Reversible Action Research Articles

Lippia citriodora (verbascoside) extract supplementation: Effect on rabbit semen quality in vivo and in vitro

Verbascoside, the main component of Lippia citriodora extract, is one of the most powerful free radical scavengers exhibiting a wide biological activity. In in vivo study 20 adult New Zealand white rabbit bucks were divided into two homogeneous groups, one control (CON) and one verbascoside-supplemented (0.1%) in feed mixture (EXP) and later in vitro effects of verbascoside on the motility aspects of rabbit spermatozoa were analysed. The spermatozoa concentration, ejaculate volume, spermatozoa motility, progressive motility, distance parameters, velocity parameters and type of spermatozoa movement were negatively affected by Lippia citriodora leaves extract after the first 4 weeks of dietary treatment, till the end of experiment (8 weeks). Four weeks after the suspension of feed additive supplementation, all spermatozoa traits values returned to the normality, and in line with CON group. For in vitro findings, ejaculates from 10 male New Zealand white bucks were collected using an artificial vagina. Then it was diluted in physiological saline solution containing different concentrations of verbascoside at the concentration of 0, 0.0024, 0.0219, 0.157, 120.0 mg/ml (Ctrl, VB1, VB2, VB3, VB4 groups, respectively), using a dilution ratio of 1 : 4. The obtained data proved that verbascoside at the concentration of 0.0024 and 0.0219 mg/ml had no adverse effect on spermatozoa. Additionally, we found that verbascoside at higher concentrations (0.157 and 120.0 mg/ml) significantly altered all the motility parameters analysed in the experiment. In conclusion a possible negative effect of verbascoside supplementation into feed mixture (0.1%) on semen quality parameters in rabbit bucks as well as in vitro can be stated, obviously considering that target organs of antioxidant activities of phenylpropanoid glycosides are various. In addition it has to be emphasized that the extract showed a reversible action, since the semen traits of treated animals returned to the normality after the dietary administration period.

Tribotronics for Active Mechanosensation and Self‐Powered Microsystems

AbstractTribotronics has attracted great attention as a new research field that encompasses the control and tuning of semiconductor transport by triboelectricity. Here, tribotronics is reviewed in terms of active mechanosensation and human–machine interfacing. As a fundamental unit, contact electrification field‐effect transistors are analyzed, in which the triboelectric potential can be used to control electrical transport in semiconductors. Several tribotronic functional devices have been developed for active control and information sensing, which has demonstrated triboelectricity‐controlled electronics and established active mechanosensation for the external environment. In addition, the universal triboelectric power management strategy and the triboelectric nanogenerator‐based constant sources are also reviewed, in which triboelectricity can be managed by electronics in the reverse action. With the implantation of triboelectric power management modules, the harvested triboelectricity by various kinds of human kinetic and environmental mechanical energy can be effectively managed as a power supply for self‐powered microsystems. In terms of the research prospects for interactions between triboelectricity and semiconductors, tribotronics is expected to demonstrate significant impact and potential applications in micro‐electro‐mechanical systems/nano‐electro‐mechanical systems (MEMS/NEMS), flexible electronics, robotics, wireless sensor network, and Internet of Things.

Efficacy of group training using Gross model-based emotion regulation strategies in reducing ‎suicidal ideation in patients with major depression disorder who had attempted suicide, ‎Bushehr, 1396‎

Background: Major depression is one of the century s most common mental illnesses, affecting 15% of the ‎population. Many factors contribute to depression including age, gender, occupation, traumatic ‎event, genetics, etc. This illness is more common in single and divorced people than married ‎ones. Due to suicidal ideation in patients, major depression is among the priorities of treatment. ‎This illness causes many problems in the families and imposes a considerable economic burden ‎on governments and families. Purpose: The present research aimed at determining the ‎effectiveness of group training using Gross model-based emotion regulation strategies in ‎reducing suicidal ideation in patients with major depression who had attempted suicide. ‎ Methods: In this research, a quasi-experimental pretest posttest design with a control group was used. ‎Statistical population included patients with major depression disorder who had attempted ‎suicide and were referred to centers of psychotherapy in the city of Bushehr. From the statistical ‎population, 20 volunteers were selected and randomly assigned to two equal groups (treatment ‎and control). Following that, eight sessions of group training using Gross model-based emotion ‎regulation strategies was run on the treatment group twice a week each 90 minutes. The sessions ‎were designed based on raising conscientiousness, detecting stressful situations and promoting ‎behavioral components such as individual growth and adaptability. In this sessions, ‎communication, conceptualization, awareness and managing positive and negative emotions ‎were instructed. Individuals were supposed to learn how to comprehend the difference between ‎types of emotional functioning, communicate with others, and regulate their mood and ‎emotions. Training on emotional drain, relaxation and reverse action and finally, assessing and ‎applying learned skills in natural situations were not included in the sessions. The control group ‎did not receive any intervention.‎ Results: Findings revealed that suicidal ideation was less in the treatment group than the control group ‎and the difference was statistically significant (p-value<0.001). ‎ Conclusion: Difficulty in regulating emotions is one of the problems patients with major depression tackle ‎with. Training such patients how to express and manage emotions can help reducing their ‎problems. Therefore, it can be resulted that Gross model-based emotion regulation strategies is ‎effective on decreasing suicidal ideation in patients with major depression and can increase ‎their power of coping and adaptation.‎

Building Functional Nanodevices with Vesicle-Templated Porous Polymer Nanocapsules.

Vesicle-templated nanocapsules offer a unique combination of properties enabled by robust shells with single-nanometer thickness containing programmed uniform pores capable of fast and selective mass transfer. These capsules emerged as a versatile platform for creating functional devices, such as nanoreactors, nanosensors, and containers for the delivery of drugs and imaging agents. Nanocapsules are synthesized by a directed assembly method using self-assembled bilayers of vesicles as temporary scaffolds. In this approach, hydrophobic building blocks are loaded into the hydrophobic interior of vesicles formed from lipids or surfactants. Pore-forming templates are codissolved with the monomers and cross-linkers in the interior of the bilayer. The polymerization forms a cross-linked shell with embedded pore-forming templates. Removal of the surfactant scaffold and pore-forming templates leads to free-standing nanocapsules with shells containing uniform imprinted nanopores. Development of reliable and scalable synthetic methods for the modular construction of capsules with tunable properties has opened the opportunity to pursue practical applications of nanocapsules. In this Account, we discuss how unique properties of vesicle-templated nanocapsules translate into the creation of functional nanodevices. Specifically, we focus the conversation on applications aiming at the delivery of drugs and imaging agents, creation of fast-acting and selective nanoreactors, and fabrication of nanoprobes for sensing and imaging. We present a brief overview of the synthesis of nanocapsules with an emphasis on recent developments leading to robust synthetic methods including the synthesis under physiological conditions and creation of biodegradable nanocapsules. We then highlight unique properties of nanocapsules essential for practical applications, such as precise control of pore size and chemical environment, selective permeability, and ultrafast transport through the pores. We discuss new motifs for catch and release of small molecules with porous nanocapsules based on controlling the microenvironment inside the nanocapsules, regulating the charge on the orifice of nanopores in the shells, and reversible synergistic action of host and guest forming a supramolecular complex in nanocapsules. We demonstrate successful creation of fast-acting and selective nanoreactors by encapsulation of diverse homogeneous and nanoparticle catalysts. Due to unhindered flow of substrates and products through the nanopores, encapsulation did not compromise catalytic efficiency and, in fact, improved the stability of entrapped catalysts. We present robust nanoprobes based on nanocapsules with entrapped sensing agents and show how the encapsulation resulted in selective measurements with fast response times in challenging conditions, such as small volumes and complex mixtures. Throughout this Account, we highlight the advantages of encapsulation and discuss the opportunities for future design of nanodevices.

The reverse logistics helping to reduce costs of raw material in a pressure aluminum casting

AbstractThis paper analyzes the influence of an aluminum smelter of reverse logistics on its reuse of domestic raw materials. It also analyzes reverse logistics financial impact on the smelter, and how reverse logistics can help reduce the purchase of raw materials, which optimizes inventory and controls costs. In addition to environmental savings, it is also possible for reverse logistics to make an organization more powerful in the competitive market. This case study was carried out based on a review of the literature on policies, programs, regulations and laws, as well as on related work in reverse logistics, particularly related to the recycling of aluminum recycling. The reverse logistics actions by the company analyzed in this study achieved annual savings (in U.S. dollars [US$]) of US$ 68,437.70. The study shows that a well‐managed reverse logistics program can be effective and can reduce phases within the organization, achieving not only considerable savings in financial resources but also constituting a social responsibility action.

Description and Intrarater Test-Retest Reliability of a Reverse-Action Method to Assess Ankle Evertor Muscle Performance: The I-to-V Test.

Purpose: Reverse action (RA) of the ankle evertor muscle is when the proximal attachment moves toward the distal attachment, moving the lower leg in the frontal plane when the foot and ankle are fixed on the ground and inducing ankle eversion. The purpose of this study was to describe an RA method for measuring ankle evertor muscle performance. Method: Eighteen healthy individuals were recruited for this study. To assess the RA of their ankle evertors, the participants sat with their knees together and their feet firmly planted on the floor, then spread their knees as far apart as possible. A tester used a measuring tape to measured the distance (in cm) between the medial tibial tuberosity of the tested side and that of the non-tested side. In the end range position of the RA, ankle evertor electromyographic activity was recorded simultaneously. The intra-class correlation coefficient (ICC) and standard error of measurement (SEM) were calculated to establish the intrarater test-retest reliability. The correlation between each performance value and muscle activity was assessed using a linear correlation model. Results: The proposed method of assessing RA performance was highly reliable (ICC=0.95) and had a low SEM (1.63 cm); in addition, the performance value showed a strong positive correlation with ankle evertor muscle activity (ρ=0.90; 95% CI: 0.79, 0.95; p=0.01). Conclusions: The proposed RA method of assessing the ankle evertor muscles can be used as a simple, reliable, economical performance test. It can also be used as an alternate method of testing the peroneal muscles rather than selectively measuring ankle evertor performance because hip external rotation occurs when performing RA.

Transynaptic Action of Botulinum Neurotoxin Type A at Central Cholinergic Boutons.

Botulinum neurotoxin Type A (BoNT/A) is an effective treatment for several movement disorders, including spasticity and dystonia. BoNT/A acts by cleaving synaptosomal-associated protein of 25 kDa (SNAP-25) at the neuromuscular junction, thus blocking synaptic transmission and weakening overactive muscles. However, not all the therapeutic benefits of the neurotoxin are explained by peripheral neuroparalysis, suggesting an action of BoNT/A on central circuits. Currently, the specific targets of BoNT/A central activity remain unclear. Here, we show that catalytically active BoNT/A is transported to the facial nucleus (FN) after injection into the nasolabial musculature of rats and mice. BoNT/A-mediated cleavage of SNAP-25 in the FN is prevented by intracerebroventricular delivery of antitoxin antibodies, demonstrating that BoNT/A physically leaves the motoneurons to enter second-order neurons. Analysis of intoxicated terminals within the FN shows that BoNT/A is transcytosed preferentially into cholinergic synapses. The cholinergic boutons containing cleaved SNAP-25 are associated with a larger size, suggesting impaired neuroexocytosis. Together, the present findings indicate a previously unrecognized source of reduced motoneuron drive after BoNT/A via blockade of central, excitatory cholinergic inputs. These data highlight the ability of BoNT/A to selectively target and modulate specific central circuits, with consequent impact on its therapeutic effectiveness in movement disorders.SIGNIFICANCE STATEMENT Botulinum neurotoxins are among the most potent toxins known. Despite this, their specific and reversible action prompted their use in clinical practice to treat several neuromuscular pathologies (dystonia, spasticity, muscle spasms) characterized by hyperexcitability of peripheral nerve terminals or even in nonpathological applications (i.e., cosmetic use). Substantial experimental and clinical evidence indicates that not all botulinum neurotoxin Type A (BoNT/A) effects can be explained solely by the local action (i.e., silencing of the neuromuscular junction). In particular, there are cases in which the clinical benefit exceeds the duration of peripheral neurotransmission blockade. In this study, we demonstrate that BoNT/A is transported to facial motoneurons, released, and internalized preferentially into cholinergic terminals impinging onto the motoneurons. Our data demonstrate a direct central action of BoNT/A.

Abstract 3905: Strategic combination of the cyclin-dependent kinase inhibitor CYC065 with venetoclax to target anti-apoptotic proteins in chronic lymphocytic leukemia

Abstract CYC065 is a cyclin-dependent kinase (Cdk) inhibitor that is highly selective towards Cdk2 and Cdk9. In chronic lymphocytic leukemia (CLL), a disease that is addicted to the over-expression of anti-apoptotic proteins for survival, inhibition of Cdk9 by CYC065 reduced phosphorylation of the C-terminal domain of RNA polymerase II and blocked transcription. These actions depleted the intrinsically short-lived anti-apoptotic protein Mcl-1, but not Bcl-2, and induced apoptosis in CLL cells in vitro. The IC50 for CYC065-induced CLL cell death after a 24-hr incubation was 0.8 μM, a concentration that is achievable in the clinic at tolerated doses. CYC065 killed the CLL cells equally efficiently in the presence or absence of the human stromal cell line, StromaNKtert, and with or without a stimulation condition that mimics the lymphoid tissue microenvironment (anti-IgM, anti-CD-40, IL-4). Venetoclax, which specifically inhibits Bcl-2 function, is approved for treatment of CLL with del(17p); however upregulation of Mcl-1 is associated with resistance to venetoclax in the lymph nodes. Therefore, we hypothesized that the combination of CYC065 with venetoclax would target the parallel mechanisms that promote the survival control in CLL cells, and induce synergistic cell death by apoptosis. A time course study of the single agents showed that under conditions that mimic the lymph node microenvironment, cell death induction by venetoclax required 6-8 hr to reach the plateau of cell killing and maximal killing by CYC065 occurred after 24 hr, consistent with the different mechanisms of action of the two compounds. Following the removal of CYC065 or venetoclax after 4, 8, 12, or 24 hr incubations, there was no evidence for additional cell death after an additional 48 hr in drug-free medium regardless of the duration of drug incubation. Immunoblots showed recovery of RNA pol II phosphorylation, and restored Mcl-1 expression upon washout of CYC065. The reversible action of these compounds has potential implications for clinical scheduling combining these compounds. Median effect analysis indicated that CYC065 and venetoclax combined synergistically in CLL samples with or without 17p deletion. A dose reduction analysis confirmed mutual potentiation of each other when combined. Combination of IC50 concentrations of CYC065 and venetoclax for 24 hr was sufficient to decrease the viability of CLL cells by over 90% in the lymph node mimicking microenvironment. Thus, these data provided rationale for clinical combination of CYC065 and venetoclax in CLL. CYC065 is currently in a Phase I clinical trial in patients with advanced solid tumors (NCT02552953) using an intermittent dosing regimen which causes at least 24 hr Mcl-1 downregulation in patient PBMCs at well tolerated dose levels. Citation Format: Rong Chen, Yuling Chen, Sheelagh Frame, David Blake, William G. Wierda, Daniella Zheleva, William Plunkett. Strategic combination of the cyclin-dependent kinase inhibitor CYC065 with venetoclax to target anti-apoptotic proteins in chronic lymphocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3905.

Potent block of potassium channels by MEK inhibitor U0126 in primary cultures and brain slices

U0126 (1,4-diamino-2,3-dicyano-1,4-bis (2-aminophenylthio) butadiene), a widely used mitogen-activated protein kinase kinase (MEK) inhibitor, was found to accelerate voltage-gated K+ channel (KV) inactivation in heterologous cells expressing several types of KV. The goal of this study was to examine whether U0126 at a concentration thought to specifically inhibit MEK signaling also inhibits KV in native neurons of primary cultures or brain slices. U0126 caused a dose-dependent inhibition of both the transient (IA) and sustained (IDR) components of K+ currents in hippocampal neurons. U0126 also exhibited much higher potency on the IA and IDR than the classical KV blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Consistent with its inhibitory effect on KV, U0126 broadened action potential duration, profoundly affected the repolarizing phase, and dramatically reduced firing frequency in response to current pulse injections. Despite the potent and reversible action of U0126 on Kv channels, PD98059, a structurally-unrelated MEK inhibitor, did not induce such an effect, suggesting U0126 may act independently of MEK inhibition. Together, these results raise cautions for using U0126 as a specific inhibitor for studying MEK signaling in neurons; on the other hand, further studies on the blocking mechanisms of U0126 as a potent inhibitor of KV may provide useful insights into the structure-function relationship of KV in general.

Single-Chain Glycopolymer Folding via Host-Guest Interactions and Its Unprecedented Effect on DC-SIGN Binding.

Reversible self-folding actions of natural biomacromolecules play crucial roles for specific and unique biological functions in Nature. Hence, controlled folding of single polymer chains has attracted significant attention in recent years. Herein, reversible single-chain folded glycopolymer structures in α-shape with different density of sugar moieties in the knot were created. The influence of folding as well as the sugar density in the knot was investigated on the binding capability with lectins, such as ConA, DC-SIGN, and DC-SIGNR. The synthesis of triblock glycocopolymers bearing β-CD and adamantane for the host-guest interaction and also mannose residues for the lectin interaction was achieved using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique. The reversible single-chain folding of glycopolymers was achieved under a high dilution of an aqueous solution and the self-assembled folding was monitored by 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR and dynamic light scattering. The lectin binding profiles consistently provided an unprecedented effect of single chain folding as the single-chain folded structures enhanced greatly the binding ability in comparison to the unfolded linear structures.

Ionic Liquid Functionalized Cathode Catalyst Support for Carbon Dioxide Conversion Using Proton Exchange Membrane Fuel Cell

Carbon dioxide is a major anthropogenic greenhouse gas produced primarily from combustion of fossil fuels (coal, natural gas and oil), automobile emission and from industrial exhausts that has posed a huge danger for the environment in recent times. About 81 % of the overall greenhouse gases production is contributed by CO2. Electroreduction of CO2 into useful fuels has gained huge attention in the past few years. The advantage of polymer electrolyte membranes (PEM) is already well recognized in fuel cells. The reverse action of fuel cell can be employed for protonation of CO2 to fuels, which has an advantage in prevention of products from re-oxidation. Several studies on PEM cell based electrochemical conversion of CO2 into useful hydrocarbons have been reported. In this particular work, we aim to convert CO2 into some useful nontoxic hydrocarbon using proton exchange membrane fuel cell by selectively functionalizing the cathode catalyst support material. Room temperature ionic liquids exhibit some significant properties, which owe to their popularity such as low vapour pressure, high chemical and thermal stability, tunable properties, good ionic conductivity and high CO2 solubility. Due to their negligible vapour pressure and nonflamability, they are often called “green solvents”. The cathode catalyst support used in this present work is iron carbide encapsulated nitrogen doped carbon nanotubes, which is anticipated to increase both the CO2 reduction and catalytic activity of cathode electrode. Further, surface functionalization of the cathode catalyst support with ionic liquid moieties and dispersion of Pt catalytic nanoparticles were performed to use in a Proton Exchange Membrane (PEM) CO2 conversion cell. The ionic functionalized sample shows better CO2 reduction than the pure support material due to improved interaction of the ionic functionalized catalyst with CO2 molecules and also facilitates the reaction kinetics due to the presence of high electrical conductivity and preferable catalytic sites. Moreover, Fe containing precursors also participate in CO2 electroreduction. The present investigation describes the synergistic effect of Fe as well as nitrogen doped ionic functionalized CNT for electrochemical reduction of CO2.

AKTIVITAS PERDAGANGAN SAHAM SEBELUM DAN SESUDAH PERUSAHAAN MELAKUKAN PEMECAHAN SAHAM DAN PENGGABUNGAN SAHAM DI BURSA EFEK INDONESIA TAHUN 2014-2016 (Studi Komparatif Pada Harga, Likuiditas, Volume dan Frekuensi Perdagangan Saham)

This research uses 11 day observation method 5 days before stock split / reversesplit, 1 day as observation method, and 5 days after stock split / reverse split event. Dataanalysis method used is paired sample different test. After testing the normality there are2 tests that is different test method wilcoxon signed rank test to test stock trading activityon companies doing stock split action and test method different paired sample t-test totest stock trading activity in company doing reverse split. showed no price difference,liquidity, volume and frequency of shares for companies doing reverse split action. Thisshows that stock split action does have a positive signal to attract investors, while StockLikuidity (stock split) and reverse split action are not.

Interaction of a Gas Flow Carrying Nonspherical Microparticles with a Cross Cylinder

A model of the dynamics of the particles-spheroids carried by a gas flow over a cross cylindrical body and rebounding from it has been developed. In this model, the gas flow around the particles is assumed to be viscous, and the reverse action of the particles on the gas and the collisions between them are not taken into account. The coefficients of recovery of the velocity components of the particles rebounded from the cylinder were determined on the basis of the heuristic theory in which the physical and mechanical properties of colliding bodies are considered. The influence of the ratio between the axes of particles-spheroids on the coefficient of wetting of the cylinder by them, the distributions of the mass-flow density of the particles and their velocity components over the cylinder surface, and the spatial distribution of the indicated quantities of the rotating particles rebounded from the cylinder was investigated numerically. The model proposed can be used for estimating the action of ice microcrystals and particles of volcanic ash emissions and dust storms on the structural elements of aircraft engines and small-size flying vehicles.

Modelling reversible execution of robotic assembly

SUMMARYProgramming robotic assembly for industrial small-batch production is challenging; hence, it is vital to increase robustness and reduce development effort in order to achieve flexible robotic automation. A human who has made an assembly error will often simply undo the process until the error is undone and then restart the assembly. Conceptually, robots could do the same. This paper introduces a programming model that enables robot assembly programs to be executed in reverse. We investigate the challenges in running robot programs backwards and present a classification of reversibility characteristics. We demonstrate how temporarily switching the direction of program execution can be an efficient error recovery mechanism. Moreover, we demonstrate additional benefits arising from supporting reversibility in an assembly language, such as increased code reuse and automatically derived disassembly sequences. As a default approach to reversibility, we use program inversion and statement-level inversion of commands, but with a novel override option providing alternative sequences for asymmetric reverse actions. To efficiently program for this model, this paper introduces a new domain-specific language, SCP-RASQ (Simple C++ Reversible Assembly SeQuences). In initial experiments, where 200 consecutive assemblies of two industrial cases were performed, 18 of 22 errors were corrected automatically using only the trial-and-error capabilities that come from reverse execution.

Robust Persistence and Permanence of Polynomial and Power Law Dynamical Systems

A persistent dynamical system in $\mathbb{R}^d_{> 0}$ is one whose solutions have positive lower bounds for large $t$, while a permanent dynamical system in $\mathbb{R}^d_{> 0}$ is one whose solutions have uniform upper and lower bounds for large $t$. These properties have important applications for the study of mathematical models in biochemistry, cell biology, and ecology. Inspired by reaction network theory, we define a class of polynomial dynamical systems called tropically endotactic. We show that two-dimensional tropically endotactic polynomial dynamical systems are permanent, regardless of the values of (possibly time-dependent) parameters in these systems. These results generalize the permanence of two-dimensional reversible, weakly reversible, and endotactic mass action systems.

Impact of co-exposure of aldrin and titanium dioxide nanoparticles at biochemical and molecular levels in Zebrafish

Aldrin (ALD), a persistent-organic-pollutant (POP), an organochlorine-cyclodiene-pesticide is highly toxic in nature. Titanium dioxide nanoparticles (TNP) are widely used for various industrial applications. Despite the remarkable research on pesticide toxicity, the work with impact of nanoparticles on POP has been dealt with marginally. Chemicals co-exist in the environment and exhibit interactive effects. An investigation was carried out to evaluate the individual and combined effects of ALD (6 ppm) and TNP (60 ppm) exposure at sub-lethal concentration for 24 h in zebrafish. Significant reversal of lipid peroxidation level in liver and brain tissues and restoration in enhanced catalase activity in all examined tissues were observed in combined group. For other parameters, combined exposure of ALD and TNP does not show significant reversal action on ALD toxicity. Further studies are inline to understand combined effects of both to achieve significant reversal of ALD toxicity by TNP nanoparticles with threshold concentration of aldrin.

Effect of outdoor exposure on the moisture diffusion and mechanical properties of epoxy polymers

Specimens of epoxy polymers of four compositions based on 2,2 di-(4-hydroxyphenyl) propane cured by a cycloaliphatic amine hardener were exposed during 3, 6, 9, and 12 months on an open bench in a moderately warm marine climate of Gelendzhik. In the initial state and at various stages of exposure the moisture diffusion coefficient and maximum moisture content of flat rectangular specimens-coupons are determined for drying and humidification at a temperature of 60 °C. Properties of polymers in three states have been studied: after a stop of climatic tests without conditioning and after additional stages of humidification and drying using stress-strain tensile tests, dynamic mechanical analysis, optical microscopy, fractography. After the exposure in the climatic conditions, different amounts of moisture accumulate in the specimens depending on relative air humidity and precipitation amounts in different year seasons. At the drying stage, moisture transfer obeys Fick's second law. At the humidification stage, a change of mass of specimens depends on sorption of moisture and desorption of hydrolysis products. Tensile strength decreases after the climatic action and differs by a value of 20–66% for the dried and moistened specimens. A method of dynamic mechanical analysis revealed processes of post-curing and destruction depending on the polymer composition and duration of exposure. The humidification also affected a failure mode of specimens. In the initial state and after different exposure times in open climatic conditions after the humidification on fractographs an area of a mirror zone corresponding to plastic fracture increases. After drying, an area of a rough (relief) zone increases. It is shown that in order to obtain reliable information about mechanisms of climatic aging of epoxy polymers it is necessary to compare the properties of controlled specimens taking into account the moisture content to determine a degree of reversible plasticizing action of moisture against the background of irreversible changes.

Abstract P219: Vascular Cross-talk Between Redox and Calcium Signaling in Hypertension Involves Transient Receptor Potential Melastatin 2 Channel Activation

The transient receptor potential melastatin 2 cation channel (TRPM2) is redox-sensitive and promotes Ca 2+ influx after H 2 O 2 activation through oxidative modification and PARP-ADPR-dependent mechanisms. TRPM2 also regulates Na + influx, and by increasing [Na + ]i interferes with the Na + -Ca 2+ exchanger (NCX) inducing reverse mode action, promoting Ca 2+ influx. These processes may be driven by Nox4-derived H 2 O 2. We tested the hypothesis that vascular dysfunction in hypertension involves oxidative stress-induced TRPM2 activation through H 2 O 2 production, which in turn promotes Ca 2+ influx. Mesenteric arteries isolated from wildtype (WT), LinA3 (mice expressing human renin with Ang II-dependent hypertension), Nox4 -/- and LinA3/Nox4 -/- mice and vascular smooth muscle cells (VSMCs) from hypertensive and normotensive patients were used. Arteries from hypertensive LinA3 mice, exhibit increased U46619-induced vasoconstriction versus WT mice (Emax - LinA3 vs WT: 9.37 ± 0.51 vs 6.79 ± 0.29), an effect attenuated by olaparib (PARP-ADPR inhibitor) and 2-APB (TRPM2 blocker) and also increased mRNA expression (Fold change - related to control) of NOX4 (3.05 ± 0.30), TRPM2 (1.38 ± 0.24), NCX (1.973 ± 0.34) and salt inducible kinase 1 (1.833 ± 0.12) and sodium-potassium pump (1.43 ± 0.16), which are activated when intracellular levels of Na + rise beyond a critical point. These events seem to be regulated by NOX4, since they were not observed in mesenteric arteries from LinA3/Nox4 -/- mice. Ang II-induced Ca 2+ influx is potentiated in VSMCs from hypertensive patients (AUC-Ex490/Em535: normotensive: 15400±917.5 vs hypertensive - 22460±2388), a response followed by increased generation of O 2 - and H 2 O 2 in cells from hypertensive patients. These ROS effects were attenuated by catalase, and 2-APB, 8-br and olaparib (TRPM2 inhibitors) and benzamil, KB-R7943 and YM244769 (NCX inhibitors). Our data indicate that TRPM2 ion channel activation contributes to redox-sensitive vascular dysfunction in hypertension. These findings suggest that dysregulation of TRPM2-NOX4-derived ROS and NCX may contribute to redox- and Ca 2+ signalling important in vascular function in hypertension. TRPM2 may be a point of cross-talk between ROS and Ca 2+ signalling.

Safety, Rehabilitation and Seismic Improvement of San Silvestro’s Church in Crevalcore (BO), after 2012 Seismic Event in Emilia

The design and realization of seismic improvement interventions have proceeded a logic and temporal process: first at all the damage analysis, safety compatible and reversible actions, detailed surveys and direct and historic-documental investigations concerning typologies, geometries, materials and building’s damages; analysis of vulnerability and seismic improvement design of interventions, all approved by Regional Seismic Service and Superintendence of Cultural Heritage; lastly, realization of works according to the project and the law, the quality and the prescriptions of control authorities. The interventions have respected principal design’s purposes, in synthesis: 60% of seismic improvement to the actual laws, even if not compulsory for an heritage building; compatible materials with the originals under the mechanical, physical and chemical aspect; reversible structural interventions respectful to the artefact behaviour before the realization and focused to not modify the spatial, material and chromatic aspect of architectural complex. The principal structural interventions are: restoration, partial rebuilding and reinforcing of groin vaults, mechanical anchors and ringing elements; restoration of load bearing wall elements and improvement of their mechanical characteristics.

Abstract LB-268: Rate of temporal citrate efflux from malignant mitochondria predicts clinical aggressiveness in breast tumors

Abstract Background: Mitochondrial citrate has been shown to serve as a central substrate for many cytosolic processes critical for tumor progression. Experiments with stable isotopes and mass spectrometry have been used for this conclusion, but fixed pools of metabolites yielding from those studies do not help us understand kinetics of subcellular metabolic fluxes. New methods are necessary for such measurements. In clinical setting, luminal-A subtype of breast cancer progresses slower than triple negative subtype and we hypothesize that mitochondrial citrate efflux in more aggressive tumors must be greater than that in slow-growing tumors to support the faster progression. Methods: New permeabilization-based method for quantifying time-dependent mitochondrial fluxes was developed. Luminal-A type MCF7 and triple negative MDA-MB-231 cell lines were used; excised primary tumors were used from human subjects (luminal-A n=21, triple negative n=10). Mitochondrial substrate-to-citrate efflux was measured using glutamate (GM), pyruvate (PV) or palmitoylcarnitine (PC) as substrates. Finally, samples were analyzed using HPLC or UV-spectroscopy. Summary: Mitochondrial GM-to-citrate efflux in less aggressive MCF7 cells was 91.5% lower than that in the faster growing MDA-MB-231 cells (4.1 vs. 48.4 ng/min*106cell, respectively). Difference in PV-to-citrate efflux was smaller, yielding 25.0% lower result for MCF7 compared to MDA-MB-231. An opposite result was observed for PC-to-citrate efflux as the conversion of PC was 20.1% higher in MCF7 cells compared to MDA-MB-231. Significant amount of cytosolic GM-to-citrate was measured only for MDA-MB-231, possibly a result of reverse IDH1 action. In primary tumor samples from breast cancer patients, mitochondrial GM-to-citrate efflux in luminal-A subtype was 27.4% lower than that in more aggressive triple-negative subtype (92.9 vs. 127.9 ng/h*mg, respectively). The respective differences were 24.7% for PV-to-citrate efflux and 8.2% for PC-to-citrate. Conclusions: Here we showed for the first time that temporal mitochondrial fluxes can be directly quantified in cell lines and clinical tumors. Results from the new method showed that less aggressive breast cancer samples have significantly lower mitochondrial citrate efflux and GM-to-citrate increases the most as aggressiveness increases. Clinical cancer samples showed heterogeneity in citrate profile and it can be an addition in predicting individual disease progression as standard subtype is often not sufficient for it. Further studies are warranted to expand the use of this method to other mitochondrial targets (e.g. fluxes of folate or glutamine metabolism) and to conduct studies in tumor types other than breast cancer where usable aggressiveness markers are missing. In addition, suitability of this method for predicting tumor response to mitochondrial cancer drugs will be evaluated. Citation Format: Andre Koit, Natalja Timohhina, Vladimir Chekulayev, Vahur Valvere, Tuuli Kaambre. Rate of temporal citrate efflux from malignant mitochondria predicts clinical aggressiveness in breast tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-268. doi:10.1158/1538-7445.AM2017-LB-268