bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ENLIGHTENMENT IN NEW FOCUS
Authors: ROBERTSON RITCHIE
Published: September 2017

Enlightenment scholars have had some difficulty in getting the German Enlightenment in focus. If one's conception of the Enlightenment has been shaped by reading Peter Gay and Robert Darnton, then the German Enlightenment fails to fit their model. France offers us the picture of an intelligentsia, largely located in the capital, maintaining a degree of independence with some help from patrons, and in many cases opposed to the governing regime. Whether, like Gay, one focuses on the high-profile frequenters of the Parissalons, or, like Darnton, on half-starved hack writers, one has something approaching the modern conception of the intellectual, and hence a flattering genealogy for present-day intellectuals. It is easy to forget thatphilosophescould also be professional administrators, like the economist Anne-Robert-Jacques Turgot, and that Enlightened thinking was also diffused throughout the provinces by academies and scholarly networks.
Validity of Self-Reported Birth Weight: Results from a Norwegian Twin Sample
Authors: Nilsen Thomas S. , Kutschke Julia , Brandt Ingunn , Harris Jennifer R.
Published: September 2017

The association between birth weight and later life outcomes is of considerable interest in life-course epidemiology. Research often relies on self-reported measures of birth weight, and its validity is consequently of importance. We assessed agreement between self-reported birth weight and official birth records for Norwegian twins born 1967–1974. The intraclass correlation between self-reported birth weight and register-based birth weight was 0.91 in our final sample of 363 twins. It could be expected that 95% of self-reported birth-weight values will deviate from official records within a maximum of +446 grams and a minimum of −478 grams — around a mean deviation of 16 grams. Self-reported birth weight had a sensitivity of 0.78–0.89 and a positive predictive value of 0.59–0.85, and an overall weighted kappa of 0.71. We further assessed agreement by conducting two linear regression models where we respectively regressed self-reported birth weight and register-based birth weight on adult body mass index, a known association. The two models were not significantly different; however, there were different levels of significance in parameter estimates that warrant some caution in using self-reported birth weight. Reliability of self-reported birth weight was also assessed, based on self-reports in another sample of twins born 1935–1960 who had reported their birth weight in two questionnaires 34 years apart. The intraclass correlation was 0.86, which indicates a high degree of reliability. In conclusion, self-reported birth weight, depending on context and age when birth weight was reported, can be cautiously used.
Coherent diffractive imaging of single helium nanodroplets with a high harmonic generation source
Authors: Rupp Daniela , Monserud Nils , Langbehn Bruno , Sauppe Mario , Zimmermann Julian , Ovcharenko Yevheniy , Möller Thomas , Frassetto Fabio , Poletto Luca , Trabattoni Andrea , Calegari Francesca , Nisoli Mauro , Sander Katharina , Peltz Christian , J. Vrakking Marc , Fennel Thomas , Rouzée Arnaud
Published: September 2017

Coherent diffractive imaging of individual free nanoparticles has opened routes for the in situ analysis of their transient structural, optical, and electronic properties. So far, single-shot single-particle diffraction was assumed to be feasible only at extreme ultraviolet and X-ray free-electron lasers, restricting this research field to large-scale facilities. Here we demonstrate single-shot imaging of isolated helium nanodroplets using extreme ultraviolet pulses from a femtosecond-laser-driven high harmonic source. We obtain bright wide-angle scattering patterns, that allow us to uniquely identify hitherto unresolved prolate shapes of superfluid helium droplets. Our results mark the advent of single-shot gas-phase nanoscopy with lab-based short-wavelength pulses and pave the way to ultrafast coherent diffractive imaging with phase-controlled multicolor fields and attosecond pulses.
Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities
Authors: Didychuk Allison L. , Montemayor Eric J. , Carrocci Tucker J. , DeLaitsch Andrew T. , Lucarelli Stefani E. , Westler William M. , Brow David A. , Hoskins Aaron A. , Butcher Samuel E.
Published: September 2017

U6 small nuclear ribonucleoprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood. Here, we report structures of the U6 RNA processing enzyme Usb1 from yeast and a substrate analog bound complex from humans. Unlike the human ortholog, we show that yeast Usb1 has cyclic phosphodiesterase activity that leaves a terminal 3′ phosphate which prevents overprocessing. Usb1 processing of U6 RNA dramatically alters its affinity for cognate RNA-binding proteins. We reconstitute the post-transcriptional assembly of yeast U6 snRNP in vitro, which occurs through a complex series of handoffs involving 10 proteins (Lhp1, Prp24, Usb1 and Lsm2–8) and anti-cooperative interactions between Prp24 and Lhp1. We propose a model for U6 snRNP assembly that explains how evolutionarily divergent and seemingly antagonistic proteins cooperate to protect and chaperone the nascent snRNA during its journey to the spliceosome.
Evolution of protein-coupled RNA dynamics during hierarchical assembly of ribosomal complexes
Authors: Abeysirigunawardena Sanjaya C. , Kim Hajin , Lai Jonathan , Ragunathan Kaushik , Rappé Mollie C. , Luthey-Schulten Zaida , Ha Taekjip , Woodson Sarah A.
Published: September 2017

Assembly of 30S ribosomes involves the hierarchical addition of ribosomal proteins that progressively stabilize the folded 16S rRNA. Here, we use three-color single molecule FRET to show how combinations of ribosomal proteins uS4, uS17 and bS20 in the 16S 5′ domain enable the recruitment of protein bS16, the next protein to join the complex. Analysis of real-time bS16 binding events shows that bS16 binds both native and non-native forms of the rRNA. The native rRNA conformation is increasingly favored after bS16 binds, explaining how bS16 drives later steps of 30S assembly. Chemical footprinting and molecular dynamics simulations show that each ribosomal protein switches the 16S conformation and dampens fluctuations at the interface between rRNA subdomains where bS16 binds. The results suggest that specific protein-induced changes in the rRNA dynamics underlie the hierarchy of 30S assembly and simplify the search for the native ribosome structure.
Scalable carbon dioxide electroreduction coupled to carbonylation chemistry
Authors: Jensen Mikkel T. , Rønne Magnus H. , Ravn Anne K. , Juhl René W. , Nielsen Dennis U. , Hu Xin-Ming , Pedersen Steen U. , Daasbjerg Kim , Skrydstrup Troels
Published: September 2017

Significant efforts have been devoted over the last few years to develop efficient molecular electrocatalysts for the electrochemical reduction of carbon dioxide to carbon monoxide, the latter being an industrially important feedstock for the synthesis of bulk and fine chemicals. Whereas these efforts primarily focus on this formal oxygen abstraction step, there are no reports on the exploitation of the chemistry for scalable applications in carbonylation reactions. Here we describe the design and application of an inexpensive and user-friendly electrochemical set-up combined with the two-chamber technology for performing Pd-catalysed carbonylation reactions including amino- and alkoxycarbonylations, as well as carbonylative Sonogashira and Suzuki couplings with near stoichiometric carbon monoxide. The combined two-reaction process allows for milligram to gram synthesis of pharmaceutically relevant compounds. Moreover, this technology can be adapted to the use of atmospheric carbon dioxide.
Warming up human body by nanoporous metallized polyethylene textile
Authors: Cai Lili , Song Alex Y. , Wu Peilin , Hsu Po-Chun , Peng Yucan , Chen Jun , Liu Chong , Catrysse Peter B. , Liu Yayuan , Yang Ankun , Zhou Chenxing , Zhou Chenyu , Fan Shanhui , Cui Yi
Published: September 2017

Space heating accounts for the largest energy end-use of buildings that imposes significant burden on the society. The energy wasted for heating the empty space of the entire building can be saved by passively heating the immediate environment around the human body. Here, we demonstrate a nanophotonic structure textile with tailored infrared (IR) property for passive personal heating using nanoporous metallized polyethylene. By constructing an IR-reflective layer on an IR-transparent layer with embedded nanopores, the nanoporous metallized polyethylene textile achieves a minimal IR emissivity (10.1%) on the outer surface that effectively suppresses heat radiation loss without sacrificing wearing comfort. This enables 7.1 °C decrease of the set-point compared to normal textile, greatly outperforming other radiative heating textiles by more than 3 °C. This large set-point expansion can save more than 35% of building heating energy in a cost-effective way, and ultimately contribute to the relief of global energy and climate issues.
The most active Cu facet for low-temperature water gas shift reaction
Authors: Zhang Zhenhua , Wang Sha-Sha , Song Rui , Cao Tian , Luo Liangfeng , Chen Xuanye , Gao Yuxian , Lu Jiqing , Li Wei-Xue , Huang Weixin
Published: September 2017

Identification of the active site is important in developing rational design strategies for solid catalysts but is seriously blocked by their structural complexity. Here, we use uniform Cu nanocrystals synthesized by a morphology-preserved reduction of corresponding uniform Cu2O nanocrystals in order to identify the most active Cu facet for low-temperature water gas shift (WGS) reaction. Cu cubes enclosed with {100} facets are very active in catalyzing the WGS reaction up to 548 K while Cu octahedra enclosed with {111} facets are inactive. The Cu–Cu suboxide (CuxO, x ≥ 10) interface of Cu(100) surface is the active site on which all elementary surface reactions within the catalytic cycle proceed smoothly. However, the formate intermediate was found stable at the Cu–CuxO interface of Cu(111) surface with consequent accumulation and poisoning of the surface at low temperatures. Thereafter, Cu cubes-supported ZnO catalysts are successfully developed with extremely high activity in low-temperature WGS reaction.
Inhibition of Y1 receptor signaling improves islet transplant outcome
Authors: Loh Kim , Shi Yan-Chuan , Walters Stacey , Bensellam Mohammed , Lee Kailun , Dezaki Katsuya , Nakata Masanori , Ip Chi Kin , Chan Jeng Yie , Gurzov Esteban N. , Thomas Helen E. , Waibel Michaela , Cantley James , Kay Thomas W. , Yada Toshihiko , Laybutt D. Ross , Grey Shane T. , Herzog Herbert
Published: September 2017

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.
Metabolic stress-induced cardiomyopathy is caused by mitochondrial dysfunction due to attenuated Erk5 signaling
Authors: Liu Wei , Ruiz-Velasco Andrea , Wang Shoubao , Khan Saba , Zi Min , Jungmann Andreas , Dolores Camacho-Muñoz Maria , Guo Jing , Du Guanhua , Xie Liping , Oceandy Delvac , Nicolaou Anna , Galli Gina , Müller Oliver J. , Cartwright Elizabeth J. , Ji Yong , Wang Xin
Published: September 2017

The prevalence of cardiomyopathy from metabolic stress has increased dramatically; however, its molecular mechanisms remain elusive. Here, we show that extracellular signal-regulated protein kinase 5 (Erk5) is lost in the hearts of obese/diabetic animal models and that cardiac-specific deletion of Erk5 in mice (Erk5-CKO) leads to dampened cardiac contractility and mitochondrial abnormalities with repressed fuel oxidation and oxidative damage upon high fat diet (HFD). Erk5 regulation of peroxisome proliferator-activated receptor γ co-activator-1α (Pgc-1α) is critical for cardiac mitochondrial functions. More specifically, we show that Gp91phox activation of calpain-1 degrades Erk5 in free fatty acid (FFA)-stressed cardiomyocytes, whereas the prevention of Erk5 loss by blocking Gp91phox or calpain-1 rescues mitochondrial functions. Similarly, adeno-associated virus 9 (AAV9)-mediated restoration of Erk5 expression in Erk5-CKO hearts prevents cardiomyopathy. These findings suggest that maintaining Erk5 integrity has therapeutic potential for treating metabolic stress-induced cardiomyopathy.
Erratum: Inflammation of mammary adipose tissue occurs in overweight and obese patients exhibiting early-stage breast cancer
Authors: Vaysse Charlotte , Lømo Jon , Garred Øystein , Fjeldheim Frøydis , Lofteroed Trygve , Schlichting Ellen , McTiernan Anne , Frydenberg Hanne , Husøy Anders , Lundgren Steinar , Fagerland Morten W. , Richardsen Elin , Wist Erik A. , Muller Catherine , Thune Inger
Published: September 2017

A correction to this article has been published and is linked from the HTML version of this article.
Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry
Authors: Stemmer Salomon M. , Steiner Mariana , Rizel Shulamith , Geffen David B. , Nisenbaum Bella , Peretz Tamar , Soussan-Gutman Lior , Bareket-Samish Avital , Isaacs Kevin , Rosengarten Ora , Fried Georgeta , McCullough Debbie , Svedman Christer , Shak Steven , Liebermann Nicky , Ben-Baruch Noa
Published: September 2017

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18–30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18–30, and ≥ 31 group, respectively. The 5-year Kaplan–Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2–3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated (n = 27) and 2.9% in chemotherapy-untreated patients (n = 352); P = 0.245. In Recurrence Score 18–30, recurrence rate in chemotherapy-treated patients (n = 102) was significantly lower than in untreated patients (n = 156) (1.0% vs. 9.7% P = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n = 89) and 4.4% in chemotherapy-untreated patients (n = 488); P = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1–3 positive nodes and Recurrence Score < 18.
Erratum: A cubesat centrifuge for long duration milligravity research
Authors: Asphaug Erik , Thangevelautham Jekan , Klesh Andrew , Chandra Aman , Nallapu Ravi , Raura Laksh , Herreras-Martinez Mercedes , Schwartz Stephen
Published: September 2017

A correction to this article has been published and is linked from the HTML version of this article.
Erratum: Treating tobacco dependence: guidance for primary care on life-saving interventions. Position statement of the IPCRG
Authors: Schayck O. C. P. Van , Williams S. , Barchilon V. , Baxter N. , Jawad M. , Katsaounou P. A. , Kirenga B. J. , Panaitescu C. , Tsiligianni I. G. , Zwar N. , Ostrem A.
Published: September 2017

A correction to this article has been published and is linked from the HTML version of this article.
Erratum: Broken rotational symmetry on the Fermi surface of a high-Tc superconductor
Authors: Ramshaw B. J. , Harrison N. , Sebastian S. E. , Ghannadzadeh S. , Modic K. A. , Bonn D. A. , Hardy W. N. , Liang Ruixing , Goddard P. A.
Published: September 2017

A correction to this article has been published and is linked from the HTML version of this article.
Gated tuned superconductivity and phonon softening in monolayer and bilayer MoS2
Authors: Fu Yajun , Liu Erfu , Yuan Hongtao , Tang Peizhe , Lian Biao , Xu Gang , Zeng Junwen , Chen Zhuoyu , Wang Yaojia , Zhou Wei , Xu Kang , Gao Anyuan , Pan Chen , Wang Miao , Wang Baigeng , Zhang Shou-Cheng , Cui Yi , Hwang Harold Y. , Miao Feng
Published: September 2017

Superconductors at the atomic two-dimensional limit are the focus of an enduring fascination in the condensed matter community. This is because, with reduced dimensions, the effects of disorders, fluctuations, and correlations in superconductors become particularly prominent at the atomic two-dimensional limit; thus such superconductors provide opportunities to tackle tough theoretical and experimental challenges. Here, based on the observation of ultrathin two-dimensional superconductivity in monolayer and bilayer molybdenum disulfide (MoS2) with electric-double-layer gating, we found that the critical sheet carrier density required to achieve superconductivity in a monolayer MoS2 flake can be as low as 0.55 × 1014 cm−2, which is much lower than those values in the bilayer and thicker cases in previous report and also our own observations. Further comparison of the phonon dispersion obtained by ab initio calculations indicated that the phonon softening of the acoustic modes around the M point plays a key role in the gate-induced superconductivity within the Bardeen–Cooper–Schrieffer theory framework. This result might help enrich the understanding of two-dimensional superconductivity with electric-double-layer gating.
Freeform fabrication of tissue-simulating phantom for potential use of surgical planning in conjoined twins separation surgery
Authors: Shen Shuwei , Wang Haili , Xue Yue , Yuan Li , Zhou Ximing , Zhao Zuhua , Dong Erbao , Liu Bin , Liu Wendong , Cromeens Barrett , Adler Brent , Besner Gail , Xu Ronald X.
Published: September 2017

Preoperative assessment of tissue anatomy and accurate surgical planning is crucial in conjoined twin separation surgery. We developed a new method that combines three-dimensional (3D) printing, assembling, and casting to produce anatomic models of high fidelity for surgical planning. The related anatomic features of the conjoined twins were captured by computed tomography (CT), classified as five organ groups, and reconstructed as five computer models. Among these organ groups, the skeleton was produced by fused deposition modeling (FDM) using acrylonitrile-butadiene-styrene. For the other four organ groups, shell molds were prepared by FDM and cast with silica gel to simulate soft tissues, with contrast enhancement pigments added to simulate different CT and visual contrasts. The produced models were assembled, positioned firmly within a 3D printed shell mold simulating the skin boundary, and cast with transparent silica gel. The produced phantom was subject to further CT scan in comparison with that of the patient data for fidelity evaluation. Further data analysis showed that the produced model reassembled the geometric features of the original CT data with an overall mean deviation of less than 2 mm, indicating the clinical potential to use this method for surgical planning in conjoined twin separation surgery.
Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe3O4 nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug
Authors: Krishnan Poorani , Rajan Mariappan , Kumari Sharmilah , Sakinah S. , Priya Sivan Padma , Amira Fatin , Danjuma Lawal , Pooi Ling Mok , Fakurazi Sharida , Arulselvan Palanisamy , Higuchi Akon , Arumugam Ramitha , Alarfaj Abdullah A. , Munusamy Murugan A. , Hamat Rukman Awang , Benelli Giovanni , Murugan Kadarkarai , Kumar S. Suresh
Published: September 2017

Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE3O4), a composite nanoparticle of magnetic iron oxide (Fe3O4), and β-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT’s solubility and bioavailability for cancer cells. The use of magnetically responsive anti-cancer formulation is highly advantageous in cancer chemotherapy. The chemical characterisation of CPT-CEF was studied here. The ability of this nano-compound to induce apoptosis in HT29 colon cancer cells and A549 lung cancer cells was evaluated. The dose-dependent cytotoxicity of CPT-CEF was shown using MTT. Propidium iodide and Annexin V staining, mitochondrial membrane depolarisation (JC-1 dye), and caspase-3 activity were assayed to detect apoptosis in CPT-CEF-treated cancer cells. Cell cycle analysis also showed G1 phase arrest, which indicated possible synergistic effects of the nano-carrier. These study results show that CPT-CEF causes a dose-dependent cell viability reduction in HT29 and A549 cells and induces apoptosis in colon cancer cells via caspase-3 activation. These data strongly suggest that CPT could be used as a major nanocarrier for CPT to effectively treat colon cancer.
Remarkable preservation of terpenoids and record of volatile signalling in plant-animal interactions from Miocene amber
Authors: Dutta Suryendu , Mehrotra Rakesh C. , Paul Swagata , Tiwari R. P. , Bhattacharya Sharmila , Srivastava Gaurav , Ralte V. Z. , Zoramthara C.
Published: September 2017

Plants produce and release a large array of volatile organic compounds that play many ecological functions. These volatile plant metabolites serve as pollinator attractants, herbivore and pathogen repellents and protect plants from abiotic stresses. To date, the geological evolution of these organic compounds remains unknown. The preservation potential of these metabolites in the fossil record is very poor due to their low boiling points. Here we report a series of volatile sesquiterpenoids, including δ-elemene, α-copaene, β-elemene, β-caryophyllene, α-humulene, germacrene D, δ-cadiene and spathunenol, from early Miocene (~17 million year) amber from eastern India. The survival of these unaltered bioterpenoids can be attributed to the existence of extraordinary taphonomic conditions conducive to the preservation of volatile biomolecules through deep time. Furthermore, the occurrence of these volatiles in the early Miocene amber suggests that the plants from this period had evolved metabolic pathways to synthesize these organic molecules to play an active role in forest ecology, especially in plant-animal interactions.
Effects of Host-rock Fracturing on Elastic-deformation Source Models of Volcano Deflation
Authors: Holohan Eoghan P. , Sudhaus Henriette , Walter Thomas R. , Schöpfer Martin P. J. , Walsh John J.
Published: September 2017

Volcanoes commonly inflate or deflate during episodes of unrest or eruption. Continuum mechanics models that assume linear elastic deformation of the Earth’s crust are routinely used to invert the observed ground motions. The source(s) of deformation in such models are generally interpreted in terms of magma bodies or pathways, and thus form a basis for hazard assessment and mitigation. Using discontinuum mechanics models, we show how host-rock fracturing (i.e. non-elastic deformation) during drainage of a magma body can progressively change the shape and depth of an elastic-deformation source. We argue that this effect explains the marked spatio-temporal changes in source model attributes inferred for the March-April 2007 eruption of Piton de la Fournaise volcano, La Reunion. We find that pronounced deflation-related host-rock fracturing can: (1) yield inclined source model geometries for a horizontal magma body; (2) cause significant upward migration of an elastic-deformation source, leading to underestimation of the true magma body depth and potentially to a misinterpretation of ascending magma; and (3) at least partly explain underestimation by elastic–deformation sources of changes in sub-surface magma volume.
Organic-Silica Interactions in Saline: Elucidating the Structural Influence of Calcium in Low-Salinity Enhanced Oil Recovery
Authors: Desmond J. L. , Juhl K. , Hassenkam T. , Stipp S. L. S. , Walsh T. R. , Rodger P. M.
Published: September 2017

Enhanced oil recovery using low-salinity solutions to sweep sandstone reservoirs is a widely-practiced strategy. The mechanisms governing this remain unresolved. Here, we elucidate the role of Ca2+by combining chemical force microscopy (CFM) and molecular dynamics (MD) simulations. We probe the influence of electrolyte composition and concentration on the adsorption of a representative molecule, positively-charged alkylammonium, at the aqueous electrolyte/silica interface, for four electrolytes: NaCl, KCl, MgCl2, and CaCl2. CFM reveals stronger adhesion on silica in CaCl2compared with the other electrolytes, and shows a concentration-dependent adhesion not observed for the other electrolytes. Using MD simulations, we model the electrolytes at a negatively-charged amorphous silica substrate and predict the adsorption of methylammonium. Our simulations reveal four classes of surface adsorption site, where the prevalence of these sites depends only on CaCl2concentration. The sites relevant to strong adhesion feature the O−silica site and Ca2+in the presence of associated Cl−, which gain prevalence at higher CaCl2concentration. Our simulations also predict the adhesion force profile to be distinct for CaCl2compared with the other electrolytes. Together, these analyses explain our experimental data. Our findings indicate in general how silica wettability may be manipulated by electrolyte concentration.
Targeting Deficiencies in the TLR5 Mediated Vaginal Response to Treat Female Recurrent Urinary Tract Infection
Authors: Ali Ased S. M. , Mowbray Catherine , Lanz Marcelo , Stanton Anna , Bowen Samantha , Varley Claire L. , Hilton Paul , Brown Karen , Robson Wendy , Southgate Jennifer , Aldridge Phillip D. , Tyson-Capper Alison , Abraham Soman , Pickard Robert S. , Hall Judith
Published: September 2017

The identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, particularly those carrying the TLR5_C1174T SNP. Urinary tract infections (UTIs) are a microbial disease reported worldwide. Women are particularly susceptible with many suffering debilitating recurrent (r) infections. Treatment is by antibiotics, but such therapy is linked to antibiotic resistance and re-infection. This study explored the innate protective mechanisms of the urogenital tract with the aim of boosting such defences therapeutically. Modelling UTIs in vitro, human vaginal and bladder epithelial cells were challenged with uropathogenic Escherichia coli (CFT073) and microbial PAMPs including flagellin, LPS and peptidoglycan. Flagellin functioning via the TLR5/NFκB pathway was identified as the key UPEC virulence factor causing a significant increase (P < 0.05) in the production of the host-defence peptide (HDP), BD2. BD2-depleted urine samples from bladder infected mice supported increased UPEC growth, strengthening the significance of the HDPs in protecting the urogenital tissues from infection. Clinically, vaginal-douche BD2 concentrations were reduced (p < 0.05) in women suffering rUTIs, compared to age-matched healthy controls with concentrations further decreased (p < 0.05) in a TLR5392Stop SNP rUTI subgroup. Topical vaginal estrogen treatment increased (p < 0.001) BD2 concentrations in all women, including those carrying the SNP. These data identify therapeutic and antibiotic sparing roles for vaginal immunomodulatory agents that specifically target HDP induction, facilitate bacterial killing and disrupt the UPEC infection cycle.
Role of interfacial mode coupling of optical phonons on thermal boundary conductance
Authors: Giri Ashutosh , Hopkins Patrick E.
Published: September 2017

We investigate the influence of optical phonon coupling across interfaces comprised of different materials with varying crystallographic orientations on the overall thermal boundary conductance. We show that for interfaces formed between a fcc solid and a L10 solid (where L10 solids exhibit alternating atomic layers in certain orientations), coupling between acoustic phonons in the fcc crystal and optical phonons on the L10-side of the interface leads to a highly anisotropic thermal boundary conductance, where optical phonons can considerably enhance the conductance in a preferred crystallographic orientation of the layered solid. We attribute this in part to directionally dependent group velocities of optical phonons in the different crystallographic directions. For interfaces comprised of materials exhibiting diamond cubic crystal structures, higher conductances are observed for interfaces where there is a better overlap of acoustic phonons on either side of the interface, whereas, acoustic phonons directly coupling with high frequency optical phonons is shown to lower the overall conductance, especially at high temperatures where anharmonic interactions become important. Unique to the interfaces formed between the materials with diamond cubic crystal structures studied in this work, the presence of localized interfacial optical modes mediate thermal conductance across these interfaces.
The Aging of the Social Mind - Differential Effects on Components of Social Understanding
Authors: Reiter Andrea M. F. , Kanske Philipp , Eppinger Ben , Li Shu-Chen
Published: September 2017

Research in younger adults dissociates cognitive from affective facets of social information processing, rather than promoting a monolithic view of social intelligence. An influential theory on adult development suggests differential effects of aging on cognitive and affective functions. However, this dissociation has not been directly tested in the social domain. Employing a newly developed naturalistic paradigm that disentangles facets of the social mind within an individual, we show multi-directionality of age-related differences. Specifically, components of the socio-cognitive route – Theory of Mind and metacognition – are impaired in older relative to younger adults. Nevertheless, these social capacities are still less affected by aging than factual reasoning and metacognition regarding non-social content. Importantly, the socio-affective route is well-functioning, with no decline in empathy and elevated compassion in the elderly. These findings contribute to an integrated theory of age-related change in social functioning and inform interventions tailored to specifically reinstate socio-cognitive skills in old age.
Complete sequence-based pathway analysis by differential on-chip DNA and RNA extraction from a single cell
Authors: van Strijp D. , Vulders R. C. M. , Larsen N. A. , Schira J. , Baerlocher L. , van Driel M. A. , Pødenphant M. , Hansen T. S. , Kristensen A. , Mir K. U. , Olesen T. , Verhaegh W. F. J. , Marie R. , van der Zaag P. J.
Published: September 2017

We demonstrate on-chip, differential DNA and RNA extraction from a single cell using a microfluidic chip and a two-stage lysis protocol. This method enables direct use of the whole extract, without additional washing steps, reducing sample loss. Using this method, the tumor driving pathway in individual cells from a colorectal cancer cell line was determined by applying a Bayesian computational pathway model to sequences obtained from the RNA fraction of a single cell and, the mutations driving the pathway were determined by analyzing sequences obtained from the DNA fraction of the same single cell. This combined functional and mutational pathway assessment of a single cell could be of significant value for dissecting cellular heterogeneity in tumors and analyzing single circulating tumor cells.
The association of young age with local recurrence in women with early-stage breast cancer after breast-conserving therapy: a meta-analysis
Authors: He Xiang-Ming , Zou De-Hong
Published: September 2017

The aim of this meta-analysis is to determine the relationship between young age and local recurrence in patients with early-stage breast cancer after breast-conserving therapy. Eligible studies were retrieved from various electronic databases. Among the 19 studies included, 14 studies were analyzed for 5-year local recurrence rate and 8 studies for 10-year local recurrence rate using random effects models. Both results showed that young patients were at higher risk of local recurrence compared to old patients (5-year: RR = 2.64, 95% CI (1.94–3.60); 10-year: RR = 2.37, 95% CI (1.57–3.58)). Harbord’s modified test showed the presence of publication bias in both 5- and 10-year local recurrence rates (P = 0.019 and P = 0.01, respectively). While the Trim and Fill analysis showed that the presence of publication bias did not affect the overall outcome of the 5-year local recurrence rate (RR = 2.21, 95% CI (1.62, 3.02)), it significantly affected the effect size of the 10-year local recurrence rate (RR = 1.47, 95% CI (0.96, 2.27)). Young age is a significant risk factor for local recurrence developed within 5 years of breast-conserving therapy in patients with early-stage breast cancer. Further high-quality studies are needed to elucidate the relationship between young age and the risk of local recurrence developed within 10 years.
Long-term impact of Amazon river runoff on northern hemispheric climate
Authors: Jahfer S. , Vinayachandran P. N. , Nanjundiah Ravi S.
Published: September 2017

Amazon discharges a large volume of freshwater into the ocean, yet its impact on climate is largely unknown. Climate projections show that a warmer northern tropical Atlantic Ocean together with a warmer equatorial Pacific lead to extreme droughts in the Amazonia, considerably reducing the Amazon runoff. Here we present results from coupled model simulations and observations on the climatic response to a significant reduction in Amazon runoff into the Atlantic Ocean. Climate model simulation without Amazon runoff resulted in cooler equatorial Atlantic, weakening the Hadley cell and thereby the atmospheric meridional cells. Consequently, the extratropical westerlies turned weaker, leading to prevalent negative North Atlantic Oscillation (NAO) like climate, similar to the observed anomalies during Amazon drought years. This study reaffirms that spatial signature of NAO is in part driven by sea surface temperature (SST) anomalies in the tropical Atlantic. Winters of northern Europe and eastern Canada turned cooler and drier whereas southern Europe and the eastern United States experienced warmer and wetter winters without Amazon runoff. Significant warming over the Arctic reduced the local sea-ice extent and enhanced the high latitude river runoff. More importantly, our simulations caution against extreme exploitation of rivers for its far-reaching consequences on climate.
Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations
Authors: Prins Bram P. , Kuchenbaecker Karoline B. , Bao Yanchun , Smart Melissa , Zabaneh Delilah , Fatemifar Ghazaleh , Luan Jian’an , Wareham Nick J. , Scott Robert A. , Perry John R. B. , Langenberg Claudia , Benzeval Michaela , Kumari Meena , Zeggini Eleftheria
Published: September 2017

Serum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. We establish a polygenic heritability for all biomarkers, confirm associations of fifty-four established loci, and identify five novel, replicating associations at genome-wide significance. A low-frequency variant, rs28929474, (beta = 0.04, P = 2 × 10−10) was associated with levels of alanine transaminase, an indicator of liver damage. The variant is located in the gene encoding serine protease inhibitor, low levels of which are associated with alpha-1 antitrypsin deficiency which leads to liver disease. We identified novel associations (rs78900934, beta = 0.05, P = 6 × 10−12; rs2911280, beta = 0.09, P = 6 × 10−10) for dihydroepiandrosterone sulphate, a precursor to major sex-hormones, and for glycated haemoglobin (rs12819124, beta = −0.03, P = 4 × 10−9; rs761772, beta = 0.05, P = 5 × 10−9). rs12819124 is nominally associated with risk of type 2 diabetes. Our study offers insights into the genetic architecture of well-known and less well-studied biomarkers.
Delayed hypersensitivity to nanosecond pulsed electric field in electroporated cells
Authors: Jensen Sarah D. , Khorokhorina Vera A. , Muratori Claudia , Pakhomov Andrei G. , Pakhomova Olga N.
Published: September 2017

We demonstrate that conditioning of mammalian cells by electroporation with nanosecond pulsed electric field (nsPEF) facilitates their response to the next nsPEF treatment. The experiments were designed to unambiguously separate the electroporation-induced sensitization and desensitization effects. Electroporation was achieved by bursts of 300-ns, 9 kV/cm pulses (50 Hz, n = 3–100) and quantified by propidium dye uptake within 11 min after the nsPEF exposure. We observed either sensitization to nsPEF or no change (when the conditioning was either too weak or too intense, or when the wait time after conditioning was too short). Within studied limits, conditioning never caused desensitization. With settings optimal for sensitization, the second nsPEF treatment became 2.5 times (25 °C) or even 6 times (37 °C) more effective than the same nsPEF treatment delivered without conditioning. The minimum wait time required for sensitization development was 30 s, with still longer delays increasing the effect. We show that the delayed hypersensitivity was not mediated by either cell swelling or oxidative effect of the conditioning treatment; biological mechanisms underlying the delayed electrosensitization remain to be elucidated. Optimizing nsPEF delivery protocols to induce sensitization can reduce the dose and adverse side effects of diverse medical treatments which require multiple pulse applications.
Spatially encoded fast single-molecule fluorescence spectroscopy with full field-of-view
Authors: Tang Jialei , Sun Yangyang , Pang Shuo , Han Kyu Young
Published: September 2017

We report a simple single-molecule fluorescence imaging method that increases the temporal resolution of any type of array detector by >5-fold with full field-of-view. We spread single-molecule spots to adjacent pixels by rotating a mirror in the detection path during the exposure time of a single frame, which encodes temporal information into the spatial domain. Our approach allowed us to monitor fast blinking of an organic dye, the dissociation kinetics of very short DNA and conformational changes of biomolecules with much improved temporal resolution than the conventional method. Our technique is useful when a large field-of-view is required, for example, in the case of weakly interacting biomolecules or cellular imaging.
Host immune status-specific production of gliotoxin and bis-methyl-gliotoxin during invasive aspergillosis in mice
Authors: Sugui Janyce A. , Rose Stacey R. , Nardone Glenn , Swamydas Muthulekha , Lee Chyi-Chia R. , Kwon-Chung Kyung J. , Lionakis Michail S.
Published: September 2017

Delayed diagnosis in invasive aspergillosis (IA) contributes to its high mortality. Gliotoxin (GT) and bis-methyl-gliotoxin (bmGT) are secondary metabolites produced by Aspergillus during invasive, hyphal growth and may prove diagnostically useful. Because IA pathophysiology and GT’s role in virulence vary depending on the underlying host immune status, we hypothesized that GT and bmGT production in vivo may differ in three mouse models of IA that mimic human disease. We defined temporal kinetics of GT and bmGT in serum, bronchoalveolar lavage fluid (BALF) and lungs of A. fumigatus-infected chronic granulomatous disease (CGD), hydrocortisone-treated, and neutropenic mice. We harvested lungs for assessment of fungal burden, histology and GT/bmGT biosynthetic genes’ mRNA induction. GT levels were higher in neutropenic versus CGD or steroid-treated lungs. bmGT was persistently detected only in CGD lungs. GT, but not bmGT, was detected in 71% of sera and 50% of BALF of neutropenic mice; neither was detected in serum/BALF of CGD or steroid-treated mice. Enrichment of GT in Aspergillus-infected neutropenic lung correlated with fungal burden and hyphal length but not induction of GT biosynthetic genes. In summary, GT is detectable in mouse lungs, serum and BALF during neutropenic IA, suggesting that GT may be useful to diagnose IA in neutropenic patients.
Optimal stress and deformation partition in gradient materials for better strength and tensile ductility: A numerical investigation
Authors: Wang Yao , Yang Guangxue , Wang Wenjing , Wang Xi , Li Qiang , Wei Yujie
Published: September 2017

Inspired by recent progress in developing gradient materials with excellent performances, here we report a systematic finite-element based investigation to show how the strength and tensile ductility of gradient crystalline metals depend on their microstructure characteristics. We reveal that the yielding strength of polycrystalline metals with gradient grain size can be significantly enhanced at no reduction in ductility. By employing a representative 3D voronoi gradient sample, we demonstrate that the redistribution of stress and deformation in the gradient structure - stronger grains carry more load and ductile ones share more deformation - accounts for the realized optimal property in strength and ductility. In addition, the hardenability of the ductile domain is beneficial to circumvent pre-mature plastic instability in gradient samples.
Functional Characterization of Two Elongases of Very Long-Chain Fatty Acid from Tenebrio molitor L. (Coleoptera: Tenebrionidae)
Authors: Zheng Tianxiang , Li Hongshuang , Han Na , Wang Shengyin , Hackney Price Jennifer , Wang Minzi , Zhang Dayu
Published: September 2017

The elongases of very long chain fatty acid (ELOVL or ELO) are essential in the biosynthesis of fatty acids longer than C14. Here, two ELO full-length cDNAs (TmELO1, TmELO2) from the yellow mealworm (Tenebrio molitor L.) were isolated and the functions were characterized. The open reading frame (ORF) lengths of TmELO1 and TmELO2 were 1005 bp and 972 bp, respectively and the corresponding peptide sequences each contained several conserved motifs including the histidine-box motif HXXHH. Phylogenetic analysis demonstrated high similarity with the ELO of Tribolium castaneum and Drosophila melanogaster. Both TmELO genes were expressed at various levels in eggs, 1st and 2nd instar larvae, mature larvae, pupae, male and female adults. Injection of dsTmELO1 but not dsTmELO2 RNA into mature larvae significantly increased mortality although RNAi did not produce any obvious changes in the fatty acid composition in the survivors. Heterologous expression of TmELO genes in yeast revealed that TmELO1 and TmELO2 function to synthesize long chain and very long chain fatty acids.
Hemoglobin level, a prognostic factor for nasal extranodal natural killer/T-cell lymphoma patients from stage I to IV: A validated prognostic nomogram
Authors: Cao Jianzhong , Lan Shengmin , Shen Liuhai , Si Hongwei , Xiao Huan , Yuan Qiang , Li Xue , Li Hongwei , Guo Ruyuan
Published: September 2017

Although nasal extranodal natural killer/T-cell lymphoma (nasal ENKL) shares some prognostic factors with other lymphomas, seldom studies had explored the prognostic value of hemoglobin. The ENKL cases in stage I–IV during 2000 to 2015 were collected from two medical centers (group A, n = 192), and were randomly divided into the group B (n = 155) and C (n = 37). Although the significant factors identified by the univariate analysis differed between the group A and B, the multivariate Cox regression indicated the same factors. C-index of the model was slightly better than Yang’s, but its integrated Brier score (IBS) was obviously lower than Yang’s both in the group A and B. Additionally, minimal depth of random survival forest (RSF) classifier confirmed that the prognostic ability of hemoglobin was better than age both in the group A and B. In the calibration of the nomogram, the predicted 3-year or 5-year OS of our nomogram well agreed with the corresponding actual OS. In conclusion, Hemoglobin is a prognostic factor for nasal ENKL patients in stage I - IV, and integrating it into a validated prognostic nomogram, whose generalization error is the smallest among the evaluated models, can be used to predict the patients’ outcome.
Increased 15-PGDH expression leads to dysregulated resolution responses in stromal cells from patients with chronic tendinopathy
Authors: Dakin Stephanie G. , Ly Lucy , Colas Romain A. , Oppermann Udo , Wheway Kim , Watkins Bridget , Dalli Jesmond , Carr Andrew J.
Published: September 2017

The mechanisms underpinning the failure of inflammation to resolve in diseased musculoskeletal soft tissues are unknown. Herein, we studied bioactive lipid mediator (LM) profiles of tendon-derived stromal cells isolated from healthy donors and patients with chronic tendinopathy. Interleukin(IL)-1β treatment markedly induced prostaglandin biosynthesis in diseased compared to healthy tendon cells, and up regulated the formation of several pro-resolving mediators including 15-epi-LXA4 and MaR1. Incubation of IL-1β stimulated healthy tendon cells with 15-epi-LXA4 or MaR1 down-regulated PGE2 and PGD2 production. When these mediators were incubated with diseased cells, we only found a modest down regulation in prostanoid concentrations, whereas it led to significant decreases in IL-6 and Podoplanin expression. In diseased tendon cells, we also found increased 15-Prostaglandin Dehydrogenase (15-PGDH) expression as well as increased concentrations of both 15-epi-LXA4 and MaR1 further metabolites, 15-oxo-LXA4 and 14-oxo-MaR1. Inhibition of 15-PGDH using either indomethacin or SW033291 significantly reduced the further conversion of 15-epi-LXA4 and MaR1 and regulated expression of IL-6, PDPN and STAT-1. Taken together these results suggest that chronic inflammation in musculoskeletal soft tissues may result from dysregulated LM-SPM production, and that inhibition of 15-PGDH activity together with promoting resolution using SPM represents a novel therapeutic strategy to resolve chronic tendon inflammation.