bluuebunny/crossref_metadata_2025 huggingface dataset:
Industrial Aerodynamics
Authors: Chalot Frédéric L.
Published: December 2017

This chapter describes the use of computational fluid mechanics at Dassault Aviation. A historical perspective gives a measure of the successive giant steps that have been made over the past 30 years. A rather detailed description of industrial codes leads to a good understanding of the key numerical concepts assembled to create a powerful tool for computational aerodynamics. The fundamental issue of turbulence modeling is addressed in detail. A large range of complex applications is described to illustrate the variety of problems solved. The status of the development and application of shape optimization techniques and multidisciplinary design are finally illustrated.
Discontinuous
P
etrov–
G
alerkin (
DPG
) Method
Authors: Demkowicz Leszek , Gopalakrishnan Jay
Published: December 2017

This chapter reviews the fundamentals of the discontinuous Petrov–Galerkin (DPG) method with optimal test functions. The main idea admits three different interpretations: a Petrov–Galerkin method with (optimal) test functions that realize the supremum in the inf–sup condition; a minimum‐residual method with residual measured in a dual norm; and a mixed formulation where one solves simultaneously for the Riesz representation of the residual. The methodology can be applied to any well‐posed variational problem, but it is especially effective in context of discontinuous (broken) test spaces. We discuss how one can “break” test functions in any variational formulation, and use the convection‐dominated diffusion model problem to illustrate challenges related to the choice of an appropriate test norm.
Investigation of DNA‐Binding Activities of Zinc(II) and Cobalt(II) Phthalocyanine Compounds with 3,4,5‐Trimethoxybenzyloxy Substituents
Authors: Arslantas Ali , Agirtas Mehmet Salih
Published: December 2017

In this study, DNA‐binding activities of previously synthesized tetrakis(3,4,5‐trimethoxybenzyloxy)‐substituted Zn(II) and Co(II) phthalocyanines (Pc4 and Pc5) have been chosen for the study. The interaction of synthesized tetrakis(3,4,5‐trimethoxybenzyloxy)‐substituted Zn(II) and Co(II) phthalocyanine compounds with CT‐DNA was investigated by using UV/Vis titrimetric method, fluorescence spectroscopy, cyclic voltammetry, thermal denaturation profile, gel electrophoresis and viscosty measurement in a Tris‐HCI buffer at pH 7.0. The results indicated that tetrakis(3,4,5‐trimethoxybenzyloxy)‐substituted Zn(II) and Co(II) phthalocyanines (Pc4 and Pc5) can interact with CT‐DNA via intercalation binding mode.
Polycystic ovary syndrome
Authors: Kayemba-Kay's Simon , Pambou Armelle , Heron Anne , Benosman Sidi Mohammed
Published: December 2017

Background:

Polycystic ovary syndrome (PCOS) is a common reproductive endocrinopathy in women of childbearing age, affecting 5–15% women in this age group. Suggestive cardinal features comprise hyperandrogenism, ovulatory dysfunction and/or polycystic ovary appearance. The gold standard radiological tool is the pelvic ultrasound (PUS) whose yield may be limited in overweight and obese adolescent girls.

Objective and hypotheses:

To evaluate the contribution of pelvic MRI to the diagnosis of PCOS in a specific group of virginal overweight and obese adolescent girls.

Method:

Eight adolescent girls seen for menstrual irregularities or amenorrhea, with features of hyperandrogenism were biochemically screened (LH, FSH, testosterone, S-DHEA, delta-4 androstenedi- one, 17 (OH) P, SHBG, TSH, free T4, prolactin and lipid profile, fasting blood sugar and HOMA-IR and HOMA-B). Each had PUS and/or pelvic MRI (PMRI) performed. Other causes of hyperandrogenism were excluded.

Imaging:

PUS with the trans-abdominal transducer was attempted in only one patient Acuson© scanner, using 3.5–7.5 MHz transducer; PMRI was performed in all patients with phased array coil of 1.5 T Siemens MRI scanner, with T1 and T2-weighted axial and coronal images. PCOS was defined according to the Rotterdam PCOS consensus Workshop.

Results:

Eight girls (mean age 14,6 ± 1.47 years) are reported, one was overweight (BMI Z-score > 1 SDS), seven others were obese (BMI Z-score > 2 SDS). Mean age at menarche was 11.58 ± 1.11 years, except for one who had not yet entered menarche. All had menstrual irregularities, acanthosis nigricans, acne, hirsutism, and biochemical characteristics of PCOS (high plasma androgens, insulin resistance, glucose/ insulin ratio <4.5, decreased SHBG).

PUS was not contributive to the diagnosis of PCOS, whereas PMRI showed typical aspect (well delineated peripheral ovarian cysts), with increased ovarian volume and stroma.

Conclusion:

Although PUS remains the gold standard for the diagnosis of PCOS in most cases, its limitations in overweight and obese girls are real and must be considered.

If utilization of endovaginal transducer not being feasible in young virginal girls, PMRI could be a useful alternative, allowing greater delineation of structural components of the ovary and better appreciation of both its volume and structural alterations.
Uncertainty Driven Action (UDA) model: A foundation for unifying perspectives on design activity
Authors: Cash Philip , Kreye Melanie
Published: December 2017

This paper proposes the Uncertainty Driven Action (UDA) model, which unifies the fragmented literature on design activity. The UDA model conceptualises design activity as a process consisting of three core actions: information action, knowledge-sharing action, and representation action, which are linked via uncertainty perception. The foundations of the UDA model in the design literature are elaborated in terms of the three core actions and their links to designer cognition and behaviour, utilising definitions and concepts from Activity Theory. The practical relevance and theoretical contributions of the UDA model are discussed. This paper contributes to the design literature by offering a comprehensive formalisation of design activity of individual designers, which connects cognition and action, to provide a foundation for understanding previously disparate descriptions of design activity.
Preparation of ultra-broadband antireflective coatings for amplifier blast shields by a sol–gel method
Authors: Xiong Huai , Shen Bin , Chen Zhiya , Zhang Xu , Li Haiyuan , Tang Yongxing , Hu Lili
Published: December 2017

A type of $\unicode[STIX]{x1D706}/4$–$\unicode[STIX]{x1D706}/4$ ultra-broadband antireflective coating has been developed using modified low refractive silica and high refractive silica layers by a sol–gel dip coating method for amplifier blast shields of the Shen Guang II high power laser facility (SG-II facility). Deposition of the first layer (high refractive index silica) involves baking at $200\,^{\circ }\text{C}$ in the post-treatment step. The second layer (low refractive index, $n=1.20$) uses low refractive index silica sol modified by acid catalysis. Thermal baking at temperatures no less than $500\,^{\circ }\text{C}$ for 60 min offers chemical stability, ethanol scratch resistance, and resistance to washing with water. The average residual reflection of dual-side-coated fused silica glass was less than 1% in the spectral range from 450 to 950 nm. Transmission gain has been evaluated by taking into account angular light, and the results show that the transmission gain increases with increasing light incidence. Even at $60^{\circ }$, the transmission spectrum of the broadband antireflective coating effectively covered the main absorption peak of Nd:glass.
Israeli National Policy for Carbapenem-Resistant Enterobacteriaceae Screening, Carrier Isolation and Discontinuation of Isolation
Authors: Solter Ester , Adler Amos , Rubinovitch Bina , Temkin Elizabeth , Schwartz David , Ben-David Debby , Masarwa Samira , Carmeli Yehuda , Schwaber Mitchell J.
Published: December 2017

Since 2006, Israel has been confronting an outbreak of carbapenem-resistant Enterobacteriaceae (CRE), and in 2007 Israel implemented a national strategy to contain spread. The intervention was initially directed toward acute-care hospitals and later expanded to include an established reservoir of carriage in long-term-care hospitals. It included regular reporting of CRE cases to a central registry and daily oversight of management of the outbreak at the institutional level. Microbiological methodologies were standardized in clinical laboratories nationwide. Uniform requirements for carrier screening and isolation were established, and a protocol for discontinuation of carrier status was formulated. In response to the evolving epidemiology of CRE in Israel and the continued need for uniform guidelines for carrier detection and isolation, the Ministry of Health in 2016 issued a regulatory circular updating the requirements for CRE screening, laboratory diagnosis, molecular characterization, and carrier isolation, as well as reporting and discontinuation of isolation in healthcare institutions nationwide. The principal elements of the circular are contained herein.

Infect Control Hosp Epidemiol 2018;39:85–89
100 % Fruit juice and measures of glucose control and insulin sensitivity: a systematic review and meta-analysis of randomised controlled trials
Authors: Murphy Mary M. , Barrett Erin C. , Bresnahan Kara A. , Barraj Leila M.
Published: December 2017

Studies on the effects of consuming 100 % fruit juice on measures of glycaemic control are conflicting. The purpose of the present study was to systematically review and quantitatively summarise results from randomised controlled trials (RCT) examining effects of 100 % fruit juice on glucose–insulin homeostasis. Eligible studies were identified from a systematic review of PubMed and EMBASE and hand searches of reference lists from reviews and relevant papers. Using data from eighteen RCT, meta-analyses evaluated the mean difference in fasting blood glucose (sixteen studies), fasting blood insulin (eleven studies), the homeostatic model assessment of insulin resistance (HOMA-IR; seven studies) and glycosylated Hb (HbA1c; three studies) between the 100 % fruit juice intervention and control groups using a random-effects model. Compared with the control group, 100 % fruit juice had no significant effect on fasting blood glucose (−0·13 (95 % CI −0·28, 0·01) mmol/l;P = 0·07), fasting blood insulin (−0·24 (95 % CI −3·54, 3·05) pmol/l;P = 0·89), HOMA-IR (−0·22 (95 % CI −0·50, 0·06);P = 0·13) or HbA1c (−0·001 (95 % CI −0·38, 0·38) %;P = 0·28). Results from stratified analyses and univariate meta-regressions also largely showed no significant associations between 100 % fruit juice and the measures of glucose control. Overall, findings from this meta-analysis of RCT suggest a neutral effect of 100 % fruit juice on glycaemic control. These findings are consistent with findings from some observational studies suggesting that consumption of 100 % fruit juice is not associated with increased risk of diabetes.
INAHTA IMPACT STORY: LEGISLATIVE AND ACCREDITATION REQUIREMENTS FOR OFFICE-BASED SURGERY IN AUSTRALIA
Authors: Tivey David , Ma Ning , Duncan Joanna , Atukorale Yasoba , Lambert Robyn , Maddern Guy
Published: December 2017

Background:There is growing trend for some surgical procedures previously performed in hospitals to be done in alternative settings, including office-based facilities. There has been some safety concerns reported in the media, which document serious adverse events following procedures performed in an office-based setting. To understand the current regulatory oversight of surgery in this setting ASERNIP-S conducted a review of the legislative and accreditation process governing these facilities in Australia.

Methods:Using rapid review methodology, internet searches targeted government Web sites for relevant publicly-available documents. Use of consolidated versions of legislative instruments ensured currency of information. Standards were sourced directly from the issuing authorities or those that oversee the accreditation process.

Results:Within Australia, healthcare facilities for surgery and their licensing are defined by each state and territory, which results in significant jurisdictional variation. These variations relate to the need for anesthesia beyond conscious sedation and listing of procedures in legislative instruments. In 2013, Australia adopted National Safety and Quality Health Service standards (NSQHS standards) for the accreditation of hospitals and day surgery centers; however, there is no NSQHS standard for office-based facilities. The main legislative driver for compliance is access to reimbursement schemes for service delivery.

Conclusions:The legislative and accreditation framework creates a situation whereby healthcare facilities that provide services outside the various legal definitions of surgery and those not covered by a reimbursement scheme, can operate without licensing and accreditation oversight. This situation exposes patients to potential increased risk of harm when receiving treatment in such unregulated facilities.
Airborne Surveys Examine Water Levels of Lakes Perched on Permafrost
Authors: Leman Jennifer
Published: December 2017

Do water levels in high-latitude Canadian lakes fluctuate as one body or as separate entities? The answer could reveal clues to how melting permafrost influences the environment.
Lessons from ten years of genome‐wide association studies of asthma
Authors: Vicente Cristina T , Revez Joana A , Ferreira Manuel A R
Published: December 2017

Twenty‐five genome‐wide association studies (GWAS) of asthma were published between 2007 and 2016, the largest with a sample size of 157242 individuals. Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with each other were reported to associate with disease risk at a significance threshold of P<5 × 10−8, including 31 in populations of European ancestry. Results from analyses of the UK Biobank data (n=380 503) indicate that at least 28 of the 31 associations reported in Europeans represent true‐positive findings, collectively explaining 2.5% of the variation in disease liability (median of 0.06% per variant). We identified 49 transcripts as likely target genes of the published asthma risk variants, mostly based on LD with expression quantitative trait loci (eQTL). Of these genes, 16 were previously implicated in disease pathophysiology by functional studies, including TSLP, TNFSF4, ADORA1, CHIT1 and USF1. In contrast, at present, there is limited or no functional evidence directly implicating the remaining 33 likely target genes in asthma pathophysiology. Some of these genes have a known function that is relevant to allergic disease, including F11R, CD247, PGAP3, AAGAB, CAMK4 and PEX14, and so could be prioritized for functional follow‐up. We conclude by highlighting three areas of research that are essential to help translate GWAS findings into clinical research or practice, namely validation of target gene predictions, understanding target gene function and their role in disease pathophysiology and genomics‐guided prioritization of targets for drug development.
Cortical high gamma network oscillations and connectivity: a translational index for antipsychotics to normalize aberrant neurophysiological activity
Authors: Ahnaou A. , Huysmans H. , Van de Casteele T. , Drinkenburg W. H. I. M.
Published: December 2017

Oscillatory activity in the gamma frequency range is a critical mechanism, which integrates neural networks within and across brain structures during cognitive processes. In schizophrenia, abnormalities in high gamma oscillations are ubiquitous and most likely reflect dysfunction in neuronal networks. In conscious rats, disturbed network oscillations associated with positive symptoms and cognitive deficits were modeled in different cortical areas by the dopaminergic agonist (amphetamine) and the N-methyl-D-aspartate (NMDA) receptor antagonists (PCP and MK801). Subsequently, the efficacies of marketed atypical antipsychotics (olanzapine, risperidone, and clozapine) to normalize dysfunctional oscillations and network connectivity were examined. Acute NMDA antagonists elicited aberrant synchrony in the gamma frequency oscillations. In addition, coherent slow alpha network activity was observed with MK801 and amphetamine, both of whose oscillatory rhythms were correlated with pronounced locomotor activity. All antipsychotics commonly decreased slow alpha and high gamma network oscillations in different cortical regions as well as motion behavior. In the combined treatments, antipsychotics attenuated NMDA antagonist-induced abnormalities in functional network oscillations and connectivity, whose effects on motor behavior is mechanistically related. These results suggest that pharmacologically induced disruption of cortical gamma oscillations and network connectivity in rats is a candidate model to study dysfunctional oscillatory patterns described in positive and negative symptoms of schizophrenia. The efficacy of antipsychotics to rescue cortical network oscillatory patterns is in line with the idea that glutamatergic and dopaminergic systems play a role in maintaining the integrity of cortical circuits. Thus, gamma oscillations could provide a powerful translational index to assess the integrity of neural networks and to evaluate the efficacy of drugs with potential antipsychotic properties.
Possible role of the gut microbiota–brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model
Authors: Yang Chun , Qu Youge , Fujita Yuko , Ren Qian , Ma Min , Dong Chao , Hashimoto Kenji
Published: December 2017

Accumulating evidence suggests that the gut microbiota–brain axis plays a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. (R)-ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here, we investigated whether the gut microbiota plays a role in the antidepressant effects of these two ketamine enantiomers. The role of the gut microbiota in the antidepressant effects of ketamine enantiomers in a chronic social defeat stress (CSDS) model of depression was examined using 16S ribosomal RNA gene sequencing of fecal samples. At the phylum level, CSDS-susceptible mice showed alterations in the levels of Tenericutes and Actinobacteria; however, neither ketamine enantiomers influenced these alterations. At the class level, both ketamine enantiomers significantly attenuated the increase in the levels of Deltaproteobacteria in the susceptible mice after CSDS. Furthermore, (R)-ketamine, but not (S)-ketamine, significantly attenuated the reduction in the levels of Mollicutes in the susceptible mice. At the genus level, both ketamine enantiomers significantly attenuated the decrease in the levels of Butyricimonas in the susceptible mice. Notably, (R)-ketamine was more potent than (S)-ketamine at reducing the levels of Butyricimonas in the susceptible mice. In conclusion, this study suggests that the antidepressant effects of two enantiomers of ketamine in CSDS model may be partly mediated by the restoration of the gut microbiota. Furthermore, the specific effect of (R)-ketamine on the levels of Mollicutes and Butyricimonas may explain its robust antidepressant action.
Endosomal binding kinetics of Eps15 and Hrs specifically regulate the degradation of RTKs
Authors: Haugen Linda Hofstad , Skjeldal Frode Miltzow , Bergeland Trygve , Bakke Oddmund
Published: December 2017

Activation of EGF-R and PDGF-R triggers autophosphorylation and the recruitment of Eps15 and Hrs. These two endosomal proteins are important for specific receptor sorting. Hrs is recruiting ubiquitinated receptors to early endosomes to further facilitate degradation through the ESCRT complex. Upon receptor activation Hrs becomes phosphorylated and is relocated to the cytosol, important for receptor degradation. In this work we have studied the endosomal binding dynamics of Eps15 and Hrs upon EGF-R and PDGF-R stimulation. By analysing the fluorescence intensity on single endosomes after ligand stimulation we measured a time-specific decrease in the endosomal fluorescence level of Eps15-GFP and Hrs-YFP. Through FRAP experiments we could further register a specific change in the endosomal-membrane to cytosol binding properties of Eps15-GFP and Hrs-YFP. This specific change in membrane fractions proved to be a redistribution of the immobile fraction, which was not shown for the phosphorylation deficient mutants. We here describe a mechanism that can explain the previously observed relocation of Hrs from the endosomes to cytosol after EGF stimulation and show that Eps15 follows a similar mechanism. Moreover, this specific redistribution of the endosomal protein binding dynamics proved to be of major importance for receptor degradation.
Bacterial community structure and novel species of magnetotactic bacteria in sediments from a seamount in the Mariana volcanic arc
Authors: Liu Jia , Zhang Wenyan , Li Xuegong , Li Xuegang , Chen Xumiao , Li Jin-Hua , Teng Zhaojie , Xu Cong , Santini Claire-Lise , Zhao Li , Zhao Yuan , Zhang Heng , Zhang Wei-Jia , Xu Kuidong , Li Chaolun , Pan Yongxin , Xiao Tian , Pan Hongmiao , Wu Long-Fei
Published: December 2017

Seamounts are undersea mountains rising abruptly from the sea floor and interacting dynamically with underwater currents. They represent unique biological habitats with various microbial community structures. Certain seamount bacteria form conspicuous extracellular iron oxide structures, including encrusted stalks, flattened bifurcating tubes, and filamentous sheaths. To extend our knowledge of seamount ecosystems, we performed an integrated study on population structure and the occurrence of magnetotactic bacteria (MTB) that synthesize intracellular iron oxide nanocrystals in sediments of a seamount in the Mariana volcanic arc. We found Proteobacteria dominant at 13 of 14 stations, but ranked second in abundance to members of the phylum Firmicutes at the deep-water station located on a steep slope facing the Mariana-Yap Trench. Live MTB dwell in biogenic sediments from all 14 stations ranging in depth from 238 to 2,023 m. Some magnetotactic cocci possess the most complex flagellar apparatus yet reported; 19 flagella are arranged in a 3:4:5:4:3 array within a flagellar bundle. Phylogenetic analysis of 16S rRNA gene sequences identified 16 novel species of MTB specific to this seamount. Together the results obtained indicate that geographic properties of the seamount stations are important in shaping the bacterial community structure and the MTB composition.
Burst intensification by singularity emitting radiation in multi-stream flows
Authors: Pirozhkov A. S. , Esirkepov T. Zh. , Pikuz T. A. , Faenov A. Ya. , Ogura K. , Hayashi Y. , Kotaki H. , Ragozin E. N. , Neely D. , Kiriyama H. , Koga J. K. , Fukuda Y. , Sagisaka A. , Nishikino M. , Imazono T. , Hasegawa N. , Kawachi T. , Bolton P. R. , Daido H. , Kato Y. , Kondo K. , Bulanov S. V. , Kando M.
Published: December 2017

Burst Intensification by Singularity Emitting Radiation (BISER) is proposed. Singularities in multi-stream flows of emitting media cause constructive interference of emitted travelling waves, forming extremely localized sources of bright coherent emission. Here we for the first time demonstrate this extreme localization of BISER by direct observation of nano-scale coherent x-ray sources in a laser plasma. The energy emitted into the spectral range from 60 to 100 eV is up to ~100 nJ, corresponding to ~1010photons. Simulations reveal that these sources emit trains of attosecond x-ray pulses. Our findings establish a new class of bright laboratory sources of electromagnetic radiation. Furthermore, being applicable to travelling waves of any nature (e.g. electromagnetic, gravitational or acoustic), BISER provides a novel framework for creating new emitters and for interpreting observations in many fields of science.
Disposable aptamer-sensor aided by magnetic nanoparticle enrichment for detection of salivary cortisol variations in obstructive sleep apnea patients
Authors: Fernandez Renny Edwin , Umasankar Yogeswaran , Manickam Pandiaraj , Nickel Jeffrey C. , Iwasaki Laura R. , Kawamoto Burt K. , Todoki Kristen C. , Scott JoAnna M. , Bhansali Shekhar
Published: December 2017

We report a disposable point-of-care sensing platform specific to salivary cortisol detection. The sensor is inkjet printed on a paper substrate with a metalloporphyrin based macrocyclic catalyst ink that can electrochemically reduce cortisol, captured by aptamer functionalized magnetic nanoparticles. The sensor consists of a thin magnet disc, aligned at the back of the electrode, in order to populate the magnetic nanoparticle bound cortisol at the sensing electrode area. Proof of concept studies were performed to detect salivary cortisol levels in human subjects with high and low risks for obstructive sleep apnea (OSA). High selectivity was observed to salivary cortisol against a background of closely related steroids.
Conditionally reprogrammed primary airway epithelial cells maintain morphology, lineage and disease specific functional characteristics
Authors: Martinovich Kelly M. , Iosifidis Thomas , Buckley Alysia G. , Looi Kevin , Ling Kak-Ming , Sutanto Erika N. , Kicic-Starcevich Elizabeth , Garratt Luke W. , Shaw Nicole C. , Montgomery Samuel , Lannigan Francis J. , Knight Darryl A. , Kicic Anthony , Stick Stephen M.
Published: December 2017

Current limitations to primary cell expansion led us to test whether airway epithelial cells derived from healthy children and those with asthma and cystic fibrosis (CF), co-cultured with an irradiated fibroblast feeder cell in F-medium containing 10 µM ROCK inhibitor could maintain their lineage during expansion and whether this is influenced by underlying disease status. Here, we show that conditionally reprogrammed airway epithelial cells (CRAECs) can be established from both healthy and diseased phenotypes. CRAECs can be expanded, cryopreserved and maintain phenotypes over at least 5 passages. Population doublings of CRAEC cultures were significantly greater than standard cultures, but maintained their lineage characteristics. CRAECs from all phenotypes were also capable of fully differentiating at air-liquid interface (ALI) and maintained disease specific characteristics including; defective CFTR channel function cultures and the inability to repair wounds. Our findings indicate that CRAECs derived from children maintain lineage, phenotypic and importantly disease-specific functional characteristics over a specified passage range.
Identification of minimal parameters for optimal suppression of chaos in dissipative driven systems
Authors: Martínez Pedro J. , Euzzor Stefano , Gallas Jason A. C. , Meucci Riccardo , Chacón Ricardo
Published: December 2017

Taming chaos arising from dissipative non-autonomous nonlinear systems by applying additional harmonic excitations is a reliable and widely used procedure nowadays. But the suppressory effectiveness of generic non-harmonic periodic excitations continues to be a significant challenge both to our theoretical understanding and in practical applications. Here we show how the effectiveness of generic suppressory excitations is optimally enhanced when the impulse transmitted by them (time integral over two consecutive zeros) is judiciously controlled in a not obvious way. Specifically, the effective amplitude of the suppressory excitation is minimal when the impulse transmitted is maximum. Also, by lowering the impulse transmitted one obtains larger regularization areas in the initial phase difference-amplitude control plane, the price to be paid being the requirement of larger amplitudes. These two remarkable features, which constitute our definition of optimum control, are demonstrated experimentally by means of an analog version of a paradigmatic model, and confirmed numerically by simulations of such a damped driven system including the presence of noise. Our theoretical analysis shows that the controlling effect of varying the impulse is due to a subsequent variation of the energy transmitted by the suppressory excitation.
Deep sequencing of blood and gut T-cell receptor β-chains reveals gluten-induced immune signatures in celiac disease
Authors: Yohannes Dawit A. , Freitag Tobias L. , de Kauwe Andrea , Kaukinen Katri , Kurppa Kalle , Wacklin Pirjo , Mäki Markku , Arstila T. Petteri , Anderson Robert P. , Greco Dario , Saavalainen Päivi
Published: December 2017

Celiac disease (CD) patients mount an abnormal immune response to gluten. T-cell receptor (TCR) repertoires directed to some immunodominant gluten peptides have previously been described, but the global immune response to in vivo gluten exposure in CD has not been systematically investigated yet. Here, we characterized signatures associated with gluten directed immune activity and identified gluten-induced T-cell clonotypes from total blood and gut TCR repertoires in an unbiased manner using immunosequencing. CD patient total TCR repertoires showed increased overlap and substantially altered TRBV-gene usage in both blood and gut samples, and increased diversity in the gut during gluten exposure. Using differential abundance analysis, we identified gluten-induced clonotypes in each patient that were composed of a large private and an important public component. Hierarchical clustering of public clonotypes associated with dietary gluten exposure identified subsets of highly similar clonotypes, the most proliferative of which showing significant enrichment for the motif ASS[LF]R[SW][TD][DT][TE][QA][YF] in PBMC repertoires. These results show that CD-associated clonotypes can be identified and that common gluten associated immune response features can be characterized in vivo from total repertoires, with potential use in disease stratification and monitoring.
Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis
Authors: Kay Alasdair G. , Long Grace , Tyler George , Stefan Andrei , Broadfoot Stephen J. , Piccinini Anna M. , Middleton Jim , Kehoe Oksana
Published: December 2017

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis.
Morphological stabilization and KPZ scaling by electrochemically induced co-deposition of nanostructured NiW alloy films
Authors: Orrillo P. A. , Santalla S. N. , Cuerno R. , Vázquez L. , Ribotta S. B. , Gassa L. M. , Mompean F. J. , Salvarezza R. C. , Vela M. E.
Published: December 2017

We have assessed the stabilizing role that induced co-deposition has in the growth of nanostructured NiW alloy films by electrodeposition on polished steel substrates, under pulsed galvanostatic conditions. We have compared the kinetic roughening properties of NiW films with those of Ni films deposited under the same conditions, as assessed by Atomic Force Microscopy. The surface morphologies of both systems are super-rough at short times, but differ at long times: while a cauliflower-like structure dominates for Ni, the surfaces of NiW films display a nodular morphology consistent with more stable, conformal growth, whose height fluctuations are in the Kardar-Parisi-Zhang universality class of rough two-dimensional interfaces. These differences are explained by the mechanisms controlling surface growth in each case: mass transport through the electrolyte (Ni) and attachment of the incoming species to the growing interface (NiW). Thus, the long-time conformal growth regime is characteristic of electrochemical induced co-deposition under current conditions in which surface kinetics is hindered due to a complex reaction mechanism. These results agree with a theoretical model of surface growth in diffusion-limited systems, in which the key parameter is the relative importance of mass transport with respect to the kinetics of the attachment reaction.
Effects of the Qinghai-Tibet Railway on the Landscape Genetics of the Endangered Przewalski’s Gazelle (Procapra przewalskii)
Authors: Yu He , Song Shiya , Liu Jiazi , Li Sheng , Zhang Lu , Wang Dajun , Luo Shu-Jin
Published: December 2017

The Przewalski’s gazelle (Procapra przewalskii) is one of the most endangered ungulates in the world, with fewer than 2,000 individuals surviving in nine habitat fragments on the Qinghai-Tibet Plateau and isolated by human settlements and infrastructure. In particular, the Qinghai-Tibet railway, which crosses the largest part of the gazelle’s distribution, remains a major concern because of its potential to intensify landscape genetic differentiation. Here, using mtDNA sequencing and microsatellite genotyping to analyze 275 Przewalski’s gazelle samples collected throughout the range, we observed low level of genetic diversity (mtDNA π = 0.0033) and strong phylogeographic structure. Overall, the nine patches of gazelles can be further clustered into five populations, with a strong division between the eastern vs. western side of Qinghai Lake. Our study provides the first evidence of the genetic divergence between the Haergai North and Haergai South gazelle populations, corresponding to the recent construction of a wired enclosure along the Qinghai-Tibet railway less than ten years ago, an equivalent of five generations. Well-designed wildlife corridors across the railway along with long-term monitoring of the anthropogenic effects are therefore recommended to alleviate further habitat fragmentation and loss of genetic diversity in Przewalski’s gazelle.
Minimizing carry-over PCR contamination in expanded CAG/CTG repeat instability applications
Authors: Aeschbach Lorène , Dion Vincent
Published: December 2017

Expanded CAG/CTG repeats underlie the aetiology of 14 neurological and neuromuscular disorders. The size of the repeat tract determines in large part the severity of these disorders with longer tracts causing more severe phenotypes. Expanded CAG/CTG repeats are also unstable in somatic tissues, which is thought to modify disease progression. Routine molecular biology applications involving these repeats, including quantifying their instability, are plagued by low PCR yields. This leads to the need for setting up more PCRs of the same locus, thereby increasing the risk of carry-over contamination. Here we aimed to reduce this risk by pre-treating the samples with a Uracil N-Glycosylase (Ung) and using dUTP instead of dTTP in PCRs. We successfully applied this method to the PCR amplification of expanded CAG/CTG repeats, their sequencing, and their molecular cloning. In addition, we optimized the gold-standard method for measuring repeat instability, small-pool PCR (SP-PCR), such that it can be used together with Ung and dUTP-containing PCRs, without compromising data quality. We performed SP-PCR on myotonic-dystrophy-derived samples containing an expansion as large as 1000 repeats, demonstrating the applicability to clinically-relevant material. Thus, we expect the protocols herein to be applicable for molecular diagnostics of expanded repeat disorders.
Broadly neutralizing antiviral responses induced by a single-molecule HPV vaccine based on thermostable thioredoxin-L2 multiepitope nanoparticles
Authors: Spagnoli Gloria , Pouyanfard Somayeh , Cavazzini Davide , Canali Elena , Maggi Stefano , Tommasino Massimo , Bolchi Angelo , Müller Martin , Ottonello Simone
Published: December 2017

Vaccines targeting the human papillomavirus (HPV) minor capsid protein L2 are emerging as chemico-physically robust and broadly protective alternatives to the current HPV (L1-VLP) vaccines. We have previously developed a trivalent L2 vaccine prototype exploiting Pyrococcus furiosus thioredoxin (PfTrx) as a thermostable scaffold for the separate presentation of three distinct HPV L2(20–38) epitopes. With the aim of achieving a highly immunogenic, yet simpler and more GMP-production affordable formulation, we report here on a novel thermostable nanoparticle vaccine relying on genetic fusion of PfTrx-L2 with the heptamerizing coiled-coil polypeptide OVX313. A prototype HPV16 monoepitope version of this nanoparticle vaccine (PfTrx-L2-OVX313; median radius: 8.6 ± 1.0 nm) proved to be approximately 10-fold more immunogenic and with a strikingly enhanced cross-neutralization capacity compared to its monomeric counterpart. Vaccine-induced (cross-)neutralizing responses were further potentiated in a multiepitope derivative displaying eight different L2(20–38) epitopes, which elicited neutralizing antibodies against 10 different HPVs including three viral types not represented in the vaccine. Considering the prospective safety of the PfTrx scaffold and of the OVX313 heptamerization module, PfTrx-OVX313 nanoparticles lend themselves as robust L2-based immunogens with a high translational potential as a 3rd generation HPV vaccine, but also as a novel and extremely versatile peptide-antigen presentation platform.
Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells
Authors: Dong Chao , Yang Runxiang , Li Hongjian , Ke Kunbin , Luo Chunxiang , Yang Fang , Shi Xi-Nan , Zhu Ying , Liu Xu , Wong Man-Hon , Lin Guimiao , Wang Xiaomei , Leung Kwong-Sak , Kung Hsiang-Fu , Chen Ceshi , Lin Marie Chia-mi
Published: December 2017

The phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in many cellular processes, including the proliferation, survival and differentiation of lung cancer cells. Thus, PI3K is a promising therapeutic target for lung cancer treatment. In this study, we applied free and open-source protein-ligand docking software, screened 3167 FDA-approved small molecules, and identified putative PI3Kα inhibitors. Among them, econazole nitrate, an antifungal agent, exhibited the highest activity in decreasing cell viability in pathological types of NSCLC cell lines, including H661 (large cell lung cancer) and A549 (adenocarcinoma). Econazole decreased the protein levels of p-AKT and Bcl-2, but had no effect on the phosphorylation level of ERK. It inhibited cell growth and promote apoptosis in a dose-dependent manner. Furthermore, the combination of econazole and cisplatin exhibited additive and synergistic effects in the H661 and A549 lung cancer cell lines, respectively. Finally, we demonstrated that econazole significantly suppressed A549 tumor growth in nude mice. Our findings suggest that econazole is a new PI3K inhibitor and a potential drug that can be used in lung cancer treatment alone or in combination with cisplatin.
Modeling and prediction of copper removal from aqueous solutions by nZVI/rGO magnetic nanocomposites using ANN-GA and ANN-PSO
Authors: Fan Mingyi , Hu Jiwei , Cao Rensheng , Xiong Kangning , Wei Xionghui
Published: December 2017

Reduced graphene oxide-supported nanoscale zero-valent iron (nZVI/rGO) magnetic nanocomposites were prepared and then applied in the Cu(II) removal from aqueous solutions. Scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and superconduction quantum interference device magnetometer were performed to characterize the nZVI/rGO nanocomposites. In order to reduce the number of experiments and the economic cost, response surface methodology (RSM) combined with artificial intelligence (AI) techniques, such as artificial neural network (ANN), genetic algorithm (GA) and particle swarm optimization (PSO), has been utilized as a major tool that can model and optimize the removal processes, because a tremendous advance has recently been made on AI that may result in extensive applications. Based on RSM, ANN-GA and ANN-PSO were employed to model the Cu(II) removal process and optimize the operating parameters, e.g., operating temperature, initial pH, initial concentration and contact time. The ANN-PSO model was proven to be an effective tool for modeling and optimizing the Cu(II) removal with a low absolute error and a high removal efficiency. Furthermore, the isotherm, kinetic, thermodynamic studies and the XPS analysis were performed to explore the mechanisms of Cu(II) removal process.
A gradient relationship between low birth weight and IQ: A meta-analysis
Authors: Gu Huaiting , Wang Lixia , Liu Lingfei , Luo Xiu , Wang Jia , Hou Fang , Nkomola Pauline Denis , Li Jing , Liu Genyi , Meng Heng , Zhang Jiajia , Song Ranran
Published: December 2017

Multiple studies have reported that individuals with low birth weights (LBW, <2500 g) have a lower intelligence quotient (IQ) than those with normal birth weights (NBW, ≥2500 g). Based on 57 eligible individual studies including 12,137 participants, we performed a meta-analysis to estimate the association between low birth weight and individuals’ IQ scores (IQs). The pooled weight mean difference (WMD) in IQs between NBW and LBW individuals was 10 (95% CI 9.26–11.68). The WMD was stable regardless of age. No publication bias was detected. The mean IQs of the extremely low birth weight (ELBW, <1000 g), very low birth weight (VLBW, 1000–1499 g), moderately low birth weight (MLBW, 1500–2499 g) and NBW individuals were 91, 94, 99 and 104, respectively. Additionally, the WMD in IQs with NBW were 14, 10 and 7 for ELBW, VLBW, and MLBW individuals, respectively. Two studies permitted estimates of the influence of social determinants of health to the discrepancy in IQs, which was 13%. Since IQ is inherited and influenced by environmental factors, parental IQs and other factors contribute to residual confounding of the results. As the conclusion was based on population studies, it may not be applicable to a single individual.
Human Sexual Cycles are Driven by Culture and Match Collective Moods
Authors: Wood Ian B. , Varela Pedro L. , Bollen Johan , Rocha Luis M. , Gonçalves-Sá Joana
Published: December 2017

Human reproduction does not happen uniformly throughout the year and what drives human sexual cycles is a long-standing question. The literature is mixed with respect to whether biological or cultural factors best explain these cycles. The biological hypothesis proposes that human reproductive cycles are an adaptation to the seasonal (hemisphere-dependent) cycles, while the cultural hypothesis proposes that conception dates vary mostly due to cultural factors, such as holidays. However, for many countries, common records used to investigate these hypotheses are incomplete or unavailable, biasing existing analysis towards Northern Hemisphere Christian countries. Here we show that interest in sex peaks sharply online during major cultural and religious celebrations, regardless of hemisphere location. This online interest, when shifted by nine months, corresponds to documented human births, even after adjusting for numerous factors such as language and amount of free time due to holidays. We further show that mood, measured independently on Twitter, contains distinct collective emotions associated with those cultural celebrations. Our results provide converging evidence that the cyclic sexual and reproductive behavior of human populations is mostly driven by culture and that this interest in sex is associated with specific emotions, characteristic of major cultural and religious celebrations.
Influence of body mass index on incidence and prognosis of acute myeloid leukemia and acute promyelocytic leukemia: A meta-analysis
Authors: Li Shufen , Chen Li , Jin Wen , Ma Xuefei , Ma Yunlin , Dong Fangyi , Zhu Hongming , Li Junmin , Wang Kankan
Published: December 2017

Previous studies have demonstrated an association between high body mass index (BMI) and acute myeloid leukemias (AML), particularly acute promyelocytic leukemia (APL). However, the effect of obesity and overweight on the incidence of AML is not supported by all studies, and the relationship between obesity and prognosis of AML and APL has not been established. Thus, we conducted a meta-analysis to determine the role of BMI on the risk and clinical outcome of AML, including APL. Twenty-six eligible studies enrolling 12,971 AML (including 866 APL) patients were retrieved and analyzed. Overweight and obesity was associated with an increased incidence of AML (relative risk [RR], 1.23; 95% confidence interval [CI], 1.12–1.35; P < 0.001). High BMI did not significantly affect overall survival (OS) (hazard ratio [HR], 0.97; 95% CI, 0.92–1.03; P = 0.323) or disease-free survival (HR, 0.98; 95% CI, 0.88–1.10; P = 0.755) in patients with non-APL AML. By contrast, APL patients with high BMI had shorter OS (HR, 1.77; 95% CI, 1.26–2.48; P = 0.001) and a higher risk of differentiation syndrome (HR, 1.53; 95% CI, 1.03–2.27, P = 0.04). Overall, our findings suggest that patients with overweight or obesity have a higher incidence of AML, and high BMI is a predictor of adverse clinical outcomes in APL.
Water quality assessment based on the water quality index method in Lake Poyang: The largest freshwater lake in China
Authors: Wu Zhaoshi , Zhang Dawen , Cai Yongjiu , Wang Xiaolong , Zhang Lu , Chen Yuwei
Published: December 2017

Twenty-four samplings were conducted every 3 months at 15 sites from January 2009 to October 2014 in Lake Poyang, and 20 parameters were analyzed and classified into three groups (toxic metals, easily treated parameters, and others). The assessment results based on water quality index (WQI) showed that the water quality in Lake Poyang was generally “moderate”, according to the classification of the surface water quality standard (GB3838-2002) in China, but a deteriorating trend was observed at the interannual scale. Seasonally, the water quality was best in summer and worst in winter. Easily treated parameters generally determined the WQI value in the assessment, especially total nitrogen (TN) and total phosphorus (TP), while toxic metals and other parameters in Lake Poyang were generally at low and safe levels for drinking water. Water level (WL) has a net positive effect on water quality in Lake Poyang through dilution of environmental parameters, which in practice means TN. Consequently, local management agencies should pay more attention to nutrient concentrations during the monitoring schedule, as well as during the low-water periods which manifest a relatively bad water quality state, especially with the prevailing low WL observed recently in Lake Poyang.