Physical stabilization of low-molecular-weight amorphous drugs in the solid state: a material science approach.

PubMed

Qi, Sheng; McAuley, William J; Yang, Ziyi; Tipduangta, Pratchaya

2014-07-01

Use of the amorphous state is considered to be one of the most effective approaches for improving the dissolution and subsequent oral bioavailability of poorly water-soluble drugs. However as the amorphous state has much higher physical instability in comparison with its crystalline counterpart, stabilization of amorphous drugs in a solid-dosage form presents a major challenge to formulators. The currently used approaches for stabilizing amorphous drug are discussed in this article with respect to their preparation, mechanism of stabilization and limitations. In order to realize the potential of amorphous formulations, significant efforts are required to enable the prediction of formulation performance. This will facilitate the development of computational tools that can inform a rapid and rational formulation development process for amorphous drugs.

Stabilized TiN nanowire arrays for high-performance and flexible supercapacitors.

PubMed

Lu, Xihong; Wang, Gongming; Zhai, Teng; Yu, Minghao; Xie, Shilei; Ling, Yichuan; Liang, Chaolun; Tong, Yexiang; Li, Yat

2012-10-10

Metal nitrides have received increasing attention as electrode materials for high-performance supercapacitors (SCs). However, most of them are suffered from poor cycling stability. Here we use TiN as an example to elucidate the mechanism causing the capacitance loss. X-ray photoelectron spectroscopy analyses revealed that the instability is due to the irreversible electrochemical oxidation of TiN during the charging/discharging process. Significantly, we demonstrate for the first time that TiN can be stabilized without sacrificing its electrochemical performance by using poly(vinyl alcohol) (PVA)/KOH gel as the electrolyte. The polymer electrolyte suppresses the oxidation reaction on electrode surface. Electrochemical studies showed that the TiN solid-state SCs exhibit extraordinary stability up to 15,000 cycles and achieved a high volumetric energy density of 0.05 mWh/cm(3). The capability of effectively stabilizing nitride materials could open up new opportunities in developing high-performance and flexible SCs.

Practical Methodology for the Inclusion of Nonlinear Slosh Damping in the Stability Analysis of Liquid-Propelled Space Vehicles

NASA Technical Reports Server (NTRS)

Ottander, John A.; Hall, Robert A.; Powers, J. F.

2018-01-01

A method is presented that allows for the prediction of the magnitude of limit cycles due to adverse control-slosh interaction in liquid propelled space vehicles using non-linear slosh damping. Such a method is an alternative to the industry practice of assuming linear damping and relying on: mechanical slosh baffles to achieve desired stability margins; accepting minimal slosh stability margins; or time domain non-linear analysis to accept time periods of poor stability. Sinusoidal input describing functional analysis is used to develop a relationship between the non-linear slosh damping and an equivalent linear damping at a given slosh amplitude. In addition, a more accurate analytical prediction of the danger zone for slosh mass locations in a vehicle under proportional and derivative attitude control is presented. This method is used in the control-slosh stability analysis of the NASA Space Launch System.

Stability and Reactivity: Positive and Negative Aspects for Nanoparticle Processing.

PubMed

Xu, Liang; Liang, Hai-Wei; Yang, Yuan; Yu, Shu-Hong

2018-04-11

Nanoparticles exist far from the equilibrium state due to their high surface energy. Nanoparticles are therefore extremely unstable and easily change themselves or react with active substances to reach a relatively stable state in some cases. This causes desired changes or undesired changes to nanoparticles and thus makes them exhibit a high reactivity and a poor stability. Such dual nature (poor stability and high reactivity) of nanoparticles may result in both negative and positive effects for nanoparticle processing. However, the existing studies mainly focus on the high reactivity of nanoparticles, whereas their poor stability has been neglected or considered inconsequential. In fact, in some cases the unstable process, which is derived from the poor stability of nanoparticles, offers an opportunity to design and fabricate unique nanomaterials, such as by chemically transforming the "captured" intermediate nanostructures during a changing process, assembling destabilized nanoparticles into larger ordered assemblies, or shrinking/processing pristine materials into the desired size or shape via selective etching. In this review, we aim to present the stability and reactivity of nanoparticles on three levels: the foundation, concrete manifestations, and applications. We start with a brief introduction of dangling bonds and the surface chemistry of nanoparticles. Then, concrete manifestations of the poor stability and high reactivity of nanoparticles are presented from four perspectives: dispersion stability, thermal stability, structural stability, and chemical stability/reactivity. Next, we discuss some issues regarding the stability and reactivity of nanomaterials during applications. Finally, conclusions and perspectives on this field are presented.

Shaped Apertures in Photoresist Films Enhance the Lifetime and Mechanical Stability of Suspended Lipid Bilayers

PubMed Central

Kalsi, Sumit; Powl, Andrew M.; Wallace, B.A.; Morgan, Hywel; de Planque, Maurits R.R.

2014-01-01

Planar lipid bilayers suspended in apertures provide a controlled environment for ion channel studies. However, short lifetimes and poor mechanical stability of suspended bilayers limit the experimental throughput of bilayer electrophysiology experiments. Although bilayers are more stable in smaller apertures, ion channel incorporation through vesicle fusion with the suspended bilayer becomes increasingly difficult. In an alternative bilayer stabilization approach, we have developed shaped apertures in SU8 photoresist that have tapered sidewalls and a minimum diameter between 60 and 100 μm. Bilayers formed at the thin tip of these shaped apertures, either with the painting or the folding method, display drastically increased lifetimes, typically >20 h, and mechanical stability, being able to withstand extensive perturbation of the buffer solution. Single-channel electrical recordings of the peptide alamethicin and of the proteoliposome-delivered potassium channel KcsA demonstrate channel conductance with low noise, made possible by the small capacitance of the 50 μm thick SU8 septum, which is only thinned around the aperture, and unimpeded proteoliposome fusion, enabled by the large aperture diameter. We anticipate that these shaped apertures with micrometer edge thickness can substantially enhance the throughput of channel characterization by bilayer lipid membrane electrophysiology, especially in combination with automated parallel bilayer platforms. PMID:24739164

Effect of Isomorphous Substitution on the Thermal Decomposition Mechanism of Hydrotalcites

PubMed Central

Crosby, Sergio; Tran, Doanh; Cocke, David; Duraia, El-Shazly M.; Beall, Gary W.

2014-01-01

Hydrotalcites have many important applications in catalysis, wastewater treatment, gene delivery and polymer stabilization, all depending on preparation history and treatment scenarios. In catalysis and polymer stabilization, thermal decomposition is of great importance. Hydrotalcites form easily with atmospheric carbon dioxide and often interfere with the study of other anion containing systems, particularly if formed at room temperature. The dehydroxylation and decomposition of carbonate occurs simultaneously, making it difficult to distinguish the dehydroxylation mechanisms directly. To date, the majority of work on understanding the decomposition mechanism has utilized hydrotalcite precipitated at room temperature. In this study, evolved gas analysis combined with thermal analysis has been used to show that CO2 contamination is problematic in materials being formed at RT that are poorly crystalline. This has led to some dispute as to the nature of the dehydroxylation mechanism. In this paper, data for the thermal decomposition of the chloride form of hydrotalcite are reported. In addition, carbonate-free hydrotalcites have been synthesized with different charge densities and at different growth temperatures. This combination of parameters has allowed a better understanding of the mechanism of dehydroxylation and the role that isomorphous substitution plays in these mechanisms to be delineated. In addition, the effect of anion type on thermal stability is also reported. A stepwise dehydroxylation model is proposed that is mediated by the level of aluminum substitution. PMID:28788231

First principles study on electrochemical and chemical stability of solid electrolyte–electrode interfaces in all-solid-state Li-ion batteries

DOE PAGES

Zhu, Yizhou; He, Xingfeng; Mo, Yifei

2015-12-11

All-solid-state Li-ion batteries based on ceramic solid electrolyte materials are a promising next-generation energy storage technology with high energy density and enhanced cycle life. The poor interfacial conductance is one of the key limitations in enabling all-solid-state Li-ion batteries. However, the origin of this poor conductance has not been understood, and there is limited knowledge about the solid electrolyte–electrode interfaces in all-solid-state Li-ion batteries. In this paper, we performed first principles calculations to evaluate the thermodynamics of the interfaces between solid electrolyte and electrode materials and to identify the chemical and electrochemical stabilities of these interfaces. Our computation results revealmore » that many solid electrolyte–electrode interfaces have limited chemical and electrochemical stability, and that the formation of interphase layers is thermodynamically favorable at these interfaces. These formed interphase layers with different properties significantly affect the electrochemical performance of all-solid-state Li-ion batteries. The mechanisms of applying interfacial coating layers to stabilize the interface and to reduce interfacial resistance are illustrated by our computation. This study demonstrates a computational scheme to evaluate the chemical and electrochemical stability of heterogeneous solid interfaces. Finally, the enhanced understanding of the interfacial phenomena provides the strategies of interface engineering to improve performances of all-solid-state Li-ion batteries.« less

Strong, ductile, and thermally stable Cu-based metal-intermetallic nanostructured composites.

PubMed

Dusoe, Keith J; Vijayan, Sriram; Bissell, Thomas R; Chen, Jie; Morley, Jack E; Valencia, Leopolodo; Dongare, Avinash M; Aindow, Mark; Lee, Seok-Woo

2017-01-09

Bulk metallic glasses (BMGs) and nanocrystalline metals (NMs) have been extensively investigated due to their superior strengths and elastic limits. Despite these excellent mechanical properties, low ductility at room temperature and poor microstructural stability at elevated temperatures often limit their practical applications. Thus, there is a need for a metallic material system that can overcome these performance limits of BMGs and NMs. Here, we present novel Cu-based metal-intermetallic nanostructured composites (MINCs), which exhibit high ultimate compressive strengths (over 2 GPa), high compressive failure strain (over 20%), and superior microstructural stability even at temperatures above the glass transition temperature of Cu-based BMGs. Rapid solidification produces a unique ultra-fine microstructure that contains a large volume fraction of Cu 5 Zr superlattice intermetallic compound; this contributes to the high strength and superior thermal stability. Mechanical and microstructural characterizations reveal that substantial accumulation of phase boundary sliding at metal/intermetallic interfaces accounts for the extensive ductility observed.

Stability and Evolution of Multiple Planet and Satellite Systems

NASA Astrophysics Data System (ADS)

Quillen, Alice

Numerous multiple planet systems have recently been discovered with the Kepler Mission, suggesting that multiple planet systems are common. Multiple- body nearly coplanar satellite systems are also found in the Solar system. Multiple planet and satellite systems exhibit rich dynamics as they are affected by three-body and secular resonances affecting short timescale behavior and long timescale stability. Interactions with debris disks and planetesimal belts and tidal interactions can both reduce and induce instability. Using both numerical and analytical studies, we propose to develop a broadly applicable framework to estimate diffusion rates and stability regimes both in resonant and non- resonant configurations. Understanding of resonant dynamics is needed to understand each of these systems and a broader general theory would cover scenarios and mechanisms that are relevant for all of them. Architectures and dynamical mechanisms will be used to test scenarios for formation and evolution of multiple body systems and constrain poorly known quantities such as masses, eccentricities, inclinations, radii, and the existence of undetected bodies.

Temperature-dependent spectroscopic evidences of curcumin in aqueous medium: a mechanistic study of its solubility and stability.

PubMed

Jagannathan, Ramya; Abraham, Priya Mary; Poddar, Pankaj

2012-12-20

In curcumin, keto-enol-enolate equilibrium of the heptadiene-dione moiety determines its physiochemical and antioxidant properties. However, its poor solubility in water at neutral pH and room temperature decreases its bioavailability. Potential therapeutic applications have triggered an interest in manipulating the solubility of curcumin in water as its stability and solubility in water remains poorly understood. Here, the mechanism behind its solubility at various temperatures and the influence of interplay of temperature, intramolecular H-bonding, and intermolecular forces is reported, which leads to aggregation-disaggregation at various temperatures. Remarkable change is observed in temperature-dependent electronic transition behavior of curcumin, however, the absorption spectra after cooling and heating cycles remain unchanged, hinting much better thermal stability of curcumin in water than previously thought. This study indicates that it is perhaps the breaking of intramolecular hydrogen bonding which leads to exposure of polar groups and hence responsible for the dissolution of curcumin at higher temperature. The formation of intermolecular aggregates might be responsible behind a better room temperature stability of the molecules after cooling its aqueous suspension from 90 to 25 °C. These curcumin solubility studies have great application in biological research with reference to bioavailability and to understand target oriented mode of action of curcumin.

Long-term stability and properties of zirconia ceramics for heavy duty diesel engine components

NASA Technical Reports Server (NTRS)

Larsen, D. C.; Adams, J. W.

1985-01-01

Physical, mechanical, and thermal properties of commercially available transformation-toughened zirconia are measured. Behavior is related to the material microstructure and phase assemblage. The stability of the materials is assessed after long-term exposure appropriate for diesel engine application. Properties measured included flexure strength, elastic modulus, fracture toughness, creep, thermal shock, thermal expansion, internal friction, and thermal diffusivity. Stability is assessed by measuring the residual property after 1000 hr/1000C static exposure. Additionally static fatigue and thermal fatigue testing is performed. Both yttria-stabilized and magnesia-stabilized materials are compared and contrasted. The major limitations of these materials are short term loss of properties with increasing temperature as the metastable tetragonal phase becomes more stable. Fine grain yttria-stabilized material (TZP) is higher strength and has a more stable microstructure with respect to overaging phenomena. The long-term limitation of Y-TZP is excessive creep deformation. Magnesia-stabilized PSZ has relatively poor stability at elevated temperature. Overaging, decomposition, and/or destabilization effects are observed. The major limitation of Mg-PSZ is controlling unwanted phase changes at elevated temperature.

IMP3 Stabilization of WNT5B mRNA Facilitates TAZ Activation in Breast Cancer.

PubMed

Samanta, Sanjoy; Guru, Santosh; Elaimy, Ameer L; Amante, John J; Ou, Jianhong; Yu, Jun; Zhu, Lihua J; Mercurio, Arthur M

2018-05-29

Insulin-like growth factor-2 mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with many aggressive cancers and implicated in the function of breast cancer stem cells (CSCs). The mechanisms involved, however, are poorly understood. We observed that IMP3 facilitates the activation of TAZ, a transcriptional co-activator of Hippo signaling that is necessary for the function of breast CSCs. The mechanism by which IMP3 activates TAZ involves both mRNA stability and transcriptional regulation. IMP3 stabilizes the mRNA of an alternative WNT ligand (WNT5B) indirectly by repressing miR145-5p, which targets WNT5B, resulting in TAZ activation by alternative WNT signaling. IMP3 also facilitates the transcription of SLUG, which is necessary for TAZ nuclear localization and activation, by a mechanism that is also mediated by WNT5B. These results demonstrate that TAZ can be regulated by an mRNA-binding protein and that this regulation involves the integration of Hippo and alternative WNT-signaling pathways. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Exploring the mechanisms of DNA hybridization on a surface

NASA Astrophysics Data System (ADS)

Schmitt, Terry J.; Rogers, J. Brandon; Knotts, Thomas A.

2013-01-01

DNA microarrays are a potentially disruptive technology in the medical field, but their use in such settings is limited by poor reliability. Microarrays work on the principle of hybridization and can only be as reliable as this process is robust, yet little is known at the molecular level about how the surface affects the hybridization process. This work uses advanced molecular simulation techniques and an experimentally parameterized coarse-grain model to determine the mechanism by which hybridization occurs on surfaces. The results show that hybridization proceeds through a mechanism where the untethered (target) strand often flips orientation. For evenly lengthed strands, the surface stabilizes hybridization (compared to the bulk system) by reducing the barriers involved in the flipping event. For unevenly lengthed strands, the surface destabilizes hybridization compared to the bulk, but the degree of destabilization is dependent on the location of the matching sequence. Taken as a whole, the results offer an unprecedented view into the hybridization process on surfaces and provide some insights as to the poor reproducibility exhibited by microarrays.

Why Do Lithium-Oxygen Batteries Fail: Parasitic Chemical Reactions and Their Synergistic Effect.

PubMed

Yao, Xiahui; Dong, Qi; Cheng, Qingmei; Wang, Dunwei

2016-09-12

As an electrochemical energy-storage technology with the highest theoretical capacity, lithium-oxygen batteries face critical challenges in terms of poor stabilities and low charge/discharge round-trip efficiencies. It is generally recognized that these issues are connected to the parasitic chemical reactions at the anode, electrolyte, and cathode. While the detailed mechanisms of these reactions have been studied separately, the possible synergistic effects between these reactions remain poorly understood. To fill in the knowledge gap, this Minireview examines literature reports on the parasitic chemical reactions and finds the reactive oxygen species a key chemical mediator that participates in or facilitates nearly all parasitic chemical reactions. Given the ubiquitous presence of oxygen in all test cells, this finding is important. It offers new insights into how to stabilize various components of lithium-oxygen batteries for high-performance operations and how to eventually materialize the full potentials of this promising technology. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Material and Device Stability in Perovskite Solar Cells.

PubMed

Kim, Hui-Seon; Seo, Ja-Young; Park, Nam-Gyu

2016-09-22

Organic-inorganic halide perovskite solar cells have attracted great attention because of their superb efficiency reaching 22 % and low-cost, facile fabrication processing. Nevertheless, stability issues in perovskite solar cells seem to block further advancements toward commercialization. Thus, device stability is one of the important topics in perovskite solar cell research. In the beginning, the poor moisture resistivity of the perovskite layer was considered as a main problem that hindered further development of perovskite solar cells, which encouraged engineering of the perovskite or protection of the perovskite by a buffer layer. Soon after, other parameters affecting long-term stability were sequentially found and various attempts have been made to enhance intrinsic and extrinsic stability. Here we review the recent progresses addressing stability issues in perovskite solar cells. In this report, we investigated factors affecting stability from material and device points of view. To gain a better understanding of the stability of the bulk perovskite material, decomposition mechanisms were investigated in relation to moisture, photons, and heat. Stability of full device should also be carefully examined because its stability is dependent not only on bulk perovskite but also on the interfaces and selective contacts. In addition, ion migration and current-voltage hysteresis were found to be closely related to stability. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quinacrine pretreatment reduces microwave-induced neuronal damage by stabilizing the cell membrane

PubMed Central

Ding, Xue-feng; Wu, Yan; Qu, Wen-rui; Fan, Ming; Zhao, Yong-qi

2018-01-01

Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine (20 and 40 mM) and irradiated them with 50 mW/cm2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation. PMID:29623929

The Affordable Housing Crisis: Residential Mobility of Poor Families and School Mobility of Poor Children.

ERIC Educational Resources Information Center

Crowley, Sheila

2003-01-01

Helping poor families increase their residential stability can have direct bearing on school stability and student academic achievement. Discusses the role of housing in child and family wellbeing; residential mobility and school performance; residential mobility and housing problems; housing affordability; (federal housing policy); homeownership;…

Dynamic processes in regulation and some implications for biofeedback and biobehavioral interventions.

PubMed

Lehrer, Paul; Eddie, David

2013-06-01

Systems theory has long been used in psychology, biology, and sociology. This paper applies newer methods of control systems modeling for assessing system stability in health and disease. Control systems can be characterized as open or closed systems with feedback loops. Feedback produces oscillatory activity, and the complexity of naturally occurring oscillatory patterns reflects the multiplicity of feedback mechanisms, such that many mechanisms operate simultaneously to control the system. Unstable systems, often associated with poor health, are characterized by absence of oscillation, random noise, or a very simple pattern of oscillation. This modeling approach can be applied to a diverse range of phenomena, including cardiovascular and brain activity, mood and thermal regulation, and social system stability. External system stressors such as disease, psychological stress, injury, or interpersonal conflict may perturb a system, yet simultaneously stimulate oscillatory processes and exercise control mechanisms. Resonance can occur in systems with negative feedback loops, causing high-amplitude oscillations at a single frequency. Resonance effects can be used to strengthen modulatory oscillations, but may obscure other information and control mechanisms, and weaken system stability. Positive as well as negative feedback loops are important for system function and stability. Examples are presented of oscillatory processes in heart rate variability, and regulation of autonomic, thermal, pancreatic and central nervous system processes, as well as in social/organizational systems such as marriages and business organizations. Resonance in negative feedback loops can help stimulate oscillations and exercise control reflexes, but also can deprive the system of important information. Empirical hypotheses derived from this approach are presented, including that moderate stress may enhance health and functioning.

Design and implementation of workflow engine for service-oriented architecture

NASA Astrophysics Data System (ADS)

Peng, Shuqing; Duan, Huining; Chen, Deyun

2009-04-01

As computer network is developed rapidly and in the situation of the appearance of distribution specialty in enterprise application, traditional workflow engine have some deficiencies, such as complex structure, bad stability, poor portability, little reusability and difficult maintenance. In this paper, in order to improve the stability, scalability and flexibility of workflow management system, a four-layer architecture structure of workflow engine based on SOA is put forward according to the XPDL standard of Workflow Management Coalition, the route control mechanism in control model is accomplished and the scheduling strategy of cyclic routing and acyclic routing is designed, and the workflow engine which adopts the technology such as XML, JSP, EJB and so on is implemented.

Epigenetic alterations mediate iPSC normalization of DNA-repair expression and TNR stability in Huntington's disease.

PubMed

Mollica, Peter A; Zamponi, Martina; Reid, John A; Sharma, Deepak K; White, Alyson E; Ogle, Roy C; Bruno, Robert D; Sachs, Patrick C

2018-06-13

Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat (TNR) expansion within the HTT gene. The mechanisms underlying HD-associated cellular dysfunction during pluripotency and neurodevelopment, are poorly understood. Here we tested the hypothesis that hypomethylation during cellular reprogramming leads to up-regulation of DNA repair genes and stabilization of TNRs in HD cells. We sought to determine how the HD TNR region is affected by global epigenetic changes through cellular reprogramming and early neurodifferentiation. We find that early-stage HD-affected neural stem cells (NSCs) contain increased levels of global 5-hydroxymethylation (5-hmC) and normalized DNA repair gene expression. We confirm TNR stability is induced during pluripotency, and maintained in HD-NSCs. We also identify up-regulation of 5-hmC catalyzing ten-eleven translocation (TET1/2) proteins, and show their knockdown leads to a corresponding decrease in select DNA repair gene expression. We further confirm decreased expression of TET regulating miR-29 family members in HD-NSCs. Our findings demonstrate that mechanisms involved in pluripotency recover the selected DNA repair gene expression and stabilizes pathogenic TNRs in HD. © 2018. Published by The Company of Biologists Ltd.

USP22 acts as an oncogene by regulating the stability of cyclooxygenase-2 in non-small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Haibo; Tian, Yue; Yang, Yang

2015-05-08

The histone ubiquitin hydrolase ubiquitin-specific protease 22 (USP22) is an epigenetic modifier and an oncogene that is upregulated in many types of cancer. In non-small cell lung cancer (NSCLC), aberrant expression of USP22 is a predictor of poor survival, as is high expression of cyclooxygenase-2 (COX-2). Despite its oncogenic role, few substrates of USP22 have been identified and its mechanism of action in cancer remains unclear. Here, we identified COX-2 as a direct substrate of USP22 and showed that its levels are modulated by USP22 mediated deubiquitination. Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cellmore » proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status. The findings of the present study suggest a potential mechanism underlying the oncogenic role of USP22 mediated by the modulation of the stability and activity of COX-2. - Highlights: • USP22 interacts with COX-2. • USP22 deubiquitinates and stabilizes COX-2. • USP22 is required for COX-2-mediated upregulation of prostaglandin E2.« less

Probing Immobilization Mechanism of alpha-chymotrypsin onto Carbon Nanotube in Organic Media by Molecular Dynamics Simulation

PubMed Central

Zhang, Liyun; Xiao, Xiuchan; Yuan, Yuan; Guo, Yanzhi; Li, Menglong; Pu, Xuemei

2015-01-01

The enzyme immobilization has been adopted to enhance the activity and stability of enzymes in non-aqueous enzymatic catalysis. However, the activation and stabilization mechanism has been poorly understood on experiments. Thus, we used molecular dynamics simulation to study the adsorption of α-chymotrypsin (α-ChT) on carbon nanotube (CNT) in aqueous solution and heptane media. The results indicate that α-ChT has stronger affinity with CNT in aqueous solution than in heptane media, as confirmed by more adsorption atoms, larger contact area and higher binding free energies. Although the immobilization causes significant structure deviations from the crystal one, no significant changes in secondary structure of the enzyme upon adsorption are observed in the two media. Different from aqueous solution, the stabilization effects on some local regions far from the surface of CNT were observed in heptane media, in particular for S1 pocket, which should contribute to the preservation of specificity reported by experiments. Also, CNT displays to some extent stabilization role in retaining the catalytic H-bond network of the active site in heptane media, which should be associated with the enhanced activity of enzymes. The observations from the work can provide valuable information for improving the catalytic properties of enzymes in non-aqueous media. PMID:25787884

Two-dimensional NMR spectroscopy reveals cation-triggered backbone degradation in polysulfone-based anion exchange membranes

PubMed Central

Arges, Christopher G.; Ramani, Vijay

2013-01-01

Anion exchange membranes (AEMs) find widespread applications as an electrolyte and/or electrode binder in fuel cells, electrodialysis stacks, flow and metal-air batteries, and electrolyzers. AEMs exhibit poor stability in alkaline media; their degradation is induced by the hydroxide ion, a potent nucleophile. We have used 2D NMR techniques to investigate polymer backbone stability (as opposed to cation stability) of the AEM in alkaline media. We report the mechanism behind a peculiar, often-observed phenomenon, wherein a demonstrably stable polysulfone backbone degrades rapidly in alkaline solutions upon derivatization with alkaline stable fixed cation groups. Using COSY and heteronuclear multiple quantum correlation spectroscopy (2D NMR), we unequivocally demonstrate that the added cation group triggers degradation of the polymer backbone in alkaline via quaternary carbon hydrolysis and ether hydrolysis, leading to rapid failure. This finding challenges the existing perception that having a stable cation moiety is sufficient to yield a stable AEM and emphasizes the importance of the often ignored issue of backbone stability. PMID:23335629

Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator

PubMed Central

Grabek, Katharine R; Diniz Behn, Cecilia; Barsh, Gregory S; Hesselberth, Jay R; Martin, Sandra L

2015-01-01

During hibernation, animals cycle between torpor and arousal. These cycles involve dramatic but poorly understood mechanisms of dynamic physiological regulation at the level of gene expression. Each cycle, Brown Adipose Tissue (BAT) drives periodic arousal from torpor by generating essential heat. We applied digital transcriptome analysis to precisely timed samples to identify molecular pathways that underlie the intense activity cycles of hibernator BAT. A cohort of transcripts increased during torpor, paradoxical because transcription effectively ceases at these low temperatures. We show that this increase occurs not by elevated transcription but rather by enhanced stabilization associated with maintenance and/or extension of long poly(A) tails. Mathematical modeling further supports a temperature-sensitive mechanism to protect a subset of transcripts from ongoing bulk degradation instead of increased transcription. This subset was enriched in a C-rich motif and genes required for BAT activation, suggesting a model and mechanism to prioritize translation of key proteins for thermogenesis. DOI: http://dx.doi.org/10.7554/eLife.04517.001 PMID:25626169

Development of Biodegradable Poly(citrate)-Polyhedral Oligomeric Silsesquioxanes Hybrid Elastomers with High Mechanical Properties and Osteogenic Differentiation Activity.

PubMed

Du, Yuzhang; Yu, Meng; Chen, Xiaofeng; Ma, Peter X; Lei, Bo

2016-02-10

Biodegradable elastomeric biomaterials have attracted much attention in tissue engineering due to their biomimetic viscoelastic behavior and biocompatibility. However, the low mechanical stability at hydrated state, fast biodegradation in vivo, and poor osteogenic activity greatly limited bioelastomers applications in bone tissue regeneration. Herein, we develop a series of poly(octanediol citrate)-polyhedral oligomeric silsesquioxanes (POC-POSS) hybrids with highly tunable elastomeric behavior (hydrated state) and biodegradation and osteoblasts biocompatibility through a facile one-pot thermal polymerization strategy. POC-POSS hybrids show significantly improved stiffness and ductility in either dry or hydrated conditions, as well as good antibiodegradation ability (20-50% weight loss in 3 months). POC-POSS hybrids exhibit significantly enhanced osteogenic differentiation through upregulating alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenic markers (ALPL, BGLAP, and Runx2). The high mechanical stability at hydrated state and enhanced osteogenic activity make POC-POSS hybrid elastomers promising as scaffolds and nanoscale vehicles for bone tissue regeneration and drug delivery. This study may also provide a new strategy (controlling the stiffness under hydrated condition) to design advanced hybrid biomaterials with high mechanical properties under physiological condition for tissue regeneration applications.

Solubilization of poorly water-soluble drugs using solid dispersions.

PubMed

Tran, Thao T-D; Tran, Phuong H-L; Khanh, Tran N; Van, Toi V; Lee, Beom-Jin

2013-08-01

Many new drugs have been discovered in pharmaceutical industry and exposed their surprised potential therapeutic effects. Unfortunately, these drugs possess low absorption and bioavailability since their solubility limitation in water. Solid dispersion (SD) is the current technique gaining so many attractions from scientists due to its effect on improving solubility and dissolution rate of poorly water-soluble drugs. A number of patents including the most recent inventions have been undertaken in this review to address various respects of this strategy in solubilization of poorly watersoluble drugs including type of carriers, preparation methods and view of technologies used to detect SD properties and mechanisms with the aim to accomplish a SD not only effective on enhanced bioavailability but also overcome difficulties associated with stability and production. Future prospects are as well discussed with an only hope that many developments and researches in this field will be successfully reached and contributed to commercial use for treatment as much as possible.

Multi-Sensor Based Online Attitude Estimation and Stability Measurement of Articulated Heavy Vehicles.

PubMed

Zhu, Qingyuan; Xiao, Chunsheng; Hu, Huosheng; Liu, Yuanhui; Wu, Jinjin

2018-01-13

Articulated wheel loaders used in the construction industry are heavy vehicles and have poor stability and a high rate of accidents because of the unpredictable changes of their body posture, mass and centroid position in complex operation environments. This paper presents a novel distributed multi-sensor system for real-time attitude estimation and stability measurement of articulated wheel loaders to improve their safety and stability. Four attitude and heading reference systems (AHRS) are constructed using micro-electro-mechanical system (MEMS) sensors, and installed on the front body, rear body, rear axis and boom of an articulated wheel loader to detect its attitude. A complementary filtering algorithm is deployed for sensor data fusion in the system so that steady state margin angle (SSMA) can be measured in real time and used as the judge index of rollover stability. Experiments are conducted on a prototype wheel loader, and results show that the proposed multi-sensor system is able to detect potential unstable states of an articulated wheel loader in real-time and with high accuracy.

Multi-Sensor Based Online Attitude Estimation and Stability Measurement of Articulated Heavy Vehicles

PubMed Central

Xiao, Chunsheng; Liu, Yuanhui; Wu, Jinjin

2018-01-01

Articulated wheel loaders used in the construction industry are heavy vehicles and have poor stability and a high rate of accidents because of the unpredictable changes of their body posture, mass and centroid position in complex operation environments. This paper presents a novel distributed multi-sensor system for real-time attitude estimation and stability measurement of articulated wheel loaders to improve their safety and stability. Four attitude and heading reference systems (AHRS) are constructed using micro-electro-mechanical system (MEMS) sensors, and installed on the front body, rear body, rear axis and boom of an articulated wheel loader to detect its attitude. A complementary filtering algorithm is deployed for sensor data fusion in the system so that steady state margin angle (SSMA) can be measured in real time and used as the judge index of rollover stability. Experiments are conducted on a prototype wheel loader, and results show that the proposed multi-sensor system is able to detect potential unstable states of an articulated wheel loader in real-time and with high accuracy. PMID:29342850

Understanding the role of histidine in the GHSxG acyltransferase active site motif: Evidence for histidine stabilization of the malonyl-enzyme intermediate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poust, Sean; Yoon, Isu; Adams, Paul D.

Acyltransferases determine which extender units are incorporated into polyketide and fatty acid products. Thus, the ping-pong acyltransferase mechanism utilizes a serine in a conserved GHSxG motif. However, the role of the conserved histidine in this motif is poorly understood. We observed that a histidine to alanine mutation (H640A) in the GHSxG motif of the malonyl-CoA specific yersiniabactin acyltransferase results in an approximately seven-fold higher hydrolysis rate over the wildtype enzyme, while retaining transacylation activity. We propose two possibilities for the reduction in hydrolysis rate: either H640 structurally stabilizes the protein by hydrogen bonding with a conserved asparagine in the ferredoxin-likemore » subdomain of the protein, or a water-mediated hydrogen bond between H640 and the malonyl moiety stabilizes the malonyl-O-AT ester intermediate.« less

Understanding the role of histidine in the GHSxG acyltransferase active site motif: Evidence for histidine stabilization of the malonyl-enzyme intermediate

DOE PAGES

Poust, Sean; Yoon, Isu; Adams, Paul D.; ...

2014-10-06

Acyltransferases determine which extender units are incorporated into polyketide and fatty acid products. Thus, the ping-pong acyltransferase mechanism utilizes a serine in a conserved GHSxG motif. However, the role of the conserved histidine in this motif is poorly understood. We observed that a histidine to alanine mutation (H640A) in the GHSxG motif of the malonyl-CoA specific yersiniabactin acyltransferase results in an approximately seven-fold higher hydrolysis rate over the wildtype enzyme, while retaining transacylation activity. We propose two possibilities for the reduction in hydrolysis rate: either H640 structurally stabilizes the protein by hydrogen bonding with a conserved asparagine in the ferredoxin-likemore » subdomain of the protein, or a water-mediated hydrogen bond between H640 and the malonyl moiety stabilizes the malonyl-O-AT ester intermediate.« less

[Rubella virus genetic determinant of attenuation].

PubMed

Dmitriev, G V; Borisova, T K; Faizuloev, E B; Desiatskova, R G; Zverev, V V

2014-01-01

Vaccination is the most effective and available way to prevent Rubella. Presently, 9 vaccine strains were registered. Nevertheless, the molecular mechanisms of the attenuation were poorly elucidated for the rubella virus. However, the study of these mechanisms identifying genotypic and phenotypic markers of attenuation, which together with sequence analysis could be used for the genetic stability control of vaccine strains, is still of current interest. Common trends of genetic changes in the process of adaptation to cold were found due to comparison of nucleic acid and amino acid sequences of the Russian strain C-77 with corresponding positions of the known rubella virus strains and its wild type progenitors, if available.

Dynamic Processes in Regulation and Some Implications for Biofeedback and Biobehavioral Interventions

PubMed Central

Lehrer, Paul; Eddie, David

2013-01-01

Systems theory has long been applied in psychology, biology, and sociology. This paper applies newer methods of control systems modeling to the assessment of system stability in health and disease. Control systems can be characterized as open or closed systems with feedback loops. Feedback produces oscillatory activity, and the complexity of naturally occurring oscillatory patterns reflects the multiplicity of feedback mechanisms, such that many mechanisms operate simultaneously to control the system. Unstable systems, often associated with poor health, are characterized by absence of oscillation, random noise, or a very simple pattern of oscillation. This modeling approach can be applied to a diverse range of phenomena, including cardiovascular and brain activity, mood and thermal regulation, and social system stability. External system stressors such as disease, psychological stress, injury, or interpersonal conflict may perturb a system, yet simultaneously stimulate oscillatory processes and exercise control mechanisms. Resonance can occur in systems with negative feedback loops, causing high-amplitude oscillations at a single frequency. Resonance effects can be used to strengthen modulatory oscillations, but may obscure other information and control mechanisms, and weaken system stability. Positive as well as negative feedback loops are important for system function and stability. Examples are presented of oscillatory processes in heart rate variability, and regulation of autonomic, thermal, pancreatic and central nervous system processes, as well as in social/organizational systems such as marriages and business organizations. Resonance in negative feedback loops can help stimulate oscillations and exercise control reflexes, but also can deprive the system of important information. Empirical hypotheses derived from this approach are presented, including that moderate stress may enhance health and functioning. PMID:23572244

Strong mechanical adhesion of gold electroless contacts on CdZnTe deposited by alcoholic solutions

NASA Astrophysics Data System (ADS)

Benassi, G.; Nasi, L.; Bettelli, M.; Zambelli, N.; Calestani, D.; Zappettini, A.

2017-02-01

CdZnTe crystals are nowadays employed as X-ray detectors for a number of applications, such as medical imaging, security, and environmental monitoring. One of the main difficulties connected with CdZnTe-based detector processing is the poor contact adhesion that affect bonding procedures and device long term stability. We have shown that it is possible to obtain mechanically stable contacts by common electroless deposition using alcoholic solutions instead of water solutions. The contacts show blocking current-voltage characteristic that is required for obtaining spectroscopic detectors. Nanoscale-resolved chemical analysis indicated that the improved mechanical adhesion is due to a better control of the stoichiometry of the CdZnTe layer below the contact.

Regulation of the catalytic activity of the EGF receptor

PubMed Central

Endres, Nicholas F.; Engel, Kate; Das, Rahul; Kovacs, Erika; Kuriyan, John

2011-01-01

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in cell growth that is often misregulated in cancer. Several recent studies highlight the unique structural mechanisms involved in its regulation. Some elucidate the important role that the juxtamembrane segment and the transmembrane helix play in stabilizing the activating asymmetric kinase dimer, and suggest that its activation mechanism is likely to be conserved amongst the other human EGFR-related receptors. Other studies provide new explanations for two long observed, but poorly understood phenomena, the apparent heterogeneity in ligand binding and the formation of ligand-independent dimers. New insights into the allosteric mechanisms utilized by intracellular regulators of EGFR provide hope that allosteric sites could be used as targets for drug development. PMID:21868214

Reduced transcript stabilization restricts TNF-alpha expression in RAW264.7 macrophages infected with pathogenic mycobacteria: evidence for an involvement of lipomannan.

PubMed

Basler, Tina; Holtmann, Helmut; Abel, Jens; Eckstein, Torsten; Baumer, Wolfgang; Valentin-Weigand, Peter; Goethe, Ralph

2010-01-01

Despite the critical role that TNF-alpha plays in the containment of mycobacterial infection, the mechanisms involved in regulation of its expression by mycobacteria are poorly defined. We addressed this question by studying MAP, which causes a chronic enteritis in ruminants and is linked to human Crohn's disease. We found that in MAP infected macrophages, TNF-alpha gene expression was substantially lower than in macrophages infected with nonpathogenic MS or stimulated with LPS. TNF-alpha transcriptional one could not fully explain the differential TNF-alpha mRNA expression, suggesting that there must be a substantial contribution by post-transcriptional mechanisms.Accordingly, we found reduced TNF-alpha mRNA stability in MAP-infected macrophages. Further comparison of MAP- and MS-infected macrophages revealed that lower TNF-alpha mRNA stability combined with lower mRNA and protein expression in MAP-infected macrophages correlated with lower p38 MAPK phosphorylation. These findings were independent of viability of MAP and MS. We demonstrate that the major mycobacterial cell-wall lipoglycan LM of MAP and MS induced TNF-alpha mRNA transcription,but only the MS-LM induced p38 MAPK-dependent transcript stabilization. Overall, our data suggest that pathogenic mycobacteria cause weak p38 and TNF-alpha mRNA stabilization as a result of their structural cell-wall components such as LM and thereby, restrict TNF-alpha expression in macrophages.

Understanding the initial irreversibility of metal sulfides for sodium-ion batteries via operando techniques

DOE PAGES

Wang, Liguang; Wang, Jiajun; Guo, Fangmin; ...

2018-11-13

Transition metal sulfides are promising high capacity anodes for sodium-ion batteries in terms of the conversion reaction with multiple alkali metal ions. Nonetheless, some inherent challenges such as sluggish sodium ion diffusion kinetics, large volume change, and poor cycle stability limit their implementation. Addressing these issues necessitates a comprehensive understanding the complex sodium ion storage mechanism particularly at the initial cycle. Here, taking nickel subsulfide as a model material, we reveal the complicated conversion reaction mechanism upon the first cycle by combining in operando 2D transmission X-ray microscopy with X-ray absorption spectroscopy, ex-situ 3D nano-tomography, high-energy X-ray diffraction and electrochemicalmore » impedance spectroscopy. This study demonstrates that the microstructure evolution, inherent slow sodium ions diffusion kinetics, and slow ion mobility at the two-phase interface contribute to the high irreversible capacity upon the first cycle. Finally, such understandings are critical for developing the conversion reaction materials with the desired electrochemical activity and stability.« less

Understanding the initial irreversibility of metal sulfides for sodium-ion batteries via operando techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Liguang; Wang, Jiajun; Guo, Fangmin

Transition metal sulfides are promising high capacity anodes for sodium-ion batteries in terms of the conversion reaction with multiple alkali metal ions. Nonetheless, some inherent challenges such as sluggish sodium ion diffusion kinetics, large volume change, and poor cycle stability limit their implementation. Addressing these issues necessitates a comprehensive understanding the complex sodium ion storage mechanism particularly at the initial cycle. Here, taking nickel subsulfide as a model material, we reveal the complicated conversion reaction mechanism upon the first cycle by combining in operando 2D transmission X-ray microscopy with X-ray absorption spectroscopy, ex-situ 3D nano-tomography, high-energy X-ray diffraction and electrochemicalmore » impedance spectroscopy. This study demonstrates that the microstructure evolution, inherent slow sodium ions diffusion kinetics, and slow ion mobility at the two-phase interface contribute to the high irreversible capacity upon the first cycle. Finally, such understandings are critical for developing the conversion reaction materials with the desired electrochemical activity and stability.« less

Tailoring chain length and cross-link density in dielectric elastomer toward enhanced actuation strain

NASA Astrophysics Data System (ADS)

Zhang, Quan-Ping; Liu, Jun-Hua; Liu, Hai-Dong; Jia, Fei; Zhou, Yuan-Lin; Zheng, Jian

2017-10-01

Adding ceramic or conductive fillers into polymers for increasing permittivity is a direct and effective approach to enhance the actuation strain of dielectric elastomer actuators (DEAs). Unfortunately, the major dielectric loss caused by weak interfaces potentially harms the electro-mechanical stability and lifetime of DEAs. Here, we construct a desired macromolecular network with a long chain length and low cross-link density to reduce the elastic modulus of silicone elastomers. Selecting a high molecular weight of polymethylvinylsiloxane and a low dose of the cross-linker leads the soft but tough networks with rich entanglements, poor cross-links, and a low amount of defects. Then, a ductile material with low elastic modulus but high elongation at break is obtained. It accounts for much more excellent actuation strain of Hl in comparison to that of the other silicone elastomers. Importantly, without other fillers, the ultralow dielectric loss, conductivity, and firm networks possibly promote the electro-mechanical stability and lifetime for the DEA application.

Electrochemical stabilization as a means of preventing ground failure in railroads

USGS Publications Warehouse

Solntzev, D.I.; Sorkov, V.S.; Sokoloff, V.P.

1947-01-01

Laboratory and field data on electrochemical stabilization of clays, by three Russian authors, are here presented in translation. Abstracts of the Russian papers were published in May 1947 issue of the Engineering News Record (pp. 100-101). There exists also a small body of literature, in German and English, dealing with the electrochemical stabilization and related subjects. Elements of the electrochemical process were patented by Casagrande in Germany, shortly before the last war. Results of the Russians and of others, including the German patent, appear to be sound and interesting accordingly. Mechanism of the electrochemical stabilization, however, appears to be surmised rather than established. Unless the mechanism of such stabilization is understood in detail, little progress may be expected in field applications of the electrochemical method. Electroosmosis, a poorly reversible coagulation of the soil colloids, and introduction of exchangeable aluminum into the clay complex have been given credit for the ground-stabilizing effects of direct electrical current. Much remains to be done, as the reader may see, in developing further the theory of the method. A critical study is indicated, in this connection, by agencies or individuals qualified and equipped for basic research in soil physics. Optimum schedules for field treatments need be ascertained with particular care, to suit any given kind of material and environment. A wide range of variation in such schedules, is most certainly to be encountered in dealing with materials as diverse in their composition and properties as are clays. Any generalization on relationships between soil, electrolytes, moisture, and current could be premature if based on the Russian work alone. Stabilization of ground is a major engineering geologic problem of national interest. Needless to say, perhaps, that failures are to be expected, in laboratory and in the field, in this as well as in any other kind of research. To minimize probabilities of such failures, it may be recommended that investigators develop the electrochemical stabilization problem not merely against the relatively narrow background of soil mechanics, but with a certain feeling for geology, mineralogy, pedology, soil physics, and soil chemistry.

A structural equation model relating impaired sensorimotor function, fear of falling and gait patterns in older people.

PubMed

Menz, Hylton B; Lord, Stephen R; Fitzpatrick, Richard C

2007-02-01

Many falls in older people occur while walking, however the mechanisms responsible for gait instability are poorly understood. Therefore, the aim of this study was to develop a plausible model describing the relationships between impaired sensorimotor function, fear of falling and gait patterns in older people. Temporo-spatial gait parameters and acceleration patterns of the head and pelvis were obtained from 100 community-dwelling older people aged between 75 and 93 years while walking on an irregular walkway. A theoretical model was developed to explain the relationships between these variables, assuming that head stability is a primary output of the postural control system when walking. This model was then tested using structural equation modeling, a statistical technique which enables the testing of a set of regression equations simultaneously. The structural equation model indicated that: (i) reduced step length has a significant direct and indirect association with reduced head stability; (ii) impaired sensorimotor function is significantly associated with reduced head stability, but this effect is largely indirect, mediated by reduced step length, and; (iii) fear of falling is significantly associated with reduced step length, but has little direct influence on head stability. These findings provide useful insights into the possible mechanisms underlying gait characteristics and risk of falling in older people. Particularly important is the indication that fear-related step length shortening may be maladaptive.

Copper plasmonics and catalysis: role of electron-phonon interactions in dephasing localized surface plasmons

NASA Astrophysics Data System (ADS)

Sun, Qi-C.; Ding, Yuchen; Goodman, Samuel M.; H. Funke, Hans; Nagpal, Prashant

2014-10-01

Copper metal can provide an important alternative for the development of efficient, low-cost and low-loss plasmonic nanoparticles, and selective nanocatalysts. However, poor chemical stability and lack of insight into photophysics and plasmon decay mechanisms has impeded study. Here, we use smooth conformal ALD coating on copper nanoparticles to prevent surface oxidation, and study dephasing time for localized surface plasmons on different sized copper nanoparticles. Using dephasing time as a figure of merit, we elucidate the role of electron-electron, electron-phonon, impurity, surface and grain boundary scattering on the decay of localized surface plasmon waves. Using our quantitative analysis and different temperature dependent measurements, we show that electron-phonon interactions dominate over other scattering mechanisms in dephasing plasmon waves. While interband transitions in copper metal contributes substantially to plasmon losses, tuning surface plasmon modes to infrared frequencies leads to a five-fold enhancement in the quality factor. These findings demonstrate that conformal ALD coatings can improve the chemical stability for copper nanoparticles, even at high temperatures (>300 °C) in ambient atmosphere, and nanoscaled copper is a good alternative material for many potential applications in nanophotonics, plasmonics, catalysis and nanoscale electronics.Copper metal can provide an important alternative for the development of efficient, low-cost and low-loss plasmonic nanoparticles, and selective nanocatalysts. However, poor chemical stability and lack of insight into photophysics and plasmon decay mechanisms has impeded study. Here, we use smooth conformal ALD coating on copper nanoparticles to prevent surface oxidation, and study dephasing time for localized surface plasmons on different sized copper nanoparticles. Using dephasing time as a figure of merit, we elucidate the role of electron-electron, electron-phonon, impurity, surface and grain boundary scattering on the decay of localized surface plasmon waves. Using our quantitative analysis and different temperature dependent measurements, we show that electron-phonon interactions dominate over other scattering mechanisms in dephasing plasmon waves. While interband transitions in copper metal contributes substantially to plasmon losses, tuning surface plasmon modes to infrared frequencies leads to a five-fold enhancement in the quality factor. These findings demonstrate that conformal ALD coatings can improve the chemical stability for copper nanoparticles, even at high temperatures (>300 °C) in ambient atmosphere, and nanoscaled copper is a good alternative material for many potential applications in nanophotonics, plasmonics, catalysis and nanoscale electronics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04719b

The Enhancement of Bone Allograft Incorporation by the Local Delivery of the Sphingosine 1-phosphate Receptor Targeted Drug FTY720

PubMed Central

Aronin, Caren E Petrie; Shin, Soo J; Naden, Kimberly B; Rios, Peter D; Sefcik, Lauren S; Zawodny, Sarah R; Bagayoko, Namory D; Cui, Quanjun; Khan, Yusuf

2010-01-01

Poor vascularization coupled with mechanical instability is the leading cause of post-operative complications and poor functional prognosis of massive bone allografts. To address this limitation, we designed a novel continuous polymer coating system to provide sustained localized delivery of pharmacological agent, FTY720, a selective agonist for sphingosine 1-phosphate receptors, within massive tibial defects. In vitro drug release studies validated 64% loading efficiency with complete release of compound following 14 days. Mechanical evaluation following six weeks of healing suggested significant enhancement of mechanical stability in FTY720 treatment groups compared with unloaded controls. Furthermore, superior osseous integration across the host-graft interface, significant enhancement in smooth muscle cell investment, and reduction in leukocyte recruitment was evident in FTY720 treated groups compared with untreated groups. Using this approach, we can capitalize on the existing mechanical and biomaterial properties of devitalized bone, add a controllable delivery system while maintaining overall porous structure, and deliver a small molecule compound to constitutively target vascular remodeling, osseous remodeling, and minimize fibrous encapsulation within the allograft-host bone interface. Such results support continued evaluation of drug-eluting allografts as a viable strategy to improve functional outcome and long-term success of massive cortical allograft implants. PMID:20621764

Nicotiana alata Defensin Chimeras Reveal Differences in the Mechanism of Fungal and Tumor Cell Killing and an Enhanced Antifungal Variant

PubMed Central

Payne, Jennifer A. E.; Hayes, Brigitte M. E.; Durek, Thomas; Craik, David J.; Shafee, Thomas M. A.; Poon, Ivan K. H.; Hulett, Mark D.; van der Weerden, Nicole L.

2016-01-01

The plant defensin NaD1 is a potent antifungal molecule that also targets tumor cells with a high efficiency. We examined the features of NaD1 that contribute to these two activities by producing a series of chimeras with NaD2, a defensin that has relatively poor activity against fungi and no activity against tumor cells. All plant defensins have a common tertiary structure known as a cysteine-stabilized α-β motif which consists of an α helix and a triple-stranded β-sheet stabilized by four disulfide bonds. The chimeras were produced by replacing loops 1 to 7, the sequences between each of the conserved cysteine residues on NaD1, with the corresponding loops from NaD2. The loop 5 swap replaced the sequence motif (SKILRR) that mediates tight binding with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and is essential for the potent cytotoxic effect of NaD1 on tumor cells. Consistent with previous reports, there was a strong correlation between PI(4,5)P2 binding and the tumor cell killing activity of all of the chimeras. However, this correlation did not extend to antifungal activity. Some of the loop swap chimeras were efficient antifungal molecules, even though they bound poorly to PI(4,5)P2, suggesting that additional mechanisms operate against fungal cells. Unexpectedly, the loop 1B swap chimera was 10 times more active than NaD1 against filamentous fungi. This led to the conclusion that defensin loops have evolved as modular components that combine to make antifungal molecules with variable mechanisms of action and that artificial combinations of loops can increase antifungal activity compared to that of the natural variants. PMID:27503651

Natural graphene microsheets/sulfur as Li-S battery cathode towards >99% coulombic efficiency of long cycles

NASA Astrophysics Data System (ADS)

Zhang, Yan; Duan, Xiaoyong; Wang, Jie; Wang, Congwei; Wang, Junying; Wang, Jianlong; Wang, Junzhong

2018-02-01

Lithium-sulfur battery receives intense attention owing to its high theoretical energy density. However, poor electrical conductivity of sulfur and poor cycle stability of the battery hinder its application. Here, we report that graphene microsheets prepared from microcrystalline graphite minerals by an electrochemical & mechanical approach work as a special conductive support to load sulfur as the cathode of lithium-sulfur battery. The graphene microsheets have the features of excellent conductivity and low defect, small sheet sizes of <1 μm2 and ≤6 atomic layers as well as natural silicate residue covered. Li-S batteries of graphene microsheets/S as cathode exhibit long-term cyclability and high coulombic efficiency. At 1 C for 2000 cycles, average coulombic efficiency of 99.7% is reached.

[Composition and stability of soil aggregates in hedgerow-crop slope land].

PubMed

Pu, Yu-Lin; Lin, Chao-Wen; Xie, De-Ti; Wei, Chao-Fu; Ni, Jiu-Pai

2013-01-01

Based on a long-term experiment of using hedgerow to control soil and water loss, this paper studied the composition and stability of soil aggregates in a hedgerow-crop slope land. Compared with those under routine contour cropping, the contents of > 0.25 mm soil mechanical-stable and water-stable aggregates under the complex mode hedgerow-crop increased significantly by 13.3%-16.1% and 37.8% -55.6%, respectively. Under the complex mode, the contents of > 0.25 mm soil water-stable aggregates on each slope position increased obviously, and the status of > 0.25 mm soil water-stable aggregates being relatively rich at low slope and poor at top slope was improved. Planting hedgerow could significantly increase the mean mass diameter and geometric mean diameter of soil aggregates, decrease the fractal dimension of soil aggregates and the destruction rate of > 0.25 mm soil aggregates, and thus, increase the stability and erosion-resistance of soil aggregates in slope cropland. No significant effects of slope and hedgerow types were observed on the composition, stability and distribution of soil aggregates.

Review on effect of chemical, thermal, additive treatment on mechanical properties of basalt fiber and their composites

NASA Astrophysics Data System (ADS)

Jain, Naman; Singh, Vinay Kumar; Chauhan, Sakshi

2017-12-01

Basalt fiber is emerging out the new reinforcing material for composites. To overcome some of the disadvantages of fibers such as poor bonding to polymers, low thermal stability and high moisture absorption fiber characteristics are modified with chemical, thermal and additive treatments. Chemical treatment corrosive resistance to alkali and acid were investigated which were used to clean and modify the surface of fiber for higher bonding with resins. To improve the thermal stability and reduce moisture uptake thermal treatment such as plasma and non thermal plasma were used which increased the surface roughness and change the chemical composition of surface of basalt fiber. Additive treatment is used to improve the mechanical properties of fibers, in basalt fiber additive treatment was done with SiO2 additive because of its chemical composition which contains major content of SiO2. In present investigation review on the effect of different treatment such as chemical, thermal and additive were studied. Effect of these treatment on chemical composition of the surface of basalt fiber and corrosion to acidic and alkali solution were studied with their effect on mechanical properties of basalt fiber and their composite.

Increasing Mechanical Strength of Gelatin Hydrogels by Divalent Metal Ion Removal

PubMed Central

Xing, Qi; Yates, Keegan; Vogt, Caleb; Qian, Zichen; Frost, Megan C.; Zhao, Feng

2014-01-01

The usage of gelatin hydrogel is limited due to its instability and poor mechanical properties, especially under physiological conditions. Divalent metal ions present in gelatin such as Ca2+ and Fe2+ play important roles in the gelatin molecule interactions. The objective of this study was to determine the impact of divalent ion removal on the stability and mechanical properties of gelatin gels with and without chemical crosslinking. The gelatin solution was purified by Chelex resin to replace divalent metal ions with sodium ions. The gel was then chemically crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Results showed that the removal of divalent metal ions significantly impacted the formation of the gelatin network. The purified gelatin hydrogels had less interactions between gelatin molecules and form larger-pore network which enabled EDC to penetrate and crosslink the gel more efficiently. The crosslinked purified gels showed small swelling ratio, higher crosslinking density and dramatically increased storage and loss moduli. The removal of divalent ions is a simple yet effective method that can significantly improve the stability and strength of gelatin hydrogels. The in vitro cell culture demonstrated that the purified gelatin maintained its ability to support cell attachment and spreading. PMID:24736500

Correlation between mechanical properties and retained austenite characteristics in a low-carbon medium manganese alloyed steel plate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jun, E-mail: cjer19841011@163.com; Lv, Mengyang; Tang, Shuai

2015-08-15

The effects of retained austenite characteristics on tensile properties and low-temperature impact toughness have been investigated by means of transmission electron microscopy and X-ray diffraction. It was found that only part of austenite phase formed during heat treating was left at room temperature. Moreover, the film-like retained austenite is displayed between bcc-martensite laths after heat treating at 600 °C, while the block-form retained austenite with thin hcp-martensite laths is observed after heat treating at 650 °C. It has been demonstrated that the film-like retained austenite possesses relatively high thermal and mechanical stability, and it can greatly improve low-temperature impact toughness,more » but its contribution to strain hardening capacity is limited. However, the block-form retained austenite can greatly enhance ultimate tensile strength and strain hardening capacity, but its contribution to low-temperature impact toughness is poor. - Highlights: • Correlation between retained austenite and impact toughness was elucidated. • The impact toughness is related to mechanical stability of retained austenite. • The effect of retained austenite on tensile and impact properties is inconsistent.« less

Evaluating the oxidative, photothermal and electrical stability of colloidal nanocrystal solids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Law, Matt

2016-02-16

IV-VI quantum dot (QD) solids are a novel class of granular electronic materials with great technological potential (e.g., in photodetectors, field-effect transistors (FETs), and solar cells), but their oxidative and thermal instability present a barrier to practical applications [1]. Poor stability is a fundamental issue facing many nanoscale materials due to high surface area and surface energy. Basic studies are needed to elucidate the most important mechanisms of degradation and develop robust countermeasures if QD materials are to become technologically important. This project determined the degradation mechanisms of IV-VI QD solids (primarily PbSe and PbS) and introduced new chemical strategiesmore » to drastically improve their performance, stability, and operating lifetimes [2-5]. Our approach was based on (1) detailed testing of QD thin film materials (principally FETs and solar cells) as a function of oxidative and thermal stress, and (2) the use of organic and inorganic approaches to link the QDs into strongly electronically coupled, high-mobility films, prevent their oxidation, and eliminate internal degrees of freedom that lead to film instability and degradation in response to electrical and thermal stress. Stability against oxidation and thermal degradation was the major focus of this project. We have evaluated the stability of QD thin films and interfaces at temperatures less than 100°C (the regime most relevant to solar and transistor applications). Low-temperature oxidation and sintering of QD films have been investigated using optical absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), current-voltage scanning of transistors and solar cells, X-ray photoelectron spectroscopy, and scanning Kelvin probe microscopy (SKPM). SKPM was used to map the potential profiles of operating QD FETs and solar cells as a function of bias and illumination, which provides detailed information on how the work functions, potential drops and electric field within these devices determine device operation, and set the stage for future studies targeted at understanding and preventing device failure. We pursued two strategies to fabricate QD films with stable electrical characteristics: (1) the use of robust molecular surface ligands [2], and (2) “matrix engineering,” i.e., infilling the QD solid with metal oxide or metal sulfide matrices by low-temperature atomic layer deposition (ALD) to passivate surface states, prevent oxidation, lock the QDs into position, inhibit diffusion, and tune the height and width of the inter-QD potential barriers that govern charge transport [5,6]. Poor stability is a common feature of nanoscale electronic materials, yet stability is all too rarely the focus of basic research. Fundamental studies are therefore needed to elucidate the most important mechanisms of degradation and develop simple yet effective countermeasures. By revealing both how QD solids degrade in response to environmental stresses (oxidative, photothermal, and electric) and how to prevent this degradation, the project has greatly improved our ability to develop stable, high-performance QD materials for real-world applications.« less

Stability and tribological performances of fluid phospholipid bilayers: effect of buffer and ions.

PubMed

Dekkiche, F; Corneci, M C; Trunfio-Sfarghiu, A-M; Munteanu, B; Berthier, Y; Kaabar, W; Rieu, J-P

2010-10-15

We have investigated the mechanical and tribological properties of supported Dioleoyl phosphatidylcholine (DOPC) bilayers in different solutions: ultrapure water (pH 5.5), saline solution (150 mM NaCl, pH 5.8), Tris buffer (pH 7.2) and Tris saline buffer (150 mM NaCl, pH 7.2). Friction forces are measured using a homemade biotribometer. Lipid bilayer degradation is controlled in situ during friction tests using fluorescence microscopy. Mechanical resistance to indentation is measured by force spectroscopy with an atomic force microscope. This study confirms that mechanical stability under shear or normal load is essential to obtain low and constant friction coefficients. In ultrapure water, bilayers are not resistant and have poor lubricant properties. On the other hand, in Tris saline buffer, they fully resist to indentation and exhibit low (micro=0.035) and stable friction coefficient with no visible wear during the 50 min of the friction test. The unbuffered saline solution improves the mechanical resistance to indentation but not the lubrication. These results suggest that the adsorption of ions to the zwiterrionic bilayers has different effects on the mechanical and tribological properties of bilayers: higher resistance to normal indentation due to an increase in bilayer cohesion, higher lubrication due to an increase in bilayer-bilayer repulsion. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Interaction of thermal and mechanical processes in steep permafrost rock walls: A conceptual approach

NASA Astrophysics Data System (ADS)

Draebing, D.; Krautblatter, M.; Dikau, R.

2014-12-01

Degradation of permafrost rock wall decreases stability and can initiate rock slope instability of all magnitudes. Rock instability is controlled by the balance of shear forces and shear resistances. The sensitivity of slope stability to warming results from a complex interplay of shear forces and resistances. Conductive, convective and advective heat transport processes act to warm, degrade and thaw permafrost in rock walls. On a seasonal scale, snow cover changes are a poorly understood key control of the timing and extent of thawing and permafrost degradation. We identified two potential critical time windows where shear forces might exceed shear resistances of the rock. In early summer combined hydrostatic and cryostatic pressure can cause a peak in shear force exceeding high frozen shear resistance and in autumn fast increasing shear forces can exceed slower increasing shear resistance. On a multiannual system scale, shear resistances change from predominantly rock-mechanically to ice-mechanically controlled. Progressive rock bridge failure results in an increase of sensitivity to warming. Climate change alters snow cover and duration and, hereby, thermal and mechanical processes in the rock wall. Amplified thawing of permafrost will result in higher rock slope instability and rock fall activity. We present a holistic conceptual approach connecting thermal and mechanical processes, validate parts of the model with geophysical and kinematic data and develop future scenarios to enhance understanding on system scale.

Molecular mechanism of polymer-assisting supersaturation of poorly water-soluble loratadine based on experimental observations and molecular dynamic simulations.

PubMed

Zhang, Shenwu; Sun, Mengchi; Zhao, Yongshan; Song, Xuyang; He, Zhonggui; Wang, Jian; Sun, Jin

2017-10-01

Polymers have been usually used to retard nucleation and crystal growth in order to maintain supersaturation, yet their roles in inhibition of nucleation and crystal growth are poorly understood. In our work, the polymer-based supersaturation performances and molecular mechanisms of poorly aqueous soluble loratadine were investigated. Two common hydrophilic polymers (hydroxylpropylmethyl cellulose acetate succinate (HPMC-AS) and poly(vinylpyrrolidone-co-vinyl-acetate) (PVP-VA)) were used. It was found that HPMC-AS was a better polymer to prevent drug molecules from aggregation and to maintain the supersaturated state in solution than PVP-VA. The in vitro dissolution experiments showed that HPMC-AS solid dispersions had more rapid release at pH 4.5 and 6.8 media than PVP-VA solid dispersions under the un-sink condition. Moreover, molecular dynamic simulation results showed that HPMC-AS was more firmly absorbed onto a surface of the drug nanoparticles than PVP-VA due to bigger hydrophobic areas of HPMC-AS. Thereby, crystallization process of loratadine was inhibited in the presence of water to provide prolonged stability of the supersaturated state. In conclusion, polymers played a key role in maintaining supersaturation state of loratadine solid dispersions by strong drug-polymer interactions and the hydrophobic characteristic of polymers.

Long-Term Delivery of Protein Therapeutics

PubMed Central

Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

2015-01-01

Introduction Proteins are effective biotherapetics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. Areas covered This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Expert opinion Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery related issues. A large number of protein molecules are under clinical trials and hence there is an urgent need to develop new methods to deliver these highly potent biologics. PMID:25251334

Long-term delivery of protein therapeutics.

PubMed

Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

2015-03-01

Proteins are effective biotherapeutics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability, frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel-based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery-related issues. A large number of protein molecules are under clinical trials, and hence, there is an urgent need to develop new methods to deliver these highly potent biologics.

Stabilization of Tetanus Toxoid Encapsulated in PLGA Microspheres

PubMed Central

Jiang, Wenlei; Schwendeman, Steven P.

2014-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT) in PLGA microspheres. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: 1) protein aggregation mediated by formaldehyde and 2) acid-induced protein unfolding and epitope damage. Further, we systemically identified excipients which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA. PMID:18710256

A thorough experimental study of CH/π interactions in water: quantitative structure-stability relationships for carbohydrate/aromatic complexes.

PubMed

Jiménez-Moreno, Ester; Jiménez-Osés, Gonzalo; Gómez, Ana M; Santana, Andrés G; Corzana, Francisco; Bastida, Agatha; Jiménez-Barbero, Jesus; Asensio, Juan Luis

2015-11-13

CH/π interactions play a key role in a large variety of molecular recognition processes of biological relevance. However, their origins and structural determinants in water remain poorly understood. In order to improve our comprehension of these important interaction modes, we have performed a quantitative experimental analysis of a large data set comprising 117 chemically diverse carbohydrate/aromatic stacking complexes, prepared through a dynamic combinatorial approach recently developed by our group. The obtained free energies provide a detailed picture of the structure-stability relationships that govern the association process, opening the door to the rational design of improved carbohydrate-based ligands or carbohydrate receptors. Moreover, this experimental data set, supported by quantum mechanical calculations, has contributed to the understanding of the main driving forces that promote complex formation, underlining the key role played by coulombic and solvophobic forces on the stabilization of these complexes. This represents the most quantitative and extensive experimental study reported so far for CH/π complexes in water.

Effect of osmolytes on the thermal stability of proteins: replica exchange simulations of Trp-cage in urea and betaine solutions.

PubMed

Adamczak, Beata; Kogut, Mateusz; Czub, Jacek

2018-04-25

Although osmolytes are known to modulate the folding equilibrium, the molecular mechanism of their effect on thermal denaturation of proteins is still poorly understood. Here, we simulated the thermal denaturation of a small model protein (Trp-cage) in the presence of denaturing (urea) and stabilizing (betaine) osmolytes, using the all-atom replica exchange molecular dynamics simulations. We found that urea destabilizes Trp-cage by enthalpically-driven association with the protein, acting synergistically with temperature to induce unfolding. In contrast, betaine is sterically excluded from the protein surface thereby exerting entropic depletion forces that contribute to the stabilization of the native state. In fact, we find that while at low temperatures betaine slightly increases the folding free energy of Trp-cage by promoting another near-native conformation, it protects the protein against temperature-induced denaturation. This, in turn, can be attributed to enhanced exclusion of betaine at higher temperatures that arises from less attractive interactions with the protein surface.

Getting off on the Wrong Foot: Longitudinal Effects of Hispanic Students' Stability Attributions Following Poor Initial Test Performance

ERIC Educational Resources Information Center

Cox, Cody B.; Yang, Yan

2012-01-01

Though studies have established that following poor performance, attributions to stable causes affect the performance of minority students, few studies have explored the impact of stability attributions over time. This study explored attributions following initial failure among a predominantly Hispanic student population. We measured students'…

Caspase-2-mediated cleavage of Mdm2 creates p53-induced positive feedback loop

PubMed Central

Oliver, Trudy G.; Meylan, Etienne; Chang, Gregory P.; Xue, Wen; Burke, James R.; Humpton, Timothy J.; Hubbard, Diana; Bhutkar, Arjun; Jacks, Tyler

2011-01-01

SUMMARY Caspase-2 is an evolutionarily conserved caspase, yet its biological function and cleavage targets are poorly understood. Caspase-2 is activated by the p53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome. We show that PIDD expression promotes growth arrest and chemotherapy resistance by a mechanism that depends on Caspase-2 and wild-type p53. PIDD-induced Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367, leading to loss of the C-terminal RING domain responsible for p53 ubiquitination. As a consequence, N-terminally truncated Mdm2 binds p53 and promotes its stability. Upon DNA damage, p53 induction of the Caspase-2-PIDDosome creates a positive feedback loop that inhibits Mdm2 and reinforces p53 stability and activity, contributing to cell survival and drug resistance. These data establish Mdm2 as a cleavage target of Caspase-2 and provide insight into a mechanism of Mdm2 inhibition that impacts p53 dynamics upon genotoxic stress. PMID:21726810

Mechanical Fracturing of Core-Shell Undercooled Metal Particles for Heat-Free Soldering.

PubMed

Çınar, Simge; Tevis, Ian D; Chen, Jiahao; Thuo, Martin

2016-02-23

Phase-change materials, such as meta-stable undercooled (supercooled) liquids, have been widely recognized as a suitable route for complex fabrication and engineering. Despite comprehensive studies on the undercooling phenomenon, little progress has been made in the use of undercooled metals, primarily due to low yields and poor stability. This paper reports the use of an extension of droplet emulsion technique (SLICE) to produce undercooled core-shell particles of structure; metal/oxide shell-acetate ('/' = physisorbed, '-' = chemisorbed), from molten Field's metal (Bi-In-Sn) and Bi-Sn alloys. These particles exhibit stability against solidification at ambient conditions. Besides synthesis, we report the use of these undercooled metal, liquid core-shell, particles for heat free joining and manufacturing at ambient conditions. Our approach incorporates gentle etching and/or fracturing of outer oxide-acetate layers through mechanical stressing or shearing, thus initiating a cascade entailing fluid flow with concomitant deformation, combination/alloying, shaping, and solidification. This simple and low cost technique for soldering and fabrication enables formation of complex shapes and joining at the meso- and micro-scale at ambient conditions without heat or electricity.

Longitudinal Stability and Predictors of Poor Oral Comprehenders and Poor Decoders

PubMed Central

Elwér, Åsa; Keenan, Janice M.; Olson, Richard K.; Byrne, Brian; Samuelsson, Stefan

2012-01-01

Two groups of 4th grade children were selected from a population sample (N= 926) to either be Poor Oral Comprehenders (poor oral comprehension but normal word decoding), or Poor Decoders (poor decoding but normal oral comprehension). By examining both groups in the same study with varied cognitive and literacy predictors, and examining them both retrospectively and prospectively, we could assess how distinctive and stable the predictors of each deficit are. Predictors were assessed retrospectively at preschool, at the end of kindergarten, 1st, and 2nd grades. Group effects were significant at all test occasions, including those for preschool vocabulary (worse in poor oral comprehenders) and rapid naming (RAN) (worse in poor decoders). Preschool RAN and Vocabulary prospectively predicted grade 4 group membership (77–79% correct classification) within the selected samples. Reselection in preschool of at-risk poor decoder and poor oral comprehender subgroups based on these variables led to significant but relatively weak prediction of subtype membership at grade 4. Implications of the predictive stability of our results for identification and intervention of these important subgroups are discussed. PMID:23528975

Stiff, Thermally Stable and Highly Anisotropic Wood-Derived Carbon Composite Monoliths for Electromagnetic Interference Shielding.

PubMed

Yuan, Ye; Sun, Xianxian; Yang, Minglong; Xu, Fan; Lin, Zaishan; Zhao, Xu; Ding, Yujie; Li, Jianjun; Yin, Weilong; Peng, Qingyu; He, Xiaodong; Li, Yibin

2017-06-28

Electromagnetic interference (EMI) shielding materials for electronic devices in aviation and aerospace not only need lightweight and high shielding effectiveness, but also should withstand harsh environments. Traditional EMI shielding materials often show heavy weight, poor thermal stability, short lifetime, poor tolerance to chemicals, and are hard-to-manufacture. Searching for high-efficiency EMI shielding materials overcoming the above weaknesses is still a great challenge. Herein, inspired by the unique structure of natural wood, lightweight and highly anisotropic wood-derived carbon composite EMI shielding materials have been prepared which possess not only high EMI shielding performance and mechanical stable characteristics, but also possess thermally stable properties, outperforming those metals, conductive polymers, and their composites. The newly developed low-cost materials are promising for specific applications in aerospace electronic devices, especially regarding extreme temperatures.

The efficacy of a supervised and a home-based core strengthening programme in adults with poor core stability: a three-arm randomised controlled trial.

PubMed

Chuter, V H; de Jonge, X A K Janse; Thompson, B M; Callister, R

2015-03-01

Poor core stability is linked to a range of musculoskeletal pathologies and core-strengthening programmes are widely used as treatment. Treatment outcomes, however, are highly variable, which may be related to the method of delivery of core strengthening programmes. We investigated the effect of identical 8 week core strengthening programmes delivered as either supervised or home-based on measures of core stability. Participants with poor core stability were randomised into three groups: supervised (n=26), home-based (n=26) or control (n=26). Primary outcomes were the Sahrmann test and the Star Excursion Balance Test (SEBT) for dynamic core stability and three endurance tests (side-bridge, flexor and Sorensen) for static core stability. The exercise programme was devised and supervised by an exercise physiologist. Analysis of covariance on the change from baseline over the 8 weeks showed that the supervised group performed significantly better on all core stability measures than both the home-based and control group. The home-based group produced significant improvements compared to the control group in all static core stability tests, but not in most of the dynamic core stability tests (Sahrmann test and two out of three directions of the SEBT). Our results support the use of a supervised core-strengthening programme over a home-based programme to maximise improvements in core stability, especially in its dynamic aspects. Based on our findings in healthy individuals with low core stability, further research is recommended on potential therapeutic benefits of supervised core-strengthening programmes for pathologies associated with low core stability. ACTRN12613000233729. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Influence of trabecular bone quality and implantation direction on press-fit mechanics.

PubMed

Damm, Niklas B; Morlock, Michael M; Bishop, Nicholas E

2017-02-01

Achieving primary stability of uncemented press-fit prostheses in patients with poor quality bone can involve axial implantation forces large enough to cause bone fracture. Radial implantation eliminates intraoperative impaction forces and could prevent this damage. Platens of two commercial implant surfaces ("Beaded" and "Flaked") were implanted onto trabecular bone specimens of varying quality in a press-fit simulator. Samples were implanted with varying interference, either axially (shear) or radially (normal). Push-in and pull-out forces were measured to assess stability. Microstructural changes in the bone were determined from μCT analysis. For force-defined implantation analysis, push-in and pull-out forces both increased proportionally with increasing radial force, independent of implantation direction, bone quality or implant surface. For position-defined implantation analysis, pull-out forces were generally found to increase with interference and to be greater for radial than axial implantation direction, and to be lower for poor quality bone. Bone density increased locally at the tested interface due to implantation, in particular for the Beaded surface under axial implantation. If a safe radial stress can be determined for cortical bone in a particular patient, the associated implantation force, and pull-out force which represents primary stability, can be directly derived, regardless of implantation direction, bone quality or implant surface. Radial implantation delivers primary stability that is no worse than that for axial implantation and may eliminate potentially damaging impaction forces. Development of implant designs based on this principal might improve implant fixation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:224-233, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Stabilization of the dimeric birch pollen allergen Bet v 1 impacts its immunological properties.

PubMed

Kofler, Stefan; Ackaert, Chloé; Samonig, Martin; Asam, Claudia; Briza, Peter; Horejs-Hoeck, Jutta; Cabrele, Chiara; Ferreira, Fatima; Duschl, Albert; Huber, Christian; Brandstetter, Hans

2014-01-03

Many allergens share several biophysical characteristics, including the capability to undergo oligomerization. The dimerization mechanism in Bet v 1 and its allergenic properties are so far poorly understood. Here, we report crystal structures of dimeric Bet v 1, revealing a noncanonical incorporation of cysteine at position 5 instead of genetically encoded tyrosine. Cysteine polysulfide bridging stabilized different dimeric assemblies, depending on the polysulfide linker length. These dimers represent quaternary arrangements that are frequently observed in related proteins, reflecting their prevalence in unmodified Bet v 1. These conclusions were corroborated by characteristic immunologic properties of monomeric and dimeric allergen variants. Hereby, residue 5 could be identified as an allergenic hot spot in Bet v 1. The presented results refine fundamental principles in protein chemistry and emphasize the importance of protein modifications in understanding the molecular basis of allergenicity.

The addition of body armor diminishes dynamic postural stability in military soldiers.

PubMed

Sell, Timothy C; Pederson, Jonathan J; Abt, John P; Nagai, Takashi; Deluzio, Jennifer; Wirt, Michael D; McCord, Larry J; Lephart, Scott M

2013-01-01

Poor postural stability has been identified as a risk factor for lower extremity musculoskeletal injury. The additional weight of body armor carried by Soldiers alters static postural stability and may predispose Soldiers to lower extremity musculoskeletal injuries. However, static postural stability tasks poorly replicate the dynamic military environment, which places considerable stress on the postural control system during tactical training and combat. Therefore, the purpose of this study was to examine the effects of body armor on dynamic postural stability during single-leg jump landings. Thirty-six 101st Airborne Division (Air Assault) Soldiers performed single-leg jump landings in the anterior direction with and without wearing body armor. The dynamic postural stability index and the individual stability indices (medial-lateral stability index, anterior-posterior stability index, and vertical stability index) were calculated for each condition. Paired sample t-tests were performed to determine differences between conditions. Significant differences existed for the medial-lateral stability index, anterior-posterior stability index, vertical stability index, and dynamic postural stability index (p < 0.05). The addition of body armor resulted in diminished dynamic postural stability, which may result in increased lower extremity injuries. Training programs should address the altered dynamic postural stability while wearing body armor in attempts to promote adaptations that will result in safer performance during dynamic tasks.

Impact of polymer type on bioperformance and physical stability of hot melt extruded formulations of a poorly water soluble drug.

PubMed

Mitra, Amitava; Li, Li; Marsac, Patrick; Marks, Brian; Liu, Zhen; Brown, Chad

2016-05-30

Amorphous solid dispersion formulations have been widely used to enhance bioavailability of poorly soluble drugs. In these formulations, polymer is included to physically stabilize the amorphous drug by dispersing it in the polymeric carrier and thus forming a solid solution. The polymer can also maintain supersaturation and promote speciation during dissolution, thus enabling better absorption as compared to crystalline drug substance. In this paper, we report the use of hot melt extrusion (HME) to develop amorphous formulations of a poorly soluble compound (FaSSIF solubility=1μg/mL). The poor solubility of the compound and high dose (300mg) necessitated the use of amorphous formulation to achieve adequate bioperformance. The effect of using three different polymers (HPMCAS-HF, HPMCAS-LF and copovidone), on the dissolution, physical stability, and bioperformance of the formulations was demonstrated. In this particular case, HPMCAS-HF containing HME provided the highest bioavailability and also had better physical stability as compared to extrudates using HPMCAS-LF and copovidone. The data demonstrated that the polymer type can have significant impact on the formulation bioperformance and physical stability. Thus a thorough understanding of the polymer choice is imperative when designing an amorphous solid dispersion formulation, such that the formulation provides robust bioperformance and has adequate shelf life. Copyright © 2016 Elsevier B.V. All rights reserved.

The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

PubMed

Gaiko-Shcherbak, Aljona; Fabris, Gloria; Dreissen, Georg; Merkel, Rudolf; Hoffmann, Bernd; Noetzel, Erik

2015-01-01

The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa) experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN) without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

In Situ Observation of Failure Mechanisms Controlled by Rock Masses with Weak Interlayer Zones in Large Underground Cavern Excavations Under High Geostress

NASA Astrophysics Data System (ADS)

Duan, Shu-Qian; Feng, Xia-Ting; Jiang, Quan; Liu, Guo-Feng; Pei, Shu-Feng; Fan, Yi-Lin

2017-09-01

A weak interlayer zone (WIZ) is a poor rock mass system with loose structure, weak mechanical properties, variable thickness, random distribution, strong extension, and high risk due to the shear motion of rock masses under the action of tectonism, bringing many stability problems and geological hazards, especially representing a potential threat to the overall stability of rock masses with WIZs in large underground cavern excavations. Focusing on the deformation and failure problems encountered in the process of excavation unloading, this research proposes comprehensive in situ observation schemes for rock masses with WIZs in large underground cavern on the basis of the collection of geological, construction, monitoring, and testing data. The schemes have been fully applied in two valuable project cases of an underground cavern group under construction in the southwest of China, including the plastic squeezing-out tensile failure and the structural stress-induced collapse of rock masses with WIZs. In this way, the development of rock mass failure, affected by the step-by-step excavations along the cavern's axis and the subsequent excavation downward, could be observed thoroughly. Furthermore, this paper reveals the preliminary analyses of failure mechanism of rock masses with WIZs from several aspects, including rock mass structure, strength, high stress, ground water effects, and microfracture mechanisms. Finally, the failure particularities of rock masses with WIZs and rethink on prevention and control of failures are discussed. The research results could provide important guiding reference value for stability analysis, as well as for rethinking the excavation and support optimization of rock masses with WIZs in similar large underground cavern under high geostress.

3D printing of Mg-substituted wollastonite reinforcing diopside porous bioceramics with enhanced mechanical and biological performances.

PubMed

He, Dongshuang; Zhuang, Chen; Xu, Sanzhong; Ke, Xiurong; Yang, Xianyan; Zhang, Lei; Yang, Guojing; Chen, Xiaoyi; Mou, Xiaozhou; Liu, An; Gou, Zhongru

2016-09-01

Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head. Considering the long-term stability of diopside (DIO) ceramic but poor mechanical strength, we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional (3D) printing. The experimental results showed that the secondary phase (i.e. 10% magnesium substituting calcium silicate; CSM10) could readily improve the sintering property of the bioceramic composites (DIO/CSM10- x , x  = 0-30) with increasing the CSM10 content from 0% to 30%, and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds. Furthermore, the flexible strength (12.5-30 MPa) and compressive strength (14-37 MPa) of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content, and the compressive strength of DIO/CSM10-30 showed a limited decay (from 37 MPa to 29 MPa) in the Tris buffer solution for a long time stage (8 weeks). These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic, especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod.

High-temperature superconductor bulk magnets that can trap magnetic fields of over 17 tesla at 29 K.

PubMed

Tomita, Masaru; Murakami, Masato

2003-01-30

Large-grain high-temperature superconductors of the form RE-Ba-Cu-O (where RE is a rare-earth element) can trap magnetic fields of several tesla at low temperatures, and so can be used for permanent magnet applications. The magnitude of the trapped field is proportional to the critical current density and the volume of the superconductor. Various potential engineering applications for such magnets have emerged, and some have already been commercialized. However, the range of applications is limited by poor mechanical stability and low thermal conductivity of the bulk superconductors; RE-Ba-Cu-O magnets have been found to fracture during high-field activation, owing to magnetic pressure. Here we present a post-fabrication treatment that improves the mechanical properties as well as thermal conductivity of a bulk Y-Ba-Cu-O magnet, thereby increasing its field-trapping capacity. First, resin impregnation and wrapping the materials in carbon fibre improves the mechanical properties. Second, a small hole drilled into the centre of the magnet allows impregnation of Bi-Pb-Sn-Cd alloy into the superconductor and inclusion of an aluminium wire support, which results in a significant enhancement of thermal stability and internal mechanical strength. As a result, 17.24 T could be trapped, without fracturing, in a bulk Y-Ba-Cu-O sample of 2.65 cm diameter at 29 K.

Inhomogeneous degradation in metal halide perovskites

NASA Astrophysics Data System (ADS)

Yang, Rong; Zhang, Li; Cao, Yu; Miao, Yanfeng; Ke, You; Wei, Yingqiang; Guo, Qiang; Wang, Ying; Rong, Zhaohua; Wang, Nana; Li, Renzhi; Wang, Jianpu; Huang, Wei; Gao, Feng

2017-08-01

Although the rapid development of organic-inorganic metal halide perovskite solar cells has led to certified power conversion efficiencies of above 20%, their poor stability remains a major challenge, preventing their practical commercialization. In this paper, we investigate the intrinsic origin of the poor stability in perovskite solar cells by using a confocal fluorescence microscope. We find that the degradation of perovskite films starts from grain boundaries and gradually extend to the center of the grains. Firmly based on our findings, we further demonstrate that the device stability can be significantly enhanced by increasing the grain size of perovskite crystals. Our results have important implications to further enhance the stability of optoelectronic devices based on metal halide perovskites.

Effects of Pedogenic Fe Oxides on Soil Aggregate-Associated Carbon

NASA Astrophysics Data System (ADS)

Asefaw Berhe, A.; Jin, L.

2017-12-01

Carbon sequestration is intimately related to the soil structure, mainly soil aggregate dynamics. Carbon storage in soil aggregates has been recognized as an important carbon stabilization mechanism in soils. Organic matter and pedogenic Fe oxides are major binding agents that facilitate soil aggregate formation and stability. However, few studies have investigated how different forms of pedogenic Fe oxides can affect soil carbon distribution in different aggregate-size fractions. We investigated sequentially extracted pedogenic Fe oxides (in the order of organically complexed Fe extracted with sodium pyrophosphate, poorly-crystalline Fe oxides extracted with hydroxylamine hydrochloride, and crystalline Fe oxides extracted with dithionite hydrochloride) and determined the amount and nature of C in macroaggregates (2-0.25mm), microaggregates (0.25-0.053mm), and two silt and clay fractions (0.053-0.02mm, and <0.02mm) in Musick soil from Sierra Nevada mountain in California. We also determined how pedogenic Fe oxides affect soil carbon distribution along soil depth gradients. Findings of our study revealed that the proportion of organic matter complexed Fe decreased, but the proportion of crystalline Fe increased with increasing soil depths. Poorly crystalline Fe oxides (e.g. ferrihydrite) was identified as a major Fe oxide in surface soil, whereas crystalline Fe oxides (e.g. goethite) were found in deeper soil layers. These results suggest that high concentration of organic matter in surface soil suppressed Fe crystallization. Calcium cation was closely related to the pyrophosphate extractable Fe and C, which indicates that calcium may be a major cation that contribute to the organic matter complexed Fe and C pool. Increasing concentrations of extractable Fe and C with decreasing aggregate size fractions also suggests that Fe oxides play an important role in formation and stability of silt and clay fractions, and leading to further stabilization of carbon in soil. Our findings provide mechanistic understanding of how pedogenic Fe oxides play important role in carbon stabilization in different aggregate-size fractions in soil.

Beyond Anchoring: the Expanding Role of the Hendra Virus Fusion Protein Transmembrane Domain in Protein Folding, Stability, and Function

PubMed Central

Smith, Everett Clinton; Culler, Megan R.; Hellman, Lance M.; Fried, Michael G.; Creamer, Trevor P.

2012-01-01

While work with viral fusion proteins has demonstrated that the transmembrane domain (TMD) can affect protein folding, stability, and membrane fusion promotion, the mechanism(s) remains poorly understood. TMDs could play a role in fusion promotion through direct TMD-TMD interactions, and we have recently shown that isolated TMDs from three paramyxovirus fusion (F) proteins interact as trimers using sedimentation equilibrium (SE) analysis (E. C. Smith, et al., submitted for publication). Immediately N-terminal to the TMD is heptad repeat B (HRB), which plays critical roles in fusion. Interestingly, addition of HRB decreased the stability of the trimeric TMD-TMD interactions. This result, combined with previous findings that HRB forms a trimeric coiled coil in the prefusion form of the whole protein though HRB peptides fail to stably associate in isolation, suggests that the trimeric TMD-TMD interactions work in concert with elements in the F ectodomain head to stabilize a weak HRB interaction. Thus, changes in TMD-TMD interactions could be important in regulating F triggering and refolding. Alanine insertions between the TMD and HRB demonstrated that spacing between these two regions is important for protein stability while not affecting TMD-TMD interactions. Additional mutagenesis of the C-terminal end of the TMD suggests that β-branched residues within the TMD play a role in membrane fusion, potentially through modulation of TMD-TMD interactions. Our results support a model whereby the C-terminal end of the Hendra virus F TMD is an important regulator of TMD-TMD interactions and show that these interactions help hold HRB in place prior to the triggering of membrane fusion. PMID:22238302

Vestibular rehabilitation therapy: review of indications, mechanisms, and key exercises.

PubMed

Han, Byung In; Song, Hyun Seok; Kim, Ji Soo

2011-12-01

Vestibular rehabilitation therapy (VRT) is an exercise-based treatment program designed to promote vestibular adaptation and substitution. The goals of VRT are 1) to enhance gaze stability, 2) to enhance postural stability, 3) to improve vertigo, and 4) to improve activities of daily living. VRT facilitates vestibular recovery mechanisms: vestibular adaptation, substitution by the other eye-movement systems, substitution by vision, somatosensory cues, other postural strategies, and habituation. The key exercises for VRT are head-eye movements with various body postures and activities, and maintaining balance with a reduced support base with various orientations of the head and trunk, while performing various upper-extremity tasks, repeating the movements provoking vertigo, and exposing patients gradually to various sensory and motor environments. VRT is indicated for any stable but poorly compensated vestibular lesion, regardless of the patient's age, the cause, and symptom duration and intensity. Vestibular suppressants, visual and somatosensory deprivation, immobilization, old age, concurrent central lesions, and long recovery from symptoms, but there is no difference in the final outcome. As long as exercises are performed several times every day, even brief periods of exercise are sufficient to facilitate vestibular recovery. Here the authors review the mechanisms and the key exercises for each of the VRT goals.

Vestibular Rehabilitation Therapy: Review of Indications, Mechanisms, and Key Exercises

PubMed Central

Song, Hyun Seok; Kim, Ji Soo

2011-01-01

Vestibular rehabilitation therapy (VRT) is an exercise-based treatment program designed to promote vestibular adaptation and substitution. The goals of VRT are 1) to enhance gaze stability, 2) to enhance postural stability, 3) to improve vertigo, and 4) to improve activities of daily living. VRT facilitates vestibular recovery mechanisms: vestibular adaptation, substitution by the other eye-movement systems, substitution by vision, somatosensory cues, other postural strategies, and habituation. The key exercises for VRT are head-eye movements with various body postures and activities, and maintaining balance with a reduced support base with various orientations of the head and trunk, while performing various upper-extremity tasks, repeating the movements provoking vertigo, and exposing patients gradually to various sensory and motor environments. VRT is indicated for any stable but poorly compensated vestibular lesion, regardless of the patient's age, the cause, and symptom duration and intensity. Vestibular suppressants, visual and somatosensory deprivation, immobilization, old age, concurrent central lesions, and long recovery from symptoms, but there is no difference in the final outcome. As long as exercises are performed several times every day, even brief periods of exercise are sufficient to facilitate vestibular recovery. Here the authors review the mechanisms and the key exercises for each of the VRT goals. PMID:22259614

Poor chest compression quality with mechanical compressions in simulated cardiopulmonary resuscitation: a randomized, cross-over manikin study.

PubMed

Blomberg, Hans; Gedeborg, Rolf; Berglund, Lars; Karlsten, Rolf; Johansson, Jakob

2011-10-01

Mechanical chest compression devices are being implemented as an aid in cardiopulmonary resuscitation (CPR), despite lack of evidence of improved outcome. This manikin study evaluates the CPR-performance of ambulance crews, who had a mechanical chest compression device implemented in their routine clinical practice 8 months previously. The objectives were to evaluate time to first defibrillation, no-flow time, and estimate the quality of compressions. The performance of 21 ambulance crews (ambulance nurse and emergency medical technician) with the authorization to perform advanced life support was studied in an experimental, randomized cross-over study in a manikin setup. Each crew performed two identical CPR scenarios, with and without the aid of the mechanical compression device LUCAS. A computerized manikin was used for data sampling. There were no substantial differences in time to first defibrillation or no-flow time until first defibrillation. However, the fraction of adequate compressions in relation to total compressions was remarkably low in LUCAS-CPR (58%) compared to manual CPR (88%) (95% confidence interval for the difference: 13-50%). Only 12 out of the 21 ambulance crews (57%) applied the mandatory stabilization strap on the LUCAS device. The use of a mechanical compression aid was not associated with substantial differences in time to first defibrillation or no-flow time in the early phase of CPR. However, constant but poor chest compressions due to failure in recognizing and correcting a malposition of the device may counteract a potential benefit of mechanical chest compressions. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Enhancement of toughness and wear resistance in boron nitride nanoplatelet (BNNP) reinforced Si3N4 nanocomposites

PubMed Central

Lee, Bin; Lee, Dongju; Lee, Jun Ho; Ryu, Ho Jin; Hong, Soon Hyung

2016-01-01

Ceramics have superior hardness, strength and corrosion resistance, but are also associated with poor toughness. Here, we propose the boron nitride nanoplatelet (BNNP) as a novel toughening reinforcement component to ceramics with outstanding mechanical properties and high-temperature stability. We used a planetary ball-milling process to exfoliate BNNPs in a scalable manner and functionalizes them with polystyrene sulfonate. Non-covalently functionalized BNNPs were homogeneously dispersed with Si3N4 powders using a surfactant and then consolidated by hot pressing. The fracture toughness of the BNNP/Si3N4 nanocomposite increased by as much as 24.7% with 2 vol.% of BNNPs. Furthermore, BNNPs enhanced strength (9.4%) and the tribological properties (26.7%) of the ceramic matrix. Microstructural analyzes have shown that the toughening mechanisms are combinations of the pull-out, crack bridging, branching and blunting mechanisms. PMID:27271465

Massive cellular disruption occurs during early imbibition of Cuphea seeds containing crystallized triacylglycerols.

PubMed

Volk, Gayle M; Crane, Jennifer; Caspersen, Ann M; Hill, Lisa M; Gardner, Candice; Walters, Christina

2006-11-01

The transition from anhydrobiotic to hydrated state occurs during early imbibition of seeds and is lethal if lipid reserves in seeds are crystalline. Low temperatures crystallize lipids during seed storage. We examine the nature of cellular damage observed in seeds of Cuphea wrightii and C. lanceolata that differ in triacylglycerol composition and phase behavior. Intracellular structure, observed using transmission electron microscopy, is profoundly and irreversibly perturbed if seeds with crystalline triacylglycerols are imbibed briefly. A brief heat treatment that melts triacylglycerols before imbibition prevents the loss of cell integrity; however, residual effects of cold treatments in C. wrightii cells are reflected by the apparent coalescence of protein and oil bodies. The timing and temperature dependence of cellular changes suggest that damage arises via a physical mechanism, perhaps as a result of shifts in hydrophobic and hydrophilic interactions when triacylglycerols undergo phase changes. Stabilizers of oil body structure such as oleosins that rely on a balance of physical forces may become ineffective when triacylglycerols crystallize. Recent observations linking poor oil body stability and poor seed storage behavior are potentially explained by the phase behavior of the storage lipids. These findings directly impact the feasibility of preserving genetic resources from some tropical and subtropical species.

Lateglacial landscape and vegetation change and the younger dryas climatic oscillation in New Zealand

NASA Astrophysics Data System (ADS)

McGlone, M. S.

Lateglacial sequences in New Zealand show progressive afforestation and landscape stabilization reflecting a warming climate. Between 14,500 BP and 11,500 BP, afforestation and landscape stability was achieved throughout most of the North Island and the northwest sector of the South Island. In the South Island, scrub and tree ferns were replacing previous grasslands in the east by 11,000 BP, and broadleaved forest was spreading in the west. No significant reversals of these trends occurred and afforestation was complete by 9500 BP. Glaciers of the high central part of the Southern Alps made a series of advances between 14,000 and 9000 BP Most of these advances are poorly dated but two moraines are of Younger Dryas age. Glacial advances in the face of the general Lateglacial warming trend may have been driven by stronger westerly winds increasing snowfall on high altitude névés, and by reduced ablation as a consequence of moist, cloudy, low insolation summers. The cause of the northern hemisphere Younger Dryas cooling is still uncertain, and expected Southern Hemisphere responses may differ according to the mechanism proposed for the cooling. Poor chronological resolution and apparent conflict between the various types of evidence for climatic change make detection of an unambiguous Younger Dryas in New Zealand problematical.

[Organic waste treatment by earthworm vermicomposting and larvae bioconversion: review and perspective].

PubMed

Zhang, Zhi-jian; Liu, Meng; Zhu, Jun

2013-05-01

There is a growing attention on the environmental pollution and loss of potential regeneration of resources due to the poor handling of organic wastes, while earthworm vermicomposting and larvae bioconversion are well-known as two promising biotechnologies for sustainable wastes treatments, where earthworms or housefly larvae are employed to convert the organic wastes into humus like material, together with value-added worm product. Taken earthworm ( Eisenia foetida) and housefly larvae ( Musca domestica) as model species, this work illustrates fundamental definition and principle, operational process, technical mechanism, main factors, and bio-chemical features of organisms of these two technologies. Integrated with the physical and biochemical mechanisms, processes of biomass conversion, intestinal digestion, enzyme degradation and microflora decomposition are comprehensively reviewed on waste treatments with purposes of waste reduction, value-addition, and stabilization.

Models for small-scale structure on cosmic strings. II. Scaling and its stability

NASA Astrophysics Data System (ADS)

Vieira, J. P. P.; Martins, C. J. A. P.; Shellard, E. P. S.

2016-11-01

We make use of the formalism described in a previous paper [Martins et al., Phys. Rev. D 90, 043518 (2014)] to address general features of wiggly cosmic string evolution. In particular, we highlight the important role played by poorly understood energy loss mechanisms and propose a simple Ansatz which tackles this problem in the context of an extended velocity-dependent one-scale model. We find a general procedure to determine all the scaling solutions admitted by a specific string model and study their stability, enabling a detailed comparison with future numerical simulations. A simpler comparison with previous Goto-Nambu simulations supports earlier evidence that scaling is easier to achieve in the matter era than in the radiation era. In addition, we also find that the requirement that a scaling regime be stable seems to notably constrain the allowed range of energy loss parameters.

Nonequilibrium stabilization of an RNA/protein droplet emulsion by nuclear actin

NASA Astrophysics Data System (ADS)

Brangwynne, Clifford

2013-03-01

Actin plays a structural role in the cytoplasm. However, actin takes on new functions and structures in the nucleus that are poorly understood. The nuclei of the large oocytes of the frog X. laevisspecifically accumulate actin to reach high concentrations; however, it remains unclear if this actin polymerizes into a network, and what, if any, structural role such an actin network might play. Here, we use microrheological and confocal imaging techniques to probe the local architecture and mechanics of the nucleus. Our data show that actin forms a weak network that spatially organizes the nucleus by kinetically stabilizing embedded liquid-like RNA/protein bodies which are important for cell growth. In actin-disrupted nuclei this RNA/protein droplet emulsion is destabilized leading to homotypic coalescence into single large droplets. Our data provide intriguing new insights into why large cell nuclei require an actin-based structural scaffold.

Microtubule-dependent regulation of mitotic protein degradation

PubMed Central

Song, Ling; Craney, Allison; Rape, Michael

2014-01-01

Accurate cell division depends on tightly regulated ubiquitylation events catalyzed by the anaphase-promoting complex. Among its many substrates, the APC/C triggers the degradation of proteins that stabilize the mitotic spindle, and loss or accumulation of such spindle assembly factors can result in aneuploidy and cancer. Although critical for cell division, it has remained poorly understood how the timing of spindle assembly factor degradation is established during mitosis. Here, we report that active spindle assembly factors are protected from APC/C-dependent degradation by microtubules. In contrast, those molecules that are not bound to microtubules are highly susceptible to proteolysis and turned over immediately after APC/C-activation. The correct timing of spindle assembly factor degradation, as achieved by this regulatory circuit, is required for accurate spindle structure and function. We propose that the localized stabilization of APC/C-substrates provides a mechanism for the selective disposal of cell cycle regulators that have fulfilled their mitotic roles. PMID:24462202

Application of small-signal modeling and measurement techniques to the stability analysis of an integrated switching-mode power system. [onboard Dynamics Explorer Satellite

NASA Technical Reports Server (NTRS)

Wong, R. C.; Owen, H. A., Jr.; Wilson, T. G.; Rodriguez, G. E.

1980-01-01

Small-signal modeling techniques are used in a system stability analysis of a breadboard version of a complete functional electrical power system. The system consists of a regulated switching dc-to-dc converter, a solar-cell-array simulator, a solar-array EMI filter, battery chargers and linear shunt regulators. Loss mechanisms in the converter power stage, including switching-time effects in the semiconductor elements, are incorporated into the modeling procedure to provide an accurate representation of the system without requiring frequency-domain measurements to determine the damping factor. The small-signal system model is validated by the use of special measurement techniques which are adapted to the poor signal-to-noise ratio encountered in switching-mode systems. The complete electrical power system with the solar-array EMI filter is shown to be stable over the intended range of operation.

Irc3 is a mitochondrial DNA branch migration enzyme

PubMed Central

Gaidutšik, Ilja; Sedman, Tiina; Sillamaa, Sirelin; Sedman, Juhan

2016-01-01

Integrity of mitochondrial DNA (mtDNA) is essential for cellular energy metabolism. In the budding yeast Saccharomyces cerevisiae, a large number of nuclear genes influence the stability of mitochondrial genome; however, most corresponding gene products act indirectly and the actual molecular mechanisms of mtDNA inheritance remain poorly characterized. Recently, we found that a Superfamily II helicase Irc3 is required for the maintenance of mitochondrial genome integrity. Here we show that Irc3 is a mitochondrial DNA branch migration enzyme. Irc3 modulates mtDNA metabolic intermediates by preferential binding and unwinding Holliday junctions and replication fork structures. Furthermore, we demonstrate that the loss of Irc3 can be complemented with mitochondrially targeted RecG of Escherichia coli. We suggest that Irc3 could support the stability of mtDNA by stimulating fork regression and branch migration or by inhibiting the formation of irregular branched molecules. PMID:27194389

Exhaust gas measurements in a propane fueled swirl stabilized combustor

NASA Technical Reports Server (NTRS)

Aanad, M. S.

1982-01-01

Exhaust gas temperature, velocity, and composition are measured and combustor efficiencies are calculated in a lean premixed swirl stabilized laboratory combustor. The radial profiles of the data between the co- and the counter swirl cases show significant differences. Co-swirl cases show evidence of poor turbulent mixing across the combustor in comparison to the counter-swirl cases. NO sub x levels are low in the combustor but substantial amounts of CO are present. Combustion efficiencies are low and surprisingly constant with varying outer swirl in contradiction to previous results under a slightly different inner swirl condition. This difference in the efficiency trends is expected to be a result of the high sensitivity of the combustor to changes in the inner swirl. Combustor operation is found to be the same for propane and methane fuels. A mechanism is proposed to explain the combustor operation and a few important characteristics determining combustor efficiency are identified.

Solubility, stability, and electrochemical studies of sulfur-sulfide solutions in organic solvents

NASA Technical Reports Server (NTRS)

Fielder, W. L.; Singer, J.

1978-01-01

A preliminary study of the sulfur electrode in organic solvents suggests that the system warrants further investigation for use in a low temperature (100 deg to 120 C) Na-S secondary battery. A qualitative screening was undertaken at 120 C to determine the solubilities and stabilities of Na2S and Na2S2 in representatives of many classes of organic solvents. From the screening and quantitative studies, two classes of solvents were selected for work; amides and cyclic polyalcohols. Voltammetric and Na-S cell charge discharge studies of sulfide solutions in organic solvents (e.g., N, N-dimethylformamide) at 120 C suggested that the reversibilities of the reactions on Pt or high density graphite were moderately poor. However, the sulfur electrode was indeed reducible (and oxidizable) through the range of elemental sulfur to Na2S. Reactions and mechanisms are proposed for the oxidation reduction processes occurring at the sulfur electrode.

Simulation studies of nucleation of ferroelectric polarization reversal.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brennecka, Geoffrey L.; Winchester, Benjamin Michael

2014-08-01

Electric field-induced reversal of spontaneous polarization is the defining characteristic of a ferroelectric material, but the process(es) and mechanism(s) associated with the initial nucleation of reverse-polarity domains are poorly understood. This report describes studies carried out using phase field modeling of LiTaO 3, a relatively simple prototype ferroelectric material, in order to explore the effects of either mechanical deformation or optically-induced free charges on nucleation and resulting domain configuration during field-induced polarization reversal. Conditions were selected to approximate as closely as feasible those of accompanying experimental work in order to provide not only support for the experimental work but alsomore » ensure that additional experimental validation of the simulations could be carried out in the future. Phase field simulations strongly support surface mechanical damage/deformation as effective for dramatically reducing the overall coercive field (Ec) via local field enhancements. Further, optically-nucleated polarization reversal appears to occur via stabilization of latent nuclei via the charge screening effects of free charges.« less

An overview of structure, mechanical properties, and treatment for age-related tendinopathy.

PubMed

Zhou, B; Zhou, Y; Tang, K

2014-04-01

Tendons transfer tensile loads from muscle to bone, which enable joint motions and stabilize joints. Tendons sustain large mechanical loads in vivo and as a result, tendons were frequently injured. Aging has been confirmed as a predisposing factor of tendinopathy and bad recovery quality following tendon repair. Current treatment methods are generally not effective and involve either symptomatic relief with non-steroidal antiinflammatory drugs and physical therapy or surgery when conservative treatments failed. The limitation in treatment options is due to our incomplete knowledge of age-related tendinopathy. Studies over the past decades have uncovered a number of important mechanical and cellular changes of aging tendon. However, the basis of aging as a major risk factor for tendon injury and impaired tendon healing remained poorly understood. The objectives of this review are to provide an overview of the current knowledge about the aging-associated changes of structure, mechanical properties and treatment in tendon and highlight causes and therapies for age-related tendinopathy.

Thermal and mechanical properties of selected 3D printed thermoplastics in the cryogenic temperature regime

NASA Astrophysics Data System (ADS)

Weiss, K.-P.; Bagrets, N.; Lange, C.; Goldacker, W.; Wohlgemuth, J.

2015-12-01

Insulating materials for use in cryogenic boundary conditions are still limited to a proved selection as Polyamid, Glasfiber reinforced resins, PEEK, Vespel etc. These materials are usually formed to parts by mechanical machining or sometimes by cast methods. Shaping complex geometries in one piece is limited. Innovative 3D printing is now an upcoming revolutionary technology to construct functional parts from a couple of thermoplastic materials as ABS, Nylon and others which possess quite good mechanical stability and allow realizing very complex shapes with very subtle details. Even a wide range of material mixtures is an option and thermal treatments can be used to finish the material structure for higher performance. The use of such materials in cryogenic environment is very attractive but so far poor experience exists. In this paper, first investigations of the thermal conductivity, expansion and mechanical strength are presented for a few selected commercial 3D material samples to evaluate their application prospects in the cryogenic temperature regime.

Covalently Connecting Crystal Grains with Polyvinylammonium Carbochain Backbone To Suppress Grain Boundaries for Long-Term Stable Perovskite Solar Cells.

PubMed

Li, Han; Liang, Chao; Liu, Yingliang; Zhang, Yiqiang; Tong, Jincheng; Zuo, Weiwei; Xu, Shengang; Shao, Guosheng; Cao, Shaokui

2017-02-22

Grain boundaries act as rapid pathways for nonradiative carrier recombination, anion migration, and water corrosion, leading to low efficiency and poor stability of organometal halide perovskite solar cells (PSCs). In this work, the strategy suppressing the crystal grain boundaries is applied to improve the photovoltaic performance, especially moisture-resistant stability, with polyvinylammonium carbochain backbone covalently connecting the perovskite crystal grains. This cationic polyelectrolyte additive serves as nucleation sites and template for crystal growth of MAPbI 3 and afterward the immobilized adjacent crystal grains grow into the continuous compact, pinhole-free perovskite layer. As a result, the unsealed PSC devices, which are fabricated under low-temperature fabrication protocol with a proper content of polymer additive PVAm·HI, currently exhibit the maximum efficiency of 16.3%. Remarkably, these unsealed devices follow an "outside-in" corrosion mechanism and respectively retain 92% and 80% of the initial PCE value after being exposed under ambient environment for 50 days and 100 days, indicating the superiority of carbochain polymer additives in solving the long-term stability problem of PSCs.

Structural characterization, formation mechanism and stability of curcumin in zein-lecithin composite nanoparticles fabricated by antisolvent co-precipitation.

PubMed

Dai, Lei; Sun, Cuixia; Li, Ruirui; Mao, Like; Liu, Fuguo; Gao, Yanxiang

2017-12-15

Curcumin (Cur) exhibits a range of bioactive properties, but its application is restrained due to its poor water solubility and sensitivity to environmental stresses. In this study, zein-lecithin composite nanoparticles were fabricated by antisolvent co-precipitation technique for delivery of Cur. The result showed that the encapsulation efficiency of Cur was significantly enhanced from 42.03% in zein nanoparticles to 99.83% in zein-lecithin composite nanoparticles. The Cur entrapped in the nanoparticles was in an amorphous state confirmed by differential scanning calorimetry and X-ray diffraction. Fourier transform infrared analysis revealed that hydrogen bonding, electrostatic interaction and hydrophobic attraction were the main interactions among zein, lecithin, and Cur. Compared with single zein and lecithin nanoparticles, zein-lecithin composite nanoparticles significantly improved the stability of Cur against thermal treatment, UV irradiation and high ionic strength. Therefore, zein-lecithin composite nanoparticles could be a potential delivery system for water-insoluble bioactive compounds with enhanced encapsulation efficiency and chemical stability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stabilization of tetanus toxoid encapsulated in PLGA microspheres.

PubMed

Jiang, Wenlei; Schwendeman, Steven P

2008-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine based on PLGA microspheres have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT), in the polymer. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: (1) protein aggregation mediated by formaldehyde and (2) acid-induced protein unfolding and epitope damage. Further, we systematically identified excipients, which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA.

RETRACTED: Chemical densification of plasma sprayed yttria stabilized zirconia (YSZ) coatings for high temperature wear and corrosion resistance

NASA Astrophysics Data System (ADS)

Ye, Yaping; Fehr, Karl Thomas; Faulstich, Martin; Wolf, Gerhard

2012-12-01

Plasma-sprayed yttria stabilized zirconia (YSZ) ceramic coatings have been widely used as wear- and corrosion-resistant coatings in high temperature applications and an aggressive environment due to their high hardness, wear resistance, heat and chemical resistance, and low thermal conductivity. The highly porous structure of plasma-sprayed ceramic coatings and their poor adhesion to the substrate usually lead to the coating degradation and failure. In this study, a two-layer system consisting of atmospheric plasma-sprayed 8 wt.% yttria-stabilized zirconia (8YSZ) and Ni-based alloy coatings was post-treated by means of a novel chemical sealing process at moderate temperatures of 600-800 °C. Microstructure characteristics of the YSZ coatings were studied using an electron probe micro-analyzer (EPMA). Results revealed that the ceramic top coat was densified by the precipitated zirconia in the open pores. Therefore, the sealed YSZ coatings exhibit reduced porosity, higher hardness and a better adhesion onto the bond coat. The mechanisms for the sealing process were also proposed.

Effect of natural phenolics on the thermal and processing behaviour of poly(3-hydroxybutyrate)

NASA Astrophysics Data System (ADS)

Auriemma, Maria; Piscitelli, Amodio; Pasquino, Rossana; Cerruti, Pierfrancesco; Angelini, Stefania; Scarinzi, Gennaro; Malinconico, Mario; Grizzuti, Nino

2015-12-01

Poly(3-hydroxybutyrate) (PHB) is a biodegradable polymer, whose applicability is limited by its relatively poor mechanical properties and narrow processing window. In this paper, different natural phenol-based additives, including tannic acid (TA), grape bagasse extract (EP), and a lignocellulosic biomass (LC) were used as thermal and processing stabilizers for PHB. The thermal stability of both neat and doped PHB samples was studied by rheology and calorimetry. The experimental results showed that neat PHB massively degrades and that the addition of phenol additives enhances the thermal stability of PHB, preserving the polymer molecular weight after processing. This finding was in agreement with the slower decay in viscosity observed through rheological tests. Physical and chemical interactions between polymer and additive were considered as key factors to interpret the experimental data. LC affected the melt crystallization kinetics of PHB enhancing crystallization upon cooling. This finding suggests that LC was a heterogeneous nucleating agent, potentially able to control the physical aging of PHB. The described results are of interest for the development of sustainable alternatives to synthetic polymer additives, by increasing the applicability of bio-based materials.

Interactions between drugs and polymers influencing hot melt extrusion.

PubMed

Li, Yongcheng; Pang, Huishi; Guo, Zhefei; Lin, Ling; Dong, Yixuan; Li, Ge; Lu, Ming; Wu, Chuangbin

2014-02-01

Hot melt extrusion (HME) as a technique for producing amorphous solid dispersion (ASD) has been widely used in pharmaceutical research. The biggest challenge for the application of HME is the thermal degradation of drug, poor physical stability of ASD and precipitation of drug during dissolution. Interactions between drugs and polymers may play an important role in overcoming these barriers. In this review, influence of drug-polymer interactions on HME and the methods for characterizing the drug-polymer interactions were reviewed. Strong drug-polymer interactions, especially ionic interactions and hydrogen bonds, are helpful to improving the thermal stability of drug during HME, enhancing the physical stability of ASD during storage and maintaining supersaturated solution after dissolution in gastrointestinal tract. The interactions can be quantitatively and qualitatively characterized by many analysing methods. As many factors collectively determine the properties of HME products, drug-polymer interactions play an extremely important role. However, the action mechanisms of drug-polymer interactions need intensive investigation to provide more useful information for optimizing the formulation and the process parameters of HME. © 2013 Royal Pharmaceutical Society.

The effect of copper, MDA, and accelerated aging on jet fuel thermal stability as measured by the gravimetric JFTOT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pande, S.G.; Hardy, D.R.

1995-05-01

Thermally unstable jet fuels pose operational problems. In order to adequately identify such fuels, factors that realistically impact on thermal stability were examined. Evaluation was based on a quantitative method of measuring thermal stability, viz., NRL`s recently developed gravimetric JFTOT. This method gives a quantitative measurement of both the strip deposit and filterables formed. The pertinent factors examined, included the individual and interactive effects of: soluble copper, MDA (metal deactivator), and aging. The latter was accelerated to simulate field conditions of approximately six months aging at ambient temperature and pressure. The results indicate that the individual and interactive effects ofmore » copper, MDA, and accelerated aging appear to be fuel dependent. Based on the results, the three test fuels examined (one JP-8 and two JP-5s) were categorized as exhibiting very good, typical, and poor thermal stabilities, respectively. For both the very good and poor thermal stability fuels, the effect of copper in conjunction with accelerated aging did not significantly increase the total thermal deposits of the neat fuels. In contrast, for the typical thermal stability fuel, the combined effects of copper and accelerated aging, did. Furthermore, the addition of MDA prior to aging of the copper-doped, typical stability fuel significantly counteracted the adverse effect of copper and aging. A similar beneficial effect of MDA was not observed for the poor stability fuel. These results focus on the compositional differences among fuels and the need to elucidate these differences (physical and chemical) for a better understanding and prediction of their performance.« less

Collagen hydrogels incorporated with surface-aminated mesoporous nanobioactive glass: Improvement of physicochemical stability and mechanical properties is effective for hard tissue engineering.

PubMed

El-Fiqi, Ahmed; Lee, Jae Ho; Lee, Eun-Jung; Kim, Hae-Won

2013-12-01

Collagen (Col) hydrogels have poor physicochemical and mechanical properties and are susceptible to substantial shrinkage during cell culture, which limits their potential applications in hard tissue engineering. Here, we developed novel nanocomposite hydrogels made of collagen and mesoporous bioactive glass nanoparticles (mBGns) with surface amination, and addressed the effects of mBGn addition (Col:mBG = 2:1, 1:1 and 1:2) and its surface amination on the physicochemical and mechanical properties of the hydrogels. The amination of mBGn was shown to enable chemical bonding with collagen molecules. As a result, the nanocomposite hydrogels exhibited a significantly improved physicochemical and mechanical stability. The hydrolytic and enzymatic degradation of the Col-mBGn hydrogels were slowed down due to the incorporation of mBGn and its surface amination. The mechanical properties of the hydrogels, specifically the resistance to loading as well as the stiffness, significantly increased with the addition of mBGn and its aminated form, as assessed by a dynamic mechanical analysis. Mesenchymal stem cells cultivated within the Col-mBGn hydrogels were highly viable, with enhanced cytoskeletal extensions, due to the addition of surface aminated mBGn. While the Col hydrogel showed extensive shrinkage (down to ∼20% of initial size) during a few days of culture, the shrinkage of the mBGn-added hydrogel was substantially reduced, and the aminated mBGn-added hydrogel had no observable shrinkage over 21 days. Results demonstrated the effective roles of aminated mBGn in significantly improving the physicochemical and mechanical properties of Col hydrogel, which are ultimately favorable for applications in stem cell culture for bone tissue engineering. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Critical material attributes (CMAs) of strip films loaded with poorly water-soluble drug nanoparticles: III. Impact of drug nanoparticle loading.

PubMed

Krull, Scott M; Moreno, Jacqueline; Li, Meng; Bilgili, Ecevit; Davé, Rajesh N

2017-05-15

Polymer strip films have emerged as a robust platform for poorly water-soluble drug delivery. However, the common conception is that films cannot exceed low drug loadings, mainly due to poor drug stability, slow release, and film brittleness. This study explores the ability to achieve high loadings of poorly water-soluble drug nanoparticles in strip films while retaining good mechanical properties and enhanced dissolution rate. Aqueous suspensions containing up to 30wt% griseofulvin nanoparticles were prepared via wet stirred media milling and incorporated into hydroxypropyl methylcellulose (HPMC) films. Griseofulvin loading in films was adjusted to be between 9 and 49wt% in HPMC-E15 films and 30 and 73wt% in HPMC-E4M films by varying the mixing ratio of HPMC solution-to-griseofulvin suspension. All films exhibited good content uniformity and nanoparticle redispersibility up to 50wt% griseofulvin, while E4M films above 50wt% griseofulvin had slightly worse content uniformity and poor nanoparticle redispersibility. Increasing drug loading in films generally required more time to achieve 100% release during dissolution, although polymer-drug clusters dispersed from E4M films above 50wt% griseofulvin, resulting in similar dissolution profiles. While all films exhibited good tensile strength, a significant decrease in percent elongation was observed above 40-50wt% GF, resulting in brittle films. Copyright © 2017 Elsevier B.V. All rights reserved.

Region-specific role of water in collagen unwinding and assembly.

PubMed

Ravikumar, Krishnakumar M; Hwang, Wonmuk

2008-09-01

Conformational stability of the collagen triple helix affects its turnover and determines tissue homeostasis. Although it is known that the presence of imino acids (prolines or hydroxyprolines) confer stability to the molecule, little is known regarding the stability of the imino-poor region lacking imino acids, which plays a key role in collagen cleavage. In particular, there have been continuing debates about the role of water in collagen stability. We addressed these issues using molecular dynamics simulations on 30-residue long collagen triple helices, including a structure that has a biologically relevant 9-residue imino-poor region from type III collagen (PDB ID: 1BKV). A torsional map approach was used to characterize the conformational motion of the molecule that differ between imino-rich and imino-poor regions. At temperatures 300 K and above, unwinding initiates at a common cleavage site, the glycine-isoleucine bond in the imino-poor region. This provides a linkage between previous observations that unwinding of the imino-poor region is a requirement for collagenase cleavage, and that isolated collagen molecules are unstable at body temperature. We found that unwinding of the imino-poor region is controlled by dynamic water bridges between backbone atoms with average lifetimes on the order of a few picoseconds, as the degree of unwinding strongly correlated with the loss of water bridges, and unwinding could be either prevented or enhanced, respectively by enforcing or forbidding water bridge formation. While individual water bridges were short-lived in the imino-poor region, the hydration shell surrounding the entire molecule was stable even at 330 K. The diameter of the hydrated collagen including the first hydration shell was about 14 A, in good agreement with the experimentally measured inter-collagen distances. These results elucidate the general role of water in collagen turnover: water not only affects collagen cleavage by controlling its torsional motion, but it also forms a larger-scale lubrication layer mediating collagen self-assembly. 2008 Wiley-Liss, Inc.

Nano-aggregates: emerging delivery tools for tumor therapy.

PubMed

Sharma, Vinod Kumar; Jain, Ankit; Soni, Vandana

2013-01-01

A plethora of formulation techniques have been reported in the literature for site-specific targeting of water-soluble and -insoluble anticancer drugs. Along with other vesicular and particulate carrier systems, nano-aggregates have recently emerged as a novel supramolecular colloidal carrier with promise for using poorly water-soluble drugs in molecular targeted therapies. Nano-aggregates possess some inherent properties such as size in the nanometers, high loading efficiency, and in vivo stability. Nano-aggregates can provide site-specific drug delivery via either a passive or active targeting mechanism. Nano-aggregates are formed from a polymer-drug conjugated amphiphilic block copolymer. They are suitable for encapsulation of poorly water-soluble drugs by covalent conjugation as well as physical encapsulation. Because of physical encapsulation, a maximum amount of drug can be loaded in nano-aggregates, which helps to achieve a sufficiently high drug concentration at the target site. Active transport can be achieved by conjugating a drug with vectors or ligands that bind specifically to receptors being overexpressed in the tumor cells. In this review, we explore synthesis and tumor targeting potential of nano-aggregates with active and passive mechanisms, and we discuss various characterization parameters, ex vivo studies, biodistribution studies, clinical trials, and patents.

Self-perceived gait stability modulates the effect of daily life gait quality on prospective falls in older adults.

PubMed

Weijer, R H A; Hoozemans, M J M; van Dieën, J H; Pijnappels, M

2018-05-01

Quality of gait during daily life activities and perceived gait stability are both independent risk factors for future falls in older adults. We investigated whether perceived gait stability modulates the association between gait quality and falling in older adults. In this prospective cohort study, we used one-week daily-life trunk acceleration data of 272 adults over 65 years of age. Sample entropy (SE) of the 3D acceleration signals was calculated to quantify daily life gait quality. To quantify perceived gait stability, the level of concern about falling was assessed using the Falls Efficacy Scale international (FES-I) questionnaire and step length, estimated from the accelerometer data. A fall calendar was used to record fall incidence during a six-month follow up period. Logistic regression analyses were performed to study the association between falling and SE, step length or FES-I score, and their interactions. High (i.e., poor) SE in vertical direction was significantly associated with falling. FES-I scores significantly modulated this association, whereas step length did not. Subgroup analyses based on FES-I scores showed that high SE in the vertical direction was a risk factor for falls only in older adults who had a high (i.e. poor) FES-I score. In conclusion, perceived gait stability modulates the association between gait quality and falls in older adults such that an association between gait quality and falling is only present when perceived gait stability is poor. The results of the present study indicate that the effectiveness of interventions for fall prevention, aimed at improving gait quality, may be affected by a modulating effect of perceived gait stability. Results indicate that interventions to reduce falls in older adults might sort most effectiveness in populations with both a poor physiological and psychological status. Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical probes and engineered constructs reveal a detailed unfolding mechanism for a solvent-free multi-domain protein

PubMed Central

Eschweiler, Joseph D.; Martini, Rachel M.; Ruotolo, Brandon T.

2017-01-01

Despite the growing application of gas-phase measurements in structural biology and drug discovery, the factors that govern protein stabilities and structures in a solvent-free environment are still poorly understood. Here, we examine the solvent-free unfolding pathway for a group of homologous serum albumins. Utilizing a combination of chemical probes and non-covalent reconstructions, we draw new specific conclusions regarding the unfolding of albumins in the gas-phase, as well as more-general inferences regarding the sensitivity of collision induced unfolding to changes in protein primary and tertiary structure. Our findings suggest that the general unfolding pathway of low charge state albumin ions is largely unaffected by changes in primary structure; however, the stabilities of intermediates along these pathways vary widely as sequences diverge. Additionally, we find that human albumin follows a domain associated unfolding pathway, and are able to assign each unfolded form observed in our gas-phase dataset to the disruption of specific domains within the protein. The totality of our data informs the first detailed mechanism for multi-domain protein unfolding in the gas phase, and highlights key similarities and differences from the known the solution-phase pathway. PMID:27959526

Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437.

PubMed

Nandi, Nilay; Tyra, Lauren K; Stenesen, Drew; Krämer, Helmut

2017-12-11

Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Drosophila melanogaster Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels. The phospho-mimetic S437D mutation stabilizes Acn and promotes basal autophagy. In p35 mutants, basal autophagy and lifespan are reduced, but restored to near wild-type levels in the presence of stabilized Acn S437D . Expression of aggregation-prone polyQ-containing proteins or the Amyloid-β42 peptide, but not alpha-Synuclein, enhances Cdk5-dependent phosphorylation of S437-Acn. Our data indicate that Cdk5 is required to maintain the protective role of basal autophagy in the initial responses to a subset of neurodegenerative challenges.

The role of H-bond in the high-pressure chemistry of model molecules

NASA Astrophysics Data System (ADS)

Fanetti, Samuele; Citroni, Margherita; Dziubek, Kamil; Medre Nobrega, Marcelo; Bini, Roberto

2018-03-01

Pressure is an extraordinary tool to modify direction and strength of intermolecular interactions with important consequences on the chemical stability of molecular materials. The decrease of the distance among nearest neighbour molecules can give rise to reactive configurations reflecting the crystal arrangement and leading to association processes. In this context, the role of the H-bonds is very peculiar because their usual strengthening with rising pressure does not necessarily configure a decrease of the reaction activation energy but, on the contrary, can give rise to an anomalous stability of the system. In spite of this central role, the mechanisms by which a chemical reaction is favoured or prevented by H-bonding under high pressure conditions is a poorly explored field. Here we review a few studies where the chemical behaviour of simple molecular systems under static compression was related to the H-bonding evolution with pressure. These results are able to clarify a wealth of changes of the chemical and physical properties caused by the strengthening with pressure of the H-bonding network and provide additional tools to understand the mechanisms of high-pressure reactivity, a mandatory step to make these synthetic methods of potential interest for applicative purposes.

Mechanical Fracturing of Core-Shell Undercooled Metal Particles for Heat-Free Soldering

PubMed Central

Çınar, Simge; Tevis, Ian D.; Chen, Jiahao; Thuo, Martin

2016-01-01

Phase-change materials, such as meta-stable undercooled (supercooled) liquids, have been widely recognized as a suitable route for complex fabrication and engineering. Despite comprehensive studies on the undercooling phenomenon, little progress has been made in the use of undercooled metals, primarily due to low yields and poor stability. This paper reports the use of an extension of droplet emulsion technique (SLICE) to produce undercooled core-shell particles of structure; metal/oxide shell-acetate (‘/’ = physisorbed, ‘-’ = chemisorbed), from molten Field’s metal (Bi-In-Sn) and Bi-Sn alloys. These particles exhibit stability against solidification at ambient conditions. Besides synthesis, we report the use of these undercooled metal, liquid core-shell, particles for heat free joining and manufacturing at ambient conditions. Our approach incorporates gentle etching and/or fracturing of outer oxide-acetate layers through mechanical stressing or shearing, thus initiating a cascade entailing fluid flow with concomitant deformation, combination/alloying, shaping, and solidification. This simple and low cost technique for soldering and fabrication enables formation of complex shapes and joining at the meso- and micro-scale at ambient conditions without heat or electricity. PMID:26902483

Fish scale-derived collagen patch promotes growth of blood and lymphatic vessels in vivo.

PubMed

Wang, Jun Kit; Yeo, Kim Pin; Chun, Yong Yao; Tan, Timothy Thatt Yang; Tan, Nguan Soon; Angeli, Véronique; Choong, Cleo

2017-11-01

In this study, Type I collagen was extracted from fish scales asa potential alternative source of collagen for tissue engineering applications. Since unmodified collagen typically has poor mechanical and degradation stability both in vitro and in vivo, additional methylation modification and 1,4-butanediol diglycidyl ether (BDE) crosslinking steps were used to improve the physicochemical properties of fish scale-derived collagen. Subsequently, in vivo studies using a murine model demonstrated the biocompatibility of the different fish scale-derived collagen patches. In general, favorable integration of the collagen patches to the surrounding tissues, with good infiltration of cells, blood vessels (BVs) and lymphatic vessels (LVs) were observed under growth factor-free conditions. Interestingly, significantly higher (p<0.05) number of LVs was found to be more abundant around collagen patches with methylation modification and BDE crosslinking. Overall, we have demonstrated the potential application of fish scale-derived collagen as a promising scaffolding material for various biomedical applications. Currently the most common sources of collagen are of bovine and porcine origins, although the industrial use of collagen obtained from non-mammalian species is growing in importance, particularly since they have a lower risk of disease transmission and are not subjected to any cultural or religious constraints. However, unmodified collagen typically has poor mechanical and degradation stability both in vitro and in vivo. Hence, in this study, Type I collagen was successfully extracted from fish scales and chemically modified and crosslinked. In vitro studies showed overall improvement in the physicochemical properties of the material, whilst in vivo implantation studies showed improvements in the growth of blood and lymphatic host vessels in the vicinity of the implants. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Influence of dioctyl phthalate (DOP) on the mechanical, optical and thermal properties of formulations for the industrial manufacture of radiation sterilizable medical disposables

NASA Astrophysics Data System (ADS)

Ahmed, Shamshad; Mehmood, Mazhar; Iqbal, Rashid

2010-03-01

Shelf life of the formulations designed for the industrial manufacture of radiation sterilizable syringes and other medical disposables is a very important issue world over. Radiation compatible formulations were developed earlier in the laboratory by the incorporation of primary and secondary antioxidants along with processing stabilizers in a random polypropylene copolymer. It has been reported in literature that the mobilizing agents namely hydrocarbons, greases, wax and the plasticizer, dioctyl phthalate (DOP) impart radiation resistance to the polypropylene by providing free volume. It was envisaged that the addition of DOP to the afore-mentioned formulation might favorably influence the mechanical, optical and thermal properties of our formulation. To study the influence of addition of DOP on the afore-mentioned properties, the addition of 1%, 2% and 3% of the mobilizer was made, followed by the irradiation of resulting heat pressed sheets to the industrial standard dose of 25 kGy. Two important characteristic mechanical properties to determine the suitability of the radiation sterilized materials comprise angle of breakage and the haze percent. After irradiation and even on accelerated ageing of the irradiated material, the angle of breakage of heat press sheets of formulations containing 1%, 2% and 3% of DOP was found to be 180°, demonstrating the role of DOP, in imparting additional radiation stability. In case of the irradiated control sample, the angle of breakage was much lower. In the heat pressed sheets containing the DOP, a remarkable retention in the tensile strength, percentage elongation at break, along with improved thermal stability was observed. The formulation devoid of DOP demonstrated poor retention of the afore-mentioned characteristic properties .The observed improvement in thermal stability of the formulations containing DOP hints at the likely possibility of reuse of these materials by autoclaving which is considered an additional attribute.

Influence of low temperature ageing on optical and mechanical properties of transparent yittria stabilized-zirconia cranial prosthesis

NASA Astrophysics Data System (ADS)

Davoodzadeh, Nami; Uahengo, Gottlieb; Halaney, David; Garay, Javier E.; Aguilar, Guillermo

2018-02-01

Laser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of cranial bone limits the spatial resolution and interaction depth that can be achieved. We addressed this limitation previously, by introducing a novel cranial prosthesis made of a transparent nanocrystalline yttria-stabilized zirconia (nc-YSZ) which aims to enhance the diagnosis and treatment of neurological diseases by providing chronic optical access to the brain. By using optical coherence tomography, we have demonstrated the initial feasibility of ncYSZ implants for cortical imaging in an acute murine model. Although zirconia-based implants have been known for their excellent mechanical properties, the in vivo application was found to be affected by long-term failures, due to low temperature degradation. Accelerated aging simulations in humid environments at slightly elevated temperatures and over long periods typically transforms the ceramic surface into a monoclinic structure through a stress-corrosion-type mechanism. It was expected that the new nc-YSZ would show sufficient resistance to humid environments in comparison to the conventional zirconia implant. However, even a modest amount of transformation can change optical characteristics such as transparency. Herein we present the results of a simulated ageing study following the guidelines from the ISO 13356:2008 on aging of surgical zirconia ceramics. Comparison of %monoclinic transformation, optical transparency and mechanical hardness of nc-YSZ samples at baseline and following 25 and 100 h hydrothermal treatments shows our implant can withstand these extended ageing treatments.

Self-Standing Polypyrrole/Black Phosphorus Laminated Film: Promising Electrode for Flexible Supercapacitor with Enhanced Capacitance and Cycling Stability.

PubMed

Luo, Shaojuan; Zhao, Jinlai; Zou, Jifei; He, Zhiliang; Xu, Changwen; Liu, Fuwei; Huang, Yang; Dong, Lei; Wang, Lei; Zhang, Han

2018-01-31

With the rapid development of portable electronics, solid-state flexible supercapacitors (SCs) are considered as one of the promising energy devices in powering electronics because of their intrinsic advantages. Polypyrrole (PPy) is an ideal electrode material in constructing flexible SCs owing to its high electrochemical activity and inherent flexibility, although its relatively low capacitance and poor cycling stability are still worthy of improvement. Herein, through the innovative introduction of black phosphorus (BP) nanosheets, we developed a laminated PPy/BP self-standing film with enhanced capacitance and cycling stability via a facile one-step electrochemical deposition method. The film exhibits a high capacitance of 497.5 F g -1 (551.7 F cm -3 ) and outstanding cycling stability of 10 000 charging/discharging cycles, thanks to BP nanosheets inducing laminated assembly which hinder dense and disordered stacking of PPy during electrodeposition, consequently providing a precise pathway for ion diffusion and electron transport together with alleviation of the structural deterioration during charge/discharge. The flexible SC fabricated by laminated films delivers a high capacitance of 452.8 F g -1 (7.7 F cm -3 ) besides its remarkable mechanical flexibility and cycling stability. Our facile strategy paves the way to improve the electrochemical performance of PPy-based SC that could serve as promising flexible energy device for portable electronics.

Suppression of OsMADS7 in rice endosperm stabilizes amylose content under high temperature stress.

PubMed

Zhang, Hua; Xu, Heng; Feng, Mengjie; Zhu, Ying

2018-01-01

High temperature significantly alters the amylose content of rice, resulting in mature grains with poor eating quality. However, only few genes and/or quantitative trait loci involved in this process have been isolated and the molecular mechanisms of this effect remain unclear. Here, we describe a floral organ identity gene, OsMADS7, involved in stabilizing rice amylose content at high temperature. OsMADS7 is greatly induced by high temperature at the early filling stage. Constitutive suppression of OsMADS7 stabilizes amylose content under high temperature stress but results in low spikelet fertility. However, rice plants with both stable amylose content at high temperature and normal spikelet fertility can be obtained by specifically suppressing OsMADS7 in endosperm. GBSSI is the major enzyme responsible for amylose biosynthesis. A low filling rate and high expression of GBSSI were detected in OsMADS7 RNAi plants at high temperature, which may be correlated with stabilized amylose content in these transgenic seeds under high temperature. Thus, specific suppression of OsMADS7 in endosperm could improve the stability of rice amylose content at high temperature, and such transgenic materials may be a valuable genetic resource for breeding rice with elite thermal resilience. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

M4Ag44(p-MBA)30 Molecular Nanoparticles

NASA Astrophysics Data System (ADS)

Conn, Brian E.

In recent years, molecular nanoparticles have attracted much attention due to their unique physical, optical, and electronic properties. The properties of molecular nanoparticles are shown to deviate from their larger bulk counterparts, due to quantum confinement effects and large surface-to-volume ratios. As the size of the nanoparticle shrinks to a cluster of metal atoms (<3 nm in diameter), there is an emergence of a HOMO-LUMO band gap, which is not present in transitional d-block metals. The HOMO-LUMO band gap gives rise to discrete electronic states, leading to new chemical and physical properties. Molecular nanoparticles have had a substantial impact across a diverse range of fields, including catalysis, sensing, photochemistry, optoelectronic, energy conversion, and medicine. Currently many of the synthetic procedures for molecular nanoparticles require low temperatures, long incubation times, multistep purification and hazardous reagents that produce low yields and polydisperse molecular nanoparticles with poor stability. Although silver has very desirable physical properties, good relative abundance and low cost, gold molecular nanoparticles have been widely favored owing to their proved stability and ease of use. Unlike gold, silver is notorious for its susceptibility to oxidation, i.e., tarnishing, which has limited the development of silver-based nanotechnologies. Despite two decades of synthetic efforts, silver molecular nanoparticles that are inert or have long-term stability have remained unrealized. Herein we report a simple synthetic protocol for producing ultrastable M4Ag44(p-MBA)30 nanoparticles as a single-sized molecular product and in exceptionally large quantities. The stability, purity, and yield are substantially better than other metal nanoparticles, including gold, due to several stabilization mechanisms. Also, reported are the structural and mechanical properties of extended crystalline solids of Na4Ag44(p-MBA)30 from large-scale quantum-mechanical simulations based on the atomically-precise X-ray measured structure. Calculations show that cohesion is derived from hydrogen bonds between bundled p-MBA ligands and that the superlattice's mechanical response to hydrostatic compression is characterized by a molecular-solid-like bulk modulus B0 = 16.7 GPa, exhibiting anomalous pressure softening and a compression-induced transition to a soft-solid phase. Such a transition involves ligand flexure, which causes gear-like correlated chiral rotation of the nanoparticles.

Chromosome End Repair and Genome Stability in Plasmodium falciparum.

PubMed

Calhoun, Susannah F; Reed, Jake; Alexander, Noah; Mason, Christopher E; Deitsch, Kirk W; Kirkman, Laura A

2017-08-08

The human malaria parasite Plasmodium falciparum replicates within circulating red blood cells, where it is subjected to conditions that frequently cause DNA damage. The repair of DNA double-stranded breaks (DSBs) is thought to rely almost exclusively on homologous recombination (HR), due to a lack of efficient nonhomologous end joining. However, given that the parasite is haploid during this stage of its life cycle, the mechanisms involved in maintaining genome stability are poorly understood. Of particular interest are the subtelomeric regions of the chromosomes, which contain the majority of the multicopy variant antigen-encoding genes responsible for virulence and disease severity. Here, we show that parasites utilize a competitive balance between de novo telomere addition, also called "telomere healing," and HR to stabilize chromosome ends. Products of both repair pathways were observed in response to DSBs that occurred spontaneously during routine in vitro culture or resulted from experimentally induced DSBs, demonstrating that both pathways are active in repairing DSBs within subtelomeric regions and that the pathway utilized was determined by the DNA sequences immediately surrounding the break. In combination, these two repair pathways enable parasites to efficiently maintain chromosome stability while also contributing to the generation of genetic diversity. IMPORTANCE Malaria is a major global health threat, causing approximately 430,000 deaths annually. This mosquito-transmitted disease is caused by Plasmodium parasites, with infection with the species Plasmodium falciparum being the most lethal. Mechanisms underlying DNA repair and maintenance of genome integrity in P. falciparum are not well understood and represent a gap in our understanding of how parasites survive the hostile environment of their vertebrate and insect hosts. Our work examines DNA repair in real time by using single-molecule real-time (SMRT) sequencing focused on the subtelomeric regions of the genome that harbor the multicopy gene families important for virulence and the maintenance of infection. We show that parasites utilize two competing molecular mechanisms to repair double-strand breaks, homologous recombination and de novo telomere addition, with the pathway used being determined by the surrounding DNA sequence. In combination, these two pathways balance the need to maintain genome stability with the selective advantage of generating antigenic diversity. Copyright © 2017 Calhoun et al.

Influence of Heat Treatments on the Microstructural Evolution and Resultant Mechanical Properties in a Low Carbon Medium Mn Heavy Steel Plate

NASA Astrophysics Data System (ADS)

Chen, Jun; Lv, Meng-yang; Liu, Zhen-yu; Wang, Guo-dong

2016-05-01

In this study, the microstructural evolution and resultant mechanical properties in a low carbon medium Mn heavy steel plate were investigated in detail. The results show that the introduction of medium manganese alloy design in the heavy steel plate has been shown to achieve the outstanding combination of strength, ductility, low-temperature impact toughness, and strain hardening capacity. It has been found that the austenite phase mainly displays at martensitic lath boundaries and shows lath shape for the heat treating at 873 K (600 °C) for 1 to 10 hours or 893 K (620 °C) for 2 hours, and not all the austenite phase obeys the K-S or N-W orientation relationship with respect to abutting martensitic lath. Although the microstructure in the steel after heat treating at 873 K (600 °C) for 1 to 10 hours is similar to each other, the resultant mechanical properties are very different because the volume fraction and stability of retained austenite vary with the heat treatments. The best low-temperature impact toughness is achieved after heat treating at 873 K (600 °C) for 2 hours due to the formation of a considerable volume fraction of retained austenite with relatively high stability, but the strain hardening capacity and ductility are disappointing because of insufficient TRIP effect. Based on enhancing TRIP effect, the two methods have been suggested. One is to increase the isothermal holding temperature to 893 K (620 °C), and the other one is to prolong the isothermal holding time to 10 hours at 873 K (600 °C). The two methods can significantly increase strain hardening capacity and ductility nearly without harming low-temperature impact toughness. In addition, the stability of retained austenite has been discussed by the quantitative analysis and it has been demonstrated that the stability of retained austenite is related to the chemical composition, size, and morphology. Moreover, the isothermal holding temperature has a great effect on the stability of retained austenite, while the effect of the isothermal holding time is relatively poor.

The initial instability and finite-amplitude stability of alternate bars in straight channels

USGS Publications Warehouse

Nelson, J.M.

1990-01-01

The initial instability and fully developed stability of alternate bars in straight channels are investigated using linearized and nonlinear analyses. The fundamental instability leading to these features is identified through a linear stability analysis of the equations governing the flow and sediment transport fields. This instability is explained in terms of topographically induced steering of the flow and the associated pattern of erosion and deposition on the bed. While the linear theory is useful for examining the instability mechanism, this approach is shown to yield relatively little information about well-developed alternate bars and, specifically, the linear analysis is shown to yield poor predictions of the fully developed bar wavelength. A fully nonlinear approach is presented that permits computation of the evolution of these bed features from an initial perturbation to their fully developed morphology. This analysis indicates that there is typically substantial elongation of the bar wavelength during the evolution process, a result that is consistent with observations of bar development in flumes and natural channels. The nonlinear approach demonstrates that the eventual stability of these features is a result of the interplay between topographic steering effects, secondary flow production as a result of streamline curvature, and gravitationally induced modifications of sediment fluxes over a sloping bed. ?? 1990.

Investigation of performance and durability of polymer electrolytes for electrochemical energy storage and conversion technologies

NASA Astrophysics Data System (ADS)

Jung, Min-Suk

Polymeric ion exchange membranes are integral components of electrochemical conversion/storage devices such as fuel cells, water electrolyzers, and redox flow batteries. There has been dramatic progress in the research and development of cation exchange membranes (CEM). NafionRTM (perfluorosulfonic acid membranes) is one example of a state-of-the-art CEM and has been successfully demonstrated in various electrochemical energy devices. Unlike CEMs, anion exchange membranes (AEMs) have been of limited utility to date due to their drawbacks, including poor chemical/mechanical stability and low ionic conductivity. However, alkaline environments result in better activity for electrochemical reactions and afford the possibility of using non-platinum group metal (PGM) electrocatalysts. AEMs, therefore, are still being studied in order to resolve existing challenges in terms of conductivity and stability in alkaline media and in strongly oxidizing solutions. In this work, AEMs derived from different types of polymer backbones were prepared, and their chemical stability and electrochemical property were investigated. Polysulfone (PSF) AEMs were prepared by first chloromethylating polysulfone, then by functionalizing chloromethylated polysulfone (CMPSF) with different base reagents. PSF-trimethylamine (TMA) AEMs showed a 40-fold reduction in vanadium (IV) ion (VO2+) permeability when compared to a NafionRTM membrane and exceptional oxidative stability after exposure to a 1.5 M vanadium (V) ion (VO2+) solution for 90 days. PSF-TMA AEMs were successfully demonstrated in the all-vanadium redox flow battery. Excellent energy efficiencies (>75 %) were attained and sustained over 75 charge-discharge cycles for a vanadium redox flow battery prepared using the PSF-TMA separator. Crosslinking of poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) AEMs using diamine was tried with intentions to improve the mechanical stability and electrochemical property of PPO AEM. Crosslinked PPO AEMs (30 +/- 4 % at 25 °C) showed less liquid water uptake than non-crosslinked PPO AEMs (46 +/- 5% at 25 °C) while maintaining comparable ionic conductivities (hydroxide ion conductivity of 45 mS/cm at 60 °C). Crosslinked PPO AEMs maintained mechanical integrity and still showed some mechanical stability (ultimate tensile strength of 3˜4 MPa and elongation at break of 13˜17 %) after exposure to 1 M KOH at 60 °C for 14 days, while non-crosslinked PPO AEMs completely lost their mechanical durability. Finally, this dissertation presents research related to perfluorinated AEMs prepared using a Grignard reagent. These membranes exhibited 0.7 mmol/g of Cl- ion exchange capacity (IEC), 20 mS/cm of hydroxide ion conductivity at 20 °C, and 10 % of water uptake at room temperature. The membranes also maintained 90 % of their initial conductivity after an exposure to 1.5 M VO2+ in 3 M H2SO4 solution for seven days.

Study on structure, mechanical property and cell cytocompatibility of electrospun collagen nanofibers crosslinked by common agents.

PubMed

Luo, Xueshi; Guo, Zhenzhao; He, Ping; Chen, Tian; Li, Lihua; Ding, Shan; Li, Hong

2018-07-01

Collagen electrospun scaffolds properly reproduce the framework of the extracellular matrix (ECM) of tissues that are natural with the fibrous morphology of the protein by coupling large biomimetism of the biological material. However, traditional solvents employed for collagen electrospinning lead to poor mechanical attributes and bad hydro-stability. In this work, by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride with N-hydroxysulfosuccinimide (EDC-NHS), glutaraldehyde (GTA) and genipin (GP) respectively, electrospun collagen fibers cross-linked, effectively stabilized the fiber morphology over 2months and improved the mechanical properties in both dry and wet state, especially EDC-NHS with large ultimate tensile stress and ε b . The secondary structure of collagen structure still remained and had no obvious difference among various crosslinked samples according to FTIR. On the cell assessment, electrospun collagen fibers crosslinked by EDC-NHS, GTA and GP, were found to support cell adhesion, spreading and proliferation of MC3T3-E1. By contrast, GTA was more effective in preserving explicit fibrous morphology with a relatively lower cell viability both in FBS and BSA soaked mats. Interestingly, GP also had the similar cytocompatibility of MC3T3-E1 as EDC-NHS did. The study proved the feasibility of chemical crosslinker to electrospun collagen for biomedical application. Copyright © 2018. Published by Elsevier B.V.

Balance control during gait initiation: State-of-the-art and research perspectives.

PubMed

Yiou, Eric; Caderby, Teddy; Delafontaine, Arnaud; Fourcade, Paul; Honeine, Jean-Louis

2017-11-18

It is well known that balance control is affected by aging, neurological and orthopedic conditions. Poor balance control during gait and postural maintenance are associated with disability, falls and increased mortality. Gait initiation - the transient period between the quiet standing posture and steady state walking - is a functional task that is classically used in the literature to investigate how the central nervous system (CNS) controls balance during a whole-body movement involving change in the base of support dimensions and center of mass progression. Understanding how the CNS in able-bodied subjects exerts this control during such a challenging task is a pre-requisite to identifying motor disorders in populations with specific impairments of the postural system. It may also provide clinicians with objective measures to assess the efficiency of rehabilitation programs and better target interventions according to individual impairments. The present review thus proposes a state-of-the-art analysis on: (1) the balance control mechanisms in play during gait initiation in able bodied subjects and in the case of some frail populations; and (2) the biomechanical parameters used in the literature to quantify dynamic stability during gait initiation. Balance control mechanisms reviewed in this article included anticipatory postural adjustments, stance leg stiffness, foot placement, lateral ankle strategy, swing foot strike pattern and vertical center of mass braking. Based on this review, the following viewpoints were put forward: (1) dynamic stability during gait initiation may share a principle of homeostatic regulation similar to most physiological variables, where separate mechanisms need to be coordinated to ensure stabilization of vital variables, and consequently; and (2) rehabilitation interventions which focus on separate or isolated components of posture, balance, or gait may limit the effectiveness of current clinical practices.

Balance control during gait initiation: State-of-the-art and research perspectives

PubMed Central

Yiou, Eric; Caderby, Teddy; Delafontaine, Arnaud; Fourcade, Paul; Honeine, Jean-Louis

2017-01-01

It is well known that balance control is affected by aging, neurological and orthopedic conditions. Poor balance control during gait and postural maintenance are associated with disability, falls and increased mortality. Gait initiation - the transient period between the quiet standing posture and steady state walking - is a functional task that is classically used in the literature to investigate how the central nervous system (CNS) controls balance during a whole-body movement involving change in the base of support dimensions and center of mass progression. Understanding how the CNS in able-bodied subjects exerts this control during such a challenging task is a pre-requisite to identifying motor disorders in populations with specific impairments of the postural system. It may also provide clinicians with objective measures to assess the efficiency of rehabilitation programs and better target interventions according to individual impairments. The present review thus proposes a state-of-the-art analysis on: (1) the balance control mechanisms in play during gait initiation in able bodied subjects and in the case of some frail populations; and (2) the biomechanical parameters used in the literature to quantify dynamic stability during gait initiation. Balance control mechanisms reviewed in this article included anticipatory postural adjustments, stance leg stiffness, foot placement, lateral ankle strategy, swing foot strike pattern and vertical center of mass braking. Based on this review, the following viewpoints were put forward: (1) dynamic stability during gait initiation may share a principle of homeostatic regulation similar to most physiological variables, where separate mechanisms need to be coordinated to ensure stabilization of vital variables, and consequently; and (2) rehabilitation interventions which focus on separate or isolated components of posture, balance, or gait may limit the effectiveness of current clinical practices. PMID:29184756

Using foamed asphalt as a stabilizing agent in full depth reclamation of Route 8 in Belgrade.

DOT National Transportation Integrated Search

2002-02-01

Maine has a variety of soil types throughout the state. Most of these soil types degrade rapidly and have : poor stability. To eliminate the cost of supplying quality road base material from a distant source and : increase the stability of existing s...

pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs.

PubMed

Wang, Xue-Qing; Zhang, Qiang

2012-10-01

pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers' dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

Probabilistic Reversal Learning in Schizophrenia: Stability of Deficits and Potential Causal Mechanisms.

PubMed

Reddy, Lena Felice; Waltz, James A; Green, Michael F; Wynn, Jonathan K; Horan, William P

2016-07-01

Although individuals with schizophrenia show impaired feedback-driven learning on probabilistic reversal learning (PRL) tasks, the specific factors that contribute to these deficits remain unknown. Recent work has suggested several potential causes including neurocognitive impairments, clinical symptoms, and specific types of feedback-related errors. To examine this issue, we administered a PRL task to 126 stable schizophrenia outpatients and 72 matched controls, and patients were retested 4 weeks later. The task involved an initial probabilistic discrimination learning phase and subsequent reversal phases in which subjects had to adjust their responses to sudden shifts in the reinforcement contingencies. Patients showed poorer performance than controls for both the initial discrimination and reversal learning phases of the task, and performance overall showed good test-retest reliability among patients. A subgroup analysis of patients (n = 64) and controls (n = 49) with good initial discrimination learning revealed no between-group differences in reversal learning, indicating that the patients who were able to achieve all of the initial probabilistic discriminations were not impaired in reversal learning. Regarding potential contributors to impaired discrimination learning, several factors were associated with poor PRL, including higher levels of neurocognitive impairment, poor learning from both positive and negative feedback, and higher levels of indiscriminate response shifting. The results suggest that poor PRL performance in schizophrenia can be the product of multiple mechanisms. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Employment stability and mental health in Spain: towards understanding the influence of gender and partner/marital status.

PubMed

Cortès-Franch, Imma; Escribà-Agüir, Vicenta; Benach, Joan; Artazcoz, Lucía

2018-04-02

The growing demand for labour flexibility has resulted in decreasing employment stability that could be associated with poor mental health status. Few studies have analysed the whole of the work force in considering this association since research on flexible forms of employment traditionally analyses employed and unemployed people separately. The gender division of work, and family characteristics related to employment situation, could modify its association with mental wellbeing. The objective of the study was to examine the relationship between a continuum of employment stability and mental health taking into account gender and partner/marital status. We selected 6859 men and 5106 women currently salaried or unemployed from the 2006 Spanish National Health Survey. Employment stability was measured through a continuum from the highest stability among employed to lowest probability of finding a stable job among the long-term unemployed. Mental health was measured with the 12-item version of the General Health Questionnaire. Logistic regression models were fitted for each combination of partner/marital status and gender. In all groups except among married women employment stability was related to poor mental health and a gradient between a continuum of employment stability and mental health status was found. For example, compared with permanent civil servants, married men with temporary contract showed an aOR = 1.58 (95%CI = 1.06-2.35), those working without a contract aOR = 2.15 (95%CI = 1.01-4.57) and aOR = 3.73 (95%CI = 2.43-5.74) and aOR = 5.35 (95%CI = 2.71-10.56) among unemployed of up to two years and more than two years, respectively. Among married and cohabiting people, the associations were stronger among men. Poor mental health status was related to poor employment stability among cohabiting women but not among married ones. The strongest association was observed among separated or divorced people. There is a rise in poor mental health as the distance from stable employment grows. This result differs according to the interaction with gender and partner/marital status. In Spain this relationship seems to follow a pattern related to the gender division of work in married people but not in other partner/marital situations. Family and socioeconomic context can contribute to explain previous mixed results. Recommendations for research and for action are given.

Interactions between extracellular polymeric substances and clay minerals affect soil aggregation

NASA Astrophysics Data System (ADS)

Vogel, Cordula; Rehschuh, Stephanie; Kemi Olagoke, Folasade; Redmile Gordon, Marc; Kalbiltz, Karsten

2017-04-01

Soil aggregation is crucial for carbon (C) sequestration and microbial processes have been recognised as important control of aggregate turnover (formation, stability, and destruction). However, how microorganisms contribute to these processes is still a matter of debate. An enthralling mechanism determining aggregate turnover and therefore C sequestration may be the excretion of extracellular polymeric substances (EPS) as microbial glue, but effects of EPS on aggregation is largely unknown. Moreover, interdependencies between important aggregation factors like the amount of fine-sized particles (clay content), the decomposability of organic matter and the microbial community (size and composition, as well as the excretion of EPS) are still poorly understood. Therefore, we studied the complex interactions between these factors and their role in aggregate turnover. It was hypothesized that an increase in microbial activity, induced by the input of organic substrates, will stimulate EPS production and therefore the formation and stability of aggregates. To test this hypothesis, an incubation experiment has been conducted across a gradient of clay content (montmorillonite) and substrate decomposability (starch and glucose) as main drivers of the microbial activity. A combination of aggregate separation and stability tests were applied. This results will be examined with respect to the obtained microbial parameters (amount and composition of EPS, CO2 emission, microbial biomass, phospholipid fatty acid), to disentangle the mechanisms and factors controlling aggregate turnover affected by soil microorganisms. This study is expected to provide insights on the role of EPS in the stability of aggregates. Thus, the results of this study will provide an improved understanding of the underlying processes of aggregate turnover in soils, which is necessary to implement strategies for enhanced C sequestration in agricultural soils.

Comparison of 99mTc-UBI 29-41, 99mTc-Ciprofloxacin, 99mTc-Ciprofloxacin dithiocarbamate and 111In-biotin for targeting experimental Staphylococcus aureus and Escherichia coli foreign-body infections: an ex-vivo study.

PubMed

Auletta, Sveva; Baldoni, Daniela; Varani, Michela; Galli, Filippo; Hajar, Iman A; Duatti, Adriano; Ferro-Flores, Guillermina; Trampuz, Andrej; Signore, Alberto

2017-08-28

Diagnosis of implant-associated infection is challenging. Several radiopharmaceuticals have been described but direct comparisons are limited. Here we compared in vitro and in an animal model 99mTc-UBI, 99mTc-Ciprofloxacin, 99mTcN-CiproCS2 and 111In-DTPA-biotin for targeting E. coli (ATCC 25922) and S. aureus (ATCC 43335). Stability controls were performed with the labelled radiopharmaceuticals during 6 h in saline and serum. The in vitro binding to viable or killed bacteria was evaluated at 37 °C and 4 °C. For in vivo studies, Teflon cages were subcutaneously implanted in mice, followed by percutaneous infection. Biodistribution of i.v. injected radiolabelled radiopharmaceuticals were evaluated during 24 h in cages and dissected tissues. Labelling efficiency of all radiopharmaceuticals ranged between 94% and 98%, with high stability both in saline and in human serum. In vitro binding assays displayed a rapid but poor bacterial binding for all tested agents. Similar binding kinetic occurred also with heat-killed and ethanol-killed bacteria. In the tissue cage model, infection was detected at different time points: 99mTc-UBI and 99mTcN-CiproCS2 showed higher infected cage/sterile cage ratio at 24 h for both E. coli and S. aureus; 99mTc-Ciprofloxacin at 24 h for both E. coli and at 4 h for S. aureus; 111In-DTPA-biotin accumulates faster in both E. coli and S. aureus infected cages. 99mTc-UBI, 99mTcN-CiproCS2 showed poor in vitro binding but good in vivo binding to E. coli only. 111In-DTPA-biotin showed poor in vitro binding but good in vivo binding to S. aureus and poor to E. coli. 99mTc-Ciprofloxacin showed poor in vitro binding but good in vivo binding to all tested bacteria. The mechanism of accumulation in infected sites remains to be elucidated.

Thermal Characterization of Fe3O4 Nanoparticles Formed from Poorly Crystalline Siderite

NASA Technical Reports Server (NTRS)

Lauer, H. V., Jr.; Ming, D. W.; Golden, D. C.

2005-01-01

Increasing interest in environmental geochemistry has led to the recognition that crystals with sizes in the nanometer range (e.g., colloids and nanoscale precipitates) and poorly crystalline compounds (e.g., ferrihydrites) may comprise the majority of reactive mineral surface area near the Earth s surface. When the diameters of individual particles are in the range of 100 nm or less, the surface energy contribution to the free energy modifies phase stability. This results in stabilization of polymorphs not normally encountered in the macrocrystal domain. These phases potentially have very different surface-site geometries, adsorptive properties, and growth mechanisms, and exhibit size-dependent kinetic behavior. Thus nanophases dramatically modify the physical and chemical properties of soils and sediments. In a more general sense, the characteristics of nanocrystals are of intense technological interest because small particle size confers novel chemical, optical, and electronic properties. Thus, nanocrystalline materials are finding applications as catalytic substrates, gas phase separation materials, and even more importantly in the field of medicine. This is an opportune time for mineral physicists working on nanocrystalline materials to develop collaborative efforts with materials scientists, chemists, and others working on nanophase materials of technological interest (e.g., for magnetic memories). Our objective in this study was to synthesize submicron (<200 nm) magnetite and to study their thermal and particle size properties.

FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma.

PubMed

Suryo Rahmanto, Aldwin; Savov, Vasil; Brunner, Andrä; Bolin, Sara; Weishaupt, Holger; Malyukova, Alena; Rosén, Gabriela; Čančer, Matko; Hutter, Sonja; Sundström, Anders; Kawauchi, Daisuke; Jones, David Tw; Spruck, Charles; Taylor, Michael D; Cho, Yoon-Jae; Pfister, Stefan M; Kool, Marcel; Korshunov, Andrey; Swartling, Fredrik J; Sangfelt, Olle

2016-10-17

SOX9 is a master transcription factor that regulates development and stem cell programs. However, its potential oncogenic activity and regulatory mechanisms that control SOX9 protein stability are poorly understood. Here, we show that SOX9 is a substrate of FBW7, a tumor suppressor, and a SCF (SKP1/CUL1/F-box)-type ubiquitin ligase. FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is phosphorylated by GSK3 kinase and consequently degraded by SCF FBW 7α Failure to degrade SOX9 promotes migration, metastasis, and treatment resistance in medulloblastoma, one of the most common childhood brain tumors. FBW7 is either mutated or downregulated in medulloblastoma, and in cases where FBW7 mRNA levels are low, SOX9 protein is significantly elevated and this phenotype is associated with metastasis at diagnosis and poor patient outcome. Transcriptional profiling of medulloblastoma cells expressing a degradation-resistant SOX9 mutant reveals activation of pro-metastatic genes and genes linked to cisplatin resistance. Finally, we show that pharmacological inhibition of PI3K/AKT/mTOR pathway activity destabilizes SOX9 in a GSK3/FBW7-dependent manner, rendering medulloblastoma cells sensitive to cytostatic treatment. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Using foamed asphalt as a stabilizing agent in full depth reclamation of Route 8 in Belgrade : final report.

DOT National Transportation Integrated Search

2009-03-01

Maine has a variety of soil types throughout the state. A majority of these soil types degrade rapidly and : have poor stability. To eliminate the cost of supplying quality road base material from a distant source and : increase the stability of exis...

Automated selection of stabilizing mutations in designed and natural proteins.

PubMed

Borgo, Benjamin; Havranek, James J

2012-01-31

The ability to engineer novel protein folds, conformations, and enzymatic activities offers enormous potential for the development of new protein therapeutics and biocatalysts. However, many de novo and redesigned proteins exhibit poor hydrophobic packing in their predicted structures, leading to instability or insolubility. The general utility of rational, structure-based design would greatly benefit from an improved ability to generate well-packed conformations. Here we present an automated protocol within the RosettaDesign framework that can identify and improve poorly packed protein cores by selecting a series of stabilizing point mutations. We apply our method to previously characterized designed proteins that exhibited a decrease in stability after a full computational redesign. We further demonstrate the ability of our method to improve the thermostability of a well-behaved native protein. In each instance, biophysical characterization reveals that we were able to stabilize the original proteins against chemical and thermal denaturation. We believe our method will be a valuable tool for both improving upon designed proteins and conferring increased stability upon native proteins.

Automated selection of stabilizing mutations in designed and natural proteins

PubMed Central

Borgo, Benjamin; Havranek, James J.

2012-01-01

The ability to engineer novel protein folds, conformations, and enzymatic activities offers enormous potential for the development of new protein therapeutics and biocatalysts. However, many de novo and redesigned proteins exhibit poor hydrophobic packing in their predicted structures, leading to instability or insolubility. The general utility of rational, structure-based design would greatly benefit from an improved ability to generate well-packed conformations. Here we present an automated protocol within the RosettaDesign framework that can identify and improve poorly packed protein cores by selecting a series of stabilizing point mutations. We apply our method to previously characterized designed proteins that exhibited a decrease in stability after a full computational redesign. We further demonstrate the ability of our method to improve the thermostability of a well-behaved native protein. In each instance, biophysical characterization reveals that we were able to stabilize the original proteins against chemical and thermal denaturation. We believe our method will be a valuable tool for both improving upon designed proteins and conferring increased stability upon native proteins. PMID:22307603

Preparation and evaluation of high dispersion stable nanocrystal formulation of poorly water-soluble compounds by using povacoat.

PubMed

Yuminoki, Kayo; Seko, Fuko; Horii, Shota; Takeuchi, Haruka; Teramoto, Katsuya; Nakada, Yuichiro; Hashimoto, Naofumi

2014-11-01

In this study, we reported the application of Povacoat®, a hydrophilic polyvinylalcohol copolymer, as a dispersion stabilizer of nanoparticles of poorly water-soluble compounds. In addition, the influence of aggregation of the nanoparticles on their solubility and oral absorption was studied. Griseofulvin (GF) was used as a model compound with poor water solubility and was milled to nanoparticles by wet bead milling. The dispersion stability of GF milled with Povacoat® or the generally used polymers (polyvinylalcohol, hydroxypropylcellulose SSL, and polyvinylpyrrolidone K30) was compared. Milled GF suspended in Povacoat® aqueous solution with D-mannitol, added to improve the disintegration rate of freeze-dried GF, exhibited high dispersion stability without aggregation (D90 = ca. 0.220 μm), whereas milled GF suspended in aqueous solutions of the other polymers aggregated (D90 > 5 μm). Milled GF with Povacoat® showed improved aqueous solubility and bioavailability compared with the other polymers. The aggregation of nanoparticles had significant impact on the solubility and bioavailability of GF. Povacoat® also prevented the aggregation of the various milled poorly water-soluble compounds (hydrochlorothiazide and tolbutamide, etc.) more effectively than the other polymers. These results showed that Povacoat® could have wide applicability to the development of nanoformulations of poorly water-soluble compounds. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effects of ions on the solubility transition and the phase-separation of N-isopropylacrylamide in water.

PubMed

Sasaki, Shigeo; Okabe, Satoshi

2011-11-10

The effects of NaCl, NaOH, and HCl on the solubility transition and the phase-separation of N-isopropylacrylamide (NIPA) were investigated for the purpose of clarifying the physicochemical mechanism of salting-out and salting-in phenomena. The discrete change in the solubility of NIPA in the salt-free water at the solubility transition (reported in J. Phys. Chem. B 2010, 114, 14995-15002) decreased with the addition of HCl and disappeared in the HCl solutions at concentrations higher than 2 M, while it increased with additions of NaOH and NaCl. A difference in NIPA concentration between the phase-separated solutions decreases with the addition of HCl and increases with additions of NaOH and NaCl. Partition coefficients of HCl in the phase-separated NIPA-rich solutions are higher than those in the NIPA poor solutions, while partition coefficients of NaCl and NaOH between the NIPA-rich and -poor solutions have trends opposite to those of HCl. The present results clearly indicate that the HCl favors the dehydrated NIPA and stabilizes the H(2)O-poor state of the NIPA molecule more than NaCl.

A metabolic way to investigate related hurdles causing poor bioavailability in oral delivery of isoacteoside in rats employing ultrahigh-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry.

PubMed

Cui, Qingling; Pan, Yingni; Yan, Xiaowei; Qu, Bao; Liu, Xiaoqiu; Xiao, Wei

2017-02-28

Isoacteoside (ISAT), a phenylethanoid glycoside that acts as the principal bioactive component in traditional Chinese medicines, possesses broad pharmacological effects such as neuroprotective, antihypertensive and hepatoprotective activities. However, its pharmaceutical development has been severely limited due to the poor oral bioavailability. It is essential and significant to investigate related hurdles leading to the poor bioavailability of isoacteoside. Whole animal metabolism studies were conducted in rats, followed by metabolic mechanism including gastrointestinal stability, intestinal flora metabolism and intestinal enzyme metabolism employing the powerful method ultrahigh-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC/QTOF-MS/MS). A simple, rapid and sensitive method has been developed which comprehensively revealed the underlying cause of poor bioavailability of ISAT in a metabolic manner. The prototype of ISAT and its combined metabolites have not been detected in plasma. Furthermore, the residual content of the parent compound in in vitro experiments was approximately 59%, 5% and barely none in intestinal bacteria, intestinal S9 and simulated intestinal juice at 6 h, respectively. The present work has demonstrated that the factors causing the poor bioavailability of isoacteoside should be attributed to the metabolism. In general, the metabolism that resulted from intestinal flora and intestinal enzymes were predominant reasons giving rise to the poor bioavailability of ISAT, which also suggested that metabolites might be responsible for the excellent pharmacological effect of ISAT. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Highly conductive transparent organic electrodes with multilayer structures for rigid and flexible optoelectronics.

PubMed

Guo, Xiaoyang; Liu, Xingyuan; Lin, Fengyuan; Li, Hailing; Fan, Yi; Zhang, Nan

2015-05-27

Transparent electrodes are essential components for optoelectronic devices, such as touch panels, organic light-emitting diodes, and solar cells. Indium tin oxide (ITO) is widely used as transparent electrode in optoelectronic devices. ITO has high transparency and low resistance but contains expensive rare elements, and ITO-based devices have poor mechanical flexibility. Therefore, alternative transparent electrodes with excellent opto-electrical performance and mechanical flexibility will be greatly demanded. Here, organics are introduced into dielectric-metal-dielectric structures to construct the transparent electrodes on rigid and flexible substrates. We show that organic-metal-organic (OMO) electrodes have excellent opto-electrical properties (sheet resistance of below 10 Ω sq(-1) at 85% transmission), mechanical flexibility, thermal and environmental stabilities. The OMO-based polymer photovoltaic cells show performance comparable to that of devices based on ITO electrodes. This OMO multilayer structure can therefore be used to produce transparent electrodes suitable for use in a wide range of optoelectronic devices.

Dynamin and PTP-PEST cooperatively regulate Pyk2 dephosphorylation in osteoclasts

PubMed Central

Eleniste, Pierre P.; Du, Liping; Shivanna, Mahesh; Bruzzaniti, Angela

2012-01-01

Bone loss is caused by the dysregulated activity of osteoclasts which degrade the extracellular bone matrix. The tyrosine kinase Pyk2 is highly expressed in osteoclasts, and mice lacking Pyk2 exhibit an increase in bone mass, in part due to impairment of osteoclast function. Pyk2 is activated by phosphorylation at Y402 following integrin activation, but the mechanisms leading to Pyk2 dephosphorylation are poorly understood. In the current study, we examined the mechanism of action of the dynamin GTPase on Pyk2 dephosphorylation. Our studies reveal a novel mechanism for the interaction of Pyk2 with dynamin, which involves the binding of Pyk2’s FERM domain with dynamin’s plextrin homology domain. In addition, we demonstrate that the dephosphorylation of Pyk2 requires dynamin’s GTPase activity and is mediated by the tyrosine phosphatase PTP-PEST. The dephosphorylation of Pyk2 by dynamin and PTP-PEST may be critical for terminating outside-in integrin signaling, and for stabilizing cytoskeletal reorganization during osteoclast bone resorption. PMID:22342188

Formation and Stability of Microbially Derived Soil Organic Matter

NASA Astrophysics Data System (ADS)

Waldrop, M. P.; Creamer, C.; Foster, A. L.; Lawrence, C. R.; Mcfarland, J. W.; Schulz, M. S.

2017-12-01

Soil carbon is vital to soil health, food security, and climate change mitigation, but the underlying mechanisms controlling the stabilization and destabilization of soil carbon are still poorly understood. There has been a conceptual paradigm shift in how soil organic matter is formed which now emphasizes the importance of microbial activity to build stable (i.e. long-lived) and mineral-associated soil organic matter. In this conceptual model, the consumption of plant carbon by microorganisms, followed by subsequent turnover of microbial bodies closely associated with mineral particles, produces a layering of amino acid and lipid residues on the surfaces of soil minerals that remains protected from destabilization by mineral-association and aggregation processes. We tested this new model by examining how isotopically labeled plant and microbial C differ in their fundamental stabilization and destabilization processes on soil minerals through a soil profile. We used a combination of laboratory and field-based approaches to bridge multiple spatial scales, and used soil depth as well as synthetic minerals to create gradients of soil mineralogy. We used Raman microscopy as a tool to probe organic matter association with mineral surfaces, as it allows for the simultaneous quantification and identification of living microbes, carbon, minerals, and isotopes through time. As expected, we found that the type of minerals present had a strong influence on the amount of C retained, but the stabilization of new C critically depends on growth, death, and turnover of microbial cells. Additionally, the destabilization of microbial residue C on mineral surfaces was little affected by flushes of DOC relative to wet-dry cycles alone. We believe this new insight into microbial mechanisms of C stabilization in soils will eventually lead to new avenues for measuring and modeling SOM dynamics in soils, and aid in the management of soil C to mediate global challenges.

Nek7 Protects Telomeres from Oxidative DNA Damage by Phosphorylation and Stabilization of TRF1.

PubMed

Tan, Rong; Nakajima, Satoshi; Wang, Qun; Sun, Hongxiang; Xue, Jing; Wu, Jian; Hellwig, Sabine; Zeng, Xuemei; Yates, Nathan A; Smithgall, Thomas E; Lei, Ming; Jiang, Yu; Levine, Arthur S; Su, Bing; Lan, Li

2017-03-02

Telomeric repeat binding factor 1 (TRF1) is essential to the maintenance of telomere chromatin structure and integrity. However, how telomere integrity is maintained, especially in response to damage, remains poorly understood. Here, we identify Nek7, a member of the Never in Mitosis Gene A (NIMA) kinase family, as a regulator of telomere integrity. Nek7 is recruited to telomeres and stabilizes TRF1 at telomeres after damage in an ATM activation-dependent manner. Nek7 deficiency leads to telomere aberrations, long-lasting γH2AX and 53BP1 foci, and augmented cell death upon oxidative telomeric DNA damage. Mechanistically, Nek7 interacts with and phosphorylates TRF1 on Ser114, which prevents TRF1 from binding to Fbx4, an Skp1-Cul1-F box E3 ligase subunit, thereby alleviating proteasomal degradation of TRF1, leading to a stable association of TRF1 with Tin2 to form a shelterin complex. Our data reveal a mechanism of efficient protection of telomeres from damage through Nek7-dependent stabilization of TRF1. Copyright © 2017 Elsevier Inc. All rights reserved.

Stability and Responsiveness in a Self-Organized Living Architecture

PubMed Central

Garnier, Simon; Murphy, Tucker; Lutz, Matthew; Hurme, Edward; Leblanc, Simon; Couzin, Iain D.

2013-01-01

Robustness and adaptability are central to the functioning of biological systems, from gene networks to animal societies. Yet the mechanisms by which living organisms achieve both stability to perturbations and sensitivity to input are poorly understood. Here, we present an integrated study of a living architecture in which army ants interconnect their bodies to span gaps. We demonstrate that these self-assembled bridges are a highly effective means of maintaining traffic flow over unpredictable terrain. The individual-level rules responsible depend only on locally-estimated traffic intensity and the number of neighbours to which ants are attached within the structure. We employ a parameterized computational model to reveal that bridges are tuned to be maximally stable in the face of regular, periodic fluctuations in traffic. However analysis of the model also suggests that interactions among ants give rise to feedback processes that result in bridges being highly responsive to sudden interruptions in traffic. Subsequent field experiments confirm this prediction and thus the dual nature of stability and flexibility in living bridges. Our study demonstrates the importance of robust and adaptive modular architecture to efficient traffic organisation and reveals general principles regarding the regulation of form in biological self-assemblies. PMID:23555219

Ultra-flexible and robust transparent electrodes by embedding silver nanowires into polyimide matrix

NASA Astrophysics Data System (ADS)

Zhao, Rong Rong; Yu, Ming Shi; Wang, Guan Cheng; Liu, Wei; Chen, Tong Lai

2018-06-01

Silver nanowires (AgNWs) percolated films have been extensively considered as promising candidates for alternative transparent electrodes. However, due to their high surface roughness, poor adhesion and thermal stability, their practical use in transparent conducting film application is still heavily limited. In this paper, we report ultra-flexible transparent electrodes by imbedding AgNWs into polyimide (PI) thin films to achieve smooth surface, pronounced thermal stability, and high adhesion. Besides the excellent electrical conductivity of about 7-13Ω/□ in sheet resistance, the obtained AgNWs/PI films have excellent transparency and mechanical resilience due to the intrinsic physical and chemical properties of PI organic polymer. By embedding AgNWs into PI, the surface roughness of AgNWs percolated films can be reduced from 39.5 nm to 6 nm (RMS values), and the adhesion of AgNWs to PI is greatly enhanced if compared to the case of only AgNWs onto glass or plastic substrates. Additionally, the AgNWs/PI films show extraordinary stability in terms of electrical conductivity after the arbitrary twisting and thermal heating test, respectively, which are demonstrated by the electrical-thermal measurements via thermal IR imaging.

Note: A temperature-stable low-noise transimpedance amplifier for microcurrent measurement.

PubMed

Xie, Kai; Shi, Xueyou; Zhao, Kai; Guo, Lixin; Zhang, Hanlu

2017-02-01

Temperature stability and noise characteristics often run contradictory in microcurrent (e.g., pA-scale) measurement instruments because low-noise performance requires high-value resistors with relatively poor temperature coefficients. A low-noise transimpedance amplifier with high-temperature stability, which involves an active compensation mechanism to overcome the temperature drift mainly caused by high-value resistors, is presented. The implementation uses a specially designed R-2R compensating network to provide programmable current gain with extra-fine trimming resolution. The temperature drifts of all components (e.g., feedback resistors, operational amplifiers, and the R-2R network itself) are compensated simultaneously. Therefore, both low-temperature drift and ultra-low-noise performance can be achieved. With a current gain of 10 11 V/A, the internal current noise density was about 0.4 fA/√Hz, and the average temperature coefficient was 4.3 ppm/K at 0-50 °C. The amplifier module maintains accuracy across a wide temperature range without additional thermal stabilization, and its compact size makes it especially suitable for high-precision, low-current measurement in outdoor environments for applications such as electrochemical emission supervision, air pollution particles analysis, radiation monitoring, and bioelectricity.

Note: A temperature-stable low-noise transimpedance amplifier for microcurrent measurement

NASA Astrophysics Data System (ADS)

Xie, Kai; Shi, Xueyou; Zhao, Kai; Guo, Lixin; Zhang, Hanlu

2017-02-01

Temperature stability and noise characteristics often run contradictory in microcurrent (e.g., pA-scale) measurement instruments because low-noise performance requires high-value resistors with relatively poor temperature coefficients. A low-noise transimpedance amplifier with high-temperature stability, which involves an active compensation mechanism to overcome the temperature drift mainly caused by high-value resistors, is presented. The implementation uses a specially designed R-2R compensating network to provide programmable current gain with extra-fine trimming resolution. The temperature drifts of all components (e.g., feedback resistors, operational amplifiers, and the R-2R network itself) are compensated simultaneously. Therefore, both low-temperature drift and ultra-low-noise performance can be achieved. With a current gain of 1011 V/A, the internal current noise density was about 0.4 fA/√Hz, and the average temperature coefficient was 4.3 ppm/K at 0-50 °C. The amplifier module maintains accuracy across a wide temperature range without additional thermal stabilization, and its compact size makes it especially suitable for high-precision, low-current measurement in outdoor environments for applications such as electrochemical emission supervision, air pollution particles analysis, radiation monitoring, and bioelectricity.

Side effects of stabilization occlusal splints: a report of three cases and literature review.

PubMed

Magdaleno, Fernando; Ginestal, Eduardo

2010-04-01

Stabilization splints are frequently used for the treatment of temporomandibular disorders (TMD) and bruxism, despite the fact that little is known about their mechanism of action or the precise conditions under which they can be recommended. Moreover, information about their possible adverse effects, which in the majority of cases include occlusal modifications of little clinical relevance, is scarce. On occasions, these splints can provoke severe occlusal alterations and other complications, which are rarely alluded to in the literature. Here presented in this paper are three case reports in which part-time stabilization splints led to irreversible occlusal alterations and a discussion of the relevant clinical implications. Such splints are reported to negatively affect the condyle-disk relation in patients who exhibit disk displacement with reduction and to modify breathing features in patients with obstructive sleep apnea, although further studies are required to unequivocally demonstrate these findings. Finally, the splint seems to modify peripheral information at the level of the Central Nervous System, leading to modifications in corporal postural tone. The clinical repercussions of such alterations are currently poorly understood. It is our hope that future research will throw fresh light on these important topics.

Curvature of Double-Membrane Organelles Generated by Changes in Membrane Size and Composition

PubMed Central

Knorr, Roland L.; Dimova, Rumiana; Lipowsky, Reinhard

2012-01-01

Transient double-membrane organelles are key players in cellular processes such as autophagy, reproduction, and viral infection. These organelles are formed by the bending and closure of flat, double-membrane sheets. Proteins are believed to be important in these morphological transitions but the underlying mechanism of curvature generation is poorly understood. Here, we describe a novel mechanism for this curvature generation which depends primarily on three membrane properties: the lateral size of the double-membrane sheets, the molecular composition of their highly curved rims, and a possible asymmetry between the two flat faces of the sheets. This mechanism is evolutionary advantageous since it does not require active processes and is readily available even when resources within the cell are restricted as during starvation, which can induce autophagy and sporulation. We identify pathways for protein-assisted regulation of curvature generation, organelle size, direction of bending, and morphology. Our theory also provides a mechanism for the stabilization of large double-membrane sheet-like structures found in the endoplasmic reticulum and in the Golgi cisternae. PMID:22427874

Experimental and Theoretical Insights into the Inhibition Mechanism of Prion Fibrillation by Resveratrol and its Derivatives.

PubMed

Li, Lanlan; Zhu, Yongchang; Zhou, Shuangyan; An, Xiaoli; Zhang, Yan; Bai, Qifeng; He, Yong-Xing; Liu, Huanxiang; Yao, Xiaojun

2017-12-20

Resveratrol and its derivatives have been shown to display beneficial effects to neurodegenerative diseases. However, the molecular mechanism of resveratrol and its derivatives on prion conformational conversion is poorly understood. In this work, the interaction mechanism between prion and resveratrol as well as its derivatives was investigated using steady-state fluorescence quenching, Thioflavin T binding assay, Western blotting, and molecular dynamics simulation. Protein fluorescence quenching method and Thioflavin T assay revealed that resveratrol and its derivatives could interact with prion and interrupt prion fibril formation. Molecular dynamics simulation results indicated that resveratrol can stabilize the PrP 127-147 peptide mainly through π-π stacking interactions between resveratrol and Tyr128. The hydrogen bonds interactions between resveratrol and the PrP 127-147 peptide could further reduce the flexibility and the propensity to aggregate. The results of this study not only can provide useful information about the interaction mechanism between resveratrol and prion, but also can provide useful clues for further design of new inhibitors inhibiting prion aggregation.

Robust and biodegradable elastomers based on corn starch and polydimethylsiloxane (PDMS).

PubMed

Ceseracciu, Luca; Heredia-Guerrero, José Alejandro; Dante, Silvia; Athanassiou, Athanassia; Bayer, Ilker S

2015-02-18

Designing starch-based biopolymers and biodegradable composites with durable mechanical properties and good resistance to water is still a challenging task. Although thermoplastic (destructured) starch has emerged as an alternative to petroleum-based polymers, its poor dimensional stability under humid and dry conditions extensively hinders its use as the biopolymer of choice in many applications. Unmodified starch granules, on the other hand, suffer from incompatibility, poor dispersion, and phase separation issues when compounded into other thermoplastics above a concentration level of 5%. Herein, we present a facile biodegradable elastomer preparation method by incorporating large amounts of unmodified corn starch, exceeding 80% by volume, in acetoxy-polyorganosiloxane thermosets to produce mechanically robust, hydrophobic bioelastomers. The naturally adsorbed moisture on the surface of starch enables autocatalytic rapid hydrolysis of polyorganosiloxane to form Si-O-Si networks. Depending on the amount of starch granules, the mechanical properties of the bioelastomers can be easily tuned with high elastic recovery rates. Moreover, starch granules considerably lowered the surface friction coefficient of the polyorganosiloxane network. Stress relaxation measurements indicated that the bioelastomers have strain energy dissipation factors that are lower than those of conventional rubbers, rendering them as promising green substitutes for plastic mechanical energy dampeners. Corn starch granules also have excellent compatibility with addition-cured polysiloxane chemistry that is used extensively in microfabrication. Regardless of the starch concentration, all of the developed bioelastomers have hydrophobic surfaces with lower friction coefficients and much less water uptake capacity than those of thermoplastic starch. The bioelastomers are biocompatible and are estimated to biodegrade in Mediterranean seawater within three to six years.

The stability of water- and fat-soluble vitamin in dentifrices according to pH level and storage type.

PubMed

Park, Jung-Eun; Kim, Ki-Eun; Choi, Yong-Jun; Park, Yong-Duk; Kwon, Ha-Jeong

2016-02-01

The purpose of this study is to evaluate the vitamin stabilities in dentifrices by analyzing various vitamins according to the level and storage temperature. The stabilities of water- and fat-soluble vitamins were investigated in buffer solution at different pH values (4, 7, 8, 10 and 11) for 14 days and in dentifrices at different pH (7 and 10) for 5 months at two temperature conditions (room and refrigeration temperature) by analyzing the remaining amounts using HPLC methods. In the buffer solution, the stability of vitamins B1 , B6 and C was increased as the pH values increased. Vitamins E and K showed poor stability at pH 4, and vitamin B3 showed poor stability at pH 11. In dentifrices, the storage temperature highly influenced vitamin stability, especially vitamins C and E, but the stabilities of vitamins B1 and C according to pH values did not correspond to the buffer solution tests. Vitamin B group was relatively stable in dentifrices, but vitamin C completely disappeared after 5 months. Vitamin K showed the least initial preservation rates. Vitamins were not detected in commercial dentifrices for adults and detected amounts were less than the advertised contents in dentifrices for children. Copyright © 2015 John Wiley & Sons, Ltd.

Use of nanotechnology for improved pharmacokinetics and activity of immunogenic cell death inducers used in cancer chemotherapy.

PubMed

Janicka, Martyna; Gubernator, Jerzy

2017-09-01

Immunogenic cell death inducers (ICD inducers) are a diverse group of therapeutic molecules capable of eliciting an adaptive immune response against the antigens present on the surface of dying cancer cells. Most of these molecules suffer from low bioavailability, high toxicity and poor pharmacokinetics which limit their application. It is believed that nanotechnology, in particular nano-sized nanocarriers, can address most of the issues that limit the use of ICD inducers. Area covered: The mechanism of action of ICD inducers and their limitations is discussed. In addition, we cover the novel possibilities arising from the use of nanotechnology to improve delivery of ICD inducers to the target tissue as well as the restrictions of modern nanotechnology. Expert opinion: At present, nanocarrier formulations suffer from low bioavailability, poor pharmacokinetics and stability issues. Nonetheless, there is a tremendous future for combinatorial immune-pharmacological treatments of human tumors based on nanocarrier delivery of ICD inducers.

Overcoming the crystallization and designability issues in the ultrastable zirconium phosphonate framework system

DOE PAGES

Zheng, Tao; Yang, Zaixing; Gui, Daxiang; ...

2017-05-30

Metal-organic frameworks (MOFs) based on zirconium phosphonates exhibit superior chemical stability suitable for applications under harsh conditions. These compounds mostly exist as poorly crystallized precipitates, and precise structural information has therefore remained elusive. Furthermore, a zero-dimensional zirconium phosphonate cluster acting as secondary building unit has been lacking, leading to poor designability in this system. We overcome these challenges and obtain single crystals of three zirconium phosphonates that are suitable for structural analysis. Furthermore, these compounds are built by previously unknown isolated zirconium phosphonate clusters and exhibit combined high porosity and ultrastability even in fuming acids. SZ-2 possesses the largest voidmore » volume recorded in zirconium phosphonates and SZ-3 represents the most porous crystalline zirconium phosphonate and the only porous MOF material reported to survive in aqua regia. SZ-2 and SZ-3 can effectively remove uranyl ions from aqueous solutions over a wide pH range, and we have elucidated the removal mechanism.« less

Overcoming the crystallization and designability issues in the ultrastable zirconium phosphonate framework system

PubMed Central

Zheng, Tao; Yang, Zaixing; Gui, Daxiang; Liu, Zhiyong; Wang, Xiangxiang; Dai, Xing; Liu, Shengtang; Zhang, Linjuan; Gao, Yang; Chen, Lanhua; Sheng, Daopeng; Wang, Yanlong; Diwu, Juan; Wang, Jianqiang; Zhou, Ruhong; Chai, Zhifang; Albrecht-Schmitt, Thomas E.; Wang, Shuao

2017-01-01

Metal-organic frameworks (MOFs) based on zirconium phosphonates exhibit superior chemical stability suitable for applications under harsh conditions. These compounds mostly exist as poorly crystallized precipitates, and precise structural information has therefore remained elusive. Furthermore, a zero-dimensional zirconium phosphonate cluster acting as secondary building unit has been lacking, leading to poor designability in this system. Herein, we overcome these challenges and obtain single crystals of three zirconium phosphonates that are suitable for structural analysis. These compounds are built by previously unknown isolated zirconium phosphonate clusters and exhibit combined high porosity and ultrastability even in fuming acids. SZ-2 possesses the largest void volume recorded in zirconium phosphonates and SZ-3 represents the most porous crystalline zirconium phosphonate and the only porous MOF material reported to survive in aqua regia. SZ-2 and SZ-3 can effectively remove uranyl ions from aqueous solutions over a wide pH range, and we have elucidated the removal mechanism. PMID:28555656

Overcoming the crystallization and designability issues in the ultrastable zirconium phosphonate framework system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Tao; Yang, Zaixing; Gui, Daxiang

Metal-organic frameworks (MOFs) based on zirconium phosphonates exhibit superior chemical stability suitable for applications under harsh conditions. These compounds mostly exist as poorly crystallized precipitates, and precise structural information has therefore remained elusive. Furthermore, a zero-dimensional zirconium phosphonate cluster acting as secondary building unit has been lacking, leading to poor designability in this system. We overcome these challenges and obtain single crystals of three zirconium phosphonates that are suitable for structural analysis. Furthermore, these compounds are built by previously unknown isolated zirconium phosphonate clusters and exhibit combined high porosity and ultrastability even in fuming acids. SZ-2 possesses the largest voidmore » volume recorded in zirconium phosphonates and SZ-3 represents the most porous crystalline zirconium phosphonate and the only porous MOF material reported to survive in aqua regia. SZ-2 and SZ-3 can effectively remove uranyl ions from aqueous solutions over a wide pH range, and we have elucidated the removal mechanism.« less

Dispersion stability of a ceramic glaze achieved through ionic surfactant adsorption.

PubMed

Panya, Preecha; Arquero, Orn-anong; Franks, George V; Wanless, Erica J

2004-11-01

The adsorption of cetylpyridinium chloride (CPC) and sodium dodecylbenzenesulfonate (SDBS) onto a ceramic glaze mixture composed of limestone, feldspar, quartz, and kaolin has been investigated. Both adsorption isotherms and the average particle zeta potential have been studied in order to understand the suspension stability as a function of pH, ionic strength, and surfactant concentration. The adsorption of small amounts of cationic CPC onto the primarily negatively charged surfaces of the particles at pH 7 and 9 results in strong attraction and flocculation due to hydrophobic interactions. At higher surfactant concentrations a zeta potential of more than +60 mV results from the bilayered adsorbed surfactant, providing stability at salt concentrations < or = 0.01 M. At 0.1 M salt poor stability results despite substantial zeta potential values. Three mechanisms for SDBS adsorption have been identified. When anionic SDBS monomers either adsorb by electrostatic interactions with the few positive surface sites at high pH or adsorb onto like charged negative surface sites due to dispersion or hydrophobic interactions, the magnitude of the negative zeta potential increases slightly. At pH 9 this increase is enough to promote stability with an average zeta potential of more than -55 mV, whereas at pH 7 the zeta potential is lower at about -45 mV. The stability of suspensions at pH 7 is additionally due to steric repulsion caused by the adsorption of thick layers of neutrally charged Ca(DBS)2 complexes created when the surfactant interacts with dissolved calcium ions from the calcium carbonate component.

In Situ Salt Formation during Melt Extrusion for Improved Chemical Stability and Dissolution Performance of a Meloxicam-Copovidone Amorphous Solid Dispersion.

PubMed

Haser, Abbe; Cao, Tu; Lubach, Joseph W; Zhang, Feng

2018-03-05

As the pipeline for poorly soluble compounds continues to grow, drug degradation during melt extrusion must be addressed. We present a novel method for stabilizing a thermally labile drug substance while preserving its physical stability and even improving its dissolution performance. In a previous study, we found that incorporating meglumine during extrusion of meloxicam results in chemical stabilization that cannot be achieved using process optimization alone. The purpose of this study is to understand the mechanism behind this stabilization and its impact on the performance of a meloxicam-Kollidon VA64 amorphous solid dispersion. The meloxicam concentration was maintained at 10% (w/w) for blends with and without meglumine. The optimal meglumine blend contained an equimolar amount of meloxicam to meglumine with the remainder consisting of Kollidon VA64. Both formulations were processed with optimized extrusion conditions and analyzed by HPLC for purity. Meglumine at a 1:1 molar ratio with meloxicam results in 100% purity of meloxicam after melt extrusion. Solid-state NMR revealed a proton transfer between the meloxicam and meglumine indicating an in situ salt formation. During non-sink dissolution, the meglumine ASD enables meloxicam to maintain supersaturatation (≅50 times more than meloxicam free acid) for >7.25 h. The ASD without meglumine began precipitating 2.25 h following the pH shift. The ASDs were placed at 40 °C/75% RH for 6 months, and their stability was assessed. No significant chemical degradation, recrystallization, or significant moisture uptake was observed after six months' storage at 40 °C/75% RH.

A case study of energy transfer mechanism from uranium to europium in ZnAl2O4 spinel host by photoluminescence spectroscopy

NASA Astrophysics Data System (ADS)

Kumar, Mithlesh; Mohapatra, M.

2016-04-01

Zinc aluminate (ZAO), a member of spinel class of inorganic compounds has been of much interest of late due to its wide range of use in catalysis, optical, electronic and ceramic industries. When doped with several lanthanides, this material has proved to be a potential host matrix for phosphors. As lanthanides suffer from poor (direct) excitation and emission cross sections, the use of a co-dopant ion can help to circumvent this and extract better emission from a lanthanide doped ZAO system. In this connection, energy transfer mechanism from uranium to europium in the ZAO host was investigated by photoluminescence spectroscopic technique. It was seen that uranium gets stabilized in the hexavalent state as UO66 - (octahedral uranate) where as the lanthanide ion, Eu is stabilized in its trivalent state in the ZAO host. In the co-doped system, an efficient energy transfer pathway from the uranate to europium ion was observed. Based upon emission and life time data a suitable mechanism was proposed for the energy transfer (quenching) process. It was proposed that after excitation by photons, the uranate ions transfer their energy to nearby 5D1 level of Eu3 + ions which non-radiatively de-excites to the corresponding lower levels of 5D0. Further this 5D0 level decays in a radiative mode to the 7F manifold giving the characteristic emission profile of trivalent Eu. It was proposed that both static and dynamic types of energy transfer mechanism were responsible for this process.

Use of a screening method to determine excipients which optimize the extent and stability of supersaturated drug solutions and application of this system to solid formulation design.

PubMed

Vandecruys, Roger; Peeters, Jef; Verreck, Geert; Brewster, Marcus E

2007-09-05

Assessing the effect of excipients on the ability to attain and maintain supersaturation of drug-based solution may provide useful information for the design of solid formulations. Judicious selection of materials that affect either the extent or stability of supersaturating drug delivery systems may be enabling for poorly soluble drug candidates or other difficult-to-formulate compounds. The technique suggested herein is aimed at providing a screening protocol to allow preliminary assessment of these factors based on small to moderate amounts of drug substance. A series of excipients were selected that may, by various mechanisms, affect supersaturation including pharmaceutical polymers such as HMPC and PVP, surfactants such as Polysorbate 20, Cremophor RH40 and TPGS and hydrophilic cyclodextrins such as HPbetaCD. Using a co-solvent based method and 25 drug candidates, the data suggested, on the whole, that the surfactants and the selected cyclodextrin seemed to best augment the extent of supersaturation but had variable benefits as stabilizers, while the pharmaceutical polymers had useful effect on supersaturation stability but were less helpful in increasing the extent of supersaturation. Using these data, a group of simple solid dosage forms were prepared and tested in the dog for one of the drug candidates. Excipients that gave the best extent and stability for the formed supersaturated solution in the screening assay also gave the highest oral bioavailability in the dog.

Solubilization of Therapeutic Agents in Micellar Nanomedicines

PubMed Central

Vuković, Lela; Madriaga, Antonett; Kuzmis, Antonina; Banerjee, Amrita; Tang, Alan; Tao, Kevin; Shah, Neil; Král, Petr; Onyuksel, Hayat

2014-01-01

We use atomistic molecular dynamics simulations to reveal the binding mechanisms of therapeutic agents in PEG-ylated micellar nanocarriers (SSM). In our experiments, SSM in buffer solutions can solubilize either ≈ 11 small bexarotene molecules or ≈ 6 (2 in low ionic strength buffer) human vasoactive intestinal peptide (VIP) molecules. Free energy calculations reveal that molecules of the poorly water soluble drug bexarotene can reside at the micellar ionic interface of the PEG corona, with their polar ends pointing out. Alternatively, they can reside in the alkane core center, where several bexarotene molecules can self-stabilize by forming a cluster held together by a network of hydrogen bonds. We also show that highly charged molecules, such as VIP, can be stabilized at the SSM ionic interface by Coulombic coupling between their positively charged residues and the negatively charged phosphate head-groups of the lipids. The obtained results illustrate that atomistic simulations can reveal drug solubilization character in nanocarriers and be used in efficient optimization of novel nanomedicines. PMID:24283508

Cortactin promotes exosome secretion by controlling branched actin dynamics

PubMed Central

Sinha, Seema; Hoshino, Daisuke; Hong, Nan Hyung; Seiki, Motoharu; Tyska, Matthew J.

2016-01-01

Exosomes are extracellular vesicles that influence cellular behavior and enhance cancer aggressiveness by carrying bioactive molecules. The mechanisms that regulate exosome secretion are poorly understood. Here, we show that the actin cytoskeletal regulatory protein cortactin promotes exosome secretion. Knockdown or overexpression of cortactin in cancer cells leads to a respective decrease or increase in exosome secretion, without altering exosome cargo content. Live-cell imaging revealed that cortactin controls both trafficking and plasma membrane docking of multivesicular late endosomes (MVEs). Regulation of exosome secretion by cortactin requires binding to the branched actin nucleating Arp2/3 complex and to actin filaments. Furthermore, cortactin, Rab27a, and coronin 1b coordinately control stability of cortical actin MVE docking sites and exosome secretion. Functionally, the addition of purified exosomes to cortactin-knockdown cells rescued defects of those cells in serum-independent growth and invasion. These data suggest a model in which cortactin promotes exosome secretion by stabilizing cortical actin-rich MVE docking sites. PMID:27402952

Cortactin promotes exosome secretion by controlling branched actin dynamics.

PubMed

Sinha, Seema; Hoshino, Daisuke; Hong, Nan Hyung; Kirkbride, Kellye C; Grega-Larson, Nathan E; Seiki, Motoharu; Tyska, Matthew J; Weaver, Alissa M

2016-07-18

Exosomes are extracellular vesicles that influence cellular behavior and enhance cancer aggressiveness by carrying bioactive molecules. The mechanisms that regulate exosome secretion are poorly understood. Here, we show that the actin cytoskeletal regulatory protein cortactin promotes exosome secretion. Knockdown or overexpression of cortactin in cancer cells leads to a respective decrease or increase in exosome secretion, without altering exosome cargo content. Live-cell imaging revealed that cortactin controls both trafficking and plasma membrane docking of multivesicular late endosomes (MVEs). Regulation of exosome secretion by cortactin requires binding to the branched actin nucleating Arp2/3 complex and to actin filaments. Furthermore, cortactin, Rab27a, and coronin 1b coordinately control stability of cortical actin MVE docking sites and exosome secretion. Functionally, the addition of purified exosomes to cortactin-knockdown cells rescued defects of those cells in serum-independent growth and invasion. These data suggest a model in which cortactin promotes exosome secretion by stabilizing cortical actin-rich MVE docking sites. © 2016 Sinha et al.

Large Fluorescence Response by Alcohol from a Bis(benzoxazole)-Zinc(II) Complex: The Role of Excited State Intramolecular Proton Transfer

PubMed Central

Wang, Junfeng; Chu, Qinghui; Liu, Xiumin; Wesdemiotis, Chrys

2013-01-01

The formation of a bis(HBO) anion is known to turn-on the fluorescence to give red emission, via controlling the excited-state intramolecular proton transfer (ESIPT). The poor stability of the formed anion, however, hampered its application. The anion stability is found to be greatly improved by attaching the anion to Zn2+ cation (i.e. forming zinc complex), whose emission is at λem ≈ 550 and 760 nm. Interestingly, addition of methanol to the zinc complex induces a remarkable red fluorescence (λem ≈ 630 nm, ϕfl ≈ 0.8). With the aid of spectroscopic studies (1H NMR, UV-vis, fluorescence, and mass spectra), the structures of the zinc complexes are characterized. The emission species is identified as a dimer-like structure. The study thus reveals an effective fluorescence switching mechanism that could further advance the application of ESIPT-based sensors. PMID:23514312

Stabilization, not polymerization, of microtubules inhibits the nuclear translocation of STATs in adipocytes.

PubMed

Gleason, Evanna L; Hogan, Jessica C; Stephens, Jacqueline M

2004-12-17

Signal transducers and activators of transcriptions (STATs) are a family of latent transcription factors which are activated by a variety of growth factors and cytokines in many cell types. However, the mechanism by which these transcription factors translocate to the nucleus is poorly understood. The goal of this study was to determine the requirement of microfilaments and microtubules for cytokine induced STAT activation in cultured adipocytes. We used seven different actin-specific and microtubule-specific agents that are well-established effectors of these cytoskeletal networks. Our results clearly demonstrate that inhibition of microfilaments or the prevention of microtubule polymerization has no effect on the ability of STATs to be tyrosine phosphorylated or to translocate to the nucleus. However, we observed that paclitaxel, a microtubule stabilizer, resulted in a significant decrease in the nuclear translocation of STATs without affecting the cytosolic tyrosine phosphorylation of these transcription factors. In summary, our results demonstrate that the dynamic instability, but not the polymerization, of microtubules contributes to nuclear translocation of STAT proteins in adipocytes.

Construction and characterization of curcumin nanoparticles system

NASA Astrophysics Data System (ADS)

Sun, Weitong; Zou, Yu; Guo, Yaping; Wang, Lu; Xiao, Xue; Sun, Rui; Zhao, Kun

2014-03-01

This study was aimed at developing a nanoparticles system for curcumin, a widely used traditional Chinese medicine, but with the disadvantage of poor aqueous solubility. The objective was intended to improve in vitro release characteristics, enhance blood and gastrointestinal stability, increase bioavailability and pharmacological activities. Curcumin nanoparticles system (Cur-NS) was prepared by ionotropic gelation technique. Cur-NS was characterized by particle size, zeta potential, drug entrapment efficiency, drug loading, and physical stability, respectively. Cur-NS presented controlled release properties, and the release properties of Cur from NS were fit non-Fickian mechanism, controlled by the expected diffusional release and the erosion or solubilization from the crosslink layer of polymer carrier. In addition, the pharmacokinetic study in rats revealed a notable improved oral bioavailability of Cur, and the anti-tumor activity in vivo of Cur-NS on tumor growth was investigated. Cur-NS significantly inhibited tumor effect compared with non-vehicle group, thus making it a potential candidate for cancer therapy.

Edge Stabilized Ribbon (ESR); Stress, Dislocation Density and Electronic Performance

NASA Technical Reports Server (NTRS)

Sachs, E. M.

1984-01-01

The edge stabilized ribbon (ESR) silicon ribbon was grown in widths of 1, 2.2 and 4.0 inches at speeds ranging from .6 to 7 in/min, which result in ribbon thicknesses of 5 to 400 microns. One of the primary problems remaining in ESR growth is that of thermally induced mechanical stresses. This problem is manifested as ribbon with a high degree of residual stress or as ribbon with buckled ribbon. Thermal stresses result in a high dislocation density in the grown material, resulting in compromised electronic performance. Improvements in ribbon flatness were accomplished by modification of the ribbon cooling profile. Ribbon flatness and other experimental observations of ESR ribbon are discussed. Laser scanner measurements show a good correlation between diffusion length and dislocation density which indicates that the high dislocation densities are the primary cause of the poor current performance of ESR materials. Dislocation densities were reduced and improved electronic performance resulted. Laser scanner data on new and old material are presented.

Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation

NASA Astrophysics Data System (ADS)

Hou, Xuben; Rooklin, David; Fang, Hao; Zhang, Yingkai

2016-11-01

Resveratrol is a natural compound found in red wine that has been suggested to exert its potential health benefit through the activation of SIRT1, a crucial member of the mammalian NAD+-dependent deacetylases. SIRT1 has emerged as an attractive therapeutic target for many aging related diseases, however, how its activity can only be activated toward some specific substrates by resveratrol has been poorly understood. Herein, by employing extensive molecular dynamics simulations as well as fragment-centric topographical mapping of binding interfaces, we have clarified current controversies in the literature and elucidated that resveratrol plays an important activation role by stabilizing SIRT1/peptide interactions in a substrate-specific manner. This new mechanism highlights the importance of the N-terminal domain in substrate recognition, explains the activity restoration role of resveratrol toward some “loose-binding” substrates of SIRT1, and has significant implications for the rational design of new substrate-specific SIRT1 modulators.

The crystal structure of a partial mouse Notch-1 ankyrin domain: Repeats 4 through 7 preserve an ankyrin fold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lubman, Olga Y.; Kopan, Raphael; Waksman, Gabriel

Folding and stability of proteins containing ankyrin repeats (ARs) is of great interest because they mediate numerous protein-protein interactions involved in a wide range of regulatory cellular processes. Notch, an ankyrin domain containing protein, signals by converting a transcriptional repression complex into an activation complex. The Notch ANK domain is essential for Notch function and contains seven ARs. Here, we present the 2.2 {angstrom} crystal structure of ARs 4-7 from mouse Notch 1 (m1ANK). These C-terminal repeats were resistant to degradation during crystallization, and their secondary and tertiary structures are maintained in the absence of repeats 1-3. The crystallized fragmentmore » adopts a typical ankyrin fold including the poorly conserved seventh AR, as seen in the Drosophila Notch ANK domain (dANK). The structural preservation and stability of the C-terminal repeats shed a new light onto the mechanism of hetero-oligomeric assembly during Notch-mediated transcriptional activation.« less

Mode-locking evolution in ring fiber lasers with tunable repetition rate.

PubMed

Korobko, D A; Fotiadi, A A; Zolotovskii, I O

2017-09-04

We have applied a simple approach to analyze behavior of the harmonically mode-locked fiber laser incorporating an adjustable Mach-Zehnder interferometer (MZI). Our model is able to describe key features of the laser outputs and explore limitations of physical mechanisms responsible for laser operation at different pulse repetition rates tuned over a whole GHz range. At low repetition rates the laser operates as a harmonically mode-locked soliton laser triggered by a fast saturable absorber. At high repetition rates the laser mode-locking occurs due to dissipative four-wave mixing seeded by MZI and gain spectrum filtering. However, the laser stability in this regime is rather low due to poor mode selectivity provided by MZI that is able to support the desired laser operation just near the lasing threshold. The use of a double MZI instead of a single MZI could improve the laser stability and extends the range of the laser tunability. The model predicts a gap between two repetitive rate ranges where pulse train generation is not supported.

The tumour suppressor CYLD regulates the p53 DNA damage response

PubMed Central

Fernández-Majada, Vanesa; Welz, Patrick-Simon; Ermolaeva, Maria A.; Schell, Michael; Adam, Alexander; Dietlein, Felix; Komander, David; Büttner, Reinhard; Thomas, Roman K.; Schumacher, Björn; Pasparakis, Manolis

2016-01-01

The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress. Ubiquitin chain-restriction analysis provides evidence that CYLD removes K48 ubiquitin chains from p53 indirectly by cleaving K63 linkages, suggesting that p53 is decorated with complex K48/K63 chains. Moreover, CYLD deficiency also diminishes CEP-1/p53-dependent DNA damage-induced germ cell apoptosis in the nematode Caenorhabditis elegans. Collectively, our results identify CYLD as a deubiquitinase facilitating DNA damage-induced p53 activation and suggest that regulation of p53 responses to genotoxic stress contributes to the tumour suppressor function of CYLD. PMID:27561390

A visual tracking method based on improved online multiple instance learning

NASA Astrophysics Data System (ADS)

He, Xianhui; Wei, Yuxing

2016-09-01

Visual tracking is an active research topic in the field of computer vision and has been well studied in the last decades. The method based on multiple instance learning (MIL) was recently introduced into the tracking task, which can solve the problem that template drift well. However, MIL method has relatively poor performance in running efficiency and accuracy, due to its strong classifiers updating strategy is complicated, and the speed of the classifiers update is not always same with the change of the targets' appearance. In this paper, we present a novel online effective MIL (EMIL) tracker. A new update strategy for strong classifier was proposed to improve the running efficiency of MIL method. In addition, to improve the t racking accuracy and stability of the MIL method, a new dynamic mechanism for learning rate renewal of the classifier and variable search window were proposed. Experimental results show that our method performs good performance under the complex scenes, with strong stability and high efficiency.

Resveratrol serves as a protein-substrate interaction stabilizer in human SIRT1 activation.

PubMed

Hou, Xuben; Rooklin, David; Fang, Hao; Zhang, Yingkai

2016-11-30

Resveratrol is a natural compound found in red wine that has been suggested to exert its potential health benefit through the activation of SIRT1, a crucial member of the mammalian NAD + -dependent deacetylases. SIRT1 has emerged as an attractive therapeutic target for many aging related diseases, however, how its activity can only be activated toward some specific substrates by resveratrol has been poorly understood. Herein, by employing extensive molecular dynamics simulations as well as fragment-centric topographical mapping of binding interfaces, we have clarified current controversies in the literature and elucidated that resveratrol plays an important activation role by stabilizing SIRT1/peptide interactions in a substrate-specific manner. This new mechanism highlights the importance of the N-terminal domain in substrate recognition, explains the activity restoration role of resveratrol toward some "loose-binding" substrates of SIRT1, and has significant implications for the rational design of new substrate-specific SIRT1 modulators.

Recent Insights into the Control of Human Papillomavirus (HPV) Genome Stability, Loss, and Degradation.

PubMed

Fisher, Chris

2015-01-01

Most human papillomavirus (HPV) antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their hosts. They must replicate and hide from the DNA damage response (DDR) and innate immune systems, which serve to protect cells from foreign or "non-self" DNA, and yet they draft these same systems to support their life cycles. DNA binding antiviral agents promoting massive viral DNA instability and elimination are reviewed. Mechanistic studies of these agents have identified genetic antiviral enhancers and repressors, antiviral sensitizers, and host cell elements that protect and stabilize HPV genomes. Viral DNA degradation appears to be an important means of controlling HPV DNA levels in some cases, but the underlying mechanisms remain poorly understood. These findings may prove useful not only for understanding viral DNA persistence but also in devising future antiviral strategies.

Using foamed asphalt as a stabilizing agent in full depth reclamation of Route 8 in Belgrade : interim report - first year, December 2003.

DOT National Transportation Integrated Search

2003-12-01

Maine has a variety of soil types throughout the state. Most of these soil types degrade rapidly and have : poor stability. To eliminate the cost of supplying quality road base material from a distant source and : increase the stability of existing s...

Using foamed asphalt as a stabilizing agent in full depth reclamation of Route 8 in Belgrade : interim report - third and fourth year, October 2006.

DOT National Transportation Integrated Search

2006-10-01

Maine has a variety of soil types throughout the state. A majority of these soil types degrade rapidly and : have poor stability. To eliminate the cost of supplying quality road base material from a distant source and : increase the stability of exis...

Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease.

PubMed

Louis, John M; Tözsér, József; Roche, Julien; Matúz, Krisztina; Aniana, Annie; Sayer, Jane M

2013-10-29

During treatment, mutations in HIV-1 protease (PR) are selected rapidly that confer resistance by decreasing affinity to clinical protease inhibitors (PIs). As these unique drug resistance mutations can compromise the fitness of the virus to replicate, mutations that restore conformational stability and activity while retaining drug resistance are selected on further evolution. Here we identify several compensating mechanisms by which an extreme drug-resistant mutant bearing 20 mutations (PR20) with >5-fold increased Kd and >4000-fold decreased affinity to the PI darunavir functions. (1) PR20 cleaves, albeit poorly, Gag polyprotein substrates essential for viral maturation. (2) PR20 dimer, which exhibits distinctly enhanced thermal stability, has highly attenuated autoproteolysis, thus likely prolonging its lifetime in vivo. (3) The enhanced stability of PR20 results from stabilization of the monomer fold. Both monomeric PR20(T26A) and dimeric PR20 exhibit Tm values 6-7.5 °C higher than those for their PR counterparts. Two specific mutations in PR20, L33F and L63P at sites of autoproteolysis, increase the Tm of monomeric PR(T26A) by ~8 °C, similar to PR20(T26A). However, without other compensatory mutations as seen in PR20, L33F and L63P substitutions, together, neither restrict autoproteolysis nor significantly reduce binding affinity to darunavir. To determine whether dimer stability contributes to binding affinity for inhibitors, we examined single-chain dimers of PR and PR(D25N) in which the corresponding identical monomer units were covalently linked by GGSSG sequence. Linking of the subunits did not appreciably change the ΔTm on inhibitor binding; thus stabilization by tethering appears to have little direct effect on enhancing inhibitor affinity.

Polymeric membranes for guided bone regeneration.

PubMed

Gentile, Piergiorgio; Chiono, Valeria; Tonda-Turo, Chiara; Ferreira, Ana M; Ciardelli, Gianluca

2011-10-01

In this review, different barrier membranes for guided bone regeneration (GBR) are described as a useful surgical technique to enhance bone regeneration in damaged alveolar sites before performing implants and fitting other dental appliances. The GBR procedure encourages bone regeneration through cellular exclusion and avoids the invasion of epithelial and connective tissues that grow at the defective site instead of bone tissue. The barrier membrane should satisfy various properties, such as biocompatibility, non-immunogenicity, non-toxicity, and a degradation rate that is long enough to permit mechanical support during bone formation. Other characteristics such as tissue integration, nutrient transfer, space maintenance and manageability are also of interest. In this review, various non-resorbable and resorbable commercially available membranes are described, based on expanded polytetrafluoroethylene, poly(lactic acid), poly(glycolic acid) and their copolymers. The polyester-based membranes are biodegradable, permit a single-stage procedure, and have higher manageability than non-resorbable membranes; however, they have shown poor biocompatibility. In contrast, membranes based on natural materials, such as collagen, are biocompatible but are characterized by poor mechanical properties and stability due to their early degradation. Moreover, new approaches are described, such as the use of multi-layered, graft-copolymer-based and composite membranes containing osteoconductive ceramic fillers as alternatives to conventional membranes. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.

PubMed

Nishino, Yukiko; Kubota, Aya; Kanazawa, Takanori; Takashima, Yuuki; Ozeki, Tetsuya; Okada, Hiroaki

2012-11-01

A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration. Copyright © 2012 Wiley Periodicals, Inc.

Close encounters: Moving along bumps, breaks, and bubbles on expanded trinucleotide tracts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polyzos, Aris A.; McMurray, Cynthia T.

2017-06-09

Expansion of simple triplet repeats (TNR) underlies greater than 30 severe degenerative diseases. There is a good understanding of the major pathways generating an expansion, and the associated polymerases that operate during gap filling synthesis at these “difficult to copy” sequences. However, the mechanism by which a TNR is repaired depends on the type of lesion, the structural features imposed by the lesion, the assembled replication/repair complex, and the polymerase that encounters it. The relationships among these parameters are exceptionally complex and how they direct pathway choice is poorly understood. In this review, we consider the properties of polymerases, andmore » how encounters with GC-rich or abnormal structures might influence polymerase choice and the success of replication and repair. Insights over the last three years have highlighted new mechanisms that provide interesting choices to consider in protecting genome stability.« less

Uniaxial Drawing of Graphene-PVA Nanocomposites: Improvement in Mechanical Characteristics via Strain-Induced Exfoliation of Graphene

NASA Astrophysics Data System (ADS)

Jan, Rahim; Habib, Amir; Akram, Muhammad Aftab; Zia, Tanveer-ul-Haq; Khan, Ahmad Nawaz

2016-08-01

Polyvinyl alcohol (PVA)-stabilized graphene nanosheets (GNS) of lateral dimension ( L) ~1 μm are obtained via liquid phase exfoliation technique to prepare its composites in the PVA matrix. These composites show low levels of reinforcements due to poor alignment of GNS within the matrix as predicted by the modified Halpin-Tsai model. Drawing these composites up to 200 % strain, a significant improvement in mechanical properties is observed. Maximum values for Young's modulus and strength are ~×4 and ~×2 higher respectively than that of neat PVA. Moreover, the rate of increase of the modulus with GNS volume fraction is up to 700 GPa, higher than the values predicted using the Halpin-Tsai theory. However, alignment along with strain-induced de-aggregation of GNS within composites accounts well for the obtained results as confirmed by X-ray diffraction (XRD) characterization.

Uniaxial Drawing of Graphene-PVA Nanocomposites: Improvement in Mechanical Characteristics via Strain-Induced Exfoliation of Graphene.

PubMed

Jan, Rahim; Habib, Amir; Akram, Muhammad Aftab; Zia, Tanveer-Ul-Haq; Khan, Ahmad Nawaz

2016-12-01

Polyvinyl alcohol (PVA)-stabilized graphene nanosheets (GNS) of lateral dimension (L) ~1 μm are obtained via liquid phase exfoliation technique to prepare its composites in the PVA matrix. These composites show low levels of reinforcements due to poor alignment of GNS within the matrix as predicted by the modified Halpin-Tsai model. Drawing these composites up to 200 % strain, a significant improvement in mechanical properties is observed. Maximum values for Young's modulus and strength are ~×4 and ~×2 higher respectively than that of neat PVA. Moreover, the rate of increase of the modulus with GNS volume fraction is up to 700 GPa, higher than the values predicted using the Halpin-Tsai theory. However, alignment along with strain-induced de-aggregation of GNS within composites accounts well for the obtained results as confirmed by X-ray diffraction (XRD) characterization.

Synthesis, Processing, and Characterization of Inorganic-Organic Hybrid Cross-Linked Silica, Organic Polyimide, and Inorganic Aluminosilicate Aerogels

NASA Technical Reports Server (NTRS)

Nguyen, Baochau N.; Guo, Haiquan N.; McCorkle, Linda S.

2014-01-01

As aerospace applications become ever more demanding, novel insulation materials with lower thermal conductivity, lighter weight and higher use temperature are required to fit the aerospace application needs. Having nanopores and high porosity, aerogels are superior thermal insulators, among other things. The use of silica aerogels in general is quite restricted due to their inherent fragility, hygroscopic nature, and poor mechanical properties, especially in extereme aerospace environments. Our research goal is to develop aerogels with better mechanical and environmental stability for a variety of aeronautic and space applications including space suit insulation for planetary surface missions, insulation for inflatable structures for habitats, inflatable aerodynamic decelerators for entry, descent and landing (EDL) operations, and cryotank insulation for advance space propulsion systems. Different type of aerogels including organic-inorganic polymer reinforced (hybrid) silica-based aerogels, polyimide aerogels and inorganic aluminosilicate aerogels have been developed and examined.

Friction Stir Welding of ODS and RAFM Steels

DOE PAGES

Yu, Zhenzhen; Feng, Zhili; Hoelzer, David; ...

2015-09-14

Advanced structural materials such as oxide dispersion strengthened steels and reduced-activation ferritic/martensitic steels are desired in fusion reactors as primary candidate materials for first wall and blanket structures, due to their excellent radiation and high-temperature creep resistance. However, their poor fusion weldability has been the major technical challenge limiting practical applications. For this reason, solid-state friction stir welding (FSW) has been considered for such applications. In this paper, the effect of FSW parameters on joining similar and dissimilar advanced structural steels was investigated. Scanning electron microscopy and electron backscatter diffraction methods were used to reveal the effects of FSW onmore » grain size, micro-texture distribution, and phase stability. Hardness mapping was performed to evaluate mechanical properties. Finally, post weld heat treatment was also performed to tailor the microstructure in the welds in order to match the weld zone mechanical properties to the base material.« less

Mitotic Recombination and Genetic Changes in Saccharomyces cerevisiae during Wine Fermentation

PubMed Central

Puig, Sergi; Querol, Amparo; Barrio, Eladio; Pérez-Ortín, José E.

2000-01-01

Natural strains of Saccharomyces cerevisiae are prototrophic homothallic yeasts that sporulate poorly, are often heterozygous, and may be aneuploid. This genomic constitution may confer selective advantages in some environments. Different mechanisms of recombination, such as meiosis or mitotic rearrangement of chromosomes, have been proposed for wine strains. We studied the stability of the URA3 locus of a URA3/ura3 wine yeast in consecutive grape must fermentations. ura3/ura3 homozygotes were detected at a rate of 1 × 10−5 to 3 × 10−5 per generation, and mitotic rearrangements for chromosomes VIII and XII appeared after 30 mitotic divisions. We used the karyotype as a meiotic marker and determined that sporulation was not involved in this process. Thus, we propose a hypothesis for the genome changes in wine yeasts during vinification. This putative mechanism involves mitotic recombination between homologous sequences and does not necessarily imply meiosis. PMID:10788381

Diagnosis and treatment of neuropathic pain.

PubMed

Chong, M Sam; Bajwa, Zahid H

2003-05-01

Currently, no consensus on the optimal management of neuropathic pain exists and practices vary greatly worldwide. Possible explanations for this include difficulties in developing agreed diagnostic protocols and the coexistence of neuropathic, nociceptive and, occasionally, idiopathic pain in the same patient. Also, neuropathic pain has historically been classified according to its etiology (e.g., painful diabetic neuropathy, trigeminal neuralgia, spinal cord injury) without regard for the presumed mechanism(s) underlying the specific symptoms. A combined etiologic/mechanistic classification might improve neuropathic pain management. The treatment of neuropathic pain is largely empirical, often relying heavily on data from small, generally poorly-designed clinical trials or anecdotal evidence. Consequently, diverse treatments are used, including non-invasive drug therapies (antidepressants, antiepileptic drugs and membrane stabilizing drugs), invasive therapies (nerve blocks, ablative surgery), and alternative therapies (e.g., acupuncture). This article reviews the current and historical practices in the diagnosis and treatment of neuropathic pain, and focuses on the USA, Europe and Japan.

SCFSlmb E3 ligase-mediated degradation of Expanded is inhibited by the Hippo pathway in Drosophila

PubMed Central

Zhang, Hongtao; Li, Changqing; Chen, Hanqing; Wei, Chuanxian; Dai, Fei; Wu, Honggang; Dui, Wen; Deng, Wu-Min; Jiao, Renjie

2015-01-01

Deregulation of the evolutionarily conserved Hippo pathway has been implicated in abnormal development of animals and in several types of cancer. One mechanism of Hippo pathway regulation is achieved by controlling the stability of its regulatory components. However, the executive E3 ligases that are involved in this process, and how the process is regulated, remain poorly defined. In this study, we identify, through a genetic candidate screen, the SCFSlmb E3 ligase as a novel negative regulator of the Hippo pathway in Drosophila imaginal tissues via mediation of the degradation of Expanded (Ex). Mechanistic study shows that Slmb-mediated degradation of Ex is inhibited by the Hippo signaling. Considering the fact that Hippo signaling suppresses the transcription of ex, we propose that the Hippo pathway employs a double security mechanism to ensure fine-tuned homeostasis during development. PMID:25522691

Eye motion triggered self-powered mechnosensational communication system using triboelectric nanogenerator.

PubMed

Pu, Xianjie; Guo, Hengyu; Chen, Jie; Wang, Xue; Xi, Yi; Hu, Chenguo; Wang, Zhong Lin

2017-07-01

Mechnosensational human-machine interfaces (HMIs) can greatly extend communication channels between human and external devices in a natural way. The mechnosensational HMIs based on biopotential signals have been developing slowly owing to the low signal-to-noise ratio and poor stability. In eye motions, the corneal-retinal potential caused by hyperpolarization and depolarization is very weak. However, the mechanical micromotion of the skin around the corners of eyes has never been considered as a good trigger signal source. We report a novel triboelectric nanogenerator (TENG)-based micromotion sensor enabled by the coupling of triboelectricity and electrostatic induction. By using an indium tin oxide electrode and two opposite tribomaterials, the proposed flexible and transparent sensor is capable of effectively capturing eye blink motion with a super-high signal level (~750 mV) compared with the traditional electrooculogram approach (~1 mV). The sensor is fixed on a pair of glasses and applied in two real-time mechnosensational HMIs-the smart home control system and the wireless hands-free typing system with advantages of super-high sensitivity, stability, easy operation, and low cost. This TENG-based micromotion sensor is distinct and unique in its fundamental mechanism, which provides a novel design concept for intelligent sensor technique and shows great potential application in mechnosensational HMIs.

Advanced study of thermal behaviour of CSZ comparing with the classic YSZ coating

NASA Astrophysics Data System (ADS)

Dragomirescu, A.; Constantin, N.; Ştefan, A.; Manoliu, V.; Truşcă, R.

2017-01-01

Thermal barrier coatings (TBC) are advanced materials typically applied to metal surfaces subjected to extreme temperatures to protect them and increase their lifetime. Ceria stabilized zirconia ceramic layer (CSZ) is increasingly used as an alternative improved as replace for classical TBC system - yttria stabilized zirconia - thanks to superior properties, including mechanical and high resistance to thermal corrosion. The paper describes the thermal shock testing of two types of thermal barrier coatings used to protect a nickel super alloy. For the experimental procedure, it was used plate samples from nickel super alloy with a bond coat and a ceramic top coat. The top coat was different: on some samples, it was used YSZ and on others CSZ. Ni based super alloys have good corrosion resistance in reducing environments action, but poor in oxidizing conditions. Extreme environments can lead to loss of material by oxidation / corrosion, along with decreased mechanical properties of the substrate due to damaging elements which diffuses into the substrate at high temperatures. Using laboratory equipment, the TBC systems were exposed repeatedly to extreme high temperatures for a short time and then cooled. After the thermal shock tests, the samples were morph-structured characterized using electronic microscopy to analyze the changes. The experimental results were compared to rank the TBC systems in order of performance.

A Mechanism of Land Degradation in Turf-Mantled Slopes of the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Okin, Gregory S.; D'Odorico, Paolo; Liu, Jianquan

2018-05-01

Kobresia pygmaea meadows are typical of Tibetan Plateau landscapes in the 3,000 to 5,500 m elevation range and constitute the most extensive alpine ecosystem in the world. Kobresia pygmaea forms turf mats that stabilize the surface and shelter the underlying soils from water erosion. Large tracts of the Plateau, however, exhibit signs of ongoing degradation of the turf and erosion of the underlying soil. Despite the crucial role played by K. pygmaea turf mats in the stabilization of the headwaters of major Asian rivers, the mechanisms responsible for their degradation remain poorly investigated. Here we develop a process-based model of land degradation of Tibetan Plateau slopes, which accounts for (i) turf cracking, (ii) water flow concentration in the cracks, (iii) crack widening by scouring, and (iv) sheet-flow erosion. As expected, soil erosion increases with the slope and drainage area (hence the observation of stronger erosion in relatively steep downhill sites). Model simulations indicate that with a sensible set of parameters representative of soil and hydrologic conditions in the region, Tibetan Plateau landscapes are vulnerable to turf mat degradation and soil erosion. As soon as polygonal cracks develop, water flow widens them until the landscape is completely barren. At this point sheet flow eventually erodes the mineral soil leaving behind a highly degraded landscape.

Eye motion triggered self-powered mechnosensational communication system using triboelectric nanogenerator

PubMed Central

Pu, Xianjie; Guo, Hengyu; Chen, Jie; Wang, Xue; Xi, Yi; Hu, Chenguo; Wang, Zhong Lin

2017-01-01

Mechnosensational human-machine interfaces (HMIs) can greatly extend communication channels between human and external devices in a natural way. The mechnosensational HMIs based on biopotential signals have been developing slowly owing to the low signal-to-noise ratio and poor stability. In eye motions, the corneal-retinal potential caused by hyperpolarization and depolarization is very weak. However, the mechanical micromotion of the skin around the corners of eyes has never been considered as a good trigger signal source. We report a novel triboelectric nanogenerator (TENG)–based micromotion sensor enabled by the coupling of triboelectricity and electrostatic induction. By using an indium tin oxide electrode and two opposite tribomaterials, the proposed flexible and transparent sensor is capable of effectively capturing eye blink motion with a super-high signal level (~750 mV) compared with the traditional electrooculogram approach (~1 mV). The sensor is fixed on a pair of glasses and applied in two real-time mechnosensational HMIs—the smart home control system and the wireless hands-free typing system with advantages of super-high sensitivity, stability, easy operation, and low cost. This TENG-based micromotion sensor is distinct and unique in its fundamental mechanism, which provides a novel design concept for intelligent sensor technique and shows great potential application in mechnosensational HMIs. PMID:28782029

Considerations for opto-mechanical vs. digital stabilization in surveillance systems

NASA Astrophysics Data System (ADS)

Kowal, David

2015-05-01

Electro-optical surveillance and reconnaissance systems are frequently mounted on unstable or vibrating platforms such as ships, vehicles, aircraft and masts. Mechanical coupling between the platform and the cameras leads to angular vibration of the line of sight. Image motion during detector and eye integration times leads to image smear and a resulting loss of resolution. Additional effects are wavy images for detectors based on a rolling shutter mechanism and annoying movement of the image at low frequencies. A good stabilization system should yield sub-pixel stabilization errors and meet cost and size requirements. There are two main families of LOS stabilization methods: opto-mechanical stabilization and electronic stabilization. Each family, or a combination of both, can be implemented by a number of different techniques of varying complexity, size and cost leading to different levels of stabilization. Opto-mechanical stabilization is typically based on gyro readings, whereas electronic stabilization is typically based on gyro readings or image registration calculations. A few common stabilization techniques, as well as options for different gimbal arrangements will be described and analyzed. The relative merits and drawbacks of the different techniques and their applicability to specific systems and environments will be discussed. Over the years Controp has developed a large number of stabilized electro-optical payloads. A few examples of payloads with unique stabilization mechanisms will be described.

Mechanics of brittle deformation and slope failure at the North Menan Butte tuff cone, Eastern Snake River Plain, Idaho

NASA Astrophysics Data System (ADS)

Okubo, C. H.

2013-12-01

The Menan Volcanic Complex consists of phreatomagmatic tuff cones that were emplaced as part of the regional volcanic activity in the Snake River Plain during the late Pleistocene. These tuff cones, the ';Menan Buttes', resulted from the eruption of basaltic magma through water-saturated alluvium and older basalts along the Snake River. The tuffs are composed primarily of basaltic glass with occasional plagioclase and olivine phenocrysts. The tuff is hydrothermally altered to a massive palagonitic tuff at depth but is otherwise poorly welded. Mass movements along the flanks of the cones were contemporaneous with tuff deposition. These slope failures are manifest as cm- to meter-scale pure folds, faults and fault-related folds, as well as larger slumps that are tens to a few hundred meters wide. Previous investigations classified the structural discontinuities at North Menan Butte based on orientation and sense of displacement, and all were recognized as opening-mode or shear fractures (Russell and Brisbin, 1990). This earlier work also used a generalized model of static (i.e., aseismic) gravity-driven shear failure within cohesionless soils to infer a possible origin for these fractures through slope failure. Recent work at North Menan Butte has provided novel insight into the styles of brittle deformation present, the effect of this deformation on the circulation of subsurface fluids within the tuff cone, as well as the mechanisms of the observed slope failures. Field observations reveal that the brittle deformation, previously classified as fractures, is manifest as deformation bands within the non-altered, poorly welded portions of the tuff. Both dilational and compactional bands, with shear, are observed. Slumps are bounded by normal faults, which are found to have developed within clusters of deformation bands. Deformation bands along the down-slope ends of these failure surfaces are predominantly compactional in nature. These bands have a ~3800 millidarcy permeability, a decrease from the ~9400 millidarcy permeability typical of the non-deformed, poorly-welded tuff. As such, these bands would have acted to slow to the circulation of local fluids through the tuff cone, possibly reducing the slopes' stability further. Future work will employ slope stability models to investigate the tendency for slumping of these tuffs shortly after their emplacement, accounting for water-saturated conditions and the effects of eruption-related seismicity. These results will improve current understanding of the mechanics of fault growth within basaltic tuff and enable more rigorous assessments of the hazards posed by slope instability on active phreatomagmatic tuff cones.

Mechanically Strong Graphene/Aramid Nanofiber Composite Electrodes for Structural Energy and Power.

PubMed

Kwon, Se Ra; Harris, John; Zhou, Tianyang; Loufakis, Dimitrios; Boyd, James G; Lutkenhaus, Jodie L

2017-07-25

Structural energy and power systems offer both mechanical and electrochemical performance in a single multifunctional platform. These are of growing interest because they potentially offer reduction in mass and/or volume for aircraft, satellites, and ground transportation. To this end, flexible graphene-based supercapacitors have attracted much attention due to their extraordinary mechanical and electrical properties, yet they suffer from poor strength. This problem may be exacerbated with the inclusion of functional guest materials, often yielding strengths of <15 MPa. Here, we show that graphene paper supercapacitor electrodes containing aramid nanofibers as guest materials exhibit extraordinarily high tensile strength (100.6 MPa) and excellent electrochemical stability. This is achieved by extensive hydrogen bonding and π-π interactions between the graphene sheets and aramid nanofibers. The trade-off between capacitance and mechanical properties is evaluated as a function of aramid nanofiber loading, where it is shown that these electrodes exhibit multifunctionality superior to that of other graphene-based supercapacitors, nearly rivaling those of graphene-based pseudocapacitors. We anticipate these composite electrodes to be a starting point for structural energy and power systems that harness the mechanical properties of aramid nanofibers.

Si/Ti2O3/Reduced Graphene Oxide Nanocomposite Anodes for Lithium-Ion Batteries with Highly Enhanced Cyclic Stability.

PubMed

Park, A Reum; Son, Dae-Yong; Kim, Jung Sub; Lee, Jun Young; Park, Nam-Gyu; Park, Juhyun; Lee, Joong Kee; Yoo, Pil J

2015-08-26

Silicon (Si) has attracted tremendous attention as a high-capacity anode material for next generation Li-ion batteries (LIBs); unfortunately, it suffers from poor cyclic stability due to excessive volume expansion and reduced electrical conductivity after repeated cycles. To circumvent these issues, we propose that Si can be complexed with electrically conductive Ti2O3 to significantly enhance the reversible capacity and cyclic stability of Si-based anodes. We prepared a ternary nanocomposite of Si/Ti2O3/reduced graphene oxide (rGO) using mechanical blending and subsequent thermal reduction of the Si, TiO2 nanoparticles, and rGO nanosheets. As a result, the obtained ternary nanocomposite exhibited a specific capacity of 985 mAh/g and a Coulombic efficiency of 98.4% after 100 cycles at a current density of 100 mA/g. Furthermore, these ternary nanocomposite anodes exhibited outstanding rate capability characteristics, even with an increased current density of 10 A/g. This excellent electrochemical performance can be ascribed to the improved electron and ion transport provided by the Ti2O3 phase within the Si domains and the structurally reinforced conductive framework comprised of the rGO nanosheets. Therefore, it is expected that our approach can also be applied to other anode materials to enable large reversible capacity, excellent cyclic stability, and good rate capability for high-performance LIBs.

Nano-extrusion: a promising tool for continuous manufacturing of solid nano-formulations.

PubMed

Baumgartner, Ramona; Eitzlmayr, Andreas; Matsko, Nadejda; Tetyczka, Carolin; Khinast, Johannes; Roblegg, Eva

2014-12-30

Since more than 40% of today's drugs have low stability, poor solubility and/or limited ability to cross certain biological barriers, new platform technologies are required to address these challenges. This paper describes a novel continuous process that converts a stabilized aqueous nano-suspension into a solid oral formulation in a single step (i.e., the NANEX process) in order to improve the solubility of a model drug (phenytoin). Phenytoin nano-suspensions were prepared via media milling using different stabilizers. A stable nano-suspension was obtained using Tween(®) 80 as a stabilizer. The matrix material (Soluplus(®)) was gravimetrically fed into the hot melt extruder. The suspension was introduced through a side feeding device and mixed with the molten polymer to immediately devolatilize the water in the nano-suspension. Phenytoin nano-crystals were dispersed and embedded in the molten polymer. Investigation of the nano-extrudates via transmission electron microscopy and atomic force microscopy showed that the nano-crystals were embedded de-aggregated in the extrudates. Furthermore, no changes in the crystallinity (due to the mechanical and thermal stress) occurred. The dissolution studies confirmed that the prepared nano-extrudates increased the solubility of nano-crystalline phenytoin, regardless of the polymer. Our work demonstrates that NANEX represents a promising new platform technology in the design of novel drug delivery systems to improve drug performance. Copyright © 2014 Elsevier B.V. All rights reserved.

Patterns of international normalized ratio values among new warfarin patients with nonvalvular atrial fibrillation.

PubMed

Nelson, Winnie W; Milentijevic, Dejan; Wang, Li; Baser, Onur; Damaraju, C V; Schein, Jeffrey R

2016-12-01

Limited information exists regarding the relationship between international normalized ratio (INR) control/stability and the discontinuation of warfarin therapy among patients with nonvalvular atrial fibrillation (NVAF). This study evaluated the association between INR stabilization and warfarin discontinuation and assessed INR patterns before and after INR stabilization among patients (≥18 years) with NVAF who newly initiated warfarin (Veterans Health Administration datasets; October 1, 2007 through September 30, 2012). Achievement of INR stabilization (≥3 consecutive in-range therapeutic INR measurements ≥7 days apart) was examined from warfarin initiation through the end of warfarin exposure. Proportion of time in therapeutic range during warfarin exposure was calculated (Rosendaal method) and categorized as at least 60% or less than 60%. Among 34 346 patients, 49.4% achieved INR stabilization (mean time to stabilization, 98 days). Approximately 40% of INR values were out-of-range, even after achieving stabilization. During 30 days following an INR 4.0 or higher, patients had more INR testing than the overall mean (2.51 vs. 1.67 tests). Warfarin discontinuation was 4.2 times more likely among patients without INR stabilization versus those with INR stabilization (P < 0.00001). Patients with poor INR control (time in therapeutic range <60%) were 1.76 times more likely to discontinue warfarin within 1 year (P < 0.0001). INR stabilization is a better predictor of warfarin discontinuation than poor INR control. Improved approaches are necessary to maintain appropriate anticoagulation levels among patients with NVAF.

Batch and continuous production of stable dense suspensions of drug nanoparticles in a wet stirred media mill

NASA Astrophysics Data System (ADS)

Afolabi, Afola we mi

One way to improve the bioavailability of poorly water-soluble drugs is to reduce particle size of drug crystals down to nanoscale via wet stirred media milling. An increase in total surface area per mass loading of the drug and specific surface area as well as reduced external mass transfer resistance allow a faster dissolution of the poorly-water soluble drug from nanocrystals. To prevent aggregation of nanoparticles, polymers and surfactants are dissolved in water acting as stabilizers via adsorption onto the drug crystals. In the last two decades, ample experimental data were generated in the area of wet stirred media milling for the production of drug nanoparticle suspensions. However, a fundamental scientific/engineering understanding of various aspects of this process is still lacking. These challenges include elucidation of the governing mechanism(s) during nanoparticle formation and physical stabilization of the nanosuspension with the use of polymers and surfactants (formulation parameters), understanding the impact of process parameters in the context of first-principle-based models, and production of truly nanosized drug particles (10-100 nm) with acceptable physical stability and minimal contamination with the media. Recirculation mode of milling operation, where the drug suspension in a holding tank continuously circulates through the stirred media mill, has been commonly used in lab, pilot, and commercial scales. Although the recirculation is continuous, the recirculation operation mode is overall a batch operation, requiring significant number of batches for a large-volume pharmaceutical product. Hence, development and investigation of a truly continuous process should offer significant advantages. To explain the impact of some of the processing parameters, stress intensity and stress number concepts were widely used in literature, which do not account for the effect of suspension viscosity explicitly. The impact of the processing parameters has not been explained in a predictive and reliable manner. In this dissertation, a comprehensive investigation of the production of Griseofulvin nanosuspensions in a wet stirred media mill operating in both the recirculation and continuous modes has been conducted to address the aforementioned fundamental challenges. Griseofulvin has been selected as a model poorly water-soluble BCS Class II drug. Impact of various formulation parameters such as stabilizer type and loading as well as processing parameters such as rotor speed, bead loading, bead size, suspension flow rate and drug loading was studied. A major novelty of the present contribution is that the impact of processing and formulation parameters has been analyzed and interpreted using a combined experimental-theoretical (microhydrodynamic model) approach. Such a comprehensive approach allowed us to intensify the process for the production of sub-100 nm drug particles, which could not be produced with top-down approaches in the literature so far. In addition, a multi-pass mode of continuous operation was developed and the so-called "Rehbinder effect", which has not been shown for the breakage of drug particles, was also elucidated. The dissertation work (1) indicated the need for a minimum polymeric stabilizer-to-drug ratio for proper stabilization of drug nanosuspensions as dictated by polymer adsorption and synergistic interactions between a polymeric stabilizer and a surfactant, (2) demonstrated the existence of an optimum polymer concentration from a breakage rate perspective in the presence of a surfactant, which results from the competing effects of viscous dampening and enhanced steric stabilization at higher polymer concentration, (3) developed fundamental understanding of the breakage dynamics-processing-formulation relationships and rationalized preparation of a single highly drug- loaded batch (20% or higher) instead of multiple dilute batches, (4) designed an intensified process for faster preparation of sub-100 nm particles with reduced specific energy consumption and media wear (i.e. minimal drug contamination), and (5) provided first evidence for the proof of Rehbinder effect during the milling of drugs. Not only do the polymers and surfactants allow proper physical stabilization of the nanoparticles in the suspensions, but they also do facilitate drug particle breakage. This dissertation also discusses applications of nanosuspensions and practical issues encountered during wet media milling.

MEMS inertial sensors with integral rotation means.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kohler, Stewart M.

The state-of-the-art of inertial micro-sensors (gyroscopes and accelerometers) has advanced to the point where they are displacing the more traditional sensors in many size, power, and/or cost-sensitive applications. A factor limiting the range of application of inertial micro-sensors has been their relatively poor bias stability. The incorporation of an integral sensitive axis rotation capability would enable bias mitigation through proven techniques such as indexing, and foster the use of inertial micro-sensors in more accuracy-sensitive applications. Fabricating the integral rotation mechanism in MEMS technology would minimize the penalties associated with incorporation of this capability, and preserve the inherent advantages of inertialmore » micro-sensors.« less

Soil erosion-runoff relationships: insights from laboratory studies

NASA Astrophysics Data System (ADS)

Mamedov, Amrakh; Warrington, David; Levy, Guy

2016-04-01

Understanding the processes and mechanisms affecting runoff generation and subsequent soil erosion in semi-arid regions is essential for the development of improved soil and water conservation management practices. Using a drip type laboratory rain simulator, we studied runoff and soil erosion, and the relationships between them, in 60 semi-arid region soils varying in their intrinsic properties (e.g., texture, organic matter) under differing extrinsic conditions (e.g., rain properties, and conditions prevailing in the field soil). Both runoff and soil erosion were significantly affected by the intrinsic soil and rain properties, and soil conditions within agricultural fields or watersheds. The relationship between soil erosion and runoff was stronger when the rain kinetic energy was higher rather than lower, and could be expressed either as a linear or exponential function. Linear functions applied to certain limited cases associated with conditions that enhanced soil structure stability, (e.g., slow wetting, amending with soil stabilizers, minimum tillage in clay soils, and short duration exposure to rain). Exponential functions applied to most of the cases under conditions that tended to harm soil stability (e.g., fast wetting of soils, a wide range of antecedent soil water contents and rain kinetic energies, conventional tillage, following biosolid applications, irrigation with water of poor quality, consecutive rain simulations). The established relationships between runoff and soil erosion contributed to a better understanding of the mechanisms governing overland flow and soil loss, and could assist in (i) further development of soil erosion models and research techniques, and (ii) the design of more suitable management practices for soil and water conservation.

Stability Mechanisms of a Thermophilic Laccase Probed by Molecular Dynamics

PubMed Central

Christensen, Niels J.; Kepp, Kasper P.

2013-01-01

Laccases are highly stable, industrially important enzymes capable of oxidizing a large range of substrates. Causes for their stability are, as for other proteins, poorly understood. In this work, multiple-seed molecular dynamics (MD) was applied to a Trametes versicolor laccase in response to variable ionic strengths, temperatures, and glycosylation status. Near-physiological conditions provided excellent agreement with the crystal structure (average RMSD ∼0.92 Å) and residual agreement with experimental B-factors. The persistence of backbone hydrogen bonds was identified as a key descriptor of structural response to environment, whereas solvent-accessibility, radius of gyration, and fluctuations were only locally relevant. Backbone hydrogen bonds decreased systematically with temperature in all simulations (∼9 per 50 K), probing structural changes associated with enthalpy-entropy compensation. Approaching T opt (∼350 K) from 300 K, this change correlated with a beginning “unzipping” of critical β-sheets. 0 M ionic strength triggered partial denucleation of the C-terminal (known experimentally to be sensitive) at 400 K, suggesting a general salt stabilization effect. In contrast, F− (but not Cl−) specifically impaired secondary structure by formation of strong hydrogen bonds with backbone NH, providing a mechanism for experimentally observed small anion destabilization, potentially remedied by site-directed mutagenesis at critical intrusion sites. N-glycosylation was found to support structural integrity by increasing persistent backbone hydrogen bonds by ∼4 across simulations, mainly via prevention of F− intrusion. Hydrogen-bond loss in distinct loop regions and ends of critical β-sheets suggest potential strategies for laboratory optimization of these industrially important enzymes. PMID:23658618

Effects of tree species and wood particle size on the properties of cement-bonded particleboard manufacturing from tree prunings.

PubMed

Nasser, Ramadan A; Al-Mefarrej, H A; Abdel-Aal, M A; Alshahrani, T S

2014-09-01

This study investigated the possibility of using the prunings of six locally grown tree species in Saudi Arabia for cement-bonded particleboard (CBP) production. Panels were made using four different wood particle sizes and a constant wood/cement ratio (1/3 by weight) and target density (1200 kg/m3). The mechanical properties and dimensional stability of the produced panels were determined. The interfacial area and distribution of the wood particles in cement matrix were also investigated by scanning electron microscopy. The results revealed that the panels produced from these pruning materials at a target density of 1200 kg m(-3) meet the strength and dimensional stability requirements of the commercial CBP panels. The mean moduli of rupture and elasticity (MOR and MOE) ranged from 9.68 to 11.78 N mm2 and from 3952 to 5667 N mm2, respectively. The mean percent water absorption for twenty four hours (WA24) ranged from 12.93% to 23.39%. Thickness swelling values ranged from 0.62% to 1.53%. For CBP panels with high mechanical properties and good dimensional stability, mixed-size or coarse particles should be used. Using the tree prunings for CBPs production may help to solve the problem of getting rid of these residues by reducing their negative effects on environment, which are caused by poor disposal of such materials through direct combustion process and appearance of black cloud and then the impact on human health or the random accumulation and its indirect effects on the environment.

Stability of volcanic conduits: insights from magma ascent modelling and possible consequences on eruptive dynamics

NASA Astrophysics Data System (ADS)

Aravena, Alvaro; de'Michieli Vitturi, Mattia; Cioni, Raffaello; Neri, Augusto

2017-04-01

Geological evidences of changes in volcanic conduit geometry (i.e. erosive processes) are common in the volcanic record, as revealed by the occurrence of lithic fragments in most pyroclastic deposits. However, the controlling factors of conduit enlargement mechanisms are still partially unclear, as well as the influence of conduit geometry in the eruptive dynamics. Despite physical models have been systematically used for studying volcanic conduits, their mechanical stability has been poorly addressed. In order to study the mechanical stability of volcanic conduits during explosive eruptions, we present a 1D steady-state model which considers the main processes experimented by ascending magmas, such as crystallization, drag forces, fragmentation, outgassing and degassing; and the application of the Mogi-Coulomb collapse criterion, using a set of constitutive equations for studying typical cases of rhyolitic and trachytic explosive volcanism. From our results emerge that conduit stability is mainly controlled by magma rheology and conduit dimensions. Indeed, in order to be stable, feeding conduits of rhyolitic eruptions need larger radii respect to their trachytic counterparts, which is manifested in the higher eruption rates usually observed in rhyolitic explosive eruptions, as confirmed by a small compilation of global data. Additionally, for both magma compositions, we estimated a minimum magma flux for developing stable conduits (˜3ṡ106 kg/s for trachytic magmas and ˜8ṡ107 kg/s for rhyolitic magmas), which is consistent with the unsteady character commonly observed in low-mass flux events (e.g. sub-Plinian eruptions), which would be produced by episodic collapse events of the volcanic conduit, opposite to the mainly stationary high-mass flux events (e.g. Plinian eruptions), characterized by stable conduits. For a given magma composition, a minimum radius for reaching stable conditions can be computed, as a function of inlet overpressure and water content. Under the assumption that magma chamber conditions during a typical volcanic eruption follow a depressurizing trend, a continuous conduit widening process is expected. This process could explain the pervasive and continuous presence of lithic fragments in most pyroclastic deposits, even with stationary properties and conditions of the magma source (e.g. water content, temperature, composition).

Effects of chloride additives on the mechanical stability and environmental durability of porous MgF2 thin films

NASA Astrophysics Data System (ADS)

Schütz, F.; Scheurell, K.; Scholz, G.; Kemnitz, E.

2016-09-01

Porous antireflective thin films, prepared of nanoscopic MgF2 sols, exhibit a low refraction index and are useful for various optical applications. Due to their porosity, film stability and durability suffer from mechanical abrasion and water solubility, respectively. Hence, we present approaches of improved mechanical stability of MgF2 layers induced by chloride addition. Antireflective (AR) films were produced by dip-coating followed by thermal treatment. Afterwards, film stability and environmental durability was strained by crockmeter and water stability tests, respectively. In comparison to films prepared from chloride-free MgF2 sols, chloride mingled sols form coatings with increased mechanical stability and a lower solubility.

NaTi2(PO4)3 as an Aqueous Anode: Degradation Mechanisms and Mitigation Techniques

NASA Astrophysics Data System (ADS)

Mohamed, Alexander I.

With the proliferation of renewable energy sources, there has been a growing interest in battery chemistries for grid scale energy storage. Aqueous sodium ion batteries are particularly interesting for large scale energy storage because of their low cost and high safety, however, they tend to show poor long term stability. NaTi2(PO4)3 (NTP) shows promise as an anode for these systems with excellent long term stability when cycled quickly. When cycled slowly, NaTi2(PO4) 3 shows rapid capacity fade. The reasons for this rate depend capacity fade is poorly understood and is the topic of this document. It has been found that the products of the hydrogen evolution reaction, H2(g) and OH-, are the two largest contributors to capacity fade. High electrolyte pH caused by generation of OH- promotes dissolution of NTP during extend cycling, this is exacerbated when the pH increase above 11. The single greatest cause of apparent capacity fade for this material is loss of electrochemical surface area due to hydrogen gas entrapment within the porous structure of the electrode. Capacity lost in this manner can be recovered through reinfiltration of the electrode. The detrimental effects of gas entrapment within the electrode can be partially mitigated through compositing of the electrode with activated carbon and enhancing the wettability of the pores through addition of a surfactant to the electrolyte.

Reframing Stability Operations: using Social Science to Identify Pillars of Stability Operations to Bridge the Gap Between the Principles of Joint Operations and Stability Operations Framework

DTIC Science & Technology

2009-12-11

demographics, and instability. Many of the essays contained within Too Poor detail issues related to Military Aged Males (MAMs) and the effects of youth......cohorts who come of working age with more education than previous generations are particularly vulnerable when they are unable to find “appropriate

Formulation and characterization of fisetin nanosuspension

NASA Astrophysics Data System (ADS)

Dzakwan, M.; Pramukantoro, G. E.; Mauludin, R.; Wikarsa, S.

2017-11-01

Fisetin (3,3,4,7-tetrahydroxyflavone) is a natural antioxidant that has shown to posses anticancer, antioxidant and anti-inflammatory properties. However, the poor solubility leads to poor bioavailability and limits its development. The aim of the study is to investigate the effect of fisetin nanosuspension using a precipitation-sonication method and additional stabilizers polysorbat 80, SLS, F68, PVP, PVA and HPMC on particle size average and the polydispersity index. The suspensions of microcrystalline FIS were prepared by a precipitation method with different proportion of stabilizers fixed. The nanosuspension produced was then characterized using Photon Correlation Spectroscopy (PCS) in term of particle size distribution, polydispersity index and morphology particle (SEM). Result showed fisetin nanosuspension were successfully prepared by anti-solvent precipitation with additional stabilizer SLS and PVA. The nanosuspension containing PVA showed smaller average particle size of 406 nm, a polydispersity index of 0.22±0.1 was obtained. The drug particles precipitated with the PVA as stabilizer were spherical in shape.

Deformation partitioning provides insight into elastic, plastic, and viscous contributions to bone material behavior.

PubMed

Ferguson, V L

2009-08-01

The relative contributions of elastic, plastic, and viscous material behavior are poorly described by the separate extraction and analysis of the plane strain modulus, E('), the contact hardness, H(c) (a hybrid parameter encompassing both elastic and plastic behavior), and various viscoelastic material constants. A multiple element mechanical model enables the partitioning of a single indentation response into its fundamental elastic, plastic, and viscous deformation components. The objective of this study was to apply deformation partitioning to explore the role of hydration, tissue type, and degree of mineralization in bone and calcified cartilage. Wet, ethanol-dehydrated, and PMMA-embedded equine cortical bone samples and PMMA-embedded human femoral head tissues were analyzed for contributions of elastic, plastic and viscous deformation to the overall nanoindentation response at each site. While the alteration of hydration state had little effect on any measure of deformation, unembedded tissues demonstrated significantly greater measures of resistance to plastic deformation than PMMA-embedded tissues. The PMMA appeared to mechanically stabilize the tissues and prevent extensive permanent deformation within the bone material. Increasing mineral volume fraction correlated with positive changes in E('), H(c), and resistance to plastic deformation, H; however, the partitioned deformation components were generally unaffected by mineralization. The contribution of viscous deformation was minimal and may only play a significant role in poorly mineralized tissues. Deformation partitioning enables a detailed interpretation of the elastic, plastic, and viscous contributions to the nanomechanical behavior of mineralized tissues that is not possible when examining modulus and contact hardness alone. Varying experimental or biological factors, such as hydration or mineralization level, enables the understanding of potential mechanisms for specific mechanical behavior patterns that would otherwise be hidden within a more complex set of material property parameters.

Crosslinked hydrogels-a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs.

PubMed

Sun, Dajun D; Lee, Ping I

2014-02-01

Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

Crosslinked hydrogels—a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

PubMed Central

Sun, Dajun D.; Lee, Ping I.

2014-01-01

Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs. PMID:26579361

Stability and Degradation Mechanisms of Metal-Organic Frameworks Containing the Zr6O4(OH)4 Secondary Building Unit

DTIC Science & Technology

2013-03-18

0188 3. DATES COVERED (From - To) - UU UU UU UU Approved for public release; distribution is unlimited. Stability and degradation mechanisms of metal ...Stability and degradation mechanisms of metal –organic frameworks containing the Zr6O4(OH)4 secondary building unit Report Title See publication. 3...Stability and degradation mechanisms of metal –organic frameworks containing the Zr6O4(OH)4 secondary building unit Approved for public release; distribution

Continuity of Genetic and Environmental Influences on Cognition across the Life Span: A Meta-Analysis of Longitudinal Twin and Adoption Studies

PubMed Central

Tucker-Drob, Elliot M.; Briley, Daniel A.

2014-01-01

The longitudinal rank-order stability of cognitive ability increases dramatically over the lifespan. Multiple theoretical perspectives have proposed that genetic and/or environmental mechanisms underlie the longitudinal stability of cognition, and developmental trends therein. However, the patterns of stability of genetic and environmental influences on cognition over the lifespan largely remain poorly understood. We searched for longitudinal studies of cognition that reported raw genetically-informative longitudinal correlations or parameter estimates from longitudinal behavior genetic models. We identified 150 combinations of time points and measures from 15 independent longitudinal samples. In total, longitudinal data came from 4,538 monozygotic twin pairs raised together, 7,777 dizygotic twin pairs raised together, 34 monozygotic twin pairs raised apart, 78 dizygotic twin pairs raised apart, 141 adoptive sibling pairs, and 143 non-adoptive sibling pairs, ranging in age from infancy through late adulthood. At all ages, cross-time genetic correlations and shared environmental correlations were substantially larger than cross-time nonshared environmental correlations. Cross-time correlations for genetic and shared environmental components were low during early childhood, increased sharply over child development, and remained relatively high from adolescence through late adulthood. Cross-time correlations for nonshared environmental components were low across childhood and increased gradually to moderate magnitudes in adulthood. Increasing phenotypic stability over child development was almost entirely mediated by genetic factors. Time-based decay of genetic and shared environmental stability was more pronounced earlier in child development. Results are interpreted in reference to theories of gene-environment interaction and correlation. PMID:24611582

Polymer brush hexadecyltrimethylammonium bromide (CTAB) modified poly (propylene-g-styrene sulphonic acid) fiber (ZB-1): CTAB/ZB-1 as a promising strategy for improving the dissolution and physical stability of poorly water-soluble drugs.

PubMed

Cao, Jinxu; Yang, Baixue; Wang, Yumei; Wei, Chen; Wang, Hongyu; Li, Sanming

2017-11-01

The feasibility of polymer brush as drug delivery vehicle was demonstrated with the goal of improving the dissolution and physical stability of poorly water-soluble drugs. Polymer brush CTAB/ZB-1 was synthesized by electrostatic interaction using a physical modification method with anionic poly (propylene-g-styrene sulphonic acid) fiber (ZB-1) as the substrate and cationic hexadecyltrimethylammonium bromide (CTAB) as the modifier. The polymer brush structure of CTAB/ZB-1 was validated by atomic force microscopy (AFM) and the channels of brush provided the drug loading sites. Flurbiprofen (FP), a BCS class II representative drug, was selected as the model poorly water-soluble drug to be loaded into this polymer brush. Then the drug loading and release were systematically investigated. Besides, the transformation from crystalline FP to amorphous state was observed by differential scanning calorimeter (DSC). In vitro dissolution in pure water and pH1.2 HCl media with/without 0.1% sodium dodecyl sulfate (SDS) was tested. Moreover, the optimal formulations (namely carrier/drug ratios) were determined. The results demonstrated prominent improvement of dissolution when FP was released from CTAB/ZB-1. After a long time storage, FP remained amorphous in CTAB/ZB-1 according to DSC determinations and performed an approximately equivalent dissolution compared with fresh samples, suggesting the advantage of CTAB/ZB-1 as carrier in enhancing the physical stability of drugs. The study introduced the versatile easily formulated polymer brush CTAB/ZB-1 and demonstrated the potential of polymer brush as an alternative approach for improving the dissolution and physical stability of poorly water-soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Bench-scale screening tests for a boiling sodium-potassium alloy solar receiver

NASA Astrophysics Data System (ADS)

Moreno, J. B.; Moss, T. A.

1993-06-01

Bench-scale tests were carried out in support of the design of a second-generation 75-kW(sub t) reflux pool-boiler solar receiver. The receiver will be made from Haynes Alloy 230 and will contain the sodium-potassium alloy NaK-78. The bench-scale tests used quartz lamp heated boilers to screen candidate boiling stabilization materials and methods at temperatures up to 750 degree C. Candidates that provided stable boiling were tested for hot-restart behavior. Poor stability was obtained with single 1/4-inch diameter patches of powdered metal hot press sintered onto the wetted side of the heat-input area. Laser-drilled and electric discharge machined cavities in the heated surface also performed poorly. Small additions of xenon, and heated-surface tilt out of the vertical, dramatically improved poor boiling stability; additions of helium or oxygen did not. The most stable boiling was obtained when the entire heat-input area was covered by a powdered-metal coating. The effect of heated-area size was assessed for one coating: at low incident fluxes, when even this coating performed poorly, increasing the heated-area size markedly improved boiling stability. Good hot-restart behavior was not observed with any candidate, although results were significantly better with added xenon in a boiler shortened from 3 to 2 feet. In addition to the screening tests, flash-radiography imaging of metal-vapor bubbles during boiling was attempted. Contrary to the Cole-Rohsenow correlation, these bubble-size estimates did not vary with pressure; instead they were constant, consistent with the only other alkali metal measurements, but about 1/2 their size.

Effect of Pore Pressure on Slip Failure of an Impermeable Fault: A Coupled Micro Hydro-Geomechanical Model

NASA Astrophysics Data System (ADS)

Yang, Z.; Juanes, R.

2015-12-01

The geomechanical processes associated with subsurface fluid injection/extraction is of central importance for many industrial operations related to energy and water resources. However, the mechanisms controlling the stability and slip motion of a preexisting geologic fault remain poorly understood and are critical for the assessment of seismic risk. In this work, we develop a coupled hydro-geomechanical model to investigate the effect of fluid injection induced pressure perturbation on the slip behavior of a sealing fault. The model couples single-phase flow in the pores and mechanics of the solid phase. Granular packs (see example in Fig. 1a) are numerically generated where the grains can be either bonded or not, depending on the degree of cementation. A pore network is extracted for each granular pack with pore body volumes and pore throat conductivities calculated rigorously based on geometry of the local pore space. The pore fluid pressure is solved via an explicit scheme, taking into account the effect of deformation of the solid matrix. The mechanics part of the model is solved using the discrete element method (DEM). We first test the validity of the model with regard to the classical one-dimensional consolidation problem where an analytical solution exists. We then demonstrate the ability of the coupled model to reproduce rock deformation behavior measured in triaxial laboratory tests under the influence of pore pressure. We proceed to study the fault stability in presence of a pressure discontinuity across the impermeable fault which is implemented as a plane with its intersected pore throats being deactivated and thus obstructing fluid flow (Fig. 1b, c). We focus on the onset of shear failure along preexisting faults. We discuss the fault stability criterion in light of the numerical results obtained from the DEM simulations coupled with pore fluid flow. The implication on how should faults be treated in a large-scale continuum model is also presented.

Complexation of phytochemicals with cyclodextrin derivatives - An insight.

PubMed

Suvarna, Vasanti; Gujar, Parul; Murahari, Manikanta

2017-04-01

Natural compounds have been attracting huge attention because of their broad therapeutic properties with specificity in their action in human health care as functional foods, pharmaceuticals and nutraceuticals. However poor bioavailability and reduced bioactivity attributed to poor solubility and instability is the major drawback hindering the incorporation of these therapeutically potential molecules in novel drug delivery systems. Based on the findings of reported research investigations; complexation of poorly water soluble phytochemicals with cyclodextrins has emerged to be a promising approach to improve their aqueous solubility, stability, rate of dissolution and bioavailability. The present article summarizes the encapsulation of natural compounds ranging from various flavonoids, phenolic derivatives, coumestans to triterpenes, with cyclodextrin and their derivatives. Also the article highlights the method of complexation, complexation ability, drug solubility, stability, bioavailability and safety aspects of reported natural compounds. Additionally we present the glimpses of patents published in recent 10-15 years to highlight the significance of inclusion of phytochemicals in cyclodextrins. In patents narrated, improvement in stability and solubility of curcumin by complexation with alkyl ether derivative of gamma-cyclodextrin is claimed. Another patent mentioned, complexation of artemisinins with β-cyclodextrin, improved the stability and integrity of peroxide part of artemisinins for long period. On the other hand the complex of dihydromyricetin with γ-CD has shown improved solubility, stability and bioavailability. Thus it can be concluded that phytochemicals have multiple biological activities with broader safety index and improvement of their solubility will be truly beneficial to aid their effective delivery in healthcare. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Surface Chemistry in Cobalt Phosphide-Stabilized Lithium-Sulfur Batteries.

PubMed

Zhong, Yiren; Yin, Lichang; He, Peng; Liu, Wen; Wu, Zishan; Wang, Hailiang

2018-01-31

Chemistry at the cathode/electrolyte interface plays an important role for lithium-sulfur batteries in which stable cycling of the sulfur cathode requires confinement of the lithium polysulfide intermediates and their fast electrochemical conversion on the electrode surface. While many materials have been found to be effective for confining polysulfides, the underlying chemical interactions remain poorly understood. We report a new and general lithium polysulfide-binding mechanism enabled by surface oxidation layers of transition-metal phosphide and chalcogenide materials. We for the first time find that CoP nanoparticles strongly adsorb polysulfides because their natural oxidation (forming Co-O-P-like species) activates the surface Co sites for binding polysulfides via strong Co-S bonding. With a surface oxidation layer capable of confining polysulfides and an inner core suitable for conducting electrons, the CoP nanoparticles are thus a desirable candidate for stabilizing and improving the performance of sulfur cathodes in lithium-sulfur batteries. We demonstrate that sulfur electrodes that hold a high mass loading of 7 mg cm -2 and a high areal capacity of 5.6 mAh cm -2 can be stably cycled for 200 cycles. We further reveal that this new surface oxidation-induced polysulfide-binding scheme applies to a series of transition-metal phosphide and chalcogenide materials and can explain their stabilizing effects for lithium-sulfur batteries.

Chemical compatibility of some ceramic matrix composite structures with fusion reactor helium coolant at high temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez, F.J.; Ghoniem, N.M.

The thermodynamic stability of SiC/SiC composite structures proposed for fusion applications is presented in this paper. Minimization of the free energy for reacting species in the temperature range 773-1273 K is achieved by utilizing the NASA-Lewis Chemical Equilibrium Thermodynamics Code (CET). The chemical stability of the matrix (SiC), as well as several potential fiber coatings are studied. Helium coolant is assumed to contain O{sub 2} and water moisture impurities in the range 100-1000 ppm. The work is applied to recent Magnetic and Inertial Confinement Conceptual designs. The present study indicated that the upper useful temperature limit for SiC/SiC composites, frommore » the standpoint of high-temperature corrosion, will be in the neighborhood of 1273 K. Up to this temperature, corrosion of SiC is shown to be negligible. The main mechanism of weight loss will be by evaporation to the plasma side. The presence of a protective SiO{sub 2} condensed phase is discussed, and is shown to result in further reduction of high-temperature corrosion. The thermodynamic stability of C and BN is shown to be very poor under typical fusion reactor conditions. Further development of chemically stable interface materials is required.« less

RNA-DNA and DNA-DNA base-pairing at the upstream edge of the transcription bubble regulate translocation of RNA polymerase and transcription rate.

PubMed

KIreeva, Maria; Trang, Cyndi; Matevosyan, Gayane; Turek-Herman, Joshua; Chasov, Vitaly; Lubkowska, Lucyna; Kashlev, Mikhail

2018-06-20

Translocation of RNA polymerase (RNAP) along DNA may be rate-limiting for transcription elongation. The Brownian ratchet model posits that RNAP rapidly translocates back and forth until the post-translocated state is stabilized by NTP binding. An alternative model suggests that RNAP translocation is slow and poorly reversible. To distinguish between these two models, we take advantage of an observation that pyrophosphorolysis rates directly correlate with the abundance of the pre-translocated fraction. Pyrophosphorolysis by RNAP stabilized in the pre-translocated state by bacteriophage HK022 protein Nun was used as a reference point to determine the pre-translocated fraction in the absence of Nun. The stalled RNAP preferentially occupies the post-translocated state. The forward translocation rate depends, among other factors, on melting of the RNA-DNA base pair at the upstream edge of the transcription bubble. DNA-DNA base pairing immediately upstream from the RNA-DNA hybrid stabilizes the post-translocated state. This mechanism is conserved between E. coli RNAP and S. cerevisiae RNA polymerase II and is partially dependent on the lid domain of the catalytic subunit. Thus, the RNA-DNA hybrid and DNA reannealing at the upstream edge of the transcription bubble emerge as targets for regulation of the transcription elongation rate.

Stabilization of primary mobile radiation defects in MgF2 crystals

NASA Astrophysics Data System (ADS)

Lisitsyn, V. M.; Lisitsyna, L. A.; Popov, A. I.; Kotomin, E. A.; Abuova, F. U.; Akilbekov, A.; Maier, J.

2016-05-01

Non-radiative decay of the electronic excitations (excitons) into point defects (F-H pairs of Frenkel defects) is main radiation damage mechanism in many ionic (halide) solids. Typical time scale of the relaxation of the electronic excitation into a primary, short-lived defect pair is about 1-50 ps with the quantum yield up to 0.2-0.8. However, only a small fraction of these primary defects are spatially separated and survive after transformation into stable, long-lived defects. The survival probability (or stable defect accumulation efficiency) can differ by orders of magnitude, dependent on the material type; e.g. ∼10% in alkali halides with f.c.c. or b.c.c. structure, 0.1% in rutile MgF2 and <0.001% in fluorides MeF2 (Me: Ca, Sr, Ba). The key factor determining accumulation of stable radiation defects is stabilization of primary defects, first of all, highly mobile hole H centers, through their transformation into more complex immobile defects. In this talk, we present the results of theoretical calculations of the migration energies of the F and H centers in poorely studied MgF2 crystals with a focus on the H center stabilization in the form of the interstitial F2 molecules which is supported by presented experimental data.

How PEGylation enhances the stability and potency of insulin: a molecular dynamics simulation.

PubMed

Yang, Cheng; Lu, Diannan; Liu, Zheng

2011-04-05

While the effectiveness of PEGylation in enhancing the stability and potency of protein pharmaceuticals has been validated for years, the underlying mechanism remains poorly understood, particularly at the molecular level. A molecular dynamics simulation was developed using an annealing procedure that allowed an all-atom level examination of the interaction between PEG polymers of different chain lengths and a conjugated protein represented by insulin. It was shown that PEG became entangled around the protein surface through hydrophobic interaction and concurrently formed hydrogen bonds with the surrounding water molecules. In addition to enhancing its structural stability, as indicated by the root-mean-square difference (rmsd) and secondary structure analyses, conjugation increased the size of the protein drug while decreasing the solvent accessible surface area of the protein. All these thus led to prolonged circulation life despite kidney filtration, proteolysis, and immunogenic side effects, as experimentally demonstrated elsewhere. Moreover, the simulation results indicated that an optimal chain length exists that would maximize drug potency underpinned by the parameters mentioned above. The simulation provided molecular insight into the interaction between PEG and the conjugated protein at the all-atom level and offered a tool that would allow for the design of PEGylated protein pharmaceuticals for given applications.

Development of LRFD resistance factors for mechanically stabilized earth (MSE) walls.

DOT National Transportation Integrated Search

2013-12-01

Over 100 centrifuge tests were conducted to assess Load and Resistance Factor : Design (LRFD) resistance factors for external stability of Mechanically Stabilized Earth (MSE) walls : founded on granular soils. In the case of sliding stability, the te...

Curvature-Induced Instabilities of Shells

NASA Astrophysics Data System (ADS)

Pezzulla, Matteo; Stoop, Norbert; Steranka, Mark P.; Bade, Abdikhalaq J.; Holmes, Douglas P.

2018-01-01

Induced by proteins within the cell membrane or by differential growth, heating, or swelling, spontaneous curvatures can drastically affect the morphology of thin bodies and induce mechanical instabilities. Yet, the interaction of spontaneous curvature and geometric frustration in curved shells remains poorly understood. Via a combination of precision experiments on elastomeric spherical shells, simulations, and theory, we show how a spontaneous curvature induces a rotational symmetry-breaking buckling as well as a snapping instability reminiscent of the Venus fly trap closure mechanism. The instabilities, and their dependence on geometry, are rationalized by reducing the spontaneous curvature to an effective mechanical load. This formulation reveals a combined pressurelike term in the bulk and a torquelike term in the boundary, allowing scaling predictions for the instabilities that are in excellent agreement with experiments and simulations. Moreover, the effective pressure analogy suggests a curvature-induced subcritical buckling in closed shells. We determine the critical buckling curvature via a linear stability analysis that accounts for the combination of residual membrane and bending stresses. The prominent role of geometry in our findings suggests the applicability of the results over a wide range of scales.

Sensing Exocytosis and Triggering Endocytosis at Synapses: Synaptic Vesicle Exocytosis–Endocytosis Coupling

PubMed Central

Lou, Xuelin

2018-01-01

The intact synaptic structure is critical for information processing in neural circuits. During synaptic transmission, rapid vesicle exocytosis increases the size of never terminals and endocytosis counteracts the increase. Accumulating evidence suggests that SV exocytosis and endocytosis are tightly connected in time and space during SV recycling, and this process is essential for synaptic function and structural stability. Research in the past has illustrated the molecular details of synaptic vesicle (SV) exocytosis and endocytosis; however, the mechanisms that timely connect these two fundamental events are poorly understood at central synapses. Here we discuss recent progress in SV recycling and summarize several emerging mechanisms by which synapses can “sense” the occurrence of exocytosis and timely initiate compensatory endocytosis. They include Ca2+ sensing, SV proteins sensing, and local membrane stress sensing. In addition, the spatial organization of endocytic zones adjacent to active zones provides a structural basis for efficient coupling between SV exocytosis and endocytosis. Through linking different endocytosis pathways with SV fusion, these mechanisms ensure necessary plasticity and robustness of nerve terminals to meet diverse physiological needs. PMID:29593500

Predicting Fluid Flow in Stressed Fractures: A Quantitative Evaluation of Methods

NASA Astrophysics Data System (ADS)

Weihmann, S. A.; Healy, D.

2015-12-01

Reliable estimation of fracture stability in the subsurface is crucial to the success of exploration and production in the petroleum industry, and also for wider applications to earthquake mechanics, hydrogeology and waste disposal. Previous work suggests that fracture stability is related to fluid flow in crystalline basement rocks through shear or tensile instabilities of fractures. Our preliminary scoping analysis compares the fracture stability of 60 partly open (apertures 1.5-3 cm) and electrically conductive (low acoustic amplitudes relative to matrix) fractures from a 16 m section of a producing zone in a basement well in Bayoot field, Yemen, to a non-producing zone in the same well (also 16 m). We determine the Critically Stressed Fractures (CSF; Barton et al., 1995) and dilatation tendency (Td; Ferrill et al., 1999). We find that: 1. CSF (Fig. 1) is a poor predictor of high fluid flow in the inflow zone; 88% of the fractures are predicted to be NOT critically stressed and yet they all occur within a zone of high fluid flow rate 2. Td (Fig. 2) is also a poor predictor of high fluid flow in the inflow zone; 67% of the fractures have a LOW Td(< 0.6) 3. For the non-producing zone CSF is a very reliable predictor (100% are not critically stressed) whereas the values of Tdare consistent with their location in non-producing interval (81% are < 0.6) (Fig. 3 & 4). In summary, neither method correlates well with the observed abundance of hydraulically conductive fractures within the producing zone. Within the non-producing zone CSF and Td make reasonably accurate predictions. Fractures may be filled or partially filled with drilling mud or a lower density and electrically conductive fill such as clay in the producing zone and therefore appear (partly) open. In situ stress, fluid pressure, rock properties (friction, strength) and fracture orientation data used as inputs for the CSF and Td calculations are all subject to uncertainty. Our results suggest that scope exists to systematically quantify and explore the impacts of these uncertainties for better predictions of geomechanical stability and fluid conductivity in the subsurface.

The enhanced anti-tissue adhesive effect of injectable pluronic-HA hydrogel by poly(γ-glutamic acid).

PubMed

Kim, Manse; Hwang, Youngmin; Tae, Giyoong

2016-12-01

The stability of tissue barrier in physiological condition is a key factor to isolate the damaged site from adjacent tissue for anti-tissue adhesion. Although pluronic or pluronic-hyaluronic acid (HA) hydrogel as an injectable formulation can prevent tissue adhesion at the injection site, the anti-tissue adhesion effect is limited due to its poor stability. Herein, we prepared tissue barrier formulations composed of pluronic F127 (F127) and HA mixture (F127-HA) and the effect of the addition of poly(γ-glutamic acid) (PGA) was characterized. All of F127, HA, and F127-HA mixture showed the poor in vitro residence stability less than 3 days. However, by adding PGA into F127-HA mixture, their stability was significantly enhanced by the control of the molecular weight and concentration of PGA. Thus, F127-HA with 10wt% PGA (2000kDa) showed the long-term stability over 10 days. Similarly, the enhanced stability of F127-HA with PGA resulted in the enhanced and excellent in vivo anti-tissue adhesion effect, evidenced by histological analysis and grading of tissue adhesion. Therefore, F127-HA containing PGA could be applied as an efficient injectable tissue barrier for anti-tissue adhesion. Copyright © 2016 Elsevier B.V. All rights reserved.

A Molecular-Level View of the Physical Stability of Amorphous Solid Dispersions

NASA Astrophysics Data System (ADS)

Yuan, Xiaoda

Many pharmaceutical compounds being developed in recent years are poorly soluble in water. This has led to insufficient oral bioavailability of many compounds in vitro. The amorphous formulation is one of the promising techniques to increase the oral bioavailability of these poorly water-soluble compounds. However, an amorphous drug substance is inherently unstable because it is a high energy form. In order to increase the physical stability, the amorphous drug is often formulated with a suitable polymer to form an amorphous solid dispersion. Previous research has suggested that the formation of an intimately mixed drug-polymer mixture contributes to the stabilization of the amorphous drug compound. The goal of this research is to better understand the role of miscibility, molecular interactions and mobility on the physical stability of amorphous solid dispersions. Methods were developed to detect different degrees of miscibility on nanometer scale and to quantify the extent of hydrogen-bonding interactions between the drug and the polymer. Miscibility, hydrogen-bonding interactions and molecular mobility were correlated with physical stability during a six-month period using three model systems. Overall, this research provides molecular-level insights into many factors that govern the physical stability of amorphous solid dispersions which can lead to a more effective design of stable amorphous formulations.

The capacity fading mechanism and improvement of cycling stability in MoS2-based anode materials for lithium-ion batteries

NASA Astrophysics Data System (ADS)

Shu, Haibo; Li, Feng; Hu, Chenli; Liang, Pei; Cao, Dan; Chen, Xiaoshuang

2016-01-01

Two-dimensional (2D) layered MoS2 nanosheets possess great potential as anode materials for lithium ion batteries (LIBs), but they still suffer from poor cycling performance. Improving the cycling stability of electrode materials depends on a deep understanding of their dynamic structural evolution and reaction kinetics in the lithiation process. Herein, thermodynamic phase diagrams and the lithiation dynamics of MoS2-based nanostructures with the intercalation of lithium ions are studied by using first-principles calculations and ab initio molecular dynamics simulations. Our results demonstrate that the continuous intercalation of Li ions induces structural destruction of 2H phase MoS2 nanosheets in the discharge process that follows a layer-by-layer dissociation mechanism. Meanwhile, the intercalation of Li ions leads to a structural transition of MoS2 nanosheets from the 2H to the 1T phase due to the ultralow transition barriers (~0.1 eV). We find that the phase transition can slow down the dissociation of MoS2 nanosheets during lithiation. The result can be applied to explain extensive experimental observation of the fast capacity fading of MoS2-based anode materials between the first and the subsequent discharges. To suppress the dissociation of MoS2 nanosheets in the lithiation process, we propose a strategy by constructing a sandwich-like graphene/MoS2/graphene structure that indicates high chemical stability, superior conductivity, and high Li-ion mobility in the charge/discharge process, implying the possibility to induce an improvement in the anode cycling performance. This work opens a new route to rational design layered transition-metal disulfide (TMD) anode materials for LIBs with superior cycling stability and electrochemical performance.Two-dimensional (2D) layered MoS2 nanosheets possess great potential as anode materials for lithium ion batteries (LIBs), but they still suffer from poor cycling performance. Improving the cycling stability of electrode materials depends on a deep understanding of their dynamic structural evolution and reaction kinetics in the lithiation process. Herein, thermodynamic phase diagrams and the lithiation dynamics of MoS2-based nanostructures with the intercalation of lithium ions are studied by using first-principles calculations and ab initio molecular dynamics simulations. Our results demonstrate that the continuous intercalation of Li ions induces structural destruction of 2H phase MoS2 nanosheets in the discharge process that follows a layer-by-layer dissociation mechanism. Meanwhile, the intercalation of Li ions leads to a structural transition of MoS2 nanosheets from the 2H to the 1T phase due to the ultralow transition barriers (~0.1 eV). We find that the phase transition can slow down the dissociation of MoS2 nanosheets during lithiation. The result can be applied to explain extensive experimental observation of the fast capacity fading of MoS2-based anode materials between the first and the subsequent discharges. To suppress the dissociation of MoS2 nanosheets in the lithiation process, we propose a strategy by constructing a sandwich-like graphene/MoS2/graphene structure that indicates high chemical stability, superior conductivity, and high Li-ion mobility in the charge/discharge process, implying the possibility to induce an improvement in the anode cycling performance. This work opens a new route to rational design layered transition-metal disulfide (TMD) anode materials for LIBs with superior cycling stability and electrochemical performance. Electronic supplementary information (ESI) available: Models and energetics of Li adsorption/intercalation onto MoS2 sheets, details of the phase diagram calculations, schematic illustration for the structural evolution of lithiated MoS2 nanosheets, AIMD trajectories for lithiated silicene/MoS2/silicene composites, and movies for recording the AIMD simulation results. See DOI: 10.1039/c5nr07909h

Quantifying Stability in Complex Networks: From Linear to Basin Stability

NASA Astrophysics Data System (ADS)

Kurths, Jürgen

The human brain, power grids, arrays of coupled lasers and the Amazon rainforest are all characterized by multistability. The likelihood that these systems will remain in the most desirable of their many stable states depends on their stability against significant perturbations, particularly in a state space populated by undesirable states. Here we claim that the traditional linearization-based approach to stability is in several cases too local to adequately assess how stable a state is. Instead, we quantify it in terms of basin stability, a new measure related to the volume of the basin of attraction. Basin stability is non-local, nonlinear and easily applicable, even to high-dimensional systems. It provides a long-sought-after explanation for the surprisingly regular topologies of neural networks and power grids, which have eluded theoretical description based solely on linear stability. Specifically, we employ a component-wise version of basin stability, a nonlinear inspection scheme, to investigate how a grid's degree of stability is influenced by certain patterns in the wiring topology. Various statistics from our ensemble simulations all support one main finding: The widespread and cheapest of all connection schemes, namely dead ends and dead trees, strongly diminish stability. For the Northern European power system we demonstrate that the inverse is also true: `Healing' dead ends by addition of transmission lines substantially enhances stability. This indicates a crucial smart-design principle for tomorrow's sustainable power grids: add just a few more lines to avoid dead ends. Further, we analyse the particular function of certain network motifs to promote the stability of the system. Here we uncover the impact of so-called detour motifs on the appearance of nodes with a poor stability score and discuss the implications for power grid design. Moreover, it will be shown that basin stability enables uncovering the mechanism for explosive synchronization and understanding of evolving networks. Reference: P. Menck, J. Heitzig, N. Marwan, and J. Kurths, Nature Physics 9, 89 (2013) P. Menck, J. Heitzig, J. Kurths, and H. Schellnhuber, Nature Communication 5, 3969 (2014) P. Schultz, J. Heitzig, and J. Kurths, New Journal Physics 16, 125001 (2014) V. Kohar, P. Ji, A. Choudhary, S. Sinha, and J. Kurths, Phys. Rev. E 90, 022812 (2014) Y. Zou, T. Pereira, M. Small, Z. Liu, and J. Kurths, Phys. Rev. Lett. 112, 114102 (2014)

Kinetics and mechanical stability of the fibril state control fibril formation time of polypeptide chains: A computational study

NASA Astrophysics Data System (ADS)

Kouza, Maksim; Co, Nguyen Truong; Li, Mai Suan; Kmiecik, Sebastian; Kolinski, Andrzej; Kloczkowski, Andrzej; Buhimschi, Irina Alexandra

2018-06-01

Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite much progress in the understanding of the protein aggregation process, the factors governing fibril formation rates and fibril stability have not been fully understood. Using lattice models, we have shown that the fibril formation time is controlled by the kinetic stability of the fibril state but not by its energy. Having performed all-atom explicit solvent molecular dynamics simulations with the GROMOS43a1 force field for full-length amyloid beta peptides Aβ40 and Aβ42 and truncated peptides, we demonstrated that kinetic stability can be accessed via mechanical stability in such a way that the higher the mechanical stability or the kinetic stability, the faster the fibril formation. This result opens up a new way for predicting fibril formation rates based on mechanical stability that may be easily estimated by steered molecular dynamics.

Nanoparticles: A Challenging Vehicle for Neural Stimulation

PubMed Central

Colombo, Elisabetta; Feyen, Paul; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio

2016-01-01

Neurostimulation represents a powerful and well-established tool for the treatment of several diseases affecting the central nervous system. Although, effective in reducing the symptoms or the progression of brain disorders, the poor accessibility of the deepest areas of the brain currently hampers the possibility of a more specific and controlled therapeutic stimulation, depending on invasive surgical approaches and long-term stability, and biocompatibility issues. The massive research of the last decades on nanomaterials and nanoscale devices favored the development of new tools to address the limitations of the available neurostimulation approaches. This mini-review focuses on the employment of nanoparticles for the modulation of the electrophysiological activity of neuronal networks and the related transduction mechanisms underlying the nanostructure-neuron interfaces. PMID:27047327

Comparison of Numerical Modeling Methods for Soil Vibration Cutting

NASA Astrophysics Data System (ADS)

Jiang, Jiandong; Zhang, Enguang

2018-01-01

In this paper, we studied the appropriate numerical simulation method for vibration soil cutting. Three numerical simulation methods, commonly used for uniform speed soil cutting, Lagrange, ALE and DEM, are analyzed. Three models of vibration soil cutting simulation model are established by using ls-dyna.The applicability of the three methods to this problem is analyzed in combination with the model mechanism and simulation results. Both the Lagrange method and the DEM method can show the force oscillation of the tool and the large deformation of the soil in the vibration cutting. Lagrange method shows better effect of soil debris breaking. Because of the poor stability of ALE method, it is not suitable to use soil vibration cutting problem.

Amination with Pd-NHC complexes: rate and computational studies involving substituted aniline substrates.

PubMed

Hoi, Ka Hou; Çalimsiz, Selçuk; Froese, Robert D J; Hopkinson, Alan C; Organ, Michael G

2012-01-02

The amination of aryl chlorides with various aniline derivatives using the N-heterocyclic carbene-based Pd complexes Pd-PEPPSI-IPr and Pd-PEPPSI-IPent (PEPPSI=pyridine, enhanced precatalyst, preparation, stabilization, and initiation; IPr=diisopropylphenylimidazolium derivative; IPent= diisopentylphenylimidazolium derivative) has been studied. Rate studies have shown a reliance on the aryl chloride to be electron poor, although oxidative addition is not rate limiting. Anilines couple best when they are electron rich, which would seem to discount deprotonation of the intermediate metal ammonium complex as being rate limiting in favour of reductive elimination. In previous studies with secondary amines using PEPPSI complexes, deprotonation was proposed to be the slow step in the cycle. These experimental findings relating to mechanism were corroborated by computation. Pd-PEPPSI-IPr and the more hindered Pd-PEPPSI-IPent catalysts were used to couple deactivated aryl chlorides with electron poor anilines; while the IPr catalysis was sluggish, the IPent catalyst performed extremely well, again showing the high reactivity of this broadly useful catalyst. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The interplay between mechanics and stability of viral cages

NASA Astrophysics Data System (ADS)

Hernando-Pérez, Mercedes; Pascual, Elena; Aznar, María; Ionel, Alina; Castón, José R.; Luque, Antoni; Carrascosa, José L.; Reguera, David; de Pablo, Pedro J.

2014-02-01

The stability and strength of viral nanoparticles are crucial to fulfill the functions required through the viral cycle as well as using capsids for biomedical and nanotechnological applications. The mechanical properties of viral shells obtained through Atomic Force Microscopy (AFM) and continuum elasticity theory, such as stiffness or Young's modulus, have been interpreted very often in terms of stability. However, viruses are normally subjected to chemical rather than to mechanical aggression. Thus, a correct interpretation of mechanics in terms of stability requires an adequate linkage between the ability of viral cages to support chemical and mechanical stresses. Here we study the mechanical fragility and chemical stability of bacteriophage T7 in two different maturation states: the early proheads and the final mature capsids. Using chemical stress experiments we show that proheads are less stable than final mature capsids. Still, both particles present similar anisotropic stiffness, indicating that a continuum elasticity description in terms of Young's modulus is not an adequate measure of viral stability. In combination with a computational coarse-grained model we demonstrate that mechanical anisotropy of T7 emerges out of the discrete nature of the proheads and empty capsids. Even though they present the same stiffness, proheads break earlier and have fractures ten times larger than mature capsids, in agreement with chemical stability, thus demonstrating that fragility rather than stiffness is a better indicator of viral cages' stability.The stability and strength of viral nanoparticles are crucial to fulfill the functions required through the viral cycle as well as using capsids for biomedical and nanotechnological applications. The mechanical properties of viral shells obtained through Atomic Force Microscopy (AFM) and continuum elasticity theory, such as stiffness or Young's modulus, have been interpreted very often in terms of stability. However, viruses are normally subjected to chemical rather than to mechanical aggression. Thus, a correct interpretation of mechanics in terms of stability requires an adequate linkage between the ability of viral cages to support chemical and mechanical stresses. Here we study the mechanical fragility and chemical stability of bacteriophage T7 in two different maturation states: the early proheads and the final mature capsids. Using chemical stress experiments we show that proheads are less stable than final mature capsids. Still, both particles present similar anisotropic stiffness, indicating that a continuum elasticity description in terms of Young's modulus is not an adequate measure of viral stability. In combination with a computational coarse-grained model we demonstrate that mechanical anisotropy of T7 emerges out of the discrete nature of the proheads and empty capsids. Even though they present the same stiffness, proheads break earlier and have fractures ten times larger than mature capsids, in agreement with chemical stability, thus demonstrating that fragility rather than stiffness is a better indicator of viral cages' stability. Electronic supplementary information (ESI) available: Purification of T7 proheads and capsids, coarse-grained simulations of the indentation of T7 empty capsids, Finite Element (FE) simulations, and justification of the anisotropic stiffness based on structural information. See DOI: 10.1039/c3nr05763a

Construction of Hierarchical α-MnO2 Nanowires@Ultrathin δ-MnO2 Nanosheets Core-Shell Nanostructure with Excellent Cycling Stability for High-Power Asymmetric Supercapacitor Electrodes.

PubMed

Ma, Zhipeng; Shao, Guangjie; Fan, Yuqian; Wang, Guiling; Song, Jianjun; Shen, Dejiu

2016-04-13

Poor electrical conductivity and mechanical instability are two major obstacles to realizing high performance of MnO2 as pseudocapacitor material. The construction of unique hierarchical core-shell nanostructures, therefore, plays an important role in the efficient enhancement of the rate capacity and the stability of this material. We herein report the fabrication of a hierarchical α-MnO2 nanowires@ultrathin δ-MnO2 nanosheets core-shell nanostructure by adopting a facile and practical solution-phase technique. The novel hierarchical nanostructures are composed of ultrathin δ-MnO2 nanosheets with a few atomic layers growing well on the surface of the ultralong α-MnO2 nanowires. The first specific capacitance of hierarchical core-shell nanostructure reached 153.8 F g(-1) at the discharge current density of as high as 20 A g(-1), and the cycling stability is retained at 98.1% after 10,000 charge-discharge cycles, higher than those in the literature. The excellent rate capacity and stability of the hierarchical core-shell nanostructures can be attributed to the structural features of the two MnO2 crystals, in which a 1D α-MnO2 nanowire core provides a stable structural backbone and the ultrathin 2D δ-MnO2 nanosheet shell creates more reactive active sites. The synergistic effects of different dimensions also contribute to the superior rate capability.

Improvement of posture stability by vibratory stimulation following anterior cruciate ligament reconstruction.

PubMed

Brunetti, O; Filippi, G M; Lorenzini, M; Liti, A; Panichi, R; Roscini, M; Pettorossi, V E; Cerulli, G

2006-11-01

Surgical reconstruction of the anterior cruciate ligament (ACL) may reduce, but it does not always eliminate, knee and body instability because of a persisting proprioceptive deficit. In order to enhance body stability, a new protocol of treatment has been proposed consisting of mechanical vibration (100 Hz frequency and < 20 microm amplitude) of the quadriceps muscle in the leg that has undergone ACL reconstruction. In our trials, stimulation was performed when the quadriceps muscle was kept isometrically contracted. Treatment was started one month after surgery. Vibration was applied for short periods over three consecutive days. Nine months after treatment, postural stability was re-evaluated with the subjects standing on one leg with open and with closed eyes. The postural stability of the subjects having undergone vibration treatment, standing on the operated leg was significantly improved one day after treatment when evaluated as mean of speed and elliptic area of the center of pressure. The improvement persisted and increased during the following weeks. Peak torques of the operated leg extensor muscles also increased and reached values close to that of the leg, which had not been operated. Conversely, the balance of the untreated subjects standing on the operated leg did not improve and the restoration of the extensor muscle peak torque was poor. It is concluded that short lasting proprioceptive activation by vibration may lead to a faster and more complete equilibrium recovery probably by permanently changing the network controlling knee posture.

Short-Range-Order Mineral Physical Protection On Black Carbon Stabilization

NASA Astrophysics Data System (ADS)

Liang, B.; Weng, Y. T.; Wang, C. C.; Song, Y. F.; Lehmann, J.; Wang, C. H.

2015-12-01

Soil organic matter is one of the largest reservoirs in global carbon cycle, and black carbon (BC) represents a chemical resistant component. Black C plays an important role in global climate change. Generally considered recalcitrant due to high aromaticity, the reactive surface and functional groups of BC are crucial for carbon sequestration in soils. Mineral sorption and physical protection is an important mechanism for BC long term stabilization and sequestration in environments. Previous studies on mineral protection of BC were limited to analysis techniques in two-dimensions, for example, by SEM, TEM, and NanoSIMS. Little is known about the scope of organo-mineral association, the in-situ distribution and forms of minerals, and the ultimate interplay of BC and minerals. The aim of this study is to investigate the three-dimensional interaction of organic C and minerals in submicron scale using synchrotron-based Transmission X-ray Microcopy (TXM) and Fourier-Transform Infrared Spectroscopy (FTIR). Abundant poorly-crystallined nano-minerals particles were observed. These short-range-order (SRO) minerals also aggregate into clusters and sheets, and form envelops-like structures on the surface of BC. On top of large surface contact area, the intimate interplay between BC and minerals reinforces the stability of both organic C and minerals, resulting from chemical bonding through cation bridging and ligand exchange. The mineral protection enhances BC stabilization and sequestration and lowers its bioavailability in environment. The results suggest that mineral physical protection for BC sequestration may be more important than previous understanding.

Highly stable and finely tuned magnetic fields generated by permanent magnet assemblies.

PubMed

Danieli, E; Perlo, J; Blümich, B; Casanova, F

2013-05-03

Permanent magnetic materials are the only magnetic source that can be used to generate magnetic fields without power consumption or maintenance. Such stand-alone magnets are very attractive for many scientific and engineering areas, but they suffer from poor temporal field stability, which arises from the strong sensitivity of the magnetic materials and mechanical support to temperature variation. In this work, we describe a highly efficient method useful to cancel the temperature coefficient of permanent magnet assemblies in a passive and accurate way. It is based on the combination of at least two units made of magnetic materials with different temperature coefficients arranged in such a way that the ratio of the fields generated by each unit matches the ratio of their effective temperature coefficients defined by both the magnetic and mechanical contributions. Although typically available magnetic materials have negative temperature coefficients, the cancellation is achieved by aligning the fields generated by each unit in the opposite direction. We demonstrate the performance of this approach by stabilizing the field generated by a dipolar Halbach magnet, recently proposed to achieve high field homogeneity. Both the field drift and the homogeneity are monitored via nuclear magnetic resonance spectroscopy experiments. The results demonstrate the compatibility of the thermal compensation approach with existing strategies useful to fine-tune the spatial dependence of the field generated by permanent magnet arrays.

Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers

PubMed Central

Pappas, Andrea L.; Bey, Alexandra L.; Wang, Xiaoming; Rossi, Mark; Kim, Yong Ho; Yan, Haidun; Porkka, Fiona; Duffney, Lara J.; Phillips, Samantha M.; Cao, Xinyu; Ding, Jin-dong; Rodriguiz, Ramona M.; Yin, Henry H.; Wetsel, William C.

2017-01-01

Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24–/– mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors. While these phenotypes recapitulate the pleotropic behaviors associated with human SHANK2-related disorders, major behavioral features in these mice are reminiscent of bipolar disorder. For instance, their hyperactivity was augmented with amphetamine but was normalized with the mood stabilizers lithium and valproate. Shank2 deficiency limited to the forebrain recapitulated the bipolar mania phenotype. The composition and functions of NMDA and AMPA receptors were altered at Shank2-deficient synapses, hinting toward the mechanism underlying these behavioral abnormalities. Human genetic findings support construct validity, and the behavioral features in Shank2 Δe24 mice support face and predictive validities of this model for bipolar mania. Further genetic studies to understand the contribution of SHANK2 deficiencies in bipolar disorder are warranted. PMID:29046483

Development and application of bio-sample quantification to evaluate stability and pharmacokinetics of inulin-type fructo-oligosaccharides from Morinda Officinalis.

PubMed

Chi, Liandi; Chen, Lingxiao; Zhang, Jiwen; Zhao, Jing; Li, Shaoping; Zheng, Ying

2018-07-15

Inulin-type fructooligosaccharides (FOS) purified from Morinda Officinalis, with degrees of polymerization (DP) from 3 to 9, have been approved in China as an oral prescribed drug for mild and moderate depression episode, while the stability and oral absorption of this FOS mixtures are largely unknown. As the main active component and quality control marker for above FOS, DP5 was selected as the representative FOS in this study. Desalting method by ion exchange resin was developed to treat bio-sample, followed by separation and quantification by high performance liquid chromatography-charged aerosol detector. Results showed that the DP5 was stepwisely hydrolyzed in simulated gastric fluid and gut microbiota, while maintained stable in intestinal fluid. DP5 has poor permeability across Caco-2 monolayer with P app of 5.22 × 10 -7  cm/s, and very poor oral absorption with bioavailability of (0.50 ± 0.12)% in rat. In conclusion, FOS in Morinda Officinalis demonstrated poor chemical stability in simulated gastric fluid and human gut microbiota, and low oral absorption in rats. Copyright © 2018 Elsevier B.V. All rights reserved.

Supersaturation-nucleation behavior of poorly soluble drugs and its impact on the oral absorption of drugs in thermodynamically high-energy forms.

PubMed

Ozaki, Shunsuke; Minamisono, Takuma; Yamashita, Taro; Kato, Takashi; Kushida, Ikuo

2012-01-01

In order to better understand the oral absorption behavior of poorly water-soluble drugs, their supersaturation-nucleation behavior was characterized in fasted state simulated intestinal fluid. The induction time (t(ind)) for nucleation was measured for four model drugs: itraconazole, erlotinib, troglitazone, and PLX4032. Supersaturated solutions were prepared by solvent shift method, and nucleation initiation was monitored by ultraviolet detection. The relationship between t(ind) and degree of supersaturation was analyzed in terms of classical nucleation theory. The defined supersaturation stability proved to be compound specific. Clinical data on oral absorption were investigated for drugs in thermodynamically high-energy forms such as amorphous forms and salts and was compared with in vitro supersaturation-nucleation characteristics. Solubility-limited maximum absorbable dose was proportionate to intestinal effective drug concentrations, which are related to supersaturation stability and thermodynamic solubility. Supersaturation stability was shown to be an important factor in determining the effect of high-energy forms. The characterization of supersaturation-nucleation behavior by the presented method is, therefore, valuable for assessing the potential absorbability of poorly water-soluble drugs. Copyright © 2011 Wiley-Liss, Inc.

Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin

PubMed Central

2018-01-01

Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease, the fundamental principles of their behavior under mechanical load are poorly understood. Talin and α-catenin are two key molecules in focal adhesions and adherens junctions, respectively. In this study, we used a combination of atomistic steered molecular dynamics (SMD) simulations, polyprotein engineering, and single-molecule atomic force microscopy (smAFM) to investigate unfolding of these proteins. SMD simulations revealed that talin rod α-helix bundles as well as α-catenin α-helix domains unfold through stable 3-helix intermediates. While the 5-helix bundles were found to be mechanically stable, a second stable conformation corresponding to the 3-helix state was revealed. Mechanically weaker 4-helix bundles easily unfolded into a stable 3-helix conformation. The results of smAFM experiments were in agreement with the findings of the computational simulations. The disulfide clamp mutants, designed to protect the stable state, support the 3-helix intermediate model in both experimental and computational setups. As a result, multiple discrete unfolding intermediate states in the talin and α-catenin unfolding pathway were discovered. Better understanding of the mechanical unfolding mechanism of α-helix proteins is a key step towards comprehensive models describing the mechanoregulation of proteins. PMID:29698481

Vibration control of uncertain multiple launch rocket system using radial basis function neural network

NASA Astrophysics Data System (ADS)

Li, Bo; Rui, Xiaoting

2018-01-01

Poor dispersion characteristics of rockets due to the vibration of Multiple Launch Rocket System (MLRS) have always restricted the MLRS development for several decades. Vibration control is a key technique to improve the dispersion characteristics of rockets. For a mechanical system such as MLRS, the major difficulty in designing an appropriate control strategy that can achieve the desired vibration control performance is to guarantee the robustness and stability of the control system under the occurrence of uncertainties and nonlinearities. To approach this problem, a computed torque controller integrated with a radial basis function neural network is proposed to achieve the high-precision vibration control for MLRS. In this paper, the vibration response of a computed torque controlled MLRS is described. The azimuth and elevation mechanisms of the MLRS are driven by permanent magnet synchronous motors and supposed to be rigid. First, the dynamic model of motor-mechanism coupling system is established using Lagrange method and field-oriented control theory. Then, in order to deal with the nonlinearities, a computed torque controller is designed to control the vibration of the MLRS when it is firing a salvo of rockets. Furthermore, to compensate for the lumped uncertainty due to parametric variations and un-modeled dynamics in the design of the computed torque controller, a radial basis function neural network estimator is developed to adapt the uncertainty based on Lyapunov stability theory. Finally, the simulated results demonstrate the effectiveness of the proposed control system and show that the proposed controller is robust with regard to the uncertainty.

Degradation analysis of anode-supported intermediate temperature-solid oxide fuel cells under various failure modes

NASA Astrophysics Data System (ADS)

Lee, Tae-Hee; Park, Ka-Young; Kim, Ji-Tae; Seo, Yongho; Kim, Ki Buem; Song, Sun-Ju; Park, Byoungnam; Park, Jun-Young

2015-02-01

This study focuses on mechanisms and symptoms of several simulated failure modes, which may have significant influences on the long-term durability and operational stability of intermediate temperature-solid oxide fuel cells (IT-SOFCs), including fuel/oxidation starvation by breakdown of fuel/air supply components and wet and dry cycling atmospheres. Anode-supported IT-SOFCs consisting of a Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF)-Nd0.1Ce0.9O2-δ (NDC) composite cathode with an NDC electrolyte on a Ni-NDC anode substrate are fabricated via dry-pressings followed by the co-firing method. Comprehensive and systematic research based on the failure mode and effect analysis (FMEA) of anode-supported IT-SOFCs is conducted using various electrochemical and physiochemical analysis techniques to extend our understanding of the major mechanisms of performance deterioration under SOFC operating conditions. The fuel-starvation condition in the fuel-pump failure mode causes irreversible mechanical degradation of the electrolyte and cathode interface by the dimensional expansion of the anode support due to the oxidation of Ni metal to NiO. In contrast, the BSCF cathode shows poor stability under wet and dry cycling modes of cathode air due to the strong electroactivity of SrO with H2O. On the other hand, the air-depletion phenomena under air-pump failure mode results in the recovery of cell performance during the long-term operation without the visible microstructural transformation through the reduction of anode overvoltage.

The influence of droplet size on the stability, in vivo digestion, and oral bioavailability of vitamin E emulsions.

PubMed

Parthasarathi, S; Muthukumar, S P; Anandharamakrishnan, C

2016-05-18

Vitamin E (α-tocopherol) is a nutraceutical compound, which has been shown to possess potent antioxidant and anticancer activity. However, its biological activity may be limited by its poor bioavailability. Colloidal delivery systems have shown wide applications in the food and pharmaceutical industries to deliver lipophilic bioactive compounds. In this study, we have developed conventional and nanoemulsions of vitamin E from food grade ingredients (sunflower oil, saponin, and water) and showed the nanoemulsion formulation increased the oral bioavailability when compared to the conventional emulsion. The mean droplet diameters in the nano and conventional emulsions were 0.277 and 1.285 μm, respectively. The stability of the emulsion formulation after thermal processing, long-term storage at different temperatures, mechanical stress and in plasma was determined. The results showed that the saponin coated nanoemulsion was stable to droplet coalescence during thermal processing (30-90 °C), long-term storage and mechanical stress when compared to the conventional emulsion. The biological fate of the emulsion formulations were studied using male Wistar rats as an animal model. The emulsion droplet stability during passage through the gastrointestinal tract was evaluated by their introduction into rat stomachs. Microscopy was used to investigate the structural changes that occurred during digestion. Both the conventional emulsion and nanoemulsion formulations showed strong evidence of droplet flocculation and coalescence during in vivo digestion. The in vivo oral bioavailability study revealed that vitamin E in a nanoemulsion form showed a 3-fold increase in the AUC when compared to the conventional emulsion. The information reported in this study will facilitate the design of colloidal delivery systems using nanoemulsion formulations.

Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells.

PubMed

Safina, Alfiya; Garcia, Henry; Commane, Mairead; Guryanova, Olga; Degan, Seamus; Kolesnikova, Kateryna; Gurova, Katerina V

2013-08-01

Facilitates chromatin transcription (FACT) is a chromatin remodeling complex with two subunits: SSRP1 and SPT16. Mechanisms controlling FACT levels are of interest, since the complex is not expressed in most differentiated cells, but is frequently upregulated in cancer, particularly in poorly differentiated, aggressive tumors. Moreover, inhibition of FACT expression or function in tumor cells interferes with their survival. Here we demonstrate that SSRP1 and SPT16 protein levels decline upon induction of cellular differentiation or senescence in vitro and that similar declines in protein levels for both SSRP1 and SPT16 occur upon RNAi-mediated knockdown of either SSRP1 or SPT16. The interdependence of SSRP1 and SPT16 protein levels was found to be due to their association with SSRP1 and SPT16 mRNAs, which stabilizes the proteins. In particular, presence of SSRP1 mRNA is critical for SPT16 protein stability. In addition, binding of SSRP1 and SPT16 mRNAs to the FACT complex increases the stability and efficiency of translation of the mRNAs. These data support a model in which the FACT complex is stable when SSRP1 mRNA is present, but quickly degrades when SSRP1 mRNA levels drop. In the absence of FACT complex, SSRP1 and SPT16 mRNAs are unstable and inefficiently translated, making reactivation of FACT function unlikely in normal cells. Thus, we have described a complex and unusual mode of regulation controlling cellular FACT levels that results in amplified and stringent control of FACT activity. The FACT dependence of tumor cells suggests that mechanisms controlling FACT levels could be targeted for anticancer therapy.

Microscopic significance of hydrophobic residues in the protein-stabilizing effect of trimethylamine N-oxide (TMAO).

PubMed

Yang, Yanmei; Mu, Yuguang; Li, Weifeng

2016-08-10

Although it is widely known that trimethylamine N-oxide (TMAO) stabilizes the native structure of proteins, the underlying mechanism of its action is poorly documented. To obtain an in-depth understanding of this important osmolyte molecule, we conducted large-scale molecular dynamic simulations of model proteins, namely, wild-type villin headpiece protein HP35 and its doubly norleucine-substituent mutant (Lys24/29Nle) HP35NN in pure urea and urea + TMAO mixed solutions for direct comparison. From extensive sampling, the protective capability of TMAO was well captured in the simulations, where HP35NN demonstrated a significantly more stable native structure than HP35 in the presence of TMAO, whereas in pure urea solution, the former denatured in a shorter time. These findings highlight the importance of the two norleucine residues that regulates the interactions of proteins with urea and TMAO. By accessing the hydration and conformational dynamics of both proteins, we were able to directly probe how TMAO compensates the denaturing effect of urea at the atomic level. The accumulation of urea around hydrophobic residues is clearly suppressed, which indicates that the van der Waals interactions between urea and proteins are weakened by TMAO. As a consequence, the hydrophobic core of protein is preferentially protected by TMAO against urea attack. Although the hydrogen bonds (H-bonds) between proteins and urea are suppressed by TMAO, this plays a very minor role than expected in the enhanced protein stability. In addition, TMAO was found to be always excluded from the protein surface and incapable of forming H-bonds with proteins. Thus, the present study provides solid evidence to support the indirect mechanism of TMAO counteracting the denaturing effects of urea.

Chemical, computational and functional insights into the chemical stability of the Hedgehog pathway inhibitor GANT61.

PubMed

Calcaterra, Andrea; Iovine, Valentina; Botta, Bruno; Quaglio, Deborah; D'Acquarica, Ilaria; Ciogli, Alessia; Iazzetti, Antonia; Alfonsi, Romina; Lospinoso Severini, Ludovica; Infante, Paola; Di Marcotullio, Lucia; Mori, Mattia; Ghirga, Francesca

2018-12-01

This work aims at elucidating the mechanism and kinetics of hydrolysis of GANT61, the first and most-widely used inhibitor of the Hedgehog (Hh) signalling pathway that targets Glioma-associated oncogene homologue (Gli) proteins, and at confirming the chemical nature of its bioactive form. GANT61 is poorly stable under physiological conditions and rapidly hydrolyses into an aldehyde species (GANT61-A), which is devoid of the biological activity against Hh signalling, and a diamine derivative (GANT61-D), which has shown inhibition of Gli-mediated transcription. Here, we combined chemical synthesis, NMR spectroscopy, analytical studies, molecular modelling and functional cell assays to characterise the GANT61 hydrolysis pathway. Our results show that GANT61-D is the bioactive form of GANT61 in NIH3T3 Shh-Light II cells and SuFu -/- mouse embryonic fibroblasts, and clarify the structural requirements for GANT61-D binding to Gli1. This study paves the way to the design of GANT61 derivatives with improved potency and chemical stability.

Different distribution of in-situ thin carbon layer in hollow cobalt sulfide nanocages and their application for supercapacitors

NASA Astrophysics Data System (ADS)

Jin, Meng; Lu, Shi-Yu; Ma, Li; Gan, Meng-Yu; Lei, Yao; Zhang, Xiu-Ling; Fu, Gang; Yang, Pei-Shu; Yan, Mao-Fa

2017-02-01

Recently, cobalt sulfides emerge as a candidate for energy reserve and conversation. However, the problem of poor stability and low rate capability for cobalt sulfides restrict its practical application. Thin carbon layer (TCL) coated has been regarded as a promising constructing strategy for high performance supercapacitors, because TCL can promote the tremendous properties of bare materials. In this literature, we report a very interesting phenomenon that different distribution of in-situ carbon coated hollow CoS2 nanocages (external and both external and interior) can be synthesized only by adjusting sulfuration time, followed by calcination. Moreover, it is clearly observed that CoS2-C@TCL exhibits significant improvement for specific capacitance and good stability (better than CoS2@TCL and CoS2). These results compel us to design a series of experiments to figure out the reason and the more detailed mechanism is discussed in paper. More importantly, it will provide a new strategy for synthesis of special structure with in-situ carbon coated sulfide for energy conversion.

A one-piece 3D printed flexure translation stage for open-source microscopy

NASA Astrophysics Data System (ADS)

Sharkey, James P.; Foo, Darryl C. W.; Kabla, Alexandre; Baumberg, Jeremy J.; Bowman, Richard W.

2016-02-01

Open source hardware has the potential to revolutionise the way we build scientific instruments; with the advent of readily available 3D printers, mechanical designs can now be shared, improved, and replicated faster and more easily than ever before. However, printed parts are typically plastic and often perform poorly compared to traditionally machined mechanisms. We have overcome many of the limitations of 3D printed mechanisms by exploiting the compliance of the plastic to produce a monolithic 3D printed flexure translation stage, capable of sub-micron-scale motion over a range of 8 × 8 × 4 mm. This requires minimal post-print clean-up and can be automated with readily available stepper motors. The resulting plastic composite structure is very stiff and exhibits remarkably low drift, moving less than 20 μm over the course of a week, without temperature stabilisation. This enables us to construct a miniature microscope with excellent mechanical stability, perfect for time-lapse measurements in situ in an incubator or fume hood. The ease of manufacture lends itself to use in containment facilities where disposability is advantageous and to experiments requiring many microscopes in parallel. High performance mechanisms based on printed flexures need not be limited to microscopy, and we anticipate their use in other devices both within the laboratory and beyond.

The Relationship Between Postural and Movement Stability.

PubMed

Feldman, Anatol G

2016-01-01

Postural stabilization is provided by stretch reflexes, intermuscular reflexes, and intrinsic muscle properties. Taken together, these posture-stabilizing mechanisms resist deflections from the posture at which balance of muscle and external forces is maintained. Empirical findings suggest that for each muscle, these mechanisms become functional at a specific, spatial threshold-the muscle length or respective joint angle at which motor units begin to be recruited. Empirical data suggest that spinal and supraspinal centers can shift the spatial thresholds for a group of muscles that stabilized the initial posture. As a consequence, the same stabilizing mechanisms, instead of resisting motion from the initial posture, drive the body to another stable posture. In other words by shifting spatial thresholds, the nervous system converts movement resisting to movement-producing mechanisms. It is illustrated that, contrary to conventional view, this control strategy allows the system to transfer body balance to produce locomotion and other actions without loosing stability at any point of them. It also helps orient posture and movement with the direction of gravity. It is concluded that postural and movement stability is provided by a common mechanism.

Back-channel-etch amorphous indium-gallium-zinc oxide thin-film transistors: The impact of source/drain metal etch and final passivation

NASA Astrophysics Data System (ADS)

Nag, Manoj; Bhoolokam, Ajay; Steudel, Soeren; Chasin, Adrian; Myny, Kris; Maas, Joris; Groeseneken, Guido; Heremans, Paul

2014-11-01

We report on the impact of source/drain (S/D) metal (molybdenum) etch and the final passivation (SiO2) layer on the bias-stress stability of back-channel-etch (BCE) configuration based amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). It is observed that the BCE configurations TFTs suffer poor bias-stability in comparison to etch-stop-layer (ESL) TFTs. By analysis with transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS), as well as by a comparative analysis of contacts formed by other metals, we infer that this poor bias-stability for BCE transistors having Mo S/D contacts is associated with contamination of the back channel interface, which occurs by Mo-containing deposits on the back channel during the final plasma process of the physical vapor deposited SiO2 passivation.

Theoretical limits on the stability of single-phase kesterite-Cu{sub 2}ZnSnS{sub 4}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarker, Pranab; Huda, Muhammad N., E-mail: huda@uta.edu; Al-Jassim, Mowafak M.

2015-01-21

The single-phase stability of Cu{sub 2}ZnSnS{sub 4} (CZTS), after an intrinsic defect was incorporated in it, has been examined here for the first time based on ab initio calculations. The stability analysis of such a non-stoichiometric-defect incorporated CZTS shows that the single-phase formation is unlikely at thermodynamic equilibrium conditions. In addition, the effective growth condition of CZTS is determined and quantified for all the elements (Cu-poor, Zn-rich, Sn-poor, and S-rich) to extract maximum photovoltaic efficiency from CZTS. These conditions promote (i) spontaneous formation of Cu vacancy (V{sub Cu}), which might benefit p-type conduction, and (ii) the co-existence of ZnS whilemore » suppressing other harmful defects and secondary phases. Further, the results presented here explain the unavailability of single-phase CZTS to date.« less

A comparison of theory and experiment for coupled rotor-body stability of a hingeless rotor model in hover

NASA Technical Reports Server (NTRS)

Bousman, William G.

1988-01-01

Three cases were selected for correlation from an experiment that examined the aeromechanical stability of a small-scale model of a hingeless rotor and fuselage in hover. The first case examined the stability of a configuration with 0 degree blade pitch so that coupling between dynamic modes was minimized. The second case was identical to the first except the blade pitch was set to 9 degrees which provides flap-lag coupling of the rotor modes. The third case had 9 degrees of blade pitch and also included negative pitch-lag coupling, and therefore was the most highly coupled configuration. Analytical calculations were made by Bell Helicopter Textron, Boeing Vertol, Hughes Helicopters, Sikorsky Aircraft, the U.S. Army Aeromechanics Laboratory, and NASA Ames Research Center and compared to some or all of the experimental cases. Overall, the correlation ranged from very poor-to-poor to good.

C-5 Propynyl Modifications Enhance the Mechanical Stability of DNA.

PubMed

Aschenbrenner, Daniela; Baumann, Fabian; Milles, Lukas F; Pippig, Diana A; Gaub, Hermann E

2015-07-20

Increased thermal or mechanical stability of DNA duplexes is desired for many applications in nanotechnology or -medicine where DNA is used as a programmable building block. Modifications of pyrimidine bases are known to enhance thermal stability and have the advantage of standard base-pairing and easy integration during chemical DNA synthesis. Through single-molecule force spectroscopy experiments with atomic force microscopy and the molecular force assay we investigated the effect of pyrimidines harboring C-5 propynyl modifications on the mechanical stability of double-stranded DNA. Utilizing these complementary techniques, we show that propynyl bases significantly increase the mechanical stability if the DNA is annealed at high temperature. In contrast, modified DNA complexes formed at room temperature and short incubation times display the same stability as non-modified DNA duplexes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relationships between mechanical joint stability and somatosensory function in individuals with chronic ankle instability.

PubMed

Kirby, Jessica L; Houston, Megan N; Gabriner, Michael L; Hoch, Matthew C

2016-08-01

Individuals with chronic ankle instability (CAI) have demonstrated alterations in ankle mechanics and deficits in sensory function. However, relationships between mechanical stability and somatosensory function have not been examined, nor have those between somatosensory function and injury history characteristics. Therefore, the objective of this study was to examine relationships between (1) somatosensory function and mechanical stability and (2) somatosensory function and injury history characteristics. Forty adults with CAI volunteered to participate. In a single testing session, participants completed mechanical and sensory assessments in a counterbalanced order. Dependent variables included anterior/posterior displacement (mm), inversion/eversion rotation (°), SWM index values, JPS absolute error (°), number of previous ankle sprains, and number of "giving way" episodes in the previous 3 months. Spearman's Rho correlations examined the relationships between somatosensory function and (1) mechanical stability and (2) injury history characteristics (p<0.05). No significant correlations were identified between any variables (p>0.11), and all r-values were considered weak. These results revealed somatosensory function was not significantly correlated to mechanical stability or injury history characteristics. This indicates peripheral sensory impairments associated with CAI are likely caused by factors other than mechanical stability and injury history characteristics. Copyright © 2016 Elsevier Ltd. All rights reserved.

MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling

PubMed Central

Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

2014-01-01

Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. PMID:25224226

MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling.

PubMed

Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

2014-11-01

Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

Structural Basis of Actin Filament Nucleation by Tandem W Domains

PubMed Central

Chen, Xiaorui; Ni, Fengyun; Tian, Xia; Kondrashkina, Elena; Wang, Qinghua; Ma, Jianpeng

2013-01-01

SUMMARY Spontaneous nucleation of actin is very inefficient in cells. To overcome this barrier, cells have evolved a set of actin filament nucleators to promote rapid nucleation and polymerization in response to specific stimuli. However, the molecular mechanism of actin nucleation remains poorly understood. This is hindered largely by the fact that actin nucleus, once formed, rapidly polymerizes into filament, thus making it impossible to capture stable multisubunit actin nucleus. Here, we report an effective double-mutant strategy to stabilize actin nucleus by preventing further polymerization. Employing this strategy, we solved the crystal structure of AMPPNP-actin in complex with the first two tandem W domains of Cordon-bleu (Cobl), a potent actin filament nucleator. Further sequence comparison and functional studies suggest that the nucleation mechanism of Cobl is probably shared by the p53 cofactor JMY, but not Spire. Moreover, the double-mutant strategy opens the way for atomic mechanistic study of actin nucleation and polymerization. PMID:23727244

Clayey Landslide Initiation and Acceleration Strongly Modulated by Soil Swelling

NASA Astrophysics Data System (ADS)

Schulz, William H.; Smith, Joel B.; Wang, Gonghui; Jiang, Yao; Roering, Joshua J.

2018-02-01

Largely unknown mechanisms restrain motion of clay-rich, slow-moving landslides that are widespread worldwide and rarely accelerate catastrophically. We studied a clayey, slow-moving landslide typical of thousands in Northern California, USA, to decipher hydrologic-mechanical interactions that modulate landslide dynamics. Similar to some other studies, observed pore-water pressures correlated poorly with landslide reactivation and speed. In situ and laboratory measurements strongly suggested that variable pressure along the landslide's lateral shear boundaries resulting from seasonal soil expansion and contraction modulated its reactivation and speed. Slope-stability modeling suggested that the landslide's observed behavior could be predicted by including transient swell pressure as a resistance term, whereas modeling considering only transient hydrologic conditions predicted movement five to six months prior to when it was observed. All clayey soils swell to some degree; hence, our findings suggest that swell pressure likely modulates motion of many landslides and should be considered to improve forecasts of clayey landslide initiation and mobility.

Clayey landslide initiation and acceleration strongly modulated by soil swelling

USGS Publications Warehouse

Schulz, William; Smith, Joel B.; Wang, Gonghui; Jiang, Yao; Roering, Joshua J.

2018-01-01

Largely unknown mechanisms restrain motion of clay-rich, slow-moving landslides that are widespread worldwide and rarely accelerate catastrophically. We studied a clayey, slow-moving landslide typical of thousands in northern California, USA, to decipher hydrologic-mechanical interactions that modulate landslide dynamics. Similar to some other studies, observed pore-water pressures correlated poorly with landslide reactivation and speed. In situ and laboratory measurements strongly suggested that variable pressure along the landslide's lateral shear boundaries resulting from seasonal soil expansion and contraction modulated its reactivation and speed. Slope-stability modeling suggested that the landslide's observed behavior could be predicted by including transient swell pressure as a resistance term, whereas modeling considering only transient hydrologic conditions predicted movement 5–6 months prior to when it was observed. All clayey soils swell to some degree; hence, our findings suggest that swell pressure likely modulates motion of many landslides and should be considered to improve forecasts of clayey landslide initiation and mobility.

Novel Approach to Strengthening Ceramic Cathode Contact and Validation in a Generic Stack Test Fixture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, Yeong-Shyung; Bonnett, Jeff F.; Stevenson, Jeffry W.

The ceramic contact material at the cathode side has been identified as the weakest mechanical link in solid oxide fuel cells, due to poor sintering at low stack fabrication temperatures. In this work, a novel approach of mechanical interlocking with an engineered surface was proposed to strengthen LSM-type contacts. The engineered cathode surface was made by depositing large LSM20 granules onto a wet cathode print, followed by sintering. Granules of three sizes were tested (mesh #35, #60, and #100). Small coupons of anode-supported YSZ electrolyte with LSM cathode were joined at 850 and 950oC for 2h with LSM contact usingmore » either the engineered surface or plain surfaces. The results of contact strength measurements showed about 14 times increase with engineered surface compared to plain surfaces. Validation with a 2”x2” LSM-based cell in a generic stack fixture showed good thermal cycle stability with minimal change in ohmic impedance over ten cycles.« less

Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia

PubMed Central

Baeyens, Nicolas; Larrivée, Bruno; Ola, Roxana; Hayward-Piatkowskyi, Brielle; Dubrac, Alexandre; Huang, Billy; Ross, Tyler D.; Coon, Brian G.; Min, Elizabeth; Tsarfati, Maya; Tong, Haibin; Eichmann, Anne

2016-01-01

Morphogenesis of the vascular system is strongly modulated by mechanical forces from blood flow. Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal-dominant disease in which arteriovenous malformations and telangiectasias accumulate with age. Most cases are linked to heterozygous mutations in Alk1 or Endoglin, receptors for bone morphogenetic proteins (BMPs) 9 and 10. Evidence suggests that a second hit results in clonal expansion of endothelial cells to form lesions with poor mural cell coverage that spontaneously rupture and bleed. We now report that fluid shear stress potentiates BMPs to activate Alk1 signaling, which correlates with enhanced association of Alk1 and endoglin. Alk1 is required for BMP9 and flow responses, whereas endoglin is only required for enhancement by flow. This pathway mediates both inhibition of endothelial proliferation and recruitment of mural cells; thus, its loss blocks flow-induced vascular stabilization. Identification of Alk1 signaling as a convergence point for flow and soluble ligands provides a molecular mechanism for development of HHT lesions. PMID:27646277

Prospect of Thermal Insulation by Silica Aerogel: A Brief Review

NASA Astrophysics Data System (ADS)

Hasan, Mohammed Adnan; Sangashetty, Rashmi; Esther, A. Carmel Mary; Patil, Sharanabasappa B.; Sherikar, Baburao N.; Dey, Arjun

2017-10-01

Silica aerogel is a unique ultra light weight nano porous material which offers superior thermal insulation property as compared to the conventional thermal insulating materials. It can be applied not only for ground and aerospace applications but also in low and high temperatures and pressure regimes. Aerogel granules and monolith are synthesized by the sol-gel route while aerogel based composites are fabricated by the reinforcement of fibers, particle and opacifiers. Due to the characteristic brittleness (i.e., poor mechanical properties) of monolith or bulk aerogel, it is restricted in several applications. To improve the mechanical integrity and flexibility, usually different fibers are reinforced with aerogel and hence it can be used as flexible thermal insulation blankets. Further, to achieve effective thermal insulation behaviour particularly at high temperature, often opacifiers are doped with silica aerogel. In the present brief review, the prospects of bulk aerogel and aerogel based composites are discussed for the application of thermal insulation and thermal stability.

Influence of fluctuations of historic water bodies on fault stability and earthquake recurrence interval: The Dead Sea Rift as a case study

NASA Astrophysics Data System (ADS)

Belferman, Mariana; Katsman, Regina; Agnon, Amotz; Ben-Avraham, Zvi

2017-04-01

Despite the global, social and scientific impact of earthquakes, their triggering mechanisms remain often poorly defined. We suggest that dynamic changes in the levels of the historic water bodies occupying tectonic depressions at the Dead Sea Rift cause significant variations in the shallow crustal stress field and affect local fault systems in a way that may promote or suppress earthquakes. This mechanism and its spatial and temporal scales differ from those in tectonically-driven deformations. We use analytical and numerical poroelastic models to simulate immediate and delayed seismic responses resulting from the observed historic water level changes. The role of variability in the poroelastic and the elastic properties of the rocks composing the upper crust in inducing or retarding deformations under a strike-slip faulting regime is studied. The solution allows estimating a possible reduction in a seismic recurrence interval. Considering the historic water level fluctuation, our preliminary simulations show a promising agreement with paleo-seismic rates identified in the field.

How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA.

PubMed

Hur, Sun; Stroud, Robert M

2007-04-27

Translational accuracy and efficiency depend upon modification of uridines in the tRNA anticodon stem loop (ASL) by a highly conserved pseudouridine synthase TruA. TruA specifically modifies uridines at positions 38, 39, and/or 40 of tRNAs with highly divergent sequences and structures through a poorly characterized mechanism that differs from previously studied RNA-modifying enzymes. The molecular basis for the site and substrate "promiscuity" was studied by determining the crystal structures of E. coli TruA in complex with two different leucyl tRNAs in conjunction with functional assays and computer simulation. The structures capture three stages of the TruA*tRNA reaction, revealing the mechanism by which TruA selects the target site. We propose that TruA utilizes the intrinsic flexibility of the ASL for site promiscuity and also to select against intrinsically stable tRNAs to avoid their overstabilization through pseudouridylation, thereby maintaining the balance between the flexibility and stability required for its biological function.

Phase Behavior of a Single Structured Ionomer Chain in Solution

DOE PAGES

Aryal, Dipak; Etampawala, Thusitha; Perahia, Dvora; ...

2014-08-14

Structured polymers offer a means to tailor transport pathways within mechanically stable manifolds. Here we examine the building block of such a membrane, namely a single large pentablock co-polymer that consist of a center block of a randomly sulfonated polystyrene, designed for transport, tethered to poly-ethylene-r-propylene and end-capped by poly-t-butyl styrene, for mechanical stability,using molecular dynamics simulations. The polymer structure in a cyclohexane-heptane mixture, a technologically viable solvent, and in water, a poor solvent for all segments and a ubiquitous substance is extracted. In all solvents the pentablock collapsed into nearly spherical aggregates where the ionic block is segregated. Inmore » hydrophobic solvents, the ionic block resides in the center, surrounded by swollen intermix of flexible and end blocks. In water all blocks are collapsed with the sulfonated block residing on the surface. Our results demonstrate that solvents drive different local nano-segregation, providing a gateway to assemble membranes with controlled topology.« less

The Impact of Placement Stability on Behavioral Well-Being for Children in Foster Care

ERIC Educational Resources Information Center

Rubin, David M.; O'Reilly, Amanda L. R.; Luan, Xianqun; Localio, A. Russell

2007-01-01

Objective: The problems children have upon entering foster care can potentially explain prior research findings that frequent placement changes are associated with poor outcomes. This study sought to disentangle this cascading relationship in order to identify the independent impact of placement stability on behavioral outcomes downstream.…

An optimal modification of a Kalman filter for time scales

NASA Technical Reports Server (NTRS)

Greenhall, C. A.

2003-01-01

The Kalman filter in question, which was implemented in the time scale algorithm TA(NIST), produces time scales with poor short-term stability. A simple modification of the error covariance matrix allows the filter to produce time scales with good stability at all averaging times, as verified by simulations of clock ensembles.

Towards Intravenous Drug Delivery: Augmenting the Stability and Dispersity of Bis-Demethoxy Curcumin Analog by Bottom-Up Strategy.

PubMed

Francis, Arul Prakash; Ramaprabhu, Sundara; Devasena, Thiyagarajan

2016-01-01

Intravenous route is the best strategy to accomplish fastest and highest delivery of drugs. Hydrophobic drugs like curcumin and its analog exhibit disadvantages like low bioavailability, poor absorption and rapid precipitation on intravenous delivery, all leading to its poor therapeutic value. These can be by-passed by enhancing the dispersity, stability and decreasing the size of the drug by nanotization. Thus, with an intention to deliver bis-demethoxy curcumin analog via intravenous route, we have studied the effect of DMSO, ethanol and acetone on the size, size distribution, stability and yield and identified the best solvent in terms of smallest size, narrow size distribution, more stability and high yield of nano bis-demethoxy curcumin analog (NBDMCA). NBDMCA prepared using DMSO showed the lowest mean particle size cum polydispersity index and highest zeta potential when compared to ethanol and acetone. Hence the DMSO based formulation can provide prolonged action and better efficacy at minimal doses. Thus, the DMSO based NBDMCA can emerge as an ideal therapeutic tool for human use.

Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly water soluble drug felodipine.

PubMed

Sarode, Ashish L; Malekar, Swapnil A; Cote, Catherine; Worthen, David R

2014-11-04

Overcoming the low oral bioavailability of many drugs due to their poor aqueous solubility is one of the major challenges in the pharmaceutical industry. The production of amorphous solid dispersions (ASDs) of these drugs using hydrophilic polymers may significantly improve their solubility. However, their storage stability and the stability of their supersaturated solutions in the gastrointestinal tract upon administration are unsolved problems. We have investigated the potential of a low viscosity grade of a cellulosic polymer, hydroxypropyl cellulose (HPC-SSL), and compared it with a commonly used vinyl polymer, polyvinylpyrrolidone vinyl acetate (PVP-VA), for stabilizing the ASDs of a poorly water soluble drug, felodipine. The ASDs were produced using hot melt mixing and stored under standard and accelerated stability conditions. The ASDs were characterized using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. Drug dissolution and partitioning rates were evaluated using single- and biphasic dissolution studies. The ASDs displayed superior drug dissolution and partitioning as compared to the pure crystalline drug, which might be attributed to the formation of a drug-polymer molecular dispersion, amorphous conversion of the drug, and drug-polymer hydrogen bonding interactions. Late phase separation and early re-crystallization occurred at lower and higher storage temperatures, respectively, for HPC-SSL ASDs, whereas early phase separation, even at low storage temperatures, was noted for PVP-VA ASDs. Consequently, the partitioning rates for ASDs dispersed in HPC-SSL were greater than those of PVP-VA at lower and room temperature storage, whereas the performance of both of the ASDs was similar when stored at higher temperatures. Copyright © 2014. Published by Elsevier Ltd.

Relationship of dough thermomechanical properties with oil uptake, cooking and textural properties of instant fried noodles.

PubMed

Gulia, Neelam; Khatkar, B S

2014-04-01

Instant noodles were prepared from fifteen diverse wheat cultivars varying widely in their flour quality and dough rheology. Dough thermomechanical parameters obtained by Mixolab and flour analytical properties were correlated with the quality of instant noodles including oil uptake, cooking quality and textural attributes. The Mixolab parameters dough development time and dough stability showed significant positive correlation with cooking time, cooked weight, overall acceptability, hardness, springiness, cohesiveness and chewiness of noodles, while negatively correlated with oil uptake and cooking loss, therefore, exhibiting a marked positive effect on quality of instant noodles. Lower protein breakdown represented by C2 torque was also positively related with overall acceptability, hardness, springiness, cohesiveness and chewiness of noodles. Stickiness/adhesiveness of noodles was revealed to be mainly conferred by falling number values (R (2 )= 0.671) and damaged starch (R (2 )= 0.523) content of wheat flour samples. Flour samples with lesser values of protein content, sodium dodecyl sulphate sedimentation volume, thermal stability of proteins, dough stability and dough development time were found to be linked with poor noodle quality. Medium strong flours performed better in noodle making, while weaker flours demonstrated poor noodle quality. Dough rheology of good noodle making flours was characterized with higher dough development time, dough stability, C2, C3, C4 as well as C5 values. Noodles with higher overall acceptability showed a more continuous and uniform protein starch matrix in comparison to the poor counterparts.

Size-Controlled Synthesis of Sub-10 nm PtNi3 Alloy Nanoparticles and their Unusual Volcano-Shaped Size Effect on ORR Electrocatalysis.

PubMed

Gan, Lin; Rudi, Stefan; Cui, Chunhua; Heggen, Marc; Strasser, Peter

2016-06-01

Dealloyed Pt bimetallic core-shell catalysts derived from low-Pt bimetallic alloy nanoparticles (e.g, PtNi3 ) have recently shown unprecedented activity and stability on the cathodic oxygen reduction reaction (ORR) under realistic fuel cell conditions and become today's catalyst of choice for commercialization of automobile fuel cells. A critical step toward this breakthrough is to control their particle size below a critical value (≈10 nm) to suppress nanoporosity formation and hence reduce significant base metal (e.g., Ni) leaching under the corrosive ORR condition. Fine size control of the sub-10 nm PtNi3 nanoparticles and understanding their size dependent ORR electrocatalysis are crucial to further improve their ORR activity and stability yet still remain unexplored. A robust synthetic approach is presented here for size-controlled PtNi3 nanoparticles between 3 and 10 nm while keeping a constant particle composition and their size-selected growth mechanism is studied comprehensively. This enables us to address their size-dependent ORR activities and stabilities for the first time. Contrary to the previously established monotonic increase of ORR specific activity and stability with increasing particle size on Pt and Pt-rich bimetallic nanoparticles, the Pt-poor PtNi3 nanoparticles exhibit an unusual "volcano-shaped" size dependence, showing the highest ORR activity and stability at the particle sizes between 6 and 8 nm due to their highest Ni retention during long-term catalyst aging. The results of this study provide important practical guidelines for the size selection of the low Pt bimetallic ORR electrocatalysts with further improved durably high activity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Nb2O5 doping on improving the thermo-mechanical stability of sealing interfaces for solid oxide fuel cells.

PubMed

Zhang, Qi; Du, Xinhang; Tan, Shengwei; Tang, Dian; Chen, Kongfa; Zhang, Teng

2017-07-13

Nb 2 O 5 is added to a borosilicate sealing system to improve the thermo-mechanical stability of the sealing interface between the glass and Fe-Cr metallic interconnect (Crofer 22APU) in solid oxide fuel cells (SOFCs). The thermo-mechanical stability of the glass/metal interface is evaluated experimentally as well as by using a finite element analysis (FEA) method. The sealing glass doped with 4 mol.% Nb 2 O 5 shows the best thermo-mechanical stability, and the sealing couple of Crofer 22APU/glass/GDC (Gd 0.2 Ce 0.8 O 1.9 ) remains intact after 50 thermal cycles. In addition, all sealing couples show good joining after being held at 750 °C for 1000 h. Moreover, the possible mechanism on the thermo-mechanical stability of sealing interface is investigated in terms of stress-based and energy-based perspectives.

Improving the Mechanical Performance and Thermal Stability of a PVA-Clay Nanocomposite by Electron Beam Irradiation

NASA Astrophysics Data System (ADS)

Shokuhi Rad, A.; Ebrahimi, D.

2017-07-01

The effects of electron beam irradiation and presence of clay on the mechanical properties and thermal stability of montmorillonite clay-modified polyvinyl alcohol nanocomposites were studied. By using the X-ray diffraction (XRD) and transmission electron microscopy (TEM), the microstructure of the nanocomposites was investigated. The results obtained from TEM and XRD tests showed that montmorillonite clay nanoparticles were located in the polyvinyl alcohol phase. The XRD analysis confirmed the formation of an exfoliated structure in nanocomposites samples. Increasing the amount of clay to 20 wt.% increased the tensile strength and modulus of the nanocomposite. Irradiation up to an absorbed dose of 100 kGy increased its mechanical properties and thermal stability, but at higher irradiation levels, the mechanical strength and thermal stability declined. The sample with 20 wt.% of the nanofiller, exposed to 100 kGy, showed the highest mechanical strength and thermal stability.

Amino acids as co-amorphous stabilizers for poorly water soluble drugs--Part 1: preparation, stability and dissolution enhancement.

PubMed

Löbmann, Korbinian; Grohganz, Holger; Laitinen, Riikka; Strachan, Clare; Rades, Thomas

2013-11-01

Poor aqueous solubility of an active pharmaceutical ingredient (API) is one of the most pressing problems in pharmaceutical research and development because up to 90% of new API candidates under development are poorly water soluble. These drugs usually have a low and variable oral bioavailability, and therefore an unsatisfactory therapeutic effect. One of the most promising approaches to increase dissolution rate and solubility of these drugs is the conversion of a crystalline form of the drug into its respective amorphous form, usually by incorporation into hydrophilic polymers, forming glass solutions. However, this strategy only led to a small number of marketed products usually because of inadequate physical stability of the drug (crystallization). In this study, we investigated a fundamentally different approach to stabilize the amorphous form of drugs, namely the use of amino acids as small molecular weight excipients that form specific molecular interactions with the drug resulting in co-amorphous forms. The two poorly water soluble drugs carbamazepine and indomethacin were combined with amino acids from the binding sites of the biological receptors of these drugs. Mixtures of drug and the amino acids arginine, phenylalanine, tryptophan and tyrosine were prepared by vibrational ball milling. Solid-state characterization with X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) revealed that the various blends could be prepared as homogeneous, single phase co-amorphous formulations indicated by the appearance of an amorphous halo in the XRPD diffractograms and a single glass transition temperature (Tg) in the DSC measurements. In addition, the Tgs of the co-amorphous mixtures were significantly increased over those of the individual drugs. The drugs remained chemically stable during the milling process and the co-amorphous formulations were generally physically stable over at least 6 months at 40 °C under dry conditions. The dissolution rate of all co-amorphous drug-amino acid mixtures was significantly increased over that of the respective crystalline and amorphous pure drugs. Amino acids thus appear as promising excipients to solve challenges connected with the stability and dissolution of amorphous drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Stabilization of Telomere G-Quadruplexes Interferes with Human Herpesvirus 6A Chromosomal Integration.

PubMed

Gilbert-Girard, Shella; Gravel, Annie; Artusi, Sara; Richter, Sara N; Wallaschek, Nina; Kaufer, Benedikt B; Flamand, Louis

2017-07-15

Human herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes using a mechanism that remains poorly understood. To achieve a better understanding of the HHV-6A/B integration mechanism, we made use of BRACO-19, a compound that stabilizes G-quadruplex secondary structures and prevents telomere elongation by the telomerase complex. First, we analyzed the folding of telomeric sequences into G-quadruplex structures and their binding to BRACO-19 using G-quadruplex-specific antibodies and surface plasmon resonance. Circular dichroism studies indicate that BRACO-19 modifies the conformation and greatly stabilizes the G-quadruplexes formed in G-rich telomeric DNA. Subsequently we assessed the effects of BRACO-19 on the HHV-6A initial phase of infection. Our results indicate that BRACO-19 does not affect entry of HHV-6A DNA into cells. We next investigated if stabilization of G-quadruplexes by BRACO-19 affected HHV-6A's ability to integrate its genome into host chromosomes. Incubation of telomerase-expressing cells with BRACO-19, such as HeLa and MCF-7, caused a significant reduction in the HHV-6A integration frequency ( P < 0.002); in contrast, BRACO-19 had no effect on HHV-6 integration frequency in U2OS cells that lack telomerase activity and elongate their telomeres through alternative lengthening mechanisms. Our data suggest that the fluidity of telomeres is important for efficient chromosomal integration of HHV-6A and that interference with telomerase activity negatively affects the generation of cellular clones containing integrated HHV-6A. IMPORTANCE HHV-6A/B can integrate their genomes into the telomeres of infected cells. Telomeres consist of repeated hexanucleotides (TTAGGG) of various lengths (up to several kilobases) and end with a single-stranded 3' extension. To avoid recognition and induce a DNA damage response, the single-stranded overhang folds back on itself and forms a telomeric loop (T-loop) or adopts a tertiary structure, referred to as a G-quadruplex. In the current study, we have examined the effects of a G-quadruplex binding and stabilizing agent, BRACO-19, on HHV-6A chromosomal integration. By stabilizing G-quadruplex structures, BRACO-19 affects the ability of the telomerase complex to elongate telomeres. Our results indicate that BRACO-19 reduces the number of clones harboring integrated HHV-6A. This study is the first of its kind and suggests that telomerase activity is essential to restore a functional telomere of adequate length following HHV-6A integration. Copyright © 2017 American Society for Microbiology.

The effects of the mineral phase on C stabilization mechanisms and the microbial community along an eroding slope transect

NASA Astrophysics Data System (ADS)

Doetterl, S.; Opfergelt, S.; Cornelis, J.; Boeckx, P. F.; van oost, K.; Six, J.

2013-12-01

An increasing number of studies show the importance of including soil redistribution processes in understanding carbon (C) dynamics in eroding landscapes. The quality and quantity of soil organic carbon in sloping cropland differs with topographic position. These differences are commonly more visible in the subsoil, while the size and composition of topsoil C pools are similar along the hillslope. The type (plant- or microbial-derived) and quality (level of degradation) of C found in a specific soil fraction depends on the interplay between the temporal dynamic of the specific mechanism and it's strength to protect C from decomposition. Here, we present an analysis that aims to clarify the bio/geo-chemical and mineralogical components involved in stabilizing C at various depths and slope positions and how they affect the microbial community and the degradation of C. For this we analyzed soil samples from different soil depths along a slope transect applying (i) a sequential extraction of the reactive soil phase using pyrophosphate, oxalate and dithionite-citrate-bicarbonate, (ii) a semi-quantitative and qualitative analysis of the clay mineralogy, (iii) an analysis of the microbial community using amino sugars and (iv) an analysis of the level of degradation of C in different soil fractions focusing on the soil Lignin signature. The results show that the pattern of minerals and their relative importance in stabilizing C varies greatly along the transect. In the investigated soils, pyrophosphate extractable Manganese, and not Iron or Aluminum as often observed, is strongly correlated to C in the bulk soil and in the non-aggregated silt and clay fractions. This suggests a certain role of Manganese for C stabilization where physical protection is absent. In contrast, pyrophosphate extractable Iron and Aluminum components are largely abundant in water-stable soil aggregates but not correlated to C, suggesting importance of these extracts to stabilize aggregates and, hence, providing physical protection of C. Oxalate extractable amorphous and poorly crystalline minerals are correlated to C, especially for the more recalcitrant C fractions, but only at the depositional site. However, decreasing contents of oxalate extractable elements with depth indicate a temporal limitation of this stabilization mechanism and this is also supported by the results of our lignin extraction. Non-expandable clay minerals experience a relative enrichment at the depositional site while expandable clay minerals experience the same at the eroding site. These changes in clay mineralogy along the slope are partly responsible for the abundance of silt and clay associated C. The changes in soil mineralogy and micro-scale environmental conditions led to an adaptation of the microbial community in comparison to sites not affected by soil redistribution.

Stressed Stability Techniques for Adjuvant Formulations.

PubMed

Hasija, Manvi; Sheung, Anthony; Rahman, Nausheen; Ausar, Salvador F

2017-01-01

Stressed stability testing is crucial to the understanding of mechanisms of degradation and the effects of external stress factors on adjuvant stability. These studies vastly help the development of stability indicating tests and the selection of stabilizing conditions for long term storage. In this chapter, we provide detailed protocols for the execution of forced degradation experiments that evaluate the robustness of adjuvant formulations against thermal, mechanical, freeze-thawing, and photo stresses.

Multisystemic Therapy for Adolescents with Poorly Controlled Type I Diabetes: Stability of Treatment Effects in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Ellis, Deborah A.; Templin, Thomas; Naar-King, Sylvie; Frey, Maureen A.; Cunningham, Phillippe B.; Podolski, Cheryl-Lynn; Cakan, Nedim

2007-01-01

The primary purpose of the present study was to determine whether multisystemic therapy (MST), an intensive, home-based psychotherapy, improved regimen adherence, metabolic control, and rates of hospitalization for diabetic ketoacidosis (DKA) among adolescents with chronically poorly controlled Type 1 diabetes 6 months after the completion of…

Structure and Mechanical Properties of Al-Cu-Fe-X Alloys with Excellent Thermal Stability.

PubMed

Školáková, Andrea; Novák, Pavel; Mejzlíková, Lucie; Průša, Filip; Salvetr, Pavel; Vojtěch, Dalibor

2017-11-05

In this work, the structure and mechanical properties of innovative Al-Cu-Fe based alloys were studied. We focused on preparation and characterization of rapidly solidified and hot extruded Al-Cu-Fe, Al-Cu-Fe-Ni and Al-Cu-Fe-Cr alloys. The content of transition metals affects mechanical properties and structure. For this reason, microstructure, phase composition, hardness and thermal stability have been investigated in this study. The results showed exceptional thermal stability of these alloys and very good values of mechanical properties. Alloying by chromium ensured the highest thermal stability, while nickel addition refined the structure of the consolidated alloy. High thermal stability of all tested alloys was described in context with the transformation of the quasicrystalline phases to other types of intermetallics.

Structure and Mechanical Properties of Al-Cu-Fe-X Alloys with Excellent Thermal Stability

PubMed Central

Školáková, Andrea; Novák, Pavel; Mejzlíková, Lucie; Průša, Filip; Salvetr, Pavel; Vojtěch, Dalibor

2017-01-01

In this work, the structure and mechanical properties of innovative Al-Cu-Fe based alloys were studied. We focused on preparation and characterization of rapidly solidified and hot extruded Al-Cu-Fe, Al-Cu-Fe-Ni and Al-Cu-Fe-Cr alloys. The content of transition metals affects mechanical properties and structure. For this reason, microstructure, phase composition, hardness and thermal stability have been investigated in this study. The results showed exceptional thermal stability of these alloys and very good values of mechanical properties. Alloying by chromium ensured the highest thermal stability, while nickel addition refined the structure of the consolidated alloy. High thermal stability of all tested alloys was described in context with the transformation of the quasicrystalline phases to other types of intermetallics. PMID:29113096

The Persistence and Stability of Psychiatric Problems in Adolescents with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Simonoff, Emily; Jones, Catherine R. G.; Baird, Gillian; Pickles, Andrew; Happe, Francesca; Charman, Tony

2013-01-01

Background: Psychiatric problems are common in autism spectrum disorders (ASDs), but the reasons are poorly understood. We use a longitudinal population-representative cohort to examine for the first time the persistence of psychiatric problems and to identify risk factors for their occurrence and stability. Methods: Eighty-one 16-year olds (75…

Ceramics breakthrough

NASA Astrophysics Data System (ADS)

Shim, Joon Hyung

2018-03-01

Protonic ceramic fuel cells (PCFCs) are a potential alternative to solid oxide fuel cells at temperatures below 600 °C, but they suffer from low power output and poor chemical stability. Now, PCFCs with a power density of over 500 mW per cm2 at 500 °C and long-term stability are demonstrated using optimized perovskite-based electrolyte and electrodes.

Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

PubMed

Kawakami, Kohsaku

2009-09-01

Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

Evaluation of microstructure stability at the interfaces of Al-6061 welds fabricated using ultrasonic additive manufacturing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sridharan, Niyanth S.; Gussev, Maxim N.; Parish, Chad M.

Here, ultrasonic additive manufacturing (UAM) is a solid-state additive manufacturing process that uses fundamental principles of ultrasonic welding and sequential layering of tapes to fabricate complex three-dimensional (3-D) components. One of the factors limiting the use of this technology is the poor tensile strength along the z-axis. Recent work has demonstrated the improvement of the z-axis properties after post-processing treatments. The abnormally high stability of the grains at the interface during post-weld heat treatments is, however, not yet well understood. In this work we use multiscale characterization to understand the stability of the grains during post-weld heat treatments. Aluminum alloymore » (6061) builds, fabricated using ultrasonic additive manufacturing, were post-weld heat treated at 180, 330 and 580 °C. The grains close to the tape interfaces are stable during post-weld heat treatments at high temperatures (i.e., 580 °C). This is in contrast to rapid grain growth that takes place in the bulk. Transmission electron microscopy and atom-probe tomography display a significant enrichment of oxygen and magnesium near the stable interfaces. Based on the detailed characterization, two mechanisms are proposed and evaluated: nonequilibrium nano-dispersed oxides impeding the grain growth due to grain boundary pinning, or grain boundary segregation of magnesium and oxygen reducing the grain boundary energy.« less

Evaluation of microstructure stability at the interfaces of Al-6061 welds fabricated using ultrasonic additive manufacturing

DOE PAGES

Sridharan, Niyanth S.; Gussev, Maxim N.; Parish, Chad M.; ...

2018-03-06

Here, ultrasonic additive manufacturing (UAM) is a solid-state additive manufacturing process that uses fundamental principles of ultrasonic welding and sequential layering of tapes to fabricate complex three-dimensional (3-D) components. One of the factors limiting the use of this technology is the poor tensile strength along the z-axis. Recent work has demonstrated the improvement of the z-axis properties after post-processing treatments. The abnormally high stability of the grains at the interface during post-weld heat treatments is, however, not yet well understood. In this work we use multiscale characterization to understand the stability of the grains during post-weld heat treatments. Aluminum alloymore » (6061) builds, fabricated using ultrasonic additive manufacturing, were post-weld heat treated at 180, 330 and 580 °C. The grains close to the tape interfaces are stable during post-weld heat treatments at high temperatures (i.e., 580 °C). This is in contrast to rapid grain growth that takes place in the bulk. Transmission electron microscopy and atom-probe tomography display a significant enrichment of oxygen and magnesium near the stable interfaces. Based on the detailed characterization, two mechanisms are proposed and evaluated: nonequilibrium nano-dispersed oxides impeding the grain growth due to grain boundary pinning, or grain boundary segregation of magnesium and oxygen reducing the grain boundary energy.« less

Carbonic Anhydrase Generates CO2 and H+ That Drive Spider Silk Formation Via Opposite Effects on the Terminal Domains

PubMed Central

Otikovs, Martins; Landreh, Michael; Nordling, Kerstin; Kronqvist, Nina; Westermark, Per; Jörnvall, Hans; Knight, Stefan; Ridderstråle, Yvonne; Holm, Lena; Meng, Qing; Jaudzems, Kristaps; Chesler, Mitchell; Johansson, Jan; Rising, Anna

2014-01-01

Spider silk fibers are produced from soluble proteins (spidroins) under ambient conditions in a complex but poorly understood process. Spidroins are highly repetitive in sequence but capped by nonrepetitive N- and C-terminal domains (NT and CT) that are suggested to regulate fiber conversion in similar manners. By using ion selective microelectrodes we found that the pH gradient in the silk gland is much broader than previously known. Surprisingly, the terminal domains respond in opposite ways when pH is decreased from 7 to 5: Urea denaturation and temperature stability assays show that NT dimers get significantly stabilized and then lock the spidroins into multimers, whereas CT on the other hand is destabilized and unfolds into ThT-positive β-sheet amyloid fibrils, which can trigger fiber formation. There is a high carbon dioxide pressure (pCO2) in distal parts of the gland, and a CO2 analogue interacts with buried regions in CT as determined by nuclear magnetic resonance (NMR) spectroscopy. Activity staining of histological sections and inhibition experiments reveal that the pH gradient is created by carbonic anhydrase. Carbonic anhydrase activity emerges in the same region of the gland as the opposite effects on NT and CT stability occur. These synchronous events suggest a novel CO2 and proton-dependent lock and trigger mechanism of spider silk formation. PMID:25093327

Improved Ionic Diffusion through the Mesoporous Carbon Skin on Silicon Nanoparticles Embedded in Carbon for Ultrafast Lithium Storage.

PubMed

An, Geon-Hyoung; Kim, Hyeonjin; Ahn, Hyo-Jin

2018-02-21

Because of their combined effects of outstanding mechanical stability, high electrical conductivity, and high theoretical capacity, silicon (Si) nanoparticles embedded in carbon are a promising candidate as electrode material for practical utilization in Li-ion batteries (LIBs) to replace the conventional graphite. However, because of the poor ionic diffusion of electrode materials, the low-grade ultrafast cycling performance at high current densities remains a considerable challenge. In the present study, seeking to improve the ionic diffusion, we propose a novel design of mesoporous carbon skin on the Si nanoparticles embedded in carbon by hydrothermal reaction, poly(methyl methacrylate) coating process, and carbonization. The resultant electrode offers a high specific discharge capacity with excellent cycling stability (1140 mA h g -1 at 100 mA g -1 after 100 cycles), superb high-rate performance (969 mA h g -1 at 2000 mA g -1 ), and outstanding ultrafast cycling stability (532 mA h g -1 at 2000 mA g -1 after 500 cycles). The battery performances are surpassing the previously reported results for carbon and Si composite-based electrodes on LIBs. Therefore, this novel approach provides multiple benefits in terms of the effective accommodation of large volume expansions of the Si nanoparticles, a shorter Li-ion diffusion pathway, and stable electrochemical conditions from a faster ionic diffusion during cycling.

Improved thermal stability of polylactic acid (PLA) composite film via PLA-β-cyclodextrin-inclusion complex systems.

PubMed

Byun, Youngjae; Rodriguez, Katia; Han, Jung H; Kim, Young Teck

2015-11-01

The effects of the incorporation of PLA-β-cyclodextrin-inclusion complex (IC) and β-cyclodextrin (β-CD) on biopolyester PLA films were investigated. Thermal stability, surface morphology, barrier, and mechanical properties of the films were measured at varying IC (1, 3, 5, and 7%) and β-CD (1 and 5%) concentrations. The PLA-IC-composite films (IC-PLA-CFs) showed uniform morphological structure, while samples containing β-CD (β-CD-PLA-CFs) showed high agglomeration of β-CD due to poor interfacial interaction between β-CD and PLA moieties. According to the thermal property analysis, the 5% IC-PLA-CFs showed 6.6 times lower dimensional changes (6.5%) at the temperature range of 20-80°C than that of pure PLA film (43.0%). The increase of IC or β-CD content in the PLA-composite films shifted the glass transition and crystallization temperature to higher temperature regions. The crystallinity of both composite films improved by increasing IC or β-CD content. Both composite films had higher oxygen and water vapor permeability as IC or β-CD content increased in comparison to pure PLA film. All the composite films had less flexibility and lower tensile strength than the pure PLA film. In conclusion, this study shows that the IC technique is valuable to improve the thermal expansion stability of PLA-based films. Published by Elsevier B.V.

Improving bioactivity of inert bioceramics by a novel Mg-incorporated solution treatment

NASA Astrophysics Data System (ADS)

Dehestani, Mahdi; Zemlyanov, Dmitry; Adolfsson, Erik; Stanciu, Lia A.

2017-12-01

Zirconia/alumina ceramics possess outstanding mechanical properties for dental and orthopedic applications, but due to their poor surface bioactivities they exhibit a weak bone-bonding ability. This work proposes an effective 30-min solution treatment which could successfully induce formation of bone-like apatite on the surface of 3Y-TZP and a ternary composite composed of yttria-stabilized zirconia, ceria-stabilized zirconia, and alumina (35 vol% 3Y-TZP + 35 vol% 12Ce-TZP + 30 vol% Al2O3) after 3 weeks immersion in simulated body fluid (SBF). XRD was used for phase identification in the ceramic materials. The influence of solution treatment on the surface chemistry and its role on apatite formation were investigated via SEM, EDS and XPS. In vitro apatite-forming ability for the solution-treated and untreated samples of the composite and individual substrates of 3Y-TZP, 12Ce-TZP, and Al2O3 was evaluated by immersion in SBF. Apatite crystals were formed only on 3Y-TZP and composite substrates, implying that it is mainly the 3Y-TZP constituent that contributes to the bioactivity of the composite. Further, it was found from the XPS analysis that the zirconia material with higher phase stability (12Ce-TZP) produced less Zrsbnd OH functional groups on its surface after solution treatment which accounts for its weaker bioactivity compared to 3Y-TZP.

Metal-coupled folding as the driving force for the extreme stability of Rad50 zinc hook dimer assembly

NASA Astrophysics Data System (ADS)

Kochańczyk, Tomasz; Nowakowski, Michał; Wojewska, Dominika; Kocyła, Anna; Ejchart, Andrzej; Koźmiński, Wiktor; Krężel, Artur

2016-11-01

The binding of metal ions at the interface of protein complexes presents a unique and poorly understood mechanism of molecular assembly. A remarkable example is the Rad50 zinc hook domain, which is highly conserved and facilitates the Zn2+-mediated homodimerization of Rad50 proteins. Here, we present a detailed analysis of the structural and thermodynamic effects governing the formation and stability (logK12 = 20.74) of this evolutionarily conserved protein assembly. We have dissected the determinants of the stability contributed by the small β-hairpin of the domain surrounding the zinc binding motif and the coiled-coiled regions using peptides of various lengths from 4 to 45 amino acid residues, alanine substitutions and peptide bond-to-ester perturbations. In the studied series of peptides, an >650 000-fold increase of the formation constant of the dimeric complex arises from favorable enthalpy because of the increased acidity of the cysteine thiols in metal-free form and the structural properties of the dimer. The dependence of the enthalpy on the domain fragment length is partially compensated by the entropic penalty of domain folding, indicating enthalpy-entropy compensation. This study facilitates understanding of the metal-mediated protein-protein interactions in which the metal ion is critical for the tight association of protein subunits.

Metal-coupled folding as the driving force for the extreme stability of Rad50 zinc hook dimer assembly

PubMed Central

Kochańczyk, Tomasz; Nowakowski, Michał; Wojewska, Dominika; Kocyła, Anna; Ejchart, Andrzej; Koźmiński, Wiktor; Krężel, Artur

2016-01-01

The binding of metal ions at the interface of protein complexes presents a unique and poorly understood mechanism of molecular assembly. A remarkable example is the Rad50 zinc hook domain, which is highly conserved and facilitates the Zn2+-mediated homodimerization of Rad50 proteins. Here, we present a detailed analysis of the structural and thermodynamic effects governing the formation and stability (logK12 = 20.74) of this evolutionarily conserved protein assembly. We have dissected the determinants of the stability contributed by the small β-hairpin of the domain surrounding the zinc binding motif and the coiled-coiled regions using peptides of various lengths from 4 to 45 amino acid residues, alanine substitutions and peptide bond-to-ester perturbations. In the studied series of peptides, an >650 000-fold increase of the formation constant of the dimeric complex arises from favorable enthalpy because of the increased acidity of the cysteine thiols in metal-free form and the structural properties of the dimer. The dependence of the enthalpy on the domain fragment length is partially compensated by the entropic penalty of domain folding, indicating enthalpy-entropy compensation. This study facilitates understanding of the metal-mediated protein-protein interactions in which the metal ion is critical for the tight association of protein subunits. PMID:27808280

Porous hydrogels from shark skin collagen crosslinked under dense carbon dioxide atmosphere.

PubMed

Fernandes-Silva, Susana; Moreira-Silva, Joana; Silva, Tiago H; Perez-Martin, Ricardo I; Sotelo, Carmen G; Mano, João F; Duarte, Ana Rita C; Reis, Rui L

2013-11-01

The possibility to fabricate marine collagen porous structures crosslinked with genipin under high pressure carbon dioxide is investigated. Collagen from shark skin is used to prepare pre-scaffolds by freeze-drying. The poor stability of the structures and low mechanical properties require crosslinking of the structures. Under dense CO2 atmosphere, crosslinking of collagen pre-scaffolds is allowed for 16 h. Additionally, the hydrogels are foamed and the scaffolds obtained present a highly porous structure. In vitro cell culture tests performed with a chondrocyte-like cell line show good cell adherence and proliferation, which is a strong indication of the potential of these scaffolds to be used in tissue cartilage tissue engineering. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Facile Bottom-Up Approach to Construct Hybrid Flexible Cathode Scaffold for High-Performance Lithium-Sulfur Batteries.

PubMed

Ghosh, Arnab; Manjunatha, Revanasiddappa; Kumar, Rajat; Mitra, Sagar

2016-12-14

Lithium-sulfur batteries mostly suffer from the low utilization of sulfur, poor cycle life, and low rate performances. The prime factors that affect the performance are enormous volume change of the electrode, soluble intermediate product formation, poor electronic and ionic conductivity of S, and end discharge products (i.e., Li 2 S 2 and Li 2 S). The attractive way to mitigate these challenges underlying in the fabrication of a sulfur nanocomposite electrode consisting of different nanoparticles with distinct properties of lithium storage capability, mechanical reinforcement, and ionic as well as electronic conductivity leading to a mechanically robust and mixed conductive (ionic and electronic conductive) sulfur electrode. Herein, we report a novel bottom-up approach to synthesize a unique freestanding, flexible cathode scaffold made of porous reduced graphene oxide, nanosized sulfur, and Mn 3 O 4 nanoparticles, and all are three-dimensionally interconnected to each other by hybrid polyaniline/sodium alginate (PANI-SA) matrix to serve individual purposes. A capacity of 1098 mAh g -1 is achieved against lithium after 200 cycles at a current rate of 2 A g -1 with 97.6% of initial capacity at a same current rate, suggesting the extreme stability and cycling performance of such electrode. Interestingly, with the higher current density of 5 A g -1 , the composite electrode exhibited an initial capacity of 1015 mA h g -1 and retained 71% of the original capacity after 500 cycles. The in situ Raman study confirms the polysulfide absorption capability of Mn 3 O 4 . This work provides a new strategy to design a mechanically robust, mixed conductive nanocomposite electrode for high-performance lithium-sulfur batteries and a strategy that can be used to develop flexible large power storage devices.

Pullout resistance of mechanically stabilized earth wall steel strip reinforcement in uniform aggregate.

DOT National Transportation Integrated Search

2015-11-01

A wide range of reinforcement-backfill combinations have been used in mechanically stabilized earth (MSE) walls. Steel : strips are one type of reinforcement used to stabilize aggregate backfill through anchorage. In the current MSE wall design, pull...

Are ecosystem services stabilized by differences among species? A test using crop pollination.

PubMed

Winfree, Rachael; Kremen, Claire

2009-01-22

Biological diversity could enhance ecosystem service provision by increasing the mean level of services provided, and/or by providing more consistent (stable) services over space and time. Ecological theory predicts that when an ecosystem service is provided by many species, it will be stabilized against disturbance by a variety of 'stabilizing mechanisms.' However, few studies have investigated whether stabilizing mechanisms occur in real landscapes affected by human disturbance. We used two datasets on crop pollination by wild native bees to screen for and differentiate among three stabilizing mechanisms: density compensation (negative co-variance among species' abundances); response diversity (differential response to environmental variables among species); and cross-scale resilience (response to the same environmental variable at different scales by different species). In both datasets, we found response diversity and cross-scale resilience, but not density compensation. We conclude that stabilizing mechanisms may contribute to the stability of pollination services in our study areas, emphasizing the insurance value of seemingly 'redundant' species. Furthermore, the absence of density compensation that we found at the landscape scale contrasts with findings of previous small-scale experimental and modelling work, suggesting that we should not assume that density compensation will stabilize ecosystem services in real landscapes.

Unraveling protein stabilization mechanisms: vitrification and water replacement in a glass transition temperature controlled system.

PubMed

Grasmeijer, N; Stankovic, M; de Waard, H; Frijlink, H W; Hinrichs, W L J

2013-04-01

The aim of this study was to elucidate the role of the two main mechanisms used to explain the stabilization of proteins by sugar glasses during drying and subsequent storage: the vitrification and the water replacement theory. Although in literature protein stability is often attributed to either vitrification or water replacement, both mechanisms could play a role and they should be considered simultaneously. A model protein, alkaline phosphatase, was incorporated in either inulin or trehalose by spray drying. To study the storage stability at different glass transition temperatures, a buffer which acts as a plasticizer, ammediol, was incorporated in the sugar glasses. At low glass transition temperatures (<50°C), the enzymatic activity of the protein strongly decreased during storage at 60°C. Protein stability increased when the glass transition temperature was raised considerably above the storage temperature. This increased stability could be attributed to vitrification. A further increase of the glass transition temperature did not further improve stability. In conclusion, vitrification plays a dominant role in stabilization at glass transition temperatures up to 10 to 20°C above storage temperature, depending on whether trehalose or inulin is used. On the other hand, the water replacement mechanism predominantly determines stability at higher glass transition temperatures. Copyright © 2013 Elsevier B.V. All rights reserved.

Essential Tremor: What We Can Learn from Current Pharmacotherapy.

PubMed

Ondo, William

2016-01-01

The pathophysiology of essential tremor, especially at the cellular level, is poorly understood. Although no drug has been specifically designed to treat essential tremor, several medications improve tremor, and others worsen it. Studying the mechanism of actions of these medications can help our understanding of tremor pathophysiology and contribute to future rational drug design. We reviewed literature, concentrating on mechanisms of action, of various medications that mitigate tremor. Many medications have multiple mechanisms of actions, making simple correlations difficult. Medications that increase the duration of opening of gamma-aminobutyric acid (GABA)-A receptors are most consistently associated with tremor improvement. Interestingly, drugs that increase GABA availability have not been associated with improved tremor. Other mechanisms possibly associated with tremor improvement include antagonism of alpha-2 delta subunits associated with calcium channels, inhibition of carbonic anhydrase, and inhibition of the synaptic vesicle protein 2A. Drugs that block voltage-gaited sodium channels do not affect tremor. The ideal beta-adrenergic blocker requires B2 affinity (non-cardiac selective), has no sympathomimetic properties, does not require membrane stabilization properties, and may benefit from good central nervous system penetration. To date, serendipitous observations have provided most of our understanding of tremor cellular physiology. Based on similarities to currently effective drugs or rational approximations and inferences, several currently available agents should be considered for tremor trials.

Silver nanoparticles in aquatic environments: Physiochemical behavior and antimicrobial mechanisms.

PubMed

Zhang, Chiqian; Hu, Zhiqiang; Deng, Baolin

2016-01-01

Nanosilver (silver nanoparticles or AgNPs) has unique physiochemical properties and strong antimicrobial activities. This paper provides a comprehensive review of the physicochemical behavior (e.g., dissolution and aggregation) and antimicrobial mechanisms of nanosilver in aquatic environments. The inconsistency in calculating the Gibbs free energy of formation of nanosilver [ΔGf(AgNPs)] in aquatic environments highlights the research needed to carefully determine the thermodynamic stability of nanosilver. The dissolutive release of silver ion (Ag(+)) in the literature is often described using a pseudo-first-order kinetics, but the fit is generally poor. This paper proposes a two-stage model that could better predict silver ion release kinetics. The theoretical analysis suggests that nanosilver dissolution could occur under anoxic conditions and that nanosilver may be sulfidized to form silver sulfide (Ag2S) under strict anaerobic conditions, but more investigation with carefully-designed experiments is required to confirm the analysis. Although silver ion release is likely the main antimicrobial mechanism of nanosilver, the contributions of (ion-free) AgNPs and reactive oxygen species (ROS) generation to the overall toxicity of nanosilver must not be neglected. Several research directions are proposed to better understand the dissolution kinetics of nanosilver and its antimicrobial mechanisms under various aquatic environmental conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanism of drug release from polymethacrylate-based extrudates and milled strands prepared by hot-melt extrusion.

PubMed

Albers, Jessica; Alles, Rainer; Matthée, Karin; Knop, Klaus; Nahrup, Julia Schulze; Kleinebudde, Peter

2009-02-01

The aim of the study was the formulation of solid dispersions of the poorly water-soluble drug celecoxib and a polymethacrylate carrier by hot-melt extrusion. The objectives were to elucidate the mechanism of drug release from obtained extrudates and milled strands addicted to the solid-state properties of the solid dispersions and to examine and eliminate stability problems occurring under storage, exposure of mechanical stress, and in vitro dissolution. Transparent extrudates containing up to 60% drug could be prepared with a temperature setting below the melting point of celecoxib. XRPD and DSC measurements indicated the formation of a glassy solid solution, where the drug is molecularly dispersed in the carrier. The amorphous state of the glassy solid solution could be maintained during the exposure of mechanical stress in a milling process, and was stable under storage for at least 6 months. Solid-state properties and SEM images of extrudates after dissolution indicated a carrier-controlled dissolution, whereby the drug is molecularly dispersed within the concentrated carrier layer. The glassy solid solution showed a 58-fold supersaturation in 0.1 N HCl within the first 10 min, which was followed by a recrystallization process. Recrystallization could be inhibited by an external addition of HPMC.

Peripheral Administration of a Long-Acting Peptide Oxytocin Receptor Agonist Inhibits Fear-Induced Freezing.

PubMed

Modi, Meera E; Majchrzak, Mark J; Fonseca, Kari R; Doran, Angela; Osgood, Sarah; Vanase-Frawley, Michelle; Feyfant, Eric; McInnes, Heather; Darvari, Ramin; Buhl, Derek L; Kablaoui, Natasha M

2016-08-01

Oxytocin (OT) modulates the expression of social and emotional behaviors and consequently has been proposed as a pharmacologic treatment of psychiatric diseases, including autism spectrum disorders and schizophrenia; however, endogenous OT has a short half-life in plasma and poor permeability across the blood-brain barrier. Recent efforts have focused on the development of novel drug delivery methods to enhance brain penetration, but few efforts have aimed at improving its half-life. To explore the behavioral efficacy of an OT analog with enhanced plasma stability, we developed PF-06655075 (PF1), a novel non-brain-penetrant OT receptor agonist with increased selectivity for the OT receptor and significantly increased pharmacokinetic stability. PF-06478939 was generated with only increased stability to disambiguate changes to selectivity versus stability. The efficacy of these compounds in evoking behavioral effects was tested in a conditioned fear paradigm. Both central and peripheral administration of PF1 inhibited freezing in response to a conditioned fear stimulus. Peripheral administration of PF1 resulted in a sustained level of plasma concentrations for greater than 20 hours but no detectable accumulation in brain tissue, suggesting that plasma or cerebrospinal fluid exposure was sufficient to evoke behavioral effects. Behavioral efficacy of peripherally administered OT receptor agonists on conditioned fear response opens the door to potential peripheral mechanisms in other behavioral paradigms, whether they are mediated by direct peripheral activation or feed-forward responses. Compound PF1 is freely available as a tool compound to further explore the role of peripheral OT in behavioral response. Copyright © 2016 The Author(s).

Body stability and muscle and motor cortex activity during walking with wide stance

PubMed Central

Farrell, Brad J.; Bulgakova, Margarita A.; Beloozerova, Irina N.; Sirota, Mikhail G.

2014-01-01

Biomechanical and neural mechanisms of balance control during walking are still poorly understood. In this study, we examined the body dynamic stability, activity of limb muscles, and activity of motor cortex neurons [primarily pyramidal tract neurons (PTNs)] in the cat during unconstrained walking and walking with a wide base of support (wide-stance walking). By recording three-dimensional full-body kinematics we found for the first time that during unconstrained walking the cat is dynamically unstable in the forward direction during stride phases when only two diagonal limbs support the body. In contrast to standing, an increased lateral between-paw distance during walking dramatically decreased the cat's body dynamic stability in double-support phases and prompted the cat to spend more time in three-legged support phases. Muscles contributing to abduction-adduction actions had higher activity during stance, while flexor muscles had higher activity during swing of wide-stance walking. The overwhelming majority of neurons in layer V of the motor cortex, 82% and 83% in the forelimb and hindlimb representation areas, respectively, were active differently during wide-stance walking compared with unconstrained condition, most often by having a different depth of stride-related frequency modulation along with a different mean discharge rate and/or preferred activity phase. Upon transition from unconstrained to wide-stance walking, proximal limb-related neuronal groups subtly but statistically significantly shifted their activity toward the swing phase, the stride phase where most of body instability occurs during this task. The data suggest that the motor cortex participates in maintenance of body dynamic stability during locomotion. PMID:24790167

Alanine scan of core positions in ubiquitin reveals links between dynamics, stability, and function

PubMed Central

Lee, Shirley Y.; Pullen, Lester; Virgil, Daniel J.; Castañeda, Carlos A.; Abeykoon, Dulith; Bolon, Daniel N. A.; Fushman, David

2014-01-01

Mutations at solvent inaccessible core positions in proteins can impact function through many biophysical mechanisms including alterations to thermodynamic stability and protein dynamics. As these properties of proteins are difficult to investigate, the impacts of core mutations on protein function are poorly understood for most systems. Here, we determined the effects of alanine mutations at all 15 core positions in ubiquitin on function in yeast. The majority (13 of 15) of alanine substitutions supported yeast growth as the sole ubiquitin. The two null mutants (I30A and L43A) were both less stable to temperature-induced unfolding in vitro than wild-type, but were well folded at physiological temperatures. Heteronuclear NMR studies indicated that the L43A mutation reduces temperature stability while retaining a ground-state structure similar to wild-type. This structure enables L43A to bind to common ubiquitin receptors in vitro. Many of the core alanine ubiquitin mutants, including one of the null variants (I30A), exhibited an increased accumulation of high molecular weight species, suggesting that these mutants caused a defect in the processing of ubiquitin-substrate conjugates. In contrast, L43A exhibited a unique accumulation pattern with reduced levels of high molecular weight species and undetectable levels of free ubiquitin. When conjugation to other proteins was blocked, L43A ubiquitin accumulated as free ubiquitin in yeast. Based on these findings we speculate that ubiquitin's stability to unfolding may be required for efficient recycling during proteasome-mediated substrate degradation. PMID:24361330

Enhanced effect and mechanism of water-in-oil microemulsion as an oral delivery system of hydroxysafflor yellow A

PubMed Central

Qi, Jianping; Zhuang, Jie; Wu, Wei; Lu, Yi; Song, Yunmei; Zhang, Zhetao; Jia, Jia; Ping, Qineng

2011-01-01

Background: A microemulsion is an effective formulation for improving the oral bioavailability of poorly soluble drugs. In this paper, a water-in-oil (w/o) microemulsion was investigated as a system for enhancing the oral bioavailability of Biopharmaceutic Classification System (BCS) III drugs. Methods: The microemulsion formulation was optimized using a pseudoternary phase diagram, comprising propylene glycol dicaprylocaprate (PG), Cremophor® RH40, and water (30/46/24 w/w). Results: The microemulsion increased the oral bioavailability of hydroxysafflor yellow A which was highly water-soluble but very poorly permeable. The relative bioavailability of hydroxysafflor yellow A microemulsion was about 1937% compared with a control solution in bile duct-nonligated rats. However, the microemulsion showed lower enhanced absorption ability in bile duct-ligated rats, and the relative bioavailability was only 181%. In vitro experiments were further employed to study the mechanism of the enhanced effect of the microemulsion. In vitro lipolysis showed that the microemulsion was digested very quickly by pancreatic lipase. About 60% of the microemulsion was digested within 1 hour. Furthermore, the particle size of the microemulsion after digestion was very small (53.3 nm) and the digested microemulsion had high physical stability. An everted gut sac model demonstrated that cumulative transport of the digested microemulsion was significantly higher than that of the diluted microemulsion. Conclusion: These results suggested that digestion of the microemulsion by pancreatic lipase plays an important role in enhancing oral bioavailability of water-soluble drugs. PMID:21720510

Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression.

PubMed

Reineke, Lucas C; Merrick, William C

2009-12-01

Cap-independent initiation of translation is thought to promote protein synthesis on some mRNAs during times when cap-dependent initiation is down-regulated. However, the mechanism of cap-independent initiation is poorly understood. We have previously reported the secondary structure within the yeast minimal URE2 IRES element. In this study, we sought to investigate the mechanism of internal initiation in yeast by assessing the functional role of nucleotides within the minimal URE2 IRES element, and delineating the cis-sequences that modulate levels of internal initiation using a monocistronic reporter vector. Furthermore, we compared the eIF2A sensitivity of the URE2 IRES element with some of the invasive growth IRES elements using DeltaeIF2A yeast. We found that the stability of the stem-loop structure within the minimal URE2 IRES element is not a critical determinant of optimal IRES activity, and the downstream sequences that modulate URE2 IRES-mediated translation can be defined to discrete regions within the URE2 coding region. Repression of internal initiation on the URE2 minimal IRES element by eIF2A is not dependent on the stability of the secondary structure within the URE2 IRES element. Our data also indicate that eIF2A-mediated repression is not specific to the URE2 IRES element, as both the GIC1 and PAB1 IRES elements are repressed by eIF2A. These data provide valuable insights into the mRNA requirements for internal initiation in yeast, and insights into the mechanism of eIF2A-mediated suppression.

Hydrogeomorphic and ecological control on carbonate dissolution in a patterned landscape in South Florida

NASA Astrophysics Data System (ADS)

Dong, X.; Heffernan, J. B.; Murray, A. B.; Cohen, M. J.; Martin, J. B.

2016-12-01

The evolution of the critical zone both shapes and reflects hydrologic, geochemical, and ecological processes. These interactions are poorly understood in karst landscapes with highly soluble bedrock. In this study, we used the regular-dispersed wetland basins of Big Cypress National Preserve in Florida as a focal case to model the hydrologic, geochemical, and biological mechanisms that affect soil development in karst landscapes. We addressed two questions: (1) What is the minimum timescale for wetland basin development, and (2) do changes in soil depth feed back on dissolution processes and if so by what mechanism? We developed an atmosphere-water-soil model with coupled water-solute transport, incorporating major ion equilibria and kinetic non-equilibrium chemistry, and biogenic acid production via roots distributed through the soil horizon. Under current Florida climate, weathering to a depth of 2 m (a typical depth of wetland basins) would take 4000 6000 yrs, suggesting that landscape pattern could have origins as recent as the most recent stabilization of sea level. Our model further illustrates that interactions between ecological and hydrologic processes influence the rate and depth-dependence of weathering. Absent inundation, dissolution rate decreased exponentially with distance from the bedrock to groundwater table. Inundation generally increased bedrock dissolution, but surface water chemistry and residence time produced complex and non-linear effects on dissolution rate. Biogenic acidity accelerated the dissolution rate by 50 and 1,000 times in inundated and exposed soils. Phase portrait analysis indicated that exponential decreases in bedrock dissolution rate with soil depth could produce stable basin depths. Negative feedback between hydro-period and total basin volume could stabilize the basin radius, but the lesser strength of this mechanism may explain the coalescence of wetland basins observed in some parts of the Big Cypress Landscape.

Kinetic mechanism and structural requirements of the amine-catalyzed decarboxylation of oxaloacetic acid.

PubMed

Thalji, Nabil K; Crowe, William E; Waldrop, Grover L

2009-01-02

The kinetic and chemical mechanism of amine-catalyzed decarboxylation of oxaloacetic acid at pH 8.0 has been reevaluated using a new and versatile assay. Amine-catalyzed decarboxylation of oxaloacetic acid proceeds via the formation of an imine intermediate, followed by decarboxylation of the intermediate and hydrolysis to yield pyruvate. The decrease in oxaloacetic acid was coupled to NADH formation by malate dehydrogenase, which allowed the rates of both initial carbinolamine formation (as part of the imination step) and decarboxylation to be determined. By comparing the rates observed for a variety of amines and, in particular, diamines, the structural and electronic requirements for diamine-catalyzed decarboxylation at pH 8.0 were identified. At pH 8.0, monoamines were found to be very poor catalysts, whereas some diamines, most notably ethylenediamine, were excellent catalysts. The results indicate that the second amino group of diamines enhances the rate of imine formation by acting as a proton shuttle during the carbinolamine formation step, which enables diamines to overcome high levels of solvation that would otherwise inhibit carbinolamine, and thus imine, formation. The presence of the second amino group may also enhance the rate of the carbinolamine dehydration step. In contrast to the findings of previous reports, the second amino group participates in the reaction by enhancing the rate of decarboxylation via hydrogen-bonding to the imine nitrogen to either stabilize the negative charge that develops on the imine during decarboxylation or preferentially stabilize the reactive imine over the unreactive enamine tautomer. These results provide insight into the precise catalytic mechanism of several enzymes whose reactions are known to proceed via an imine intermediate.

Fe II/Fe III mixed-valence state induced by Li-insertion into the metal-organic-framework Mil53(Fe): A DFT+U study

NASA Astrophysics Data System (ADS)

Combelles, C.; Ben Yahia, M.; Pedesseau, L.; Doublet, M.-L.

The iron-based metal-organic-framework MIL53(Fe) has recently been tested as a cathode materials for Li-Ion batteries, leading to promising cycling life and rate capability. Despite a poor capacity of 70 mAh g -1 associated with the exchange of almost 0.5Li/Fe, this result is the first evidence of a reversible lithium insertion never observed in a MOF system. In the present study, the MIL53(Fe) redox mechanism is investigated through first-principles DFT+U calculations. The results show that MIL53(Fe) is a weak antiferromagnetic charge transfer insulator at T = 0 K, with iron ions in the high-spin S = 5/2 state. Its reactivity vs elemental lithium is then investigated as a function of lithium composition and distribution over the most probable Li-sites of the MOF structure. The redox mechanism is fully interpreted as a two-step insertion/conversion mechanism, associated with the stabilization of the Fe 3+/Fe 2+ mixed-valence state prior to the complete decomposition of the inorganic-organic interactions within the porous MOF architecture.

Pullout resistance of mechanically stabilized earth wall steel strip reinforcement in uniform aggregate : [technical summary].

DOT National Transportation Integrated Search

2015-11-01

A wide range of reinforcement-backfill combinations have been used in mechanically : stabilized earth (MSE) walls. Steel strips are one type of reinforcement used to stabilize : aggregate backfill through anchorage. In the current MSE wall design, pu...

The Hydromechanics of Vegetation for Slope Stabilization

NASA Astrophysics Data System (ADS)

Mulyono, A.; Subardja, A.; Ekasari, I.; Lailati, M.; Sudirja, R.; Ningrum, W.

2018-02-01

Vegetation is one of the alternative technologies in the prevention of shallow landslide prevention that occurs mostly during the rainy season. The application of plant for slope stabilization is known as bioengineering. Knowledge of the vegetative contribution that can be considered in bioengineering was the hydrological and mechanical aspects (hydromechanical). Hydrological effect of the plant on slope stability is to reduce soil water content through transpiration, interception, and evapotranspiration. The mechanical impact of vegetation on slope stability is to stabilize the slope with mechanical reinforcement of soils through roots. Vegetation water consumption varies depending on the age and density, rainfall factors and soil types. Vegetation with high ability to absorb water from the soil and release into the atmosphere through a transpiration process will reduce the pore water stress and increase slope stability, and vegetation with deep root anchoring and strong root binding was potentially more significant to maintain the stability of the slope.

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs.

PubMed

Censi, Roberta; Di Martino, Piera

2015-10-15

Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations.

Properties of pellets manufactured by wet extrusion/spheronization process using kappa-carrageenan: effect of process parameters.

PubMed

Thommes, Markus; Kleinebudde, Peter

2007-11-09

The aim of this study was to systematically evaluate the pelletization process parameters of kappa-carrageenan-containing formulations. The study dealt with the effect of 4 process parameters--screw speed, number of die holes, friction plate speed, and spheronizer temperature--on the pellet properties of shape, size, size distribution, tensile strength, and drug release. These parameters were varied systematically in a 2(4) full factorial design. In addition, 4 drugs--phenacetin, chloramphenicol, dimenhydrinate, and lidocaine hydrochloride--were investigated under constant process conditions. The most spherical pellets were achieved in a high yield by using a large number of die holes and a high spheronizer speed. There was no relevant influence of the investigated process parameters on the size distribution, mechanical stability, and drug release. The poorly soluble drugs, phenacetin and chloramphenicol, resulted in pellets with adequate shape, size, and tensile strength and a fast drug release. The salts of dimenhydrinate and lidocaine affected pellet shape, mechanical stability, and the drug release properties using an aqueous solution of pH 3 as a granulation liquid. In the case of dimenhydrinate, this was attributed to the ionic interactions with kappa-carrageenan, resulting in a stable matrix during dissolution that did not disintegrate. The effect of lidocaine is comparable to the effect of sodium ions, which suppress the gelling of carrageenan, resulting in pellets with fast disintegration and drug release characteristics. The pellet properties are affected by the process parameters and the active pharmaceutical ingredient used.

AKT Kinase Activity Is Required for Lithium to Modulate Mood-Related Behaviors in Mice

PubMed Central

Pan, Jen Q; Lewis, Michael C; Ketterman, Josh K; Clore, Elizabeth L; Riley, Misha; Richards, Keenan R; Berry-Scott, Erin; Liu, Xiulin; Wagner, Florence F; Holson, Edward B; Neve, Rachael L; Biechele, Travis L; Moon, Randall T; Scolnick, Edward M; Petryshen, Tracey L; Haggarty, Stephen J

2011-01-01

Bipolar disorder (BP) is a debilitating psychiatric disorder, affecting ∼2% of the worldwide population, for which the etiological basis, pathogenesis, and neurocircuitry remain poorly understood. Individuals with BP suffer from recurrent episodes of mania and depression, which are commonly treated with the mood stabilizer lithium. However, nearly half of BP patients do not respond adequately to lithium therapy and the clinically relevant mechanisms of lithium for mood stabilization remain elusive. Here, we modeled lithium responsiveness using cellular assays of glycogen synthase kinase 3 (GSK-3) signaling and mood-related behavioral assays in inbred strains of mice that differ in their response to lithium. We found that activating AKT through phosphosrylation of a key regulatory site (Thr308) was associated with lithium response—activation of signaling pathways downstream of GSK-3 in cells and attenuation of mood-related behaviors in mice—and this response was attenuated by selective and direct inhibition of AKT kinase activity. Conversely, the expression of constitutively active AKT1 in both the cellular and behavioral assays conferred lithium sensitivity. In contrast, selective and direct GSK-3 inhibition by the ATP-competitive inhibitor CHIR99021 bypassed the requirement for AKT activation and modulated behavior in both lithium-responsive and non-responsive mouse strains. These results distinguish the mechanism of action of lithium from direct GSK-3 inhibition both in vivo and in vitro, and highlight the therapeutic potential for selective GSK-3 inhibitors in BP treatment. PMID:21389981

A new twist in the coil: functions of the coiled-coil domain of structural maintenance of chromosome (SMC) proteins.

PubMed

Matityahu, Avi; Onn, Itay

2018-02-01

The higher-order organization of chromosomes ensures their stability and functionality. However, the molecular mechanism by which higher order structure is established is poorly understood. Dissecting the activity of the relevant proteins provides information essential for achieving a comprehensive understanding of chromosome structure. Proteins of the structural maintenance of chromosome (SMC) family of ATPases are the core of evolutionary conserved complexes. SMC complexes are involved in regulating genome dynamics and in maintaining genome stability. The structure of all SMC proteins resembles an elongated rod that contains a central coiled-coil domain, a common protein structural motif in which two α-helices twist together. In recent years, the imperative role of the coiled-coil domain to SMC protein activity and regulation has become evident. Here, we discuss recent advances in the function of the SMC coiled coils. We describe the structure of the coiled-coil domain of SMC proteins, modifications and interactions that are mediated by it. Furthermore, we assess the role of the coiled-coil domain in conformational switches of SMC proteins, and in determining the architecture of the SMC dimer. Finally, we review the interplay between mutations in the coiled-coil domain and human disorders. We suggest that distinctive properties of coiled coils of different SMC proteins contribute to their distinct functions. The discussion clarifies the mechanisms underlying the activity of SMC proteins, and advocates future studies to elucidate the function of the SMC coiled coil domain.

Micromachined silicon acoustic delay line with improved structural stability and acoustic directivity for real-time photoacoustic tomography

NASA Astrophysics Data System (ADS)

Cho, Young; Kumar, Akhil; Xu, Song; Zou, Jun

2017-03-01

Recent studies have shown that micromachined silicon acoustic delay lines can provide a promising solution to achieve real-time photoacoustic tomography without the need for complex transducer arrays and data acquisition electronics. However, as its length increases to provide longer delay time, the delay line becomes more vulnerable to structural instability due to reduced mechanical stiffness. In addition, the small cross-section area of the delay line results in a large acoustic acceptance angle and therefore poor directivity. To address these two issues, this paper reports the design, fabrication, and testing of a new silicon acoustic delay line enhanced with 3D printed polymer micro linker structures. First, mechanical deformation of the silicon acoustic delay line (with and without linker structures) under gravity was simulated by using finite element method. Second, the acoustic crosstalk and acoustic attenuation caused by the polymer micro linker structures were evaluated with both numerical simulation and ultrasound transmission testing. The result shows that the use of the polymer micro linker structures significantly improves the structural stability of the silicon acoustic delay lines without creating additional acoustic attenuation and crosstalk. In addition, a new tapered design for the input terminal of the delay line was also investigate to improve its acoustic directivity by reducing the acoustic acceptance angle. These two improvements are expected to provide an effective solution to eliminate current limitations on the achievable acoustic delay time and out-of-plane imaging resolution of micromachined silicon acoustic delay line arrays.

Climate Change and Poor Water Resource Management Will Have Serious Security Implications in the Balkan Peninsula

DTIC Science & Technology

2015-06-12

develop in the following order: Water Security, Rivers, Agreements, Population, Water Resource Management, Deforestation, History , Threats , and Climate...and political stability. To achieve peace , solutions can be developed through the use of international institutions, signing agreements...influences population, economy, energy, peace , and political stability. Achieveing peaceful solutions must come through the use of international

Security Cooperation Activities: Strengthening a Partner Military and its Governing Institutions

DTIC Science & Technology

2016-05-26

governments suffered from economic instability , corruption, poor rule of law, and low administration of justice. Government and economic stability ...types of programs applied. Conditions defining allied state characteristics are military structure, government polity rating, and economic stability ...regional instability . Dr. Michael Mihalka and Mr. Mark Wilcox covered the trends in liberal democracy in the South Caucasus in light of economic

Raising the cycling stability of aqueous lithium-ion batteries by eliminating oxygen in the electrolyte.

PubMed

Luo, Jia-Yan; Cui, Wang-Jun; He, Ping; Xia, Yong-Yao

2010-09-01

Aqueous lithium-ion batteries may solve the safety problem associated with lithium-ion batteries that use highly toxic and flammable organic solvents, and the poor cycling life associated with commercialized aqueous rechargeable batteries such as lead-acid and nickel-metal hydride systems. But all reported aqueous lithium-ion battery systems have shown poor stability: the capacity retention is typically less than 50% after 100 cycles. Here, the stability of electrode materials in an aqueous electrolyte was extensively analysed. The negative electrodes of aqueous lithium-ion batteries in a discharged state can react with water and oxygen, resulting in capacity fading upon cycling. By eliminating oxygen, adjusting the pH values of the electrolyte and using carbon-coated electrode materials, LiTi(2)(PO(4))(3)/Li(2)SO(4)/LiFePO(4) aqueous lithium-ion batteries exhibited excellent stability with capacity retention over 90% after 1,000 cycles when being fully charged/discharged in 10 minutes and 85% after 50 cycles even at a very low current rate of 8 hours for a full charge/discharge offering an energy storage system with high safety, low cost, long cycling life and appropriate energy density.

Contracts, Vouchers, and Child Care Subsidy Stability: A Preliminary Look at Associations between Subsidy Payment Mechanism and Stability of Subsidy Receipt

ERIC Educational Resources Information Center

Holod, Aleksandra; Johnson, Anna D.; Martin, Anne; Gardner, Margo; Brooks-Gunn, Jeanne

2012-01-01

Background: The federal child care subsidy program, funded through the Child Care and Development Fund (CCDF), is the nation's largest public investment in early child care. However, little is known about whether and how subsidy payment mechanisms relate to the stability of subsidy receipt or the stability of children's care arrangements.…

Robust Trypsin Coating on Electrospun Polymer Nanofibers in Rigorous Conditions and Its Uses for Protein Digestion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Hye-Kyung; Kim, Byoung Chan; Jun, Seung-Hyun

2010-12-15

An efficient protein digestion in proteomic analysis requires the stabilization of proteases such as trypsin. In the present work, trypsin was stabilized in the form of enzyme coating on electrospun polymer nanofibers (EC-TR), which crosslinks additional trypsin molecules onto covalently-attached trypsin (CA-TR). EC-TR showed better stability than CA-TR in rigorous conditions, such as at high temperatures of 40 °C and 50 °C, in the presence of organic co-solvents, and at various pH's. For example, the half-lives of CA-TR and EC-TR were 0.24 and 163.20 hours at 40 ºC, respectively. The improved stability of EC-TR can be explained by covalent-linkages onmore » the surface of trypsin molecules, which effectively inhibits the denaturation, autolysis, and leaching of trypsin. The protein digestion was performed at 40 °C by using both CA-TR and EC-TR in digesting a model protein, enolase. EC-TR showed better performance and stability than CA-TR by maintaining good performance of enolase digestion under recycled uses for a period of one week. In the same condition, CA-TR showed poor performance from the beginning, and could not be used for digestion at all after a few usages. The enzyme coating approach is anticipated to be successfully employed not only for protein digestion in proteomic analysis, but also for various other fields where the poor enzyme stability presently hampers the practical applications of enzymes.« less

The Effect of Core Stability Training on Functional Movement Patterns in Collegiate Athletes.

PubMed

Bagherian, Sajad; Ghasempoor, Khodayar; Rahnama, Nader; Wikstrom, Erik A

2018-02-06

Pre-participation examinations are the standard approach for assessing poor movement quality that would increase musculoskeletal injury risk. However, little is known about how core stability influences functional movement patterns. The primary purpose of this study was to determine the effect of an 8-week core stability program on functional movement patterns in collegiate athletes. The secondary purpose was to determine if the core stability training program would be more effective in those with worse movement quality (i.e. ≤14 baseline FMS score). Quasi-experimental design. Athletic Training Facility. One-hundred collegiate athletes. Functional movement patterns included the Functional Movement Screen (FMS), Lateral step down (LSD) and Y balance test (YBT) and were assessed before and after the 8-week program. Participants were placed into 1 of the 2 groups: intervention and control. The intervention group was required to complete a core stability training program that met 3 times per week for 8-week. Significant group x time interactions demonstrated improvements in FMS, LSD and YBT scores in the experimental group relative to the control group (p<0.001). Independent sample t-tests demonstrate that change scores were larger (greater improvement) for the FMS total score and Hurdle step (p<0.001) in athletes with worse movement quality. An 8-week core stability training program enhances functional movement patterns and dynamic postural control in collegiate athletes. The benefits are more pronounced in collegiate athletes with poor movement quality.

Novel Biocompatible Thermoresponsive Poly(N-vinyl Caprolactam)/Clay Nanocomposite Hydrogels with Macroporous Structure and Improved Mechanical Characteristics.

PubMed

Shi, Kun; Liu, Zhuang; Yang, Chao; Li, Xiao-Ying; Sun, Yi-Min; Deng, Yi; Wang, Wei; Ju, Xiao-Jie; Xie, Rui; Chu, Liang-Yin

2017-07-05

Poly(N-vinyl caprolactam) (PVCL) hydrogels usually suffer from the imporous structure and poor mechanical characteristics as well as the toxicity of cross-linkers, although PVCL itself is biocompatible. In this paper, novel biocompatible thermoresponsive poly(N-vinyl caprolactam)/clay nanocomposite (PVCL-Clay) hydrogels with macroporous structure and improved mechanical characteristics are developed for the first time. The macroporosity in the hydrogel is introduced by using Pickering emulsions as templates, which contain N-vinyl caprolactam (VCL) monomer as dispersed phase and clay sheets as stabilizers at the interface. After polymerization, macropores are formed inside the hydrogels with the residual unreacted VCL droplets as templates. The three-dimensional PVCL polymer networks are cross-linked by the clay nanosheets. Due to the nanocomposite structure, the hydrogel exhibits better mechanical characteristics in comparison to the conventional PVCL hydrogels cross-linked by N,N'-methylene diacrylamide (BIS). The prepared PVCL-Clay hydrogel possesses remarkable temperature-responsive characteristics with a volume phase transition temperature (VPTT) around 35 °C, and provides a feasible platform for cell culture. With macroporous structure and good mechanical characteristics as well as flexible assembly performance, the proposed biocompatible thermoresponsive PVCL-Clay nanocomposite hydrogels are ideal material candidates for biomedical, analytical, and other applications such as entrapment of enzymes, cell culture, tissue engineering, and affinity and displacement chromatography.

Role of clinician's experience and implant design on implant stability. An ex vivo study in artificial soft bones.

PubMed

Romanos, Georgios E; Basha-Hijazi, Abdulaziz; Gupta, Bhumija; Ren, Yan-Fang; Malmstrom, Hans

2014-04-01

Clinical experience in implant placement is important in order to prevent implant failures. However, the implant design affects the primary implant stability (PS) especially in poor quality bones. Therefore, the aim of this study was to compare the effect of clinician surgical experience on PS, when placing different type of implant designs. A total of 180 implants (90 parallel walled-P and 90 tapered-T) were placed in freshly slaughtered cow ribs. Bone quality was evaluated by two examiners during surgery and considered as 'type IV' bone. Implants (ø 5 mm, length: 15 mm, Osseotite, BIOMET 3i, Palm Beach Gardens, FL, USA) were placed by three different clinicians (master/I, good/II, non-experienced/III, under direct supervision of a manufacturer representative; 30 implants/group). An independent observer assessed the accuracy of placement by resonance frequency analysis (RFA) with implant stability quotient (ISQ) values. Two-way analysis of variance (ANOVA) and Tukey's post hoc test were used to detect the surgical experience of the clinicians and their interaction and effects of implant design on the PS. All implants were mechanically stable. The mean ISQ values were: 49.57(± 18.49) for the P-implants and 67.07(± 8.79) for the T-implants. The two-way ANOVA showed significant effects of implant design (p < .0001), clinician (p < .0001), and their interaction (p < .0001). The Tukey's multiple comparison test showed significant differences in RFA for the clinician group I/II (p = .015) and highly significant (p < .0001) between I/III and II/III. The P-implants presented (for I, II, and III) mean ISQ values 31.25/49.18/68.17 and the T-implants showed higher ISQ values, 70.15/62.08/68.98, respectively. Clinicians I and II did not show extreme differences for T-implants (p = .016). In contrast, clinician III achieved high ISQ values using P- and T-implants following the exact surgical protocol based on the manufacturer guidelines. T-implants provided high stability for experienced clinicians compared with P-implants. T-implants achieved greater PS than the P-implants. All clinicians consistently achieved PS; however, experienced clinicians achieved higher ISQ values with T-implants in poor quality bone. © 2012 Wiley Periodicals, Inc.

Oct1 and OCA-B are selectively required for CD4 memory T cell function.

PubMed

Shakya, Arvind; Goren, Alon; Shalek, Alex; German, Cody N; Snook, Jeremy; Kuchroo, Vijay K; Yosef, Nir; Chan, Raymond C; Regev, Aviv; Williams, Matthew A; Tantin, Dean

2015-11-16

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4(+) memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4(+) T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4(+) T cell memory. © 2015 Shakya et al.

Oct1 and OCA-B are selectively required for CD4 memory T cell function

PubMed Central

Shakya, Arvind; Goren, Alon; Shalek, Alex; German, Cody N.; Snook, Jeremy; Kuchroo, Vijay K.; Yosef, Nir; Chan, Raymond C.; Regev, Aviv

2015-01-01

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4+ memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4+ T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4+ T cell memory. PMID:26481684

Quantum Mechanical Approach to Understanding Structural, Electronic and Mechanical Properties of Intermetallics

DTIC Science & Technology

1989-01-26

Understanding Structural , Electronic and Mechanical Properties of Tntermetallics by A.J. Freeman, Principal Investigator ABSTRACT The primary goal of...like LI or Mg would lower EF into the minimum in the DOS and hence stabilize the L1 2 . A. Structural Phase Stability of Titanium Aluminides Most...34 Structural Stability Calculations in the Titanium -Aluminium System", Conf. on Titanium Aluminides , Wright-Patterson Air Force Base, Nov. 1986

Poor readers' retrieval mechanism: efficient access is not dependent on reading skill

PubMed Central

Johns, Clinton L.; Matsuki, Kazunaga; Van Dyke, Julie A.

2015-01-01

A substantial body of evidence points to a cue-based direct-access retrieval mechanism as a crucial component of skilled adult reading. We report two experiments aimed at examining whether poor readers are able to make use of the same retrieval mechanism. This is significant in light of findings that poor readers have difficulty retrieving linguistic information (e.g., Perfetti, 1985). Our experiments are based on a previous demonstration of direct-access retrieval in language processing, presented in McElree et al. (2003). Experiment 1 replicates the original result using an auditory implementation of the Speed-Accuracy Tradeoff (SAT) method. This finding represents a significant methodological advance, as it opens up the possibility of exploring retrieval speeds in non-reading populations. Experiment 2 provides evidence that poor readers do use a direct-access retrieval mechanism during listening comprehension, despite overall poorer accuracy and slower retrieval speeds relative to skilled readers. The findings are discussed with respect to hypotheses about the source of poor reading comprehension. PMID:26528212

Stability of Molasse: TLS for structural analysis in the valley of Gotteron-Fribourg, Switzerland

NASA Astrophysics Data System (ADS)

Ben Hammouda, Mariam; Jaboyedoff, Michel; Derron, Marc Henri; Bouaziz, Samir; Mazotti, Benoit

2016-04-01

The marine molasses of Fribourg (Switzerland) is an area where the cliff collapses and rockfalls are quite frequent and difficult to predict due to this particular lithology, a poorly consolidated greywacke. Because of some recent rockfall events, the situation became critical especially in the valley of Gotteron where a big block has slightly moved down and might destroy a house in case of rupture. The cliff made of jointed sandstone and thin layers of clay and siltstone presents many fractures, joints and massive cross bedding surfaces which increases the possibility of slab failure. This paper presents a detailed structural analysis of the cliff and the identification of the potential failure mechanisms. The methodology is about combining field observation and terrestrial LiDAR scanning point cloud in order to assess the stability of potential slope instabilities of molasses. Three LiDAR scans were done i) to extract discontinuity families depending to the dip and the dip direction of joints and ii) to run kinematic tests in order to identify responsible sets for each potential failure mechanisms. Raw point clouds were processed using IMAlign module of Polyworks and CloudCompare software. The structural analysis based on COLTOP 3D (Jaboyedoff et al. 2007) allowed the identification of four discontinuity sets that were not measured in the field. Two different failure mechanisms have been identified as critical: i) planar sliding which is the main responsible mechanism of the present fallen block and ii) wedge sliding. The planar sliding is defined by the discontinuity sets J1 and J5 with a direction parallel to the slope and with a steep dip angle. The wedges, defined by couples of discontinuity sets, contribute to increase cracks' opening and to the detachment of slabs. The use of TLS combined with field survey provides us a first interpretation of instabilities and a very promising structural analysis.

β-adrenergic receptors reduce the threshold for induction and stabilization of LTP and enhance its magnitude via multiple mechanisms in the ventral but not the dorsal hippocampus.

PubMed

Papaleonidopoulos, Vassilios; Papatheodoropoulos, Costas

2018-05-01

The hippocampus is a functionally heterogeneous structure with the cognitive and emotional signal processing ascribed to the dorsal (DH) and the ventral hippocampus (VH) respectively. However, the underlying mechanisms are poorly understood. Noradrenaline is released in hippocampus during emotional arousal modulating synaptic plasticity and memory consolidation through activation of β adrenergic receptors (β-ARs). Using recordings of field excitatory postsynaptic potentials from the CA1 field of adult rat hippocampal slices we demonstrate that long-term potentiation (LTP) induced either by theta-burst stimulation (TBS) that mimics a physiological firing pattern of hippocampal neurons or by high-frequency stimulation is remarkably more sensitive to β-AR activation in VH than in DH. Thus, pairing of subthreshold primed burst stimulation with activation of β-ARs by their agonist isoproterenol (1 μM) resulted in a reliable induction of NMDA receptor-dependent LTP in the VH without affecting LTP in the DH. Activation of β-ARs by isoproterenol during application of intense TBS increased the magnitude of LTP in both hippocampal segments but facilitated voltage-gated calcium channel-dependent LTP in VH only. Endogenous β-AR activation contributed to the stabilization and the magnitude of LTP in VH but not DH as demonstrated by the effects of the β-ARs antagonist propranolol (10 μM). Exogenous (but not endogenous) β-AR activation strongly increased TBS-induced facilitation of postsynaptic excitability in VH. In DH, isoproterenol only produced a moderate and GABAergic inhibition-dependent enhancement in the facilitation of synaptic burst responses. Paired-pulse facilitation did not change with LTP at any experimental condition suggesting that expression of LTP does not involve presynaptic mechanisms. These findings suggest that β-AR may act as a switch that selectively promotes synaptic plasticity in VH through multiple ways and provide thus a first clue to mechanisms that underlie VH involvement in emotionality. Copyright © 2018 Elsevier Inc. All rights reserved.

ABCB5 promotes melanoma metastasis through enhancing NF-κB p65 protein stability.

PubMed

Wang, Shenghao; Tang, Li; Lin, Junyu; Shen, Zhongliang; Yao, Yikun; Wang, Wei; Tao, Shuai; Gu, Chenjian; Ma, Jie; Xie, Youhua; Liu, Yanfeng

2017-10-07

Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis. ABCB5 positive (ABCB5 + ) malignant melanoma initiating cells (MMICs) display a higher metastatic potential compared with ABCB5 negative (ABCB5 - ) melanoma subpopulation. Knockdown of ABCB5 expression reduces melanoma cell migration and invasion in vitro and melanoma pulmonary metastasis in tumor xenograft mice. ABCB5 and NF-κB p65 expression levels are positively correlated in both melanoma tissues and cell lines. Consequently, ABCB5 activates the NF-κB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro-metastasis factor and provides a potential therapeutic target for melanoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Styrene-Acrylic Sizing on the Mechanical Properties of Carbon Fiber Thermoplastic Towpregs and Their Composites.

PubMed

Bowman, Sean; Jiang, Qiuran; Memon, Hafeezullah; Qiu, Yiping; Liu, Wanshuang; Wei, Yi

2018-03-01

Thermoplastic towpregs are convenient and scalable raw materials for the fabrication of continuous fiber-reinforced thermoplastic matrix composites. In this paper, the potential to employ epoxy and styrene-acrylic sizing agents was evaluated for the making of carbon fiber thermoplastic towpregs via a powder-coating method. The protective effects and thermal stability of these sizing agents were investigated by single fiber tensile test and differential scanning calorimetry (DSC) measurement. The results indicate that the epoxy sizing agent provides better protection to carbon fibers, but it cannot be used for thermoplastic towpreg processing due to its poor chemical stability at high temperature. The bending rigidity of the tows and towpregs with two styrene-acrylic sizing agents was measured by cantilever and Kawabata methods. The styrene-acrylic sized towpregs show low torque values, and are suitable for further processing, such as weaving, preforming, and winding. Finally, composite panels were fabricated directly from the towpregs by hot compression molding. Both of the composite panels show superior flexural strength (>400 MPa), flexural modulus (>63 GPa), and interlaminar shear strength (>27 MPa), indicating the applicability of these two styrene-acrylic sizing agents for carbon fiber thermoplastic towpregs.

Enzyme reactor design under thermal inactivation.

PubMed

Illanes, Andrés; Wilson, Lorena

2003-01-01

Temperature is a very relevant variable for any bioprocess. Temperature optimization of bioreactor operation is a key aspect for process economics. This is especially true for enzyme-catalyzed processes, because enzymes are complex, unstable catalysts whose technological potential relies on their operational stability. Enzyme reactor design is presented with a special emphasis on the effect of thermal inactivation. Enzyme thermal inactivation is a very complex process from a mechanistic point of view. However, for the purpose of enzyme reactor design, it has been oversimplified frequently, considering one-stage first-order kinetics of inactivation and data gathered under nonreactive conditions that poorly represent the actual conditions within the reactor. More complex mechanisms are frequent, especially in the case of immobilized enzymes, and most important is the effect of catalytic modulators (substrates and products) on enzyme stability under operation conditions. This review focuses primarily on reactor design and operation under modulated thermal inactivation. It also presents a scheme for bioreactor temperature optimization, based on validated temperature-explicit functions for all the kinetic and inactivation parameters involved. More conventional enzyme reactor design is presented merely as a background for the purpose of highlighting the need for a deeper insight into enzyme inactivation for proper bioreactor design.

The Galway astronomical Stokes polarimeter: an all-Stokes optical polarimeter with ultra-high time resolution

NASA Astrophysics Data System (ADS)

Collins, Patrick; Kyne, Gillian; Lara, David; Redfern, Michael; Shearer, Andy; Sheehan, Brendan

2013-12-01

Many astronomical objects emit polarised light, which can give information both about their source mechanisms, and about (scattering) geometry in their source regions. To date (mostly) only the linearly polarised components of the emission have been observed in stellar sources. Observations have been constrained because of instrumental considerations to periods of excellent observing conditions, and to steady, slowly or periodically-varying sources. This leaves a whole range of interesting objects beyond the range of observation at present. The Galway Astronomical Stokes Polarimeter (GASP) has been developed to enable us to make observations on these very sources. GASP measures the four components of the Stokes Vector simultaneously over a broad wavelength range 400-800 nm., with a time resolution of order microseconds given suitable detectors and a bright source - this is possible because the optical design contains no moving or modulating components. The initial design of GASP is presented and we include some preliminary observational results demonstrating that components of the Stokes vector can be measured to % in conditions of poor atmospheric stability. Issues of efficiency and stability are addressed. An analysis of suitable astronomical targets, demanding the unique properties of GASP, is also presented.

Enhanced Electrochemical and Thermal Transport Properties of Graphene/MoS2 Heterostructures for Energy Storage: Insights from Multiscale Modeling.

PubMed

Gong, Feng; Ding, Zhiwei; Fang, Yin; Tong, Chuan-Jia; Xia, Dawei; Lv, Yingying; Wang, Bin; Papavassiliou, Dimitrios V; Liao, Jiaxuan; Wu, Mengqiang

2018-05-02

Graphene has been combined with molybdenum disulfide (MoS 2 ) to ameliorate the poor cycling stability and rate performance of MoS 2 in lithium ion batteries, yet the underlying mechanisms remain less explored. Here, we develop multiscale modeling to investigate the enhanced electrochemical and thermal transport properties of graphene/MoS 2 heterostructures (GM-Hs) with a complex morphology. The calculated electronic structures demonstrate the greatly improved electrical conductivity of GM-Hs compared to MoS 2 . Increasing the graphene layers in GM-Hs not only improves the electrical conductivity but also stabilizes the intercalated Li atoms in GM-Hs. It is also found that GM-Hs with three graphene layers could achieve and maintain a high thermal conductivity of 85.5 W/(m·K) at a large temperature range (100-500 K), nearly 6 times that of pure MoS 2 [∼15 W/(m·K)], which may accelerate the heat conduction from electrodes to the ambient. Our quantitative findings may shed light on the enhanced battery performances of various graphene/transition-metal chalcogenide composites in energy storage devices.

DEC1 regulates breast cancer cell proliferation by stabilizing cyclin E protein and delays the progression of cell cycle S phase

PubMed Central

Bi, H; Li, S; Qu, X; Wang, M; Bai, X; Xu, Z; Ao, X; Jia, Z; Jiang, X; Yang, Y; Wu, H

2015-01-01

Breast cancer that is accompanied by a high level of cyclin E expression usually exhibits poor prognosis and clinical outcome. Several factors are known to regulate the level of cyclin E during the cell cycle progression. The transcription factor DEC1 (also known as STRA13 and SHARP2) plays an important role in cell proliferation and apoptosis. Nevertheless, the mechanism of its role in cell proliferation is poorly understood. In this study, using the breast cancer cell lines MCF-7 and T47D, we showed that DEC1 could inhibit the cell cycle progression of breast cancer cells independently of its transcriptional activity. The cell cycle-dependent timing of DEC1 overexpression could affect the progression of the cell cycle through regulating the level of cyclin E protein. DEC1 stabilized cyclin E at the protein level by interacting with cyclin E. Overexpression of DEC1 repressed the interaction between cyclin E and its E3 ligase Fbw7α, consequently reducing the level of polyunbiquitinated cyclin E and increased the accumulation of non-ubiquitinated cyclin E. Furthermore, DEC1 also promoted the nuclear accumulation of Cdk2 and the formation of cyclin E/Cdk2 complex, as well as upregulating the activity of the cyclin E/Cdk2 complex, which inhibited the subsequent association of cyclin A with Cdk2. This had the effect of prolonging the S phase and suppressing the growth of breast cancers in a mouse xenograft model. These events probably constitute the essential steps in DEC1-regulated cell proliferation, thus opening up the possibility of a protein-based molecular strategy for eliminating cancer cells that manifest a high-level expression of cyclin E. PMID:26402517

Mechanical and water barrier properties of isolated soy protein composite edible films as affected by carvacrol and cinnamaldehyde micro and nanoemulsions

USDA-ARS?s Scientific Manuscript database

Edible films may be used in food packaging, for which they must deliver good barrier and mechanical properties. Films based on proteins have good gas barrier and mechanical properties, but poor water barrier properties. Films made from lipids have good water barrier properties, but poor mechanical p...

[Stabilization and long-term effect of chromium contaminated soil].

PubMed

Wang, Jing; Luo, Qi-Shi; Zhang, Chang-Bo; Tan, Liang; Li, Xu

2013-10-01

Short-term (3 d and 28 d) and long-term (1 a) stabilization effects of Cr contaminated soil were investigated through nature curing, using four amendments including ferrous sulfide, ferrous sulfate, zero-valent iron and sodium dithionite. The results indicated that ferrous sulfide and zero-valent iron were not helpful for the stabilization of Cr(VI) when directly used because of their poor solubility and immobility. Ferrous sulfate could effectively and rapidly decrease total leaching Cr and Cr(VI) content. The stabilization effect was further promoted by the generation of iron hydroxides after long-term curing. Sodium dithionite also had positive effect on soil stabilization. Appropriate addition ratio of the two chemicals could help maintain the soil pH in range of 6-8.

Stability of Fluvial and Gravity-flow Antidunes

NASA Astrophysics Data System (ADS)

Fedele, J. J.; Hoyal, D. C. J. D.; Demko, T. M.

2017-12-01

Antidunes develop as a consequence of interface (free surface) deformation and sediment transport feedback in supercritical flows. Fluvial (open-channel flow) antidunes have been studied extensively in the laboratory and the field, and recognized in ancient sedimentary deposits. Experiments on gravity flow (turbidity and density currents) antidunes indicate that they are more stable and long-lived than their fluvial counterpart but the mechanism controlling this stability is poorly understood. Sea floor bathymetric and subsurface data suggest that large-scale, antidune-like sediment waves are extremely common in deep-water, found in a wide range of settings and sediment characteristics. While most of these large features have been interpreted as cyclic steps, the term has been most likely overused due to the lack of recognition criteria and basic understanding on the differences between antidunes and cyclic steps formed under gravity flows. In principle, cyclic steps should be more common in confined or channel-lobe transition settings where flows tend to be more energetic or focused, while antidunes should prevail in regions of less confinement, under sheet-like or expanding flows. Using published, fluvial stable-antidune data, we show that the simplified 1D, mechanical-energy based analysis of flow over a localized fixed obstacle (Long, 1954; Baines, 1995; Kubo and Yokokawa, 2001) is inaccurate for representing flow over antidunes and their stability. Instead, a more detailed analysis of a flow along a long-wavelength (in relation to flow thickness) wavy bed that also considers the interactions between flow and sediment transport is used to infer conditions of antidune stability and the breaking of surface waves. In particular, the position of the surface wave crest in relation to the bedform crest, along with the role of average flow velocity, surface velocity, and surface wave celerity appear relevant in determining antidune instability. The analysis is extended to the case of gravity flow antidunes to explain differences with subaerial antidunes on the basis of the particularities of both velocity and density profiles in these flows. Laboratory experimental data on gravity flow antidunes are used to compare with the theory presented.

Omecamtiv mercabil and blebbistatin modulate cardiac contractility by perturbing the regulatory state of the myosin filament.

PubMed

Kampourakis, Thomas; Zhang, Xuemeng; Sun, Yin-Biao; Irving, Malcolm

2018-01-01

Omecamtiv mecarbil and blebbistatin perturb the regulatory state of the thick filament in heart muscle. Omecamtiv mecarbil increases contractility at low levels of activation by stabilizing the ON state of the thick filament. Omecamtiv mecarbil decreases contractility at high levels of activation by disrupting the acto-myosin ATPase cycle. Blebbistatin reduces contractility by stabilizing the thick filament OFF state and inhibiting acto-myosin ATPase. Thick filament regulation is a promising target for novel therapeutics in heart disease. Contraction of heart muscle is triggered by a transient rise in intracellular free calcium concentration linked to a change in the structure of the actin-containing thin filaments that allows the head or motor domains of myosin from the thick filaments to bind to them and induce filament sliding. It is becoming increasingly clear that cardiac contractility is also regulated through structural changes in the thick filaments, although the molecular mechanisms underlying thick filament regulation are still relatively poorly understood. Here we investigated those mechanisms using small molecules - omecamtiv mecarbil (OM) and blebbistatin (BS) - that bind specifically to myosin and respectively activate or inhibit contractility in demembranated cardiac muscle cells. We measured isometric force and ATP utilization at different calcium and small-molecule concentrations in parallel with in situ structural changes determined using fluorescent probes on the myosin regulatory light chain in the thick filaments and on troponin C in the thin filaments. The results show that BS inhibits contractility and actin-myosin ATPase by stabilizing the OFF state of the thick filament in which myosin head domains are more parallel to the filament axis. In contrast, OM stabilizes the ON state of the thick filament, but inhibits contractility at high intracellular calcium concentration by disrupting the actin-myosin ATPase pathway. The effects of BS and OM on the calcium sensitivity of isometric force and filament structural changes suggest that the co-operativity of calcium activation in physiological conditions is due to positive coupling between the regulatory states of the thin and thick filaments. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Omecamtiv mercabil and blebbistatin modulate cardiac contractility by perturbing the regulatory state of the myosin filament

PubMed Central

Kampourakis, Thomas; Zhang, Xuemeng; Sun, Yin‐Biao

2017-01-01

Key points Omecamtiv mecarbil and blebbistatin perturb the regulatory state of the thick filament in heart muscle.Omecamtiv mecarbil increases contractility at low levels of activation by stabilizing the ON state of the thick filament.Omecamtiv mecarbil decreases contractility at high levels of activation by disrupting the acto‐myosin ATPase cycle.Blebbistatin reduces contractility by stabilizing the thick filament OFF state and inhibiting acto‐myosin ATPase.Thick filament regulation is a promising target for novel therapeutics in heart disease. Abstract Contraction of heart muscle is triggered by a transient rise in intracellular free calcium concentration linked to a change in the structure of the actin‐containing thin filaments that allows the head or motor domains of myosin from the thick filaments to bind to them and induce filament sliding. It is becoming increasingly clear that cardiac contractility is also regulated through structural changes in the thick filaments, although the molecular mechanisms underlying thick filament regulation are still relatively poorly understood. Here we investigated those mechanisms using small molecules – omecamtiv mecarbil (OM) and blebbistatin (BS) – that bind specifically to myosin and respectively activate or inhibit contractility in demembranated cardiac muscle cells. We measured isometric force and ATP utilization at different calcium and small‐molecule concentrations in parallel with in situ structural changes determined using fluorescent probes on the myosin regulatory light chain in the thick filaments and on troponin C in the thin filaments. The results show that BS inhibits contractility and actin‐myosin ATPase by stabilizing the OFF state of the thick filament in which myosin head domains are more parallel to the filament axis. In contrast, OM stabilizes the ON state of the thick filament, but inhibits contractility at high intracellular calcium concentration by disrupting the actin‐myosin ATPase pathway. The effects of BS and OM on the calcium sensitivity of isometric force and filament structural changes suggest that the co‐operativity of calcium activation in physiological conditions is due to positive coupling between the regulatory states of the thin and thick filaments. PMID:29052230

Highly Soluble p-Terphenyl and Fluorene Derivatives as Efficient Dopants in Plastic Scintillators for Sensitive Nuclear Material Detection.

PubMed

Yemam, Henok A; Mahl, Adam; Tinkham, Jonathan S; Koubek, Joshua T; Greife, Uwe; Sellinger, Alan

2017-07-03

Plastic scintillators are commonly used as first-line detectors for special nuclear materials. Current state-of-the-art plastic scintillators based on poly(vinyltoluene) (PVT) matrices containing high loadings (>15.0 wt %) of 2,5-diphenyloxazole (PPO) offer neutron signal discrimination in gamma radiation background (termed pulse shape discrimination, PSD), however, they suffer from poor mechanical properties. In this work, a series of p-terphenyl and fluorene derivatives were synthesized and tested as dopants in PVT based plastic scintillators as possible alternatives to PPO to address the mechanical property issue and to study the PSD mechanism. The derivatives were synthesized from low cost starting materials in high yields using simple chemistry. The photophysical and thermal properties were investigated for their influence on radiation sensitivity/detection performance, and mechanical stability. A direct correlation was found between the melting point of the dopants and the subsequent mechanical properties of the PVT based plastic scintillators. For example, select fluorene derivatives used as dopants produced scintillator samples with mechanical properties exceeding those of the commercial PPO-based scintillators while producing acceptable PSD capabilities. The physical properties of the synthesized dopants were also investigated to examine their effect on the final scintillator samples. Planar derivatives of fluorene were found to be highly soluble in PVT matrices with little to no aggregation induced effects. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Academic and Mental Health Outcomes of Youth Placed in Out-of-Home Care: The Role of School Stability and Engagement

ERIC Educational Resources Information Center

Leonard, Skyler S.; Gudiño, Omar G.

2016-01-01

Background: Youth placed in out-of-home care are at significant risk of low academic achievement and poor mental health. Few studies have considered the potential effects of school-related factors, such as school placement stability and school engagement, on youth outcomes. Objective: The current study examined the potential main effects of school…

Stabilization and delivery approaches for protein and peptide pharmaceuticals: an extensive review of patents.

PubMed

Swain, Suryakanta; Mondal, Debanik; Beg, Sarwar; Patra, Chinam Niranjan; Dinda, Subas Chandra; Sruti, Jammula; Rao, Muddana Eswara Bhanoji

2013-04-01

Proteins and peptides are the building blocks of human body and act as the arsenal to combat against the invading pathogenic organisms for treatment and management of diseases. Majority of such biomacromolecules are synthesized by the human body itself. However, entry of disease causing pathogens causes misleading in the synthesis of desired proteins for antibody formation. In such alarming situations, the delivery of requisite protein and peptide from external source helps in augmenting the body's immunity. The major drawbacks underlying poor biopharmaceutical performance of high molecular weight protein and peptide drugs are due to poor oral absorption, formulation stability, degradation in the gastric milieu, susceptible to presystemic metabolism. Numerous literature recounts the application of myriad drug delivery strategies for the effective delivery of protein and peptides viz. parentral, oral, transdermal, nasal, pulmonary, rectal, buccal and ocular drug delivery systems. There are many reviews on various delivery strategies for protein and peptide pharmaceuticals, but the present review article provides a bird's eye view on various novel drug delivery systems used for enhanced delivery of protein and peptide pharmaceuticals in the light of patent literature. Apart from this, the present manuscript endeavor provides idea on possible causes and major degradation pathways responsible for poor stability of protein and peptide drugs along with recent market instances on them utilizing novel drug delivery systems.

Enhanced Mechanical Stability of Gold Nanotips through Carbon Nanocone Encapsulation

PubMed Central

Cano-Marquez, Abraham G.; Schmidt, Wesller G.; Ribeiro-Soares, Jenaina; Gustavo Cançado, Luiz; Rodrigues, Wagner N.; Santos, Adelina P.; Furtado, Clascidia A.; Autreto, Pedro A.S.; Paupitz, Ricardo; Galvão, Douglas S.; Jorio, Ado

2015-01-01

Gold is a noble metal that, in comparison with silver and copper, has the advantage of corrosion resistance. Despite its high conductivity, chemical stability and biocompatibility, gold exhibits high plasticity, which limits its applications in some nanodevices. Here, we report an experimental and theoretical study on how to attain enhanced mechanical stability of gold nanotips. The gold tips were fabricated by chemical etching and further encapsulated with carbon nanocones via nanomanipulation. Atomic force microscopy experiments were carried out to test their mechanical stability. Molecular dynamics simulations show that the encapsulated nanocone changes the strain release mechanisms at the nanoscale by blocking gold atomic sliding, redistributing the strain along the whole nanostructure. The carbon nanocones are conducting and can induce magnetism, thus opening new avenues on the exploitation of transport, mechanical and magnetic properties of gold covered by sp2 carbon at the nanoscale. PMID:26083864

Dual mechanisms regulate ecosystem stability under decade-long warming and hay harvest

PubMed Central

Shi, Zheng; Xu, Xia; Souza, Lara; Wilcox, Kevin; Jiang, Lifen; Liang, Junyi; Xia, Jianyang; García-Palacios, Pablo; Luo, Yiqi

2016-01-01

Past global change studies have identified changes in species diversity as a major mechanism regulating temporal stability of production, measured as the ratio of the mean to the standard deviation of community biomass. However, the dominant plant functional group can also strongly determine the temporal stability. Here, in a grassland ecosystem subject to 15 years of experimental warming and hay harvest, we reveal that warming increases while hay harvest decreases temporal stability. This corresponds with the biomass of the dominant C4 functional group being higher under warming and lower under hay harvest. As a secondary mechanism, biodiversity also explains part of the variation in temporal stability of production. Structural equation modelling further shows that warming and hay harvest regulate temporal stability through influencing both temporal mean and variation of production. Our findings demonstrate the joint roles that dominant plant functional group and biodiversity play in regulating the temporal stability of an ecosystem under global change. PMID:27302085

A unified mechanism for the stability of surface nanobubbles: contact line pinning and supersaturation.

PubMed

Liu, Yawei; Zhang, Xianren

2014-10-07

In this paper, we apply the molecular dynamics simulation method to study the stability of surface nanobubbles in both pure fluids and gas-liquid mixtures. First, we demonstrate with molecular simulations, for the first time, that surface nanobubbles can be stabilized in superheated or gas supersaturated liquid by the contact line pinning caused by the surface heterogeneity. Then, a unified mechanism for nanobubble stability is put forward here that stabilizing nanobubbles require both the contact line pinning and supersaturation. In the mechanism, the supersaturation refers to superheating for pure fluids and gas supersaturation or superheating for the gas-liquid mixtures, both of which exert the same effect on nanobubble stability. As the level of supersaturation increases, we found a Wenzel or Cassie wetting state for undersaturated and saturated fluids, stable nanobubbles at moderate supersaturation with decreasing curvature radius and contact angle, and finally the liquid-to-vapor phase transition at high supersaturation.

Linear stability analysis of a levitated nanomagnet in a static magnetic field: Quantum spin stabilized magnetic levitation

NASA Astrophysics Data System (ADS)

Rusconi, C. C.; Pöchhacker, V.; Cirac, J. I.; Romero-Isart, O.

2017-10-01

We theoretically study the levitation of a single magnetic domain nanosphere in an external static magnetic field. We show that, apart from the stability provided by the mechanical rotation of the nanomagnet (as in the classical Levitron), the quantum spin origin of its magnetization provides two additional mechanisms to stably levitate the system. Despite the Earnshaw theorem, such stable phases are present even in the absence of mechanical rotation. For large magnetic fields, the Larmor precession of the quantum magnetic moment stabilizes the system in full analogy with magnetic trapping of a neutral atom. For low magnetic fields, the magnetic anisotropy stabilizes the system via the Einstein-de Haas effect. These results are obtained with a linear stability analysis of a single magnetic domain rigid nanosphere with uniaxial anisotropy in a Ioffe-Pritchard magnetic field.

Improving the durability of a drag-reducing nanocoating by enhancing its mechanical stability.

PubMed

Cheng, Mengjiao; Zhang, Songsong; Dong, Hongyu; Han, Shihui; Wei, Hao; Shi, Feng

2015-02-25

The durability of superhydrophobic surface is a major problem to restrict industrial application of superhydrophobic materials from laboratory research, which can be attributed to a more general issue of mechanical stability for superhydrophobic coatings. Therefore, in order to handle this issue, we have fabricated a mechanically stable drag-reducing coating composed of elastic polydimethylsiloxane (PDMS) and hydrophobic copper particles on model ships, which can resist mechanical abrasion and has displayed a durable drag-reducing effect. In comparison with normal Au superhydrophobic coatings, the as-prepared PDMS/copper coatings showed durable drag reduction performance with a similar drag-reducing rate before (26%) and after (24%) mechanical abrasion. The mechanism for the enhanced mechanical stability and maintained drag reduction of the superhydrophobic surfaces was investigated through characterizations of surface morphology, surface wettability, and water adhesive force evaluation before and after abrasion. This is the first demonstration to realize the application of durable drag reduction by improving the mechanical stability of superhydrophobic coatings. We do believe that superhydrophobic surfaces with good resistance to mechanical abrasion or scratching may draw wide attention and gain significant applications with durable drag-reducing properties.

Differential Effects of Hydrophobic Core Packing Residues for Thermodynamic and Mechanical Stability of a Hyperthermophilic Protein.

PubMed

Tych, Katarzyna M; Batchelor, Matthew; Hoffmann, Toni; Wilson, Michael C; Hughes, Megan L; Paci, Emanuele; Brockwell, David J; Dougan, Lorna

2016-07-26

Proteins from organisms that have adapted to environmental extremes provide attractive systems to explore and determine the origins of protein stability. Improved hydrophobic core packing and decreased loop-length flexibility can increase the thermodynamic stability of proteins from hyperthermophilic organisms. However, their impact on protein mechanical stability is not known. Here, we use protein engineering, biophysical characterization, single-molecule force spectroscopy (SMFS), and molecular dynamics (MD) simulations to measure the effect of altering hydrophobic core packing on the stability of the cold shock protein TmCSP from the hyperthermophilic bacterium Thermotoga maritima. We make two variants of TmCSP in which a mutation is made to reduce the size of aliphatic groups from buried hydrophobic side chains. In the first, a mutation is introduced in a long loop (TmCSP L40A); in the other, the mutation is introduced on the C-terminal β-strand (TmCSP V62A). We use MD simulations to confirm that the mutant TmCSP L40A shows the most significant increase in loop flexibility, and mutant TmCSP V62A shows greater disruption to the core packing. We measure the thermodynamic stability (ΔGD-N) of the mutated proteins and show that there is a more significant reduction for TmCSP L40A (ΔΔG = 63%) than TmCSP V62A (ΔΔG = 47%), as might be expected on the basis of the relative reduction in the size of the side chain. By contrast, SMFS measures the mechanical stability (ΔG*) and shows a greater reduction for TmCSP V62A (ΔΔG* = 8.4%) than TmCSP L40A (ΔΔG* = 2.5%). While the impact on the mechanical stability is subtle, the results demonstrate the power of tuning noncovalent interactions to modulate both the thermodynamic and mechanical stability of a protein. Such understanding and control provide the opportunity to design proteins with optimized thermodynamic and mechanical properties.

Displaced clavicle fractures in adolescents: facts, controversies, and current trends.

PubMed

Pandya, Nirav K; Namdari, Surena; Hosalkar, Harish S

2012-08-01

There is an increasing trend toward stabilization and fixation of markedly displaced midshaft clavicle fractures in adolescents. Recent studies in the adult literature have shown a greater prevalence of symptomatic malunion, nonunion, and poor functional outcomes after nonsurgical management of displaced fractures. Fixation of displaced midshaft clavicle fractures can restore length and alignment, resulting in shorter time to union. Symptomatic malunion after significantly displaced fractures in adolescents may be more common than previously thought. Adolescents often have high functional demands, and their remodeling potential is limited. Knowledge of bone biology and the effects of shortening, angulation, and rotation on shoulder girdle mechanics is critical in decision making in order to increase the likelihood of optimal results at skeletal maturity. Selection of fixation is dependent on many factors, including fracture type, patient age, skeletal maturity, and surgeon comfort.

Magnetic studies of nickel hydride nanoparticles embedded in chitosan matrix

NASA Astrophysics Data System (ADS)

Araújo-Barbosa, S.; Morales, M. A.

2017-11-01

In this work we present a method to produce NiH (β-NiH phase) nanoparticles from Ni-Cu solid solution. The reduction of Ni2+ and Cu2+ occurred at high temperatures and in presence of glutaraldehyde, citric acid and chitosan biopolymer. The samples are mainly composed of Ni and NiH phases with particles sizes ranging from 9 to 27 nm. DC magnetization studies reveal the presence of hydrogen-poor nickel hydride phase (α-NiH phase) which enhances the saturation magnetization at temperatures below 50 K. Stability of samples stored in air after 8 months was verified, and thermal treatment at 350 oC in presence of air transformed the samples to Ni and Cu oxides. Furthermore, we present a discussion regarding the mechanism of Ni2+ and Cu2+ chemical reduction.

Preclinical evaluation of biomarkers associated with antitumor activity of MELK inhibitor.

PubMed

Chung, Suyoun; Kijima, Kyoko; Kudo, Aiko; Fujisawa, Yoshiko; Harada, Yosuke; Taira, Akiko; Takamatsu, Naofumi; Miyamoto, Takashi; Matsuo, Yo; Nakamura, Yusuke

2016-04-05

MELK is upregulated in various types of human cancer and is known to be associated with cancer progression, maintenance of stemness, and poor prognosis. OTS167, a MELK kinase inhibitor, shows potent growth-suppressive effect on human tumors in a xenograft model, but the detailed mode of action has not been fully elucidated. In this study, we demonstrate the molecular mechanism of action of MELK inhibitor OTS167 in a preclinical model. OTS167-treated cells caused morphological transformation, induced the differentiation markers, and reduced stem-cell marker expression. Furthermore, we identified DEPDC1, known as an oncogene, as an additional downstream molecule of the MELK signaling pathway. MELK enhanced DEPDC1 phosphorylation and its stability. The expression of MELK and downstream molecules was decreased in OTS167-treated xenograft tumor tissues, which revealed central necrosis and significant growth suppression. Our data should further shed light on the mechanism of action how OTS167 suppresses tumor growth through the inhibition of the MELK signaling pathway and suggest the possibility of biomarkers for the assessment of clinical efficacy.

Preclinical evaluation of biomarkers associated with antitumor activity of MELK inhibitor

PubMed Central

Chung, Suyoun; Kijima, Kyoko; Kudo, Aiko; Fujisawa, Yoshiko; Harada, Yosuke; Taira, Akiko; Takamatsu, Naofumi; Miyamoto, Takashi; Matsuo, Yo; Nakamura, Yusuke

2016-01-01

MELK is upregulated in various types of human cancer and is known to be associated with cancer progression, maintenance of stemness, and poor prognosis. OTS167, a MELK kinase inhibitor, shows potent growth-suppressive effect on human tumors in a xenograft model, but the detailed mode of action has not been fully elucidated. In this study, we demonstrate the molecular mechanism of action of MELK inhibitor OTS167 in a preclinical model. OTS167-treated cells caused morphological transformation, induced the differentiation markers, and reduced stem-cell marker expression. Furthermore, we identified DEPDC1, known as an oncogene, as an additional downstream molecule of the MELK signaling pathway. MELK enhanced DEPDC1 phosphorylation and its stability. The expression of MELK and downstream molecules was decreased in OTS167-treated xenograft tumor tissues, which revealed central necrosis and significant growth suppression. Our data should further shed light on the mechanism of action how OTS167 suppresses tumor growth through the inhibition of the MELK signaling pathway and suggest the possibility of biomarkers for the assessment of clinical efficacy. PMID:26918358

Investigating the Effects of Underplating at Raukumara Peninsula, New Zealand: Insights from DEM Modeling

NASA Astrophysics Data System (ADS)

Farrell, W. C.; Morgan, J.

2017-12-01

It is thought that subcretion and underplating are important processes at subduction zones worldwide. Despite its proposed common occurrence, the physical mechanisms controlling if underplating occurs and the rate of its associated uplift are poorly understood. Basic questions about the tectonic and geomechanical parameters governing subduction channel stability, subcretion, and the rate and shape of associated uplift have proven difficult to answer. In this study we employ the Discrete Element Method (DEM) to address these questions, using the Raukumara Peninsula of New Zealand as the real-world basis of many of our model inputs. Multiple geophysical datasets suggest that the Raukumara Peninsula is underlain by underplated sediments at Moho depths, and these may be responsible for anomalously high rates of uplift in the area. The combined geologic, geophysical, and geodetic data from the region serve to constrain model geometries and boundary conditions, allowing us to test the mechanisms for underplating and upper crustal response. The effects of surface processes and potential for shallow trenchward sliding are also investigated in the modeling effort.

Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis.

PubMed

Di Paolo, Julie A; Huang, Tao; Balazs, Mercedesz; Barbosa, James; Barck, Kai H; Bravo, Brandon J; Carano, Richard A D; Darrow, James; Davies, Douglas R; DeForge, Laura E; Diehl, Lauri; Ferrando, Ronald; Gallion, Steven L; Giannetti, Anthony M; Gribling, Peter; Hurez, Vincent; Hymowitz, Sarah G; Jones, Randall; Kropf, Jeffrey E; Lee, Wyne P; Maciejewski, Patricia M; Mitchell, Scott A; Rong, Hong; Staker, Bart L; Whitney, J Andrew; Yeh, Sherry; Young, Wendy B; Yu, Christine; Zhang, Juan; Reif, Karin; Currie, Kevin S

2011-01-01

Bruton's tyrosine kinase (Btk) is a therapeutic target for rheumatoid arthritis, but the cellular and molecular mechanisms by which Btk mediates inflammation are poorly understood. Here we describe the discovery of CGI1746, a small-molecule Btk inhibitor chemotype with a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 has exquisite selectivity for Btk and inhibits both auto- and transphosphorylation steps necessary for enzyme activation. Using CGI1746, we demonstrate that Btk regulates inflammatory arthritis by two distinct mechanisms. CGI1746 blocks B cell receptor-dependent B cell proliferation and in prophylactic regimens reduces autoantibody levels in collagen-induced arthritis. In macrophages, Btk inhibition abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. Accordingly, in myeloid- and FcγR-dependent autoantibody-induced arthritis, CGI1746 decreases cytokine levels within joints and ameliorates disease. These results provide new understanding of the function of Btk in both B cell- or myeloid cell-driven disease processes and provide a compelling rationale for targeting Btk in rheumatoid arthritis.

Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Junyu; Xia, Hengchuan; Zhou, Jiahai

The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity, but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domainmore » stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif-containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly.« less

LIN28 phosphorylation by MAPK/ERK couples signaling to the post-transcriptional control of pluripotency

PubMed Central

Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Triboulet, Robinson; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Kane, Susan; Gygi, Steven P.; Gregory, Richard I.; Daley, George Q.

2016-01-01

Signaling and post-transcriptional gene control are both critical for the regulation of pluripotency1,2, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein (RBP), has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA (miRNA) biogenesis and direct modulation of mRNA translation3. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells (PSCs), which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced LIN28’s effect on its direct mRNA targets, revealing a mechanism that uncouples LIN28’s let-7-dependent and independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naïve to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signaling, post-transcriptional gene control, and cell fate regulation. PMID:27992407

Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Paolo, Julie A; Huang, Tao; Balazs, Mercedesz

Bruton's tyrosine kinase (Btk) is a therapeutic target for rheumatoid arthritis, but the cellular and molecular mechanisms by which Btk mediates inflammation are poorly understood. Here we describe the discovery of CGI1746, a small-molecule Btk inhibitor chemotype with a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 has exquisite selectivity for Btk and inhibits both auto- and transphosphorylation steps necessary for enzyme activation. Using CGI1746, we demonstrate that Btk regulates inflammatory arthritis by two distinct mechanisms. CGI1746 blocks B cell receptor–dependent B cell proliferation and in prophylactic regimens reduces autoantibody levels in collagen-induced arthritis. In macrophages, Btkmore » inhibition abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. Accordingly, in myeloid- and FcγR-dependent autoantibody-induced arthritis, CGI1746 decreases cytokine levels within joints and ameliorates disease. These results provide new understanding of the function of Btk in both B cell– or myeloid cell–driven disease processes and provide a compelling rationale for targeting Btk in rheumatoid arthritis.« less

Microstructural disintegration in dense hydroxyapatite and hydroxyapatite-coated metal implants

NASA Astrophysics Data System (ADS)

Seo, Dong Seok; Lee, Jong Kook

2007-08-01

Hydroxyapatite (HA) has been widely used as a coating for orthopedic metal implants. An important concern regarding HA coating is its degradation of the biological milieu. In this study, the microstructure of a retrieved HA-coated acetabular cup implanted for four years after total hip arthroplasty (THA) was investigated by field emission scanning electron microscopy. In order to understand the underlying mechanism, of degradation and exfoliation of the HA coating, degradation of phase-pure and dense HA ceramics was also observed by in vitro and in vivo testing. The surface morphology and fracture surfaces of HA ceramics revealed that the dissolution starting at the surface extended inwards resulting in particle loosening and microstructural-level degradation. The dissolution features of HA ceramics were similar to the case of HA coating. It was found that extensive dissolution of the coating occurred and most of the coating disappeared. The majority of the remaining graints were fractured by the intergranular mode, suggesting that grain boundaries should be predominantly dissolved. These observations may explain the mechanism through which the biological stability of the HA coated layer becomes unexpectedly poor.

Valeriana officinalis Dry Plant Extract for Direct Compression: Preparation and Characterization.

PubMed

Gallo, Loreana; Ramírez-Rigo, María Veronica; Piña, Juliana; Palma, Santiago; Allemandi, Daniel; Bucalá, Verónica

2012-01-01

Valeriana officinalis L. (Valerianaceae) is one of the most widely used plants for the treatment of anxiety and insomnia. Usually dry plant extracts, including V. officinalis, are hygroscopic materials with poor physico-mechanical properties that can be directly compressed.A V. officinalis dry extract with moderate hygroscocity is suitable for direct compression, and was obtained by using a simple and economical technique. The V. officinalis fluid extract was oven-dried with colloidal silicon dioxide as a drying adjuvant. The addition of colloidal silicon dioxide resulted in a dry plant extract with good physico-mechanical properties for direct compression and lower hygroscopicity than the dry extract without the carrier. The dry plant extract glass transition temperature was considerably above room temperature (about 72 °C). The colloidal silicon dioxide also produced an antiplasticizing effect, improving the powder's physical stability.The pharmaceutical performance of the prepared V. officinalis dry extract was studied through the design of tablets. The manufactured tablets showed good compactability, friability, hardness, and disintegration time. Those containing a disintegrant (Avicel PH 101) exhibited the best pharmaceutical performance, having the lowest disintegration time of around 40 seconds.

DCAF1 controls T-cell function via p53-dependent and -independent mechanisms.

PubMed

Guo, Zengli; Kong, Qing; Liu, Cui; Zhang, Song; Zou, Liyun; Yan, Feng; Whitmire, Jason K; Xiong, Yue; Chen, Xian; Wan, Yisong Y

2016-01-05

On activation, naive T cells grow in size and enter cell cycle to mount immune response. How the fundamental processes of T-cell growth and cell cycle entry are regulated is poorly understood. Here we report that DCAF1 (Ddb1-cullin4-associated-factor 1) is essential for these processes. The deletion of DCAF1 in T cells impairs their peripheral homeostasis. DCAF1 is upregulated on T-cell receptor activation and critical for activation-induced T-cell growth, cell cycle entry and proliferation. In addition, DCAF1 is required for T-cell expansion and function during anti-viral and autoimmune responses in vivo. DCAF1 deletion leads to a drastic stabilization of p53 protein, which can be attributed to a requirement of DCAF1 for MDM2-mediated p53 poly-ubiquitination. Importantly, p53 deletion rescues the cell cycle entry defect but not the growth defect of DCAF1-deficient cells. Therefore, DCAF1 is vital for T-cell function through p53-dependent and -independent mechanisms.

DCAF1 controls T-cell function via p53-dependent and -independent mechanisms

PubMed Central

Guo, Zengli; Kong, Qing; Liu, Cui; Zhang, Song; Zou, Liyun; Yan, Feng; Whitmire, Jason K.; Xiong, Yue; Chen, Xian; Wan, Yisong Y.

2016-01-01

On activation, naive T cells grow in size and enter cell cycle to mount immune response. How the fundamental processes of T-cell growth and cell cycle entry are regulated is poorly understood. Here we report that DCAF1 (Ddb1–cullin4-associated-factor 1) is essential for these processes. The deletion of DCAF1 in T cells impairs their peripheral homeostasis. DCAF1 is upregulated on T-cell receptor activation and critical for activation-induced T-cell growth, cell cycle entry and proliferation. In addition, DCAF1 is required for T-cell expansion and function during anti-viral and autoimmune responses in vivo. DCAF1 deletion leads to a drastic stabilization of p53 protein, which can be attributed to a requirement of DCAF1 for MDM2-mediated p53 poly-ubiquitination. Importantly, p53 deletion rescues the cell cycle entry defect but not the growth defect of DCAF1-deficient cells. Therefore, DCAF1 is vital for T-cell function through p53-dependent and -independent mechanisms. PMID:26728942

Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Paolo, Julie A.; Huang, Tao; Balazs, Mercedesz

Bruton's tyrosine kinase (Btk) is a therapeutic target for rheumatoid arthritis, but the cellular and molecular mechanisms by which Btk mediates inflammation are poorly understood. Here we describe the discovery of CGI1746, a small-molecule Btk inhibitor chemotype with a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 has exquisite selectivity for Btk and inhibits both auto- and transphosphorylation steps necessary for enzyme activation. Using CGI1746, we demonstrate that Btk regulates inflammatory arthritis by two distinct mechanisms. CGI1746 blocks B cell receptor-dependent B cell proliferation and in prophylactic regimens reduces autoantibody levels in collagen-induced arthritis. In macrophages, Btkmore » inhibition abolishes Fc{gamma}RIII-induced TNF{alpha}, IL-1{beta} and IL-6 production. Accordingly, in myeloid- and Fc{gamma}R-dependent autoantibody-induced arthritis, CGI1746 decreases cytokine levels within joints and ameliorates disease. These results provide new understanding of the function of Btk in both B cell- or myeloid cell-driven disease processes and provide a compelling rationale for targeting Btk in rheumatoid arthritis.« less

Structural basis of Vta1 function in the multi-vesicular body sorting pathway

PubMed Central

Xiao, Junyu; Xia, Hengchuan; Zhou, Jiahai; Azmi, Ishara; Davies, Brian A.; Katzmann, David J.; Xu, Zhaohui

2009-01-01

Summary The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domain stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly. PMID:18194651

Fast dissolution of poorly water soluble drugs from fluidized bed coated nanocomposites: Impact of carrier size.

PubMed

Azad, Mohammad; Moreno, Jacqueline; Bilgili, Ecevit; Davé, Rajesh

2016-11-20

Formation of core-shell nanocomposites of Fenofibrate and Itraconazole, model poorly water soluble drugs, via fluidized bed (FB) coating of their well-stabilized high drug loaded nanosuspensions is investigated. Specifically, the extent of dissolution enhancement, when fine carrier particles (sub-50μm) as opposed to the traditional large carrier particles (>300μm) are used, is examined. This allows testing the hypothesis that greatly increased carrier surface area and more importantly, thinner shell for finer carriers at the same drug loading can significantly increase the dissolution rate when spray-coated nanosuspensions are well-stabilized. Fine sub-50μm lactose (GranuLac ® 200) carrier particles were made fluidizable via dry coating with nano-silica, enabling decreased cohesion, fluidization and subsequent nanosuspension coating. For both drugs, 30% drug loaded suspensions were prepared via wet-stirred media milling using hydroxypropyl methyl cellulose and sodium dodecyl sulfate as stabilizers. The stabilizer concentrations were varied to affect the milled particle size and prepare a stable nanosuspension. The suspensions were FB coated onto hydrophilic nano-silica (M-5P) dry coated sub-50μm lactose (GranuLac ® 200) carrier particles or larger carrier particles of median size >300μm (PrismaLac ® 40). The resulting finer composite powders (sub-100μm) based on GranuLac ® 200 were freely flowing, had high bulk density, and had much faster, immediate dissolution of the poorly water-soluble drugs, in particular for Itraconazole. This is attributed to a much higher specific surface area of the carrier and corresponding thinner coating layer for fine carriers as opposed to those for large carrier particles. Copyright © 2016 Elsevier B.V. All rights reserved.

An adaptive optics imaging system designed for clinical use.

PubMed

Zhang, Jie; Yang, Qiang; Saito, Kenichi; Nozato, Koji; Williams, David R; Rossi, Ethan A

2015-06-01

Here we demonstrate a new imaging system that addresses several major problems limiting the clinical utility of conventional adaptive optics scanning light ophthalmoscopy (AOSLO), including its small field of view (FOV), reliance on patient fixation for targeting imaging, and substantial post-processing time. We previously showed an efficient image based eye tracking method for real-time optical stabilization and image registration in AOSLO. However, in patients with poor fixation, eye motion causes the FOV to drift substantially, causing this approach to fail. We solve that problem here by tracking eye motion at multiple spatial scales simultaneously by optically and electronically integrating a wide FOV SLO (WFSLO) with an AOSLO. This multi-scale approach, implemented with fast tip/tilt mirrors, has a large stabilization range of ± 5.6°. Our method consists of three stages implemented in parallel: 1) coarse optical stabilization driven by a WFSLO image, 2) fine optical stabilization driven by an AOSLO image, and 3) sub-pixel digital registration of the AOSLO image. We evaluated system performance in normal eyes and diseased eyes with poor fixation. Residual image motion with incremental compensation after each stage was: 1) ~2-3 arc minutes, (arcmin) 2) ~0.5-0.8 arcmin and, 3) ~0.05-0.07 arcmin, for normal eyes. Performance in eyes with poor fixation was: 1) ~3-5 arcmin, 2) ~0.7-1.1 arcmin and 3) ~0.07-0.14 arcmin. We demonstrate that this system is capable of reducing image motion by a factor of ~400, on average. This new optical design provides additional benefits for clinical imaging, including a steering subsystem for AOSLO that can be guided by the WFSLO to target specific regions of interest such as retinal pathology and real-time averaging of registered images to eliminate image post-processing.

Math and numeracy in young adults with spina bifida and hydrocephalus.

PubMed

Dennis, Maureen; Barnes, Marcia

2002-01-01

The developmental stability of poor math skill was studied in 31 young adults with spina bifida and hydrocephalus (SBH), a neurodevelopmental disorder involving malformations of the brain and spinal cord. Longitudinally, individuals with poor math problem solving as children grew into adults with poor problem solving and limited functional numeracy. As a group, young adults with SBH had poor computation accuracy, computation speed, problem solving, a ndfunctional numeracy. Computation accuracy was related to a supporting cognitive system (working memory for numbers), and functional numeracy was related to one medical history variable (number of lifetime shunt revisions). Adult functional numeracy, but not functional literacy, was predictive of higher levels of social, personal, and community independence.

Contact Stress and Kinematic Analysis of All-Epiphyseal and Over-the-Top Pediatric Reconstruction Techniques for the Anterior Cruciate Ligament

PubMed Central

McCarthy, Moira M.; Tucker, Scott; Nguyen, Joseph T.; Green, Daniel W.; Imhauser, Carl W.; Cordasco, Frank A.

2014-01-01

Background Anterior cruciate ligament (ACL) injuries are an increasingly recognized problem in the pediatric population. Unfortunately, outcomes with conservative treatment are extremely poor. Furthermore, adult reconstruction techniques may be inappropriate to treat skeletally immature patients due to the risk of physeal complications. “Physeal-sparing” reconstruction techniques exist but their ability to restore knee stability and contact mechanics is not well understood. Purpose (1) To assess the ability of the all-epiphyseal (AE) and over-the-top (OT) reconstructions to restore knee kinematics; (2) to assess whether these reconstructions decrease the high posterior contact stresses seen with ACL deficiency; (3) to determine whether the AE or OT produce abnormal tibiofemoral contact stresses. Hypothesis The AE reconstruction will restore contact mechanics and kinematics similarly to that of the ACL intact knee. Methods Ten fresh-frozen human cadaveric knees were tested using a robotic manipulator. Tibiofemoral motions were recorded with the ACL intact, after sectioning the ACL, and after both reconstructions in each of the 10 specimens. The AE utilized an all-inside technique with tunnels exclusively within the epiphysis and fixed with suspensory cortical fixation devices. The OT had a central and vertical tibial tunnel with an over-the-top femur position and was fixed with staples and posts on both ends. Anterior stability was assessed with 134N anterior force at 0, 15, 30, 60, and 90° of knee flexion. Rotational stability was assessed with combined 8 Nm and 4 Nm of abduction and internal rotation, respectively, at 5, 15, and 30° of knee flexion. Results Both reconstruction techniques offloaded the posterior aspect of the tibial plateau compared to the ACL deficient knee in response to both anterior loads and combined moments as demonstrated by reduced contact stresses in this region at all flexion angles. Compared to the ACL intact condition, both the AE and OT had increased posteromedial contact stresses in response to anterior load at some flexion angles and the OT had increased peripheral posterolateral contact stresses at 15° in response to combined moments. Neither reconstruction completely restored the mid-joint contact stresses. Both reconstruction techniques restored anterior stability at flexion angles less than or equal to 30°. In contrast, neither reconstruction restored anterior stability at 60 and 90° flexion. Both reconstructions restored coupled anterior translation under combined moments. Additionally, the AE over-constrained internal rotation in response to the combined moments by 12% at 15° flexion. Conclusions Both reconstructions provide anterior and rotational stability, and decrease posterior joint contact stresses compared to the ACL deficient knee. However, neither reconstruction restored the contact mechanics and kinematics of the ACL intact knee. Clinical Relevance Since the AE reconstruction has clinical advantages over the OT, our results support the hypothesis that the new AE technique is a potential candidate for use in the skeletally immature athlete. PMID:23613444

The effect of combined mechanism ankle support on postural control of patients with chronic ankle instability.

PubMed

Hadadi, Mohammad; Ebrahimi, Ismaeil; Mousavi, Mohammad Ebrahim; Aminian, Gholamreza; Esteki, Ali; Rahgozar, Mehdi

2017-02-01

Chronic ankle instability is associated with neuromechanical changes and poor postural stability. Despite variety of mechanisms of foot and ankle orthoses, almost none apply comprehensive mechanisms to improve postural control in all subgroups of chronic ankle instability patients. The purpose of this study was to investigate the effect of an ankle support implementing combined mechanisms to improve postural control in chronic ankle instability patients. Cross-sectional study. An ankle support with combined mechanism was designed based on most effective action mechanisms of foot and ankle orthoses. The effect of this orthosis on postural control was evaluated in 20 participants with chronic ankle instability and 20 matched healthy participants. The single-limb stance balance test was measured in both groups with and without the new orthosis using a force platform. The results showed that application of combined mechanism ankle support significantly improved all postural sway parameters in chronic ankle instability patients. There were no differences in means of investigated parameters with and without the orthosis in the healthy group. No statistically significant differences were found in postural sway between chronic ankle instability patients and healthy participants after applying the combined mechanism ankle support. The combined mechanism ankle support is effective in improving static postural control of chronic ankle instability patients to close to the postural sway of healthy individual. the orthosis had no adverse effects on balance performance of healthy individuals. Clinical relevance Application of the combined mechanism ankle support for patients with chronic ankle instability is effective in improving static balance. This may be helpful in reduction of recurrence of ankle sprain although further research about dynamic conditions is needed.

Mechanism of Stabilization of Labile Compounds by Silk Fibroin Proteins

DTIC Science & Technology

2017-04-05

AFRL-AFOSR-VA-TR-2017-0076 Mechanism of Stabilization of Labile Compounds by Silk Fibroin Proteins David Kaplan TRUSTEES OF TUFTS COLEGE INC 169... Proteins 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-14-1-0015 5c.  PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) David Kaplan 5d.  PROJECT NUMBER 5e...objective of this research was to elucidate the fundamental mechanisms by which labile compounds are entrapped and stabilized by silk fibroin protein . The

Cryo-electron Microscopy Reconstruction and Stability Studies of the Wild Type and the R432A Variant of Adeno-associated Virus Type 2 Reveal that Capsid Structural Stability Is a Major Factor in Genome Packaging

PubMed Central

Drouin, Lauren M.; Lins, Bridget; Janssen, Maria; Bennett, Antonette; Chipman, Paul; McKenna, Robert; Chen, Weijun; Muzyczka, Nicholas; Cardone, Giovanni

2016-01-01

ABSTRACT The adeno-associated viruses (AAV) are promising therapeutic gene delivery vectors and better understanding of their capsid assembly and genome packaging mechanism is needed for improved vector production. Empty AAV capsids assemble in the nucleus prior to genome packaging by virally encoded Rep proteins. To elucidate the capsid determinants of this process, structural differences between wild-type (wt) AAV2 and a packaging deficient variant, AAV2-R432A, were examined using cryo-electron microscopy and three-dimensional image reconstruction both at an ∼5.0-Å resolution (medium) and also at 3.8- and 3.7-Å resolutions (high), respectively. The high resolution structures showed that removal of the arginine side chain in AAV2-R432A eliminated hydrogen bonding interactions, resulting in altered intramolecular and intermolecular interactions propagated from under the 3-fold axis toward the 5-fold channel. Consistent with these observations, differential scanning calorimetry showed an ∼10°C decrease in thermal stability for AAV2-R432A compared to wt-AAV2. In addition, the medium resolution structures revealed differences in the juxtaposition of the less ordered, N-terminal region of their capsid proteins, VP1/2/3. A structural rearrangement in AAV2-R432A repositioned the βA strand region under the icosahedral 2-fold axis rather than antiparallel to the βB strand, eliminating many intramolecular interactions. Thus, a single amino acid substitution can significantly alter the AAV capsid integrity to the extent of reducing its stability and possibly rendering it unable to tolerate the stress of genome packaging. Furthermore, the data show that the 2-, 3-, and 5-fold regions of the capsid contributed to producing the packaging defect and highlight a tight connection between the entire capsid in maintaining packaging efficiency. IMPORTANCE The mechanism of AAV genome packaging is still poorly understood, particularly with respect to the capsid determinants of the required capsid-Rep interaction. Understanding this mechanism may aid in the improvement of AAV packaging efficiency, which is currently ∼1:10 (10%) genome packaged to empty capsid in vector preparations. This report identifies regions of the AAV capsid that play roles in genome packaging and that may be important for Rep recognition. It also demonstrates the need to maintain capsid stability for the success of this process. This information is important for efforts to improve AAV genome packaging and will also inform the engineering of AAV capsid variants for improved tropism, specific tissue targeting, and host antibody escape by defining amino acids that cannot be altered without detriment to infectious vector production. PMID:27440903

Dynamics and stability of mechanical systems with follower forces

NASA Technical Reports Server (NTRS)

Herrmann, G.

1971-01-01

A monograph on problems of stability of equilibrium of mechanical systems with follower forces is presented. Concepts of stability and criteria of stability are reviewed briefly, together with means of analytical specification of follower forces. Nondissipative systems with two degrees of freedom are discussed, and destabilizing effects due to various types of dissipative forces both in discrete and continuous systems, are treated. The analyses are accompanied by some quantative experiments and observations on demonstrational laboratory models.

Turbulent transport stabilization by ICRH minority fast ions in low rotating JET ILW L-mode plasmas

NASA Astrophysics Data System (ADS)

Bonanomi, N.; Mantica, P.; Di Siena, A.; Delabie, E.; Giroud, C.; Johnson, T.; Lerche, E.; Menmuir, S.; Tsalas, M.; Van Eester, D.; Contributors, JET

2018-05-01

The first experimental demonstration that fast ion induced stabilization of thermal turbulent transport takes place also at low values of plasma toroidal rotation has been obtained in JET ILW (ITER-like wall) L-mode plasmas with high (3He)-D ICRH (ion cyclotron resonance heating) power. A reduction of the gyro-Bohm normalized ion heat flux and higher values of the normalized ion temperature gradient have been observed at high ICRH power and low NBI (neutral beam injection) power and plasma rotation. Gyrokinetic simulations indicate that ITG (ion temperature gradient) turbulence stabilization induced by the presence of high-energetic 3He ions is the key mechanism in order to explain the experimental observations. Two main mechanisms have been identified to be responsible for the turbulence stabilization: a linear electrostatic wave-fast particle resonance mechanism and a nonlinear electromagnetic mechanism. The dependence of the stabilization on the 3He distribution function has also been studied.

Bring Laws to Life: The Methodology to Ensure Stability and Peace in Vietnam

DTIC Science & Technology

2013-10-31

term solution for the continued transition and growth of Vietnam’s economic markets. 9 3 The current formal legal system in Vietnam certainly...violence and the overthrow of several autocratic governments. The Arab Spring was sparked by poor economic conditions, oppression, and tyranny. Many...resulting in violence and the overthrow of several autocratic governments. The Arab Spring was sparked by poor economic conditions, oppression, and

Problems with Interagency Integration in Contemporary Operations

DTIC Science & Technology

2014-12-04

IBM Center for the Business of Government, 2013. Adobe PDF eBook . Journals Armstrong, Nicholas J., and Corri Zoli. "Post 9/11 Stability... issues are due to poor use of existing doctrine to facilitate integrated planning. Past and current doctrine offers guidelines and principles to direct...sharing, and undefined roles created conflict in civil- military relationships. These issues are due to poor use of existing doctrine to facilitate

Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs: physicochemical and in vitro pharmaceutical investigations.

PubMed

Yasmin, Rokhsana; Tan, Angel; Bremmell, Kristen E; Prestidge, Clive A

2014-09-01

Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH) carrier for oral delivery of poorly water-soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti-inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica-stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre-sized particles (<5 μm). The lyophilized SLH produced approximately 1.5-fold and fivefold increased drug solubilization than the pure drug under nondigesting and digesting conditions, respectively. The feasibility of lyophilization for producing nanostructured SLH formulations with desirable lipid loading and drug solubilization properties for enhanced oral delivery of poorly water-soluble therapeutics is confirmed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Direct NMR Monitoring of Phase Separation Behavior of Highly Supersaturated Nifedipine Solution Stabilized with Hypromellose Derivatives.

PubMed

Ueda, Keisuke; Higashi, Kenjirou; Moribe, Kunikazu

2017-07-03

We investigated the phase separation behavior and maintenance mechanism of the supersaturated state of poorly water-soluble nifedipine (NIF) in hypromellose (HPMC) derivative solutions. Highly supersaturated NIF formed NIF-rich nanodroplets through phase separation from aqueous solution containing HPMC derivative. Dissolvable NIF concentration in the bulk water phase was limited by the phase separation of NIF from the aqueous solution. HPMC derivatives stabilized the NIF-rich nanodroplets and maintained the NIF supersaturation with phase-separated NIF for several hours. The size of the NIF-rich phase was different depending on the HPMC derivatives dissolved in aqueous solution, although the droplet size had no correlation with the time for which NIF supersaturation was maintained without NIF crystallization. HPMC acetate and HPMC acetate succinate (HPMC-AS) effectively maintained the NIF supersaturation containing phase-separated NIF compared with HPMC. Furthermore, HPMC-AS stabilized NIF supersaturation more effectively in acidic conditions. Solution 1 H NMR measurements of NIF-supersaturated solution revealed that HPMC derivatives distributed into the NIF-rich phase during the phase separation of NIF from the aqueous solution. The hydrophobicity of HPMC derivative strongly affected its distribution into the NIF-rich phase. Moreover, the distribution of HPMC-AS into the NIF-rich phase was promoted at lower pH due to the lower aqueous solubility of HPMC-AS. The distribution of a large amount of HPMC derivatives into NIF-rich phase induced the strong inhibition of NIF crystallization from the NIF-rich phase. Polymer distribution into the drug-rich phase directly monitored by solution NMR technique can be a useful index for the stabilization efficiency of drug-supersaturated solution containing a drug-rich phase.

Genotype-property patient-phenotype relations suggest that proteome exhaustion can cause amyotrophic lateral sclerosis.

PubMed

Kepp, Kasper P

2015-01-01

Late-onset neurodegenerative diseases remain poorly understood as search continues for the perceived pathogenic protein species. Previously, variants in Superoxide Dismutase 1 (SOD1) causing Amyotrophic Lateral Sclerosis (ALS) were found to destabilize and reduce net charge, suggesting a pathogenic aggregation mechanism. This paper reports analysis of compiled patient data and experimental and computed protein properties for variants of human SOD1, a major risk factor of ALS. Both stability and reduced net charge correlate significantly with disease, with larger significance than previously observed. Using two independent methods and two data sets, a probability < 3% (t-statistical test) is found that ALS-causing mutations share average stability with all possible 2907 SOD1 mutations. Most importantly, un-weighted patient survival times correlate strongly with the misfolded/unfolded protein copy number, expressed as an exponential function of the experimental stabilities (R2 = 0.31, p = 0.002), and this phenotype is further aggravated by charge (R2 = 0.51, p = 1.8 x 10-5). This finding suggests that disease relates to the copy number of misfolded proteins. Exhaustion of motor neurons due to expensive protein turnover of misfolded protein copies is consistent with the data but can further explain e.g. the expression-dependence of SOD1 pathogenicity, the lack of identification of a molecular toxic mode, elevated SOD1 mRNA levels in sporadic ALS, bioenergetic effects and increased resting energy expenditure in ALS patients, genetic risk factors affecting RNA metabolism, and recent findings that a SOD1 mutant becomes toxic when proteasome activity is recovered after washout of a proteasome inhibitor. Proteome exhaustion is also consistent with energy-producing mitochondria accumulating at the neuromuscular junctions where ALS often initiates. If true, this exhaustion mechanism implies a complete change of focus in treatment of ALS towards actively nursing the energy state and protein turnover of the motor neurons.

Stabilization mechanism of γ-Mg17Al12 and β-Mg2Al3 complex metallic alloys

NASA Astrophysics Data System (ADS)

Vrtnik, S.; Jazbec, S.; Jagodič, M.; Korelec, A.; Hosnar, L.; Jagličić, Z.; Jeglič, P.; Feuerbacher, M.; Mizutani, U.; Dolinšek, J.

2013-10-01

Large-unit-cell complex metallic alloys (CMAs) frequently achieve stability by lowering the kinetic energy of the electron system through formation of a pseudogap in the electronic density of states (DOS) across the Fermi energy ɛF. By employing experimental techniques that are sensitive to the electronic DOS in the vicinity of ɛF, we have studied the stabilization mechanism of two binary CMA phases from the Al-Mg system: the γ-Mg17Al12 phase with 58 atoms in the unit cell and the β-Mg2Al3 phase with 1178 atoms in the unit cell. Since the investigated alloys are free from transition metal elements, orbital hybridization effects must be small and we were able to test whether the alloys obey the Hume-Rothery stabilization mechanism, where a pseudogap in the DOS is produced by the Fermi surface-Brillouin zone interactions. The results have shown that the DOS of the γ-Mg17Al12 phase exhibits a pronounced pseudogap centered almost exactly at ɛF, which is compatible with the theoretical prediction that this phase is stabilized by the Hume-Rothery mechanism. The disordered cubic β-Mg2Al3 phase is most likely entropically stabilized at high temperatures, whereas at lower temperatures stability is achieved by undergoing a structural phase transition to more ordered rhombohedral β‧ phase at 214 ° C, where all atomic sites become fully occupied. No pseudogap in the vicinity of ɛF was detected for the β‧ phase on the energy scale of a few 100 meV as determined by the ‘thermal observation window’ of the Fermi-Dirac function, so that the Hume-Rothery stabilization mechanism is not confirmed for this compound. However, the existence of a much broader shallow pseudogap due to several critical reciprocal lattice vectors \\buildrel{\\rightharpoonup}\\over{G} that simultaneously satisfy the Hume-Rothery interference condition remains the most plausible stabilization mechanism of this phase. At Tc = 0.85 K, the β‧ phase undergoes a superconducting transition, which slightly increases the cohesive energy and may contribute to relative stability of this phase against competing neighboring phases.

Site-to-site interdomain communication may mediate different loss-of-function mechanisms in a cancer-associated NQO1 polymorphism

NASA Astrophysics Data System (ADS)

Medina-Carmona, Encarnación; Neira, Jose L.; Salido, Eduardo; Fuchs, Julian E.; Palomino-Morales, Rogelio; Timson, David J.; Pey, Angel L.

2017-03-01

Disease associated genetic variations often cause intracellular enzyme inactivation, dysregulation and instability. However, allosteric communication of mutational effects to distant functional sites leading to loss-of-function remains poorly understood. We characterize here interdomain site-to-site communication by which a common cancer-associated single nucleotide polymorphism (c.C609T/p.P187S) reduces the activity and stability in vivo of NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a FAD-dependent, two-domain multifunctional stress protein acting as a Phase II enzyme, activating cancer pro-drugs and stabilizing p53 and p73α oncosuppressors. We show that p.P187S causes structural and dynamic changes communicated to functional sites far from the mutated site, affecting the FAD binding site located at the N-terminal domain (NTD) and accelerating proteasomal degradation through dynamic effects on the C-terminal domain (CTD). Structural protein:protein interaction studies reveal that the cancer-associated polymorphism does not abolish the interaction with p73α, indicating that oncosuppressor destabilization largely mirrors the low intracellular stability of p.P187S. In conclusion, we show how a single disease associated amino acid change may allosterically perturb several functional sites in an oligomeric and multidomain protein. These results have important implications for the understanding of loss-of-function genetic diseases and the identification of novel structural hot spots as targets for pharmacological intervention.

Antitumor efficacy and tolerability of systemically administered gallium acetylacetonate-loaded gelucire-stabilized nanoparticles.

PubMed

Wehrung, Daniel; Bi, Lipeng; Geldenhuys, Werner J; Oyewumi, Moses O

2013-06-01

The widespread clinical success with most gallium compounds in cancer therapy is markedly hampered by lack of tumor specific accumulation, poor tumor permeability and undesirable toxicity to healthy tissues. The aim of this work was to investigate for the first time antitumor mechanism of a new gallium compound (gallium acetylacetonate; GaAcAc) while assessing effectiveness of gelucire-stabilized nanoparticles (NPs) for potential application in gallium-based lung cancer therapy. NPs loaded with GaAcAc (Ga-NPs) were prepared using mixtures of cetyl alcohol with Gelucire 44/14 (Ga-NP-1) or Gelucire 53/13 (Ga-NP-2) as matrix materials. Of special note from this work is the direct evidence of involvement of microtubule disruption in antitumor effects of GaAcAc on human lung adenocarcinoma (A549). In-vivo tolerability studies were based on plasma ALT, creatinine levels and histopathological examination of tissues. The superior in-vivo antitumor efficacy of Ga-NPs over GaAcAc was depicted in marked reduction of tumor weight and tumor volume as well as histological assessment of excised tumors. Compared to free GaAcAc, Ga-NPs showed a 3-fold increase in tumor-to-blood gallium concentrations with minimized overall exposure to healthy tissues. Overall, enhancement of antitumor effects of GaAcAc by gelucire-stabilized NPs coupled with reduced exposure of healthy tissues to gallium would likely ensure desired therapeutic outcomes and safety of gallium-based cancer treatment.

Stress- and Rho-activated ZO-1–associated nucleic acid binding protein binding to p21 mRNA mediates stabilization, translation, and cell survival

PubMed Central

Nie, Mei; Balda, Maria S.; Matter, Karl

2012-01-01

A central component of the cellular stress response is p21WAF1/CIP1, which regulates cell proliferation, survival, and differentiation. Inflammation and cell stress often up-regulate p21 posttranscriptionally by regulatory mechanisms that are poorly understood. ZO-1–associated nucleic acid binding protein (ZONAB)/DbpA is a Y-box transcription factor that is regulated by components of intercellular junctions that are affected by cytokines and tissue damage. We therefore asked whether ZONAB activation is part of the cellular stress response. Here, we demonstrate that ZONAB promotes cell survival in response to proinflammatory, hyperosmotic, and cytotoxic stress and that stress-induced ZONAB activation involves the Rho regulator GEF-H1. Unexpectedly, stress-induced ZONAB activation does not stimulate ZONAB’s activity as a transcription factor but leads to the posttranscriptional up-regulation of p21 protein and mRNA. Up-regulation is mediated by ZONAB binding to specific sites in the 3′-untranslated region of the p21 mRNA, resulting in mRNA stabilization and enhanced translation. Binding of ZONAB to mRNA is activated by GEF-H1 via Rho stimulation and also mediates Ras-induced p21 expression. We thus identify a unique type of stress and Rho signaling activated pathway that drives mRNA stabilization and translation and links the cellular stress response to p21 expression and cell survival. PMID:22711822

Cargo-shell and cargo-cargo couplings govern the mechanics of artificially loaded virus-derived cages

NASA Astrophysics Data System (ADS)

Llauró, Aida; Luque, Daniel; Edwards, Ethan; Trus, Benes L.; Avera, John; Reguera, David; Douglas, Trevor; Pablo, Pedro J. De; Castón, José R.

2016-04-01

Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers' stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo-shell and cargo-cargo interactions on shell stability after encapsulating two types of proteinaceous payloads. While bound cargo to the inner capsid surface mechanically reinforced the capsid in a structural manner, unbound cargo diffusing freely within the shell cavity pressurized the cages up to ~30 atm due to steric effects. Strong cargo-cargo coupling reduces the resilience of these nanocompartments in ~20% when bound to the shell. Understanding the stability of artificially loaded nanocages will help to design more robust and durable molecular nanocontainers.Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers' stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo-shell and cargo-cargo interactions on shell stability after encapsulating two types of proteinaceous payloads. While bound cargo to the inner capsid surface mechanically reinforced the capsid in a structural manner, unbound cargo diffusing freely within the shell cavity pressurized the cages up to ~30 atm due to steric effects. Strong cargo-cargo coupling reduces the resilience of these nanocompartments in ~20% when bound to the shell. Understanding the stability of artificially loaded nanocages will help to design more robust and durable molecular nanocontainers. Electronic supplementary information (ESI) available: 6 figures, 3 tables and theory. See DOI: 10.1039/c6nr01007e

Homogenizing and diversifying effects of intensive agricultural land-use on plant species beta diversity in Central Europe - A call to adapt our conservation measures

Treesearch

Constanze Buhk; Martin Alt; Manuel J. Steinbauer; Carl Beierkuhnlein; Steve Warren; Anke Jentsch

2017-01-01

The prevention of biodiversity loss in agricultural landscapes to protect ecosystem stability and functions is of major importance to stabilize overall diversity. Intense agriculture leads to a loss in species richness and homogenization of species pools, but the processes behind are poorly understood due to a lack of systematic case studies: The specific...

Stabilization and Anomalous Hydration of Collagen Fibril under Heating

PubMed Central

Gevorkian, Sasun G.; Allahverdyan, Armen E.; Gevorgyan, David S.; Simonian, Aleksandr L.; Hu, Chin-Kun

2013-01-01

Background Type I collagen is the most common protein among higher vertebrates. It forms the basis of fibrous connective tissues (tendon, chord, skin, bones) and ensures mechanical stability and strength of these tissues. It is known, however, that separate triple-helical collagen macromolecules are unstable at physiological temperatures. We want to understand the mechanism of collagen stability at the intermolecular level. To this end, we study the collagen fibril, an intermediate level in the collagen hierarchy between triple-helical macromolecule and tendon. Methodology/Principal Finding When heating a native fibril sample, its Young’s modulus decreases in temperature range 20–58°C due to partial denaturation of triple-helices, but it is approximately constant at 58–75°C, because of stabilization by inter-molecular interactions. The stabilization temperature range 58–75°C has two further important features: here the fibril absorbs water under heating and the internal friction displays a peak. We relate these experimental findings to restructuring of collagen triple-helices in fibril. A theoretical description of the experimental results is provided via a generalization of the standard Zimm-Bragg model for the helix-coil transition. It takes into account intermolecular interactions of collagen triple-helices in fibril and describes water adsorption via the Langmuir mechanism. Conclusion/Significance We uncovered an inter-molecular mechanism that stabilizes the fibril made of unstable collagen macromolecules. This mechanism can be relevant for explaining stability of collagen. PMID:24244320

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xue, Teng; Lin, Zhaoyang; Chiu, Chin-Yi

Metallic nanoparticles are emerging as an exciting class of heterogeneous catalysts with the potential advantages of exceptional activity, stability, recyclability, and easier separation than homogeneous catalysts. The traditional colloid nanoparticle syntheses usually involve strong surface binding ligands that could passivate the surface active sites and result in poor catalytic activity. The subsequent removal of surface ligands could reactivate the surface but often leads to metal ion leaching and/or severe Ostwald ripening with diminished catalytic activity or poor stability. Molecular ligand engineering represents a powerful strategy for the design of homogeneous molecular catalysts but is insufficiently explored for nanoparticle catalysts tomore » date. We report a systematic investigation on molecular ligand modulation of palladium (Pd) nanoparticle catalysts. Our studies show that β-functional groups of butyric acid ligand on Pd nanoparticles can significantly modulate the catalytic reaction process to modify the catalytic activity and stability for important aerobic reactions. With a β-hydroxybutyric acid ligand, the Pd nanoparticle catalysts exhibit exceptional catalytic activity and stability with an unsaturated turnover number (TON) >3000 for dehydrogenative oxidation of cyclohexenone to phenol, greatly exceeding that of homogeneous Pd(II) catalysts (TON, ~30). This study presents a systematic investigation of molecular ligand modulation of nanoparticle catalysts and could open up a new pathway toward the design and construction of highly efficient and robust heterogeneous catalysts through molecular ligand engineering.« less

First-principles study on the stability and magnetoelectric properties of multiferroic materials XTiO3 (X = Mn, Fe, Co, Ni)

NASA Astrophysics Data System (ADS)

Chen, Xing-Yuan; Lai, Guo-Xia; Gu, Di; Zhu, Wei-Ling; Lai, Tian-Shu; Zhao, Yu-Jun

2018-04-01

The XTiO3 (X = Mn, Fe, Co and Ni) materials with R3c structure could be grown under critical conditions based on first-principles calculations and thermodynamic stability analysis. FeTiO3 and MnTiO3 could be synthesized relatively easily under metal-rich and O-poor conditions, while NiTiO3 could be stable under Ni-rich, O-rich and Ti-poor conditions. The predicted R3c CoTiO3 under thermodynamic equilibrium conditions is suggested to be synthesized under Co-rich, O-rich and Ti-poor conditions, but the calculated phonon dispersion indicates R3c CoTiO3 becomes unstable under the dynamical conditions. The ferroelectric behavior in the XTiO3 (X = Mn, Fe, Co and Ni) system could be dominated by the Ti ion with d0 state and the strong hybridization between Ti and O, while the magnetic property is mainly caused by the contribution of 3d transition metal.

Analysis of Motorcycle Weave Mode by using Energy Flow Method

NASA Astrophysics Data System (ADS)

Marumo, Yoshitaka; Katayama, Tsuyoshi

The activation mechanism of motorcycle weave mode is clarified within the framework of the energy flow method, which calculates energy flow of mechanical forces in each motion. It is demonstrated that only a few mechanical forces affect the stability of the weave mode from among a total of about 40 mechanical forces. The activation of the lateral, yawing and rolling motions destabilize the weave mode, while activation of the steering motion stabilizes the weave mode. A detailed investigation of the energy flow of the steering motion reveals that the steering motion plays an important role in clarifying the characteristics of the weave mode. As activation of the steering motion progresses the phase of the front tire side force, and the weave mode is consequently stabilized. This paper provides a design guide for stabilizing the weave mode and the wobble mode compatibility.

Thermal Noise Limit in Frequency Stabilization of Lasers with Rigid Cavities

NASA Technical Reports Server (NTRS)

Numata, Kenji; Kemery, Amy; Camp, Jordan

2005-01-01

We evaluated thermal noise (Brownian motion) in a rigid reference cavity Used for frequency stabilization of lasers, based on the mechanical loss of cavity materials and the numerical analysis of the mirror-spacer mechanics with the direct application of the fluctuation dissipation theorem. This noise sets a fundamental limit for the frequency stability achieved with a rigid frequency-reference cavity of order 1 Hz/rtHz at 10mHz at room temperature. This level coincides with the world-highest level stabilization results.

Essential Tremor: What We Can Learn from Current Pharmacotherapy

PubMed Central

Ondo, William

2016-01-01

Background The pathophysiology of essential tremor, especially at the cellular level, is poorly understood. Although no drug has been specifically designed to treat essential tremor, several medications improve tremor, and others worsen it. Studying the mechanism of actions of these medications can help our understanding of tremor pathophysiology and contribute to future rational drug design. Methods We reviewed literature, concentrating on mechanisms of action, of various medications that mitigate tremor. Results Many medications have multiple mechanisms of actions, making simple correlations difficult. Medications that increase the duration of opening of gamma-aminobutyric acid (GABA)-A receptors are most consistently associated with tremor improvement. Interestingly, drugs that increase GABA availability have not been associated with improved tremor. Other mechanisms possibly associated with tremor improvement include antagonism of alpha-2 delta subunits associated with calcium channels, inhibition of carbonic anhydrase, and inhibition of the synaptic vesicle protein 2A. Drugs that block voltage-gaited sodium channels do not affect tremor. The ideal beta-adrenergic blocker requires B2 affinity (non-cardiac selective), has no sympathomimetic properties, does not require membrane stabilization properties, and may benefit from good central nervous system penetration. Discussion To date, serendipitous observations have provided most of our understanding of tremor cellular physiology. Based on similarities to currently effective drugs or rational approximations and inferences, several currently available agents should be considered for tremor trials. PMID:26989572

Studies of the structure-antioxidant activity relationships and antioxidant activity mechanism of iridoid valepotriates and their degradation products

PubMed Central

Wang, Feifei; Zhang, Yumei; Wu, Shouhai; He, Yi; Dai, Zhong; Liu, Bin

2017-01-01

Oxidative stress has been associated with diverse diseases, including obesity, cancer and neurodegeneration. In fact, Valeriana jatamansi Jones (valerian) and its extracts possess strong antioxidant activities that extend their application in clinical practice to the treatment of these illnesses, even though the underlying mechanisms are not well understood. Iridoid valepotriate, a characteristic iridoid ester in valerian with poor chemical stability, possesses considerable antioxidant components. The original compounds and their degradation products have been found to exhibit strong antioxidant activities. However, the relationship between their structure and antioxidant effects and the mechanism underlying their oxidation resistance remain unclear. A forced degradation study using three iridoid valepotriates (valtrate, acevaltrate and 1-β acevaltrate) was performed in this work, and the structures of their degradation products were estimated by TLC-MS and LC-MS. Comparison of the antioxidant activities of the iridoid valepotriates before and after forced degradation revealed that degradation reduced the activities of the iridoid valepotriates in free radical scavenging and cytotoxic and cell apoptosis tests. The results suggested that the oxirane nucleus is important for defining the antioxidant profile of iridoid valepotriate. We uncovered possible mechanisms that could explain the antioxidant activities, including the generation of two hydroxyl groups through intramolecular transfer of an H• from an oxirane ring and a reduction in ROS levels through interactions with GABAergic signalling pathways. PMID:29232391

Organic Heat Stabilizers for Polyvinyl Chloride (PVC): A Synergistic Behavior of Eugenol and Uracil Derivative

NASA Astrophysics Data System (ADS)

Asawakosinchai, Aran; Jubsilp, Chanchira; Mora, Phattarin; Rimdusit, Sarawut

2017-10-01

Recycling ability, mechanical, and thermal properties of PVC stabilized with organic heat stabilizers, i.e., uracil (DAU) and eugenol were investigated to substitute PVCs stabilized with commercial lead, Ca/Zn, and organic-based stabilizer for PVC pipe production. PVC stabilized with the DAU and the eugenol can be processable at 30 °C lower than that of the PVC stabilized with commercial heat stabilizers. The most remarkable short-term thermal stability belonged to the PVC stabilized with the DAU, and its original color can be maintained at least up to 3 processing cycles. Synergistic behavior in thermal stability of the PVC mixed with DAU and eugenol at mass ratios of 1.5:1.5 was observed. Mechanical properties of DAU- and eugenol-stabilized PVC were higher than the samples with other heat stabilizers. Glass transition temperature of the PVC stabilized with all heat stabilizers was determined to be 99 °C with the exception of the value of 89 °C for eugenol-stabilized PVC. Therefore, the DAU and the eugenol showed high potential to be used as an organic heat stabilizer for PVC because of their non-toxic and good heat resistance properties.

Thermo-mechanical mechanism of laser-assisted alteration and stabilization of micro pore structure in eye-sclera

NASA Astrophysics Data System (ADS)

Baum, Olga; Wachsmann-Hogiu, Sebastian; Sobol, Emil

2018-02-01

Thermo-mechanical effect of laser radiation is a basis of new method of normalization of intraocular pressure in glaucomatous eyes due to laser-assisted pore formation in eye sclera. Laser-induced creation of pores in sclera increases hydraulic permeability. Stability of laser-induced pore system is achieved via gas nano-bubbles arisen in the sclera under laser radiation as a result of temperature dependency of gas solubility. The stabilization of laser-induced gas and pore systems in the tissue is an important mechanism for a long lasting healing of glaucoma observed in clinical trials with one year follow-up.

Rich in life but poor in data: the known knowns and known unknowns of modelling how soil biology drives soil structure

NASA Astrophysics Data System (ADS)

Hallett, Paul; Ogden, Mike

2015-04-01

Soil biology has a fascinating capacity to manipulate pore structure by altering or overcoming hydrological and mechanical properties of soil. Many have postulated, quite rightly, that this capacity of soil biology to 'engineer' its habitat drives its diversity, improves competitiveness and increases resilience to external stresses. A large body of observational research has quantified pore structure evolution accompanied by the growth of organisms in soil. Specific compounds that are exuded by organisms or the biological structures they create have been isolated and found to correlate well with observed changes to pore structure or soil stability. This presentation will provide an overview of basic mechanical and hydrological properties of soil that are affected by biology, and consider missing data that are essential to model how they impact soil structure evolution. Major knowledge gaps that prevent progress will be identified and suggestions will be made of how research in this area should progress. We call for more research to gain a process based understanding of structure formation by biology, to complement observational studies of soil structure before and after imposed biological activity. Significant advancement has already been made in modelling soil stabilisation by plant roots, by combining data on root biomechanics, root-soil interactions and soil mechanical properties. Approaches for this work were developed from earlier materials science and geotechnical engineering research, and the same ethos should be adopted to model the impacts of other biological compounds. Fungal hyphae likely reinforce soils in a similar way to plant roots, with successful biomechanical measurements of these micron diameter structures achieved with micromechanical test frames. Extending root reinforcement models to fungi would not be a straightforward exercise, however, as interparticle bonding and changes to pore water caused by fungal exudates could have a major impact on structure formation and stability. Biological exudates from fungi, bacteria or roots have been found to decrease surface tension and increase viscosity of pore water, with observed impacts to soil strength and water retention. Modelling approaches developed in granular mechanics and geotechnical engineering could be built upon to incorporate biological transformations of hydrological and mechanical properties of soil. With new testing approaches, adapted from materials science, pore scale hydromechanical impacts from biological exudates can be quantified. The research can be complemented with model organisms with differences in biological structures (e.g. root hair mutants), exudation or other properties. Coupled with technological advances that provide 4D imaging of soil structure at relatively rapid capture rates, the potential opportunities to disentangle and model how biology drives soil structure evolution and stability are vast. By quantifying basic soil hydrological and mechanical processes that are driven by soil biology, unknown unknowns may also emerge, providing new insight into how soils function.

Nano-indentation investigation on the mechanical stability of individual austenite in high-carbon steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiao, Xun; Han, Lizhan; Zhang, Weimin

2015-12-15

Quenching (AQ) and cryogenic treatments (QC) were conducted on the high-carbon SAE 52100 steel to investigate the mechanical stability of individual retained austenite (RA) by nano-indentation. The cross-sections of indented RA region prepared by focused ion beam (FIB) were examined by using transmission electron microscopy (TEM). For the first time, it was directly observed that some parts of RA grain, closest to the indent, in AQ specimen had transformed into strain-induced martensite (SIM). However, not any pop-in or transformation was detected in the indented QC specimen. This clearly indicates that the mechanical stability of RA in QC seems significantly enhanced,more » which is mainly attributed to the cryogenic treatment resulting in a higher carbon enrichment of RA compared to that in AQ. Furthermore, a higher load of external stress may need to trigger its martensitic transformation in QC specimen. - Highlights: • Mechanical stability of retained austenite was studied by nano-indentation and TEM. • The strain-induced martensite transformation in RA was observed under applied load. • Cryogenic treatment enhances mechanical stability of RA due to carbon enrichment.« less

Chemical Stabilization of Perovskite Solar Cells with Functional Fulleropyrrolidines

PubMed Central

2017-01-01

While perovskite solar cells have invigorated the photovoltaic research community due to their excellent power conversion efficiencies (PCEs), these devices notably suffer from poor stability. To address this crucial issue, a solution-processable organic chemical inhibition layer (OCIL) was integrated into perovskite solar cells, resulting in improved device stability and a maximum PCE of 16.3%. Photoenhanced self-doping of the fulleropyrrolidine mixture in the interlayers afforded devices that were advantageously insensitive to OCIL thickness, ranging from 4 to 190 nm. X-ray photoelectron spectroscopy (XPS) indicated that the fulleropyrrolidine mixture improved device stability by stabilizing the metal electrode and trapping ionic defects (i.e., I–) that originate from the perovskite active layer. Moreover, degraded devices were rejuvenated by repeatedly peeling away and replacing the OCIL/Ag electrode, and this repeel and replace process resulted in further improvement to device stability with minimal variation of device efficiency. PMID:29532021

Chemical Stabilization of Perovskite Solar Cells with Functional Fulleropyrrolidines.

PubMed

Liu, Yao; Page, Zachariah A; Zhou, Dongming; Duzhko, Volodimyr V; Kittilstved, Kevin R; Emrick, Todd; Russell, Thomas P

2018-02-28

While perovskite solar cells have invigorated the photovoltaic research community due to their excellent power conversion efficiencies (PCEs), these devices notably suffer from poor stability. To address this crucial issue, a solution-processable organic chemical inhibition layer (OCIL) was integrated into perovskite solar cells, resulting in improved device stability and a maximum PCE of 16.3%. Photoenhanced self-doping of the fulleropyrrolidine mixture in the interlayers afforded devices that were advantageously insensitive to OCIL thickness, ranging from 4 to 190 nm. X-ray photoelectron spectroscopy (XPS) indicated that the fulleropyrrolidine mixture improved device stability by stabilizing the metal electrode and trapping ionic defects (i.e., I - ) that originate from the perovskite active layer. Moreover, degraded devices were rejuvenated by repeatedly peeling away and replacing the OCIL/Ag electrode, and this repeel and replace process resulted in further improvement to device stability with minimal variation of device efficiency.

Surface Stabilized InP/GaP/ZnS Quantum Dots with Mg Ions for WLED Application.

PubMed

Park, Joong Pill; Kim, Sang-Wook

2016-05-01

One of the most highlighted cadmium-free quantum dots (QDs), InP-based QDs, have improved their optical properties. However, InP-based QDs have some practical drawbacks, for example, stability, compared with CdSe-based QDs. Poor stability of InP-based QDs yields critical problems, such as agglomeration and photoluminescence quenching in light emitting diode (LED). It has to be solved for applications and most research has focused on thick outer shells as an effective solution. We introduced magnesium cations for improving stability of InP-based QDs. We applied very small amounts of Mg cations as surface stabilizers, as a result, stability of QDs is clearly improved. Then, QD based LED chips also yield improved values including RA of 84.4, CCT of 3799 K, and luminous efficiency of 129.57 Im/W, which are highly improved data compared with our previous results.

In situ spectroscopic studies on vapor phase catalytic decomposition of dimethyl oxalate.

PubMed

Hegde, Shweta; Tharpa, Kalsang; Akuri, Satyanarayana Reddy; K, Rakesh; Kumar, Ajay; Deshpande, Raj; Nair, Sreejit A

2017-03-15

Dimethyl Oxalate (DMO) has recently gained prominence as a valuable intermediate for the production of compounds of commercial importance. The stability of DMO is poor and hence this can result in the decomposition of DMO under reaction conditions. The mechanism of DMO decomposition is however not reported and more so on catalytic surfaces. Insights into the mechanism of decomposition would help in designing catalysts for its effective molecular transformation. It is well known that DMO is sensitive to moisture, which can also be a factor contributing to its decomposition. The present work reports the results of decomposition of DMO on various catalytic materials. The materials studied consist of acidic (γ-Al 2 O 3 ), basic (MgO), weakly acidic (ZnAl 2 O 4 ) and neutral surfaces such as α-Al 2 O 3 and mesoporous precipitated SiO 2 . Infrared spectroscopy is used to identify the nature of adsorption of the molecule on the various surfaces. The spectroscopy study is done at a temperature of 200 °C, which is the onset of gas phase decomposition of DMO. The results indicate that the stability of DMO is lower than the corresponding acid, i.e. oxalic acid. It is also one of the products of decomposition. Spectroscopic data suggest that DMO decomposition is related to surface acidity and the extent of decomposition depends on the number of surface hydroxyl groups. Decomposition was also observed on α-Al 2 O 3 , which was attributed to the residual surface hydroxyl groups. DMO decomposition to oxalic acid was not observed on the basic surface (MgO).

Native backfill materials for mechanically stabilized earth walls.

DOT National Transportation Integrated Search

2005-01-01

Mechanically stabilized earth walls are an attractive alternative to conventional reinforced concrete retaining walls. The economy of these walls for non-critical applications might be improved by using alternative backfills consisting of on-site soi...

Electrical resistivity measurement of mechanically stabilized Earth wall backfill : technical summary.

DOT National Transportation Integrated Search

2016-06-01

In Kansas, mechanically stabilized earth (MSE) retaining walls are typically : backfilled with coarse aggregate. Current backfill material testing procedures used : by the Kansas Department of Transportation (KDOT) utilize on-site observations for : ...

V67L Mutation Fills an Internal Cavity To Stabilize RecA Mtu Intein

DOE PAGES

Zwarycz, Allison S.; Fossat, Martin; Akanyeti, Otar; ...

2017-05-10

Inteins mediate protein splicing, which has found extensive applications in protein science and biotechnology. In the Mycobacterium tuberculosis RecA mini–mini intein (ΔΔIhh), a single valine to leucine substitution at position 67 (V67L) dramatically increases intein stability and activity. However, crystal structures show that the V67L mutation causes minimal structural rearrangements, with a root-mean-square deviation of 0.2 Å between ΔΔIhh-V67 and ΔΔIhh-L67. Thus, the structural mechanisms for V67L stabilization and activation remain poorly understood. In this paper, we used intrinsic tryptophan fluorescence, high-pressure nuclear magnetic resonance (NMR), and molecular dynamics (MD) simulations to probe the structural basis of V67L stabilization ofmore » the intein fold. Guanidine hydrochloride denaturation monitored by fluorescence yielded free energy changes (ΔG f°) of -4.4 and -6.9 kcal mol –1 for ΔΔIhh-V67 and ΔΔIhh-L67, respectively. High-pressure NMR showed that ΔΔIhh-L67 is more resistant to pressure-induced unfolding than ΔΔIhh-V67 is. The change in the volume of folding (ΔV f) was significantly larger for V67 (71 ± 2 mL mol –1) than for L67 (58 ± 3 mL mol –1) inteins. The measured difference in ΔV f (13 ± 3 mL mol –1) roughly corresponds to the volume of the additional methylene group for Leu, supporting the notion that the V67L mutation fills a nearby cavity to enhance intein stability. In addition, we performed MD simulations to show that V67L decreases side chain dynamics and conformational entropy at the active site. Finally, it is plausible that changes in cavities in V67L can also mediate allosteric effects to change active site dynamics and enhance intein activity.« less

V67L Mutation Fills an Internal Cavity To Stabilize RecA Mtu Intein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zwarycz, Allison S.; Fossat, Martin; Akanyeti, Otar

Inteins mediate protein splicing, which has found extensive applications in protein science and biotechnology. In the Mycobacterium tuberculosis RecA mini–mini intein (ΔΔIhh), a single valine to leucine substitution at position 67 (V67L) dramatically increases intein stability and activity. However, crystal structures show that the V67L mutation causes minimal structural rearrangements, with a root-mean-square deviation of 0.2 Å between ΔΔIhh-V67 and ΔΔIhh-L67. Thus, the structural mechanisms for V67L stabilization and activation remain poorly understood. In this paper, we used intrinsic tryptophan fluorescence, high-pressure nuclear magnetic resonance (NMR), and molecular dynamics (MD) simulations to probe the structural basis of V67L stabilization ofmore » the intein fold. Guanidine hydrochloride denaturation monitored by fluorescence yielded free energy changes (ΔG f°) of -4.4 and -6.9 kcal mol –1 for ΔΔIhh-V67 and ΔΔIhh-L67, respectively. High-pressure NMR showed that ΔΔIhh-L67 is more resistant to pressure-induced unfolding than ΔΔIhh-V67 is. The change in the volume of folding (ΔV f) was significantly larger for V67 (71 ± 2 mL mol –1) than for L67 (58 ± 3 mL mol –1) inteins. The measured difference in ΔV f (13 ± 3 mL mol –1) roughly corresponds to the volume of the additional methylene group for Leu, supporting the notion that the V67L mutation fills a nearby cavity to enhance intein stability. In addition, we performed MD simulations to show that V67L decreases side chain dynamics and conformational entropy at the active site. Finally, it is plausible that changes in cavities in V67L can also mediate allosteric effects to change active site dynamics and enhance intein activity.« less

Predictors for mechanical ventilation and short-term prognosis in patients with Guillain-Barré syndrome.

PubMed

Wu, Xiujuan; Li, Chunrong; Zhang, Bing; Shen, Donghui; Li, Ting; Liu, Kangding; Zhang, Hong-Liang

2015-09-02

Guillain-Barré syndrome (GBS) is an immune-mediated disorder of the peripheral nervous system. Respiratory failure requiring mechanical ventilation (MV) is a serious complication of GBS. Identification of modifiable risk factors for MV and poor short-term prognosis in mechanically ventilated patients with GBS may contribute to the individualized management and may help improve the outcome of the patients. We retrospectively analyzed the clinical data of 541 patients who were diagnosed with GBS from 2003 to 2014. Independent predictors for MV and short-term prognosis in mechanically ventilated patients were identified via multivariate logistic regression analysis. The mean age was 41.6 years with a male predilection (61.2%). Eighty patients (14.8%) required MV. Multivariate analysis revealed that shorter interval from onset to admission (p < 0.05), facial nerve palsy (p < 0.01), glossopharyngeal and vagal nerve deficits (p < 0.01) and lower Medical Research Council (MRC) sum score at nadir (p < 0.01) were risk factors for MV; disease occurrence in summer (p < 0.01) was a protective factor. As to prognostic factors, absence of antecedent infections (p < 0.01) and lower MRC sum score at nadir (p < 0.01) were predictors of poor short-term prognosis in mechanically ventilated patients regardless of treatment modality. We further investigated the predictors of poor short-term prognosis in patients requiring MV with different nadir MRC sum scores. Combined use of intravenous corticosteroids with intravenous immunoglobulin (odds ratio 10.200, 95% confidence interval 1.068-97.407, p < 0.05) was an independent predictor of poor short-term prognosis in mechanically ventilated patients with a nadir MRC sum score from 0 to 12 points, regardless of existence of antecedent infection. Clinical predictors of MV and poor short-term prognosis in mechanically ventilated GBS patients were distinct. Add-on use of intravenous corticosteroids was a risk factor for poor short-term prognosis in mechanically ventilated patients with a nadir MRC sum score from 0 to 12 points.

Mechanisms of kinetic stabilization by the drugs paclitaxel and vinblastine

PubMed Central

Castle, Brian T.; McCubbin, Seth; Prahl, Louis S.; Bernens, Jordan N.; Sept, David; Odde, David J.

2017-01-01

Microtubule-targeting agents (MTAs), widely used as biological probes and chemotherapeutic drugs, bind directly to tubulin subunits and “kinetically stabilize” microtubules, suppressing the characteristic self-assembly process of dynamic instability. However, the molecular-level mechanisms of kinetic stabilization are unclear, and the fundamental thermodynamic and kinetic requirements for dynamic instability and its elimination by MTAs have yet to be defined. Here we integrate a computational model for microtubule assembly with nanometer-scale fluorescence microscopy measurements to identify the kinetic and thermodynamic basis of kinetic stabilization by the MTAs paclitaxel, an assembly promoter, and vinblastine, a disassembly promoter. We identify two distinct modes of kinetic stabilization in live cells, one that truly suppresses on-off kinetics, characteristic of vinblastine, and the other a “pseudo” kinetic stabilization, characteristic of paclitaxel, that nearly eliminates the energy difference between the GTP- and GDP-tubulin thermodynamic states. By either mechanism, the main effect of both MTAs is to effectively stabilize the microtubule against disassembly in the absence of a robust GTP cap. PMID:28298489

Mechanical stability of ordered droplet packings in microfluidic channels

NASA Astrophysics Data System (ADS)

Fleury, Jean-Baptiste; Claussen, Ohle; Herminghaus, Stephan; Brinkmann, Martin; Seemann, Ralf

2011-12-01

The mechanical response and stability of one and two-row packing of monodisperse emulsion droplets are studied in quasi 2d microchannels under longitudinal compression. Depending on the choice of parameter, a considered droplet arrangement is either transformed continuously into another packing under longitudinal compression or becomes mechanically unstable and segregates into domains of higher and lower packing fraction. Our experimental results are compared to analytical calculations for 2d-droplet arrangements with good quantitative agreement. This study also predicts important consequences for the stability of droplet arrangements in flowing systems.

NASA space materials research

NASA Technical Reports Server (NTRS)

Tenney, D. R.; Tompkins, S. S.; Sykes, G. F.

1985-01-01

The effect of the space environment on: (1) thermal control coatings and thin polymer films; (2) radiation stability of 250 F and 350 F cured graphite/epoxy composites; and (3) the thermal mechanical stability of graphite/epoxy, graphite/glass composites are considered. Degradation in mechanical properties due to combined radiation and thermal cycling is highlighted. Damage mechanisms are presented and chemistry modifications to improve stability are suggested. The dimensional instabilities in graphite/epoxy composites associated with microcracking during thermal cycling is examined as well as the thermal strain hysteresis found in metal-matrix composites.

The type VI secretion system impacts bacterial invasion and population dynamics in a model intestinal microbiota

NASA Astrophysics Data System (ADS)

Logan, Savannah L.; Shields, Drew S.; Hammer, Brian K.; Xavier, Joao B.; Parthasarathy, Raghuveer

Animal gastrointestinal tracts are home to a diverse community of microbes. The mechanisms by which microbial species interact and compete in this dense, physically dynamic space are poorly understood, limiting our understanding of how natural communities are assembled and how different communities could be engineered. Here, we focus on a physical mechanism for competition: the type VI secretion system (T6SS). The T6SS is a syringe-like organelle used by certain bacteria to translocate effector proteins across the cell membranes of target bacterial cells, killing them. Here, we use T6SS+ and T6SS- strains of V. cholerae, the pathogen that causes cholera in humans, and light sheet fluorescence microscopy for in vivo imaging to show that the T6SS provides an advantage to strains colonizing the larval zebrafish gut. Furthermore, we show that T6SS+ bacteria can invade and alter an existing population of a different species in the zebrafish gut, reducing its abundance and changing the form of its population dynamics. This work both demonstrates a mechanism for altering the gut microbiota with an invasive species and explores the processes controlling the stability and dynamics of the gut ecosystem. Research Corporation, Gordon and Betty Moore Foundation, and the Simons Foundation.

Effect of mechanical site preparation treatments on oak survival in a retired field afforestation effort -- first-year results

Treesearch

Andrew B. Self; Andrew W. Ezell; Damon B. Hollis; Derek. Alkire

2011-01-01

Mechanical site preparation is frequently proposed to alleviate poor soil conditions when afforesting retired agricultural fields. Without management of soil problems, oak seedlings planted in these areas may exhibit poor survival. While mechanical site preparation methods currently employed in hardwood afforestation are proven, there is a substantial void in research...

Three-dimensional modelling of slope stability using the Local Factor of Safety concept

NASA Astrophysics Data System (ADS)

Moradi, Shirin; Huisman, Sander; Beck, Martin; Vereecken, Harry; Class, Holger

2017-04-01

Slope stability is governed by coupled hydrological and mechanical processes. The slope stability depends on the effective stress, which in turn depends on the weight of the soil and the matrix potential. Therefore, changes in water content and matrix potential associated with infiltration will affect slope stability. Most available models describing these coupled hydro-mechanical processes either rely on a one- or two-dimensional representation of hydrological and mechanical properties and processes, which obviously is a strong simplification in many applications. Therefore, the aim of this work is to develop a three-dimensional hydro-mechanical model that is able to capture the effect of spatial and temporal variability of both mechanical and hydrological parameters on slope stability. For this, we rely on DuMux, which is a free and open-source simulator for flow and transport processes in porous media that facilitates coupling of different model approaches and offers flexibility for model development. We use the Richards equation to model unsaturated water flow. The simulated water content and matrix potential distribution is used to calculate the effective stress. We only consider linear elasticity and solve for statically admissible fields of stress and displacement without invoking failure or the redistribution of post-failure stress or displacement. The Local Factor of Safety concept is used to evaluate slope stability in order to overcome some of the main limitations of commonly used methods based on limit equilibrium considerations. In a first step, we compared our model implementation with a 2D benchmark model that was implemented in COMSOL Multiphysics. In a second step, we present in-silico experiments with the newly developed 3D model to show the effect of slope morphology, spatial variability in hydraulic and mechanical material properties, and spatially variable soil depth on simulated slope stability. It is expected that this improved physically-based three-dimensional hydro-mechanical model is able to provide more reliable slope instability predictions in more complex situations.

What would you do? The effect of verbal persuasion on task choice.

PubMed

Lamarche, Larkin; Gionfriddo, Alicia M; Cline, Lindsay E; Gammage, Kimberley L; Adkin, Allan L

2014-01-01

Verbal persuasion has been shown to influence psychological and behavioral outcomes. The present study had two objectives: (1) to examine the effect of verbal persuasion on task choice in a balance setting and (2) to evaluate the use of verbal persuasion as an approach to experimentally induce mismatches between perceived and actual balance. Healthy young adults (N=68) completed an 8-m tandem walk task without vision and then were randomly assigned to a feedback group (good, control, or poor), regardless of actual balance. Following the feedback, participants chose to perform the task in one of three conditions differing in level of challenge and also were required to perform the task under the same pre-feedback conditions. Balance efficacy and perceived stability were rated before and after each pre- and post-feedback task, respectively. Balance performance measures were also collected. Following the feedback, participants in the good group were more likely to choose the most challenging task while those in the poor group were more likely to choose the least challenging task. Following the feedback, all groups showed improved balance performance. However, balance efficacy and perceived stability increased for the good and control groups but balance efficacy decreased and perceived stability was unchanged for the poor group. Thus, these findings demonstrate that verbal persuasion can influence task choice and may be used as an approach to experimentally create mismatches between perceived and actual balance. Copyright © 2013 Elsevier B.V. All rights reserved.

β-Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs.

PubMed

di Cagno, Massimiliano; Terndrup Nielsen, Thorbjørn; Lambertsen Larsen, Kim; Kuntsche, Judith; Bauer-Brandl, Annette

2014-07-01

The aim of this study was to assess the potential of novel β-cyclodextrin (βCD)-dextran polymers for drug delivery. The size distribution of βCD-dextrans (for eventual parenteral administration), the influence of the dextran backbones on the stability of the βCD/drug complex, the solubilization efficiency of poorly soluble drugs and drug release properties were investigated. Size analysis of different βCD-dextrans was measured by size exclusion chromatography (SEC) and asymmetrical flow field-flow fractionation (AF4). Stability of drug/βCD-dextrans was assessed by isothermal titration calorimetry (ITC) and molar enthalpies of complexation and equilibrium constants compared to some commercially available βCD derivatives. For evaluation of the solubilization efficiency, phase-solubility diagrams were made employing hydrocortisone (HC) as a model of poorly soluble drugs, whereas reverse dialysis was used to detect potential drug supersaturation (increased molecularly dissolved drug concentration) as well as controlled release effects. Results indicate that all investigated βCD-polymers are of appropriate sizes for parenteral administration. Thermodynamic results demonstrate that the presence of the dextran backbone structure does not affect the stability of the βCD/drug complex, compared to native βCD and commercially available derivatives. Solubility studies evidence higher solubilizing abilities of these new polymers in comparison to commercially available βCDs, but no supersaturation states were induced. Moreover, drug release studies evidenced that diffusion of HC was influenced by the solubilization induced by the βCD-derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of LRFD resistance factors for mechanically stabilized earth (MSE) walls : [technical summary].

DOT National Transportation Integrated Search

2013-12-01

Bridge approach embankments and many other : transportation-related applications make use of : reinforced earth retaining structures. Mechanically : Stabilized Earth (MSE) walls are designed under : the Load and Resistance Factor Design (LRFD) : meth...

Electrical resistivity measurement of mechanically stabilized Earth wall backfill : final report.

DOT National Transportation Integrated Search

2016-06-01

In Kansas, mechanically stabilized earth (MSE) retaining walls are typically backfilled with coarse aggregate. : Current backfill material testing procedures used by the Kansas Department of Transportation (KDOT) utilize on-site : observations for co...

Evaluation of a Heuristic Model for Tropical Cyclone Resilience

DTIC Science & Technology

2015-01-26

in which the effective static stability vanishes in rising and sinking regions, the 13 heuristic model yields a poor approximation to the simulated...tilt configuration. However, in the moist-neutral 12 limit, in which the effective static stability vanishes in rising and sinking regions, the 13...larger, leading to more effective 13 damping of the tilt mode (e.g., Schecter and Montgomery 2007; see their Figs. 10 and 11 14 and accompanying

SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability.

PubMed

Scott, Katherine A; Kotecha, Abhay; Seago, Julian; Ren, Jingshan; Fry, Elizabeth E; Stuart, David I; Charleston, Bryan; Maree, Francois F

2017-05-15

Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for the potential use of such mutants in improving the stability of SAT2 vaccines in countries where FMD is endemic, which rely heavily on the maintenance of the cold chain, with potential improvement to the duration of immune responses. Copyright © 2017 American Society for Microbiology.

SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability

PubMed Central

Scott, Katherine A.; Kotecha, Abhay; Seago, Julian; Ren, Jingshan; Fry, Elizabeth E.; Stuart, David I.; Charleston, Bryan

2017-01-01

ABSTRACT Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for the potential use of such mutants in improving the stability of SAT2 vaccines in countries where FMD is endemic, which rely heavily on the maintenance of the cold chain, with potential improvement to the duration of immune responses. PMID:28298597

Hospital charge exemptions for the poor in Shandong, China.

PubMed

Meng, Qingyue; Sun, Qiang; Hearst, Norman

2002-12-01

Rapid economic changes in China have produced soaring hospital charges, a breakdown of the old social health insurance system, a resulting crisis in hospital affordability and renewed interest in mechanisms for discounts or exemptions from hospital charges for the poor. Little is known, however, about how effective such systems are in practice. We studied nine public hospitals in Shandong Province that offer discount or exemption mechanisms for the poor. Methods included document review, key informant interviews, detailed review of financial records and focus group discussions. These hospitals receive little government subsidy and must support themselves almost entirely through user fees. Hospital managers saw discount mechanisms primarily as marketing tools and designed them to limit their cost. Only a small fraction of hospital services were eligible for discount, and these were usually low cost or low utilization items. Discounts were generally 10-50% for selected items with very few services exempted from charge. The total value of discounts granted was 1% or less of total hospital operating budgets. Correct identification of indigents was a major difficulty for hospitals. Only a minority of indigents received discounts, the process was sometimes arbitrary and some who received discounts were not really poor. Government policies requiring discounts for the poor were vague and not enforced. The exemption programmes studied do not provide effective protection from hospital charges for the poor. To be effective, exemption mechanisms would likely require both financing and regulation by the government as well as an accurate way to identify the poor.

How nanobubbles lose stability: Effects of surfactants

NASA Astrophysics Data System (ADS)

Xiao, Qianxiang; Liu, Yawei; Guo, Zhenjiang; Liu, Zhiping; Zhang, Xianren

2017-09-01

In contrast to stability theories of nanobubbles, the molecular mechanism of how nanobubbles lose stability is far from being understood. In this work, we try to interpret recent experimental observations that the addition of surfactants destabilizes nanobubbles with an unclear mechanism. Using molecular dynamics simulations, we identify two surfactant-induced molecular mechanisms for nanobubbles losing stability, either through depinning of a contact line or reducing vapor-liquid surface tension. One corresponds to the case with significant adsorption of surfactants on the substrates, which causes depinning of the nanobubble contact line and thus leads to nanobubble instability. The other stresses surfactant adsorption on the vapor-liquid interface of nanobubbles, especially for insoluble surfactants, which reduces the surface tension of the interface and leads to an irreversible liquid-to-vapor phase transition. Our finding can help improve our understanding in nanobubble stability, and the insight presented here has implications for surface nanobubbles involving with other amphiphilic molecules, such as proteins and contaminations.

Nonlinear differential system applied of a mechanical plan model of the automotives used for the nonlinear stability analysis

NASA Astrophysics Data System (ADS)

Simniceanu, Loreta; Mihaela, Bogdan; Otat, Victor; Trotea, Mario

2017-10-01

This paper proposes a plan mechanical model for the vehicles with two axles, taking into account the lateral deflection of the tire. For this mechanical model are determined two mathematical models under the nonlinear differential equations systems form without taking into account the action of the driver and taking into account. The analysis of driver-vehicle system consists in the mathematical description of vehicle dynamics, coupled with the possibilities and limits of the human factor. Description seeks to emphasize the significant influence of the driver in handling and stability analyzes of vehicles and vehicle-driver system stability until the advent of skidding. These mathematical models are seen as very useful tools to analyzing the vehicles stability. The paper analyzes the influence of some parameters of the vehicle on its behavior in terms of stability of dynamic systems.

Does surface roughness influence the primary stability of acetabular cups? A numerical and experimental biomechanical evaluation.

PubMed

Le Cann, Sophie; Galland, Alexandre; Rosa, Benoît; Le Corroller, Thomas; Pithioux, Martine; Argenson, Jean-Noël; Chabrand, Patrick; Parratte, Sébastien

2014-09-01

Most acetabular cups implanted today are press-fit impacted cementless. Anchorage begins with the primary stability given by insertion of a slightly oversized cup. This primary stability is key to obtaining bone ingrowth and secondary stability. We tested the hypothesis that primary stability of the cup is related to surface roughness of the implant, using both an experimental and a numerical models to analyze how three levels of surface roughness (micro, macro and combined) affect the primary stability of the cup. We also investigated the effect of differences in diameter between the cup and its substrate, and of insertion force, on the cups' primary stability. The results of our study show that primary stability depends on the surface roughness of the cup. The presence of macro-roughness on the peripheral ring is found to decrease primary stability; there was excessive abrasion of the substrate, damaging it and leading to poor primary stability. Numerical modeling indicates that oversizing the cup compared to its substrate has an impact on primary stability, as has insertion force. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Fibrin mechanical properties and their structural origins.

PubMed

Litvinov, Rustem I; Weisel, John W

2017-07-01

Fibrin is a protein polymer that is essential for hemostasis and thrombosis, wound healing, and several other biological functions and pathological conditions that involve extracellular matrix. In addition to molecular and cellular interactions, fibrin mechanics has been recently shown to underlie clot behavior in the highly dynamic intra- and extravascular environments. Fibrin has both elastic and viscous properties. Perhaps the most remarkable rheological feature of the fibrin network is an extremely high elasticity and stability despite very low protein content. Another important mechanical property that is common to many filamentous protein polymers but not other polymers is stiffening occurring in response to shear, tension, or compression. New data has begun to provide a structural basis for the unique mechanical behavior of fibrin that originates from its complex multi-scale hierarchical structure. The mechanical behavior of the whole fibrin gel is governed largely by the properties of single fibers and their ensembles, including changes in fiber orientation, stretching, bending, and buckling. The properties of individual fibrin fibers are determined by the number and packing arrangements of double-stranded half-staggered protofibrils, which still remain poorly understood. It has also been proposed that forced unfolding of sub-molecular structures, including elongation of flexible and relatively unstructured portions of fibrin molecules, can contribute to fibrin deformations. In spite of a great increase in our knowledge of the structural mechanics of fibrin, much about the mechanisms of fibrin's biological functions remains unknown. Fibrin deformability is not only an essential part of the biomechanics of hemostasis and thrombosis, but also a rapidly developing field of bioengineering that uses fibrin as a versatile biomaterial with exceptional and tunable biochemical and mechanical properties. Copyright © 2016 Elsevier B.V. All rights reserved.

Food protein-stabilized nanoemulsions as potential delivery systems for poorly water-soluble drugs: preparation, in vitro characterization, and pharmacokinetics in rats

PubMed Central

He, Wei; Tan, Yanan; Tian, Zhiqiang; Chen, Lingyun; Hu, Fuqiang; Wu, Wei

2011-01-01

Nanoemulsions stabilized by traditional emulsifiers raise toxicological concerns for long-term treatment. The present work investigates the potential of food proteins as safer stabilizers for nanoemulsions to deliver hydrophobic drugs. Nanoemulsions stabilized by food proteins (soybean protein isolate, whey protein isolate, β-lactoglobulin) were prepared by high-pressure homogenization. The toxicity of the nanoemulsions was tested in Caco-2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide viability assay. In vivo absorption in rats was also evaluated. Food protein-stabilized nanoemulsions, with small particle size and good size distribution, exhibited better stability and biocompatibility compared with nanoemulsions stabilized by traditional emulsifiers. Moreover, β-lactoglobulin had a better emulsifying capacity and biocompatibility than the other two food proteins. The pancreatic degradation of the proteins accelerated drug release. It is concluded that an oil/water nanoemulsion system with good biocompatibility can be prepared by using food proteins as emulsifiers, allowing better and more rapid absorption of lipophilic drugs. PMID:21468355

Food protein-stabilized nanoemulsions as potential delivery systems for poorly water-soluble drugs: preparation, in vitro characterization, and pharmacokinetics in rats.

PubMed

He, Wei; Tan, Yanan; Tian, Zhiqiang; Chen, Lingyun; Hu, Fuqiang; Wu, Wei

2011-01-01

Nanoemulsions stabilized by traditional emulsifiers raise toxicological concerns for long-term treatment. The present work investigates the potential of food proteins as safer stabilizers for nanoemulsions to deliver hydrophobic drugs. Nanoemulsions stabilized by food proteins (soybean protein isolate, whey protein isolate, β-lactoglobulin) were prepared by high-pressure homogenization. The toxicity of the nanoemulsions was tested in Caco-2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide viability assay. In vivo absorption in rats was also evaluated. Food protein-stabilized nanoemulsions, with small particle size and good size distribution, exhibited better stability and biocompatibility compared with nanoemulsions stabilized by traditional emulsifiers. Moreover, β-lactoglobulin had a better emulsifying capacity and biocompatibility than the other two food proteins. The pancreatic degradation of the proteins accelerated drug release. It is concluded that an oil/water nanoemulsion system with good biocompatibility can be prepared by using food proteins as emulsifiers, allowing better and more rapid absorption of lipophilic drugs.

Cargo–shell and cargo–cargo couplings govern the mechanics of artificially loaded virus-derived cages†

PubMed Central

Llauró, Aida; Luque, Daniel; Edwards, Ethan; Trus, Benes L.; Avera, John; Reguera, David; Douglas, Trevor

2016-01-01

Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers’ stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo–shell and cargo–cargo interactions on shell stability after encapsulating two types of proteinaceous payloads. While bound cargo to the inner capsid surface mechanically reinforced the capsid in a structural manner, unbound cargo diffusing freely within the shell cavity pressurized the cages up to ~30 atm due to steric effects. Strong cargo–cargo coupling reduces the resilience of these nanocompartments in ~20% when bound to the shell. Understanding the stability of artificially loaded nanocages will help to design more robust and durable molecular nanocontainers. PMID:27091107

Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics

NASA Astrophysics Data System (ADS)

Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

2015-12-01

Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains.

Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics.

PubMed

Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

2015-12-22

Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains.

Stability of Electrodeposition at Solid-Solid Interfaces and Implications for Metal Anodes

NASA Astrophysics Data System (ADS)

Ahmad, Zeeshan; Viswanathan, Venkatasubramanian

2017-08-01

We generalize the conditions for stable electrodeposition at isotropic solid-solid interfaces using a kinetic model which incorporates the effects of stresses and surface tension at the interface. We develop a stability diagram that shows two regimes of stability: a previously known pressure-driven mechanism and a new density-driven stability mechanism that is governed by the relative density of metal in the two phases. We show that inorganic solids and solid polymers generally do not lead to stable electrodeposition, and provide design guidelines for achieving stable electrodeposition.

Design of Fucoidan Functionalized - Iron Oxide Nanoparticles for Biomedical Applications.

PubMed

Tran, Khanh Nghia; Tran, Phuong Ha-Lien; Vo, Toi Van; Tran, Thao Truong-Dinh

2016-01-01

This research aims to develop an iron oxide nanoparticle drug delivery system utilizing a recent material discovered from ocean, fucoidan. The material has drawn much interest due to many biomedical functions that have been proven for human health. One interesting point herein is that fucoidan is not only a sulfated polysaccharide, a polymer for stabilization of iron oxide nanoparticles, but plays a role of an anticancer agent also. Various approaches were investigated to optimize the high loading efficiency and explain the mechanism of nanoparticle formations. Fucoidan was functionalized on iron oxide nanoparticles by a direct coating or via amine groups. Also, a hydrophobic part of oleic acid was conjugated to the amine groups for a more favorable loading of poorly water-soluble anticancer drugs. This study proposed a novel system and an efficient method to functionalize fucoidan on iron oxide nanoparticle systems which will lead to a facilitation of a double strength treatment of cancer.

The mechanical response of talin

NASA Astrophysics Data System (ADS)

Yao, Mingxi; Goult, Benjamin T.; Klapholz, Benjamin; Hu, Xian; Toseland, Christopher P.; Guo, Yingjian; Cong, Peiwen; Sheetz, Michael P.; Yan, Jie

2016-07-01

Talin, a force-bearing cytoplasmic adapter essential for integrin-mediated cell adhesion, links the actin cytoskeleton to integrin-based cell-extracellular matrix adhesions at the plasma membrane. Its C-terminal rod domain, which contains 13 helical bundles, plays important roles in mechanosensing during cell adhesion and spreading. However, how the structural stability and transition kinetics of the 13 helical bundles of talin are utilized in the diverse talin-dependent mechanosensing processes remains poorly understood. Here we report the force-dependent unfolding and refolding kinetics of all talin rod domains. Using experimentally determined kinetics parameters, we determined the dynamics of force fluctuation during stretching of talin under physiologically relevant pulling speeds and experimentally measured extension fluctuation trajectories. Our results reveal that force-dependent stochastic unfolding and refolding of talin rod domains make talin a very effective force buffer that sets a physiological force range of only a few pNs in the talin-mediated force transmission pathway.

Predicting Great Lakes fish yields: tools and constraints

USGS Publications Warehouse

Lewis, C.A.; Schupp, D.H.; Taylor, W.W.; Collins, J.J.; Hatch, Richard W.

1987-01-01

Prediction of yield is a critical component of fisheries management. The development of sound yield prediction methodology and the application of the results of yield prediction are central to the evolution of strategies to achieve stated goals for Great Lakes fisheries and to the measurement of progress toward those goals. Despite general availability of species yield models, yield prediction for many Great Lakes fisheries has been poor due to the instability of the fish communities and the inadequacy of available data. A host of biological, institutional, and societal factors constrain both the development of sound predictions and their application to management. Improved predictive capability requires increased stability of Great Lakes fisheries through rehabilitation of well-integrated communities, improvement of data collection, data standardization and information-sharing mechanisms, and further development of the methodology for yield prediction. Most important is the creation of a better-informed public that will in turn establish the political will to do what is required.

Lipid- and sugar-modified endomorphins: novel targets for the treatment of neuropathic pain

PubMed Central

Varamini, Pegah; Toth, Istvan

2013-01-01

Endomorphins are endogenous opioid peptides that cause potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, endomorphins are poorly suited to clinical applications because of low membrane permeability and a susceptibility to enzymatic degradation. Glycosylation and lipidation have proven to be two of the most robust approaches for the generation of new therapeutic endomorphin derivatives. Conjugation with lipoamino acids (LAA) confers an amphipathic character to the peptide, which improved interaction between the peptide and the lipid bilayer of the cell membranes, increasing permeability. Glycosylation can also improve peptide stability and blood brain barrier (BBB) transport. It is believed that an endocytotic mechanism (transcytosis) is responsible for the systemic delivery of water-soluble glycopeptides. This review discusses the application of glycosylation and lipidation strategies to improve the drug-like properties of endomorphins. Pharmacologically active endomorphin analogs with less adverse effects are also discussed. PMID:24379782

Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling.

PubMed

Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K; Marmer, Barry; Goldberg, Gregory I; Neuman, Keir C

2016-07-26

Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal-strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments.

Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity.

PubMed

Marusyk, Andriy; Tabassum, Doris P; Altrock, Philipp M; Almendro, Vanessa; Michor, Franziska; Polyak, Kornelia

2014-10-02

Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.

Care Challenges in the Bathroom: The Views of Professional Care Providers Working in Clients' Homes.

PubMed

King, Emily C; Holliday, Pamela J; Andrews, Gavin J

2018-04-01

In home care, bathroom activities-particularly bathing and toileting-present a unique set of challenges. In this focus group study, professional home care providers identified factors that increase the danger and difficulty of assisting their clients with bathing and toileting. These included small restrictive spaces, a poor fit between available equipment and the environment, a reliance on manual handling techniques (but insufficient space to use optimal body mechanics), attempts to maintain normalcy, and caring for unsteady and unpredictable clients. Specific elements of each activity that care providers found difficult included multitasking to support client stability while performing care below the waist (dressing/undressing, providing perineal care) and helping clients to lift their legs in and out of a bathtub. Participants did not feel that available assistive devices provided enough assistance to reduce the danger and difficulty of these activities.

Degradation and biological properties of Ca-P contained micro-arc oxidation self-sealing coating on pure magnesium for bone fixation

PubMed Central

Wang, Weidan; Wan, Peng; Liu, Chen; Tan, Lili; Li, Weirong; Li, Lugee; Yang, Ke

2015-01-01

Poor corrosion resistance is one of the main disadvantages for biodegradable magnesium-based metals, especially applied for bone fixation, where there is a high demand of bio-mechanical strength and stability. Surface coating has been proved as an effective method to control the in vivo degradation. In this study a Ca-P self-sealing micro-arc oxidation (MAO) coating was studied to verify its efficacy and biological properties by in vitro and in vivo tests. It was found that the MAO coating could effectively retard the degradation according to immersion and electrochemical tests as well as 3D reconstruction by X-ray tomography after implantation. The MAO coating exhibited no toxicity and could stimulate the new bone formation. Therefore, the Ca-P self-sealing MAO coating could be a potential candidate for application of biodegradable Mg-based implant in bone fixations. PMID:26816635

Infection's Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility.

PubMed

Taylor, Steven L; McGuckin, Michael A; Wesselingh, Steve; Rogers, Geraint B

2018-02-01

Glycans form a highly variable constituent of our mucosal surfaces and profoundly affect our susceptibility to infection and disease. The diversity and importance of these surface glycans can be seen in individuals who lack a functional copy of the fucosyltransferase gene, FUT2. Representing around one-fifth of the population, these individuals have an altered susceptibility to many bacterial and viral infections and diseases. The mediation of host-pathogen interactions by mucosal glycans, such as those added by FUT2, is poorly understood. We highlight, with specific examples, important mechanisms by which host glycans influence infection dynamics, including by: acting as pathogen receptors (or receptor-decoys), promoting microbial stability, altering the physical characteristics of mucus, and acting as immunological markers. We argue that the effect glycans have on infection dynamics has profound implications for many aspects of healthcare and policy, including clinical management, outbreak control, and vaccination policy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1.

PubMed

Ruthenborg, Robin J; Ban, Jae-Jun; Wazir, Anum; Takeda, Norihiko; Kim, Jung-Whan

2014-09-01

Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

Enabling the Tablet Product Development of 5-Fluorocytosine by Conjugate Acid Base Cocrystals.

PubMed

Perumalla, Sathyanarayana R; Paul, Shubhajit; Sun, Changquan C

2016-06-01

5-Fluorocytosine (FC) is a high-dose antifungal drug that challenges the development of a tablet product due to poor solid-state stability and tabletability. Using 2 pharmaceutically acceptable conjugate acid base (CAB) cocrystals of FC with HCl and acesulfame, we have developed commercially viable high loading FC tablets. The tablets were prepared by direct compression using nano-coated microcrystalline cellulose Avicel PH105 as a tablet binder, which provided both excellent tabletability and good flowability. Commercial manufacturability of formulations based on both CAB cocrystals was verified on a compaction simulator. The results from an expedited friability study were used to set the compaction force, which yielded tablets with sufficient mechanical strength and rapid tablet disintegration. This work demonstrates the potential value of CAB cocrystals in drug product development. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling

PubMed Central

Dittmore, Andrew; Silver, Jonathan; Sarkar, Susanta K.; Marmer, Barry; Goldberg, Gregory I.; Neuman, Keir C.

2016-01-01

Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal–strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments. PMID:27402741

Epigallocatechin-3-gallate(EGCG) : mechanisms and the combined applications.

PubMed

Song, Xuekun; Du, Juan; Zhao, Wenyuan; Guo, Zheng

2017-12-17

EGCG is the most important pharmacological component in tea. Researches have confirmed its effects, including anti-tumor, anti-inflammation, anti-aging, anti-obesity, anti-diabetic, cardiovascular disease prevention and protection, immunoregulation and neuroprotection. Paradoxically, the clinical application of EGCG is very rare. One of the most important reasons is its poor stability and low bioavailability. Excepting for altering the dosage form or synthesizing the analogues to overcome the loss during absorption, an increasing number of studies indicate that EGCG can exert certain auxiliary effect and enhance chemosensitivity in combined medication. The pharmacological action, the pharmacology network including mutation of signaling receptor and modulation of intracellular signaling pathway, and the combination treatment strategy of EGCG are clarified and sorted out, both the possible targets and combinatorial applications based on the characteristics of EGCG are systematically summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mechanical design of proteins studied by single-molecule force spectroscopy and protein engineering.

PubMed

Carrion-Vazquez, M; Oberhauser, A F; Fisher, T E; Marszalek, P E; Li, H; Fernandez, J M

2000-01-01

Mechanical unfolding and refolding may regulate the molecular elasticity of modular proteins with mechanical functions. The development of the atomic force microscopy (AFM) has recently enabled the dynamic measurement of these processes at the single-molecule level. Protein engineering techniques allow the construction of homomeric polyproteins for the precise analysis of the mechanical unfolding of single domains. alpha-Helical domains are mechanically compliant, whereas beta-sandwich domains, particularly those that resist unfolding with backbone hydrogen bonds between strands perpendicular to the applied force, are more stable and appear frequently in proteins subject to mechanical forces. The mechanical stability of a domain seems to be determined by its hydrogen bonding pattern and is correlated with its kinetic stability rather than its thermodynamic stability. Force spectroscopy using AFM promises to elucidate the dynamic mechanical properties of a wide variety of proteins at the single molecule level and provide an important complement to other structural and dynamic techniques (e.g., X-ray crystallography, NMR spectroscopy, patch-clamp).

Production, characterization, and mechanical behavior of cementitious materials incorporating carbon nanofibers

NASA Astrophysics Data System (ADS)

Yazdanbakhsh, Ardavan

Carbon nanotubes (CNTs) and carbon nanofirbers (CNFs) have excellent properties (mechanical, electrical, magnetic, etc.), which can make them effective nanoreinforcements for improving the properties of materials. The incorporation of CNT/Fs in a wide variety of materials has been researched extensively in the past decade. However, the past study on the reinforcement of cementitious materials with these nanofilaments has been limited. The findings from those studies indicate that CNT/Fs did not significantly improve the mechanical properties of cementitious materials. Two major parameters influence the effectiveness of any discrete inclusion in composite material: The dispersion quality of the inclusions and the interfacial bond between the inclusions and matrix. The main focus of this dissertation is on the dispersion factor, and consists of three main tasks: First a novel thermodynamic-based method for dispersion quantification was developed. Second, a new method, incorporating the utilization of silica fume, was devised to improve and stabilize the dispersion of CNFs in cement paste. And third, the dispersion quantification method and mechanical testing were employed to measure, compare, and correlate the dispersion and mechanical properties of CNF-incorporated cement paste produced with the conventional and new methods. Finally, the main benefits, including the increase in strength and resistance to shrinkage cracking, obtained from the utilization of CNFs in cement paste will be presented. The investigations and the corresponding results show that the novel dispersion quantification method can be implemented easily to perform a wide variety of tasks ranging from measuring dispersion of nanofilaments in composites using their optical/SEM micrographs as input, to measuring the effect of cement particle/clump size on the dispersion of nano inclusions in cement paste. It was found that cement particles do not affect the dispersion of nano inclusions in cement paste significantly while the dispersion of nano inclusions can notably degenerates if the cement particles are agglomerated. The novel dispersion quantification method shows that, the dispersion of CNFs in cement paste significantly improves by utilizing silica fume. However, it was found that the dispersion of silica fume particles is an important parameter and poorly dispersed silica fume cannot enhance the overall dispersion of nano inclusions in cementitious materials. Finally, the mechanical testing and experimentations showed that CNFs, in absence of moist curing, even if poorly dispersed, can provide important benefits in terms of strength and crack resistance.

Bioavailability Challenges Associated with Development of Anti-Cancer Phenolics

PubMed Central

Gao, Song; Hu, Ming

2010-01-01

Phenolics including many polyphenols and flavonoids have the potentials to become chemoprevention and chemotherapy agents. However, poor bioavailability limits their biological effects in vivo. This paper reviews the factors that affect phenolics absorption and their bioavailabilities from the points of view of their physicochemical properties and disposition in the gastrointestinal tract. The up-to-date research data suggested that solubility and metabolism are the primary reasons that limit phenolic aglycones’ bioavailability although stability and poor permeation may also contribute to the poor bioavailabilities of the glycosides. Future investigations should further optimize phenolics’ bioavailabilities and realize their chemopreventive and chemotherapeutic effects in vivo. PMID:20370701

[RESEARCH PROGRESS OF BIOMECHANICS OF PROXIMAL ROW CARPAL INSTABILITY].

PubMed

Guo, Jinhai; Huang, Fuguo

2015-01-01

To review the research progress of the biomechanics of proximal row carpal instability (IPRC). The related literature concerning IPRC was extensively reviewed. The biomechanical mechanism of the surrounding soft tissue in maintaining the stability of the proximal row carpal (PRC) was analyzed, and the methods to repair or reconstruct the stability and function of the PRC were summarized from two aspects including basic biomechanics and clinical biomechanics. The muscles and ligaments of the PRC are critical to its stability. Most scholars have reached a consensus about biomechanical mechanism of the PRC, but there are still controversial conclusions on the biomechanics mechanism of the surrounding soft tissue to stability of distal radioulnar joint when the triangular fibrocartilage complex are damaged and the biomechanics mechanism of the scapholunate ligament. At present, there is no unified standard about the methods to repair or reconstruct the stability and function of the PRC. So, it is difficult for clinical practice. Some strides have been made in the basic biomechanical study on muscle and ligament and clinical biomechanical study on the methods to repair or reconstruct the stability and function of PRC, but it will be needed to further study the morphology of carpal articular surface and the adjacent articular surface, the pressure of distal carpals to proximal carpal and so on.

Comparison on Promotion Effect of Various Types of Surfactants on HCFC-141b Hydrate Induction Time

NASA Astrophysics Data System (ADS)

Li, Juan; Sun, Zhigao; Liu, Chenggang; Zhu, Minggui

2018-03-01

Cold storage in air conditioning based on refrigerant hydrate is a new-type energy saving technology to reduce initial investment and running cost of air conditioning equipments and improve system stability. Refrigerant hydrate is generated under critical temperature and pressure condition, while surfactant is an effective medium to promote its phase equilibrium. In this paper, in order to research such promotion effect, different type of surfactants with unique mechanism, SDS, Tween80 and Span80, n-BA were selected to compare the respective impact on HCFC141b hydrate induction time based on temperature curve. Experimental results showed that no obvious change had been discovered when no surfactant was added into pure water system, which coincided with phase equilibrium diagram of HCFC141b. All the four kinds of surfactants had realized promotion effect to various degrees. For each hydration system, a large gap existed between the longest and the shortest induction time in 6 groups of parallel experiments, meaning relatively poor system stability. Under the combined effect of Tween80 (2wt%), Span80 (0.1wt%) and n-BA (0.1wt%), average and the shortest induction time was 20.9min and 17.5min respectively, corresponding to the best promotion effect.

Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance.

PubMed

Xia, Wenmin; Pessentheiner, Ariane R; Hofer, Dina C; Amor, Melina; Schreiber, Renate; Schoiswohl, Gabriele; Eichmann, Thomas O; Walenta, Evelyn; Itariu, Bianca; Prager, Gerhard; Hackl, Hubert; Stulnig, Thomas; Kratky, Dagmar; Rülicke, Thomas; Bogner-Strauss, Juliane G

2018-05-15

Elevated circulating fatty acids (FAs) contribute to obesity-associated metabolic complications, but the mechanisms by which insulin suppresses lipolysis are poorly understood. We show that α/β-hydrolase domain-containing 15 (ABHD15) is required for the anti-lipolytic action of insulin in white adipose tissue (WAT). Neither insulin nor glucose treatments can suppress FA mobilization in global and conditional Abhd15-knockout (KO) mice. Accordingly, insulin signaling is impaired in Abhd15-KO adipocytes, as indicated by reduced AKT phosphorylation, glucose uptake, and de novo lipogenesis. In vitro data reveal that ABHD15 associates with and stabilizes phosphodiesterase 3B (PDE3B). Accordingly, PDE3B expression is decreased in the WAT of Abhd15-KO mice, mechanistically explaining increased protein kinase A (PKA) activity, hormone-sensitive lipase (HSL) phosphorylation, and undiminished FA release upon insulin signaling. Ultimately, Abhd15-KO mice develop insulin resistance. Notably, ABHD15 expression is decreased in humans with obesity and diabetes compared to humans with obesity and normal glucose tolerance, identifying ABHD15 as a potential therapeutic target to mitigate insulin resistance. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Experimental and density functional theory (DFT) studies on the interactions of Ru(II) polypyridyl complexes with the RAN triplex poly(U)˙poly(A)*poly(U).

PubMed

Zhang, Hong; Liu, Xuewen; He, Xiaojun; Liu, Ying; Tan, Lifeng

2014-11-01

There is renewed interest in investigating triple helices because these novel structures have been implicated as a possible means of controlling cellular processes by endogenous or exogenous mechanisms. Due to the Hoogsteen base pairing, triple helices are, however, thermodynamically less stable than the corresponding duplexes. The poor stability of triple helices limits their practical applications under physiological conditions. In contrast to DNA triple helices, small molecules stabilizing RNA triple helices at present are less well established. Furthermore, most of these studies are limited to organic compounds and, to a far lesser extent, to metal complexes. In this work, two Ru(II) complexes, [Ru(bpy)2(btip)](2+) (Ru1) and [Ru(phen)2(btip)](2+) (Ru2), have been synthesized and characterized. The binding properties of the two metal complexes with the triple RNA poly(U)˙poly(A)*poly(U) were studied by various biophysical and density functional theory methods. The main results obtained here suggest that the slight binding difference in Ru1 and Ru2 may be attributed to the planarity of the intercalative ligand and the LUMO level of Ru(II) complexes. This study further advances our knowledge on the triplex RNA-binding by metal complexes, particularly Ru(II) complexes.

Single-cell-based breeding: Rational strategy for the establishment of cell lines from a single cell with the most favorable properties.

PubMed

Yoshimoto, Nobuo; Kuroda, Shun'ichi

2014-04-01

For efficient biomolecule production (e.g., antibodies, recombinant proteins), mammalian cells with high expression rates should be selected from cell libraries, propagated while maintaining a homogenous expression rate, and subsequently stabilized at their high expression rate. Clusters of isogenic cells (i.e., colonies) have been used for these processes. However, cellular heterogeneity makes it difficult to obtain cell lines with the highest expression rates by using single-colony-based breeding. Furthermore, even among the single cells in an isogenic cell population, the desired cell properties fluctuate stochastically during long-term culture. Therefore, although the molecular mechanisms underlying stochastic fluctuation are poorly understood, it is necessary to establish excellent cell lines in order to breed single cells to have higher expression, higher stability, and higher homogeneity while suppressing stochastic fluctuation (i.e., single-cell-based breeding). In this review, we describe various methods for manipulating single cells and facilitating single-cell analysis in order to better understand stochastic fluctuation. We demonstrated that single-cell-based breeding is practical and promising by using a high-throughput automated system to analyze and manipulate single cells. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Honeycomb-Like Interconnected Network of Nickel Phosphide Heteronanoparticles with Superior Electrochemical Performance for Supercapacitors.

PubMed

Liu, Shude; Sankar, Kalimuthu Vijaya; Kundu, Aniruddha; Ma, Ming; Kwon, Jang-Yeon; Jun, Seong Chan

2017-07-05

Transition-metal-based heteronanoparticles are attracting extensive attention in electrode material design for supercapacitors owing to their large surface-to-volume ratios and inherent synergies of individual components; however, they still suffer from limited interior capacity and cycling stability due to simple geometric configurations, low electrochemical activity of the surface, and poor structural integrity. Developing an elaborate architecture that endows a larger surface area, high conductivity, and mechanically robust structure is a pressing need to tackle the existing challenges of electrode materials. This work presents a supercapacitor electrode consisting of honeycomb-like biphasic Ni 5 P 4 -Ni 2 P (Ni x P y ) nanosheets, which are interleaved by large quantities of nanoparticles. The optimized Ni x P y delivers an ultrahigh specific capacity of 1272 C g -1 at a current density of 2 A g -1 , high rate capability, and stability. An asymmetric supercapacitor employing as-synthesized Ni x P y as the positive electrode and activated carbon as the negative electrode exhibits significantly high power and energy densities (67.2 W h kg -1 at 0.75 kW kg -1 ; 20.4 W h kg -1 at 15 kW kg -1 ). These results demonstrate that the novel nanostructured Ni x P y can be potentially applied in high-performance supercapacitors.

Molecular Docking of Potential Inhibitors of Broccoli Myrosinase.

PubMed

Román, J; Castillo, A; Mahn, A

2018-05-30

Glucosinolates are secondary metabolites occurring in Brassicaceae plants whose hydrolysis may yield isothiocyanates, widely recognized as health-promoting compounds. Myrosinase catalyzes this conversion. The chemical mechanism involves an unstable intermediary (thiohydroxamate- O -sulfonate) that spontaneously decomposes into isothiocyanates or other non-bioactive compounds depending on pH and cofactors. At acidic pH, non-bioactive compounds such as nitriles and thiocyanates are formed, while at neutral pH isothiocyanates are obtained. Broccoli myrosinase has been poorly studied so far. Recently, its amino acidic sequence was elucidated, and a structural model was built. The aim of this work was to study the molecular interaction of broccoli myrosinase with different ligands at acidic pH to propose possible inhibitors that prevent formation of undesirable compounds at acidic pH, and that at neutral pH dissociate from the enzyme, allowing formation of isothiocyanates. The interaction between broccoli myrosinase and 40 ligands was studied by molecular docking simulations. Both the enzyme and each inhibitor were set at pH 3.0. Amygdaline and arbutin showed the highest affinity to broccoli myrosinase in this condition. The residues that stabilize the complexes agree with those that stabilize the substrate (Gln207, Glu429, Tyr352, and Ser433). Accordingly, amygdaline and arbutin would perform as competitive inhibitors of myrosinase at pH 3.0.

Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential.

PubMed

Kuche, Kaushik; Maheshwari, Rahul; Tambe, Vishakha; Mak, Kit-Kay; Jogi, Hardi; Raval, Nidhi; Pichika, Mallikarjuna Rao; Kumar Tekade, Rakesh

2018-05-17

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

Functional and stability orientation synthesis of materials and structures in aprotic Li-O2 batteries.

PubMed

Zhang, Peng; Zhao, Yong; Zhang, Xinbo

2018-04-23

The lithium-O2 battery is one of most promising energy storage and conversion devices due to its ultrahigh theoretical energy density and hence has broad application potential in electrical vehicles and stationary power systems. However, the present Li-O2 battery suffers from a series of challenges for its practical application, such as its low capacity and rate capability, poor round-trip efficiency and short cycle life. These challenges mainly arise from the sluggish and unsustainable discharge and charge reactions at lithium and oxygen electrodes, which determine the performance and durability of a battery. In this review, we first provide insights on the present understanding of the discharge/charge mechanism of such a battery and follow up with establishing a correlation between the specific materials/structures of the battery modules and their functionality/stability within the recent progress in electrodes, electrolytes and redox mediators. Considerable emphasis is paid to the importance of functional orientation design and the synthesis of materials/structures towards accelerating and sustaining the electrode reactions of Li-O2 batteries. Moreover, the future directions and perspectives of rationally constructed material and surface/interface structures, as well as their optimal combinations are proposed for enhancement of the electrode reaction rate and sustainability, and consequently for a better performance and durability of such batteries.

Light-current-induced acceleration of degradation of methylammonium lead iodide perovskite solar cells

NASA Astrophysics Data System (ADS)

Xiang, Yuren; Zhang, Fan; He, Junjie; Lian, Jiarong; Zeng, Pengju; Song, Jun; Qu, Junle

2018-04-01

The photo-conversion efficiency of perovskite solar cells (PSCs) has been improved considerably in recent years, but the poor stability of PSCs still prevents their commercialization. In this report, we use the rate of the integrated short-circuit current change (Drate) to investigate the performance degradation kinetics and identify the degradation of PSCs that is accelerated by the light current. The value of Drate increases by an order of magnitude from about 0.02 to 0.35 mA cm-2·min-1 after light-IV testing. The accelerated degradation progress is proven to be dominated by the hydration process and the migration of the iodine ions of the light current. The migration of the iodine ions enhances the hydration process through a chain reaction, enabling the formation of fast diffusion channels for both H2O and O2, which induce the rapid decomposition of the perovskite film and increase the density of the trap state. The X-ray photoelectron spectroscopy measurement data also indicate that the super oxygen may be formed due to the PCBM damage caused by the migration iodine ions. An understanding of the degradation acceleration mechanism would provide an insight into the effect of ion migration on the stability of PSCs.

Highly Durable Na2V6O16·1.63H2O Nanowire Cathode for Aqueous Zinc-Ion Battery.

PubMed

Hu, Ping; Zhu, Ting; Wang, Xuanpeng; Wei, Xiujuan; Yan, Mengyu; Li, Jiantao; Luo, Wen; Yang, Wei; Zhang, Wencui; Zhou, Liang; Zhou, Zhiqiang; Mai, Liqiang

2018-03-14

Rechargeable aqueous zinc-ion batteries are highly desirable for grid-scale applications due to their low cost and high safety; however, the poor cycling stability hinders their widespread application. Herein, a highly durable zinc-ion battery system with a Na 2 V 6 O 16 ·1.63H 2 O nanowire cathode and an aqueous Zn(CF 3 SO 3 ) 2 electrolyte has been developed. The Na 2 V 6 O 16 ·1.63H 2 O nanowires deliver a high specific capacity of 352 mAh g -1 at 50 mA g -1 and exhibit a capacity retention of 90% over 6000 cycles at 5000 mA g -1 , which represents the best cycling performance compared with all previous reports. In contrast, the NaV 3 O 8 nanowires maintain only 17% of the initial capacity after 4000 cycles at 5000 mA g -1 . A single-nanowire-based zinc-ion battery is assembled, which reveals the intrinsic Zn 2+ storage mechanism at nanoscale. The remarkable electrochemical performance especially the long-term cycling stability makes Na 2 V 6 O 16 ·1.63H 2 O a promising cathode for a low-cost and safe aqueous zinc-ion battery.

Fibromyalgia is Associated with Impaired Balance and Falls

PubMed Central

Jones, Kim D.; Horak, Fay B.; Winters, Kerri Stone; Morea, Jessica M.; Bennett, Robert M.

2010-01-01

Background/Objective The purpose of this study was to determine whether FM patients differ from matched healthy controls in clinical tests of balance ability and fall frequency. Methods 34 FM patients and 32 age matched controls were administered the Balance Evaluation-Systems Test (BESTest), rated their balance confidence with the Activities-Specific Balance Confidence Scale (ABC) and reported the number of falls in the last 6 months. The Fibromyalgia Impact Questionnaire (FIQ) was used to assess FM severity. Results FM patients had significantly impaired balance in all components of the BESTest compared to controls. They also scored more poorly on balance confidence. Overall fibromyalgia severity (FIQ) correlated significantly with the BESTest, and the ABC scale. The BESTest and ABC correlated significantly with 6 commonly reported FM symptoms (excluding pain). FM patients reported a total of 37 falls over the last six-months compared to 6 falls in healthy controls. Conclusion Fibromyalgia is associated with balance problems and increased fall frequency. Patients were aware of their balance problems. These results suggest that FM may affect peripheral and/or central mechanisms of postural control. Further objective study is needed to identify the relative contributions of neural and musculoskeletal impairments to postural stability in FM, thus providing clinicians with exercise prescriptions that maximize postural stability. PMID:19125137

Field monitoring of mechanically stabilized earth walls to investigate secondary reinforcement effects.

DOT National Transportation Integrated Search

2015-12-01

Mechanically stabilized earth (MSE) walls have been commonly used in highway construction. AASHTO (2007) has : detailed design procedures for such a wall system. In the current AASHTO design, only primary reinforcements are used in : relatively large...

Design parameters and methodology for mechanically stabilized earth (MSE) walls.

DOT National Transportation Integrated Search

2014-10-01

Since its appearance in 1970s, mechanically stabilized earth (MSE) walls have become a majority among all types of retaining walls due to their economics and satisfactory performance. The Texas Department of Transportation (TxDOT) has primarily adopt...

Psychosocial mechanisms linking the social environment to mental health in African Americans

USDA-ARS?s Scientific Manuscript database

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African Amer...

Investigating the Pressure-Induced Amorphization of Zeolitic Imidazolate Framework ZIF-8: Mechanical Instability Due to Shear Mode Softening.

PubMed

Ortiz, Aurélie U; Boutin, Anne; Fuchs, Alain H; Coudert, François-Xavier

2013-06-06

We provide the first molecular dynamics study of the mechanical instability that is the cause of pressure-induced amorphization of zeolitic imidazolate framework ZIF-8. By measuring the elastic constants of ZIF-8 up to the amorphization pressure, we show that the crystal-to-amorphous transition is triggered by the mechanical instability of ZIF-8 under compression, due to shear mode softening of the material. No similar softening was observed under temperature increase, explaining the absence of temperature-induced amorphization in ZIF-8. We also demonstrate the large impact of the presence of adsorbate in the pores on the mechanical stability and compressibility of the framework, increasing its shear stability. This first molecular dynamics study of ZIF mechanical properties under variations of pressure, temperature, and pore filling opens the way to a more comprehensive understanding of their mechanical stability, structural transitions, and amorphization.

Influence of the visual environment on the postural stability in healthy older women.

PubMed

Brooke-Wavell, K; Perrett, L K; Howarth, P A; Haslam, R A

2002-01-01

A poor postural stability in older people is associated with an increased risk of falling. It is recognized that visual environment factors (such as poor lighting and repeating patterns on escalators) may contribute to falls, but little is known about the effects of the visual environment on postural stability in the elderly. To determine whether the postural stability of older women (using body sway as a measure) differed under five different visual environment conditions. Subjects were 33 healthy women aged 65-76 years. Body sway was measured using an electronic force platform which identified the location of their centre of gravity every 0.05 s. Maximal lateral sway and anteroposterior sway were determined and the sway velocity calculated over 1-min trial periods. Body sway was measured under each of the following conditions: (1) normal laboratory lighting (186 lx); (2) moderate lighting (10 lx); (3) dim lighting (1 lx); (4) eyes closed, and (5) repeating pattern projected onto a wall. Each measure of the postural stability was significantly poorer in condition 4 (eyes closed) than in all other conditions. Anteroposterior sway was greater in condition 3 than in conditions 1 and 2, whilst the sway velocity was greater in condition 3 than in condition 2. Lateral sway did not differ significantly between different lighting levels (conditions 1-3). A projected repeating pattern (condition 5) did not significantly influence the postural stability relative to condition 1. The substantially greater body sway with eyes closed than with eyes open confirms the importance of vision in maintaining the postural stability. At the lowest light level, the body sway was significantly increased as compared with the other light levels, but was still substantially smaller than on closing the eyes. A projected repeating pattern did not influence the postural stability. Dim lighting levels and removing visual input appear to be associated with a poorer postural stability in older people and hence might be associated with an increased risk of falls. Copyright 2002 S. Karger AG, Basel

Nanoemulsions stabilized by non-ionic surfactants: stability and degradation mechanisms.

PubMed

Koroleva, M; Nagovitsina, T; Yurtov, E

2018-04-18

The prevailing opinion in the literature is that the main mechanism of O/W nanoemulsion degradation is Ostwald ripening. Nevertheless, the experimental rates of Ostwald ripening are usually several orders of magnitude higher than the theoretical values. This suggests that other mechanisms, such as coalescence, flocculation and subsequent creaming, significantly influence nanoemulsion breakdown. We investigated O/W nanoemulsions stabilized by Brij 30 or by a mixture of Tween 80 and Span 80 and with liquid paraffin as a dispersed phase. The results indicate that Ostwald ripening is the main process leading to nanoemulsion coarsening only in nanoemulsions with low oil phase fractions of up to 0.05. For quasi-steady state conditions the rates of Ostwald ripening are equal to (1.5 ± 0.3) × 10-29 and (1.1 ± 0.3) × 10-29 m3 s-1 in nanoemulsions with Brij 30 and Tween 80 & Span 80, respectively. In nanoemulsions with oil phase fractions of 0.15-0.45, different mechanisms are identified. Flocculation prevails over other processes during the first days in nanoemulsions stabilized by Brij 30. Coalescence is the main mechanism of nanoemulsion degradation for long times. An increase in droplet size 5-10 days after nanoemulsion preparation due to Ostwald ripening takes place in the case of nanoemulsion stabilization by Tween 80 and Span 80. The stability behavior of these nanoemulsions at later stages is distinctly affected by coalescence and flocculation.

Formulating food protein-stabilized indomethacin nanosuspensions into pellets by fluid-bed coating technology: physical characterization, redispersibility, and dissolution.

PubMed

He, Wei; Lu, Yi; Qi, Jianping; Chen, Lingyun; Yin, Lifang; Wu, Wei

2013-01-01

Drug nanosuspensions are very promising for enhancing the dissolution and bioavailability of drugs that are poorly soluble in water. However, the poor stability of nanosuspensions, reflected in particle growth, aggregation/agglomeration, and change in crystallinity state greatly limits their applications. Solidification of nanosuspensions is an ideal strategy for addressing this problem. Hence, the present work aimed to convert drug nanosuspensions into pellets using fluid-bed coating technology. Indomethacin nanosuspensions were prepared by the precipitation-ultrasonication method using food proteins (soybean protein isolate, whey protein isolate, β-lactoglobulin) as stabilizers. Dried nanosuspensions were prepared by coating the nanosuspensions onto pellets. The redispersibility, drug dissolution, solid-state forms, and morphology of the dried nanosuspensions were evaluated. The mean particle size for the nanosuspensions stabilized using soybean protein isolate, whey protein isolate, and β-lactoglobulin was 588 nm, 320 nm, and 243 nm, respectively. The nanosuspensions could be successfully layered onto pellets with high coating efficiency. Both the dried nanosuspensions and nanosuspensions in their original amorphous state and not influenced by the fluid-bed coating drying process could be redispersed in water, maintaining their original particle size and size distribution. Both the dried nanosuspensions and the original drug nanosuspensions showed similar dissolution profiles, which were both much faster than that of the raw crystals. Fluid-bed coating technology has potential for use in the solidification of drug nanosuspensions.

Molecular ligand modulation of palladium nanocatalysts for highly efficient and robust heterogeneous oxidation of cyclohexenone to phenol

DOE PAGES

Xue, Teng; Lin, Zhaoyang; Chiu, Chin-Yi; ...

2017-01-06

Metallic nanoparticles are emerging as an exciting class of heterogeneous catalysts with the potential advantages of exceptional activity, stability, recyclability, and easier separation than homogeneous catalysts. The traditional colloid nanoparticle syntheses usually involve strong surface binding ligands that could passivate the surface active sites and result in poor catalytic activity. The subsequent removal of surface ligands could reactivate the surface but often leads to metal ion leaching and/or severe Ostwald ripening with diminished catalytic activity or poor stability. Molecular ligand engineering represents a powerful strategy for the design of homogeneous molecular catalysts but is insufficiently explored for nanoparticle catalysts tomore » date. We report a systematic investigation on molecular ligand modulation of palladium (Pd) nanoparticle catalysts. Our studies show that β-functional groups of butyric acid ligand on Pd nanoparticles can significantly modulate the catalytic reaction process to modify the catalytic activity and stability for important aerobic reactions. With a β-hydroxybutyric acid ligand, the Pd nanoparticle catalysts exhibit exceptional catalytic activity and stability with an unsaturated turnover number (TON) >3000 for dehydrogenative oxidation of cyclohexenone to phenol, greatly exceeding that of homogeneous Pd(II) catalysts (TON, ~30). This study presents a systematic investigation of molecular ligand modulation of nanoparticle catalysts and could open up a new pathway toward the design and construction of highly efficient and robust heterogeneous catalysts through molecular ligand engineering.« less

Planning for Action: Campaign Concepts and Tools

DTIC Science & Technology

2012-08-01

142 10-15. Stability Mechanisms – Army .................................... 143 10-16. Stability Mechanisms – Joint...defeat mechanisms, which focus 143 the destructive and coercive capabilities of the force to provide security and public order and safety for...Matthew B. Ridgway. GEN Ridgway successfully led the 82d Airborne Division and XVIII Airborne Corps in the ETO during World War II and Eighth (US

Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients.

PubMed

Tsoi, H; Lam, K C; Dong, Y; Zhang, X; Lee, C K; Zhang, J; Ng, S C; Ng, S S M; Zheng, S; Chen, Y; Fang, J; Yu, J

2017-11-02

One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression level of pre-45s rRNA is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients.

Preparation of novel porous starch microsphere foam for loading and release of poorly water soluble drug.

PubMed

Jiang, Tongying; Wu, Chao; Gao, Yikun; Zhu, Wenquan; Wan, Long; Wang, Zhanyou; Wang, Siling

2014-02-01

Organic porous material is a promising carrier for enhancing the dissolution of poorly water soluble drug. The aim of the present study was to enhance dissolution and oral bioavailability of lovastatin (LV) by preparing a porous starch microsphere foam (PSM) using a novel method, meanwhile, looking into the mechanism of improving dissolution of LV. PSM was prepared by the W/O emulsion-freeze thawing method. The porous structure of PSM was characterized by scanning electron microscopy (SEM) and nitrogen adsorption/desorption analysis. The adsorption role of nanopores on the drug dissolution and physical state of LV was systematically studied by instrumental analysis, and in vitro and in vivo drug dissolution studies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate carrier cytotoxicity. The SEM images of PSM showed nanometer-sized pores. Physical state characterization indicated that porous structure effectively limited the degree of crystallinity of LV. The results of in vitro and in vivo tests testified that PSM accelerated the release of LV and enhanced its oral bioavailability in comparison with crude LV and commercial capsules. The loaded PSM powder indicated a good physical stability under storage for 12 months. MTT assay shows PSM has no toxicity for Caco-2 cell. The preparation was a promising method to produce small and uniform PSM with markedly enhanced dissolution rate and oral bioavailability due to the spatial confinement effect of porous structure. The present work demonstrates the significant potential for the use of PSM as a novel delivery system for poorly water soluble drugs.

Thermal and aqueous stability improvement of graphene oxide enhanced diphenylalanine nanocomposites

NASA Astrophysics Data System (ADS)

Ryan, Kate; Neumayer, Sabine M.; Maraka, Harsha Vardhan R.; Buchete, Nicolae-Viorel; Kholkin, Andrei L.; Rice, James H.; Rodriguez, Brian J.

2017-12-01

Nanocomposites of diphenylalanine (FF) and carbon based materials provide an opportunity to overcome drawbacks associated with using FF micro- and nanostructures in nanobiotechnology applications, in particular their poor structural stability in liquid solutions. In this study, FF/graphene oxide (GO) composites were found to self-assemble into layered micro- and nanostructures, which exhibited improved thermal and aqueous stability. Dependent on the FF/GO ratio, the solubility of these structures was reduced to 35.65% after 30 min as compared to 92.4% for pure FF samples. Such functional nanocomposites may extend the use of FF structures to e.g. biosensing, electrochemical, electromechanical or electronic applications.

On the mechanical stability of uranyl peroxide hydrates: Implications for nuclear fuel degradation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weck, Philippe F.; Kim, Eunja; Buck, Edgar C.

The mechanical properties and stability of studtite, (UO2)(O2)(H2O)2·2H2O, and metastudtite, (UO2)(O2)(H2O)2, two important corrosion phases observed on spent nuclear fuel exposed to water, have been investigated using density functional perturbation theory. While (UO2)(O2)(H2O)2 satisfies the necessary and sufficient Born criteria for mechanical stability, (UO2)(O2)(H2O)2·2H2O is found to be mechanically metastable, which might be the underlying cause of the irreversibility of the studtite to metastudtite transformation. According to Pugh’s and Poisson’s ratios and the Cauchy pressure, both phases are considered ductile and shear modulus is the parameter limiting their mechanical stability. Debye temperatures of 294 and 271 K are predicted formore » polycrystalline (UO2)(O2)(H2O)2·2H2O and (UO2)(O2)(H2O)2, suggesting a lower micro-hardness of metastudtite.« less

On the mechanical stability of uranyl peroxide hydrates: Implications for nuclear fuel degradation

DOE PAGES

Weck, Philippe F.; Kim, Eunja; Buck, Edgar C.

2015-09-11

The mechanical properties and stability of studtite, (UO 2)(O 2)(H 2O) 2·2H 2O, and metastudtite, (UO 2)(O 2)(H 2O) 2, two important corrosion phases observed on spent nuclear fuel exposed to water, have been investigated using density functional perturbation theory. While (UO 2)(O 2)(H 2O) 2 satisfies the necessary and sufficient Born criteria for mechanical stability, (UO 2)(O 2)(H 2O) 2·2H 2O is found to be mechanically metastable, which might be the underlying cause of the irreversibility of the studtite to metastudtite transformation. According to Pugh's and Poisson's ratios and the Cauchy pressure, both phases are considered ductile and shearmore » modulus is the parameter limiting their mechanical stability. Furthermore, debye temperatures of 294 and 271 K are predicted for polycrystalline (UO 2)(O 2)(H 2O) 2·2H 2O and (UO 2)(O 2)(H 2O) 2, suggesting a lower micro-hardness of metastudtite.« less

The Impact of Osseous Malalignment and Realignment Procedures in Knee Ligament Surgery: A Systematic Review of the Clinical Evidence.

PubMed

Tischer, Thomas; Paul, Jochen; Pape, Dietrich; Hirschmann, Michael T; Imhoff, Andreas B; Hinterwimmer, Stefan; Feucht, Matthias J

2017-03-01

Failure rates of knee ligament surgery may be high, and the impact of osseous alignment on surgical outcome remains controversial. Basic science studies have demonstrated that osseous malalignment can negatively affect ligament strain and that realignment procedures may improve knee joint stability. The purpose of this review was to summarize the clinical evidence concerning the impact of osseous malalignment and realignment procedures in knee ligament surgery. The hypotheses were that lower extremity malalignment would be an important contributor to knee ligament surgery failure and that realignment surgery would contribute to increased knee stability and improved outcome in select cases. Systematic review; Level of evidence, 4. According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic electronic search of the PubMed database was performed in November 2015 to identify clinical studies investigating (A) the influence of osseous alignment on postoperative stability and/or failure rates after knee ligament surgery and (B) the impact of osseous realignment procedures in unstable knees with or without additional knee ligament surgery on postoperative knee function and stability. Methodological quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence and the Coleman Methodological Score (CMS). Of the 1466 potentially relevant articles, 28 studies fulfilled the inclusion and exclusion criteria. Average study quality was poor (CMS, 40). For part A, studies showed increased rerupture rate after anterior cruciate ligament (ACL) replacement in patients with increased tibial slope. Concerning the posterior cruciate ligament (PCL)/posterolateral corner (PLC)/lateral collateral ligament (LCL), varus malalignment was considered a significant risk factor for failure. For part B, studies showed decreased anterior tibial translation after slope-decreasing high tibial osteotomy in ACL-deficient knees. Correcting varus malalignment in PCL/PLC/LCL instability also showed increased stability and better outcomes. In cases of complex knee instability, the 3-dimensional osseous alignment of the knee should be considered (eg, mechanical weightbearing line and tibial slope). In cases of failed ACL reconstruction, the tibial slope should be considered, and slope-reducing osteotomies are often helpful in the patient revised multiple times. In cases of chronic PCL and/or PLC instability, osseous correction of the varus alignment may reduce the failure rate and is often the first step in treatment. Changes in the mechanical axis should be considered in all cases of instability accompanied by early unicompartmental osteoarthritis.

The Impact of Osseous Malalignment and Realignment Procedures in Knee Ligament Surgery: A Systematic Review of the Clinical Evidence

PubMed Central

Tischer, Thomas; Paul, Jochen; Pape, Dietrich; Hirschmann, Michael T.; Imhoff, Andreas B.; Hinterwimmer, Stefan; Feucht, Matthias J.

2017-01-01

Background: Failure rates of knee ligament surgery may be high, and the impact of osseous alignment on surgical outcome remains controversial. Basic science studies have demonstrated that osseous malalignment can negatively affect ligament strain and that realignment procedures may improve knee joint stability. Hypothesis/Purpose: The purpose of this review was to summarize the clinical evidence concerning the impact of osseous malalignment and realignment procedures in knee ligament surgery. The hypotheses were that lower extremity malalignment would be an important contributor to knee ligament surgery failure and that realignment surgery would contribute to increased knee stability and improved outcome in select cases. Study Design: Systematic review; Level of evidence, 4. Methods: According to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic electronic search of the PubMed database was performed in November 2015 to identify clinical studies investigating (A) the influence of osseous alignment on postoperative stability and/or failure rates after knee ligament surgery and (B) the impact of osseous realignment procedures in unstable knees with or without additional knee ligament surgery on postoperative knee function and stability. Methodological quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence and the Coleman Methodological Score (CMS). Results: Of the 1466 potentially relevant articles, 28 studies fulfilled the inclusion and exclusion criteria. Average study quality was poor (CMS, 40). For part A, studies showed increased rerupture rate after anterior cruciate ligament (ACL) replacement in patients with increased tibial slope. Concerning the posterior cruciate ligament (PCL)/posterolateral corner (PLC)/lateral collateral ligament (LCL), varus malalignment was considered a significant risk factor for failure. For part B, studies showed decreased anterior tibial translation after slope-decreasing high tibial osteotomy in ACL-deficient knees. Correcting varus malalignment in PCL/PLC/LCL instability also showed increased stability and better outcomes. Conclusion: In cases of complex knee instability, the 3-dimensional osseous alignment of the knee should be considered (eg, mechanical weightbearing line and tibial slope). In cases of failed ACL reconstruction, the tibial slope should be considered, and slope-reducing osteotomies are often helpful in the patient revised multiple times. In cases of chronic PCL and/or PLC instability, osseous correction of the varus alignment may reduce the failure rate and is often the first step in treatment. Changes in the mechanical axis should be considered in all cases of instability accompanied by early unicompartmental osteoarthritis. PMID:28451605

Supramolecular Complexation of Carbohydrates for the Bioavailability Enhancement of Poorly Soluble Drugs.

PubMed

Cho, Eunae; Jung, Seunho

2015-10-27

In this review, a comprehensive overview of advances in the supramolecular complexes of carbohydrates and poorly soluble drugs is presented. Through the complexation process, poorly soluble drugs could be efficiently delivered to their desired destinations. Carbohydrates, the most abundant biomolecules, have diverse physicochemical properties owing to their inherent three-dimensional structures, hydrogen bonding, and molecular recognition abilities. In this regard, oligosaccharides and their derivatives have been utilized for the bioavailability enhancement of hydrophobic drugs via increasing the solubility or stability. By extension, polysaccharides and their derivatives can form self-assembled architectures with poorly soluble drugs and have shown increased bioavailability in terms of the sustained or controlled drug release. These supramolecular systems using carbohydrate will be developed consistently in the field of pharmaceutical and medical application.

Experimental investigations on mechanical behavior of unsaturated subgrade soil with lime stabilization and fiber reinforcement : final report.

DOT National Transportation Integrated Search

2003-11-01

In the present report, experimental investigations on mechanical behavior of unsaturated subgrade soil : with fiber reinforcement and lime stabilization were conducted. : The soil samples were collected from the soil/aggregate laboratory at the Maryl...

Interaction between drilled shaft and mechanically stabilized earth (MSE) wall : technical report.

DOT National Transportation Integrated Search

2017-04-01

Drilled shafts are being constructed within the reinforced zone of mechanically stabilized earth (MSE) walls especially in the case of overpass bridges where the drilled shafts carry the bridge deck or traffic signs. The interaction between the drill...

0-6716 : design parameters and methodology for mechanically stabilized earth (MSE) walls.

DOT National Transportation Integrated Search

2013-08-01

Since their appearance in the 1970s, mechanically : stabilized earth (MSE) walls have become a majority : among all types of retaining walls due to their economics : and satisfactory performance. The Texas Department of : Transportation (TxDOT) has p...

Field monitoring of mechanically stabilized earth walls to investigate secondary reinforcement effects : [technical summary].

DOT National Transportation Integrated Search

2015-12-01

Mechanically stabilized earth (MSE) walls have been commonly used in highway : construction. AASHTO (2007) has detailed design procedures for such a wall system. : In the current AASHTO design, only primary reinforcements are used in relatively : lar...

Consequences of Growing Up Poor.

ERIC Educational Resources Information Center

Duncan, Greg J., Ed.; Brooks-Gunn, Jeanne, Ed.

The consequences and correlates of growing up poor as well as the mechanisms through which poverty influences children are explored. This book is organized with a primary focus on research findings and a secondary concern with policy implications. The chapters are: (1) "Poor Families, Poor Outcomes: The Well-Being of Children and Youth" (Jeanne…

Rotational accelerations stabilize leading edge vortices on revolving fly wings.

PubMed

Lentink, David; Dickinson, Michael H

2009-08-01

The aerodynamic performance of hovering insects is largely explained by the presence of a stably attached leading edge vortex (LEV) on top of their wings. Although LEVs have been visualized on real, physically modeled, and simulated insects, the physical mechanisms responsible for their stability are poorly understood. To gain fundamental insight into LEV stability on flapping fly wings we expressed the Navier-Stokes equations in a rotating frame of reference attached to the wing's surface. Using these equations we show that LEV dynamics on flapping wings are governed by three terms: angular, centripetal and Coriolis acceleration. Our analysis for hovering conditions shows that angular acceleration is proportional to the inverse of dimensionless stroke amplitude, whereas Coriolis and centripetal acceleration are proportional to the inverse of the Rossby number. Using a dynamically scaled robot model of a flapping fruit fly wing to systematically vary these dimensionless numbers, we determined which of the three accelerations mediate LEV stability. Our force measurements and flow visualizations indicate that the LEV is stabilized by the ;quasi-steady' centripetal and Coriolis accelerations that are present at low Rossby number and result from the propeller-like sweep of the wing. In contrast, the unsteady angular acceleration that results from the back and forth motion of a flapping wing does not appear to play a role in the stable attachment of the LEV. Angular acceleration is, however, critical for LEV integrity as we found it can mediate LEV spiral bursting, a high Reynolds number effect. Our analysis and experiments further suggest that the mechanism responsible for LEV stability is not dependent on Reynolds number, at least over the range most relevant for insect flight (100

SOCIODEMOGRAPHIC DOMAINS OF DEPRIVATION AND PRETERM BIRTH

EPA Science Inventory

Area-level deprivation is consistently associated with poor health outcomes. Using US census data (2000) and principal components analysis, a priori defined socio-demographic indices of poverty, housing, residential stability, occupation, employment and education were created fo...

Enhanced colloidal stability, solubility and rapid dissolution of resveratrol by nanocomplexation with soy protein isolate.

PubMed

Pujara, Naisarg; Jambhrunkar, Siddharth; Wong, Kuan Yau; McGuckin, Michael; Popat, Amirali

2017-02-15

The polyphenolic compound resveratrol has received significant attention due to its many pharmacological actions such as anti-cancer, anti-inflammatory, antioxidant and antimicrobial activities. However, poor solubility and stability are major impediments for resveratrol's clinical effectiveness. In this work we have encapsulated resveratrol into soy protein isolate nanoparticles using a simple rotary evaporation technique. Resveratrol-loaded nanoparticles were around 100nm in diameter and negatively charged. Nano-encapsulated resveratrol was found to be in amorphous form and showed more than two times higher solubility with significantly increased dissolution when compared to free resveratrol. Finally, an in-vitro NF-κB inhibition assay revealed that encapsulated resveratrol was stable and retained bioactivity. This new formulation of resveratrol has the potential to boost the clinical effectiveness of this drug and could be utilised for other poorly soluble hydrophobic drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Contingency in the Direction and Mechanics of Soil Organic Matter Responses to Increased Rainfall

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berhe, Asmeret A.; Suttle, K. Blake; Burton, Sarah D.

2012-09-03

Shifts in regional precipitation patterns will be a major component of global climate change. Rainfall will show greater and more variable changes in response to rising earth surface temperatures than most other climatic variables, and will be a major driver of ecosystem change. We studied the consequences of predicted changes in California’s rainy season for storage and stabilization mechanisms of soil organic matter (SOM). In a controlled and replicated experiment, we amended rainfall over large plots of natural grassland in accordance with alternative scenarios of future climate change. Results show that increases in annual rainfall have important consequences for soilmore » C storage, but that the strength and even direction of these effects depend entirely on seasonal timing. Rainfall increases during the winter rainy season led to pronounced C loss from soil while rainfall increases after the typical rainy season increased soil C stocks. Analysis of mineral-OM associations reveals a powerful mechanism underlying this difference: increased winter rainfall vastly diminished the role of Fe and Al oxides in SOM stabilization. Dithionite extractable crystalline Fe oxides explained more than 35 percent of the variability in C storage in ambient control and spring-addition treatments, compared to less than 0.01 percent in the winter-addition treatment. Likewise, poorly crystalline Fe and Al oxides explained more than 25 and 40 percent of the variability in C storage, respectively, in the control and spring-addition treatments compared to less than 5 percent in the -winter-addition treatment. Increases in annual precipitation identical in amount but at three-month offsets produced opposite effects on soil C storage. These results highlight the complexity inherent in biospheric feedbacks to the climate system, and the way that careful experimentation can penetrate that complexity to improve predictions of ecosystem and climatic change.« less

Investigating the Thermal and Phase Stability of Nanocrystalline Ni-W Produced by Electrodeposition, Sputtering, and Mechanical Alloying

NASA Astrophysics Data System (ADS)

Marvel, Christopher Jonathan

The development of nanocrystalline materials has been increasingly pursued over the last few decades. They have been shown to exhibit superior properties compared to their coarse-grain counterparts, and thus present a tremendous opportunity to revolutionize the performance of nanoscale devices or bulk structural materials. However, nanocrystalline materials are highly prone to grain growth, and if the nanocrystalline grains coarsen, the beneficial properties are lost. There is a strong effort to determine the most effective thermal stability mechanisms to avoid grain growth, but the physical nature of nanocrystalline grain growth is still unclear due to a lack of detailed understanding of nanocrystalline microstructures. Furthermore, the influence of contamination has scarcely been explored with advanced transmission electron microscopy techniques, nor has there been a direct comparison of alloys fabricated with different bulk processes. Therefore, this research has applied aberration-corrected scanning transmission electron microscopy to characterize nanocrystalline Ni-W on the atomic scale and elucidate the physical grain growth behavior. Three primary objectives were pursued: (1) explore the thermal stability mechanisms of nanocrystalline Ni-W, (2) evaluate the phase stability of Ni-W and link any findings to grain growth behavior, and (3) compare the influences of bulk fabrication processing, including electrodeposition, DC magnetron sputtering, and mechanical alloying, on the thermal stability and phase stability of Ni-W. Several thermal stability mechanisms were identified throughout the course of this research. First and foremost, W-segregation was scarcely observed to grain boundaries, and it is unclear if W-segregation improves thermal stability contrary to most reports in the 2 literature. Long-range Ni4W chemical ordering was observed in alloys with more than 20 at.% W, and it is likely Ni4W domains reduce grain boundary mobility. In addition, lattice diffusivity calculations conceptually suggested that increasing W alloying concentrations can decrease the grain growth rate. The strongest evidence of grain growth stagnation was via nanoscale oxide particle drag in highly contaminated electrodeposited alloys. Interestingly, W-segregation was also detected to the oxide phase boundaries and revealed a potential indirect mechanism of thermal stability. The phase stability of pure and contaminated Ni-W alloys was investigated with density functional theory. Primarily, the calculations suggested that the intermetallic phases NiW and NiW2 are thermodynamically unstable, meaning the binary phase diagram is incorrect, but the ternary carbides Ni 6W6C and Ni2W4C are stable. Several Ni-W binary and Ni-W-C ternary phase diagrams were constructed using a simplified CALPHAD approach to improve the understanding of Ni-W phase stability. Lastly, it was determined that the fabrication process greatly influences the impurity types and concentrations of the alloys, and therefore greatly dictate which thermal stability mechanisms are active. Mechanically alloyed samples were found to be the most resistant to grain growth. The findings of this research will hopefully guide future efforts to design more thermally stable nanocrystalline alloys. The link between phase stability and grain growth behavior of Ni-W was thoroughly discussed, as well as the dependence of bulk fabrication processing on the contamination found in the alloys. Ultimately, this research has greatly expanded the general understanding of nanocrystalline Ni-W microstructures, and it is likely that similar phenomena occur in other nanocrystalline systems.

An assessment of the mechanical stability of wells offshore Nigeria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowrey, J.P.; Ottesen, S.

In 1991 lost time due to stuck pipe related drilling problems accounted for approximately 18% of total drilling time in Mobil Producing Nigeria Ultd.`s (MPN) offshore operations. The primary cause of stuck pipe was identified as mechanical wellbore instability. This paper presents an assessment of the mechanical stability of MPN`s wells offshore Nigeria. The objectives of the study were to: (1) determine the magnitude of the in-situ principal stresses and material properties of the troublesome Intra-Biafra and Qua Iboe shale sequences; (2) quantify the drilling fluid densities required to drill mechanically stable wells through these formations; (3) review and recommendmore » well planning and operational parameters which aid in minimizing wellbore stability-related drilling problems. The well-bore stability assessment was carried out with the aid of a 3-dimensional wellbore stability model using field derived data from the study area to corroborate the results. The collection and analysis of drilling data (borehole geometry and density logs, pore pressure, leak-off tests, local geology and other relevant well records) to determine the magnitude of the in-situ principal stresses, together with compressive strength tests on formation cores are discussed. Minimum safe drilling fluid densities to promote wellbore stability as a function of well geometry and depth are presented for the most troublesome shales drilled in the study area. Implementation of the results reduced wellbore stability related problems and associated trouble time to less than 5% in 1992.« less