoplastid protozoan parasites are of immense interest as drug target because they take part in replication of unusual kinetoplast DNA network. In this study, we have taken target‐based therapeutic approaches to combat leishmaniasis. Two isobenzofuranone compounds, viz., (1) 3,5‐bis(4‐chlorophenyl)‐7‐hydroxyisobenzofuran‐1(3H)‐one (JVPH3) and (2) (4‐bromo)‐3′‐hydroxy‐5′‐(4‐bromophenyl)‐benzophenone(JVPH4) were synthesized chemically and characterized by NMR and mass spectrometry analysis. Activity of type II DNA topoisomerase of leishmania (LdTOPII) was monitored by decatenation assay and plasmid cleavage assay. The antiparasitic activity of these compounds was checked in experimental BALB/c mice model of visceral leishmaniasis. Isobenzofuranone derivatives exhibited potent antileishmanial effect on both antimony (Sb) sensitive and resistant parasites. Treatment with isobenzofuranone derivatives on promastigotes caused induction of reactive oxygen species (ROS)‐mediated apoptosis like cell death in leishmania. Both the compounds inhibited the decatenation activity of LdTOPII but have no effect on bi‐subunit topoisomerase IB. Treatment of LdTOPII with isobenzofuranone derivatives did not stabilize cleavage complex formation both in vitro and in vivo. Moreover, treatment with isobenzofuranone derivatives on Leishmania donovani‐infected mice resulted in clearance of parasites in liver and spleen by induction of Th1 cytokines. Taken together, our data suggest that these compounds can be exploited as potential antileishmanial agents targeted to DNA topoisomerase II of the parasite.
Analysis of FK506, timcodar (VX‐853) and FKBP51 and FKBP52 chaperones in control of glucocorticoid receptor activity and phosphorylation
Authors: Hinds Terry D. , Stechschulte Lance A. , Elkhairi Fadel , Sanchez Edwin R.
Published: September 2014

The immunosuppressive ligand FK506 and the FK506‐binding protein FKBP52 are stimulatory to glucocorticoid receptor (GR) activity. Here, we explore the underlying mechanism by comparing GR activity and phosphorylation status in response to FK506 and the novel nonimmunosuppressive ligand timcodar (VX‐853) and in the presence and absence of FKBP52 and the closely related protein FKBP51. Using mouse embryonic fibroblast cells (MEFs) deficient knockout (KO) in FKBP51 or FKBP52, we show decreased GR activity at endogenous genes in 52KO cells, but increased activity in 51KO cells. In 52KO cells, elevated phosphorylation occurred at inhibitory serine 212 and decreased phosphorylation at the stimulatory S220 residue. In contrast, 51KO cells showed increased GR phosphorylation at the stimulatory residues S220 and S234. In wild‐type (WT) MEF cells, timcodar, like FK506, potentiated dexamethasone‐induced GR transcriptional activity at two endogenous genes. Using 52KO and 51KO MEF cells, FK506 potentiated GR activity in 51KO cells but could not do so in 52KO cells, suggesting FKBP52 as the major target of FK506 action. Like FK506, timcodar potentiated GR in 51KO cells, but it also increased GR activity in 52KO cells. Knock‐down of FKBP51 in the 52KO cells showed that the latter effect of timcodar required FKBP51. Thus, timcodar appears to have a dual specificity for FKBP51 and FKBP52. This work demonstrates phosphorylation as an important mechanism in FKBP control of GR and identifies the first nonimmunosuppressive macrolide capable of targeting GR action.
Use of a novel rapid and resource‐efficient cassette dosing approach to determine the pharmacokinetics and CNS distribution of small molecule 7‐transmembrane receptor allosteric modulators in rat
Authors: Bridges Thomas. M. , Morrison Ryan D. , Byers Frank W. , Luo Shuanghui , Scott Daniels J.
Published: September 2014

Approaches to efficiently and accurately define the pharmacokinetics (PK) of large sets of small molecules in rodents have been previously described. Likewise, a variety of methods for determining brain tissue distribution (BTD) have been reported for use in the discovery of therapeutics targeting the central nervous system (CNS). Herein we describe a novel cassette approach to efficiently obtain concurrent PK and BTD data from a dose of up to five compounds in one rat over 24 h. In conjunction with fraction unbound (fu) data obtained in plasma and brain homogenate, this approach serves as an efficient means to determine compound unbound brain:unbound plasma partition coefficients (Kp,uu), thereby providing insight to compounds bearing poor permeability and/or active transporter activity impacting their permeation of the blood–brain barrier (BBB). This integrated approach was utilized in a lead optimization effort towards the discovery of CNS‐penetrant allosteric modulators of a seven‐transmembrane (7TM) receptor target. Rat PK and brain distribution was rapidly obtained for 70 compounds and correlated to data obtained from in vitro assessments. Two compounds that were evaluated in cassette and discrete studies, displayed agreement in PK (compound 1: cassette CLp = 1.6 mL min−1 kg−1, discrete CLp = 1.6 mL min−1 kg−1; compound 2: cassette CLp = 11 mL min−1 kg−1, discrete CLp = 8.1 mL min−1 kg−1) and BTD (compound 1: cassette Kp = 0.11, discrete Kp = 0.09; compound 2: cassette Kp < 0.05, discrete Kp = 0.04). The resulting data were used to guide medicinal chemistry efforts and to enable the progression of optimized compounds to in vivo pharmacodynamic assessments.
Deposition of semiconducting single‐walled carbon nanotubes using light‐assisted dielectrophoresis
Authors: Li Wenshan , Pyatkov Feliks , Dehm Simone , Flavel Benjamin S. , Krupke Ralph
Published: September 2014

Dielectrophoresis (DEP) is an established method for the integration of solution‐processed single‐walled carbon nanotubes into nanoscale device structures. However, this method is less effective for small‐diameter semiconducting nanotubes and leads to an enrichment of metallic tubes in multi‐tube devices. In this work, we present the first results of a novel light‐assisted DEP technique, which enhances the deposition of (6,5) semiconducting carbon nanotubes. Transistors fabricated with this technique show higher on/off ratios compared to transistors that were fabricated by conventional DEP. We explain this effect by an enhanced polarizability of the irradiated semiconducting nanotubes and discuss spontaneous and field‐driven exciton dissociation as the underlying mechanism. Strategies to further improve the effect are also proposed.
Proxy signcryption scheme in the standard model
Authors: Ming Yang , Wang Yumin
Published: September 2014

Proxy signcryption is a novel cryptographic primitive that combines the functionality of a proxy signature with that of a signcryption. However, the security of all the known proxy signcryption schemes were proven in the random oracle, which has received a lot of criticism that the proofs in the random oracle model are not sound with respect to the standard model. Hence, it is an interesting research problem on how to construct a provably secure proxy signcryption scheme in the standard model. In this paper, motivated by Waters' signature scheme, we propose a new construction of proxy signcryption scheme based on bilinear pairing without using random oracles. Then, we use the techniques from provable security to show that the proposed scheme is indistinguishability under adaptive chosen ciphertext attacks secure under the decisional bilinear Diffie–Hellman assumption and existentially unforgeable under the computational Diffie–Hellman assumptions. Compared with the existing schemes with formal security proof, we show that no pairing computation is required in our proxy signcrypt phase with pre‐computations. To the best of our knowledge, our proposed scheme is the first provably secure proxy signcryption scheme in the standard model. Copyright © 2014 John Wiley & Sons, Ltd.
Cold‐formed steel columns under L‐D‐G interaction
Authors: Souza dos Santos Eliane , de Miranda Batista Eduardo , Camotim Dinar
Published: September 2014

The paper addresses an experimental programme that is part of an ongoing investigation on the behaviour, strength and design of cold‐formed steel lipped channel columns undergoing mode interaction involving local, distortional and global buckling. The 16 column specimens tested were selected to exhibit either (i) close local, distortional and critical buckling loads (PcrL ≈︁ PcrD ≈︁ PcrG) or (ii) PcrL ≈︁ PcrD (condition ensured via the cross‐sectional dimensions) and PcrG up to around 20 % below or above that value (difference controlled via the column length). The test set‐up, procedure and results are presented and discussed, and the failure load data obtained are used to explore the possibility of developing a design approach based on the direct strength method (DSM).
CHD7 Maintains Neural Stem Cell Quiescence and Prevents Premature Stem Cell Depletion in the Adult Hippocampus
Authors: Jones Kieran M. , Sarić Nemanja , Russell John P. , Andoniadou Cynthia L. , Scambler Peter J. , Basson M. Albert
Published: September 2014

Neural stem/progenitor cells (NSCs) in the hippocampus produce new neurons throughout adult life. NSCs are maintained in a state of reversible quiescence and the failure to maintain the quiescent state can result in the premature depletion of the stem cell pool. The epigenetic mechanisms that maintain this quiescent state have not been identified. Using an inducible knockout mouse model, we show that the chromatin remodeling factor chromodomain–helicase-DNA-binding protein 7 (CHD7) is essential for maintaining NSC quiescence. CHD7 inactivation in adult NSCs results in a loss of stem cell quiescence in the hippocampus, a transient increase in cell divisions, followed by a significant decline in neurogenesis. This loss of NSC quiescence is associated with the premature loss of NSCs in middle-aged mice. We find that CHD7 represses the transcription of several positive regulators of cell cycle progression and is required for full induction of the Notch target gene Hes5 in quiescent NSCs. These findings directly link CHD7 to pathways involved in NSC quiescence and identify the first chromatin-remodeling factor with a role in NSC quiescence and maintenance. As CHD7 haplo-insufficiency is associated with a range of cognitive disabilities in CHARGE syndrome, our observations may have implications for understanding the basis of these deficits. Stem Cells  2015;33:196–210
Nonlinear hysteretic behavior simulation of reinforced concrete shear walls using the force analogy method
Authors: Li Gang , Zhang Feng , Zhang Yu , Li Hong‐Nan
Published: September 2014

Reinforced concrete (RC) shear walls that provide high strength and stiffness are widely used in buildings to resist lateral loads. It often exhibits complex and multiple hysteretic behaviors, including shear behavior, flexural behavior, strength softening, and deterioration, which are often influenced by the reinforcement and concrete material characteristics, vertical loads, and so on. Significant effort has gone toward developing accurate and efficient models, and these models fall into two categories: macroscopic and microscopic models. The microscopic models are accurate but computationally expensive and need more material information and experimental results for calibration. The present research is to implement an existing macroscopic model for use in the force analogy method, which is an accurate, efficient, and stable algorithm for conducting dynamic analysis when coupled with the state space formulation. The RC shear wall model with two vertical sliding hinges and one horizontal sliding hinge assigned to capture the relationship of the lateral deflection or rotation versus the RC shear wall force is validated against prior experimental results. The proposed model is also implemented in a frame, in which inelastic response occurs in both the frame and the RC shear wall members, to demonstrate the application of the model and the potential for simulating complex inelastic dynamic RC frame‐wall structural behavior with the force analogy method. Copyright © 2014 John Wiley & Sons, Ltd.
Transmission network expansion planning considering renewable energy target with Taguchi's orthogonal array testing
Authors: Chatthaworn Rongrit , Chaitusaney Surachai
Published: September 2014

Nowadays, renewable energy resources are becoming more and more popular. The intermittent nature of renewable energy sources will affect transmission network expansion planning (TNEP). Consequently, this paper presents a new problem formulation and solution procedure for TNEP which can cope with the intermittent characteristics. Taguchi's orthogonal array testing (TOAT) is used to select the scenarios that represent the loads and renewable energy resource uncertainties. In this paper, a new index called the ‘renewable energy leak’ (REL) is proposed to evaluate the ‘unutilized or leaked’ renewable energy in the TNEP. For minimizing the investment cost of transmission network expansion, annual generator operation cost, and annual transmission line loss cost, the meta‐heuristic adaptive Tabu search (ATS) algorithm is used, while the system operating limits including the REL index are taken into account as the optimization constraints. The proposed procedure is tested in a modified IEEE Reliability Test System 79. The results show that the proposed method is efficient and promising. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Realistic model for the multiple‐input floating‐gate transistor
Authors: Cisneros‐Sinencio Luis Fortino , Diaz‐Sanchez Alejandro , Ramirez‐Angulo Jaime , Vazquez‐Leal Hector
Published: September 2014

Multiple‐input floating‐gate transistor (FGMOS) circuit designers face a serious problem along the design process: the lack of a realistic simulation model. For this reason, a solution that properly predicts the initial voltage at the floating gates is presented in this paper. In order to assess the performance of the proposal, a comparison is made against a test circuit fabricated in a 0.5‐µm On‐Semiconductor CMOS process. Based on this comparison, the proposed model is shown to be a fundamental tool in the design of FGMOS circuits. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
A study of biplanar crossed pin construct in the management of displaced pediatric supracondylar humeral fractures
Authors: Mohammed Riazuddin , Bhogadi Prabhudheer , Metikala Sreenivasulu
Published: September 2014

Purpose

Study of a biplanar crossed pin construct by two crossed Kirschner wires in the management of displaced extension type supracondylar humeral fractures in children.

Methods

Sixty-four patients with such fractures were included and treated according to the study protocol: after achieving closed reduction under general anesthesia with fluoroscopic control, two crossed Kirschner wires of equal diameter were inserted percutaneously. The first lateral wire tracts from the posterolateral corner of the epicondyle to the anteromedial cortex proximally. Then, the medial wire is inserted from the anteromedial corner of the epicondyle to the posterolateral cortex proximally after crossing the fracture site. Thus, a biplanar crossed pin construct was achieved, as each wire had two separate fixation points and the crossed construct was achieved not only in the coronal plane but also in the sagittal plane. Every effort was made to get this construct right at the very first attempt without repetition.

Results

Two patients were lost to follow-up during the first postoperative year. The mean follow-up for the remaining 62 patients was 14.5 months (range 6–24 months). At the final follow-up, using Flynn's overall modified classification, the clinical result was considered to be satisfactory in 60 (96.8 %) patients and unsatisfactory with poor result in two (3.2 %) patients. Technical error was thought to be the cause of the poor results. There were no postoperative neural or vascular complications.

Conclusion

A biplanar crossed pin construct achieved by two Kirschner wires crossed in the coronal and sagittal planes is efficient to stabilize a displaced extension type supracondylar fracture of the humerus in children.
SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) 2014
Authors: Garcia-Carbonero R. , JImenez-Fonseca P. , Teulé A. , Barriuso J. , Sevilla I.
Published: September 2014

GEP-NENs are a challenging family of tumors of growing incidence and varied clinical management and behavior. Diagnostic techniques have substantially improved over the past decades and significant advances have been achieved in the understanding of the molecular pathways governing tumor initiation and progression. This has already translated into relevant advances in the clinic. This guideline aims to provide practical recommendations for the diagnosis and treatment of GEP-NENs. Diagnostic workup, histological and staging classifications, and the different available therapeutic approaches, including surgery, liver-directed ablative therapies, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are briefly discussed in this manuscript. Clinical presentation (performance status, comorbidities, tumor-derived symptoms and hormone syndrome in functioning tumors), histological features [tumor differentiation, proliferation rate (Ki-67), and expression of somatostatin receptors], disease localization and extent, and resectability of primary and metastatic disease, are all key issues that shall be taken into consideration to appropriately tailor therapeutic strategies and surveillance of these patients.
Membranproteinsynthese: Zellfrei geht’s schneller!
Authors: Sachse Rita , Quast Robert B. , Sonnabend Andrei , Stech Marlitt , Kubick Stefan
Published: September 2014

Difficult to express membrane proteins represent an increasing amount of therapeutic molecules. Considerable optimization is often required for downstream applications such as assay development and functional characterization. Cell-free systems emerged as powerful tools for the synthesis of structurally and functionally divergent membrane proteins. Vesicle-based eukaryotic cell-free systems enable co-translational protein translocation and posttranslational modifications. Hence, these systems provide a multitude of options for membrane protein studies.
Brief report: Parent–adolescent child concordance in social norms related to gender equity in marriage – findings from rural India
Authors: Raj Anita , Ghule Mohan , Battala Madhusudana , Dasgupta Anindita , Ritter Julie , Nair Saritha , Saggurti Niranjan , Silverman Jay G. , Balaiah Donta
Published: September 2014

The purpose of this exploratory study was to assess parent–adolescent child concordance on social norms related to gender equity in marriage in rural Maharashtra, India. Survey data on marital norms related to girl's marital age and choice, contraception, and marital violence (MV) were collected from unmarried adolescents (n = 113 girls, 116 boys) and their parents (n = 227 mothers, 203 fathers). Concordance was assessed using a Cohen's unweighted Kappa statistic, with analyses stratified by sex of parent and child. Analyses revealed fair (K = .25–.27) mother‐daughter concordance on girls' right to choose when to marry, contraception use, and acceptability of MV. Father‐son concordance was seen on girls' right to choose when (K = .22, slight) and who (K = .20, fair) to marry and MV acceptability (K = .53, moderate). No opposite sex parent‐child concordance was revealed. Results indicate same but not opposite sex parent‐child concordance on gender equity social norms related to marriage, suggesting same sex transfer of these norms.
Smoking, alcohol consumption, and drug use among adolescents with psychiatric disorders compared with a population based sample
Authors: Mangerud Wenche Langfjord , Bjerkeset Ottar , Holmen Turid Lingaas , Lydersen Stian , Indredavik Marit Sæbø
Published: September 2014

This study investigated frequencies of smoking, alcohol use, and illicit drug use by diagnostic category in 566 adolescent psychiatric patients, comparing this sample with 8173 adolescents from the general population in Norway who completed the Young‐HUNT 3 survey. Frequencies of current alcohol use were high in both samples but were lower among psychiatric patients. Compared with adolescents in the general population, adolescents in the clinical sample had a higher prevalence of current smoking and over four times higher odds of having tried illicit drugs. In the clinical sample, those with mood disorders reported the highest frequencies of smoking, alcohol use, and illicit drug use, whereas those with autism spectrum disorders reported the lowest frequencies. Our results show an increased prevalence of risky health behaviors among adolescents with psychiatric disorders compared with the general population. The awareness of disorder‐specific patterns of smoking and substance use may guide preventive measures.
Quercetin‐3‐glucoside increases low‐density lipoprotein receptor (LDLR) expression, attenuates proprotein convertase subtilisin/kexin 9 (PCSK9) secretion, and stimulates LDL uptake by Huh7 human hepatocytes in culture
Authors: Mbikay Majambu , Sirois Francine , Simoes Sonia , Mayne Janice , Chrétien Michel
Published: September 2014

Low‐density lipoprotein receptor (LDLR) mediates hepatic clearance of plasma cholesterol; proprotein convertase subtilisin/kexin 9 (PCSK9) opposes this clearance by promoting LDLR degradation. The plant flavonoid quercetin‐3‐β‐d‐glucoside (Q3G) has been shown to reduce hypercholesterolemia in experimental animals. Here, we examined how it affects LDLR and PCSK9 expression as well as LDL uptake by human Huh7 hepatocytes. At low micromolar concentrations, Q3G increased LDLR expression, reduced PCSK9 secretion, and stimulated LDL uptake. It also diminished intracellular sortilin, a sorting receptor known to facilitate PCSK9 secretion. Thus, as an LDLR inducer and a PCSK9 anti‐secretagogue, Q3G may represent an effective anti‐cholesterolemic agent.
Is there a link between proprotein convertase PC7 activity and human lipid homeostasis?
Authors: Guillemot Johann , Essalmani Rachid , Hamelin Josée , Seidah Nabil G.
Published: September 2014

A genome‐wide association study suggested that a R504H mutation in the proprotein convertase PC7 is associated with increased circulating levels of HDL and reduced triglycerides in black Africans. Our present results show that PC7 and PC7‐R504H exhibit similar processing of transferrin receptor‐1, proSortilin, and apolipoprotein‐F. Plasma analyses revealed no change in the lipid profiles, insulin or glucose of wild type and PC7 KO mice. Thus, the R504H mutation does not modify the proteolytic activity of PC7. The mechanisms behind the implication of PC7 in the regulation of human HDL, triglycerides and in modifying the levels of atherogenic small dense LDL remain to be elucidated.
Expanding the Use of Noninvasive Ventilation During an Epidemic
Authors: Kopić Jasminka , Paradžik Maja Tomić
Published: September 2014

Noninvasive ventilation (NIV) is a proved and effective therapeutic option for some patients with respiratory failure. During an epidemic, NIV can free up respirators and other intensive care unit equipment for patients with respiratory insufficiency whose survival depends exclusively on invasive ventilation. Some guidelines have indicated that NIV is potentially hazardous and should not be recommended for use during epidemics, given the perceived potential risk of transmission from aerosolized pathogen dispersion to other patients or medical staff. Conversely, some reports of previous epidemics describe NIV as a very efficient and safe modality of respiratory support, if strict infection control measures are implemented.

We discuss NIV use during epidemics and indicate the need for prospective randomized clinical studies on the efficacy of NIV in epidemic conditions to provide important information to the current body of literature. Meanwhile, the use of NIV under strict infection control guidelines should be incorporated into epidemic preparedness planning. (Disaster Med Public Health Preparedness. 2014;8:1-5)