Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications.

PubMed

Adisakwattana, Sirichai

2017-02-21

With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients.

Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications

PubMed Central

Adisakwattana, Sirichai

2017-01-01

With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients. PMID:28230764

Lung-Derived Mediators Induce Cytokine Production in Downstream Organs via an NF-κ B-Dependent Mechanism

PubMed Central

Patterson, E. K.; Yao, L. J.; Ramic, N.; Lewis, J. F.; Cepinskas, G.; McCaig, L.; Veldhuizen, R. A. W.; Yamashita, C. M.

2013-01-01

In the setting of acute lung injury, levels of circulating inflammatory mediators have been correlated with adverse outcomes. Previous studies have demonstrated that injured, mechanically ventilated lungs represent the origin of the host inflammatory response; however, mechanisms which perpetuate systemic inflammation remain uncharacterized. We hypothesized that lung-derived mediators generated by mechanical ventilation (MV) are amplified by peripheral organs in a “feed forward” mechanism of systemic inflammation. Herein, lung-derived mediators were collected from 129X1/SVJ mice after 2 hours of MV while connected to the isolated perfused mouse lung model setup. Exposure of liver endothelial cells to lung-derived mediators resulted in a significant increase in G-CSF, IL-6, CXCL-1, CXCL-2, and MCP-1 production compared to noncirculated control perfusate media (P < 0.05). Furthermore, inhibition of the NF-κB pathway significantly mitigated this response. Changes in gene transcription were confirmed using qPCR for IL-6, CXCL-1, and CXCL-2. Additionally, liver tissue obtained from mice subjected to 2 hours of in vivo MV demonstrated significant increases in hepatic gene transcription of IL-6, CXCL-1, and CXCL-2 compared to nonventilated controls. Collectively, this data demonstrates that lung-derived mediators, generated in the setting of MV, are amplified by downstream organs in a feed forward mechanism of systemic inflammation. PMID:23606793

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.

Synthesis and anti-H5N1 activity of chiral gossypol derivatives and its analogs implicated by a viral entry blocking mechanism.

PubMed

Yang, Jian; Chen, Gang; Li, Long Long; Pan, Wei; Zhang, Fang; Yang, Jingxiang; Wu, Shuwen; Tien, Po

2013-05-01

A series of chiral gossypol derivatives and its analogs were synthesized and tested in vitro for their anti-H5N1 activity. Interestingly, (+)-gossypol derivatives and its analogs were more active against H5N1 than the corresponding (-)-gossypol derivatives and its analogs. Through a simple chemical modification with amino acids, less active chiral gossypol could be converted into more active derivatives, and most of chiral gossypol derivatives were more potent against H5N1 than 1-adamantylamine. With regard to the mechanism of action, chiral gossypol derivatives and its analogs might impair the virus entry step of cell infection, likely targeting to HA2 protein. Copyright © 2013 Elsevier Ltd. All rights reserved.

Post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon lithography [A post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon polymerization

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

Oakdale, James S.; Ye, Jianchao; Smith, William L.

Here, two photon polymerization (TPP) is a precise, reliable, and increasingly popular technique for rapid prototyping of micro-scale parts with sub-micron resolution. The materials of choice underlying this process are predominately acrylic resins cross-linked via free-radical polymerization. Due to the nature of the printing process, the derived parts are only partially cured and the corresponding mechanical properties, i.e. modulus and ultimate strength, are lower than if the material were cross-linked to the maximum extent. Herein, post-print curing via UV-driven radical generation, is demonstrated to increase the overall degree of cross-linking of low density, TPP-derived structures.

Post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon lithography [A post-print UV curing method for improving the mechanical properties of prototypes derived from two-photon polymerization

DOE PAGES

Oakdale, James S.; Ye, Jianchao; Smith, William L.; ...

2016-11-28

Here, two photon polymerization (TPP) is a precise, reliable, and increasingly popular technique for rapid prototyping of micro-scale parts with sub-micron resolution. The materials of choice underlying this process are predominately acrylic resins cross-linked via free-radical polymerization. Due to the nature of the printing process, the derived parts are only partially cured and the corresponding mechanical properties, i.e. modulus and ultimate strength, are lower than if the material were cross-linked to the maximum extent. Herein, post-print curing via UV-driven radical generation, is demonstrated to increase the overall degree of cross-linking of low density, TPP-derived structures.

Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages.

PubMed

Sumiya, Yu; Ishikawa, Mami; Inoue, Takahiro; Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Uto, Yoshihiro; Nishikata, Takahito

2015-08-01

Although the mechanisms of macrophage activation are important for cancer immunotherapy, they are poorly understood. Recently, easy and robust assay systems for assessing the macrophage-activating factor (MAF) using monocytic cell line-derived macrophages were established. Gene-expression profiles of U937- and THP-1-derived macrophages were compared using gene expression microarray analysis and their responses against several MAFs were examined by in vitro experiments. Activated states of these macrophages could not be assigned to a specific sub-type but showed, however, different unique characteristics. The unique of monocytic cell line-derived macrophages could provide clues to understand the activation mechanism of macrophages and, therefore, help to develop effective cancer immunotherapy with MAFs. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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.

47 CFR 54.709 - Computations of required contributions to universal service support mechanisms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... contributors' interstate and international revenues derived from domestic end users for telecommunications or... will be contributors' projected collected interstate and international revenues derived from domestic... mechanisms to the total end-user interstate and international telecommunications revenues, net of prior...

Menzerath-Altmann Law: Statistical Mechanical Interpretation as Applied to a Linguistic Organization

NASA Astrophysics Data System (ADS)

Eroglu, Sertac

2014-10-01

The distribution behavior described by the empirical Menzerath-Altmann law is frequently encountered during the self-organization of linguistic and non-linguistic natural organizations at various structural levels. This study presents a statistical mechanical derivation of the law based on the analogy between the classical particles of a statistical mechanical organization and the distinct words of a textual organization. The derived model, a transformed (generalized) form of the Menzerath-Altmann model, was termed as the statistical mechanical Menzerath-Altmann model. The derived model allows interpreting the model parameters in terms of physical concepts. We also propose that many organizations presenting the Menzerath-Altmann law behavior, whether linguistic or not, can be methodically examined by the transformed distribution model through the properly defined structure-dependent parameter and the energy associated states.

Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway in depressive disorder☆

PubMed Central

Wang, Hongyan; Zhang, Yingquan; Qiao, Mingqi

2013-01-01

The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression. PMID:25206732

Derivation of Performance Statements for the Automotive Mechanics Basic Trade Course: Research Documentation.

ERIC Educational Resources Information Center

Fox, A. P.; Kuhl, D. H.

A project was conducted to derive a comprehensive list of the performances of a competence mechanic to satisfy the planning needs of automotive engineering lecturers, curriculum committees, researchers, course designers, and staff developers. A list of 127 tasks together with information about their relative importance and the frequency with which…

Photochemistry of Naphthopyrans and Derivatives: A Computational Experiment for Upper-Level Undergraduates or Graduate Students

ERIC Educational Resources Information Center

Castet, Frédéric; Méreau, Raphaël; Liotard, Daniel

2014-01-01

In this computational experiment, students use advanced quantum chemistry tools to simulate the photochromic reaction mechanism in naphthopyran derivatives. The first part aims to make students familiar with excited-state reaction mechanisms and addresses the photoisomerization of the benzopyran molecule by means of semiempirical quantum chemical…

Beyond velocity and acceleration: jerk, snap and higher derivatives

NASA Astrophysics Data System (ADS)

Eager, David; Pendrill, Ann-Marie; Reistad, Nina

2016-11-01

The higher derivatives of motion are rarely discussed in the teaching of classical mechanics of rigid bodies; nevertheless, we experience the effect not only of acceleration, but also of jerk and snap. In this paper we will discuss the third and higher order derivatives of displacement with respect to time, using the trampolines and theme park roller coasters to illustrate this concept. We will also discuss the effects on the human body of different types of acceleration, jerk, snap and higher derivatives, and how they can be used in physics education to further enhance the learning and thus the understanding of classical mechanics concepts.

Proteomic Analysis of the Extracellular Matrix Produced by Mesenchymal Stromal Cells: Implications for Cell Therapy Mechanism

PubMed Central

Harvey, Adam; Yen, Ten-Yang; Aizman, Irina; Tate, Ciara; Case, Casey

2013-01-01

Mesenchymal stromal cells (MSCs) transiently transfected with notch1 intracellular domain (NICD) are beneficial for neurological disorders as observed in several preclinical studies. Extracellular matrix (ECM) derived from NICD-transfected MSCs has been previously shown to support in vitro neural cell growth and survival better than that of un-transfected MSCs. To understand the underlying mechanism(s) by which NICD-transfected MSC-derived ECM supports neural cell growth and survival, we investigated the differences in NICD-transfected MSC- and MSC-derived ECM protein quantity and composition. To compare the ECM derived from MSCs and NICD-transfected MSCs, the proteins were sequentially solubilized using sodium dodecyl sulfate (SDS) and urea, quantified, and compared across four human donors. We then analyzed ECM proteins using either in-gel digests or in-solution surfactant-assisted trypsin digests (SAISD) coupled with reverse phase nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Analyses using nLC-MS/MS identified key components of ECM from NICD-transfected MSCs and un-transfected MSCs and revealed significant differences in their respective compositions. This work provides a reproducible method for identifying and comparing in vitro cell-derived ECM proteins, which is crucial for exploring the mechanisms underlying cellular therapy. PMID:24244468

Inhibition of Staphylococcus epidermidis biofilms using polymerizable vancomycin derivatives.

PubMed

Lawson, McKinley C; Hoth, Kevin C; Deforest, Cole A; Bowman, Christopher N; Anseth, Kristi S

2010-08-01

Biofilm formation on indwelling medical devices is a ubiquitous problem causing considerable patient morbidity and mortality. In orthopaedic surgery, this problem is exacerbated by the large number and variety of material types that are implanted. Metallic hardware in conjunction with polymethylmethacrylate (PMMA) bone cement is commonly used. We asked whether polymerizable derivatives of vancomycin might be useful to (1) surface modify Ti-6Al-4V alloy and to surface/bulk modify PMMA bone cement to prevent Staphylococcus epidermidis biofilm formation and (2) whether the process altered the compressive modulus, yield strength, resilience, and/or fracture strength of cement copolymers. A Ti-6Al-4V alloy was silanized with methacryloxypropyltrimethoxysilane in preparation for subsequent polymer attachment. Surfaces were then coated with polymers formed from PEG(375)-acrylate or a vancomycin-PEG(3400)-PEG(375)-acrylate copolymer. PMMA was loaded with various species, including vancomycin and several polymerizable vancomycin derivatives. To assess antibiofilm properties of these materials, initial bacterial adherence to coated Ti-6Al-4V was determined by scanning electron microscopy (SEM). Biofilm dry mass was determined on PMMA coupons; the compressive mechanical properties were also determined. SEM showed the vancomycin-PEG(3400)-acrylate-type surface reduced adherent bacteria numbers by approximately fourfold when compared with PEG(375)-acrylate alone. Vancomycin-loading reduced all mechanical properties tested; in contrast, loading a vancomycin-acrylamide derivative restored these deficits but demonstrated no antibiofilm properties. A polymerizable, PEGylated vancomycin derivative reduced biofilm attachment but resulted in inferior cement mechanical properties. The approaches presented here may offer new strategies for developing biofilm-resistant orthopaedic materials. Specifically, polymerizable derivatives of traditional antibiotics may allow for direct polymerization into existing materials such as PMMA bone cement while minimizing mechanical property compromise. Questions remain regarding ideal monomer structure(s) that confer biologic and mechanical benefits.

Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

PubMed

Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

2016-07-01

Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Canonical quantization of classical mechanics in curvilinear coordinates. Invariant quantization procedure

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

Błaszak, Maciej, E-mail: blaszakm@amu.edu.pl; Domański, Ziemowit, E-mail: ziemowit@amu.edu.pl

In the paper is presented an invariant quantization procedure of classical mechanics on the phase space over flat configuration space. Then, the passage to an operator representation of quantum mechanics in a Hilbert space over configuration space is derived. An explicit form of position and momentum operators as well as their appropriate ordering in arbitrary curvilinear coordinates is demonstrated. Finally, the extension of presented formalism onto non-flat case and related ambiguities of the process of quantization are discussed. -- Highlights: •An invariant quantization procedure of classical mechanics on the phase space over flat configuration space is presented. •The passage tomore » an operator representation of quantum mechanics in a Hilbert space over configuration space is derived. •Explicit form of position and momentum operators and their appropriate ordering in curvilinear coordinates is shown. •The invariant form of Hamiltonian operators quadratic and cubic in momenta is derived. •The extension of presented formalism onto non-flat case and related ambiguities of the quantization process are discussed.« less

Axioms for quantum mechanics: relativistic causality, retrocausality, and the existence of a classical limit

NASA Astrophysics Data System (ADS)

Rohrlich, Daniel

Y. Aharonov and A. Shimony both conjectured that two axioms - relativistic causality (``no superluminal signalling'') and nonlocality - so nearly contradict each other that only quantum mechanics reconciles them. Can we indeed derive quantum mechanics, at least in part, from these two axioms? No: ``PR-box'' correlations show that quantum correlations are not the most nonlocal correlations consistent with relativistic causality. Here we replace ``nonlocality'' with ``retrocausality'' and supplement the axioms of relativistic causality and retrocausality with a natural and minimal third axiom: the existence of a classical limit, in which macroscopic observables commute. That is, just as quantum mechanics has a classical limit, so must any generalization of quantum mechanics. In this limit, PR-box correlations violaterelativistic causality. Generalized to all stronger-than-quantum bipartite correlations, this result is a derivation of Tsirelson's bound (a theorem of quantum mechanics) from the three axioms of relativistic causality, retrocausality and the existence of a classical limit. Although the derivation does not assume quantum mechanics, it points to the Hilbert space structure that underlies quantum correlations. I thank the John Templeton Foundation (Project ID 43297) and the Israel Science Foundation (Grant No. 1190/13) for support.

Health Promoting Effects of Brassica-Derived Phytochemicals: From Chemopreventive and Anti-Inflammatory Activities to Epigenetic Regulation

PubMed Central

Wagner, Anika Eva; Terschluesen, Anna Maria; Rimbach, Gerald

2013-01-01

A high intake of brassica vegetables may be associated with a decreased chronic disease risk. Health promoting effects of Brassicaceae have been partly attributed to glucosinolates and in particular to their hydrolyzation products including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through the redox-sensitive transcription factor Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in humans support an anti-inflammatory effect of brassica-derived phytochemicals. However, the underlying mechanisms of how these compounds mediate their health promoting effects are yet not fully understood. Recent findings suggest that brassica-derived compounds are regulators of epigenetic mechanisms. It has been shown that isothiocyanates may inhibit histone deacetylase transferases and DNA-methyltransferases in cultured cells. Only a few papers have dealt with the effect of brassica-derived compounds on epigenetic mechanisms in laboratory animals, whereas data in humans are currently lacking. The present review aims to summarize the current knowledge regarding the biological activities of brassica-derived phytochemicals regarding chemopreventive, anti-inflammatory, and epigenetic pathways. PMID:24454992

Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

USDA-ARS?s Scientific Manuscript database

Probiotics are health-promoting bacteria which may protect the intestines from injury and inflammatory diseases but our understanding of the mechanisms for probiotic action are limited. In this study, we hypothesized that a protein, known as p40, which is derived from the probiotic bacteria, Lactoba...

Basic mechanics of laminated composite plates

NASA Technical Reports Server (NTRS)

Nettles, Alan T.

1994-01-01

The mechanics of laminated composite materials is presented in a clear manner with only essential derivations included. The constitutive equations in all of their forms are developed and then summarized in a separate section. The effects of hygrothermal effects are included. The prediction of the engineering constants for a laminate are derived. Strength of laminated composites is not covered.

A detailed kinetic mechanism including methanol and nitrogen pollutants relevant to the gas-phase combustion and pyrolysis of biomass-derived fuels

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

Coda Zabetta, Edgardo; Hupa, Mikko

2008-01-15

A detailed chemical kinetic mechanism for the simulation of the gas-phase combustion and pyrolysis of biomass-derived fuels was compiled by assembling selected reaction subsets from existing mechanisms (parents). The mechanism, here referred to as ''AaA,'' includes reaction subsets for the oxidation of hydrogen (H{sub 2}), carbon monoxide (CO), light hydrocarbons (C{sub 1} and C{sub 2}), and methanol (CH{sub 3}OH). The mechanism also takes into account reaction subsets of nitrogen pollutants, including the reactions relevant to staged combustion, reburning, and selective noncatalytic reduction (SNCR). The AaA mechanism was validated against suitable experimental data from the literature. Overall, the AaA mechanism gavemore » more accurate predictions than three other mechanisms of reference, although the reference mechanisms performed better occasionally. The predictions from AaA were also found to be consistent with the predictions of its parent mechanisms within most of their range of validity, thus transferring the validity of the parents to the inheriting mechanism (AaA). In parametric studies the AaA mechanism predicted that the effect of methanol on combustion and pollutants is often similar to that of light hydrocarbons, but it also showed that there are important exceptions, thus suggesting that methanol should be taken into account when simulating biomass combustion. To our knowledge, the AaA mechanism is currently the only mechanism that accounts for the chemistry of methanol and nitrogen relevant to the gas-phase combustion and pyrolysis of biomass-derived fuels. (author)« less

Schistosomal-derived lysophosphatidylcholine triggers M2 polarization of macrophages through PPARγ dependent mechanisms.

PubMed

Assunção, Leonardo Santos; Magalhães, Kelly G; Carneiro, Alan Brito; Molinaro, Raphael; Almeida, Patrícia E; Atella, Georgia C; Castro-Faria-Neto, Hugo C; Bozza, Patrícia T

2017-02-01

Mansonic schistosomiasis is a disease caused by the trematode Schistosoma mansoni, endemic to tropical countries. S. mansoni infection induces the formation of granulomas and potent polarization of Th2-type immune response. There is great interest in understanding the mechanisms used by this parasite that causes a modulation of the immune system. Recent studies from our group demonstrated that lipids of S. mansoni, including lysophosphatidylcholine (LPC) have immunomodulatory activity. In the present study, our aim was to investigate the role of lipids derived from S. mansoni in the activation and polarization of macrophages and to characterize the mechanisms involved in this process. Peritoneal macrophages obtained from wild type C57BL/6mice or bone marrow derived macrophages were stimulated in vitro with lipids extracted from adult worms of S. mansoni. We demonstrated that total schistosomal-derived lipids as well as purified LPC induced alternatively activated macrophages/M2 profile observed by increased expression of arginase-1, mannose receptor, Chi3l3, TGFβ and production of IL-10 and PGE 2 24h after stimulation. The involvement of the nuclear receptor PPARγ in macrophage response against LPC was investigated. Through Western blot and immunofluorescence confocal microscopy we demonstrated that schistosomal-derived LPC induces increased expression of PPARγ in macrophages. The LPC-induced increased expression of arginase-1 were significantly inhibited by the PPAR-γ antagonist GW9662. Together, these results demonstrate an immunomodulatory role of schistosomal-derived LPC in activating macrophages to a profile of the type M2 through PPARγ-dependent mechanisms, indicating a novel pathway for macrophage polarization triggered by parasite-derived LPC with potential implications to disease pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

[Antitumor effect research progress of shikonin and its derivatives].

PubMed

Zhu, Meng-Yuan; Wang, Ru-Bing; Zhou, Wen; Li, Shao-Shun

2012-05-01

Shikonin, the main active ingredient of Lithospermum, and its derivatives have been proved to have antitumor effects, and the anti-tumor mechanisms involve multiple targets. Based on recent literatures, this review focuses on the antitumor effects and its mechanisms. More emphases are given on the aspects of induction of apoptosis, induction of necrosis, acting on matrix metalloproteinase, acting on the protein tyrosine kinase and antiangiogenesis. The current status and problems of shikonin derivatives in antitumor effects are simply summarized and lookout for the development of antitumor drugs with shikonin as leading compounds.

Quantum mechanics as classical statistical mechanics with an ontic extension and an epistemic restriction.

PubMed

Budiyono, Agung; Rohrlich, Daniel

2017-11-03

Where does quantum mechanics part ways with classical mechanics? How does quantum randomness differ fundamentally from classical randomness? We cannot fully explain how the theories differ until we can derive them within a single axiomatic framework, allowing an unambiguous account of how one theory is the limit of the other. Here we derive non-relativistic quantum mechanics and classical statistical mechanics within a common framework. The common axioms include conservation of average energy and conservation of probability current. But two axioms distinguish quantum mechanics from classical statistical mechanics: an "ontic extension" defines a nonseparable (global) random variable that generates physical correlations, and an "epistemic restriction" constrains allowed phase space distributions. The ontic extension and epistemic restriction, with strength on the order of Planck's constant, imply quantum entanglement and uncertainty relations. This framework suggests that the wave function is epistemic, yet it does not provide an ontic dynamics for individual systems.

An Introductory Organic Chemistry Review Homework Exercise: Deriving Potential Mechanisms for Glucose Ring Opening in Mutarotation

ERIC Educational Resources Information Center

Murdock, Margaret; Holman, R. W.; Slade, Tyler; Clark, Shelley L. D.; Rodnick, Kenneth J.

2014-01-01

A unique homework assignment has been designed as a review exercise to be implemented near the end of the one-year undergraduate organic chemistry sequence. Within the framework of the exercise, students derive potential mechanisms for glucose ring opening in the aqueous mutarotation process. In this endeavor, 21 general review principles are…

Unexpected Reduction of Iminoquinone and Quinone Derivatives in Positive Electrospray Ionization Mass Spectrometry and Possible Mechanism Exploration

NASA Astrophysics Data System (ADS)

Pei, Jiying; Hsu, Cheng-Chih; Zhang, Ruijie; Wang, Yinghui; Yu, Kefu; Huang, Guangming

2017-08-01

Unexpected reduction of iminoquinone (IQ) and quinone derivatives was first reported during positive electrospray ionization mass spectrometry. Upon increasing spray voltage, the intensities of IQ and quinone derivatives decreased drastically, accompanying the increase of the intensities of the reduction products, amodiaquine (AQ) and phenol derivatives. To gain more insight into the mechanism of such reduction, we explored the experimental factors that are influential to corona discharge (CD). The results show that experimental parameters that favor severe CD, including metal spray emitter, using water as spray solvent, sheath gas with low dielectric strength (e.g., nitrogen), and shorter spray tip-to-mass spectrometer inlet distance, facilitated the reduction of IQ and quinone derivatives, implying that the reduction should be closely related to CD in the gas phase. [Figure not available: see fulltext.

Epoxide reduction with hydrazine on graphene: a first principles study.

PubMed

Kim, Min Chan; Hwang, Gyeong S; Ruoff, Rodney S

2009-08-14

Mechanisms for epoxide reduction with hydrazine on a single-layer graphene sheet are examined using quantum mechanical calculations within the framework of gradient-corrected spin-polarized density-functional theory. We find that the reduction reaction is mainly governed by epoxide ring opening which is initiated by H transfer from hydrazine or its derivatives. In addition, our calculations suggest that the epoxide reduction by hydrazine may predominantly follow a direct Eley-Rideal mechanism rather than a Langmuir-Hinshelwood mechanism. We also discuss the generation of various hydrazine derivatives during the reduction of graphene oxide with hydrazine and their potential contribution to lowering the barrier height of epoxide ring opening.

The Antiviral Activities and Mechanisms of Marine Polysaccharides: An Overview

PubMed Central

Wang, Wei; Wang, Shi-Xin; Guan, Hua-Shi

2012-01-01

Recently, the studies on the antiviral activities of marine natural products, especially marine polysaccharides, are attracting more and more attention all over the world. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities. This paper will review the recent progress in research on the antiviral activities and the mechanisms of these polysaccharides obtained from marine organisms. In particular, it will provide an update on the antiviral actions of the sulfated polysaccharides derived from marine algae including carrageenans, alginates, and fucans, relating to their structure features and the structure–activity relationships. In addition, the recent findings on the different mechanisms of antiviral actions of marine polysaccharides and their potential for therapeutic application will also be summarized in detail. PMID:23235364

Thermodynamics of viscoelastic rate-type fluids with stress diffusion

NASA Astrophysics Data System (ADS)

Málek, Josef; Průša, Vít; Skřivan, Tomáš; Süli, Endre

2018-02-01

We propose thermodynamically consistent models for viscoelastic fluids with a stress diffusion term. In particular, we derive variants of compressible/incompressible Maxwell/Oldroyd-B models with a stress diffusion term in the evolution equation for the extra stress tensor. It is shown that the stress diffusion term can be interpreted either as a consequence of a nonlocal energy storage mechanism or as a consequence of a nonlocal entropy production mechanism, while different interpretations of the stress diffusion mechanism lead to different evolution equations for the temperature. The benefits of the knowledge of the thermodynamical background of the derived models are documented in the study of nonlinear stability of equilibrium rest states. The derived models open up the possibility to study fully coupled thermomechanical problems involving viscoelastic rate-type fluids with stress diffusion.

Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals.

PubMed

Lynch, Maureen E; Chiou, Aaron E; Lee, Min Joon; Marcott, Stephen C; Polamraju, Praveen V; Lee, Yeonkyung; Fischbach, Claudia

2016-08-01

Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis.

Effect of addition of plants-derived polyamide 11 elastomer on the mechanical and tribological properties of hemp fiber reinforced polyamide 1010 composites

NASA Astrophysics Data System (ADS)

Mukaida, Jun; Nishitani, Yosuke; Kitano, Takeshi

2015-05-01

For the purpose of developing the new engineering materials such as structural materials and tribomaterials based on all plants-derived materials, the effect of the addition of plant-derived polyamide 11 Elastomer (PA11E) on the mechanical and tribological properties of hemp fiber(HF) reinforced polyamide 1010 (HF/PA1010) composites was investigated. PA1010 and PA11E (except the polyether groups used as soft segment) were made from plant-derived castor oil. Hemp fiber was surface-treated by two types of treatment: alkali treatment by NaOH solution and surface treatment by ureido silane coupling agent. HF/PA1010/PA11E ternary composites were extruded by a twin screw extruder and injection-molded. Their mechanical properties such as tensile, bending, Izod impact and tribological properties by ring-on-plate type sliding wear testing were evaluated. The effect of the addition of PA11E on the mechanical and tribological properties of HF/PA1010 composite differed for each property. Izod impact strength and specific wear rate improved with the addition of PA11E although tensile strength, modulus, and friction coefficient decreased with PA11E. It follows from these results that it may be possible to develop the new engineering materials with sufficient balance between mechanical and tribological properties.

Robust Derivation of Risk Reduction Strategies

NASA Technical Reports Server (NTRS)

Richardson, Julian; Port, Daniel; Feather, Martin

2007-01-01

Effective risk reduction strategies can be derived mechanically given sufficient characterization of the risks present in the system and the effectiveness of available risk reduction techniques. In this paper, we address an important question: can we reliably expect mechanically derived risk reduction strategies to be better than fixed or hand-selected risk reduction strategies, given that the quantitative assessment of risks and risk reduction techniques upon which mechanical derivation is based is difficult and likely to be inaccurate? We consider this question relative to two methods for deriving effective risk reduction strategies: the strategic method defined by Kazman, Port et al [Port et al, 2005], and the Defect Detection and Prevention (DDP) tool [Feather & Cornford, 2003]. We performed a number of sensitivity experiments to evaluate how inaccurate knowledge of risk and risk reduction techniques affect the performance of the strategies computed by the Strategic Method compared to a variety of alternative strategies. The experimental results indicate that strategies computed by the Strategic Method were significantly more effective than the alternative risk reduction strategies, even when knowledge of risk and risk reduction techniques was very inaccurate. The robustness of the Strategic Method suggests that its use should be considered in a wide range of projects.

Synthesis of pyrido[1,2-a]benzimidazoles and other fused imidazole derivatives with a bridgehead nitrogen atom

NASA Astrophysics Data System (ADS)

Begunov, Roman S.; Ryzvanovich, Galina A.

2013-01-01

Main methods for the synthesis of fused imidazole derivatives with a bridgehead nitrogen atom are systematically considered and summarized. The reaction mechanisms that underlie the methods for the synthesis of pyrido[1,2-a]benzimidazoles and related compounds are described. Biological properties and mechanisms of the biological activity of fused azaheterocycles are discussed. The bibliography includes 152 references.

Characterization of corncob-derived biochar and pyrolysis kinetics in comparison with corn stalk and sawdust.

PubMed

Liu, Xuan; Zhang, Yang; Li, Zifu; Feng, Rui; Zhang, Yaozhong

2014-10-01

In this study, thermal and physicochemical characterization results of corncob (CC) and its derived biochars were analyzed and differentiated from sawdust (SD) and cornstalk (CS). The pyrolysis temperature shows the largest effect on the yield of biochar produced compare with residing time, heating rate, and feedstock particle size. The CC-derived biochars produced at temperatures ranging from 300 to 600°C were analyzed. The CC was thermochemically altered to a stable biochar when the pyrolysis temperature was set to over 500°C. To deduce the reaction mechanism of the CC during the major thermal decomposition stage, 16 mechanisms in solid-state reactions were applied. The reaction order and nucleation mechanisms described the thermal decomposition of the CC. By using the best-fitted mechanisms, the kinetic parameters were calculated. The weight active energy of the CC was 122.42kJ/mol, which was the lowest value compared to those of CS and SD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel daidzein analogs enhance osteogenic activity of bone marrow-derived mesenchymal stem cells and adipose-derived stromal/stem cells through estrogen receptor dependent and independent mechanisms

USDA-ARS?s Scientific Manuscript database

Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein anddaidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal s...

Intraspinal Rewiring of the Corticospinal Tract Requires Target-Derived Brain-Derived Neurotrophic Factor and Compensates Lost Function after Brain Injury

ERIC Educational Resources Information Center

Ueno, Masaki; Hayano, Yasufumi; Nakagawa, Hiroshi; Yamashita, Toshihide

2012-01-01

Brain injury that results in an initial behavioural deficit is frequently followed by spontaneous recovery. The intrinsic mechanism of this functional recovery has never been fully understood. Here, we show that reorganization of the corticospinal tract induced by target-derived brain-derived neurotrophic factor is crucial for spontaneous recovery…

Advance in Anti-tumor Mechanisms of Shikonin, Alkannin and their Derivatives.

PubMed

Zhang, Xu; Cui, Jia-Hua; Meng, Qing-Qing; Li, Shao-Shun; Zhou, Wen; Xiao, Sui

2018-01-01

Shikonin, alkannin and their derivatives, the main ingredient of Lithospermum erythrorhizon and Arnebia euchroma (Royle) Johnst native to Inner Mongolian and Northwest of China respectively, hold promising potentials for antitumor effects via multiple-target mechanisms. This review will emphasize the importance of their antitumor activity in apoptosis, necroptosis and immunogenic cell death, and expound the relationship of their antitumor activity and naphthoquinone scaffold that could generate ROS and alkylating agent. Meanwhile, the antitumor mechanisms of naturally-occurring shikonin, alkannin and their derivatives, which were divided into the direct interaction involved in alkylating agent, covalently binding the DNA and protein, as well as the indirect interaction mediated by ROS, nonspecifically influencing the mitochondria or multiple signal pathways, will be systematically summarized and discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus

PubMed Central

Guardado-Mendoza, Rodolfo; Prioletta, Annamaria; Jiménez-Ceja, Lilia M.; Sosale, Aravind

2013-01-01

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide, presenting a great challenge to the public health systems due to high morbidity and mortality, because of frequent micro-/macro-vascular complications. Many treatment options are now available, with different efficacy as well as mechanisms of action to improve deranged glucose metabolism. We review some of the available data on derivatives of meglitinide, namely nateglinide and repaglinide. These two compounds increase insulin secretion by a mechanism similar to the one of sulfonylureas, but with a shorter half-life. Nateglinide and repaglinide, derivatives of meglitinides, have characteristic pharmacodynamic and pharmacokinetic properties that, together with their proposed mechanism of action, make them useful for type 2 diabetes mellitus, especially when used in combination therapy. PMID:24273582

A Moisture Function of Soil Heterotrophic Respiration Derived from Pore-scale Mechanisms

NASA Astrophysics Data System (ADS)

Yan, Z.; Todd-Brown, K. E.; Bond-Lamberty, B. P.; Bailey, V.; Liu, C.

2017-12-01

Soil heterotrophic respiration (HR) is an important process controlling carbon (C) flux, but its response to changes in soil water content (θ) is poorly understood. Earth system models (ESMs) use empirical moisture functions developed from specific sites to describe the HR-θ relationship in soils, introducing significant uncertainty. Generalized models derived from mechanisms that control substrate availability and microbial respiration are thus urgently needed. Here we derive, present, and test a novel moisture function fp developed from pore-scale mechanisms. This fp encapsulates primary physicochemical and biological processes controlling HR response to moisture variation in soils. We tested fp against a wide range of published data for different soil types, and found that fp reliably predicted diverse HR- relationships. The mathematical relationship between the parameters in fp and macroscopic soil properties such as porosity and organic C content was also established, enabling to estimate fp using soil properties. Compared with empirical moisture functions used in ESMs, this derived fp could reduce uncertainty in predicting the response of soil organic C stock to climate changes. In addition, this work is one of the first studies to upscale a mechanistic soil HR model based on pore-scale processes, thus linking the pore-scale mechanisms with macroscale observations.

Influence of wood-derived biochar on the physico-mechanical and chemical characteristics of agricultural soils

NASA Astrophysics Data System (ADS)

Ahmed, Ahmed S. F.; Raghavan, Vijaya

2018-01-01

Amendment of soil with biochar has been shown to enhance fertility and increase crop productivity, but the specific influence of biochar on soil workability remains unclear. Select physico-mechanical and chemical properties of clay loam and sandy loam soils were measured after amendment with wood-derived biochar of two particle size ranges (0.5-425 and 425-850 µm) at five dosages ranging from 0.5 to 10% dry weight. Whereas the clay loam soil workability decreased when the finer wood-derived biochar was applied at rates of 6 or 10%, soil fertility was not enhanced. The sandy loam soil, due to Proctor compaction, significantly decreased in bulk density with 6 and 10% wood-derived biochar amendments indicating higher soil resistance to compaction.

Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals

PubMed Central

Lynch, Maureen E.; Chiou, Aaron E.; Lee, Min Joon; Marcott, Stephen C.; Polamraju, Praveen V.; Lee, Yeonkyung

2016-01-01

Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis. PMID:27401765

A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange during Mechanical Ventilation

PubMed Central

Kim, Chang-Sei; Ansermino, J. Mark; Hahn, Jin-Oh

2016-01-01

The goal of this study is to derive a minimally complex but credible model of respiratory CO2 gas exchange that may be used in systematic design and pilot testing of closed-loop end-tidal CO2 controllers in mechanical ventilation. We first derived a candidate model that captures the essential mechanisms involved in the respiratory CO2 gas exchange process. Then, we simplified the candidate model to derive two lower-order candidate models. We compared these candidate models for predictive capability and reliability using experimental data collected from 25 pediatric subjects undergoing dynamically varying mechanical ventilation during surgical procedures. A two-compartment model equipped with transport delay to account for CO2 delivery between the lungs and the tissues showed modest but statistically significant improvement in predictive capability over the same model without transport delay. Aggregating the lungs and the tissues into a single compartment further degraded the predictive fidelity of the model. In addition, the model equipped with transport delay demonstrated superior reliability to the one without transport delay. Further, the respiratory parameters derived from the model equipped with transport delay, but not the one without transport delay, were physiologically plausible. The results suggest that gas transport between the lungs and the tissues must be taken into account to accurately reproduce the respiratory CO2 gas exchange process under conditions of wide-ranging and dynamically varying mechanical ventilation conditions. PMID:26870728

Electrochemical Behavior of Quinoxalin-2-one Derivatives at Mercury Electrodes and Its Analytical Use

PubMed Central

Zimpl, Milan; Skopalova, Jana; Jirovsky, David; Bartak, Petr; Navratil, Tomas; Sedonikova, Jana; Kotoucek, Milan

2012-01-01

Derivatives of quinoxalin-2-one are interesting compounds with potential pharmacological activity. From this point of view, understanding of their electrochemical behavior is of great importance. In the present paper, a mechanism of electrochemical reduction of quinoxalin-2-one derivatives at mercury dropping electrode was proposed. Pyrazine ring was found to be the main electroactive center undergoing a pH-dependent two-electron reduction process. The molecule protonization of nitrogen in the position 4 precedes the electron acceptance forming a semiquinone radical intermediate which is relatively stable in acidic solutions. Its further reduction is manifested by separated current signal. A positive mesomeric effect of the nonprotonized amino group in the position 7 of the derivative III accelerates the semiquinone reduction yielding a single current wave. The suggested reaction mechanism was verified by means of direct current polarography, differential pulse, cyclic and elimination voltammetry, and coulometry with subsequent GC/MS analysis. The understanding of the mechanism was applied in developing of analytical method for the determination of the studied compounds. PMID:22666117

Seeking new anti-cancer agents from autophagy-regulating natural products.

PubMed

Hua, Fang; Shang, Shuang; Hu, Zhuo-Wei

2017-04-01

Natural products are an important original source of many widely used drugs, including anti-cancer drugs. Early research efforts for seeking anti-cancer therapy from the natural products are mainly focused on the compounds with cytotoxicity capability. The good examples include vinblastine, vincristine, the camptothecin derivatives; topotecan, irinotecan, epipodophyllotoxin derivatives and paclitaxel. In a recent decade, the fundamental progression has been made in the understanding of molecular and cellular mechanisms regarding tumor initiation, metastasis, therapeutic resistance, immune escape, and relapse, which provide a great opportunity for the development of new mechanism-based anticancer drugs, especially drugs against new molecular and cellular targets. Autophagy, a critical cell homeostasis mechanism and promising drug target involved in a verity of human diseases including cancer, can be modulated by many compounds derived from natural products. In this review, we'll give a short introduction of autophagy and discuss the roles of autophagy in the tumorigenesis and progression. And then, we summarize the accumulated evidences to show the anti-tumor effects of several compounds derived from natural products through modulation of autophagy activity.

Thermodynamics and statistical mechanics. [thermodynamic properties of gases

NASA Technical Reports Server (NTRS)

1976-01-01

The basic thermodynamic properties of gases are reviewed and the relations between them are derived from the first and second laws. The elements of statistical mechanics are then formulated and the partition function is derived. The classical form of the partition function is used to obtain the Maxwell-Boltzmann distribution of kinetic energies in the gas phase and the equipartition of energy theorem is given in its most general form. The thermodynamic properties are all derived as functions of the partition function. Quantum statistics are reviewed briefly and the differences between the Boltzmann distribution function for classical particles and the Fermi-Dirac and Bose-Einstein distributions for quantum particles are discussed.

Feasibility of pig and human-derived aortic valve interstitial cells seeding on fixative-free decellularized animal pericardium.

PubMed

Santoro, Rosaria; Consolo, Filippo; Spiccia, Marco; Piola, Marco; Kassem, Samer; Prandi, Francesca; Vinci, Maria Cristina; Forti, Elisa; Polvani, Gianluca; Fiore, Gianfranco Beniamino; Soncini, Monica; Pesce, Maurizio

2016-02-01

Glutaraldehyde-fixed pericardium of animal origin is the elective material for the fabrication of bio-prosthetic valves for surgical replacement of insufficient/stenotic cardiac valves. However, the pericardial tissue employed to this aim undergoes severe calcification due to chronic inflammation resulting from a non-complete immunological compatibility of the animal-derived pericardial tissue resulting from failure to remove animal-derived xeno-antigens. In the mid/long-term, this leads to structural deterioration, mechanical failure, and prosthesis leaflets rupture, with consequent need for re-intervention. In the search for novel procedures to maximize biological compatibility of the pericardial tissue into immunocompetent background, we have recently devised a procedure to decellularize the human pericardium as an alternative to fixation with aldehydes. In the present contribution, we used this procedure to derive sheets of decellularized pig pericardium. The decellularized tissue was first tested for the presence of 1,3 α-galactose (αGal), one of the main xenoantigens involved in prosthetic valve rejection, as well as for mechanical tensile behavior and distensibility, and finally seeded with pig- and human-derived aortic valve interstitial cells. We demonstrate that the decellularization procedure removed the αGAL antigen, maintained the mechanical characteristics of the native pig pericardium, and ensured an efficient surface colonization of the tissue by animal- and human-derived aortic valve interstitial cells. This establishes, for the first time, the feasibility of fixative-free pericardial tissue seeding with valve competent cells for derivation of tissue engineered heart valve leaflets. © 2015 Wiley Periodicals, Inc.

A practical iterative PID tuning method for mechanical systems using parameter chart

NASA Astrophysics Data System (ADS)

Kang, M.; Cheong, J.; Do, H. M.; Son, Y.; Niculescu, S.-I.

2017-10-01

In this paper, we propose a method of iterative proportional-integral-derivative parameter tuning for mechanical systems that possibly possess hidden mechanical resonances, using a parameter chart which visualises the closed-loop characteristics in a 2D parameter space. We employ a hypothetical assumption that the considered mechanical systems have their upper limit of the derivative feedback gain, from which the feasible region in the parameter chart becomes fairly reduced and thus the gain selection can be extremely simplified. Then, a two-directional parameter search is carried out within the feasible region in order to find the best set of parameters. Experimental results show the validity of the assumption used and the proposed parameter tuning method.

The injury of fine particulate matter from cooking oil fumes on umbilical cord blood vessels in vitro.

PubMed

Hou, Lijuan; Zhang, Jian; Zhang, Chao; Xu, Yachun; Zhu, Xiaoxia; Yao, Cijiang; Liu, Ying; Li, Tao; Cao, Jiyu

2017-01-01

Cooking oil fumes (COFs) derived PM 2.5 is the major source of indoor air pollution in Asia. For this, a pregnant rat model within different doses of cooking oil fumes (COFs) derived PM 2.5 was established in pregnancy in our research. Our previous studies have showed that exposure to COFs-derived PM 2.5 was related to adverse pregnancy outcomes. However, the mechanisms of signaling pathways remain unknown. Therefore, this study aimed to investigate the underlying mechanisms induced by COFs-derived PM2.5 injury on umbilical cord blood vessels (UCs) in vitro. Exposure to COFs-derived PM 2.5 resulted in changing the expression of eNOS, ET-1, ETRA, and ETRB. In additions, western blot analysis indicated that the HIF-1α/iNOS/NO signaling pathway and VEGF/VEGFR1/iNOS signaling pathway were involved in UCs injury triggered by COFs-derived PM 2.5 . In conclusion, our data suggested that exposure to COFs-derived PM 2.5 resulted in increasing of oxidative stress and inflammation, as well as dysfunction of UCs. Copyright © 2016 Elsevier B.V. All rights reserved.

Generalized Weyl-Wigner map and Vey quantum mechanics

NASA Astrophysics Data System (ADS)

Dias, Nuno Costa; Prata, João Nuno

2001-12-01

The Weyl-Wigner map yields the entire structure of Moyal quantum mechanics directly from the standard operator formulation. The covariant generalization of Moyal theory, also known as Vey quantum mechanics, was presented in the literature many years ago. However, a derivation of the formalism directly from standard operator quantum mechanics, clarifying the relation between the two formulations, is still missing. In this article we present a covariant generalization of the Weyl order prescription and of the Weyl-Wigner map and use them to derive Vey quantum mechanics directly from the standard operator formulation. The procedure displays some interesting features: it yields all the key ingredients and provides a more straightforward interpretation of the Vey theory including a direct implementation of unitary operator transformations as phase space coordinate transformations in the Vey idiom. These features are illustrated through a simple example.

Carpatizine, a novel bridged oxazine derivative generated by non-enzymatic reactions.

PubMed

Fu, Peng; MacMillan, John B

2017-06-27

Carpatizine (1), a new bridged oxazine derivative, was isolated from a marine-derived Streptomyces strain SNE-011. The structure was fully determined by spectroscopic analysis, ECD calculations and chemical methods. A plausible non-enzymatic reaction mechanism from daryamide D leading to carpatizine was presented, which was confirmed by chemical transformation.

Theoretical Design of a Two-Photon Fluorescent Probe for Nitric Oxide with Enhanced Emission Induced by Photoninduced Electron Transfer.

PubMed

Zhang, Yujin; Leng, Jiancai; Hu, Wei

2018-04-25

In the present work, we systematically investigate the sensing abilities of two recently literature-reported two-photon fluorescent NO probes, i.e., the o-phenylenediamine derivative of Nile Red and the p-phenylenediamine derivative of coumarin. The recognition mechanisms of these probes are studied by using the molecular orbital classifying method, which demonstrates the photoinduced electron transfer process. In addition, we have designed two new probes by swapping receptor units present on fluorophores, i.e., the p-phenylenediamine derivative of Nile Red and the o-phenylenediamine derivative of coumarin. However, it illustrates that only the latter has ability to function as off-on typed fluorescent probe for NO. More importantly, calculations on the two-photon absorption properties of the probes demonstrate that both receptor derivatives of coumarin possess larger TPA cross-sections than Nile Red derivatives, which makes a better two photon fluorescent probe. Our theoretical investigations reveal that the underlying mechanism satisfactorily explain the experimental results, providing a theoretical basis on the structure-property relationships which is beneficial to developing new two-photon fluorescent probes for NO.

The synthesis, structure-toxicity relationship of cisplatin derivatives for the mechanism research of cisplatin-induced nephrotoxicity.

PubMed

Hu, Jing; Wu, Tian-Ming; Li, Hong-Ze; Zuo, Ze-Ping; Zhao, Ying-Lan; Yang, Li

2017-08-01

Cisplatin is a widely used antineoplastic drug, while its nephrotoxicity limits the clinical application. Although several mechanisms contributing to nephrotoxicity have been reported, the direct protein targets are unclear. Herein we reported the synthesis of 29 cisplatin derivatives and the structure-toxicity relationship (STR) of these compounds with MTT assay in human renal proximal tubule cells (HK-2) and pig kidney epithelial cells (LLC-PK1). To the best of our knowledge, this study represented the first report regarding the structure-toxicity relationship (STR) of cisplatin derivatives. The potency of biotin-pyridine conjugated derivative 3 met the requirement for target identification, and the preliminary chemical proteomics results suggested that it is a promising tool for further target identification of cisplatin-induced nephrotoxicity. Copyright © 2017. Published by Elsevier Ltd.

Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship.

PubMed

Roohbakhsh, Ali; Iranshahy, Milad; Iranshahi, Mehrdad

2016-01-01

The anti-cancer properties of liquorice have been attributed, at least in part, to glycyrrhizin (GL). However, GL is not directly absorbed through the gastrointestinal tract. It is hydrolyzed to 18-β-glycyrrhetinic acid (GA), the pharmacologically active metabolite, by human intestinal microflora. GA exhibits remarkable cytotoxic and anti-tumor properties. The pro-apoptotic targets and mechanisms of action of GA have been extensively studied over the past decade. In addition, GA is an inexpensive and available triterpene with functional groups (COOH and OH) in its structure, which make it an attractive lead compound for medicinal chemists to prepare a large number of analogues. To date, more than 400 cytotoxic derivatives have been prepared on the basis of GA scaffold, including 128 cytotoxic derivatives with IC50 values less than 30 µM. Researchers have also succeeded in synthesizing very potent cytotoxic derivatives with IC50s ≤ 1 µM. Studies have shown that the introduction of a double bound at the C1-C2 position combined with an electronegative functional group, such as CN, CF3 or iodine at C2 position, and the oxidation of the hydroxyl group of C3 to the carbonyl group, significantly increased cytotoxicity. This review describes the cytotoxic and anti-tumor properties of GA and its derivatives, targets and mechanisms of action and provides insight into the structure-activity relationship of GA derivatives.

Using Functional Signature Ontology (FUSION) to Identify Mechanisms of Action for Natural Products

PubMed Central

Potts, Malia B.; Kim, Hyun Seok; Fisher, Kurt W.; Hu, Youcai; Carrasco, Yazmin P.; Bulut, Gamze Betul; Ou, Yi-Hung; Herrera-Herrera, Mireya L.; Cubillos, Federico; Mendiratta, Saurabh; Xiao, Guanghua; Hofree, Matan; Ideker, Trey; Xie, Yang; Huang, Lily Jun-shen; Lewis, Robert E.; MacMillan, John B.; White, Michael A.

2014-01-01

A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, we developed a new marine-derived, renewable natural products resource and a method for linking bioactive derivatives of this library to the proteins and biological processes that they target in cells. We used cell-based screening and computational analysis to match gene expression signatures produced by natural products to those produced by siRNA and synthetic microRNA libraries. With this strategy, we matched proteins and microRNAs with diverse biological processes and also identified putative protein targets and mechanisms of action for several previously undescribed marine-derived natural products. We confirmed mechanistic relationships for selected short-interfering RNAs, microRNAs, and compounds with functional roles in autophagy, chemotaxis mediated by discoidin domain receptor 2, or activation of the kinase AKT. Thus, this approach may be an effective method for screening new drugs while simultaneously identifying their targets. PMID:24129700

Potential formulation of sleep dynamics

NASA Astrophysics Data System (ADS)

Phillips, A. J. K.; Robinson, P. A.

2009-02-01

A physiologically based model of the mechanisms that control the human sleep-wake cycle is formulated in terms of an equivalent nonconservative mechanical potential. The potential is analytically simplified and reduced to a quartic two-well potential, matching the bifurcation structure of the original model. This yields a dynamics-based model that is analytically simpler and has fewer parameters than the original model, allowing easier fitting to experimental data. This model is first demonstrated to semiquantitatively match the dynamics of the physiologically based model from which it is derived, and is then fitted directly to a set of experimentally derived criteria. These criteria place rigorous constraints on the parameter values, and within these constraints the model is shown to reproduce normal sleep-wake dynamics and recovery from sleep deprivation. Furthermore, this approach enables insights into the dynamics by direct analogies to phenomena in well studied mechanical systems. These include the relation between friction in the mechanical system and the timecourse of neurotransmitter action, and the possible relation between stochastic resonance and napping behavior. The model derived here also serves as a platform for future investigations of sleep-wake phenomena from a dynamical perspective.

An introduction to generalized functions with some applications in aerodynamics and aeroacoustics

NASA Technical Reports Server (NTRS)

Farassat, F.

1994-01-01

In this paper, we start with the definition of generalized functions as continuous linear functionals on the space of infinitely differentiable functions with compact support. The concept of generalization differentiation is introduced next. This is the most important concept in generalized function theory and the applications we present utilize mainly this concept. First, some of the results of classical analysis, such as Leibniz rule of differentiation under the integral sign and the divergence theorem, are derived using the generalized function theory. It is shown that the divergence theorem remains valid for discontinuous vector fields provided that the derivatives are all viewed as generalized derivatives. This implies that all conservation laws of fluid mechanics are valid as they stand for discontinuous fields with all derivatives treated as generalized deriatives. Once these derivatives are written as ordinary derivatives and jumps in the field parameters across discontinuities, the jump conditions can be easily found. For example, the unsteady shock jump conditions can be derived from mass and momentum conservation laws. By using a generalized function theory, this derivative becomes trivial. Other applications of the generalized function theory in aerodynamics discussed in this paper are derivation of general transport theorems for deriving governing equations of fluid mechanics, the interpretation of finite part of divergent integrals, derivation of Oswatiitsch integral equation of transonic flow, and analysis of velocity field discontinuities as sources of vorticity. Applications in aeroacoustics presented here include the derivation of the Kirchoff formula for moving surfaces,the noise from moving surfaces, and shock noise source strength based on the Ffowcs Williams-Hawkings equation.

Brandon Knott | NREL

Science.gov Websites

-6223 Research Interests Molecular mechanisms of cellulose-degrading enzymes Structure-function relationships of biomass-derived polymers Structure-function relationships in glycoside hydrolases Methane potential protein engineering targets. Structure-Function Relationships of Biomass-Derived Polymers

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

PubMed Central

Kralova, Jarmila; Kolar, Michal; Kahle, Michal; Truksa, Jaroslav; Lettlova, Sandra; Balusikova, Kamila; Bartunek, Petr

2017-01-01

The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design. PMID:28295025

Factors, fiction and endothelium-derived hyperpolarizing factor.

PubMed

Sandow, Shaun L

2004-09-01

1. The principal mediators of vascular tone are neural, endothelial and physical stimuli that result in the initiation of dilator and constrictor responses to facilitate the control of blood pressure. Two primary vasodilatory stimuli produced by the endothelium are nitric oxide (NO) and prostaglandins. An additional endothelium-dependent vasodilatory mechanism is characterized as the hyperpolarization-mediated relaxation that remains after the inhibition of the synthesis of NO and prostaglandins. This mechanism is due to the action of a so-called endothelium-derived hyperpolarizing factor (EDHF) and is dependent on either the release of diffusible factor(s) and/or to a direct contact-mediated mechanism. 2. Most evidence supports the concept that 'EDHF' activity is dependent on contact-mediated mechanisms. This involves the transfer of an endothelium-derived electrical current, as an endothelium-derived hyperpolarization (EDH), through direct heterocellular coupling of endothelial cells and smooth muscle cells via myoendothelial gap junctions (MEGJ). However, there is a lack of consensus with regard to the nature and mechanism of action of EDHF/EDH (EDH(F)), which has been shown to vary within and between vascular beds, as well as among species, strains, sex and during development, ageing and disease. 3. In addition to actual heterogeneity in EDH(F), further heterogeneity has resulted from the less-than-optimal design, analysis and interpretation of data in some key papers in the EDHF literature; with such views being perpetuated in the subsequent literature. 4. The focus of the present brief review is to examine what factors are proposed as EDH(F) and highlight the correlative structural and functional studies from our laboratory that demonstrate an integral role for MEGJ in the conduction of EDH, which account for the heterogeneity in EDH(F), while incorporating the reported diffusible mechanisms in the regulation of this activity. Furthermore, in addition to the reported heterogeneity in the nature and mechanism of action of EDH(F), the contribution of experimental design and technique to this heterogeneity will be examined.

Derivation of the Second Law of Thermodynamics from Boltzmann's Distribution Law.

ERIC Educational Resources Information Center

Nelson, P. G.

1988-01-01

Shows how the thermodynamic condition for equilibrium in an isolated system can be derived by the application of Boltzmann's law to a simple physical system. States that this derivation could be included in an introductory course on chemical equilibrium to help prepare students for a statistical mechanical treatment presented in the curriculum.…

Molecular Mechanisms of Aldehyde Toxicity: A Chemical Perspective

PubMed Central

2015-01-01

Aldehydes are electrophilic compounds to which humans are pervasively exposed. Despite a significant health risk due to exposure, the mechanisms of aldehyde toxicity are poorly understood. This ambiguity is likely due to the structural diversity of aldehyde derivatives and corresponding differences in chemical reactions and biological targets. To gain mechanistic insight, we have used parameters based on the hard and soft, acids and bases (HSAB) theory to profile the different aldehyde subclasses with respect to electronic character (softness, hardness), electrophilic reactivity (electrophilic index), and biological nucleophilic targets. Our analyses indicate that short chain aldehydes and longer chain saturated alkanals are hard electrophiles that cause toxicity by forming adducts with hard biological nucleophiles, e.g., primary nitrogen groups on lysine residues. In contrast, α,β-unsaturated carbonyl derivatives, alkenals, and the α-oxoaldehydes are soft electrophiles that preferentially react with soft nucleophilic thiolate groups on cysteine residues. The aldehydes can therefore be grouped into subclasses according to common electronic characteristics (softness/hardness) and molecular mechanisms of toxicity. As we will discuss, the toxic potencies of these subgroups are generally related to corresponding electrophilicities. For some aldehydes, however, predictions of toxicity based on electrophilicity are less accurate due to inherent physicochemical variables that limit target accessibility, e.g., steric hindrance and solubility. The unsaturated aldehydes are also members of the conjugated type-2 alkene chemical class that includes α,β-unsaturated amide, ketone, and ester derivatives. Type-2 alkenes are electrophiles of varying softness and electrophilicity that share a common mechanism of toxicity. Therefore, exposure to an environmental mixture of unsaturated carbonyl derivatives could cause “type-2 alkene toxicity” through additive interactions. Finally, we propose that environmentally derived aldehydes can accelerate diseases by interacting with endogenous aldehydes generated during oxidative stress. This review provides a basis for understanding aldehyde mechanisms and environmental toxicity through the context of electronic structure, electrophilicity, and nucleophile target selectivity. PMID:24911545

Lys314 is a nucleophile in non-classical reactions of orotidine-5'-monophosphate decarboxylase.

PubMed

Heinrich, Daniel; Diederichsen, Ulf; Rudolph, Markus Georg

2009-07-06

Orotidine-5'-monophosphate decarboxylase (OMPD) catalyzes the decarboxylation of orotidine-5'-monophosphate (OMP) to uridine-5'-monophosphate (UMP) in an extremely proficient manner. The reaction does not require any cofactors and proceeds by an unknown mechanism. In addition to decarboxylation, OMPD is able to catalyze other reactions. We show that several C6-substituted UMP derivatives undergo hydrolysis or substitution reactions that depend on a lysine residue (Lys314) in the OMPD active site. 6-Cyano-UMP is converted to UMP, and UMP derivatives with good leaving groups inhibit OMPD by a suicide mechanism in which Lys314 covalently binds to the substrate. These non-classical reactivities of human OMPD were characterized by cocrystallization and freeze-trapping experiments with wild-type OMPD and two active-site mutants by using substrate and inhibitor nucleotides. The structures show that the C6-substituents are not coplanar with the pyrimidine ring. The extent of this substrate distortion is a function of the substituent geometry. Structure-based mechanisms for the reaction of 6-substituted UMP derivatives are extracted in accordance with results from mutagenesis, mass spectrometry, and OMPD enzyme activity. The Lys314-based mechanisms explain the chemodiversity of OMPD, and offer a strategy to design mechanism-based inhibitors that could be used for antineoplastic purposes for example.

Quantum mechanics from Newton's second law and the canonical commutation relation [X, P] = i

NASA Astrophysics Data System (ADS)

Palenik, Mark C.

2014-07-01

Despite the fact that it has been known since the time of Heisenberg that quantum operators obey a quantum version of Newton's laws, students are often told that derivations of quantum mechanics must necessarily follow from the Hamiltonian or Lagrangian formulations of mechanics. Here, we first derive the existing Heisenberg equations of motion from Newton's laws and the uncertainty principle using only the equations F=\\frac{dP}{dt}, P=m\\frac{dV}{dt}, and [X, P] = i. Then, a new expression for the propagator is derived that makes a connection between time evolution in quantum mechanics and the motion of a classical particle under Newton's laws. The propagator is solved for three cases where an exact solution is possible: (1) the free particle; (2) the harmonic oscillator; and (3) a constant force, or linear potential in the standard interpretation. We then show that for a general for a general force F(X), by Taylor expanding X(t) in time, we can use this methodology to reproduce the Feynman path integral formula for the propagator. Such a picture may be useful for students as they make the transition from classical to quantum mechanics and help solidify the equivalence of the Hamiltonian, Lagrangian, and Newtonian pictures of physics in their minds.

Melanoma patient derived xenografts acquire distinct Vemurafenib resistance mechanisms

PubMed Central

Monsma, David J; Cherba, David M; Eugster, Emily E; Dylewski, Dawna L; Davidson, Paula T; Peterson, Chelsea A; Borgman, Andrew S; Winn, Mary E; Dykema, Karl J; Webb, Craig P; MacKeigan, Jeffrey P; Duesbery, Nicholas S; Nickoloff, Brian J; Monks, Noel R

2015-01-01

Variable clinical responses, tumor heterogeneity, and drug resistance reduce long-term survival outcomes for metastatic melanoma patients. To guide and accelerate drug development, we characterized tumor responses for five melanoma patient derived xenograft models treated with Vemurafenib. Three BRAFV600E models showed acquired drug resistance, one BRAFV600E model had a complete and durable response, and a BRAFV600V model was expectedly unresponsive. In progressing tumors, a variety of resistance mechanisms to BRAF inhibition were uncovered, including mutant BRAF alternative splicing, NRAS mutation, COT (MAP3K8) overexpression, and increased mutant BRAF gene amplification and copy number. The resistance mechanisms among the patient derived xenograft models were similar to the resistance pathways identified in clinical specimens from patients progressing on BRAF inhibitor therapy. In addition, there was both inter- and intra-patient heterogeneity in resistance mechanisms, accompanied by heterogeneous pERK expression immunostaining profiles. MEK monotherapy of Vemurafenib-resistant tumors caused toxicity and acquired drug resistance. However, tumors were eradicated when Vemurafenib was combined the MEK inhibitor. The diversity of drug responses among the xenograft models; the distinct mechanisms of resistance; and the ability to overcome resistance by the addition of a MEK inhibitor provide a scheduling rationale for clinical trials of next-generation drug combinations. PMID:26101714

Probing nitrobenzhydrol uncaging mechanisms using FerriCast.

PubMed

Kennedy, Daniel P; Brown, Daniel C; Burdette, Shawn C

2010-10-15

The FerriCast derivative FC-NDBF was synthesized from 3-methyl-2-nitrodibenzofuran (NDBF). The photochemistry of the target Fe(3+) photocage and several related congeners provides mechanistic insight into the uncaging quantum yields of nitrobenzhydrol-derived ligands.

Mechanisms of Nanoparticle Mediated siRNA Transfection by Melittin-Derived Peptides

PubMed Central

Hou, Kirk K.; Pan, Hua; Ratner, Lee; Schlesinger, Paul H.; Wickline, Samuel A.

2014-01-01

Traditional peptide-mediated siRNA transfection via peptide transduction domains exhibits limited cytoplasmic delivery of siRNA due to endosomal entrapment. This work overcomes these limitations with the use of membrane-destabilizing peptides derived from melittin for the knockdown of NFkB signaling in a model of adult T-Cell leukemia/lymphoma. While the mechanism of siRNA delivery into the cytoplasmic compartment by peptide transduction domains has not been well studied, our analysis of melittin derivatives indicates that concurrent nanocomplex disassembly and peptide-mediated endosomolysis are crucial to siRNA transfection. Importantly, in the case of the most active derivative, p5RHH, this process is initiated by acidic pH, indicating that endosomal acidification after macropinocytosis can trigger siRNA release into the cytoplasm. These data provide general principles regarding nanocomplex response to endocytosis which may guide the development of peptide/siRNA nanocomplex-based transfection. PMID:24053333

What Bell proved: A reply to Blaylock

NASA Astrophysics Data System (ADS)

Maudlin, Tim

2010-01-01

Blaylock argues that the derivation of Bell's inequality requires a hidden assumption, counterfactual definiteness, of which Bell was unaware. A careful analysis of Bell's argument shows that Bell presupposes only locality and the predictions of standard quantum mechanics. Counterfactual definiteness, insofar as it is required, is derived in the course of the argument rather than presumed. Bell's theorem has no direct bearing on the many worlds interpretation not because that interpretation denies counterfactual definiteness but because it does not recover the predictions of standard quantum mechanics.

Mechanical stabilization of proteolytically degradable polyethylene glycol dimethacrylate hydrogels through peptide interaction.

PubMed

Lim, Hyun Ju; Khan, Zara; Lu, Xi; Perera, T Hiran; Wilems, Thomas S; Ravivarapu, Krishna T; Smith Callahan, Laura A

2018-04-15

Balancing enhancement of neurite extension against loss of matrix support in synthetic hydrogels containing proteolytically degradable and bioactive signaling peptides to optimize tissue formation is difficult. Using a systematic approach, polyethylene glycol hydrogels containing concurrent continuous concentration gradients of the laminin derived bioactive signaling peptide, Ile-Lys-Val-Ala-Val (IKVAV), and collagen derived matrix metalloprotease degradable peptide, GPQGIWGQ, were fabricated and characterized. During proteolytic degradation of the concentration gradient hydrogels, the IKVAV and IWGQ cleavage fragment from GPQGIWGQ were found to interact and stabilize the bulk Young's Modulus of the hydrogel. Further testing of discrete samples containing GPQGIWGQ or its cleavage fragments, GPQG and IWGQ, indicates hydrophobic interactions between the peptides are not necessary for mechanical stabilization of the hydrogel, but changes in the concentration ratio between the peptides tethered in the hydrogel and salts and ions in the swelling solution can affect the stabilization. Encapsulation of human induced pluripotent stem cell derived neural stem cells did not reduce the mechanical properties of the hydrogel over a 14 day neural differentiation culture period, and IKVAV was found to maintain concentration dependent effects on neurite extension and mRNA gene expression of neural cytoskeletal markers, similar to previous studies. As a result, this work has significant implications for the analysis of biological studies in matrices, as the material and mechanical properties of the hydrogel may be unexpectedly temporally changing during culture due to interactions between peptide signaling elements, underscoring the need for greater matrix characterization during the degradation and cell culture. Greater emulation of the native extracellular matrix is necessary for tissue formation. To achieve this, matrices are becoming more complex, often including multiple bioactive signaling elements. However, peptide signaling in polyethylene glycol matrices and amino acids interactions between peptides can affect hydrogel material and mechanical properties, but are rarely studied. The current study identifies such an interaction between laminin derived peptide, IKVAV, and collagen derived matrix metalloprotease degradable peptide, GPQGIWGQ. Previous studies using these peptides did not identify their interactions' ability to mechanically stabilize the hydrogel during degradation. This work underscores the need for greater matrix characterization and consideration of bioactive signaling element effects temporally on the matrix's material and mechanical properties, as they can contribute to cellular response. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Embryonic stem cell-derived osteocytes are capable of responding to mechanical oscillatory hydrostatic pressure.

PubMed

Ehnes, D D; Price, F D; Shrive, N G; Hart, D A; Rancourt, D E; zur Nieden, N I

2015-07-16

Osteoblasts can be derived from embryonic stem cells (ESCs) by a 30 day differentiation process, whereupon cells spontaneously differentiate upon removal of LIF and respond to exogenously added 1,25α(OH)2 vitamin D3 with enhanced matrix mineralization. However, bone is a load-bearing tissue that has to perform under dynamic pressure changes during daily movement, a capacity that is executed by osteocytes. At present, it is unclear whether ESC-derived osteogenic cultures contain osteocytes and whether these are capable of responding to a relevant cyclic hydrostatic compression stimulus. Here, we show that ESC-osteoblastogenesis is followed by the generation of osteocytes and then mechanically load ESC-derived osteogenic cultures in a compression chamber using a cyclic loading protocol. Following mechanical loading of the cells, iNOS mRNA was upregulated 31-fold, which was consistent with a role for iNOS as an immediate early mechanoresponsive gene. Further analysis of matrix and bone-specific genes suggested a cellular response in favor of matrix remodeling. Immediate iNOS upregulation also correlated with a concomitant increase in Ctnnb1 and Tcf7l2 mRNAs along with increased nuclear TCF transcriptional activity, while the mRNA for the repressive Tcf7l1 was downregulated, providing a possible mechanistic explanation for the noted matrix remodeling. We conclude that ESC-derived osteocytes are capable of responding to relevant mechanical cues, at least such that mimic oscillatory compression stress, which not only provides new basic understanding, but also information that likely will be important for their use in cell-based regenerative therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

On some new properties of fractional derivatives with Mittag-Leffler kernel

NASA Astrophysics Data System (ADS)

Baleanu, Dumitru; Fernandez, Arran

2018-06-01

We establish a new formula for the fractional derivative with Mittag-Leffler kernel, in the form of a series of Riemann-Liouville fractional integrals, which brings out more clearly the non-locality of fractional derivatives and is easier to handle for certain computational purposes. We also prove existence and uniqueness results for certain families of linear and nonlinear fractional ODEs defined using this fractional derivative. We consider the possibility of a semigroup property for these derivatives, and establish extensions of the product rule and chain rule, with an application to fractional mechanics.

Structure Properties and Mechanisms of Action of Naturally Originated Phenolic Acids and Their Derivatives against Human Viral Infections.

PubMed

Wu, Yi-Hang; Zhang, Bing-Yi; Qiu, Li-Peng; Guan, Rong-Fa; Ye, Zi-Hong; Yu, Xiao-Ping

2017-01-01

A great effort has been made to develop efficacious antiviral drugs, but many viral infections are still lack of efficient antiviral therapies so far. The related exploration of natural products to fight viruses has been raised in recent years. Natural compounds with structural diversity and complexity offer a great chance to find new antiviral agents. Particularly, phenolic acids have attracted considerable attention owing to their potent antiviral abilities and unique mechanisms. The aim of this review is to report new discoveries and updates pertaining to antiviral phenolic acids. The relevant references on natural phenolic acids were searched. The antiviral phenolic acids were classified according to their structural properties and antiviral types. Meanwhile, the antiviral characteristics and structure-activity relationships of phenolic acids and their derivatives were summarized. The review finds that natural phenolic acids and their derivatives possessed potent inhibitory effects on multiple virus in humans such as human immunodeficiency virus, hepatitis C virus, hepatitis B virus, herpes simplex virus, influenza virus and respiratory syncytial virus. In particular, caffeic acid/gallic acid and their derivatives exhibited outstanding antiviral properties by a variety of modes of action. Naturally derived phenolic acids especially caffeic acid/gallic acid and their derivatives may be regarded as novel promising antiviral leads or candidates. Additionally, scarcely any of these compounds has been used as antiviral treatment in clinical practice. Therefore, these phenolic acids with diverse skeletons and mechanisms provide us an excellent resource for finding novel antiviral drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The biogenesis pathway of tRNA-derived piRNAs in Bombyx germ cells

PubMed Central

Honda, Shozo; Kawamura, Takuya; Loher, Phillipe; Morichika, Keisuke; Rigoutsos, Isidore

2017-01-01

Abstract Transfer RNAs (tRNAs) function in translational machinery and further serves as a source of short non-coding RNAs (ncRNAs). tRNA-derived ncRNAs show differential expression profiles and play roles in many biological processes beyond translation. Molecular mechanisms that shape and regulate their expression profiles are largely unknown. Here, we report the mechanism of biogenesis for tRNA-derived Piwi-interacting RNAs (td-piRNAs) expressed in Bombyx BmN4 cells. In the cells, two cytoplasmic tRNA species, tRNAAspGUC and tRNAHisGUG, served as major sources for td-piRNAs, which were derived from the 5′-part of the respective tRNAs. cP-RNA-seq identified the two tRNAs as major substrates for the 5′-tRNA halves as well, suggesting a previously uncharacterized link between 5′-tRNA halves and td-piRNAs. An increase in levels of the 5′-tRNA halves, induced by BmNSun2 knockdown, enhanced the td-piRNA expression levels without quantitative change in mature tRNAs, indicating that 5′-tRNA halves, not mature tRNAs, are the direct precursors for td-piRNAs. For the generation of tRNAHisGUG-derived piRNAs, BmThg1l-mediated nucleotide addition to −1 position of tRNAHisGUG was required, revealing an important function of BmThg1l in piRNA biogenesis. Our study advances the understanding of biogenesis mechanisms and the genesis of specific expression profiles for tRNA-derived ncRNAs. PMID:28645172

Quantum identities for the action

NASA Astrophysics Data System (ADS)

Gozzi, E.

2018-04-01

In this paper we derive various identities involving the action functional which enters the path-integral formulation of quantum mechanics. They provide some kind of generalisations of the Ehrenfest theorem giving correlations between powers of the action and its functional derivatives.

Shikonin and its derivatives: a patent review.

PubMed

Wang, Rubing; Yin, Runting; Zhou, Wen; Xu, Defeng; Li, Shaoshun

2012-09-01

Shikonin and its derivatives are the main components of red pigment extracts from Lithospermum erythrorhizon, whose medicinal properties have been confirmed for a long history, and have aroused great interest as the hallmark molecules responsible for their significant biological activities, especially for their striking anticancer effects. Areas covered in this paper include a review of the total synthesis, biological effects and mechanisms of shikonin and its derivatives for their anticancer activities in the past decade, basing on literature and patents. The current state and problems are also discussed. At present, screening for anticancer shikonin derivatives is based on cellular level to find compounds with stronger cytotoxicity. Though several compounds have been discovered with striking cytotoxicity in vitro, however, no selectivity was observed and undoubtedly, the further outcomes have been disappointing because of their great damage to normal cells. Meanwhile, the presumed mechanisms of action are also established in terms of their cytotoxicity. From a pharmacological point of view, most of the shikonin derivatives are at an early stage of their development, and thus it is difficult to determine the exact effectiveness in cancer treatment. With research in this field going deeper, it can be expected that, despite the difficulties, shikonin derivatives as potential anticancer agents will soon follow.

Statistical mechanical foundation of the peridynamic nonlocal continuum theory: energy and momentum conservation laws.

PubMed

Lehoucq, R B; Sears, Mark P

2011-09-01

The purpose of this paper is to derive the energy and momentum conservation laws of the peridynamic nonlocal continuum theory using the principles of classical statistical mechanics. The peridynamic laws allow the consideration of discontinuous motion, or deformation, by relying on integral operators. These operators sum forces and power expenditures separated by a finite distance and so represent nonlocal interaction. The integral operators replace the differential divergence operators conventionally used, thereby obviating special treatment at points of discontinuity. The derivation presented employs a general multibody interatomic potential, avoiding the standard assumption of a pairwise decomposition. The integral operators are also expressed in terms of a stress tensor and heat flux vector under the assumption that these fields are differentiable, demonstrating that the classical continuum energy and momentum conservation laws are consequences of the more general peridynamic laws. An important conclusion is that nonlocal interaction is intrinsic to continuum conservation laws when derived using the principles of statistical mechanics.

Mechanical Balance Laws for Boussinesq Models of Surface Water Waves

NASA Astrophysics Data System (ADS)

Ali, Alfatih; Kalisch, Henrik

2012-06-01

Depth-integrated long-wave models, such as the shallow-water and Boussinesq equations, are standard fare in the study of small amplitude surface waves in shallow water. While the shallow-water theory features conservation of mass, momentum and energy for smooth solutions, mechanical balance equations are not widely used in Boussinesq scaling, and it appears that the expressions for many of these quantities are not known. This work presents a systematic derivation of mass, momentum and energy densities and fluxes associated with a general family of Boussinesq systems. The derivation is based on a reconstruction of the velocity field and the pressure in the fluid column below the free surface, and the derivation of differential balance equations which are of the same asymptotic validity as the evolution equations. It is shown that all these mechanical quantities can be expressed in terms of the principal dependent variables of the Boussinesq system: the surface excursion η and the horizontal velocity w at a given level in the fluid.

Alternative Derivations of the Statistical Mechanical Distribution Laws

PubMed Central

Wall, Frederick T.

1971-01-01

A new approach is presented for the derivation of statistical mechanical distribution laws. The derivations are accomplished by minimizing the Helmholtz free energy under constant temperature and volume, instead of maximizing the entropy under constant energy and volume. An alternative method involves stipulating equality of chemical potential, or equality of activity, for particles in different energy levels. This approach leads to a general statement of distribution laws applicable to all systems for which thermodynamic probabilities can be written. The methods also avoid use of the calculus of variations, Lagrangian multipliers, and Stirling's approximation for the factorial. The results are applied specifically to Boltzmann, Fermi-Dirac, and Bose-Einstein statistics. The special significance of chemical potential and activity is discussed for microscopic systems. PMID:16578712

Alternative derivations of the statistical mechanical distribution laws.

PubMed

Wall, F T

1971-08-01

A new approach is presented for the derivation of statistical mechanical distribution laws. The derivations are accomplished by minimizing the Helmholtz free energy under constant temperature and volume, instead of maximizing the entropy under constant energy and volume. An alternative method involves stipulating equality of chemical potential, or equality of activity, for particles in different energy levels. This approach leads to a general statement of distribution laws applicable to all systems for which thermodynamic probabilities can be written. The methods also avoid use of the calculus of variations, Lagrangian multipliers, and Stirling's approximation for the factorial. The results are applied specifically to Boltzmann, Fermi-Dirac, and Bose-Einstein statistics. The special significance of chemical potential and activity is discussed for microscopic systems.

Predicting transport regime and local electrostatic environment from Coulomb blockade diamond sizes

NASA Astrophysics Data System (ADS)

Olsen, Stine T.; Hansen, Thorsten; Mikkelsen, Kurt V.

2017-03-01

Electron transport through a molecule is often described in one of the two regimes: the coherent tunnelling regime or the Coulomb blockade regime. The twilight zone of the two regimes still possesses many unsolved questions. A theoretical analysis of the oligophenylenevinylene OPV3 experiments by Bjørnholm and co-workers is performed. The experiments showed how two OPV3 derivatives performed very differently despite the strong similarity of the molecular structure, hence the experimental data showed two different transport mechanisms. The different transport mechanisms of the two OPV3 derivatives are explained from quantum mechanical calculations of the molecular redox energies and from the experimentally accessible window size.

Confocal arthroscopy-based patient-specific constitutive models of cartilaginous tissues - II: prediction of reaction force history of meniscal cartilage specimens.

PubMed

Taylor, Zeike A; Kirk, Thomas B; Miller, Karol

2007-10-01

The theoretical framework developed in a companion paper (Part I) is used to derive estimates of mechanical response of two meniscal cartilage specimens. The previously developed framework consisted of a constitutive model capable of incorporating confocal image-derived tissue microstructural data. In the present paper (Part II) fibre and matrix constitutive parameters are first estimated from mechanical testing of a batch of specimens similar to, but independent from those under consideration. Image analysis techniques which allow estimation of tissue microstructural parameters form confocal images are presented. The constitutive model and image-derived structural parameters are then used to predict the reaction force history of the two meniscal specimens subjected to partially confined compression. The predictions are made on the basis of the specimens' individual structural condition as assessed by confocal microscopy and involve no tuning of material parameters. Although the model does not reproduce all features of the experimental curves, as an unfitted estimate of mechanical response the prediction is quite accurate. In light of the obtained results it is judged that more general non-invasive estimation of tissue mechanical properties is possible using the developed framework.

Thermally induced oscillations in fluid flow

NASA Technical Reports Server (NTRS)

Zuber, N.

1970-01-01

Theoretical investigation distinguishes the various mechanisms responsible for oscillations of pressure, temperature, and flow velocity, derives a quantitative description of the most troublesome mechanisms, and develops a capability to predict the occurrence of unstable flow.

An Iron 13S-Lipoxygenase with an α-Linolenic Acid Specific Hydroperoxidase Activity from Fusarium oxysporum

PubMed Central

Brodhun, Florian; Cristobal-Sarramian, Alvaro; Zabel, Sebastian; Newie, Julia; Hamberg, Mats; Feussner, Ivo

2013-01-01

Jasmonates constitute a family of lipid-derived signaling molecules that are abundant in higher plants. The biosynthetic pathway leading to plant jasmonates is initiated by 13-lipoxygenase-catalyzed oxygenation of α-linolenic acid into its 13-hydroperoxide derivative. A number of plant pathogenic fungi (e.g. Fusarium oxysporum) are also capable of producing jasmonates, however, by a yet unknown biosynthetic pathway. In a search for lipoxygenase in F. oxysporum, a reverse genetic approach was used and one of two from the genome predicted lipoxygenases (FoxLOX) was cloned. The enzyme was heterologously expressed in E. coli, purified via affinity chromatography, and its reaction mechanism characterized. FoxLOX was found to be a non-heme iron lipoxygenase, which oxidizes C18-polyunsaturated fatty acids to 13S-hydroperoxy derivatives by an antarafacial reaction mechanism where the bis-allylic hydrogen abstraction is the rate-limiting step. With α-linolenic acid as substrate FoxLOX was found to exhibit a multifunctional activity, because the hydroperoxy derivatives formed are further converted to dihydroxy-, keto-, and epoxy alcohol derivatives. PMID:23741422

Ghost-Free Theory with Third-Order Time Derivatives

NASA Astrophysics Data System (ADS)

Motohashi, Hayato; Suyama, Teruaki; Yamaguchi, Masahide

2018-06-01

As the first step to extend our understanding of higher-derivative theories, within the framework of analytic mechanics of point particles, we construct a ghost-free theory involving third-order time derivatives in Lagrangian. While eliminating linear momentum terms in the Hamiltonian is necessary and sufficient to kill the ghosts associated with higher derivatives for Lagrangian with at most second-order derivatives, we find that this is necessary but not sufficient for the Lagrangian with higher than second-order derivatives. We clarify a set of ghost-free conditions under which we show that the Hamiltonian is bounded, and that equations of motion are reducible into a second-order system.

Molecular Mechanics: The Method and Its Underlying Philosophy.

ERIC Educational Resources Information Center

Boyd, Donald B.; Lipkowitz, Kenny B.

1982-01-01

Molecular mechanics is a nonquantum mechanical method for solving problems concerning molecular geometries and energy. Methodology based on: the principle of combining potential energy functions of all structural features of a particular molecule into a total force field; derivation of basic equations; and use of available computer programs is…

Interplant Aboveground Signaling Prompts Upregulation of Auxin Promoter and Malate Transporter as Part of Defensive Response in the Neighboring Plants.

PubMed

Sweeney, Connor; Lakshmanan, Venkatachalam; Bais, Harsh P

2017-01-01

When disrupted by stimuli such as herbivory, pathogenic infection, or mechanical wounding, plants secrete signals such as root exudates and volatile organic compounds (VOCs). The emission of VOCs induces a response in the neighboring plant communities and can improve plant fitness by alerting nearby plants of an impending threat and prompting them to alter their physiology for defensive purposes. In this study, we investigated the role of plant-derived signals, released as a result of mechanical wounding, that may play a role in intraspecific communication between Arabidopsis thaliana communities. Plant-derived signals released by the wounded plant resulted in more elaborate root development in the neighboring, unwounded plants. Such plant-derived signals also upregulated the Aluminum-activated malate transporter ( ALMT1 ) responsible for the secretion of malic acid (MA) and the DR5 promoter, an auxin responsive promoter concentrated in root apex of the neighboring plants. We speculate that plant-derived signal-induced upregulation of root-specific ALMT1 in the undamaged neighboring plants sharing the environment with stressed plants may associate more with the benign microbes belowground. We also observed increased association of beneficial bacterium Bacillus subtilis UD1022 on roots of the neighboring plants sharing environment with the damaged plants. Wounding-induced plant-derived signals therefore induce defense mechanisms in the undamaged, local plants, eliciting a two-pronged preemptive response of more rapid root growth and up-regulation of ALMT1 , resulting in increased association with beneficial microbiome.

Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

PubMed

Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

2014-03-01

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

Mechanism of Resistance to an Antitubercular 2-Thiopyridine Derivative That Is Also Active against Burkholderia cenocepacia

PubMed Central

Scoffone, Viola C.; Spadaro, Francesca; Udine, Claudia; Makarov, Vadim; Fondi, Marco; Fani, Renato; De Rossi, Edda; Riccardi, Giovanna

2014-01-01

The discovery of new compounds that are able to inhibit the growth of Burkholderia cenocepacia is of primary importance for cystic fibrosis patients. Here, the mechanism of resistance to a new pyridine derivative already shown to be effective against Mycobacterium tuberculosis and to have good activity toward B. cenocepacia was investigated. Increased expression of a resistance-nodulation-cell division (RND) efflux system was detected in the resistant mutants, thus confirming their important roles in B. cenocepacia antibiotic resistance. PMID:24395233

Control theory for scanning probe microscopy revisited.

PubMed

Stirling, Julian

2014-01-01

We derive a theoretical model for studying SPM feedback in the context of control theory. Previous models presented in the literature that apply standard models for proportional-integral-derivative controllers predict a highly unstable feedback environment. This model uses features specific to the SPM implementation of the proportional-integral controller to give realistic feedback behaviour. As such the stability of SPM feedback for a wide range of feedback gains can be understood. Further consideration of mechanical responses of the SPM system gives insight into the causes of exciting mechanical resonances of the scanner during feedback operation.

Discrimination of nuclear spin isomers exploiting the excited state dynamics of a quinodimethane derivative

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

Obaid, Rana; Faculty of Pharmacy, Al-Quds University, Abu Dis, Palestine; Kinzel, Daniel

2014-10-28

Despite the concept of nuclear spin isomers (NSIs) exists since the early days of quantum mechanics, only few approaches have been suggested to separate different NSIs. Here, a method is proposed to discriminate different NSIs of a quinodimethane derivative using its electronic excited state dynamics. After electronic excitation by a laser field with femtosecond time duration, a difference in the behavior of several quantum mechanical operators can be observed. A pump-probe experimental approach for separating these different NSIs is then proposed.

Antimicrobial peptides of the genus Bacillus: a new era for antibiotics.

PubMed

Sumi, Chandra Datta; Yang, Byung Wook; Yeo, In-Cheol; Hahm, Young Tae

2015-02-01

The rapid onset of resistance reduces the efficacy of most conventional antimicrobial drugs and is a general cause of concern for human well-being. Thus, there is great demand for a continuous supply of novel antibiotics to combat this problem. Bacteria-derived antimicrobial peptides (AMPs) have long been used as food preservatives; moreover, prior to the development of conventional antibiotics, these AMPs served as an efficient source of antibiotics. Recently, peptides produced by members of the genus Bacillus were shown to have a broad spectrum of antimicrobial activity against pathogenic microbes. Bacillus-derived AMPs can be synthesized both ribosomally and nonribosomally and can be classified according to peptide biosynthesis, structure, and molecular weight. The precise mechanism of action of these AMPs is not yet clear; however, one proposed mechanism is that these AMPs kill bacteria by forming channels in and (or) disrupting the bacterial cell wall. Bacillus-derived AMPs have potential in the pharmaceutical industry, as well as the food and agricultural sectors. Here, we focus on Bacillus-derived AMPs as a novel alternative approach to antibacterial drug development. We also provide an overview of the biosynthesis, mechanisms of action, applications, and effectiveness of different AMPs produced by members of the Bacillus genus, including several recently identified novel AMPs.

Characterization of Shikonin Derivative Secretion in Lithospermum erythrorhizon Hairy Roots as a Model of Lipid-Soluble Metabolite Secretion from Plants

PubMed Central

Tatsumi, Kanade; Yano, Mariko; Kaminade, Kenta; Sugiyama, Akifumi; Sato, Mayuko; Toyooka, Kiminori; Aoyama, Takashi; Sato, Fumihiko; Yazaki, Kazufumi

2016-01-01

Shikonin derivatives are specialized lipophilic metabolites, secreted in abundant amounts from the root epidermal cells of Lithospermum erythrorhizon. Because they have anti-microbial activities, these compounds, which are derivatives of red naphthoquinone, are thought to serve as a chemical barrier for plant roots. The mechanism by which they are secreted from cells is, however, largely unknown. The shikonin production system in L. erythrorhizon is an excellent model for studying the mechanism by which lipophilic compounds are secreted from plant cells, because of the abundant amounts of these compounds produced by L. erythrorhizon, the 0 to 100% inducibility of their production, the light-specific inhibition of production, and the visibility of these products as red pigments. To date, many factors regulating shikonin biosynthesis have been identified, but no mechanism that regulates shikonin secretion without inhibiting biosynthesis has been detected. This study showed that inhibitors of membrane traffic strongly inhibit shikonin secretion without inhibiting shikonin production, suggesting that the secretion of shikonin derivatives into the apoplast utilizes pathways common to the ADP-ribosylation factor/guanine nucleotide exchange factor (ARF/GEF) system and actin filament polymerization, at least in part. These findings provide clues about the machinery involved in secreting lipid-soluble metabolites from cells. PMID:27507975

Characterization of Shikonin Derivative Secretion in Lithospermum erythrorhizon Hairy Roots as a Model of Lipid-Soluble Metabolite Secretion from Plants.

PubMed

Tatsumi, Kanade; Yano, Mariko; Kaminade, Kenta; Sugiyama, Akifumi; Sato, Mayuko; Toyooka, Kiminori; Aoyama, Takashi; Sato, Fumihiko; Yazaki, Kazufumi

2016-01-01

Shikonin derivatives are specialized lipophilic metabolites, secreted in abundant amounts from the root epidermal cells of Lithospermum erythrorhizon. Because they have anti-microbial activities, these compounds, which are derivatives of red naphthoquinone, are thought to serve as a chemical barrier for plant roots. The mechanism by which they are secreted from cells is, however, largely unknown. The shikonin production system in L. erythrorhizon is an excellent model for studying the mechanism by which lipophilic compounds are secreted from plant cells, because of the abundant amounts of these compounds produced by L. erythrorhizon, the 0 to 100% inducibility of their production, the light-specific inhibition of production, and the visibility of these products as red pigments. To date, many factors regulating shikonin biosynthesis have been identified, but no mechanism that regulates shikonin secretion without inhibiting biosynthesis has been detected. This study showed that inhibitors of membrane traffic strongly inhibit shikonin secretion without inhibiting shikonin production, suggesting that the secretion of shikonin derivatives into the apoplast utilizes pathways common to the ADP-ribosylation factor/guanine nucleotide exchange factor (ARF/GEF) system and actin filament polymerization, at least in part. These findings provide clues about the machinery involved in secreting lipid-soluble metabolites from cells.

Additive In Vitro Antiplasmodial Effect of N-Alkyl and N-Benzyl-1,10-Phenanthroline Derivatives and Cysteine Protease Inhibitor E64

PubMed Central

Wijayanti, Mahardika Agus; Sholikhah, Eti Nurwening; Hadanu, Ruslin; Jumina, Jumina; Supargiyono, Supargiyono; Mustofa, Mustofa

2010-01-01

Potential new targets for antimalarial chemotherapy include parasite proteases, which are required for several cellular functions during the Plasmodium falciparum life cycle. Four new derivatives of N-alkyl and N-benzyl-1,10-phenanthroline have been synthesized. Those are (1)-N-methyl-1,10-phenanthrolinium sulfate, (1)-N-ethyl-1,10-phenanthrolinium sulfate, (1)-N-benzyl-1,10-phenanthrolinium chloride, and (1)-N-benzyl-1,10-phenanthrolinium iodide. Those compounds had potential antiplasmodial activity with IC50 values from 260.42 to 465.38 nM. Cysteine proteinase inhibitor E64 was used to investigate the mechanism of action of N-alkyl and N-benzyl-1,10-phenanthroline derivatives. A modified fixed-ratio isobologram method was used to study the in vitro interactions between the new compounds with either E64 or chloroquine. The interaction between N-alkyl and N-benzyl-1,10-phenanthroline derivatives and E64 was additive as well as their interactions with chloroquine were also additive. Antimalarial mechanism of chloroquine is mainly on the inhibition of hemozoin formation. As the interaction of chloroquine and E64 was additive, the results indicated that these new compounds had a mechanism of action by inhibiting Plasmodium proteases. PMID:22332022

Effects of molecular structure of the resins on the volumetric shrinkage and the mechanical strength of dental restorative composites.

PubMed

Kim, L U; Kim, J W; Kim, C K

2006-09-01

To prepare a dental composite that has a low amount of curing shrinkage and excellent mechanical strength, various 2,2-bis[4-(2-hydroxy-3-methacryloyloxy propoxy) phenyl] propane (Bis-GMA) derivatives were synthesized via molecular structure design, and afterward, properties of their mixtures were explored. Bis-GMA derivatives, which were obtained by substituting methyl groups for hydrogen on the phenyl ring in the Bis-GMA, exhibited lower curing shrinkage than Bis-GMA, whereas their viscosities were higher than that of Bis-GMA. Other Bis-GMA derivatives, which contained a glycidyl methacrylate as a molecular end group exhibited reduced curing shrinkage and viscosity. Methoxy substitution for hydroxyl groups on the Bis-GMA derivatives was performed for the further reduction of the viscosity and curing shrinkage. Various resin mixtures, which had the same viscosity as the commercial one, were prepared, and their curing shrinkage was examined. A resin mixture containing 2,2-bis[3,5-dimethyl, 4-(2-methoxy-3-methacryloyloxy propoxy) phenyl] propane] (TMBis-M-GMA) as a base resin and 4-tert-butylphenoxy-2-methyoxypropyl methacrylate (t-BP-M-GMA) as a diluent exhibited the lowest curing shrinkage among them. The composite prepared from this resin mixture also exhibited the lowest curing shrinkage along with enhanced mechanical properties.

Kinetics and the mass transfer mechanism of hydrogen sulfide removal by biochar derived from rice hull.

PubMed

Shang, Guofeng; Liu, Liang; Chen, Ping; Shen, Guoqing; Li, Qiwu

2016-05-01

The biochar derived from rice hull was evaluated for its abilities to remove hydrogen sulfide (H2S) from gas phase. The surface area and pH of the biochar were compared. The biochar derived from rice hull was evaluated for its abilities to remove hydrogen sulfide (H2S) from gas phase. The surface area and pH of the biochar were compared. The different pyrolysis temperature has great influence on the adsorption of H2S. At the different pyrolysis temperature, the H2S removal efficiency of rice hull-derived biochar was different. The adsorption capacities of biochar were 2.09 mg·g(-1), 2.65 mg·g(-1), 16.30 mg·g(-1), 20.80 mg·g(-1), and 382.70 mg·g(-1), which their pyrolysis temperatures were 100 °C, 200 °C, 300 °C, 400 °C and 500 °C respectively. Based on the Yoon-Nelson model, it analyzed the mass transfer mechanism of hydrogen sulfide adsorption by biochar. The paper focuses on the biochar derived from rice hull-removed hydrogen sulfide (H2S) from gas phase. The surface area and pH of the biochar were compared. The different pyrolysis temperatures have great influence on the adsorption of H2S. At the different pyrolysis temperatures, the H2S removal efficiency of rice hull-derived biohar was different. The adsorption capacities of biochar were 2.09, 2.65, 16.30, 20.80, and 382.70 mg·g(-1), and their pyrolysis temperatures were 100, 200, 300, 400, and 500 °C, respectively. Based on the Yoon-Nelson model, the mass transfer mechanism of hydrogen sulfide adsorption by biochar was analyzed.

Mechanical Properties of Mineralized Collagen Fibrils As Influenced By Demineralization

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

Balooch, M.; Habelitz, S.; Kinney, J.H.

2009-05-11

Dentin and bone derive their mechanical properties from a complex arrangement of collagen type-I fibrils reinforced with nanocrystalline apatite mineral in extra- and intrafibrillar compartments. While mechanical properties have been determined for the bulk of the mineralized tissue, information on the mechanics of the individual fibril is limited. Here, atomic force microscopy was used on individual collagen fibrils to study structural and mechanical changes during acid etching. The characteristic 67 nm periodicity of gap zones was not observed on the mineralized fibril, but became apparent and increasingly pronounced with continuous demineralization. AFM-nanoindentation showed a decrease in modulus from 1.5 GPamore » to 50 MPa during acid etching of individual collagen fibrils and revealed that the modulus profile followed the axial periodicity. The nanomechanical data, Raman spectroscopy and SAXS support the hypothesis that intrafibrillar mineral etches at a substantially slower rate than the extrafibrillar mineral. These findings are relevant for understanding the biomechanics and design principles of calcified tissues derived from collagen matrices.« less

Directing bone marrow-derived stromal cell function with mechanics.

PubMed

Potier, E; Noailly, J; Ito, K

2010-03-22

Because bone marrow-derived stromal cells (BMSCs) are able to generate many cell types, they are envisioned as source of regenerative cells to repair numerous tissues, including bone, cartilage, and ligaments. Success of BMSC-based therapies, however, relies on a number of methodological improvements, among which better understanding and control of the BMSC differentiation pathways. Since many years, the biochemical environment is known to govern BMSC differentiation, but more recent evidences show that the biomechanical environment is also directing cell functions. Using in vitro systems that aim to reproduce selected components of the in vivo mechanical environment, it was demonstrated that mechanical loadings can affect BMSC proliferation and improve the osteogenic, chondrogenic, or myogenic phenotype of BMSCs. These effects, however, seem to be modulated by parameters other than mechanics, such as substrate nature or soluble biochemical environment. This paper reviews and discusses recent experimental data showing that despite some knowledge limitation, mechanical stimulation already constitutes an additional and efficient tool to drive BMSC differentiation. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

PubMed Central

Arlia-Ciommo, Anthony; Piano, Amanda; Svistkova, Veronika; Mohtashami, Sadaf; Titorenko, Vladimir I.

2014-01-01

Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research. PMID:25238416

Using psychophysics to ask if the brain samples or maximizes

PubMed Central

Acuna, Daniel E.; Berniker, Max; Fernandes, Hugo L.; Kording, Konrad P.

2015-01-01

The two-alternative forced-choice (2AFC) task is the workhorse of psychophysics and is used to measure the just-noticeable difference, generally assumed to accurately quantify sensory precision. However, this assumption is not true for all mechanisms of decision making. Here we derive the behavioral predictions for two popular mechanisms, sampling and maximum a posteriori, and examine how they affect the outcome of the 2AFC task. These predictions are used in a combined visual 2AFC and estimation experiment. Our results strongly suggest that subjects use a maximum a posteriori mechanism. Further, our derivations and experimental paradigm establish the already standard 2AFC task as a behavioral tool for measuring how humans make decisions under uncertainty. PMID:25767093

Cosmological implications of quantum corrections and higher-derivative extension

NASA Astrophysics Data System (ADS)

Chialva, Diego; Mazumdar, Anupam

2015-02-01

We discuss the challenges for the early universe cosmology from quantum corrections, and in particular higher-derivative terms, in the gravitational and inflaton sectors of the models. The work is divided in two parts. In the first one we review the already well-known issues due to quantum corrections to the inflaton potential, in particular focusing on chaotic/slow-roll single-field models. We will point out some issues concerning the proposed mechanisms to cope with the corrections, and also argue how the presence of higher-derivative corrections could be problematic for those mechanisms. In the second part we will more directly focus on higher-derivative corrections. We will show how, in order to discuss a number of high-energy phenomena relevant to inflation (such as its actual onset) one has to deal with energy scales where the derivative expansion breaks down, presenting problems such as quantum vacuum instability and ghosts. To discuss such phenomena in the convenient framework of the effective theory, one must then abandon the derivative expansion and resort to the full nonlocal formulation of the theory, which is in fact equivalent to re-integrating back the relevant physics, but with the benefit of using a more compact single-field formalism. Finally, we will briefly discuss possible advantages offered by the presence of higher derivatives and a nonlocal theory to build better controlled UV models of inflation.

Foundations of Quantum Mechanics: Derivation of a dissipative Schrödinger equation from first principles

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

Gonçalves, L.A.; Olavo, L.S.F., E-mail: olavolsf@gmail.com

Dissipation in Quantum Mechanics took some time to become a robust field of investigation after the birth of the field. The main issue hindering developments in the field is that the Quantization process was always tightly connected to the Hamiltonian formulation of Classical Mechanics. In this paper we present a quantization process that does not depend upon the Hamiltonian formulation of Classical Mechanics (although still departs from Classical Mechanics) and thus overcome the problem of finding, from first principles, a completely general Schrödinger equation encompassing dissipation. This generalized process of quantization is shown to be nothing but an extension ofmore » a more restricted version that is shown to produce the Schrödinger equation for Hamiltonian systems from first principles (even for Hamiltonian velocity dependent potential). - Highlights: • A Quantization process independent of the Hamiltonian formulation of quantum Mechanics is proposed. • This quantization method is applied to dissipative or absorptive systems. • A Dissipative Schrödinger equation is derived from first principles.« less

The use of index tests to determine the mechanical properties of crushed aggregates from Precambrian basement complex rocks, Ado-Ekiti, SW Nigeria

NASA Astrophysics Data System (ADS)

Afolagboye, Lekan Olatayo; Talabi, Abel Ojo; Oyelami, Charles Adebayo

2017-05-01

This study assessed the possibility of using index tests to determine the mechanical properties of crushed aggregates. The aggregates used in this study were derived from major Precambrian basement rocks in Ado-Ekiti, Nigeria. Regression analyses were performed to determine the empirical relations that mechanical properties of the aggregates may have with the point load strength (IS(50)), Schmidt rebound hammer value (SHR) and unconfined compressive strength (UCS) of the rocks. For all the data, strong correlation coefficients were found between IS(50), SHR, UCS, and mechanical properties of the aggregates. The regression analysis conducted on the different rocks separately showed that correlations coefficients obtained between the IS(50), SHR, UCS and mechanical properties of the aggregates were stronger than those of the grouped rocks. The T-test and F-test showed that the derived models were valid. This study has shown that the mechanical properties of the aggregates can be estimated from IS(50), SHR and USC but the influence of rock type on the relationships should be taken into consideration.

Emerging paradigms and questions on pro-angiogenic bone marrow-derived myelomonocytic cells.

PubMed

Laurent, Julien; Touvrey, Cédric; Botta, Francesca; Kuonen, François; Ruegg, Curzio

2011-01-01

Cancer-related inflammation has emerged in recent years as a major event contributing to tumor angiogenesis, tumor progression and metastasis formation. Bone marrow-derived and inflammatory cells promote tumor angiogenesis by providing endothelial progenitor cells that differentiate into mature endothelial cells, and by secreting pro-angiogenic factors and remodeling the extracellular matrix to stimulate angiogenesis though paracrine mechanisms. Several bone marrow-derived myelonomocytic cells, including monocytes and macrophages, have been identified and characterized by several laboratories in recent years. While the central role of these cells in promoting tumor angiogenesis, tumor progression and metastasis is nowadays well established, many questions remain open and new ones are emerging. These include the relationship between their phenotype and function, the mechanisms of pro-angiogenic programming, their contribution to resistance to anti-angiogenic treatments and to metastasis and their potential clinical use as biomarkers of angiogenesis and anti-angiogenic therapies. Here, we will review phenotypical and functional aspects of bone marrow-derived myelonomocytic cells and discuss some of the current outstanding questions.

Passive immunization of mice pups through oral immunization of dams with a plant-derived vaccine.

PubMed

Walmsley, Amanda M; Kirk, Dwayne D; Mason, Hugh S

2003-03-03

Passive immunization plays an important role in protecting young mammals against pathogens before the maturation of their own immune systems. Although many reports have shown active immunization of animals and human through the use of plant-derived vaccines, only one report has given evidence of passive immunization of offspring through oral immunization of parents using plant-derived vaccines. In this case, a challenge alone provided the evidence of passive immunization and the mechanism through which this occurred was not investigated. This report describes the first step in elucidating the mechanism of passive immunization of offspring through actively immunizing the female parent through an orally delivered, plant-derived vaccine. The authors found passive immunization of offspring was caused by transfer of antigen-specific IgG through either transplacental transfer or ingesting colostrum. Future studies will investigate the roles of transplacental antibody transfer and ingesting colostrum in passive immunization and the possible involvement of IgA in this immunization route.

Exploration of Novel Botanical Insecticide Leads: Synthesis and Insecticidal Activity of β-Dihydroagarofuran Derivatives.

PubMed

Zhao, Ximei; Xi, Xin; Hu, Zhan; Wu, Wenjun; Zhang, Jiwen

2016-02-24

The discovery of novel leads and new mechanisms of action is of vital significance to the development of pesticides. To explore lead compounds for botanical insecticides, 77 β-dihydroagarofuran derivatives were designed and synthesized. Their structures were mainly confirmed by (1)H NMR, (13)C NMR, DEPT-135°, IR, MS, and HRMS. Their insecticidal activity was evaluated against the third-instar larvae of Mythimna separata Walker, and the results indicated that, of these derivatives, eight exhibited more promising insecticidal activity than the positive control, celangulin-V. Particularly, compounds 5.7, 6.6, and 6.7 showed LD50 values of 37.9, 85.1, and 21.1 μg/g, respectively, which were much lower than that of celangulin-V (327.6 μg/g). These results illustrated that β-dihydroagarofuran ketal derivatives can be promising lead compounds for developing novel mechanism-based and highly effective botanical insecticides. Moreover, some newly discovered structure-activity relationships are discussed, which may provide some important guidance for insecticide development.

Application of in operando UV/Vis spectroscopy in lithium-sulfur batteries.

PubMed

Patel, Manu U M; Dominko, Robert

2014-08-01

Application of UV/Vis spectroscopy for the qualitative and quantitative determination of differences in the mechanism of lithium-sulfur battery behavior is presented. With the help of catholytes prepared from chemically synthesized stoichiometric mixtures of lithium and sulfur, calibration curves for two different types of electrolyte can be constructed. First-order derivatives of UV/Vis spectra show five typical derivative peak positions in both electrolytes. In operando measurements show a smooth change in the UV/Vis spectra in the wavelength region between λ=650 and 400 nm. Derivatives are in agreement with derivative peak positions observed with catholytes. Recalculation of normalized reflections of UV/Vis spectra obtained in operando mode enable the formation of polysulfides and their concentrations to be followed. In such a way, it is possible to distinguish differences in the mechanism of polysulfide shuttling between two electrolytes and to correlate differences in capacity fading. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On the distribution of saliency.

PubMed

Berengolts, Alexander; Lindenbaum, Michael

2006-12-01

Detecting salient structures is a basic task in perceptual organization. Saliency algorithms typically mark edge-points with some saliency measure, which grows with the length and smoothness of the curve on which these edge-points lie. Here, we propose a modified saliency estimation mechanism that is based on probabilistically specified grouping cues and on curve length distributions. In this framework, the Shashua and Ullman saliency mechanism may be interpreted as a process for detecting the curve with maximal expected length. Generalized types of saliency naturally follow. We propose several specific generalizations (e.g., gray-level-based saliency) and rigorously derive the limitations on generalized saliency types. We then carry out a probabilistic analysis of expected length saliencies. Using ergodicity and asymptotic analysis, we derive the saliency distributions associated with the main curves and with the rest of the image. We then extend this analysis to finite-length curves. Using the derived distributions, we derive the optimal threshold on the saliency for discriminating between figure and background and bound the saliency-based figure-from-ground performance.

Unravelling the effects of mechanical physiological conditioning on cardiac adipose tissue-derived progenitor cells in vitro and in silico.

PubMed

Llucià-Valldeperas, Aida; Bragós, Ramon; Soler-Botija, Carolina; Roura, Santiago; Gálvez-Montón, Carolina; Prat-Vidal, Cristina; Perea-Gil, Isaac; Bayes-Genis, Antoni

2018-01-11

Mechanical conditioning is incompletely characterized for stimulating therapeutic cells within the physiological range. We sought to unravel the mechanism of action underlying mechanical conditioning of adipose tissue-derived progenitor cells (ATDPCs), both in vitro and in silico. Cardiac ATDPCs, grown on 3 different patterned surfaces, were mechanically stretched for 7 days at 1 Hz. A custom-designed, magnet-based, mechanical stimulator device was developed to apply ~10% mechanical stretching to monolayer cell cultures. Gene and protein analyses were performed for each cell type and condition. Cell supernatants were also collected to analyze secreted proteins and construct an artificial neural network. Gene and protein modulations were different for each surface pattern. After mechanostimulation, cardiac ATDPCs increased the expression of structural genes and there was a rising trend on cardiac transcription factors. Finally, secretome analyses revealed upregulation of proteins associated with both myocardial infarction and cardiac regeneration, such as regulators of the immune response, angiogenesis or cell adhesion. To conclude, mechanical conditioning of cardiac ATDPCs enhanced the expression of early and late cardiac genes in vitro. Additionally, in silico analyses of secreted proteins showed that mechanical stimulation of cardiac ATDPCs was highly associated with myocardial infarction and repair.

Microstructure and mechanical properties of horns derived from three domestic bovines.

PubMed

Zhang, Quan-bin; Li, Chun; Pan, Yan-ting; Shan, Guang-hua; Cao, Ping; He, Jia; Lin, Zhong-shi; Ao, Ning-jian; Huang, Yao-xiong

2013-12-01

The microstructure and mechanical properties of horns derived from three domestic bovines (buffalo, cattle and sheep) were examined. The effects of water content, sampling position and orientation of three bovid horns on mechanical properties were systematically investigated by uniaxial tension and micron indentation tests. Meanwhile, the material composition and metal element contents were determined by Raman spectroscopy and elemental analysis respectively, and the microstructures of the horns were measured by scanning electron microscopy (SEM). Results show that the mechanical properties of horns have negative correlation with water contents and depend on sampling position and orientation. The spatial variations of the mechanical properties in horns are attributed to the different keratinization degrees in the proximal, middle and distal parts. And the mechanical properties of horns in the longitudinal direction are better than those in transverse. Among the three kinds of horns, the mechanical properties of buffalo horn are the best, followed by cattle horn, and those in sheep horn are the worst. This is due to the differences in material composition, metal element, and the microstructures of the horns. But the mechanical properties of buffalo horns are not dependent on the source of the buffalo. Therefore, regular engineered buffalo keratinous materials with standard mechanical properties can be obtained from different buffalo horns by using proper preparation methods. © 2013.

Concept for Highly Mechanized Data Processing, Project 111.

DTIC Science & Technology

A concept is developed for a highly mechanized maintenance data processing system capable of deriving factors, influences, and correlations to raise...the level of logistics knowledge and lead to the design of a management-control system. (Author)

Methods And Systms For Analyzing The Degradation And Failure Of Mechanical Systems

DOEpatents

Jarrell, Donald B.; Sisk, Daniel R.; Hatley, Darrel D.; Kirihara, Leslie J.; Peters, Timothy J.

2005-02-08

Methods and systems for identifying, understanding, and predicting the degradation and failure of mechanical systems are disclosed. The methods include measuring and quantifying stressors that are responsible for the activation of degradation mechanisms in the machine component of interest. The intensity of the stressor may be correlated with the rate of physical degradation according to some determinable function such that a derivative relationship exists between the machine performance, degradation, and the underlying stressor. The derivative relationship may be used to make diagnostic and prognostic calculations concerning the performance and projected life of the machine. These calculations may be performed in real time to allow the machine operator to quickly adjust the operational parameters of the machinery in order to help minimize or eliminate the effects of the degradation mechanism, thereby prolonging the life of the machine. Various systems implementing the methods are also disclosed.

Derived virtual devices: a secure distributed file system mechanism

NASA Technical Reports Server (NTRS)

VanMeter, Rodney; Hotz, Steve; Finn, Gregory

1996-01-01

This paper presents the design of derived virtual devices (DVDs). DVDs are the mechanism used by the Netstation Project to provide secure shared access to network-attached peripherals distributed in an untrusted network environment. DVDs improve Input/Output efficiency by allowing user processes to perform I/O operations directly from devices without intermediate transfer through the controlling operating system kernel. The security enforced at the device through the DVD mechanism includes resource boundary checking, user authentication, and restricted operations, e.g., read-only access. To illustrate the application of DVDs, we present the interactions between a network-attached disk and a file system designed to exploit the DVD abstraction. We further discuss third-party transfer as a mechanism intended to provide for efficient data transfer in a typical NAP environment. We show how DVDs facilitate third-party transfer, and provide the security required in a more open network environment.

Experimental and theoretical study on DPPH radical scavenging mechanism of some chalcone quinoline derivatives

NASA Astrophysics Data System (ADS)

Hamlaoui, Ikram; Bencheraiet, Reguia; Bensegueni, Rafik; Bencharif, Mustapha

2018-03-01

In this study, the antioxidant capacity of three chalcone derivatives was evaluated by DPPH free radical scavenging. Experimental data showed low antioxidant activity (IC50±SD) of these molecules in comparison with BHT. The mechanism of DPPH radical scavenging elucidated by means of density functional theory (DFT) calculations. The tested compounds and their corresponding radicals and anions were optimized using B3LYP functional with 6-31G (d,p) basis set in the gas phase. The C-PCM model was used to perform solvent medium calculations. On the basis of theoretical calculations, it was shown that HAT mechanism was predominant in the gas phase, whereas SET-PT and SPLET mechanisms were favored in the presence of the solvent. Moreover, the HOMO orbitals and spin density distribution was evaluated to predict the probable sites for free radical attack.

Study of a Car Body Tilting System Using a Variable Link Mechanism: Fundamental Characteristics of Pendulum Motion and Strategy for Perfect Tilting

NASA Astrophysics Data System (ADS)

Yoshida, Hidehisa; Nagai, Masao

This paper analyzes the fundamental dynamic characteristics of a tilting railway vehicle using a variable link mechanism for compensating both the lateral acceleration experienced by passengers and the wheel load imbalance between the inner and outer rails. The geometric relations between the center of rotation, the center of gravity, and the positions of all four links of the tilting system are analyzed. Then, equations of the pendulum motions of the railway vehicle body with a four-link mechanism are derived. A theoretically discussion is given on the geometrical shapes employed in the link mechanism that can simultaneously provide zero lateral acceleration and zero wheel load fluctuation. Then, the perfect tilting condition, which is the control target of the feedforward tilting control, is derived from the linear equation of tilting motion.

Thermo-mechanical behaviors of thermoplastic starch derived from sugar palm tree (Arenga pinnata).

PubMed

Sahari, J; Sapuan, S M; Zainudin, E S; Maleque, M A

2013-02-15

In recent years, increasing environmental concerns focused greater attention on the development of biodegradable materials. A thermoplastic starch derived from bioresources, sugar palm tree was successfully developed in the presence of biodegradable glycerol as a plasticizer. Sugar palm starch (SPS) was added with 15-40 w/w% of glycerol to prepare workable bioplastics and coded as SPS/G15, SPS/G20, SPS/G30 and SPS/G40. The samples were characterized for thermal properties, mechanical properties and moisture absorption on exposure to humidity were evaluated. Morphological studies through scanning electron microscopy (SEM) were used to explain the observed mechanical properties. Generally, the addition of glycerol decrease the transition temperature of plasticized SPS. The mechanical properties of plasticized SPS increase with the increasing of glycerol but up to 30 w/w%. Meanwhile, the water absorption of plasticized SPS decrease with increasing of glycerol. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cooperative catalysis by tertiary amino-thioureas: mechanism and basis for enantioselectivity of ketone cyanosilylation.

PubMed

Zuend, Stephan J; Jacobsen, Eric N

2007-12-26

The mechanism of the enantioselective cyanosilylation of ketones catalyzed by tertiary amino-thiourea derivatives was investigated using a combination of experimental and theoretical methods. The kinetic analysis is consistent with a cooperative mechanism in which both the thiourea and the tertiary amine of the catalyst are involved productively in the rate-limiting cyanide addition step. Density functional theory calculations were used to distinguish between mechanisms involving thiourea activation of ketone or of cyanide in the enantioselectivity-determining step. The strong correlation obtained between experimental and calculated ee's for a range of substrates and catalysts provides support for the most favorable calculated transition structures involving amine-bound HCN adding to thiourea-bound ketone. The calculations suggest that enantioselectivity arises from direct interactions between the ketone substrate and the amino-acid derived portion of the catalyst. On the basis of this insight, more enantioselective catalysts with broader substrate scope were prepared and evaluated experimentally.

Derivative chameleons

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

Noller, Johannes, E-mail: johannes.noller08@imperial.ac.uk

2012-07-01

We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂{sub μ}φ∂{sup μ}φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂{sub μ}φ∂{sup μ}φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly thismore » points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.« less

Systematic and Automated Development of Quantum Mechanically Derived Force Fields: The Challenging Case of Halogenated Hydrocarbons.

PubMed

Prampolini, Giacomo; Campetella, Marco; De Mitri, Nicola; Livotto, Paolo Roberto; Cacelli, Ivo

2016-11-08

A robust and automated protocol for the derivation of sound force field parameters, suitable for condensed-phase classical simulations, is here tested and validated on several halogenated hydrocarbons, a class of compounds for which standard force fields have often been reported to deliver rather inaccurate performances. The major strength of the proposed protocol is that all of the parameters are derived only from first principles because all of the information required is retrieved from quantum mechanical data, purposely computed for the investigated molecule. This a priori parametrization is carried out separately for the intra- and intermolecular contributions to the force fields, respectively exploiting the Joyce and Picky programs, previously developed in our group. To avoid high computational costs, all quantum mechanical calculations were performed exploiting the density functional theory. Because the choice of the functional is known to be crucial for the description of the intermolecular interactions, a specific procedure is proposed, which allows for a reliable benchmark of different functionals against higher-level data. The intramolecular and intermolecular contribution are eventually joined together, and the resulting quantum mechanically derived force field is thereafter employed in lengthy molecular dynamics simulations to compute several thermodynamic properties that characterize the resulting bulk phase. The accuracy of the proposed parametrization protocol is finally validated by comparing the computed macroscopic observables with the available experimental counterparts. It is found that, on average, the proposed approach is capable of yielding a consistent description of the investigated set, often outperforming the literature standard force fields, or at least delivering results of similar accuracy.

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

Akerstroem, Sara; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Solna; Gunalan, Vithiagaran

Nitric oxide is an important molecule playing a key role in a broad range of biological process such as neurotransmission, vasodilatation and immune responses. While the anti-microbiological properties of nitric oxide-derived reactive nitrogen intermediates (RNI) such as peroxynitrite, are known, the mechanism of these effects are as yet poorly studied. Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) belongs to the family Coronaviridae, was first identified during 2002-2003. Mortality in SARS patients ranges from between 6 to 55%. We have previously shown that nitric oxide inhibits the replication cycle of SARS-CoV in vitro by an unknown mechanism. In this study, we havemore » further investigated the mechanism of the inhibition process of nitric oxide against SARS-CoV. We found that peroxynitrite, an intermediate product of nitric oxide in solution formed by the reaction of NO with superoxide, has no effect on the replication cycle of SARS-CoV, suggesting that the inhibition is either directly effected by NO or a derivative other than peroxynitrite. Most interestingly, we found that NO inhibits the replication of SARS-CoV by two distinct mechanisms. Firstly, NO or its derivatives cause a reduction in the palmitoylation of nascently expressed spike (S) protein which affects the fusion between the S protein and its cognate receptor, angiotensin converting enzyme 2. Secondly, NO or its derivatives cause a reduction in viral RNA production in the early steps of viral replication, and this could possibly be due to an effect on one or both of the cysteine proteases encoded in Orf1a of SARS-CoV.« less

Receptor-Targeted, Magneto-Mechanical Stimulation of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

PubMed Central

Hu, Bin; El Haj, Alicia J; Dobson, Jon

2013-01-01

Mechanical cues are employed to promote stem cell differentiation and functional tissue formation in tissue engineering and regenerative medicine. We have developed a Magnetic Force Bioreactor (MFB) that delivers highly targeted local forces to cells at a pico-newton level, utilizing magnetic micro- and nano-particles to target cell surface receptors. In this study, we investigated the effects of magnetically targeting and actuating specific two mechanical-sensitive cell membrane receptors—platelet-derived growth factor receptor α (PDGFRα) and integrin ανβ3. It was found that a higher mineral-to-matrix ratio was obtained after three weeks of magneto-mechanical stimulation coupled with osteogenic medium culture by initially targeting PDGFRα compared with targeting integrin ανβ3 and non-treated controls. Moreover, different initiation sites caused a differentiated response profile when using a 2-day-lagged magneto-mechanical stimulation over culture periods of 7 and 12 days). However, both resulted in statistically higher osteogenic marker genes expression compared with immediate magneto-mechanical stimulation. These results provide insights into important parameters for designing appropriate protocols for ex vivo induced bone formation via magneto-mechanical actuation. PMID:24065106

Evolutionary Trends in the Jaw Adductor Mechanics of Ornithischian Dinosaurs.

PubMed

Nabavizadeh, Ali

2016-03-01

Jaw mechanics in ornithischian dinosaurs have been widely studied for well over a century. Most of these studies, however, use only one or few taxa within a given ornithischian clade as a model for feeding mechanics across the entire clade. In this study, mandibular mechanical advantages among 52 ornithischian genera spanning all subclades are calculated using 2D lever arm methods. These lever arm calculations estimate the effect of jaw shape and difference in adductor muscle line of action on relative bite forces along the jaw. Results show major instances of overlap between taxa in tooth positions at which there was highest mechanical advantage. A relatively low bite force is seen across the tooth row among thyreophorans (e.g., stegosaurs and ankylosaurs), with variation among taxa. A convergent transition occurs from a more evenly distributed bite force along the jaw in basal ornithopods and basal marginocephalians to a strong distal bite force in hadrosaurids and ceratopsids, respectively. Accordingly, adductor muscle vector angles show repeated trends from a mid-range caudodorsal orientation in basal ornithischians to a decrease in vector angles indicating more caudally oriented jaw movements in derived taxa (e.g., derived thyreophorans, basal ornithopods, lambeosaurines, pachycephalosaurs, and derived ceratopsids). Analyses of hypothetical jaw morphologies were also performed, indicating that both the coronoid process and lowered jaw joint increase moment arm length therefore increasing mechanical advantage of the jaw apparatus. Adaptive trends in craniomandibular anatomy show that ornithischians evolved more complex feeding apparatuses within different clades as well as morphological convergences between clades. © 2016 Wiley Periodicals, Inc.

Mansouramycin C kills cancer cells through reactive oxygen species production mediated by opening of mitochondrial permeability transition pore

PubMed Central

Kuang, Shan; Liu, Ge; Cao, Ruobing; Zhang, Linlin; Yu, Qiang; Sun, Chaomin

2017-01-01

Cancer is one of the deadliest diseases in the world and the search for novel anticancer agents is urgently required. Marine-derived isoquinolinequinones have exhibited promising anticancer activities. However, the exact mechanisms of cytotoxic activities of these isoquinolinequinones are poorly characterized. In this study, we investigated the anticancer effects and molecular mechanisms of mansouramycin C (Mm C), a cytotoxic isoquinolinequinone isolated from a marine streptomycete. We demonstrated that Mm C preferentially killed cancer cells and the cytotoxic effects were mediated by reactive oxygen species (ROS) generation. Mass spectrometry based proteomic analysis of Mm C-treated A549 cells revealed that many ROS-related proteins were differentially expressed. Proteomic-profiling after Mm C treatment identified oxidative phosphorylation as the most significant changes in pathways. Analysis also revealed extensive defects in mitochondrial structure and function. Furthermore, we disclosed that Mm C-induced ROS generation was caused by opening of mitochondrial permeability transition pore. Notably, Mm C synergized with sorafenib to induce cell death in A549 cells. Hence, we propose that the marine-derived natural compound Mm C is a potent inducer of the mitochondrial permeability transition and a promising anticancer drug candidate. Moreover, molecular mechanisms of Mm C shed new light on the understanding of the cytotoxic mechanisms of marine-derived isoquinolinequiones. PMID:29262621

The mechanisms of substance P-mediated migration of bone marrow-derived mesenchymal stem cell-like ST2 cells.

PubMed

Dubon, Maria Jose; Park, Ki-Sook

2016-04-01

Substance P (SP) is known to induce the mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) and thus participates in wound repair. However, the cellular and molecular mechanisms responsible for the SP-mediated migration of BM-MSCs were not fully understood. In the present study, we studied the molecular mechanisms that mediate the migration of the BM-derived MSC-like cell line ST2 in response to SP. Using a migration assay and western blot analysis, we noted that SP induced the chemotactic migration of ST2 cells through the intrinsic activation of extracellular signal-regulated kinases (ERKs) and protein kinase B (Akt), the phosphorylated expression levels of which were increased. We noted that Src is involved in the SP-mediated migration of ST2 cells and that focal adhesion kinase (FAK) was activated in the ST2 cells following SP treatment. Membrane ruffling increased in the ST2 cells after SP treatment, as was clearly demonstrated by immunocytochemical analysis. Importantly, using a blocking antibody against N-cadherin (GC-4), we studied cell migration and noted that SP mediated the migration of the ST2 cells through N-cadherin. The present study thus advanced our understanding of the mechanisms through which SP induces BM-MSC migration.

Characterizing Mechanical and Flow Properties using Injection Falloff Tests, March 28, 2011

EPA Pesticide Factsheets

This presentation asserts that Injection Fall-off Testing is an efficient way to derive in-situ information on most rock types, after-closure analysis can derive rock transmissibility and pore fluid pressure, and this is used to assist in the HF process.

Preparation Methods and Antioxidant Activities of Polysaccharides and Their Derivatives.

PubMed

Mei, Xinya; Yi, Chengkun; Huang, Gangliang

2017-01-01

In recent years, the antioxidant effects of polysaccharides have become a hot spot in the field of polysaccharide research. Herein, the action mechanisms of polysaccharide antioxidation and scavenging free radicals were analyzed. The research progresses on the preparation methods and antioxidant properties of polysaccharides and their derivatives were summarized. Investigating the antioxidant activities of polysaccharides and their derivatives can find useful polysaccharides and their derivatives, which have great potential as natural antioxidants used in functional foods or medicines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The potential mechanism of Bursal-derived BPP-II on the antibody production and avian pre-B cell.

PubMed

Feng, Xiuli; Cao, Ruibing; Zhou, Bin; Liu, Qingtao; Liu, Ke; Liu, Xiaodong; Zhang, Yuanpeng; Gu, Jinyan; Miao, Denian; Chen, Puyan

2013-03-01

The bursa of Fabricius is critical for the normal development of the B lymphocytes responsible for antibody production. However, the mechanism of the bursal-derived bioactive factor on B cell development is little reported. In this paper, chicks were immunized with BPP-II and AIV vaccine or AIV antigen, and antibody and IL-4 production were detected. The results showed that BPP-II played strongly inducing roles on the humoral immune responses. To investigate the gene expression at transcriptional level, avian pre-B lymphocyte DT40 cells were treated with BPP-II, and were analyzed with the gene microarray. The results proved that BPP-II treatment regulated 11 pathways, in which homologous recombination is a vital mechanism which is involved in antibody Ig gene conversion and diversification during B cell development. These results suggested Bursal-derived biological active factor BPP-II might be involved in the antibody production processes and B cell development, which is vital to the humoral central immune organ, the bursa of Fabricius. Copyright © 2012 Elsevier Ltd. All rights reserved.

ON THE DYNAMICAL DERIVATION OF EQUILIBRIUM STATISTICAL MECHANICS

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

Prigogine, I.; Balescu, R.; Henin, F.

1960-12-01

Work on nonequilibrium statistical mechanics, which allows an extension of the kinetic proof to all results of equilibrium statistical mechanics involving a finite number of degrees of freedom, is summarized. As an introduction to the general N-body problem, the scattering theory in classical mechanics is considered. The general N-body problem is considered for the case of classical mechanics, quantum mechanics with Boltzmann statistics, and quantum mechanics including quantum statistics. Six basic diagrams, which describe the elementary processes of the dynamics of correlations, were obtained. (M.C.G.)

Crystallization and textural porosity of synthetic clay minerals.

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

Carrado, K. A.; Csencsits, R.; Thiyagarajan, P.

2002-12-01

The crystallization of synthetic layered magnesium silicate hectorite clays from both silica sol and organosilane sources is compared. For the silica sol-derived clays, a templating method is employed wherein organic or polymeric molecules are included during clay crystallization that are then removed from the composites via calcination. The mechanism of silane-derived hectorite formation is followed by XRD, TGA, 29Si MAS NMR, and small angle X-ray scattering (SAXS), and results are compared to those obtained for the sol-derived hectorite. The mechanism appears to be similar but the rate is approximately doubled when the silane is used rather than silica sol. Analyticalmore » transmission electron microscopy (TEM) is exploited to glean structural morphology information towards resolving the nature of the resulting pore network structures. Results are compared with nitrogen adsorption-desorption isotherm behavior; dominant hysteresis loops are present in the type IV isotherms. Pore size distributions based on both the adsorption and desorption isotherms are compared. Small angle neutron scattering (SANS) experiments reveal that the average particle size increases as synthetic laponite < sol-derived hectorite < silane-derived hectorite < natural hectorite. Contrast matching SANS studies in aqueous and organic solvents are carried out to extract information about pore accessibility.« less

Synthesis, Characterization, and Cross-Linking Strategy of a Quercetin-Based Epoxidized Monomer as a Naturally-Derived Replacement for BPA in Epoxy Resins.

PubMed

Kristufek, Samantha L; Yang, Guozhen; Link, Lauren A; Rohde, Brian J; Robertson, Megan L; Wooley, Karen L

2016-08-23

The natural polyphenolic compound quercetin was functionalized and cross-linked to afford a robust epoxy network. Quercetin was selectively methylated and functionalized with glycidyl ether moieties using a microwave-assisted reaction on a gram scale to afford the desired monomer (Q). This quercetin-derived monomer was treated with nadic methyl anhydride (NMA) to obtain a cross-linked network (Q-NMA). The thermal and mechanical properties of this naturally derived network were compared to those of a conventional diglycidyl ether bisphenol A-derived counterpart (DGEBA-NMA). Q-NMA had similar thermal properties [i.e., glass transition (Tg ) and decomposition (Td ) temperatures] and comparable mechanical properties (i.e., Young's Modulus, storage modulus) to that of DGEBA-NMA. However, it had a lower tensile strength and higher flexural modulus at elevated temperatures. The application of naturally derived, sustainable compounds for the replacement of commercially available petrochemical-based epoxies is of great interest to reduce the environmental impact of these materials. Q-NMA is an attractive candidate for the replacement of bisphenol A-based epoxies in various specialty engineering applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antihypertensive properties of lactoferricin B-derived peptides.

PubMed

Ruiz-Giménez, Pedro; Ibáñez, Aida; Salom, Juan B; Marcos, Jose F; López-Díez, Jose Javier; Vallés, Salvador; Torregrosa, Germán; Alborch, Enrique; Manzanares, Paloma

2010-06-09

A set of eight lactoferricin B (LfcinB)-derived peptides was examined for inhibitory effects on angiotensin I-converting enzyme (ACE) activity and ACE-dependent vasoconstriction, and their hypotensive effect in spontaneously hypertensive rats (SHR). Peptides were derived from different elongations both at the C-terminal and N-terminal ends of the representative peptide LfcinB(20-25), which is known as the LfcinB antimicrobial core. All of the eight LfcinB-derived peptides showed in vitro inhibitory effects on ACE activity with different IC(50) values. Moreover, seven of them showed ex vivo inhibitory effects on ACE-dependent vasoconstriction. No clear correlation between in vitro and ex vivo inhibitory effects was found. Only LfcinB(20-25) and one of its fragments, F1, generated after a simulated gastrointestinal digestion, showed significant antihypertensive effects in SHR after oral administration. Remarkably, F1 did not show any effect on ACE-dependent vasoconstriction in contrast to the inhibitory effect showed by LfcinB(20-25). In conclusion, two LfcinB-derived peptides lower blood pressure and exhibit potential as orally effective antihypertensive compounds, yet a complete elucidation of the mechanism(s) involved deserves further ongoing research.

Reaction mechanisms in cellulose pyrolysis: a literature review

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

Molton, P.M.; Demmitt, T.F.

1977-08-01

A bibliographic review of 195 references is presented outlining the history of the research into the mechanisms of cellulose pyrolysis. Topics discussed are: initial product identification, mechanism of initial formation of levoglucosan, from cellulose and from related compounds, decomposition of cellulose to other compounds, formation of aromatics, pyrolysis of levoglucosan, crosslinking of cellulose, pyrolytic reactions of cellulose derivatives, and the effects of inorganic salts on the pyrolysis mechanism. (JSR)

Plasma-derived exosomes contribute to inflammation via the TLR9-NF-κB pathway in chronic heart failure patients.

PubMed

Ye, Wei; Tang, Xiaojun; Yang, Zhengquan; Liu, Chu; Zhang, Xin; Jin, Jing; Lyu, Jianxin

2017-07-01

Exosomes are small vesicles that contain proteins, DNA and RNA, and play an important role in inflammation; however, the underlying mechanism remains unclear. In the present study, we found increased plasma-derived exosomes in chronic heart failure patients compared with healthy controls. Further, our data demonstrated that plasma-derived exosomes carried mtDNA, and triggered an inflammatory response via the TLR9-NF-κB pathway, as well, the inflammatory effect was closely related to exosomal mtDNA copy number. However, the effect could be blocked by chloroquine (CQ), a TLR9 inhibitor. These findings reveal a new mechanism of exosome-induced inflammation, and provide a new perspective for intervention and treatment of inflammation-related diseases, such as chronic heart failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Jarzynski equality in the context of maximum path entropy

NASA Astrophysics Data System (ADS)

González, Diego; Davis, Sergio

2017-06-01

In the global framework of finding an axiomatic derivation of nonequilibrium Statistical Mechanics from fundamental principles, such as the maximum path entropy - also known as Maximum Caliber principle -, this work proposes an alternative derivation of the well-known Jarzynski equality, a nonequilibrium identity of great importance today due to its applications to irreversible processes: biological systems (protein folding), mechanical systems, among others. This equality relates the free energy differences between two equilibrium thermodynamic states with the work performed when going between those states, through an average over a path ensemble. In this work the analysis of Jarzynski's equality will be performed using the formalism of inference over path space. This derivation highlights the wide generality of Jarzynski's original result, which could even be used in non-thermodynamical settings such as social systems, financial and ecological systems.

Statistical mechanics of self-driven Carnot cycles.

PubMed

Smith, E

1999-10-01

The spontaneous generation and finite-amplitude saturation of sound, in a traveling-wave thermoacoustic engine, are derived as properties of a second-order phase transition. It has previously been argued that this dynamical phase transition, called "onset," has an equivalent equilibrium representation, but the saturation mechanism and scaling were not computed. In this work, the sound modes implementing the engine cycle are coarse-grained and statistically averaged, in a partition function derived from microscopic dynamics on criteria of scale invariance. Self-amplification performed by the engine cycle is introduced through higher-order modal interactions. Stationary points and fluctuations of the resulting phenomenological Lagrangian are analyzed and related to background dynamical currents. The scaling of the stable sound amplitude near the critical point is derived and shown to arise universally from the interaction of finite-temperature disorder, with the order induced by self-amplification.

REGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR MESSENGER RNA LEVELS IN AVIAN HYPOTHALAMIC SLICE CULTURES. (R825294)

EPA Science Inventory

Mechanisms regulating the expression of brain-derived neurotrophic factor, a member of the neurotrophin family, have been extensively studied in the rat cerebral cortex, hippocampus and cerebellum. In contrast, little is known regarding the regulation of this growth factor in ...

Statistical mechanics of neocortical interactions. Derivation of short-term-memory capacity

NASA Astrophysics Data System (ADS)

Ingber, Lester

1984-06-01

A theory developed by the author to describe macroscopic neocortical interactions demonstrates that empirical values of chemical and electrical parameters of synaptic interactions establish several minima of the path-integral Lagrangian as a function of excitatory and inhibitory columnar firings. The number of possible minima, their time scales of hysteresis and probable reverberations, and their nearest-neighbor columnar interactions are all consistent with well-established empirical rules of human short-term memory. Thus, aspects of conscious experience are derived from neuronal firing patterns, using modern methods of nonlinear nonequilibrium statistical mechanics to develop realistic explicit synaptic interactions.

Integrated approach to nitric oxide in animals and plants (mechanism and bioactivity): cell signaling and radicals.

PubMed

Kovacic, Peter; Somanathan, Ratnasamy

2011-04-01

Nitric oxide was first the object of extensive investigation in animals. It has been designated as the most widespread signaling molecule. An overview is presented with emphasis on cell signaling, mechanism, and physiological activity. Hence, a basis is provided for comparison of NO in plants with a similar approach. Mechanistically, cell signaling, electron transfer, radicals, and antioxidants are involved. A role is played by NO derivatives, such as peroxynitrite, nitroxyl, nitrite, nitrate, and S-nitroso derivatives. Comparison is made with ethylene. The multifaceted, interdisciplinary approach provides novel insight.

Fenton-like initiation of a toluene transformation mechanism

EPA Science Inventory

In Fenton-driven oxidation treatment systems, reaction intermediates derived from parent compounds can play a significant role in the overall treatment process. Fenton-like reactions in the presence of toluene or benzene, involved a transformation mechanism that was highly effici...

Fractional corresponding operator in quantum mechanics and applications: A uniform fractional Schrödinger equation in form and fractional quantization methods

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

Zhang, Xiao; Science and Technology on Electronic Information Control Laboratory, 610036, Chengdu, Sichuan; Wei, Chaozhen

2014-11-15

In this paper we use Dirac function to construct a fractional operator called fractional corresponding operator, which is the general form of momentum corresponding operator. Then we give a judging theorem for this operator and with this judging theorem we prove that R–L, G–L, Caputo, Riesz fractional derivative operator and fractional derivative operator based on generalized functions, which are the most popular ones, coincide with the fractional corresponding operator. As a typical application, we use the fractional corresponding operator to construct a new fractional quantization scheme and then derive a uniform fractional Schrödinger equation in form. Additionally, we find thatmore » the five forms of fractional Schrödinger equation belong to the particular cases. As another main result of this paper, we use fractional corresponding operator to generalize fractional quantization scheme by using Lévy path integral and use it to derive the corresponding general form of fractional Schrödinger equation, which consequently proves that these two quantization schemes are equivalent. Meanwhile, relations between the theory in fractional quantum mechanics and that in classic quantum mechanics are also discussed. As a physical example, we consider a particle in an infinite potential well. We give its wave functions and energy spectrums in two ways and find that both results are the same.« less

Identification of the key pathway of oxazolinoanthracyclines mechanism of action in cells derived from human solid tumors

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

Denel-Bobrowska, Marta, E-mail: mdenel@biol.uni.lo

Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are novel anthracycline derivatives with a modified daunosamine moiety. In the present study, we evaluated the cytotoxicities, genotoxicities and abilities of O-DOX and O-DAU to induce apoptosis in cancer cell lines (SKOV-3; A549; HepG2), and compared the results with their parent drugs. We assessed antiproliferative activity by MTT assay. We evaluated apoptosis-inducing ability by double-staining with fluorescent probes (Hoechst 33258/propidium iodide), and by determining expression levels of genes involved in programmed cell death by reverse transcription-polymerase chain reaction. Genotoxicities of the compounds were tested by comet assays. Oxazolinoanthracyclines demonstrated high anti-tumor activity. O-DOX had significantlymore » higher cytotoxicity, apoptosis-inducing ability, and genotoxicity compared with parental doxorubicin (DOX) in all tested conditions, while O-DAU activity differed among cell lines. The mechanism of oxazoline analog action appeared to involve the mitochondrial pathway of programmed cell death. These results provide further information about oxazoline derivatives of commonly used anthracycline chemotherapy agents. O-DOX and O-DAU have the ability to induce apoptosis in tumor cells. - Highlights: • Substituted amino group increased the anticancer activity of anthracyclines. • Mitochondrial apoptotic pathway seems to be involved in the mechanism of action. • Favorable biological properties of oxazoline derivatives were confirmed.« less

Molecular mechanism of action of oxazolinoanthracyclines in cells derived from human solid tumors. Part 2.

PubMed

Denel-Bobrowska, Marta; Łukawska, Małgorzata; Bukowska, Barbara; Gajek, Arkadiusz; Oszczapowicz, Irena; Marczak, Agnieszka

2018-02-01

Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are derivatives of anthracyclines (DOX and DAU) with a modified daunosamine moiety. We aimed to clarify their mechanisms of action by investigating intracellular accumulation and effects on the cell cycle, phosphatidylserine externalization, and proteasome 20S activity. Experimental model consisted of SKOV-3, A549 and HepG2 cells. Compounds were used at the concentration of 80nM. Intracellular accumulation, drug uptake, and proteasome 20S activity were evaluated by fluorimetric methods. The effects on the cell cycle and phosphatidylserine externalization were measured by flow cytometry. O-DOX was equivalent to DOX in terms of inducing G2/M arrest, but O-DAU was less potent in SKOV-3, HepG2, and A549 cells. O-DOX had the greatest effect on initiating apoptosis in all tested cells. Externalization of phosphatidylserine was significantly higher following O-DOX treatment compared with control cells and cells incubated with DOX. The intracellular accumulation and uptake of the derivatives were similar to those of the reference drugs. Tested compounds are able to activate proteasome 20S activity. Our results extended the understanding of the toxicity, mechanism of action, and biochemical properties of oxazoline derivatives of doxorubicin and daunorubicin, including their effects on cell cycle, apoptosis and DNA degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathologic Mechanical Stress and Endotoxin Exposure Increases Lung Endothelial Microparticle Shedding

PubMed Central

Letsiou, Eleftheria; Sammani, Saad; Zhang, Wei; Zhou, Tong; Quijada, Hector; Moreno-Vinasco, Liliana; Dudek, Steven M.

2015-01-01

Acute lung injury (ALI) results from infectious challenges and from pathologic lung distention produced by excessive tidal volume delivered during mechanical ventilation (ventilator-induced lung injury [VILI]) and is characterized by extensive alveolar and vascular dysfunction. Identification of novel ALI therapies is hampered by the lack of effective ALI/VILI biomarkers. We explored endothelial cell (EC)-derived microparticles (EMPs) (0.1–1 μm) as potentially important markers and potential mediators of lung vascular injury in preclinical models of ALI and VILI. We characterized EMPs (annexin V and CD31 immunoreactivity) produced from human lung ECs exposed to physiologic or pathologic mechanical stress (5 or 18% cyclic stretch [CS]) or to endotoxin (LPS). EC exposure to 18% CS or to LPS resulted in increased EMP shedding compared with static cells (∼ 4-fold and ∼ 2.5-fold increases, respectively). Proteomic analysis revealed unique 18% CS–derived (n = 10) and LPS-derived EMP proteins (n = 43). VILI-challenged mice (40 ml/kg, 4 h) exhibited increased plasma and bronchoalveolar lavage CD62E (E-selectin)-positive MPs compared with control mice. Finally, mice receiving intratracheal instillation of 18% CS–derived EMPs displayed significant lung inflammation and injury. These findings indicate that ALI/VILI-producing stimuli induce significant shedding of distinct EMP populations that may serve as potential ALI biomarkers and contribute to the severity of lung injury. PMID:25029266

Adipose-derived stromal cells for the reconstruction of a human vesical equivalent.

PubMed

Rousseau, Alexandre; Fradette, Julie; Bernard, Geneviève; Gauvin, Robert; Laterreur, Véronique; Bolduc, Stéphane

2015-11-01

Despite a wide panel of tissue-engineering models available for vesical reconstruction, the lack of a differentiated urothelium remains their main common limitation. For the first time to our knowledge, an entirely human vesical equivalent, free of exogenous matrix, has been reconstructed using the self-assembly method. Moreover, we tested the contribution of adipose-derived stromal cells, an easily available source of mesenchymal cells featuring many potential advantages, by reconstructing three types of equivalent, named fibroblast vesical equivalent, adipose-derived stromal cell vesical equivalent and hybrid vesical equivalent--the latter containing both adipose-derived stromal cells and fibroblasts. The new substitutes have been compared and characterized for matrix composition and organization, functionality and mechanical behaviour. Although all three vesical equivalents displayed adequate collagen type I and III expression, only two of them, fibroblast vesical equivalent and hybrid vesical equivalent, sustained the development of a differentiated and functional urothelium. The presence of uroplakins Ib, II and III and the tight junction marker ZO-1 was detected and correlated with impermeability. The mechanical resistance of these tissues was sufficient for use by surgeons. We present here in vitro tissue-engineered vesical equivalents, built without the use of any exogenous matrix, able to sustain mechanical stress and to support the formation of a functional urothelium, i.e. able to display a barrier function similar to that of native tissue. Copyright © 2013 John Wiley & Sons, Ltd.

On the role of second number-conserving functional derivatives

NASA Astrophysics Data System (ADS)

Gál, Tamás

2006-06-01

It is found that number-conserving second derivatives, of functional differentiation constrained to the domain of functional variables ρ(x) of a given norm ∫ρ(x)dx, are not obtained via two successive number-conserving differentiations, contrary to the case of unrestricted second derivatives. Investigating the role of second number-conserving derivatives, with the density-functional formulation of time-dependent quantum mechanics in focus, it is shown how number-conserving differentiation handles the dual nature of the Kohn Sham potential arising in the practical use of the theory. On the other hand, it is pointed out that number-conserving derivatives cannot resolve the causality paradox connected with the second derivative of the exchange-correlation part of the action density functional.

Benzene Exposures and Risk Potential for Vehicle Mechanics from Gasoline and Petroleum-Derived Products.

PubMed

Williams, Pamela R D; Mani, Ashutosh

2015-01-01

Benzene exposures among vehicle mechanics in the United States and abroad were characterized using available data from published and unpublished studies. In the United States, the time-weighted-average (TWA) airborne concentration of benzene for vehicle mechanics averaged 0.01-0.05 ppm since at least the late 1970s, with maximal TWA concentrations ranging from 0.03 to 0.38 ppm. Benzene exposures were notably lower in the summer than winter and in the Southwest compared to other geographic regions, but significantly higher during known gasoline-related tasks such as draining a gas tank or changing a fuel pump or fuel filter. Measured airborne concentrations of benzene were also generally greater for vehicle mechanics in other countries, likely due to the higher benzene content of gasoline and other factors. Short-term airborne concentrations of benzene frequently exceeded 1 ppm during gasoline-related tasks, but remained below 0.2 ppm for tasks involving other petroleum-derived products such as carburetor and brake cleaner or parts washer solvent. Application of a two-zone mathematical model using reasonable input values from the literature yielded predicted task-based benzene concentrations during gasoline and aerosol spray cleaner scenarios similar to those measured for vehicle mechanics during these types of tasks. When evaluated using appropriate biomarkers, dermal exposures were found to contribute little to total benzene exposures for this occupational group. Available data suggest that vehicle mechanics have not experienced significant exposures to benzene in the workplace, except perhaps during short-duration gasoline-related tasks, and full-shift benzene exposures have remained well below current and contemporaneous occupational exposure limits. These findings are consistent with epidemiology studies of vehicle mechanics, which have not demonstrated an increased risk of benzene-induced health effects in this cohort of workers. Data and information presented here may be used to assess past, current, or future exposures and risks to benzene for vehicle mechanics who may be exposed to gasoline or other petroleum-derived products.

Optimization evaluation of cutting technology based on mechanical parts

NASA Astrophysics Data System (ADS)

Wang, Yu

2018-04-01

The relationship between the mechanical manufacturing process and the carbon emission is studied on the basis of the process of the mechanical manufacturing process. The formula of carbon emission calculation suitable for mechanical manufacturing process is derived. Based on this, a green evaluation method for cold machining process of mechanical parts is proposed. The application verification and data analysis of the proposed evaluation method are carried out by an example. The results show that there is a great relationship between the mechanical manufacturing process data and carbon emissions.

Solid State Kinetic Parameters and Chemical Mechanism of the Dehydration of CoCl2.6H2O.

ERIC Educational Resources Information Center

Ribas, Joan; And Others

1988-01-01

Presents an experimental example illustrating the most common methods for the determination of kinetic parameters. Discusses the different theories and equations to be applied and the mechanism derived from the kinetic results. (CW)

Solvable Quantum Macroscopic Motions and Decoherence Mechanisms in Quantum Mechanics on Nonstandard Space

NASA Technical Reports Server (NTRS)

Kobayashi, Tsunehiro

1996-01-01

Quantum macroscopic motions are investigated in the scheme consisting of N-number of harmonic oscillators in terms of ultra-power representations of nonstandard analysis. Decoherence is derived from the large internal degrees of freedom of macroscopic matters.

Celestial mechanics with geometric algebra

NASA Technical Reports Server (NTRS)

Hestenes, D.

1983-01-01

Geometric algebra is introduced as a general tool for Celestial Mechanics. A general method for handling finite rotations and rotational kinematics is presented. The constants of Kepler motion are derived and manipulated in a new way. A new spinor formulation of perturbation theory is developed.

Albert Einstein and the Quantum Riddle

ERIC Educational Resources Information Center

Lande, Alfred

1974-01-01

Derives a systematic structure contributing to the solution of the quantum riddle in Einstein's sense by deducing quantum mechanics from the postulates of symmetry, correspondence, and covariance. Indicates that the systematic presentation is in agreement with quantum mechanics established by Schroedinger, Born, and Heisenberg. (CC)

Distinct Analgesic Actions of DHA and DHA-Derived Specialized Pro-Resolving Mediators on Post-operative Pain After Bone Fracture in Mice.

PubMed

Zhang, Linlin; Terrando, Niccolò; Xu, Zhen-Zhong; Bang, Sangsu; Jordt, Sven-Eric; Maixner, William; Serhan, Charles N; Ji, Ru-Rong

2018-01-01

Mechanisms of pain resolution are largely unclear. Increasing evidence suggests that specialized pro-resolving mediators (SPMs), derived from fish oil docosahexaenoic acid (DHA), promote the resolution of acute inflammation and potently inhibit inflammatory and neuropathic pain. In this study, we examined the analgesic impact of DHA and DHA-derived SPMs in a mouse model of post-operative pain induced by tibial bone fracture (fPOP). Intravenous perioperative treatment with DHA (500 μg), resolvin D1 (RvD1, 500 ng) and maresin 1 (MaR1, 500 ng), 10 min and 24 h after the surgery, delayed the development of fPOP (mechanical allodynia and cold allodynia). In contrast, post-operative intrathecal (IT) administration of DHA (500 μg) 2 weeks after the surgery had no effects on established mechanical and cold allodynia. However, by direct comparison, IT post-operative treatment (500 ng) with neuroprotectin D1 (NPD1), MaR1, and D-resolvins, RvD1 and RvD5, but not RvD3 and RvD4, effectively reduced mechanical and cold allodynia. ELISA analysis showed that perioperative DHA treatment increased RvD1 levels in serum and spinal cord samples after bone fracture. Interestingly, sham surgery resulted in transient allodynia and increased RvD1 levels, suggesting a correlation of enhanced SPM levels with acute pain resolution after sham surgery. Our findings suggest that (1) perioperative treatment with DHA is effective in preventing and delaying the development of fPOP and (2) post-treatment with some SPMs can attenuate established fPOP. Our data also indicate that orthopedic surgery impairs SPM production. Thus, DHA and DHA-derived SPMs should be differentially supplemented for treating fPOP and improving recovery.

Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment

PubMed Central

Hosseini-Beheshti, Elham; Choi, Wendy; Weiswald, Louis-Bastien; Kharmate, Geetanjali; Ghaffari, Mazyar; Roshan-Moniri, Mani; Hassona, Mohamed D.; Chan, Leslie; Chin, Mei Yieng; Tai, Isabella T.; Rennie, Paul S.; Fazli, Ladan; Guns, Emma S. Tomlinson

2016-01-01

Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression. PMID:26840259

Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication.

PubMed

Qin, Yiwen; Peng, Yuanzhen; Zhao, Wei; Pan, Jianping; Ksiezak-Reding, Hanna; Cardozo, Christopher; Wu, Yingjie; Divieti Pajevic, Paola; Bonewald, Lynda F; Bauman, William A; Qin, Weiping

2017-06-30

Muscle and bone are closely associated in both anatomy and function, but the mechanisms that coordinate their synergistic action remain poorly defined. Myostatin, a myokine secreted by muscles, has been shown to inhibit muscle growth, and the disruption of the myostatin gene has been reported to cause muscle hypertrophy and increase bone mass. Extracellular vesicle-exosomes that carry microRNA (miRNA), mRNA, and proteins are known to perform an important role in cell-cell communication. We hypothesized that myostatin may play a crucial role in muscle-bone interactions and may promote direct effects on osteocytes and on osteocyte-derived exosomal miRNAs, thereby indirectly influencing the function of other bone cells. We report herein that myostatin promotes expression of several bone regulators such as sclerostin (SOST), DKK1, and RANKL in cultured osteocytic (Ocy454) cells, concomitant with the suppression of miR-218 in both parent Ocy454 cells and derived exosomes. Exosomes produced by Ocy454 cells that had been pretreated with myostatin could be taken up by osteoblastic MC3T3 cells, resulting in a marked reduction of Runx2, a key regulator of osteoblastic differentiation, and in decreased osteoblastic differentiation via the down-regulation of the Wnt signaling pathway. Importantly, the inhibitory effect of myostatin-modified osteocytic exosomes on osteoblast differentiation is completely reversed by expression of exogenous miR-218, through a mechanism involving miR-218-mediated inhibition of SOST. Together, our findings indicate that myostatin directly influences osteocyte function and thereby inhibits osteoblastic differentiation, at least in part, through the suppression of osteocyte-derived exosomal miR-218, suggesting a novel mechanism in muscle-bone communication. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice.

PubMed

Bentzon, Jacob F; Sondergaard, Claus S; Kassem, Moustapha; Falk, Erling

2007-10-30

Signs of preceding episodes of plaque rupture and smooth muscle cell (SMC)-mediated healing are common in atherosclerotic plaques, but the source of the healing SMCs is unknown. Recent studies suggest that activated platelets adhering to sites of injury recruit neointimal SMCs from circulating bone marrow-derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE-/-) mice. To determine the origin of SMCs after spontaneous plaque disruption, irradiated 18-month-old apoE-/- mice were reconstituted with bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic apoE-/- mice and examined when they died up to 9 months later. Plaque hemorrhage, indicating previous plaque disruption, was widely present, but no bone marrow-derived eGFP+ SMCs were detected. To examine the origin of healing SMCs in a model that recapitulates more features of human plaque rupture and healing, we developed a mechanical technique that produced consistent plaque disruption, superimposed thrombosis, and SMC-mediated plaque healing in apoE-/- mice. Mechanical plaque disruption was produced in irradiated apoE-/- mice reconstituted with eGFP+ apoE-/- bone marrow cells and in carotid bifurcations cross-grafted between apoE-/- and eGFP+ apoE-/- mice. Apart from few non-graft-derived SMCs near the anastomosis site in 1 transplanted carotid bifurcation, no SMCs originating from outside the local arterial segment were detected in healed plaques. Healing SMCs after atherosclerotic plaque disruption are derived entirely from the local arterial wall and not circulating progenitor cells in apoE-/- mice.

Neural dynamics of motion processing and speed discrimination.

PubMed

Chey, J; Grossberg, S; Mingolla, E

1998-09-01

A neural network model of visual motion perception and speed discrimination is presented. The model shows how a distributed population code of speed tuning, that realizes a size-speed correlation, can be derived from the simplest mechanisms whereby activations of multiple spatially short-range filters of different size are transformed into speed-turned cell responses. These mechanisms use transient cell responses to moving stimuli, output thresholds that covary with filter size, and competition. These mechanisms are proposed to occur in the V1-->MT cortical processing stream. The model reproduces empirically derived speed discrimination curves and simulates data showing how visual speed perception and discrimination can be affected by stimulus contrast, duration, dot density and spatial frequency. Model motion mechanisms are analogous to mechanisms that have been used to model 3-D form and figure-ground perception. The model forms the front end of a larger motion processing system that has been used to simulate how global motion capture occurs, and how spatial attention is drawn to moving forms. It provides a computational foundation for an emerging neural theory of 3-D form and motion perception.

Human obesity associated with an intronic SNP in the brain-derived neurotrophic factor locus

USDA-ARS?s Scientific Manuscript database

Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 ...

Synthesis and evaluation of thermo-rheological behaviour and ionotropic crosslinking of new gellan gum-alkyl derivatives.

PubMed

Agnello, Stefano; Palumbo, Fabio Salvatore; Pitarresi, Giovanna; Fiorica, Calogero; Giammona, Gaetano

2018-04-01

This paper reports the synthesis and the physicochemical characterization of two series of gellan gum (GG) derivatives functionalized with alkyl chains with different number of carbon, from 8 to 18. In particular, low molecular weight gellan gum samples with 52.6 or 96.7 kDa, respectively, were functionalized with octylamine (C 8 ), dodecylamine (C 12 ) and octadecylamine (C 18 ) by using bis(4-nitrophenyl) carbonate (4-NPBC) as a coupling agent. Thermo-rheological and ionotropic crosslinking properties of these gellan gum-alkyl derivatives were evaluated and related to the degree of derivatization in alkyl chains. Results suggested as length and degree of derivatization differently influenced coil-to-helix gelation mechanism of GG derivatives, ionotropic crosslinking, and strength of crosslinked hydrogels obtained in CaCl 2 0.102 M and NaCl 0.15 M. Statement of hypothesis: The insertion of alkyl chains on the gellan gum backbone interferes with coil-to-helix transition mechanism and allows the production of hydrophobically assembled hydrogels. Copyright © 2018 Elsevier Ltd. All rights reserved.

Calculating the Malliavin derivative of some stochastic mechanics problems

PubMed Central

Hauseux, Paul; Hale, Jack S.

2017-01-01

The Malliavin calculus is an extension of the classical calculus of variations from deterministic functions to stochastic processes. In this paper we aim to show in a practical and didactic way how to calculate the Malliavin derivative, the derivative of the expectation of a quantity of interest of a model with respect to its underlying stochastic parameters, for four problems found in mechanics. The non-intrusive approach uses the Malliavin Weight Sampling (MWS) method in conjunction with a standard Monte Carlo method. The models are expressed as ODEs or PDEs and discretised using the finite difference or finite element methods. Specifically, we consider stochastic extensions of; a 1D Kelvin-Voigt viscoelastic model discretised with finite differences, a 1D linear elastic bar, a hyperelastic bar undergoing buckling, and incompressible Navier-Stokes flow around a cylinder, all discretised with finite elements. A further contribution of this paper is an extension of the MWS method to the more difficult case of non-Gaussian random variables and the calculation of second-order derivatives. We provide open-source code for the numerical examples in this paper. PMID:29261776

Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor

PubMed Central

Perretti, Mauro; Chiang, Nan; La, Mylinh; Fierro, Iolanda M.; Marullo, Stefano; Getting, Stephen J; Solito, Egle; Serhan, Charles N.

2009-01-01

Aspirin (ASA) and dexamethasone (DEX) are widely used anti-inflammatory agents yet their mechanism(s) for blocking polymorphonuclear neutrophil (PMN) accumulation at sites of inflammation remains unclear. Here, we report that inhibition of PMN infiltration by ASA and DEX is a property shared by aspirin-triggered lipoxins (ATL) and the glucocorticoid-induced annexin 1 (ANXA1)-derived peptides that are both generated in vivo and act at the lipoxin A4 receptor (ALXR/FPRL1) to halt PMN diapedesis. These structurally diverse ligands specifically interact directly with recombinant human ALXR demonstrated by specific radioligand binding and function as well as immunoprecipitation of PMN receptors. In addition, the combination of both ATL and ANXA1-derived peptides limited PMN infiltration and reduced production of inflammatory mediators (that is, prostaglandins and chemokines) in vivo. Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci. PMID:12368905

Effects of strychnine on the sodium conductance of the frog node of Ranvier

PubMed Central

1977-01-01

Strychnine blocks sodium conductance in the frog node of Ranvier. This block was studied by reducing and slowing sodium inactivation with scorpion venom. The block is voltage and time dependent. The more positive the axoplasm the greater the block and the faster the approach to equilibrium. Some evidence is presented suggesting that only open channels can be blocked. The block is reduced by raising external sodium or lithium but not impermeant cations. A quaternary derivative of strychnine was synthesized and found to have the same action only when applied intracellularly. We conclude that strychnine blocks sodium channels by a mechanism analogous to that by which it blocks potassium channels. The potassium channel block had previously been found to be identical to that by tetraethylammonium ion derivatives. In addition, strychnine resembles procaine and its derivatives in both its structure and the mechanism of sodium channel block. PMID:302321

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

PubMed Central

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. PMID:28928987

THz spectra of 1,4-naphthoquinones and its four derivatives

NASA Astrophysics Data System (ADS)

Wang, Weining; Li, Hongqi; Luo, Xiang; Zeng, Xiaoni

2008-03-01

Recently some naphthoquinone derivatives have been found with anticancer or other therapeutic properties, but also have some negative side effects. Numerous research projects have been conducted to investigate their properties and therapeutic mechanisms. With Terahertz Time-Domain Spectroscopy (THz-TDS), we have successfully obtained THz spectra of 1,4-naphthoquinone and its four derivatives in a series of naphthazarin - juglone - 1,4-naphthoquinone - menadione - plumbagin, in the range between 0.2 and 2.4~2.8 THz. Although these molecules are almost identical to each other, they have very distinctive THz spectra so that they can be identified much more easily than using conventional spectroscopy. We have comparatively analyzed their THz spectra, and found some possible correlations between THz spectra and molecular structures. These THz spectra cannot only be used as spectral fingerprint, but also provide us their conformational properties that can be used in study of their interaction with biomolecules to reveal their pharmaceutical mechanisms.

Application of bioethanol derived lignin for improving physico-mechanical properties of thermoset biocomposites.

PubMed

Bajwa, Dilpreet S; Wang, Xinnan; Sitz, Evan; Loll, Tyler; Bhattacharjee, Sujal

2016-08-01

Lignin is the most abundant of renewable polymers next to cellulose with a global annual production of 70million tons, largely produced from pulping and second generation biofuel industries. Low value of industrial lignin makes it an attractive biomaterial for wide range of applications. The study investigated the application of wheat straw and corn stover based lignin derived from ethanol production for use in thermoset biocomposites. The biocomposite matrix constituted a two component low viscosity Araldite(®)LY 8601/Aradur(®) 8602 epoxy resin system and the lignin content varied from 0 to 25% by weight fraction. The analysis of the physical and mechanical properties of the biocomposites show bioethanol derived lignin can improve selective properties such as impact strength, and thermal stability without compromising the modulus and strength attributes. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.

PubMed

Phillips, Cristy

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

Green tea extracts reduce leukocyte cell-Derived chemotaxin 2 and selenoprotein P levels in the livers of C57BL/6J mice fed a high-fat diet.

PubMed

Onishi, Shintaro; Kitazawa, Hidefumi; Meguro, Shinichi; Tokimitsu, Ichiro

2018-05-31

Epidemiological studies suggest that green tea extracts (GTEs), including catechins such as epigallocatechin gallate and epicatechin gallate, have a beneficial effect on obesity, hyperglycemia, insulin resistance, endothelial dysfunction, and inflammation. Although several studies have shown that catechins directly modulate the cellular and molecular alterations in the liver tissue, the contributions of indirect mechanisms underlying these systemic effects of catechins remain unclear. In this study, we report that, in the C57BL/6J mouse liver, GTEs reduce high-fat diet-induced increases in the levels of hepatokines, liver-derived secretary proteins such as leukocyte cell-derived chemotaxin 2 and selenoprotein P production, which have been shown to induce systemic adverse effects, including several metabolic diseases. These findings suggest that the systemic effects of GTEs involve the regulation of hepatokine production as an indirect mechanism.

When push comes to shove: Exclusion processes with nonlocal consequences

NASA Astrophysics Data System (ADS)

Almet, Axel A.; Pan, Michael; Hughes, Barry D.; Landman, Kerry A.

2015-11-01

Stochastic agent-based models are useful for modelling collective movement of biological cells. Lattice-based random walk models of interacting agents where each site can be occupied by at most one agent are called simple exclusion processes. An alternative motility mechanism to simple exclusion is formulated, in which agents are granted more freedom to move under the compromise that interactions are no longer necessarily local. This mechanism is termed shoving. A nonlinear diffusion equation is derived for a single population of shoving agents using mean-field continuum approximations. A continuum model is also derived for a multispecies problem with interacting subpopulations, which either obey the shoving rules or the simple exclusion rules. Numerical solutions of the derived partial differential equations compare well with averaged simulation results for both the single species and multispecies processes in two dimensions, while some issues arise in one dimension for the multispecies case.

Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review.

PubMed

Ahmadi, Azin; Zorofchian Moghadamtousi, Soheil; Abubakar, Sazaly; Zandi, Keivan

2015-01-01

From food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. Among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. Over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate candidates for pharmaceutical research. Numerous studies have isolated various algal polysaccharides possessing antiviral activities, including carrageenan, alginate, fucan, laminaran, and naviculan. In addition, different mechanisms of action have been reported for these polysaccharides, such as inhibiting the binding or internalization of virus into the host cells or suppressing DNA replication and protein synthesis. This review strives for compiling previous antiviral studies of algae-derived polysaccharides and their mechanism of action towards their development as natural antiviral agents for future investigations.

Neuronal apoptotic signaling pathways probed and intervened by synthetically and modularly modified (SMM) chemokines.

PubMed

Choi, Won-Tak; Kaul, Marcus; Kumar, Santosh; Wang, Jun; Kumar, I M Krishna; Dong, Chang-Zhi; An, Jing; Lipton, Stuart A; Huang, Ziwei

2007-03-09

As the main coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, CXCR4 and CCR5 play important roles in HIV-associated dementia (HAD). HIV-1 glycoprotein gp120 contributes to HAD by causing neuronal damage and death, either directly by triggering apoptotic pathways or indirectly by stimulating glial cells to release neurotoxins. Here, to understand the mechanism of CXCR4 or CCR5 signaling in neuronal apoptosis associated with HAD, we have applied synthetically and modularly modified (SMM)-chemokine analogs derived from natural stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II as chemical probes of the mechanism(s) whereby these SMM-chemokines prevent or promote neuronal apoptosis. We show that inherently neurotoxic natural ligands of CXCR4, such as stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II, can be modified to protect neurons from apoptosis induced by CXCR4-preferring gp120(IIIB), and that the inhibition of CCR5 by antagonist SMM-chemokines, unlike neuroprotective CCR5 natural ligands, leads to neurotoxicity by activating a p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Furthermore, we discover distinct signaling pathways activated by different chemokine ligands that are either natural agonists or synthetic antagonists, thus demonstrating a chemical biology strategy of using chemically engineered inhibitors of chemokine receptors to study the signaling mechanism of neuronal apoptosis and survival.

Comparison of Classical and Quantum Mechanical Uncertainties.

ERIC Educational Resources Information Center

Peslak, John, Jr.

1979-01-01

Comparisons are made for the particle-in-a-box, the harmonic oscillator, and the one-electron atom. A classical uncertainty principle is derived and compared with its quantum-mechanical counterpart. The results are discussed in terms of the statistical interpretation of the uncertainty principle. (Author/BB)

Diesel Mechanics. Ohio's Competency Analysis Profile.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

This Ohio Competency Analysis Profile (OCAP), derived from a modified Developing a Curriculum (DACUM) process, is a current comprehensive and verified employer competency program list for diesel mechanics. Each unit (with or without subunits) contains competencies and competency builders that identify the occupational, academic, and employability…

Ontology-based Vaccine and Drug Adverse Event Representation and Theory-guided Systematic Causal Network Analysis toward Integrative Pharmacovigilance Research.

PubMed

He, Yongqun

2016-06-01

Compared with controlled terminologies ( e.g. , MedDRA, CTCAE, and WHO-ART), the community-based Ontology of AEs (OAE) has many advantages in adverse event (AE) classifications. The OAE-derived Ontology of Vaccine AEs (OVAE) and Ontology of Drug Neuropathy AEs (ODNAE) serve as AE knowledge bases and support data integration and analysis. The Immune Response Gene Network Theory explains molecular mechanisms of vaccine-related AEs. The OneNet Theory of Life treats the whole process of a life of an organism as a single complex and dynamic network ( i.e. , OneNet). A new "OneNet effectiveness" tenet is proposed here to expand the OneNet theory. Derived from the OneNet theory, the author hypothesizes that one human uses one single genotype-rooted mechanism to respond to different vaccinations and drug treatments, and experimentally identified mechanisms are manifestations of the OneNet blueprint mechanism under specific conditions. The theories and ontologies interact together as semantic frameworks to support integrative pharmacovigilance research.

Hybrid anticancer 1,2-diazine derivatives with multiple mechanism of action. Part 3.

PubMed

Antoci, Vasilichia; Mantu, Dorina; Cozma, Danut Gabriel; Usru, Cornelia; Mangalagiu, Ionel I

2014-01-01

Antitumour chemotherapy is nowadays a very active field of research, DNA targeting drugs being the most widely used group in therapy. The design, synthesis and anticancer activity of a new class of anticancer derivatives with pyrrolo-1,2-diazine and benzoquinone skeleton is presented. The synthesis is direct and efficient, involving an alkylation followed by a [3+2] dipolar cycloaddition. The penta- and tetra-cyclic pyrrolo-1,2-diazine were evaluated for their in vitro anticancer activity against an NCI 60 human tumour cell line panel. The pentacyclic-1,2-diazine exhibit a significant anticancer activity against Non-Small Cell Lung Cancer NCI-H460, Leukemia MOLT-4, Leukemia CCRF-CEM and Breast Cancer MCF7. We hypothesize that these molecules will exert their anticancer activity through multiple mechanisms of action: intercalating the DNA, inhibiting the topoisomerase enzymes and, destroying the DNA strands via electron transfer mechanism. However, the intercalation with the DNA seems to prevail in competition with the others mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Time-dependent slowly-reversible inhibition of monoamine oxidase A by N-substituted 1,2,3,6-tetrahydropyridines.

PubMed

Wichitnithad, Wisut; O'Callaghan, James P; Miller, Diane B; Train, Brian C; Callery, Patrick S

2011-12-15

A novel class of N-substituted tetrahydropyridine derivatives was found to have multiple kinetic mechanisms of monoamine oxidase A inhibition. Eleven structurally similar tetrahydropyridine derivatives were synthesized and evaluated as inhibitors of MAO-A and MAO-B. The most potent MAO-A inhibitor in the series, 2,4-dichlorophenoxypropyl analog 12, displayed time-dependent mixed noncompetitive inhibition. The inhibition was reversed by dialysis, indicating reversible enzyme inhibition. Evidence that the slow-binding inhibition of MAO-A with 12 involves a covalent bond was gained from stabilizing a covalent reversible intermediate product by reduction with sodium borohydride. The reduced enzyme complex was not reversible by dialysis. The results are consistent with slowly reversible, mechanism-based inhibition. Two tetrahydropyridine analogs that selectively inhibited MAO-A were characterized by kinetic mechanisms differing from the kinetic mechanism of 12. As reversible inhibitors of MAO-A, tetrahydropyridine analogs are at low risk of having an adverse effect of tyramine-induced hypertension. Copyright © 2011 Elsevier Ltd. All rights reserved.

Of worms, mice and man: an overview of experimental and clinical helminth-based therapy for inflammatory bowel disease.

PubMed

Heylen, Marthe; Ruyssers, Nathalie E; Gielis, Els M; Vanhomwegen, Els; Pelckmans, Paul A; Moreels, Tom G; De Man, Joris G; De Winter, Benedicte Y

2014-08-01

The incidence of inflammatory and autoimmune disorders is highest in well-developed countries which is directly related to their higher hygienic standards: it is suggested that the lack of exposure to helminths contributes to the susceptibility for immune-related diseases. Epidemiological, experimental and clinical data support the idea that helminths provide protection against immune-mediated diseases such as inflammatory bowel disease (IBD). The most likely mechanism for the suppression of immune responses by helminths is the release of helminth-derived immunomodulatory molecules. This article reviews the experimental and clinical studies investigating the therapeutic potential of helminth-based therapy in IBD and also focuses on the current knowledge of its immunomodulatory mechanisms of action highlighting innate as well as adaptive immune mechanisms. Identifying the mechanisms by which these helminths and helminth-derived molecules modulate the immune system will help in creating novel drugs for the treatment of IBD and other disorders that result from an overactive immune response. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone volume fraction and structural parameters for estimation of mechanical stiffness and failure load of human cancellous bone samples; in-vitro comparison of ultrasound transit time spectroscopy and X-ray μCT.

PubMed

Alomari, Ali Hamed; Wille, Marie-Luise; Langton, Christian M

2018-02-01

Conventional mechanical testing is the 'gold standard' for assessing the stiffness (N mm -1 ) and strength (MPa) of bone, although it is not applicable in-vivo since it is inherently invasive and destructive. The mechanical integrity of a bone is determined by its quantity and quality; being related primarily to bone density and structure respectively. Several non-destructive, non-invasive, in-vivo techniques have been developed and clinically implemented to estimate bone density, both areal (dual-energy X-ray absorptiometry (DXA)) and volumetric (quantitative computed tomography (QCT)). Quantitative ultrasound (QUS) parameters of velocity and attenuation are dependent upon both bone quantity and bone quality, although it has not been possible to date to transpose one particular QUS parameter into separate estimates of quantity and quality. It has recently been shown that ultrasound transit time spectroscopy (UTTS) may provide an accurate estimate of bone density and hence quantity. We hypothesised that UTTS also has the potential to provide an estimate of bone structure and hence quality. In this in-vitro study, 16 human femoral bone samples were tested utilising three techniques; UTTS, micro computed tomography (μCT), and mechanical testing. UTTS was utilised to estimate bone volume fraction (BV/TV) and two novel structural parameters, inter-quartile range of the derived transit time (UTTS-IQR) and the transit time of maximum proportion of sonic-rays (TTMP). μCT was utilised to derive BV/TV along with several bone structure parameters. A destructive mechanical test was utilised to measure the stiffness and strength (failure load) of the bone samples. BV/TV was calculated from the derived transit time spectrum (TTS); the correlation coefficient (R 2 ) with μCT-BV/TV was 0.885. For predicting mechanical stiffness and strength, BV/TV derived by both μCT and UTTS provided the strongest correlation with mechanical stiffness (R 2 =0.567 and 0.618 respectively) and mechanical strength (R 2 =0.747 and 0.736 respectively). When respective structural parameters were incorporated to BV/TV, multiple regression analysis indicated that none of the μCT histomorphometric parameters could improve the prediction of mechanical stiffness and strength, while for UTTS, adding TTMP to BV/TV increased the prediction of mechanical stiffness to R 2 =0.711 and strength to R 2 =0.827. It is therefore envisaged that UTTS may have the ability to estimate BV/TV along with providing an improved prediction of osteoporotic fracture risk, within routine clinical practice in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation

PubMed Central

Lohans, Christopher T.; van Groesen, Emma; Kumar, Kiran; Tooke, Catherine L.; Spencer, James; Paton, Robert S.; Brem, Jürgen

2018-01-01

Abstract β‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required. PMID:29236332

Are arc lower crustal metasediments derived from above or below? A detrital zircon study in the lower crust of the Sierra Nevada, California

NASA Astrophysics Data System (ADS)

Klein, B. Z.; Jagoutz, O. E.; VanTongeren, J. A.

2016-12-01

Multiple hypotheses exist to explain the presence of metasedimentary rocks within arc lower crust. Relamination and subduction underplating require that sediments are derived from the subducted slab, while processes such as wall-rock return flow and retro-arc underthrusting imply that the sediments originated in the crust of the upper plate. Evaluating these proposed mechanisms has wide-reaching implications, including better constraining the mass-balance of active arcs, characterizing a theorized trigger mechanism for magmatic flare-up events, and more broadly for describing the tectonic construction of continental arcs. The southernmost Sierra Nevada, California, exposes a continuous continental arc cross-section that spans pressures from 3 to <10 kbar. Metasedimentary rocks are exposed at all crustal levels within this section and are intruded by 100 Ma igneous rocks. These metasediments offer a unique opportunity to evaluate the source, and emplacement of lower crustal metasediments into an active arc. The proposed mechanisms for the transport of sediments to the lower crust predict distinct sedimentary protoliths with unique detrital zircon (DZ) age spectra. Specifically, slab-derived sediments are likely to resemble the underplated Polona-Oroccopia-Rand schists to the south, with dominantly Mesozoic DZ peaks and few to no older grains. Upper plate derived sediments are predicted to have significant Paleozoic and Proterozoic DZ populations, in addition to arc-derived, Mesozoic meta-volcanic material. We have conducted a detailed DZ study of metasedimentary rocks in the Sierran lower and middle crust to assess these hypotheses. Initial results show that at least some of this material has an unambiguous slab-derived signature implying that relamination and/or subduction underplating were active processes during the construction of the Sierran arc system. We explore the implications of these processes for the magmatic and tectonic history of the Sierra Nevada, as well as for the generation of new continental crust.

Hypoxia enhances the protective effects of placenta-derived mesenchymal stem cells against scar formation through hypoxia-inducible factor-1α.

PubMed

Du, Lili; Lv, Runxiao; Yang, Xiaoyi; Cheng, Shaohang; Xu, Jing; Ma, Tingxian

2016-06-01

To explore the effect of placenta-derived mesenchymal stem cells on scar formation as well as the underlying mechanism. The isolated placenta-derived mesenchymal stem cells from mice were distributed in the wounded areas of scalded mouse models, attenuated inflammatory responses and decreased the deposition of collagens, thus performing a beneficial effect against scar formation. Hypoxia enhanced the protective effect of placenta-derived mesenchymal stem cells and hypoxia-inducible factor-1α was involved in the protective effect of placenta-derived mesenchymal stem cells in hypoxic condition. Hypoxia enhanced the protective effect of placenta-derived mesenchymal stem cells through hypoxia-inducible factor-1α and PMSCs may have a potential application in the treatment of wound.

A Tutorial Review on Fractal Spacetime and Fractional Calculus

NASA Astrophysics Data System (ADS)

He, Ji-Huan

2014-11-01

This tutorial review of fractal-Cantorian spacetime and fractional calculus begins with Leibniz's notation for derivative without limits which can be generalized to discontinuous media like fractal derivative and q-derivative of quantum calculus. Fractal spacetime is used to elucidate some basic properties of fractal which is the foundation of fractional calculus, and El Naschie's mass-energy equation for the dark energy. The variational iteration method is used to introduce the definition of fractional derivatives. Fractal derivative is explained geometrically and q-derivative is motivated by quantum mechanics. Some effective analytical approaches to fractional differential equations, e.g., the variational iteration method, the homotopy perturbation method, the exp-function method, the fractional complex transform, and Yang-Laplace transform, are outlined and the main solution processes are given.

Bone-Derived Stem Cells Repair the Heart after Myocardial Infarction Through Transdifferentiation and Paracrine Signaling Mechanisms

PubMed Central

Duran, Jason M.; Makarewich, Catherine A.; Sharp, Thomas E.; Starosta, Timothy; Fang, Zhu; Hoffman, Nicholas E.; Chiba, Yumi; Madesh, Muniswamy; Berretta, Remus M.; Kubo, Hajime; Houser, Steven R.

2013-01-01

Rationale Autologous bone marrow- or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is key toward improving clinical outcomes. Objective To determine the mechanism by which novel bone-derived stem cells support the injured heart. Methods and Results Cortical bone stem cells (CBSCs) and cardiac-derived stem cells (CDCs) were isolated from EGFP+ transgenic mice and were shown to express c-kit and Sca-1 as well as 8 paracrine factors involved in cardioprotection, angiogenesis and stem cell function. Wild-type C57BL/6 mice underwent sham operation (n=21) or myocardial infarction (MI) with injection of CBSCs (n=67), CDCs (n=36) or saline (n=60). Cardiac function was monitored using echocardiography. Only 2/8 paracrine factors were detected in EGFP+ CBSCs in vivo (basic fibroblast growth factor and vascular endothelial growth factor) and this expression was associated with increased neovascularization of the infarct border zone. CBSC therapy improved survival, cardiac function, regional strain, attenuated remodeling, and decreased infarct size relative to CDC- or saline-treated MI controls. By 6 weeks, EGFP+ cardiomyocytes, vascular smooth muscle and endothelial cells could be identified in CBSC- but not in CDC-treated animals. EGFP+ CBSC-derived isolated myocytes were smaller and more frequently mononucleated, but were functionally indistinguishable from EGFP- myocytes. Conclusions CBSCs improve survival, cardiac function, and attenuate remodeling through two mechanisms:1) secretion of pro-angiogenic factors that stimulate endogenous neovascularization, and 2) differentiation into functional adult myocytes and vascular cells. PMID:23801066

Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

PubMed Central

Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

2011-01-01

Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulations vary among different neoplastic models. Thus, it is thought that the type and quantities of inflammatory mediators generated during neoplasia dictate the composition of the resultant MDSC response. Although much interest has been devoted to monocytic MDSC biology, a fundamental gap remains in our understanding of the derivation of granulocytic MDSC. In settings of heightened granulocytic MDSC responses, we hypothesized that inappropriate production of G-CSF is a key initiator of granulocytic MDSC accumulation. We observed abundant amounts of G-CSF in vivo, which correlated with robust granulocytic MDSC responses in multiple tumor models. Using G-CSF loss- and gain-of-function approaches, we demonstrated for the first time that: 1) abrogating G-CSF production significantly diminished granulocytic MDSC accumulation and tumor growth; 2) ectopically over-expressing G-CSF in G-CSF-negative tumors significantly augmented granulocytic MDSC accumulation and tumor growth; and 3) treatment of naïve healthy mice with recombinant G-CSF protein elicited granulocytic-like MDSC remarkably similar to those induced under tumor-bearing conditions. Collectively, we demonstrated that tumor-derived G-CSF enhances tumor growth through granulocytic MDSC-dependent mechanisms. These findings provide us with novel insights into MDSC subset development and potentially new biomarkers or targets for cancer therapy. PMID:22110722

Cyclic stretch induces upregulation of endothelin-1 with keratinocytes in vitro: Possible role in mechanical stress-induced hyperpigmentation

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

Kurita, Masakazu, E-mail: masakazukurita@gmail.com; Okazaki, Mutsumi; Fujino, Takashi

2011-05-27

Highlights: {yields} Influence of cyclic stretch on melanogenetic paracrine cytokines was investigated. {yields} Keratinocyte-derived endothelin-1 was upregulated with cyclic stretch. {yields} Degree of upregulation increases dose-dependently. {yields} This upregulation possibly plays a role in the pathogenesis of pigmented disorders. -- Abstract: The aim of this study was to investigate the possible pathological relation between mechanical stress and hyperpigmentation. We did this by investigating the influence of cyclic stretch on the expression of keratinocyte- and fibroblast-derived melanogenetic paracrine cytokines in vitro. Using primary human keratinocytes and fibroblasts, alterations of mRNA expression of melanogenetic paracrine cytokines due to cyclic stretch were investigatedmore » using a real-time polymerase chain reaction (PCR). The cytokines included basic fibroblast growth factor (bFGF), stem cell factor (SCF), granulocyte/macrophage colony-stimulating factor, interleukin-1{alpha}, and endothelin-1 (ET-1) for keratinocytes and bFGF, SCF, and hepatocyte growth factor for fibroblasts. The dose dependence of keratinocyte-derived ET-1 upregulation was further investigated using real-time PCR and an enzyme-linked immunosorbent assay. We also investigated the effects of cyclic stretch on the proliferation and differentiation of keratinocytes. Among the melanogenetic paracrine cytokines investigated, keratinocyte-derived ET-1 was consistently upregulated in all four cell lines. The degree of upregulation increased with the degree of the length and frequency of the stretch; in contrast, cell number and differentiation markers showed no obvious alterations with cyclic stretch. Keratinocyte-derived ET-1 upregulation possibly plays a significant role in the pathogenesis of pigmented disorders, such as friction melanosis, caused by mechanical stress.« less

Tunable catalytic properties of bi-functional mixed oxides in ethanol conversion to high value compounds

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

Ramasamy, Karthikeyan K.; Gray, Michel J.; Job, Heather M.

2016-04-10

tA highly versatile ethanol conversion process to selectively generate high value compounds is pre-sented here. By changing the reaction temperature, ethanol can be selectively converted to >C2alcohols/oxygenates or phenolic compounds over hydrotalcite derived bi-functional MgO–Al2O3cata-lyst via complex cascade mechanism. Reaction temperature plays a role in whether aldol condensationor the acetone formation is the path taken in changing the product composition. This article containsthe catalytic activity comparison between the mono-functional and physical mixture counterpart to thehydrotalcite derived mixed oxides and the detailed discussion on the reaction mechanisms.

Masquerading as self? Endoparasitic Strepsiptera (Insecta) enclose themselves in host-derived epidermal bag

PubMed Central

Kathirithamby, Jeyaraney; Ross, Larry D.; Johnston, J. Spencer

2003-01-01

We report here the case of a metazoan parasite, a strepsipteran, that manipulates host epidermal tissue and wraps itself within it; which probably camouflages the endoparasite and is recognized as ``self'' by the host. This mechanism is one of immune avoidance among parasitoid insects. The host-derived epidermal ``bag'' might have enabled Strepsiptera to radiate to disparate hosts compared with the relatively few taxa (596 species) described so far. They have been recorded as parasitizing 34 families belonging to seven orders of Insecta. We also report a mechanism of insect ecdysis between the first- and second-instar larva, while enclosed in the bag. PMID:12788973

A combined molecular dynamics/micromechanics/finite element approach for multiscale constitutive modeling of nanocomposites with interface effects

NASA Astrophysics Data System (ADS)

Yang, B. J.; Shin, H.; Lee, H. K.; Kim, H.

2013-12-01

We introduce a multiscale framework based on molecular dynamic (MD) simulation, micromechanics, and finite element method (FEM). A micromechanical model, which considers influences of the interface properties, nanoparticle (NP) size, and microcracks, is developed. Then, we perform MD simulations to characterize the mechanical properties of the nanocomposite system (silica/nylon 6) with varying volume fraction and size of NPs. By comparing the MD with micromechanics results, intrinsic physical properties at interfacial region are derived. Finally, we implement the developed model in the FEM code with the derived interfacial parameters, and predict the mechanical behavior of the nanocomposite at the macroscopic scale.

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives.

PubMed

Lamonaca, Palma; Prinzi, Giulia; Kisialiou, Aliaksei; Cardaci, Vittorio; Fini, Massimo; Russo, Patrizia

2017-03-20

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).

Inhibiting Microbial Toxins Using Plant-Derived Compounds and Plant Extracts

PubMed Central

Upadhyay, Abhinav; Mooyottu, Shankumar; Yin, Hsinbai; Surendran Nair, Meera; Bhattaram, Varunkumar; Venkitanarayanan, Kumar

2015-01-01

Many pathogenic bacteria and fungi produce potentially lethal toxins that cause cytotoxicity or impaired cellular function either at the site of colonization or other locations in the body through receptor-mediated interactions. Various factors, including biotic and abiotic environments, competing microbes, and chemical cues affect toxin expression in these pathogens. Recent work suggests that several natural compounds can modulate toxin production in pathogenic microbes. However, studies explaining the mechanistic basis for their effect are scanty. This review discusses the potential of various plant-derived compounds for reducing toxin production in foodborne and other microbes. In addition, studies highlighting their anti-toxigenic mechanism(s) are discussed. PMID:28930207

Tunable catalytic properties of bi-functional mixed oxides in ethanol conversion to high value compounds

DOE PAGES

Ramasamy, Karthikeyan K.; Gray, Michel; Job, Heather; ...

2016-02-03

Here, a highly versatile ethanol conversion process to selectively generate high value compounds is presented here. By changing the reaction temperature, ethanol can be selectively converted to >C 2 alcohols/oxygenates or phenolic compounds over hydrotalcite derived bi-functional MgO–Al 2O 3 catalyst via complex cascade mechanism. Reaction temperature plays a role in whether aldol condensation or the acetone formation is the path taken in changing the product composition. This article contains the catalytic activity comparison between the mono-functional and physical mixture counterpart to the hydrotalcite derived mixed oxides and the detailed discussion on the reaction mechanisms.

Exploring molecular insights into the interaction mechanism of cholesterol derivatives with the Mce4A: A combined spectroscopic and molecular dynamic simulation studies.

PubMed

Khan, Shagufta; Khan, Faez Iqbal; Mohammad, Taj; Khan, Parvez; Hasan, Gulam Mustafa; Lobb, Kevin A; Islam, Asimul; Ahmad, Faizan; Imtaiyaz Hassan, Md

2018-05-01

Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns. In silico studies were further validated by fluorescence-binding studies to calculate actual binding affinity and number of binding site(s). The non-toxicity of all ligands was confirmed on human monocytic cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism of interaction of Mce4A to cholesterol derivatives, which may be further exploited to design potential and specific inhibitors to ameliorate the Mycobacterium pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Fault-slip directions in central and southern Greece measured from striated and corrugated fault planes: Comparison with focal mechanism and geodetic data

NASA Astrophysics Data System (ADS)

Roberts, Gerald P.; Ganas, Athanassios

2000-10-01

Fault-slip directions recorded by outcropping striated and corrugated fault planes in central and southern Greece have been measured for comparison with extension directions derived from focal mechanism and Global Positioning System (GPS) data for the last ˜100 years to test how far back in time velocity fields and deformation dynamics derived from the latter data sets can be extrapolated. The fault-slip data have been collected from the basin-bounding faults to Plio-Pleistocene to recent extensional basins and include data from arrays of footwall faults formed during the early stages of fault growth. We show that the orientation of the inferred stress field varies along faults and earthquake ruptures, so we use only slip-directions from the centers of faults, where dip-slip motion occurs, to constrain regionally significant extension directions. The fault-slip directions for the Peloponnese and Gulfs of Evia and Corinth are statistically different at the 99% confidence level but statistically the same as those implied by earthquake focal mechanisms for each region at the 99% confidence level; they are also qualitatively similar to the principal strain axes derived from GPS studies. Extension directions derived from fault-slip data are 043-047° for the southern Peloponnese, 353° for the Gulf of Corinth, and 015-014° for the Gulf of Evia. Extension on active normal faults in the two latter areas appears to grade into strike-slip along the North Anatolian Fault through a gradual change in fault-slip directions and fault strikes. To reconcile the above with 5° Myr-1 clockwise rotations suggested for the area, we suggest that the faults considered formed during a single phase of extension. The deformation and formation of the normal fault systems examined must have been sufficiently rapid and recent for rotations about vertical axes to have been unable to disperse the fault-slip directions from the extension directions implied by focal mechanisms and GPS data. Thus, in central and southern Greece the velocity fields derived from focal mechanism and GPS data may help explain the dynamics of the deformation over longer time periods than the ˜100 years over which they were measured; this may include the entire deformation history of the fault systems considered, a time period that may exceed 1-2 Myr.

Recent advances in gossypol derivatives and analogs: a chemistry and biology view.

PubMed

Lu, Yuzhi; Li, Jun; Dong, Chun-E; Huang, Jian; Zhou, Hai-Bing; Wang, Wei

2017-07-01

Gossypol as a natural occurring polyphenol has been studied in a wide range of therapeutic contexts for a long time. The chemical modifications on gossypol were limited due to the unique chemical properties of polyphenols. The design and synthesis of gossypol derivatives and the exploration of their biological activities are the interest of the synthetic chemists, medicinal chemists and pharmacologists. Thus, the progress of diverse gossypol derivatives and analogs' synthesis, biological activities, mechanism elucidation and drug discovery based on gossypol scaffold is summarized.

Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

PubMed Central

Gomes, Nelson G. M.; Lefranc, Florence; Kijjoa, Anake; Kiss, Robert

2015-01-01

Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term “cytotoxicity” to be synonymous with “anticancer agent”, which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms. PMID:26090846

Novel flurbiprofen derivatives with improved brain delivery: synthesis, in vitro and in vivo evaluations.

PubMed

Zheng, Dan; Shuai, Xiao; Li, Yanping; Zhou, Peng; Gong, Tao; Sun, Xun; Zhang, Zhirong

2016-09-01

Tarenflurbil (R-flurbiprofen) was acknowledged as a promising candidate in Alzheimer's disease (AD) therapy. However, the Phase III study of tarenflurbil was extremely restricted by its poor delivery efficiency to the brain. To tackle this problem, the novel carriers for tarenflurbil, racemic flurbiprofen (FLU) derivatives (FLU-D1 and FLU-D2) modified by N,N-dimethylethanolamine-related structures were synthesized and characterized. These derivatives showed good safety level in vitro and they possessed much higher cellular uptake efficiency in brain endothelial cells than FLU did. More importantly, the uptake experiments suggested that they were internalized via active transport mechanisms. Biodistribution studies in rats also illustrated a remarkably enhanced accumulation of these derivatives in the brain. FLU-D2, the ester linkage form of these derivatives, achieved a higher brain-targeting efficiency. Its C max and AUC 0- t were enhanced by 12.09-fold and 4.61-fold, respectively compared with those of FLU. Additionally, it could be hydrolyzed by esterase in the brain to release the parent FLU, which might facilitate its therapeutic effect. These in vitro and in vivo results highlighted the improvement of the brain-targeted delivery of FLU by making use of N,N-dimethylethanolamine ligand, with which an active transport mechanism was involved.

CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration.

PubMed

Xu, Suining; Li, Lihua; Yan, Jinchuan; Ye, Fei; Shao, Chen; Sun, Zhen; Bao, Zhengyang; Dai, Zhiyin; Zhu, Jie; Jing, Lele; Wang, Zhongqun

2018-01-01

Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE -/- mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

PubMed

Gomes, Nelson G M; Lefranc, Florence; Kijjoa, Anake; Kiss, Robert

2015-06-19

Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term "cytotoxicity" to be synonymous with "anticancer agent", which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.

On the role of covariance information for GRACE K-band observations in the Celestial Mechanics Approach

NASA Astrophysics Data System (ADS)

Bentel, Katrin; Meyer, Ulrich; Arnold, Daniel; Jean, Yoomin; Jäggi, Adrian

2017-04-01

The Astronomical Institute at the University of Bern (AIUB) derives static and time-variable gravity fields by means of the Celestial Mechanics Approach (CMA) from GRACE (level 1B) data. This approach makes use of the close link between orbit and gravity field determination. GPS-derived kinematic GRACE orbit positions, inter-satellite K-band observations, which are the core observations of GRACE, and accelerometer data are combined to rigorously estimate orbit and spherical harmonic gravity field coefficients in one adjustment step. Pseudo-stochastic orbit parameters are set up to absorb unmodeled noise. The K-band range measurements in along-track direction lead to a much higher correlation of the observations in this direction compared to the other directions and thus, to north-south stripes in the unconstrained gravity field solutions, so-called correlated errors. By using a full covariance matrix for the K-band observations the correlation can be taken into account. One possibility is to derive correlation information from post-processing K-band residuals. This is then used in a second iteration step to derive an improved gravity field solution. We study the effects of pre-defined covariance matrices and residual-derived covariance matrices on the final gravity field product with the CMA.

Testing Nonassociative Quantum Mechanics.

PubMed

Bojowald, Martin; Brahma, Suddhasattwa; Büyükçam, Umut

2015-11-27

The familiar concepts of state vectors and operators in quantum mechanics rely on associative products of observables. However, these notions do not apply to some exotic systems such as magnetic monopoles, which have long been known to lead to nonassociative algebras. Their quantum physics has remained obscure. This Letter presents the first derivation of potentially testable physical results in nonassociative quantum mechanics, based on effective potentials. They imply new effects which cannot be mimicked in usual quantum mechanics with standard magnetic fields.

Traffic management mechanism for intranets with available-bit-rate access to the Internet

NASA Astrophysics Data System (ADS)

Hassan, Mahbub; Sirisena, Harsha R.; Atiquzzaman, Mohammed

1997-10-01

The design of a traffic management mechanism for intranets connected to the Internet via an available bit rate access- link is presented. Selection of control parameters for this mechanism for optimum performance is shown through analysis. An estimate for packet loss probability at the access- gateway is derived for random fluctuation of available bit rate of the access-link. Some implementation strategies of this mechanism in the standard intranet protocol stack are also suggested.

Potentiation of mitochondrial dysfunction in tumor cells by conjugates of metabolic modulator dichloroacetate with a Pt(IV) derivative of oxaliplatin.

PubMed

Zajac, Juraj; Kostrhunova, Hana; Novohradsky, Vojtech; Vrana, Oldrich; Raveendran, Raji; Gibson, Dan; Kasparkova, Jana; Brabec, Viktor

2016-03-01

The molecular and cellular mechanisms of enhanced toxic effects in tumor cells of the Pt(IV) derivatives of antitumor oxaliplatin containing axial dichloroacetate (DCA) ligands were investigated. DCA ligands were chosen because DCA has shown great potential as an apoptosis sensitizer and anticancer agent reverting the Wartburg effect. In addition, DCA reverses mitochondrial changes in a wide range of cancers, promoting tumor cell apoptosis in a mitochondrial-dependent pathway. We demonstrate that (i) the transformation of oxaliplatin to its Pt(IV) derivatives containing axial DCA ligands markedly enhances toxicity in cancer cells and helps overcome inherent and acquired resistance to cisplatin and oxaliplatin; (ii) a significant fraction of the intact molecules of DCA conjugates with Pt(IV) derivative of oxaliplatin accumulates in cancer cells where it releases free DCA; (iii) mechanism of biological action of the Pt(IV) derivatives of oxaliplatin containing DCA ligands is connected with the effects of DCA released in cancer cells from the Pt(IV) prodrugs on mitochondria and metabolism of glucose; (iv) treatments with the Pt(IV) derivatives of oxaliplatin containing DCA ligands activate an autophagic response in human colorectal cancer cells; (v) the toxic effects in cancer cells of the Pt(IV) derivatives of oxaliplatin containing DCA ligands can be potentiated if cells are treated with these prodrugs in combination with 5-fluorouracil. These properties of the Pt(IV) derivatives of oxaliplatin containing DCA ligands provide opportunities for further development of new platinum-based agents with the capability of killing cancer cells resistant to conventional antitumor platinum drugs used in the clinic. Copyright © 2015 Elsevier Inc. All rights reserved.

The Effects of Mechanical Transparency on Adjustment to a Complex Visuomotor Transformation at Early and Late Working Age

ERIC Educational Resources Information Center

Heuer, Herbert; Hegele, Mathias

2010-01-01

Mechanical tools are transparent in the sense that their input-output relations can be derived from their perceptible characteristics. Modern technology creates more and more tools that lack mechanical transparency, such as in the control of the position of a cursor by means of a computer mouse or some other input device. We inquired whether an…

Genetic Associations and Mechanisms in Oncology (GAME-ON): A Network of Consortia for Post-Genome Wide Association (Post-GWA) Research

Cancer.gov

The Genetic Associations and Mechanisms in Oncology's (GAME-ON) overall goal is to foster an intra-disciplinary and collaborative approach to the translation of promising research leads deriving from the initial wave of cancer GWAS.

The mechanism of action of piperazine-phosphonates derivatives in cotton fabric

USDA-ARS?s Scientific Manuscript database

Piperazine-phosphonates additives are known to be very effective flame retardants on different polymeric systems, especially cotton cellulose. In order to understand their mechanism of action, we carried out the investigation of their thermal behavior on cotton fabric by, first, employing the attenu...

Differentiation-associated alteration in human monocyte-macrophage accessory cell function.

PubMed

Mayernik, D G; Ul-Haq, A; Rinehart, J J

1983-05-01

Human monocyte (Mo) to macrophage (Mx) differentiation is associated with marked and well studied changes in morphology, biochemical parameters, and effector cell function. Nevertheless, the comparative accessory cell (AC) function of blood Mo and differentiated Mx has not been carefully studied. We, therefore, examined the kinetics and mechanisms of change in AC function during in vitro Mo to Mx differentiation. The system utilized has two distinctive features: blood Mo and resultant cultured Mx represent a cohort of cells derived from the bone marrow within a 12-hr period. Moreover, the in vitro derived Mx utilized herein have been characterized extensively and are functionally and biochemically similar to pulmonary macrophages (PMx). In the experiments reported, AC functions of blood Mo, Mx derived from Mo after 1 to 6 days of culture, and PMx was compared. AC were cultured with nylon wool column-purified autologous T cells and were stimulated with concanavalin A (Con A) or streptokinase-streptodornase (SKSD). Blood T cell proliferation to Con A or SKSD was inhibited greater than 90% by the removal of Mo and was reconstituted by 20% Mo. Mx derived from Mo by culture for 1 to 3 days exhibited the same (or better) AC function as Mo when T cells were stimulated with either SKSD or Con A. In marked contrast, Mx derived from 6-day cultures exhibited less than or equal to 15% of Mo (i.e., control) capacity to support T cell proliferative response to SKSD. Six-day Mx support T cell proliferation to Con A was somewhat variable. Similar to 6-day cultured Mx, PMx failed to function as AC. The mechanism of loss of AC function was examined: a) cultured Mx maintained Ia antigen positivity for greater than 8 days; b) mixing experiments with Mo + 6-day cultured Mx or Mo + PMx demonstrated no T cell suppression; c) the normal capacity of most 6-day cultured Mx to support Con A but not SKSD induced T cell proliferation, apparently ruled out the loss of the ability to deliver a nonspecific "second signal" as the involved mechanism; d) inhibition of Mo to Mx differentiation by dexamethasone preserved AC activity. Thus, human culture-derived Mx and PMx exhibit deficit AC function through loss of an undefined mechanism. However, loss of AC antigen processing or presentation may occur.

Theoretical derivation of laser-dressed atomic states by using a fractal space

NASA Astrophysics Data System (ADS)

Duchateau, Guillaume

2018-05-01

The derivation of approximate wave functions for an electron submitted to both a Coulomb and a time-dependent laser electric fields, the so-called Coulomb-Volkov (CV) state, is addressed. Despite its derivation for continuum states does not exhibit any particular problem within the framework of the standard theory of quantum mechanics (QM), difficulties arise when considering an initially bound atomic state. Indeed the natural way of translating the unperturbed momentum by the laser vector potential is no longer possible since a bound state does not exhibit a plane wave form explicitly including a momentum. The use of a fractal space permits to naturally define a momentum for a bound wave function. Within this framework, it is shown how the derivation of laser-dressed bound states can be performed. Based on a generalized eikonal approach, a new expression for the laser-dressed states is also derived, fully symmetric relative to the continuum or bound nature of the initial unperturbed wave function. It includes an additional crossed term in the Volkov phase which was not obtained within the standard theory of quantum mechanics. The derivations within this fractal framework have highlighted other possible ways to derive approximate laser-dressed states in QM. After comparing the various obtained wave functions, an application to the prediction of the ionization probability of hydrogen targets by attosecond XUV pulses within the sudden approximation is provided. This approach allows to make predictions in various regimes depending on the laser intensity, going from the non-resonant multiphoton absorption to tunneling and barrier-suppression ionization.

Development of an accurate and high-throughput methodology for structural comprehension of chlorophylls derivatives. (II) Dephytylated derivatives.

PubMed

Chen, Kewei; Ríos, José Julián; Roca, María; Pérez-Gálvez, Antonio

2015-09-18

Dephytylated chlorophylls (chlorophyllides and pheophorbides) are the starting point of the chlorophyll catabolism in green tissues, components of the chlorophyll pattern in storage/processed food vegetables, as well as the favoured structural arrangement for chlorophyll absorption. In addition, dephytylated native chlorophylls are prone to several modifications of their structure yielding pyro-, 13(2)-hydroxy- and 15(1)-hydroxy-lactone derivatives. Despite of these outstanding remarks only few of them have been analysed by MS(n). Besides new protocols for obtaining standards, we have developed a new high throughput methodology able to determine the fragmentation pathway of 16 dephytylated chlorophyll derivatives, elucidating the structures of the new product ions and new mechanisms of fragmentation. The new methodology combines, by first time, high resolution time-of-flight mass spectrometry and powerful post-processing software. Native chlorophyllides and pheophorbides mainly exhibit product ions that involve the fragmentation of D ring, as well as additional exclusive product ions. The introduction of an oxygenated function at E ring enhances the progress of fragmentation reactions through the β-keto ester group, developing also exclusive product ions for 13(2)-hydroxy derivatives and for 15(1)-hydroxy-lactone ones. Consequently, while MS(2)-based reactions of phytylated chlorophyll derivatives point to fragmentations at the phytyl and propionic chains, dephytylated chlorophyll derivatives behave different as the absence of phytyl makes β-keto ester group and E ring more prone to fragmentation. Proposals of the key reaction mechanisms underlying the origin of new product ions have been made. Copyright © 2015 Elsevier B.V. All rights reserved.

Deriving allowable properties of lumber : a practical guide for interpretation of ASTM standards

Treesearch

Alan Bendtsen; William L. Galligan

1978-01-01

The ASTM standards for establishing clear wood mechanical properties and for deriving structural grades and related allowable properties for visually graded lumber can be confusing and difficult for the uninitiated to interpret. This report provides a practical guide to using these standards for individuals not familiar with their application. Sample stress...

Engineering Students' Conceptions of the Derivative and Some Implications for Their Mathematical Education

ERIC Educational Resources Information Center

Bingolbali, E.; Monaghan, J.; Roper, T.

2007-01-01

This paper explores Mechanical Engineering students' conceptions of and preferences for conceptions of the derivative, and their views on mathematics. Data comes from pre-, post- and delayed post-tests, a preference test, interviews with students and an analysis of calculus courses. Data from Mathematics students is used to make comparisons with…

Preparation of four 1,4-dihydropyridine derivatives (DHPs) labeled with carbon-14.

PubMed

Ahmadi Faghih, Mohammad Amin; Moslemin, Mohammad Hossein; Shirvani, Gholamhossein; Javaheri, Mohsen

2018-05-23

The importance of DHPs compounds and the need for examining the mechanism of their effect, mandated us to synthesize a number of carbon-14 labeled 1,4-dihydropyridine derivatives for pharmacological studies. Simple preparation and suitable radiochemical yield were advantages of this preparation. This article is protected by copyright. All rights reserved.

Dual/multitargeted xanthone derivatives for Alzheimer's disease: where do we stand?

PubMed

Cruz, Maria I; Cidade, Honorina; Pinto, Madalena

2017-09-01

To date, the current therapy for Alzheimer's disease (AD) based on acetylcholinesterase inhibitors is only symptomatic, being its efficacy limited. Hence, the recent research has been focused in the development of different pharmacological approaches. Here we discuss the potential of xanthone derivatives as new anti-Alzheimer agents. The interference of xanthone derivatives with acetylcholinesterase and other molecular targets and cellular mechanisms associated with AD have been recently systematically reported. Therefore, we report xanthones with anticholinesterase, monoamine oxidase and amyloid β aggregation inhibitory activities as well as antioxidant properties, emphasizing xanthone derivatives with dual/multitarget activity as potential agents to treat AD. We also propose the structural features for these activities that may guide the design of new, more effective xanthone derivatives. [Formula: see text].

Qualitative analysis of the stability of the oxazine ring of various benzoxazine and pyridooxazine derivatives with proton nuclear magnetic resonance spectroscopy.

PubMed

Moloney, G P; Craik, D J; Iskander, M N

1992-07-01

A series of 3,4-dihydro-1,3-benzoxazine and 3,4-dihydro-1,3-pyridooxazine derivatives was synthesized, and the hydrolysis of the derivatives was studied with proton nuclear magnetic resonance spectroscopy. The oxazine derivatives underwent various degrees of hydrolysis when H2O was added to dimethyl sulfoxide solutions of the compounds. The rates and extents of decomposition of the oxazine ring systems depended on the electronic effects of substituents within the molecules. Examination of the proton nuclear magnetic resonance spectra that were generated during decomposition of the oxazines and trends in stability of the oxazine derivatives suggest the formation of an intermediate in the hydrolysis mechanism.

Marine-derived angiogenesis inhibitors for cancer therapy.

PubMed

Wang, Ying-Qing; Miao, Ze-Hong

2013-03-15

Angiogenesis inhibitors have been successfully used for cancer therapy in the clinic. Many marine-derived natural products and their analogues have been reported to show antiangiogenic activities. Compared with the drugs in the clinic, these agents display interesting characteristics, including diverse sources, unique chemical structures, special modes of action, and distinct activity and toxicity profiles. This review will first provide an overview of the current marine-derived angiogenesis inhibitors based on their primary targets and/or mechanisms of action. Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the marine-derived antiangiogenic agents will be discussed, with special emphasis on their application potentials, problems and possible coping strategies in their future development as anticancer drugs.

Structure, Content, and Bioactivity of Food-Derived Peptides in the Body.

PubMed

Sato, Kenji

2018-03-28

Orally administered peptides are assumed to be degraded into amino acids in the body. However, our recent studies revealed some food-derived prolyl and pyroglutamyl peptides with 2-3 amino acid residues in the blood of humans and animals, while most of the peptides in the endoproteinase digest of food protein are degraded by exopeptidase. Some food-derived dipeptides in the body display in vitro and in vivo biological activities. These facts indicate that the biological activities of food-derived peptides in the body rather than those in food are crucial to understanding the mechanism of the beneficial effects of orally administered peptides.

Statistical foundations of liquid-crystal theory: II: Macroscopic balance laws.

PubMed

Seguin, Brian; Fried, Eliot

2013-01-01

Working on a state space determined by considering a discrete system of rigid rods, we use nonequilibrium statistical mechanics to derive macroscopic balance laws for liquid crystals. A probability function that satisfies the Liouville equation serves as the starting point for deriving each macroscopic balance. The terms appearing in the derived balances are interpreted as expected values and explicit formulas for these terms are obtained. Among the list of derived balances appear two, the tensor moment of inertia balance and the mesofluctuation balance, that are not standard in previously proposed macroscopic theories for liquid crystals but which have precedents in other theories for structured media.

Statistical foundations of liquid-crystal theory

PubMed Central

Seguin, Brian; Fried, Eliot

2013-01-01

Working on a state space determined by considering a discrete system of rigid rods, we use nonequilibrium statistical mechanics to derive macroscopic balance laws for liquid crystals. A probability function that satisfies the Liouville equation serves as the starting point for deriving each macroscopic balance. The terms appearing in the derived balances are interpreted as expected values and explicit formulas for these terms are obtained. Among the list of derived balances appear two, the tensor moment of inertia balance and the mesofluctuation balance, that are not standard in previously proposed macroscopic theories for liquid crystals but which have precedents in other theories for structured media. PMID:23554513

Justice-Sensitive Education: The Implications of Transitional Justice Mechanisms for Teaching and Learning

ERIC Educational Resources Information Center

Davies, Lynn

2017-01-01

This article introduces the notion of "justice-sensitive education"--derived from the ideals and practices of transitional justice (TJ) in countries emerging from conflict. It describes three mechanisms for this: structural reforms (relating to inequity and division); curriculum change (the treatment of history, human rights and…

Hemogenic endothelial cell specification requires c-kit, notch signaling, and p27-mediated cell-cycle control

USDA-ARS?s Scientific Manuscript database

Delineating the mechanism or mechanisms that regulate the specification of hemogenic endothelial cells from primordial endothelium is critical for optimizing their derivation from human stem cells for clinical therapies. We previously determined that retinoic acid (RA) is required for hemogenic spec...

Metabolomic Response of Human Embryonic Stem Cell Derived Germ-like Cells after Exposure to Steroid Hormones

EPA Science Inventory

To assess the potential risks of human exposure to endocrine active compounds (EACs), the mechanisms of toxicity must first be identified and characterized. Currently, there are no robust in vitro models for identifying the mechanisms of toxicity in germ cells resulting from EAC ...

Biomarker metabolite signatures pave the way for electronic-nose applications in early clinical disease diagnoses

Treesearch

Alphus Dan Wilson

2017-01-01

Background: Analysis of volatile metabolites derived from the human breath or biofluids provides noninvasive means of detecting and monitoring diseases that occur throughout the body. Diseases arise from different mechanisms that cause alterations in normal physiological processes. Mechanisms of disease (pathogenesis) result in the...

A Simple Relativistic Bohr Atom

ERIC Educational Resources Information Center

Terzis, Andreas F.

2008-01-01

A simple concise relativistic modification of the standard Bohr model for hydrogen-like atoms with circular orbits is presented. As the derivation requires basic knowledge of classical and relativistic mechanics, it can be taught in standard courses in modern physics and introductory quantum mechanics. In addition, it can be shown in a class that…

Understanding the mechanism of action of triazine-phosphonate derivatives as flame retardants for cotton fabrics

USDA-ARS?s Scientific Manuscript database

Countless hours of research and studies on triazine, phosphonate and their combination have provided insightful information into their flame retardant properties on polymeric systems. However, only limited number of studies shed light on the mechanism of flame retardant cotton fabrics. The purpose...

Development of an accurate and high-throughput methodology for structural comprehension of chlorophylls derivatives. (I) Phytylated derivatives.

PubMed

Chen, Kewei; Ríos, José Julián; Pérez-Gálvez, Antonio; Roca, María

2015-08-07

Phytylated chlorophyll derivatives undergo specific oxidative reactions through the natural metabolism or during food processing or storage, and consequently pyro-, 13(2)-hydroxy-, 15(1)-hydroxy-lactone chlorophylls, and pheophytins (a and b) are originated. New analytical procedures have been developed here to reproduce controlled oxidation reactions that specifically, and in reasonable amounts, produce those natural target standards. At the same time and under the same conditions, 16 natural chlorophyll derivatives have been analyzed by APCI-HPLC-hrMS(2) and most of them by the first time. The combination of the high-resolution MS mode with powerful post-processing software has allowed the identification of new fragmentation patterns, characterizing specific product ions for some particular standards. In addition, new hypotheses and reaction mechanisms for the established MS(2)-based reactions have been proposed. As a general rule, the main product ions involve the phytyl and the propionic chains but the introduction of oxygenated functional groups at the isocyclic ring produces new and specific productions and at the same time inhibits some particular fragmentations. It is noteworthy that all b derivatives, except 15(1)-hydroxy-lactone compounds, undergo specific CO losses. We propose a new reaction mechanism based in the structural configuration of a and b chlorophyll derivatives that explain the exclusive CO fragmentation in all b series except for 15(1)-hydroxy-lactone b and all a series compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Contact geometry and quantum mechanics

NASA Astrophysics Data System (ADS)

Herczeg, Gabriel; Waldron, Andrew

2018-06-01

We present a generally covariant approach to quantum mechanics in which generalized positions, momenta and time variables are treated as coordinates on a fundamental "phase-spacetime". We show that this covariant starting point makes quantization into a purely geometric flatness condition. This makes quantum mechanics purely geometric, and possibly even topological. Our approach is especially useful for time-dependent problems and systems subject to ambiguities in choices of clock or observer. As a byproduct, we give a derivation and generalization of the Wigner functions of standard quantum mechanics.

Effects of Chitin and Its Derivative Chitosan on Postharvest Decay of Fruits: A Review

PubMed Central

Zhang, Hongyin; Li, Renping; Liu, Weimin

2011-01-01

Considerable economic losses to harvested fruits are caused by postharvest fungal decay during transportation and storage, which can be significantly controlled by synthetic fungicides. However, considering public concern over pesticide residues in food and the environment, there is a need for safer alternatives for the control of postharvest decay to substitute synthetic fungicides. As the second most abundant biopolymer renewable source in nature, chitin and its derivative chitosan are widely used in controlling postharvest decay of fruits. This review aims to introduce the effect of chitin and chitosan on postharvest decay in fruits and the possible modes of action involved. We found most of the actions discussed in these researches rest on physiological mechanisms. All of the mechanisms are summarized to lay the groundwork for further studies which should focus on the molecular mechanisms of chitin and chitosan in controlling postharvest decay of fruits. PMID:21541034

Mechanics of active surfaces

NASA Astrophysics Data System (ADS)

Salbreux, Guillaume; Jülicher, Frank

2017-09-01

We derive a fully covariant theory of the mechanics of active surfaces. This theory provides a framework for the study of active biological or chemical processes at surfaces, such as the cell cortex, the mechanics of epithelial tissues, or reconstituted active systems on surfaces. We introduce forces and torques acting on a surface, and derive the associated force balance conditions. We show that surfaces with in-plane rotational symmetry can have broken up-down, chiral, or planar-chiral symmetry. We discuss the rate of entropy production in the surface and write linear constitutive relations that satisfy the Onsager relations. We show that the bending modulus, the spontaneous curvature, and the surface tension of a passive surface are renormalized by active terms. Finally, we identify active terms which are not found in a passive theory and discuss examples of shape instabilities that are related to active processes in the surface.

Nondestructive methods of integrating energy harvesting systems with structures

NASA Astrophysics Data System (ADS)

Inamdar, Sumedh; Zimowski, Krystian; Crawford, Richard; Wood, Kristin; Jensen, Dan

2012-04-01

Designing an attachment structure that is both novel and meets the system requirements can be a difficult task especially for inexperienced designers. This paper presents a design methodology for concept generation of a "parent/child" attachment system. The "child" is broadly defined as any device, part, or subsystem that will attach to any existing system, part, or device called the "parent." An inductive research process was used to study a variety of products, patents, and biological examples that exemplified the parent/child system. Common traits among these products were found and categorized as attachment principles in three different domains: mechanical, material, and field. The attachment principles within the mechanical domain and accompanying examples are the focus of this paper. As an example of the method, a case study of generating concepts for a bridge mounted wind energy harvester using the mechanical attachment principles derived from the methodology and TRIZ principles derived from Altshuller's matrix of contradictions is presented.

The role of proton shuttling mechanisms in solvent-free and catalyst-free acetalization reactions of imines.

PubMed

Lillo, Victor J; Mansilla, Javier; Saá, José M

2018-06-06

Proton transfer is central to the understanding of chemical processes. More so in addition reactions of the type NuH + E → Nu-EH taking place under solvent-free and catalyst-free conditions. Herein we show that the addition of alcohols or amines (the NuH component) to imine derivatives (the E component), in 1 : 1 ratio, under solvent-free and catalyst-free conditions, are efficient methods to access N,O and N,N-acetal derivatives. In addition, computational studies reveal that they are catalyzed reactions involving two or even three NuH molecules operating in a cooperative manner as H-bonded NuH(NuH)nNuH associates (many body effects) in the transition state through a concerted proton shuttling mechanism (addition of alcohols) or stepwise proton shuttling mechanism (addition of amines), thereby facilitating the key proton transfer step.

Rapid control of male typical behaviors by brain-derived estrogens

PubMed Central

Cornil, Charlotte A.; Ball, Gregory F.; Balthazart, Jacques

2012-01-01

Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanism that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators. PMID:22983088

Finite element procedures for coupled linear analysis of heat transfer, fluid and solid mechanics

NASA Technical Reports Server (NTRS)

Sutjahjo, Edhi; Chamis, Christos C.

1993-01-01

Coupled finite element formulations for fluid mechanics, heat transfer, and solid mechanics are derived from the conservation laws for energy, mass, and momentum. To model the physics of interactions among the participating disciplines, the linearized equations are coupled by combining domain and boundary coupling procedures. Iterative numerical solution strategy is presented to solve the equations, with the partitioning of temporal discretization implemented.

Investigation of spin-zero bosons in q-deformed relativistic quantum mechanics

NASA Astrophysics Data System (ADS)

Sobhani, H.; Chung, W. S.; Hassanabadi, H.

2018-04-01

In this article, Scattering states of Klein-Gordon equation for three scatter potentials of single and double Dirac delta and a potential well in the q-deformed formalism of relativistic quantum mechanics have been derived. At first, we discussed how q-deformed formalism can be constructed and used. Postulates of this q-deformed quantum mechanics are noted. Then scattering problems for spin-zero bosons are studied.

FTIR spectra and mechanical strength analysis of some selected rubber derivatives.

PubMed

Gunasekaran, S; Natarajan, R K; Kala, A

2007-10-01

Rubber materials have wide range of commercial applications such as, infant diapers, famine hygiene products, drug delivery devices and incontinency products such as rubber tubes, tyres, etc. In the present work, studies on mechanical properties of some selected rubber materials viz., natural rubber (NR), styrene butadiene rubber (SBR), nitrile butadiene rubber (NBR) and ethylene propylene diene monomer (EPDM) have been carried out in three states viz., raw, vulcanized and reinforced. To enhance the quality of rubber elastomers, an attempt is made to prepare new elastomers called polyblends. In the present study an attempt is made to blend NR with NBR and with EPDM. We here report, a novel approach for the evaluation of various physico-mechanical properties such as mechanical strength, tensile strength, elongation and hardness. The method is simple, direct and fast and involves infrared spectral measurements for the evaluation of these properties. With the applications of modern infrared spectroscopy, the mechanical strength of these rubber materials have been analyzed by calculating the internal standards among the methyl and methylene group vibrational frequencies obtained from FTIR spectroscopy. Also the tensile strength measurements carried out by universal testing machine. The results pertaining physico-mechanical properties of the rubber derivatives undertaken in the present study obtained by IR-based method are in good agreement with data resulted from the standard methods.

FTIR spectra and mechanical strength analysis of some selected rubber derivatives

NASA Astrophysics Data System (ADS)

Gunasekaran, S.; Natarajan, R. K.; Kala, A.

2007-10-01

Rubber materials have wide range of commercial applications such as, infant diapers, famine hygiene products, drug delivery devices and incontinency products such as rubber tubes, tyres, etc. In the present work, studies on mechanical properties of some selected rubber materials viz., natural rubber (NR), styrene butadiene rubber (SBR), nitrile butadiene rubber (NBR) and ethylene propylene diene monomer (EPDM) have been carried out in three states viz., raw, vulcanized and reinforced. To enhance the quality of rubber elastomers, an attempt is made to prepare new elastomers called polyblends. In the present study an attempt is made to blend NR with NBR and with EPDM. We here report, a novel approach for the evaluation of various physico-mechanical properties such as mechanical strength, tensile strength, elongation and hardness. The method is simple, direct and fast and involves infrared spectral measurements for the evaluation of these properties. With the applications of modern infrared spectroscopy, the mechanical strength of these rubber materials have been analyzed by calculating the internal standards among the methyl and methylene group vibrational frequencies obtained from FTIR spectroscopy. Also the tensile strength measurements carried out by universal testing machine. The results pertaining physico-mechanical properties of the rubber derivatives undertaken in the present study obtained by IR-based method are in good agreement with data resulted from the standard methods.

The Molecular Mechanisms of Thalidomide Teratogenicity and Implications for Modern Medicine.

PubMed

Knobloch, J; Jungck, D; Koch, A

2017-01-01

Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and antiangiogenic activities are considered in many other refractory diseases. The aim is to develop derivatives that are not teratogenic but maintain the therapeutic potential. This requires detailed knowledge about the underlying molecular mechanisms. Much progress has been made in deciphering the teratogenic mechanisms in the last decade. Here, we summarize these mechanisms, explain thalidomide resistance of rodents, and discuss possible mechanisms that could explain why the drug primarily targets the developing limb in the embryo. We also summarize the most important therapeutic mechanisms. Finally, we discuss which therapeutic and teratogenic mechanisms do and do not overlap, and if there is a chance for the development of non-teratogenic thalidomide derivatives with therapeutic potential. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Chip-based comparison of the osteogenesis of human bone marrow- and adipose tissue-derived mesenchymal stem cells under mechanical stimulation.

PubMed

Park, Sang-Hyug; Sim, Woo Young; Min, Byoung-Hyun; Yang, Sang Sik; Khademhosseini, Ali; Kaplan, David L

2012-01-01

Adipose tissue-derived stem cells (ASCs) are considered as an attractive stem cell source for tissue engineering and regenerative medicine. We compared human bone marrow-derived mesenchymal stem cells (hMSCs) and hASCs under dynamic hydraulic compression to evaluate and compare osteogenic abilities. A novel micro cell chip integrated with microvalves and microscale cell culture chambers separated from an air-pressure chamber was developed using microfabrication technology. The microscale chip enables the culture of two types of stem cells concurrently, where each is loaded into cell culture chambers and dynamic compressive stimulation is applied to the cells uniformly. Dynamic hydraulic compression (1 Hz, 1 psi) increased the production of osteogenic matrix components (bone sialoprotein, oateopontin, type I collagen) and integrin (CD11b and CD31) expression from both stem cell sources. Alkaline phosphatase and Alrizarin red staining were evident in the stimulated hMSCs, while the stimulated hASCs did not show significant increases in staining under the same stimulation conditions. Upon application of mechanical stimulus to the two types of stem cells, integrin (β1) and osteogenic gene markers were upregulated from both cell types. In conclusion, stimulated hMSCs and hASCs showed increased osteogenic gene expression compared to non-stimulated groups. The hMSCs were more sensitive to mechanical stimulation and more effective towards osteogenic differentiation than the hASCs under these modes of mechanical stimulation.

MEAT SCIENCE AND MUSCLE BIOLOGY SYMPOSIUM--mechanism of growth hormone stimulation of skeletal muscle growth in cattle.

PubMed

Jiang, H; Ge, X

2014-01-01

Growth hormone, also called somatotropin (ST), is a polypeptide hormone produced by the anterior pituitary. The major functions of GH include stimulating bone and skeletal muscle growth, lipolysis, milk production, and expression of the IGF-I gene in the liver. Based on these functions, recombinant bovine ST (bST) and recombinant porcine ST (pST) have been used to improve milk production in dairy cows and lean tissue growth in pigs, respectively. However, despite these applications, the mechanisms of action of GH are not fully understood. Indeed, there has been a lot of controversy over the role of liver-derived circulating IGF-I and locally produced IGF-I in mediating the growth-stimulatory effect of GH during the last 15 yr. It is in this context that we have conducted studies to further understand how GH stimulates skeletal muscle growth in cattle. Our results do not support a role of skeletal muscle-derived IGF-I in GH-stimulated skeletal muscle growth in cattle. Our results indicate that GH stimulates skeletal muscle growth in cattle, in part, by stimulating protein synthesis in muscle through a GH receptor-mediated, IGF-I-independent mechanism. In this review, besides discussing these results, we also argue that liver-derived circulating IGF-I should be still considered as the major mechanism that mediates the growth-stimulatory effect of GH on skeletal muscle in cattle and other domestic animals.

Spekkens’ toy model in all dimensions and its relationship with stabiliser quantum mechanics

NASA Astrophysics Data System (ADS)

Catani, Lorenzo; E Browne, Dan

2017-07-01

Spekkens’ toy model is a non-contextual hidden variable model with an epistemic restriction, a constraint on what an observer can know about reality. The aim of the model, developed for continuous and discrete prime degrees of freedom, is to advocate the epistemic view of quantum theory, where quantum states are states of incomplete knowledge about a deeper underlying reality. Many aspects of quantum mechanics and protocols from quantum information can be reproduced in the model. In spite of its significance, a number of aspects of Spekkens’ model remained incomplete. Formal rules for the update of states after measurement had not been written down, and the theory had only been constructed for prime-dimensional and infinite dimensional systems. In this work, we remedy this, by deriving measurement update rules and extending the framework to derive models in all dimensions, both prime and non-prime. Stabiliser quantum mechanics (SQM) is a sub-theory of quantum mechanics with restricted states, transformations and measurements. First derived for the purpose of constructing error correcting codes, it now plays a role in many areas of quantum information theory. Previously, it had been shown that Spekkens’ model was operationally equivalent to SQM in the case of odd prime dimensions. Here, exploiting known results on Wigner functions, we extend this to show that Spekkens’ model is equivalent to SQM in all odd dimensions, prime and non-prime. This equivalence provides new technical tools for the study of technically difficult compound-dimensional SQM.

Chip-Based Comparison of the Osteogenesis of Human Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells under Mechanical Stimulation

PubMed Central

Min, Byoung-Hyun; Yang, Sang Sik; Khademhosseini, Ali; Kaplan, David L.

2012-01-01

Adipose tissue-derived stem cells (ASCs) are considered as an attractive stem cell source for tissue engineering and regenerative medicine. We compared human bone marrow-derived mesenchymal stem cells (hMSCs) and hASCs under dynamic hydraulic compression to evaluate and compare osteogenic abilities. A novel micro cell chip integrated with microvalves and microscale cell culture chambers separated from an air-pressure chamber was developed using microfabrication technology. The microscale chip enables the culture of two types of stem cells concurrently, where each is loaded into cell culture chambers and dynamic compressive stimulation is applied to the cells uniformly. Dynamic hydraulic compression (1 Hz, 1 psi) increased the production of osteogenic matrix components (bone sialoprotein, oateopontin, type I collagen) and integrin (CD11b and CD31) expression from both stem cell sources. Alkaline phosphatase and Alrizarin red staining were evident in the stimulated hMSCs, while the stimulated hASCs did not show significant increases in staining under the same stimulation conditions. Upon application of mechanical stimulus to the two types of stem cells, integrin (β1) and osteogenic gene markers were upregulated from both cell types. In conclusion, stimulated hMSCs and hASCs showed increased osteogenic gene expression compared to non-stimulated groups. The hMSCs were more sensitive to mechanical stimulation and more effective towards osteogenic differentiation than the hASCs under these modes of mechanical stimulation. PMID:23029565

Kinematics and dynamics of a six-degree-of-freedom robot manipulator with closed kinematic chain mechanism

NASA Technical Reports Server (NTRS)

Nguyen, Charles C.; Pooran, Farhad J.

1989-01-01

This paper deals with a class of robot manipulators built based on the kinematic chain mechanism (CKCM). This class of CKCM manipulators consists of a fixed and a moving platform coupled together via a number of in-parallel actuators. A closed-form solution is derived for the inverse kinematic problem of a six-degre-of-freedom CKCM manipulator designed to study robotic applications in space. Iterative Newton-Raphson method is employed to solve the forward kinematic problem. Dynamics of the above manipulator is derived using the Lagrangian approach. Computer simulation of the dynamical equations shows that the actuating forces are strongly dependent on the mass and centroid of the robot links.

Elastic properties of spherically anisotropic piezoelectric composites

NASA Astrophysics Data System (ADS)

Wei, En-Bo; Gu, Guo-Qing; Poon, Ying-Ming

2010-09-01

Effective elastic properties of spherically anisotropic piezoelectric composites, whose spherically anisotropic piezoelectric inclusions are embedded in an infinite non-piezoelectric matrix, are theoretically investigated. Analytical solutions for the elastic displacements and the electric potentials under a uniform external strain are derived exactly. Taking into account of the coupling effects of elasticity, permittivity and piezoelectricity, the formula is derived for estimating the effective elastic properties based on the average field theory in the dilute limit. An elastic response mechanism is revealed, in which the effective elastic properties increase as inclusion piezoelectric properties increase and inclusion dielectric properties decrease. Moreover, a piezoelectric response mechanism, of which the effective piezoelectric response vanishes due to the symmetry of spherically anisotropic composite, is also disclosed.

Statistical foundations of liquid-crystal theory

PubMed Central

Seguin, Brian; Fried, Eliot

2013-01-01

We develop a mechanical theory for systems of rod-like particles. Central to our approach is the assumption that the external power expenditure for any subsystem of rods is independent of the underlying frame of reference. This assumption is used to derive the basic balance laws for forces and torques. By considering inertial forces on par with other forces, these laws hold relative to any frame of reference, inertial or noninertial. Finally, we introduce a simple set of constitutive relations to govern the interactions between rods and find restrictions necessary and sufficient for these laws to be consistent with thermodynamics. Our framework provides a foundation for a statistical mechanical derivation of the macroscopic balance laws governing liquid crystals. PMID:23772091

Antibacterial Derivatives of Marine Algae: An Overview of Pharmacological Mechanisms and Applications

PubMed Central

Shannon, Emer; Abu-Ghannam, Nissreen

2016-01-01

The marine environment is home to a taxonomically diverse ecosystem. Organisms such as algae, molluscs, sponges, corals, and tunicates have evolved to survive the high concentrations of infectious and surface-fouling bacteria that are indigenous to ocean waters. Both macroalgae (seaweeds) and microalgae (diatoms) contain pharmacologically active compounds such as phlorotannins, fatty acids, polysaccharides, peptides, and terpenes which combat bacterial invasion. The resistance of pathogenic bacteria to existing antibiotics has become a global epidemic. Marine algae derivatives have shown promise as candidates in novel, antibacterial drug discovery. The efficacy of these compounds, their mechanism of action, applications as antibiotics, disinfectants, and inhibitors of foodborne pathogenic and spoilage bacteria are reviewed in this article. PMID:27110798

Virtual Metrology applied in Run-to-Run Control for a Chemical Mechanical Planarization process

NASA Astrophysics Data System (ADS)

Jebri, M. A.; El Adel, E. M.; Graton, G.; Ouladsine, M.; Pinaton, J.

2017-01-01

This paper deals with missing data in semiconductor manufacturing derived from a measurement sampling strategies. The idea is to construct a virtual metrology module to estimate non measured variables using a new modified Just-In-Time Learning approach (JITL). The aim of this paper is to integrate estimated data into product control loop. In collaboration with our industrial partner STMicroelectronics Rousset, the accuracy of the proposed method is illustrated by using industrial data-sets derived from Chemical Mechanical Planarization (CMP) process that enables us to compare results obtained with the classical and the modified version of JITL approach. Then, the contribution of the estimated data is shown in product quality improvement.

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

PubMed Central

Lamonaca, Palma; Prinzi, Giulia; Kisialiou, Aliaksei; Cardaci, Vittorio; Fini, Massimo; Russo, Patrizia

2017-01-01

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI). PMID:28335527

Reply to "Pericyclic or Pseudopericyclic? The Case of an Allylic Transposition in The Synthesis of a Saccharin Derivative"

ERIC Educational Resources Information Center

Fonseca, Custódia S. C.

2017-01-01

Sigmatropic rearrangement is one of the main classes of pericyclic reactions, which does not necessarily mean that these rearrangements have a pericyclic mechanism. The allylic saccharin derivative O-cinnamylsaccharin can isomerize into N-cinnamylsaccharin in the polar solvent system toluene/triethylamine in a reaction time of 2 h at 110°C. The…

A lactobacillus rhamnosus GG-derived soluble protein, p40, stimulates ligand release from intestinal epithelial cells to transactivate epidermal growth factor receptor

USDA-ARS?s Scientific Manuscript database

Protein p40, a Lactobacillus rhamnosus GG (LGG)-derived soluble protein, ameliorates intestinal injury and colitis, reduces apoptosis and preserves barrier function by activation of EGF receptor (EGFR) in intestinal epithelial cells. The aim of this study was to determine the mechanisms by which p40...

GS-2, a pyrazolo[1,5-a]indole derivative with inhibitory activity of topoisomerases, exerts its potent cytotoxic activity by ROS generation.

PubMed

Ji, Yuan Yuan; Zhu, Yong Ming; Wang, Jian Wen

2013-11-01

Pyrazolo[1,5-a]indole derivatives, a new type of topoisomerase (topo) inhibitor, demonstrate a broad spectrum of antitumor activities. However, the mechanism underlying the induced cytotoxicity remains unclear. In this study, we investigated whether GS-2, one of the derivatives, altered the levels of ROS in breast cancer MDA-231 cells and whether these ROS contributed to the observed antitumoral activity. Our data revealed that GS-2 caused a time- and dose-dependent elevation of intracellular ROS level in MDA-231 cells. GS-2 subsequently elicited notable inhibition on the expression of topos, DNA damage, activation of caspase-3, -9. The loss of mitochondrial membrane potential (MMP) was observed during the induction. The addition of N-acetyl cysteine (NAC, a well-known antioxidant) could effectively attenuate the GS-2-induced ROS enhancement and subsequent apoptosis. NAC attenuated the induced inhibition on expression of topos, indicating that topos might be the target of GS-2-induced ROS. The finding of the induced ROS provides new evidence for the molecular mechanisms of antitumor activity of pyrazolo[1,5-a]indole derivatives. Copyright © 2013 Elsevier B.V. All rights reserved.

Periodontal Biology: Stem Cells, Bmp2 Gene, Transcriptional Enhancers, and Use of Sclerostin Antibody and Pth for Treatment of Periodontal Disease and Bone Loss

PubMed Central

Harris, Stephen E; Rediske, Michael; Neitzke, Rebecca; Rakian, Audrey

2017-01-01

The periodontium is a complex tissue with epithelial components and a complex set of mesodermal derived alveolar bone, cellular and a cellular cementum, and tendon like ligaments (PDL). The current evidence demonstrates that the major pool of periodontal stem cells is derived from a population of micro vascular associated aSMA-positive stem/progenitor (PSC) cells that by lineage tracing form all three major mesodermal derived components of the periodontium. With in vitro aSMA+ stem cells, transcriptome and chip- seq experiments, the gene network and enhancer maps were determined at several differentiation states of the PSC. Current work on the role of the Bmp2 gene in the periodontal stem cell differentiation demonstrated that this Wnt regulated gene, Bmp2, is necessary for differentiation to all three major mesodermal derived component of the periodontium. The mechanism and use of Sclerostin antibody as an activator of Wnt signaling and Bmp2 gene as a potential route to treat craniofacial bone loss is discussed. As well, the mechanism and use of Pth in the treatment of periodontal bone loss or other craniofacial bone loss is presented in this review. PMID:29457146

Ruthenium(II) Complexes Containing Lutidine-Derived Pincer CNC Ligands: Synthesis, Structure, and Catalytic Hydrogenation of C-N bonds.

PubMed

Hernández-Juárez, Martín; López-Serrano, Joaquín; Lara, Patricia; Morales-Cerón, Judith P; Vaquero, Mónica; Álvarez, Eleuterio; Salazar, Verónica; Suárez, Andrés

2015-05-11

A series of Ru complexes containing lutidine-derived pincer CNC ligands have been prepared by transmetalation with the corresponding silver-carbene derivatives. Characterization of these derivatives shows both mer and fac coordination of the CNC ligands depending on the wingtips of the N-heterocyclic carbene fragments. In the presence of tBuOK, the Ru-CNC complexes are active in the hydrogenation of a series of imines. In addition, these complexes catalyze the reversible hydrogenation of phenantridine. Detailed NMR spectroscopic studies have shown the capability of the CNC ligand to be deprotonated and get involved in ligand-assisted activation of dihydrogen. More interestingly, upon deprotonation, the Ru-CNC complex 5 e(BF4 ) is able to add aldimines to the metal-ligand framework to yield an amido complex. Finally, investigation of the mechanism of the hydrogenation of imines has been carried out by means of DFT calculations. The calculated mechanism involves outer-sphere stepwise hydrogen transfer to the C-N bond assisted either by the pincer ligand or a second coordinated H2 molecule. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developmental timing differences underlie armor loss across threespine stickleback populations.

PubMed

Currey, Mark C; Bassham, Susan; Perry, Stephen; Cresko, William A

2017-11-01

Comparing ontogenetic patterns within a well-described evolutionary context aids in inferring mechanisms of change, including heterochronies or deletion of developmental pathways. Because selection acts on phenotypes throughout ontogeny, any within-taxon developmental variation has implications for evolvability. We compare ontogenetic order and timing of locomotion and defensive traits in three populations of threespine stickleback that have evolutionarily divergent adult forms. This analysis adds to the growing understanding of developmental genetic mechanisms of adaptive change in this evolutionary model species by delineating when chondrogenesis and osteogenesis in two derived populations begin to deviate from the developmental pattern in their immediate ancestors. We found that differences in adult defensive morphologies arise through abolished or delayed initiation of these traits rather than via an overall heterochronic shift, that intra-population ontogenetic variation is increased for some derived traits, and that altered armor developmental timing differentiates the derived populations from each other despite parallels in adult lateral plate armor phenotypes. We found that changes in ossified elements of the pelvic armor are linked to delayed and incomplete development of an early-forming pelvic cartilage, and that this disruption likely presages the variable pelvic vestiges documented in many derived populations. © 2017 Wiley Periodicals, Inc.

Synthesis of α,ω-polyfluorinated α-amino acid derivatives and δ,δ-difluoronorvaline.

PubMed

Ulbrich, Dirk; Daniliuc, Constantin G; Haufe, Günter

2016-03-07

Intending to synthesize ω,ω-difluoroalkyl amino acid derivatives by oxidative desulfurization-fluorination reactions of suitable arylthio-2-phthalimido butanoates and pentanoates, in addition to small amounts of the target products, mainly α,ω-polyfluorinated amino acid derivatives were formed by additional sulfur-assisted α-fluorination. This novel structural motif was verified spectroscopically as well as by X-ray analysis. A plausible mechanism of formation is suggested. Using a different approach, δ,δ-difluoronorvaline hydrochloride was synthesized with at least 36% enantiomeric excess via deoxofluorination of the corresponding aldehyde.

Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

PubMed

Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

2018-01-01

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

Reproducibility of Echocardiograph-Derived Multilevel Left Ventricular Apical Twist Mechanics.

PubMed

Stewart, Glenn M; Yamada, Akira; Kavanagh, Justin J; Haseler, Luke J; Chan, Jonathan; Sabapathy, Surendran

2016-02-01

Left ventricular (LV) twist mechanics are routinely assessed via echocardiography in clinical and research trials investigating the function of obliquely oriented myocardial fibers. However, echocardiograph-derived measures of LV twist may be compromised by nonstandardized acquisition of the apical image. This study examined the reproducibility of echocardiograph-derived parameters of apical twist mechanics at multiple levels of the apical myocardium. Two sets of 2D LV parasternal short-axis images were obtained in 30 healthy subjects (24 men; 19-57 year) via echocardiography. Images were acquired immediately distal to the papillary muscles (apical image 1), immediately above the point of LV cavity obliteration at end systole (apical image 3), and midway between apical image 1 and apical image 3 (apical image 2). Repeat scans were performed within 1 hour, and twist mechanics (rotation and rotation rate) were calculated via frame-by-frame tracking of natural acoustic echocardiographic markers (speckle tracking). The magnitude of apical rotation increased progressively toward the apex (apical image 1: 4.2 ± 2.1°, apical image 2: 7.2 ± 3.9°, apical image 3: 11.8 ± 4.6°). apical images 1, 2, and 3 each had moderate to good correlations between repeat scans (ICC: 0.531-0.856). When apical images 1, 2, and 3 were averaged, rotation was 7.7 ± 2.7° and between-scan correlation was excellent (ICC: 0.910). Similar results were observed for systolic and diastolic rotation rates. Averaging multiple standardized apical images, tending progressively toward the apex, generated the most reproducible rotation indices and may be optimal for the assessment of LV twist mechanics across therapeutic, interventional, and research studies; however, care should be taken given the influence of acquisition level on the magnitude of apical rotation. © 2015, Wiley Periodicals, Inc.

Role of integrin-linked kinase in regulating phosphorylation of Akt and fibroblast survival in type I collagen matrices through a beta1 integrin viability signaling pathway.

PubMed

Nho, Richard Seonghun; Xia, Hong; Kahm, Judy; Kleidon, Jill; Diebold, Deanna; Henke, Craig A

2005-07-15

A beta1 integrin phosphatidylinositol 3-kinase/Akt pathway regulates fibroblast survival in collagen matrices. When fibroblasts attach to collagen, Akt becomes phosphorylated, providing a survival signal. In contrast, in response to mechanical forces generated during collagen contraction, Akt is dephosphorylated and fibroblasts undergo apoptosis. The kinase(s) responsible for regulating Akt phosphorylation in response to matrix-derived mechanical signals are unclear. Integrin-linked kinase (ILK) is associated with the beta1 integrin in the focal adhesion complex and as such is a candidate kinase that may regulate Akt phosphorylation and fibroblast viability. Nevertheless, there is no direct evidence that matrix-derived mechanical forces regulate cell viability by modulating ILK activity. Here, we show that ILK activity decreased in response to collagen matrix contraction, which correlated with Akt dephosphorylation and induction of fibroblast apoptosis. In contrast, enforced activation of beta1 integrin by activating antibody preserved ILK and Akt activity during collagen matrix contraction, and this is associated with protection from collagen contraction-induced apoptosis. Knock-down of ILK by small, interfering RNA (siRNA) attenuated Akt phosphorylation in response to ligation of beta1 integrin by collagen or activating antibody and enhanced fibroblast apoptosis in response to collagen contraction. Kinase dead ILK attenuated Akt phosphorylation and enhanced fibroblast apoptosis, whereas hyperactive and wild type ILK augmented Akt phosphorylation and protected fibroblasts from apoptosis. Constitutively active Akt preserved Akt activity and rescued ILK siRNA-treated fibroblasts from collagen contraction-induced apoptosis. These data establish that matrix-derived mechanical forces sensed by beta1 integrin are capable of modulating ILK activity which regulates fibroblast viability via an Akt-dependent mechanism.

Effect of fractionated extracts and isolated pure compounds of Spondias mombin (L. Anacardiaceae) leaves on novelty-induced rearing and grooming behaviours in mice.

PubMed

Ayoka, Abiodun O; Owolabi, Rotimi A; Bamitale, Samuel K; Akomolafe, Rufus O; Aladesanmi, Joseph A; Ukponmwan, Eghe O

2013-01-01

This study attempted to elucidate the neurotransmitter systems involved in the neurophysiological properties of ethanolic extract, fractions and pure isolates of Spondias mombin leaves in mice (n = 6) after intraperitoneal (i.p.) route of administration.The crude ethanolic extract of Spondian mombin leaves was fractionated using the partitioning method to obtain the ethylacetate, butanolic and aqueous fractions. Open column chromatographic fractionation of the ethylacetate fraction yielded seven sub-fractions, out of which the pure coumaroyl, quercetin and gallic acid derivatives were obtained after purification on Sephadex LH 20. The ethanolic extract, butanolic fraction, ethylacetate subfractions and pure isolates of the Spondian mombin leaves were tested on novelty-induced rearing and grooming behaviours in mice with standard pharmacological tools using the open field method. The extract and its fractions decreased novelty-induced rearing in a dose-dependent manner. While the Coumaroyl derivative had no effect on novelty-induced rearing, it significantly reversed the inhibitory effect of yohimbine, propranolol and haloperidol on novelty-induced rearing. Quercetin significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone significantly potentiated the quercetin-induced suppression of novelty-induced rearing. Gallic acid derivative significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone, atropine and haloperidol pretreatments significantly potentiated gallic acid derivative-induced suppression of novelty-induced rearing.The extract and its fractions had biphasic effect on novelty-induced grooming in mice. Coumaroyl derivative significantly increased novelty-induced grooming, while quercetin and gallic acid derivative decreased novelty-induced grooming significantly. The three pure isolates significantly reversed the effects of yohimbine and atropine on the novelty-induced grooming in mice. Propranolol-induced increase in novelty-induced grooming was significantly reversed by coumaroyl and gallic acid derivatives. Pre-treatment with naloxone significantly increased the gallic acid derivative-induced suppression of novelty-induced grooming. Pre-treatment with haloperidol reversed the effect of coumaroyl derivative and potentiated the inhibitory effect of quercetin derivative and gallic acid derivative significantly. This study suggested that adrenergic and dopaminergic neuro-transmissions are strongly involved in the neural mechanisms of the effect of the three pure isolates derivative, while opioid neuro-transmission is strongly linked with the neural mechanism of behavioural effect of coumaroyl derivative.

Adipose-derived stem cell-derived microvesicle-released miR-210 promoted proliferation, migration and invasion of endothelial cells by regulating RUNX3.

PubMed

Zheng, Zeqi; Liu, Lijuan; Zhan, Yuliang; Yu, Songping; Kang, Ting

2018-06-18

To explore the potential mechanism of miRNA released from adipose-derived stem cell (ADSC)-derived micro vesicle (MV) on the modulation of proliferation, migration and invasion of endothelial cells. miR-210 level was detected by qT-PCR. Alix, VEGF and RUNX3 expressions were detected by Western blot. The proliferation, migration and invasion of human umbilical vein endothelial cells (HUVECs) were observed by MTT assay and Transwell assay. Luciferase reporter gene assay was conducted to validate the targeting activity of MVs-released miR-210 on RUNX3. Hypoxia significantly increased the expression of MVs-released miR-210. MVs released from ADSCs in hypoxic group significantly promoted the proliferation, migration and invasion of HUVECs. Overexpression of miR-210 significantly upregulated VEGF expression, and promoted the proliferation, migration and invasion of HUVECs. Besides, RUNX3 was identified as the direct of miR-210 in HUVECs. Overexpression of miR-210 decreased RUNX3 expression and promoted the proliferation, migration and invasion of HUVECs, while overexpression of RUNX3 inhibited these promotion effects. In vivo experiment showed that MVs derived from ADSCs under hypoxia increased miR-210 level and capillary density, and inhibition of miR-210 decreased capillary density. We also found MVs downregulated RUNX3 expression, and inhibition of miR-210 upregulated RUNX3 expression. miR-210 released from ADSCs-derived MVs promoted proliferation, migration and invasion of HUVECs by targeting RUNX3, which revealed one of the mechanisms of ADSCs-derived MVs on the promotion of proliferation, migration and invasion of HUVECs.

Induction of anaplastic lymphoma kinase (ALK) as a novel mechanism of EGFR inhibitor resistance in head and neck squamous cell carcinoma patient-derived models.

PubMed

Ouyang, Xiaoming; Barling, Ashley; Lesch, Aletha; Tyner, Jeffrey W; Choonoo, Gabrielle; Zheng, Christina; Jeng, Sophia; West, Toni M; Clayburgh, Daniel; Courtneidge, Sara A; McWeeney, Shannon K; Kulesz-Martin, Molly

2018-06-01

Head and neck squamous cell carcinoma (HNSCC) currently only has one FDA-approved cancer intrinsic targeted therapy, the epidermal growth factor receptor (EGFR) inhibitor cetuximab, to which only approximately 10% of tumors are sensitive. In order to extend therapy options, we subjected patient-derived HNSCC cells to small-molecule inhibitor and siRNA screens, first, to find effective combination therapies with an EGFR inhibitor, and second, to determine a potential mechanistic basis for repurposing the FDA approved agents for HNSCC. The combinations of EGFR inhibitor with anaplastic lymphoma kinase (ALK) inhibitors demonstrated synergy at the highest ratio in our cohort, 4/8 HNSCC patients' derived tumor cells, and this corresponded with an effectiveness of siRNA targeting ALK combined with the EGFR inhibitor gefitinib. Co-targeting EGFR and ALK decreased HNSCC cell number and colony formation ability and increased annexin V staining. Because ALK expression is low and ALK fusions are infrequent in HNSCC, we hypothesized that gefitinib treatment could induce ALK expression. We show that ALK expression was induced in HNSCC patient-derived cells both in 2D and 3D patient-derived cell culture models, and in patient-derived xenografts in mice. Four different ALK inhibitors, including two (ceritinib and brigatinib) FDA approved for lung cancer, were effective in combination with gefitinib. Together, we identified induction of ALK by EGFR inhibitor as a novel mechanism potentially relevant to resistance to EGFR inhibitor, a high ratio of response of HNSCC patient-derived tumor cells to a combination of ALK and EGFR inhibitors, and applicability of repurposing ALK inhibitors to HNSCC that lack ALK aberrations.

Isolation and expansion of human pluripotent stem cell-derived hepatic progenitor cells by growth factor defined serum-free culture conditions.

PubMed

Fukuda, Takayuki; Takayama, Kazuo; Hirata, Mitsuhi; Liu, Yu-Jung; Yanagihara, Kana; Suga, Mika; Mizuguchi, Hiroyuki; Furue, Miho K

2017-03-15

Limited growth potential, narrow ranges of sources, and difference in variability and functions from batch to batch of primary hepatocytes cause a problem for predicting drug-induced hepatotoxicity during drug development. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells in vitro are expected as a tool for predicting drug-induced hepatotoxicity. Several studies have already reported efficient methods for differentiating hPSCs into hepatocyte-like cells, however its differentiation process is time-consuming, labor-intensive, cost-intensive, and unstable. In order to solve this problem, expansion culture for hPSC-derived hepatic progenitor cells, including hepatic stem cells and hepatoblasts which can self-renewal and differentiate into hepatocytes should be valuable as a source of hepatocytes. However, the mechanisms of the expansion of hPSC-derived hepatic progenitor cells are not yet fully understood. In this study, to isolate hPSC-derived hepatic progenitor cells, we tried to develop serum-free growth factor defined culture conditions using defined components. Our culture conditions were able to isolate and grow hPSC-derived hepatic progenitor cells which could differentiate into hepatocyte-like cells through hepatoblast-like cells. We have confirmed that the hepatocyte-like cells prepared by our methods were able to increase gene expression of cytochrome P450 enzymes upon encountering rifampicin, phenobarbital, or omeprazole. The isolation and expansion of hPSC-derived hepatic progenitor cells in defined culture conditions should have advantages in terms of detecting accurate effects of exogenous factors on hepatic lineage differentiation, understanding mechanisms underlying self-renewal ability of hepatic progenitor cells, and stably supplying functional hepatic cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular Docking Studies of Catechin and Its Derivatives as Anti-bacterial Inhibitor for Glucosamine-6-Phosphate Synthase

NASA Astrophysics Data System (ADS)

Fikrika, H.; Ambarsari, L.; Sumaryada, T.

2016-01-01

Molecular docking simulation of catechin and its derivatives on Glucosamine-6- Phosphate Synthase (GlmS) has been performed in this research. GlmS inhibition by a particular ligand will suppress the production of bacterial cell wall and significantly reduce the population of invading bacteria. In this study, catechin derivatives i.e epicatechin, galloatechin and epigalloatechin were found to have stronger binding affinities as compared to natural ligand of GlmS, Fructose-6-Phosphate (F6P). Those three ligands were docked on the same pocket in GlmS target as F6P, with 70% binding sites similarity. Based on the docking results, gallocatechin turns out to be the most potent ligand for anti-bacterial agent with ΔG= -8.00 kcal/mol. The docking between GlmS and catechin derivatives are characterized by a constant present of a strong hydrogen bond between functional group O3 and Ser-349. This hydrogen bond most likely plays a significant role in the docking mechanism and binding modes selection. The surprising result is catechin itself exhibited a quite strong binding with GlmS (ΔG= -7.80 kcal.mol), but docked on a completely different pocket compared to other ligands. This results suggest that catechin might still have a curing effect but with a completely different pathway and mechanism as compared to its derivatives.

The galvanizing of Mycobacterium tuberculosis: An antimicrobial mechanism

PubMed Central

Russell, David G

2011-01-01

Summary Evolving under constant threat from invading microbes, macrophages have acquired multiple means of killing bacteria. In this issue of Cell Host & Microbe, Botella and colleagues describe a novel anti-microbial mechanism based on elevated levels of intraphagosomal Zn2+ and the corresponding induction of bacterial genes to ameliorate this host-derived stress. PMID:21925106

Shh-ushing Midline Crossing through Remote Protein Transport.

PubMed

Herrera, Eloísa; Sitko, Austen A; Bovolenta, Paola

2018-01-17

Shh contributes to neural circuit formation with different mechanisms. In this issue, Peng and colleagues (2018) identify a novel trans-axonal mechanism by which Shh derived from contralateral projecting retinal ganglion cells prevents midline crossing of Boc-expressing ipsilateral axons at the optic chiasm. Copyright © 2018 Elsevier Inc. All rights reserved.

Quasivelocities and Optimal Control for underactuated Mechanical Systems

NASA Astrophysics Data System (ADS)

Colombo, L.; de Diego, D. Martín

2010-07-01

This paper is concerned with the application of the theory of quasivelocities for optimal control for underactuated mechanical systems. Using this theory, we convert the original problem in a variational second-order lagrangian system subjected to constraints. The equations of motion are geometrically derived using an adaptation of the classical Skinner and Rusk formalism.

View Combination: A Generalization Mechanism for Visual Recognition

ERIC Educational Resources Information Center

Friedman, Alinda; Waller, David; Thrash, Tyler; Greenauer, Nathan; Hodgson, Eric

2011-01-01

We examined whether view combination mechanisms shown to underlie object and scene recognition can integrate visual information across views that have little or no three-dimensional information at either the object or scene level. In three experiments, people learned four "views" of a two dimensional visual array derived from a three-dimensional…

Quasivelocities and Optimal Control for underactuated Mechanical Systems

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

Colombo, L.; Martin de Diego, D.

2010-07-28

This paper is concerned with the application of the theory of quasivelocities for optimal control for underactuated mechanical systems. Using this theory, we convert the original problem in a variational second-order lagrangian system subjected to constraints. The equations of motion are geometrically derived using an adaptation of the classical Skinner and Rusk formalism.

Ontology-based Vaccine and Drug Adverse Event Representation and Theory-guided Systematic Causal Network Analysis toward Integrative Pharmacovigilance Research

PubMed Central

He, Yongqun

2016-01-01

Compared with controlled terminologies (e.g., MedDRA, CTCAE, and WHO-ART), the community-based Ontology of AEs (OAE) has many advantages in adverse event (AE) classifications. The OAE-derived Ontology of Vaccine AEs (OVAE) and Ontology of Drug Neuropathy AEs (ODNAE) serve as AE knowledge bases and support data integration and analysis. The Immune Response Gene Network Theory explains molecular mechanisms of vaccine-related AEs. The OneNet Theory of Life treats the whole process of a life of an organism as a single complex and dynamic network (i.e., OneNet). A new “OneNet effectiveness” tenet is proposed here to expand the OneNet theory. Derived from the OneNet theory, the author hypothesizes that one human uses one single genotype-rooted mechanism to respond to different vaccinations and drug treatments, and experimentally identified mechanisms are manifestations of the OneNet blueprint mechanism under specific conditions. The theories and ontologies interact together as semantic frameworks to support integrative pharmacovigilance research. PMID:27458549

Gravitational radiation from compact binary systems in screened modified gravity

NASA Astrophysics Data System (ADS)

Zhang, Xing; Liu, Tan; Zhao, Wen

2017-05-01

Screened modified gravity (SMG) is a kind of scalar-tensor theory with screening mechanisms, which can suppress the fifth force in dense regions and allow theories to evade the solar system and laboratory tests. In this paper, we investigate how the screening mechanisms in SMG affect the gravitational radiation damping effects, calculate in detail the rate of the energy loss due to the emission of tensor and scalar gravitational radiations, and derive their contributions to the change in the orbital period of the binary system. We find that the scalar radiation depends on the screened parameters and the propagation speed of scalar waves, and the scalar dipole radiation dominates the orbital decay of the binary system. For strongly self-gravitating bodies, all effects of scalar sector are strongly suppressed by the screening mechanisms in SMG. By comparing our results to observations of binary system PSR J 1738 +0333 , we place the stringent constraints on the screening mechanisms in SMG. As an application of these results, we focus on three specific models of SMG (chameleon, symmetron, and dilaton), and derive the constraints on the model parameters, respectively.

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

Bonding strength of glass-ceramic trabecular-like coatings to ceramic substrates for prosthetic applications.

PubMed

Chen, Qiang; Baino, Francesco; Pugno, Nicola M; Vitale-Brovarone, Chiara

2013-04-01

A new approach based on the concepts of quantized fracture mechanics (QFM) is presented and discussed in this paper to estimate the bonding strength of trabecular-like coatings, i.e. glass-ceramic scaffolds mimicking the architecture of cancellous bone, to ceramic substrates. The innovative application of glass-derived scaffolds as trabecular-like coatings is proposed in order to enhance the osteointegration of prosthetic ceramic devices. The scaffolds, prepared by polymeric sponge replication, are joined to alumina substrates by a dense glass-ceramic coating (interlayer) and the so-obtained 3-layer constructs are investigated from micro-structural, morphological and mechanical viewpoints. In particular, the fracture strengths of three different crack propagation modes, i.e. glass-derived scaffold fracture, interface delamination or mixed fracture, are predicted in agreement with those of experimental mechanical tests. The approach proposed in this work could have interesting applications towards an ever more rational design of bone tissue engineering biomaterials and coatings, in view of the optimization of their mechanical properties for making them actually suitable for clinical applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Mechanism for excitation-dependent photoluminescence from graphene quantum dots and other graphene oxide derivates: consensus, debates and challenges

NASA Astrophysics Data System (ADS)

Gan, Zhixing; Xu, Hao; Hao, Yanling

2016-04-01

Luminescent nanomaterials, with wide applications in biosensing, bioimaging, illumination and display techniques, have been consistently garnering enormous research attention. In particular, those with wavelength-controllable emissions could be highly beneficial. Carbon nanostructures, including graphene quantum dots (GQDs) and other graphene oxide derivates (GODs), with excitation-dependent photoluminescence (PL), which means their fluorescence color could be tuned simply by changing the excitation wavelength, have attracted lots of interest. However the intrinsic mechanism for the excitation-dependent PL is still obscure and fiercely debated presently. In this review, we attempt to summarize the latest efforts to explore the mechanism, including the quantum confinement effect, surface traps model, giant red-edge effect, edge states model and electronegativity of heteroatom model, as well as the newly developed synergistic model, to seek some clues to unravel the mechanism. Meanwhile the controversial difficulties for each model are further discussed. Besides this, the challenges and potential influences of the synthetic methodology and development of the materials are illustrated extensively to elicit more thought and constructive attempts toward their application.

Immobilization of PMIDA on Fe3O4 magnetic nanoparticles surface: Mechanism of bonding

NASA Astrophysics Data System (ADS)

Demin, Alexander M.; Mekhaev, Alexander V.; Esin, Alexander A.; Kuznetsov, Dmitry K.; Zelenovskiy, Pavel S.; Shur, Vladimir Ya.; Krasnov, Victor P.

2018-05-01

The mechanism of N-phosphonomethyl iminodiacetic acid (PMIDA) binding with the Fe3O4 magnetic nanoparticle (MNPs) surface by Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetry was comprehensive studied. To study of microstructure, size and core structure of synthesized nanoparticles the scanning electron microscopy, X-ray diffraction analysis and Raman spectroscopy were carried out. A new scheme for the tridentate bonding of the phosphonomethyl derivative with surface Fe atoms involving unequal Psbnd Osbnd Fe bonds was proposed. The mechanism of thermal decomposition of PMIDA molecules on the MNP surface was studied using a thermogravimetric analyzer combined with infrared spectrometer. It was shown for the first time that during the thermal treatment of phosphonomethyl-modified MNPs, PMIDA molecules are not desorbed from the surface of MNPs but gradually decompose. We believe that obtained in this work data will be useful for a deeper understanding of the mechanisms of phosphonic acid derivatives interaction with MNPs, as well as in the design of new biomedical materials, in which the conjugation of biomolecules with carboxyl groups of PMIDA-modified MNPs is assumed.

[Opportunistic pathogen Candida glabrata and the mechanisms of its resistance to antifungal drugs].

PubMed

Berila, N; Subík, J

2010-04-01

Treatment of not only bacterial but also fungal infections is currently a growing concern. A major reason is the acquisition of multidrug resistance in both prokaryotic and human cells. The multidrug resistance phenotype is a cellular response to the presence of cytotoxic substances in the environment. The basic mechanism of multidrug resistance is overexpression of the membrane proteins involved in the extrusion of toxic substances outside the cell. The resistance mechanism based on the efflux of inhibitors as a result of the overproduction of transport proteins was also observed in some plant and animal pathogens and human tumour cells. The phenomenon of multidrug resistance associated with an excessive and long-term use of antifungals, in particular of azole derivatives, was also confirmed in the yeast Candida glabrata which is becoming a growing concern for health care professionals. Reduced susceptibility to azole derivatives in particular, a high potential for adapting to stressors, and multiple mechanisms of resistance to structurally and functionally unrelated antifungal drugs make the species C. glabrata a potential threat to hospital patients.

Hair Follicle-Derived Smooth Muscle Cells and Small Intestinal Submucosa for Engineering Mechanically Robust and Vasoreactive Vascular Media

PubMed Central

Peng, Hao-Fan; Liu, Jin Yu

2011-01-01

Our laboratory recently reported a new source of smooth muscle cells (SMCs) derived from hair follicle (HF) mesenchymal stem cells. HF-SMCs demonstrated high proliferation and clonogenic potential as well as contractile function. In this study, we aimed at engineering the vascular media using HF-SMCs and a natural biomaterial, namely small intestinal submucosa (SIS). Engineering functional vascular constructs required application of mechanical force, resulting in actin reorganization and cellular alignment. In turn, cell alignment was necessary for development of receptor- and nonreceptor-mediated contractility as soon as 24 h after cell seeding. Within 2 weeks in culture, the cells migrated into SIS and secreted collagen and elastin, the two major extracellular matrix components of the vessel wall. At 2 weeks, vascular reactivity increased significantly up to three- to fivefold and mechanical properties were similar to those of native ovine arteries. Taken together, our data demonstrate that the combination of HF-SMCs with SIS resulted in mechanically strong, biologically functional vascular media with potential for arterial implantation. PMID:21083418

Quantum Hamilton equations of motion for bound states of one-dimensional quantum systems

NASA Astrophysics Data System (ADS)

Köppe, J.; Patzold, M.; Grecksch, W.; Paul, W.

2018-06-01

On the basis of Nelson's stochastic mechanics derivation of the Schrödinger equation, a formal mathematical structure of non-relativistic quantum mechanics equivalent to the one in classical analytical mechanics has been established in the literature. We recently were able to augment this structure by deriving quantum Hamilton equations of motion by finding the Nash equilibrium of a stochastic optimal control problem, which is the generalization of Hamilton's principle of classical mechanics to quantum systems. We showed that these equations allow a description and numerical determination of the ground state of quantum problems without using the Schrödinger equation. We extend this approach here to deliver the complete discrete energy spectrum and related eigenfunctions for bound states of one-dimensional stationary quantum systems. We exemplify this analytically for the one-dimensional harmonic oscillator and numerically by analyzing a quartic double-well potential, a model of broad importance in many areas of physics. We furthermore point out a relation between the tunnel splitting of such models and mean first passage time concepts applied to Nelson's diffusion paths in the ground state.

Energetic composite and system with enhanced mechanical sensitivity to initiation of self-sustained reaction

DOEpatents

Gash, Alexander E [Brentwood, CA; Barbee, Jr., Troy W.

2012-05-29

An energetic composition and system using amassed energetic multilayer pieces which are formed from the division, such as for example by cutting, scoring, breaking, crushing, shearing, etc., of a mechanically activatable monolithic energetic multilayer(s) (e.g. macro-scale sheets of multilayer films), for enhancing the sensitivity of the energetic composite and system to mechanical initiation of self-sustained reaction. In particular, mechanical initiation of the energetic composition may be achieved with significantly lower mechanical energy inputs than that typically required for initiating the monolithic energetic multilayers from which it is derived.

Theoretical Fluid Mechanics

NASA Astrophysics Data System (ADS)

Fitzpatrick, Richard

2017-12-01

'Theoretical Fluid Mechanics' has been written to aid physics students who wish to pursue a course of self-study in fluid mechanics. It is a comprehensive, completely self-contained text with equations of fluid mechanics derived from first principles, and any required advanced mathematics is either fully explained in the text, or in an appendix. It is accompanied by about 180 exercises with completely worked out solutions. It also includes extensive sections on the application of fluid mechanics to topics of importance in astrophysics and geophysics. These topics include the equilibrium of rotating, self-gravitating, fluid masses; tidal bores; terrestrial ocean tides; and the Eddington solar model.

Compendium of Mechanical Limit-States

NASA Technical Reports Server (NTRS)

Kowal, Michael

1996-01-01

A compendium was compiled and is described to provide a diverse set of limit-state relationships for use in demonstrating the application of probabilistic reliability methods to mechanical systems. The different limit-state relationships can be used to analyze the reliability of a candidate mechanical system. In determining the limit-states to be included in the compendium, a comprehensive listing of the possible failure modes that could affect mechanical systems reliability was generated. Previous literature defining mechanical modes of failure was studied, and cited failure modes were included. From this, classifications for failure modes were derived and are described in some detail.

Hypopigmenting Effects of Brown Algae-Derived Phytochemicals: A Review on Molecular Mechanisms

PubMed Central

Azam, Mohammed Shariful; Choi, Jinkyung; Lee, Min-Sup; Kim, Hyeung-Rak

2017-01-01

There is a rapid increase in the demand for natural hypopigmenting agents from marine sources for cosmeceutical and pharmaceutical applications. Currently, marine macroalgae are considered as a safe and effective source of diverse bioactive compounds. Many research groups are exploring marine macroalgae to discover and characterize novel compounds for cosmeceutical, nutraceutical, and pharmaceutical applications. Many types of bioactive secondary metabolites from marine algae, including phlorotannins, sulfated polysaccharides, carotenoids, and meroterpenoids, have already been documented for their potential applications in the pharmaceutical industry. Among these metabolites, phlorotannins from brown algae have been widely screened for their pharmaceutical and hypopigmenting effects. Unfortunately, the majority of these articles did not have detailed investigations on molecular targets, which is critical to fulfilling the criteria for their cosmeceutical and pharmaceutical use. Very recently, a few meroterpenoids have been discovered from Sargassum sp., with the examination of their anti-melanogenic properties and mechanisms. Despite the scarcity of in vivo and clinical investigations of molecular mechanistic events of marine algae-derived hypopigmenting agents, identifying the therapeutic targets and their validation in humans has been a major challenge for future studies. In this review, we focused on available data representing molecular mechanisms underlying hypopigmenting properties of potential marine brown alga-derived compounds. PMID:28946635

Tocotrienol prevents AAPH-induced neurite degeneration in neuro2a cells.

PubMed

Fukui, Koji; Sekiguchi, Hidekazu; Takatsu, Hirokatsu; Koike, Taisuke; Koike, Tatsuro; Urano, Shiro

2013-01-01

Reactive oxygen species induce neurite degeneration before inducing cell death. However, the degenerative mechanisms have not yet been elucidated. While tocotrienols have a known neuroprotective function, the underlying mechanism remains unclear and may or may not involve antioxidant action. In this study, we hypothesize that free radical-derived membrane injury is one possible mechanism for inducing neurite degeneration. Therefore, we examined the potential neuroprotective effect of tocotrienols mediated through its antioxidant activity. Mouse neuroblastoma neuro2a cells were used to examine the effect of the water-soluble free radical generator 2,2'-azobis(2-methylpropionamide) dihydrochloride (AAPH) on neurite dynamics. After 24 hours of AAPH treatment, cell viability, neurite number, and the number of altered neurites were measured in the presence or absence of α-tocotrienol. Treatment of neuro2a cells with a low concentration of AAPH induces neurite degeneration, but not cell death. Treatment with 5 µM α-tocotrienol significantly inhibited neurite degeneration in AAPH-treated neuro2a cells. Furthermore, morphological changes in AAPH-treated neuro2a cells were similar to those observed with colchicine treatment. α-Tocotrienol may scavenge AAPH-derived free radicals and alkoxyl radicals that are generated from AAPH-derived peroxyl radicals on cell membranes. Therefore, α-tocotrienol may have a neuroprotective effect mediated by its antioxidant activity.

Bio-oil from fast pyrolysis of lignin: Effects of process and upgrading parameters.

PubMed

Fan, Liangliang; Zhang, Yaning; Liu, Shiyu; Zhou, Nan; Chen, Paul; Cheng, Yanling; Addy, Min; Lu, Qian; Omar, Muhammad Mubashar; Liu, Yuhuan; Wang, Yunpu; Dai, Leilei; Anderson, Erik; Peng, Peng; Lei, Hanwu; Ruan, Roger

2017-10-01

Effects of process parameters on the yield and chemical profile of bio-oil from fast pyrolysis of lignin and the processes for lignin-derived bio-oil upgrading were reviewed. Various process parameters including pyrolysis temperature, reactor types, lignin characteristics, residence time, and feeding rate were discussed and the optimal parameter conditions for improved bio-oil yield and quality were concluded. In terms of lignin-derived bio-oil upgrading, three routes including pretreatment of lignin, catalytic upgrading, and co-pyrolysis of hydrogen-rich materials have been investigated. Zeolite cracking and hydrodeoxygenation (HDO) treatment are two main methods for catalytic upgrading of lignin-derived bio-oil. Factors affecting zeolite activity and the main zeolite catalytic mechanisms for lignin conversion were analyzed. Noble metal-based catalysts and metal sulfide catalysts are normally used as the HDO catalysts and the conversion mechanisms associated with a series of reactions have been proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Altered proliferation and networks in neural cells derived from idiopathic autistic individuals.

PubMed

Marchetto, Maria C; Belinson, Haim; Tian, Yuan; Freitas, Beatriz C; Fu, Chen; Vadodaria, Krishna; Beltrao-Braga, Patricia; Trujillo, Cleber A; Mendes, Ana P D; Padmanabhan, Krishnan; Nunez, Yanelli; Ou, Jing; Ghosh, Himanish; Wright, Rebecca; Brennand, Kristen; Pierce, Karen; Eichenfield, Lawrence; Pramparo, Tiziano; Eyler, Lisa; Barnes, Cynthia C; Courchesne, Eric; Geschwind, Daniel H; Gage, Fred H; Wynshaw-Boris, Anthony; Muotri, Alysson R

2017-06-01

Autism spectrum disorders (ASD) are common, complex and heterogeneous neurodevelopmental disorders. Cellular and molecular mechanisms responsible for ASD pathogenesis have been proposed based on genetic studies, brain pathology and imaging, but a major impediment to testing ASD hypotheses is the lack of human cell models. Here, we reprogrammed fibroblasts to generate induced pluripotent stem cells, neural progenitor cells (NPCs) and neurons from ASD individuals with early brain overgrowth and non-ASD controls with normal brain size. ASD-derived NPCs display increased cell proliferation because of dysregulation of a β-catenin/BRN2 transcriptional cascade. ASD-derived neurons display abnormal neurogenesis and reduced synaptogenesis leading to functional defects in neuronal networks. Interestingly, defects in neuronal networks could be rescued by insulin growth factor 1 (IGF-1), a drug that is currently in clinical trials for ASD. This work demonstrates that selection of ASD subjects based on endophenotypes unraveled biologically relevant pathway disruption and revealed a potential cellular mechanism for the therapeutic effect of IGF-1.

Recent Advances in Nanocomposite Materials of Graphene Derivatives with Polysaccharides

PubMed Central

Terzopoulou, Zoi; Kyzas, George Z.; Bikiaris, Dimitrios N.

2015-01-01

This review article presents the recent advances in syntheses and applications of nanocomposites consisting of graphene derivatives with various polysaccharides. Graphene has recently attracted much interest in the materials field due to its unique 2D structure and outstanding properties. To follow, the physical and mechanical properties of graphene are then introduced. However it was observed that the synthesis of graphene-based nanocomposites had become one of the most important research frontiers in the application of graphene. Therefore, this review also summarizes the recent advances in the synthesis of graphene nanocomposites with polysaccharides, which are abundant in nature and are easily synthesized bio-based polymers. Polysaccharides can be classified in various ways such as cellulose, chitosan, starch, and alginates, each group with unique and different properties. Alginates are considered to be ideal for the preparation of nanocomposites with graphene derivatives due to their environmental-friendly potential. The characteristics of such nanocomposites are discussed here and are compared with regard to their mechanical properties and their various applications. PMID:28787964

From phenothiazine to 3-phenyl-1,4-benzothiazine derivatives as inhibitors of the Staphylococcus aureus NorA multidrug efflux pump.

PubMed

Sabatini, Stefano; Kaatz, Glenn W; Rossolini, Gian Maria; Brandini, David; Fravolini, Arnaldo

2008-07-24

Overexpression of efflux pumps is an important mechanism by which bacteria evade effects of substrate antimicrobial agents and inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus multidrug efflux pump, the activity of which confers decreased susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 1,4-benzothiazine derivatives were designed and synthesized as a minimized structural template of phenothiazine MDR efflux pump inhibitors (EPIs) in an effort to identify more potent S. aureus NorA EPIs. Almost all derivatives evaluated showed good activity in combination with ciprofloxacin against S. aureus ATCC 25923; some were capable of completely restoring ciprofloxacin activity in a norA-overexpressing strain (SA-K2378). Compounds 6k and 7j displayed good activity against SA-1199B, a strain that also overexpresses norA, in an ethidium bromide (EtBr) efflux inhibition assay.

Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain.

PubMed

Nordberg, Rachel C; Bodle, Josie C; Loboa, Elizabeth G

2018-01-01

It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.

Live cell imaging reveals different modes of cytotoxic action of extracts derived from commonly used luting cements.

PubMed

Trumpaitė-Vanagienė, Rita; Čebatariūnienė, Alina; Tunaitis, Virginijus; Pūrienė, Alina; Pivoriūnas, Augustas

2018-02-01

To compare cytotoxicity of extracts derived from commonly used luting cements: Hoffmann's Zinc Phosphate (ZPC), GC Fuji Plus Resin Modified Glass Ionomer (RMGIC) and 3M ESPE RelyX Unicem Resin Cement (RC) on primary human gingival fibroblasts (HGFs). HGFs were exposed to different concentrations of the ZPC, RMGIC and RC extracts. The cytotoxicity was assessed with the PrestoBlue Cell Viability Reagent and viable cells were counted by a haemocytometer using the trypan blue exclusion test. In order to determine the primary mechanism of the cell death induced by extracts from different luting cements, the real-time monitoring of caspase-3/-7 activity and membrane integrity of cells was employed. The extracts from the RMGIC and ZPC decreased the metabolic activity and numbers of viable cells. Unexpectedly, the extracts from the RC evoked only small effects on the metabolic activity of HGFs with a decreasing number of viable cells in a dose-and time-dependent manner. The live cell imaging revealed that the apoptosis was the primary mechanism of a cell death induced by the extracts derived from the RMGIC, whereas the extracts from the RC and ZPC induced a cell death through a necrotic and caspase-independent pathway. The apoptosis was the primary mechanism of the cell death induced by the extracts derived from the RMGIC, whereas the extracts from the RC and ZPC induced a cell death via a necrotic pathway. We suggest that metabolic assays commonly used to assess the cytotoxicity of luting cements should be validated by alternative methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fusion between Intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming.

PubMed

Powell, Anne E; Anderson, Eric C; Davies, Paige S; Silk, Alain D; Pelz, Carl; Impey, Soren; Wong, Melissa H

2011-02-15

The most deadly phase in cancer progression is attributed to the inappropriate acquisition of molecular machinery leading to metastatic transformation and spread of disease to distant organs. Although it is appreciated that metastasis involves epithelial-mesenchymal interplay, the underlying mechanism defining this process is poorly understood. Specifically, how cancer cells evade immune surveillance and gain the ability to navigate the circulatory system remains a focus. One possible mechanism underlying metastatic conversion is fusion between blood-derived immune cells and cancer cells. While this notion is a century old, in vivo evidence that cell fusion occurs within tumors and imparts genetic or physiologic changes remains controversial. We have previously demonstrated in vivo cell fusion between blood cells and intestinal epithelial cells in an injury setting. Here, we hypothesize that immune cells, such as macrophages, fuse with tumor cells imparting metastatic capabilities by transferring their cellular identity. We used parabiosis to introduce fluorescent-labeled bone marrow-derived cells to mice with intestinal tumors, finding that fusion between circulating blood-derived cells and tumor epithelium occurs during the natural course of tumorigenesis. Moreover, we identify the macrophage as a key cellular partner for this process. Interestingly, cell fusion hybrids retain a transcriptome identity characteristic of both parental derivatives, while also expressing a unique subset of transcripts. Our data supports the novel possibility that tumorigenic cell fusion may impart physical behavior attributed to migratory macrophages, including navigation of circulation and immune evasion. As such, cell fusion may represent a promising novel mechanism underlying the metastatic conversion of cancer cells. ©2011 AACR.

Enterobacter gergoviae membrane modifications are involved in the adaptive response to preservatives used in cosmetic industry.

PubMed

Périamé, Marina; Pagès, Jean-Marie; Davin-Regli, Anne

2015-01-01

The objective of this study was to understand the adaptive mechanisms in Enterobacter gergoviae which are involved in recurrent contaminations in cosmetic products that are incorporated with preservatives. Bacterial strains from two backgrounds were examined for a profound understanding of the mechanisms of adaptation against preservatives. It included a series of Ent. gergoviae strain-ATCC 33028 derivatives, isolated using increasing methylisothiazolinone-chloromethylisothiazolinone (MIT-CMIT) and triclosan concentrations. The other series was of Ent. gergoviae isolates from cosmetic products exhibiting MIT-CMIT and triclosan resistance. We evaluated the outer membrane protein modifications and efflux mechanisms activities responsible for the resistant trait via immunoblotting assays. Additionally, for understanding the efflux activity real-time efflux, experiments were performed. A cross-insusceptibility between preservatives and some disinfectants was observed in MIT-CMIT-resistant derivative isolates, but antibiotics susceptibility was not altered. Resistance to EDTA was significant in all preservatives insusceptible derivative strains, indicating modifications in the LPS layer. Furthermore, an array of real-time efflux assays indicated different activity levels while no variations were detected in porins and AcrAB-TolC pumps production. Overexpression of a specific flagellin-type protein was observed in one of the MIT-CMIT- and triclosan-resistant strains. Another candidate, a 25-kDa peroxiredoxin enzyme involved in oxidative detoxification, was identified to be overexpressed in MIT-CMIT derivative. A similar profile was also observed among strains isolated from cosmetic products. Our study highlights the existence of adaptive mechanisms such as overexpression of detoxifying enzymes, flagellin, modification of membrane structure/function in Ent. gergoviae. They might be involved in recurrent episodes of contaminations occurring in the cosmetic production lines. No cross-resistance could be observed with antibiotics when MICs to preservatives were increased; however, a decrease in the disinfectants bactericidal effects was confirmed in preservative-tolerant strains. This will impact industry disinfection strategies treatment against bacteria. © 2014 The Society for Applied Microbiology.

Mechanochemical activation and patterning of an adhesive surface toward nanoparticle deposition.

PubMed

Baytekin, H Tarik; Baytekin, Bilge; Huda, Sabil; Yavuz, Zelal; Grzybowski, Bartosz A

2015-02-11

Mechanical pulling of adhesive tape creates radicals on the tape's surface. These radicals are capable of reducing metal salts to the corresponding metal nanoparticles. In this way, the mechanically activated tape can be decorated with various types of nanoparticles, including Au, Ag, Pd, or Cu. While retaining their mechanical properties and remaining "sticky," the tapes can exhibit new properties derived from the presence of metal nanoparticles (e.g., bacteriostaticity, increased electrical conductivity). They can also be patterned with nanoparticles only at selective locations of mechanical activation.

Antimicrobial and anticancer activity of some novel fluorinated thiourea derivatives carrying sulfonamide moieties: synthesis, biological evaluation and molecular docking.

PubMed

Ghorab, Mostafa M; Alsaid, Mansour S; El-Gaby, Mohamed S A; Elaasser, Mahmoud M; Nissan, Yassin M

2017-04-07

Various thiourea derivatives have been used as starting materials for compounds with better biological activities. Molecular modeling tools are used to explore their mechanism of action. A new series of thioureas were synthesized. Fluorinated pyridine derivative 4a showed the highest antimicrobial activity (with MIC values ranged from 1.95 to 15.63 µg/mL). Interestingly, thiadiazole derivative 4c and coumarin derivative 4d exhibited selective antibacterial activities against Gram positive bacteria. Fluorinated pyridine derivative 4a was the most active against HepG2 with IC50 value of 4.8 μg/mL. Molecular docking was performed on the active site of MK-2 with good results. Novel compounds were obtained with good anticancer and antibacterial activity especially fluorinated pyridine derivative 4a and molecular docking study suggest good activity as mitogen activated protein kinase-2 inhibitor. Graphical abstract Compound 4a in the active site of MK-2.

Low-Intensity Vibration as a Treatment for Traumatic Muscle Injury

DTIC Science & Technology

2017-08-01

stimulation has an anabolic effect on musculoskeletal tissues, and mechanical stimulation via LIV has been shown to accelerate bone regeneration. Our... bone marrow-derived cells (BMDC) in LIV-induced improvements in muscle healing. Third, we will identify specific cells that detect and transduce...muscle regeneration following traumatic injury. 2. Determine the role of bone marrow-derived cells (BMDC) in LIV-induced improvements in muscle

RF multicoupler design techniques to minimize problems of corona, multipaction, and stability

NASA Technical Reports Server (NTRS)

Hurley, H. S.; Kozakoff, D. J.

1971-01-01

A mathematical expression was derived describing multipacting and corona effects in a coaxial cavity. Both mechanical and electrical design techniques were investigated to minimize the susceptibility of coaxial cavity to corona and multipacting-type breakdown. To assist in the design of a multicoupler free from corona and multipactor breakdown, a flow chart obtained from the derived mathematical expression is included.

Acyl Meldrum's acid derivatives: application in organic synthesis

NASA Astrophysics Data System (ADS)

Janikowska, K.; Rachoń, J.; Makowiec, S.

2014-07-01

This review is focused on an important class of Meldrum's acid derivatives commonly known as acyl Meldrum's acids. The preparation methods of these compounds are considered including the recently proposed and rather rarely used ones. The chemical properties of acyl Meldrum's acids are described in detail, including thermal stability and reactions with various nucleophiles. The possible mechanisms of these transformations are analyzed. The bibliography includes 134 references.

Transition from the mechanics of material points to the mechanics of structured particles

NASA Astrophysics Data System (ADS)

Somsikov, V. M.

2016-01-01

In this paper, necessity of creation of mechanics of structured particles is discussed. The way to create this mechanics within the laws of classical mechanics with the use of energy equation is shown. The occurrence of breaking of time symmetry within the mechanics of structured particles is shown, as well as the introduction of concept of entropy in the framework of classical mechanics. The way to create the mechanics of non-equilibrium systems in the thermodynamic approach is shown. It is also shown that the use of hypothesis of holonomic constraints while deriving the canonical Lagrange equation made it impossible to describe irreversible dynamics. The difference between the mechanics of structured particles and the mechanics of material points is discussed. It is also shown that the matter is infinitely divisible according to the laws of classical mechanics.

Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment

PubMed Central

2013-01-01

Background Stress and anxiety-related behaviors are seen in many organisms. Studies have shown that in humans and other animals, treatment with selective serotonin reuptake inhibitors (e.g. fluoxetine) can reduce anxiety and anxiety-related behaviors. The efficacies and side effects, however, can vary between individuals. Fluoxetine can modulate anxiety in a stereospecific manner or with equal efficacy regardless of stereoisomer depending on the mechanism of action (e.g. serotonergic or GABAergic effects). Zebrafish are an emerging and valuable translational model for understanding human health related issues such as anxiety. In this study we present data showing the behavioral and whole brain transcriptome changes with fluoxetine treatment in wild-derived zebrafish and suggest additional molecular mechanisms of this widely-prescribed drug. Results We used automated behavioral analyses to assess the effects of racemic and stereoisomeric fluoxetine on male wild-derived zebrafish. Both racemic and the individual isomers of fluoxetine reduced anxiety-related behaviors relative to controls and we did not observe stereospecific fluoxetine effects. Using RNA-sequencing of the whole brain, we identified 411 genes showing differential expression with racemic fluoxetine treatment. Several neuropeptides (neuropeptide Y, isotocin, urocortin 3, prolactin) showed consistent expression patterns with the alleviation of stress and anxiety when anxiety-related behavior was reduced with fluoxetine treatment. With gene ontology and KEGG pathway analyses, we identified lipid and amino acid metabolic processes, and steroid biosynthesis among other terms to be over-enriched. Conclusion Our results demonstrate that fluoxetine reduces anxiety-related behaviors in wild-derived zebrafish and alters their neurogenomic state. We identify two biological processes, lipid and amino acid metabolic synthesis that characterize differences in the fluoxetine treated fish. Fluoxetine may be acting on several different molecular pathways to reduce anxiety-related behaviors in wild-derived zebrafish. This study provides data that could help identify common molecular mechanisms of fluoxetine action across animal taxa. PMID:23706039

SU-E-P-45: An Analytical Formula for Deriving Mechanical Iso-Center of Rotational Gantry Treatment Unit Rotational Gantry Treatment Unit

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

Ding, X; Bues, M

2015-06-15

Purpose: To present an analytical formula for deriving mechanical isocenter (MIC) of a rotational gantry treatment unit. The input data to the formula is obtained by a custom-made device. The formula has been implemented and used in an operational proton therapy facility since 2005. Methods: The custom made device consisted of 3 mutually perpendicular dial indicators and 5 clinometers, to obtain displacement data and gantry angle data simultaneously. During measurement, a steel sphere was affixed to the patient couch, and the device was attached to the snout rotating with the gantry. The displacement data and angle data were obtained simultaneouslymore » at angular increments of less than 1 degree. The analytical formula took the displacement and angle as input and derived the positions of dial indicator tips (DIT) position in room-fixed coordinate system. The formula derivation presupposes trigonometry and 3-dimentional coordinate transformations. Due to the symmetry properties of the defining equations, the DIT position can be solved for analytically without using mathematical approximations. We define the mean of all points in the DIT trajectory as the MIC. The formula was implemented in computer code, which has been employed during acceptance test, commissioning, as well as routine QA practice in an operational proton facility since 2005. Results: It took one minute for the custom-made device to acquire the measurement data for a full gantry rotation. The DIT trajectory and MIS are instantaneously available after the measurement. The MIC Result agrees well with vendor’s Result, which came from a different measurement setup, as well as different data analysis algorithm. Conclusion: An analytical formula for deriving mechanical isocenter was developed and validated. The formula is considered to be absolutely accurate mathematically. Be analyzing measured data of radial displacements as function of gantry angle, the formula calculates the MI position in room coordinate.« less

Hypoxia and alkalinization inhibit endothelium-derived nitric oxide but not endothelium-derived hyperpolarizing factor responses in porcine coronary artery.

PubMed

Shimizu, S; Paul, R J

1999-10-01

We investigated the mechanisms by which hypoxia and alkalinization inhibit the endothelium-dependent relaxation to Substance P (SP) in porcine coronary artery. In a KCl contracture, the major component of the SP response is endothelium-derived nitric oxide (EDNO), whereas with receptor-mediated 9,11-dideoxy-llalpha, 9alpha-epoxymethanoprostaglandin F(2alpha) (U46619) stimulation, the SP response is dependent on both EDNO and endothelium-derived hyperpolarization factor. Intracellular alkalinization by NH(4)Cl reduced the peak of SP responses when arteries were contracted with KCl, whereas with U46619 stimulation, the peak was little effected but the duration was shortened. In endothelial cell-denuded arteries, alkalinization with NH(4)Cl shifted the sodium nitroprusside concentration-relaxation relations rightward. The effects of NH(4)Cl in SP- and sodium nitroprusside-induced relaxations were attenuated by decreasing extracellular pH (pH(o)) from 7.4 to 7.2, which normalized intracellular pH (pH(i)) to control levels. In contrast, in U46619 contractures, the SP response in the presence of a NO synthase inhibitor was unaffected by NH(4)Cl. Moreover, hypoxia blunted but did not abolish the responses to SP for U46619 contractures; addition of KCl, however, abolished the SP response under hypoxia. Endothelial [Ca(2+)](i) was measured with fura-2 differentially loaded only into endothelial cells on intact arteries. Despite the attenuation of the SP response in KCl contractures by NH(4)Cl or hypoxia, endothelial [Ca(2+)](i) responses were unchanged. Our results suggest that hypoxia and alkalinization inhibit EDNO but not endothelium-derived hyperpolarization factor relaxations through a mechanism(s) not involving endothelial cell [Ca(2+)](i). Inhibition of EDNO relaxation by alkalinization with NH(4)Cl is likely to occur at the level of activation of guanylate cyclase and/or at a step downstream in smooth muscle.

Dynamic analysis of multirigid-body system based on the Gauss principle

NASA Astrophysics Data System (ADS)

Lilov, L.; Lorer, M.

Two different approaches can be used for solving the basic dynamic problem in the case of a multirigid body system. The first approach is based on the derivation of the nonlinear equations of motion of the mechanical system, while the second approach is concerned with the direct derivation of the unknown accelerations. Using the Gauss principle, the accelerations can be determined by using the condition for the minimum of a functional. The present investigation is concerned with an algorithm for a dynamical study of a multibody system on the basis of the Gauss principle. The system may contain an arbitrary number of closed loops. The main purpose of the proposed algorithm is the investigation of the dynamics of industrial manipulators, robots, and similar mechanisms.

Structure and performance of polymer-derived bulk ceramics determined by method of filler incorporation

NASA Astrophysics Data System (ADS)

Konegger, T.; Schneider, P.; Bauer, V.; Amsüss, A.; Liersch, A.

2013-12-01

The effect of four distinct methods of incorporating fillers into a preceramic polymer matrix was investigated with respect to the structural and mechanical properties of the resulting materials. Investigations were conducted with a polysiloxane/Al2O3/ZrO2 model system used as a precursor for mullite/ZrO2 composites. A quantitative evaluation of the uniformity of filler distribution was obtained by employing a novel image analysis. While solvent-free mixing led to a heterogeneous distribution of constituents resulting in limited mechanical property values, a strong improvement of material homogeneity and properties was obtained by using solvent-assisted methods. The results demonstrate the importance of the processing route on final characteristics of polymer-derived ceramics.

Resistance to minor groove binders.

PubMed

Colmegna, Benedetta; Uboldi, Sarah; Erba, Eugenio; D'Incalci, Maurizio

2014-03-01

In this paper multiple resistance mechanisms to minor groove binders (MGBs) are overviewed. MGBs with antitumor properties are natural products or their derivatives and, as expected, they are all substrates of P-glycoprotein (P-gp). However, a moderate expression of P-gp does not appear to reduce the sensitivity to trabectedin, the only MGB so far approved for clinical use. Resistance to this drug is often related to transcriptional mechanisms and to DNA repair pathways, particularly defects in transcription-coupled nucleotide excision repair (TC-NER). Therefore tumors resistant to trabectedin may become hypersensitive to UV rays and other DNA damaging agents acting in the major groove, such as Platinum (Pt) complexes. If this is confirmed in clinic, that will provide the rationale to combine trabectedin sequentially with Pt derivates.

Statistical foundations of liquid-crystal theory: I. Discrete systems of rod-like molecules.

PubMed

Seguin, Brian; Fried, Eliot

2012-12-01

We develop a mechanical theory for systems of rod-like particles. Central to our approach is the assumption that the external power expenditure for any subsystem of rods is independent of the underlying frame of reference. This assumption is used to derive the basic balance laws for forces and torques. By considering inertial forces on par with other forces, these laws hold relative to any frame of reference, inertial or noninertial. Finally, we introduce a simple set of constitutive relations to govern the interactions between rods and find restrictions necessary and sufficient for these laws to be consistent with thermodynamics. Our framework provides a foundation for a statistical mechanical derivation of the macroscopic balance laws governing liquid crystals.

Molecular mechanisms of maternal vascular dysfunction in preeclampsia.

PubMed

Goulopoulou, Styliani; Davidge, Sandra T

2015-02-01

In preeclampsia, as a heterogeneous syndrome, multiple pathways have been proposed for both the causal as well as the perpetuating factors leading to maternal vascular dysfunction. Postulated mechanisms include imbalance in the bioavailability and activity of endothelium-derived contracting and relaxing factors and oxidative stress. Studies have shown that placenta-derived factors [antiangiogenic factors, microparticles (MPs), cell-free nucleic acids] are released into the maternal circulation and act on the vascular wall to modify the secretory capacity of endothelial cells and alter the responsiveness of vascular smooth muscle cells to constricting and relaxing stimuli. These molecules signal their deleterious effects on the maternal vascular wall via pathways that provide the molecular basis for novel and effective therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adaptive Broadcasting Mechanism for Bandwidth Allocation in Mobile Services

PubMed Central

Horng, Gwo-Jiun; Wang, Chi-Hsuan; Chou, Chih-Lun

2014-01-01

This paper proposes a tree-based adaptive broadcasting (TAB) algorithm for data dissemination to improve data access efficiency. The proposed TAB algorithm first constructs a broadcast tree to determine the broadcast frequency of each data and splits the broadcast tree into some broadcast wood to generate the broadcast program. In addition, this paper develops an analytical model to derive the mean access latency of the generated broadcast program. In light of the derived results, both the index channel's bandwidth and the data channel's bandwidth can be optimally allocated to maximize bandwidth utilization. This paper presents experiments to help evaluate the effectiveness of the proposed strategy. From the experimental results, it can be seen that the proposed mechanism is feasible in practice. PMID:25057509

Spectroscopic and quantum-mechanical study of enol-enol tautomerism of 3-acetyltetramic acid derivatives

NASA Astrophysics Data System (ADS)

Gromak, V. V.; Avakyan, V. G.; Lakhvich, O. F.

2000-03-01

By the method of IR spectroscopy, Raman spectroscopy, and nonempirical (basis 3-21G//3-21G(d,p)) and semiempirical (approximations AM1 and PM3) quantum-mechanical methods the tautomeric structure of a series of 3-acetyltetramic acid derivatives has been investigated. It is shown that all the investigated compounds exist in vapor, in solution, and in the crystalline state mainly in the form of exo-enols among which the prevalent form is that in which lactam carbonyl participates in intrachelate hydrogen bonding. Complete series of relative stabilities of possible tautomeric forms of the investigated compounds have been established. General conlusions on the structure of 5-membered ring β,β'-triketones have been formulated.

Decomposition mechanism of an artemisinin-type compound via hemin-electrocatalysis.

PubMed

Chen, H Y; Chen, Y; Zhu, S M; Bian, N S; Shan, F; Li, Y

1999-01-01

The interaction between a typical derivative of artemisinin and hemin was investigated by electrochemical and spectroelectrochemical methods. This derivative can be reduced via hemin-catalysis at the glassy carbon electrode, the cathodic overpotential is decreased by ca. 650 mV. A HPLC method for separating the products of the catalytic reaction was established. They were identified either in H(2)O-CH(3)CN solution or in tetrahydrofuran, respectively. The structures of these products show that the hemin-catalyzed decomposition of an artemisinin-type compound on the glassy carbon or reticulated vitreous carbon electrode can be achieved by both electrochemical reduction and rearrangement. The conclusion that the reaction of artemisinin with hemin is a critical step in the antimalarial mechanism of artemisinin can be drawn.

Shadowing of non-transversal heteroclinic chains

NASA Astrophysics Data System (ADS)

Delshams, Amadeu; Simon, Adrià; Zgliczyński, Piotr

2018-03-01

We present a new result about the shadowing of non-transversal chain of heteroclinic connections based on the idea of dropping dimensions. We illustrate this new mechanism with several examples. As an application we discuss this mechanism in a simplification of a toy model system derived by Colliander et al. in the context of cubic defocusing nonlinear Schrödinger equation.

Answer to Question {number_sign}21 [{open_quote}{open_quote}Snell{close_quote}s law in quantum mechanics,{close_quote}{close_quote} Steve Blau and Brad Halfpap, Am. J. Phys. {bold 63} (7), 583 (1995)

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

Milonni, P.W.

1996-07-01

The quantum mechanical description of reflection and refraction in terms of photons is further extrapolated. The probability amplitude for a photon to be found inside or outside the medium is derived.

A Formal Derivation of the Gibbs Entropy for Classical Systems Following the Schrodinger Quantum Mechanical Approach

ERIC Educational Resources Information Center

Santillan, M.; Zeron, E. S.; Del Rio-Correa, J. L.

2008-01-01

In the traditional statistical mechanics textbooks, the entropy concept is first introduced for the microcanonical ensemble and then extended to the canonical and grand-canonical cases. However, in the authors' experience, this procedure makes it difficult for the student to see the bigger picture and, although quite ingenuous, the subtleness of…

Racemization of Isobornyl Chloride via Carbocations: A Nonclassical Look at a Classic Mechanism

ERIC Educational Resources Information Center

Rzepa, Henry S.; Allan, Charlotte S. M.

2010-01-01

Our understanding of carbonium ions as intermediates in chemical reaction mechanisms derives from the early work of Julius Stieglitz and the more famous Hans Meerwein, the latter studying the racemization of isobornyl chloride when treated with Lewis acids. This review analyzes how key mechanistic concepts for this reaction evolved and gives the…

Local U(2,2) symmetry in relativistic quantum mechanics

NASA Astrophysics Data System (ADS)

Finster, Felix

1998-12-01

Local gauge freedom in relativistic quantum mechanics is derived from a measurement principle for space and time. For the Dirac equation, one obtains local U(2,2) gauge transformations acting on the spinor index of the wave functions. This local U(2,2) symmetry allows a unified description of electrodynamics and general relativity as a classical gauge theory.

Selective epitaxial growth of zinc blende-derivative on wurtzite-derivative: the case of polytypic Cu2CdSn(S1-xSex)4 nanocrystals

NASA Astrophysics Data System (ADS)

Wu, Liang; Fan, Feng-Jia; Gong, Ming; Ge, Jin; Yu, Shu-Hong

2014-02-01

Polytypic nanocrystals with zinc blende (ZB) cores and wurtzite (WZ) arms, such as tetrapod and octopod nanocrystals, have been widely reported. However, polytypic nanocrystals with WZ cores and ZB arms or ends have been rarely reported. Here, we report a facile, solution-based approach to the synthesis of polytypic Cu2CdSn(S1-xSex)4 (CCTSSe) nanocrystals with ZB-derivative selectively engineered on (000+/-2)WZ facets of WZ-derived cores. Accordingly, two typical morphologies, i.e., bullet-like nanocrystals with a WZ-derivative core and one ZB-derivative end, and rugby ball-like nanocrystals with a WZ-derivative core and two ZB-derivative ends, can be selectively prepared. The epitaxial growth mechanism is confirmed by the time-dependent experiments. The ratio of rugby ball-like and bullet-like polytypic CCTSSe nanocrystals can be tuned through changing the amount of Cd precursor to adjust the reactivity difference between (0002)WZ and (000-2)WZ facets. These unique polytypic CCTSSe nanocrystals may find applications in energetic semiconducting materials for energy conversion in the future.Polytypic nanocrystals with zinc blende (ZB) cores and wurtzite (WZ) arms, such as tetrapod and octopod nanocrystals, have been widely reported. However, polytypic nanocrystals with WZ cores and ZB arms or ends have been rarely reported. Here, we report a facile, solution-based approach to the synthesis of polytypic Cu2CdSn(S1-xSex)4 (CCTSSe) nanocrystals with ZB-derivative selectively engineered on (000+/-2)WZ facets of WZ-derived cores. Accordingly, two typical morphologies, i.e., bullet-like nanocrystals with a WZ-derivative core and one ZB-derivative end, and rugby ball-like nanocrystals with a WZ-derivative core and two ZB-derivative ends, can be selectively prepared. The epitaxial growth mechanism is confirmed by the time-dependent experiments. The ratio of rugby ball-like and bullet-like polytypic CCTSSe nanocrystals can be tuned through changing the amount of Cd precursor to adjust the reactivity difference between (0002)WZ and (000-2)WZ facets. These unique polytypic CCTSSe nanocrystals may find applications in energetic semiconducting materials for energy conversion in the future. Electronic supplementary information (ESI) available: Detailed information about the polytypic CCTSSe nanocrystals syntheses, measurement and characterization, additional TEM and HRTEM images, PXRD analysis, EDS spectra and UV-vis-NIR spectra. See DOI: 10.1039/c3nr04948e.

Applications and assessment of QM:QM electronic embedding using generalized asymmetric Mulliken atomic charges.

PubMed

Parandekar, Priya V; Hratchian, Hrant P; Raghavachari, Krishnan

2008-10-14

Hybrid QM:QM (quantum mechanics:quantum mechanics) and QM:MM (quantum mechanics:molecular mechanics) methods are widely used to calculate the electronic structure of large systems where a full quantum mechanical treatment at a desired high level of theory is computationally prohibitive. The ONIOM (our own N-layer integrated molecular orbital molecular mechanics) approximation is one of the more popular hybrid methods, where the total molecular system is divided into multiple layers, each treated at a different level of theory. In a previous publication, we developed a novel QM:QM electronic embedding scheme within the ONIOM framework, where the model system is embedded in the external Mulliken point charges of the surrounding low-level region to account for the polarization of the model system wave function. Therein, we derived and implemented a rigorous expression for the embedding energy as well as analytic gradients that depend on the derivatives of the external Mulliken point charges. In this work, we demonstrate the applicability of our QM:QM method with point charge embedding and assess its accuracy. We study two challenging systems--zinc metalloenzymes and silicon oxide cages--and demonstrate that electronic embedding shows significant improvement over mechanical embedding. We also develop a modified technique for the energy and analytic gradients using a generalized asymmetric Mulliken embedding method involving an unequal splitting of the Mulliken overlap populations to offer improvement in situations where the Mulliken charges may be deficient.

Gastric cancer-derived exosomes promote peritoneal metastasis by destroying the mesothelial barrier.

PubMed

Deng, Guang; Qu, Jinglei; Zhang, Ye; Che, Xiaofang; Cheng, Yu; Fan, Yibo; Zhang, Simeng; Na, Di; Liu, Yunpeng; Qu, Xiujuan

2017-07-01

An intact mesothelium serves as a protective barrier to inhibit peritoneal carcinomatosis. Cancer-derived exosomes can mediate directional tumor metastasis; however, little is known about whether gastric cancer-derived exosomes will destroy the mesothelial barrier and promote peritoneal dissemination. Here, we demonstrate that gastric cancer-derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis. Injury of peritoneal mesothelial cells elicited by gastric cancer-derived exosomes is through concurrent apoptosis and mesothelial-to-mesenchymal transition (MMT). Additionally, upregulation of p-ERK in peritoneal mesothelial cells is primarily responsible for the MMT while contributing little to apoptosis. Together, these data support the concept that exosomes play a crucial role in remodeling the premetastatic microenvironment and identify a novel mechanism for peritoneal metastasis of gastric carcinoma. © 2017 Federation of European Biochemical Societies.

Automated respiratory cycles selection is highly specific and improves respiratory mechanics analysis.

PubMed

Rigo, Vincent; Graas, Estelle; Rigo, Jacques

2012-07-01

Selected optimal respiratory cycles should allow calculation of respiratory mechanic parameters focusing on patient-ventilator interaction. New computer software automatically selecting optimal breaths and respiratory mechanics derived from those cycles are evaluated. Retrospective study. University level III neonatal intensive care unit. Ten mins synchronized intermittent mandatory ventilation and assist/control ventilation recordings from ten newborns. The ventilator provided respiratory mechanic data (ventilator respiratory cycles) every 10 secs. Pressure, flow, and volume waves and pressure-volume, pressure-flow, and volume-flow loops were reconstructed from continuous pressure-volume recordings. Visual assessment determined assisted leak-free optimal respiratory cycles (selected respiratory cycles). New software graded the quality of cycles (automated respiratory cycles). Respiratory mechanic values were derived from both sets of optimal cycles. We evaluated quality selection and compared mean values and their variability according to ventilatory mode and respiratory mechanic provenance. To assess discriminating power, all 45 "t" values obtained from interpatient comparisons were compared for each respiratory mechanic parameter. A total of 11,724 breaths are evaluated. Automated respiratory cycle/selected respiratory cycle selections agreement is high: 88% of maximal κ with linear weighting. Specificity and positive predictive values are 0.98 and 0.96, respectively. Averaged values are similar between automated respiratory cycle and ventilator respiratory cycle. C20/C alone is markedly decreased in automated respiratory cycle (1.27 ± 0.37 vs. 1.81 ± 0.67). Tidal volume apparent similarity disappears in assist/control: automated respiratory cycle tidal volume (4.8 ± 1.0 mL/kg) is significantly lower than for ventilator respiratory cycle (5.6 ± 1.8 mL/kg). Coefficients of variation decrease for all automated respiratory cycle parameters in all infants. "t" values from ventilator respiratory cycle data are two to three times higher than ventilator respiratory cycles. Automated selection is highly specific. Automated respiratory cycle reflects most the interaction of both ventilator and patient. Improving discriminating power of ventilator monitoring will likely help in assessing disease status and following trends. Averaged parameters derived from automated respiratory cycles are more precise and could be displayed by ventilators to improve real-time fine tuning of ventilator settings.

The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis.

PubMed

Ferreira, Flávia Viana; Aguiar, Eric Roberto Guimarães Rocha; Olmo, Roenick Proveti; de Oliveira, Karla Pollyanna Vieira; Silva, Emanuele Guimarães; Sant'Anna, Maurício Roberto Viana; Gontijo, Nelder de Figueiredo; Kroon, Erna Geessien; Imler, Jean Luc; Marques, João Trindade

2018-06-01

Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.

Electrical and mechanical stimulation of cardiac cells and tissue constructs.

PubMed

Stoppel, Whitney L; Kaplan, David L; Black, Lauren D

2016-01-15

The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro. Copyright © 2015 Elsevier B.V. All rights reserved.

Defended to the Nines: 25 Years of Resistance Gene Cloning Identifies Nine Mechanisms for R Protein Function[OPEN

PubMed Central

2018-01-01

Plants have many, highly variable resistance (R) gene loci, which provide resistance to a variety of pathogens. The first R gene to be cloned, maize (Zea mays) Hm1, was published over 25 years ago, and since then, many different R genes have been identified and isolated. The encoded proteins have provided clues to the diverse molecular mechanisms underlying immunity. Here, we present a meta-analysis of 314 cloned R genes. The majority of R genes encode cell surface or intracellular receptors, and we distinguish nine molecular mechanisms by which R proteins can elevate or trigger disease resistance: direct (1) or indirect (2) perception of pathogen-derived molecules on the cell surface by receptor-like proteins and receptor-like kinases; direct (3) or indirect (4) intracellular detection of pathogen-derived molecules by nucleotide binding, leucine-rich repeat receptors, or detection through integrated domains (5); perception of transcription activator-like effectors through activation of executor genes (6); and active (7), passive (8), or host reprogramming-mediated (9) loss of susceptibility. Although the molecular mechanisms underlying the functions of R genes are only understood for a small proportion of known R genes, a clearer understanding of mechanisms is emerging and will be crucial for rational engineering and deployment of novel R genes. PMID:29382771

Comprehensive analysis of individual pulp fiber bonds quantifies the mechanisms of fiber bonding in paper

PubMed Central

Hirn, Ulrich; Schennach, Robert

2015-01-01

The process of papermaking requires substantial amounts of energy and wood consumption, which contributes to larger environmental costs. In order to optimize the production of papermaking to suit its many applications in material science and engineering, a quantitative understanding of bonding forces between the individual pulp fibers is of importance. Here we show the first approach to quantify the bonding energies contributed by the individual bonding mechanisms. We calculated the impact of the following mechanisms necessary for paper formation: mechanical interlocking, interdiffusion, capillary bridges, hydrogen bonding, Van der Waals forces, and Coulomb forces on the bonding energy. Experimental results quantify the area in molecular contact necessary for bonding. Atomic force microscopy experiments derive the impact of mechanical interlocking. Capillary bridges also contribute to the bond. A model based on the crystal structure of cellulose leads to values for the chemical bonds. In contrast to general believe which favors hydrogen bonding Van der Waals bonds play the most important role according to our model. Comparison with experimentally derived bond energies support the presented model. This study characterizes bond formation between pulp fibers leading to insight that could be potentially used to optimize the papermaking process, while reducing energy and wood consumption. PMID:26000898

Elastase-Sensitive Elastomeric Scaffolds with Variable Anisotropy for Soft Tissue Engineering

PubMed Central

Guan, Jianjun; Fujimoto, Kazuro L.; Wagner, William R.

2010-01-01

Purpose To develop elastase-sensitive polyurethane scaffolds that would be applicable to the engineering of mechanically active soft tissues. Methods A polyurethane containing an elastase-sensitive peptide sequence was processed into scaffolds by thermally induced phase separation. Processing conditions were manipulated to alter scaffold properties and anisotropy. The scaffold’s mechanical properties, degradation, and cytocompatibility using muscle-derived stem cells were characterized. Scaffold in vivo degradation was evaluated by subcutaneous implantation. Results When heat transfer was multidirectional, scaffolds had randomly oriented pores. Imposition of a heat transfer gradient resulted in oriented pores. Both scaffolds were flexible and relatively strong with mechanical properties dependent upon fabrication conditions such as solvent type, polymer concentration and quenching temperature. Oriented scaffolds exhibited anisotropic mechanical properties with greater tensile strength in the orientation direction. These scaffolds also supported muscle-derived stem cell growth more effectively than random scaffolds. The scaffolds expressed over 40% weight loss after 56 days in elastase containing buffer. Elastase-sensitive scaffolds were complete degraded after 8 weeks subcutaneous implantation in rats, markedly faster than similar polyurethanes that did not contain the peptide sequence. Conclusion The elastase-sensitive polyurethane scaffolds showed promise for application in soft tissue engineering where controlling scaffold mechanical properties and pore architecture are desirable. PMID:18509596

Nonlinear acoustic wave equations with fractional loss operators.

PubMed

Prieur, Fabrice; Holm, Sverre

2011-09-01

Fractional derivatives are well suited to describe wave propagation in complex media. When introduced in classical wave equations, they allow a modeling of attenuation and dispersion that better describes sound propagation in biological tissues. Traditional constitutive equations from solid mechanics and heat conduction are modified using fractional derivatives. They are used to derive a nonlinear wave equation which describes attenuation and dispersion laws that match observations. This wave equation is a generalization of the Westervelt equation, and also leads to a fractional version of the Khokhlov-Zabolotskaya-Kuznetsov and Burgers' equations. © 2011 Acoustical Society of America

Different osteochondral potential of clonal cell lines derived from adult human trabecular bone.

PubMed

Osyczka, Anna M; Nöth, Ulrich; Danielson, Keith G; Tuan, Rocky S

2002-06-01

Cells derived from human trabecular bones have been shown to have multipotential differentiation ability along osteogenic, chondrogenic, and adipogenic lineages. In this study, we have derived two clonal sublines of human trabecular bone cells by means of stable transduction with human papilloma virus E6/E7 genes. Our results showed that these clonal sublines differ in their osteochondral potential, but are equally adipogenic, indicative of the heterogeneous nature of the parental cell population. The availability of these cell lines should be useful for the analysis of the mechanisms regulating the differentiation of adult mesenchymal progenitor cells.

Gauge fixing in higher-derivative gravity

NASA Astrophysics Data System (ADS)

Bartoli, A.; Julve, J.; Sánchez, E. J.

1999-07-01

Linearized 4-derivative gravity with a general gauge-fixing term is considered. By a Legendre transform and a suitable diagonalization procedure it is cast into a second-order equivalent form where the nature of the physical degrees of freedom, the gauge ghosts, the Weyl ghosts and the intriguing `third ghosts', characteristic to higher-derivative theories, is made explicit. The symmetries of the theory and the structure of the compensating Faddeev-Popov ghost sector exhibit non-trivial peculiarities. The unitarity breaking negative-norm Weyl ghosts, already present in the diff-invariant theory, are out of the reach of the ghost cancellation BRST mechanism.

Statistical mechanical theory for steady state systems. II. Reciprocal relations and the second entropy.

PubMed

Attard, Phil

2005-04-15

The concept of second entropy is introduced for the dynamic transitions between macrostates. It is used to develop a theory for fluctuations in velocity, and is exemplified by deriving Onsager reciprocal relations for Brownian motion. The cases of free, driven, and pinned Brownian particles are treated in turn, and Stokes' law is derived. The second entropy analysis is applied to the general case of thermodynamic fluctuations, and the Onsager reciprocal relations for these are derived using the method. The Green-Kubo formulas for the transport coefficients emerge from the analysis, as do Langevin dynamics.

Platelet-Rich Plasma Peptides: Key for Regeneration

PubMed Central

Sánchez-González, Dolores Javier; Méndez-Bolaina, Enrique; Trejo-Bahena, Nayeli Isabel

2012-01-01

Platelet-derived Growth Factors (GFs) are biologically active peptides that enhance tissue repair mechanisms such as angiogenesis, extracellular matrix remodeling, and cellular effects as stem cells recruitment, chemotaxis, cell proliferation, and differentiation. Platelet-rich plasma (PRP) is used in a variety of clinical applications, based on the premise that higher GF content should promote better healing. Platelet derivatives represent a promising therapeutic modality, offering opportunities for treatment of wounds, ulcers, soft-tissue injuries, and various other applications in cell therapy. PRP can be combined with cell-based therapies such as adipose-derived stem cells, regenerative cell therapy, and transfer factors therapy. This paper describes the biological background of the platelet-derived substances and their potential use in regenerative medicine. PMID:22518192

Measuring memory with the order of fractional derivative

NASA Astrophysics Data System (ADS)

Du, Maolin; Wang, Zaihua; Hu, Haiyan

2013-12-01

Fractional derivative has a history as long as that of classical calculus, but it is much less popular than it should be. What is the physical meaning of fractional derivative? This is still an open problem. In modeling various memory phenomena, we observe that a memory process usually consists of two stages. One is short with permanent retention, and the other is governed by a simple model of fractional derivative. With the numerical least square method, we show that the fractional model perfectly fits the test data of memory phenomena in different disciplines, not only in mechanics, but also in biology and psychology. Based on this model, we find that a physical meaning of the fractional order is an index of memory.

Long Noncoding RNAs: New Players in the Osteogenic Differentiation of Bone Marrow- and Adipose-Derived Mesenchymal Stem Cells.

PubMed

Yang, Qiaolin; Jia, Lingfei; Li, Xiaobei; Guo, Runzhi; Huang, Yiping; Zheng, Yunfei; Li, Weiran

2018-06-01

Mesenchymal stem cells (MSCs) are an important population of multipotent stem cells that differentiate into multiple lineages and display great potential in bone regeneration and repair. Although the role of protein-coding genes in the osteogenic differentiation of MSCs has been extensively studied, the functions of noncoding RNAs in the osteogenic differentiation of MSCs are unclear. The recent application of next-generation sequencing to MSC transcriptomes has revealed that long noncoding RNAs (lncRNAs) are associated with the osteogenic differentiation of MSCs. LncRNAs are a class of non-coding transcripts of more than 200 nucleotides in length. Noncoding RNAs are thought to play a key role in osteoblast differentiation through various regulatory mechanisms including chromatin modification, transcription factor binding, competent endogenous mechanism, and other post-transcriptional mechanisms. Here, we review the roles of lncRNAs in the osteogenic differentiation of bone marrow- and adipose-derived stem cells and provide a theoretical foundation for future research.

Nondestructive methods of integrating energy harvesting systems for highway bridges

NASA Astrophysics Data System (ADS)

Inamdar, Sumedh; Zimowski, Krystian; Crawford, Richard; Wood, Kristin; Jensen, Dan

2012-04-01

Designing an attachment structure that is both novel and meets the system requirements can be a difficult task especially for inexperienced designers. This paper presents a design methodology for concept generation of a "parent/child" attachment system. The "child" is broadly defined as any device, part, or subsystem that will attach to any existing system, part, or device called the "parent." An inductive research process was used to study a variety of products, patents, and biological examples that exemplified the parent/child system. Common traits among these products were found and categorized as attachment principles in three different domains: mechanical, material, and field. The attachment principles within the mechanical domain and accompanying examples are the focus of this paper. As an example of the method, a case study of generating concepts for a bridge mounted wind energy harvester using the mechanical attachment principles derived from the methodology and TRIZ principles derived from Altshuller's matrix of contradictions is presented.

Interaction of cinnamic acid derivatives with β-cyclodextrin in water: experimental and molecular modeling studies.

PubMed

Liu, Benguo; Zeng, Jie; Chen, Chen; Liu, Yonglan; Ma, Hanjun; Mo, Haizhen; Liang, Guizhao

2016-03-01

Cyclodextrins (CDs) can be used to improve the solubility and stability of cinnamic acid derivatives (CAs). However, there was no detailed report about understanding the effects of the substituent groups in the benzene ring on the inclusion behavior between CAs and CDs in aqueous solution. Here, the interaction of β-CD with CAs, including caffeic acid, ferulic acid, and p-coumaric acid, in water was investigated by phase-solubility method, UV, fluorescence, and (1)H NMR spectroscopy, together with ONIOM (our Own N-layer Integrated Orbital molecular Mechanics)-based QM/MM (Quantum Mechanics/Molecular Mechanics) calculations. Experimental results demonstrated that CAs could form 1:1 stoichiometric inclusion complex with β-CD by non-covalent bonds, and that the maximum apparent stability constants were found in caffeic acid (176M(-1)) followed by p-coumaric acid (160M(-1)) and ferulic acid (133M(-1)). Moreover, our calculations reasonably illustrated the binding orientations of β-CD with CAs determined by experimental observations. Copyright © 2015. Published by Elsevier Ltd.

Cellulose-derived carbon aerogels supported goethite (α-FeOOH) nanoneedles and nanoflowers for electromagnetic interference shielding.

PubMed

Wan, Caichao; Jiao, Yue; Qiang, Tiangang; Li, Jian

2017-01-20

We describe a rapid and facile chemical precipitation method to grow goethite (α-FeOOH) nanoneedles and nanoflowers on the carbon aerogels which was obtained from the pyrolysis of cellulose aerogels. When evaluated as electromagnetic interference (EMI) shielding materials, the α-FeOOH/cellulose-derived carbon aerogels composite displays the highest SE total value of 34.0dB at the Fe 3+ /Fe 2+ concentration of 0.01M, which is about 4.8 times higher than that of the individual α-FeOOH (5.9dB). When the higher or lower Fe 3+ /Fe 2+ concentrations were used, the EMI shielding performance deterioration occurred. The integration of α-FeOOH with the carbon aerogels transforms the reflection-dominant mechanism for α-FeOOH into the adsorption-dominant mechanism for the composite. The adsorption-dominant mechanism undoubtedly makes contribution to alleviating secondary radiation, which is regarded as more attractive alternative for developing electromagnetic radiation protection products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Supramolecular gels with high strength by tuning of calix[4]arene-derived networks

NASA Astrophysics Data System (ADS)

Lee, Ji Ha; Park, Jaehyeon; Park, Jin-Woo; Ahn, Hyo-Jun; Jaworski, Justyn; Jung, Jong Hwa

2015-03-01

Supramolecular gels comprised of low-molecular-weight gelators are generally regarded as mechanically weak and unable to support formation of free-standing structures, hence, their practical use with applied loads has been limited. Here, we reveal a technique for in situ generation of high tensile strength supramolecular hydrogels derived from low-molecular-weight gelators. By controlling the concentration of hydrochloric acid during hydrazone formation between calix-[4]arene-based gelator precursors, we tune the mechanical and ductile properties of the resulting gel. Organogels formed without hydrochloric acid exhibit impressive tensile strengths, higher than 40 MPa, which is the strongest among self-assembled gels. Hydrogels, prepared by solvent exchange of organogels in water, show 7,000- to 10,000-fold enhanced mechanical properties because of further hydrazone formation. This method of molding also allows the gels to retain shape after processing, and furthermore, we find organogels when prepared as gel electrolytes for lithium battery applications to have good ionic conductivity.

Supramolecular gels with high strength by tuning of calix[4]arene-derived networks

PubMed Central

Lee, Ji Ha; Park, Jaehyeon; Park, Jin-Woo; Ahn, Hyo-Jun; Jaworski, Justyn; Jung, Jong Hwa

2015-01-01

Supramolecular gels comprised of low-molecular-weight gelators are generally regarded as mechanically weak and unable to support formation of free-standing structures, hence, their practical use with applied loads has been limited. Here, we reveal a technique for in situ generation of high tensile strength supramolecular hydrogels derived from low-molecular-weight gelators. By controlling the concentration of hydrochloric acid during hydrazone formation between calix-[4]arene-based gelator precursors, we tune the mechanical and ductile properties of the resulting gel. Organogels formed without hydrochloric acid exhibit impressive tensile strengths, higher than 40 MPa, which is the strongest among self-assembled gels. Hydrogels, prepared by solvent exchange of organogels in water, show 7,000- to 10,000-fold enhanced mechanical properties because of further hydrazone formation. This method of molding also allows the gels to retain shape after processing, and furthermore, we find organogels when prepared as gel electrolytes for lithium battery applications to have good ionic conductivity. PMID:25799459

Mechanical Behavior of a Hi-Nicalon(tm)/SiC Composite Having a Polycarbosilane Derived Matrix

NASA Technical Reports Server (NTRS)

Hurwitz, Frances I.; Calomino, Anthony M.; McCue, Terry R.

1999-01-01

Polymer infiltration of a rigidized preform, followed by pyrolysis to convert the polymer to a ceramic, potentially offers a lower cost alternative to CVD. It also offers more moderate temperature requirements than melt infiltration approaches, which should minimize potential fiber damage during processing. However, polymer infiltration and pyrolysis results in a more microcracked matrix. Preliminary mechanical property characterization, including elevated temperature (1204 C) tensile, 500 h stress rupture behavior and low cycle fatigue, was conducted on Hi-Nicalon (TM)/Si-C-(O) composites having a dual layer BN/SiC interface and a matrix derived by impregnation and pyrolysis of allylhydridopolycarbosilane (AHPCS). Microstructural evaluation of failure surfaces and of polished transverse and longitudinal cross sections of the failed specimens was used to identify predominant failure mechanisms. In stress rupture testing at 1093 C, the failure was interface dominated, while at 1204 C in both stress rupture and two hour hold/fatigue tests failure was matrix dominated, resulting in specimen delamination.

DNA-protective activities of hyperforin and aristoforin.

PubMed

Ševčovičová, A; Šemeláková, M; Plšíková, J; Loderer, D; Imreová, P; Gálová, E; Kožurková, M; Miadoková, E; Fedoročko, P

2015-04-01

The aim of this study was to explain the molecular mechanisms of action of hyperforin, a phluoroglucinol derivative found in Hypericum perforatum L. and its more stable derivative aristoforin. DNA-topology assay revealed partial DNA-protective activities of hyperforin and aristoforin against Fe(2+)-induced DNA breaks. In order to assess molecular mechanisms underlying DNA-protective activity, the potential antioxidant activity of hyperforin and aristoforin was investigated using DPPH and OH scavenging assays, reducing power assay and Fe(2+)-chelating assay. We also studied interaction of hyperforin and aristoforin with DNA using established protocols for fluorescence titration. The ability of the studied compounds to relax topoisomerase I with electrophoretic techniques was investigated. The reduction in the fluorescence of hyperforin indicated an interaction between hyperforin and DNA with a binding constant of 0.2×10(8)M(-1). We suggest that a mechanism of hyperforin/aristoforin DNA-protective abilities is based on free radicals (mainly OH) scavenging activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Final Progress Report

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

Kotov, Valeri

2016-05-29

The research in this program involves theoretical investigations of electronic, optical and mechanical properties of graphene and its derivatives, such as bi-layer graphene, graphene-based van der Waals heterostructures, strained graphene, as well as graphene on various surfaces. One line of research has been development of theoretical models that support graphene’s large array of possible technological applications. For example one of our goals has been the understanding of surface plasmons and spin relaxation mechanisms in graphene, related to novel optoelectronics and spintronics applications. Our current research focus is on understanding the role of correlations in graphene under mechanical deformations, such asmore » strain. The main goal is to describe the mutual interplay between strain and electron-electron interactions which could lead to the formation of novel elec- tronic phases with strongly modified electronic, magnetic and optical properties. This direction of research contributes to deeper understanding of interactions in graphene and related atomically-thin materials - a subject at the forefront of research on graphene and its derivatives.« less

Neural mechanisms controlling seasonal reproduction: principles derived from the sheep model and its comparison with hamsters.

PubMed

Weems, Peyton W; Goodman, Robert L; Lehman, Michael N

2015-04-01

Seasonal reproduction is a common adaptive strategy among mammals that allows for breeding to occur at times of the year when it is most advantageous for the subsequent survival and growth of offspring. A major mechanism responsible for seasonal reproduction is a striking increase in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the negative feedback effects of estradiol. The neural and neuroendocrine circuitry responsible for mammalian seasonal reproduction has been primarily studied in three animal models: the sheep, and two species of hamsters. In this review, we first describe the afferent signals, neural circuitry and transmitters/peptides responsible for seasonal reproductive transitions in sheep, and then compare these mechanisms with those derived from studies in hamsters. The results suggest common principles as well as differences in the role of specific brain nuclei and neuropeptides, including that of kisspeptin cells of the hypothalamic arcuate nucleus, in regulating seasonal reproduction among mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of the Lorentz-operator in relativistic quantum mechanics to guarentee a single-energy root

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

Ritchie, A B

1998-08-01

The Lorentz-operator form of relativistic quantum mechanics, with relativistic wave equation i{h_bar}{partial_derivative}{psi}/{partial_derivative}t=(mc{sup 2}{gamma}+e{Phi}){psi}, is implemented to guarantee a single-energy root. The Lorentz factor as modified by Pauli's ansatz is given by {gamma}={radical}1+[{rvec {sigma}}{center_dot}(i{h_bar}{rvec {del}}+(e/c){rvec A})]{sup 2}/m{sup 2}c{sup 2}, such that the theory is appropriate for electrons. Magnetic fine structure in the Lorentz relativistic wave equation emerges on the use of an appropriate operator form of the Lienard-Wiechert four- potential ({Phi},{rvec A}) from electromagnetic theory. Although computationally more intensive the advantage of the theory is the elimination of the negative-root of the energy and an interpretation of the wave function basedmore » on a one-particle, positive definite probability density like that of nonrelativistic quantum mechanics.« less

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

Akdoğan, Ender, E-mail: ender.akdogan@tpe.gov.tr; Çiftçi, Muharrem, E-mail: muharrem-ciftci@windowslive.com

This article is based on the master thesis [4] related to our invention which was published in World Intellectual Property Organization (WO/2011/048506) as a microwave water heater. In the project, a prototype was produced to use microwave in industrial heating. In order to produce the prototype, the most appropriate material kind for microwave-water experiments was determined by a new energy loss rate calculation technique. This new energy loss calculation is a determinative factor for material permeability at microwave frequency band (1-100 GHz). This experimental series aim to investigate the rationality of using microwave in heating industry. Theoretically, heating water by microwavemore » (with steady frequency 2.45 GHz) is analyzed from sub-molecular to Classical Mechanic results of heating. In the study, we examined Quantum Mechanical base of heating water by microwave experiments. As a result, we derived a Semi-Quantum Mechanical equation for microwave-water interactions and thus, Wien displacement law can be derived to verify experimental observations by this equation.« less

Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

PubMed Central

Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna; Davidson, Jeffrey M.; Guelcher, Scott A.

2013-01-01

Purpose The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering. Methods Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured. Results Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter. Conclusions Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering. PMID:18516665

Mechanisms of antifungal and anti-aflatoxigenic properties of essential oil derived from turmeric (Curcuma longa L.) on Aspergillus flavus.

PubMed

Hu, Yichen; Zhang, Jinming; Kong, Weijun; Zhao, Gang; Yang, Meihua

2017-04-01

The antifungal activity and potential mechanisms in vitro as well as anti-aflatoxigenic efficiency in vivo of natural essential oil (EO) derived from turmeric (Curcuma longa L.) against Aspergillus flavus was intensively investigated. Based on the previous chemical characterization of turmeric EO by gas chromatography-mass spectrometry, the substantially antifungal activities of turmeric EO on the mycelial growth, spore germination and aflatoxin production were observed in a dose-dependent manner. Furthermore, these antifungal effects were related to the disruption of fungal cell endomembrane system including the plasma membrane and mitochondria, specifically i.e. the inhibition of ergosterol synthesis, mitochondrial ATPase, malate dehydrogenase, and succinate dehydrogenase activities. Moreover, the down-regulation profiles of turmeric EO on the relative expression of mycotoxin genes in aflatoxin biosynthetic pathway revealed its anti-aflatoxigenic mechanism. Finally, the suppression effect of fungal contamination in maize indicated that turmeric EO has potential as an eco-friendly antifungal agent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of the bioactive and mechanical behavior of dental ceramic/sol-gel derived bioactive glass mixtures.

PubMed

Abbasi, Zahra; Bahrololoum, Mohammad E; Bagheri, Rafat; Shariat, Mohammad H

2016-02-01

Dental ceramics can be modified by bioactive glasses in order to develop apatite layer on their surface. One of the benefits of such modification is to prolong the lifetime of the fixed dental prosthesis by preventing the formation of secondary caries. Dental ceramic/sol-gel derived bioactive glass mixture is one of the options for this modification. In the current study, mixtures of dental ceramic/bioactive glass with different compositions were successfully produced. To evaluate their bioactive behavior, prepared samples were immersed in a simulated body fluid at various time intervals. The prepared and soaked specimens were characterized using Fourier transform infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. Since bioactive glasses have deleterious effects on the mechanical properties of dental ceramics, 3-point bending tests were used to evaluate the flexural strength, flexural strain, tangent modulus of elasticity and Weibull modulus of the specimens in order to find the optimal relationship between mechanical and bioactive properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

BRST Formalism for Systems with Higher Order Derivatives of Gauge Parameters

NASA Astrophysics Data System (ADS)

Nirov, Kh. S.

For a wide class of mechanical systems, invariant under gauge transformations with arbitrary higher order time derivatives of gauge parameters, the equivalence of Lagrangian and Hamiltonian BRST formalisms is proved. It is shown that the Ostrogradsky formalism establishes the natural rules to relate the BFV ghost canonical pairs with the ghosts and antighosts introduced by the Lagrangian approach. Explicit relation between corresponding gauge-fixing terms is obtained.

Design study of RL10 derivatives. Volume 3, part 1: Preliminary interface control document. [development of baseline engines for space tug vehicles

NASA Technical Reports Server (NTRS)

Adams, A.

1973-01-01

The Interface Control Document contains engine information necessary for installation of the baseline RL10 Derivative engines in the Space Tug vehicle. The ICD presents a description of the baseline engines and their operating characteristics, mass and load characteristics, and environmental criteria. The document defines the engine/vehicle mechanical, electrical, fluid and pneumatic interface requirements.

Inhibition kinetics and molecular simulation of p-substituted cinnamic acid derivatives on tyrosinase.

PubMed

Cui, Yi; Hu, Yong-Hua; Yu, Feng; Zheng, Jing; Chen, Lin-Shan; Chen, Qing-Xi; Wang, Qin

2017-02-01

This study was to investigate the inhibition effects of para-substituted cinnamic acid derivatives (4-chlorocinnamic acid, 4-ethoxycinnamic acid and 4-nitrocinnamic acid) on tyrosinase catalyzing the substrates, with the purpose of elucidating the inhibition mechanism of the tested derivatives on tyrosinase by the UV-vis spectrum, fluorescence spectroscopy, copper interacting and molecular docking, respectively. The native-PAGE results showed that 4-chlorocinnamic acid (4-CCA), 4-ethoxycinnamic acid (4-ECA) and 4-nitrocinnamic acid (4-NCA) had inhibitory effects on tyrosinase. Spectrophotometric analysis used to determine the inhibition capabilities of these compounds on tyrosinase catalyzing L-tyrosine (L-Tyr) and L-3,4-Dihydroxyphenylalanine (L-DOPA) as well. The IC 50 values and inhibition constants were further determined. Moreover, quenching mechanisms of tested compounds to tyrosinase belonged to static type and a red shift on fluorescence emission peak occurred when 4-NCA added. Copper interacting and molecular docking demonstrated that 4-CCA could not bind directly to the copper, but it could interact with residues in the active center of tyrosinase. Meanwhile, 4-ECA and 4-NCA could chelate a copper ion of tyrosinase. Anti-tyrosinase activities of para-substituted cinnamic acid derivatives would lay scientific foundation for their utilization in designing of novel tyrosinase inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.

Physiologically based microenvironment for in vitro neural differentiation of adipose-derived stem cells.

PubMed

Graziano, Adriana Carol Eleonora; Avola, Rosanna; Perciavalle, Vincenzo; Nicoletti, Ferdinando; Cicala, Gianluca; Coco, Marinella; Cardile, Venera

2018-03-26

The limited capacity of nervous system to promote a spontaneous regeneration and the high rate of neurodegenerative diseases appearance are keys factors that stimulate researches both for defining the molecular mechanisms of pathophysiology and for evaluating putative strategies to induce neural tissue regeneration. In this latter aspect, the application of stem cells seems to be a promising approach, even if the control of their differentiation and the maintaining of a safe state of proliferation should be troubled. Here, we focus on adipose tissue-derived stem cells and we seek out the recent advances on the promotion of their neural differentiation, performing a critical integration of the basic biology and physiology of adipose tissue-derived stem cells with the functional modifications that the biophysical, biomechanical and biochemical microenvironment induces to cell phenotype. The pre-clinical studies showed that the neural differentiation by cell stimulation with growth factors benefits from the integration with biomaterials and biophysical interaction like microgravity. All these elements have been reported as furnisher of microenvironments with desirable biological, physical and mechanical properties. A critical review of current knowledge is here proposed, underscoring that a real advance toward a stable, safe and controllable adipose stem cells clinical application will derive from a synergic multidisciplinary approach that involves material engineer, basic cell biology, cell and tissue physiology.

Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors

NASA Astrophysics Data System (ADS)

Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

2017-11-01

The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

An apparatus to estimate the hydrodynamic coefficients of autonomous underwater vehicles using water tunnel testing.

PubMed

Nouri, N M; Mostafapour, K; Bahadori, R

2016-06-01

Hydrodynamic coefficients or hydrodynamic derivatives of autonomous underwater vehicles (AUVs) play an important role in their development and maneuverability. The most popular way of estimating their coefficients is to implement captive model tests such as straight line tests and planar motion mechanism (PMM) tests in the towing tanks. This paper aims to develop an apparatus based on planar experiments of water tunnel in order to estimate hydrodynamic derivatives due to AUVs' acceleration and velocity. The capability of implementing straight line tests and PMM ones using mechanical oscillators located in the downstream flow of the model is considered in the design procedure of the system. The hydrodynamic derivatives that resulted from the acceleration and velocity of the AUV model were estimated using the apparatus that we developed. Static and dynamics test results were compared for the similar derivatives. The findings showed that the system provided the basis for conducting static tests, i.e., straight-line and dynamic tests that included pure pitch and pure heave. By conducting such tests in a water tunnel, we were able to eliminate errors related to the time limitation of the tests and the effects of surface waves in the towing tank on AUVs with applications in the deep sea.

Investigations on 16-Arylideno Steroids as a New Class of Neuroprotective Agents for the Treatment of Alzheimer's and Parkinson's Diseases.

PubMed

Singh, Ranjit; Bansal, Ranju

2017-01-18

Neuroinflammatory mechanisms mediated by activated glial and cytokines (TNF-α, IL-1β) might contribute to neuronal degeneration leading to Alzheimer's (AD) and Parkinson's disease (PD). Lipopolysaccharide (LPS) is an inflammogen derived from the cell wall of Gram-negative bacteria, which promotes neuroinflammation and subsequent neurodegeneration. Dehydroepiandrosterone (DHEA) and testosterone have been reported as neuroprotective steroids useful for the treatment of various neurodegenerative disorders. In the present study, several 16-arylidene steroidal derivatives have been evaluated as neuroprotective agents in LPS-treated animal models. It was observed that 16-arylidene steroidal derivatives 1a-d and 6a-h considerably improve LPS-induced learning, memory, and movement deficits in animal models. Biochemical estimations of brain serum of treated animals revealed suppression of oxidative and nitrosative stress, acetylcholinesterase activity, and reduction in TNF-α levels, which were induced through LPS mediated neuroinflammatory mechanisms leading to neurodegeneration of brain. Of all the steroidal derivatives, 16-(4-pyridylidene) steroid 1c and its 4-aza analogue 6c were found to be the most active neuroprotective agents and produced effects comparable to standard drug celecoxib at a much lower dose and better than dexamethasone at the same dose in terms of behavioral, biochemical, and molecular aspects.

Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors.

PubMed

Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

2017-11-17

The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

A new strategy for earthquake focal mechanisms using waveform-correlation-derived relative polarities and cluster analysis: Application to the 2014 Long Valley Caldera earthquake swarm

USGS Publications Warehouse

Shelly, David R.; Hardebeck, Jeanne L.; Ellsworth, William L.; Hill, David P.

2016-01-01

In microseismicity analyses, reliable focal mechanisms can typically be obtained for only a small subset of located events. We address this limitation here, presenting a framework for determining robust focal mechanisms for entire populations of very small events. To achieve this, we resolve relative P and S wave polarities between pairs of waveforms by using their signed correlation coefficients—a by-product of previously performed precise earthquake relocation. We then use cluster analysis to group events with similar patterns of polarities across the network. Finally, we apply a standard mechanism inversion to the grouped data, using either catalog or correlation-derived P wave polarity data sets. This approach has great potential for enhancing analyses of spatially concentrated microseismicity such as earthquake swarms, mainshock-aftershock sequences, and industrial reservoir stimulation or injection-induced seismic sequences. To demonstrate its utility, we apply this technique to the 2014 Long Valley Caldera earthquake swarm. In our analysis, 85% of the events (7212 out of 8494 located by Shelly et al. [2016]) fall within five well-constrained mechanism clusters, more than 12 times the number with network-determined mechanisms. Of the earthquakes we characterize, 3023 (42%) have magnitudes smaller than 0.0. We find that mechanism variations are strongly associated with corresponding hypocentral structure, yet mechanism heterogeneity also occurs where it cannot be resolved by hypocentral patterns, often confined to small-magnitude events. Small (5–20°) rotations between mechanism orientations and earthquake location trends persist when we apply 3-D velocity models and might reflect a geometry of en echelon, interlinked shear, and dilational faulting.

Detailed fault structure of the Tarutung Pull-Apart Basin in Sumatra, Indonesia, derived from local earthquake data

NASA Astrophysics Data System (ADS)

Muksin, Umar; Haberland, Christian; Nukman, Mochamad; Bauer, Klaus; Weber, Michael

2014-12-01

The Tarutung Basin is located at a right step-over in the northern central segment of the dextral strike-slip Sumatran Fault System (SFS). Details of the fault structure along the Tarutung Basin are derived from the relocations of seismicity as well as from focal mechanism and structural geology. The seismicity distribution derived by a 3D inversion for hypocenter relocation is clustered according to a fault-like seismicity distribution. The seismicity is relocated with a double-difference technique (HYPODD) involving the waveform cross-correlations. We used 46,904 and 3191 arrival differences obtained from catalogue data and cross-correlation analysis, respectively. Focal mechanisms of events were analyzed by applying a grid search method (HASH code). Although there is no significant shift of the hypocenters (10.8 m in average) and centroids (167 m in average), the application of the double difference relocation sharpens the earthquake distribution. The earthquake lineation reflects the fault system, the extensional duplex fault system, and the negative flower structure within the Tarutung Basin. The focal mechanisms of events at the edge of the basin are dominantly of strike-slip type representing the dextral strike-slip Sumatran Fault System. The almost north-south striking normal fault events along extensional zones beneath the basin correlate with the maximum principal stress direction which is the direction of the Indo-Australian plate motion. The extensional zones form an en-echelon pattern indicated by the presence of strike-slip faults striking NE-SW to NW-SE events. The detailed characteristics of the fault system derived from the seismological study are also corroborated by structural geology at the surface.

Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-β and miR23a transfer.

PubMed

Berchem, Guy; Noman, Muhammad Zaeem; Bosseler, Manon; Paggetti, Jerome; Baconnais, Sonia; Le Cam, Eric; Nanbakhsh, Arash; Moussay, Etienne; Mami-Chouaib, Fathia; Janji, Bassam; Chouaib, Salem

2016-04-01

Tumor-derived microvesicles (TD-MVs) are key mediators which are shed by cancer cells and can sensitize neighboring cells in the tumor microenvironment. TD-MVs are extracellular vesicles composed of exosomes and MVs and promote cancer invasion and metastasis. Intratumoral hypoxia is an integral component of all solid tumors. The relationship between hypoxic tumor-shed MVs and NK-mediated cytotoxicity remains unknown. In this paper, we reported that MVs derived from hypoxic tumor cells qualitatively differ from those derived from normoxic tumor cells. Using multiple tumor models, we showed that hypoxic MVs inhibit more NK cell function as compared to normoxic MVs. Hypoxic TD-MVs package two immunosuppressive factors involved in the impairment of natural killer (NK) cell cytotoxicity against different tumor cells in vitro and in vivo . We showed that following their uptake by NK cells, hypoxic TD-MVs transfer TGF-β1 to NK cells, decreasing the cell surface expression of the activating receptor NKG2D, thereby inhibiting NK cell function. MicroRNA profiling revealed the presence of high levels of miR-210 and miR-23a in hypoxic TD-MVs. We demonstrated that miR-23a in hypoxic TD-MVs operates as an additional immunomosuppressive factor, since it directly targets the expression of CD107a in NK cells. To our knowledge, this is the first study to show that hypoxic tumor cells by secreting MVs can educate NK cells and decrease their antitumor immune response. This study highlights the existence of a novel mechanism of immune suppression mediated by hypoxic TD-MVs and further improves our understanding of the immunosuppressive mechanisms prevailing in the hypoxic tumor microenvironment.

Spectra of eigenstates in fermionic tensor quantum mechanics

NASA Astrophysics Data System (ADS)

Klebanov, Igor R.; Milekhin, Alexey; Popov, Fedor; Tarnopolsky, Grigory

2018-05-01

We study the O (N1)×O (N2)×O (N3) symmetric quantum mechanics of 3-index Majorana fermions. When the ranks Ni are all equal, this model has a large N limit which is dominated by the melonic Feynman diagrams. We derive an integral formula which computes the number of group invariant states for any set of Ni. It is non-vanishing only when each Ni is even. For equal ranks the number of singlets exhibits rapid growth with N : it jumps from 36 in the O (4 )3 model to 595 354 780 in the O (6 )3 model. We derive bounds on the values of energy, which show that they scale at most as N3 in the large N limit, in agreement with expectations. We also show that the splitting between the lowest singlet and non-singlet states is of order 1 /N . For N3=1 the tensor model reduces to O (N1)×O (N2) fermionic matrix quantum mechanics, and we find a simple expression for the Hamiltonian in terms of the quadratic Casimir operators of the symmetry group. A similar expression is derived for the complex matrix model with S U (N1)×S U (N2)×U (1 ) symmetry. Finally, we study the N3=2 case of the tensor model, which gives a more intricate complex matrix model whose symmetry is only O (N1)×O (N2)×U (1 ). All energies are again integers in appropriate units, and we derive a concise formula for the spectrum. The fermionic matrix models we studied possess standard 't Hooft large N limits where the ground state energies are of order N2, while the energy gaps are of order 1.

Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models.

PubMed

Liu, Lu; Wang, Lin-Peng; He, Shan; Ma, Yan

2018-05-01

Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of IgE antibodies by B cells and a decrease of the interferon-γ/interleukin-4 (Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine (CM) research on the mechanisms and effificacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the PubMed and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specifific immunoglobulin E, inflflammatory cell infifiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.

Macrophage Control of Phagocytosed Mycobacteria Is Increased by Factors Secreted by Alveolar Epithelial Cells through Nitric Oxide Independent Mechanisms

PubMed Central

Freidl, Raphaela; Fernández, Carmen

2014-01-01

Tissue-resident macrophages are heterogeneous with tissue-specific and niche-specific functions. Thus, simplified models of macrophage activation do not explain the extent of heterogeneity seen in vivo. We focus here on the respiratory tract and ask whether factors secreted by alveolar epithelial cells (AEC) can influence the functionality of resident pulmonary macrophages (PuM). We have previously reported that factors secreted by AEC increase control of intracellular growth of BCG in macrophages. In the current study, we also aimed to investigate possible mechanisms by which AEC-derived factors increase intracellular control of BCG in both primary murine interstitial macrophages, and bone marrow-derived macrophages and characterize further the effect of these factors on macrophage differentiation. We show that; a) in contrast to other macrophage types, IFN-γ did not increase intracellular growth control of Mycobacterium bovis, Bacillus Calmette-Guérin (BCG) by interstitial pulmonary macrophages although the same macrophages could be activated by factors secreted by AEC; b) the lack of response of pulmonary macrophages to IFN-γ was apparently regulated by suppressor of cytokine signaling (SOCS)1; c) AEC-derived factors did not induce pro-inflammatory pathways induced by IFN-γ e.g. expression of inducible nitric oxide synthase (iNOS), secretion of nitric oxide (NO), or IL-12, d) in contrast to IFN-γ, intracellular bacterial destruction induced by AEC-derived factors was not dependent on iNOS transcription and NO production. Collectively, our data show that PuM were restricted in inflammatory responses mediated by IFN-γ through SOCS1 and that factors secreted by AEC- enhanced the microbicidal capacities of macrophages by iNOS independent mechanisms. PMID:25089618

Low-energy collision-induced fragmentation of negative ions derived from ortho-, meta-, and para-hydroxyphenyl carbaldehydes, ketones, and related compounds.

PubMed

Attygalle, Athula B; Ruzicka, Josef; Varughese, Deepu; Bialecki, Jason B; Jafri, Sayed

2007-09-01

Collision-induced dissociation (CID) mass spectra of anions derived from several hydroxyphenyl carbaldehydes and ketones were recorded and mechanistically rationalized. For example, the spectrum of m/z 121 ion of deprotonated ortho-hydroxybenzaldehyde shows an intense peak at m/z 93 for a loss of carbon monoxide attributable to an ortho-effect mediated by a charge-directed heterolytic fragmentation mechanism. In contrast, the m/z 121 ion derived from meta and para isomers undergoes a charge-remote homolytic cleavage to eliminate an *H and form a distonic anion radical, which eventually loses CO to produce a peak at m/z 92. In fact, for the para isomer, this two-step homolytic mechanism is the most dominant fragmentation pathway. The spectrum of the meta isomer on the other hand, shows two predominant peaks at m/z 92 and 93 representing both homolytic and heterolytic fragmentations, respectively. (18)O-isotope-labeling studies confirmed that the oxygen in the CO molecule that is eliminated from the anion of meta-hydroxybenzaldehyde originates from either the aldehydic or the phenolic group. In contrast, anions of ortho-hydroxybenzaldehyde and 2-hydroxy-1-naphthaldehyde, both of which show two consecutive CO eliminations, specifically lose the carbonyl oxygen first, followed by that of the phenolic group. Anions from 2-hydroxyphenyl alkyl ketones lose a ketene by a hydrogen transfer predominantly from the alpha position. Interestingly, a very significant charge-remote 1,4-elimination of a H(2) molecule was observed from the anion derived from 2,4-dihydroxybenzaldehyde. For this mechanism to operate, a labile hydrogen atom should be available on the hydroxyl group adjacent to the carbaldehyde functionality.

Comparative antimicrobial activity and mechanism of action of bovine lactoferricin-derived synthetic peptides.

PubMed

Liu, Yifan; Han, Feifei; Xie, Yonggang; Wang, Yizhen

2011-12-01

Lactoferricin B (LfcinB), a 25 residue peptide derived from the N-terminal of bovine lactoferrin (bLF), causes depolarization of the cytoplasmic membrane in susceptible bacteria. Its mechanism of action, however, still needs to be elucidated. In the present study, synthetic LfcinB (without a disulfide bridge) and LfcinB (C-C; with a disulfide bridge) as well as three derivatives with 15-, 11- and 9-residue peptides were prepared to investigate their antimicrobial nature and mechanisms. The antimicrobial properties were measured via minimum inhibitory concentration (MIC) determinations, killing kinetics assays and synergy testing, and hemolytic activities were assessed by hemoglobin release. Finally, the morphology of peptide-treated bacteria was determined by atomic force microscopy (AFM). We found that there was no difference in MICs between LfcinB and LfcinB (C-C). Among the derivatives, only LfcinB15 maintained nearly the same level as LfcinB, in the MIC range of 16-128 μg/ml, and the MICs of LfcinB11 (64-256 μg/ml) were 4 times more than LfcinB, while LfcinB9 exhibited the lowest antimicrobial activity. When treated at MIC for 1 h, many blebs were formed and holes of various sizes appeared on the cell surface, but the cell still maintained its integrity. This suggested that LfcinB had a major permeability effect on the cytoplasmic membrane of both Gram-positive and Gram-negative bacteria, which also indicated it may be a possible intracellular target. Among the tested antibiotics, aureomycin increased the bactericidal activity of LfcinB against E. coli, S. aureus and P. aeruginosa, but neomycin did not have such an effect. We also found that the combination of cecropin A and LfcinB had synergistic effects against E. coli.

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes.

PubMed

Gao, Song; Carson, James A

2016-01-01

Mechanical stretch can activate muscle and myotube protein synthesis through mammalian target of rapamycin complex 1 (mTORC1) signaling. While it has been established that tumor-derived cachectic factors can induce myotube wasting, the effect of this catabolic environment on myotube mechanical signaling has not been determined. We investigated whether media containing cachectic factors derived from Lewis lung carcinoma (LLC) can regulate the stretch induction of myotube protein synthesis. C2C12 myotubes preincubated in control or LLC-derived media were chronically stretched. Protein synthesis regulation by anabolic and catabolic signaling was then examined. In the control condition, stretch increased mTORC1 activity and protein synthesis. The LLC treatment decreased basal mTORC1 activity and protein synthesis and attenuated the stretch induction of protein synthesis. LLC media increased STAT3 and AMP-activated protein kinase phosphorylation in myotubes, independent of stretch. Both stretch and LLC independently increased ERK1/2, p38, and NF-κB phosphorylation. In LLC-treated myotubes, the inhibition of ERK1/2 and p38 rescued the stretch induction of protein synthesis. Interestingly, either leukemia inhibitory factor or glycoprotein 130 antibody administration caused further inhibition of mTORC1 signaling and protein synthesis in stretched myotubes. AMP-activated protein kinase inhibition increased basal mTORC1 signaling activity and protein synthesis in LLC-treated myotubes, but did not restore the stretch induction of protein synthesis. These results demonstrate that LLC-derived cachectic factors can dissociate stretch-induced signaling from protein synthesis through ERK1/2 and p38 signaling, and that glycoprotein 130 signaling is associated with the basal stretch response in myotubes. Copyright © 2016 the American Physiological Society.

Noncontact minimally invasive technique for the assessment of mechanical properties of single cardiac myocyte via magnetic field loading

NASA Astrophysics Data System (ADS)

Yin, Shizhuo; Zhang, Xueqian; Cheung, Joseph; Wu, Juntao; Zhan, Chun; Xue, Jinchao

2004-07-01

In this paper, a unique non-contact, minimum invasive technique for the assessment of mechanical properties of single cardiac myocyte is presented. The assessment process includes following major steps: (1) attach a micro magnetic bead to the cell to be measured, (2) measure the contractile performance of the cell under the different magnetic field loading, (3) calculate mechanical loading force, and (4) derive the contractile force from the measured contraction data under different magnetic field loading.

Structure-Thermodynamics-Antioxidant Activity Relationships of Selected Natural Phenolic Acids and Derivatives: An Experimental and Theoretical Evaluation

PubMed Central

Zheng, Jie; Liang, Guizhao

2015-01-01

Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH• scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH•. Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media. PMID:25803685

Structure-thermodynamics-antioxidant activity relationships of selected natural phenolic acids and derivatives: an experimental and theoretical evaluation.

PubMed

Chen, Yuzhen; Xiao, Huizhi; Zheng, Jie; Liang, Guizhao

2015-01-01

Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH• scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH•. Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media.

Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism

PubMed Central

Yan, Fang; Cao, Hanwei; Cover, Timothy L.; Washington, M. Kay; Shi, Yan; Liu, LinShu; Chaturvedi, Rupesh; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

2011-01-01

Probiotic bacteria can potentially have beneficial effects on the clinical course of several intestinal disorders, but our understanding of probiotic action is limited. We have identified a probiotic bacteria–derived soluble protein, p40, from Lactobacillus rhamnosus GG (LGG), which prevents cytokine-induced apoptosis in intestinal epithelial cells. In the current study, we analyzed the mechanisms by which p40 regulates cellular responses in intestinal epithelial cells and p40’s effects on experimental colitis using mouse models. We show that the recombinant p40 protein activated EGFR, leading to Akt activation. Activation of EGFR by p40 was required for inhibition of cytokine-induced apoptosis in intestinal epithelial cells in vitro and ex vivo. Furthermore, we developed a pectin/zein hydrogel bead system to specifically deliver p40 to the mouse colon, which activated EGFR in colon epithelial cells. Administration of p40-containing beads reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium in an EGFR-dependent manner, thereby preventing and treating DSS-induced intestinal injury and acute colitis. Furthermore, p40 activation of EGFR was required for ameliorating colon epithelial cell apoptosis and chronic inflammation in oxazolone-induced colitis. These data define what we believe to be a previously unrecognized mechanism of probiotic-derived soluble proteins in protecting the intestine from injury and inflammation. PMID:21606592

Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy.

PubMed

Lin, Bo; Li, Yang; Han, Lu; Kaplan, Aaron D; Ao, Ying; Kalra, Spandan; Bett, Glenna C L; Rasmusson, Randall L; Denning, Chris; Yang, Lei

2015-05-01

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca(2+), mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca(2+) level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients. © 2015. Published by The Company of Biologists Ltd.

Photophysical and Photochemical Properties of 3-methylpterin as a New and More Stable Pterin-type Photosensitizer.

PubMed

Estébanez, Sandra; Lorente, Carolina; Kaufman, Teodoro S; Larghi, Enrique L; Thomas, Andrés H; Serrano, Mariana P

2018-05-04

Pterin derivatives are heterocyclic compounds which are present in different biological systems. Neutral aqueous solutions of pterins presents acid-base and keto-enol equilibria. These compounds under UV-A radiation fluoresce, undergo photooxidation, generate reactive oxygen species, and photoinduce the oxidation of biological substrates. As photosensitizers, they may act through different mechanisms; mainly through an electron-transfer initiated process (type I mechanism), but they also produce singlet molecular oxygen ( 1 O 2 ) upon irradiation (type II mechanism). In general, upon UV-A excitation two triplet states, corresponding to the lactim and lactam tautomers, are formed, but only the last one is the responsible for the photosensitized reactions of biomolecules. We present a study of the photochemical properties of 3-methylpterin (3-Mep) which, in contrast to most pterin derivatives, exists only in the lactam form. Also an improvement in the synthesis of 3-Mep is reported. The spectroscopic properties 3-Mep in aqueous solution were similar to those of the unsubstituted pterin derivative (Ptr) in its acid form, such as absorption, fluorescent and phosphorescent emission spectra. Experiments using 2'-deoxyguanosine 5'-monophosphate (dGMP) as oxidizable target, demonstrated that methylation at C-3 position of the pterin moiety does not affect significantly the efficiency of photosensitization, but results in a more photostable sensitizer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Anti-tumor effect of emodin on gynecological cancer cells.

PubMed

Wang, Yaoxian; Yu, Hui; Zhang, Jin; Ge, Xin; Gao, Jing; Zhang, Yunyan; Lou, Ge

2015-10-01

Although an anti-tumor effect of emodin has been reported before, its effect on human gynecological cancer cells has so far not been studied. Here, we assessed the effect of emodin on cervical cancer-derived (Hela), choriocarcinoma-derived (JAR) and ovarian cancer-derived (HO-8910) cells, and investigated the possible underlying molecular and cellular mechanisms. The respective cells were treated with 0, 5, 10 or 15 μM emodin for 72 h. Subsequently, MTT and Transwell in vitro migration assays revealed that emodin significantly decreased the viability and invasive capacity of the gynecological cancer-derived cells tested. We found that emodin induced apoptosis and significantly decreased mitochondrial membrane potential and ATP release in these cells. We also found that emodin may exert its apoptotic effects via regulating the activity of caspase-9 and the expression of cleaved-caspase-3. Moreover, we found that emodin induced a cell cycle arrest at the G0/G1 phase, possibly through down-regulating the key cell cycle regulators Cyclin D and Cyclin E. Interestingly, emodin also led to autophagic cell death, as revealed by increased MAP LC3 expression, a marker of the autophagosome, and decreased expression of the autophagy regulators Beclin-1 and Atg12-Atg5. Finally, we found that the protein levels of both VEGF and VEGFR-2 were significantly decreased in emodin-treated cells, suggesting an anti-angiogenic effect of emodin on gynecological cancer-derived cells. Our results suggest that emodin exhibits an anti-tumor effect on gynecological cancer-derived cells, possibly through multiple mechanisms including the induction of apoptosis and autophagy, the arrest of the cell cycle, and the inhibition of angiogenesis. Our findings may provide a basis for the design of potential emodin-based strategies for the treatment of gynecological tumors.

Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells.

PubMed

Kim, Gi Dae; Oh, Jedo; Park, Hyen-Joo; Bae, Kihwan; Lee, Sang Kook

2013-08-01

Magnolol, a neolignan from the traditional medicinal plant Magnolia obovata, has been shown to possess neuroprotective, anti-inflammatory, anticancer and anti-angiogenic activities. However, the precise mechanism of the anti-angiogenic activity of magnolol remains to be elucidated. In the present study, the anti-angiogenic effect of magnolol was evaluated in mouse embryonic stem (mES)/embryoid body (EB)-derived endothelial-like cells. The endothelial-like cells were obtained by differentiation from mES/EB cells. Magnolol (20 µM) significantly suppressed the transcriptional and translational expression of platelet endothelial cell adhesion molecule (PECAM), an endothelial biomarker, in mES/EB-derived endothelial-like cells. To further understand the molecular mechanism of the suppression of PECAM expression, signaling pathways were analyzed in the mES/EB-derived endothelial-like cells. Magnolol induced the generation of reactive oxygen species (ROS) by mitochondria, a process that was associated with the induction of apoptosis as determined by positive Annexin V staining and the activation of cleaved caspase-3. The involvement of ROS generation by magnolol was confirmed by treatment with an antioxidant, N-acetyl-cysteine (NAC). NAC inhibited the magnolol-mediated induction of ROS generation and suppression of PECAM expression. In addition, magnolol suppressed the activation of MAPKs (ERK, JNK and p38) and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. Taken together, these findings demonstrate for the first time that the anti-angiogenic activity of magnolol may be associated with ROS-mediated apoptosis and the suppression of the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells.

Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling

PubMed Central

Kim, Hye-Young H.; Bauer, Rebecca N.; Fessler, Michael B.; Duncan, Kelly E.; Liu, Wei; Porter, Ned A.

2016-01-01

When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell membranes or the lung-lining fluid, generating chemically reactive oxysterols. The mechanism by which O3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and -β and secosterol A and B (Seco A and Seco B), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O3 contained elevated levels of these oxysterol species. As expected, O3-derived oxysterols have a pro-inflammatory effect and increase NF-κB activity. Interestingly, expression of the cholesterol efflux pump ATP-binding cassette transporter 1 (ABCA1), which is regulated by activation of the liver X receptor (LXR), was suppressed in epithelial cells exposed to O3. Additionally, exposure of LXR knock-out mice to O3 enhanced pro-inflammatory cytokine production in the lung, suggesting LXR inhibits O3-induced inflammation. Using alkynyl surrogates of O3-derived oxysterols, our data demonstrate adduction of LXR with Seco A. Similarly, supplementation of epithelial cells with alkynyl-tagged cholesterol followed by O3 exposure causes observable lipid-LXR adduct formation. Experiments using Seco A and the LXR agonist T0901317 (T09) showed reduced expression of ABCA1 as compared with stimulation with T0901317 alone, indicating that Seco A-LXR protein adduct formation inhibits LXR activation by traditional agonists. Overall, these data demonstrate that O3-derived oxysterols have pro-inflammatory functions and form lipid-protein adducts with LXR, thus leading to suppressed cholesterol regulatory gene expression and providing a biochemical mechanism mediating O3-derived formation of oxidized lipids in the airways and subsequent adverse health effects. PMID:27703007

Effect of phytotoxic secondary metabolites and semisynthetic compounds from endophytic fungus Xylaria feejeensis strain SM3e-1b on spinach chloroplast photosynthesis.

PubMed

Macías-Rubalcava, Martha Lydia; García-Méndez, Marbella Claudia; King-Díaz, Beatriz; Macías-Ruvalcaba, Norma Angélica

2017-01-01

We investigated the mechanism of action on the photosynthesis light reactions of three major secondary metabolites produced by the endophytic fungus Xylaria feejeensis strain SM3e-1b, isolated from Sapium macrocarpum; and four novel derivatives of coriloxine, a major compound produced by X. feejeensis. The natural phytotoxins include one epoxycyclohexenone derivative, coriloxine (1), and two quinone derivatives (2-3). The semisynthetic derivatives of coriloxine are two cyclohexenone (4-6) and two quinone compounds (5-7). Cyclohexenone (4), (4R,5S,6R)-6-chloro-4,5-dihydroxy-3-methoxy-5-methylcyclohex-2-enone, inhibited ATP synthesis in freshly lysed spinach chloroplasts from water to MV; it also partly inhibited the basal and uncoupled photosynthetic electron transport, and significantly enhanced the phosphorylating electron transport and Mg 2+ -ATPase activity, thus demonstrating its action as an uncoupler agent. On the other hand, quinone (7), 2-((4-butylphenyl)amino)-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione, inhibited ATP synthesis, and non-cyclic electron transport from water to MV in basal, phosphorylating and uncoupled conditions in a concentration-dependent manner. Hence, (7) behaves as a Hill reaction inhibitor at the PSII electron transport on the water splitting enzyme (OEC), and on the acceptor side between P 680 and Q A . This mechanism of action was confirmed by chlorophyll a fluorescence measurements. These results indicate that coriloxine derivatives 4 and 7 could work as prototype structures for the development of new herbicides. Contrastingly, natural products 1-3, and derivatives 5 and 6 did not show a significant inhibitory effect on ATP synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Gastropod-derived haemocyte extracellular traps entrap metastrongyloid larval stages of Angiostrongylus vasorum, Aelurostrongylus abstrusus and Troglostrongylus brevior.

PubMed

Lange, Malin K; Penagos-Tabares, Felipe; Muñoz-Caro, Tamara; Gärtner, Ulrich; Mejer, Helena; Schaper, Roland; Hermosilla, Carlos; Taubert, Anja

2017-01-31

Phagocyte-derived extracellular traps (ETs) were recently demonstrated mainly in vertebrate hosts as an important effector mechanism against invading parasites. In the present study we aimed to characterize gastropod-derived invertebrate extracellular phagocyte trap (InEPT) formation in response to larval stages of important canine and feline metastrongyloid lungworms. Gastropod haemocytes were isolated from the slug species Arion lusitanicus and Limax maximus, and the snail Achatina fulica, and exposed to larval stages of Angiostrongylus vasorum, Aelurostrongylus abstrusus and Troglostrongylus brevior and investigated for gastropod-derived InEPT formation. Phase contrast as well as scanning electron microscopy (SEM) analyses of lungworm larvae-exposed haemocytes revealed ET-like structures to be extruded by haemocytes thereby contacting and ensnaring the parasites. Co-localization studies of haemocyte-derived extracellular DNA with histones and myeloperoxidase in larvae-entrapping structures confirmed classical characteristics of ETs. In vivo exposure of slugs to A. vasorum larvae resulted in InEPTs being extruded from haemocytes in the slug mucous extrapallial space emphasizing the pivotal role of this effector mechanism against invasive larvae. Functional larval entrapment assays demonstrated that almost half of the haemocyte-exposed larvae were contacted or even immobilized by released InEPTs. Overall, as reported for mammalian-derived ETs, different types of InEPTs were here observed, i.e. aggregated, spread and diffused InEPTs. To our knowledge, this study represents the first report on metastrongyloid lungworm-triggered ETosis in gastropods thereby providing evidence of early mollusc host innate immune reactions against invading larvae. These findings will contribute to the better understanding on complex parasite-intermediate host interactions since different gastropod species bear different transmitting capacities for metastrongyloid infections.

The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building.

PubMed

Dupradeau, François-Yves; Pigache, Adrien; Zaffran, Thomas; Savineau, Corentin; Lelong, Rodolphe; Grivel, Nicolas; Lelong, Dimitri; Rosanski, Wilfried; Cieplak, Piotr

2010-07-28

Deriving atomic charges and building a force field library for a new molecule are key steps when developing a force field required for conducting structural and energy-based analysis using molecular mechanics. Derivation of popular RESP charges for a set of residues is a complex and error prone procedure because it depends on numerous input parameters. To overcome these problems, the R.E.D. Tools (RESP and ESP charge Derive, ) have been developed to perform charge derivation in an automatic and straightforward way. The R.E.D. program handles chemical elements up to bromine in the periodic table. It interfaces different quantum mechanical programs employed for geometry optimization and computing molecular electrostatic potential(s), and performs charge fitting using the RESP program. By defining tight optimization criteria and by controlling the molecular orientation of each optimized geometry, charge values are reproduced at any computer platform with an accuracy of 0.0001 e. The charges can be fitted using multiple conformations, making them suitable for molecular dynamics simulations. R.E.D. allows also for defining charge constraints during multiple molecule charge fitting, which are used to derive charges for molecular fragments. Finally, R.E.D. incorporates charges into a force field library, readily usable in molecular dynamics computer packages. For complex cases, such as a set of homologous molecules belonging to a common family, an entire force field topology database is generated. Currently, the atomic charges and force field libraries have been developed for more than fifty model systems and stored in the RESP ESP charge DDataBase. Selected results related to non-polarizable charge models are presented and discussed.

Distribution theory for Schrödinger’s integral equation

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

Lange, Rutger-Jan, E-mail: rutger-jan.lange@cantab.net

2015-12-15

Much of the literature on point interactions in quantum mechanics has focused on the differential form of Schrödinger’s equation. This paper, in contrast, investigates the integral form of Schrödinger’s equation. While both forms are known to be equivalent for smooth potentials, this is not true for distributional potentials. Here, we assume that the potential is given by a distribution defined on the space of discontinuous test functions. First, by using Schrödinger’s integral equation, we confirm a seminal result by Kurasov, which was originally obtained in the context of Schrödinger’s differential equation. This hints at a possible deeper connection between bothmore » forms of the equation. We also sketch a generalisation of Kurasov’s [J. Math. Anal. Appl. 201(1), 297–323 (1996)] result to hypersurfaces. Second, we derive a new closed-form solution to Schrödinger’s integral equation with a delta prime potential. This potential has attracted considerable attention, including some controversy. Interestingly, the derived propagator satisfies boundary conditions that were previously derived using Schrödinger’s differential equation. Third, we derive boundary conditions for “super-singular” potentials given by higher-order derivatives of the delta potential. These boundary conditions cannot be incorporated into the normal framework of self-adjoint extensions. We show that the boundary conditions depend on the energy of the solution and that probability is conserved. This paper thereby confirms several seminal results and derives some new ones. In sum, it shows that Schrödinger’s integral equation is a viable tool for studying singular interactions in quantum mechanics.« less

Theoretical calculations on the electron absorption spectra of selected Polycyclic Aromatic Hydrocarbons (PAH) and derivatives

NASA Technical Reports Server (NTRS)

Du, Ping

1993-01-01

As a theoretical component of the joint effort with the laboratory of Dr. Lou Allamandola to search for potential candidates for interstellar organic carbon compound that are responsible for the visible diffuse interstellar absorption bands (DIB's), quantum mechanical calculations were performed on the electron absorption spectra of selected polycyclic aromatic hydrocarbons (PAH) and derivatives. In the completed project, 15 different species of naphthalene, its hydrogen abstraction and addition derivatives, and corresponding cations and anions were studied. Using semiempirical quantum mechanical method INDO/S, the ground electronic state of each species was evaluated with restricted Hartree-Fock scheme and limited configuration interaction. The lowest energy spin state for each species was used for electron absorption calculations. Results indicate that these calculations are accurate enough to reproduce the spectra of naphthalene cation and anion observed in neon matrix. The spectral pattern of the hydrogen abstraction and addition derivatives predicted based on these results indicate that the electron configuration of the pi orbitals of these species is the dominant determinant. A combined list of 19 absorptions calculated from 4500 A to 10,400 A were compiled and suggested as potential candidates that are relevant for the DIB's absorptions. Continued studies on pyrene and derivatives revealed the ground state symmetries and multiplicities of its neutral, anionic, and cationic species. Spectral calculations show that the cation (B(sub 3g)-2) and the anion (A(sub u)-2) are more likely to have low energy absorptions in the regions between 10 kK and 20 kK, similar to naphthalene. These absorptions, together with those to be determined from the hydrogen abstraction and addition derivatives of pyrene, can be used to provide additional candidates and suggest experimental work in the search for interstellar compounds that are responsible for DIB's.

A Continuum Mechanical Approach to Geodesics in Shape Space

DTIC Science & Technology

2010-01-01

the space of shapes, where shapes are implicitly described as boundary contours of objects. The proposed shape metric is derived from a ...investigate the close link between abstract geometry on the infinite -dimen- sional space of shapes and the continuum mechanical view of shapes as boundary...are texture-coded in the bottom row. of multiple components of volumetric objects. The

Effects of wood fiber characteristics on mechanical properties of wood/polypropylene composites

Treesearch

Nicole M. Stark; Robert E. Rowlands

2003-01-01

Commercial wood flour, the most common wood-derived filler for thermoplastics, is produced in a mixture of particle sizes and generally has a lower aspect ratio than wood and other natural fibers. To understand how wood flour and fiber characteristics influence the mechanical properties of polypropylene composites, we first investigated the effect of different sizes of...

Mechanical characterization of scalable cellulose nano-fiber based composites made using liquid composite molding process

Treesearch

Bamdad Barari; Thomas K. Ellingham; Issam I. Ghamhia; Krishna M. Pillai; Rani El-Hajjar; Lih-Sheng Turng; Ronald Sabo

2016-01-01

Plant derived cellulose nano-fibers (CNF) are a material with remarkable mechanical properties compared to other natural fibers. However, efforts to produce nano-composites on a large scale using CNF have yet to be investigated. In this study, scalable CNF nano-composites were made from isotropically porous CNF preforms using a freeze drying process. An improvised...

The Utility of the Lambert Function W[a exp(a - bt)] in Chemical Kinetics

ERIC Educational Resources Information Center

Williams, Brian Wesley

2010-01-01

The mathematical Lambert function W[a exp(a - bt)] is used to find integrated rate laws for several examples, including simple enzyme and Lindemann-Christiansen-Hinshelwood (LCH) unimolecular decay kinetics. The results derived here for the well-known LCH mechanism as well as for a dimer-monomer reaction mechanism appear to be novel. A nonlinear…

Simple One-Dimensional Quantum-Mechanical Model for a Particle Attached to a Surface

ERIC Educational Resources Information Center

Fernandez, Francisco M.

2010-01-01

We present a simple one-dimensional quantum-mechanical model for a particle attached to a surface. It leads to the Schrodinger equation for a harmonic oscillator bounded on one side that we solve in terms of Weber functions and discuss the behaviour of the eigenvalues and eigenfunctions. We derive the virial theorem and other exact relationships…

Confidence versus Performance as an Indicator of the Presence of Alternative Conceptions and Inadequate Problem-Solving Skills in Mechanics

ERIC Educational Resources Information Center

Potgieter, Marietjie; Malatje, Esther; Gaigher, Estelle; Venter, Elsie

2010-01-01

This study investigated the use of performance-confidence relationships to signal the presence of alternative conceptions and inadequate problem-solving skills in mechanics. A group of 33 students entering physics at a South African university participated in the project. The test instrument consisted of 20 items derived from existing standardised…

Genomic mechanisms of stress tolerance for the industrial yeast Saccharomyces cerevisiae against the major chemical classes of inhibitors derived from lignocellulosic biomass conversion

USDA-ARS?s Scientific Manuscript database

Scientists at ARS developed tolerant industrial yeast that is able to reduce major chemical classes of inhibitors into less toxic or none toxic compounds while producing ethanol. Using genomic studies, we defined mechanisms of in situ detoxification involved in novel gene functions, vital cofactor r...

Metastasis Suppressor Gene Inactivates Actin-Based Mechanism of Tumor Cell Motility | Center for Cancer Research

Cancer.gov

Metastasis is responsible for up to 90 percent of all cancer-related deaths. Though proteins derived from nearly a dozen metastasis suppressor genes have been discovered over the past 15 years, strategies for exploiting the proteins in metastasis-prevention therapies has been hampered by the lack of knowledge regarding the mechanisms underlying the proteins’ interactions with

The effect of platelet lysate supplementation of a dextran-based hydrogel on cartilage formation.

PubMed

Moreira Teixeira, Liliana S; Leijten, Jeroen C H; Wennink, Jos W H; Chatterjea, Anindita G; Feijen, Jan; van Blitterswijk, Clemens A; Dijkstra, Pieter J; Karperien, Marcel

2012-05-01

In situ gelating dextran-tyramine (Dex-TA) injectable hydrogels have previously shown promising features for cartilage repair. Yet, despite suitable mechanical properties, this system lacks intrinsic biological signals. In contrast, platelet lysate-derived hydrogels are rich in growth factors and anti-inflammatory cytokines, but mechanically unstable. We hypothesized that the advantages of these systems may be combined in one hydrogel, which can be easily translated into clinical settings. Platelet lysate was successfully incorporated into Dex-TA polymer solution prior to gelation. After enzymatic crosslinking, rheological and morphological evaluations were performed. Subsequently, the effect of platelet lysate on cell migration, adhesion, proliferation and multi-lineage differentiation was determined. Finally, we evaluated the integration potential of this gel onto osteoarthritis-affected cartilage. The mechanical properties and covalent attachment of Dex-TA to cartilage tissue during in situ gel formation were successfully combined with the advantages of platelet lysate, revealing the potential of this enhanced hydrogel as a cell-free approach. The addition of platelet lysate did not affect the mechanical properties and porosity of Dex-TA hydrogels. Furthermore, platelet lysate derived anabolic growth factors promoted proliferation and triggered chondrogenic differentiation of mesenchymal stromal cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Influence of model order reduction methods on dynamical-optical simulations

NASA Astrophysics Data System (ADS)

Störkle, Johannes; Eberhard, Peter

2017-04-01

In this work, the influence of model order reduction (MOR) methods on optical aberrations is analyzed within a dynamical-optical simulation of a high precision optomechanical system. Therefore, an integrated modeling process and new methods have to be introduced for the computation and investigation of the overall dynamical-optical behavior. For instance, this optical system can be a telescope optic or a lithographic objective. In order to derive a simplified mechanical model for transient time simulations with low computational cost, the method of elastic multibody systems in combination with MOR methods can be used. For this, software tools and interfaces are defined and created. Furthermore, mechanical and optical simulation models are derived and implemented. With these, on the one hand, the mechanical sensitivity can be investigated for arbitrary external excitations and on the other hand, the related optical behavior can be predicted. In order to clarify these methods, academic examples are chosen and the influences of the MOR methods and simulation strategies are analyzed. Finally, the systems are investigated with respect to the mechanical-optical frequency responses, and in conclusion, some recommendations for the application of reduction methods are given.

Structure-mechanics property relationship of waste derived biochars.

PubMed

Das, Oisik; Sarmah, Ajit K; Bhattacharyya, Debes

2015-12-15

The widespread applications of biochar in agriculture and environmental remediation made the scientific community ignore its mechanical properties. Hence, to examine the scope of biochar's structural applications, its mechanical properties have been investigated in this paper through nanoindentation technique. Seven waste derived biochars, made under different pyrolysis conditions and from diverse feedstocks, were studied via nanoindentation, infrared spectroscopy, X-ray crystallography, thermogravimetry, and electron microscopy. Following this, an attempt was made to correlate the biochars' hardness/modulus with reaction conditions and their chemical properties. The pine wood biochar made at 900°C and 60min residence time was found to have the highest hardness and elastic modulus of 4.29 and 25.01GPa, respectively. It was shown that a combination of higher heat treatment (≥500°C) temperature and longer residence time (~60min) increases the values of hardness and modulus. It was further realized that pyrolysis temperature was a more dominant factor than residence time in determining the final mechanical properties of biochar particles. The degree of aromaticity and crystallinity of the biochar were also correlated with higher values of hardness and modulus. Copyright © 2015 Elsevier B.V. All rights reserved.

Constraints on primordial magnetic fields from inflation

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

Green, Daniel; Kobayashi, Takeshi, E-mail: drgreen@cita.utoronto.ca, E-mail: takeshi.kobayashi@sissa.it

2016-03-01

We present generic bounds on magnetic fields produced from cosmic inflation. By investigating field bounds on the vector potential, we constrain both the quantum mechanical production of magnetic fields and their classical growth in a model independent way. For classical growth, we show that only if the reheating temperature is as low as T{sub reh} ∼< 10{sup 2} MeV can magnetic fields of 10{sup −15} G be produced on Mpc scales in the present universe. For purely quantum mechanical scenarios, even stronger constraints are derived. Our bounds on classical and quantum mechanical scenarios apply to generic theories of inflationary magnetogenesis with a two-derivative timemore » kinetic term for the vector potential. In both cases, the magnetic field strength is limited by the gravitational back-reaction of the electric fields that are produced simultaneously. As an example of quantum mechanical scenarios, we construct vector field theories whose time diffeomorphisms are spontaneously broken, and explore magnetic field generation in theories with a variable speed of light. Transitions of quantum vector field fluctuations into classical fluctuations are also analyzed in the examples.« less

Sol-Gel Derived Hydroxyapatite Coating on Mg-3Zn Alloy for Orthopedic Application

NASA Astrophysics Data System (ADS)

Singh, Sanjay; Manoj Kumar, R.; Kuntal, Kishor Kumar; Gupta, Pallavi; Das, Snehashish; Jayaganthan, R.; Roy, Partha; Lahiri, Debrupa

2015-04-01

In recent years, magnesium and its alloys have gained a lot of interest as orthopedic implant constituents because their biodegradability and mechanical properties are closer to that of human bone. However, one major concern with Mg in orthopedics is its high corrosion rate that results in the reduction of mechanical integrity before healing the bone tissue. The current study evaluates the sol-gel-derived hydroxyapatite (HA) coating on a selected Mg alloy (Mg-3Zn) for decreasing the corrosion rate and increasing the bioactivity of the Mg surface. The mechanical integrity of the coating is established as a function of the surface roughness of the substrate and the sintering temperature of the coating. Coating on a substrate roughness of 15-20 nm and sintering at 400°C shows the mechanical properties in similar range of bone, thus making it suitable to avoid the stress-shielding effect. The hydroxyapatite coating on the Mg alloy surface also increases corrosion resistance very significantly by 40 times. Bone cells are also found proliferating better in the HA-coated surface. All these benefits together establish the candidature of sol-gel HA-coated Mg-3Zn alloy in orthopedic application.

NUMERICAL SIMULATION OF NANOINDENTATION AND PATCH CLAMP EXPERIMENTS ON MECHANOSENSITIVE CHANNELS OF LARGE CONDUCTANCE IN ESCHERICHIA COLI

PubMed Central

Tang, Yuye; Chen, Xi; Yoo, Jejoong; Yethiraj, Arun; Cui, Qiang

2010-01-01

A hierarchical simulation framework that integrates information from all-atom simulations into a finite element model at the continuum level is established to study the mechanical response of a mechanosensitive channel of large conductance (MscL) in bacteria Escherichia Coli (E.coli) embedded in a vesicle formed by the dipalmitoylphosphatidycholine (DPPC) lipid bilayer. Sufficient structural details of the protein are built into the continuum model, with key parameters and material properties derived from molecular mechanics simulations. The multi-scale framework is used to analyze the gating of MscL when the lipid vesicle is subjective to nanoindentation and patch clamp experiments, and the detailed structural transitions of the protein are obtained explicitly as a function of external load; it is currently impossible to derive such information based solely on all-atom simulations. The gating pathways of E.coli-MscL qualitatively agree with results from previous patch clamp experiments. The gating mechanisms under complex indentation-induced deformation are also predicted. This versatile hierarchical multi-scale framework may be further extended to study the mechanical behaviors of cells and biomolecules, as well as to guide and stimulate biomechanics experiments. PMID:21874098

Curdlan blocks the immune suppression by myeloid-derived suppressor cells and reduces tumor burden.

PubMed

Rui, Ke; Tian, Jie; Tang, Xinyi; Ma, Jie; Xu, Ping; Tian, Xinyu; Wang, Yungang; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

2016-08-01

Tumor-elicited immunosuppression is one of the essential mechanisms for tumor evasion of immune surveillance. It is widely thought to be one of the main reasons for the failure of tumor immunotherapy. Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of cells that play an important role in tumor-induced immunosuppression. These cells expand in tumor-bearing individuals and suppress T cell responses via various mechanisms. Curdlan, the linear (1 → 3)-β-glucan from Agrobacterium, has been applied in the food industry and other sectors. The anti-tumor property of curdlan has been recognized for a long time although the underlying mechanism still needs to be explored. In this study, we investigated the effect of curdlan on MDSCs and found that curdlan could promote MDSCs to differentiate into a more mature state and then significantly reduce the suppressive function of MDSCs, decrease the MDSCs in vivo and down-regulate the suppression in tumor-bearing mice, thus leading to enhanced anti-tumor immune responses. We, therefore, increase the understanding of further mechanisms by which curdlan achieves anti-tumor effects.

Bisubstrate inhibition: Theory and application to N-acetyltransferases.

PubMed

Yu, Michael; Magalhães, Maria L B; Cook, Paul F; Blanchard, John S

2006-12-12

Bisubstrate inhibitors represent a potentially powerful group of compounds that have found significant therapeutic utility. Although these compounds have been synthesized and tested against a number of enzymes that catalyze sequential bireactant reactions, the detailed theory for predicting the expected patterns of inhibition against the two substrates for various bireactant kinetic mechanisms has, heretofore, not been presented. We have derived the rate equations for all likely sequential bireactant mechanisms and provide two examples in which bisubstrate inhibitors allow the kinetic mechanism to be determined. Bisubstrate inhibitor kinetics is a powerful diagnostic for the determination of kinetic mechanisms.

FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin

PubMed Central

Kode, Aruna; Mosialou, Ioanna; Silva, Barbara C.; Rached, Marie-Therese; Zhou, Bin; Wang, Ji; Townes, Tim M.; Hen, Rene; DePinho, Ronald A.; Guo, X. Edward; Kousteni, Stavroula

2012-01-01

Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element–binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation. PMID:22945629

Adsorption Characteristics of Pb(2+) onto Wine Lees-Derived Biochar.

PubMed

Zhu, Qihong; Wu, Jun; Wang, Lilin; Yang, Gang; Zhang, Xiaohong

2016-08-01

Biochar has great advantages in soil amendment and polluted soil remediation. Herein, the pore and adsorption properties of wine lees-derived biochar were explored. Specifically, the adsorption isotherm and kinetics of Pb(2+) onto wine lees-derived biochar were examined. Experimental results revealed that wine lees-derived biochar featured large specific surface area and total pore volume, and high contents of -COOH and -OH on its surface. Adsorption of Pb(2+) onto wine lees-derived biochar proceeded via a multilayer adsorption mechanism, as described by the Freundlich adsorption model. Adsorption kinetics followed the Lagergren pseudo-second-order kinetics model; adsorption equilibrium was achieved within 30-60 min. Furthermore, the effect of solution pH on the adsorption of Pb(2+) was investigated. Within the studied pH range of 3-6, the adsorption capacity increased with increasing pH. Under established optimized conditions, wine lees-derived biochar achieved a Pb(2+) adsorption capacity of 79.12 mg/g.

Chitosan derivatives targeting lipid bilayers: Synthesis, biological activity and interaction with model membranes.

PubMed

Martins, Danubia Batista; Nasário, Fábio Domingues; Silva-Gonçalves, Laiz Costa; de Oliveira Tiera, Vera Aparecida; Arcisio-Miranda, Manoel; Tiera, Marcio José; Dos Santos Cabrera, Marcia Perez

2018-02-01

The antimicrobial activity of chitosan and derivatives to human and plant pathogens represents a high-valued prospective market. Presently, two low molecular weight derivatives, endowed with hydrophobic and cationic character at different ratios were synthesized and characterized. They exhibit antimicrobial activity and increased performance in relation to the intermediate and starting compounds. However, just the derivative with higher cationic character showed cytotoxicity towards human cervical carcinoma cells. Considering cell membranes as targets, the mode of action was investigated through the interaction with model lipid vesicles mimicking bacterial, tumoral and erythrocyte membranes. Intense lytic activity and binding are demonstrated for both derivatives in anionic bilayers. The less charged compound exhibits slightly improved selectivity towards bacterial model membranes, suggesting that balancing its hydrophobic/hydrophilic character may improve efficiency. Observing the aggregation of vesicles, we hypothesize that the "charge cluster mechanism", ascribed to some antimicrobial peptides, could be applied to these chitosan derivatives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Delayed rectifier potassium channels are involved in SO2 derivative-induced hippocampal neuronal injury.

PubMed

Li, Guangke; Sang, Nan

2009-01-01

Recent studies implicate the possible neurotoxicity of SO(2), however, its mechanisms remain unclear. In the present study, we investigated SO(2) derivative-induced effect on delayed rectifier potassium channels (I(K)) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO(2) derivatives (NaHSO(3) and Na(2)SO(3), 3:1M/M) effectively augmented I(K) and promoted the activation of delayed rectifier potassium channels. Also, SO(2) derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO(2) derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not by the transient outward potassium channel blocker (4-aminopyridine, 4-AP). It implies that stimulating delayed rectifier potassium channels were involved in SO(2) derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO(2)-caused neuronal dysfunction.

Ferroquine and its derivatives: new generation of antimalarial agents.

PubMed

Wani, Waseem A; Jameel, Ehtesham; Baig, Umair; Mumtazuddin, Syed; Hun, Lee Ting

2015-08-28

Malaria has been teasing human populations from a long time. Presently, several classes of antimalarial drugs are available in market, but the issues of toxicity, lower efficacy and the resistance by malarial parasites have decreased their overall therapeutic indices. Thus, the search for new promising antimalarials continues, however, the battle against malaria is far from over. Ferroquine is a derivative of chloroquine with antimalarial properties. It is the most successful of the chloroquine derivatives. Not only ferroquine, but also its derivatives have shown promising potential as antimalarials of clinical interest. Presently, much research is dedicated to the development of ferroquine derivatives as safe alternatives to antimalarial chemotherapy. The present article describes the structural, chemical and biological features of ferroquine. Several classes of ferroquine derivatives including hydroxyferroquines, trioxaferroquines, chloroquine-bridged ferrocenophanes, thiosemicarbazone derivatives, ferrocene dual conjugates, 4-N-substituted derivatives, and others have been discussed. Besides, the mechanism of action of ferroquine has been discussed. A careful observation has been made into pharmacologically significant ferroquine derivatives with better or equal therapeutic effects to that of chloroquine and ferroquine. A brief discussion of the toxicities of ferroquine derivatives has been made. Finally, efforts have been made to discuss the current challenges and future perspectives of ferroquine-based antimalarial drug development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D collagen matrix: Effects of niche cell supplementation and mechanical stimulation.

PubMed

Zhang, W; Kong, C W; Tong, M H; Chooi, W H; Huang, N; Li, R A; Chan, B P

2017-02-01

Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as a promising source for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. Here, we fabricate cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials. Supplementation of niche cells at 3% to the number of hESC-CMs enhance the maturation of the hESC-CMs in 3D tissue matrix. The benefits of adding mesenchymal stem cells (MSCs) are comparable to that of adding fibroblasts. These two cell types demonstrate similar effects in promoting the compaction and cell spreading, as well as expression of maturation markers at both gene and protein levels. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of twitch force, elastic modulus, sarcomere length and molecular signature, when comparing to static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture. Our results therefore suggest that this 3D model can be used for in vitro cardiac maturation study. Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded as being a promising source of cells for regenerative medicine, drug testing and disease modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile structure, metabolism and electrophysiological properties. In the current study, we have fabricated cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials and demonstrated that supplementation of mesenchymal niche cells as well as provision of mechanical loading particularly stretching have significantly promoted the maturation of the cardiomyocytes and hence improved the mechanical functional characteristics of the tissue strips. Specifically, with 3% niche cells including both fibroblasts and mesenchymal stem cells, a more mature hESC-CMs derived cardiac strip was resulted, in terms of compaction and spreading of cells, and upregulation of molecular signature in both gene and protein expression of maturation. Mechanical loading, particularly cyclic stretch, produces engineered cardiac tissues with higher maturity in terms of molecular signature markers and functional parameters including twitch force, elastic modulus and sarcomere length, when comparing with static stretch or non-stretched controls. The current study demonstrates that the application of niche cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D architecture, resulting in more mature cardiac strips. Our results contribute to bioengineering of functional heart tissue strips for drug screening and disease modeling. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Organic microchemical performance of solvent resistant polycarbosilane based microreactor.

PubMed

Yoon, Tae-Ho; Jung, Sang-Hee; Kim, Dong-Pyo

2011-05-01

We report the successful fabrication of preceramic polymer allylhydridopolycarbosilane (AHPCS) derived microchannels with excellent organic solvent resistance and optical transparency via economic imprinting process, followed by UV and post thermal curing process at 160 degrees C for 3 h. The microchemical performance of the fabricated microreactors was evaluated by choosing two model micro chemical reactions under organic solvent conditions; syntheses of 2-aminothiazole in DMF and dimethylpyrazole in THF, and compared with glass-based microreactor having identical dimensions and batch system with analogy. It is clear that AHPCS derived microreactor showed excellent solvent resistance and chemical stability compare with glass derived microreactor made by high cost of photolithography and thermal bonding process. The novel preceramic polymer derived microreactors showed reliable mechanical and chemical stability and conversion yields compare with that of glass derived microreactors, which is very promising for developing an integrated microfluidics by adopting available microstructuring techniques of the polymers.

Added clinical value of applying myocardial deformation imaging to assess right ventricular function.

PubMed

Sokalskis, Vladislavs; Peluso, Diletta; Jagodzinski, Annika; Sinning, Christoph

2017-06-01

Right heart dysfunction has been found to be a strong prognostic factor predicting adverse outcome in various cardiopulmonary diseases. Conventional echocardiographic measurements can be limited by geometrical assumptions and impaired reproducibility. Speckle tracking-derived strain provides a robust quantification of right ventricular function. It explicitly evaluates myocardial deformation, as opposed to tissue Doppler-derived strain, which is computed from tissue velocity gradients. Right ventricular longitudinal strain provides a sensitive tool for detecting right ventricular dysfunction, even at subclinical levels. Moreover, the longitudinal strain can be applied for prognostic stratification of patients with pulmonary hypertension, pulmonary embolism, and congestive heart failure. Speckle tracking-derived right atrial strain, right ventricular longitudinal strain-derived mechanical dyssynchrony, and three-dimensional echocardiography-derived strain are emerging imaging parameters and methods. Their application in research is paving the way for their clinical use. © 2017, Wiley Periodicals, Inc.

A relation between deformed superspace and Lee-Wick higher-derivative theories

NASA Astrophysics Data System (ADS)

Dias, M.; Ferrari, A. F.; Palechor, C. A.; Senise, C. R., Jr.

2015-07-01

We propose a non-anticommutative superspace that relates to the Lee-Wick type of higher-derivative theories, which are known for their interesting properties and have led to proposals of phenomenologically viable higher-derivative extensions of the Standard Model. The deformation of superspace we consider does not preserve supersymmetry or associativity in general, but, we show that a non-anticommutative version of the Wess-Zumino model can be properly defined. In fact, the definition of chiral and antichiral superfields turns out to be simpler in our case than in the well known N=1/2 supersymmetric case. We show that when the theory is truncated at the first nontrivial order in the deformation parameter, supersymmetry is restored, and we end up with a well-known Lee-Wick type of higher-derivative extension of the Wess-Zumino model. Thus, we show how non-anticommutativity could provide an alternative mechanism for generating these higher-derivative theories.

tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA.

PubMed

Li, Siqi; Xu, Zhengping; Sheng, Jinghao

2018-05-10

Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions.

Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles.

PubMed

Bilyy, Rostyslav O; Shkandina, Tanya; Tomin, Andriy; Muñoz, Luis E; Franz, Sandra; Antonyuk, Volodymyr; Kit, Yuriy Ya; Zirngibl, Matthias; Fürnrohr, Barbara G; Janko, Christina; Lauber, Kirsten; Schiller, Martin; Schett, Georg; Stoika, Rostyslav S; Herrmann, Martin

2012-01-02

Inappropriate clearance of apoptotic remnants is considered to be the primary cause of systemic autoimmune diseases, like systemic lupus erythematosus. Here we demonstrate that apoptotic cells release distinct types of subcellular membranous particles (scMP) derived from the endoplasmic reticulum (ER) or the plasma membrane. Both types of scMP exhibit desialylated glycotopes resulting from surface exposure of immature ER-derived glycoproteins or from surface-borne sialidase activity, respectively. Sialidase activity is activated by caspase-dependent mechanisms during apoptosis. Cleavage of sialidase Neu1 by caspase 3 was shown to be directly involved in apoptosis-related increase of surface sialidase activity. ER-derived blebs possess immature mannosidic glycoepitopes and are prioritized by macrophages during clearance. Plasma membrane-derived blebs contain nuclear chromatin (DNA and histones) but not components of the nuclear envelope. Existence of two immunologically distinct types of apoptotic blebs may provide new insights into clearance-related diseases.

The chemical (not mechanical) paradigm of thermodynamics of colloid and interface science.

PubMed

Kaptay, George

2018-06-01

In the most influential monograph on colloid and interfacial science by Adamson three fundamental equations of "physical chemistry of surfaces" are identified: the Laplace equation, the Kelvin equation and the Gibbs adsorption equation, with a mechanical definition of surface tension by Young as a starting point. Three of them (Young, Laplace and Kelvin) are called here the "mechanical paradigm". In contrary it is shown here that there is only one fundamental equation of the thermodynamics of colloid and interface science and all the above (and other) equations of this field follow as its derivatives. This equation is due to chemical thermodynamics of Gibbs, called here the "chemical paradigm", leading to the definition of surface tension and to 5 rows of equations (see Graphical abstract). The first row is the general equation for interfacial forces, leading to the Young equation, to the Bakker equation and to the Laplace equation, etc. Although the principally wrong extension of the Laplace equation formally leads to the Kelvin equation, using the chemical paradigm it becomes clear that the Kelvin equation is generally incorrect, although it provides right results in special cases. The second row of equations provides equilibrium shapes and positions of phases, including sessile drops of Young, crystals of Wulff, liquids in capillaries, etc. The third row of equations leads to the size-dependent equations of molar Gibbs energies of nano-phases and chemical potentials of their components; from here the corrected versions of the Kelvin equation and its derivatives (the Gibbs-Thomson equation and the Freundlich-Ostwald equation) are derived, including equations for more complex problems. The fourth row of equations is the nucleation theory of Gibbs, also contradicting the Kelvin equation. The fifth row of equations is the adsorption equation of Gibbs, and also the definition of the partial surface tension, leading to the Butler equation and to its derivatives, including the Langmuir equation and the Szyszkowski equation. Positioning the single fundamental equation of Gibbs into the thermodynamic origin of colloid and interface science leads to a coherent set of correct equations of this field. The same provides the chemical (not mechanical) foundation of the chemical (not mechanical) discipline of colloid and interface science. Copyright © 2018 Elsevier B.V. All rights reserved.

Involvement of PKC and ROS in the cytotoxic mechanism of anti-leukemic decursin and its derivatives and their structure-activity relationship in human K562 erythroleukemia and U937 myeloleukemia cells.

PubMed

Kim, Hyeon Ho; Sik Bang, Sung; Seok Choi, Jin; Han, Hogyu; Kim, Ik-Hwan

2005-06-08

Protein kinase C (PKC) plays an important role in the proliferation and differentiation of various cell types including normal and leukemic hematopoietic cells. Recently, various PKC modulators were used as a chemotherapeutic agent of leukemia. Decursin (1), a pyranocoumarin from Angelica gigas, exhibits the cytotoxic effects on various human cancer cell lines and in vitro PKC activation. For the development of more effective anticancer agents with PKC modulation activity, 11 decursin derivatives 2-12 were chemically synthesized and evaluated for their ability to act as a tumor-suppressing PKC activator and as an antagonist to phorbol 12-myristate 13-acetate (PMA), a tumor-promoting PKC activator. In the presence of phosphatidylserine (PS), all of 12 compounds 1-12 activated PKC (mainly alpha, beta, and gamma isozymes) but only three compounds 1-3 activated PKC even in the absence of PS. Six compounds 1-6 containing the coumarin structure were cytotoxic to human K562 erythroleukemia and U937 myeloleukemia cells. A cytotoxic mechanism of decursin and its derivatives was investigated using TUR cells, a PKC betaII-deficient variant of U937 cells. Among six compounds 1-6 with cytotoxicity to K562 and U937 leukemia cells, only three compounds 1-3 were cytotoxic to TUR cells. Therefore, compounds 1-3 and 4-6 inhibit the proliferation of leukemia cells in a PKC betaII-independent and dependent manner, respectively, indicating that the side chain of compounds determines the dependency of their cytotoxicity on PKC betaII. To further elucidate the cytotoxic mechanism of compounds 1 and 2, levels of PKC isozymes and generation of reactive oxygen species (ROS) were investigated. Compounds 1-2 induced the down-regulation of PKC alpha and betaII in K562 cells and the production of ROS in U937 cells. Thus, PKC and ROS are probably important factors in the cytotoxic mechanism of compounds 1-2. From these results, the structure-activity relationship of decursin and its derivatives is as follows: (i) the coumarin structure is required for anti-leukemic activity and (ii) the side chain is a determinant of PKC activation and the cytotoxic mechanism in leukemia cells.

Characterisation of the natural environment: quantitative indicators across Europe.

PubMed

Smith, Graham; Cirach, Marta; Swart, Wim; Dėdelė, Audrius; Gidlow, Christopher; van Kempen, Elise; Kruize, Hanneke; Gražulevičienė, Regina; Nieuwenhuijsen, Mark J

2017-04-26

The World Health Organization recognises the importance of natural environments for human health. Evidence for natural environment-health associations comes largely from single countries or regions, with varied approaches to measuring natural environment exposure. We present a standardised approach to measuring neighbourhood natural environment exposure in cities in different regions of Europe. The Positive Health Effects of the Natural Outdoor environment in TYPical populations of different regions in Europe (PHENOTYPE) study aimed to explore the mechanisms linking natural environment exposure and health in four European cities (Barcelona, Spain; Doetinchem, the Netherlands; Kaunas, Lithuania; and Stoke-on-Trent, UK). Common GIS protocols were used to develop a hierarchy of natural environment measures, from simple measures (e.g., NDVI, Urban Atlas) using Europe-wide data sources, to detailed measures derived from local data that were specific to mechanisms thought to underpin natural environment-health associations (physical activity, social interaction, stress reduction/restoration). Indicators were created around residential addresses for a range of straight line and network buffers (100 m-1 km). For simple indicators derived from Europe-wide data, we observed differences between cities, which varied with different indicators (e.g., Kaunas and Doetinchem had equal highest mean NDVI within 100 m buffer, but mean distance to nearest natural environment in Kaunas was more twice that in Doetinchem). Mean distance to nearest natural environment for all cities suggested that most participants lived close to some kind of natural environments (64 ± 58-363 ± 281 m; mean 180 ± 204 m). The detailed classification highlighted marked between-city differences in terms of prominent types of natural environment. Indicators specific to mechanisms derived from this classification also captured more variation than the simple indicators. Distance to nearest and count indicators showed clear differences between cities, and those specific to the mechanisms showed within-city differences for Barcelona and Doetinchem. This paper demonstrates the feasibility and challenges of creating comparable GIS-derived natural environment exposure indicators across diverse European cities. Mechanism-specific indicators showed within- and between-city variability that supports their utility for ecological studies, which could inform more specific policy recommendations than the traditional proxies for natural environment access.

Lagrange thermodynamic potential and intrinsic variables for He-3 He-4 dilute solutions

NASA Technical Reports Server (NTRS)

Jackson, H. W.

1983-01-01

For a two-fluid model of dilute solutions of He-3 in liquid He-4, a thermodynamic potential is constructed that provides a Lagrangian for deriving equations of motion by a variational procedure. This Lagrangian is defined for uniform velocity fields as a (negative) Legendre transform of total internal energy, and its primary independent variables, together with their thermodynamic conjugates, are identified. Here, similarities between relations in classical physics and quantum statistical mechanics serve as a guide for developing an alternate expression for this function that reveals its character as the difference between apparent kinetic energy and intrinsic internal energy. When the He-3 concentration in the mixtures tends to zero, this expression reduces to Zilsel's formula for the Lagrangian for pure liquid He-4. An investigation of properties of the intrinsic internal energy leads to the introduction of intrinsic chemical potentials along with other intrinsic variables for the mixtures. Explicit formulas for these variables are derived for a noninteracting elementary excitation model of the fluid. Using these formulas and others also derived from quantum statistical mechanics, another equivalent expression for the Lagrangian is generated.

GDF15 is a heart-derived hormone that regulates body growth.

PubMed

Wang, Ting; Liu, Jian; McDonald, Caitlin; Lupino, Katherine; Zhai, Xiandun; Wilkins, Benjamin J; Hakonarson, Hakon; Pei, Liming

2017-08-01

The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well-established clinical observation that children with heart diseases often develop FTT. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Hypothalamic regulation of body growth and appetite by ghrelin-derived peptides during balanced nutrition or undernutrition.

PubMed

Hassouna, Rim; Labarthe, Alexandra; Tolle, Virginie

2016-12-15

Among the gastrointestinal hormones that regulate food intake and energy homeostasis, ghrelin plays a unique role as the first one identified to increases appetite and stimulate GH secretion. This review highlights the latest mechanism by which ghrelin modulates body growth, appetite and energy metabolism by exploring pharmacological actions of the hormone and consequences of genetic or pharmacological blockade of the ghrelin/GHS-R (Growth Hormone Secretagogue Receptor) system on physiological responses in specific nutritional situations. Within the hypothalamus, novel mechanisms of action of this hormone involve its interaction with other ghrelin-derived peptides, such as desacyl ghrelin and obestatin, which are thought to act as functional ghrelin antagonists, and possible modulation of the GHS-R with other G-protein coupled receptors. During chronic undernutrition such as anorexia nervosa, variations of ghrelin-derived peptides may be an adaptative metabolic response to maintain normal glycemic control. Interestingly, some of ghrelin's metabolic actions are thought to be relayed through modulation of GH, an anabolic and hyperglycemic agent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Differential Uptake Mechanisms of Fluorescent Substrates into Stem-Cell-Derived Serotonergic Neurons.

PubMed

Matthaeus, Friederike; Schloss, Patrick; Lau, Thorsten

2015-12-16

The actions of the neurotransmitters serotonin, dopamine, and norepinephrine are partly terminated by diffusion and in part by their uptake into neurons via the selective, high-affinity transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET), respectively. There is also growing evidence that all three monoamines are taken up into neurons by low-affinity, high-capacity organic cation transporters (OCT) and the plasma membrane monoamine transporter (PMAT). Pharmacological characterization of these low-affinity recombinant transporter proteins in heterologous expression systems has revealed that they are not antagonized by classical inhibitors of SERT, DAT, or NET but that decynium-22 (D22) antagonizes OCT3 and PMAT, whereas corticosterone and progesterone selectively inhibit OCT3. Here, we show that SERT, PMAT, and OCT3, but not OCT1 and OCT2, are coexpressed in murine stem cell-derived serotonergic neurons. Using selective antagonists, we provide evidence that uptake of the fluorescent substrates FFN511, ASP+, and 5-HT into stem cell-derived serotonergic neurons is mediated differentially by these transporters and also involves an as yet unknown transport mechanism.

Reinforcement of natural rubber hybrid composites based on marble sludge/Silica and marble sludge/rice husk derived silica

PubMed Central

Ahmed, Khalil; Nizami, Shaikh Sirajuddin; Riza, Nudrat Zahid

2013-01-01

A research has been carried out to develop natural rubber (NR) hybrid composites reinforced with marble sludge (MS)/Silica and MS/rice husk derived silica (RHS). The primary aim of this development is to scrutinize the cure characteristics, mechanical and swelling properties of such hybrid composite. The use of both industrial and agricultural waste such as marble sludge and rice husk derived silica has the primary advantage of being eco-friendly, low cost and easily available as compared to other expensive fillers. The results from this study showed that the performance of NR hybrid composites with MS/Silica and MS/RHS as fillers is extremely better in mechanical and swelling properties as compared with the case where MS used as single filler. The study suggests that the use of recently developed silica and marble sludge as industrial and agricultural waste is accomplished to provide a probable cost effective, industrially prospective, and attractive replacement to the in general purpose used fillers like china clay, calcium carbonate, and talc. PMID:25685484

Energy analysis in the elliptic restricted three-body problem

NASA Astrophysics Data System (ADS)

Qi, Yi; de Ruiter, Anton

2018-07-01

The gravity assist or flyby is investigated by analysing the inertial energy of a test particle in the elliptic restricted three-body problem (ERTBP), where two primary bodies are moving in elliptic orbits. First, the expression of the derivation of energy is obtained and discussed. Then, the approximate expressions of energy change in a circular neighbourhood of the smaller primary are derived. Numerical computation indicates that the obtained expressions can be applied to study the flyby problem of the nine planets and the Moon in the Solar system. Parameters related to the flyby are discussed analytically and numerically. The optimal conditions, including the position and time of the periapsis, for a flyby orbit are found to make a maximum energy gain or loss. Finally, the mechanical process of a flyby orbit is uncovered by an approximate expression in the ERTBP. Numerical computations testify that our analytical results well approximate the mechanical process of flyby orbits obtained by the numerical simulation in the ERTBP. Compared with the previous research established in the patched-conic method and numerical calculation, our analytical investigations based on a more elaborate derivation get more original results.

Photoreduction of Terrigenous Fe-Humic Substances Leads to Bioavailable Iron in Oceans.

PubMed

Blazevic, Amir; Orlowska, Ewelina; Kandioller, Wolfgang; Jirsa, Franz; Keppler, Bernhard K; Tafili-Kryeziu, Myrvete; Linert, Wolfgang; Krachler, Rudolf F; Krachler, Regina; Rompel, Annette

2016-05-23

Humic substances (HS) are important iron chelators responsible for the transport of iron from freshwater systems to the open sea, where iron is essential for marine organisms. Evidence suggests that iron complexed to HS comprises the bulk of the iron ligand pool in near-coastal waters and shelf seas. River-derived HS have been investigated to study their transport to, and dwell in oceanic waters. A library of iron model compounds and river-derived Fe-HS samples were probed in a combined X-ray absorption spectroscopy (XAS) and valence-to-core X-ray emission spectroscopy (VtC-XES) study at the Fe K-edge. The analyses performed revealed that iron complexation in HS samples is only dependent on oxygen-containing HS functional groups, such as carboxyl and phenol. The photoreduction mechanism of Fe III -HS in oceanic conditions into bioavailable aquatic Fe II forms, highlights the importance of river-derived HS as an iron source for marine organisms. Consequently, such mechanisms are a vital component of the upper-ocean iron biogeochemistry cycle.

Novel Bifunctional Quinolonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, Biological Activities and Mechanism of Action

PubMed Central

Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Artico, Marino; Lavecchia, Antonio; Marinelli, Luciana; Novellino, Ettore; Palmisano, Lucia; Andreotti, Mauro; Amici, Roberta; Galluzzo, Clementina Maria; Nencioni, Lucia; Palamara, Anna Teresa; Pommier, Yves; Marchand, Christophe

2008-01-01

The virally encoded integrase protein is an essential enzyme in the life cycle of the HIV-1 virus and represents an attractive and validated target in the development of therapeutics against HIV infection. Drugs that selectively inhibit this enzyme, when used in combination with inhibitors of reverse transcriptase and protease, are believed to be highly effective in suppressing the viral replication. Among the HIV-1 integrase inhibitors, the β-diketo acids (DKAs) represent a major lead for anti-HIV-1drug development. In this study, novel bifunctional quinolonyl diketo acid derivatives were designed, synthesized and tested for their inhibitory ability against HIV-1 integrase. The compounds are potent inhibitors of integrase activity. Particularly, derivative 8 is a potent IN inhibitor for both steps of the reaction (3′-processing and strand transfer) and exhibits both high antiviral activity against HIV-1 infected cells and low cytotoxicity. Molecular modeling studies provide a plausible mechanism of action, which is consistent with ligand SARs and enzyme photo-crosslinking experiments. PMID:16539381

Solvent effects on the absorption spectrum and first hyperpolarizability of keto-enol tautomeric forms of anil derivatives: A Monte Carlo/quantum mechanics study

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

Adriano Junior, L.; Fonseca, T. L.; Castro, M. A.

2016-06-21

Theoretical results for the absorption spectrum and electric properties of the enol and keto tautomeric forms of anil derivatives in the gas-phase and in solution are presented. The electronic properties in chloroform, acetonitrile, methanol, and water were determined by carrying out sequential Monte Carlo simulations and quantum mechanics calculations based on the time dependent density functional theory and on the second-order Møller–Plesset perturbation theory method. The results illustrate the role played by electrostatic interactions in the electronic properties of anil derivatives in a liquid environment. There is a significant increase of the dipole moment in solution (20%-100%) relative to themore » gas-phase value. Solvent effects are mild for the absorption spectrum and linear polarizability but they can be particularly important for first hyperpolarizability. A large first hyperpolarizability contrast between the enol and keto forms is observed when absorption spectra present intense lowest-energy absorption bands. Dynamic results for the first hyperpolarizability are in qualitative agreement with the available experimental results.« less

Energy Analysis in the Elliptic Restricted Three-body Problem

NASA Astrophysics Data System (ADS)

Qi, Yi; de Ruiter, Anton

2018-05-01

The gravity assist or flyby is investigated by analyzing the inertial energy of a test particle in the elliptic restricted three-body problem (ERTBP), where two primary bodies are moving in elliptic orbits. Firstly, the expression of the derivation of energy is obtained and discussed. Then, the approximate expressions of energy change in a circular neighborhood of the smaller primary are derived. Numerical computation indicates that the obtained expressions can be applied to study the flyby problem of the nine planets and the Moon in the solar system. Parameters related to the flyby are discussed analytically and numerically. The optimal conditions, including the position and time of the periapsis, for a flyby orbit are found to make a maximum energy gain or loss. Finally, the mechanical process of a flyby orbit is uncovered by an approximate expression in the ERTBP. Numerical computations testify that our analytical results well approximate the mechanical process of flyby orbits obtained by the numerical simulation in the ERTBP. Compared with the previous research established in the patched-conic method and numerical calculation, our analytical investigations based on a more elaborate derivation get more original results.

Antidiabetic plant-derived nutraceuticals: a critical review.

PubMed

Naveen, Jayapal; Baskaran, Vallikannan

2018-06-01

Diabetes mellitus (DM) is one of the major health problems in the world, especially amongst the urban population. Chemically synthesized drugs used to decrease the ill effects of DM and its secondary complications cause adverse side effects, viz., weight gain, gastrointestinal disturbances, and heart failure. Currently, various other approaches, viz., diet control, physical exercise and use of antidiabetic plant-derived molecules/foods are advocated to manage DM, as they are economical with fewer or no side effects. This review mainly focuses on antidiabetic plants, chemically characterized plant molecules and plant-based foods in the treatment of DM. Very little science-based evidence is available on the mechanism of action of plant-derived food molecules on the DM targets. Critical DM targets include α-amylase, α-glucosidase, DPP-IV, aldose reductase, PPAR-γ, AMP kinase and GLUT4. In-depth studies carried out on a few of those targets with specific mechanisms of action are addressed in this review. This review may help future researchers in identifying a right plant molecule to treat DM or to develop food formulations for DM management.

B cell–derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity

PubMed Central

Arkatkar, Tanvi

2017-01-01

Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell–derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell–derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-γ, consistent with the critical roles for B cell–intrinsic IFN-γ receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation. PMID:28899868

Uncertainty principle in loop quantum cosmology by Moyal formalism

NASA Astrophysics Data System (ADS)

Perlov, Leonid

2018-03-01

In this paper, we derive the uncertainty principle for the loop quantum cosmology homogeneous and isotropic Friedmann-Lemaiter-Robertson-Walker model with the holonomy-flux algebra. The uncertainty principle is between the variables c, with the meaning of connection and μ having the meaning of the physical cell volume to the power 2/3, i.e., v2 /3 or a plaquette area. Since both μ and c are not operators, but rather the random variables, the Robertson uncertainty principle derivation that works for hermitian operators cannot be used. Instead we use the Wigner-Moyal-Groenewold phase space formalism. The Wigner-Moyal-Groenewold formalism was originally applied to the Heisenberg algebra of the quantum mechanics. One can derive it from both the canonical and path integral quantum mechanics as well as the uncertainty principle. In this paper, we apply it to the holonomy-flux algebra in the case of the homogeneous and isotropic space. Another result is the expression for the Wigner function on the space of the cylindrical wave functions defined on Rb in c variables rather than in dual space μ variables.

Molecular targets of antihypertensive peptides: understanding the mechanisms of action based on the pathophysiology of hypertension.

PubMed

Majumder, Kaustav; Wu, Jianping

2014-12-24

There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

A study of a steering system algorithm for pleasure boats based on stability analysis of a human-machine system model

NASA Astrophysics Data System (ADS)

Ikeda, Fujio; Toyama, Shigehiro; Ishiduki, Souta; Seta, Hiroaki

2016-09-01

Maritime accidents of small ships continue to increase in number. One of the major factors is poor manoeuvrability of the Manual Hydraulic Steering Mechanism (MHSM) in common use. The manoeuvrability can be improved by using the Electronic Control Steering Mechanism (ECSM). This paper conducts stability analyses of a pleasure boat controlled by human models in view of path following on a target course, in order to establish design guidelines for the ECSM. First, to analyse the stability region, the research derives the linear approximated model in a planar global coordinate system. Then, several human models are assumed to develop closed-loop human-machine controlled systems. These human models include basic proportional, derivative, integral and time-delay actions. The stability analysis simulations for those human-machine systems are carried out. The results show that the stability region tends to spread as a ship's velocity increases in the case of the basic proportional human model. The derivative action and time-delay action of human models are effective in spreading the stability region in their respective ranges of frontal gazing points.

Label-free quantitative proteomic analysis of human plasma-derived microvesicles to find protein signatures of abdominal aortic aneurysms.

PubMed

Martinez-Pinna, Roxana; Gonzalez de Peredo, Anne; Monsarrat, Bernard; Burlet-Schiltz, Odile; Martin-Ventura, Jose Luis

2014-08-01

To find potential biomarkers of abdominal aortic aneurysms (AAA), we performed a differential proteomic study based on human plasma-derived microvesicles. Exosomes and microparticles isolated from plasma of AAA patients and control subjects (n = 10 each group) were analyzed by a label-free quantitative MS-based strategy. Homemade and publicly available software packages have been used for MS data analysis. The application of two kinds of bioinformatic tools allowed us to find differential protein profiles from AAA patients. Some of these proteins found by the two analysis methods belong to main pathological mechanisms of AAA such as oxidative stress, immune-inflammation, and thrombosis. Data analysis from label-free MS-based experiments requires the use of sophisticated bioinformatic approaches to perform quantitative studies from complex protein mixtures. The application of two of these bioinformatic tools provided us a preliminary list of differential proteins found in plasma-derived microvesicles not previously associated to AAA, which could help us to understand the pathological mechanisms related to this disease. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evolution from a natural flavones nucleus to obtain 2-(4-Propoxyphenyl)quinoline derivatives as potent inhibitors of the S. aureus NorA efflux pump.

PubMed

Sabatini, Stefano; Gosetto, Francesca; Manfroni, Giuseppe; Tabarrini, Oriana; Kaatz, Glenn W; Patel, Diixa; Cecchetti, Violetta

2011-08-25

Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of substrate antimicrobial agents. Inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant phenotype. In this work, a series of 2-phenyl-4(1H)-quinolone and 2-phenyl-4-hydroxyquinoline derivatives, obtained by modifying the flavone nucleus of known efflux pump inhibitors (EPIs), were synthesized in an effort to identify more potent S. aureus NorA EPIs. The 2-phenyl-4-hydroxyquinoline derivatives 28f and 29f display potent EPI activity against SA-1199B, a strain that overexpresses norA, in an ethidium bromide efflux inhibition assay. The same compounds, in combination with ciprofloxacin, were able to completely restore its antibacterial activity against both S. aureus SA-K2378 and SA-1199B, norA-overexpressing strains. © 2011 American Chemical Society

Towards a second law for Lovelock theories

NASA Astrophysics Data System (ADS)

Bhattacharyya, Sayantani; Haehl, Felix M.; Kundu, Nilay; Loganayagam, R.; Rangamani, Mukund

2017-03-01

In classical general relativity described by Einstein-Hilbert gravity, black holes behave as thermodynamic objects. In particular, the laws of black hole mechanics can be interpreted as laws of thermodynamics. The first law of black hole mechanics extends to higher derivative theories via the Noether charge construction of Wald. One also expects the statement of the second law, which in Einstein-Hilbert theory owes to Hawking's area theorem, to extend to higher derivative theories. To argue for this however one needs a notion of entropy for dynamical black holes, which the Noether charge construction does not provide. We propose such an entropy function for the family of Lovelock theories, treating the higher derivative terms as perturbations to the Einstein-Hilbert theory. Working around a dynamical black hole solution, and making no assumptions about the amplitude of departure from equilibrium, we construct a candidate entropy functional valid to all orders in the low energy effective field theory. This entropy functional satisfies a second law, modulo a certain subtle boundary term, which deserves further investigation in non-spherically symmetric situations.

Operational Axioms for Quantum Mechanics

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

D'Ariano, Giacomo Mauro; Department of Electrical and Computer Engineering, Northwestern University, Evanston, IL 60208

2007-02-21

The mathematical formulation of Quantum Mechanics in terms of complex Hilbert space is derived for finite dimensions, starting from a general definition of physical experiment and from five simple Postulates concerning experimental accessibility and simplicity. For the infinite dimensional case, on the other hand, a C*-algebra representation of physical transformations is derived, starting from just four of the five Postulates via a Gelfand-Naimark-Segal (GNS) construction. The present paper simplifies and sharpens the previous derivation in Ref. [1]. The main ingredient of the axiomatization is the postulated existence of faithful states that allows one to calibrate the experimental apparatus. Such notionmore » is at the basis of the operational definitions of the scalar product and of the transposed of a physical transformation. What is new in the present paper with respect to Ref. [1], is the operational deduction of an involution corresponding to the complex-conjugation for effects, whose extension to transformations allows to define the adjoint of a transformation when the extension is composition-preserving. The existence of such composition-preserving extension among possible extensions is analyzed.« less

Transfer matrix approach to the persistent current in quantum rings: Application to hybrid normal-superconducting rings

NASA Astrophysics Data System (ADS)

Nava, Andrea; Giuliano, Rosa; Campagnano, Gabriele; Giuliano, Domenico

2016-11-01

Using the properties of the transfer matrix of one-dimensional quantum mechanical systems, we derive an exact formula for the persistent current across a quantum mechanical ring pierced by a magnetic flux Φ as a single integral of a known function of the system's parameters. Our approach provides exact results at zero temperature, which can be readily extended to a finite temperature T . We apply our technique to exactly compute the persistent current through p -wave and s -wave superconducting-normal hybrid rings, deriving full plots of the current as a function of the applied flux at various system's scales. Doing so, we recover at once a number of effects such as the crossover in the current periodicity on increasing the size of the ring and the signature of the topological phase transition in the p -wave case. In the limit of a large ring size, resorting to a systematic expansion in inverse powers of the ring length, we derive exact analytic closed-form formulas, applicable to a number of cases of physical interest.

Study on the refractive index matching effect of ultrasound on optical clearing of bio-tissues based on the derivative total reflection method.

PubMed

Zeng, Huanhuan; Wang, Jin; Ye, Qing; Deng, Zhichao; Mei, Jianchun; Zhou, Wenyuan; Zhang, Chunping; Tian, Jianguo

2014-10-01

In recent years, the tissue optical clearing (OC) technique in the biomedicine field has drawn lots of attention. Various physical and chemical methods have been introduced to improve the efficacy of OC. In this study, the effect of the combination of glycerol and ultrasound treatment on OC of in vitro porcine muscle tissues has been investigated. The refractive index (RI) matching mechanism of OC was directly observed based on the derivative total reflection method. A theoretical model was used to simulate the proportion of tissue fluid in the illuminated area. Moreover, the total transmittance spectra have been obtained by a spectrometer over the range from 450 nm to 700 nm. The administration of glycerol and ultrasound has led to an increase of the RI of background medium and a more RI matching environment was achieved. The experimental results support the validity of the ultrasound treatment for OC. The RI matching mechanism has been firstly quantitatively analyzed based on the derivative total reflection method.

Linear and nonlinear equivalent circuit modeling of CMUTs.

PubMed

Lohfink, Annette; Eccardt, Peter-Christian

2005-12-01

Using piston radiator and plate capacitance theory capacitive micromachined ultrasound transducers (CMUT) membrane cells can be described by one-dimensional (1-D) model parameters. This paper describes in detail a new method, which derives a 1-D model for CMUT arrays from finite-element methods (FEM) simulations. A few static and harmonic FEM analyses of a single CMUT membrane cell are sufficient to derive the mechanical and electrical parameters of an equivalent piston as the moving part of the cell area. For an array of parallel-driven cells, the acoustic parameters are derived as a complex mechanical fluid impedance, depending on the membrane shape form. As a main advantage, the nonlinear behavior of the CMUT can be investigated much easier and faster compared to FEM simulations, e.g., for a design of the maximum applicable voltage depending on the input signal. The 1-D parameter model allows an easy description of the CMUT behavior in air and fluids and simplifies the investigation of wave propagation within the connecting fluid represented by FEM or transmission line matrix (TLM) models.

Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

PubMed Central

Majumder, Kaustav; Wu, Jianping

2014-01-01

There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides. PMID:25547491

Polyimides based on 4,4'-bis (4-aminophenoxy)-2,2'or 2,2', 6,6'-substituted biphenyl

NASA Technical Reports Server (NTRS)

Chuang, Chun-Hua K. (Inventor)

1999-01-01

This invention relates the novel diamines, the polyimide oligomers and the polyimides derived therefrom and to the method of preparing the diamines, oligomers and the polyimides. The thermoplastic polyimides derived from the aromatic diamines of this invention are characterized as having a high glass transition temperature, good mechanical properties and improved processability in the manufacture of adhesives, electronic and composite materials for use in the automotive and aerospace industry. The distinction of the novel aromatic diamines of this invention is the 2,2',6,6'-substituted biphenyl radicals which exhibit noncoplanar conformation that enhances the solubility of the diamine as well as the processability of the polyimides, while retaining a realatively high glass transition temperature and improved mechanical properties at useful temperature ranges.

Aromatic Diamines and Polyimides Based on 4,4'-Bis-(4-Aminophenoxy)-2,2' or 2,2',6,6'- Substituted Biphenyl

NASA Technical Reports Server (NTRS)

Chuang, Chun-Hua K. (Inventor)

2000-01-01

This invention relates the novel diamines. the polyimide oligomers and the polyimides derived therefrom and to the method of preparing the diamines, oligomers and the polyimides. The thermoplastic polyimides derived from the aromatic diamines of this invention are characterized as having a high glass transition temperature. good mechanical properties and improved processability in the manufacture of adhesives. electronic and composite materials for use in the automotive and aerospace industry. The distinction of the novel aromatic diamines of this invention is the 2.2',6.6substituted biphenyl radicals which exhibit noncoplanar conformation that enhances the solubility of the diamine as well as the processability of the polyimides. while retaining a relatively high glass transition temperature and improved mechanical properties at useful temperature ranges.

Statistical Mechanical Derivation of Jarzynski's Identity for Thermostated Non-Hamiltonian Dynamics

NASA Astrophysics Data System (ADS)

Cuendet, Michel A.

2006-03-01

The recent Jarzynski identity (JI) relates thermodynamic free energy differences to nonequilibrium work averages. Several proofs of the JI have been provided on the thermodynamic level. They rely on assumptions such as equivalence of ensembles in the thermodynamic limit or weakly coupled infinite heat baths. However, the JI is widely applied to NVT computer simulations involving finite numbers of particles, whose equations of motion are strongly coupled to a few extra degrees of freedom modeling a thermostat. In this case, the above assumptions are no longer valid. We propose a statistical mechanical approach to the JI solely based on the specific equations of motion, without any further assumption. We provide a detailed derivation for the non-Hamiltonian Nosé-Hoover dynamics, which is routinely used in computer simulations to produce canonical sampling.

Comparison of carbon-sulfur and carbon-amine bond in therapeutic drug: 4β-S-aromatic heterocyclic podophyllum derivatives display antitumor activity

PubMed Central

Li, Jian-Long; Zhao, Wei; Zhou, Chen; Zhang, Ya-Xuan; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

2015-01-01

Herein is a first effort to systematically study the significance of carbon-sulfur (C-S) and carbon-amine (C-NH) bonds on the antitumor proliferation activity of podophyllum derivatives and their precise mechanism of apoptosis. Compared with the derivative modified by a C-NH bond, the derivative modified by a C-S bond exhibited superior antitumor activity, the inhibition activity of target proteins tubulin or Topo II, cell cycle arrest, and apoptosis induction. Antitumor mechanistic studies showed that the death receptor and the mitochondrial apoptotic pathways were simultaneously activated by the C-S bond modified aromatic heterocyclic podophyllum derivatives with a higher cellular uptake percentage of 60–90% and induction of a higher level of reactive oxygen species (ROS). Only the mitochondrial apoptotic pathway was activated by the C-NH bond modified aromatic heterocyclic podophyllum derivatives, with a lower cellular uptake percentage of 40–50%. This study provided insight into effects of the C-S and C-NH bond modification on the improvement of the antitumor activity of Podophyllum derivatives. PMID:26443888

Comparison of closed circuit and Fick-derived oxygen consumption in patients undergoing simultaneous aortocaval occlusion.

PubMed

Hofland, J; Tenbrinck, R; van Eijck, C H J; Eggermont, A M M; Gommers, D; Erdmann, W

2003-04-01

Agreement between continuously measured oxygen consumption during quantitative closed system anaesthesia and intermittently Fick-derived calculated oxygen consumption was assessed in 11 patients undergoing simultaneous occlusion of the aorta and inferior vena cava for hypoxic treatment of pancreatic cancer. All patients were mechanically ventilated using a quantitative closed system anaesthesia machine (PhysioFlex) and had pulmonary and radial artery catheters inserted. During the varying haemodynamic conditions that accompany this procedure, 73 paired measurements were obtained. A significant correlation between Fick-derived and closed system-derived oxygen consumption was found (r = 0.78, p = 0.006). Linear regression showed that Fick-derived measure = [(1.19 x closed system derived measure) - 72], with the overall closed circuit-derived values being higher. However, the level of agreement between the two techniques was poor. Bland-Altman analysis found that the bias was 36 ml.min(-1), precision 39 ml.min(-1), difference between 95% limits of agreement 153 ml.min(-1). Therefore, we conclude that the two measurement techniques are not interchangeable in a clinical setting.

Potential roles of cell-derived microparticles in ischemic brain disease.

PubMed

Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Nordberg, Mary L; Minagar, Alireza; Alexander, J Steven; Kelley, Roger E; Ahn, Yeon S

2009-10-01

The objective of this study is to review the role of cell-derived microparticles in ischemic cerebrovascular diseases. An extensive PubMed search of literature pertaining to this study was performed in April 2009 using specific keyword search terms related to cell-derived microparticles and ischemic stroke. Some references are not cited here as it is not possible to be all inclusive or due to space limitation. Cell-derived microparticles are small membranous vesicles released from the plasma membranes of platelets, leukocytes, red cells and endothelial cells in response to diverse biochemical agents or mechanical stresses. They are the main carriers of circulating tissue factor, the principal initiator of intravascular thrombosis, and are implicated in a variety of thrombotic and inflammatory disorders. This review outlines evidence suggesting that cell-derived microparticles are involved predominantly with microvascular, as opposed to macrovascular, thrombosis. More specifically, cell-derived microparticles may substantially contribute to ischemic brain disease in several settings, as well as to neuroinflammatory conditions. If further work confirms this hypothesis, novel therapeutic strategies for minimizing cell-derived microparticles-mediated ischemia are available or can be developed, as discussed.

Brain-Derived Neurotrophic Factor (BDNF) and Traumatic Brain Injury (Head and Spinal)

DTIC Science & Technology

2000-01-01

phosphatidylinositol 3-kinase are involved in brain-derived neurotrophic factor- mediated survival and neuritogenesis of the neuroblastoma cell line ... SH - SY5Y , J. Neurochem. 73 (1999) 1409-1421. 15. Gottshalk, W.A., Jiang, H., Tartaglia, N., Feng, L., Figurov, A., Lu, B., Signaling mechanisms...NT-6), and neurotrophin-7 (NT-7) (4, 5, 24, 80). Neurotrophins are believed to promote their cell survival, growth, and differentiation effects

Comparative transcriptome profiling analyses during the lag phase uncover YAP1, PDR1, PDR3, RPN4, and HSF1 as key regulatory genes in genomic adaptation to the lignocellulose derived inhibitor HMF for Saccharomyces cerevisiae

USDA-ARS?s Scientific Manuscript database

The yeast Saccharomyces cerevisiae is able to adapt and in situ detoxify lignocellulose derived inhibitors such as furfural and hydroxymethylfurfural (HMF). The length of lag phase for cell growth in response to the inhibitor challenge has been used to measure tolerance of strain performance. Mechan...

Quantitative Tractography and Volumetric MRI in Blast and Blunt Force TBI: Predictors of Neurocognitive and Behavioral Outcome

DTIC Science & Technology

2016-10-01

are related to mechanism of injury as well as white matter integrity using diffusion tensor imaging (DTI). We are also collecting and analyzing...APOE ε4] and brain-derived neurotrophic factor [BDNF]) to brain integrity , neuropsychological functioning, and neurobehavioral outcome. 15. SUBJECT...contribution of genetic factors (Apolipoprotein-E ε-4 [APOE ε4] and brain-derived neurotrophic factor [BDNF]) to brain integrity , neuropsychological

FUSION-Guided Hypothesis Development Leads to the Identification of N⁶,N⁶-Dimethyladenosine, a Marine-Derived AKT Pathway Inhibitor. | Office of Cancer Genomics

Cancer.gov

Chemicals found in nature have evolved over geological time scales to productively interact with biological molecules, and thus represent an effective resource for pharmaceutical development. Marine-derived bacteria are rich sources of chemically diverse, bioactive secondary metabolites, but harnessing this diversity for biomedical benefit is limited by challenges associated with natural product purification and determination of biochemical mechanism.

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

Bialynicki-Birula, Iwo

Quantum-mechanical uncertainty relations for position and momentum are expressed in the form of inequalities involving the Renyi entropies. The proof of these inequalities requires the use of the exact expression for the (p,q)-norm of the Fourier transformation derived by Babenko and Beckner. Analogous uncertainty relations are derived for angle and angular momentum and also for a pair of complementary observables in N-level systems. All these uncertainty relations become more attractive when expressed in terms of the symmetrized Renyi entropies.

Fecal fermentation products of common bean-derived fiber inhibit C/EBP alpha and PPAR gamma expression and lipid accumulation but stimulate PPAR delta and UCP2 expression in the adipogenesis of 3T3-L1 cells

USDA-ARS?s Scientific Manuscript database

Background: Clinical and animal studies have suggested efficacies of common bean (Phaseolus vulgaris) consumption on weight loss. Fermentation of common bean-derived dietary fiber by gut microbiota is proposed to modulate obesity; however, the mechanism by which the adipogenesis is inhibited is uncl...

Broccoli-derived phytochemicals indole-3-carbinol and 3,3’-diindolylmethane exert concentration-dependent pleiotropic effects on prostate cancer cells: Comparison with other cancer preventive phytochemicals

USDA-ARS?s Scientific Manuscript database

In the present studies, we utilized prostate cancer cell culture models to elucidate the mechanisms of action of broccoli-derived phytochemicals 3, 3’-diindolylmethane (DIM) and indole-3-carbinol (I3C). We found DIM and I3C at 1-5 uM inhibited androgen and estrogen-mediated pathways and induced a x...

Beneficial effect of mechanical stimulation on the regenerative potential of muscle-derived stem cells is lost by inhibiting vascular endothelial growth factor.

PubMed

Beckman, Sarah A; Chen, William C W; Tang, Ying; Proto, Jonathan D; Mlakar, Logan; Wang, Bing; Huard, Johnny

2013-08-01

We previously reported that mechanical stimulation increased the effectiveness of muscle-derived stem cells (MDSCs) for tissue repair. The objective of this study was to determine the importance of vascular endothelial growth factor (VEGF) on mechanically stimulated MDSCs in a murine model of muscle regeneration. MDSCs were transduced with retroviral vectors encoding the LacZ reporter gene (lacZ-MDSCs), the soluble VEGF receptor Flt1 (sFlt1-MDSCs), or a short hairpin RNA (shRNA) targeting messenger RNA of VEGF (shRNA_VEGF MDSCs). Cells were subjected to 24 hours of mechanical cyclic strain and immediately transplanted into the gastrocnemius muscles of mdx/scid mice. Two weeks after transplantation, angiogenesis, fibrosis, and regeneration were analyzed. There was an increase in angiogenesis in the muscles transplanted with mechanically stimulated lacZ-MDSCs compared with nonstimulated lacZ-MDSCs, sFlt1-MDSCs, and shRNA _VEGF MDSCs. Dystrophin-positive myofiber regeneration was significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. In vitro proliferation of MDSCs was not decreased by inhibition of VEGF; however, differentiation into myotubes and adhesion to collagen were significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. The beneficial effects of mechanical stimulation on MDSC-mediated muscle repair are lost by inhibiting VEGF.

Beneficial Effect of Mechanical Stimulation on the Regenerative Potential of Muscle-Derived Stem Cells Is Lost by Inhibiting Vascular Endothelial Growth Factor

PubMed Central

Beckman, Sarah A.; Chen, William C.W.; Tang, Ying; Proto, Jonathan D.; Mlakar, Logan; Wang, Bing; Huard, Johnny

2016-01-01

Objective We previously reported that mechanical stimulation increased the effectiveness of muscle-derived stem cells (MDSCs) for tissue repair. The objective of this study was to determine the importance of vascular endothelial growth factor (VEGF) on mechanically stimulated MDSCs in a murine model of muscle regeneration. Approach and Results MDSCs were transduced with retroviral vectors encoding the LacZ reporter gene (lacZ-MDSCs), the soluble VEGF receptor Flt1 (sFlt1-MDSCs), or a short hairpin RNA (shRNA) targeting messenger RNA of VEGF (shRNA_VEGF MDSCs). Cells were subjected to 24 hours of mechanical cyclic strain and immediately transplanted into the gastrocnemius muscles of mdx/scid mice. Two weeks after transplantation, angiogenesis, fibrosis, and regeneration were analyzed. There was an increase in angiogenesis in the muscles transplanted with mechanically stimulated lacZMDSCs compared with nonstimulated lacZ-MDSCs, sFlt1-MDSCs, and shRNA _VEGF MDSCs. Dystrophin-positive myofiber regeneration was significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. In vitro proliferation of MDSCs was not decreased by inhibition of VEGF; however, differentiation into myotubes and adhesion to collagen were significantly lower in the shRNA_VEGF-MDSC group compared with the lacZ-MDSC and sFlt1-MDSC groups. Conclusions The beneficial effects of mechanical stimulation on MDSC-mediated muscle repair are lost by inhibiting VEGF. PMID:23723372

The effects of hyaluronic acid hydrogels with tunable mechanical properties on neural progenitor cell differentiation.

PubMed

Seidlits, Stephanie K; Khaing, Zin Z; Petersen, Rebecca R; Nickels, Jonathan D; Vanscoy, Jennifer E; Shear, Jason B; Schmidt, Christine E

2010-05-01

We report the ability to direct the differentiation pathway of neural progenitor cells (NPCs) within hydrogels having tunable mechanical properties. By modifying the polymeric sugar hyaluronic acid (HA), a major extracellular matrix component in the fetal mammalian brain, with varying numbers of photocrosslinkable methacrylate groups, hydrogels could be prepared with bulk compressive moduli spanning the threefold range measured for neonatal brain and adult spinal cord. Ventral midbrain-derived NPCs were photoencapsulated into HA hydrogels and remained viable after encapsulation. After three weeks, the majority of NPCs cultured in hydrogels with mechanical properties comparable to those of neonatal brain had differentiated into neurons (ss-III tubulin-positive), many of which had extended long, branched processes, indicative of a relatively mature phenotype. In contrast, NPCs within stiffer hydrogels, with mechanical properties comparable to those of adult brain, had differentiated into mostly astrocytes (glial fibrillary acidic protein (GFAP)-positive). Primary spinal astrocytes cultured in the hydrogel variants for two weeks acquired a spread and elongated morphology only in the stiffest hydrogels evaluated, with mechanical properties similar to adult tissue. Results demonstrate that the mechanical properties of these scaffolds can assert a defining influence on the differentiation of ventral midbrain-derived NPCs, which have strong clinical relevance because of their ability to mature into dopaminergic neurons of the substantia nigra, cells that idiopathically degenerate in individuals suffering from Parkinson's disease. Copyright 2010 Elsevier Ltd. All rights reserved.

Biomechanics of a convergently derived prey-processing mechanism in fishes: evidence from comparative tongue bite apparatus morphology and raking kinematics.

PubMed

Konow, Nicolai; Sanford, Christopher P J

2008-11-01

A tongue-bite apparatus (TBA) governs raking behaviors in two major and unrelated teleost lineages, the osteoglossomorph and salmoniform fishes. We present data on comparative morphology and kinematics from two representative species, the rainbow trout (Oncorhynchus mykiss) and the Australian arowana (Scleropages jardinii), which suggest that both the TBA and raking are convergently derived in these lineages. Similar TBA morphologies were present, except for differences in TBA dentition and shape of the novel cleithrobranchial ligament (CBL), which is arc-shaped in O. mykiss and straight in S. jardinii. Eight kinematic variables were used to quantify motion magnitude and maximum-timing in the kinematic input mechanisms of the TBA. Five variables differed inter-specifically (pectoral girdle retraction magnitude and timing, cranial and hyoid elevation and gape-distance timing), yet an incomplete taxon separation across multivariate kinematic space demonstrated an overall similarity in raking behavior. An outgroup analysis using bowfin (Amia calva) and pickerel (Esox americanus) to compare kinematics of raking with chewing and prey-capture provided robust quantitative evidence of raking being a convergently derived behavior. Support was also found for the notion that raking more likely evolved from the strike, a functionally distinct behavior, than from chewing, an alternative prey-processing behavior. Based on raking kinematic and muscle-activity data, we propose biomechanical models of the three input mechanisms that govern kinematics of the basihyal output mechanism during the raking power stroke: (1) cranial elevation protracts the upper TBA jaw from the lower (basihyal) TBA jaw; (2) basihyal retraction is caused directly by contraction of the sternohyoideus (SH); (3) hypaxial shortening, relayed via the pectoral girdle and SH-CBL complex, is an indirect basihyal retraction mechanism modeled as a four-bar linkage. These models will aid future analyses mapping structural and functional traits to the evolution of behaviors.

Cis-to- Trans Isomerization of Azobenzene Derivatives Studied with Transition Path Sampling and Quantum Mechanical/Molecular Mechanical Molecular Dynamics.

PubMed

Muždalo, Anja; Saalfrank, Peter; Vreede, Jocelyne; Santer, Mark

2018-04-10

Azobenzene-based molecular photoswitches are becoming increasingly important for the development of photoresponsive, functional soft-matter material systems. Upon illumination with light, fast interconversion between a more stable trans and a metastable cis configuration can be established resulting in pronounced changes in conformation, dipole moment or hydrophobicity. A rational design of functional photosensitive molecules with embedded azo moieties requires a thorough understanding of isomerization mechanisms and rates, especially the thermally activated relaxation. For small azo derivatives considered in the gas phase or simple solvents, Eyring's classical transition state theory (TST) approach yields useful predictions for trends in activation energies or corresponding half-life times of the cis isomer. However, TST or improved theories cannot easily be applied when the azo moiety is part of a larger molecular complex or embedded into a heterogeneous environment, where a multitude of possible reaction pathways may exist. In these cases, only the sampling of an ensemble of dynamic reactive trajectories (transition path sampling, TPS) with explicit models of the environment may reveal the nature of the processes involved. In the present work we show how a TPS approach can conveniently be implemented for the phenomenon of relaxation-isomerization of azobenzenes starting with the simple examples of pure azobenzene and a push-pull derivative immersed in a polar (DMSO) and apolar (toluene) solvent. The latter are represented explicitly at a molecular mechanical (MM) and the azo moiety at a quantum mechanical (QM) level. We demonstrate for the push-pull azobenzene that path sampling in combination with the chosen QM/MM scheme produces the expected change in isomerization pathway from inversion to rotation in going from a low to a high permittivity (explicit) solvent model. We discuss the potential of the simulation procedure presented for comparative calculation of reaction rates and an improved understanding of activated states.

Kinks in higher derivative scalar field theory

NASA Astrophysics Data System (ADS)

Zhong, Yuan; Guo, Rong-Zhen; Fu, Chun-E.; Liu, Yu-Xiao

2018-07-01

We study static kink configurations in a type of two-dimensional higher derivative scalar field theory whose Lagrangian contains second-order derivative terms of the field. The linear fluctuation around arbitrary static kink solutions is analyzed. We find that, the linear spectrum can be described by a supersymmetric quantum mechanics problem, and the criteria for stable static solutions can be given analytically. We also construct a superpotential formalism for finding analytical static kink solutions. Using this formalism we first reproduce some existed solutions and then offer a new solution. The properties of our solution is studied and compared with those preexisted. We also show the possibility in constructing twinlike model in the higher derivative theory, and give the consistency conditions for twinlike models corresponding to the canonical scalar field theory.

Synthesis, crystal structure, and biological evaluation of a series of phloretin derivatives.

PubMed

Wang, Li; Li, Zheng-Wei; Zhang, Wei; Xu, Rui; Gao, Fei; Liu, Yang-Feng; Li, Ya-Jun

2014-10-13

A one-step synthesis of phloretin derivatives 2-11 from phloretin in good to excellent yields is reported. Their structures were characterized by 1H-NMR, 13C-NMR and MS, and the structures of 8 and 11 were determined by X-ray diffraction analysis. A mechanism for the formation of 9-11 is proposed. Compared with the anticancer drug docetaxel, phloretin, phloretin derivatives and phlorizin exhibited moderate cytotoxicity toward the MDA-MB-231, SPC-A1, A549, MCF-7 and EC109 cell lines. Among all of the tested compounds, 7 exhibited the strongest cytotoxicity toward the five cell lines and was more active than docetaxel in MDA-MB-231 cells. Our findings suggest that these derivatives hold great promise for further development as anticancer agents.

Chondrogenic potential of physically treated bovine cartilage matrix derived porous scaffolds on human dermal fibroblast cells.

PubMed

Moradi, Ali; Ataollahi, Forough; Sayar, Katayoun; Pramanik, Sumit; Chong, Pan-Pan; Khalil, Alizan Abdul; Kamarul, Tunku; Pingguan-Murphy, Belinda

2016-01-01

Extracellular matrices have drawn attention in tissue engineering as potential biomaterials for scaffold fabrication because of their bioactive components. Noninvasive techniques of scaffold fabrication and cross-linking treatments are believed to maintain the integrity of bioactive molecules while providing proper architectural and mechanical properties. Cartilage matrix derived scaffolds are designed to support the maintenance of chondrocytes and provide proper signals for differentiation of chondroinducible cells. Chondroinductive potential of bovine articular cartilage matrix derived porous scaffolds on human dermal fibroblasts and the effect of scaffold shrinkage on chondrogenesis were investigated. An increase in sulfated glycosaminoglycans production along with upregulation of chondrogenic genes confirmed that physically treated cartilage matrix derived scaffolds have chondrogenic potential on human dermal fibroblasts. © 2015 Wiley Periodicals, Inc.

Plant Oil-Derived Epoxy Polymers toward Sustainable Biobased Thermosets.

PubMed

Wang, Zhongkai; Yuan, Liang; Ganewatta, Mitra S; Lamm, Meghan E; Rahman, Md Anisur; Wang, Jifu; Liu, Shengquan; Tang, Chuanbing

2017-06-01

Epoxy polymers (EPs) derived from soybean oil with varied chemical structures are synthesized. These polymers are then cured with anhydrides to yield soybean-oil-derived epoxy thermosets. The curing kinetic, thermal, and mechanical properties are well characterized. Due to the high epoxide functionality per epoxy polymer chain, these thermosets exhibit tensile strength over an order of magnitude higher than a control formulation with epoxidized soybean oil. More importantly, thermosetting materials ranging from soft elastomers to tough thermosets can be obtained simply by using different EPs and/or by controlling feed ratios of EPs to anhydrides. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural phenotyping of stem cell-derived cardiomyocytes.

PubMed

Pasqualini, Francesco Silvio; Sheehy, Sean Paul; Agarwal, Ashutosh; Aratyn-Schaus, Yvonne; Parker, Kevin Kit

2015-03-10

Structural phenotyping based on classical image feature detection has been adopted to elucidate the molecular mechanisms behind genetically or pharmacologically induced changes in cell morphology. Here, we developed a set of 11 metrics to capture the increasing sarcomere organization that occurs intracellularly during striated muscle cell development. To test our metrics, we analyzed the localization of the contractile protein α-actinin in a variety of primary and stem-cell derived cardiomyocytes. Further, we combined these metrics with data mining algorithms to unbiasedly score the phenotypic maturity of human-induced pluripotent stem cell-derived cardiomyocytes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Noncommuting observables in quantum detection and estimation theory

NASA Technical Reports Server (NTRS)

Helstrom, C. W.

1972-01-01

Basing decisions and estimates on simultaneous approximate measurements of noncommuting observables in a quantum receiver is shown to be equivalent to measuring commuting projection operators on a larger Hilbert space than that of the receiver itself. The quantum-mechanical Cramer-Rao inequalities derived from right logarithmic derivatives and symmetrized logarithmic derivatives of the density operator are compared, and it is shown that the latter give superior lower bounds on the error variances of individual unbiased estimates of arrival time and carrier frequency of a coherent signal. For a suitably weighted sum of the error variances of simultaneous estimates of these, the former yield the superior lower bound under some conditions.

Can helminths or helminth-derived products be used in humans to prevent or treat allergic diseases?

PubMed

Erb, Klaus J

2009-02-01

Recent epidemiological and experimental data indicate that infection with helminths can protect humans from the development of allergic disorders by immunosuppressive mechanisms that involve the induction of IL-10 and/or regulatory T cells. Furthermore, helminth-derived immune modulators suppress allergic responses in mice. Trichuris suis therapy has been shown to be safe and efficacious in treating inflammatory bowel disease in humans. Has the time come to treat patients who have allergic diseases or healthy humans who are at risk of developing these diseases with helminths or helminth-derived products? Here, I discuss the pros and cons of such an approach.

Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression in Cultured Rat Aortic Smooth Muscle Cells.

PubMed

Kao, Ying-Hsien; Chen, Po-Han; Sun, Cheuk-Kwan; Chang, Yo-Chen; Lin, Yu-Chun; Tsai, Ming-Shian; Lee, Po-Huang; Cheng, Cheng-I

2018-02-21

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. This study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uni-axial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition significantly blunted the IL-6 production and HDGF over-expression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration. ©2018 The Author(s).

Quantum mechanical/molecular mechanical and docking study of the novel analogues based on hybridization of common pharmacophores as potential anti-breast cancer agents

PubMed Central

Asadi, Parvin; Khodarahmi, Ghadamali; Farrokhpour, Hossein; Hassanzadeh, Farshid; Saghaei, Lotfollah

2017-01-01

In an attempt to identify some new potential leads as anti-breast cancer agents, novel hybrid compounds were designed by molecular hybridization approach. These derivatives were structurally derived from hybrid benzofuran–imidazole and quinazolinone derivatives, which had shown good cytotoxicity against the breast cancer cell line (MCF-7). Since aromatase enzyme (CYP19) is highly expressed in the MCF-7 cell line, the binding of these novel hybrid compounds to aromatase was investigated using the docking method. In this study, due to the positive charge on the imidazole ring of the designed ligands and also, the presence of heme iron in the active site of the enzyme, it was decided to optimize the ligand inside the protein to obtain more realistic atomic charges for it. Quantum mechanical/molecular mechanical (QM/MM) method was used to obtain more accurate atomic charges of ligand for docking calculations by considering the polarization effects of CYP19 on ligands. It was observed that the refitted charge improved the binding energy of the docked compounds. Also, the results showed that these novel hybrid compounds were adopted properly within the aromatase binding site, thereby suggesting that they could be potential inhibitors of aromatase. The main binding modes in these complexes were through hydrophobic and H bond interactions showing agreement with the basic physicochemical features of known anti aromatase compounds. Finally, the complex structures obtained from the docking study were used for single point QM/MM calculations to obtain more accurate electronic interaction energy, considering the electronic polarization of the ligand by its protein environment. PMID:28626481

Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor.

PubMed

Patel, Ami V; Krimm, Robin F

2012-05-01

The number of neurons in the geniculate ganglion that are available to innervate taste buds is regulated by neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF). Our goal for the current study was to examine the timing and mechanism of NT-4-mediated regulation of geniculate neuron number during development. We discovered that NT-4 mutant mice lose 33% of their geniculate neuronal cells between E10.5 and E11.5. By E11.5, geniculate axons have just reached the tongue and do not yet innervate their gustatory targets; thus, NT-4 does not function as a target-derived growth factor. At E11.5, no difference was observed in proliferating cells or the rate at which cells exit the cell cycle between NT-4 mutant and wild type ganglia. Instead, there was an increase in TUNEL-labeling, indicating an increase in cell death in Ntf4(-/-) mice compared with wild types. However, activated caspase-3, which is up-regulated in the absence of BDNF, was not increased. This finding indicates that cell death initiated by NT-4-removal occurs through a different cell death pathway than BDNF-removal. We observed no additional postnatal loss of taste buds or neurons in Ntf4(-/-) mice. Thus, during early embryonic development, NT-4 produced in the ganglion and along the projection pathway inhibits cell death through an activated caspase-3 independent mechanism. Therefore, compared to BDNF, NT-4 plays distinct roles in gustatory development; differences include timing, source of neurotrophin, and mechanism of action. Published by Elsevier Inc.

Peroxide generation by p47phox-Src activation of Nox2 has a key role in protein kinase C-induced arterial smooth muscle contraction.

PubMed

Gupte, Sachin A; Kaminski, Pawel M; George, Shimran; Kouznestova, Lioubov; Olson, Susan C; Mathew, Rajamma; Hintze, Thomas H; Wolin, Michael S

2009-04-01

Protein kinase C (PKC) stimulation of NAD(P)H oxidases (Nox) is an important component of multiple vascular disease processes; however, the relationship between oxidase activation and the regulation of vascular smooth muscle contraction by PKC remains poorly understood. Therefore, we examined the signaling cascade of PKC-elicited Nox activation and the role of superoxide and hydrogen peroxide in mediating PKC-induced vascular contraction. Endothelium-denuded bovine coronary arteries showed a PKC-dependent basal production of lucigenin (5 muM)-detected Nox oxidase-derived superoxide, which was stimulated fourfold by PKC activation with 10 muM phorbol 12,13-dibutyrate (PDBu). PDBu appeared to increase superoxide generation by Nox2 through both p47(phox) and peroxide-dependent Src activation mechanisms based on the actions of inhibitors, properties of Src phosphorylation, and the loss of responses in aorta from mice deficient in Nox2 and p47(phox). The actions of inhibitors of contractile regulating mechanisms, scavengers of superoxide and peroxide, and responses in knockout mouse aortas suggest that a major component of the contraction elicited by PDBu appeared to be mediated through peroxide derived from Nox2 activation stimulating force generation through Rho kinase and calmodulin kinase-II mechanisms. Superoxide generated by PDBu also attenuated relaxation to nitroglycerin. Peroxide-derived from Nox2 activation by PKC appeared to be a major contributor to the thromboxane A(2) receptor agonist U46619 (100 nM)-elicited contraction of coronary arteries. Thus a p47(phox) and Src kinase activation of peroxide production by Nox2 appears to be an important contributor to vascular contractile mechanisms mediated through activation of PKC.

The galvanizing of Mycobacterium tuberculosis: an antimicrobial mechanism.

PubMed

Russell, David G

2011-09-15

Evolving under constant threat from invading microbes, macrophages have acquired multiple means of killing bacteria. In this issue of Cell Host & Microbe, Botella and colleagues (Botella et al., 2011) describe a novel antimicrobial mechanism based on elevated levels of intraphagosomal Zn(2+) and the corresponding induction of bacterial genes to ameliorate this host-derived stress. Copyright © 2011 Elsevier Inc. All rights reserved.

Kinetics and mechanisms of some atomic oxygen reactions

NASA Technical Reports Server (NTRS)

Cvetanovic, R. J.

1987-01-01

Mechanisms and kinetics of some reactions of the ground state of oxygen atoms, O(3P), are briefly summarized. Attention is given to reactions of oxygen atoms with several different types of organic and inorganic compounds such as alkanes, alkenes, alkynes, aromatics, and some oxygen, nitrogen, halogen and sulfur derivatives of these compounds. References to some recent compilations and critical evaluations of reaction rate constants are given.

A Lidar-derived evaluation of watershed-scale large woody debris sources and recruitment mechanisms: costal Maine, USA

Treesearch

A. ​Kasprak; F. J. Magilligan; K. H. Nislow; N. P. Snyder

2012-01-01

In‐channel large woody debris (LWD) promotes quality aquatic habitat through sediment sorting, pool scouring and in‐stream nutrient retention and transport. LWD recruitment occurs by numerous ecological and geomorphic mechanisms including channel migration, mass wasting and natural tree fall, yet LWD sourcing on the watershed scale remains poorly constrained. We...

Metastasis Suppressor Gene Inactivates Actin-Based Mechanism of Tumor Cell Motility | Center for Cancer Research

Cancer.gov

Metastasis is responsible for up to 90 percent of all cancer-related deaths. Though proteins derived from nearly a dozen metastasis suppressor genes have been discovered over the past 15 years, strategies for exploiting the proteins in metastasis-prevention therapies has been hampered by the lack of knowledge regarding the mechanisms underlying the proteins’ interactions with other proteins.

Exciting Pools

ERIC Educational Resources Information Center

Wright, Bradford L.

1975-01-01

Advocates the creation of swimming pool oscillations as part of a general investigation of mechanical oscillations. Presents the equations, procedure for deriving the slosh modes, and methods of period estimation for exciting swimming pool oscillations. (GS)

Mesenchymal stem cells from adipose and bone marrow promote angiogenesis via distinct cytokine and protease expression mechanisms

PubMed Central

Kachgal, Suraj; Putnam, Andrew J.

2012-01-01

Using a fibrin-based angiogenesis model, we have established that there is no canonical mechanism used by ECs to degrade the surrounding extracellular matrix (ECM), but rather the set of proteases used is dependent on the mural cells providing the angiogenic cues. Mesenchymal stem cells (MSCs) originating from different tissues, which are thought to be phenotypically similar, promote angiogenesis through distinct mechanisms. Specifically, adipose-derived stem cells (ASCs) promote utilization of the plasminogen activator-plasmin axis by ECs as the primary means of vessel invasion and elongation in fibrin. Matrix metalloproteinases (MMPs) serve a purpose in regulating capillary diameter and possibly in stabilizing the nascent vessels. These proteolytic mechanisms are more akin to those involved in fibroblast-mediated angiogenesis than to those in bone marrow-derived stem cell (BMSC)-mediated angiogenesis. In addition, expression patterns of angiogenic factors such as urokinase plasminogen activator (uPA), hepatocyte growth factor (HGF), and tumor necrosis factor alpha (TNFα) were similar for ASC and fibroblast-mediated angiogenesis, and in direct contrast to BMSC-mediated angiogenesis. The present study illustrates that the nature of the heterotypic interactions between mural cells and endothelial cells depend on the identity of the mural cell used. Even MSCs which are shown to behave phenotypically similar do not stimulate angiogenesis via the same mechanisms. PMID:21104120

A new insight into the immobilization mechanism of Zn on biochar: the role of anions dissolved from ash

PubMed Central

Qian, Tingting; Wang, Yujun; Fan, Tingting; Fang, Guodong; Zhou, Dongmei

2016-01-01

Biochar is considered to be a promising material for heavy metal immobilization in soil. However, the immobilization mechanisms of Zn2+ on biochars derived from many common waste biomasses are not completely understood. Herein, biochars (denoted as PN350, PN550, WS350, and WS550) derived from pine needle (PN) and wheat straw (WS) were prepared at two pyrolysis temperatures (350 °C and 550 °C). The immobilization behaviors and mechanisms of Zn2+ on these biochars were systematically investigated. The results show that compared with biochars produced at low temperature, biochars produced at high temperature contained higher amounts of ash and exhibited much higher sorption capacities of Zn2+. By using Zn K-edge EXAFS spectroscopy, we find that the formation of various Zn precipitates/minerals, which was caused by the release of OH−, CO32−, and Si species from biochar, was the immobilization mechanism of Zn2+ on PN and WS biochars. Hydrozincite and Zn(OH)2 were the main species formed on PN350, PN550, and WS350; while on WS550, besides hydrozincite, a large fraction of hemimorphite was formed. The occurrence of hydrozincite and hemimorphite on biochar during Zn2+ immobilization is firstly reported in our study, which provides a new insight into the immobilization mechanism of Zn2+ on biochar. PMID:27641899

A new insight into the immobilization mechanism of Zn on biochar: the role of anions dissolved from ash

NASA Astrophysics Data System (ADS)

Qian, Tingting; Wang, Yujun; Fan, Tingting; Fang, Guodong; Zhou, Dongmei

2016-09-01

Biochar is considered to be a promising material for heavy metal immobilization in soil. However, the immobilization mechanisms of Zn2+ on biochars derived from many common waste biomasses are not completely understood. Herein, biochars (denoted as PN350, PN550, WS350, and WS550) derived from pine needle (PN) and wheat straw (WS) were prepared at two pyrolysis temperatures (350 °C and 550 °C). The immobilization behaviors and mechanisms of Zn2+ on these biochars were systematically investigated. The results show that compared with biochars produced at low temperature, biochars produced at high temperature contained higher amounts of ash and exhibited much higher sorption capacities of Zn2+. By using Zn K-edge EXAFS spectroscopy, we find that the formation of various Zn precipitates/minerals, which was caused by the release of OH-, CO32-, and Si species from biochar, was the immobilization mechanism of Zn2+ on PN and WS biochars. Hydrozincite and Zn(OH)2 were the main species formed on PN350, PN550, and WS350; while on WS550, besides hydrozincite, a large fraction of hemimorphite was formed. The occurrence of hydrozincite and hemimorphite on biochar during Zn2+ immobilization is firstly reported in our study, which provides a new insight into the immobilization mechanism of Zn2+ on biochar.

A new insight into the immobilization mechanism of Zn on biochar: the role of anions dissolved from ash.

PubMed

Qian, Tingting; Wang, Yujun; Fan, Tingting; Fang, Guodong; Zhou, Dongmei

2016-09-19

Biochar is considered to be a promising material for heavy metal immobilization in soil. However, the immobilization mechanisms of Zn(2+) on biochars derived from many common waste biomasses are not completely understood. Herein, biochars (denoted as PN350, PN550, WS350, and WS550) derived from pine needle (PN) and wheat straw (WS) were prepared at two pyrolysis temperatures (350 °C and 550 °C). The immobilization behaviors and mechanisms of Zn(2+) on these biochars were systematically investigated. The results show that compared with biochars produced at low temperature, biochars produced at high temperature contained higher amounts of ash and exhibited much higher sorption capacities of Zn(2+). By using Zn K-edge EXAFS spectroscopy, we find that the formation of various Zn precipitates/minerals, which was caused by the release of OH(-), CO3(2-), and Si species from biochar, was the immobilization mechanism of Zn(2+) on PN and WS biochars. Hydrozincite and Zn(OH)2 were the main species formed on PN350, PN550, and WS350; while on WS550, besides hydrozincite, a large fraction of hemimorphite was formed. The occurrence of hydrozincite and hemimorphite on biochar during Zn(2+) immobilization is firstly reported in our study, which provides a new insight into the immobilization mechanism of Zn(2+) on biochar.

Defended to the Nines: 25 Years of Resistance Gene Cloning Identifies Nine Mechanisms for R Protein Function.

PubMed

Kourelis, Jiorgos; van der Hoorn, Renier A L

2018-02-01

Plants have many, highly variable resistance ( R ) gene loci, which provide resistance to a variety of pathogens. The first R gene to be cloned, maize ( Zea mays ) Hm1 , was published over 25 years ago, and since then, many different R genes have been identified and isolated. The encoded proteins have provided clues to the diverse molecular mechanisms underlying immunity. Here, we present a meta-analysis of 314 cloned R genes. The majority of R genes encode cell surface or intracellular receptors, and we distinguish nine molecular mechanisms by which R proteins can elevate or trigger disease resistance: direct (1) or indirect (2) perception of pathogen-derived molecules on the cell surface by receptor-like proteins and receptor-like kinases; direct (3) or indirect (4) intracellular detection of pathogen-derived molecules by nucleotide binding, leucine-rich repeat receptors, or detection through integrated domains (5); perception of transcription activator-like effectors through activation of executor genes (6); and active (7), passive (8), or host reprogramming-mediated (9) loss of susceptibility. Although the molecular mechanisms underlying the functions of R genes are only understood for a small proportion of known R genes, a clearer understanding of mechanisms is emerging and will be crucial for rational engineering and deployment of novel R genes. © 2018 American Society of Plant Biologists. All rights reserved.

Static Mechanical Loading Influences the Expression of Extracellular Matrix and Cell Adhesion Proteins in Vaginal Cells Derived From Premenopausal Women With Severe Pelvic Organ Prolapse.

PubMed

Kufaishi, Hala; Alarab, May; Drutz, Harold; Lye, Stephen; Shynlova, Oksana

2016-08-01

Primary human vaginal cells derived from women with severe pelvic organ prolapse (POP-HVCs) demonstrate altered cellular characteristics as compared to cells derived from asymptomatic women (control-HVCs). Using computer-controllable Flexcell stretch unit, we examined whether POP-HVCs react differently to mechanical loading as compared to control-HVCs by the expression of extracellular matrix (ECM) components, cell-ECM adhesion proteins, and ECM degrading and maturating enzymes. Vaginal tissue biopsies from premenopausal patients with Pelvic Organ Prolapse Quantification System stage ≥3 (n = 8) and asymptomatic controls (n = 7) were collected during vaginal hysterectomy or repair. Human vaginal cells were isolated by enzymatic digestion, seeded on collagen (COLI)-coated plates, and stretched (24 hours, 25% elongation). Total RNA was extracted, and 84 genes were screened using Human ECM and Adhesion Molecules polymerase chain reaction array; selected genes were verified by quantitative reverse transcription-polymerase chain reaction. Stretch-conditioned media (SCM) were collected and analyzed by protein array, immunoblotting, and zymography. In mechanically stretched control-HVCs, transcript levels of integrins (ITGA1, ITGA4, ITGAV, and ITGB1) and matrix metalloproteinases (MMPs) 2, 8, and 13 were downregulated (P < .05); in POP-HVCs, MMP1, MMP3, and MMP10, ADAMTS8 and 13, tissue inhibitor of metalloproteinases (TIMPs) 1 to 3, ITGA2, ITGA4, ITGA6, ITGB1, contactin (CNTN1), catenins (A1 and B1), and laminins (A3 and C1) were significantly upregulated, whereas COLs (1, 4, 5, 6, 11, and 12) and LOXL1 were downregulated. Human vaginal cells massively secrete MMPs and TIMPs proteins; MMP1, MMP8, MMP9 protein expression and MMP2 gelatinase activity were increased, whereas TIMP2 decreased in SCM from POP-HVCs compared to control-HVCs. Primary human vaginal cells derived from women with severe pelvic organ prolapse and control-HVCs react differentially to in vitro mechanical stretch. Risk factors that induce stretch may alter ECM composition and cell-ECM interaction in pelvic floor tissue leading to the abatement of pelvic organ support and subsequent POP development. © The Author(s) 2016.

Bioluminescent imaging demonstrates transplanted human embryonic stem cell-derived CD34+ cells preferentially develop into endothelial cells

PubMed Central

Tian, Xinghui; Hexum, Melinda K.; Penchev, Vesselin R.; Taylor, Russell J.; Shultz, Leonard D.; Kaufman, Dan S

2010-01-01

Human embryonic stem cells (hESCs) provide an important resource for novel regenerative medicine therapies and have been used to derive diverse cell populations, including hematopoietic and endothelial cells. However, it remains a challenge to achieve significant engraftment of hESC-derived blood cells when transplanted into animal models. To better understand mechanisms that enhance or limit the in vivo developmental potential of hESC-derived cells, we utilized hESCs that express firefly luciferase (luc) to allow non-invasive, real-time bioluminescent imaging of hESC-derived CD34+ cells transplanted into the liver of neonatal immunodeficient mice. Serial imaging demonstrated stable engraftment and expansion of the luc+ hESC-derived cells in vivo over several months. While we found that these hESC-derived CD34+ cells have bipotential ability to generate both hematopoietic and endothelial lineages in vitro, these studies demonstrate preferential differentiation into endothelial cells in vivo, with only low levels of hematopoietic cell engraftment. Therefore, these studies reveal key differences in the developmental potential of hESC-derived cells using in vitro and in vivo analyses. While transplanted hESC-derived CD34+ cells are well suited for revascularization therapies, additional measures are needed to provide higher levels of long-term hematopoietic engraftment. PMID:19711457

Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives

PubMed Central

Tan, Hui-Li; Chan, Kok-Gan; Pusparajah, Priyia; Saokaew, Surasak; Duangjai, Acharaporn; Lee, Learn-Han; Goh, Bey-Hing

2016-01-01

Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs. PMID:27445824

Differentiation and Application of Induced Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells.

PubMed

Maguire, Eithne Margaret; Xiao, Qingzhong; Xu, Qingbo

2017-11-01

Vascular smooth muscle cells (VSMCs) play a role in the development of vascular disease, for example, neointimal formation, arterial aneurysm, and Marfan syndrome caused by genetic mutations in VSMCs, but little is known about the mechanisms of the disease process. Advances in induced pluripotent stem cell technology have now made it possible to derive VSMCs from several different somatic cells using a selection of protocols. As such, researchers have set out to delineate key signaling processes involved in triggering VSMC gene expression to grasp the extent of gene regulatory networks involved in phenotype commitment. This technology has also paved the way for investigations into diseases affecting VSMC behavior and function, which may be treatable once an identifiable culprit molecule or gene has been repaired. Moreover, induced pluripotent stem cell-derived VSMCs are also being considered for their use in tissue-engineered blood vessels as they may prove more beneficial than using autologous vessels. Finally, while several issues remains to be clarified before induced pluripotent stem cell-derived VSMCs can become used in regenerative medicine, they do offer both clinicians and researchers hope for both treating and understanding vascular disease. In this review, we aim to update the recent progress on VSMC generation from stem cells and the underlying molecular mechanisms of VSMC differentiation. We will also explore how the use of induced pluripotent stem cell-derived VSMCs has changed the game for regenerative medicine by offering new therapeutic avenues to clinicians, as well as providing researchers with a new platform for modeling of vascular disease. © 2017 American Heart Association, Inc.

Identification of Diet-Derived Constituents as Potent Inhibitors of Intestinal Glucuronidation

PubMed Central

Gufford, Brandon T.; Chen, Gang; Lazarus, Philip; Graf, Tyler N.; Oberlies, Nicholas H.

2014-01-01

Drug-metabolizing enzymes within enterocytes constitute a key barrier to xenobiotic entry into the systemic circulation. Furanocoumarins in grapefruit juice are cornerstone examples of diet-derived xenobiotics that perpetrate interactions with drugs via mechanism-based inhibition of intestinal CYP3A4. Relative to intestinal CYP3A4-mediated inhibition, alternate mechanisms underlying dietary substance–drug interactions remain understudied. A working systematic framework was applied to a panel of structurally diverse diet-derived constituents/extracts (n = 15) as inhibitors of intestinal UDP-glucuronosyl transferases (UGTs) to identify and characterize additional perpetrators of dietary substance–drug interactions. Using a screening assay involving the nonspecific UGT probe substrate 4-methylumbelliferone, human intestinal microsomes, and human embryonic kidney cell lysates overexpressing gut-relevant UGT1A isoforms, 14 diet-derived constituents/extracts inhibited UGT activity by >50% in at least one enzyme source, prompting IC50 determination. The IC50 values of 13 constituents/extracts (≤10 μM with at least one enzyme source) were well below intestinal tissue concentrations or concentrations in relevant juices, suggesting that these diet-derived substances can inhibit intestinal UGTs at clinically achievable concentrations. Evaluation of the effect of inhibitor depletion on IC50 determination demonstrated substantial impact (up to 2.8-fold shift) using silybin A and silybin B, two key flavonolignans from milk thistle (Silybum marianum) as exemplar inhibitors, highlighting an important consideration for interpretation of UGT inhibition in vitro. Results from this work will help refine a working systematic framework to identify dietary substance–drug interactions that warrant advanced modeling and simulation to inform clinical assessment. PMID:25008344

Cancer Cell-derived Exosomes Induce Mitogen-activated Protein Kinase-dependent Monocyte Survival by Transport of Functional Receptor Tyrosine Kinases*

PubMed Central

Song, Xiao; Ding, Yanping; Liu, Gang; Yang, Xiao; Zhao, Ruifang; Zhang, Yinlong; Zhao, Xiao; Anderson, Gregory J.; Nie, Guangjun

2016-01-01

Tumor-associated macrophages (TAM) play pivotal roles in cancer initiation and progression. Monocytes, the precursors of TAMs, normally undergo spontaneous apoptosis within 2 days, but can subsist in the inflammatory tumor microenvironment for continuous survival and generation of sufficient TAMs. The mechanisms underlying tumor-driving monocyte survival remain obscure. Here we report that cancer cell-derived exosomes were crucial mediators for monocyte survival in the inflammatory niche. Analysis of the survival-promoting molecules in monocytes revealed that cancer cell-derived exosomes activated Ras and extracellular signal-regulated kinases in the mitogen-activated protein kinase (MAPK) pathway, resulting in the prevention of caspase cleavage. Phosphorylated receptor tyrosine kinases (RTKs), such as phosphorylated epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), were abundantly expressed in cancer cell-derived exosomes. Knock-out of EGFR or/and HER-2, or alternatively, inhibitors against their phosphorylation significantly disturbed the exosome-mediated activation of the MAPK pathway, inhibition of caspase cleavage, and increase in survival rate in monocytes. Moreover, the deprived survival-stimulating activity of exosomes due to null expression of EGFR and HER-2 could be restored by activation of another RTK, insulin receptor. Overall, our study uncovered a mechanism of tumor-associated monocyte survival and demonstrated that cancer cell-derived exosomes can stimulate the MAPK pathway in monocytes through transport of functional RTKs, leading to inactivation of apoptosis-related caspases. This work provides insights into the long sought question on monocyte survival prior to formation of plentiful TAMs in the tumor microenvironment. PMID:26895960

Maternal nutrient restriction in baboon programs later-life cellular growth and respiration of cultured skin fibroblasts: a potential model for the study of aging-programming interactions.

PubMed

Salmon, Adam B; Dorigatti, Jonathan; Huber, Hillary F; Li, Cun; Nathanielsz, Peter W

2018-05-25

Compelling data exist for programming of chronic later-life diseases and longevity by perinatal developmental programming challenges. Understanding mechanisms by which life course health trajectory and longevity are set is fundamental to understanding aging. Appropriate approaches are needed to determine programming effects on cellular function. We have developed a baboon model in which control mothers eat ad libitum while a second group eat 70% of the global diet fed controls, leading to male and female offspring intrauterine growth restriction (IUGR). We have shown that IUGR suffer from acceleration of several age-related physiological declines. Here, we report on a skin-derived fibroblast model with potential relevance for mechanistic studies on how IUGR impacts aging. Fibroblasts were cultured from the skin biopsies taken from adult baboons from control and IUGR cohorts. IUGR-derived fibroblasts grew in culture less well than controls and those derived from male, but not female, IUGR baboons had a significant reduction in maximum respiration rate compared to control-derived fibroblasts. We also show that relative levels of several mitochondrial protein subunits, including NDUFB8 and cytochrome c oxidase subunit IV, were reduced in IUGR-derived fibroblasts even after serial passaging in culture. The lower levels of electron transport system components provide potential mechanisms for accelerated life course aging in the setting of programmed IUGR. This observation fits with the greater sensitivity of males compared with females to many, but not all, outcomes in response to programming challenges. These approaches will be powerful in the determination of programming-aging interactions.

Curare-Like Activity of Mono-Quaternary Salts Containing Adamantyl Residue at the Nitrogen Atom

DTIC Science & Technology

As shown in previous works, mono-quaternary salts of alkamine esters of benzoic and cinnamic acids types and exhibit a pronounced curare like action...A series of methiodides of alkamine esters of benzoic and cinnamic acids were synthesized, containing at the quaternary nitrogen atom a 1-adamantyl...adamantyl causes a change of the substance’s mechanism of action, this applying both to the benzoic acid derivatives and to the cinnamic acid derivatives

Cumulative Index to NASA Tech Briefs

NASA Technical Reports Server (NTRS)

1969-01-01

Tech Briefs are short announcements of new technology derived from the R&D activities of the National Aeronautics and Space Administration. This Index to NASA Tech Briefs lists the technological innovations derived from the U.S. space program and published during the period January through December 1968. A new five year cycle of cumulative indexes begins with this index. The main section is arranged in six categories: Electrical (Electronic); Physical Sciences (Energy Sources); Materials (Chemistry); Life Sciences; Mechanical; and Computer Programs.

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

Célérier, Marie-Noëlle; Nottale, Laurent, E-mail: marie-noelle.celerier@obspm.fr, E-mail: laurent.nottale@obspm.fr

Owing to the non-differentiable nature of the theory of Scale Relativity, the emergence of complex wave functions, then of spinors and bi-spinors occurs naturally in its framework. The wave function is here a manifestation of the velocity field of geodesics of a continuous and non-differentiable (therefore fractal) space-time. In a first paper (Paper I), we have presented the general argument which leads to this result using an elaborate and more detailed derivation than previously displayed. We have therefore been able to show how the complex wave function emerges naturally from the doubling of the velocity field and to revisit themore » derivation of the non-relativistic Schrödinger equation of motion. In the present paper (Paper II), we deal with relativistic motion and detail the natural emergence of the bi-spinors from such first principles of the theory. Moreover, while Lorentz invariance has been up to now inferred from mathematical results obtained in stochastic mechanics, we display here a new and detailed derivation of the way one can obtain a Lorentz invariant expression for the expectation value of the product of two independent fractal fluctuation fields in the sole framework of the theory of Scale Relativity. These new results allow us to enhance the robustness of our derivation of the two main equations of motion of relativistic quantum mechanics (the Klein-Gordon and Dirac equations) which we revisit here at length.« less

Breast milk-derived exosomes promote intestinal epithelial cell growth.

PubMed

Hock, Alison; Miyake, Hiromu; Li, Bo; Lee, Carol; Ermini, Leonardo; Koike, Yuhki; Chen, Yong; Määttänen, Pekka; Zani, Augusto; Pierro, Agostino

2017-05-01

Breast milk administration prevents necrotizing enterocolitis (NEC). However, the mechanism remains unclear. Exosomes are cell-derived vesicles highly present in human milk and regulate intercellular signaling, inflammation, and immune response. We hypothesized that milk-derived exosomes beneficially affect intestinal epithelial cells. Rat milk was collected, and exosomes were isolated using ExoQuick reagent and visualized by Nanoparticle Tracking Analysis. Protein was extracted from encapsulating exosomes, and concentration was measured. 2×10 4 intestinal epithelial cells (IEC-18) were treated for five hours with 0.5-μg/μl exosomes, an equal volume of exosome-free milk, or control solution (PBS). IEC-18 viability was measured using a colorimetric assay (MTT), and gene expression was analyzed by qRT-PCR. Data were compared using one-way ANOVA with Bonferroni post-test. Rat milk was collected, and exosome isolation was confirmed. Compared to control, treatment with exosomes significantly increased IEC viability, proliferation, and stem cell activity (all p<0.05). However, administration of exosome-free milk had less significant effects. Rat milk-derived exosomes promote IEC viability, enhance proliferation, and stimulate intestinal stem cell activity. These findings provide insight into the mechanism of action of breast milk in the intestines. Exosome administration is a promising prevention method for infants at risk of developing NEC when breastfeeding is not tolerated. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and biological evaluation of coumarin derivatives containing imidazole skeleton as potential antibacterial agents.

PubMed

Hu, Yang; Shen, Yufeng; Wu, Xiaohu; Tu, Xiao; Wang, Gao-Xue

2018-01-01

Emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Here, we report on the design, synthesis, and biological evaluation of thirty-nine coumarin derivatives in order to solve the antibacterial resistance by targeting at the inhibition of biosynthesis pathway of fatty acids. Their antibacterial activities against Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, and Flavobacterium cloumnare are tested and action mechanism against the key enzyme in bacterial fatty acid synthesis pathway are studied. The results show that compounds 13 and 18 have potent and broad spectrum antimicrobial activity. In addition, 9, 14 and 19 show eminent antimicrobial efficacy toward S. aureus, S. agalactiae, and F. cloumnare. Mechanistically, coumarin derivatives display the antibacterial activity via the control of FabI and FabK function. The structure-activity relationship analysis indicate that the length of linker and imidazole substitute group could significantly influence the antimicrobial activity, as well as the inhibitory activity against FabI and FabK. The structural optimization analysis of coumarin suggest that derivatives 9, 13, 14, 18 and 19 could be a viable way of preventing and controlling bacteria and considered as promising lead compounds for the development of commercial drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Engineering-derived approaches for iPSC preparation, expansion, differentiation and applications.

PubMed

Li, Yang; Li, Ling; Chen, Zhi-Nan; Gao, Ge; Yao, Rui; Sun, Wei

2017-07-31

Remarkable achievements have been made since induced pluripotent stem cells (iPSCs) were first introduced in 2006. Compared with non-pluripotent stem cells, iPSC research faces several additional complexities, such as the choice of extracellular matrix proteins, growth and differentiation factors, as well as technical challenges related to self-renewal and directed differentiation. Overcoming these challenges requires the integration of knowledge and technologies from multiple fields including cell biology, biomaterial science, engineering, physics and medicine. Here, engineering-derived iPSC approaches are reviewed according to three aspects of iPSC studies: preparation, expansion, differentiation and applications. Engineering strategies, such as 3D systems establishment, cell-matrix mechanics and the regulation of biophysical and biochemical cues, together with engineering techniques, such as 3D scaffolds, cell microspheres and bioreactors, have been applied to iPSC studies and have generated insightful results and even mini-organs such as retinas, livers and intestines. Specific results are given to demonstrate how these approaches impact iPSC behavior, and related mechanisms are discussed. In addition, cell printing technologies are presented as an advanced engineering-derived approach since they have been applied in both iPSC studies and the construction of diverse tissues and organs. Further development and possible innovations of cell printing technologies are presented in terms of creating complex and functional iPSC-derived living tissues and organs.

Derivation and characterization of human embryonic stem cell lines from poor quality embryos.

PubMed

Liu, Weiqiang; Yin, Yifei; Long, Xiaolin; Luo, Yumei; Jiang, Yonghua; Zhang, Wenhong; Du, Hongzi; Li, Shaoying; Zheng, Yuhong; Li, Qing; Chen, Xinjie; Liao, Baoping; Xiao, Guohong; Wang, Weihua; Sun, Xiaofang

2009-04-01

Poor quality embryos discarded from in vitro fertilization (IVF) laboratories are good sources for deriving human embryonic stem cell (hESC) lines. In this study, 166 poor quality embryos donated from IVF centers on day 3 were cultured in a blastocyst medium for 2 days, and 32 early blastocysts were further cultured in a blastocyst optimum culture medium for additional 2 days so that the inner cell masses (ICMs) could be identified and isolated easily. The ICMs of 17 blastocysts were isolated by a mechanical method, while those of the other 15 blastocysts were isolated by immunosurgery. All isolated ICMs were inoculated onto a feeder layer for subcultivation. The rates of ICM attachment, primary ICM colony formation and the efficiency of hESC derivation were similar between the ICMs isolated by the two methods (P>0.05). As a result, four new hESC lines were established. Three cell lines had normal karyotypes and one had an unbalanced Robertsonian translocation. All cell lines showed normal hESC characteristics and had the differentiation ability. In conclusion, we established a stable and effective method for hESC isolation and culture, and it was confirmed that the mechanical isolation was an effective method to isolate ICMs from poor embryos. These results further indicate that hESC lines can be derived from poor quality embryos discarded by IVF laboratories.

Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng.

PubMed

An, Ya-Nan; Zhang, Xue; Zhang, Tian-Yuan; Zhang, Meng-Yue; Qian-Zhang; Deng, Xiao-Yu; Zhao, Feng; Zhu, Ling-Juan; Wang, Guan; Zhang, Jie; Zhang, Yi-Xuan; Liu, Bo; Yao, Xin-Sheng

2016-06-08

Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1-5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6), and six known biogenetically related derivatives (7-12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher's method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2-4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2-hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2-4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS.

Physiologically based microenvironment for in vitro neural differentiation of adipose-derived stem cells

PubMed Central

Graziano, Adriana Carol Eleonora; Avola, Rosanna; Perciavalle, Vincenzo; Nicoletti, Ferdinando; Cicala, Gianluca; Coco, Marinella; Cardile, Venera

2018-01-01

The limited capacity of nervous system to promote a spontaneous regeneration and the high rate of neurodegenerative diseases appearance are keys factors that stimulate researches both for defining the molecular mechanisms of pathophysiology and for evaluating putative strategies to induce neural tissue regeneration. In this latter aspect, the application of stem cells seems to be a promising approach, even if the control of their differentiation and the maintaining of a safe state of proliferation should be troubled. Here, we focus on adipose tissue-derived stem cells and we seek out the recent advances on the promotion of their neural differentiation, performing a critical integration of the basic biology and physiology of adipose tissue-derived stem cells with the functional modifications that the biophysical, biomechanical and biochemical microenvironment induces to cell phenotype. The pre-clinical studies showed that the neural differentiation by cell stimulation with growth factors benefits from the integration with biomaterials and biophysical interaction like microgravity. All these elements have been reported as furnisher of microenvironments with desirable biological, physical and mechanical properties. A critical review of current knowledge is here proposed, underscoring that a real advance toward a stable, safe and controllable adipose stem cells clinical application will derive from a synergic multidisciplinary approach that involves material engineer, basic cell biology, cell and tissue physiology. PMID:29588808

Identification of Baribis fault - West Java using second vertical derivative method of gravity

NASA Astrophysics Data System (ADS)

Sari, Endah Puspita; Subakti, Hendri

2015-04-01

Baribis fault is one of West Java fault zones which is an active fault. In modern era, the existence of fault zone can be observed by gravity anomaly. Baribis fault zone has not yet been measured by gravity directly. Based on this reason, satellite data supported this research. Data used on this research are GPS satellite data downloaded from TOPEX. The purpose of this research is to determine the type and strike of Baribis fault. The scope of this research is Baribis fault zone which lies on 6.50o - 7.50o S and 107.50o - 108.80o E. It consists of 5146 points which one point to another is separated by 1 minute meridian. The method used in this research is the Second Vertical Derivative (SVD) of gravity anomaly. The Second Vertical Derivative of gravity anomaly show as the amplitude of gravity anomaly caused by fault structure which appears as residual anomaly. The zero value of residual gravity anomaly indicates that the contact boundary of fault plane. Second Vertical Derivative method of gravity was applied for identifying Baribis fault. The result of this research shows that Baribis fault has a thrust mechanism. It has a lineament strike varies from 107o to 127o. This result agrees with focal mechanism data of earthquakes occurring on this region based on Global CMT catalogue.

Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes.

PubMed

Ong, Huan Ting; Redmond, Sharon L; Marano, Robert J; Atlas, Marcus D; von Unge, Magnus; Aabel, Peder; Dilley, Rodney J

2017-03-15

Stem cell therapies for tympanic membrane repair have shown initial experimental success using mesenchymal stem cells in rat models to promote healing; however, the mechanisms providing this benefit are not known. We investigated in vitro the paracrine effects of human adipose-derived stem cells (ADSCs) on wound healing mechanisms for human tympanic membrane-derived keratinocytes (hTM) and immortalized human keratinocytes (HaCaT). ADSC conditioned media (CM ADSC ) were assessed for paracrine activity on keratinocyte proliferation and migration, with hypoxic conditions for ADSC culture used to generate contrasting effects on cytokine gene expression. Keratinocytes cultured in CM ADSC showed a significant increase in cell number compared to serum-free cultures and further significant increases in hypoxic CM ADSC . Assessment of ADSC gene expression on a cytokine array showed a range of wound healing cytokines expressed and under stringent hypoxic and serum-free conditions was upregulated (VEGF A, MMP9, Tissue Factor, PAI-1) or downregulated (CXCL5, CCL7, TNF-α). Several of these may contribute to the activity of conditioned media on the keratinocytes with potential applications in TM perforation repair. VEGFA protein was confirmed by immunoassay to be increased in conditioned media. Together with gene regulation associated with hypoxia in ADSCs, this study has provided several strong leads for a stem cell-derived approach to TM wound healing.