bluuebunny/crossref_metadata_2025 huggingface dataset:
Liquid Biopsy in Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society
Authors: Sholl Lynette M. , Aisner Dara L. , Allen Timothy Craig , Beasley Mary Beth , Cagle Philip T. , Capelozzi Vera L. , Dacic Sanja , Hariri Lida P. , Kerr Keith M. , Lantuejoul Sylvie , Mino-Kenudson Mari , Raparia Kirtee , Rekhtman Natasha , Roy-Chowdhuri Sinchita , Thunnissen Eric , Tsao Ming , Vivero Marina , Yatabe Yasushi
Published: May 2016

Liquid biopsy has received extensive media coverage and has been called the holy grail of cancer detection. Attempts at circulating tumor cell and genetic material capture have been progressing for several years, and recent financially and technically feasible improvements of cell capture devices, plasma isolation techniques, and highly sensitive polymerase chain reaction– and sequencing-based methods have advanced the possibility of liquid biopsy of solid tumors. Although practical use of circulating RNA-based testing has been hindered by the need to fractionate blood to enrich for RNAs, the detection of circulating tumor cells has profited from advances in cell capture technology. In fact, the US Food and Drug Administration has approved one circulating tumor cell selection platform, the CellSearch System. Although the use of liquid biopsy in a patient population with a genomically defined solid tumor may potentially be clinically useful, it currently does not supersede conventional pretreatment tissue diagnosis of lung cancer. Liquid biopsy has not been validated for lung cancer diagnosis, and its lower sensitivity could lead to significant diagnostic delay if liquid biopsy were to be used in lieu of tissue biopsy. Ultimately, notwithstanding the enthusiasm encompassing liquid biopsy, its clinical utility remains unproven.
Considerations for the Management of Medial Orbital Wall Blowout Fracture
Authors: Kim Yong-Ha , Park Youngsoo , Chung Kyu Jin
Published: May 2016

Recently, diagnoses of and operations for medial orbital blowout fracture have increased because of the development of imaging technology. In this article, the authors review the literature, and overview the accumulated knowledge about the orbital anatomy, fracture mechanisms, surgical approaches, reconstruction materials, and surgical methods. In terms of surgical approaches, transcaruncular, transcutaneous, and transnasal endoscopic approaches are discussed. Reconstruction methods including onlay covering, inlay implantation, and repositioning methods are also discussed. Consideration and understanding of these should lead to more optimal outcomes.
Melatonin Protects Human Adipose-Derived Stem Cells from Oxidative Stress and Cell Death
Authors: Tan Shaun S. , Han Xiaolian , Sivakumaran Priyadharshini , Lim Shiang Y. , Morrison Wayne A.
Published: May 2016

Background Adipose-derived stem cells (ASCs) have applications in regenerative medicine based on their therapeutic potential to repair and regenerate diseased and damaged tissue. They are commonly subject to oxidative stress during harvest and transplantation, which has detrimental effects on their subsequent viability. By functioning as an antioxidant against free radicals, melatonin may exert cytoprotective effects on ASCs.

Methods We cultured human ASCs in the presence of varying dosages of hydrogen peroxide and/or melatonin for a period of 3 hours. Cell viability and apoptosis were determined with propidium iodide and Hoechst 33342 staining under fluorescence microscopy.

Results Hydrogen peroxide (1–2.5 mM) treatment resulted in an incremental increase in cell death. 2 mM hydrogen peroxide was thereafter selected as the dose for co-treatment with melatonin. Melatonin alone had no adverse effects on ASCs. Co-treatment of ASCs with melatonin in the presence of hydrogen peroxide protected ASCs from cell death in a dose-dependent manner, and afforded maximal protection at 100 µM (n=4, one-way analysis of variance P<0.001). Melatonin co-treated ASCs displayed significantly fewer apoptotic cells, as demonstrated by condensed and fragmented nuclei under fluorescence microscopy.

Conclusions Melatonin possesses cytoprotective properties against oxidative stress in human ASCs and might be a useful adjunct in fat grafting and cell-assisted lipotransfer.
Pilotprosjekt infrastruktur for forskningsdata ved UiT
Authors: Longva Leif , Amundsen Espen Thijssen , Dragseth Roy , Østhus Randi , Høydalsvik Stein
Published: May 2016

Rapporten oppsummerer erfaringer fra etablering av et institusjonelt arkiv for åpne data ved UiT Norges arktiske universitet.
Dynamic population balance and flow models for granular solids in a linear vibrating screen
Authors: Rotich Nicolus , Tuunila Ritva , Elkamel Ali , Louhi‐Kultanen Marjatta
Published: May 2016

Vibrating screens are a widely applied form of particle separations. In spite of this significance, their understanding is still an obstacle. Three approaches were used to characterize the flow of granular material in a linear vibrating screen. The statistical model, mass action, and kinetic model based on conservation of momentum were derived. Experiments were then conducted on a multi‐sized prototype screen and glass beads of sizes 0.75, 1, 2, 3 mm. Deck inclinations were varied over 7.5,12.5, and 17.5°, and frequencies over 7, 15, and 20 Hz. A total of 72 feed batches and a constant power of 50 W was used. The experimental data was then used to validate the models. The three models provided accurate flow prediction over the screens. Additionally, the kinetic model also provided a basis for optimal design of the screening unit operation, by allowing manipulation of seven design variables to obtain a 95–100% efficient vibrating screen. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3889–3898, 2016
Self‐Assembly Directed Organization of Nanodiamond During Ionic Liquid Crystalline Polymer Formation
Authors: Ringstrand Bryan S. , Seifert Sönke , Podlesak David W. , Firestone Millicent A.
Published: May 2016

The UV‐initiated free radical polymerization of a lyotropic mesophase prepared by co‐assembly of an aqueous mixture of an ionic liquid (IL) monomer, 3‐decyl‐1‐vinylimidazolium chloride, in a dimethyl sulfoxide dispersion of an IL‐monomer nanodiamond conjugate yields a well‐ordered 2D hexagonally structured network–polymer composite. The IL monomer is covalently bound to carboxylated detonation diamond via ester‐linked 3‐decyl‐1‐vinylimidazolium bromide. Successful preparation of the amphiphile‐functionalized nanodiamond is determined by ATR/FT‐IR, thermogravimetric analysis, and small‐angle X‐ray scattering (SAXS). Mesophase and composite structure are evaluated by SAXS, revealing a columnar architecture composed of amphiphilic ionic liquid cylinders containing solvent‐rich cores. Self‐assembly directed site localization of the nanodiamond positions the particles in the alkyl chain continuum upon polymerization. The composite reversibly swells in ethanol allowing structural variation and modulation of the nanoparticle internal packing arrangement. This work demonstrates that through careful molecular design, self‐organization and site‐directed assembly of nanodiamond into chemically distinct regions of a nanostructured organogel can be achieved.

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Diving into the rat plasma proteome to get to the bottom of decompression sickness
Authors: Eftedal Ingrid
Published: May 2016

Decompression sickness (DCS) is the collective term for an array of signs and symptoms triggered by ambient pressure reduction. It is of particular concern to divers as they decompress on ascend from depth to sea surface, but despite a long history of studies the determinants of DCS risk are incompletely understood and there are no validated biomarkers. In this issue of Proteomics Clinical Applications, Lautridou et al. [8] report on their search for DCS biomarkers in rats exposed to simulated diving. By comparing the plasma proteomes from animals showing neurological symptoms to those emerging from dives unaffected, they identified several high‐abundance proteins not previously associated with DCS. The most significant finding was a near depletion of thyroxine‐ and vitamin A transporter transthyretin in symptomatic rats. In addition to their potential role as diagnostic biomarkers, the proteins identified in Lautridou's study may offer new pieces in the yet incomplete puzzle of DCS etiology.
Mycoprotein reduces energy intake and postprandial insulin release without altering glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations in healthy overweight and obese adults: a randomised-controlled trial
Authors: Bottin Jeanne H. , Swann Jonathan R. , Cropp Eleanor , Chambers Edward S. , Ford Heather E. , Ghatei Mohammed A. , Frost Gary S.
Published: May 2016

Dietary mycoprotein decreases energy intake in lean individuals. The effects in overweight individuals are unclear, and the mechanisms remain to be elucidated. This study aimed to investigate the effect of mycoprotein on energy intake, appetite regulation, and the metabolic phenotype in overweight and obese volunteers. In two randomised-controlled trials, fifty-five volunteers (age: 31 (95 % CI 27, 35) years), BMI: 28·0 (95 % CI 27·3, 28·7) kg/m2) consumed a test meal containing low (44 g), medium (88 g) or high (132 g) mycoprotein or isoenergetic chicken meals. Visual analogue scales and blood samples were collected to measure appetite, glucose, insulin, peptide tyrosine-tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Ad libitum energy intake was assessed after 3 h in part A (n 36). Gastric emptying by the paracetamol method, resting energy expenditure and substrate oxidation were recorded in part B (n 14). Metabonomics was used to compare plasma and urine samples in response to the test meals. Mycoprotein reduced energy intake by 10 % (280 kJ (67 kcal)) compared with chicken at the high content (P=0·009). All mycoprotein meals reduced insulin concentrations compared with chicken (incremental AUClow (IAUClow): −8 %, IAUCmedium: −12 %, IAUChigh: −21 %, P=0·004). There was no significant difference in glucose, PYY, GLP-1, gastric emptying rate and energy expenditure. Following chicken intake, paracetamol-glucuronide was positively associated with fullness. After mycoprotein, creatinine and the deamination product of isoleucine, α-keto-β-methyl-N-valerate, were inversely related to fullness, whereas the ketone body, β-hydroxybutyrate, was positively associated. In conclusion, mycoprotein reduces energy intake and insulin release in overweight volunteers. The mechanism does not involve changes in PYY and GLP-1. The metabonomics analysis may bring new understanding to the appetite regulatory properties of food.
Ruthless Manipulation or Benevolent Amnesia? The role of the history of the Fifteen-year War in China's diplomacy towards Japan before the 1982 Textbook Incident
Authors: YANG CHAN
Published: May 2016

Exploring how the history of the Fifteen-year War was dealt with in pre-1982 mainland China is an essential step towards understanding the currently explosive Sino-Japanese History Problem; furthermore, this might shed light on various issues in the post-war history of China and Sino-Japanese relations. However, available research on the pre-1982 period is scarce and problematic. Earlier political scientists argue that the history of the war was ruthlessly manipulated by the Chinese Communist Party regime, while some recent studies believe that the war was conveniently ‘forgotten’ as Sino-Japanese friendship was vital for the government of the People's Republic of China. This article aims at providing an accurate and thorough picture of how the history of the Fifteen-year War was positioned in the diplomatic practice of the Chinese Communist Party regime in relation to Japan during the period.
Asymptotic structure of free product von Neumann algebras
Authors: HOUDAYER CYRIL , UEDA YOSHIMICHI
Published: May 2016

Let (M, ϕ) = (M1, ϕ1) * (M2, ϕ2) be the free product of any σ-finite von Neumann algebras endowed with any faithful normal states. We show that whenever Q ⊂ M is a von Neumann subalgebra with separable predual such that both Q and Q ∩ M1 are the ranges of faithful normal conditional expectations and such that both the intersection Q ∩ M1 and the central sequence algebra Q′ ∩ Mω are diffuse (e.g. Q is amenable), then Q must sit inside M1. This result generalizes the previous results of the first named author in [Ho14] and moreover completely settles the questions of maximal amenability and maximal property Gamma of the inclusion M1 ⊂ M in arbitrary free product von Neumann algebras.
Imagination, Inference, Intimacy: The Psychology of Pride and Prejudice
Authors: Oatley Keith
Published: May 2016

A novel is based on suggestions from which readers construct characters and events in an imagined story world. In Pride and Prejudice, Jane Austen's suggestions derive from 3 sets of cues: (a) characters’ utterances; (b) thoughts of characters, of the narrator, and even of readers; and (c) narrated depictions of settings, characters, actions and events. Tracing people's simulations of stories offers a route into the psychology of imagination, in which readers make inferences about what happens in a story. Austen invites intimacy with readers by metonymy, playfulness, and irony. Her novel does not seek to persuade; it communicates indirectly and with ambiguity. Among psychological effects of literary art such as Pride and Prejudice, readers can become better able to empathize and understand other people, and better able to understand and change themselves. For psychology, imaginative engagement in the simulations of fiction may be as important as empirical findings of causes of behavior.
Mechanistic insight into cadmium-induced inactivation of the Bloom protein
Authors: Qin Wei , Bazeille Nicolas , Henry Etienne , Zhang Bo , Deprez Eric , Xi Xu-Guang
Published: May 2016

Cadmium is a toxic metal that inactivates DNA-repair proteins via multiple mechanisms, including zinc substitution. In this study, we investigated the effect of Cd2+ on the Bloom protein (BLM), a DNA-repair helicase carrying a zinc-binding domain (ZBD) and playing a critical role to ensure genomic stability. One characteristics of BLM-deficient cells is the elevated rate of sister chromatid exchanges, a phenomenon that is also induced by Cd2+. Here, we show that Cd2+ strongly inhibits both ATPase and helicase activities of BLM. Cd2+ primarily prevents BLM-DNA interaction via its binding to sulfhydryl groups of solvent-exposed cysteine residues and, concomitantly, promotes the formation of large BLM multimers/aggregates. In contrast to previously described Cd2+ effects on other zinc-containing DNA-repair proteins, the ZBD appears to play a minor role in the Cd2+-mediated inhibition. While the Cd2+-dependent formation of inactive multimers and the defect of DNA-binding were fully reversible upon addition of EDTA, the inhibition of the DNA unwinding activity was not counteracted by EDTA, indicating another mechanism of inhibition by Cd2+ relative to the targeting of a catalytic residue. Altogether, our results provide new clues for understanding the mechanism behind the ZBD-independent inactivation of BLM by Cd2+ leading to accumulation of DNA double-strand breaks.
Development of antithrombotic nanoconjugate blocking integrin α2β1-collagen interactions
Authors: Zhang Chao , Zhang Lin , Zhang Youcai , Sun Na , Jiang Shaoyi , Fujihara Timothy J. , Sun Yan
Published: May 2016

An antithrombotic nanoconjugate was designed in which a designed biomimetic peptide LWWNSYY was immobilized to the surface of poly(glycidyl methacrylate) nanoparticles (PGMA NPs). Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin α2β1-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a Kd of 3.45 ± 1.06 μM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion in vitro with a reduced IC50 of 1.83 ± 0.29 μg/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed in vivo with a 50% reduction of thrombus weight. Therefore, L-PGMA NPs were developed as a high-efficiency antithrombotic nanomedicine targeted for collagen exposed on diseased blood vessel wall.
LPA1extracellular loop residues 115 and 191 are not required for receptor activation but prevent Ki16425 super-antagonism
Authors: Omotuyi Olaposi I. , Adebowale Desmond D. , Famuti Ayodeji , Tsuyoshi Hamada
Published: May 2016

Extracellular loop residues (R115 and D191) are not required for receptor activation but repress Ki16425-type super-antagonism but not LPA-analogue antagonists using a combination of site-directed mutagenesis and intracellular calcium assay procedures.
Fabrication of a new modified gold electrode based on gold nanoparticles and nanomagnetic Fe3O4/SiO2–(CH2)3–SH core shell for electrochemical evaluation and determination of dinitramine herbicide in water
Authors: Irandoust Mohsen , Haghighi Maryam
Published: May 2016

A novel sensitive voltammetric method is described for the determination of dinitramine based on its electrochemical oxidation on gold electrodes modified with Fe3O4@SiO2–Si–(CH2)3–SH core shell (Au/Au–NPs–S–(CH2)3–Si–SiO2@Fe3O4).
Flipping and scooping of curved 2D rigid fibers in simple shear: The Jeffery equations
Authors: Crowdy Darren
Published: May 2016

The dynamical system governing the motion of a curved rigid two-dimensional circular-arc fiber in simple shear is derived in analytical form. This is achieved by finding the solution for the associated low-Reynolds-number flow around such a fiber using the methods of complex analysis. Solutions of the dynamical system display the “flipping” and “scooping” recently observed in computational studies of three-dimensional fibers using linked rigid rod and bead-shell models [J. Wang et al., “Flipping, scooping, and spinning: Drift of rigid curved nonchiral fibers in simple shear flows,” Phys. Fluids 24, 123304 (2012)]. To complete the Jeffery-type equations for a curved fiber in a linear flow field we also derive its evolution equations in an extensional flow. It is expected that the equations derived here also govern the motion of slender, curved, three-dimensional rigid fibers when they evolve purely in the plane of shear or strain.
Investigation of organic magnetoresistance dependence on spin-orbit coupling using 8-hydroxyquinolinate rare-earth based complexes
Authors: Carvalho R. S. , Costa D. G. , Ávila H. C. , Paolini T. B. , Brito H. F. , Capaz Rodrigo B. , Cremona M.
Published: May 2016

The recently discovered organic magnetoresistance effect (OMAR) reveals the spin-dependent behavior of the charge transport in organic semiconductors. So far, it is known that hyperfine interactions play an important role in this phenomenon and also that spin-orbit coupling is negligible for light-atom based compounds. However, in the presence of heavy atoms, spin-orbit interactions should play an important role in OMAR. It is known that these interactions are responsible for singlet and triplet states mixing via intersystem crossing and the change of spin-charge relaxation time in the charge mobility process. In this work, we report a dramatic change in the OMAR effect caused by the presence of strong intramolecular spin-orbit coupling in a series of rare-earth quinolate organic complex-based devices. Our data show a different OMAR lineshape compared with the OMAR lineshape of tris(8-hydroxyquinolinate) aluminum-based devices, which are well described in the literature. In addition, electronic structure calculations based on density functional theory help to establish the connection between this results and the presence of heavy central ions in the different complexes.
Note: Arc discharge plasma source with plane segmented LaB6 cathode
Authors: Akhmetov T. D. , Davydenko V. I. , Ivanov A. A. , Kreter A. , Mishagin V. V. , Savkin V. Ya. , Shulzhenko G. I. , Unterberg B.
Published: May 2016

A plane cathode composed of close-packed hexagonal LaB6 (lanthanum hexaboride) segments is described. The 6 cm diameter circular cathode is heated by radiation from a graphite foil flat spiral. The cathode along with a hollow copper anode is used for the arc discharge plasma production in a newly developed linear plasma device. A separately powered coil located around the anode is used to change the magnetic field strength and geometry in the anode region. Different discharge regimes were realized using this coil.
Phase separation in LuFeO3 films
Authors: Cao Shi , Zhang Xiaozhe , Sinha Kishan , Wang Wenbin , Wang Jian , Dowben Peter A. , Xu Xiaoshan
Published: May 2016

The structural transition at about 1000 °C, from the hexagonal to the orthorhombic phase of LuFeO3, has been investigated in thin films of LuFeO3. Separation of the two structural phases of LuFeO3 occurs on a length scale of micrometer, as visualized in real space using X-ray photoemission electron microscopy. The results are consistent with X-ray diffraction and atomic force microscopy obtained from LuFeO3 thin films undergoing the irreversible structural transition from the hexagonal to the orthorhombic phase of LuFeO3, at elevated temperatures. The sharp phase boundaries between the structural phases are observed to align with the crystal planes of the hexagonal LuFeO3 phase. The coexistence of different structural domains indicates that the irreversible structural transition, from the hexagonal to the orthorhombic phase in LuFeO3, is a first order transition, for epitaxial hexagonal LuFeO3 films grown on Al2O3.
High performance as-grown and annealed high band gap tunnel junctions: Te behavior at the interface
Authors: Bedair S. M. , Harmon Jeffrey L. , Carlin C. Zachary , Hashem Sayed Islam E. , Colter P. C.
Published: May 2016

The performance of n+-InGaP(Te)/p+-AlGaAs(C) high band gap tunnel junctions (TJ) is critical for achieving high efficiency in multijunction photovoltaics. Several limitations for as grown and annealed TJ can be attributed to the Te doping of InGaP and its behavior at the junction interface. Te atoms in InGaP tend to get attached at step edges, resulting in a Te memory effect. In this work, we use the peak tunneling current (Jpk) in this TJ as a diagnostic tool to study the behavior of the Te dopant at the TJ interface. Additionally, we used our understanding of Te behavior at the interface, guided by device modeling, to modify the Te source shut-off procedure and the growth rate. These modifications lead to a record performance for both the as-grown (2000 A/cm2) and annealed (1000 A/cm2) high band gap tunnel junction.
MAXI observations of long-term variations of Cygnus X-1 in the low/hard and the high/soft states
Authors: Sugimoto Juri , Mihara Tatehiro , Kitamoto Shunji , Matsuoka Masaru , Sugizaki Mutsumi , Negoro Hitoshi , Nakahira Satoshi , Makishima Kazuo
Published: May 2016

The long-term X-ray variability of the black hole binary Cygnus X-1 was studied with five years of MAXI data from 2009 to 2014, which include substantial periods of the high/soft state, as well as the low/hard state. In each state, normalized power spectrum densities (NPSDs) were calculated in three energy bands of 2–4 keV, 4–10 keV, and 10–20 keV. The NPSDs for frequencies from 10−7 Hz to 10−4 Hz are all approximated by a power-law function with an index −1.35–1.29. The fractional RMS variation η, calculated in the above frequency range, was found to show the following three properties: (1) η slightly decreases with energy in the low/hard state; (2) η increases towards higher energies in the high/soft state; and (3) in the 10–20 keV band, η is three times higher in the high/soft state than in the low/hard state. These properties were confirmed through studies of intensity-correlated changes of the MAXI spectra. Of these three findings, the first one is consistent with that seen in the short-term variability during the low/hard state. The latter two can be understood as a result of high variability of the hard-tail component seen in the high/soft state with the above very low frequency range, although the origin of the variability remains inconclusive.
“Silent Sinus Syndrome” Following Orbital Trauma: A Case Series and Review of the Literature
Authors: Brown Sebastian J. , Hardy Thomas G. , McNab Alan A.
Published: May 2016

Purpose:

To describe the demographics, presentation, and treatment of “silent sinus syndrome” (SSS) diagnosed following orbital trauma and review the literature on this topic.

Methods:

A retrospective review of 6 consecutive cases of SSS following trauma seen by the authors from 2004 to 2015. Data collected included patient demographics, details of previous trauma, clinical presentation, imaging findings, surgery performed, outcome, and follow up.

Results:

Six patients were identified presenting with SSS following orbital floor fracture. All cases developed progressive enophthalmos due to maxillary sinus atelectasis on average 8 months after their initial trauma (range, 3–16 months). The appearance of the maxillary sinus on CT was indistinguishable from the changes seen in spontaneous SSS. All 6 patients had surgical repair, which included maxillary sinus reventilation and surgery to build up the orbital floor and correct the enophthalmos in 4 patients, maxillary sinus reventilation surgery only in 1 patient and surgery to build up the orbital floor only in 1 patient. There was a reduction of enophthalmos and globe dystopia in all cases with no significant complications.

Conclusions:

Changes in the maxillary sinus after orbital floor fracture may occur in the months following the initial trauma and the changes are indistinguishable from those seen in spontaneous SSS. The mechanism is presumed to be obstruction of the natural ostium of the maxillary sinus, accumulation of secretions and the development of negative pressure within the sinus leading to its collapse.
Deriving shape-based features for C. elegans locomotion using dimensionality reduction methods
Authors: Gyenes Bertalan , Brown André E.X.
Published: May 2016

High-throughput analysis of animal behavior has become a reality with the advance of recording technology, leading to large high-dimensional data sets. This dimensionality can sometimes be reduced while still retaining relevant information. In the case of the nematode worm Caenorhabditis elegans, more than 90% of the shape variance can be captured using just four principal components. However, it remains unclear if other methods can achieve a more compact representation or contribute further biological insight to worm locomotion. Here we take a data-driven approach to worm shape analysis using independent component analysis (ICA), non-negative matrix factorization (NMF), a cosine series, and jPCA and confirm that the dimensionality of worm shape space is close to four. Projecting worm shapes onto the bases derived using each method gives interpretable features ranging from head movements to tail oscillation. We use these as a comparison method to find differences between the wild type N2 worms and various mutants. The different bases provide complementary views of worm behavior and we expect that closer examination of the time series of projected amplitudes will lead to new results in the future.
The Enok acetyltransferase complex interacts with Elg1 and negatively regulates PCNA unloading to promote the G1/S transition
Authors: Huang Fu , Saraf Anita , Florens Laurence , Kusch Thomas , Swanson Selene K. , Szerszen Leanne T. , Li Ge , Dutta Arnob , Washburn Michael P. , Abmayr Susan M. , Workman Jerry L.
Published: May 2016

KAT6 histone acetyltransferases (HATs) are highly conserved in eukaryotes and are involved in cell cycle regulation. However, information regarding their roles in regulating cell cycle progression is limited. Here, we report the identification of subunits of the Drosophila Enok complex and demonstrate that all subunits are important for its HAT activity. We further report a novel interaction between the Enok complex and the Elg1 proliferating cell nuclear antigen (PCNA)-unloader complex. Depletion of Enok in S2 cells resulted in a G1/S cell cycle block, and this block can be partially relieved by depleting Elg1. Furthermore, depletion of Enok reduced the chromatin-bound levels of PCNA in both S2 cells and early embryos, suggesting that the Enok complex may interact with the Elg1 complex and down-regulate its PCNA-unloading function to promote the G1/S transition. Supporting this hypothesis, depletion of Enok also partially rescued the endoreplication defects in Elg1-depleted nurse cells. Taken together, our study provides novel insights into the roles of KAT6 HATs in cell cycle regulation through modulating PCNA levels on chromatin.
Histone H3K4 methylation regulates deactivation of the spindle assembly checkpoint through direct binding of Mad2
Authors: Schibler Andria , Koutelou Evangelia , Tomida Junya , Wilson-Pham Marenda , Wang Li , Lu Yue , Cabrera Alexa Parra , Chosed Renee J. , Li Wenqian , Li Bing , Shi Xiaobing , Wood Richard D. , Dent Sharon Y.R.
Published: May 2016

Histone H3 methylation on Lys4 (H3K4me) is associated with active gene transcription in all eukaryotes. InSaccharomyces cerevisiae, Set1 is the sole lysine methyltransferase required for mono-, di-, and trimethylation of this site. Although H3K4me3 is linked to gene expression, whether H3K4 methylation regulates other cellular processes, such as mitosis, is less clear. Here we show that both Set1 and H3K4 mutants display a benomyl resistance phenotype that requires components of the spindle assembly checkpoint (SAC), including Bub3 and Mad2. These proteins inhibit Cdc20, an activator of the anaphase-promoting complex/cyclosome (APC/C). Mutations in Cdc20 that block Mad2 interactions suppress the benomyl resistance of bothset1and H3K4 mutant cells. Furthermore, the HORMA domain in Mad2 directly binds H3, identifying a new histone H3 “reader” motif. Mad2 undergoes a conformational change important for execution of the SAC. We found that the closed (active) conformation of both yeast and human Mad2 is capable of binding methylated H3K4, but, in contrast, the open (inactive) Mad2 conformation limits interaction with methylated H3. Collectively, our data indicate that interactions between Mad2 and H3K4 regulate resolution of the SAC by limiting closed Mad2 availability for Cdc20 inhibition.
Nostalgia in online brand communities
Authors: Koetz Clara , Tankersley John Daniel
Published: May 2016

Purpose

The purpose of this paper is to analyze the characteristics of a subculture of consumption organized toward a nostalgic brand on a social media platform. More specifically, the authors examine the role of these nostalgic feelings in the development of a community identity and the benefits they promote in the creation and perpetuation of this group.

Design/methodology/approach

The authors conducted a netnographic study to examine the case of Caloi 10 on Facebook. The data collection was carried out by following interactions among members of this community for seven months. Besides this, field observations and interviews were also considered in the analysis.

Findings

Four categories emerged from the analysis: Identity and nostalgia, the subculture’s ethos, consumption habits and hierarchical social structure. Nostalgia was shown to have a collective dimension, connecting the group around the brand, and positively affecting the ties between members and members and the brand.

Practical implications

On-line brand communities can be promoted to strengthen connections between consumers and a brand, and between consumers with each other. For that, it is important to understand the characteristics and specificities of these groups.

Originality/value

Few studies have dealt with the characteristics of brand communities in social media, as well as the role of nostalgia in these groups. This research fills these gaps, exploring aspects related to consumption as a way of transmitting symbolic meanings and expressing nostalgic feelings in on-line brand communities.
Development and feasibility testing of an oral hygiene intervention for stroke unit care
Authors: Smith Craig J. , Horne Maria , McCracken Giles , Young David , Clements Ian , Hulme Sharon , Ardron Claire , Hamdy Shaheen , Vail Andy , Walls Angus , Tyrrell Pippa J.
Published: May 2016

Objective

To develop an oral hygiene complex intervention and evaluate its feasibility in a single UK stroke centre.

Background

Oral hygiene interventions might improve clinical outcomes after stroke but evidence‐based practice is lacking.

Materials and methods

We used a sequential mixed methods approach and developed an oral hygiene complex intervention comprising: (i) web‐based education and ‘hands‐on’ practical training for stroke unit nursing staff, (ii) a pragmatic oral hygiene protocol consisting of twice‐daily powered (or manual if preferred) brushing with chlorhexidine gel (or non‐foaming toothpaste) ± denture care. We evaluated feasibility of (i) the staff education and training and (ii) the oral hygiene protocol in consenting inpatients with confirmed stroke, requiring assistance with at least one aspect of personal care.

Results

The staff education and training were feasible, acceptable and raised knowledge and awareness. Several barriers to completing the education and training were identified. The oral hygiene protocol was feasible and well‐tolerated. 22% of eligible patients screened declined participation in the study. Twenty‐nine patients (median age = 78 year; National Institutes of Health Stroke Scale score = 8.5; 73% dentate) were recruited at a median of 7 days from stroke onset. 97% of participants chose the default chlorhexidine‐based protocol; the remainder chose the non‐foaming toothpaste‐based protocol. The mouth hygiene protocol was administered as prescribed on 95% of occasions, over a median duration of 28 days. There were no adverse events attributed to the oral hygiene protocol.

Conclusion

Our oral hygiene complex intervention was feasible in a single UK stroke centre. Further studies to optimise patient selection, model health economics and explore efficacy are now required.
Slit‐Like Deformation of the Coronary Sinus Orifice due to Compression of the Inferior Pyramidal Space by the Severely Dilated Left Ventricle
Authors: ICHIBORI HIROTOSHI , MORI SHUMPEI , TAKAYA TOMOFUMI , KIUCHI KUNIHIRO , ITO TATSURO , FUJIWARA SEI , FUKUZAWA KOJI , TATSUMI KAZUHIRO , TANAKA HIDEKAZU , NISHII TATSUYA , KONO ATSUSHI K. , HIRATA KEN‐ICHI
Published: May 2016

The coronary sinus is located within the inferior pyramidal space, which is the part of the epicardial visceral fibroadipose tissue wedging between the four cardiac chambers from the bottom of the heart. Therefore, this region is susceptible to the morphological changes of the cardiac chambers. We present a case of slit‐like deformation of the coronary sinus orifice due to compression of the inferior pyramidal space by the severely dilated left ventricle, which has not been previously described.
Patterns of lymph node metastasis identified following bilateral mandibular and medial retropharyngeal lymphadenectomy in 31 dogs with malignancies of the head
Authors: Skinner Owen T. , Boston Sarah E. , Souza Carlos H. de M.
Published: May 2016

Variable pathways of lymphatic drainage have been described in the dog head and neck. The aim of this study was to retrospectively assess the patterns of lymph node metastasis in dogs with malignancies of the head following bilateral mandibular and medial retropharyngeal lymphadenectomy. Thirty‐one dogs were included. Median age at surgery was 10 years (range: 5 months to 14 years) and mean bodyweight was 21.4 ± 11.9 kg. Lymph node metastasis occurred in 14 dogs (45%), with spread to mandibular lymph nodes in 14 dogs and medial retropharyngeal metastasis in 11 dogs. Eight of 13 dogs (62%) with lymphatic metastasis and a lateralised lesion showed contralateral dissemination, while 12/13 (92%) showed ipsilateral metastasis. Of 13 dogs with oral malignant melanoma, four showed metastasis to all four lymph centres. Contralateral metastasis may occur in dogs with malignancies of the head and should be considered during staging and management.
Effect of CoCr Counterface Roughness on the Wear of UHMWPE in the Noncyclic RandomPOD Simulation
Authors: Saikko Vesa , Vuorinen Vesa , Revitzer Hannu
Published: May 2016

With the random motion and load pin-on-disk (RandomPOD) wear test system, conventional and highly crosslinked ultrahigh molecular weight polyethylenes (UHMWPE) were run against CoCr counterfaces with different surface roughnesses. The unique 16-station, computer-controlled pin-on-disk device produced noncyclic motion and load. With appropriate specimen shapes, simulations of wear mechanisms of both hip and knee prostheses were performed. Against polished counterfaces, the crosslinked UHMWPE showed negligible wear. Its wear against severely roughened counterfaces was close to that of conventional UHMWPE against polished counterfaces. The reduction in wear with crosslinked versus conventional UHMWPE was 80–86% in the hip and 87–96% in the knee wear simulation. The wear particles were of clinically relevant size and shape which indicated realistic wear mechanisms.
Supporting human service workers following the Canterbury earthquakes
Authors: Van Heugten Kate
Published: May 2016

In the aftermath of the 2010 and 2011 earthquakes in Canterbury, many human service workers, including social workers, struggled to meet the needs of distressed service users at the same time as they were dealing with the personal impacts of these disasters. The consequences of the earthquakes have been particularly complex and long lasting. There is no known end point for the aftershocks, and the socio-economic repercussions continue to unfold. Forty-three human service workers participated in qualitative research interviews during late 2011. The challenges they identified included the taxing nature of work involving emotional labour in a context of shared trauma; environmental stress; complex demands and fewer resources; ethical dilemmas and moral distress. Many participants re-evaluated their personal and professional priorities, and questioned the fit of those priorities with the values of their employing organisations. In doing so, some had become disenchanted, particularly if they felt they had not been consulted about decisions that impacted on their work with service users. By contrast, some participants expressed a strong sense of loyalty and engagement with organisations where workplace culture was experienced as reflective of the importance of caring for human needs and relationships.
Public perception of social work and social workers in Aotearoa New Zealand
Authors: Staniforth Barbara , Fouché Christa , Beddoe Liz
Published: May 2016

There have been limited studies that have looked at how the public perceive social workers and the profession of social work. This study reports results of a telephone survey in which 386 members of the public in Aotearoa New Zealand were asked about their beliefs and impressions about social work and social workers. Study findings demonstrate that members of the public surveyed appeared relatively well informed about what social workers do, and were generally positive in their views.
Research opens more doors
Authors: Davison Lucy
Published: May 2016

Having gained some clinical experience before pursuing a research career, Lucy Davison is now seeking the best of both worlds as a clinician scientist
Reorganization of porphyrin nanoparticle morphology driven by surface energetics
Authors: Xu Chang , Wan Albert , Gong Xianchang , Bhupathiraju N. V. S. Dinesh K. , Batteas James D. , Drain Charles Michael
Published: May 2016

Organic nanoparticles (ONp) of an Fe(III) porphyrin appended with four [Formula: see text]-polyethyleneglyco-pyridinium moieties prepared in acetonitrile were deposited onto hydrophilic or hydrophobic Si surfaces. Self-organized by intermolecular interactions, ONp reorganize in response to environmental changes. Mechanisms for the control of nanoparticle morphologies and surface patterning by varying surface energies are discussed.
Abstract C190: Potent and selective inhibition of CDK7 by novel covalent inhibitors
Authors: Poddutoori Ramulu , Satyam Leena K. , Daginakatte Girish , Mukherjee Subhendu , Marappan Sivapriya , Gopinath Sreevalsam , Ramachandra Raghuveer , Lakshminarasimhan Anirudha , Pothuganti Manoj , Nayak Shilpa , C Nandish , Naik Chandranath , MV Ravindra , Dabbeeru Madhu , Antony Thomas , Pandit Chetan , Ramachandra Murali , Chelur Shekar , Samajdar Susanta
Published: May 2016

Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional machinery, where it phosphorylates the C-terminal domain (CTD) of RNAP polymerase II (RNAPII). Because many tumor types are critically dependent on transcription for maintenance of their oncogenic state, pharmacological modulation of CDK7 kinase activity is considered as an approach to treat cancer. Multiple series of CDK7 inhibitors were identified by iterative medicinal chemistry efforts and SAR based approach. Early compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumor activity. We have identified compounds from two distinct chemical series that are highly potent in inhibiting CDK7 in biochemical assays. These inhibitors demonstrate time-dependent inhibition of CDK7 indicating covalent nature of binding. The compounds showed potent anti-proliferative activity in cell lines derived from various tumor types and this was accompanied by CDK7 modulation in cells as monitored by pS5RNAPII levels. They have excellent drug-like characteristics including solubility, permeability, metabolic stability and good oral bioavailability. In a broad panel of kinases (332 kinase), selected compounds from both series showed good selectivity profile. Tolerability and efficacy studies are ongoing with selected early leads to test their impact on tumor growth inhibition in xenograft models. We have identified novel and selective CDK7 covalent inhibitors from two series with desirable drug-like properties, which are being evauated for anti-tumor activity in xenograft models.

Citation Format: Ramulu Poddutoori, Leena K. Satyam, Girish Daginakatte, Subhendu Mukherjee, Sivapriya Marappan, Sreevalsam Gopinath, Raghuveer Ramachandra, Anirudha Lakshminarasimhan, Manoj Pothuganti, Shilpa Nayak, Nandish C, Chandranath Naik, Ravindra MV, Madhu Dabbeeru, Thomas Antony, Chetan Pandit, Murali Ramachandra, Shekar Chelur, Susanta Samajdar. Potent and selective inhibition of CDK7 by novel covalent inhibitors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C190.
Abstract P4-09-09: Verification of the breast cancer progression-associated miRNA hsa-miR-199a-5p using NanoString® platform
Authors: Fehm T , Schultz S , Bartsch H , Petat-Dutter K , Kahlert S , Sotlar K , Niederacher D , Neubauer H
Published: May 2016

A fundamental and clinically important step during breast tumourigenesis is the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Improved knowledge of this transition from pre-invasive to invasive breast cancer will pave the way for novel preventative and therapeutic strategies.

We have previously reported on differential expression of the miRNA hsa-miR-199a-5p in 15 matched pairs of DCIS and IDC areas isolated by laser capture microdissection (LCM) from formalin fixed and paraffin embedded (FFPE) breast cancer tissues using Illumina miRNA BeadChip microarray platform. Differential expression of hsa-miR-199a-5p was validated by quantitative RT-PCR in additional independent DCIS/IDC sample pairs from 25 breast cancer patients. Knock down of hsa-miR-199a-5p in invasive MDA-MB-231 and TMX2-28 breast cancer cells using a specific inhibitor significantly reduced invasiveness by approx. 73% and 71%, respectively (P <0.01 and P<0.05).

Now we report on experiments to validate differential expression of hsa-miR-199a-5p using a new platform – NanoString® (nCounter® miRNA Expression Assay, NanoString Technologies®). The NanoString® System is an automated, digital detection and counting system which uses a novel barcoding technology to directly profile up to 800 miRNAs simultaneously from a single sample. Total RNA from 6 DCIS/IDC FFPE tumours was used for miRNA expression analysis.

This analysis resulted in 10 differentially expressed miRNAs including hsa-miR-199a-5p which is upregulated in IDC (P <0.05). Besides hsa-mir-199a-5p, hsa-miR-222 is significantly differentially expressed between DCIS and IDC which could be found in both expression data sets (Illumina® and NanoString®).

In this project we identified candidate progression-associated miRNAs which are differentially expressed between DCIS and IDC. Hsa-miR-199a-5p was validated in an independent sample cohort and its expression was further verified using the new miRNA expression analysis platform NanoString®. Hsa-miR-199a5-p is influencing in vitro cell invasiveness and may therefore be a potential drugable regulator of tumour progression and invasion in breast cancer.

Citation Format: Fehm T, Schultz S, Bartsch H, Petat-Dutter K, Kahlert S, Sotlar K, Niederacher D, Neubauer H. Verification of the breast cancer progression-associated miRNA hsa-miR-199a-5p using NanoString® platform. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-09.