bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, theoretical studies, and effect on the photosynthetic electron transport of trifluoromethyl arylamides
Authors: Teixeira Róbson Ricardo , de Andrade Barros Marcus Vinícius , Bressan Gustavo Costa , Siqueira Raoni Pais , dos Santos Fabíola Suelen , Bertazzini Michele , Kiralj Rudolf , Ferreira Márcia Miguel Castro , Forlani Giuseppe
Published: May 2017

BACKGROUND

The photosynthetic apparatus is targeted by various herbicides, including several amides such as diuron and linuron. Considering the need for the discovery of new active ingredients to cope with weed resistance, the synthesis of a series of trifluoromethyl aryl amides is herein described whose inhibitory properties were assessed in vitro on the photosynthetic electron transport chain, and in vivo on the growth of a model cyanobacterial strain. Theoretical studies were also carried out.

RESULTS

Starting with 1‐fluoro‐2‐nitro‐4‐(trifluoromethyl) benzene, the preparation of the amides was achieved via a three‐step sequence, namely nucleophilic aromatic substitution, reduction with SnCl2/HCl, and acylation reactions. The measurement of ferricyanide reduction by functionally intact spinach chloroplasts showed that several derivatives are capable of inhibiting the photosynthetic apparatus. The most active amides presented IC50 values close to 1 μmol L−1, and showed the presence of a 4‐bromophenyl group as a common structural feature. The addition of these brominated amides to the culture medium of a model cyanobacterial strain, Synechococcus elongatus PCC 6301, caused various degrees of growth inhibition. Theoretical studies (molecular modeling and quantitative structure–activity relationship) of all amides and their comparison with some known herbicides confirmed these experimental findings and provided more in‐depth information about the possible molecular target of these compounds.

CONCLUSION

Trifluoromethyl amides herein described, which were shown to act at the PSII level, may represent a novel scaffold to be exploited aiming at the development of new active ingredients for weed control. © 2017 Society of Chemical Industry
Investigating Creep in Corrugated Packaging
Authors: Hussain Sadakat , Coffin Douglas W. , Todoroki Christine
Published: May 2017

In this study, the inverse relationship between lifetime and secondary creep rate was verified suggesting that shorter duration tests can be used to evaluate lifetimes. Also, the variability in creep rate was significantly lower than previous studies suggesting that using enhanced testing facilities could reduce required number of repetitions. A novel finding was an observed transition point in applied loading level where cyclic humidity conditions had the highest creep rates at low loads and constant high humidity conditions had the highest creep rate at high loads. Finally, it was determined that a standard moisture cycling history for a standard test protocol will be difficult to determine and the moisture sorption behaviour of each box type must be accounted for. Copyright © 2017 John Wiley & Sons, Ltd.
Measurements and models of the temperature change of water samples in sea‐surface temperature buckets
Authors: Carella G. , Morris A. K. R. , Pascal R. W. , Yelland M. J. , Berry D. I. , Morak‐Bozzo S. , Merchant C. J. , Kent E. C.
Published: May 2017

Uncertainty in the bias adjustments applied to historical sea‐surface temperature (SST) measurements made using buckets are thought to make the largest contribution to uncertainty in global surface temperature trends. Measurements of the change in temperature of water samples in wooden and canvas buckets are compared with the predictions of models that have been used to estimate bias adjustments applied in widely used gridded analyses of SST. The results show that the models are broadly able to predict the dependence of the temperature change of the water over time on the thermal forcing and the bucket characteristics: volume and geometry; structure and material. Both the models and the observations indicate that the most important environmental parameter driving temperature biases in historical bucket measurements is the difference between the water and wet‐bulb temperatures. However, assumptions inherent in the derivation of the models are likely to affect their applicability. We observed that the water sample needed to be vigorously stirred to agree with results from the model, which assumes well‐mixed conditions. There were inconsistencies between the model results and previous measurements made in a wind tunnel in 1951. The model assumes non‐turbulent incident flow and consequently predicts an approximately square‐root dependence on airflow speed. The wind tunnel measurements, taken over a wide range of airflows, showed a much stronger dependence. In the presence of turbulence the heat transfer will increase with the turbulent intensity; for measurements made on ships the incident airflow is likely to be turbulent and the intensity of the turbulence is always unknown. Taken together, uncertainties due to the effects of turbulence and the assumption of well‐mixed water samples are expected to be substantial and may represent the limiting factor for the direct application of these models to adjust historical SST observations.
Robust control for uncertain linear delay systems via sliding mode control
Authors: Loukianov A. G. , Caballero‐Barragán H. , Osuna‐Ibarra L. , Espinosa‐Guerra O. , Castillo‐Toledo B.
Published: May 2017

In this paper, a novel discontinuous control strategy for robust stabilization of a class of uncertain multivariable linear time‐delay systems with delays in both the state and control variables is proposed. Two predictors are first designed to compensate the delay effect in the control input, and then an integral sliding mode control technique is applied to compensate partially the effect of the perturbation term. Finally, a nominal delay‐free component of the full control input is designed to stabilize the sliding mode dynamics. Conditions for the stability of the closed‐loop perturbed system are then derived. The proposed framework is then extended to the class of systems modeled in regular form. Some examples illustrate the feasibility of the proposed scheme. Copyright © 2017 John Wiley & Sons, Ltd.
Early Passage Mesenchymal Stem Cells Display Decreased Radiosensitivity and Increased DNA Repair Activity
Authors: Wu Po-Kuei , Wang Jir-You , Chen Cheng-Fong , Chao Kuang-Yu , Chang Ming-Chau , Chen Wei-Ming , Hung Shih-Chieh
Published: May 2017

Cell therapies using human mesenchymal stem cells (MSCs) have received much attention in the past decade. In pursuit of the therapeutic potential of MSCs, cell expansion is required to generate a great number of cells with desired phenotype and functionality. Long-term expansion in vitro, however, can lead to altered functions. To explore the changes in DNA damage responses (DDR) in MSCs expanded, DDR pathways following irradiation were characterized in early- and late-passage bone marrow MSCs. Seventy-two hours after irradiation, the percentage of sub-G1 cells in early-passage MSCs did not change significantly. Reduced TUNEL staining was observed in early-passage MSCs compared to late-passage MSCs 4 h after irradiation. Comet assay also revealed that early-passage MSCs were more resistant to irradiation or DNA damages induced by genotoxic agents than late-passage MSCs. ATM phosphorylation and γ-H2AX and phospho-p53 increased in early-passage MSCs while decreased in late-passage MSCs. Through inhibition by KU55933, DDR pathway in early-passage MSCs was shown to be ATM-dependent. Higher levels of poly (ADP-ribose) polymerase-1 (PARP-1) and PAR synthesis were observed in early-passage MSCs than in late-passage MSCs. Knockdown of PARP-1 in early-passage MSCs resulted in sensitization to irradiation-induced apoptosis. Overexpression of PARP-1 in late passage MSCs could render irradiation resistance. Lower activity of DDR in late-passage MSCs was associated with rapid proteasomal degradation of PARP-1. In conclusion, early-passage MSCs are more irradiation-resistant and have increased DDR activity involving PARP-1, ATM and their downstream signals.
Smooth semi‐nonparametric (SNP) estimation of the cumulative incidence function
Authors: Duc Anh Nguyen , Wolbers Marcel
Published: May 2017

This paper presents a novel approach to estimation of the cumulative incidence function in the presence of competing risks. The underlying statistical model is specified via a mixture factorization of the joint distribution of the event type and the time to the event. The time to event distributions conditional on the event type are modeled using smooth semi‐nonparametric densities. One strength of this approach is that it can handle arbitrary censoring and truncation while relying on mild parametric assumptions. A stepwise forward algorithm for model estimation and adaptive selection of smooth semi‐nonparametric polynomial degrees is presented, implemented in the statistical software R, evaluated in a sequence of simulation studies, and applied to data from a clinical trial in cryptococcal meningitis. The simulations demonstrate that the proposed method frequently outperforms both parametric and nonparametric alternatives. They also support the use of ‘ad hoc’ asymptotic inference to derive confidence intervals. An extension to regression modeling is also presented, and its potential and challenges are discussed. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Chemically Modified Indium‐Tin‐Oxide Electrodes for Heterojunction Organic Solar Cells Based on Different Organic Donors
Authors: Tumen‐Ulzii Ganbaatar , Altantsetseg Delgerjargal , Ochirkhuyag Nyamjargal , Byambasuren Delgertsetseg , Sakomura Masaru , Khayankhyarvaa Sarangerel , Chimed Ganzorig
Published: May 2017

In this study, we have examined the correlation between work function (WF) of indium‐tin‐oxide (ITO) and open‐circuit voltage (Voc) of heterojunction photovoltaic (PV) cells based on different donor materials. Device configurations of ITO(modified)/SubPc/C60/BCP/Al and ITO(modified)/ZnPc/C60/BCP/Al were used in this study. Surface modification of ITO electrode through p‐substituted benzenesulfonyl chlorides with different electron withdrawing terminal groups (C6H5‐, Cl‐ and NO2‐) has exploited to change the WF of ITO up to 5.28 eV with NO2‐. Chemically modified ITOs and SubPc, ZnPc were used as anode electrode and donor materials, respectively. In order to find the correlation of Voc, two different donor materials with different HOMO levels were used in PV cells. When the SubPc was used as a donor in PV cells, the Voc was strongly dependent on WF of ITO. However, for ZnPc, the Voc was almost independent on WF of ITO due to its low HOMO level and formed ohmic contact at the interface between chemically modified ITO electrodes and ZnPc.
A shortened, two-enzyme pathway for 2,3-butanediol production in Escherichia coli
Authors: Reshamwala Shamlan M S , Deb Shalini S , Lali Arvind M
Published: May 2017

The platform chemical 2,3-butanediol (2,3-BDO) is produced by a number of microorganisms via a three-enzyme pathway starting from pyruvate. Here, we report production of 2,3-BDO via a shortened, two-enzyme pathway in Escherichia coli. A synthetic operon consisting of the acetolactate synthase (ALS) and acetoin reductase (AR) genes from Enterobacter under control of the T7 promoter was cloned in an episomal plasmid. E. coli transformed with this plasmid produced 2,3-BDO and the pathway intermediate acetoin, demonstrating that the shortened pathway was functional. To assemble a synthetic operon for inducer- and plasmid-free production of 2,3-BDO, ALS and AR genes were integrated in the E. coli genome under control of the constitutive ackA promoter. Shake flask-level cultivation led to accumulation of ~1 g/L acetoin and ~0.66 g/L 2,3-BDO in the medium. The novel biosynthetic route for 2,3-BDO biosynthesis described herein provides a simple and cost-effective approach for production of this important chemical.
The relaxation time for viscous and porous gravity currents following a change in flux
Authors: Ball Thomasina V. , Huppert Herbert E. , Lister John R. , Neufeld Jerome A.
Published: May 2017

The equilibration time $\unicode[STIX]{x1D70F}$ in response to a change in flux from $Q$ to $\unicode[STIX]{x1D6EC}Q$ after an injection period $T$ applied to either a low-Reynolds-number gravity current or one propagating through a porous medium, in both axisymmetric and one-dimensional geometries, is shown to be of the form $\unicode[STIX]{x1D70F}=Tf(\unicode[STIX]{x1D6EC})$, independent of all the remaining physical parameters. Numerical solutions are used to investigate $f(\unicode[STIX]{x1D6EC})$ for each of these situations and compare very well with experimental results in the case of an axisymmetric current propagating over a rigid horizontal boundary. Analysis of the relaxation towards self-similarity provides an illuminating connection between the excess (deficit) volume from early times and an asymptotically equivalent shift in time origin, and hence a good quantitative estimate of $\unicode[STIX]{x1D70F}$. The case $\unicode[STIX]{x1D6EC}=0$ of equilibration after ceasing injection at time $T$ is a singular limit. Extensions to high-Reynolds-number currents and to the case of a constant-volume release followed by constant-flux injection are discussed briefly.
Implicit Virtual Boundary Method for Moving Boundary Problems on Non-Staggered Cartesian Patch Grids
Authors: Lee S. L. , Cyue G. S. , Chen K. W.
Published: May 2017

A simple numerical method is proposed in the paper for fluid flow around a moving boundary of irregular shape. The unsteady term is discretized with the implicit scheme such that large time step is allowed. All of the computations are performed on non-staggered Cartesian grid system. Fine Cartesian patch grid system covering the moving object is employed to resolve the solution around the solid body. A closed curve defined by connecting the solid grid points adjacent to the solid-liquid interface is referred to as virtual boundary. The narrow irregular strip of solid between the virtual boundary and the actual solid-fluid interface is called pseudo-fluid. The general fluid region consisting of both fluid and pseudo-fluid is a regular domain that can be efficiently solved with conventional numerical method. In this connection, external force is imposed at each fluid grid point adjacent to the solid-fluid interface to compensate for the numerical error arising from the assumption of pseudo-fluid. The solution procedure is iterated until the required external force converges. Accuracy of the new numerical method is validated through three test problems. The numerical method then is used to investigate the flow induced by the flapping wings of a tethered dragonfly in literature. The corresponding CFL numbers of the four examples are infinity, 20, 100, and 3.29.
Impulsive Control of a Cam-Follower Oblique-Impact System
Authors: Lu N. , Ren X. M. , Jiang T. D. , Yang Y. F.
Published: May 2017

The transient impact hypothesis was extended, and the oblique collision model was established by considering the tangential slip. In order to solve this problem, the oblique-impact equations for cam-follower were transformed into a linear complementarity problem. Impulsive control method was employed to control or anti-control the nonlinear responses. The simulation results show that the cam-follower system performs very complex nonlinear characteristics, such as period, quasi-period and chaos responses. Using the impulsive control method, the nonlinear responses of the cam-follower system can be controlled to P(n, n) and P(∞, n) or anti-controlled to chaos.
International Organizations: Then and Now
Authors: Alvarez José E.
Published: May 2017

International organizations (or IOs)—intergovernmental entities established by treaty, usually composed of permanent secretariats, plenary assemblies involving all member states, and executive organs with more limited participation—are a twentieth-century phenomenon having little in common with earlier forms of institutionalized cooperation, including those in the ancient world. The story of how, shortly after the turn of the last century, the Euro-American lawyers that dominated the field of international law sought to transcend the chaos of war by “moving to institutions” has been told elsewhere and needs no repeating here. David Kennedy, Martti Koskenniemi, and David Bederman, among others, have described the disparate individuals, separated by nationality, juridical philosophy, and competing “idealist”/“realist” schools of thought, who nevertheless shared a messianic, quasi-religious, and coherent “internationalist sensibility” that sought to institutionalize multilateral diplomacy with a view to promoting civilization and progress. Kennedy locates the move to international organization in turn-of-the-century reformist aspirations for parliamentary, administrative, and judicial mechanisms that, in the Victorian language of the day, would convert “passion into reason.” By the time thisJournalwas established, the Congress of Vienna’s concert system had provided a model for an incipient (albeit only periodic) pseudo-parliament; diverse public administrative unions and river commissions suggested the possibilities for international administration and even the interstate pooling of funds; and the Permanent Court of Arbitration presaged an international judiciary.
The Fifty-Seventh Session of the International Law Commission
Authors: Matheson Michael J.
Published: May 2017

The International Law Commission held its fifty-seventh session in Geneva from May 2 to June 3, and from July 11 to August 5, 2005. The Commission continued its work on shared natural resources, reservations to treaties, responsibility of international organizations, unilateral acts of states, and fragmentation of international law. It began work on the effect of armed conflict on treaties and expulsion of aliens, and decided to begin work next year on the obligation to prosecute or extradite. It took no further action for the time being on diplomatic protection or on international liability for transboundary harm, pending the receipt of comments from governments on the texts adopted on first reading in 2004.
The effect of increased fruit and vegetable consumption on selected macronutrient and micronutrient intakes in four randomised-controlled trials
Authors: Fulton Sharon L. , McKinley Michelle C. , Neville Charlotte E. , Baldrick Francina R. , Mulligan Ciara , McCall Damian O. , McCance David R. , Edgar J. D. , Elborn J. S. , Young Ian S. , Patterson Chris C. , Woodside Jayne V.
Published: May 2017

Fruit and vegetable (FV) intake is associated with reduced risk of a number of non-communicable diseases. Research tends to focus on antioxidants, flavonoids and polyphenols contained in FV as the main beneficial components to health; however, increasing FV may also alter overall diet profile. Extra FV may be substituted for foods thought to be less healthy, therefore altering the overall macronutrient and/or micronutrient content in the diet. This analysis merged dietary data from four intervention studies in participants with varying health conditions and examined the effect of increased FV consumption on diet profile. Dietary intake was assessed by either diet diaries or diet histories used in four FV randomised intervention studies. All food and drink intake recorded was analysed using WISP version 3.0, and FV portions were manually counted using household measures. Regression analysis revealed significant increases in intakes of energy (172 kJ (+41 kcal)), carbohydrate (+3·9 g/4184 kJ (1000 kcal)), total sugars (+6·0 g/4184 kJ (1000 kcal)) and fibre (+0·8 g/4184 kJ (1000 kcal)) and significant decreases in intakes of total fat (−1·4 g/4184 kJ (1000 kcal)), SFA (−0·6 g/4184 kJ (1000 kcal)), MUFA (−0·6 g/4184 kJ (1000 kcal)), PUFA (−0·1 g/4184 kJ (1000 kcal)) and starch (−2·1 g/4184 kJ (1000 kcal)) per one portion increase in FV. Significant percentage increases were also observed in vitamin C (+24 %) and -carotene (+20 %) intake, per one portion increase in FV. In conclusion, pooled analysis of four FV intervention studies, that used similar approaches to achieving dietary change, in participants with varying health conditions, demonstrated an increase in energy, total carbohydrate, sugars and fibre intake, and a decrease in fat intake alongside an expected increase in micronutrient intake.
Studies on Echinochasmus perfoliantus (Ratz, 1908) Dietz, 1909: Incidence in Dogs and Development of the Miracidium
Authors: Sahai B. N. , Srivastava H. D.
Published: May 2017

Chand ler (1925) described Echinochasmus perfoliatns as a common parasite of Indian dogs in Calcutta. Bhalerao (1936) reported its occurrence in cats of Calcutta and Mukteswar and Patnaik (1959) in dogs of Orissa. Maplestone and Bhaduri (1940) reported Echinochasmus sp. from dogs in Calcutta. Gupta and Pand e (19G3) mentioned that Echinochasmus is represented in Indian carnivores by three species: E. perfoliatns, E. corvus (Syn. E. caninum) and E. canai.
Digenetic Trematodes of Marine Fishes from Ghana: Family Lepocreadiidae
Authors: Fischthal Jacob H. , Thomas J. D.
Published: May 2017

The trematodes of this report were killed in hot water, transferred immediately to Lavdowsky's FAA fixative for 24 hours, and then stored in 70% alcohol plus 2% glycerine. Whole mounts were stained in Mayer's carmalum and mounted in permount. Specimens have been deposited in the U.S. National Museum Helminthological Collection as indicated. All measurements are in microns (ftm).
Spatio-temporal distribution and habitat preferences of cetaceans in Algoa Bay, South Africa
Authors: Melly B. L. , McGregor G. , Hofmeyr G.J.G. , Plön S.
Published: May 2017

Increasingly, baseline knowledge of habitat preferences and movement patterns of marine species is required to inform anthropogenic developments. The aim of this study was to determine baseline spatio-temporal distribution and habitat preference of cetaceans in the coastal waters of Algoa Bay. Areas of potential conflict with anthropogenic activities were also assessed. Monthly sea-based surveys were conducted between June 2008 and May 2011. A total of 500 cetacean sightings comprising six species were recorded in 106 surveys. Tursiops aduncus (Indo-Pacific bottlenose dolphin), Sousa plumbea (Indian Ocean humpback dolphin), Delphinus capensis (long-beaked common dolphin) and Balaenoptera brydei (Bryde's whale) were observed year-round, while Eubalaena australis (southern right whale) and Megaptera novaeangliae (humpback whale) were recorded from May to December. A large portion of sightings were associated with a Marine Protected Area and shipping zones. Eubalaena australis, T. aduncus and S. plumbea were found inshore (water depths < 12 m), while the other species were associated with deeper waters. Tursiops aduncus were most commonly seen (233 sightings). Megaptera novaeangliae were sighted often in austral winter, with 113 sightings. Only nine D. capensis sightings were recorded. Spatial distributions of species were corrected for search effort to identify habitat preferences. A number of key observations were made, including opportunistic foraging in M. novaeangliae, and the expansion of nursery grounds for E. australis, to include Algoa Bay. Four preferred habitat areas are proposed, providing important information for conservation and management of cetaceans in Algoa Bay. The spatial approach can be used to inform future relevant management decisions elsewhere.
Cislunar Navigation Constellation by Displaced Solar Sails
Authors: Pan Xiao , Xu Ming
Published: May 2017

Increasing lunar exploration activities are giving rise to higher demands for a navigation constellation system in cislunar space. A novel constellation of solar sails around the Sun-Earth Artificial Lagrangian Points (ALPs) is proposed for cislunar navigation in this paper, which benefits from the numberless and out-of-plane advantages of ALPs compared with the classical Lagrangian points. To relieve the technical pressure on sail equipment, a two-layer optimisation strategy including the navigation constellation architecture and trajectory design is developed to reduce the desired lightness number of the sail's motion. The constellation architecture is constructed in the shape of a regular tetrahedron, whose size and orientation are derived from the realisable lightness number at the ALPs. The powerful Hamiltonian structure-preserving controller and differential evolution algorithm are adopted to propagate the bounded quasi-periodic trajectory with minimum lightness number variation. With the premise of the sail's high feasibility in the mechanism, the numerical navigation simulations for a typical trans-lunar weak stability boundary trajectory indicate that the proposed navigation constellation has a low geometric dilution of precision factor and a good navigation performance.
CSOLNP: Numerical Optimization Engine for Solving Non-linearly Constrained Problems
Authors: Zahery Mahsa , Maes Hermine H. , Neale Michael C.
Published: May 2017

We introduce the optimizer CSOLNP, which is a C++ implementation of the R package RSOLNP (Ghalanos & Theussl, 2012, Rsolnp: General non-linear optimization using augmented Lagrange multiplier method. R package version, 1) alongside some improvements. CSOLNP solves non-linearly constrained optimization problems using a Sequential Quadratic Programming (SQP) algorithm. CSOLNP, NPSOL (a very popular implementation of SQP method in FORTRAN (Gill et al., 1986, User's guide for NPSOL (version 4.0): A Fortran package for nonlinear programming (No. SOL-86-2). Stanford, CA: Stanford University Systems Optimization Laboratory), and SLSQP (another SQP implementation available as part of the NLOPT collection (Johnson, 2014, The NLopt nonlinear-optimization package. Retrieved fromhttp://ab-initio.mit.edu/nlopt)) are three optimizers available in OpenMx package. These optimizers are compared in terms of runtimes, final objective values, and memory consumption. A Monte Carlo analysis of the performance of the optimizers was performed on ordinal and continuous models with five variables and one or two factors. While the relative difference between the objective values is less than 0.5%, CSOLNP is in general faster than NPSOL and SLSQP for ordinal analysis. As for continuous data, none of the optimizers performs consistently faster than the others. In terms of memory usage, we used Valgrind's heap profiler tool, called Massif, on one-factor threshold models. CSOLNP and NPSOL consume the same amount of memory, while SLSQP uses 71 MB more memory than the other two optimizers.
Wiederkehrende abdominelle Schmerzen, Übelkeit und heisses Baden – eine neue Trias?
Authors: Ormachea Oscar , Bernasconi Enos , Pons Marco , Fusi-Schmidhauser Tanja
Published: May 2017

Zusammenfassung. Eine 34-jährige Patientin wird mit starken, hartnäckigen Bauchschmerzen, rezidivierendem Erbrechen und Schwindel stationär aufgenommen. Einzig und allein ausgedehntes heisses Baden oder Duschen lindert die Beschwerden, die kaum auf eine medikamentöse Behandlung ansprechen. Ihrer Anamnese ist zu entnehmen, dass dieser Symptomenkomplex seit sechs Jahren immer wieder auftritt, weswegen bereits zahlreiche und aufwändige diagnostische und therapeutische Massnahmen ohne Erfolg durchgeführt wurden. Schliesslich räumte sie den regelmässigen Konsum von Cannabis ein. Die vollständige Abstinenz von der Droge führte zum Sistieren der Symptomatik.
An enhanced bioluminescence-based Annexin V probe for apoptosis detection in vitro and in vivo
Authors: Head Trajen , Dau Peter , Duffort Stephanie , Daftarian Pirouz , Joshi Pratibha M , Vazquez-Padron Roberto , Deo Sapna K , Daunert Sylvia
Published: May 2017

The process of controlled cellular death known as apoptosis has an important central role not only in normal homeostatic maintenance of tissues, but also in numerous diseases such as cancer, neurodegenerative, autoimmune, and cardiovascular diseases. As a result, new technologies with the capability to selectively detect apoptotic cells represent a central focus of research for the study of these conditions. We have developed a new biosensor for the detection of apoptotic cells, incorporating the targeted selectivity for apoptotic cells from Annexin V with the sensitivity of bioluminescence signal generation from a serum-stable mutant of Renilla luciferase (RLuc8). Our data presents a complete characterization of the structural and biochemical properties of this new Annexin-Renilla fusion protein (ArFP) construct, as well as a validation of its ability to detect apoptosis in vitro. Moreover, this work represents the first report of a bioluminescent Annexin V apoptosis sensor utilized in vivo. With this new construct, we examine apoptosis within disease-relevant animal models of surgery-induced ischemia/reperfusion, corneal injury, and retinal cell death as a model of age-related macular degeneration. In each of these experiments, we demonstrate successful application of the ArFP construct for detection and bioluminescence imaging of apoptosis within each disease or treatment model. ArFP represents an important new tool in the continuously growing kit of technologies for apoptosis detection, and our results from both in vitro and in vivo experiments suggest a diverse range of potential clinically relevant applications including cancer therapeutic screening and efficacy analysis, atherosclerosis and cardiovascular disease detection, and the monitoring of any number of other conditions in which apoptosis has a central role.
Phosphorylated CAV1 activates autophagy through an interaction with BECN1 under oxidative stress
Authors: Nah Jihoon , Yoo Seung-Min , Jung Sunmin , Jeong Eun Il , Park Moonju , Kaang Bong-Kiun , Jung Yong-Keun
Published: May 2017

CAV1/Caveolin1, an integral membrane protein, is involved in caveolae function and cellular signaling pathways. Here, we report that CAV1 is a positive regulator of autophagy under oxidative stress and cerebral ischemic injury. Treatment with hydrogen peroxide enhanced autophagy flux and caused the localization of BECN1 to the mitochondria, whereas these changes were impaired in the absence of CAV1. Among many autophagy signals, only LC3 foci formation in response to hydrogen peroxide was abolished by CAV1 deficiency. Under oxidative stress, CAV1 interacted with a complex of BECN1/VPS34 through its scaffolding domain, and this interaction facilitated autophagosome formation. Interestingly, the phosphorylation of CAV1 at tyrosine-14 was essential for the interaction with BECN1 and their localization to the mitochondria, and the activation of autophagy in response to hydrogen peroxide. In addition, the expression of a phosphatase PTPN1 reduced the phosphorylation of CAV1 and inhibited autophagy. Further, compared to that in wild-type mice, autophagy was impaired and cerebral infarct damage was aggravated in the brain of Cav1 knockout mice. These results suggest that the phosphorylated CAV1 functions to activate autophagy through binding to the BECN1/VPS34 complex under oxidative stress and to protect against ischemic damage.
Endogenous opioids regulate social threat learning in humans
Authors: Haaker Jan , Yi Jonathan , Petrovic Predrag , Olsson Andreas
Published: May 2017

Many fearful expectations are shaped by observation of aversive outcomes to others. Yet, the neurochemistry regulating social learning is unknown. Previous research has shown that during direct (Pavlovian) threat learning, information about personally experienced outcomes is regulated by the release of endogenous opioids, and activity within the amygdala and periaqueductal gray (PAG). Here we report that blockade of this opioidergic circuit enhances social threat learning through observation in humans involving activity within the amygdala, midline thalamus and the PAG. In particular, anticipatory responses to learned threat cues (CS) were associated with temporal dynamics in the PAG, coding the observed aversive outcomes to other (observational US). In addition, pharmacological challenge of the opioid receptor function is classified by distinct brain activity patterns during the expression of conditioned threats. Our results reveal an opioidergic circuit that codes the observed aversive outcomes to others into threat responses and long-term memory in the observer.
Gigantic negative magnetoresistance in the bulk of a disordered topological insulator
Authors: Breunig Oliver , Wang Zhiwei , Taskin A A , Lux Jonathan , Rosch Achim , Ando Yoichi
Published: May 2017

With the recent discovery of Weyl semimetals, the phenomenon of negative magnetoresistance (MR) is attracting renewed interest. Large negative MR is usually related to magnetism, but the chiral anomaly in Weyl semimetals is a rare exception. Here we report a mechanism for large negative MR which is also unrelated to magnetism but is related to disorder. In the nearly bulk-insulating topological insulator TlBi0.15Sb0.85Te2, we observed gigantic negative MR reaching 98% in 14 T at 10 K, which is unprecedented in a nonmagnetic system. Supported by numerical simulations, we argue that this phenomenon is likely due to the Zeeman effect on a barely percolating current path formed in the disordered bulk. Since disorder can also lead to non-saturating linear MR in Ag2+δSe, the present finding suggests that disorder engineering in narrow-gap systems is useful for realizing gigantic MR in both positive and negative directions.
A scalable double-barcode sequencing platform for characterization of dynamic protein-protein interactions
Authors: Schlecht Ulrich , Liu Zhimin , Blundell Jamie R. , St.Onge Robert P. , Levy Sasha F.
Published: May 2017

Several large-scale efforts have systematically catalogued protein-protein interactions (PPIs) of a cell in a single environment. However, little is known about how the protein interactome changes across environmental perturbations. Current technologies, which assay one PPI at a time, are too low throughput to make it practical to study protein interactome dynamics. Here, we develop a highly parallel protein-protein interaction sequencing (PPiSeq) platform that uses a novel double barcoding system in conjunction with the dihydrofolate reductase protein-fragment complementation assay in Saccharomyces cerevisiae. PPiSeq detects PPIs at a rate that is on par with current assays and, in contrast with current methods, quantitatively scores PPIs with enough accuracy and sensitivity to detect changes across environments. Both PPI scoring and the bulk of strain construction can be performed with cell pools, making the assay scalable and easily reproduced across environments. PPiSeq is therefore a powerful new tool for large-scale investigations of dynamic PPIs.
Production of three phenylethanoids, tyrosol, hydroxytyrosol, and salidroside, using plant genes expressing in Escherichia coli
Authors: Chung Daeun , Kim So Yeon , Ahn Joong-Hoon
Published: May 2017

Polyphenols, which include phenolic acids, flavonoids, stilbenes, and phenylethanoids, are generally known as useful antioxidants. Tyrosol, hydroxytyrosol, and salidroside are typical phenylethanoids. Phenylethanoids are found in plants such as olive, green tea, andRhodiolaand have various biological activities, including the prevention of cardiovascular diseases, cancer, and brain damage. We usedEscherichia colito synthesize three phenylethanoids, tyrosol, hydroxytyrosol, and salidroside. To synthesize tyrosol, the aromatic aldehyde synthase (AAS) was expressed inE. coli. Hydroxytyrosol was synthesized usingE. coliharboringAASandHpaBC, which encodes hydroxylase. In order to synthesize salidroside, 12 uridine diphosphate-dependent glycosyltransferases (UGTs) were screened and UGT85A1 was found to convert tyrosol to salidroside. UsingE. coliharboringAASand UGT85A1, salidroside was synthesized. Through the optimization of these threeE. colistrains, we were able to synthesize 531 mg/L tyrosol, 208 mg/L hydroxytyrosol, and 288 mg/L salidroside, respectively.
Fatty Acid Binding Protein 3 And Transzonal Projections Are Involved In Lipid Accumulation During In Vitro Maturation Of Bovine Oocytes
Authors: del Collado Maite , da Silveira Juliano Coelho , Sangalli Juliano Rodrigues , Andrade Gabriella Mamede , Sousa Letícia Rabello da Silva , Silva Luciano Andrade , Meirelles Flavio Vieira , Perecin Felipe
Published: May 2017

Oocytes that undergo in vitro maturation (IVM) are metabolically abnormal and accumulate excess lipid content. However, the mechanism of lipid accumulation and the role of cumulus cells in this process are unclear. Recently, it was shown that fatty acid binding proteins (FABPs) performed intra- and extracellular fatty acid transport. We postulated that FABP3 might be responsible for fatty acid transport from cumulus cells to the oocytes via transzonal projections (TZPs) during IVM. Transcript and protein levels of FABP3 were analyzed in both in vivo- and in vitro-matured cumulus-oocyte-complexes and were increased in IVM samples. Further analysis showed increased lipid content in oocytes and cumulus cells in IVM samples compared to in vivo-derived. We therefore speculated that altered traffic of fatty acids via FABP3 during IVM was the mechanism leading to the excess of lipids accumulated within IVM oocytes. Furthermore, we demonstrated an increase in FABP3 levels and lipid content during the first 9 h of IVM, further strengthening the possibility of fatty acid transport via FABP3 and TZPs. Additionally, disruptions of TZPs during IVM decreased lipid accumulation in oocytes. Our results shed light on a possible mechanism involving FABP3 and TZPs that causes excess lipid accumulation in oocytes during IVM.
Intraspecific differences in molecular stress responses and coral pathobiome contribute to mortality under bacterial challenge in Acropora millepora
Authors: Wright Rachel M. , Kenkel Carly D. , Dunn Carly E. , Shilling Erin N. , Bay Line K. , Matz Mikhail V.
Published: May 2017

Disease causes significant coral mortality worldwide; however, factors responsible for intraspecific variation in disease resistance remain unclear. We exposed fragments of eightAcropora milleporacolonies (genotypes) to putatively pathogenic bacteria (Vibrio spp.). Genotypes varied from zero to >90% mortality, with bacterial challenge increasing average mortality rates 4–6 fold and shifting the microbiome in favor of stress-associated taxa. Constitutive immunity and subsequent immune and transcriptomic responses to the challenge were more prominent in high-mortality individuals, whereas low-mortality corals remained largely unaffected and maintained expression signatures of a healthier condition (i.e., did not launch a large stress response). Our results suggest that lesions appeared due to changes in the coral pathobiome (multiple bacterial species associated with disease) and general health deterioration after the biotic disturbance, rather than the direct activity of any specific pathogen. If diseases in nature arise because of weaknesses in holobiont physiology, instead of the virulence of any single etiological agent, environmental stressors compromising coral condition might play a larger role in disease outbreaks than is currently thought. To facilitate the diagnosis of compromised individuals, we developed and independently cross-validated a biomarker assay to predict mortality based on genes whose expression in asymptomatic individuals coincides with mortality rates.
Interaction studies of carbon nanomaterials and plasma activated carbon nanomaterials solution with telomere binding protein
Authors: Attri Pankaj , Gaur Jitender , Choi Sooho , Kim Minsup , Bhatia Rohit , Kumar Naresh , Park Ji Hoon , Cho Art. E. , Choi Eun Ha , Lee Weontae
Published: May 2017

Most cancer cells have telomerase activity because they can express the human telomerase reverse transcriptase (hTERT) gene. Therefore, the inhibition of the hTERT expression can play an important role in controlling cancer cell proliferation. Our current study aims to inhibit hTERT expression. For this, we synthesized graphene oxide (GO) and a functionalized multiwall carbon nanotube (f-MWCNT), latter treated them with cold atmospheric pressure plasma for further analysis of the hTERT expression. The inhibition of hTERT expression by GO, f-MWCNT, plasma activated GO solution (PGOS), and plasma activated f-MWCNT solution (PCNTS), was studied using two lung cancer cell lines, A549 and H460. The hTERT experimental results revealed that GO and PGOS sufficiently decreased the hTERT concentration, while f-MWCNT and PCNTS were unable to inhibit the hTERT concentration. Therefore, to understand the inhibition mechanism of hTERT, we studied the binding properties of GO and PGOS with telomere binding protein (AtTRB2). The interaction studies were carried out using circular dichroism, fluorescence, 1H-15N NMR spectroscopy, and size-exclusion chromatography (SEC) binding assay. We also used docking simulation to have an better understanding of the interactions between GO nanosheets and AtTRB2 protein. Our results may provide new insights that can benefit in biomedical treatments.
Role of interfaces on the stability and electrical properties of Ge2Sb2Te5 crystalline structures
Authors: Mio A. M. , Privitera S. M. S. , Bragaglia V. , Arciprete F. , Cecchi S. , Litrico G. , Persch C. , Calarco R. , Rimini E.
Published: May 2017

GeSbTe-based materials exhibit multiple crystalline phases, from disordered rocksalt, to rocksalt with ordered vacancy layers, and to the stable trigonal phase. In this paper we investigate the role of the interfaces on the structural and electrical properties of Ge2Sb2Te5. We find that the site of nucleation of the metastable rocksalt phase is crucial in determining the evolution towards vacancy ordering and the stable phase. By properly choosing the substrate and the capping layers, nucleation sites engineering can be obtained, thus promoting or preventing the vacancy ordering in the rocksalt structure or the conversion into the trigonal phase. The vacancy ordering occurs at lower annealing temperatures (170 °C) for films deposited in the amorphous phase on silicon (111), compared to the case of SiO2 substrate (200 °C), or in presence of a capping layer (330 °C). The mechanisms governing the nucleation have been explained in terms of interfacial energies. Resistance variations of about one order of magnitude have been measured upon transition from the disordered to the ordered rocksalt structure and then to the trigonal phase. The possibility to control the formation of the crystalline phases characterized by marked resistivity contrast is of fundamental relevance for the development of multilevel phase change data storage.
Morphologic and biometric evaluation of chick embryo eyes in ovo using 7 Tesla MRI
Authors: Lindner Tobias , Klose Ronja , Streckenbach Felix , Stahnke Thomas , Hadlich Stefan , Kühn Jens-Peter , Guthoff Rudolf F. , Wree Andreas , Neumann Anne-Marie , Frank Marcus , Glass Änne , Langner Sönke , Stachs Oliver
Published: May 2017

The purposes of this study were (1) to characterize embryonic eye development during incubation in ovo and (2) to analyze the putative influence of repetitive ultrahigh-field MRI (UHF-MRI) measurements on this development. A population of 38 fertilized chicken eggs was divided into two sub-groups: two eggs (Group A) were examined repeatedly during the developmental period from embryonic day 1 (E1) to embryonic day 20 (E20) to evaluate the influence of daily MRI scanning. A second larger group of 36 eggs was examined pairwise on one day only, from E3 to E20, and the embryos were sacrificed immediately after MR imaging (Group B). Fast T2-weighted MR sequences provided biometric data on the eye with an in-plane resolution of 74 μm. The data show rapid growth of the eye with a steep increase in intraocular dimensions in all axis directions and in eyeball volume during initial development up to E10, followed by a phase of reduced growth rate in later developmental stages. Comparison of the two groups revealed no differences in ocular development.
Stopping power beyond the adiabatic approximation
Authors: Caro M. , Correa A. A. , Artacho E. , Caro A.
Published: May 2017

Energetic ions traveling in solids deposit energy in a variety of ways, being nuclear and electronic stopping the two avenues in which dissipation is usually treated. This separation between electrons and ions relies on the adiabatic approximation in which ions interact via forces derived from the instantaneous electronic ground state. In a more detailed view, in which non-adiabatic effects are explicitly considered, electronic excitations alter the atomic bonding, which translates into changes in the interatomic forces. In this work, we use time dependent density functional theory and forces derived from the equations of Ehrenfest dynamics that depend instantaneously on the time-dependent electronic density. With them we analyze how the inter-ionic forces are affected by electronic excitations in a model of a Ni projectile interacting with a Ni target, a metallic system with strong electronic stopping and shallow core level states. We find that the electronic excitations induce substantial modifications to the inter-ionic forces, which translate into nuclear stopping power well above the adiabatic prediction. In particular, we observe that most of the alteration of the adiabatic potential in early times comes from the ionization of the core levels of the target ions, not readily screened by the valence electrons.
Nitrogen isotopes provide clues to amino acid metabolism in human colorectal cancer cells
Authors: Krishnamurthy R. V. , Suryawanshi Yogesh R. , Essani Karim
Published: May 2017

Glutamic acid and alanine make up more than 60 per cent of the total amino acids in the human body. Glutamine is a significant source of energy for cells and also a prime donor of nitrogen in the biosynthesis of many amino acids. Several studies have advocated the role of glutamic acid in cancer therapy. Identification of metabolic signatures in cancer cells will be crucial for advancement of cancer therapies based on the cell’s metabolic state. Stable nitrogen isotope ratios (15N/14N, δ15N) are of particular advantage to understand the metabolic state of cancer cells, since most biochemical reactions involve transfer of nitrogen. In our study, we used the natural abundances of nitrogen isotopes (δ15N values) of individual amino acids from human colorectal cancer cell lines to investigate isotope discrimination among amino acids. Significant effects were noticed in the case of glutamic acid, alanine, aspartic acid and proline between cancer and healthy cells. The data suggest that glutamic acid is a nitrogen acceptor while alanine, aspartic acid and proline are nitrogen donors in cancerous cells. One plausible explanation is the transamination of the three acids to produce glutamic acid in cancerous cells.
Experimental evidence for anisotropic double exchange interaction driven anisotropic transport in manganite heterostructures
Authors: Liao Z. L. , Koster G. , Huijben M. , Rijnders G.
Published: May 2017

An anisotropic double exchange interaction driven giant transport anisotropy is demonstrated in a canonic double exchange system of La2/3Sr1/3MnO3 ultrathin films epitaxially grown on NdGaO3 (110) substrates. The oxygen octahedral coupling at the La2/3Sr1/3MnO3/NdGaO3 interface induces a planar anisotropic Mn-O-Mn bond bending, which causes a significant anisotropic overlap of neighboring Mn orbitals. Due to the anisotropic double exchange interaction, it is found that the conductivity of the La2/3Sr1/3MnO3 film is enhanced when current is applied along the in-plane short crystalline axis. However, the anisotropic behavior is absent in the high temperature paramagnetic phase. Our results demonstrate anisotropic transport in the clean limit where phase separation is absent and the role of anisotropic phase percolation can be excluded.