bluuebunny/crossref_metadata_2025 huggingface dataset:
Optoelectronic Oscillators
Authors: Chi Yu‐Chieh , Lin Gong‐Ru
Published: May 2016

Without the need of any clock source, an optoelectronic oscillator (OEO) enables to simultaneously generate a high‐repetition‐rate optical clock/pulse train with low jitter and a microwave clock with high spectral purity, and it can be employed to further perform signal processing including data generation, pulse shaping, and clock recovery. Therefore, it becomes the center of attention in the microwave photonic technical area. Numerous techniques have been proposed to reduce the single‐sideband (SSB) phase noise and to improve the frequency stability of the OEO. In this article, a historical review of OEOs including different constructing methods and functionalities is introduced. Subsequently, a Mach–Zehnder modulator (MZM)‐based OEO at 40 GHz is focused to implement a synthesizer‐free 40 Gbit/s return‐to‐zero binary phase‐shifted‐keying (RZ‐BPSK) data generator. As a result, the 40 GHz microwave clock with a
Q
‐factor of up to 2 × 10
8
is observed, and its SSB phase noise can be suppressed to −120 dBc/Hz at 100 kHz frequency offset. Moreover, its spectral quality is almost independent of the intraloop fiber‐induced radio‐frequency (RF) power fading. In addition, the delivered optical RZ carrier with a pulse on/off extinction ratio (ER) of 7.7 dB, a pulse width of 10.5 ps, and a timing jitter of 150 fs is particularly suitable for 40 Gbit/s RZ‐BPSK data transmission. At a requested bit error rate (BER) of 10
−9
, a back‐to‐back receiving power sensitivity of −16.3 dBm is observed, which indicates a power penalty of 4 dB after 25 km single‐mode‐fiber (SMF) transmission.
Silane Coupling Agents
Authors: Blum Frank D.
Published: May 2016

Silane coupling agents are often used to improve the properties of composite materials by modifying interfaces. The coupling agents typically contain trichloro, trimethoxy, or triethoxy groups attached to silicon at one end. These inorganic groups hydrolyze, condense, and adsorb at oxide interfaces to form a bond with the coupling agents. The other end of the molecule typically contains organofunctional groups that are chosen to react or to be compatible with an organic polymer resin. The coupling agents are particularly effective for improving the mechanical properties of composites when water is present. The appropriate selection of the coupling agent is of importance for optimal improvement of the mechanical properties of the composite materials. Factors to be considered are the type of chemical bonding desired, compatibility between the coupling agent layer and resin, and the mechanical properties of the interphase.
Activation of focal adhesion kinase through an interaction with β4 integrin contributes to tumorigenicity of colon cancer
Authors: Tai Yu‐Ling , Lai I‐Rue , Peng Yu‐Ju , Ding Shih‐Torng , Shen Tang‐Long
Published: May 2016

High expression of either β4 integrin or focal adhesion kinase (FAK) has been reported in human colon cancer. However, it remains unclear how β4 integrin together with FAK contributes to the tumorigenicity of colon cancer. Here, we demonstrate that the co‐overexpression of β4 integrin and FAK positively correlates with advanced stages of human colon cancer. Activated β4 integrin interacts with FAK and subsequently induces FAK phosphorylation at Tyr397. Furthermore, ablation of the β4 integrin/FAK complex and/or FAK activation impair colon cancer cell proliferation, anchorage‐independent growth, and tumorigenicity. Our data indicate that the β4 integrin/FAK complex and subsequent FAK activation are essential regulators during the tumorigenicity of colon cancer, and we suggest an alternative strategy for colon cancer therapy.
Investigation of H2AX methylation by the SUV39H2 protein lysine methyltransferase
Authors: Schuhmacher Maren Kirstin , Kudithipudi Srikanth , Jeltsch Albert
Published: May 2016

The H3K9 protein lysine methyltransferase SUV39H2 was reported to methylate K134 of H2AX and stimulate H2AX phosphorylation during DNA damage response [Sone K et al. (2014) Nat Commun 5, 5691]. However, the sequence context of H2AX‐K134 differs from the specificity of SUV39H2. We performed in vitro methylation reactions with SUV39H2 (and its homolog SUV39H1) using H2AX protein and peptides, but no methylation at K134 or any other lysine in H2AX was detected. Positive controls demonstrated the functionality of the assays. While our data cannot finally exclude H2AX methylation of SUV39H2 in cells, additional experimental evidence is required to validate this claim.
Substructures within a dipolarization front revealed by high‐temporal resolution Cluster observations
Authors: Yao Zhonghua , Fazakerley A. N. , Varsani A. , Rae I. J. , Owen C. J. , Pokhotelov D. , Forsyth C. , Guo R. L. , Bai S. C. , Yao S. T. , Doss N.
Published: May 2016

The dipolarization front (DF), usually observed near the leading edge of a bursty bulk flow (BBF), is thought to carry an intense current sufficient to modify the large‐scale near‐Earth magnetotail current system. However, the physical mechanism of the current generation associated with DFs is poorly understood. This is primarily due to the limitations of conventional plasma instruments which are unable to provide a sufficient number of unaliased 3‐D distribution functions on the timescale of the DF, which usually travels past a spacecraft in only a few seconds. It is thus almost impossible to unambiguously determine the detailed plasma structure of the DF at the usual temporal resolution of such instruments. Here we present detailed plasma measurements using the Cluster Plasma Electron and Current Experiment and Cluster Ion Spectrometry‐Composition and Distribution Function ion data for an event during which it was possible to observe the full pitch angle distribution at a cadence of 1/4 s. The observations clearly show details of plasma substructure within the DF, including the presence of field‐aligned electron beams. In this event, the current density carried by the electron beam is much larger than the current obtained from the curlometer method. We also suggest that the field‐aligned current around the DF obtained from the curlometer method may have been misinterpreted in previous studies. Our results imply that the nature of the DF current system needs to be revisited using high‐resolution particle measurements, such as those observations shortly to be available from the Magnetospheric Multiscale mission.
Insights into complex layered ejecta emplacement and subsurface stratigraphy in Chryse Planitia, Mars, through an analysis of THEMIS brightness temperature data
Authors: Jones Eriita , Caprarelli Graziella , Osinski Gordon R.
Published: May 2016

Layered ejecta craters on Mars have been interpreted to indicate the presence of volatiles in the substrate, making them important targets for the investigation of sites of astrobiological significance. If the ejecta are associated with the presence of water in the substratum, specific surface grain size trends are expected. In this study we explore the distribution of grain sizes in the layered ejecta of impact craters located in Chryse Planitia, using Thermal Emission Imaging System (THEMIS) thermal infrared data. Ejecta grain size trends, in conjunction with ejecta mobility and lobateness values, are applied to assess the degree of surface flow of the ejecta, and in turn to constrain the plausible volatile abundance, cohesion, and fine particle content of the target materials. Craters with a larger fraction of small grain sizes in their ejecta showed greater ejecta mobility and lobateness, consistent with a water‐rich and/or a low‐cohesion target. Craters displaying decreasing grain size with increasing radius had smaller diameters and lower ejecta mobility and lobateness, indicating only a minimal component of surface ejecta flow. Ejecta grain size trends varied with crater diameter, from which the presence of vertical compositional stratigraphy in Chryse Planitia is inferred and interpreted. Our observations are synthesized into a number of plausible geologic scenarios for Chryse Planitia.
Influences of riverine and upwelling waters on the coastal carbonate system off Central Chile and their ocean acidification implications
Authors: Vargas Cristian A. , Contreras Paulina Y. , Pérez Claudia A. , Sobarzo Marcus , Saldías Gonzalo S. , Salisbury Joe
Published: May 2016

A combined data set, combining data from field campaigns and oceanographic cruises, was used to ascertain the influence of both river discharges and upwelling processes, covering spatial and temporal variation in dissolved inorganic carbon (DIC) and aragonite saturation state. This work was conducted in one of the most productive river‐influenced upwelling areas in the South Pacific coasts (36°S). Additionally, further work was also conducted to ascertain the contribution of different DIC sources, influencing the dynamics of DIC along the land‐ocean range. Six sampling campaigns were conducted across seven stations at the Biobío River basin, covering approximately 200 km. Three research cruises were undertaken simultaneously, covering the adjacent continental shelf, including 12 sampling stations for hydrographic measurements. Additionally, six stations were also sampled for chemical analyses, covering summer, winter, and spring conditions over 2010 and 2011. Our results evidenced that seaward extent of the river plume was more evident during the winter field campaign, when highest riverine DIC fluxes were observed. The carbonate system along the river‐ocean continuum was very heterogeneous varying over spatial and temporal scales. High DIC and pCO2 were observed in river areas with larger anthropogenic effects. CO2 supersaturation at the river plume was observed during all campaigns due to the influence of low pH river waters in winter/spring and high‐pCO2 upwelling waters in summer. δ13CDIC evidenced that main DIC sources along the river and river plume corresponded to the respiration of terrestrial organic matter. We have linked this natural process to the carbonate saturation on the adjacent river‐influenced coastal area, suggesting that Ωaragonite undersaturation in surface/subsurface waters is largely modulated by the influence of both river discharge and coastal upwelling events in this productive coastal area. Conditions of low Ωaragonite might impact negatively physiological traits for marine organisms, such as bivalves, gastropods, and crustaceans. Therefore, local populations from river‐influenced sites could be inherently more tolerant to ocean acidification than organisms living in regions with lower Ωaragonite variability.
Cutin and Suberin Polyesters
Authors: Li‐Beisson Yonghua , Verdier Gaëtan , Xu Lin , Beisson Fred
Published: May 2016

Cutin and suberin are cell wall‐associated glycerolipid polymers that are specific to plants. Cutin forms the framework of the cuticle sealing the aerial epidermis, while suberin is present in the periderm of barks and underground organs. Suberised walls are also found in the root endodermis. Barriers based on cutin and suberin restrict the transport of water and solutes across cell walls and limit pathogen invasions. Chemical analysis shows that both polymers are polyesters composed mostly of fatty hydroxyacids, diacids and epoxyacids esterified to each other and to glycerol. Suberin, whose best‐known form is cork, usually differs from cutin (which has C16 and C18 fatty acids) by a higher content of C20–C24 aliphatics and aromatics. In the last 10 years, the identification of mutants of Arabidopsis or other model plants affected in cutin and/or suberin content has allowed the construction of a more complete picture of the polyester biosynthesis pathways, which currently include acyltransferases with unique specificities, fatty acid hydroxylases, acyl‐CoA synthetases, fatty acid elongases, fatty acyl‐CoA reductases, feruloyl transferases, ABC transporters and extracellular transacylases.

Key Concepts

The epidermal cells of plant aerial organs and periderm/endoderm cells synthesise the protective cell wall lipid polymers cutin and suberin respectively.

Cutin and suberin are both polyesters containing glycerol and oxygenated fatty acids.

Cutin structure is not completely understood and suberin structure remains controversial.

Oxygenated fatty acid monomers are produced by fatty acid oxidases of the cytochrome P450 superfamily.

Acylation of oxygenated fatty acids to glycerol is catalysed by special glycerol‐3‐phosphate acyltransferases.

Cutin acylglycerol building blocks are exported to the cell wall and polymerised by extracellular transacylases.

How suberin precursors are assembled is still unknown.
Digital Image Analysis
Authors: Burri Olivier , Guiet Romain , Seitz Arne
Published: May 2016

Light microscopy offers life sciences the possibility to study a variety of organisms on widely differing spatial and temporal scales. Recent years have seen the appearance of a multitude of important light microscopy techniques. To characterise and describe biological processes, however, sheer visualisation of images is inadequate. The assembly of image‐processing algorithms, so‐called workflows, is needed to extract meaningful quantitative data. These workflows are as important as image acquisition and, therefore, are critical components for data acquisition and sample preparation. Here, we describe a variety of image‐processing workflows covering a large part of the biological landscape pointing out common themes and outlining a generic template for workflow assembly.

Key Concepts

Digital image analysis is an important tool to extract meaningful data out of an image.

Digital image analysis is the last component of a workflow comprising sample preparation and image acquisition.

Segmentation allows to identify objects in an image.

Filtering is needed to reduce noise in images from biological samples.

Digital image analysis is the key for reproducible workflows in life sciences.
Gene Therapy for Haemoglobinopathies
Authors: Goodman Michael A , Malik Punam
Published: May 2016

Haemoglobinopathies, including thalassaemia and sickle cell anaemia, are common genetic diseases with significant associated morbidity and mortality. The potentially curative modality, haematopoietic stem cell (HSC) transplant, is restricted to a minority with matched donors, and has potential immunological adverse sequelae. Autologous HSC‐based therapies, using a patient's own genetically modified HSCs as donor cells, eliminates the need for an allogeneic matched donor and the immunological adverse effects of allogeneic HSC transplants. Gene therapy for haemoglobinopathies can be categorised as: (1) gene addition, (2) gene disruption, (3) gene correction, or (4) gene modification resulting in pharmacological upregulation of foetal haemoglobin. Currently, additive gene therapies are in clinical trials, while promising therapies based on gene disruption, editing and modulation of gene regulation are currently under development. Many of these therapies use the latest innovations in gene editing, the designer nucleases, including zinc‐fingers, transcription activator‐like effector nucleases, and clustered regularly interspaced short palindromic repeats/Cas technologies.

Key Concepts

Haemoglobin exists as a heterotetramer of two α‐globin subfamily peptides and two β‐globin subfamily peptides; adult haemoglobin primarily composed of α
2
β
2.

Haemoglobinopathies are genetic diseases that affect either the function or level of globin peptides.

Haemoglobinopathies are the most prevalent genetic diseases with significant morbidity and mortality.

Of these, β‐globinopathies (sickle cell anaemia and β‐thalassaemia) are the most common monogenic diseases worldwide and manifest within 6–12 months of birth.

Severity of haemoglobinopathies can be ameliorated through the expression of the missing haemoglobin subunit beta (HBB), additional β‐like globins, or genes that upregulate alternative globins.

Additive gene therapy using lentivirus vectors has proven to be successful for both β‐thalassaemia and sickle cell anaemia clinically.

Gene editing strategies, using ZFNs, TALENs or CRISPR/Cas, can be used as a ‘fix and run’ approach and have the advantage over additive gene therapies by avoiding insertional genotoxicity and restoring innate regulatory mechanisms.

Erythroid‐specific modulation of
BCL11A
has been shown to increase expression of haemoglobin subunits gamma 1 (HBG1) and gamma 2 (HBG2), and may be a viable alternative treatment modality.
Nonparametric Estimation and Comparison of Species Richness
Authors: Chao Anne , Chiu Chun‐Huo
Published: May 2016

Species richness (the number of species) in an assemblage is a key metric in many research fields of ecology. Simple counts of species in samples typically underestimate the true species richness and strongly depend on sampling effort and sample completeness. Based on possibly unequal‐sampling effort and incomplete samples that miss many species, there are two approaches to infer species richness and make fair comparisons among multiple assemblages,: (1) An asymptotic approach via species richness estimation. This approach aims to compare species richness estimates across assemblages. We focus on the nonparametric estimators that are universally valid for all species abundance distributions. (2) A non‐asymptotic approach via the sample‐size‐ and coverage‐based rarefaction and extrapolation on the basis of standardised sample size or sample completeness (as measured by sample coverage). This approach aims to compare species richness estimates for equally large or equally complete samples. Two R packages (SpadeR and iNEXT) are applied to beetle data for illustration.

Key Concepts

Due to sampling limitation, there are undetected species in almost every biodiversity survey.

Empirical species counts underestimate species richness and highly depend on sampling efforts and sample completeness.

Based on incomplete samples, species richness (observed plus undetected) is statistically difficult to estimate accurately especially for highly diverse assemblages with many rare species.

Abundant species (which are certain to be detected in samples) contain almost no information about the undetected species richness.

Rare species (which are likely to be either undetected or infrequently detected) contain nearly all the information about the undetected species richness.

Most nonparametric estimators of the number of undetected species are based on the frequency counts of the detected rare species, e.g. singletons and doubletons for abundance data.

Nonparametric estimators of species richness are universally valid for all species abundance distributions and thus are more robust than parametric estimators that are based on specified parametric abundance models.

Rarefaction and extrapolation methods allow for fair and meaningful comparison of species richness estimates for standardised samples on the basis of sample size or sample completeness.

Sample‐size‐based rarefaction and extrapolation methods aim to compare species richness estimates for equally large samples determined by samplers.

Coverage‐based rarefaction and extrapolation methods aim to compare species richness estimates for equally complete samples or equal fractions of population individuals reliably estimated from data.
Aviation and Climate Change–The Continuing Challenge
Authors: Bows‐Larkin Alice , Mander Sarah L. , Traut Michael B. , Anderson Kevin L. , Wood F. Ruth
Published: May 2016

The latest scientific framing of climate change emphasizes the importance of limiting cumulative emissions and the need to urgently cut CO2. International agreements on avoiding a 2 °C global temperature rise make clear the scale of CO2reductions required across all sectors. Set against a context of urgent mitigation, the outlook for aviation's emissions is one of continued growth. Limited opportunities to further improve fuel efficiency, slow uptake of new innovations, coupled with anticipated rises in demand across continents collectively present a huge challenge to aviation in cutting emissions. While difficulties in decarbonizing aviation are recognized by industry and policymakers alike, the gap between what's necessary to avoid 2 °C and aviation's CO2projections has profound implications. Biofuel is one of the few innovations that could play a significant role in closing the gap, but with low anticipated penetration before 2020 its contribution would have little impact over the desired timeframe. If the aviation sector does not urgently address rising emissions, there is an increasing risk that investment in new aircraft and infrastructure could lead to stranded assets. This leaves it facing an uncomfortable reality. Either the sector acts urgently on climate change and curtails rising demand, or it will be failing to take responsibility for a considerable and growing portion of climate change impacts.
UASUses, Capabilities, Grand Challenges
Authors: Francis Michael S.
Published: May 2016

The chapter reviews the evolution of unmanned aircraft, from a few primitive flying machines incapable of all but the simplest of missions to today's wide array of high‐tech enabled unmanned air systems (UAS), potentially capable of addressing a broad range of applications in diverse, complex environments. Historical factors such as the century‐long influence of military applications and the relatively recent explosion in enabling information technology are examined, as are their impacts on the current “drone revolution” and expansion of civil and commercial uses. Opportunities for leveraging the absence of an onboard human presence to expand the design and operational envelopes are also discussed. Anticipated future capabilities such as increased levels of autonomy and their impact on potential new and enhanced mission capabilities are explored along with the limitations and constraints, especially the grand challenges, they may face in achieving their full potential.
Recent Development of Advanced Electrode Materials by Atomic Layer Deposition for Electrochemical Energy Storage
Authors: Guan Cao , Wang John
Published: May 2016

Electrode materials play a decisive role in almost all electrochemical energy storage devices, determining their overall performance. Proper selection, design and fabrication of electrode materials have thus been regarded as one of the most critical steps in achieving high electrochemical energy storage performance. As an advanced nanotechnology for thin films and surfaces with conformal interfacial features and well controllable deposition thickness, atomic layer deposition (ALD) has been successfully developed for deposition and surface modification of electrode materials, where there are considerable issues of interfacial and surface chemistry at atomic and nanometer scale. In addition, ALD has shown great potential in construction of novel nanostructured active materials that otherwise can be hardly obtained by other processing techniques, such as those solution‐based processing and chemical vapor deposition (CVD) techniques. This review focuses on the recent development of ALD for the design and delivery of advanced electrode materials in electrochemical energy storage devices, where typical examples will be highlighted and analyzed, and the merits and challenges of ALD for applications in energy storage will also be discussed.
Improving dissolution kinetics of pharmaceuticals by fluidized bed impregnation of active pharmaceutical ingredients
Authors: Grigorov Plamen I. , Glasser Benjamin J. , Muzzio Fernando J.
Published: May 2016

Investigational drugs are increasingly becoming less soluble in aqueous media, thus, presenting real challenges during development. Previous work has successfully demonstrated the manufacturing of pharmaceuticals using fluidized bed (FB) impregnation of APIs onto porous carriers. This study demonstrates the usefulness of FB impregnation in formulating poorly soluble drugs. We show that dissolution of Fenofibrate is greatly improved by FB impregnation onto Neusilin® (Fuji Health Science Inc, Burlington, NJ USA), a synthetic amorphous form of magnesium alumino‐metasilicate. We impregnate Neusilin® for range of loadings and examine Fenofibrate's physical state. Dissolution of impregnated formulations is drug loading dependent and loadings below 40% show great improvement (decrease) in release time compared to physical blend. Release times are further improved by milling. We also examine feasibility of coimpregnating Fenofibrate with additives and observe stability (1.5 years) of the amorphous form of Fenofibrate inside Neusilin®. This stabilization significantly improves Fenofibrate's dissolution kinetics, making our formulation comparable to one of the current market formulations, TriCor® tablets (AbbVie Inc, North Chicago, IL USA). © 2016 American Institute of Chemical Engineers AIChE J, 62: 4201–4214, 2016
Towards local governance of marine resources and ecosystems on Easter Island
Authors: Aburto Jaime A. , Gaymer Carlos F. , Cundill Georgina
Published: May 2016

Social‐ecological system sustainability depends in part upon the fit between ecosystems and institutions.

In 2014, the local community on Easter Island started a bottom‐up process to improve marine resources conservation and management.

Local stakeholders formed a working group that has regular meetings and goals, such as creating a sea council and some basic action plans, thus initiating a local governance transformation process.

A participatory process was conducted together with a local organization that led the marine conservation issues on the island to define the factors that could favour and/or undermine the formation of the sea council. Also, the stakeholders that must be present in such a sea council were identified.

Twelve factors that could facilitate or hinder the implementation of a sea council were identified. The lack of representativeness of public institutions is a major challenge.

Public institutions are designed to ensure compliance with central government strategies, but the decisions do not represent the worldview of islanders.

The results showed the potential value of conducting a participatory process to identify the key issues that could hinder or favour a desired governance transformation process. The participatory process also highlighted governance mismatches that are important to consider in attempts to pursue more effective fishery governance on Easter Island, and other Island communities.

Centralized governance systems do not respond rapidly to locally observed social and ecological dynamics. By contrast, a local decision‐making system based on traditional laws and local governance can more rapidly respond to observed changes.

The participatory process presented here holds the potential to support local people in their planning and coordination for marine conservation and management in order to optimize bottom‐up change processes involving multiple stakeholders with different interests, values and levels of power.

Copyright © 2016 John Wiley & Sons, Ltd.
Development of the Heart Endocardium at an Early Stage of Chick Embryos Evaluated at Light‐ and Electron‐Microscopic Levels
Authors: Hara Yaiko , Wake Kenjiro , Inoue Kouji , Kuroda Noriyuki , Sato Akie , Inamatsu Mutsumi , Tateno Chise , Sato Tetsuji
Published: May 2016

Development of the endocardium in the heart of 4 to 4·1/2‐day‐incubated chick embryos was observed light and electron microscopically, and these results were evaluated by immunohistochemistry for desmin, FLK1 (VEGFR‐2) or CD31, and by in situ hybridization assays for flk1‐mRNA expression. At this developmental stage, the atrium and the ventricle were already discriminated by formation of the atrio‐ventricular junction. The cardiac wall consisted of three layers; the inner endocardium, the middle myocardium, and the outer epicardium. The developing endocardium was seen as a chain of single‐layered endocardial cells. Along its inner surface, numerous clusters of blood corpuscles were distributed, which seemed to contain some undifferentiated endocardial cells estimated from their characteristic ultrastructure and histological topography. Several blood corpuscles were in directly contact with the myocardium at the missing portions of the developing endocardial cell‐chains. Differentiating endocardial cells individually showed roundish, small and large crescent, or flat in shapes. Such a prominent change of cell shapes appeared to be in parallel with their secretory activity during the transformation from the undifferentiated cells to the endocardial cells. Furthermore, immunohistochemistry for FLK1 or CD31, and in situ hybridization assays for flk1‐mRNA labeled the cells composing developing endocardial cell‐chains. Though these expressional analyses could not document clearly the transition of precursor cells into endocardial cells, the present study provided for the first time some important information regarding the morphological transition process toward endocardial cells at ultrastructural levels. Anat Rec, 299:1080–1089, 2016. © 2016 Wiley Periodicals, Inc.
Efficient recombinant expression of SFTI‐1 in bacterial cells using intein‐mediated protein trans‐splicing
Authors: Li Yilong , Aboye Teshome , Breindel Leonard , Shekhtman Alexander , Camarero Julio A.
Published: May 2016

We report for the first time the recombinant expression of bioactive wild‐type sunflower trypsin inhibitor 1 (SFTI‐1) inside E. coli cells by making use of intracellular protein trans‐splicing in combination with a high efficient split‐intein. SFTI‐1 is a small backbone‐cyclized polypeptide with a single disulfide bridge and potent trypsin inhibitory activity. Recombinantly produced SFTI‐1 was fully characterized by NMR and was observed to actively inhibit trypsin. The in‐cell expression of SFTI‐1 was very efficient reaching intracellular concentration ≈ 40 µM. This study clearly demonstrates the possibility of generating genetically encoded SFTI‐based peptide libraries in live E. coli cells, and is a critical first step for developing in‐cell screening and directed evolution technologies using the cyclic peptide SFTI‐1 as a molecular scaffold. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 818–824, 2016.
Characterization of the stereochemical configuration of lanthionines formed by the lanthipeptide synthetase GeoM
Authors: Garg Neha , Goto Yuki , Chen Ting , van der Donk Wilfred A.
Published: May 2016

The biosynthesis of the class II lanthipeptide geobacillin II was reconstituted in vitro. The purified precursor peptide was modified by the lanthipeptide synthetase GeoM at temperatures ranging between 37 and 80°C demonstrating the thermostability of the enzyme. Geobacillin II shares with cytolysin, haloduracin, and carnolysin a DhxDhxXxxXxxCys motif (Dhx = dehydroalanine or dehydrobutyrine) as precursor to its N‐terminal A‐ring. Like in these other three lantibiotics, the lanthionine in the A‐ring of geobacillin II had the LL stereochemical configuration as shown by chiral gas chromatography/mass spectrometry. Various analogues of geobacillin II were produced using co‐expression of mutants of the precursor peptide GeoAII and the synthetase GeoM in Escherichia coli. The findings in this study suggest that the stereochemical outcome of the A‐ring in geobacillin II is not solely dependent on the peptide sequence as previously suggested for haloduracin © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 834–842, 2016.
Stapling peptides using cysteine crosslinking
Authors: Fairlie David P , Dantas de Araujo Aline
Published: May 2016

Stapled peptides are an emerging class of cyclic peptide molecules with enhanced biophysical properties such as conformational and proteolytic stability, cellular uptake and elevated binding affinity and specificity for their biological targets. Among the limited number of chemistries available for their synthesis, the cysteine‐based stapling strategy has received considerable development in the last few years driven by facile access from cysteine‐functionalized peptide precursors. Here we present some recent advances in peptide and protein stapling where the side‐chains of cysteine residues are covalently connected with a range of different crosslinkers affording bisthioether macrocyclic peptides of varying topology and biophysical properties. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 843–852, 2016.
Cyclic peptide oral bioavailability: Lessons from the past
Authors: Wang Conan K , Craik David J.
Published: May 2016

Achieving high oral bioavailability for drugs is a key design objective in drug development. It is not surprising then that with the growing expectation of peptides as future drugs, there has also been an increasing interest in developing oral peptide therapeutics. Brought to the fore are questions such as what makes peptides orally bioavailable and how this can be achieved; questions which have inspired research into the area for decades. Early research in the area focused on linear peptides with more recent literature focusing on cyclic peptides, motivated in part by cyclic peptides like cyclosporine A that have demonstrated drug‐like oral bioavailability. In this review, we take a look at research on the oral bioavailability of peptides, focusing on factors that affect passive permeability. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 901–909, 2016.
Enhanced cell‐surface display and secretory production of cellulolytic enzymes with Saccharomyces cerevisiae Sed1 signal peptide
Authors: Inokuma Kentaro , Bamba Takahiro , Ishii Jun , Ito Yoichiro , Hasunuma Tomohisa , Kondo Akihiko
Published: May 2016

Recombinant yeast strains displaying aheterologous cellulolytic enzymes on their cell surfaces using a glycosylphosphatidylinositol (GPI) anchoring system are a promising strategy for bioethanol production from lignocellulosic materials. A crucial step for cell wall localization of the enzymes is the intracellular transport of proteins in yeast cells. Therefore, the addition of a highly efficient secretion signal sequence is important to increase the amount of the enzymes on the yeast cell surface. In this study, we demonstrated the effectiveness of a novel signal peptide (SP) sequence derived from the Saccharomyces cerevisiae SED1 gene for cell‐surface display and secretory production of cellulolytic enzymes. Gene cassettes with SP sequences derived from S. cerevisiae SED1 (SED1SP), Rhizopus oryzae glucoamylase (GLUASP), and S. cerevisiae α‐mating pheromone (MFα1SP) were constructed for cell‐surface display of Aspergillus aculeatus β‐glucosidase (BGL1) and Trichoderma reesei endoglucanase II (EGII). These gene cassettes were integrated into the S. cerevisiae genome. The recombinant strains with the SED1SP showed higher cell‐surface BGL and EG activities than those with the conventional SP sequences (GLUASP and MFα1SP). The novel SP sequence also improved the secretory production of BGL and EG in S. cerevisiae. The extracellular BGL activity of the recombinant strains with the SED1SP was 1.3‐ and 1.9‐fold higher than the GLUASP and MFα1SP strains, respectively. Moreover, the utilization of SED1SP successfully enhanced the secretory production of BGL in Pichia pastoris. The utilization of the novel SP sequence is a promising option for highly efficient cell‐surface display and secretory production of heterologous proteins in various yeast species. Biotechnol. Bioeng. 2016;113: 2358–2366. © 2016 Wiley Periodicals, Inc.
Health‐related quality of life before and after head and neck squamous cell carcinoma: Analysis of the Surveillance, Epidemiology, and End Results–Medicare Health Outcomes Survey linkage
Authors: Rettig Eleni M. , D'Souza Gypsyamber , Thompson Carol B. , Koch Wayne M. , Eisele David W. , Fakhry Carole
Published: May 2016

BACKGROUND

Understanding health‐related quality of life (HRQOL) is crucial to providing high‐quality survivorship care for patients with head and neck squamous cell carcinoma (HNSCC). Trends in and prognostic significance of HRQOL before and after HNSCC have not been well described.

METHODS

HRQOL for older individuals with HNSCC was examined using the linked Surveillance, Epidemiology, and End Results–Medicare Health Outcomes Survey database. Surveys assessing HRQOL from 5 years prediagnosis to 10 years postdiagnosis were included. HRQOL over time was modeled using multilevel linear regression with restricted cubic splines and was reported as either total HRQOL or change in HRQOL (denoted Δ). The association of prediagnosis HRQOL with survival was examined.

RESULTS

In total, 1653 individuals were included; of these, 61% completed 1 survey, and 39% completed multiple surveys. Overall HRQOL decreased progressively until 13 months postdiagnosis, then recovered toward baseline between 2 and 5 years. However, after stratification by survival group, the postdiagnosis recovery was not observed. Individuals with shorter survival had lower HRQOL prediagnosis (<2‐year survivors, 87.3; > 5‐year survivors, 96.4; P = .004) with a steeper decline in HRQOL during diagnosis and treatment (<2‐year survivors: Δ, −16.6; 95% confidence interval [CI], −23.8, −9.4; > 5‐year survivors: Δ, −0.9; 95% CI, −1.8, 0.08). Radiotherapy and advanced stage were associated with greater declines in HRQOL during diagnosis and treatment (P < .001). Higher prediagnosis HRQOL was independently associated with improved overall survival (adjusted hazard ratio for 10‐point increase, 0.91; 95% CI, 0.85‐0.97).

CONCLUSIONS

HRQOL declines before and after HNSCC, whereas any observed posttreatment recovery is likely an artifact of shorter survival among individuals with the lowest HRQOL. The prognostic implication of prediagnosis HRQOL may inform patient counseling. Cancer 2016;122:1861–70. © 2016 American Cancer Society.
Increased incidence but improved median overall survival for biliary tract cancers diagnosed in Ontario from 1994 through 2012: A population‐based study
Authors: Flemming Jennifer A. , Zhang‐Salomons Jina , Nanji Sulaiman , Booth Christopher M.
Published: May 2016

BACKGROUND

To the authors’ knowledge, the incidence of biliary tract cancer (BTC) in Canada is unknown. In the current study, the authors sought to describe the epidemiology of BTC using a large population‐based cancer database from Ontario, Canada.

METHODS

The current study was a population‐based cohort study using the Ontario Cancer Registry. Patients with intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC) diagnosed between 1994 and 2012 were included. Age‐standardized incidence and mortality rates were compared using incidence rate ratios (IRRs). Overall survival from the time of diagnosis was calculated for 3 eras: 1994 through 1999, 2000 through 2005, and 2006 through 2012. The number of patients receiving chemotherapy, radiotherapy, or surgery was determined using linked clinical data.

RESULTS

A total of 9039 cases (1569 IHCC cases, 4337 EHCC cases, and 3133 GBC cases) were identified. The rate of BTC increased by 1.6% per year (IRR, 1.016; 95% confidence interval [95% CI], 1.008‐1.024 [P<.001]). The incidence increased by 7.0% per year among cases of IHCC (IRR, 1.070; 95% CI, 1.058‐1.081 [P<.001]) and 1.8% per year in cases of EHCC (IRR, 1.018; 95% CI, 1.009‐1.027 [P<.001]), whereas the incidence of GBC remained unchanged (IRR, 0.991; 95% CI, 0.982‐1.001 [P = .086]). The median survival for the cohort was 8.3 months, with improvement noted over the study period (6.1 months for 1994‐1999 vs 8.5 months for 2000‐2005 vs 10.3 months for 2006‐2012 [P<.001]). The median survival was the longest for EHCC (11.3 months), followed by GBC (6.4 months) and IHCC (6.2 months). The percentage of patients receiving chemotherapy and/or radiotherapy increased over the study (P<.001), whereas the percentage of patients receiving surgery decreased (P<.001).

CONCLUSIONS

An increased incidence of BTC during 1994 through 2012 was observed. Explanations for the observed temporal improvement in median survival require further exploration. Cancer 2016;122:2534–43. © 2016 American Cancer Society.
Fine‐needle aspiration and core needle biopsy: An update on 2 common minimally invasive tissue sampling modalities
Authors: VanderLaan Paul A.
Published: May 2016

Fine‐needle aspiration (FNA) and core needle biopsy (CNB) represent 2 of the most common minimally invasive tissue sampling modalities. Although similar in many ways, there are significant differences in the collection, processing, interpretation, and suitability for ancillary testing that exist between FNA and CNB. This review provides a brief overview of the strengths and weaknesses of FNA compared with CNB, as well as an update regarding the landscape of recently published studies that investigate the organ‐specific comparative performance metrics of FNA and CNB. A current understanding of the benefits and limitations of FNA and CNB will help the cytopathologist and the clinician alike to select the right procedure for the right patient at the right time. Cancer Cytopathol 2016;124:862–870. © 2016 American Cancer Society.
Predictors of psychological outcome in patients with eating disorders: A routine outcome monitoring study
Authors: Dingemans Alexandra E. , van Son Gabriëlle E. , Aardoom Jiska J. , Bruidegom Kiki , Slof‐Op 't Landt Margarita C.T. , van Furth Eric F.
Published: May 2016

Background

Identifying predictors of psychological outcome for patients with eating disorders may improve the effectiveness of treatment. Patients with different pre‐treatment characteristics and symptoms may benefit from different therapies. This study aimed to identify potential predictors of treatment outcome in a large naturalistic cohort of patients with an eating disorder.

Method

The study sample included patients (N = 1153) with all types of eating disorders who were receiving residential, day, or outpatient treatment. Remission was defined by means of four different indicators based on the Eating Disorder Examination‐Questionnaire global score: 1. achieving reliable change; 2. showing a 50% reduction in baseline symptom severity; 3. reaching the clinical significance cut‐off point; and 4. a combination of indicators 2 and 3. Potential predictor variables were investigated in univariate and multivariate Cox regression models.

Results

Different predictors were found for the four outcome criteria. Patients with high levels of interpersonal distrust at baseline were less likely to have achieved reliable change in eating disorder psychopathology. Higher self‐esteem and less body dissatisfaction at baseline was independently associated with a symptom reduction of more than 50% and/or reaching the clinical significance cut‐off point. Contrary to our expectations, no differences in outcome were found between the eating disorder subtypes.

Discussion

Clinically, it is important to reduce the risk of poor outcome and to achieve a rapid response in treatment using an intervention designed for this purpose, such as shared decision making or an intervention directed at self‐esteem or body image, which may act as a catalyst for change. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:863–873)
The case for immune‐based approaches in biliary tract carcinoma
Authors: Duffy Austin G. , Makarova‐Rusher Oxana V. , Greten Tim F.
Published: May 2016

Biliary tract cancers (BTC) comprise a group of uncommon malignancies in which the standard therapies are minimally effective and evolve slowly. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune‐based approaches has yet to be seen. However, the etiological background of BTC—overlapping in almost every known causative or associated factor with inflammation—provides a strong clue that these approaches may have an impact in this group of diseases. This review covers what we currently know about the role of the immune system in the etiology of BTC, highlighting differences by subtype, and pointing to the therapeutic opportunities currently entering the clinic or about to do so. (Hepatology 2016;64:1785‐1791)
Treatment of a patient with genotype 7 hepatitis C virus infection with sofosbuvir and velpatasvir
Authors: Schreiber Jonas , McNally John , Chodavarapu Krishna , Svarovskaia Evguenia , Moreno Christophe
Published: May 2016

During a phase 3 study evaluating the combination of sofosbuvir‐velpatasvir for 12 weeks in patients with genotype 1, 2, 4, 5, and 6 hepatitis C virus (HCV) infection, we enrolled a patient who was subsequently found to be infected with genotype 7 HCV. This patient tolerated the study regimen well and achieved sustained virological response 12 weeks after treatment (SVR12). (Hepatology 2016;64:983‐985)
The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study
Authors: Sapisochin Gonzalo , Goldaracena Nicolas , Laurence Jerome M. , Dib Martin , Barbas Andrew , Ghanekar Anand , Cleary Sean P. , Lilly Les , Cattral Mark S. , Marquez Max , Selzner Markus , Renner Eberhard , Selzner Nazia , McGilvray Ian D. , Greig Paul D. , Grant David R.
Published: May 2016

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer‐related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5‐year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long‐term follow‐up (10‐years) using an intention‐to‐treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow‐up from listing was 59.7 (26.8‐103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10‐year actuarial survival from transplant between groups. On an intention‐to‐treat basis, the dropout rate was higher in the M+ group and the 5‐year and 10‐year survival rates from listing were decreased in the M+ group. An alpha‐fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. Conclusion: Tumor differentiation and cancer‐related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha‐fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077‐2088)
A multiple‐stimulus‐without‐replacement assessment for sexual partners: Purchase task validation
Authors: Jarmolowicz David P. , Lemley Shea M. , Mateos Ananya , Sofis Michael J.
Published: May 2016

The current study developed and tested a multiple‐stimulus‐without‐replacement (MSWO) assessment for potential sexual partners for use in research on human immunodeficiency virus. College students (N = 41) first completed an MSWO assessment and then completed a hypothetical purchase task for encounters with partners identified by the MSWO as high, median, and low preference. Overall, hypothetical purchase task responding was consistent with that from the MSWO, in that the highest valuation was observed for the high‐preference partner and the lowest for the low‐preference partner. Potentially interesting individual differences in purchase task responding, however, were obtained; some subjects showed differentiated responding among the 3 preference levels (n = 15), whereas others similarly valued high‐ and median‐preference partners (n = 5), and others similarly valued low‐ and median‐preference partners (n = 18).