bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Response Surface Methodology in the Optimization of Magneto-Hydrodynamic Flow Around and Through a Porous Circular Cylinder
Authors: Vahedi S. M. , Zare Ghadi A. , Valipour M. S.
Published: February 2018

In this study MHD flow around and through porous cylinder is numerically investigated. The governing equations are developed in polar coordinate arrangement in both porous and non-porous media on the basis of single-domain technique. The equations are solved numerically based on finite volume method over staggered grid structure. Nusselt number and drag coefficient are selected as two key parameters describing performance of this system. By applying response surface methodology the sensitivity of these parameters to main factors of the problem, including Stuart number, Darcy number and Reynolds number are quantified. RSM is also utilized to perform an optimization process to find the best condition in which the lowest drag force and highest heat transfer rate occur simultaneously. The CFD analysis is carried out for variant Reynolds numbers (10 ≤ Re ≤ 40), Darcy numbers (10-6 ≤ Da ≤ 10-2) and Stuart numbers (2 ≤ N ≤ 10). Streamlines and isotherms are presented to indicate the impacts of such parameters on heat and fluid flow. It can be seen that, Drag coefficient and Nusselt number increase by augmenting magnetic field strength. Beside, Darcy number and Reynolds numbers have a direct and inverse effect on Nuave and Cd, respectively. Results of optimization process show that Nuave and Cd are more sensitive to Reynolds and Stuart numbers, respectively, while they less sensitive to Darcy number. Moreover, it is revealed that the optimum condition occurs at Da = 10-2, Re = 38.1 and N = 4.49.
Discrete version of the Pythagorean theorem
Authors: Harminc Matúš , Janičková Lucia
Published: February 2018

The following observations are motivated by the facts that the area of a planar figure displayed on a screen can be expressed by a certain number of pixels; and if the figure is drawn by a plotter, then its area can be characterised by the total length of a line which fills it in.

The generalisations of the Pythagorean theorem are of three kinds. Firstly, the squares on the sides of the right triangle are substituted by other geometrically similar planar figures (Euclid's Elements Book VI, Proposition 31 [1]). Secondly, the assumption of the right angle is omitted (the law of cosines), or both of these generalizations occur simultaneously (Pappus’ area theorem [2], see also H. W. Eves [3]). Thirdly, mathematical spaces other than the plane are considered (for example, de Gua-Faulhaber theorem about trirectangular tetrahedra [3], further generalised by Tinseau [4], Euclideann-spaces, Banach spaces [5], see also [6]).
The performance of Metop Advanced SCATterometer soil moisture data as a complementary source for the estimation of crop-soil water balance in Central Europe
Authors: Thaler S. , Eitzinger J. , Trnka M. , Možný M. , Hahn S. , Wagner W. , Hlavinka P.
Published: February 2018

Simulation of the water balance in cropping systems is an essential tool, not only to monitor water status and determine drought but also to find ways in which soil water and irrigation water can be used more efficiently. However, besides the requirement that models are physically correct, the spatial representativeness of input data and, in particular, accurate precipitation data remain a challenge. In recent years, satellite-based soil moisture products have become an important data source for soil wetness information at various spatial-temporal scales. Four different study areas in the Czech Republic and Austria were selected representing Central European soil and climatic conditions. The performance of soil water content outputs from two different crop-water balance models and the Metop Advanced SCATterometer (ASCAT) soil moisture product was tested with field measurements from 2007 to 2011. The model output for soil water content shows that the crop model Decision Support System for Agrotechnology Transfer performs well during dry periods (<30% plant available soil moisture (ASM), whereas the soil water-balance model SoilClim presents the best results in humid months (>60% ASM). Moreover, the model performance is best in the early growing season and decreases later in the season due to biases in simulated crop-related above-ground biomass compared with the relatively stable grass canopy of the measurement sites. The Metop ASCAT soil moisture product, which presents a spatial average of soil surface moisture, shows the best performance under medium soil wetness conditions (30–50% ASM), which is related to low variation in precipitation frequency and under conditions of low-surface biomass (early vegetation season).
Nutritional interventions among old people receiving support at home
Authors: Beck Anne Marie
Published: February 2018

With the focus of care shifting from the hospital to the community, supportive nutritional care to old people is to become an important issue to address in the community, since undernutrition has serious consequences, both for the quality of life and for the health care costs. Several modifiable nutritional risk factors relate to undernutrition. Unfortunately, the problem with (risk of) undernutrition is aggravated due to a lack of alertness among e.g. health care staff, leading to insufficient attention for systemic screening and nutritional care. Only a few of the existing screening tools have been validated among old people receiving support at home. Few studies have assessed the beneficial effect of nutritional support among old people in their own home, and recently, it was concluded that such have shown limited effects. One reason may be that the nutritional interventions performed have not taken the multiple nutritional risk factors afore-mentioned into consideration when formulating the action/treatment plan and hence not used a multidisciplinary approach. Another reason may be that the intervention studies have not used validated screening tools to identify those old people most likely to benefit from the nutritional support. However, three recent studies have used a multidisciplinary approach and two have proven a beneficial effect on the quality of life of the old people and the health care costs. These findings suggest that when planning nutritional intervention studies for old people receiving support at home, modifiable nutritional risk factors should be taken into consideration, and a multidisciplinary approach considered.
PEER-REVIEWED JOURNAL EDITORS’ VIEWS ON REAL-WORLD EVIDENCE
Authors: Oehrlein Elisabeth M. , Graff Jennifer S. , Perfetto Eleanor M. , Mullins C. Daniel , Dubois Robert W. , Anyanwu Chinenye , Onukwugha Eberechukwu
Published: February 2018

Objectives:Peer-review publication is a critical step to the translation and dissemination of research results into clinical practice guidelines, health technology assessment (HTA) and payment policies, and clinical care. The objective of this study was to examine current views of journal editors regarding: (i) The value of real-world evidence (RWE) and how it compares with other types of studies; (ii) Education and/or resources journal editors provide to their peer reviewers or perceive as needed for authors, reviewers, and editors related to RWE.

Methods:Journal editors’ views on the value of RWE and editorial procedures for RWE manuscripts were obtained through telephone interviews, a survey, and in-person, roundtable discussion.

Results:In total, seventy-nine journals were approached, resulting in fifteen telephone interviews, seventeen survey responses and eight roundtable participants. RWE was considered valuable by all interviewed editors (n= 15). Characteristics of high-quality RWE manuscripts included: novelty/relevance, rigorous methodology, and alignment of data to research question. Editors experience challenges finding peer reviewers; however, these challenges persist across all study designs. Journals generally do not provide guidance, assistance, or training for reviewers, including for RWE studies. Health policy/health services research (HSR) editors were more likely than specialty or general medicine editors to participate in this study, potentially indicating that HSR researchers are more comfortable/interested in RWE.

Conclusions:Editors report favorable views of RWE studies provided studies examine important questions and are methodologically rigorous. Improving peer-review processes across all study designs, has the potential to improve the evidence base for decision making, including HTA.
Ruggiero Boscovich and “the Forces Existing in Nature”
Authors: Guzzardi Luca
Published: February 2018

Argument

According to a long-standing interpretation which traces back to Max Jammer'sConcepts of Force(1957), Ruggiero G. Boscovich would have developed a concept of force in the tradition of Leibniz's dynamics. In his variation on the theme, basic properties of matter such as solidity or impenetrability would be derived from an interplay of some “active” force of attraction and repulsion that any primary element of nature (“point of matter” in Boscovich's theory) would possess. In the present paper I discuss many flaws of this interpretation and argue for an alternative point of view, according to which the crucial aspect in the development of Boscovich's natural philosophy is his early definition of forces as “mathematical determinations” to have a certain state of motion. This is consistent with a Newtonian background and has as its epistemological consequence a certain agnosticism about the nature of forces and a “mathematical neutralism” (mathematics as a neutral tool, allowing for a plurality of interpretations).
Preemergence Application of Dicamba to Manage Dicamba-Resistant Kochia (Kochia scoparia)
Authors: Ou Junjun , Thompson Curtis R. , Stahlman Phillip W. , Jugulam Mithila
Published: February 2018

Dicamba-resistant crops are being rapidly embraced by growers in the United States to manage glyphosate-resistant and other difficult-to-control broadleaf weeds. However, dicamba resistance in kochia, one of the troublesome weeds of the North American Great Plains, is already widespread. Hence, POST application of dicamba may not adequately control kochia. In recent years in the High Plains Region of Colorado, Kansas, and Nebraska, dicamba has been widely applied, often in combination with atrazine or metribuzin, in early spring for PRE control of kochia. However, there is concern this use pattern may increase the selection for dicamba-resistant (DR) kochia. Hence, there is need to understand the efficacy of dicamba applied PRE versus POST for managing DR kochia. A greenhouse study was conducted to test the efficacy of PRE-applied dicamba compared with POST application using both DR and dicamba-susceptible (DS) kochia. Efficacies of PRE-applied dicamba were compared at seeding densities of 300, 600, 900 and 1200 viable seed m−2. At eight weeks after PRE and four weeks after POST treatment, control of DR kochia seeded at 300 viable seed m−2was improved from 10% with 560 g ae ha−1dicamba applied POST to 94 and 97% with 350 and 420 g ha−1dicamba applied PRE, respectively. However, the efficacy of PRE-applied dicamba was negatively correlated with seed density. When kochia seeding density was increased from 300 to 1200 seed m−2, the ED50of PRE-applied dicamba increased from 237 to 705 g ae ha−1for DR kochia, and from 129 to 361 g ae ha−1for DS kochia, respectively. Thus, PRE-applied dicamba was effective in controlling the population of DR kochia tested, suggesting that PRE-applied dicamba may still provide substantial control of some DR kochia populations. However, it is not advisable to apply dicamba alone for PRE kochia control.
Integrating Orthographic Information Across Time and	Space
Authors: Snell Joshua , Bertrand Daisy , Meeter Martijn , Grainger Jonathan
Published: February 2018

Abstract. Research has suggested that the word recognition process is influenced by the integration of orthographic information across words. The precise nature of this integration process may vary, however, depending on whether words are in temporal or spatial proximity. Here we present a lexical decision experiment, designed to compare temporal and spatial integration processes more directly. Masked priming was used to reveal effects of temporal integration, while the flanker paradigm was used to reveal effects of spatial integration. Primes/flankers were high-frequency orthographic neighbors of the target (blue-blur) or unrelated control words (head-blur). We replicated prior observations of inhibition in trials where the neighbor was used as a masked prime, while facilitation was observed in trials where the neighbor was presented as flanker. We conclude that sub-lexical orthographic information is integrated both temporally and spatially, but that spatial information is used to segregate lexical representations activated by spatially distinct sources.
Learning from an Extreme El Niño
Authors: Santoso Agus
Published: February 2018

A recent paper in Reviews of Geophysics describes new scientific insights on the El Niño-Southern Oscillation from analysis of the 2015-2016 extreme El Niño.
Managing Radio Traffic Jams with the Cloud
Authors: Underwood Emily
Published: February 2018

Sensor networks and data mining allow for fully automated, real-time monitoring of radio waves.
Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality
Authors: Pinton Giulia , Nilsson Stefan , Moro Laura
Published: February 2018

Estrogen receptor (ER) β has growth inhibitory and chemo drug potentiating effect on ovarian cancer cells. We studied the dependence of ERβ function on the presence of KDM6B and SIRT1 in human ovarian cancer cells in vitro. Activation of ERβ with the subtype-selective agonist KB9520 resulted in significant inhibition of human ovarian cancer cell growth. KB9520-activated ERβ had an additive effect on growth inhibition in combination with cisplatin and paclitaxel, respectively. Loss of KDM6B expression had a negative effect on ERβ function as a ligand-dependent inhibitor of ovarian cancer cell growth. In contrast, loss or inhibition of SIRT1 deacetylase activity restored ligand-activated ERβ functionality. Presented data suggest that selective targeting of ERβ with an agonist potentiate chemotherapy efficacy for the treatment of ovarian cancer and that downregulation or inhibition of SIRT1 may further enhance its therapeutic effect.
Photoautotrophic organisms control microbial abundance, diversity, and physiology in different types of biological soil crusts
Authors: Maier Stefanie , Tamm Alexandra , Wu Dianming , Caesar Jennifer , Grube Martin , Weber Bettina
Published: February 2018

Biological soil crusts (biocrusts) cover about 12% of the Earth’s land masses, thereby providing ecosystem services and affecting biogeochemical fluxes on a global scale. They comprise photoautotrophic cyanobacteria, algae, lichens and mosses, which grow together with heterotrophic microorganisms, forming a model system to study facilitative interactions and assembly principles in natural communities. Biocrusts can be classified into cyanobacteria-, lichen-, and bryophyte-dominated types, which reflect stages of ecological succession. In this study, we examined whether these categories include a shift in heterotrophic communities and whether this may be linked to altered physiological properties. We analyzed the microbial community composition by means of qPCR and high-throughput amplicon sequencing and utilized flux measurements to investigate their physiological properties. Our results revealed that once 16S and 18S rRNA gene copy numbers increase, fungi become more predominant and alpha diversity increases with progressing succession. Bacterial communities differed significantly between biocrust types with a shift from more generalized to specialized organisms along succession. CO2 gas exchange measurements revealed large respiration rates of late successional crusts being significantly higher than those of initial biocrusts, and different successional stages showed distinct NO and HONO emission patterns. Thus, our study suggests that the photoautotrophic organisms facilitate specific microbial communities, which themselves strongly influence the overall physiological properties of biocrusts and hence local to global nutrient cycles.
Light and temperature control the seasonal distribution of thaumarchaeota in the South Atlantic bight
Authors: Liu Qian , Tolar Bradley B , Ross Meredith J , Cheek Jelani B , Sweeney Corinne M , Wallsgrove Natalie J , Popp Brian N , Hollibaugh James T
Published: February 2018

Mid-summer peaks in the abundance of Thaumarchaeota and nitrite concentration observed on the Georgia, USA, coast could result from in situ activity or advection of populations from another source. We collected data on the distribution of Thaumarchaeota, ammonia-oxidizing betaproteobacteria (AOB), Nitrospina, environmental variables and rates of ammonia oxidation during six cruises in the South Atlantic Bight (SAB) from April to November 2014. These data were used to examine seasonality of nitrification in offshore waters and to test the hypothesis that the bloom was localized to inshore waters. The abundance of Thaumarchaeota marker genes (16S rRNA and amoA) increased at inshore and nearshore stations starting in July and peaked in August at >107 copies L−1. The bloom did not extend onto the mid-shelf, where Thaumarchaeota genes ranged from 103 to 105 copies L−1. Ammonia oxidation rates (AO) were highest at inshore stations during summer (to 840 nmol L−1 d−1) and were always at the limit of detection at mid-shelf stations. Nitrite concentrations were correlated with AO (R = 0.94) and were never elevated at mid-shelf stations. Gene sequences from samples collected at mid-shelf stations generated using Archaea 16S rRNA primers were dominated by Euryarchaeota; sequences from inshore and nearshore stations were dominated by Thaumarchaeota. Thaumarchaeota were also abundant at depth at the shelf-break; however, this population was phylogenetically distinct from the inshore/nearshore population. Our analysis shows that the bloom is confined to inshore waters during summer and suggests that Thaumarchaeota distributions in the SAB are controlled primarily by photoinhibition and secondarily by water temperature.
Nanostructuring one-dimensional and amorphous lithium peroxide for high round-trip efficiency in lithium-oxygen batteries
Authors: Dutta Arghya , Wong Raymond A. , Park Woonghyeon , Yamanaka Keisuke , Ohta Toshiaki , Jung Yousung , Byon Hye Ryung
Published: February 2018

The major challenge facing lithium–oxygen batteries is the insulating and bulk lithium peroxide discharge product, which causes sluggish decomposition and increasing overpotential during recharge. Here, we demonstrate an improved round-trip efficiency of ~80% by means of a mesoporous carbon electrode, which directs the growth of one-dimensional and amorphous lithium peroxide. Morphologically, the one-dimensional nanostructures with small volume and high surface show improved charge transport and promote delithiation (lithium ion dissolution) during recharge and thus plays a critical role in the facile decomposition of lithium peroxide. Thermodynamically, density functional calculations reveal that disordered geometric arrangements of the surface atoms in the amorphous structure lead to weaker binding of the key reaction intermediate lithium superoxide, yielding smaller oxygen reduction and evolution overpotentials compared to the crystalline surface. This study suggests a strategy to enhance the decomposition rate of lithium peroxide by exploiting the size and shape of one-dimensional nanostructured lithium peroxide.
Impaired β-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 dopamine receptor
Authors: Gray David L. , Allen John A. , Mente Scot , O’Connor Rebecca E. , DeMarco George J. , Efremov Ivan , Tierney Patrick , Volfson Dmitri , Davoren Jennifer , Guilmette Edward , Salafia Michelle , Kozak Rouba , Ehlers Michael D.
Published: February 2018

Selective activation of dopamine D1 receptors (D1Rs) has been pursued for 40 years as a therapeutic strategy for neurologic and psychiatric diseases due to the fundamental role of D1Rs in motor function, reward processing, and cognition. All known D1R-selective agonists are catechols, which are rapidly metabolized and desensitize the D1R after prolonged exposure, reducing agonist response. As such, drug-like selective D1R agonists have remained elusive. Here we report a novel series of selective, potent non-catechol D1R agonists with promising in vivo pharmacokinetic properties. These ligands stimulate adenylyl cyclase signaling and are efficacious in a rodent model of Parkinson's disease after oral administration. They exhibit distinct binding to the D1R orthosteric site and a novel functional profile including minimal receptor desensitization, reduced recruitment of β-arrestin, and sustained in vivo efficacy. These results reveal a novel class of D1 agonists with favorable drug-like properties, and define the molecular basis for catechol-specific recruitment of β-arrestin to D1Rs.
Anti-fouling graphene-based membranes for effective water desalination
Authors: Seo Dong Han , Pineda Shafique , Woo Yun Chul , Xie Ming , Murdock Adrian T. , Ang Elisa Y. M. , Jiao Yalong , Park Myoung Jun , Lim Sung Il , Lawn Malcolm , Borghi Fabricio Frizera , Han Zhao Jun , Gray Stephen , Millar Graeme , Du Aijun , Shon Ho Kyong , Ng Teng Yong , Ostrikov Kostya
Published: February 2018

The inability of membranes to handle a wide spectrum of pollutants is an important unsolved problem for water treatment. Here we demonstrate water desalination via a membrane distillation process using a graphene membrane where water permeation is enabled by nanochannels of multilayer, mismatched, partially overlapping graphene grains. Graphene films derived from renewable oil exhibit significantly superior retention of water vapour flux and salt rejection rates, and a superior antifouling capability under a mixture of saline water containing contaminants such as oils and surfactants, compared to commercial distillation membranes. Moreover, real-world applicability of our membrane is demonstrated by processing sea water from Sydney Harbour over 72 h with macroscale membrane size of 4 cm2, processing ~0.5 L per day. Numerical simulations show that the channels between the mismatched grains serve as an effective water permeation route. Our research will pave the way for large-scale graphene-based antifouling membranes for diverse water treatment applications.
Author Correction: Uncovering active precursors in colloidal quantum dot synthesis
Authors: Frenette Leah C. , Krauss Todd D.
Published: February 2018

In the original version of this Article, Fig. 3 contained several errors in the chemical structures. This has now been corrected in both the PDF and HTML versions of the Article.
Ultra-high thermal effusivity materials for resonant ambient thermal energy harvesting
Authors: Cottrill Anton L. , Liu Albert Tianxiang , Kunai Yuichiro , Koman Volodymyr B. , Kaplan Amir , Mahajan Sayalee G. , Liu Pingwei , Toland Aubrey R. , Strano Michael S.
Published: February 2018

Materials science has made progress in maximizing or minimizing the thermal conductivity of materials; however, the thermal effusivity—related to the product of conductivity and capacity—has received limited attention, despite its importance in the coupling of thermal energy to the environment. Herein, we design materials that maximize the thermal effusivity by impregnating copper and nickel foams with conformal, chemical-vapor-deposited graphene and octadecane as a phase change material. These materials are ideal for ambient energy harvesting in the form of what we call thermal resonators to generate persistent electrical power from thermal fluctuations over large ranges of frequencies. Theory and experiment demonstrate that the harvestable power for these devices is proportional to the thermal effusivity of the dominant thermal mass. To illustrate, we measure persistent energy harvesting from diurnal frequencies, extracting as high as 350 mV and 1.3 mW from approximately 10 °C diurnal temperature differences.
Publisher Correction: Development of a genetically encodable FRET system using fluorescent RNA aptamers
Authors: Jepsen Mette D. E. , Sparvath Steffen M. , Nielsen Thorbjørn B. , Langvad Ane H. , Grossi Guido , Gothelf Kurt V. , Andersen Ebbe S.
Published: February 2018

In the original version of this Article the last section of the Methods describing Fluorescence microscopy was inadvertently omitted during the production process. This has now been corrected in the PDF and HTML versions of the Article.
Biomimetic light-harvesting funnels for re-directioning of diffuse light
Authors: Pieper Alexander , Hohgardt Manuel , Willich Maximilian , Gacek Daniel Alexander , Hafi Nour , Pfennig Dominik , Albrecht Andreas , Walla Peter Jomo
Published: February 2018

Efficient sunlight harvesting and re-directioning onto small areas has great potential for more widespread use of precious high-performance photovoltaics but so far intrinsic solar concentrator loss mechanisms outweighed the benefits. Here we present an antenna concept allowing high light absorption without high reabsorption or escape-cone losses. An excess of randomly oriented pigments collects light from any direction and funnels the energy to individual acceptors all having identical orientations and emitting ~90% of photons into angles suitable for total internal reflection waveguiding to desired energy converters (funneling diffuse-light re-directioning, FunDiLight). This is achieved using distinct molecules that align efficiently within stretched polymers together with others staying randomly orientated. Emission quantum efficiencies can be >80% and single-foil reabsorption <0.5%. Efficient donor-pool energy funneling, dipole re-orientation, and ~1.5–2 nm nearest donor–acceptor transfer occurs within hundreds to ~20 ps. Single-molecule 3D-polarization experiments confirm nearly parallel emitters. Stacked pigment selection may allow coverage of the entire solar spectrum.
Probing electrochemical reactions in organic cathode materials via in operando infrared spectroscopy
Authors: Vizintin Alen , Bitenc Jan , Kopač Lautar Anja , Pirnat Klemen , Grdadolnik Jože , Stare Jernej , Randon-Vitanova Anna , Dominko Robert
Published: February 2018

Organic materials are receiving an increasing amount of attention as electrode materials for future post lithium-ion batteries due to their versatility and sustainability. However, their electrochemical reaction mechanism has seldom been investigated. This is a direct consequence of a lack of straightforward and broadly available analytical techniques. Herein, a straightforward in operando attenuated total reflectance infrared spectroscopy method is developed that allows visualization of changes of all infrared active bands that occur as a consequence of reduction/oxidation processes. In operando infrared spectroscopy is applied to the analysis of three different organic polymer materials in lithium batteries. Moreover, this in operando method is further extended to investigation of redox reaction mechanism of poly(anthraquinonyl sulfide) in a magnesium battery, where a reduction of carbonyl bond is demonstrated as a mechanism of electrochemical activity. Conclusions done by the in operando results are complemented by synthesis of model compound and density functional theory calculation of infrared spectra.
Cancer cell responses to Hsp70 inhibitor JG-98: Comparison with Hsp90 inhibitors and finding synergistic drug combinations
Authors: Yaglom Julia A. , Wang Yongmei , Li Amy , Li Zhenghu , Monti Stephano , Alexandrov Ilya , Lu Xiongbin , Sherman Michael Y.
Published: February 2018

Hsp70 is a promising anti-cancer target. Our JG-98 series of Hsp70 inhibitors show anti-cancer activities affecting both cancer cells and tumor-associated macrophages. They disrupt Hsp70 interaction with a co-chaperone Bag3 and affect signaling pathways important for cancer development. Due to a prior report that depletion of Hsp70 causes similar responses as depletion of Hsp90, interest to Hsp70 inhibitors as drug prototypes is hampered by potential similarity of their effects to effects of Hsp90 inhibitors. Here, using the Connectivity Map platform we demonstrate that physiological effects of JG-98 are dissimilar from effects of Hsp90 inhibitors, thus justifying development of these compounds. Using gene expression and ActivSignal IPAD platform, we identified pathways modulated by JG-98. Some of these pathways were affected by JG-98 in Bag3-dependent (e.g. ERK) and some in Bag3-independent manner (e.g. Akt or c-myc), indicating multiple effects of Hsp70 inhibition. Further, we identified genes that modulate cellular responses to JG-98, developed approaches to predict potent combinations of JG-98 with known drugs, and demonstrated that inhibitors of proteasome, RNApol, Akt and RTK synergize with JG-98. Overall, here we established unique effects of novel Hsp70 inhibitors on cancer cell physiology, and predicted potential drug combinations for pre-clinical development.
Thermal stabilization of the deglycating enzyme Amadoriase I by rational design
Authors: Rigoldi Federica , Donini Stefano , Giacomina Francesca , Sorana Federico , Redaelli Alberto , Bandiera Tiziano , Parisini Emilio , Gautieri Alfonso
Published: February 2018

Amadoriases are a class of FAD-dependent enzymes that are found in fungi, yeast and bacteria and that are able to hydrolyze glycated amino acids, cleaving the sugar moiety from the amino acidic portion. So far, engineered Amadoriases have mostly found practical application in the measurement of the concentration of glycated albumin in blood samples. However, these engineered forms of Amadoriases show relatively low absolute activity and stability levels, which affect their conditions of use. Therefore, enzyme stabilization is desirable prior to function-altering molecular engineering. In this work, we describe a rational design strategy based on a computational screening method to evaluate a library of potentially stabilizing disulfide bonds. Our approach allowed the identification of two thermostable Amadoriase I mutants (SS03 and SS17) featuring a significantly higher T50 (55.3 °C and 60.6 °C, respectively) compared to the wild-type enzyme (52.4 °C). Moreover, SS17 shows clear hyperstabilization, with residual activity up to 95 °C, whereas the wild-type enzyme is fully inactive at 55 °C. Our computational screening method can therefore be considered as a promising approach to expedite the design of thermostable enzymes.
Nanoanalytical electron microscopy of events predisposing to mineralisation of turkey tendon
Authors: Kłosowski Michał M. , Carzaniga Raffaella , Shefelbine Sandra J. , Porter Alexandra E. , McComb David W.
Published: February 2018

The macro- and micro-structures of mineralised tissues hierarchy are well described and understood. However, investigation of their nanostructure is limited due to the intrinsic complexity of biological systems. Preceding transmission electron microscopy studies investigating mineralising tissues have not resolved fully the initial stages of mineral nucleation and growth within the collagen fibrils. In this study, analytical scanning transmission electron microscopy and electron energy-loss spectroscopy were employed to characterise the morphology, crystallinity and chemistry of the mineral at different stages of mineralization using a turkey tendon model. In the poorly mineralised regions, calcium ions associated with the collagen fibrils and ellipsoidal granules and larger clusters composed of amorphous calcium phosphate were detected. In the fully mineralised regions, the mineral had transformed into crystalline apatite with a plate-like morphology. A change in the nitrogen K-edge was observed and related to modifications of the functional groups associated with the mineralisation process. This transformation seen in the nitrogen K-edge might be an important step in maturation and mineralisation of collagen and lend fundamental insight into how tendon mineralises.
Two Sprayer CVD Synthesis of Nitrogen-doped Carbon Sponge-type Nanomaterials
Authors: Muñoz-Sandoval Emilio , Fajardo-Díaz Juan L. , Sánchez-Salas Roque , Cortés-López Alejandro J. , López-Urías Florentino
Published: February 2018

Nitrogen-doped carbon sponge-type nanostructures (N-CSTNs) containing coaxial multiwalled carbon nanotubes are synthesized at 1020 °C by using a modified chemical vapor deposition (CVD) arrangement. Here, the CVD reactor is supplied by two flows coming from two independent sprayers (called sprayer A and sprayer B). The nebulized material in each sprayer is transported by two different gases with different flow velocities. The synthesis of carbon N-CSTNs is performed using different precursors: sprayer A contains a solution composed of ethanol, thiophene and ferrocene, whereas sprayer B contains a solution of benzylamine, thiophene and ferrocene. Samples are classified according to the position inside the reactor and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and thermogravimetric analysis (TGA). Samples collected at the beginning of the reactor contain curly structures with diameters of 10–100 nm. At the end of the reactor, the sample is mainly formed by one type of structure. A spongy-type material is mainly formed in the hottest zone of the tubular furnace. The N-CSTNs are highly hydrophobic with oil sorption properties, which could be used for adsorption of oil spills.
VPS35 depletion does not impair presynaptic structure and function
Authors: Vazquez-Sanchez Sonia , Bobeldijk Sander , Dekker Marien P. , van Keimpema Linda , van Weering Jan R. T.
Published: February 2018

The endosomal system is proposed as a mediator of synaptic vesicle recycling, but the molecular recycling mechanism remains largely unknown. Retromer is a key protein complex which mediates endosomal recycling in eukaryotic cells, including neurons. Retromer is important for brain function and mutations in retromer genes are linked to neurodegenerative diseases. In this study, we aimed to determine the role of retromer in presynaptic structure and function. We assessed the role of retromer by knocking down VPS35, the core subunit of retromer, in primary hippocampal mouse neurons. VPS35 depletion led to retromer dysfunction, measured as a decrease in GluA1 at the plasma membrane, and bypassed morphological defects previously described in chronic retromer depletion models. We found that retromer is localized at the mammalian presynaptic terminal. However, VPS35 depletion did not alter the presynaptic ultrastructure, synaptic vesicle release or retrieval. Hence, we conclude that retromer is present in the presynaptic terminal but it is not essential for the synaptic vesicle cycle. Nonetheless, the presynaptic localization of VPS35 suggests that retromer-dependent endosome sorting could take place for other presynaptic cargo.
Nonreciprocal current from electron interactions in noncentrosymmetric crystals: roles of time reversal symmetry and dissipation
Authors: Morimoto Takahiro , Nagaosa Naoto
Published: February 2018

In noncentrosymmetric crystals with broken inversion symmetry $${\boldsymbol{ {\mathcal I} }}$$
ℐ
, the I-V (I: current, V: voltage) characteristic is generally expected to depend on the direction of I, which is known as nonreciprocal response and, for example, found in p-n junction. However, it is a highly nontrivial issue in translationally invariant systems since the time-reversal symmetry T plays an essential role, where the two states at crystal momenta k and −k are connected in the band structure. Therefore, it has been considered that the external magnetic field (B) or the magnetic order which breaks the T-symmetry is necessary to realize the nonreciprocal I-V characteristics, i.e., magnetochiral anisotropy. Here we theoretically show that the electron correlation in T-broken multi-band systems can induce nonreciprocal I-V characteristics without T-breaking. An analog of Onsager’s relation shows that nonreciprocal current response without T -breaking generally requires two effects: dissipation and interactions. By using nonequilibrium Green’s functions, we derive general formula of the nonreciprocal response for two-band systems with onsite interaction. The formula is applied to Rice-Mele model, a representative 1D model with inversion breaking, and some candidate materials are discussed. This finding offers a coherent understanding of the origin of nonreciprocal I-V characteristics, and will pave a way to design it.
Bronchoscopic fibered confocal fluorescence microscopy for longitudinal in vivo assessment of pulmonary fungal infections in free-breathing mice
Authors: Vanherp Liesbeth , Poelmans Jennifer , Hillen Amy , Govaerts Kristof , Belderbos Sarah , Buelens Tinne , Lagrou Katrien , Himmelreich Uwe , Vande Velde Greetje
Published: February 2018

Respiratory diseases, such as pulmonary infections, are an important cause of morbidity and mortality worldwide. Preclinical studies often require invasive techniques to evaluate the extent of infection. Fibered confocal fluorescence microscopy (FCFM) is an emerging optical imaging technique that allows for real-time detection of fluorescently labeled cells within live animals, thereby bridging the gap between in vivo whole-body imaging methods and traditional histological examinations. Previously, the use of FCFM in preclinical lung research was limited to endpoint observations due to the invasive procedures required to access lungs. Here, we introduce a bronchoscopic FCFM approach that enabled in vivo visualization and morphological characterisation of fungal cells within lungs of mice suffering from pulmonary Aspergillus or Cryptococcus infections. The minimally invasive character of this approach allowed longitudinal monitoring of infection in free-breathing animals, thereby providing both visual and quantitative information on infection progression. Both the sensitivity and specificity of this technique were high during advanced stages of infection, allowing clear distinction between infected and non-infected animals. In conclusion, our study demonstrates the potential of this novel bronchoscopic FCFM approach to study pulmonary diseases, which can lead to novel insights in disease pathogenesis by allowing longitudinal in vivo microscopic examinations of the lungs.
Prognostic significance of nephrectomy in metastatic renal cell carcinoma treated with systemic cytokine or targeted therapy: A 16-year retrospective analysis
Authors: Kim Sung Han , Jeong Kyung-Chae , Joung Jae Young , Seo Ho Kyung , Lee Kang Hyun , Chung Jinsoo
Published: February 2018

We compared progression-free survival (PFS) and overall survival (OS) among 292 metastatic renal cell carcinoma (mRCC) patients either undergoing nephrectomy (Nx, 61.6%) or not (non-Nx, 38.4%), stratified according to the MSKCC and Heng risk models, treated with either immunotherapy (IT, 45.2%) or targeted therapy (TT, 54.8%) between 2000 and 2015. During the follow-up duration of 16.6 months, PFS/OS of the Nx (6.0/30 months) and non-Nx (3.0/6.0 months) groups were significantly different despite differences among baseline parameters (p < 0.05). The intermediate- and poor-risk patients defined using either model showed significantly longer PFS and OS in the Nx group than in the non-Nx group (p < 0.05). After stratifying groups by systemic therapy and risk models, both the Nx and non-Nx groups showed no significant differences in intermediate and poor-risk models (p > 0.05). In both synchronous and metachronous mRCC patients, both PFS and OS showed similar survivals; the Nx group had significantly longer PFS and OS than the non-Nx group, even after considering each systemic therapy and prognostic model. Nx showed a significant positive benefit in PFS and OS compared to no Nx upon patient stratification according to the MSKCC and Heng risk models. The metastatic type did not significantly affect survival between the two groups.
Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism
Authors: Caracausi Maria , Ghini Veronica , Locatelli Chiara , Mericio Martina , Piovesan Allison , Antonaros Francesca , Pelleri Maria Chiara , Vitale Lorenza , Vacca Rosa Anna , Bedetti Federica , Mimmi Maria Chiara , Luchinat Claudio , Turano Paola , Strippoli Pierluigi , Cocchi Guido
Published: February 2018

Down syndrome (DS) is caused by the presence of a supernumerary copy of the human chromosome 21 (Hsa21) and is the most frequent genetic cause of intellectual disability (ID). Key traits of DS are the distinctive facies and cognitive impairment. We conducted for the first time an analysis of the Nuclear Magnetic Resonance (NMR)-detectable part of the metabolome in plasma and urine samples, studying 67 subjects with DS and 29 normal subjects as controls selected among DS siblings. Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to of 80% accuracy) between the DS and the control groups. The univariate analysis of plasma and urine revealed a significant alteration for some interesting metabolites. Remarkably, most of the altered concentrations were consistent with the 3:2 gene dosage model, suggesting effects caused by the presence of three copies of Hsa21 rather than two: DS/normal ratio in plasma was 1.23 (pyruvate), 1.47 (succinate), 1.39 (fumarate), 1.33 (lactate), 1.4 (formate). Several significantly altered metabolites are produced at the beginning or during the Krebs cycle. Accounting for sex, age and fasting state did not significantly affect the main result of both multivariate and univariate analysis.
Magnetism and high magnetic-field-induced stability of alloy carbides in Fe-based materials
Authors: Hou T. P. , Wu K. M. , Liu W. M. , Peet M. J. , Hulme-Smith C. N. , Guo L. , Zhuang L.
Published: February 2018

Understanding the nature of the magnetic-field-induced precipitation behaviors represents a major step forward towards unravelling the real nature of interesting phenomena in Fe-based alloys and especially towards solving the key materials problem for the development of fusion energy. Experimental results indicate that the applied high magnetic field effectively promotes the precipitation of M23C6 carbides. We build an integrated method, which breaks through the limitations of zero temperature and zero external field, to concentrate on the dependence of the stability induced by the magnetic effect, excluding the thermal effect. We investigate the intimate relationship between the external field and the origins of various magnetics structural characteristics, which are derived from the interactions among the various Wyckoff sites of iron atoms, antiparallel spin of chromium and Fe-C bond distances. The high-magnetic-field-induced exchange coupling increases with the strength of the external field, which then causes an increase in the parallel magnetic moment. The stability of the alloy carbide M23C6 is more dependent on external field effects than thermal effects, whereas that of M2C, M3C and M7C3 is mainly determined by thermal effects.
Rational cell culture optimization enhances experimental reproducibility in cancer cells
Authors: Wright Muelas Marina , Ortega Fernando , Breitling Rainer , Bendtsen Claus , Westerhoff Hans V.
Published: February 2018

Optimization of experimental conditions is critical in ensuring robust experimental reproducibility. Through detailed metabolomic analysis we found that cell culture conditions significantly impacted on glutaminase (GLS1) sensitivity resulting in variable sensitivity and irreproducibility in data. Baseline metabolite profiling highlighted that untreated cells underwent significant changes in metabolic status. Both the extracellular levels of glutamine and lactate and the intracellular levels of multiple metabolites changed drastically during the assay. We show that these changes compromise the robustness of the assay and make it difficult to reproduce. We discuss the implications of the cells’ metabolic environment when studying the effects of perturbations to cell function by any type of inhibitor. We then devised ‘metabolically rationalized standard’ assay conditions, in which glutaminase-1 inhibition reduced glutamine metabolism differently in both cell lines assayed, and decreased the proliferation of one of them. The adoption of optimized conditions such as the ones described here should lead to an improvement in reproducibility and help eliminate false negatives as well as false positives in these assays.
Representational similarity analysis reveals task-dependent semantic influence of the visual word form area
Authors: Wang Xiaosha , Xu Yangwen , Wang Yuwei , Zeng Yi , Zhang Jiacai , Ling Zhenhua , Bi Yanchao
Published: February 2018

Access to semantic information of visual word forms is a key component of reading comprehension. In this study, we examined the involvement of the visual word form area (VWFA) in this process by investigating whether and how the activity patterns of the VWFA are influenced by semantic information during semantic tasks. We asked participants to perform two semantic tasks - taxonomic or thematic categorization - on visual words while obtaining the blood-oxygen-level-dependent (BOLD) fMRI responses to each word. Representational similarity analysis with four types of semantic relations (taxonomic, thematic, subjective semantic rating and word2vec) revealed that neural activity patterns of the VWFA were associated with taxonomic information only in the taxonomic task, with thematic information only in the thematic task and with the composite semantic information measured by word2vec in both semantic tasks. Furthermore, the semantic information in the VWFA cannot be explained by confounding factors including orthographic, low-level visual and phonological information. These findings provide positive evidence for the presence of both orthographic and task-relevant semantic information in the VWFA and have significant implications for the neurobiological basis of reading.
Complete Transcriptome Profiling of Normal and Age-Related Macular Degeneration Eye Tissues Reveals Dysregulation of Anti-Sense Transcription
Authors: Kim Eun Ji , Grant Gregory R. , Bowman Anita S. , Haider Naqi , Gudiseva Harini V. , Chavali Venkata Ramana Murthy
Published: February 2018

Age-related macular degeneration (AMD) predominantly affects the retina and retinal pigment epithelium in the posterior eye. While there are numerous studies investigating the non-coding transcriptome of retina and RPE, few significant differences between AMD and normal tissues have been reported. Strand specific RNA sequencing of both peripheral retina (PR) and RPE-Choroid-Sclera (PRCS), in both AMD and matched normal controls were generated. The transcriptome analysis reveals a highly significant and consistent impact on anti-sense transcription as well as moderate changes in the regulation of non-coding (sense) RNA. Hundreds of genes that do not express anti-sense transcripts in normal PR and PRCS demonstrate significant anti-sense expression in AMD in all patient samples. Several pathways are highly enriched in the upregulated anti-sense transcripts—in particular the EIF2 signaling pathway. These results call for a deeper exploration into anti-sense and noncoding RNA regulation in AMD and their potential as therapeutic targets.