bluuebunny/crossref_metadata_2025 huggingface dataset:
Interventions to improve or facilitate linkage to or retention in pre‐ART (HIV) care and initiation of ART in low‐ and middle‐income settings – a systematic review
Authors: Govindasamy Darshini , Meghij Jamilah , Negussi Eyerusalem Kebede , Baggaley Rachel Clare , Ford Nathan , Kranzer Katharina
Published: August 2014

Introduction

Several approaches have been taken to reduce pre‐antiretroviral therapy (ART) losses between HIV testing and ART initiation in low‐ and middle‐income countries, but a systematic assessment of the evidence has not yet been undertaken. The aim of this systematic review is to assess the potential for interventions to improve or facilitate linkage to or retention in pre‐ART care and initiation of ART in low‐ and middle‐income settings.

Methods

An electronic search was conducted on Medline, Embase, Global Health, Web of Science and conference databases to identify studies describing interventions aimed at improving linkage to or retention in pre‐ART care or initiation of ART. Additional searches were conducted to identify on‐going trials on this topic, and experts in the field were contacted. An assessment of the risk of bias was conducted. Interventions were categorized according to key domains in the existing literature.

Results

A total of 11,129 potentially relevant citations were identified, of which 24 were eligible for inclusion, with the majority (n=21) from sub‐Saharan Africa. In addition, 15 on‐going trials were identified. The most common interventions described under key domains included: health system interventions (i.e. integration in the setting of antenatal care); patient convenience and accessibility (i.e. point‐of‐care CD4 count (POC) testing with immediate results, home‐based ART initiation); behaviour interventions and peer support (i.e. improved communication, patient referral and education) and incentives (i.e. food support). Several interventions showed favourable outcomes: integration of care and peer supporters increased enrolment into HIV care, medical incentives increased pre‐ART retention, POC CD4 testing and food incentives increased completion of ART eligibility screening and ART initiation. Most studies focused on the general adult patient population or pregnant women. The majority of published studies were observational cohort studies, subject to an unclear risk of bias.

Conclusions

Findings suggest that streamlining services to minimize patient visits, providing adequate medical and peer support, and providing incentives may decrease attrition, but the quality of the current evidence base is low. Few studies have investigated combined interventions, or assessed the impact of interventions across the HIV cascade. Results from on‐going trials investigating POC CD4 count testing, patient navigation, rapid ART initiation and mobile phone technology may fill the quality of evidence gap. Further high‐quality studies on key population groups are required, with interventions informed by previously reported barriers to care.
General qPCR and Plate Reader Methods for Rapid Optimization of Membrane Protein Purification and Crystallization Using Thermostability Assays
Authors: Tomasiak Thomas M. , Pedersen Bjørn P. , Chaudhary Sarika , Rodriguez Andrew , Colmanares Yaneth Robles , Roe‐Zurz Zygy , Thamminana Sobha , Tessema Meseret , Stroud Robert M.
Published: August 2014

This unit describes rapid and generally applicable methods to identify conditions that stabilize membrane proteins using temperature‐based denaturation measurements as a proxy for target time‐dependent stability. Recent developments with thiol‐reactive dyes sensitive to the unmasking of cysteine residues upon protein unfolding have allowed for routine application of thermostability assays to systematically evaluate the stability of membrane protein preparations after various purification procedures. Test conditions can include different lipid cocktails, lipid‐detergent micelles, pH, salts, osmolytes, and potential active‐site ligands. Identification and use of conditions that stabilize the structure have proven successful in enabling the structure determination of numerous families of membrane proteins that otherwise were intractable. Curr. Protoc. Protein Sci. 77:29.11.1‐29.11.14 © 2014 by John Wiley & Sons, Inc.
Sensitivity of ocean oxygenation to variations in tropical zonal wind stress magnitude
Authors: Ridder Nina N. , England Matthew H.
Published: August 2014

Ocean oxygenation has been observed to have changed over the past few decades and is projected to change further under global climate change due to an interplay of several mechanisms. In this study we isolate the effect of modified tropical surface wind stress conditions on the evolution of ocean oxygenation in a numerical climate model. We find that ocean oxygenation varies inversely with low‐latitude surface wind stress. Approximately one third of this response is driven by sea surface temperature anomalies; the remaining two thirds result from changes in ocean circulation and marine biology. Global mean O2 concentration changes reach maximum values of +4 μM and −3.6 μM in the two most extreme perturbation cases of −30% and +30% wind change, respectively. Localized changes lie between +92 μM under 30% reduced winds and −56 μM for 30% increased winds. Overall, we find that the extent of the global low‐oxygen volume varies with the same sign as the wind perturbation; namely, weaker winds reduce the low‐oxygen volume on the global scale and vice versa for increased trade winds. We identify two regions, one in the Pacific Ocean off Chile and the other in the Indian Ocean off Somalia, that are of particular importance for the evolution of oxygen minimum zones in the global ocean.
Low‐temperature thermochronologic record of Eocene migmatite dome emplacement and late Cenozoic landscape development, Shuswap core complex, British Columbia
Authors: Toraman Erkan , Teyssier Christian , Whitney Donna L. , Fayon Annia K. , Thomson Stuart N. , Reiners Peter W.
Published: August 2014

Exhumed mid‐to‐lower crustal rocks offer an opportunity to determine the mechanisms, conditions, timing, and consequences of the ascent of hot rocks from deep to shallow crustal levels. We used results of low‐T thermochronology (zircon and apatite (U‐Th)/He, apatite fission track) to document the very shallow emplacement (<2 km) of high‐grade metamorphic rocks and to determine the timing and rates of Cenozoic cooling, exhumation, and subsequent incision of the Thor‐Odin migmatite dome of the Shuswap metamorphic core complex, British Columbia (Canada). Samples collected at high elevation in the dome (>1800 m) have preserved Eocene fission‐track ages and evidence of rapid cooling (≥60°C/Myr). This Eocene cooling event corresponds to rapid exhumation by upward flow of partially molten crust and final exhumation by detachment faulting. Samples collected below 1800 m in elevation display a wide range of apatite fission track ages (43–15 Ma) and track length distributions that reflect prolonged residence in the apatite partial annealing zone. These age‐elevation relations imply that the dome rocks reached the near surface (<2 km) during initial upward flow and tectonic exhumation in the Eocene and that little erosion of the Eocene surface has occurred since that time. Thermal modeling of the lowest elevation samples (≤ ~600 m) and intrasample apatite (U‐Th)/He age variations reveal enhanced erosion and relief production at the onset of continental glaciations at ~3 Ma. Our work illustrates the dynamic links between deep and shallow crustal processes and the evolution of topography in a deeply incised hot orogen.
Lunar tide contribution to thermosphere weather
Authors: Zhang Jesse T. , Forbes Jeffrey M. , Zhang Casey H. , Doornbos Eelco , Bruinsma Sean L.
Published: August 2014

As the utilization of low‐Earth orbit increases, so does the need for improved ephemeris predictions and thus more accurate density models. In this paper we quantify the density variability of the thermosphere attributable to the lunar gravitational tide, a potentially predictable component of variability not included in any operational density prediction models to date. Using accelerometer measurements from the GOCE satellite near 260 km altitude, the level of lunar tidal density variability is shown to be about half that associated with the low level of geomagnetic variability that occurs about 75% of the time (Kp ≤ 3), thus constituting an element of “space weather.” Our conclusion is that the lunar tide ought to be considered for inclusion in contemporary density models of the thermosphere for operational ephemeris predictions. Some suggested first steps are included in the conclusions of this paper.
Molecular Typing ofBorrelia burgdorferi
Authors: Wang Guiqing , Liveris Dionysios , Mukherjee Priyanka , Jungnick Sabrina , Margos Gabriele , Schwartz Ira
Published: August 2014

Borrelia burgdorferisensu lato is a group of spirochetes belonging to the genusBorreliain the family of Spirochaetaceae. The spirochete is transmitted between reservoirs and hosts by ticks of the family Ixodidae. Infection withB. burgdorferiin humans causes Lyme disease or Lyme borreliosis. Currently, 20 Lyme disease‐associatedBorreliaspecies and more than 20 relapsing fever‐associatedBorreliaspecies have been described. Identification and differentiation of differentBorreliaspecies and strains is largely dependent on analyses of their genetic characteristics. A variety of molecular techniques have been described forBorreliaisolate speciation, molecular epidemiology, and pathogenicity studies. In this unit, we focus on three basic protocols, PCR‐RFLP‐based typing of therrs‐rrlAandrrfA‐rrlBribosomal spacer,ospCtyping, and MLST. These protocols can be employed alone or in combination for characterization ofB. burgdorferiisolates or directly on uncultivated organisms in ticks, mammalian host reservoirs, and human clinical specimens.Curr. Protoc. Microbiol. 34:12C.1‐12C.31. © 2014 by John Wiley & Sons, Inc.
Palladium‐Catalyzed CP Cross‐Coupling of Arylhydrazines with H‐Phosphonates via CN Bond Cleavage
Authors: Xu Wentao , Hu Gaobo , Xu Pengxiang , Gao Yuxing , Yin Yingwu , Zhao Yufen
Published: August 2014

A novel and efficient methodology that allows for the construction of CP bonds via the palladium‐catalyzed oxygen‐based oxidative cross‐coupling of various arylhydrazines with H‐phosphonates leading to valuable arylphosphonates has been developed with the use of O2 as the green oxidant; the method has broad substrate applicability and furnishes good to excellent yields. This protocol is the first example of a transition metal‐catalyzed CP bond formation between arylhydrazines and H‐phosphonates via unactivated aryl CN bond cleavage.

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Environmental Friendly Pulping of Kenaf Using Monoethanolamine: Influence of the Process Variables on the Strength Properties
Authors: Habashi Masoud Ghahremani , Hedjazi Sahab , Ashori Alireza , Abdulkhani Ali
Published: August 2014

In this work, monoethanolamine (MEA), an organosolv material, was used as an environmentally friendly process for kenaf whole‐stem pulping. The pulping trials were carried out using MEA and MEA‐anthraquinone (MEA‐AQ) methods and the soda‐AQ process as reference. The operating conditions such as the composition of the cooking liquor, the maximum cooking temperature and the cooking time, and a solid/liquor ratio during the pulping process were investigated systematically to establish optimal pulping conditions. The optimum cooking conditions for MEA pulping were 75% MEA concentration, 90‐min cooking time, 160°C cooking temperature, 0.1% AQ, and liquor/kenaf ratio of 4/1. The laboratory‐scale experimental results indicated that this pulping process is particularly well suited for the pulping of kenaf, where the whole stem was delignified to a low kappa number value of 19.8 and the pulp yield of 55.1%. This newly developed pulping process provided a high tensile, tear, and burst indices of 19.8 N·m/g, 5.9 mN·m2/g, and 1.43 kPa·m2/g, respectively. In addition, MEA‐AQ kenaf whole‐stem pulp showed superior mechanical properties in comparison with MEA and soda‐AQ pulp. MEA‐AQ pulping is a good alternative to soda‐AQ pulping to produce high yield pulp with high strength from kenaf whole stem.
Studies on Bismaleamic Acids Cured Tetrafunctional Epoxy Resin of Bisphenol‐C and Glass‐Epoxy Composites
Authors: Patel Jignesh P. , Bhatt Ritesh D. , Parsania Parsotam H.
Published: August 2014

The tetrafunctional epoxy resin of bisphenol‐C was cured using bismaleamic acids of maleicanhydride and 4,4'‐diaminodiphenylsulfone, 4,4'‐diaminodiphenylether, and 4,4'‐diaminodiphenylmethane and characterized by infrared, differential scanning calorimetric, and thermogravimetric analysis. Cured resins showed endothermic transition at about 229–248°C, which supplemented decomposition reactions. Cured resins are thermally stable up to about 200–230°C and followed two‐step decomposition reactions. A 34–56% residue at 600°C supplemented the formation of highly thermally stable cross‐linked products. Glass composites showed 133–153 MPa tensile strength, 223–290 MPa flexural strength, 7520–8015 MPa flexural modulus, 33–38 kg m−2 impact strength, 37–40 Barcol hardness, 8.3–12.3 kV mm−1 electric strength, 8.9 × 1012 to 4.2 × 1014 ohm cm volume resistivity, and 13–14% water absorption. Good thermal, mechanical and electrical properties and excellent hydrolytic stability of the glass composites signify their industrial importance for low load bearing housing, electrical, and marine applications.
Neurodevelopment in new‐onset juvenile myoclonic epilepsy over the first 2 years
Authors: Lin Jack J. , Dabbs Kevin , Riley Jeffrey D. , Jones Jana E. , Jackson Daren C. , Hsu David A. , Stafstrom Carl E. , Seidenberg Michael , Hermann Bruce P.
Published: August 2014

Objective

Adults with juvenile myoclonic epilepsy (JME) have subtle brain structural abnormalities in the frontothalamocortical network, poorer cognitive function, and worse long‐term social outcomes, even when their seizures are controlled and/or remitted. The natural history of JME and development of abnormalities in brain structure and cognition from epilepsy onset has not been studied.

Methods

The maturational trajectories of cognitive and brain development were prospectively compared between 19 children with new‐onset JME in the first 2 years after diagnosis and 57 healthy controls.

Results

Cognitive abilities of children with JME were similar to or worse than healthy controls at baseline but failed to reach the competence level of healthy controls at follow‐up across most of the tested cognitive abilities. Abnormal patterns of brain development, as assessed by magnetic resonance imaging studies, were evident in children with JME and included attenuation of age‐related decline in cortical volume, thickness, and surface area compared to typically developing children. The altered brain developmental trajectory in the JME group was evident in higher‐association frontoparietotemporal brain regions (p < 0.05, corrected for multiple comparisons).

Interpretation

Children with JME have abnormal structural brain development and impaired cognitive development early in the course of their epilepsy. Ann Neurol 2014;76:660–668
Switchable Proline Derivatives: Tuning the Conformational Stability of the Collagen Triple Helix by pH Changes
Authors: Siebler Christiane , Erdmann Roman S. , Wennemers Helma
Published: August 2014

(4S)‐Aminoproline is introduced as a pH‐sensitive probe for tuning the conformational properties of peptides and proteins. The pH‐triggered flip of the ring puckering and the formation/release of a transannular H bond were used to switch the formation of collagen triple helices on and off reversibly.
Low expression levels of microRNA‐124‐5p correlated with poor prognosis in colorectal cancer via targeting of SMC4
Authors: Jinushi Takafumi , Shibayama Yoshihiko , Kinoshita Ichiro , Oizumi Satoshi , Jinushi Masahisa , Aota Tadahiro , Takahashi Toshiyuki , Horita Shoichi , Dosaka‐Akita Hirotoshi , Iseki Ken
Published: August 2014

A component of polycomb repressor complex 2, enhancer of zeste homolog 2 (EZH2), plays an important role in tumor malignancy and metastasis, while milk fat globule‐epidermal growth factor‐factor 8 (MFGE8) plays a key role in tumor progression and prognosis. MicroRNAs (miRs) are also critically involved in various physiological and pathological processes. We here evaluated the relationship between overall survival (OS) in colorectal cancer patients and the expression of onco‐miRs and miRs, which may target EZH2 and MFGE8. Plasma and formalin‐fixed paraffin‐embedded (FFPE) samples were obtained from 71 colorectal cancer patients. The expression levels of miRs complementary to EZH2 and MFGE8 mRNA and cancer malignancies were evaluated. The miRs analyzed were as follows: miR‐16, miR‐21, miR‐26a, miR‐34a, miR‐98, miR‐101‐3p, miR‐101‐5p, miR‐124‐5p (also known as miR‐124*), miR‐126‐3p, miR‐126‐5p, miR‐210, miR‐217, and miR‐630. The plasma expression levels of MFGE8 in completely resected patients were significantly lower than those in unresectable patients. Lower miR‐26a expression levels were correlated with a higher probability of OS. Higher miR‐124‐5p expression levels in plasma and FFPE samples were correlated with a higher probability of OS. The transfection of mimic miR‐124‐5p into WiDr and COLO201 cells inhibited the expression of structural maintenance of chromosomes 4 (SMC4) mRNA. Our results indicate that miR‐124‐5p may target the tumorigenesis gene, SMC4, which suggests that expression levels of miR‐124‐5p in plasma and FFPE samples; therefore, the expression of MFGE8, miR‐26a, and miR‐124‐5p in plasma may be used as biomarkers to determine the prognosis of colorectal cancer patients.
O6‐Alkylguanine‐DNA Alkyltransferase‐Mediated Repair of O4‐Alkylated 2′‐Deoxyuridines
Authors: McManus Francis P. , Wilds Christopher J.
Published: August 2014

O6‐Alkylguanine‐DNA alkyltransferases (AGTs) are responsible for the removal of O6‐alkyl 2′‐deoxyguanosine (dG) and O4‐alkyl thymidine (dT) adducts from the genome. Unlike the E. coli OGT (O6‐alkylguanine‐DNA‐alkyltransferase) protein, which can repair a range of O4‐alkyl dT lesions, human AGT (hAGT) only removes methyl groups poorly. To uncover the influence of the C5 methyl group of dT on AGT repair, oligonucleotides containing O4‐alkyl 2′‐deoxyuridines (dU) were prepared. The ability of E. coli AGTs (Ada‐C and OGT), human AGT, and an OGT/hAGT chimera to remove O4‐methyl and larger adducts (4‐hydroxybutyl and 7‐hydroxyheptyl) from dU were examined and compared to those relating to the corresponding dT species. The absence of the C5 methyl group resulted in an increase in repair observed for the O4‐methyl adducts by hAGT and the chimera. The chimera was proficient at repairing larger adducts at the O4 atom of dU. There was no observed correlation between the binding affinities of the AGT homologues to adduct‐containing oligonucleotides and the amounts of repair measured.
Vanadium Speciation by XANES Spectroscopy: A Three‐Dimensional Approach
Authors: Levina Aviva , McLeod Andrew I. , Lay Peter A.
Published: August 2014

A library of X‐ray absorption near‐edge structure (XANES) spectroscopic data for VV, VIV and VIII complexes with a broad range of biologically relevant ligand has been used to demonstrate that three‐dimensional plots of key XANES parameters (pre‐edge and edge energies; pre‐edge and white line intensities) can be used for the prediction of V oxidation states and coordination numbers in biological or environmental matrices. The reliability of the technique has been demonstrated by re‐analysis of the published XANES data for a VV‐dependent bromoperoxidase.
Total Synthesis of (R,R,R)‐α‐Tocopherol Through Asymmetric Cu‐Catalyzed 1,4‐Addition
Authors: Termath Andreas Ole , Sebode Hanna , Schlundt Waldemar , Stemmler René T. , Netscher Thomas , Bonrath Werner , Schmalz Hans‐Günther
Published: August 2014

By introducing a disposable activating substituent at C‐3, the asymmetric 1,4‐addition to a notoriously unreactive 2‐substituted chromenone was achieved with high levels of (2R)‐stereoselectivity in the presence of a chiral CuI‐phosphoramidite complex as a catalyst. This paved the way for an efficient and conceptually novel synthesis of (R,R,R)‐α‐tocopherol from readily available starting materials.
Implementation of a generalized heterogeneous image reconstruction system for clinical magnetic resonance
Authors: Kowalik Grzegorz Tomasz , Steeden Jennifer Anne , Muthurangu Vivek
Published: August 2014

This paper describes the development of a novel online, heterogeneous image reconstruction system for magnetic resonance data. The system integrates an external computer equipped with a graphic processing unit card into the magnetic resonance scanner's image reconstruction pipeline. The system promotes fast online reconstruction for computationally intensive algorithms making them feasible in a busy clinical service. Analysis and improvement of execution time of the complex, iterative reconstruction algorithm is presented. Specifically, optimizations were examined that allowed fast reconstruction of data that were acquired in an arbitrary manner. The system was successfully used in research and clinical studies requiring high data throughput. Copyright © 2014 John Wiley & Sons, Ltd.
One‐pot Aldol Condensation and Hydrodeoxygenation of Biomass‐derived Carbonyl Compounds for Biodiesel Synthesis
Authors: Faba Laura , Díaz Eva , Ordóñez Salvador
Published: August 2014

Integrating reaction steps is of key interest in the development of processes for transforming lignocellulosic materials into drop‐in fuels. We propose a procedure for performing the aldol condensation (reaction between furfural and acetone is taken as model reaction) and the total hydrodeoxygenation of the resulting condensation adducts in one step, yielding n‐alkanes. Different combinations of catalysts (bifunctional catalysts or mechanical mixtures), reaction conditions, and solvents (aqueous and organic) have been tested for performing these reactions in an isothermal batch reactor. The results suggest that the use of bifunctional catalysts and aqueous phase lead to an effective integration of both reactions. Therefore, selectivities to n‐alkanes higher than 50 % were obtained using this catalyst at typical hydrogenation conditions (T=493 K, P=4.5 MPa, 24 h reaction time). The use of organic solvent, carbonaceous supports, or mechanical mixtures of monofunctional catalysts leads to poorer results owing to side effects; mainly, hydrogenation of reactants and adsorption processes.
Pard3 regulates contact between neural crest cells and the timing of Schwann cell differentiation but is not essential for neural crest migration or myelination
Authors: Blasky Alex J. , Pan Luyuan , Moens Cecilia B. , Appel Bruce
Published: August 2014

Background: Schwann cells, which arise from the neural crest, are the myelinating glia of the peripheral nervous system. During development neural crest and their Schwann cell derivatives engage in a sequence of events that comprise delamination from the neuroepithelium, directed migration, axon ensheathment, and myelin membrane synthesis. At each step neural crest and Schwann cells are polarized, suggesting important roles for molecules that create cellular asymmetries. In this work we investigated the possibility that one polarity protein, Pard3, contributes to the polarized features of neural crest and Schwann cells that are associated with directed migration and myelination. Results: We analyzed mutant zebrafish embryos deficient for maternal and zygotic pard3 function. Time‐lapse imaging revealed that neural crest delamination was normal but that migrating cells were disorganized with substantial amounts of overlapping membrane. Nevertheless, neural crest cells migrated to appropriate peripheral targets. Schwann cells wrapped motor axons and, although myelin gene expression was delayed, myelination proceeded to completion. Conclusions: Pard3 mediates contact inhibition between neural crest cells and promotes timely myelin gene expression but is not essential for neural crest migration or myelination. Developmental Dynamics 243:1511–1523, 2014. © 2014 Wiley Periodicals, Inc.
Down syndrome cell adhesion molecule is important for early development in Xenopus tropicalis
Authors: Morales Diaz Heidi D.
Published: August 2014

The Down syndrome cell adhesion molecule (DSCAM) is an Ig containing cell adhesion molecule with remarkable structural conservation throughout metazoans. In insects, DSCAM has 38,000 potential isoforms that convey axon guidance, fasciculation, and dendrite morphogenesis during neurodevelopment. In vertebrates, DSCAM is expressed throughout the nervous system and seems to also mediate proper axonal guidance and synaptogenesis without the isoform diversity found in insects. Differences in DSCAM function among several vertebrate species complicate the understanding of an evolutionarily conserved role during embryogenesis. We take advantage of the frog developmental model Xenopus tropicalis to study DSCAM function in early development by expression analysis and morpholino‐mediated knockdown. Our results indicate that DSCAM is expressed early in development and restricted to the head and nervous system. Knockdown of protein expression results in early morphogenetic phenotypes characterized by failed gastrulation and improper posterior neural tube closure. Our results reveal a specific, fundamental role of DSCAM in early morphogenetic movements, presumably through its well‐known role in homophilic cell adhesion. genesis 52:849–857, 2014. © 2014 Wiley Periodicals, Inc.
σ‐ or π‐Coordination? Complexes of Univalent Gallium Salts with Aromatic Nitrogen Bases
Authors: Lichtenthaler Martin R. , Stahl Florian , Kratzert Daniel , Benkmil Boumahdi , Wegner Hermann A. , Krossing Ingo
Published: August 2014

To answer the question as to whether gallium in its oxidation state +1 favors a σ‐ or a π‐coordination of aromatic nitrogen bases, we reacted [Ga(C6H5F)2]+[Al(ORF)4]– {RF = C(CF3)} with pyrazine and 2,6‐di‐tert‐butyl‐4‐methylpyridine (DTBMP). In doing so, we obtained the first tricoordinate, nonchelated, homoleptic N‐donor complex of gallium(I): [Ga(pyrazine)3]+[Al(ORF)4]–, in which each gallium(I) cation is coordinated in a trigonal‐pyramidal fashion by three η1‐donating pyrazine ligands. Hence, the gallium(I) cations favor σ‐ over π‐coordination. Depending on the reaction conditions, and due to the bifunctionality of pyrazine, 1D coordination polymers of {[Ga(μ‐pyrazine)2(η1‐pyrazine)]+[Al(ORF)4]–}∞ were also obtained. With the sterically demanding DTBMP, which is conventionally used as a proton scavenger, the mixed complex [Ga(C6H5F)2(DTBMP)]+[Al(ORF)4]– was isolated, thus proving incorrect the perception of DTBMP being “non‐nucleophilic”. The structural findings were confirmed by multinuclear NMR investigations and density functional performed at the RI‐BP86/SV(P) level.
Synthesis of Pyrrolidines and Pyrroles by Tandem Amination/Cyanation/Alkylation and Amination/Oxidation Sequences
Authors: Han Junbin , Lu Zhichao , Hammond Gerald B. , Xu Bo
Published: August 2014

Copper‐catalyzed three‐component tandem amination/cyanation/alkylation of the primary‐amine‐tethered alkynes 1 gave α‐CN‐substituted pyrrolidines 6 in good yields and regioselectivities. In addition, silver‐mediated tandem amination/oxidation of the secondary‐amine‐tethered alkynes 7 produced functionalized pyrroles 8 in good yields. All reactions were conducted in one pot without any protection/deprotection steps.
Ratio estimators of the population mean with missing values using ranked set sampling
Authors: Al‐Omari A. I. , Bouza C. N.
Published: August 2014

The existence of missing observations (MO) is commonly solved by using imputation methods. There are ratio‐based methods for estimating the population mean, while using simple random sampling (SRS), when MO are present. Considering the existence of MO and using of ranked set sampling, we develop a study of the estimation of a population mean using ratio‐based methods. The mean square errors, bias, and gain in accuracy formulas of the suggested estimators are derived. The suggested estimators are compared with their SRS counterpart both theoretically and numerically. Copyright © 2014 John Wiley & Sons, Ltd.
Landscapes on the edge: examining the role of climatic interactions in shaping coastal watersheds using a coastal–terrestrial landscape evolution model
Authors: Hackney Christopher , Darby Stephen E. , Leyland Julian
Published: August 2014

Incised coastal gullies (ICGs) are dynamic features found at the terrestrial‐coastal interface. Their geomorphic evolution is driven by the interactions between processes of fluvial knickpoint migration and coastal cliff erosion. Under scenarios of future climate change the frequency and magnitude of the climatological drivers of both terrestrial (fluvial and hillslope) and coastal (cliff erosion) processes are likely to change, with an adjunct impact on these types of coastal features. Here we explore the response of an incised coastal gully to changes in both terrestrial and coastal climate in order to elucidate the key process interactions which drive ICG evolution.

We modify an extant landscape evolution model, CHILD, to incorporate processes of soft‐cliff erosion. This modified version, termed the Coastal‐Terrestrial‐CHILD (CT‐CHILD) model, is then employed to explore the interactions between changing terrestrial and coastal driving forces on the future evolution of an ICG found on the south‐west Isle of Wight, UK. It was found that the magnitude and frequency of storm events will play a key role in determining the future trajectory of ICGs, highlighting a need to understand the role of event sequencing in future projections of landscape evolution. Furthermore, synergistic (positive) and antagonistic (negative) interactions were identified between coastal and terrestrial parameters, such as wave height intensity and precipitation duration, which act to modulate the impact of changes in any one parameter. Of note was the role played by wave height intensity in driving coastal erosion, which was found to play a more important role than sea‐level rise in determining rates of coastal erosion. This highlights the need for a greater focus on wave height in studies of soft‐cliff erosion. Copyright © 2014 John Wiley & Sons, Ltd.
Experimental characterization of the impact of temperature and humidity on the breakdown of soil water repellency in sandy soils and composts
Authors: Whelan Amii , Kechavarzi Cedric , Coulon Frederic , Doerr Stefan H.
Published: August 2014

Soil water repellency is a widespread phenomenon with the capacity to alter hydrological and geomorphological processes. Water repellency decays with time, and the consequences are only of concern during the timescale at which the water repellency persists. This study aimed to characterize the influence of temperature and humidity on the breakdown of water repellency. Apparent contact angle measurements were carried out on samples consisting of sand treated with stearic acid as well as naturally repellent dune sands and composts. Temperature and humidity were controlled using a cooled incubator and a purpose designed enclosed box in which humidity could be raised or lowered.

Results showed the contact angle of the stearic‐acid‐treated sands decayed with time and that there was a significant increase with stearic acid concentration. For all samples, the decay in apparent contact angle could be described with a continuous breakdown model. The stearic‐acid‐treated sands showed a significant increase in contact angle with relative humidity at a temperature of 10 and 20 °C. These differences diminished with increasing temperature. Similar results were seen for the dune sands and composts. Despite the influence of temperature and humidity on contact angles, there was no significant change in the rate at which the contact angle decayed in any sample. Absolute humidity was found to provide a more relevant indicator than relative humidity when assessing the influence of humidity on repellency over a range of temperatures. The contact angle initially increased with absolute humidity before plateauing owing to the confounding effect of temperature. Copyright © 2014 John Wiley & Sons, Ltd.
K14‐EGFP‐miR‐31 transgenic mice have high susceptibility to chemical‐induced squamous cell tumorigenesis that is associating with Ku80 repression
Authors: Tseng Ssu‐Hsueh , Yang Cheng‐Chieh , Yu En‐Hao , Chang Christine , Lee Yong‐Syu , Liu Chung‐Ji , Chang Kuo‐Wei , Lin Shu‐Chun
Published: August 2014

Squamous cell carcinoma (SCC) occurring in the head and neck region and the esophagus causes tremendous cancer mortality around the world. miR‐31 is among the most eminently upregulated MicroRNAs in SCC, when it occurs in the head and neck region and the esophagus. We established miR‐31 transgenic mouse lines, in which miR‐31 is under the control of the K14 promoter. 4‐nitroquinoline 1‐oxide (4NQO) is a mutagen that causes double strand breaks. The transgenic mice exhibited a higher potential for tumor induction than wild‐type (Wt) mice of the tongue and esophagus after 4NQO treatment. After 4NQO treatment or irradiation, p‐γH2AX expression in squamous epithelium of transgenic mice was increased more than in Wt mice. Exogenous expression of miR‐31 was also found to be associated with the higher p‐γH2AX expression induced by 4NQO in human oral SCC (OSCC) cell lines. The repair genes PARP1 and Ku80 were validated as new targets of miR‐31 in human OSCC cell lines, and were found to be downregulated in the squamous epithelium of the tongue in transgenic mice. However, only the downregulation of Ku80 was essential for maintaining the high level of p‐γH2AX induced by 4NQO in OSCC cells. Inverse expression profiles for miR‐31 and Ku80 were noted in human OSCC tissue. Our study identifies the high sensitivity of K14‐EGFP‐miR‐31 transgenic mice to chemical carcinogen‐induced squamous cell tumorigenesis and shows that this seems to be associated with the downregulation of Ku80 and an impairment of repair activity in squamous cells, which are mediated by miR‐31.
Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation
Authors: Groenendijk Floris H. , Mellema Wouter W. , van der Burg Eline , Schut Eva , Hauptmann Michael , Horlings Hugo M. , Willems Stefan M. , van den Heuvel Michel M. , Jonkers Jos , Smit Egbert F. , Bernards René
Published: August 2014

The multikinase inhibitor sorafenib is under clinical investigation for the treatment of many solid tumors, but in most cases, the molecular target responsible for the clinical effect is unknown. Furthermore, enhancing the effectiveness of sorafenib using combination strategies is a major clinical challenge. Here, we identify sorafenib as an activator of AMP‐activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2. We further show in a phase II clinical trial in KRAS mutant advanced non‐small cell lung cancer (NSCLC) with single agent sorafenib an improved disease control rate in patients using the antidiabetic drug metformin. Consistent with this, sorafenib and metformin act synergistically in inhibiting cellular proliferation in NSCLC in vitro and in vivo. A synergistic effect of both drugs is also seen on phosphorylation of the AMPKα activation site. Our results provide a rationale for the synergistic antiproliferative effects, given that AMPK inhibits downstream mTOR signaling. These data suggest that the combination of sorafenib with AMPK activators could have beneficial effects on tumor regression by AMPK pathway activation. The combination of metformin or other AMPK activators and sorafenib could be tested in prospective clinical trials.
IDENTIFICATION ISSUES IN LIMITED‐INFORMATION BAYESIAN ANALYSIS OF STRUCTURAL MACROECONOMIC MODELS
Authors: Kleibergen Frank , Mavroeidis Sophocles
Published: August 2014

The likelihood of the parameters in structural macroeconomic models typically has non‐identification regions over which it is constant. When sufficiently diffuse priors are used, the posterior piles up in such non‐identification regions. Use of informative priors can lead to the opposite, so both can generate spurious inference. We propose priors/posteriors on the structural parameters that are implied by priors/posteriors on the parameters of an embedding reduced‐form model. An example of such a prior is the Jeffreys prior. We use it to conduct Bayesian limited‐information inference on the new Keynesian Phillips curve with a VAR reduced form for US data. Copyright © 2014 John Wiley & Sons, Ltd.
Adhesion and migration of cells responding to microtopography
Authors: Estévez Maruxa , Martínez Elena , Yarwood Stephen J. , Dalby Matthew J. , Samitier Josep
Published: August 2014

It is known that cells respond strongly to microtopography. However, cellular mechanisms of response are unclear. Here, we study wild‐type fibroblasts responding to 25 µm2 posts and compare their response to that of FAK−/− fibroblasts and fibroblasts with PMA treatment to stimulate protein kinase C (PKC) and the small g‐protein Rac. FAK knockout cells modulated adhesion number and size in a similar way to cells on topography; that is, they used more, smaller adhesions, but migration was almost completely stalled demonstrating the importance of FAK signaling in contact guidance and adhesion turnover. Little similarity, however, was observed to PKC stimulated cells and cells on the topography. Interestingly, with PKC stimulation the cell nuclei became highly deformable bringing focus on these surfaces to the study of metastasis. Surfaces that aid the study of cellular migration are important in developing understanding of mechanisms of wound healing and repair in aligned tissues such as ligament and tendon. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1659–1668, 2015.
Software package SIMPRE—Revisited
Authors: Karbowiak Mirosław , Rudowicz Czesław
Published: August 2014

This article elucidates the pitfalls identified in the software package SIMPRE recently developed by Baldoví et al. (J. Comput. Chem. 2013, 34, 1961) for modeling the spectroscopic and magnetic properties of single ion magnets as well as single‐molecule magnets. Analysis of the methodology used therein reveals that the crystal field parameters (CFPs), expressed nominally in the Stevens formalism, exhibit features characteristic for the CFPs expressed in the Wybourne notation. The resemblance of the two types of CFPs introduces a serious confusion that may lead to wrong comparisons of the CFPs taken from various sources. To clarify this confusion, the properties of the CFPs
(
,
) associated with the Stevens operators
(X = S, J, or L), which belong to the class of the tesseral‐tensor operators, are contrasted with those of the CFPs Bkq associated with the Wybourne operators
, which belong to the class of the spherical‐tensor operators. Importantly, the confused properties of Stevens and Wybourne operators may bear on reliability of SIMPRE calculations. To consider this question independent calculations are carried out using the complete approach and compared with those of the restricted approach utilized earlier. It appears that the numerical results of the package SIMPRE are formally acceptable, however, the meaning of the CFPs must be properly reformulated. Several other conceptual problems arising from misinterpretations of the crucial notions and the CFP notations identified therein are also discussed and clarified. © 2014 Wiley Periodicals, Inc.
Targeted elimination of activated hepatic stellate cells by an anti‐epidermal growth factor‐receptor single chain fragment variable antibody‐tumor necrosis factor‐related apoptosis‐inducing ligand (scFv425‐sTRAIL)
Authors: Arabpour Mohammad , Poelstra Klaas , Helfrich Wijnand , Bremer Edwin , Haisma Hidde J.
Published: August 2014

Background

Progressive liver fibrosis is the result of chronic liver injury and is characterized by the excessive accumulation of extracellular matrix that may result in liver failure. Activated hepatic stellate cells are known to play a central role in this process and their elimination is a crucial step towards the resolution and reversion of liver fibrosis. In the present study, we investigated the potential application of an anti‐epidermal growth factor receptor single chain fragment variable antibody‐tumor necrosis factor‐related apoptosis‐inducing ligand (scFv425‐sTRAIL) fusion protein in the targeted elimination of activated hepatic stellate cells.

Methods

Activated hepatic stellate cells (LX2 cells) were treated by adenovirus‐derived scFv425‐sTRAIL to evaluate its effect on the viability and extracellular matrix production of this type of cells.

Results

In vitro treatment of activated hepatic stellate cells with scFv425‐sTRAIL induced a significant reduction in viability (up to 100% reduction) and extracellular matrix production (60% reduction), yet no significant effect was observed on hepatic parenchymal cells. Blockage of the epidermal growth factor receptor (EGFR) by a monoclonal antibody significantly reduced the effectiveness of scFv425‐sTRAIL in activated hepatic stellate cells, whereas a reduced effectivity was also observed after inhibition of the caspase pathway.

Conclusions

Evidence is presented for the successful application of the scFv425‐sTRAIL fusion protein in the targeted elimination of activated hepatic stellate cells via EGFR and simultaneous activation of the caspase pathway. scFv425‐sTRAIL may thus represent a new therapeutic compound against liver fibrosis. Copyright © 2014 John Wiley & Sons, Ltd.
The Distribution of Immobilized Platinum and Palladium Nanoparticles within Poly(2‐vinylpyridine) Brushes
Authors: Al‐Hussein Mahmoud , Koenig Meike , Stamm Manfred , Uhlmann Petra
Published: August 2014

Novel catalytic surfaces can be prepared by in situ synthesis of metal nanoparticles (NPs) inside polymer brush systems. To gain more control over the properties of these nanocatalysts, it is important to quantify their distribution inside the polymer brush and understand their formation process better. Here, measurements of the distributions of Pt and Pd NPs within poly(2‐vinylpyridine) (P2VP) brushes are reported. The amount of surface accumulation and the extent of penetration of the two metal NPs into the brush layer are determined using X‐ray reflectivity measurements. Quantitative analysis of the data reveals a significant difference between the distributions of the two NP species. Pd NPs exhibit higher accumulation at the surface and larger penetration depth within the brush. This difference in behavior is attributed to the different adsorption mechanisms exhibited by the two metal ions. Whereas Pt ions adsorb to the polymer brush via ionic bonds, Pd ions form complex coordination bonds. The different distributions of the NPs within the polymer brush are related to the previously investigated catalytic activity of these systems. The reported unusually high specific activity of Pt hybrid brushes, as compared with Pd ones, can now be explained by buried Pd NPs that do not take part in the catalytic reaction.

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From winning strategy to Nash equilibrium
Authors: Le Roux Stéphane
Published: August 2014

Game theory is usually considered applied mathematics, but a few game‐theoretic results, such as Borel determinacy, were developed by mathematicians for mathematics in a broad sense. These results usually state determinacy, i.e., the existence of a winning strategy in games that involve two players and two outcomes saying who wins. In a multi‐outcome setting, the notion of winning strategy is irrelevant yet usually replaced faithfully with the notion of (pure) Nash equilibrium. This article shows that every determinacy result over an arbitrary game structure, e.g., a tree, is transferable into existence of multi‐outcome (pure) Nash equilibrium over the same game structure. The equilibrium‐transfer theorem requires cardinal or order‐theoretic conditions on the strategy sets and the preferences, respectively, whereas counter‐examples show that every requirement is relevant, albeit possibly improvable. When the outcomes are finitely many, the proof provides an algorithm computing a Nash equilibrium without significant complexity loss compared to the two‐outcome case. As examples of application, this article generalises Borel determinacy, positional determinacy of parity games, and finite‐memory determinacy of Muller games.
Muscle magnetic resonance imaging and histopathology in ACTA1‐related congenital nemaline myopathy
Authors: Castiglioni Claudia , Cassandrini Denis , Fattori Fabiana , Bellacchio Emanuele , D'Amico Adele , Alvarez Karin , Gejman Roger , Diaz Jorge , Santorelli Filippo M. , Romero Norma B. , Bertini Enrico , Bevilacqua Jorge A.
Published: August 2014

Introduction: Muscle biopsy is usually diagnostic in nemaline myopathy (NM), but some patients may show nonspecific findings, leading to pitfalls in diagnosis. Muscle MRI is a helpful complementary tool. Methods: We assessed the clinical, histopathological, MRI, and molecular findings in a 19‐year‐old patient with NM in whom 2 muscle biopsies with ultrastructural examination showed no nemaline bodies. We analyzed the degree and pattern of muscle MRI involvement of the entire body, including the tongue and pectoral muscles. Results: Muscle MRI abnormalities in sartorius, adductor magnus, and anterior compartment muscles of the leg suggested NM. A previously unreported fatty infiltration of the tongue was found. A third biopsy after the muscle MRI showed scant nemaline bodies. A novel heterozygous de novo ACTA1 c.611C>T/p.Thr204Ile mutation was detected. Conclusions: We highlight the contribution of muscle imaging in addressing the genetic diagnosis of ACTA1‐related NM. Muscle Nerve 50: 1011–1016, 2014
A Mickens‐type discretization of a diffusive model with nonpolynomial advection/convection and reaction terms
Authors: Macías‐Díaz Jorge E. , Villa‐Morales José
Published: August 2014

In this manuscript, we follow a nonlinear approach in the problem of numerically estimating solutions of a generic, diffusive partial differential equation with nonpolynomial advection/convection, and reaction laws. The nonlocal, finite‐difference methodology presented in this manuscript has the advantage of conditionally preserving the properties of non‐negativity, boundedness, and temporal and spatial monotonicity of approximations, which are characteristics that are inherent to some kink‐like solutions of particular forms of the mathematical model under investigation. We establish theorems on the stability of the technique, on the existence and uniqueness of non‐negative and bounded solutions of our computational model, and on the property of preservation of monotonicity. As corollaries, we show that the method is capable of preserving the spatial and temporal monotonicity of numerical approximations. We provide some illustrative, numerical simulations that support our analytical results. Our simulations show that the method provides good approximations to the exact solutions of the particular problems considered and that the properties of non‐negativity, boundedness, and monotonicity (both temporal and spatial) are conditionally preserved at each iteration. © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 652–669, 2015