bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual 5′ Cap Labeling Based on Regioselective RNA Methyltransferases and Bioorthogonal Reactions
Authors: Holstein Josephin M. , Muttach Fabian , Schiefelbein Stephan H. H. , Rentmeister Andrea
Published: November 2016

The ability to detect and localize defined RNA strands inside living cells requires probes with high specificity, sensitivity, and signal‐to‐background ratio. To track low‐abundant biomolecules, such as strands of regular mRNA, and distinguish fluorescence signal from the background after bioorthogonal reactions in cells, it is imperative to employ turn‐on concepts. Here, we have presented a straightforward enzymatic approach to allow site‐specific modification of two different positions on the 5′ cap of eukaryotic mRNA with either identical or different small functional groups. The approach relies on two methyltransferases and analogues of their natural co‐substrate, and it can be extended to a three‐enzyme cascade reaction for their in situ production. Subsequent labeling by using bioorthogonal click reactions provided access to double labeling with identical fluorophores or dual labeling with two different reporter groups, as exemplified by a Cy5 dye, a FRET pair, and a fluorophore/biotin combination. Our dual‐labeling strategy addresses the need for increased sensitivity and should improve the signal‐to‐background ratio after bioorthogonal reactions in cells.
Ring‐Opening Regio‐, Diastereo‐, and Enantioselective 1,3‐Chlorochalcogenation of Cyclopropyl Carbaldehydes
Authors: Wallbaum Jan , Garve Lennart K. B. , Jones Peter G. , Werz Daniel B.
Published: November 2016

meso‐Cyclopropyl carbaldehydes are treated in the presence of an organocatalyst with sulfenyl and selenyl chlorides to afford 1,3‐chlorochalcogenated products. The transformation is achieved by a merged iminium–enamine activation. The enantioselective desymmetrization reaction, leading to three adjacent stereocenters, furnished the target products in complete regioselectivity and moderate to high diastereo‐ and enantioselectivities (d.r. up to 15:1 and e.r. up to 93:7).
100 Jahre Einkristallzucht aus der Schmelze
Authors: Evers Jürgen , Herzog Christiane , Möckl Leonhard , von Plotho Christoph , Stallhofer Peter , Staudigl Rudolf
Published: November 2016

Im August 1916 reichte der Deutsch‐Pole Jan Czochralski eine Publikation über die Wachstumsgeschwindigkeit von Metallkristallen bei der Zeitschrift für physikalische Chemie ein. Daher wird 1916 als das Jahr der Entdeckung des Czochralski‐Kristallzuchtverfahrens angesehen. Im Metall‐Laboratorium der AEG, wo Czochralski zunächst arbeitete, wurden seine Forschungsarbeiten nicht gebührend anerkannt, sodass er zur Metallbank und Metallurgischen Gesellschaft (später: Metallgesellschaft) nach Frankfurt wechselte, wo er bald zum Laborleiter und Oberingenieur aufstieg. In Frankfurt machte er sich mit Forschungen zu Metallen und technischen Legierungen rasch einen Namen. Die Entdeckung des Czochralski‐Kristallzuchtverfahrens gehört zu den wichtigsten technologischen Erfindungen des 20. Jahrhunderts, die aber erst in dessen zweiten Hälfte mit dem Aufstieg der Halbleiterindustrie ökonomische Bedeutung erlangte. Heute werden 95 % der Weltproduktion an Siliciumeinkristallen nach dem Czochralski‐Verfahren hergestellt. Der Umsatz der Halbleiter‐Industrie betrug 2015 etwa 335 Milliarden US‐Dollar, wobei die Kristallzucht nach dem Czochralski‐Verfahren jeweils der erste Schritt bei der Herstellung ist. Der größte Teil der heute gefertigten Siliciumeinkristalle hat einen Durchmesser von 300 mm. Die industrielle Produktion von Einkristallen mit 450 mm Durchmesser scheitert bisher nicht an technologischen, sondern an ökonomischen Problemen.
Assessment of scale‐up dimensionless groups methodology of gas‐solid fluidized beds using advanced non‐invasive measurement techniques (CT and RPT)
Authors: Efhaima Abdelsalam , Al‐Dahhan Muthanna H.
Published: November 2016

The most common scale‐up methodology for gas‐solid fluidized bed reactors that has been reported in the literature is based on matching the dimensionless groups. This scale‐up methodology in the literature has been validated by only measuring global hydrodynamic parameters (overall holdups and pressure drop, etc.) without details. Therefore, in this work, we have applied advanced non‐invasive measurement techniques, gamma‐ray computed tomography (CT) and radioactive particle tracking (RPT) techniques, for the first time to evaluate such scale‐up methodology by measuring local hydrodynamic parameters. The results obtained demonstrate that the reported set of the dimensionless groups are not adequate in capturing all the interplay phenomena for achieving similarity in the local hydrodynamic parameters when the proposed set of dimensionless groups has been matched using two sizes of fluidized beds of 0.14 m and 0.44 m and sets of operating conditions. This finding confirms that the local measurements of the hydrodynamic parameters are essential for detailed assessment of scale‐up methodologies.
Infections with multiple high‐risk HPV types are associated with high‐grade and persistent low‐grade intraepithelial lesions of the cervix
Authors: De Brot Louise , Pellegrini Bruno , Moretti Sabrina Teixeira , Carraro Dirce Maria , Soares Fernando Augusto , Rocha Rafael Malagoli , Baiocchi Glauco , da Cunha Isabela Werneck , de Andrade Victor Piana
Published: November 2016

BACKGROUND

Infections with multiple human papillomavirus (HPV) types (mHPV) in Papanicolaou tests have been reported but the histologic correlation and clinical meaning remains debatable.

METHODS

The authors prospectively tested 37 HPV types using the Linear Array HPV Genotyping Test and correlated the results to cytology and histology findings in 260 women evaluated from June 2009 to October 2011 and followed for up to 60 months.

RESULTS

HPV was detected in 148 of 235 samples (63%) and high‐risk HPV was detected in 132 samples (56%). mHPV infection was found to be twice as common as single HPV (sHPV) infection and was detected more frequently in low‐grade squamous intraepithelial lesion (LSIL) (48 of 83 samples [58%]) and high‐grade squamous intraepithelial lesion or invasive carcinoma (HSIL + (26 of 47 samples [55%]) compared with other categories (P<.001). Of 34 LSIL/cervical intraepithelial neoplasia 1 (CIN1) index cases, 13 of 21 patients with mHPV (61.9%) persisted on CIN1, whereas no histologic abnormality was detected during follow‐up in all 12 patients with sHPV infection (high risk or low risk) (P<.001). Eighteen of 20 patients with HSIL/cervical intraepithelial neoplasia 2 (CIN2) (90%) and high‐risk mHPV persisted on HSIL+/CIN2 + whereas 6 of 11 patients with sHPV infection did not demonstrate HSIL+/CIN2 + on follow‐up (54.5%) (P = .066). Approximately 40% of women with HSIL were infected by high‐risk HPV types other than types 16 or 18.

CONCLUSIONS

High‐risk mHPV infection identified patients with persistent LSIL/CIN1 and may to help identify patients at higher risk of disease progression to HSIL+/CIN2+. Longer follow‐up will clarify the role of mHPV testing in patient care. Cancer Cytopathol 2017;125:138–143. © 2016 American Cancer Society.
Improving Therapeutic Odyssey: Preemptive Pharmacogenomics Utility in Patient Care
Authors: Lazaridis KN
Published: November 2016

Pharmacogenomics, studying genetic variation related to drug response, was established decades ago. Today, performing clinical pharmacogenomics testing has increased, creating great potential to improve patient care. Yet widespread implementation of pharmacogenomics in practice is currently limited, resulting in the “therapeutic odyssey” of patients. Preemptive clinical pharmacogenomics testing prior to the time of prescribing is now emerging as an option that could tailor the pharmacotherapy of patients by increasing drug effectiveness while reducing adverse drug reaction risk.
A survey on energy estimation and power modeling schemes for smartphone applications
Authors: Ahmad Raja Wasim , Gani Abdullah , Hamid Siti Hafizah Ab , Shojafar Mohammad , Ahmed Abdelmuttlib Ibrahim Abdalla , Madani Sajjad A. , Saleem Kashif , Rodrigues Joel J.P.C.
Published: November 2016

In the last decade, the rising trend in the popularity of smartphones motivated software developers to increase application functionality. However, increasing application functionality demands extra power budget that as a result, decreases smartphone battery lifetime. Optimizing energy critical sections of an application creates an opportunity to increase battery lifetime. Smartphone application energy estimation helps investigate energy consumption behavior of an application at diversified granularity (eg, coarse and fine granular) for optimal battery resource use. This study explores energy estimation and modeling schemes to highlight their advantages and shortcomings. It classifies existing smartphone application energy estimation and modeling schemes into 2 categories, ie, code analysis and mobile components power model–based estimation owing to their architectural designs. Moreover, it further classifies code analysis–based modeling and estimation schemes in simulation‐based and profiling‐based categories. It compares existing energy estimation and modeling schemes based on a set of parameters common in most literature to highlight the commonalities and differences among reported literature. Existing application energy estimation schemes are low‐accurate, resource expensive, or non‐scalable, as they consider marginally accurate smart battery's voltage/current sensors, low‐rate power capturing tools, and labor‐driven lab‐setting environment to propose power models for smartphone application energy estimation. Besides, the energy estimation overhead of the components power model–based estimation schemes is very high as they physically run the application on a smartphone for energy profiling. To optimize smartphone application energy estimation, we have highlighted several research issues to help researchers of this domain to understand the problem clearly.
Transcriptome analysis of the regenerating tail vs. the scarring limb in lizard reveals pathways leading to successful vs. unsuccessful organ regeneration in amniotes
Authors: Vitulo Nicola , Dalla Valle Luisa , Skobo Tatjana , Valle Giorgio , Alibardi Lorenzo
Published: November 2016

Background: Lizards are amniotes regenerating the tail but not the limb, and no information on their different gene expression is available.Results: Transcriptomes of regenerating tail and limb blastemas show differences in gene expression between the two organs. In tail blastemal, snoRNAs and Wnt signals appear up‐regulated probably in association with the apical epidermal peg (AEP), an epithelial region that sustains tail regeneration but is absent in the limb. A balance between pro‐oncogenes and tumor suppressors is likely present in tail blastema allowing a regulated proliferation. Small collagens, protease inhibitors, embryonic keratins are up‐regulated in the regenerating tail blastema but not in the limb where Wnt inhibitors, inflammation‐immune and extracellular matrix proteins depress cell growth.Conclusions: The AEP and the spinal cord in the tail maintains Wnt and fibroblast growth signaling that stimulate blastema cell proliferation and growth while these signals are absent in the limb as a consequence of the intense inflammation. Regeneration of amniote appendages requires a control of cell proliferation and inflammatory‐immune reactions to form an apical epidermal cap. Genes that control cell proliferation and inflammation, addressing regeneration and not tumor formation in the tail and scarring in the limb are discussed for future studies.Developmental Dynamics 246:116–134, 2017. © 2016 Wiley Periodicals, Inc.
Influence of plant traits, soil microbial properties, and abiotic parameters on nitrogen turnover of grassland ecosystems
Authors: Legay Nicolas , Lavorel Sandra , Baxendale Catherine , Krainer Ute , Bahn Michael , Binet Marie‐Noëlle , Cantarel Amélie A. M. , Colace Marie‐Pascale , Foulquier Arnaud , Kastl Eva‐Maria , Grigulis Karl , Mouhamadou Bello , Poly Franck , Pommier Thomas , Schloter Michael , Clément Jean‐Christophe , Bardgett Richard D.
Published: November 2016

Although it is known that multiple interactions among plant functional traits, microbial properties, and abiotic soil parameters influence the nutrient turnover, the relative contribution of each of these groups of variables is poorly understood. We manipulated grassland plant functional composition and soil nitrogen (N) availability in a multisite mesocosm experiment to quantify their relative effects on soil N turnover. Overall, root traits, arbuscular mycorrhizal colonization, denitrification potential, as well as N availability and water availability, best explained the variation in measured ecosystem properties, especially the trade‐off between nutrient sequestration and plant biomass production. Their relative contributions varied with soil N availability. In relatively N‐poor soils (10–20 μg·N·g−1soil), N turnover was mainly controlled by microbial properties and abiotic soil parameters, whereas in the relatively N‐rich soils (110–120 μg·N·g−1soil), N turnover was mainly controlled by plant traits and microbial properties. This experiment is a strong demonstration of the importance of functional characteristics of both plants and soil microbes, and their interplay with soil N availability, for N turnover in grassland soils.
Context‐dependent landscape of fear: algal density elicits risky herbivory in a coral reef
Authors: Gil Michael A. , Zill Julie , Ponciano José M.
Published: November 2016

Foraging theory posits that isolation from refuge habitat within a landscape increases perceived predation risk and, thus, suppresses the foraging behavior of prey species. However, these effects may depend fundamentally on resource availability, which could affect prey boldness and can change considerably through bottom‐up processes. We conducted a field survey and experiment in a coral reef to test the effects of isolation from refuge habitat (i.e., reef structure) on herbivory by reef fishes and whether these effects depend on resource density. By fitting continuous‐time, pure death Markov processes to our data, we found that at both the local and landscape scale distance from refuge habitat reduced herbivory in attractive resource patches of palatable benthic algae. However, our field experiment revealed that higher initial resource densities weakened negative effects of distance from refuge habitat on herbivory. Furthermore, we observed higher bite rates and greater total lengths of herbivorous fishes with greater distance from refuge habitat—responses consistent with higher perceived predation risk. Our results suggest that while the loss or fragmentation of refuge habitat reduces consumer control of resources, greater resource densities can partially counteract this effect by altering landscapes of fear of consumer species. Our findings emphasize the importance of considering the spatial context of species interactions that structure communities.
Feasibility of filter‐based NIR spectroscopy for the routine measurement of olive oil fruit ripening indices
Authors: Trapani Serena , Migliorini Marzia , Cecchi Lorenzo , Giovenzana Valentina , Beghi Roberto , Canuti Valentina , Fia Giovanna , Zanoni Bruno
Published: November 2016

The aim of this work was to apply and validate a NIR spectrometer based on a discrete filter system for the rapid measurement of the moisture, oil, sugar, and phenolic compounds contents of olive oil fruits. The batches of olive oil fruits were collected during seven crop seasons from several farms located in Tuscany and then they were crushed into olive paste. The water content was measured gravimetrically, oil content was measured using the Soxhlet method, sugar content was measured enzymatically and phenolic compound content was measured by HPLC. NIR spectra were recorded from 1400 to 2400 nm at 19 selected wavelengths. Calibration and validation models were processed using PLS regression. In PLS models built for moisture, oil, and sugar contents, the r2 in calibration ranged between 0.90 and 0.93 with low standard error of calibration (SEC) values (i.e. 2.5, 3.6 and 4.0, respectively). For these parameters the standard error of prediction (SEP) and the standard error of laboratory (SEL) values proved to be comparable (i.e. 2.4 vs. 3.2, 6.0 vs. 4.4, and 6.7 vs. 4.7, respectively). Instead, the calibration and validation results concerning the phenolic compounds were not satisfactory, probably because the necessary wavelengths in the section of absorbance from 1100 to 1400 nm were not covered.

Practical applications: NIR spectrometers based on discrete filter systems may be interesting since they are cost‐saving compared to the more sophisticated FT‐NIR and NIR‐AOTF instruments (i.e. the cost is approximately half). Our study also showed that with this instrument it was possible to build some effective models for predicting moisture, oil, and sugar contents in olive paste. The results obtained for moisture and oil contents are comparable with those obtained with other spectrometers, and a predictive model was obtained for sugar content for the first time. Instead the tool did not prove suitable for obtaining predictive models for total phenolic compounds or oleuropein contents. The additional use of a filter‐based NIR spectrometer is therefore to be suggested to rapidly monitor olive fruit ripening on the basis of moisture, oil, and sugar contents.

The used filter‐based NIR spectrometer, relevant spectra, and calibration‐validation results.
Determination of lithium and transition metals in Li1Ni1/3Co1/3Mn1/3O2 (NCM) cathode material for lithium‐ion batteries by capillary electrophoresis
Authors: Vortmann‐Westhoven Britta , Lürenbaum Constantin , Winter Martin , Nowak Sascha
Published: November 2016

In this work, we present a novel electrophoretic method that was developed for the determination of lithium and transition metals in LiNi1/3Co1/3Mn1/3O2 cathode material after microwave digestion. The cations in the digested LiNi1/3Co1/3Mn1/3O2 material were separated by CE and the element content was determined by UV/Vis detection. To characterize the precision of the measurements, the RSDs and concentrations were calculated and compared to those obtained with ICP‐optical emission spectrometry (ICP‐OES). Furthermore, a certified reference material (BCR 176R—fly ash) was investigated for all techniques. For active material components, the LOD and LOQ were determined. The LODs and LOQs for the metals determined by CE were as follows: lithium (LOD/LOQ): 17.41/62.70 μg/L, cobalt (LOD/LOQ): 348.4/1283 μg/L, manganese (LOD/LOQ): 540.2/2095 μg/L, and nickel (LOD/LOQ): 838.0/2982 μg/L. Recovery rates for lithium were in the range of 95–103%. It could be proven that with the new technique, the results for the determination of the lithium content of active material were comparable with those obtained by ICP‐OES and ion chromatography. Furthermore, the recovery rates of the transition metals were determined to be between 96 and 110% by CE and ICP‐OES.
Co-exposure to sunlight enhances the toxicity of naturally weathered Deepwater Horizon oil to early lifestage red drum (Sciaenops ocellatus) and speckled seatrout (Cynoscion nebulosus)
Authors: Alloy Matthew , Garner Thomas Ross , Nielsen Kristin M. , Mansfield Charles , Carney Michael , Forth Heather , Krasnec Michelle , Lay Claire , Takeshita Ryan , Morris Jeffrey , Bonnot Shane , Oris James , Roberts Aaron
Published: November 2016

The 2010 Deepwater Horizon oil spill resulted in the accidental release of millions of barrels of crude oil into the Gulf of Mexico. Photo-induced toxicity following co-exposure to ultraviolet (UV) radiation is 1 mechanism by which polycyclic aromatic hydrocarbons (PAHs) from oil spills may exert toxicity. Red drum and speckled seatrout are both important fishery resources in the Gulf of Mexico. They spawn near-shore and produce positively buoyant embryos that hatch into larvae in approximately 24 h. The goal of the present study was to determine whether exposure to UV as natural sunlight enhances the toxicity of crude oil to early lifestage red drum and speckled seatrout. Larval fish were exposed to several dilutions of high-energy water-accommodated fractions (HEWAFs) from 2 different oils collected in the field under chain of custody during the 2010 spill and 3 gradations of natural sunlight in a factorial design. Co-exposure to natural sunlight and oil significantly reduced larval survival compared with exposure to oil alone. Although both species were sensitive at PAH concentrations reported during the Deepwater Horizon spill, speckled seatrout demonstrated a greater sensitivity to photo-induced toxicity than red drum. These data demonstrate that even advanced weathering of slicks does not ameliorate the potential for photo-induced toxicity of oil to these species. Environ Toxicol Chem 2017;36:780–785. © 2016 SETAC
A Proposal to Address NFL Club Doctors’ Conflicts of Interest and to Promote Player Trust
Authors: Cohen I. Glenn , Lynch Holly Fernandez , Deubert Christopher R.
Published: November 2016

How can we ensure that players in the National Football League receive excellent health care they can trust from providers who are as free from conflicts of interest as realistically possible? NFL players typically receive care from the club's own medical staff. Club doctors are clearly important stakeholders in player health. They diagnose and treat players for a variety of ailments, physical and mental, while making recommendations to the player concerning those ailments. At the same time, club doctors have obligations to the club, namely to inform and advise clubs about the health status of players. While players and clubs share an interest in player health—both of them want players to be healthy so they can play at peak performance—there are several areas where their interests can diverge, and the divergence presents legal and ethical challenges. The current structure forces club doctors to have obligations to two parties—the club and the player—and to make difficult judgments about when one party's interests must yield to another's. None of the three parties involved should prefer this conflicted approach.

We propose to resolve the problem of dual loyalty by largely severing the club doctor's ties with the club and refashioning that role into one of singular loyalty to the player‐patient. The main idea is to separate the roles of serving the player and serving the club and replace them with two distinct sets of medical professionals: the Players' Medical Staff (with exclusive loyalty to the player) and the Club Evaluation Doctor (with exclusive loyalty to the club). We begin by explaining the broad ethical principles that guide us and that help shape our recommendation. We then provide a description of the role of the club doctor in the current system. After explaining the concern about the current NFL player health care structure, we provide a recommendation for improving this structure. We then discuss how the club medical staff fits into the broader microenvironment affecting player health.
Players’ Doctors: The Roles Should Be Very Clear
Authors: Caplan Arthur L. , Parent Brendan , Igel Lee H.
Published: November 2016

Years ago, one of us had the opportunity to talk with a starting guard in the National Basketball Association about his health care. The player, then a rookie, did not have his own personal doctor. Instead, he received his health care from the team doctor. This athlete was very well paid and could have received care anywhere he wished in the area. But he came from a very poor neighborhood. Growing up, he said, he had no health care other than hearing and eye tests done at his school and maybe (he was not sure) vaccinations given by the school nurse. The player said he now felt fine and trusted his team to look out for his health since they were paying him a lot of money and obviously wanted him on the court. While it might seem obvious that conflicts of role could arise for doctors working simultaneously for a team and for an athlete—wanting to please coaches, owners, and maybe fans while looking out for the athletes on the team—that is not how this young player saw things. He trusted his team and those who worked for them, and he figured that their interest in keeping him healthy overlapped nicely with his interest in staying healthy. As someone who did not get much access to health care as a child and had little need for it, he did not have concerns about conflicts of interest and second opinions foremost in his mind. But as is clear from a recent scandal involving the National Football League and concussion research, there are reasons for concern when athletes deal with health care workers paid by their teams.
Transient Treg depletion enhances therapeutic anti‐cancer vaccination
Authors: Fisher Scott A. , Aston Wayne J. , Chee Jonathan , Khong Andrea , Cleaver Amanda L. , Solin Jessica N. , Ma Shaokang , Lesterhuis W. Joost , Dick Ian , Holt Robert A. , Creaney Jenette , Boon Louis , Robinson Bruce , Lake Richard A.
Published: November 2016

Introduction

Regulatory T cells (Treg) play an important role in suppressing anti‐ immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti‐cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg.

Methods

Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored.

Results

DTX specifically depleted Treg in a transient, dose‐dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor‐peptide vaccination.

Conclusions

BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti‐tumor immunity. DTX‐mediated Treg depletion is transient, dose‐dependent, and leads to strong anti‐tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor‐specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies.
HIV‐protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO‐hybridized derivatives?
Authors: Maksimovic‐Ivanic Danijela , Fagone Paolo , McCubrey James , Bendtzen Klaus , Mijatovic Sanja , Nicoletti Ferdinando
Published: November 2016

The possible use of HIV protease inhibitors (HIV‐PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV‐related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma and prostate cancer suggest other mechanisms for the anti‐neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV‐PIs in the therapy of cancer relies on their relatively weak anticancer potency and important side effects. This has propelled several groups to generate derivatives of HIV‐PIs for anticancer use, through modifications such as attachment of different moieties, ligands and transporters, including saquinavir‐loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV‐PIs. In this article, we discuss the current preclinical and clinical evidences for the potential use of HIV‐PIs, and of novel derivatives, such as saquinavir‐NO in the treatment of cancer.
SYSTEMS OF SYSTEMS ENGINEERING STANDARDS
Authors: Dahmann Judith , Roedler Garry
Published: November 2016

As systems of systems engineering (SoSE) matures, there is a growing interest in SoSE standardization. This has led the ISO/IEC JTC1/SC7 to establish a study group to investigate future opportunities for SoSE standardization. This paper reviews the approach taken by the study group, the issues that were investigated and the recommendations from the study. The study addresses the current perspectives on SoSE, the state of the practice, the existing level of standardization for SoSE, and the analysis and findings of the potential need for additional SoSE standardization. In looking at the current and potential future state of SoSE standardization, the study examined the adequacy, existing support to, and gaps in current standards that support the needs of SoSE and the SoSE standardization solutions. This article discusses the move toward SoSE standards and the ISO study recommendations for SoSE standards initiatives.
BRUNEI COMMUNICATION NAVIGATION SURVEILLANCE/AIR TRAFFIC MANAGEMENT (CNS/ATM) SYSTEM OF SYSTEMS: CASE STUDY OF AN ATM PROJECT
Authors: Menard Cedric , Philippe Mathieu
Published: November 2016

National air traffic management (ATM) systems generally evolve over time and can often be considered as an evolving integration of multiple pre‐existing systems that have been supplied by different vendors through various upgrades. This article describes a major upgrade to the Brunei Communication Navigation Surveillance /Air Traffic Management (CNS/ATM) system that was commissioned in 2016. This was a very successful project and insights on this success are provided from organizational, technical, and human perspectives
RAIL SYSTEMS VIEWED FROM A SYSTEM OF SYSTEMS PERSPECTIVE
Authors: Hoehne Oliver
Published: November 2016

Transportation systems in general, and rail systems in particular, are large and geographically distributed systems. While individual carriers may be independently operated and managed, they often use the infrastructure and resources (roads, track, and stations) of other entities such as Amtrak or freight railroads.

This INSIGHT article describes why rail systems are in fact systems of systems (SoS), and what types of SoS they represent. It will use the California High‐Speed Rail System (CHSRS), a rail system currently in design and build, as an example to illustrate insights into the application of systems of systems engineering (SoSE), and how it benefits from the growing awareness of SoS Engineering.
TOOL AND TECHNIQUES – DANSE
Authors: Tim Lochow
Published: November 2016

The DANSE (Design for Adaptability and evolutioN in Systems of systems Engineering) project (2011‐2015) presents one of the first key research innovation actions launched and funded by the FP7 program (INFSO‐ICT‐287716) in the frame of systems of systems engineering research. It addressed the development of new methods and tools supporting the Design for Adaptability and evolutioN in Systems of systems Engineering (SoSE). The DANSE consortium consists of 12 European organizations including large system integrators in the aerospace/ defence and electronics domain, engineering software tool vendors, and research organisations in the domain of embedded systems.

The article provides an overview and short introduction to the large set of tangible results of the project. One of the key assets the project developed was a cohesive methodology that defines the role of SoSE as integral part of an evolutionary, adaptive, and iterative SoS lifecycle. The methods and tools elaborated along this methodology are based on the concept of contracts as semantically‐sound models for SoS interoperations allowing a step change in architecting approaches for SoS – supporting continuous and non‐disruptive constituent system integration.

More public and detailed information about the project can be also obtained on the official DANSE website (www.danse‐ip.eu).
AN SOS ANALYTICAL WORKBENCH APPROACH TO ARCHITECTURAL ANALYSIS AND EVOLUTION
Authors: Daniel DeLaurentis , Navindran Davendralingam , Karen Marais , Cesare Guariniello , Zhemei Fang , Payuna Uday
Published: November 2016

This article summarizes the development of a System of Systems Analytic Workbench (SoS AWB) that provides a set of computational tools to facilitate better‐informed decision‐making on evolving SoS architectures. The workbench motif is adopted since SoS practitioners typically generate archetypal technical queries that can be mapped to appropriate analysis methods best suited to provide outputs and insights directly relevant to posed questions. After an overview of the workbench framework, four distinct methods currently available for use are presented along with their distinctive aspects in the concept of use.
The Selective Serotonin Reuptake Inhibitor Fluoxetine Directly Inhibits Osteoblast Differentiation and Mineralization During Fracture Healing in Mice
Authors: Bradaschia-Correa Vivian , Josephson Anne M , Mehta Devan , Mizrahi Matthew , Neibart Shane S , Liu Chao , Kennedy Oran D , Castillo Alesha B , Egol Kenneth A , Leucht Philipp
Published: November 2016

Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to osteoporosis. In this study, we investigated the effect of chronic SSRI use on fracture healing in two murine models of bone regeneration. First, we performed a comprehensive analysis of endochondral bone healing in a femur fracture model. C57/BL6 mice treated with fluoxetine, the most commonly prescribed SSRI, developed a normal cartilaginous soft-callus at 14 days after fracture and demonstrated a significantly smaller and biomechanically weaker bony hard-callus at 28 days. In order to further dissect the mechanism that resulted in a smaller bony regenerate, we used an intramembranous model of bone healing and revealed that fluoxetine treatment resulted in a significantly smaller bony callus at 7 and 14 days postinjury. In order to test whether the smaller bony regenerate following fluoxetine treatment was caused by an inhibition of osteogenic differentiation and/or mineralization, we employed in vitro experiments, which established that fluoxetine treatment decreases osteogenic differentiation and mineralization and that this effect is serotonin-independent. Finally, in a translational approach, we tested whether cessation of the medication would result in restoration of the regenerative potential. However, histologic and μCT analysis revealed non-union formation in these animals with fibrous tissue interposition within the callus. In conclusion, fluoxetine exerts a direct, inhibitory effect on osteoblast differentiation and mineralization, shown in two disparate murine models of bone repair. Discontinuation of the drug did not result in restoration of the healing potential, but rather led to complete arrest of the repair process. Besides the well-established effect of SSRIs on bone homeostasis, our study provides strong evidence that fluoxetine use negatively impacts fracture healing. © 2017 American Society for Bone and Mineral Research.
Carbodicarbenes or Bent Allenes
Authors: Wang Ting‐Hsuan , Chen Wen‐Ching , Ong Tiow‐Gan
Published: November 2016

The pursuit of unusual bonding environments of carbon species with non‐octet electronic configurations has been quite active in fundamental organic and theoretical chemistry for many decades. In this respect, a distinct carbone species has been successfully isolated recently and defined as “carbodicarbene” or “bent allene.” This neutral two‐coordinated central carbon atom possesses two electron lone pairs, while its octet deficiency is overcome by σ donation of N‐heterocyclic carbenes (NHCs) bound to the central carbon. The present review is focused on the rich chemistry of carbodicarbenes in the aspects of synthesis, characterization, and ligand science of metal complex as well as their intrinsic reactivities.
TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture Model of the Corneal Epithelium
Authors: Martínez‐Rendón Jacqueline , Sánchez‐Guzmán Erika , Rueda Angélica , González James , Gulias‐Cañizo Rosario , Aquino‐Jarquín Guillermo , Castro‐Muñozledo Federico , García‐Villegas Refugio
Published: November 2016

TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4 during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells. TRPV4 is a late differentiation feature that is concentrated in the apical membrane of the outmost cell layer of the stratified epithelia. Ca2+ imaging experiments showed that TRPV4 activation with GSK1016790A produced an influx of calcium that was blunted by the specific TRPV4 blocker RN‐1734. We analyzed the involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the development of transepithelial electrical resistance (TER) as an indicator of the tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to establish the TJ. In differentiated epithelia, activation of TRPV4 increases the TER and the accumulation of claudin‐4 in cell–cell contacts. Epidermal Growth Factor (EGF) up‐regulates the TER of corneal epithelial cultures, and we show here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2, an EGF‐activated channel that forms heteromeric complexes with TRPV4, is also concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4‐TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the correct establishment of TJ in corneal epithelia and as well as the regulation of both the barrier function of TJ and its ability to respond to EGF. J. Cell. Physiol. 232: 1794–1807, 2017. © 2016 Wiley Periodicals, Inc.
Hand‐assisted laparoscopic left hepatectomy: how I do it
Authors: Cheek Susannah M. , Sucandy Iswanto , Geller David A.
Published: November 2016

Laparoscopic liver resection has been adopted slowly due to concerns for bleeding and oncologic outcomes. Currently, over 9,500 laparoscopic liver resections have been performed and reported worldwide. Numerous studies have shown the safety and oncologic equivalence of laparoscopic liver resection when compared to open resection. Pure laparoscopic and hand‐assisted laparoscopic liver resection are the two most commonly used techniques for minimally invasive liver resection surgery. Advantages of the hand‐port include tactile feedback, facilitation of liver mobilization, and ease of ability to control bleeding. We present a case report with video of a hand‐assisted laparoscopic left liver resection for a hepatocellular carcinoma in a non‐cirrhotic patient.
Patient‐specific 3D FLAIR for enhanced visualization of brain white matter lesions in multiple sclerosis
Authors: Gabr Refaat E. , Pednekar Amol S. , Govindarajan Koushik A. , Sun Xiaojun , Riascos Roy F. , Ramírez María G. , Hasan Khader M. , Lincoln John A. , Nelson Flavia , Wolinsky Jerry S. , Narayana Ponnada A.
Published: November 2016

Purpose

To improve the conspicuity of white matter lesions (WMLs) in multiple sclerosis (MS) using patient‐specific optimization of single‐slab 3D fluid‐attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI).

Materials and Methods

Sixteen MS patients were enrolled in a prospective 3.0T MRI study. FLAIR inversion time and echo time were automatically optimized for each patient during the same scan session based on measurements of the relative proton density and relaxation times of the brain tissues. The optimization criterion was to maximize the contrast between gray matter (GM) and white matter (WM), while suppressing cerebrospinal fluid. This criterion also helps increase the contrast between WMLs and WM. The performance of the patient‐specific 3D FLAIR protocol relative to the fixed‐parameter protocol was assessed both qualitatively and quantitatively.

Results

Patient‐specific optimization achieved a statistically significant 41% increase in the GM‐WM contrast ratio (P < 0.05) and 32% increase in the WML‐WM contrast ratio (P < 0.01) compared with fixed‐parameter FLAIR. The increase in WML‐WM contrast ratio correlated strongly with echo time (P < 10‐11). Two experienced neuroradiologists indicated substantially higher lesion conspicuity on the patient‐specific FLAIR images over conventional FLAIR in 3–4 cases (intrarater correlation coefficient ICC = 0.72). In no case was the image quality of patient‐specific FLAIR considered inferior to conventional FLAIR by any of the raters (ICC = 0.32).

Conclusion

Changes in proton density and relaxation times render fixed‐parameter FLAIR suboptimal in terms of lesion contrast. Patient‐specific optimization of 3D FLAIR increases lesion conspicuity without scan time penalty, and has potential to enhance the detection of subtle and small lesions in MS.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. MAGN. RESON. IMAGING 2017;46:557–564
Molecular epidemiology of HIV‐1 among the HIV infected people of Manipur, Northeastern India: Emergence of unique recombinant forms
Authors: Sharma Adhikarimayum Lakhikumar , Singh Thiyam Ramsing , Devi Khuraijam Ranjana , Singh Lisam Shanjukumar
Published: November 2016

According to the Joint National Programme on HIV/AIDS (UNAIDS), the northeastern region of India has the highest HIV prevalence in the country. This study was conducted to determine the current HIV‐1 molecular epidemiology of Manipur, a state in northeast India. Blood samples from HIV‐1 seropositive subjects were collected between June 2011 and February 2014. The partial regions of HIV‐1 genes; pol and tat‐vpu‐env were independently amplified, sequenced, analyzed, and genotyped. Based on all sequences generated from 110 samples using pol and/or tat‐vpu‐env gene, the overall HIV‐1 genotypes distribution of Manipur was as follows: 65.45% (72/110) subtype C, 32.73% (36/110) unique recombinant forms (URFs), and 1.82% (2/110) subtype B. The distribution of HIV‐1 genotypes among the risk groups was: heterosexual: 58.33% (35/60) subtype C, 38.33% (23/60) URFs, and 3.34% (2/60) subtype B; intravenous drug users (IDUs): 85.36% (35/41) subtype C, 9.76% (4/41) URFs, and 4.88% (2/41) subtype B; mother to child (MTC): 50% (3/6) URFs and 50% (3/6) subtype C and blood transfusion: 100% (3/3) subtype C. The findings for the first time revealed the emergence of URFs of HIV‐1 in Manipur which is predominant among the sexual and MTC risk groups as compared to IDUs. Taking together, this study illustrated that Manipur is the “recombinant hotspot of HIV” of India. The results will provide the clinical importance for continuous monitoring of HIV‐infections in order to design appropriate prevention measures to limit the spread of new HIV infections.
The chemical nature of organic phosphorus that accumulates in fertilized soils of a temperate pasture as determined by solution 31P NMR spectroscopy
Authors: McLaren Timothy I. , Smernik Ronald J. , Simpson Richard J. , McLaughlin Michael J. , McBeath Therese M. , Guppy Christopher N. , Richardson Alan E.
Published: November 2016

Inefficiency of fertilizer phosphorus (P) use in grazing systems is often associated with the accumulation of inorganic and organic P in fertilized soil. However, the chemical nature of the accumulated organic P remains poorly understood. The aim of this study was to use solution 31P nuclear magnetic resonance (NMR) spectroscopy on sodium hydroxide–ethylenediaminetetraacetic acid (NaOH‐EDTA) extracts to identify the chemical nature of organic P in soils from a medium‐term (13 years) permanent pasture field experiment. This included an unfertilized pasture (P0), and treatments designed to maintain soil P fertility at near ‘optimum' (P1) and ‘supra‐optimum' (P2) levels for pasture growth; pastures at all levels of soil P fertility were continuously grazed with either a moderate or high stocking rate (SR09 and SR18). Approximately 20% of the fertilizer P added to pastures was recovered as organic P in NaOH‐EDTA extracts at the P1 level of soil P fertility in the 0–10 cm soil layer, and the majority (≈ 65%) of this was detected as the broad phosphomonoester signal. In addition, several specific forms of phosphomonoesters (myo‐ and scyllo‐inositol hexakisphosphate, α‐ and β‐glycerophosphate, and RNA mononucleotides) and phosphodiesters were detected across all soils but at low concentrations. This study shows that phosphate fertilization of pastures primarily results in the accumulation of complex forms of phosphomonoesters rather than that of specific forms of recognizable biomolecules (e.g., myo‐inositol hexakisphosphate).
Distribution of exogenous phytase activity in soil solid–liquid phases and their effect on soil organic P hydrolysis
Authors: Yang Xiao Z. , Chen Li J.
Published: November 2016

The bioavailability and stability of organic phosphorus (P) in the soil may be affected by exogenous phytase (EPase) activity and distribution, but remain poorly understood. The distribution of EPase activity and hydrolysis ability of EPase on organic P in soil solid‐liquid phases was investigated. The EPase addition to soil suspension (1:20, w/v) from three soil types (red soil, brown soil, and cinnamon soil) under three treatments (untreated soil, removing clay from soil, and removing organic matter from soil) with different characters in the solution and solid phases was assayed. The results showed that the disappearance pattern of EPase activity from solution was similar for all soils, whereas the enzyme activity on the solid phase was dependent on soil types and treatments with the greatest in red soil and untreated soil. When EPase was added to soils, the adsorption ratio of organic matter and clay was 10 to 25% and 3 to 7%, respectively, with sorption capacity of organic matter being significantly (p< 0.05) stronger than that of clay. Additionally, soil dehydrogenase activity, which is the indicator of overall soil microbial activities, increased after EPase addition and the two enzymes showed significant negative relation in the soil suspension and solution. At the same time, the organic P decreased significantly (p< 0.05) after the addition of EPase in the soil solid, which had a varied rate under –40% after incubating 192 h, whereas organic P in the solution phase increased significantly (p< 0.05). This study demonstrated that organic matter had a strong protective and adsorptive effect on EPase effectiveness and microbes mightbe directly affect EPase longevity and decay. This finding suggests that EPase activity in the solid phase played a more important role in organic P hydrolysis.
Raman spectroscopy of layered lead tin disulfide (PbSnS2) thin films
Authors: Łapińska Anna , Taube Andrzej , Wąsik Michał , Żukowska Grażyna Zofia , Duzynska Anna , Judek Jarosław , Zdrojek Mariusz
Published: November 2016

Nowadays, the attention of researchers is focused on the large family of chalcogenides that poses very unique and interesting properties. One of them is the teallite – PbSnS2, almost unrevealed ternary compound, promising thermoelectric material. In this work, we present first detailed Raman studies of PbSnS2, including the polarization‐dependent and temperature‐dependent measurements (80–400 K range). The strong effect of polarization angle and temperature on the Raman spectra was observed. The polarization studies allowed to assign symmetry of observed modes. The temperature evolutions of the Raman spectra were explained by optical phonon decay into two or three acoustic phonons with equal energies. The extracted first‐order temperature coefficients are among the largest reported so far for layered materials. Our results might be helpful in understanding the anisotropic optical, thermal and electrical properties of PbSnS2. Copyright © 2016 John Wiley & Sons, Ltd.