bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic Sorting of Immune Cell Subpopulations Based on Highly Plastic Genes
Authors: Wang Pingzhang , Han Wenling , Ma Dalong
Published: June 2016

Immune cells are highly heterogeneous and plastic with regard to gene expression and cell phenotype. In this study, we categorized genes into those with low and high gene plasticity, and those categories revealed different functions and applications. We proposed that highly plastic genes could be suited for the labeling of immune cell subpopulations; thus, novel immune cell subpopulations could be identified by gene plasticity analysis. For this purpose, we systematically analyzed highly plastic genes in human and mouse immune cells. In total, 1,379 human and 883 mouse genes were identified as being extremely plastic. We also expanded our previous immunoinformatic method, electronic sorting, which surveys big data to perform virtual analysis. This approach used correlation analysis and took dosage changes into account, which allowed us to identify the differentially expressed genes. A test with human CD4+ T cells supported the method’s feasibility, effectiveness, and predictability. For example, with the use of human nonregulatory T cells, we found that FOXP3hiCD4+ T cells were highly expressive of certain known molecules, such as CD25 and CTLA4, and that this process of investigation did not require isolating or inducing these immune cells in vitro. Therefore, the sorting process helped us to discover the potential signature genes or marker molecules and to conduct functional evaluations for immune cell subpopulations. Finally, in human CD4+ T cells, 747 potential immune cell subpopulations and their candidate signature genes were identified, which provides a useful resource for big data–driven knowledge discoveries.
HIV-Infected Dendritic Cells Present Endogenous MHC Class II–Restricted Antigens to HIV-Specific CD4+ T Cells
Authors: Coulon Pierre-Grégoire , Richetta Clémence , Rouers Angéline , Blanchet Fabien P. , Urrutia Alejandra , Guerbois Mathilde , Piguet Vincent , Theodorou Ioannis , Bet Anne , Schwartz Olivier , Tangy Frédéric , Graff-Dubois Stéphanie , Cardinaud Sylvain , Moris Arnaud
Published: June 2016

It is widely assumed that CD4+ T cells recognize antigenic peptides (epitopes) derived solely from incoming, exogenous, viral particles or proteins. However, alternative sources of MHC class II (MHC-II)–restricted Ags have been described, in particular epitopes derived from newly synthesized proteins (so-called endogenous). In this study, we show that HIV-infected dendritic cells (DC) present MHC-II–restricted endogenous viral Ags to HIV-specific (HS) CD4+ T cells. This endogenous pathway functions independently of the exogenous route for HIV Ag presentation and offers a distinct possibility for the immune system to activate HS CD4+ T cells. We examined the implication of autophagy, which plays a crucial role in endogenous viral Ag presentation and thymic selection of CD4+ T cells, in HIV endogenous presentation. We show that infected DC do not use autophagy to process MHC-II–restricted HIV Ags. This is unlikely to correspond to a viral escape from autophagic degradation, as infecting DC with Nef- or Env-deficient HIV strains did not impact HS T cell activation. However, we demonstrate that, in DC, specific targeting of HIV Ags to autophagosomes using a microtubule-associated protein L chain 3 (LC3) fusion protein effectively enhances and broadens HS CD4+ T cell responses, thus favoring an endogenous MHC-II–restricted presentation. In summary, in DC, multiple endogenous presentation pathways lead to the activation of HS CD4+ T cell responses. These findings will help in designing novel strategies to activate HS CD4+ T cells that are required for CTL activation/maintenance and B cell maturation.
Language Rights as Human Rights: A Sociolinguistic Study of the Universal Declaration of Language Rights 1996
Authors: Darweesh Abbas Deygan
Published: June 2016

This study addresses a sociolinguistic evaluation of the universal declaration of linguistic rights in 1996. It aims to analyze the basic aspects and motivations of the declaration with reference to the problems that are not dealt with in it. Thus, the current paper adopts the following procedure to achieve its aim: (1) reviewing literature on language rights theories, (2) conducting a qualitative sociolinguistic analysis for each part of the declaration, (3) and discussing the results of analysis with some evaluation of the declaration. This study is supposed to be of value to sociolinguists, critical applied linguists, discourse analysts and language planners. It has been concluded that the universal declaration of linguistic rights is based on the human language rights hypothesis with some reference to the minority hypothesis. The factors that have been addressed are power, dominance, inequality, culture, and identity. Moreover, Language is seen as constituting rather than reflecting identity. The declaration treats important issues in language rights in several domains such as education, communication, politics, socio-economics, technology and public speech.
Collapsed Double Symmetry Model and Its Decomposition for Square Contingency Tables
Authors: Yamamoto Kouji , Matsuda Yuya , Tomizawa Sadao
Published: June 2016

For a square contingency table with ordinal categories, there may be a case that one wants to analyze several collapsed tables obtained by combining some adjacent categories of the original table. This paper proposes some new models which indicate double symmetry, quasi double symmetry and marginal double symmetry for the collapsed square tables. It also gives a decomposition of the double symmetry model for collapsed tables. Two kinds of occupational mobility data are analyzed using new models.
Diagonal Exponent Conditional Symmetry Model for Square Contingency Tables with Ordered Categories
Authors: Iki Kiyotaka , Shibuya Akira , Tomizawa Sadao
Published: June 2016

For square contingency tables with ordered categories, this article proposes new models which indicate that in addition to the structure of asymmetry of the probabilities with respect to the main diagonal of the table, the expected frequency has an exponential form along every subdiagonal of the table. Also it gives the new three kinds of decompositions using the proposed model and proves the orthogonality of the test statistics.
The Probability of Pathogenicity in Clinical Genetic Testing: A Solution for the Variant of Uncertain Significance
Authors: Gollob Michael , S. Rosenthal Jeffrey , Thorpe Kevin
Published: June 2016

We present a direct calculation for determining the probability that a rare genetic variant is the cause of an observed disease, under appropriate assumptions, in terms of the joint prevalence of the disease and of rare variants.  Our calculation provides a resolution of the so-called ``variant of unknown (or uncertain) significance'' problem, which has plagued medical genetics researchers.
RBM20 and RBM24 cooperatively promote the expression of short enh splice variants
Authors: Ito Jumpei , Iijima Masumi , Yoshimoto Nobuo , Niimi Tomoaki , Kuroda Shun'ichi , Maturana Andrés D.
Published: June 2016

PDZ‐LIM protein ENH1 is a scaffold protein for protein kinases and transcriptional regulators. While ENH1 promotes the hypertrophic growth of cardiomyocytes, its short splice variant (ENH3) prevents the hypertrophic growth. The mechanism underlying the alternative splicing of enh mRNA between ENH short and long isoforms has remained unknown. Here, we found that two splicing factors, RNA‐binding motif 20 (RBM20) and RNA‐binding motif 24 (RBM24) together promoted the expression of short enh splice variants and bound the 5′ intronic region of exon 11 containing an in‐phase stop codon. In addition, expression of both RBMs is repressed by hypertrophic stimulations. Collectively, our results suggest that, in healthy conditions, RBM20 and RBM24 cooperate to promote the expression of short ENH isoforms.
High‐resolution digital elevation model from tri‐stereo Pleiades‐1 satellite imagery for lava flow volume estimates at Fogo Volcano
Authors: Bagnardi Marco , González Pablo J. , Hooper Andrew
Published: June 2016

Resolving changes in topography through time using accurate high‐resolution digital elevation models (DEMs) is key to understanding active volcanic processes. For the first time in a volcanic environment, we utilize very high‐resolution tri‐stereo optical imagery acquired by the Pleiades‐1 satellite constellation and generate a 1 m resolution DEM of Fogo Volcano, Cape Verde—the most active volcano in the Eastern Atlantic region. Point cloud density is increased by a factor of 6.5 compared to conventional stereo imagery, and the number of 1 m2 pixels with no height measurements is reduced by 43%. We use the DEM to quantify topographic changes associated with the 2014–2015 eruption at Fogo. Height differences between the posteruptive Pleiades‐1 DEM and the preeruptive topography from TanDEM‐X give a lava flow volume of 45.83 ± 0.02 × 106 m3, emplaced over an area of 4.8 km2 at a mean rate of 6.8 m3 s−1.
Interplate deformation at early‐stage oblique subduction: 3‐D thermomechanical numerical modeling
Authors: Malatesta Cristina , Gerya Taras , Crispini Laura , Federico Laura , Capponi Giovanni
Published: June 2016

Oblique subduction zones are complex settings where the simultaneous action of trench‐normal and trench‐parallel components of convergence can produce heterogeneous deformational pattern of the upper plate and affect the accretional/erosional behavior of the plate margin. Here we present three‐dimensional thermomechanical numerical models that highlight some processes occurring in the early history (15–20 Myr) of intraoceanic oblique subduction zones, which so far represent the less studied case. These models have been compared with a simulation of a slab sinking under a continental plate. We test subduction starting in oceans floored by two classes of lithosphere: layered (fast spreading oceans) and serpentinite rich (slow to ultraslow spreading oceans). Two main domains develop along the margin of both type of oceanic plates: (a) a domain with a mostly stable trench, a shortening upper plate, characterized by the formation of a topographic relief, and (b) a domain with retreating trench and extending upper plate. In general, we observed that varying the subduction obliquity, the margin could either (i) record an erosional to a balanced accretion/erosion regime or (ii) be characterized by a predominant balanced accretion/erosion regime. In both cases, even where the sediment amount in the trench is high, the upper plate experiences tectonic erosion. We suggest that the formation of topographic reliefs on the fore arc is possibly related to the low amount of sediment in the trench, affecting interplate friction and promoting the upper plate indentation against the slab. The Puysegur subduction zone and the central Andes can be possibly natural examples of such a regime.
China's Banking Sector as the Foundation of Financial Reform
Authors: Hsu Sara
Published: June 2016

China is in the process of undertaking financial reform in many directions—introducing small private banks in the banking sector, promoting bond and equity finance, increasing exchange rate and capital account liberalization, enhancing financial regulation, and promoting the efficiency and scope of finance. While some foreign analysts have focused on the importance of liberalizing the exchange rate and capital account, we believe these aspects of reform take second priority to traditional banking reform, even though the ongoing process in practice is to slowly implement reforms in all areas at once.
Australia in the Asian Century
Authors: Henry Ken
Published: June 2016

The White Paper on Australia in the Asian Century, published in 2012, argued that fundamental policy and attitudinal changes would be required if Australia were to make the most of the opportunities presented by the Asian century. The White Paper presented a challenge to the core narrative that had galvanised support for two decades of economic reforms in Australia, commencing in the early 1980s. The challenge was intended to re‐energise a reform effort that had run out of steam. But Australian policy makers have ignored the White Paper.

The core economic policy narrative that motivated Australian economic reforms of the 1980s and 1990s might be labelled Australian mercantilism. The narrative's focus on something called ‘international competitiveness’, and especially its narrow interpretation in the form of the real exchange rate, was bound to generate a policy conundrum when, in the first decade of this century, Australia's terms of trade started to accelerate.

Australia's success in the Asian century calls for further investments in national capability: the development of collaborative business relationships with Asian partners; a strong contribution to sustainable security in the region; and deep and enduring people‐to‐people links across a broad sweep of human activity – commercial, social, cultural and political.
Publication boost in web of science journals and its effect on citation distributions
Authors: Šubelj Lovro , Fiala Dalibor
Published: June 2016

In this article, we show that the dramatic increase in the number of research articles indexed in the Web of Science database impacts the commonly observed distributions of citations within these articles. First, we document that the growing number of physics articles in recent years is attributed to existing journals publishing more and more articles rather than more new journals coming into being as it happens in computer science. Second, even though the references from the more recent articles generally cover a longer time span, the newer articles are cited more frequently than the older ones if the uneven article growth is not corrected for. Nevertheless, despite this change in the distribution of citations, the citation behavior of scientists does not seem to have changed.
Relative Citation Ratio (RCR): An empirical attempt to study a new field‐normalized bibliometric indicator
Authors: Bornmann Lutz , Haunschild Robin
Published: June 2016

Hutchins, Yuan, Anderson, and Santangelo (2015) proposed the Relative Citation Ratio (RCR) as a new field‐normalized impact indicator. This study investigates the RCR by correlating it on the level of single publications with established field‐normalized indicators and assessments of the publications by peers. We find that the RCR correlates highly with established field‐normalized indicators, but the correlation between RCR and peer assessments is only low to medium.
Development of cell‐penetrating peptide‐based drug leads to inhibit MDMX:p53 and MDM2:p53 interactions
Authors: Philippe Grégoire , Huang Yen‐Hua , Cheneval Olivier , Lawrence Nicole , Zhang Zhen , Fairlie David P , Craik David J. , de Araujo Aline Dantas , Henriques Sónia Troeira
Published: June 2016

The transcription factor p53 has a tumor suppressor role in leading damaged cells to apoptosis. Its activity is regulated/inhibited in healthy cells by the proteins MDM2 and MDMX. Overexpression of MDM2 and/or MDMX in cancer cells inactivates p53, facilitating tumor development. A 12‐mer dual inhibitor peptide (pDI) was previously reported to be able to target and inhibit MDMX:p53 and MDM2:p53 interactions with nanomolar potency in vitro. With the aim of improving its cellular inhibitory activity, we produced a series of constrained pDI analogs featuring lactam staples that stabilize the bioactive helical conformation and fused them with a cell‐penetrating peptide to increase cytosol delivery. We compared pDI and its analogs on their inhibitory potency, toxicity, and ability to enter cancer cells. Overall, the results show that these analogs keep their nanomolar affinity for MDM2 and MDMX and are highly active against cancer cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 853–863, 2016.
Whole exome sequencing reveals EP300 mutation in mildly affected female: expansion of the spectrum
Authors: Sellars Elizabeth A. , Sullivan Bonnie R. , Schaefer G. Bradley
Published: June 2016

Key Clinical Message

Rubinstein–Taybi syndrome is associated with intellectual and physical features. CREBBP and EP300 are causative. Few cases of EP300 mutations are reported. We report a case with mild features of RSTS and EP300 mutation on exome sequencing. This illustrates the utility of exome sequencing to expand every genetic phenotype.
Retinal ganglion cell topography and spatial resolving power in African megachiropterans: Influence of roosting microhabitat and foraging
Authors: Coimbra João Paulo , Pettigrew John D. , Kaswera‐Kyamakya Consolate , Gilissen Emmanuel , Collin Shaun P. , Manger Paul R.
Published: June 2016

Megachiropteran bats (megabats) show remarkable diversity in microhabitat occupation and trophic specializations, but information on how vision relates to their behavioral ecology is scarce. Using stereology and retinal wholemounts, we measured the topographic distribution of retinal ganglion cells and determined the spatial resolution of eight African megachiropterans with distinct roosting and feeding ecologies. We found that species roosting in open microhabitats have a pronounced streak of high retinal ganglion cell density, whereas those favoring more enclosed microhabitats have a less pronounced streak (or its absence in Hypsignathus monstrosus). An exception is the cave‐dwelling Rousettus aegyptiacus, which has a pronounced horizontal streak that potentially correlates with its occurrence in more open environments during foraging. In all species, we found a temporal area with maximum retinal ganglion cell density (∼5,000–7,000 cells/mm2) that affords enhanced resolution in the frontal visual field. Our estimates of spatial resolution based on peak retinal ganglion cell density and eye size (∼6–12 mm in axial length) range between ∼2 and 4 cycles/degree. Species that occur in more enclosed microhabitats and feed on plant material have lower spatial resolution (∼2 cycles/degree) compared with those that roost in open and semiopen areas (∼3–3.8 cycles/degree). We suggest that the larger eye and concomitant higher spatial resolution (∼4 cycles/degree) in H. monstrosus may have facilitated the carnivorous aspect of its diet. In conclusion, variations in the topographic organization and magnitude of retinal ganglion density reflect the specific ecological needs to detect food/predators and the structural complexity of the environments. J. Comp. Neurol. 525:186–203, 2017. © 2016 Wiley Periodicals, Inc.
Defense against malicious URL spreading in micro‐blog network with hub nodes
Authors: Liu Xin , Wang Feng , Yang Yang , Xu Jiuyun , Zou Pingjun , Wang Yiwen
Published: June 2016

The micro‐blog network is one of the most popular social networking platforms. By calculating the degree centrality, we found that hub nodes play an important role in micro‐blog networks, which is the main power of message forwarding. To improve the security of the micro‐blog network, we proposed a defending scheme against malicious Uniform Resource Locator (URL) diffusing in micro‐blog networks with hub nodes. After a node found a new malicious URL, it will edit a warning massage about the malicious URL. If the normal node obtains malicious URL warning message, it will send private message with the warning message to the hub node and update its blog article. The malicious URL warning messages spread rapidly in the whole networks in a short period because of the influence of Hub nodes. At the same time, we add the comparison mechanism to reduce the redundancy of spreading the warning message in the networks. So the security of entire micro‐blog networks can be improved against malicious URL without increasing the network load. Experiments show that our scheme can effectively defend against the malicious URL in the any scale of micro‐blog networks. Copyright © 2016 John Wiley & Sons, Ltd.
The Inference‐Based Approach (IBA) to the Treatment of Obsessive–Compulsive Disorder: An Open Trial Across Symptom Subtypes and Treatment‐Resistant Cases
Authors: Aardema Frederick , O`Connor Kieron P. , Delorme Marie‐Eve , Audet Jean‐Sebastien
Published: June 2016

The current open trial evaluated an inference‐based approach (IBA) to the treatment of obsessive–compulsive disorder (OCD) across symptom subtypes and treatment‐resistant cases. Following formal diagnosis through semi‐structured interview by an independent evaluator, a total of 125 OCD participants across five major symptom subtypes entered a program of 24 sessions of treatment based on the IBA. An additional group of 22 participants acted as a natural wait‐list control group. Participants were administered the Yale–Brown Obsessive–Compulsive Scale before and after treatment as the principal outcome measure, as well as measures of negative mood states, inferential confusion and obsessive beliefs. Level of overvalued ideation was assessed clinically at pre‐treatment using the Overvalued Ideation Scale. After 24 weeks of treatment, 102 treatment completers across all major subtypes of OCD showed significant reductions on the Yale–Brown Obsessive–Compulsive Scale with effect sizes ranging from 1.49 to 2.53 with a clinically significant improvement in 59.8% of participants. No improvement was observed in a natural wait‐list comparison group. In addition, IBA was effective for those with high levels of overvalued ideation. Change in inferential confusion and beliefs about threat and responsibility were uniquely associated with treatment outcome. The study is the first large‐scale open trial showing IBA to be effective across symptom subtypes and treatment‐resistant cases. The treatment may be particularly valuable for those who have previously shown an attenuated response to other treatments. Copyright © 2016 John Wiley & Sons, Ltd.

Key Practitioner Message

Psychological treatment based on the inference‐based approach is an effective treatment for all major subtypes of obsessive–compulsive disorder.

The treatment is equally effective for those with high and low levels of overvalued ideation.

Treatment based on the inference‐based approach may be particularly valuable for those who have shown an attenuated response to cognitive–behaviour therapy as usual.
“Green” Synthesis of Metal‐Organic Frameworks
Authors: Reinsch Helge
Published: June 2016

Research in the field of metal‐organic frameworks (MOFs) has been for a long time devoted to the synthesis of new compounds and the understanding of their outstanding properties. Just in the recent four or five years there has been an emerging interest in up‐scaling of synthesis procedures and the adjustment of synthesis conditions towards industrial requirements. This probably originates from the fact that, while some MOFs are already commercially available, there is still no field of application in real life which MOFs are able to fit in. One reason for this might be the attributed to the common synthetic procedures which are often unsuitable for preparations at pilot or industrial scale. Thus a recent focus in MOF research is the finding of synthesis conditions which employ non‐hazardous reactants at relatively mild synthetic conditions, producing also less waste than conventional procedures. In brief: The “green” synthesis of MOFs. This microreview is intended to give some examples of the efforts made in this field of research and show some perspectives for the future.
Determination of iohexol and iothalamate in serum and urine by capillary electrophoresis
Authors: Van Houcke Sofie K. , Seaux Liesbeth , Cavalier Etienne , Speeckaert Marijn M. , Dumoulin Els , Lecocq Elke , Delanghe Joris R.
Published: June 2016

Estimation of glomerular filtration rate (eGFR) is essential to assess kidney function. Iodine‐containing contrast agents detection by HPLC has been proposed as a safe alternative for inulin or radioactive compounds. However, HPLC is a time‐consuming and labor‐intensive method. The aim of this study was to develop an assay for iohexol and iothalamate using capillary electrophoresis. Iohexol and iothalamate were directly analyzed by CE in serum and urine, using photometric detection (246 nm). Serum peak height was proportional to iohexol and iothalamate concentrations. Detection limits for iohexol and iothalamate were 10 and 5 mg/L. Limits of quantification were 13.0 and 15.0 mg/L. Within‐run CVs were 4.9 and 6.5%; between‐run CVs 3.1–9.9% and 3.8–13.7%. A good correlation was observed between CE and HPLC: y = 1.1703x + 5.017 (iohexol) and y = 0.7807x + 11.01 (iothalamate; (y = concentration obtained by CE [mg/L], x = concentration obtained by HPLC [mg/L]). In addition, CE allowed to determine urinary iohexol concentration. Although the detection limit for CE was higher than for HPLC, CE can still be used for eGFR determination. Advantages of this high‐throughput method are the absence of sample pretreatment and a minimal sample volume requirement.
An amperometric lactate biosensor based on lactate dehydrogenase immobilized onto graphene oxide nanoparticles‐modified pencil graphite electrode
Authors: Batra Bhawna , Narwal Vinay , Pundir Chandra S.
Published: June 2016

A novel amperometric lactate biosensor was developed based on immobilization of lactate dehydrogenase onto graphene oxide nanoparticles‐decorated pencil graphite electrode. The enzyme electrode was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), and cyclic voltammetry at different stages of its construction. The biosensor showed optimum response within 5 s at pH 7.3 (0.1 M sodium phosphate buffer) and 35°C, when operated at 0.7 V. The biosensor exhibited excellent sensitivity (detection limit as low as 0.1 μM), fast response time (5 s), and wider linear range (5–50 mM). Analytical recovery of added lactic acid in serum was between 95.81–97.87% and within‐batch and between‐batch coefficients of variation were 5.04 and 5.40%, respectively. There was a good correlation between serum lactate values obtained by standard colorimetric method and the present biosensor (r = 0.99). The biosensor measured lactate levels in sera of apparently healthy subjects and persons suffering from lactate acidosis and other biological materials (milk, curd, yogurt, beer, white wine, and red wine). The enzyme electrode lost 25% of its initial activity after 60 days of its regular uses, when stored dry at 4°C.
Evaluation of fire performance of organic fire retardant free acrylic based coatings applied on various building materials by cone calorimetric method
Authors: De Silva Karnika , Ray Sudip , Blache Robert , Taylor Mark
Published: June 2016

Fire performance of water‐based plaster systems containing acrylic copolymer binder and non‐flammable mineral and ceramic fillers intended for decorative coating application was determined by cone calorimetric method. The coatings were applied on common building substrate materials used in construction sector, namely, Medium Density Fibre (MDF) boards, Gypsum Boards (GIB) and Stainless Steel (SS), and the different plaster finishes attempted on these substrates were Tierrafino, Suave and Bone China respectively. Group numbers of the different test samples were also evaluated following the Kokkala method. Based on various measurements, especially heat release, smoke evolution, mass loss data and the Group number estimates, it is evident that these organic fire retardant free coatings can offer good fire safety if applied on appropriate substrates like GIB or SS. Copyright © 2016 John Wiley & Sons, Ltd.
Synergistic anti‐tumor efficacy of immunogenic adenovirus ONCOS‐102 (Ad5/3‐D24‐GM‐CSF) and standard of care chemotherapy in preclinical mesothelioma model
Authors: Kuryk Lukasz , Haavisto Elina , Garofalo Mariangela , Capasso Cristian , Hirvinen Mari , Pesonen Sari , Ranki Tuuli , Vassilev Lotta , Cerullo Vincenzo
Published: June 2016

Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1‐year from diagnosis. Currently there are no curative treatment modalities for malignant mesothelioma, however treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase life expectancy. Pemetrexed‐Cisplatin is the only standard of care (SoC) chemotherapy for malignant mesothelioma, but the median PFS/OS (progression‐free survival/overall survival) from the initiation of treatment is only up to 12 months. Therefore, new treatment strategies against malignant mesothelioma are in high demand. ONCOS‐102 is a dual targeting, chimeric oncolytic adenovirus, coding for human GM‐CSF. The safety and immune activating properties of ONCOS‐102 have already been assessed in phase 1 study (NCT01598129). In this preclinical study, we evaluated the antineoplastic activity of combination treatment with SoC chemotherapy (Pemetrexed, Cisplatin, Carboplatin) and ONCOS‐102 in xenograft BALB/c model of human malignant mesothelioma. We demonstrated that ONCOS‐102 is able to induce immunogenic cell death of human mesothelioma cell lines in vitro and showed anti‐tumor activity in the treatment of refractory H226 malignant pleural mesothelioma (MPM) xenograft model. While chemotherapy alone showed no anti‐tumor activity in the mesothelioma mouse model, ONCOS‐102 was able to slow down tumor growth. Interestingly, a synergistic anti‐tumor effect was seen when ONCOS‐102 was combined with chemotherapy regimens. These findings give a rationale for the clinical testing of ONCOS‐102 in combination with first‐line chemotherapy in patients suffering from malignant mesothelioma.
Enhanced osteoprogenitor elongated collagen fiber matrix formation by bioactive glass ionic silicon dependent on Sp7 (osterix) transcription
Authors: Varanasi Venu G. , Odatsu Tetsurou , Bishop Timothy , Chang Joyce , Owyoung Jeremy , Loomer Peter M.
Published: June 2016

Bioactive glasses release ions, those enhance osteoblast collagen matrix synthesis and osteogenic marker expression during bone healing. Collagen matrix density and osteogenic marker expression depend on osteogenic transcription factors, (e.g., Osterix (OSX)). We hypothesize that enhanced expression and formation of collagen by Si4+ depends on enhanced expression of OSX transcription. Experimental bioactive glass (6P53‐b) and commercial BioglassTM (45S5) were dissolved in basal medium to make glass conditioned medium (GCM). ICP‐MS analysis was used to measure bioactive glass ion release rates. MC3T3‐E1 cells were cultured for 20 days, and gene expression and extracellular matrix collagen formation was analyzed. In a separate study, siRNA was used to determine the effect of OSX knockdown on impacting the effect of Si4+ on osteogenic markers and matrix collagen formation. Each bioactive glass exhibited similar ion release rates for all ions, except Mg2+ released by 6P53‐b. Gene expression results showed that GCM markedly enhanced many osteogenic markers, and 45S5 GCM showed higher levels of expression and collagen matrix fiber bundle density than 6P53‐b GCM. Upon knockdown of OSX transcription, collagen type 5, alkaline phosphatase, and matrix density were not enhanced as compared to wild type cells. This study illustrates that the enhancement of elongated collagen fiber matrix formation by Si± depends on OSX transcription. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2604–2615, 2016.
Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis
Authors: Hu Zhansheng , Zhu Zhitu , Cao Yunfeng , Wang Lixuan , Sun Xiaoyu , Dong Jun , Fang Zhongze , Fang Yanhua , Xu Xiaoxue , Gao Peng , Hongzhi Sun
Published: June 2016

Cerebral infarction (CI) and intracerebral hemorrhage are lethal cerebrovascular diseases, sometimes sharing similar clinical manifestations but with distinct therapeutic strategies. Delayed treatment usually resulted in poor prognosis. A timely diagnosis report is highly warranted especially in emergency. One hundred twenty‐nine CI patients, 73 intracerebral hemorrhage (ICH) patients, and 98 controls were enrolled in this study. A direct injection mass spectrometry metabolomics approach was adopted using dried blood spot samples. This targeted metabolomics analysis focused on absolute quantitation of 23 amino acids, 26 carnitine/carnitine esters, and 22 calculated ratios parameters. Compared to the normal control group, CI and ICH showed distinct metabolite changes, respectively. For stroke differentiation, Tyr, C5‐OH/C0, Cit, Asn, Pro, Val, Arg/Orn, Leu, and Val/Phe were elevated in the CI group. On the contrary, C5:1, Phe/Tyr, (C0 + C2 + C3 + C16 + C18:1)/Cit, and Met/Leu were of lower levels in the CI group. Using regression model based on some of the above‐mentioned parameters, 79.07% of stroke patients from a new set could be definitely confirmed. This study proved the targeted metabolomics analysis was a promising tool for rapid and timely stroke differentiation.
Applying meta‐analysis to structural equation modeling
Authors: Hedges Larry V.
Published: June 2016

Structural equation models play an important role in the social sciences. Consequently, there is an increasing use of meta‐analytic methods to combine evidence from studies that estimate the parameters of structural equation models. Two approaches are used to combine evidence from structural equation models: A direct approach that combines structural coefficients and an indirect approach that first combines correlation matrices and estimates structural coefficients from the combined correlation matrix. When there is no heterogeneity across studies, direct estimates of structural coefficients from several studies is an appealing approach. Heterogeneity of correlation matrices across studies presents both practical and conceptual problems. An alternative approach to heterogeneity is suggested as an example of how to better handle heterogeneity in this context. Copyright © 2016 John Wiley & Sons, Ltd.
Protection of Vine Plants against Esca Disease by Breathable Electrospun Antifungal Nonwovens
Authors: Buchholz Viola , Molnar Melanie , Wang Hui , Reich Steffen , Agarwal Seema , Fischer Michael , Greiner Andreas
Published: June 2016

The harmful Esca disease in vine plants caused by wood‐inhabiting fungi including Phaeomoniella chlamydospora (Pch) is spreading all across the world. This disease leads to poor vine crops and a slow decline or to a sudden dieback of the vine plants. The pruning wounds of vine plants are the main entry point for Pch. While model experiments with aerosol particles recommend electrospun nonwovens as a suitable barrier to block Pch, tests with living spores show clearly that only electrospun fibrous nonwovens do not prevent Pch invasion. However it is found, that with antifungal additives electrospun nonwovens could be applied successfully for blocking of Pch to infect the substrate. Thereby, a highly useful concept for the protection of vine plants against Esca disease is provided which could also serve as a concept for related plant diseases.

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Low Molecular Weight Gelators Bearing Electroactive Groups as Cathode Materials for Rechargeable Batteries
Authors: Wang Zhong , Fujisawa Seiya , Suzuki Masahiro , Hanabusa Kenji
Published: June 2016

Low molecular weight gelators bearing 2,2,6,6‐tetramethyl‐piperidine‐1‐oxyl (TEMPO) were synthesized and demonstrated to have reversible electrochemical redox properties. The gelation tests showed that the compounds have excellent gelation properties in γ‐butyrolactone and propylene carbonate. Atomic force microscopy and transmission electron microscopy images showed the 3D network fibrous structure with an average diameter of 20–50 nm. Fast and reversible charge storage capabilities were established for the gelators, with an average output voltage of 4.8 V.
Quantitative and textural analysis of magnetization transfer and diffusion images in the early detection of brain metastases
Authors: Ainsworth Nicola L. , McLean Mary A. , McIntyre Dominick J.O. , Honess Davina J. , Brown Anna M. , Harden Susan V , Griffiths John R.
Published: June 2016

Purpose

The sensitivity of the magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) for early detection of brain metastases was investigated in mice and humans.

Methods

Mice underwent MRI twice weekly for up to 31 d following intracardiac injection of the brain‐homing breast cancer cell line MDA‐MB231‐BR. Patients with small cell lung cancer underwent quarterly MRI for 1 year. MTR and ADC were measured in regions of metastasis and matched contralateral tissue at the final time point and in registered regions at earlier time points. Texture analysis and linear discriminant analysis were performed to detect metastasis‐containing slices.

Results

Compared with contralateral tissue, mouse metastases had significantly lower MTR and higher ADC at the final time point. Some lesions were visible at earlier time points on the MTR and ADC maps: 24% of these were not visible on corresponding T2‐weighted images. Texture analysis using the MTR maps showed 100% specificity and 98% sensitivity for metastasis at the final time point, with 77% sensitivity 2–4 d earlier and 46% 5–8 d earlier. Only 2 of 16 patients developed metastases, and their penultimate scans were normal.

Conclusions

Some brain metastases may be detected earlier on MTR than conventional T2; however, the small gain is unlikely to justify “predictive” MRI. Magn Reson Med 77:1987–1995, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Next‐generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma
Authors: Tetzlaff Michael T , Singh Rajesh R , Seviour Elena G , Curry Jonathan L , Hudgens Courtney W , Bell Diana , Wimmer Daniel A , Ning Jing , Czerniak Bogdan A , Zhang Li , Davies Michael A , Prieto Victor G , Broaddus Russell R , Ram Prahlad , Luthra Rajyalakshmi , Esmaeli Bita
Published: June 2016

Sebaceous carcinoma (SC) is a rare but aggressive malignancy with frequent recurrence and metastases. Surgery is the mainstay of therapy, but effective systemic therapies are lacking because the molecular alterations driving SC remain poorly understood. To identify these, we performed whole‐exome next‐generation sequencing of 409 cancer‐associated genes on 27 SCs (18 primary/locally recurrent ocular, 5 paired metastatic ocular, and 4 primary extraocular) from 20 patients. In ocular SC, we identified 139 non‐synonymous somatic mutations (median/lesion 3; range 0–23). Twenty‐five of 139 mutations (18%) occurred in potentially clinically actionable genes in 6 of 16 patients. The most common mutations were mutations in TP53 (n = 9), RB1 (n = 6), PIK3CA (n = 2), PTEN (n = 2), ERBB2 (n = 2), and NF1 (n = 2). TP53 and RB1 mutations were restricted to ocular SC and correlated with aberrant TP53 and RB protein expression. Systematic pathway analyses demonstrated convergence of these mutations to activation of the PI3K signalling cascade, and PI3K pathway activation was confirmed in tumours with PTEN and/or PIK3CA mutations. Considerable inter‐tumoural heterogeneity was observed between paired primary and metastatic ocular SCs. In primary extraocular SC, we identified 77 non‐synonymous somatic mutations (median/lesion 22.5; range 3–29). This overall higher mutational load was attributed to a microsatellite instability phenotype in three of four patients and somatically acquired mutations in mismatch repair genes in two of four patients. Eighteen of 77 mutations (23%) were in potentially clinically actionable genes in three of four patients, including BTK, FGFR2, PDGFRB, HRAS, and NF1 mutations. Identification of potentially clinically actionable mutations in 9 of 20 SC patients (45%) underscores the importance of next‐generation sequencing to expand the spectrum of genotype‐matched targeted therapies. Frequent activation of PI3K signalling pathways provides a strong rationale for application of mTOR inhibitors in the management of this disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Crystal structure of the N‐terminal domain of human SIRT7 reveals a three‐helical domain architecture
Authors: Priyanka Anu , Solanki Vipul , Parkesh Raman , Thakur Krishan Gopal
Published: June 2016

Human SIRT7 is an NAD+ dependent deacetylase, which belongs to sirtuin family of proteins. SIRT7, like other sirtuins has conserved catalytic domain and is flanked by N‐ and C‐terminal domains reported to play vital functional roles. Here, we report the crystal structure of the N‐terminal domain of human SIRT7 (SIRT7NTD) at 2.3 Å resolution as MBP‐SIRT7NTD fusion protein. SIRT7NTD adopts three‐helical domain architecture and comparative structural analyses suggest similarities to some DNA binding motifs and transcription regulators. We also report here the importance of N‐ and C‐terminal domains in soluble expression of SIRT7. Proteins 2016; 84:1558–1563. © 2016 Wiley Periodicals, Inc.
Effect of crocin on aged rat kidney through inhibition of oxidative stress and proinflammatory state
Authors: Samarghandian Saeed , Azimi‐Nezhad Mohsen , Borji Abasalt , Farkhondeh Tahereh
Published: June 2016

This study evaluated whether crocin, a bioactive component of saffron, has a protective effect on kidney through reducing the oxidative stress and inflammatory response in aged rats. In this study the changes in activities of antioxidant enzymes, lipid peroxidation, glutathione (GSH) levels and the expression of pro‐inflammatory cytokines in the serum and renal tissue were evaluated by ELISA and RT‐PCR, respectively. The middle and aged rats were given intraperitoneal injections of crocin (10, 20, 30 mg/kg/day) for 4 weeks. After 4 weeks, animals were anesthetized with diethyl ether. The kidney samples were taken for biochemical analysis. The results revealed the aging was associated with a significant decrease in the activities of antioxidant enzymes, and GSH content with increase in lipid peroxidation level in kidney of the aged rats (p < 0.001). The increased levels of serum renal functional parameter, oxidative parameters (p < 0.01) and also pro‐inflammatory cytokine levels were significantly reduced by crocin administration (p < 0.05). The aged rats exhibited a dysregulation of the oxidative stress, and inflammation in the kidneys, but crocin treatment significantly reduced the expression of the inflammatory genes. These results provide pivotal documentation that crocin has a renoprotective effects against the development of oxidative stress and inflammation in the kidney of old rats. Copyright © 2016 John Wiley & Sons, Ltd.
Palladium‐Catalyzed Hydroxycarbonylation of Aryl Halides with the in‐situ Generation of CO and H2O
Authors: Li Chong‐Liang , Qi Xinxin , Wu Xiao‐Feng
Published: June 2016

An interesting palladium‐catalyzed hydroxycarbonylation of aryl halides with the in‐situ generation of CO and H2O has been developed. CO was in‐situ generated from formic acid with acetic anhydride as the activator and H2O was in‐situ generated from acetic acid and alcohol esterification. A variety of benzoic acid derivatives were produced in moderate to good yields from the corresponding aryl halides. No additional water addition is required during the whole process.
Caloric Restriction Normalizes Obesity‐Induced Alterations on Regulators of Skeletal Muscle Growth Signaling
Authors: Dungan Cory M. , Li Ji , Williamson David L.
Published: June 2016

The objective of this study was to establish the impact of caloric restriction on high fat diet‐induced alterations on regulators of skeletal muscle growth. We hypothesized that caloric restriction would reverse the negative effects of high fat diet‐induced obesity on REDD1 and mTOR‐related signaling. Following an initial 8 week period of HF diet‐induced obesity, caloric restriction (CR ~30 %) was employed while mice continued to consume either a low (LF) or high fat (HF) diet for 8 weeks. Western analysis of skeletal muscle showed that CR reduced (p < 0.05) the obesity‐related effects on the lipogenic protein, SREBP1. Likewise, CR reduced (p < 0.05) the obesity‐related effects on the hyperactivation of mTORC1 and ERK1/2 signaling to levels comparable to the LF mice. CR also reduced (p < 0.05) obesity‐induced expression of negative regulators of growth, REDD1 and cleaved caspase 3. These findings have implications for on the reversibility of dysregulated growth signaling in obese skeletal muscle, using short‐term caloric restriction.
#Sleepyteens: Social media use in adolescence is associated with poor sleep quality, anxiety, depression and low self‐esteem
Authors: Woods Heather Cleland , Scott Holly
Published: June 2016

This study examined how social media use related to sleep quality, self‐esteem, anxiety and depression in 467 Scottish adolescents. We measured overall social media use, nighttime‐specific social media use, emotional investment in social media, sleep quality, self‐esteem and levels of anxiety and depression. Adolescents who used social media more – both overall and at night – and those who were more emotionally invested in social media experienced poorer sleep quality, lower self‐esteem and higher levels of anxiety and depression. Nighttime‐specific social media use predicted poorer sleep quality after controlling for anxiety, depression and self‐esteem. These findings contribute to the growing body of evidence that social media use is related to various aspects of wellbeing in adolescents. In addition, our results indicate that nighttime‐specific social media use and emotional investment in social media are two important factors that merit further investigation in relation to adolescent sleep and wellbeing.
Her Majesty's Justice Be Done: Métis Legal Mobilization and the Pitfalls to Indigenous Political Movement Building
Authors: Voth Daniel
Published: June 2016

Indigenous peoples have, to varying degrees, turned to the courts to litigate their ongoing disputes with Canada's settler colonial governments. Scholars have examined well the ways courts are used for strategic political ends by a variety of Indigenous and non-Indigenous litigants and are laden with settler values and institutional logics that are foreign to Indigenous peoples. However, it is less clear what effect turning to the courts in pursuit of strategic goals has on specific relationships between Indigenous peoples. This gap is more pronounced in Métis scholarship where there have been few final appellate cases. This paper argues the interaction between the Manitoba Métis Federation and Treaty 1 peoples seeking leave to intervene at the Manitoba Court of Appeal inMMF v. Canadailluminates the way litigating Indigenous-settler disputes can advance divisive, exclusionary, zero-sum political relationships between Indigenous peoples. These fractious interactions serve to undermine the construction of a co-ordinated and related inter-Indigenous decolonizing politics.
NEW DIRECTIONS FOR HISTORICAL ARCHAEOLOGY IN EASTERN AFRICA?
Authors: LANE PAUL J.
Published: June 2016

Recent years have seen growth in the number of historical archaeology studies in Eastern Africa. Combining critical analysis of material remains alongside the available documentary and oral sources, these offer new insights into the precolonial and colonial pasts of the region. However, the field is less well established than in either West or Southern Africa and the full potential of the subdiscipline has yet to be realised. This contribution reviews the main analytical and theoretical trends, drawing on a selection of examples. Several other research themes that might warrant investigation are also identified, and the general lack of engagement with material culture and the archaeology of the last few hundred years on the part of historians, is lamented.