Engineering nanometre-scale coherence in soft matter

NASA Astrophysics Data System (ADS)

Liu, Chaoren; Xiang, Limin; Zhang, Yuqi; Zhang, Peng; Beratan, David N.; Li, Yueqi; Tao, Nongjian

2016-10-01

Electronic delocalization in redox-active polymers may be disrupted by the heterogeneity of the environment that surrounds each monomer. When the differences in monomer redox-potential induced by the environment are small (as compared with the monomer-monomer electronic interactions), delocalization persists. Here we show that guanine (G) runs in double-stranded DNA support delocalization over 4-5 guanine bases. The weak interaction between delocalized G blocks on opposite DNA strands is known to support partially coherent long-range charge transport. The molecular-resolution model developed here finds that the coherence among these G blocks follows an even-odd orbital-symmetry rule and predicts that weakening the interaction between G blocks exaggerates the resistance oscillations. These findings indicate how sequence can be exploited to change the balance between coherent and incoherent transport. The predictions are tested and confirmed using break-junction experiments. Thus, tailored orbital symmetry and structural fluctuations may be used to produce coherent transport with a length scale of multiple nanometres in soft-matter assemblies, a length scale comparable to that of small proteins.

A nanometre-scale electronic switch consisting of a metal cluster and redox-addressable groups.

PubMed

Gittins, D I; Bethell, D; Schiffrin, D J; Nichols, R J

2000-11-02

So-called bottom-up fabrication methods aim to assemble and integrate molecular components exhibiting specific functions into electronic devices that are orders of magnitude smaller than can be fabricated by lithographic techniques. Fundamental to the success of the bottom-up approach is the ability to control electron transport across molecular components. Organic molecules containing redox centres-chemical species whose oxidation number, and hence electronic structure, can be changed reversibly-support resonant tunnelling and display promising functional behaviour when sandwiched as molecular layers between electrical contacts, but their integration into more complex assemblies remains challenging. For this reason, functionalized metal nanoparticles have attracted much interest: they exhibit single-electron characteristics (such as quantized capacitance charging) and can be organized through simple self-assembly methods into well ordered structures, with the nanoparticles at controlled locations. Here we report scanning tunnelling microscopy measurements showing that organic molecules containing redox centres can be used to attach metal nanoparticles to electrode surfaces and so control the electron transport between them. Our system consists of gold nanoclusters a few nanometres across and functionalized with polymethylene chains that carry a central, reversibly reducible bipyridinium moiety. We expect that the ability to electronically contact metal nanoparticles via redox-active molecules, and to alter profoundly their tunnelling properties by charge injection into these molecules, can form the basis for a range of nanoscale electronic switches.

Nanometric holograms based on a topological insulator material.

PubMed

Yue, Zengji; Xue, Gaolei; Liu, Juan; Wang, Yongtian; Gu, Min

2017-05-18

Holography has extremely extensive applications in conventional optical instruments spanning optical microscopy and imaging, three-dimensional displays and metrology. To integrate holography with modern low-dimensional electronic devices, holograms need to be thinned to a nanometric scale. However, to keep a pronounced phase shift modulation, the thickness of holograms has been generally limited to the optical wavelength scale, which hinders their integration with ultrathin electronic devices. Here, we break this limit and achieve 60 nm holograms using a topological insulator material. We discover that nanometric topological insulator thin films act as an intrinsic optical resonant cavity due to the unequal refractive indices in their metallic surfaces and bulk. The resonant cavity leads to enhancement of phase shifts and thus the holographic imaging. Our work paves a way towards integrating holography with flat electronic devices for optical imaging, data storage and information security.

Nanometric holograms based on a topological insulator material

PubMed Central

Yue, Zengji; Xue, Gaolei; Liu, Juan; Wang, Yongtian; Gu, Min

2017-01-01

Holography has extremely extensive applications in conventional optical instruments spanning optical microscopy and imaging, three-dimensional displays and metrology. To integrate holography with modern low-dimensional electronic devices, holograms need to be thinned to a nanometric scale. However, to keep a pronounced phase shift modulation, the thickness of holograms has been generally limited to the optical wavelength scale, which hinders their integration with ultrathin electronic devices. Here, we break this limit and achieve 60 nm holograms using a topological insulator material. We discover that nanometric topological insulator thin films act as an intrinsic optical resonant cavity due to the unequal refractive indices in their metallic surfaces and bulk. The resonant cavity leads to enhancement of phase shifts and thus the holographic imaging. Our work paves a way towards integrating holography with flat electronic devices for optical imaging, data storage and information security. PMID:28516906

The morphology of cometary dust: Subunit size distributions down to tens of nanometres

NASA Astrophysics Data System (ADS)

Mannel, Thurid; Bentley, Mark; Boakes, Peter; Jeszenszky, Harald; Levasseur-Regourd, Anny-Chantal; Schmied, Roland; Torkar, Klaus

2017-04-01

The Rosetta orbiter carried a dedicated analysis suite for cometary dust. One of the key instruments was MIDAS (Micro-Imaging Dust Analysis System), an atomic force microscope that scanned the surfaces of hundreds of (sub-)micrometre particles in 3D with resolutions down to nanometres. This provided the opportunity to study the morphology of the smallest cometary dust; initial investigation revealed that the particles are agglomerates of smaller subunits [1] with different structural properties [2]. To understand the (surface-) structure of the dust particles and the origin of their smallest building blocks, a number of particles were investigated in detail and the size distribution of their subunits determined [3]. Here we discuss the subunit size distributions ranging from tens of nanometres to a few micrometres. The differences between the subunit size distributions for particles collected pre-perihelion, close to perihelion, and during a huge outburst are examined, as well as the dependence of subunit size on particle size. A case where a particle was fragmented in consecutive scans allows a direct comparison of fragment and subunit size distributions. Finally, the small end of the subunit size distribution is investigated: the smallest determined sizes will be reviewed in the context of other cometary missions, interplanetary dust particles believed to originate from comets, and remote observations. It will be discussed if the smallest subunits can be interpreted as fundamental building blocks of our early Solar System and if their origin was in our protoplanetary disc or the interstellar material. References: [1] M.S. Bentley, R. Schmied, T. Mannel et al., Aggregate dust particles at comet 67P/Chruyumov-Gerasimenko, Nature, 537, 2016. doi:10.1038/nature19091 [2] T. Mannel, M.S. Bentley, R. Schmied et al., Fractal cometary dust - a window into the early Solar system, MNRAS, 462, 2016. doi:10.1093/mnras/stw2898 [3] R. Schmied, T. Mannel, H. Jeszenszky, M

Study of radiative heat transfer in Ångström- and nanometre-sized gaps

DOE PAGES

Cui, Longji; Jeong, Wonho; Fernández-Hurtado, Víctor; ...

2017-02-15

Radiative heat transfer in Ångström- and nanometre-sized gaps is of great interest because of both its technological importance and open questions regarding the physics of energy transfer in this regime. Here in this paper we report studies of radiative heat transfer in few Å to 5nm gap sizes, performed under ultrahigh vacuum conditions between a Au-coated probe featuring embedded nanoscale thermocouples and a heated planar Au substrate that were both subjected to various surface-cleaning procedures. By drawing on the apparent tunnelling barrier height as a signature of cleanliness, we found that upon systematically cleaning via a plasma or locally pushingmore » the tip into the substrate by a few nanometres, the observed radiative conductances decreased from unexpectedly large values to extremely small ones—below the detection limit of our probe—as expected from our computational results. Our results show that it is possible to avoid the confounding effects of surface contamination and systematically study thermal radiation in Ångström- and nanometre-sized gaps.« less

Universal Long-Range Nanometric Bending of Water by Light.

PubMed

Verma, Gopal; Singh, Kamal P

2015-10-02

Resolving mechanical effects of light on fluids has fundamental importance with wide applications. Most experiments to date on optofluidic interface deformation exploited radiation forces exerted by normally incident lasers. However, the intriguing effects of photon momentum for any configuration, including the unique total internal reflection regime, where an evanescent wave leaks above the interface, remain largely unexplored. A major difficulty in resolving nanomechanical effects has been the lack of a sensitive detection technique. Here, we devise a simple setup whereby a probe laser produces high-contrast Newton-ring-like fringes from a sessile water drop. The mechanical action of the photon momentum of a pump beam modulates the fringes, thus allowing us to perform a direct noninvasive measurement of a nanometric bulge with sub-5-nm precision. Remarkably, a <10  nm difference in the height of the bulge due to different laser polarizations and nonlinear enhancement in the bulge near total internal reflection is isolated. In addition, the nanometric bulge is shown to extend far longer, 100 times beyond the pump spot. Our high precision data validate the century-old Minkowski theory for a general angle and offer potential for novel optofluidic devices and noncontact nanomanipulation strategies.

Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime

NASA Astrophysics Data System (ADS)

Du, Bujie; Jiang, Xingya; Das, Anindita; Zhou, Qinhan; Yu, Mengxiao; Jin, Rongchao; Zheng, Jie

2017-11-01

The glomerular filtration barrier is known as a 'size cutoff' slit, which retains nanoparticles or proteins larger than 6-8 nm in the body and rapidly excretes smaller ones through the kidneys. However, in the sub-nanometre size regime, we have found that this barrier behaves as an atomically precise 'bandpass' filter to significantly slow down renal clearance of few-atom gold nanoclusters (AuNCs) with the same surface ligands but different sizes (Au18, Au15 and Au10-11). Compared to Au25 (∼1.0 nm), just few-atom decreases in size result in four- to ninefold reductions in renal clearance efficiency in the early elimination stage, because the smaller AuNCs are more readily trapped by the glomerular glycocalyx than larger ones. This unique in vivo nano-bio interaction in the sub-nanometre regime also slows down the extravasation of sub-nanometre AuNCs from normal blood vessels and enhances their passive targeting to cancerous tissues through an enhanced permeability and retention effect. This discovery highlights the size precision in the body's response to nanoparticles and opens a new pathway to develop nanomedicines for many diseases associated with glycocalyx dysfunction.

Heterodyne interferometric technique for displacement control at the nanometric scale

NASA Astrophysics Data System (ADS)

Topcu, Suat; Chassagne, Luc; Haddad, Darine; Alayli, Yasser; Juncar, Patrick

2003-11-01

We propose a method of displacement control that addresses the measurement requirements of the nanotechnology community and provide a traceability to the definition of the mèter at the nanometric scale. The method is based on the use of both a heterodyne Michelson's interferometer and a homemade high frequency electronic circuit. The system so established allows us to control the displacement of a translation stage with a known step of 4.945 nm. Intrinsic relative uncertainty on the step value is 1.6×10-9. Controls of the period of repetition of these steps with a high-stability quartz oscillator permits to impose an uniform speed to the translation stage with the same accuracy. This property will be used for the watt balance project of the Bureau National de Métrologie of France.

Properties of Diamond and Diamond-Like Clusters in Nanometric Dimensions

NASA Technical Reports Server (NTRS)

Halicioglu, Timur; Langhoff, Stephen R. (Technical Monitor)

1996-01-01

Variations in materials properties of small clusters of nanometric dimensions were investigated. Investigations were carried out for diamond and diamond-like particles in spherical shapes. Calculations were performed for clusters containing over 1000 carbon atoms. Results indicate that as the cluster size diminishes, (i) the average cohesive energy becomes weaker, (ii) the excess surface energy increases, and (iii) the value for stiffness decreases.

Energy dependent track structure parametrisations for protons and carbon ions based on nanometric simulations

NASA Astrophysics Data System (ADS)

Alexander, Frauke; Villagrasa, Carmen; Rabus, Hans; Wilkens, Jan J.

2015-09-01

The BioQuaRT project within the European Metrology Research Programme aims at correlating ion track structure characteristics with the biological effects of radiation and develops measurement and simulation techniques for determining ion track structure on different length scales from about 2 nm to about 10 μm. Within this framework, we investigate methods to translate track-structure quantities derived on a nanometre scale to macroscopic dimensions. Input data sets were generated by simulations of ion tracks of protons and carbon ions in liquid water using the Geant 4 Monte Carlo toolkit with the Geant4-DNA processes. Based on the energy transfer points - recorded with nanometre resolution - we investigated parametrisations of overall properties of ion track structure. Three different track structure parametrisations have been developed using the distances to the 10 next neighbouring ionisations, the radial energy distribution and ionisation cluster size distributions. These parametrisations of nanometric track structure build a basis for deriving biologically relevant mean values which are essential in the clinical situation where each voxel is exposed to a mixed radiation field. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey Solov'yov, Nigel Mason, Gustavo García, Eugene Surdutovich.

A novel avalanche-confinement TEPC for microdosimetry at nanometric level

NASA Astrophysics Data System (ADS)

Bortot, D.; Agosteo, S.; Colautti, P.; Conte, V.; Introini, M. V.; Lorenzoli, M.; Pasquato, S.; Pola, A.

2017-09-01

The tissue equivalent proportional counter (TEPC) is the most accurate device for measuring the microdosimetric properties of a particle beam, showing to properly assess the relative biological effectiveness by linking the physical parameters of the radiation with the corresponding biological response. Nevertheless no detailed information on the track structure of the impinging particles can be obtained, since the lower operation limit of the common TEPCs is about 0.3 ?m. On the other hand, the pattern of particle interactions at the nanometer level, which demonstrated to have a strong correlation with radiation-induced damages to the DNA, is directly measured by only three different nanodosimeters worldwide: practical instruments are not yet available. The gap between microdosimetry and track-nanodosimetry can be filled partially by extending the TEPC response down to the nanometric region. A feasibility study of a novel TEPC designed to simulate biological sites in the nanometric domain was performed. The present paper aims at describing the design, the development and the characterization of this avalanche-confinement TEPC. Irradiations with photons, fast neutrons and low-energy carbon ions demonstrated the capability of this TEPC of measuring in the range 0.3 μm - 25 nm.

What holds paper together: Nanometre scale exploration of bonding between paper fibres

PubMed Central

Schmied, Franz J.; Teichert, Christian; Kappel, Lisbeth; Hirn, Ulrich; Bauer, Wolfgang; Schennach, Robert

2013-01-01

Paper, a man-made material that has been used for hundreds of years, is a network of natural cellulosic fibres. To a large extent, it is the strength of bonding between these individual fibres that controls the strength of paper. Using atomic force microscopy, we explore here the mechanical properties of individual fibre-fibre bonds on the nanometre scale. A single fibre-fibre bond is loaded with a calibrated cantilever statically and dynamically until the bond breaks. Besides the calculation of the total energy input, time dependent processes such as creep and relaxation are studied. Through the nanometre scale investigation of the formerly bonded area, we show that fibrils or fibril bundles play a crucial role in fibre-fibre bonding because they act as bridging elements. With this knowledge, new fabrication routes can be deduced to increase the strength of an ancient product that is in fact an overlooked high-tech material. PMID:23969946

Experimental Investigation on Cutting Characteristics in Nanometric Plunge-Cutting of BK7 and Fused Silica Glasses

PubMed Central

An, Qinglong; Ming, Weiwei; Chen, Ming

2015-01-01

Ductile cutting are most widely used in fabricating high-quality optical glass components to achieve crack-free surfaces. For ultra-precision machining of brittle glass materials, critical undeformed chip thickness (CUCT) commonly plays a pivotal role in determining the transition point from ductile cutting to brittle cutting. In this research, cutting characteristics in nanometric cutting of BK7 and fused silica glasses, including machined surface morphology, surface roughness, cutting force and specific cutting energy, were investigated with nanometric plunge-cutting experiments. The same cutting speed of 300 mm/min was used in the experiments with single-crystal diamond tool. CUCT was determined according to the mentioned cutting characteristics. The results revealed that 320 nm was found as the CUCT in BK7 cutting and 50 nm was determined as the size effect of undeformed chip thickness. A high-quality machined surface could be obtained with the undeformed chip thickness between 50 and 320 nm at ductile cutting stage. Moreover, no CUCT was identified in fused silica cutting with the current cutting conditions, and brittle-fracture mechanism was confirmed as the predominant chip-separation mode throughout the nanometric cutting operation. PMID:28788010

Experimental Investigation on Cutting Characteristics in Nanometric Plunge-Cutting of BK7 and Fused Silica Glasses.

PubMed

An, Qinglong; Ming, Weiwei; Chen, Ming

2015-03-27

Ductile cutting are most widely used in fabricating high-quality optical glass components to achieve crack-free surfaces. For ultra-precision machining of brittle glass materials, critical undeformed chip thickness (CUCT) commonly plays a pivotal role in determining the transition point from ductile cutting to brittle cutting. In this research, cutting characteristics in nanometric cutting of BK7 and fused silica glasses, including machined surface morphology, surface roughness, cutting force and specific cutting energy, were investigated with nanometric plunge-cutting experiments. The same cutting speed of 300 mm/min was used in the experiments with single-crystal diamond tool. CUCT was determined according to the mentioned cutting characteristics. The results revealed that 320 nm was found as the CUCT in BK7 cutting and 50 nm was determined as the size effect of undeformed chip thickness. A high-quality machined surface could be obtained with the undeformed chip thickness between 50 and 320 nm at ductile cutting stage. Moreover, no CUCT was identified in fused silica cutting with the current cutting conditions, and brittle-fracture mechanism was confirmed as the predominant chip-separation mode throughout the nanometric cutting operation.

Direct observation of molecular cooperativity near the glass transition.

PubMed

Russell, E V; Israeloff, N E

2000-12-07

The increasingly sluggish response of a supercooled liquid as it nears its glass transition (for example, refrigerated honey) is prototypical of glassy dynamics found in proteins, neural networks and superconductors. The notion that molecules rearrange cooperatively has long been postulated to explain diverging relaxation times and broadened (non-exponential) response functions near the glass transition. Recently, cooperativity was observed and analysed in colloid glasses and in simulations of binary liquids well above the glass transition. But nanometre-scale studies of cooperativity at the molecular glass transition are lacking. Important issues to be resolved include the precise form of the cooperativity and its length scale, and whether the broadened response is intrinsic to individual cooperative regions, or arises only from heterogeneity in an ensemble of such regions. Here we describe direct observations of molecular cooperativity near the glass transition in polyvinylacetate (PVAc), using nanometre-scale probing of dielectric fluctuations. Molecular clusters switched spontaneously among two to four distinct configurations, producing random telegraph noise. Our analysis of these noise signals and their power spectra reveals that individual clusters exhibit transient dynamical heterogeneity and non-exponential kinetics.

Theoretical study of a molecular turbine.

PubMed

Perez-Carrasco, R; Sancho, J M

2013-10-01

We present an analytic and stochastic simulation study of a molecular engine working with a flux of particles as a turbine. We focus on the physical observables of velocity, flux, power, and efficiency. The control parameters are the external conservative force and the particle densities. We revise a simpler previous study by using a more realistic model containing multiple equidistant vanes complemented by stochastic simulations of the particles and the turbine. Here we show that the effect of the thermal fluctuations into the flux and the efficiency of these nanometric devices are relevant to the working scale of the system. The stochastic simulations of the Brownian motion of the particles and turbine support the simplified analytical calculations performed.

Application of a parallel genetic algorithm to the global optimization of medium-sized Au-Pd sub-nanometre clusters

NASA Astrophysics Data System (ADS)

Hussein, Heider A.; Demiroglu, Ilker; Johnston, Roy L.

2018-02-01

To contribute to the discussion of the high activity and reactivity of Au-Pd system, we have adopted the BPGA-DFT approach to study the structural and energetic properties of medium-sized Au-Pd sub-nanometre clusters with 11-18 atoms. We have examined the structural behaviour and stability as a function of cluster size and composition. The study suggests 2D-3D crossover points for pure Au clusters at 14 and 16 atoms, whereas pure Pd clusters are all found to be 3D. For Au-Pd nanoalloys, the role of cluster size and the influence of doping were found to be extensive and non-monotonic in altering cluster structures. Various stability criteria (e.g. binding energies, second differences in energy, and mixing energies) are used to evaluate the energetics, structures, and tendency of segregation in sub-nanometre Au-Pd clusters. HOMO-LUMO gaps were calculated to give additional information on cluster stability and a systematic homotop search was used to evaluate the energies of the generated global minima of mono-substituted clusters and the preferred doping sites, as well as confirming the validity of the BPGA-DFT approach.

Coherent Diffractive Imaging: From Nanometric Down to Picometric Resolution

NASA Astrophysics Data System (ADS)

De Caro, Liberato; Carlino, Elvio; Siliqi, Dritan; Giannini, Cinzia

Coherent diffractive imaging (CDI) is a novel technique for inspecting (crystalline and non-crystalline) matter from nanometric down to picometric resolution. It was used originally with X-rays and, more recently, with electrons (so-called electron diffractive imaging, or EDI). This chapter introduces basic concepts concerning CDI and addresses the different types of X-ray CDI experiments that have been conducted, namely plane wave CDI from isolated objects in forward scattering, focused-beam Fresnel CDI from isolated objects in forward scattering, Bragg CDI from nanocrystals, and keyhole CDI and ptychography from extended objects. A CDI experiment with a transmission electron microscope, alternatively named an EDI experiment, is also introduced.

Nanometric summation architecture based on optical near-field interaction between quantum dots.

PubMed

Naruse, Makoto; Miyazaki, Tetsuya; Kubota, Fumito; Kawazoe, Tadashi; Kobayashi, Kiyoshi; Sangu, Suguru; Ohtsu, Motoichi

2005-01-15

A nanoscale data summation architecture is proposed and experimentally demonstrated based on the optical near-field interaction between quantum dots. Based on local electromagnetic interactions between a few nanometric elements via optical near fields, we can combine multiple excitations at a certain quantum dot, which allows construction of a summation architecture. Summation plays a key role for content-addressable memory, which is one of the most important functions in optical networks.

Capacitance-voltage characteristics of sub-nanometric Al2O3 / TiO2 laminates: dielectric and interface charge densities.

PubMed

Kahouli, Abdelkader; Elbahri, Marwa Ben; Lebedev, Oleg; Lüders, Ulrike

2017-07-12

Advanced amorphous sub-nanometric laminates based on TiO 2 and Al 2 O 3 were deposited by atomic layer deposition at low temperature. Low densities of 'slow' and 'fast' interface states are achieved with values of 3.96 · 10 10 cm -2 and 4.85 · 10 -9 eV -1 cm -2 , respectively, by using a 40 nm laminate constituted of 0.7 nm TiO 2 and 0.8 nm Al 2 O 3 . The sub-nanometric laminate shows a low hysteresis width of 20 mV due to the low oxide charge density of about 3.72 · 10 11 cm -2 . Interestingly, such properties are required for stable and reliable performance of MOS capacitors and transistor operation. Thus, decreasing the individual layer thickness to the sub-nanometric range and combining two dielectric materials with oppositely charged defects may play a major role in the electrical response, highly promising for the application in future micro and nano-electronics applications.

Molecular gearing systems

DOE PAGES

Gakh, Andrei A.; Sachleben, Richard A.; Bryan, Jeff C.

1997-11-01

The race to create smaller devices is fueling much of the research in electronics. The competition has intensified with the advent of microelectromechanical systems (MEMS), in which miniaturization is already reaching the dimensional limits imposed by physics of current lithographic techniques. Also, in the realm of biochemistry, evidence is accumulating that certain enzyme complexes are capable of very sophisticated modes of motion. Complex synergistic biochemical complexes driven by sophisticated biomechanical processes are quite common. Their biochemical functions are based on the interplay of mechanical and chemical processes, including allosteric effects. In addition, the complexity of this interplay far exceeds thatmore » of typical chemical reactions. Understanding the behavior of artificial molecular devices as well as complex natural molecular biomechanical systems is difficult. Fortunately, the problem can be successfully resolved by direct molecular engineering of simple molecular systems that can mimic desired mechanical or electronic devices. These molecular systems are called technomimetics (the name is derived, by analogy, from biomimetics). Several classes of molecular systems that can mimic mechanical, electronic, or other features of macroscopic devices have been successfully synthesized by conventional chemical methods during the past two decades. In this article we discuss only one class of such model devices: molecular gearing systems.« less

Self-assembly of organic monolayers as protective and conductive bridges for nanometric surface-mount applications.

PubMed

Platzman, Ilia; Haick, Hossam; Tannenbaum, Rina

2010-09-01

In this work, we present a novel surface-mount placement process that could potentially overcome the inadequacies of the currently used stencil-printing technology, when applied to devices in which either their lateral and/or their horizontal dimensions approach the nanometric scale. Our novel process is based on the "bottom-up" design of an adhesive layer, operative in the molecular/nanoscale level, through the use of self-assembled monolayers (SAMs) that could form protective and conductive bridges between pads and components. On the basis of previous results, 1,4-phenylene diisocyanide (PDI) and terephthalic acid (TPA) were chosen to serve as the best candidates for the achievement of this goal. The quality and stability of these SAMs on annealed Cu surfaces (Rrms=0.15-1.1 nm) were examined in detail. Measurements showed that the SAMs of TPA and PDI molecules formed on top of Cu substrates created thermally stable organic monolayers with high surface coverage (∼90%), in which the molecules were closely packed and well-ordered. Moreover, the molecules assumed a standing-up phase conformation, in which the molecules bonded to the Cu substrate through one terminal functional group, with the other terminal group residing away from the substrate. To examine the ability of these monolayers to serve as "molecular wires," i.e., the capability to provide electrical conductivity, we developed a novel fabrication method of a parallel plate junction (PPJ) in order to create symmetric Cu-SAM-Cu electrical junctions. The current-bias measurements of these junctions indicated high tunneling efficiency. These achievements imply that the SAMs used in this study can serve as conductive molecular bridges that can potentially bind circuital pads/components.

Efficient molecular density functional theory using generalized spherical harmonics expansions.

PubMed

Ding, Lu; Levesque, Maximilien; Borgis, Daniel; Belloni, Luc

2017-09-07

We show that generalized spherical harmonics are well suited for representing the space and orientation molecular density in the resolution of the molecular density functional theory. We consider the common system made of a rigid solute of arbitrary complexity immersed in a molecular solvent, both represented by molecules with interacting atomic sites and classical force fields. The molecular solvent density ρ(r,Ω) around the solute is a function of the position r≡(x,y,z) and of the three Euler angles Ω≡(θ,ϕ,ψ) describing the solvent orientation. The standard density functional, equivalent to the hypernetted-chain closure for the solute-solvent correlations in the liquid theory, is minimized with respect to ρ(r,Ω). The up-to-now very expensive angular convolution products are advantageously replaced by simple products between projections onto generalized spherical harmonics. The dramatic gain in speed of resolution enables to explore in a systematic way molecular solutes of up to nanometric sizes in arbitrary solvents and to calculate their solvation free energy and associated microscopic solvent structure in at most a few minutes. We finally illustrate the formalism by tackling the solvation of molecules of various complexities in water.

A 17 GHz molecular rectifier

PubMed Central

Trasobares, J.; Vuillaume, D.; Théron, D.; Clément, N.

2016-01-01

Molecular electronics originally proposed that small molecules sandwiched between electrodes would accomplish electronic functions and enable ultimate scaling to be reached. However, so far, functional molecular devices have only been demonstrated at low frequency. Here, we demonstrate molecular diodes operating up to 17.8 GHz. Direct current and radio frequency (RF) properties were simultaneously measured on a large array of molecular junctions composed of gold nanocrystal electrodes, ferrocenyl undecanethiol molecules and the tip of an interferometric scanning microwave microscope. The present nanometre-scale molecular diodes offer a current density increase by several orders of magnitude compared with that of micrometre-scale molecular diodes, allowing RF operation. The measured S11 parameters show a diode rectification ratio of 12 dB which is linked to the rectification behaviour of the direct current conductance. From the RF measurements, we extrapolate a cut-off frequency of 520 GHz. A comparison with the silicon RF-Schottky diodes, architecture suggests that the RF-molecular diodes are extremely attractive for scaling and high-frequency operation. PMID:27694833

Contact mechanics at nanometric scale using nanoindentation technique for brittle and ductile materials.

PubMed

Roa, J J; Rayon, E; Morales, M; Segarra, M

2012-06-01

In the last years, Nanoindentation or Instrumented Indentation Technique has become a powerful tool to study the mechanical properties at micro/nanometric scale (commonly known as hardness, elastic modulus and the stress-strain curve). In this review, the different contact mechanisms (elastic and elasto-plastic) are discussed, the recent patents for each mechanism (elastic and elasto-plastic) are summarized in detail, and the basic equations employed to know the mechanical behaviour for brittle and ductile materials are described.

Amorphous sub-nanometre Tb-doped SiO(x)N(y)/SiO2 superlattices for optoelectronics.

PubMed

Ramírez, Joan Manel; Wojcik, Jacek; Berencén, Yonder; Ruiz-Caridad, Alícia; Estradé, Sònia; Peiró, Francesca; Mascher, Peter; Garrido, Blas

2015-02-27

Amorphous sub-nanometre Tb-doped SiOxNy/SiO2 superlattices were fabricated by means of alternating deposition of 0.7 nm thick Tb-doped SiOxNy layers and of 0.9 nm thick SiO2 barrier layers in an electron-cyclotron-resonance plasma enhanced chemical vapour deposition system with in situ Tb-doping capability. High resolution transmission electron microscopy images showed a well-preserved superlattice morphology after annealing at a high temperature of 1000 °C. In addition, transparent indium tin oxide (ITO) electrodes were deposited by electron beam evaporation using a shadow mask approach to allow for the optoelectronic characterization of superlattices. Tb(3+) luminescent spectral features were obtained using three different excitation sources: UV laser excitation (photoluminescence (PL)), under a bias voltage (electroluminescence (EL)) and under a highly energetic electron beam (cathodoluminescence (CL)). All techniques displayed Tb(3+) inner transitions belonging to (5)D4 levels except for the CL spectrum, in which (5)D3 transition levels were also observed. Two competing mechanisms were proposed to explain the spectral differences observed between PL (or EL) and CL excitation: the population rate of the (5)D3 state and the non-radiative relaxation rate of the (5)D3-(5)D4 transition due to a resonant OH-mode. Moreover, the large number of interfaces (trapping sites) that electrons have to get through was identified as the main reason for observing a bulk-limited charge transport mechanism governed by Poole-Frenkel conduction in the J-V characteristic. Finally, a linear EL-J dependence was measured, with independent spectral shape and an EL onset voltage as low as 6.7 V. These amorphous sub-nanometre superlattices are meant to provide low-cost solutions in different areas including sensing, photovoltaics or photonics.

Micromagnetic computer simulations of spin waves in nanometre-scale patterned magnetic elements

NASA Astrophysics Data System (ADS)

Kim, Sang-Koog

2010-07-01

Current needs for further advances in the nanotechnologies of information-storage and -processing devices have attracted a great deal of interest in spin (magnetization) dynamics in nanometre-scale patterned magnetic elements. For instance, the unique dynamic characteristics of non-uniform magnetic microstructures such as various types of domain walls, magnetic vortices and antivortices, as well as spin wave dynamics in laterally restricted thin-film geometries, have been at the centre of extensive and intensive researches. Understanding the fundamentals of their unique spin structure as well as their robust and novel dynamic properties allows us to implement new functionalities into existing or future devices. Although experimental tools and theoretical approaches are effective means of understanding the fundamentals of spin dynamics and of gaining new insights into them, the limitations of those same tools and approaches have left gaps of unresolved questions in the pertinent physics. As an alternative, however, micromagnetic modelling and numerical simulation has recently emerged as a powerful tool for the study of a variety of phenomena related to spin dynamics of nanometre-scale magnetic elements. In this review paper, I summarize the recent results of simulations of the excitation and propagation and other novel wave characteristics of spin waves, highlighting how the micromagnetic computer simulation approach contributes to an understanding of spin dynamics of nanomagnetism and considering some of the merits of numerical simulation studies. Many examples of micromagnetic modelling for numerical calculations, employing various dimensions and shapes of patterned magnetic elements, are given. The current limitations of continuum micromagnetic modelling and of simulations based on the Landau-Lifshitz-Gilbert equation of motion of magnetization are also discussed, along with further research directions for spin-wave studies.

A review of recent work in sub-nanometre displacement measurement using optical and X-ray interferometry.

PubMed

Peggs, G N; Yacoot, A

2002-05-15

This paper reviews recent work in the field of displacement measurement using optical and X-ray interferometry at the sub-nanometre level of accuracy. The major sources of uncertainty in optical interferometry are discussed and a selection of recent designs of ultra-precise, optical-interferometer-based, displacement measuring transducers presented. The use of X-ray interferometry and its combination with optical interferometry is discussed.

Nanometric depth resolution from multi-focal images in microscopy.

PubMed

Dalgarno, Heather I C; Dalgarno, Paul A; Dada, Adetunmise C; Towers, Catherine E; Gibson, Gavin J; Parton, Richard M; Davis, Ilan; Warburton, Richard J; Greenaway, Alan H

2011-07-06

We describe a method for tracking the position of small features in three dimensions from images recorded on a standard microscope with an inexpensive attachment between the microscope and the camera. The depth-measurement accuracy of this method is tested experimentally on a wide-field, inverted microscope and is shown to give approximately 8 nm depth resolution, over a specimen depth of approximately 6 µm, when using a 12-bit charge-coupled device (CCD) camera and very bright but unresolved particles. To assess low-flux limitations a theoretical model is used to derive an analytical expression for the minimum variance bound. The approximations used in the analytical treatment are tested using numerical simulations. It is concluded that approximately 14 nm depth resolution is achievable with flux levels available when tracking fluorescent sources in three dimensions in live-cell biology and that the method is suitable for three-dimensional photo-activated localization microscopy resolution. Sub-nanometre resolution could be achieved with photon-counting techniques at high flux levels.

Mechanochemical models of processive molecular motors

NASA Astrophysics Data System (ADS)

Lan, Ganhui; Sun, Sean X.

2012-05-01

Motor proteins are the molecular engines powering the living cell. These nanometre-sized molecules convert chemical energy, both enthalpic and entropic, into useful mechanical work. High resolution single molecule experiments can now observe motor protein movement with increasing precision. The emerging data must be combined with structural and kinetic measurements to develop a quantitative mechanism. This article describes a modelling framework where quantitative understanding of motor behaviour can be developed based on the protein structure. The framework is applied to myosin motors, with emphasis on how synchrony between motor domains give rise to processive unidirectional movement. The modelling approach shows that the elasticity of protein domains are important in regulating motor function. Simple models of protein domain elasticity are presented. The framework can be generalized to other motor systems, or an ensemble of motors such as muscle contraction. Indeed, for hundreds of myosins, our framework can be reduced to the Huxely-Simmons description of muscle movement in the mean-field limit.

Environmentally benign nanometric neem-laced urea emulsion for controlling mosquito population in environment.

PubMed

Mishra, Prabhakar; Samuel, Merlyn Keziah; Reddy, Ruchishya; Tyagi, Brij Kishore; Mukherjee, Amitava; Chandrasekaran, Natarajan

2018-01-01

The increasing risk of vector-borne diseases and the environmental pollution in the day-to-day life due to the usage of the conventional pesticides makes the role of nanotechnology to come into the action. The current study deals with one of the applications of nanotechnology through the formulation of neem urea nanoemulsion (NUNE). NUNE was formulated using neem oil, Tween 20, and urea using the microfluidization method. Prior to the development of nanoemulsion, the ratio of oil/surfactant/urea was optimized using the response surface modeling method. The mean droplet size of the nanoemulsion was found to be 19.3 ± 1.34 nm. The nanoemulsion was found to be stable for the period of 4 days in the field conditions which aids to its mosquitocidal activity. The nanoemulsion exhibited a potent ovicidal and larvicidal activity against A. aegypti and C. tritaeniorhynchus vectors. This result was corroborated with the histopathological analysis of the NUNE-treated larvae. Further, the effect of NUNE on the biochemical profile of the target host was assessed and was found to be efficacious compared to the bulk counterpart. The nanoemulsion was then checked for its biosafety towards the non-target species like plant beneficial bacterium (E. ludwigii), and phytotoxicity was assessed towards the paddy plant (O. sativa). Nanometric emulsion at the concentration used for the mosquitocidal application was found to be potentially safe towards the environment. Therefore, the nanometric neem-laced urea emulsion tends to be an efficient mosquito control agent with an environmentally benign property.

Accounting for intra-molecular vibrational modes in open quantum system description of molecular systems.

PubMed

Roden, Jan; Strunz, Walter T; Whaley, K Birgitta; Eisfeld, Alexander

2012-11-28

Electronic-vibrational dynamics in molecular systems that interact with an environment involve a large number of degrees of freedom and are therefore often described by means of open quantum system approaches. A popular approach is to include only the electronic degrees of freedom into the system part and to couple these to a non-Markovian bath of harmonic vibrational modes that is characterized by a spectral density. Since this bath represents both intra-molecular and external vibrations, it is important to understand how to construct a spectral density that accounts for intra-molecular vibrational modes that couple further to other modes. Here, we address this problem by explicitly incorporating an intra-molecular vibrational mode together with the electronic degrees of freedom into the system part and using the Fano theory for a resonance coupled to a continuum to derive an "effective" bath spectral density, which describes the contribution of intra-molecular modes. We compare this effective model for the intra-molecular mode with the method of pseudomodes, a widely used approach in simulation of non-Markovian dynamics. We clarify the difference between these two approaches and demonstrate that the respective resulting dynamics and optical spectra can be very different.

Some Considerations on the Dynamics of Nanometric Suspensions in Fluid Media

NASA Astrophysics Data System (ADS)

Lungu, Mihai; Neculae, Adrian; Bunoiu, Madalin

2009-05-01

Nano-sized particles received considerable interest in the last decade. The manipulation of nanoparticles is becoming an important issue as they are more and more produced as a result of material synthesis and combustion emission. The nanometric particles represent a very important threat for human health because they can readily enter the human body through inhalation and their toxicity is relatively high due to the large specific surface area. The separation of the nano-sized particles into distinct bands, spatially separated one of each other had also brought recently considerable attention in many scientific areas; the usages of nanoparticles are very promising for the new technologies. The behavior of a suspension of sub-micronic particles under the action of dielectrophoretic force is numerically investigated and a theoretical model is proposed.

Evolutionary grinding model for nanometric control of surface roughness for aspheric optical surfaces.

PubMed

Han, Jeong-Yeol; Kim, Sug-Whan; Han, Inwoo; Kim, Geon-Hee

2008-03-17

A new evolutionary grinding process model has been developed for nanometric control of material removal from an aspheric surface of Zerodur substrate. The model incorporates novel control features such as i) a growing database; ii) an evolving, multi-variable regression equation; and iii) an adaptive correction factor for target surface roughness (Ra) for the next machine run. This process model demonstrated a unique evolutionary controllability of machining performance resulting in the final grinding accuracy (i.e. averaged difference between target and measured surface roughness) of -0.2+/-2.3(sigma) nm Ra over seven trial machine runs for the target surface roughness ranging from 115 nm to 64 nm Ra.

Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

PubMed

Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

2016-03-01

Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

Determination of the thermodynamic correction factor of fluids confined in nano-metric slit pores from molecular simulation

NASA Astrophysics Data System (ADS)

Collell, Julien; Galliero, Guillaume

2014-05-01

The multi-component diffusive mass transport is generally quantified by means of the Maxwell-Stefan diffusion coefficients when using molecular simulations. These coefficients can be related to the Fick diffusion coefficients using the thermodynamic correction factor matrix, which requires to run several simulations to estimate all the elements of the matrix. In a recent work, Schnell et al. ["Thermodynamics of small systems embedded in a reservoir: A detailed analysis of finite size effects," Mol. Phys. 110, 1069-1079 (2012)] developed an approach to determine the full matrix of thermodynamic factors from a single simulation in bulk. This approach relies on finite size effects of small systems on the density fluctuations. We present here an extension of their work for inhomogeneous Lennard Jones fluids confined in slit pores. We first verified this extension by cross validating the results obtained from this approach with the results obtained from the simulated adsorption isotherms, which allows to determine the thermodynamic factor in porous medium. We then studied the effects of the pore width (from 1 to 15 molecular sizes), of the solid-fluid interaction potential (Lennard Jones 9-3, hard wall potential) and of the reduced fluid density (from 0.1 to 0.7 at a reduced temperature T* = 2) on the thermodynamic factor. The deviation of the thermodynamic factor compared to its equivalent bulk value decreases when increasing the pore width and becomes insignificant for reduced pore width above 15. We also found that the thermodynamic factor is sensitive to the magnitude of the fluid-fluid and solid-fluid interactions, which softens or exacerbates the density fluctuations.

Determination of the thermodynamic correction factor of fluids confined in nano-metric slit pores from molecular simulation

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

Collell, Julien; Galliero, Guillaume, E-mail: guillaume.galliero@univ-pau.fr

2014-05-21

The multi-component diffusive mass transport is generally quantified by means of the Maxwell-Stefan diffusion coefficients when using molecular simulations. These coefficients can be related to the Fick diffusion coefficients using the thermodynamic correction factor matrix, which requires to run several simulations to estimate all the elements of the matrix. In a recent work, Schnell et al. [“Thermodynamics of small systems embedded in a reservoir: A detailed analysis of finite size effects,” Mol. Phys. 110, 1069–1079 (2012)] developed an approach to determine the full matrix of thermodynamic factors from a single simulation in bulk. This approach relies on finite size effectsmore » of small systems on the density fluctuations. We present here an extension of their work for inhomogeneous Lennard Jones fluids confined in slit pores. We first verified this extension by cross validating the results obtained from this approach with the results obtained from the simulated adsorption isotherms, which allows to determine the thermodynamic factor in porous medium. We then studied the effects of the pore width (from 1 to 15 molecular sizes), of the solid-fluid interaction potential (Lennard Jones 9-3, hard wall potential) and of the reduced fluid density (from 0.1 to 0.7 at a reduced temperature T* = 2) on the thermodynamic factor. The deviation of the thermodynamic factor compared to its equivalent bulk value decreases when increasing the pore width and becomes insignificant for reduced pore width above 15. We also found that the thermodynamic factor is sensitive to the magnitude of the fluid-fluid and solid-fluid interactions, which softens or exacerbates the density fluctuations.« less

Nanometric depth resolution from multi-focal images in microscopy

PubMed Central

Dalgarno, Heather I. C.; Dalgarno, Paul A.; Dada, Adetunmise C.; Towers, Catherine E.; Gibson, Gavin J.; Parton, Richard M.; Davis, Ilan; Warburton, Richard J.; Greenaway, Alan H.

2011-01-01

We describe a method for tracking the position of small features in three dimensions from images recorded on a standard microscope with an inexpensive attachment between the microscope and the camera. The depth-measurement accuracy of this method is tested experimentally on a wide-field, inverted microscope and is shown to give approximately 8 nm depth resolution, over a specimen depth of approximately 6 µm, when using a 12-bit charge-coupled device (CCD) camera and very bright but unresolved particles. To assess low-flux limitations a theoretical model is used to derive an analytical expression for the minimum variance bound. The approximations used in the analytical treatment are tested using numerical simulations. It is concluded that approximately 14 nm depth resolution is achievable with flux levels available when tracking fluorescent sources in three dimensions in live-cell biology and that the method is suitable for three-dimensional photo-activated localization microscopy resolution. Sub-nanometre resolution could be achieved with photon-counting techniques at high flux levels. PMID:21247948

Study of Effect of Impacting Direction on Abrasive Nanometric Cutting Process with Molecular Dynamics

NASA Astrophysics Data System (ADS)

Li, Junye; Meng, Wenqing; Dong, Kun; Zhang, Xinming; Zhao, Weihong

2018-01-01

Abrasive flow polishing plays an important part in modern ultra-precision machining. Ultrafine particles suspended in the medium of abrasive flow removes the material in nanoscale. In this paper, three-dimensional molecular dynamics (MD) simulations are performed to investigate the effect of impacting direction on abrasive cutting process during abrasive flow polishing. The molecular dynamics simulation software Lammps was used to simulate the cutting of single crystal copper with SiC abrasive grains at different cutting angles (0o-45o). At a constant friction coefficient, we found a direct relation between cutting angle and cutting force, which ultimately increases the number of dislocation during abrasive flow machining. Our theoretical study reveal that a small cutting angle is beneficial for improving surface quality and reducing internal defects in the workpiece. However, there is no obvious relationship between cutting angle and friction coefficient.

Study of Effect of Impacting Direction on Abrasive Nanometric Cutting Process with Molecular Dynamics.

PubMed

Li, Junye; Meng, Wenqing; Dong, Kun; Zhang, Xinming; Zhao, Weihong

2018-01-11

Abrasive flow polishing plays an important part in modern ultra-precision machining. Ultrafine particles suspended in the medium of abrasive flow removes the material in nanoscale. In this paper, three-dimensional molecular dynamics (MD) simulations are performed to investigate the effect of impacting direction on abrasive cutting process during abrasive flow polishing. The molecular dynamics simulation software Lammps was used to simulate the cutting of single crystal copper with SiC abrasive grains at different cutting angles (0 o -45 o ). At a constant friction coefficient, we found a direct relation between cutting angle and cutting force, which ultimately increases the number of dislocation during abrasive flow machining. Our theoretical study reveal that a small cutting angle is beneficial for improving surface quality and reducing internal defects in the workpiece. However, there is no obvious relationship between cutting angle and friction coefficient.

Ultrafast fluorescent decay induced by metal-mediated dipole–dipole interaction in two-dimensional molecular aggregates

DOE PAGES

Hu, Qing; Jin, Dafei; Xiao, Jun; ...

2017-09-05

Two-dimensional molecular aggregate (2DMA), a thin sheet of strongly interacting dipole molecules self-assembled at close distance on an ordered lattice, is a fascinating fluorescent material. It is distinctively different from the conventional (single or colloidal) dye molecules and quantum dots. Here, in this paper, we verify that when a 2DMA is placed at a nanometric distance from a metallic substrate, the strong and coherent interaction between the dipoles inside the 2DMA dominates its fluorescent decay at a picosecond timescale. Our streak-camera lifetime measurement and interacting lattice–dipole calculation reveal that the metal-mediated dipole–dipole interaction shortens the fluorescent lifetime to about one-halfmore » and increases the energy dissipation rate by 10 times that expected from the noninteracting single-dipole picture. In conclusion, our finding can enrich our understanding of nanoscale energy transfer in molecular excitonic systems and may designate a unique direction for developing fast and efficient optoelectronic devices.« less

Synthesis of Nanometric-Sized Barium Titanate Powders Using Acetylacetone as the Chelating Agent in a Sol-Precipitation Process

NASA Astrophysics Data System (ADS)

Hung, Kun Ming; Hsieh, Ching Shieh; Yang, Wein Duo; Tsai, Hui Ju

2007-03-01

Nanometric-sized barium titanate powders were prepared by using titanium isopropoxid as the raw material and acetylacetone as a chelating agent, in a strong alkaline solution (pH > 13) through the sol-precipitation method. The preparatory variables affect the extent of cross-linking in the structure, change the mode of condensation of the gels, and even control the particle size of the powder. The reaction rate of forming powder, at a higher temperature such as 100°C and more water content (the molar ratio of water to titanium isopropoxide is 25) or fewer acetylacetone (the molar ratio of acetylacetone to titanium isopropoxide is 1), is rapid and the particle size formed is finer at 60 80 nm. On the contrary, that of forming powder, at lower temperature (40°C) and less water content (molar ratio of water/titanium isopropoxide = 5) or higher acetylacetone (acetylacetone/titanium isopropoxide = 7), is slow and the particle size of the powder is larger. The optimal preparatory conditions were obtained by using the experimental statistical method; as a result, nanometric-sized BaTiO3 powder with an average particle size of about 50 nm was prepared.

Spearhead Nanometric Field-Effect Transistor Sensors for Single-Cell Analysis.

PubMed

Zhang, Yanjun; Clausmeyer, Jan; Babakinejad, Babak; Córdoba, Ainara López; Ali, Tayyibah; Shevchuk, Andrew; Takahashi, Yasufumi; Novak, Pavel; Edwards, Christopher; Lab, Max; Gopal, Sahana; Chiappini, Ciro; Anand, Uma; Magnani, Luca; Coombes, R Charles; Gorelik, Julia; Matsue, Tomokazu; Schuhmann, Wolfgang; Klenerman, David; Sviderskaya, Elena V; Korchev, Yuri

2016-03-22

Nanometric field-effect-transistor (FET) sensors are made on the tip of spear-shaped dual carbon nanoelectrodes derived from carbon deposition inside double-barrel nanopipettes. The easy fabrication route allows deposition of semiconductors or conducting polymers to comprise the transistor channel. A channel from electrodeposited poly pyrrole (PPy) exhibits high sensitivity toward pH changes. This property is exploited by immobilizing hexokinase on PPy nano-FETs to give rise to a selective ATP biosensor. Extracellular pH and ATP gradients are key biochemical constituents in the microenvironment of living cells; we monitor their real-time changes in relation to cancer cells and cardiomyocytes. The highly localized detection is possible because of the high aspect ratio and the spear-like design of the nano-FET probes. The accurately positioned nano-FET sensors can detect concentration gradients in three-dimensional space, identify biochemical properties of a single living cell, and after cell membrane penetration perform intracellular measurements.

Spearhead Nanometric Field-Effect Transistor Sensors for Single-Cell Analysis

PubMed Central

Córdoba, Ainara López; Ali, Tayyibah; Shevchuk, Andrew; Takahashi, Yasufumi; Novak, Pavel; Edwards, Christopher; Lab, Max; Gopal, Sahana; Chiappini, Ciro; Anand, Uma; Magnani, Luca; Coombes, R. Charles; Gorelik, Julia; Matsue, Tomokazu; Schuhmann, Wolfgang; Klenerman, David; Sviderskaya, Elena V.; Korchev, Yuri

2016-01-01

Nanometric field-effect-transistor (FET) sensors are made on the tip of spear-shaped dual carbon nanoelectrodes derived from carbon deposition inside double-barrel nanopipettes. The easy fabrication route allows deposition of semiconductors or conducting polymers to comprise the transistor channel. A channel from electrodeposited poly pyrrole (PPy) exhibits high sensitivity toward pH changes. This property is exploited by immobilizing hexokinase on PPy nano-FETs to give rise to a selective ATP biosensor. Extracellular pH and ATP gradients are key biochemical constituents in the microenvironment of living cells; we monitor their real-time changes in relation to cancer cells and cardiomyocytes. The highly localized detection is possible because of the high aspect ratio and the spear-like design of the nano-FET probes. The accurately positioned nano-FET sensors can detect concentration gradients in three-dimensional space, identify biochemical properties of a single living cell, and after cell membrane penetration perform intracellular measurements. PMID:26816294

Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging

PubMed Central

Jayasinghe, Isuru D.; Munro, Michelle; Baddeley, David; Launikonis, Bradley S.; Soeller, Christian

2014-01-01

Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. PMID:25100314

In-depth analysis and modelling of self-heating effects in nanometric DGMOSFETs

NASA Astrophysics Data System (ADS)

Roldán, J. B.; González, B.; Iñiguez, B.; Roldán, A. M.; Lázaro, A.; Cerdeira, A.

2013-01-01

Self-heating effects (SHEs) in nanometric symmetrical double-gate MOSFETs (DGMOSFETs) have been analysed. An equivalent thermal circuit for the transistors has been developed to characterise thermal effects, where the temperature and thickness dependency of the thermal conductivity of the silicon and oxide layers within the devices has been included. The equivalent thermal circuit is consistent with simulations using a commercial technology computer-aided design (TCAD) tool (Sentaurus by Synopsys). In addition, a model for DGMOSFETs has been developed where SHEs have been considered in detail, taking into account the temperature dependence of the low-field mobility, saturation velocity, and inversion charge. The model correctly reproduces Sentaurus simulation data for the typical bias range used in integrated circuits. Lattice temperatures predicted by simulation are coherently reproduced by the model for varying silicon layer geometry.

Synthesis and characterization of nanometric magnetite coated by oleic acid and the surfactant CTAB. Surfactant coated nanometric magnetite/maghemite

NASA Astrophysics Data System (ADS)

Celis, J. Almazán; Olea Mejía, O. F.; Cabral-Prieto, A.; García-Sosa, I.; Derat-Escudero, R.; Baggio Saitovitch, E. M.; Alzamora Camarena, M.

2017-11-01

Nanometric magnetite ( nm-Fe3O4) particles were prepared by the reverse co-precipitation synthesis method, obtaining particle sizes that ranged from 4 to 8.5 nm. In their synthesis, the concentration of iron salts of ferric nitrate, Fe(NO3)3ṡ9H2O, and ferrous sulfate, FeSO4ṡ7H2O, were varied relative to the chemical reaction volume and by using different surfactants such as oleic acid (OA) and hexadecyltrimethylammonium bromide (CTAB). The nm-Fe3O4 particles were characterized by transmission electron microscopy (TEM), Mössbauer spectroscopy (MS), magnetic and X-ray diffraction (XRD) measurements. Typical asymmetrical and/or broad lines shapes appeared in all Mössbauer spectra of the as prepared samples suggesting strong magnetic inter-particle interactions, reducing these interactions to some extent by gentle mechanical grinding. For the smallest particles, maghemite instead of magnetite was the main preparation product as low temperature Mössbauer and magnetic measurements indicated. For the intermediate and largest particles a mixture of magnetite and maghemite phases were produced as the saturation magnetization values of MS ˜ 60 emu/g indicated; these values were measured for most samples, independently of the coating surfactant concentration, and according to the ZFC-FC curves the blocking temperatures were 225K and 275K for the smallest and largest magnetite nanoparticles, respectively. The synthesis method was highly reproducible.

Alignment hierarchies: engineering architecture from the nanometre to the micrometre scale.

PubMed

Kureshi, Alvena; Cheema, Umber; Alekseeva, Tijna; Cambrey, Alison; Brown, Robert

2010-12-06

Natural tissues are built of metabolites, soluble proteins and solid extracellular matrix components (largely fibrils) together with cells. These are configured in highly organized hierarchies of structure across length scales from nanometre to millimetre, with alignments that are dominated by anisotropies in their fibrillar matrix. If we are to successfully engineer tissues, these hierarchies need to be mimicked with an understanding of the interaction between them. In particular, the movement of different elements of the tissue (e.g. molecules, cells and bulk fluids) is controlled by matrix structures at distinct scales. We present three novel systems to introduce alignment of collagen fibrils, cells and growth factor gradients within a three-dimensional collagen scaffold using fluid flow, embossing and layering of construct. Importantly, these can be seen as different parts of the same hierarchy of three-dimensional structure, as they are all formed into dense collagen gels. Fluid flow aligns collagen fibrils at the nanoscale, embossed topographical features provide alignment cues at the microscale and introducing layered configuration to three-dimensional collagen scaffolds provides microscale- and mesoscale-aligned pathways for protein factor delivery as well as barriers to confine protein diffusion to specific spatial directions. These seemingly separate methods can be employed to increase complexity of simple extracellular matrix scaffolds, providing insight into new approaches to directly fabricate complex physical and chemical cues at different hierarchical scales, similar to those in natural tissues.

Agent-Based Modeling in Molecular Systems Biology.

PubMed

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-07-01

Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

Chopped molecular beam multiplexing system

NASA Technical Reports Server (NTRS)

Adams, Billy R. (Inventor)

1986-01-01

The integration of a chopped molecular beam mass spectrometer with a time multiplexing system is described. The chopping of the molecular beam is synchronized with the time intervals by a phase detector and a synchronous motor. Arithmetic means are generated for phase shifting the chopper with respect to the multiplexer. A four channel amplifier provides the capacity to independently vary the baseline and amplitude in each channel of the multiplexing system.

Enrichment of ODMR-active nitrogen-vacancy centres in five-nanometre-sized detonation-synthesized nanodiamonds: Nanoprobes for temperature, angle and position.

PubMed

Sotoma, Shingo; Terada, Daiki; Segawa, Takuya F; Igarashi, Ryuji; Harada, Yoshie; Shirakawa, Masahiro

2018-04-03

The development of sensors to estimate physical properties, and their temporal and spatial variation, has been a central driving force in scientific breakthroughs. In recent years, nanosensors based on quantum measurements, such as nitrogen-vacancy centres (NVCs) in nanodiamonds, have been attracting much attention as ultrastable, sensitive, accurate and versatile physical sensors for quantitative cellular measurements. However, the nanodiamonds currently available for use as sensors have diameters of several tens of nanometres, much larger than the usual size of a protein. Therefore, their actual applications remain limited. Here we show that NVCs in an aggregation of 5-nm-sized detonation-synthesized nanodiamond treated by Krüger's surface reduction (termed DND-OH) retains the same characteristics as observed in larger diamonds. We show that the negative charge at the NVC are stabilized, have a relatively long T 2 spin relaxation time of up to 4 μs, and are applicable to thermosensing, one-degree orientation determination and nanometric super-resolution imaging. Our results clearly demonstrate the significant potential of DND-OH as a physical sensor. Thus, DND-OH will raise new possibilities for spatiotemporal monitoring of live cells and dynamic biomolecules in individual cells at single-molecule resolution.

Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging.

PubMed

Jayasinghe, Isuru D; Munro, Michelle; Baddeley, David; Launikonis, Bradley S; Soeller, Christian

2014-10-06

Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres in the molecular organization of ryanodine receptors (RyRs; the primary calcium release channels) within triads. With the improved resolution offered by dSTORM, abutting arrays of RyRs in transverse view of fast fibres were observed in contrast to the fragmented distribution on slow-twitch muscle that were approximately 1.8 times shorter and consisted of approximately 1.6 times fewer receptors. To the best of our knowledge, for the first time, we have quantified the nanometre-scale spatial association between triadic proteins using multi-colour super-resolution, an analysis difficult to conduct with electron microscopy. Our findings confirm that junctophilin-1 (JPH1), which tethers the sarcoplasmic reticulum ((SR) intracellular calcium store) to the tubular (t-) system at triads, was present throughout the RyR array, whereas JPH2 was contained within much smaller nanodomains. Similar imaging of the primary SR calcium buffer, calsequestrin (CSQ), detected less overlap of the triad with CSQ in slow-twitch muscle supporting greater spatial heterogeneity in the luminal Ca2+ buffering when compared with fast twitch muscle. Taken together, these nanoscale differences can explain the fundamentally different physiologies of fast- and slow-twitch muscle. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Uranium(III)-carbon multiple bonding supported by arene δ-bonding in mixed-valence hexauranium nanometre-scale rings.

PubMed

Wooles, Ashley J; Mills, David P; Tuna, Floriana; McInnes, Eric J L; Law, Gareth T W; Fuller, Adam J; Kremer, Felipe; Ridgway, Mark; Lewis, William; Gagliardi, Laura; Vlaisavljevich, Bess; Liddle, Stephen T

2018-05-29

Despite the fact that non-aqueous uranium chemistry is over 60 years old, most polarised-covalent uranium-element multiple bonds involve formal uranium oxidation states IV, V, and VI. The paucity of uranium(III) congeners is because, in common with metal-ligand multiple bonding generally, such linkages involve strongly donating, charge-loaded ligands that bind best to electron-poor metals and inherently promote disproportionation of uranium(III). Here, we report the synthesis of hexauranium-methanediide nanometre-scale rings. Combined experimental and computational studies suggest overall the presence of formal uranium(III) and (IV) ions, though electron delocalisation in this Kramers system cannot be definitively ruled out, and the resulting polarised-covalent U = C bonds are supported by iodide and δ-bonded arene bridges. The arenes provide reservoirs that accommodate charge, thus avoiding inter-electronic repulsion that would destabilise these low oxidation state metal-ligand multiple bonds. Using arenes as electronic buffers could constitute a general synthetic strategy by which to stabilise otherwise inherently unstable metal-ligand linkages.

Ab initio potential-energy surfaces for complex, multichannel systems using modified novelty sampling and feedforward neural networks

NASA Astrophysics Data System (ADS)

Raff, L. M.; Malshe, M.; Hagan, M.; Doughan, D. I.; Rockley, M. G.; Komanduri, R.

2005-02-01

A neural network/trajectory approach is presented for the development of accurate potential-energy hypersurfaces that can be utilized to conduct ab initio molecular dynamics (AIMD) and Monte Carlo studies of gas-phase chemical reactions, nanometric cutting, and nanotribology, and of a variety of mechanical properties of importance in potential microelectromechanical systems applications. The method is sufficiently robust that it can be applied to a wide range of polyatomic systems. The overall method integrates ab initio electronic structure calculations with importance sampling techniques that permit the critical regions of configuration space to be determined. The computed ab initio energies and gradients are then accurately interpolated using neural networks (NN) rather than arbitrary parametrized analytical functional forms, moving interpolation or least-squares methods. The sampling method involves a tight integration of molecular dynamics calculations with neural networks that employ early stopping and regularization procedures to improve network performance and test for convergence. The procedure can be initiated using an empirical potential surface or direct dynamics. The accuracy and interpolation power of the method has been tested for two cases, the global potential surface for vinyl bromide undergoing unimolecular decomposition via four different reaction channels and nanometric cutting of silicon. The results show that the sampling methods permit the important regions of configuration space to be easily and rapidly identified, that convergence of the NN fit to the ab initio electronic structure database can be easily monitored, and that the interpolation accuracy of the NN fits is excellent, even for systems involving five atoms or more. The method permits a substantial computational speed and accuracy advantage over existing methods, is robust, and relatively easy to implement.

K-Ar dating and delta O-18-delta D characterization of nanometric illite from Ordovician K-bentonites of the Appalachians: illitization and the Acadian-Alleghenian tectonic activity

USGS Publications Warehouse

Clauer, Norbert; Fallick, Anthony E.; Eberl, Dennis D.; Honty, Miroslav; Huff, Warren D.; Auberti, Amelie

2013-01-01

Nanometric (2 diagram that illitization occurred in all fractions by simultaneous nucleation and crystal growth, except for one sample. In that sample, a period of growth without nucleation was detected on top of the nucleation and growth episode. The K-Ar ages organize into two isochrons, the first at 319.9 ± 2.0 Ma with an initial 40Ar/36Ar ratio of 271 ± 66 Ma, and the second at 284.9 ± 1.2 Ma with an initial 40Ar/36Ar ratio of 310 ± 44. One data point above the older isochron and three between the two isochrons suggest a detrital contamination for the former separate and a possible further generation of nanoparticles for the three others. The samples with the older crystallization age consist of illite and illite-rich mixed-layers, and those with the younger age contain smectite-rich mixed-layers without illite, or illite-enriched illite-smectite mixed-layers. The K-Ar ages fit the age trends published previously for similar K-bentonites with regional age patterns between 240 and 270 Ma in the southwestern region, between 270 and 300 Ma in the central zone and the southern Appalachians, and between 315 and 370 Ma in the northernmost. Each of the two generations of illite crystals yields very consistent δ18O (V-SMOW) values at 17 ± 1‰ for the older and at 21 ± 1‰ for the younger. If crystallization temperatures of the nanometric illite were between 100 and 200 °C, as suggested by microthermometric determinations, the hydrothermal fluids had δ18O values of 4 ± 1‰ in the Dalton district and of 8 ± 1‰ in the Lafayette, Trenton, and Dirtseller districts at 100 °C, and of 11 ± 1 and 15 ± 1‰ in the same locations at 200 °C, probably because the water-rock isotope exchanges at elevated temperature occurred in rock-dominated systems. The δ18O of the fluids remained unchanged during local crystal growth, but varied depending on the geographic location of the samples and timing of illitization. The δD (V-SMOW) values of the different size

Biologically-Mediated Weathering of Minerals From Nanometre Scale to Environmental Systems

NASA Astrophysics Data System (ADS)

Brown, D. J.; Banwart, S. A.; Smits, M. M.; Leake, J. R.; Bonneville, S.; Benning, L. G.; Haward, S. J.; Ragnarsdottir, K.

2007-12-01

The Weathering Science Consortium is a multi-disciplinary project that aims to create a step change in understanding how biota control mineral weathering and soil formation (http://www.wun.ac.uk/wsc). Our hypothesis is that rates of biotic weathering are driven by the energy supply from plants to the organisms, controlling their biomass, surface area of contact with minerals and their capacity to interact chemically with minerals. Symbiotic fungal mycorrhiza of 90% of plant species are empowered with an available carbohydrate supply from plants that is unparalleled amongst soil microbes. They develop extensive mycelial networks that intimately contact minerals, which they weather aggressively. We hypothesise that mycorrhiza play a critical role through their focussing of photosynthate energy from plants into sub-surface weathering environments. Our work identifies how these fungal cells, and their secretions, interact with mineral surfaces and affect the rates of nutrient transfer from minerals to the organism. Investigating these living systems allows us to create new concepts and mathematical models that can describe biological weathering and be used in computer simulations of soil weathering dynamics. We are studying these biochemical interactions at 3 levels of observation: 1. At the molecular scale to understand interactions between living cells and minerals and to quantify the chemistry that breaks down the mineral structure; 2. At the soil grain scale to quantify the activity and spatial distribution of the fungi, roots and other organisms (e.g. bacteria) and their effects on the rates at which minerals are dissolved to release nutrients; 3. At soil profile scale to test models for the spatial distribution of active fungi and carbon energy and their seasonal variability and impact on mineral dissolution rates. Here we present early results from molecular and soil grain scale experiments. We have grown pure culture (Suillus bovinus, Paxillus involutus

Mixed matrix formulations with MOF molecular sieving for key energy-intensive separations

NASA Astrophysics Data System (ADS)

Liu, Gongping; Chernikova, Valeriya; Liu, Yang; Zhang, Kuang; Belmabkhout, Youssef; Shekhah, Osama; Zhang, Chen; Yi, Shouliang; Eddaoudi, Mohamed; Koros, William J.

2018-03-01

Membrane-based separations can improve energy efficiency and reduce the environmental impacts associated with traditional approaches. Nevertheless, many challenges must be overcome to design membranes that can replace conventional gas separation processes. Here, we report on the incorporation of engineered submicrometre-sized metal-organic framework (MOF) crystals into polymers to form hybrid materials that successfully translate the excellent molecular sieving properties of face-centred cubic (fcu)-MOFs into the resultant membranes. We demonstrate, simultaneously, exceptionally enhanced separation performance in hybrid membranes for two challenging and economically important applications: the removal of CO2 and H2S from natural gas and the separation of butane isomers. Notably, the membrane molecular sieving properties demonstrate that the deliberately regulated and contracted MOF pore-aperture size can discriminate between molecular pairs. The improved performance results from precise control of the linkers delimiting the triangular window, which is the sole entrance to the fcu-MOF pore. This rational-design hybrid approach provides a general toolbox for enhancing the transport properties of advanced membranes bearing molecular sieve fillers with sub-nanometre-sized pore-apertures.

Nanometre-scale 3D defects in Cr2AlC thin films.

PubMed

Chen, Y T; Music, D; Shang, L; Mayer, J; Schneider, J M

2017-04-20

MAX-phase Cr 2 AlC containing thin films were synthesized by magnetron sputtering in an industrial system. Nanometre-scale 3D defects are observed near the boundary between regions of Cr 2 AlC and of the disordered solid solution (CrAl) x C y . Shrinkage of the Cr-Cr interplanar distance and elongation of the Cr-Al distance in the vicinity of the defects are detected using transmission electron microscopy. The here observed deformation surrounding the defects was described using density functional theory by comparing the DOS of bulk Cr 2 AlC with the DOS of a strained and unstrained Cr 2 AlC(0001) surface. From the partial density of states analysis, it can be learned that Cr-C bonds are stronger than Cr-Al bonds in bulk Cr 2 AlC. Upon Cr 2 AlC(0001) surface formation, both bonds are weakened. While the Cr-C bonds recover their bulk strength as Cr 2 AlC(0001) is strained, the Cr-Al bonds experience only a partial recovery, still being weaker than their bulk counterparts. Hence, the strain induced bond strengthening in Cr 2 AlC(0001) is larger for Cr d - C p bonds than for Cr d - Al p bonds. The here observed changes in bonding due to the formation of a strained surface are consistent with the experimentally observed elongation of the Cr-Al distance in the vicinity of nm-scale 3D defects in Cr 2 AlC thin films.

Tracking of fluorescence nanoparticles with nanometre resolution in a biological system: assessing local viscosity and microrheology.

PubMed

Marki, Alex; Ermilov, Eugeny; Zakrzewicz, Andreas; Koller, Akos; Secomb, Timothy W; Pries, Axel R

2014-04-01

The aim of the study was to establish a user-friendly approach for single fluorescence particle 3D localization and tracking with nanometre precision in a standard fluorescence microscope using a point spread function (PSF) approach, and to evaluate validity and precision for different analysis methods and optical conditions with particular application to microcirculatory flow dynamics and cell biology. Images of fluorescent particles were obtained with a standard fluorescence microscope equipped with a piezo positioner for the objective. Whole pattern (WP) comparison with a PSF recorded for the specific set-up and measurement of the outermost ring radius (ORR) were used for analysis. Images of fluorescent particles were recorded over a large range (about 7μm) of vertical positions, with and without distortion by overlapping particles as well as in the presence of cultured endothelial cells. For a vertical range of 6.5μm the standard deviation (SD) from the predicted value, indicating validity, was 9.3/8.7 nm (WP/ORR) in the vertical and 8.2/11.7 nm in the horizontal direction. The precision, determined by repeated measurements, was 5.1/3.8 nm in the vertical and 2.9/3.7 nm in the horizontal direction. WP was more robust with respect to underexposure or overlapping images. On the surface of cultured endothelial cells, a layer with 2.5 times increased viscosity and a thickness of about 0.8μm was detected. With a validity in the range of 10 nm and a precision down to about 3-5 nm obtained by standard fluorescent microscopy, the PSF approach offers a valuable tool for a variety of experimental investigations of particle localizations, including the assessment of endothelial cell microenvironment.

Thermal Effusivity Determination of Metallic Films of Nanometric Thickness by the Electrical Micropulse Method

NASA Astrophysics Data System (ADS)

Lugo, J. M.; Oliva, A. I.

2017-02-01

The thermal effusivity of gold, aluminum, and copper thin films of nanometric thickness (20 nm to 200 nm) was investigated in terms of the films' thickness. The metallic thin films were deposited onto glass substrates by thermal evaporation, and the thermal effusivity was estimated by using experimental parameters such as the specific heat, thermal conductivity, and thermal diffusivity values obtained at room conditions. The specific heat, thermal conductivity, and thermal diffusivity values of the metallic thin films are determined with a methodology based on the behavior of the thermal profiles of the films when electrical pulses of few microseconds are applied at room conditions. For all the investigated materials, the thermal effusivity decreases with decreased thickness. The thermal effusivity values estimated by the presented methodology are consistent with other reported values obtained under vacuum conditions and more elaborated methodologies.

Conformational Transitions in Molecular Systems

NASA Astrophysics Data System (ADS)

Bachmann, M.; Janke, W.

2008-11-01

Proteins are the "work horses" in biological systems. In almost all functions specific proteins are involved. They control molecular transport processes, stabilize the cell structure, enzymatically catalyze chemical reactions; others act as molecular motors in the complex machinery of molecular synthetization processes. Due to their significance, misfolds and malfunctions of proteins typically entail disastrous diseases, such as Alzheimer's disease and bovine spongiform encephalopathy (BSE). Therefore, the understanding of the trinity of amino acid composition, geometric structure, and biological function is one of the most essential challenges for the natural sciences. Here, we glance at conformational transitions accompanying the structure formation in protein folding processes.

Measuring nanometre-scale electric fields in scanning transmission electron microscopy using segmented detectors.

PubMed

Brown, H G; Shibata, N; Sasaki, H; Petersen, T C; Paganin, D M; Morgan, M J; Findlay, S D

2017-11-01

Electric field mapping using segmented detectors in the scanning transmission electron microscope has recently been achieved at the nanometre scale. However, converting these results to quantitative field measurements involves assumptions whose validity is unclear for thick specimens. We consider three approaches to quantitative reconstruction of the projected electric potential using segmented detectors: a segmented detector approximation to differential phase contrast and two variants on ptychographical reconstruction. Limitations to these approaches are also studied, particularly errors arising from detector segment size, inelastic scattering, and non-periodic boundary conditions. A simple calibration experiment is described which corrects the differential phase contrast reconstruction to give reliable quantitative results despite the finite detector segment size and the effects of plasmon scattering in thick specimens. A plasmon scattering correction to the segmented detector ptychography approaches is also given. Avoiding the imposition of periodic boundary conditions on the reconstructed projected electric potential leads to more realistic reconstructions. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct evidence for coastal iodine particles from Laminaria macroalgae - linkage to emissions of molecular iodine

NASA Astrophysics Data System (ADS)

McFiggans, G.; Coe, H.; Burgess, R.; Allan, J.; Cubison, M.; Alfarra, M. R.; Saunders, R.; Saiz-Lopez, A.; Plane, J. M. C.; Wevill, D.; Carpenter, L.; Rickard, A. R.; Monks, P. S.

2004-05-01

Renewal of ultrafine aerosols in the marine boundary layer may lead to repopulation of the marine distribution and ultimately determine the concentration of cloud condensation nuclei (CCN). Thus the formation of nanometre-scale particles can lead to enhanced scattering of incoming radiation and a net cooling of the atmosphere. The recent demonstration of the chamber formation of new particles from the photolytic production of condensable iodine-containing compounds from diiodomethane (CH2I2), (O'Dowd et al., 2002; Kolb, 2002; Jimenez et al., 2003a; Burkholder and Ravishankara, 2003), provides an additional mechanism to the gas-to-particle conversion of sulphuric acid formed in the photo-oxidation of dimethylsulphide for marine aerosol repopulation. CH2I2 is emitted from seaweeds (Carpenter et al., 1999, 2000) and has been suggested as an initiator of particle formation. We demonstrate here for the first time that ultrafine iodine-containing particles are produced by intertidal macroalgae exposed to ambient levels of ozone. The particle composition is very similar both to those formed in the chamber photo-oxidation of diiodomethane and in the oxidation of molecular iodine by ozone. The particles formed in all three systems are similarly aspherical. When small, those formed in the molecular iodine system swell only moderately when exposed to increased humidity environments, and swell progressively less with increasing size; this behaviour occurs whether they are formed in dry or humid environments, in contrast to those in the CH2I2 system. Direct coastal boundary layer observations of molecular iodine, ultrafine particle production and iodocarbons are reported. Using a newly measured molecular iodine photolysis rate, it is shown that, if atomic iodine is involved in the observed particle bursts, it is of the order of at least 1000 times more likely to result from molecular iodine photolysis than diiodomethane photolysis. A hypothesis for molecular iodine release from

A Molecular atlas of Xenopus respiratory system development.

PubMed

Rankin, Scott A; Thi Tran, Hong; Wlizla, Marcin; Mancini, Pamela; Shifley, Emily T; Bloor, Sean D; Han, Lu; Vleminckx, Kris; Wert, Susan E; Zorn, Aaron M

2015-01-01

Respiratory system development is regulated by a complex series of endoderm-mesoderm interactions that are not fully understood. Recently Xenopus has emerged as an alternative model to investigate early respiratory system development, but the extent to which the morphogenesis and molecular pathways involved are conserved between Xenopus and mammals has not been systematically documented. In this study, we provide a histological and molecular atlas of Xenopus respiratory system development, focusing on Nkx2.1+ respiratory cell fate specification in the developing foregut. We document the expression patterns of Wnt/β-catenin, fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) signaling components in the foregut and show that the molecular mechanisms of respiratory lineage induction are remarkably conserved between Xenopus and mice. Finally, using several functional experiments we refine the epistatic relationships among FGF, Wnt, and BMP signaling in early Xenopus respiratory system development. We demonstrate that Xenopus trachea and lung development, before metamorphosis, is comparable at the cellular and molecular levels to embryonic stages of mouse respiratory system development between embryonic days 8.5 and 10.5. This molecular atlas provides a fundamental starting point for further studies using Xenopus as a model to define the conserved genetic programs controlling early respiratory system development. © 2014 Wiley Periodicals, Inc.

Sub-nanometre resolution imaging of polymer–fullerene photovoltaic blends using energy-filtered scanning electron microscopy

PubMed Central

Masters, Robert C.; Pearson, Andrew J.; Glen, Tom S.; Sasam, Fabian-Cyril; Li, Letian; Dapor, Maurizio; Donald, Athene M.; Lidzey, David G.; Rodenburg, Cornelia

2015-01-01

The resolution capability of the scanning electron microscope has increased immensely in recent years, and is now within the sub-nanometre range, at least for inorganic materials. An equivalent advance has not yet been achieved for imaging the morphologies of nanostructured organic materials, such as organic photovoltaic blends. Here we show that energy-selective secondary electron detection can be used to obtain high-contrast, material-specific images of an organic photovoltaic blend. We also find that we can differentiate mixed phases from pure material phases in our data. The lateral resolution demonstrated is twice that previously reported from secondary electron imaging. Our results suggest that our energy-filtered scanning electron microscopy approach will be able to make major inroads into the understanding of complex, nano-structured organic materials. PMID:25906738

Sub-nanometre resolution imaging of polymer-fullerene photovoltaic blends using energy-filtered scanning electron microscopy.

PubMed

Masters, Robert C; Pearson, Andrew J; Glen, Tom S; Sasam, Fabian-Cyril; Li, Letian; Dapor, Maurizio; Donald, Athene M; Lidzey, David G; Rodenburg, Cornelia

2015-04-24

The resolution capability of the scanning electron microscope has increased immensely in recent years, and is now within the sub-nanometre range, at least for inorganic materials. An equivalent advance has not yet been achieved for imaging the morphologies of nanostructured organic materials, such as organic photovoltaic blends. Here we show that energy-selective secondary electron detection can be used to obtain high-contrast, material-specific images of an organic photovoltaic blend. We also find that we can differentiate mixed phases from pure material phases in our data. The lateral resolution demonstrated is twice that previously reported from secondary electron imaging. Our results suggest that our energy-filtered scanning electron microscopy approach will be able to make major inroads into the understanding of complex, nano-structured organic materials.

Study on the dielectric properties of Al2O3/TiO2 sub-nanometric laminates: effect of the bottom electrode and the total thickness

NASA Astrophysics Data System (ADS)

Ben Elbahri, M.; Kahouli, A.; Mercey, B.; Lebedev, O.; Donner, W.; Lüders, U.

2018-02-01

Dielectrics based on amorphous sub-nanometric laminates of TiO2 and Al2O3 are subject to elevated dielectric losses and leakage currents, in large parts due to the extremely thin individual layer thickness chosen for the creation of the Maxwell-Wagner relaxation and therefore the high apparent dielectric constants. The optimization of performances of the laminate itself being strongly limited by this contradiction concerning its internal structure, we will show in this study that modifications of the dielectric stack of capacitors based on these sub-nanometric laminates can positively influence the dielectric losses and the leakage, as for example the nature of the electrodes, the introduction of thick insulating layers at the laminate/electrode interfaces and the modification of the total laminate thickness. The optimization of the dielectric stack leads to the demonstration of a capacitor with an apparent dielectric constant of 90, combined with low dielectric loss (tan δ) of 7 · 10-2 and with leakage currents smaller than 1  ×  10-6 A cm-2 at 10 MV m-1.

High sensitivity optical molecular imaging system

NASA Astrophysics Data System (ADS)

An, Yu; Yuan, Gao; Huang, Chao; Jiang, Shixin; Zhang, Peng; Wang, Kun; Tian, Jie

2018-02-01

Optical Molecular Imaging (OMI) has the advantages of high sensitivity, low cost and ease of use. By labeling the regions of interest with fluorescent or bioluminescence probes, OMI can noninvasively obtain the distribution of the probes in vivo, which play the key role in cancer research, pharmacokinetics and other biological studies. In preclinical and clinical application, the image depth, resolution and sensitivity are the key factors for researchers to use OMI. In this paper, we report a high sensitivity optical molecular imaging system developed by our group, which can improve the imaging depth in phantom to nearly 5cm, high resolution at 2cm depth, and high image sensitivity. To validate the performance of the system, special designed phantom experiments and weak light detection experiment were implemented. The results shows that cooperated with high performance electron-multiplying charge coupled device (EMCCD) camera, precision design of light path system and high efficient image techniques, our OMI system can simultaneously collect the light-emitted signals generated by fluorescence molecular imaging, bioluminescence imaging, Cherenkov luminance and other optical imaging modality, and observe the internal distribution of light-emitting agents fast and accurately.

Electrochemical behaviour of naked sub-nanometre sized copper clusters and effect of CO 2

DOE PAGES

Passalacqua, Rosalba; Parathoner, Siglinda; Centi, Gabriele; ...

2016-08-04

The study of the electrochemical behavior (in the presence of N 2 or CO 2) of size-controlled naked Cu 5 and Cu 20 nanoclusters, prepared using a combination of gas-phase cluster ion sources, mass spectrometry, and soft-landing techniques, evidences some relevant results regarding the redox behavior of these sub-nanometre sized copper particles and the effect of CO 2 on them. Cu 20 nanoclusters show anodic redox processes occurring at much lower potential with respect to Cu 5 nanoclusters, which behave relatively similar to much larger Cu particles. However, Cu 5 nanoclusters coordinate effectively CO 2 (hydrogen carbonate) in solution, differentmore » from Cu 20 nanoclusters and larger Cu particles. This effect, rather than the redox behavior, is apparently connected to the ability of Cu 5 nanoclusters to reduce CO 2 under cathodic conditions at low overpotential. In conclusion, although preliminary, these results provide rather exciting indications on the possibility of realizing low overpotential electrocatalytic conversion of CO 2.« less

Electrochemical behaviour of naked sub-nanometre sized copper clusters and effect of CO 2

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

Passalacqua, Rosalba; Parathoner, Siglinda; Centi, Gabriele

The study of the electrochemical behavior (in the presence of N 2 or CO 2) of size-controlled naked Cu 5 and Cu 20 nanoclusters, prepared using a combination of gas-phase cluster ion sources, mass spectrometry, and soft-landing techniques, evidences some relevant results regarding the redox behavior of these sub-nanometre sized copper particles and the effect of CO 2 on them. Cu 20 nanoclusters show anodic redox processes occurring at much lower potential with respect to Cu 5 nanoclusters, which behave relatively similar to much larger Cu particles. However, Cu 5 nanoclusters coordinate effectively CO 2 (hydrogen carbonate) in solution, differentmore » from Cu 20 nanoclusters and larger Cu particles. This effect, rather than the redox behavior, is apparently connected to the ability of Cu 5 nanoclusters to reduce CO 2 under cathodic conditions at low overpotential. In conclusion, although preliminary, these results provide rather exciting indications on the possibility of realizing low overpotential electrocatalytic conversion of CO 2.« less

Top-down fabrication of sub-nanometre semiconducting nanoribbons derived from molybdenum disulfide sheets.

PubMed

Liu, Xiaofei; Xu, Tao; Wu, Xing; Zhang, Zhuhua; Yu, Jin; Qiu, Hao; Hong, Jin-Hua; Jin, Chuan-Hong; Li, Ji-Xue; Wang, Xin-Ran; Sun, Li-Tao; Guo, Wanlin

2013-01-01

Developments in semiconductor technology are propelling the dimensions of devices down to 10 nm, but facing great challenges in manufacture at the sub-10 nm scale. Nanotechnology can fabricate nanoribbons from two-dimensional atomic crystals, such as graphene, with widths below the 10 nm threshold, but their geometries and properties have been hard to control at this scale. Here we find that robust ultrafine molybdenum-sulfide ribbons with a uniform width of 0.35 nm can be widely formed between holes created in a MoS2 sheet under electron irradiation. In situ high-resolution transmission electron microscope characterization, combined with first-principles calculations, identifies the sub-1 nm ribbon as a Mo5S4 crystal derived from MoS2, through a spontaneous phase transition. Further first-principles investigations show that the Mo5S4 ribbon has a band gap of 0.77 eV, a Young's modulus of 300GPa and can demonstrate 9% tensile strain before fracture. The results show a novel top-down route for controllable fabrication of functional building blocks for sub-nanometre electronics.

DESIGN NOTE: From nanometre to millimetre: a feasibility study of the combination of scanning probe microscopy and combined optical and x-ray interferometry

NASA Astrophysics Data System (ADS)

Yacoot, Andrew; Koenders, Ludger

2003-09-01

This feasibility study investigates the potential combination of an x-ray interferometer and optical interferometer as a one-dimensional long range high resolution scanning stage for an atomic force microscope (AFM) in order to overcome the problems of non-linearity associated with conventional AFMs and interferometers. Preliminary results of measurements of the uniformity of the period of a grating used as a transfer standards show variations in period at the nanometre level.

Diffusion-controlled interface kinetics-inclusive system-theoretic propagation models for molecular communication systems

NASA Astrophysics Data System (ADS)

Chude-Okonkwo, Uche A. K.; Malekian, Reza; Maharaj, B. T.

2015-12-01

Inspired by biological systems, molecular communication has been proposed as a new communication paradigm that uses biochemical signals to transfer information from one nano device to another over a short distance. The biochemical nature of the information transfer process implies that for molecular communication purposes, the development of molecular channel models should take into consideration diffusion phenomenon as well as the physical/biochemical kinetic possibilities of the process. The physical and biochemical kinetics arise at the interfaces between the diffusion channel and the transmitter/receiver units. These interfaces are herein termed molecular antennas. In this paper, we present the deterministic propagation model of the molecular communication between an immobilized nanotransmitter and nanoreceiver, where the emission and reception kinetics are taken into consideration. Specifically, we derived closed-form system-theoretic models and expressions for configurations that represent different communication systems based on the type of molecular antennas used. The antennas considered are the nanopores at the transmitter and the surface receptor proteins/enzymes at the receiver. The developed models are simulated to show the influence of parameters such as the receiver radius, surface receptor protein/enzyme concentration, and various reaction rate constants. Results show that the effective receiver surface area and the rate constants are important to the system's output performance. Assuming high rate of catalysis, the analysis of the frequency behavior of the developed propagation channels in the form of transfer functions shows significant difference introduce by the inclusion of the molecular antennas into the diffusion-only model. It is also shown that for t > > 0 and with the information molecules' concentration greater than the Michaelis-Menten kinetic constant of the systems, the inclusion of surface receptors proteins and enzymes in the models

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System

PubMed Central

Okaty, Benjamin W.; Freret, Morgan E.; Rood, Benjamin D.; Brust, Rachael D.; Hennessy, Morgan L.; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N.; Dymecki, Susan M.

2016-01-01

Summary Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-Seq to deconstruct the mouse 5HT system at multiple levels of granularity—from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal: principles underlying system organization, novel 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers new subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. PMID:26549332

Molecular-beam gas-sampling system

NASA Technical Reports Server (NTRS)

Young, W. S.; Knuth, E. L.

1972-01-01

A molecular beam mass spectrometer system for rocket motor combustion chamber sampling is described. The history of the sampling system is reviewed. The problems associated with rocket motor combustion chamber sampling are reported. Several design equations are presented. The results of the experiments include the effects of cooling water flow rates, the optimum separation gap between the end plate and sampling nozzle, and preliminary data on compositions in a rocket motor combustion chamber.

Molecular Spintronics: Theory of Spin-Dependent Electron Transport in Fe/BDT/Fe Molecular Wire Systems

NASA Astrophysics Data System (ADS)

Dalgleish, Hugh; Kirczenow, George

2004-03-01

Metal/Molecule/Metal junction systems forming molecular wires are currently the focus of intense study. Recently, spin-dependent electron transport in molecular wires with magnetic Ni electrodes has been studied theoretically, and spin-valve effects have been predicted.* Here we explore theoretically another magnetic molecular wire system, namely, ferromagnetic Fe nano-contacts bridged with 1,4-benzene-dithiolate (BDT). We estimate the essential structural and electronic parameters for this system based on ab initio density functional calculations (DFT) for some simple model systems involving thiol groups and Fe clusters as well as semi-empirical considerations and the known electronic structure of bulk Fe. We then use Lippmann-Schwinger and Green's function techniques together with the Landauer formalism to study spin-dependent transport. *E. G. Emberly and G. Kirczenow, Chem. Phys. 281, 311 (2002); R. Pati, L. Senapati, P.M. Ajayan and S.K. Nayak, Phys. Rev. B68, 100407 (2003).

Systems biology for molecular life sciences and its impact in biomedicine.

PubMed

Medina, Miguel Ángel

2013-03-01

Modern systems biology is already contributing to a radical transformation of molecular life sciences and biomedicine, and it is expected to have a real impact in the clinical setting in the next years. In this review, the emergence of systems biology is contextualized with a historic overview, and its present state is depicted. The present and expected future contribution of systems biology to the development of molecular medicine is underscored. Concerning the present situation, this review includes a reflection on the "inflation" of biological data and the urgent need for tools and procedures to make hidden information emerge. Descriptions of the impact of networks and models and the available resources and tools for applying them in systems biology approaches to molecular medicine are provided as well. The actual current impact of systems biology in molecular medicine is illustrated, reviewing two cases, namely, those of systems pharmacology and cancer systems biology. Finally, some of the expected contributions of systems biology to the immediate future of molecular medicine are commented.

Probing the electromagnetic field of a 15-nanometre hotspot by single molecule imaging.

PubMed

Cang, Hu; Labno, Anna; Lu, Changgui; Yin, Xiaobo; Liu, Ming; Gladden, Christopher; Liu, Yongmin; Zhang, Xiang

2011-01-20

When light illuminates a rough metallic surface, hotspots can appear, where the light is concentrated on the nanometre scale, producing an intense electromagnetic field. This phenomenon, called the surface enhancement effect, has a broad range of potential applications, such as the detection of weak chemical signals. Hotspots are believed to be associated with localized electromagnetic modes, caused by the randomness of the surface texture. Probing the electromagnetic field of the hotspots would offer much insight towards uncovering the mechanism generating the enhancement; however, it requires a spatial resolution of 1-2 nm, which has been a long-standing challenge in optics. The resolution of an optical microscope is limited to about half the wavelength of the incident light, approximately 200-300 nm. Although current state-of-the-art techniques, including near-field scanning optical microscopy, electron energy-loss spectroscopy, cathode luminescence imaging and two-photon photoemission imaging have subwavelength resolution, they either introduce a non-negligible amount of perturbation, complicating interpretation of the data, or operate only in a vacuum. As a result, after more than 30 years since the discovery of the surface enhancement effect, how the local field is distributed remains unknown. Here we present a technique that uses Brownian motion of single molecules to probe the local field. It enables two-dimensional imaging of the fluorescence enhancement profile of single hotspots on the surfaces of aluminium thin films and silver nanoparticle clusters, with accuracy down to 1.2 nm. Strong fluorescence enhancements, up to 54 and 136 times respectively, are observed in those two systems. This strong enhancement indicates that the local field, which decays exponentially from the peak of a hotspot, dominates the fluorescence enhancement profile.

Top–down fabrication of sub-nanometre semiconducting nanoribbons derived from molybdenum disulfide sheets

PubMed Central

Liu, Xiaofei; Xu, Tao; Wu, Xing; Zhang, Zhuhua; Yu, Jin; Qiu, Hao; Hong, Jin-Hua; Jin, Chuan-Hong; Li, Ji-Xue; Wang, Xin-Ran; Sun, Li-Tao; Guo, Wanlin

2013-01-01

Developments in semiconductor technology are propelling the dimensions of devices down to 10 nm, but facing great challenges in manufacture at the sub-10 nm scale. Nanotechnology can fabricate nanoribbons from two-dimensional atomic crystals, such as graphene, with widths below the 10 nm threshold, but their geometries and properties have been hard to control at this scale. Here we find that robust ultrafine molybdenum-sulfide ribbons with a uniform width of 0.35 nm can be widely formed between holes created in a MoS2 sheet under electron irradiation. In situ high-resolution transmission electron microscope characterization, combined with first-principles calculations, identifies the sub-1 nm ribbon as a Mo5S4 crystal derived from MoS2, through a spontaneous phase transition. Further first-principles investigations show that the Mo5S4 ribbon has a band gap of 0.77 eV, a Young’s modulus of 300GPa and can demonstrate 9% tensile strain before fracture. The results show a novel top–down route for controllable fabrication of functional building blocks for sub-nanometre electronics. PMID:23653188

Breakdown of the Debye approximation for the acoustic modes with nanometric wavelengths in glasses

PubMed Central

Monaco, Giulio; Giordano, Valentina M.

2009-01-01

On the macroscopic scale, the wavelengths of sound waves in glasses are large enough that the details of the disordered microscopic structure are usually irrelevant, and the medium can be considered as a continuum. On decreasing the wavelength this approximation must of course fail at one point. We show here that this takes place unexpectedly on the mesoscopic scale characteristic of the medium range order of glasses, where it still works well for the corresponding crystalline phases. Specifically, we find that the acoustic excitations with nanometric wavelengths show the clear signature of being strongly scattered, indicating the existence of a cross-over between well-defined acoustic modes for larger wavelengths and ill-defined ones for smaller wavelengths. This cross-over region is accompanied by a softening of the sound velocity that quantitatively accounts for the excess observed in the vibrational density of states of glasses over the Debye level at energies of a few milli-electronvolts. These findings thus highlight the acoustic contribution to the well-known universal low-temperature anomalies found in the specific heat of glasses. PMID:19240211

Dynamic behaviour of nanometre-sized defect clusters emitted from an atomic displacement cascade in Au at 50 K

NASA Astrophysics Data System (ADS)

Ono, K.; Miyamoto, M.; Arakawa, K.; Birtcher, R. C.

2017-09-01

We demonstrate the emission of nanometre-sized defect clusters from an isolated displacement cascade formed by irradiation of high-energy self-ions and their subsequent 1-D motion in Au at 50 K, using in situ electron microscopy. The small defect clusters emitted from a displacement cascade exhibited correlated back-and-forth 1-D motion along the [-1 1 0] direction and coalescence which results in their growth and reduction of their mobility. From the analysis of the random 1-D motion, the diffusivity of the small cluster was evaluated. Correlated 1-D motion and coalescence of clusters were understood via elastic interaction between small clusters. These results provide direct experimental evidence of the migration of small defect clusters and defect cascade evolution at low temperature.

Supramolecular chemistry: from molecular information towards self-organization and complex matter

NASA Astrophysics Data System (ADS)

Lehn, Jean-Marie

2004-03-01

Molecular chemistry has developed a wide range of very powerful procedures for constructing ever more sophisticated molecules from atoms linked by covalent bonds. Beyond molecular chemistry lies supramolecular chemistry, which aims at developing highly complex chemical systems from components interacting via non-covalent intermolecular forces. By the appropriate manipulation of these interactions, supramolecular chemistry became progressively the chemistry of molecular information, involving the storage of information at the molecular level, in the structural features, and its retrieval, transfer, and processing at the supramolecular level, through molecular recognition processes operating via specific interactional algorithms. This has paved the way towards apprehending chemistry also as an information science. Numerous receptors capable of recognizing, i.e. selectively binding, specific substrates have been developed, based on the molecular information stored in the interacting species. Suitably functionalized receptors may perform supramolecular catalysis and selective transport processes. In combination with polymolecular organization, recognition opens ways towards the design of molecular and supramolecular devices based on functional (photoactive, electroactive, ionoactive, etc) components. A step beyond preorganization consists in the design of systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined supramolecular architectures by self-assembly from their components. Self-organization processes, directed by the molecular information stored in the components and read out at the supramolecular level through specific interactions, represent the operation of programmed chemical systems. They have been implemented for the generation of a variety of discrete functional architectures of either organic or inorganic nature. Self-organization processes also give access to advanced supramolecular materials, such as

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

PubMed

Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

2015-11-18

Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of substrates on the molecular orientation of silicon phthalocyanine dichloride thin films

NASA Astrophysics Data System (ADS)

Deng, Juzhi; Baba, Yuji; Sekiguchi, Tetsuhiro; Hirao, Norie; Honda, Mitsunori

2007-05-01

Molecular orientations of silicon phthalocyanine dichloride (SiPcCl2) thin films deposited on three different substrates have been measured by near-edge x-ray absorption fine structure (NEXAFS) spectroscopy using linearly polarized synchrotron radiation. The substrates investigated were highly oriented pyrolitic graphite (HOPG), polycrystalline gold and indium tin oxide (ITO). For thin films of about five monolayers, the polarization dependences of the Si K-edge NEXAFS spectra showed that the molecular planes of SiPcCl2 on three substrates were nearly parallel to the surface. Quantitative analyses of the polarization dependences revealed that the tilted angle on HOPG was only 2°, which is interpreted by the perfect flatness of the HOPG surface. On the other hand, the tilted angle on ITO was 26°. Atomic force microscopy (AFM) observation of the ITO surface showed that the periodicity of the horizontal roughness is of the order of a few nanometres, which is larger than the molecular size of SiPcCl2. It is concluded that the morphology of the top surface layer of the substrate affects the molecular orientation of SiPcCl2 molecules not only for mono-layered adsorbates but also for multi-layered thin films.

Magnetotactic bacteria form magnetite from a phosphate-rich ferric hydroxide via nanometric ferric (oxyhydr)oxide intermediates.

PubMed

Baumgartner, Jens; Morin, Guillaume; Menguy, Nicolas; Perez Gonzalez, Teresa; Widdrat, Marc; Cosmidis, Julie; Faivre, Damien

2013-09-10

The iron oxide mineral magnetite (Fe3O4) is produced by various organisms to exploit magnetic and mechanical properties. Magnetotactic bacteria have become one of the best model organisms for studying magnetite biomineralization, as their genomes are sequenced and tools are available for their genetic manipulation. However, the chemical route by which magnetite is formed intracellularly within the so-called magnetosomes has remained a matter of debate. Here we used X-ray absorption spectroscopy at cryogenic temperatures and transmission electron microscopic imaging techniques to chemically characterize and spatially resolve the mechanism of biomineralization in those microorganisms. We show that magnetite forms through phase transformation from a highly disordered phosphate-rich ferric hydroxide phase, consistent with prokaryotic ferritins, via transient nanometric ferric (oxyhydr)oxide intermediates within the magnetosome organelle. This pathway remarkably resembles recent results on synthetic magnetite formation and bears a high similarity to suggested mineralization mechanisms in higher organisms.

Molecular transport through capillaries made with atomic-scale precision

NASA Astrophysics Data System (ADS)

Radha, B.; Esfandiar, A.; Wang, F. C.; Rooney, A. P.; Gopinadhan, K.; Keerthi, A.; Mishchenko, A.; Janardanan, A.; Blake, P.; Fumagalli, L.; Lozada-Hidalgo, M.; Garaj, S.; Haigh, S. J.; Grigorieva, I. V.; Wu, H. A.; Geim, A. K.

2016-10-01

Nanometre-scale pores and capillaries have long been studied because of their importance in many natural phenomena and their use in numerous applications. A more recent development is the ability to fabricate artificial capillaries with nanometre dimensions, which has enabled new research on molecular transport and led to the emergence of nanofluidics. But surface roughness in particular makes it challenging to produce capillaries with precisely controlled dimensions at this spatial scale. Here we report the fabrication of narrow and smooth capillaries through van der Waals assembly, with atomically flat sheets at the top and bottom separated by spacers made of two-dimensional crystals with a precisely controlled number of layers. We use graphene and its multilayers as archetypal two-dimensional materials to demonstrate this technology, which produces structures that can be viewed as if individual atomic planes had been removed from a bulk crystal to leave behind flat voids of a height chosen with atomic-scale precision. Water transport through the channels, ranging in height from one to several dozen atomic planes, is characterized by unexpectedly fast flow (up to 1 metre per second) that we attribute to high capillary pressures (about 1,000 bar) and large slip lengths. For channels that accommodate only a few layers of water, the flow exhibits a marked enhancement that we associate with an increased structural order in nanoconfined water. Our work opens up an avenue to making capillaries and cavities with sizes tunable to ångström precision, and with permeation properties further controlled through a wide choice of atomically flat materials available for channel walls.

Towards nanometric resolution in multilayer depth profiling: a comparative study of RBS, SIMS, XPS and GDOES.

PubMed

Escobar Galindo, Ramón; Gago, Raul; Duday, David; Palacio, Carlos

2010-04-01

An increasing amount of effort is currently being directed towards the development of new functionalized nanostructured materials (i.e., multilayers and nanocomposites). Using an appropriate combination of composition and microstructure, it is possible to optimize and tailor the final properties of the material to its final application. The analytical characterization of these new complex nanostructures requires high-resolution analytical techniques that are able to provide information about surface and depth composition at the nanometric level. In this work, we comparatively review the state of the art in four different depth-profiling characterization techniques: Rutherford backscattering spectroscopy (RBS), secondary ion mass spectrometry (SIMS), X-ray photoelectron spectroscopy (XPS) and glow discharge optical emission spectroscopy (GDOES). In addition, we predict future trends in these techniques regarding improvements in their depth resolutions. Subnanometric resolution can now be achieved in RBS using magnetic spectrometry systems. In SIMS, the use of rotating sample holders and oxygen flooding during analysis as well as the optimization of floating low-energy ion guns to lower the impact energy of the primary ions improves the depth resolution of the technique. Angle-resolved XPS provides a very powerful and nondestructive technique for obtaining depth profiling and chemical information within the range of a few monolayers. Finally, the application of mathematical tools (deconvolution algorithms and a depth-profiling model), pulsed sources and surface plasma cleaning procedures is expected to greatly improve GDOES depth resolution.

Size of submicrometric and nanometric particles affect cellular uptake and biological activity of macrophages in vitro.

PubMed

Leclerc, L; Rima, W; Boudard, D; Pourchez, J; Forest, V; Bin, V; Mowat, P; Perriat, P; Tillement, O; Grosseau, P; Bernache-Assollant, D; Cottier, M

2012-08-01

Micrometric and nanometric particles are increasingly used in different fields and may exhibit variable toxicity levels depending on their physicochemical characteristics. The aim of this study was to determine the impact of the size parameter on cellular uptake and biological activity, working with well-characterized fluorescent particles. We focused our attention on macrophages, the main target cells of the respiratory system responsible for the phagocytosis of the particles. FITC fluorescent silica particles of variable submicronic sizes (850, 500, 250 and 150 nm) but with similar surface coating (COOH) were tailored and physico-chemically characterized. These particles were then incubated with the RAW 264.7 macrophage cell line. After microscopic observations (SEM, TEM, confocal), a quantitative evaluation of the uptake was carried out. Fluorescence detected after a quenching with trypan blue allows us to distinguish and quantify entirely engulfed fluorescent particles from those just adhering to the cell membrane. Finally, these data were compared to the in vitro toxicity assessed in terms of cell damage, inflammation and oxidative stress (evaluated by LDH release, TNF-α and ROS production respectively). Particles were well characterized (fluorescence, size distribution, zeta potential, agglomeration and surface groups) and easily visualized after cellular uptake using confocal and electron microscopy. The number of internalized particles was precisely evaluated. Size was found to be an important parameter regarding particles uptake and in vitro toxicity but this latter strongly depends on the particles doses employed.

Direct evidence for coastal iodine particles from Laminaria macroalgae - linkage to emissions of molecular iodine

NASA Astrophysics Data System (ADS)

McFiggans, G.; Coe, H.; Burgess, R.; Allan, J.; Cubison, M.; Rami Alfarra, M.; Saunders, R.; Saiz-Lopez, A.; Plane, J. M. C.; Wevill, D.; Carpenter, L.; Rickard, A. R.; Monks, P. S.

2004-02-01

Renewal of ultrafine aerosols in the marine boundary layer may lead to repopulation of the marine distribution and ultimately determine the concentration of cloud condensation nuclei (CCN). Thus the formation of nanometre-scale particles can lead to enhanced scattering of incoming radiation and a net cooling of the atmosphere. The recent demonstration of the chamber formation of new particles from the photolytic production of condensable iodine-containing compounds from diiodomethane (CH2I2), (O'Dowd et al., 2002; Kolb, 2002; Jimenez et al., 2003a; Burkholder and Ravishankara, 2003), provides an additional mechanism to the gas-to-particle conversion of sulphuric acid formed in the photo-oxidation of dimethylsulphide for marine aerosol repopulation. CH2I2 is emitted from seaweeds (Carpenter et al., 1999, 2000) and has been suggested as an initiator of particle formation. We demonstrate here for the first time that ultrafine iodine-containing particles are produced by intertidal macroalgae exposed to ambient levels of ozone. The particle composition is very similar both to those formed in the chamber photo-oxidation of diiodomethane and in the oxidation of molecular iodine by ozone. The particles formed in all three systems are similarly aspherical and behave alike when exposed to increased humidity environments. Direct coastal boundary layer observations of molecular iodine, ultrafine particle production and iodocarbons are reported. Using a newly measured molecular iodine photolysis rate, it is shown that, if atomic iodine is involved in the observed particle bursts, it is of the order of at least 1000 times more likely to result from molecular iodine photolysis than diiodomethane photolysis. A hypothesis for molecular iodine release from intertidal macroalgae is presented and the potential importance of macroalgal iodine particles in their contribution to CCN and global radiative forcing are discussed.

Distributed information system on molecular spectroscopy

NASA Astrophysics Data System (ADS)

Bykov, A. D.; Fazliev, A. Z.; Kozodoev, A. V.; Privezentsev, A. I.; Sinitsa, L. N.; Tonkov, M. V.; Filippov, N. N.; Tretyakov, M. Yu.

2006-12-01

The urgency of creating the information-computational systems (ICS) on molecular spectroscopy follows from the circumstance that for some molecules the number of calculated energy levels counts hundreds of thousands, and the number of spectral lines sometimes reaches hundreds of millions. Publication of such data volumes in regular journals is inappropriate. Comparison of different calculated spectral characteristics or their comparison with experimental data beyond computer processing is hopeless. We find information systems to be an adequate form for holding such data volumes and a toolkit for handling them. Correct digital data processing requires appropriate sets of metadata arranged in the form of ontology of molecular spectroscopy. Our information system provides the data on spectral line parameters, water molecule energy levels, and absorption coefficients. Within this distributed IS one can solve two types of problems: manipulation with data and calculation of spectral functions. Among the latest experimental data in the IS there are data obtained at the Institute of Applied Physics RAS. To calculate the absorption coefficients for the molecules of carbonic acid gas, we take into consideration spectral line interference.

A molecular dynamics study of polymer/graphene interfacial systems

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

Rissanou, Anastassia N.; Harmandaris, Vagelis

2014-05-15

Graphene based polymer nanocomposites are hybrid materials with a very broad range of technological applications. In this work, we study three hybrid polymer/graphene interfacial systems (polystyrene/graphene, poly(methyl methacrylate)/graphene and polyethylene/graphene) through detailed atomistic molecular dynamics (MD) simulations. Density profiles, structural characteristics and mobility aspects are being examined at the molecular level for all model systems. In addition, we compare the properties of the hybrid systems to the properties of the corresponding bulk ones, as well as to theoretical predictions.

Microstructural effects on ignition sensitivity in Ni/Al systems subjected to high strain rate impacts

NASA Astrophysics Data System (ADS)

Reeves, Robert; Mukasyan, Alexander; Son, Steven

2011-06-01

The effect of microstructural refinement on the sensitivity of the Ni/Al (1:1 at%) system to ignition via high strain rate impacts is investigated. The tested microstructures include compacts of irregularly convoluted lamellar structures with nanometric features created through high-energy ball milling (HEBM) of micron size Ni/Al powders and compacts of nanometric Ni and Al powders. The test materials were subjected to high strain rate impacts through Asay shear experiments powered by a light gas gun. Muzzle velocities up to 1.1 km/s were used. It was found that the nanometric powder exhibited a greater sensitivity to ignition via impact than the HEBM material, despite greater thermal sensitivity of the HEBM. A previously unseen fast reaction mode where the reaction front traveled at the speed of the input stress wave was also observed in the nanometric mixtures at high muzzle energies. This fast mode is considered to be a mechanically induced thermal explosion mode dependent on the magnitude of the traveling stress wave, rather than a self-propagating detonation, since its propagation rate decreases rapidly across the sample. A similar mode is not exhibited by HEBM samples, although local, nonpropagating reaction zones occur in shear bands formed during the impact event.

Microstructural effects on ignition sensitivity in Ni/Al systems subjected to high strain rate impacts

NASA Astrophysics Data System (ADS)

Reeves, Robert V.; Mukasyan, Alexander S.; Son, Steven

2012-03-01

The effect of microstructural refinement on the sensitivity of the Ni/Al (1:1 mol%) system to ignition via high strain rate impacts is investigated. The tested microstructures include compacts of irregularly convoluted lamellar structures with nanometric features created through high-energy ball milling (HEBM) of micron size Ni/Al powders and compacts of nanometric Ni and Al powders. The test materials were subjected to high strain rate impacts through Asay shear experiments powered by a light gas gun. Muzzle velocities up to 1.1 km/s were used. It was found that the nanometric powder exhibited a greater sensitivity to ignition via impact than the HEBM material, despite greater thermal sensitivity of the HEBM. A previously unseen fast reaction mode where the reaction front traveled at the speed of the input stress wave was also observed in the nanometric mixtures at high muzzle energies. This fast mode is considered to be a mechanically induced thermal explosion mode dependent on the magnitude of the traveling stress wave, rather than a self-propagating detonation, since its propagation rate decreases rapidly across the sample. A similar mode is not exhibited by HEBM samples, although local, nonpropagating reaction zones shear bands formed during the impact event are observed.

pysimm: A Python Package for Simulation of Molecular Systems

NASA Astrophysics Data System (ADS)

Fortunato, Michael; Colina, Coray

pysimm, short for python simulation interface for molecular modeling, is a python package designed to facilitate the structure generation and simulation of molecular systems through convenient and programmatic access to object-oriented representations of molecular system data. This poster presents core features of pysimm and design philosophies that highlight a generalized methodology for incorporation of third-party software packages through API interfaces. The integration with the LAMMPS simulation package is explained to demonstrate this methodology. pysimm began as a back-end python library that powered a cloud-based application on nanohub.org for amorphous polymer simulation. The extension from a specific application library to general purpose simulation interface is explained. Additionally, this poster highlights the rapid development of new applications to construct polymer chains capable of controlling chain morphology such as molecular weight distribution and monomer composition.

Molecular dynamics coupled with a virtual system for effective conformational sampling.

PubMed

Hayami, Tomonori; Kasahara, Kota; Nakamura, Haruki; Higo, Junichi

2018-07-15

An enhanced conformational sampling method is proposed: virtual-system coupled canonical molecular dynamics (VcMD). Although VcMD enhances sampling along a reaction coordinate, this method is free from estimation of a canonical distribution function along the reaction coordinate. This method introduces a virtual system that does not necessarily obey a physical law. To enhance sampling the virtual system couples with a molecular system to be studied. Resultant snapshots produce a canonical ensemble. This method was applied to a system consisting of two short peptides in an explicit solvent. Conventional molecular dynamics simulation, which is ten times longer than VcMD, was performed along with adaptive umbrella sampling. Free-energy landscapes computed from the three simulations mutually converged well. The VcMD provided quicker association/dissociation motions of peptides than the conventional molecular dynamics did. The VcMD method is applicable to various complicated systems because of its methodological simplicity. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Testing of Streckeisen STS-5A and Nanometrics Trillium 120PH Sensors for the Alaska Transportable Array

NASA Astrophysics Data System (ADS)

Abbasi Baghbadorani, A.; Aderhold, K.; Bloomquist, D.; Frassetto, A.; Miller, P. E.; Busby, R. W.

2017-12-01

Starting in 2014, the IRIS Transportable Array facility began to install and operate seismic stations in Alaska and western Canada. By the end of the project, the full deployment of the array will cover a grid of 280 stations spaced about 85 km apart covering all of mainland Alaska and parts of the Yukon, British Columbia, and the Northwest Territories. Approximately 200 stations will be operated directly by IRIS through at least 2019. A key aspect of the Alaska TA is the need for stations to operate autonomously, on account of the high cost of installation and potential subsequent visits to remote field-sites to repair equipment. The TA is using newly developed broadband seismometers Streckeisen STS-5A and Nanometrics Trillium-120PH, designed for installation in shallow posthole emplacements. These new instruments were extensively vetted beforehand, but they are still relatively new to the TA inventory. Here we will assess their performance under deployment conditions and after repeated commercial shipping and travel to the field. Our objective is to provide a thorough accounting of the identified failures of the existing inventory of posthole instruments. We will assess the practices and results of instrument testing by the PASSCAL Instrument Center/Array Operations Facility (PIC/AOF), Alaska Operations Center (AOC), and broadband seismic sensor manufacturers (Streckeisen, Nanometrics) in order to document potential factors in and stages during the process for instrument failures. This will help to quantify the overall reliability of the TA seismic sensors and quality of TA practices and data collection, and identify potential considerations in future TA operations. Our results show that the overall rate of failure of all posthole instruments is <4% out of 260. This is lower than the rates seen for vault sensor failures in the operation of the Lower 48 Transportable Array. For telemetered stations such as these installed in the TA Alaska array, we also show that

Synthesis and characterization of nanometric zinc oxide for a stationary phase in liquid chromatography

NASA Astrophysics Data System (ADS)

Gordillo-Delgado, F.; Soto-Barrera, C. C.; Plazas-Saldaña, J.

2017-01-01

The increasing demand for equipment to remove organic compounds in industry and research activity has led to evaluate nanometric zinc oxide (ZnO). In this work, we present the ZnO nanoparticles synthesis for reusing of discarded columns, as a low-cost alternative. The compound was obtained by sol-gel technique using zinc chloride and sodium hydroxide as precursors and a drying temperature of 169°C. An X-ray diffractometer was used to estimate the average particle size at 20.3±0.2nm the adsorption capacity was 0.0144L/g and the chemical resistance was tested with HCl and NaOH. The ZnO nanopowder was packed with 100psi pressure in an empty C-18 column cavity. The column packing resolution was evaluated using a high performance liquid chromatographer (HPLC-Thermo Scientific Dionex UltiMate 3000); using a caffeine standard, the following parameters were established: solvent flow: 1.2mL/min, average column temperature: 40°C, running time: 10 minutes, mobile phase acetonitrile-water composition (9:1). These results validate the potential of ZnO nanopowder as a column packing material in HPLC technique.

Molecular System for the Division of Self-Propelled Oil Droplets by Component Feeding.

PubMed

Banno, Taisuke; Toyota, Taro

2015-06-30

Unique dynamics using inanimate molecular assemblies have drawn a great amount of attention for demonstrating prebiomimetic molecular systems. For the construction of an organized logic combining two fundamental dynamics of life, we demonstrate here a molecular system that exhibits both division and self-propelled motion using oil droplets. The key molecule of this molecular system is a novel cationic surfactant containing a five-membered acetal moiety, and the molecular system can feed the self-propelled oil droplet composed of a benzaldehyde derivative and an alkanol. The division dynamics of the self-propelled oil droplets were observed through the hydrolysis of the cationic surfactant in bulk solution. The mechanism of the current dynamics is argued to be based on the supply of "fresh" oil components in the moving oil droplets, which is induced by the Marangoni instability. We consider this molecular system to be a prototype of self-reproducing inanimate molecular assembly exhibiting self-propelled motion.

Linear conduction in N-type organic field effect transistors with nanometric channel lengths and graphene as electrodes

NASA Astrophysics Data System (ADS)

Chianese, F.; Candini, A.; Affronte, M.; Mishra, N.; Coletti, C.; Cassinese, A.

2018-05-01

In this work, we test graphene electrodes in nanometric channel n-type Organic Field Effect Transistors (OFETs) based on thermally evaporated thin films of the perylene-3,4,9,10-tetracarboxylic acid diimide derivative. By a thorough comparison with short channel transistors made with reference gold electrodes, we found that the output characteristics of the graphene-based devices respond linearly to the applied bias, in contrast with the supralinear trend of gold-based transistors. Moreover, short channel effects are considerably suppressed in graphene electrode devices. More specifically, current on/off ratios independent of the channel length (L) and enhanced response for high longitudinal biases are demonstrated for L down to ˜140 nm. These results are rationalized taking into account the morphological and electronic characteristics of graphene, showing that the use of graphene electrodes may help to overcome the problem of Space Charge Limited Current in short channel OFETs.

Enhanced sampling techniques in molecular dynamics simulations of biological systems.

PubMed

Bernardi, Rafael C; Melo, Marcelo C R; Schulten, Klaus

2015-05-01

Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes. Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

An antilock molecular braking system.

PubMed

Sun, Wei-Ting; Huang, Shou-Ling; Yao, Hsuan-Hsiao; Chen, I-Chia; Lin, Ying-Chih; Yang, Jye-Shane

2012-08-17

A light-driven molecular brake displaying an antilock function is constructed by introducing a nonradiative photoinduced electron transfer (PET) decay channel to compete with the trans (brake-off) → cis (brake-on) photoisomerization. A fast release of the brake can be achieved by deactivating the PET process through addition of protons. The cycle of irradiation-protonation-irradiation-deprotonation conducts the brake function and mimics the antilock braking system (ABS) of vehicles.

Unidirectional rotary motion in a molecular system

NASA Astrophysics Data System (ADS)

Kelly, T. Ross; de Silva, Harshani; Silva, Richard A.

1999-09-01

The conversion of energy into controlled motion plays an important role in both man-made devices and biological systems. The principles of operation of conventional motors are well established, but the molecular processes used by `biological motors' such as muscle fibres, flagella and cilia to convert chemical energy into co-ordinated movement remain poorly understood. Although `brownian ratchets' are known to permit thermally activated motion in one direction only, the concept of channelling random thermal energy into controlled motion has not yet been extended to the molecular level. Here we describe a molecule that uses chemical energy to activate and bias a thermally induced isomerization reaction, and thereby achieve unidirectional intramolecular rotary motion. The motion consists of a 120° rotation around a single bond connecting a three-bladed subunit to the bulky remainder of the molecule, and unidirectional motion is achieved by reversibly introducing a tether between the two units to energetically favour one of the two possible rotation directions. Although our system does not achieve continuous and fast rotation, the design principles that we have used may prove relevant for a better understanding of biological and synthetic molecular motors producing unidirectional rotary motion.

Molecular marker systems for Oenothera genetics.

PubMed

Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G; Greiner, Stephan

2008-11-01

The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome-genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9.8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed.

The Influence of Chitosan Substrate and Its Nanometric Form Toward the Green Power Generation in Sediment Microbial Fuel Cell.

PubMed

Karthikeyan, C; Sathishkumar, Y; Lee, Yang Soo; Kim, Ae Rhan; Yoo, Dong Jin; Kumar, G Gnana

2017-01-01

A simple, environmental friendly and biologically important sediment interfaced fuel cell was developed for the green energy generation. The soil sediment used for the study is enriched of rich anthropogenic free organic carbon, sufficient manganese and high level potassium contents as evidenced from the geochemical characterizations. The saccharides produced by the catalytic reaction of substrate chitosan were utilized for the growth of microorganisms and electron shuttling processes. Chitosan substrate influenced sediment microbial fuel cells exhibited the nearly two fold power increment over the substrate free fuel cells. The fuel cell efficiencies were further increased by bringing the substrate chitosan at nanometric level, which is nearly three and two fold higher than that of substrate free and chitosan influenced sediment microbial fuel cells, respectively, and the influential parameters involved in the power and longevity issues were addressed with different perspectives.

Protonation free energy levels in complex molecular systems.

PubMed

Antosiewicz, Jan M

2008-04-01

All proteins, nucleic acids, and other biomolecules contain residues capable of exchanging protons with their environment. These proton transfer phenomena lead to pH sensitivity of many molecular processes underlying biological phenomena. In the course of biological evolution, Nature has invented some mechanisms to use pH gradients to regulate biomolecular processes inside cells or in interstitial fluids. Therefore, an ability to model protonation equilibria in molecular systems accurately would be of enormous value for our understanding of biological processes and for possible rational influence on them, like in developing pH dependent drugs to treat particular diseases. This work presents a derivation, by thermodynamic and statistical mechanical methods, of an expression for the free energy of a complex molecular system at arbitrary ionization state of its titratable residues. This constitutes one of the elements of modeling protonation equilibria. Starting from a consideration of a simple acid-base equilibrium of a model compound with a single tritratable group, we arrive at an expression which is of general validity for complex systems. The only approximation used in this derivation is the postulating that the interaction energy between any pair of titratable sites does not depend on the protonation states of all the remaining ionizable groups.

Molecularly Engineered Polymer-Based Systems in Drug Delivery and Regenerative Medicine.

PubMed

Piluso, Susanna; Soultan, Al Halifa; Patterson, Jennifer

2017-01-01

Polymer-based systems are attractive in drug delivery and regenerative medicine due to the possibility of tailoring their properties and functions to a specific application. The present review provides several examples of molecularly engineered polymer systems, including stimuli responsive polymers and supramolecular polymers. The advent of controlled polymerization techniques has enabled the preparation of polymers with controlled molecular weight and well-defined architecture. By using these techniques coupled to orthogonal chemical modification reactions, polymers can be molecularly engineered to incorporate functional groups able to respond to small changes in the local environment or to a specific biological signal. This review highlights the properties and applications of stimuli-responsive systems and polymer therapeutics, such as polymer-drug conjugates, polymer-protein conjugates, polymersomes, and hyperbranched systems. The applications of polymeric membranes in regenerative medicine are also discussed. The examples presented in this review suggest that the combination of membranes with polymers that are molecularly engineered to respond to specific biological functions could be relevant in the field of regenerative medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anticipatory dynamics of biological systems: from molecular quantum states to evolution

NASA Astrophysics Data System (ADS)

Igamberdiev, Abir U.

2015-08-01

Living systems possess anticipatory behaviour that is based on the flexibility of internal models generated by the system's embedded description. The idea was suggested by Aristotle and is explicitly introduced to theoretical biology by Rosen. The possibility of holding the embedded internal model is grounded in the principle of stable non-equilibrium (Bauer). From the quantum mechanical view, this principle aims to minimize energy dissipation in expense of long relaxation times. The ideas of stable non-equilibrium were developed by Liberman who viewed living systems as subdivided into the quantum regulator and the molecular computer supporting coherence of the regulator's internal quantum state. The computational power of the cell molecular computer is based on the possibility of molecular rearrangements according to molecular addresses. In evolution, the anticipatory strategies are realized both as a precession of phylogenesis by ontogenesis (Berg) and as the anticipatory search of genetic fixation of adaptive changes that incorporates them into the internal model of genetic system. We discuss how the fundamental ideas of anticipation can be introduced into the basic foundations of theoretical biology.

MOLECULAR BONDING SYSTEM - INNOVATIVE TECHNOLOGY EVALUATION REPORT

EPA Science Inventory

This document presents an evaluation of the Molecular Bonding System (MBS) and its ability to chemically stabilize three metals-contaminated wstes/soils during a SITe demo. The MBS process treated approximately 500 tons each of soil/Fill, Slag, and Miscellaneous Smelter Waste wit...

Atomic and Molecular Systems in Intense Ultrashort Laser Pulses

NASA Astrophysics Data System (ADS)

Saenz, A.

2008-07-01

The full quantum mechanical treatment of atomic and molecular systems exposed to intense laser pulses is a so far unsolved challenge, even for systems as small as molecular hydrogen. Therefore, a number of simplified qualitative and quantitative models have been introduced in order to provide at least some interpretational tools for experimental data. The assessment of these models describing the molecular response is complicated, since a comparison to experiment requires often a number of averages to be performed. This includes in many cases averaging of different orientations of the molecule with respect to the laser field, focal volume effects, etc. Furthermore, the pulse shape and even the peak intensity is experimentally not known with very high precision; considering, e.g., the exponential intensity dependence of the ionization signal. Finally, experiments usually provide only relative yields. As a consequence of all these averagings and uncertainties, it is possible that different models may successfully explain some experimental results or features, although these models disagree substantially, if their predictions are compared before averaging. Therefore, fully quantum-mechanical approaches at least for small atomic and molecular systems are highly desirable and have been developed in our group. This includes efficient codes for solving the time-dependent Schrodinger equation of atomic hydrogen, helium or other effective one- or two-electron atoms as well as for the electronic motion in linear (effective) one-and two-electron diatomic molecules like H_2.Very recently, a code for larger molecular systems that adopts the so-called single-active electron approximation was also successfully implemented and applied. In the first part of this talk popular models describing intense laser-field ionization of atoms and their extensions to molecules are described. Then their validity is discussed on the basis of quantum-mechanical calculations. Finally, some

Molecular-based design and emerging applications of nanoporous carbon spheres

NASA Astrophysics Data System (ADS)

Liu, Jian; Wickramaratne, Nilantha P.; Qiao, Shi Zhang; Jaroniec, Mietek

2015-08-01

Over the past decade, considerable progress has been made in the synthesis and applications of nanoporous carbon spheres ranging in size from nanometres to micrometres. This Review presents the primary techniques for preparing nanoporous carbon spheres and the seminal research that has inspired their development, presented potential applications and uncovered future challenges. First we provide an overview of the synthesis techniques, including the Stöber method and those based on templating, self-assembly, emulsion and hydrothermal carbonization, with special emphasis on the design and functionalization of nanoporous carbon spheres at the molecular level. Next, we cover the key applications of these spheres, including adsorption, catalysis, separation, energy storage and biomedicine -- all of which might benefit from the regular geometry, good liquidity, tunable porosity and controllable particle-size distribution offered by nanoporous carbon spheres. Finally, we present the current challenges and opportunities in the development and commercial applications of nanoporous carbon spheres.

Molecular-based design and emerging applications of nanoporous carbon spheres.

PubMed

Liu, Jian; Wickramaratne, Nilantha P; Qiao, Shi Zhang; Jaroniec, Mietek

2015-08-01

Over the past decade, considerable progress has been made in the synthesis and applications of nanoporous carbon spheres ranging in size from nanometres to micrometres. This Review presents the primary techniques for preparing nanoporous carbon spheres and the seminal research that has inspired their development, presented potential applications and uncovered future challenges. First we provide an overview of the synthesis techniques, including the Stöber method and those based on templating, self-assembly, emulsion and hydrothermal carbonization, with special emphasis on the design and functionalization of nanoporous carbon spheres at the molecular level. Next, we cover the key applications of these spheres, including adsorption, catalysis, separation, energy storage and biomedicine — all of which might benefit from the regular geometry, good liquidity, tunable porosity and controllable particle-size distribution offered by nanoporous carbon spheres. Finally, we present the current challenges and opportunities in the development and commercial applications of nanoporous carbon spheres.

Immune-Enhancing Effect of Nanometric Lactobacillus plantarum nF1 (nLp-nF1) in a Mouse Model of Cyclophosphamide-Induced Immunosuppression.

PubMed

Choi, Dae-Woon; Jung, Sun Young; Kang, Jisu; Nam, Young-Do; Lim, Seong-Il; Kim, Ki Tae; Shin, Hee Soon

2018-02-28

Nanometric Lactobacillus plantarum nF1 (nLp-nF1) is a biogenics consisting of dead L. plantarum cells pretreated with heat and a nanodispersion process. In this study, we investigated the immune-enhancing effects of nLp-nF1 in vivo and in vitro. To evaluate the immunostimulatory effects of nLp-nF1, mice immunosuppressed by cyclophosphamide (CPP) treatment were administered with nLp-nF1. As expected, CPP restricted the immune response of mice, whereas oral administration of nLp-nF1 significantly increased the total IgG in the serum, and cytokine production (interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α)) in bone marrow cells. Furthermore, nLp-nF1 enhanced the production of splenic cytokines such as IL-12, TNF-α, and interferon gamma (IFN-γ). In vitro, nLp-nF1 stimulated the immune response by enhancing the production of cytokines such as IL-12, TNF-α, and IFN-γ. Moreover, nLp-nF1 given a food additive enhanced the immune responses when combined with various food materials in vitro. These results suggest that nLp-nF1 could be used to strengthen the immune system and recover normal immunity in people with a weak immune system, such as children, the elderly, and patients.

Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems

DTIC Science & Technology

2017-08-01

Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems The views, opinions and/or findings contained in...University of California - San Diego Title: Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems Report Term...including enzymatic reactions , occurring at the aqueous interfaces of thermotropic LCs show promise as the basis of biomolecular triggers of LC

Integrative pathway knowledge bases as a tool for systems molecular medicine.

PubMed

Liang, Mingyu

2007-08-20

There exists a sense of urgency to begin to generate a cohesive assembly of biomedical knowledge as the pace of knowledge accumulation accelerates. The urgency is in part driven by the emergence of systems molecular medicine that emphasizes the combination of systems analysis and molecular dissection in the future of medical practice and research. A potentially powerful approach is to build integrative pathway knowledge bases that link organ systems function with molecules.

Materials learning from life: concepts for active, adaptive and autonomous molecular systems.

PubMed

Merindol, Rémi; Walther, Andreas

2017-09-18

Bioinspired out-of-equilibrium systems will set the scene for the next generation of molecular materials with active, adaptive, autonomous, emergent and intelligent behavior. Indeed life provides the best demonstrations of complex and functional out-of-equilibrium systems: cells keep track of time, communicate, move, adapt, evolve and replicate continuously. Stirred by the understanding of biological principles, artificial out-of-equilibrium systems are emerging in many fields of soft matter science. Here we put in perspective the molecular mechanisms driving biological functions with the ones driving synthetic molecular systems. Focusing on principles that enable new levels of functionalities (temporal control, autonomous structures, motion and work generation, information processing) rather than on specific material classes, we outline key cross-disciplinary concepts that emerge in this challenging field. Ultimately, the goal is to inspire and support new generations of autonomous and adaptive molecular devices fueled by self-regulating chemistry.

Molecular Marker Systems for Oenothera Genetics

PubMed Central

Rauwolf, Uwe; Golczyk, Hieronim; Meurer, Jörg; Herrmann, Reinhold G.; Greiner, Stephan

2008-01-01

The genus Oenothera has an outstanding scientific tradition. It has been a model for studying aspects of chromosome evolution and speciation, including the impact of plastid nuclear co-evolution. A large collection of strains analyzed during a century of experimental work and unique genetic possibilities allow the exchange of genetically definable plastids, individual or multiple chromosomes, and/or entire haploid genomes (Renner complexes) between species. However, molecular genetic approaches for the genus are largely lacking. In this study, we describe the development of efficient PCR-based marker systems for both the nuclear genome and the plastome. They allow distinguishing individual chromosomes, Renner complexes, plastomes, and subplastomes. We demonstrate their application by monitoring interspecific exchanges of genomes, chromosome pairs, and/or plastids during crossing programs, e.g., to produce plastome–genome incompatible hybrids. Using an appropriate partial permanent translocation heterozygous hybrid, linkage group 7 of the molecular map could be assigned to chromosome 9·8 of the classical Oenothera map. Finally, we provide the first direct molecular evidence that homologous recombination and free segregation of chromosomes in permanent translocation heterozygous strains is suppressed. PMID:18791241

Chemical synthesis, characterisation, and biocompatibility of nanometre scale porous anodic aluminium oxide membranes for use as a cell culture substrate for the vero cell line: a preliminary study.

PubMed

Poinern, Gérrard Eddy Jai; Le, Xuan Thi; O'Dea, Mark; Becker, Thomas; Fawcett, Derek

2014-01-01

In this preliminary study we investigate for the first time the biomedical potential of using porous anodic aluminium oxide (AAO) membranes as a cell substrate for culturing the Cercopithecus aethiops (African green monkey) Kidney (Vero) epithelial cell line. One advantage of using the inorganic AAO membrane is the presence of nanometre scale pore channels that allow the exchange of molecules and nutrients across the membrane. The size of the pore channels can be preselected by adjusting the controlling parameters of a temperature controlled two-step anodization process. The cellular interaction and response of the Vero cell line with an in-house synthesised AAO membrane, a commercially available membrane, and a glass control were assessed by investigating cell adhesion, morphology, and proliferation over a 72 h period. The number of viable cells proliferating over the respective membrane surfaces revealed that the locally produced in-house AAO membrane had cells numbers similar to the glass control. The study revealed evidence of focal adhesion sites over the surface of the nanoporous membranes and the penetration of cellular extensions into the pore structure as well. The outcome of the study has revealed that nanometre scale porous AAO membranes have the potential to become practical cell culture scaffold substrates with the capability to enhance adhesion and proliferation of Vero cells.

Chemical Synthesis, Characterisation, and Biocompatibility of Nanometre Scale Porous Anodic Aluminium Oxide Membranes for Use as a Cell Culture Substrate for the Vero Cell Line: A Preliminary Study

PubMed Central

Poinern, Gérrard Eddy Jai; Le, Xuan Thi; Becker, Thomas; Fawcett, Derek

2014-01-01

In this preliminary study we investigate for the first time the biomedical potential of using porous anodic aluminium oxide (AAO) membranes as a cell substrate for culturing the Cercopithecus aethiops (African green monkey) Kidney (Vero) epithelial cell line. One advantage of using the inorganic AAO membrane is the presence of nanometre scale pore channels that allow the exchange of molecules and nutrients across the membrane. The size of the pore channels can be preselected by adjusting the controlling parameters of a temperature controlled two-step anodization process. The cellular interaction and response of the Vero cell line with an in-house synthesised AAO membrane, a commercially available membrane, and a glass control were assessed by investigating cell adhesion, morphology, and proliferation over a 72 h period. The number of viable cells proliferating over the respective membrane surfaces revealed that the locally produced in-house AAO membrane had cells numbers similar to the glass control. The study revealed evidence of focal adhesion sites over the surface of the nanoporous membranes and the penetration of cellular extensions into the pore structure as well. The outcome of the study has revealed that nanometre scale porous AAO membranes have the potential to become practical cell culture scaffold substrates with the capability to enhance adhesion and proliferation of Vero cells. PMID:24579077

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.

PubMed

Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

2015-05-01

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.

Molecular spectral imaging system for quantitative immunohistochemical analysis of early diabetic retinopathy.

PubMed

Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng

2009-12-01

A molecular spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring molecular spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some molecular spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from molecular spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of molecular spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.

Catecholaminergic systems in stress: structural and molecular genetic approaches.

PubMed

Kvetnansky, Richard; Sabban, Esther L; Palkovits, Miklos

2009-04-01

Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct

Polysaccharide-Based Nanobiomaterials as Controlled Release Systems for Tissue Engineering Applications.

PubMed

Rodriguez-Velazquez, Eustolia; Alatorre-Meda, Manuel; Mano, Joao F

2015-01-01

Polysaccharides belong to a special class of biopolymers that has been used in different areas of research and technology for some years now. They present distinctive features attractive for the biomedical field. Among others, as extracted from natural sources, these materials are usually biocompatible and possess a significant ability to absorb water. Moreover, they can be conveniently modified by chemical means so as to display improved biological and physicochemical properties. The last but not the least, they are abundant in the natural Extracellular Matrix (ECM) and have a tremendous affinity for different endogenous macromolecules. Accordingly, these particular materials constitute outstanding candidates for a variety of biomimetic approaches entailing the entrapment/stabilization of bioactive molecules (e.g. growth factors, siRNA, and DNA) that could be delivered and have an effect on relevant cellular mechanisms, such as gene expression and cell viability, -proliferation, and -differentiation. This review will explore the current status of nano-scale drug delivery devices based on polysaccharides that could be used in tissue engineering and regenerative medicine (TERM). Aiming to contextualize the topics here discussed, especially for non-experts in the field, section 1 (Introduction) will present a brief overview of TERM and the principal polysaccharides herein employed. In order to get a broader perspective on both issues, this section will include a brief description of non-nanometric systems with relevant characteristics for TERM, such as injectable microparticles and macroscopic hydrogels, just to cite a few. Section 2 will illustrate the contributions of nanotechnology to the development of TERM, in particular to the development of biomimetic systems capable of replicating the natural, endogenous ECMs. Next, sections 3 to 6 will describe representative systems in the nanometric scale presenting 0D (nanoparticles), 1D (nanorods and nanowires), 2D (thin

Raster microdiffraction with synchrotron radiation of hydrated biopolymers with nanometre step-resolution: case study of starch granules

PubMed Central

Riekel, C.; Burghammer, M.; Davies, R. J.; Di Cola, E.; König, C.; Lemke, H.T.; Putaux, J.-L.; Schöder, S.

2010-01-01

X-ray radiation damage propagation is explored for hydrated starch granules in order to reduce the step resolution in raster-microdiffraction experiments to the nanometre range. Radiation damage was induced by synchrotron radiation microbeams of 5, 1 and 0.3 µm size with ∼0.1 nm wavelength in B-type potato, Canna edulis and Phajus grandifolius starch granules. A total loss of crystallinity of granules immersed in water was found at a dose of ∼1.3 photons nm−3. The temperature dependence of radiation damage suggests that primary radiation damage prevails up to about 120 K while secondary radiation damage becomes effective at higher temperatures. Primary radiation damage remains confined to the beam track at 100 K. Propagation of radiation damage beyond the beam track at room temperature is assumed to be due to reactive species generated principally by water radiolysis induced by photoelectrons. By careful dose selection during data collection, raster scans with 500 nm step-resolution could be performed for granules immersed in water. PMID:20975219

System Concept for Remote Measurement of Asteroid Molecular Composition

NASA Astrophysics Data System (ADS)

Hughes, G. B.; Lubin, P. M.; Zhang, Q.; Brashears, T.; Cohen, A. N.; Madajian, J.

2016-12-01

We propose a method for probing the molecular composition of cold solar system targets (asteroids, comets, planets, moons) from a distant vantage, such as from a spacecraft orbiting the object. A directed energy beam is focused on the target. With sufficient flux, the spot temperature rises rapidly, and evaporation of surface materials occurs. The melted spot creates a high-temperature blackbody source, and ejected material creates a plume of surface materials in front of the spot. Molecular and atomic absorption of the blackbody radiation occurs within the ejected plume. Bulk composition of the surface material is investigated by using a spectrometer to view the heated spot through the ejected material. Our proposed method differs from technologies such as Laser-Induced Breakdown Spectroscopy (LIBS), which atomizes and ionizes materials in the target; scattered ions emit characteristic radiation, and the LIBS detector performs atomic composition analysis by observing emission spectra. Standoff distance for LIBS is limited by the strength of characteristic emission, and distances greater than 10 m are problematic. Our proposed method detects atomic and molecular absorption spectra in the plume; standoff distance is limited by the size of heated spot, and the plume opacity; distances on the order of tens of kilometers are immediately feasible. Simulations have been developed for laser heating of a rocky target, with concomitant evaporation. Evaporation rates lead to determination of plume density and opacity. Absorption profiles for selected materials are estimated from plume properties. Initial simulations of absorption profiles with laser heating show great promise for molecular composition analysis from tens of kilometers distance. This paper explores the feasibility a hypothetical mission that seeks to perform surface molecular composition analysis of a near-earth asteroid while the craft orbits the asteroid. Such a system has compelling potential benefit for

Application to processing system using intra-molecular BRET

NASA Astrophysics Data System (ADS)

Otsuji, Tomomi; Okuda-Ashitaka, Emiko; Kojima, Satoshi; Akiyama, Hidehumi; Ito, Seiji; Ohmiya, Yoshihiro

2003-07-01

Luciferases are used as the reporter gene for promoter activity, whereas a green fluorescent protein (GFP) is used as marker for cellular function and localization. Recently, bioluminescence resonance energy transfer (BRET) between luciferase and YFP is used for analysis of inter-molecular reaction such as ligand-receptor in the living cells. The neuropeptides nocistatin (NST) and nociceptin/orphanin FQ (Noc/OFQ) are derived from the same precursor protein, while NST exhibits antagonism against Noc/OFQ-actions. In this study, we attempt an intra-molecular BRET system for monitoring dynamic biological process of the production of NST and Noc/OFQ in the living cells. At first, we constructed a fusion protein (Rluc-GFP) covalently linking luciferase (Renilla luciferase; Rluc) to Aequorea GFP as an intra-molecular BRET partner. Furthermore, we inserted constructs of mouse NST and Noc/OFQ (Rluc-m-GFP) or bovine NST and Noc/OFQ (Rluc-b-GFP) containing a proteolytic cleavage motif (Lys-Arg) within Rluc-GFP. When these constructions were transfected into Cos7 cells, all fusion proteins had luciferase activity and specific fluorescence. Luminescence spectra of Rluc-GFP, Rluc-m-GFP and Rluc-b-GFP fusion proteins with DeepBlueC as a substrate showed two peaks centered at 400 nm and 510 nm, whereas Rluc showed one peak centered at 400 nm. These results indicate that the proteolytic cleavage motif inserted fusion proteins between luciferase and GFP are available for intra-molecular BRET systems at first step.

Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation.

PubMed

Abou, D S; Pickett, J E; Thorek, D L J

2015-10-01

Molecular imaging provides considerable insight into biological processes for greater understanding of health and disease. Numerous advances in medical physics, chemistry and biology have driven the growth of this field in the past two decades. With exquisite sensitivity, depth of detection and potential for theranostics, radioactive imaging approaches have played a major role in the emergence of molecular imaging. At the same time, developments in materials science, characterization and synthesis have led to explosive progress in the nanoparticle (NP) sciences. NPs are generally defined as particles with a diameter in the nanometre size range. Unique physical, chemical and biological properties arise at this scale, stimulating interest for applications as diverse as energy production and storage, chemical catalysis and electronics. In biomedicine, NPs have generated perhaps the greatest attention. These materials directly interface with life at the subcellular scale of nucleic acids, membranes and proteins. In this review, we will detail the advances made in combining radioactive imaging and NPs. First, we provide an overview of the NP platforms and their properties. This is followed by a look at methods for radiolabelling NPs with gamma-emitting radionuclides for use in single photon emission CT and planar scintigraphy. Next, utilization of positron-emitting radionuclides for positron emission tomography is considered. Finally, recent advances for multimodal nuclear imaging with NPs and efforts for clinical translation and ongoing trials are discussed.

Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation

PubMed Central

Abou, D S; Pickett, J E

2015-01-01

Molecular imaging provides considerable insight into biological processes for greater understanding of health and disease. Numerous advances in medical physics, chemistry and biology have driven the growth of this field in the past two decades. With exquisite sensitivity, depth of detection and potential for theranostics, radioactive imaging approaches have played a major role in the emergence of molecular imaging. At the same time, developments in materials science, characterization and synthesis have led to explosive progress in the nanoparticle (NP) sciences. NPs are generally defined as particles with a diameter in the nanometre size range. Unique physical, chemical and biological properties arise at this scale, stimulating interest for applications as diverse as energy production and storage, chemical catalysis and electronics. In biomedicine, NPs have generated perhaps the greatest attention. These materials directly interface with life at the subcellular scale of nucleic acids, membranes and proteins. In this review, we will detail the advances made in combining radioactive imaging and NPs. First, we provide an overview of the NP platforms and their properties. This is followed by a look at methods for radiolabelling NPs with gamma-emitting radionuclides for use in single photon emission CT and planar scintigraphy. Next, utilization of positron-emitting radionuclides for positron emission tomography is considered. Finally, recent advances for multimodal nuclear imaging with NPs and efforts for clinical translation and ongoing trials are discussed. PMID:26133075

Autonomous Agents: The Origins and Co-Evolution of Reproducing Molecular Systems

NASA Technical Reports Server (NTRS)

Kauffman, Stuart

1999-01-01

The central aim of this award concerned an investigation into, and adequate formulation of, the concept of an "autonomous agent." If we consider a bacterium swimming upstream in a glucose gradient, we are willing to say of the bacterium that it is going to get food. That is, we are willing, and do, describe the bacterium as acting on its own behalf in an environment. All free living cells are, in this sense, autonomous agents. But the bacterium is "just" a set of molecules. We define an autonomous agent as a physical system able to act on its own behalf in an environment, then ask, "What must a physical system be to be an autonomous agent?" The tentative definition for a molecular autonomous agent is that it must be self-reproducing and carry out at least one thermodynamic work cycle. The work carried out in this grant involved, among other features, the development of a detailed model of a molecular autonomous agent, and study of the kinetics of this system. In particular, a molecular autonomous agent must, by the above tentative definition, not only reproduce, but must carry out at least one work cycle. I took, as a simple example of a self-reproducing molecular system, the single-stranded DNA hexamer 3'CCGCGG5' which can line up and ligate its two complementary trimers, 5'CCG3' and 5'CGG3'. But the two ligated trimers constitute the same molecular sequence in the 3' to 5' direction as the initial hexamer, hence this system is autocatalytic. On the other hand the above system is not yet an autonomous agent. At the minimum, autonomous agents, as I have defined them, are a new class of chemical reaction network. At a maximum, they may constitute a proper definition of life itself.

Molecular-Flow Properties of RIB Type Vapor-Transport Systems Using a Fast-Valve

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

Alton, Gerald D; Bilheux, Hassina Z; Zhang, Y.

2014-01-01

The advent of the fast-valve device, described previously, permits measurement of molecular-flow times of chemically active or inactive gaseous species through radioactive ion beam (RIB) target ion source systems, independent of size, geometry and materials of construction. Thus, decay losses of short-half-life RIBs can be determined for a given target/vapor-transport system in advance of on-line operation, thereby ascertaining the feasibility of the system design for successful processing of a given isotope. In this article, molecular-flow-time theory and experimentally measured molecular-flow time data are given for serial- and parallel-coupled Ta metal RIB vapor-transport systems similar to those used at ISOL basedmore » RIB facilities. In addition, the effect of source type on the molecular-flow time properties of a given system is addressed, and a chemical passivation method for negating surface adsorption enthalpies for chemically active gaseous species on Ta surfaces is demonstrated.« less

Cryogenic molecular separation system for radioactive (11)C ion acceleration.

PubMed

Katagiri, K; Noda, A; Suzuki, K; Nagatsu, K; Boytsov, A Yu; Donets, D E; Donets, E D; Donets, E E; Ramzdorf, A Yu; Nakao, M; Hojo, S; Wakui, T; Noda, K

2015-12-01

A (11)C molecular production/separation system (CMPS) has been developed as part of an isotope separation on line system for simultaneous positron emission tomography imaging and heavy-ion cancer therapy using radioactive (11)C ion beams. In the ISOL system, (11)CH4 molecules will be produced by proton irradiation and separated from residual air impurities and impurities produced during the irradiation. The CMPS includes two cryogenic traps to separate specific molecules selectively from impurities by using vapor pressure differences among the molecular species. To investigate the fundamental performance of the CMPS, we performed separation experiments with non-radioactive (12)CH4 gases, which can simulate the chemical characteristics of (11)CH4 gases. We investigated the separation of CH4 molecules from impurities, which will be present as residual gases and are expected to be difficult to separate because the vapor pressure of air molecules is close to that of CH4. We determined the collection/separation efficiencies of the CMPS for various amounts of air impurities and found desirable operating conditions for the CMPS to be used as a molecular separation device in our ISOL system.

Molecular mechanisms of aging and immune system regulation in Drosophila.

PubMed

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

Quantitative computational models of molecular self-assembly in systems biology

PubMed Central

Thomas, Marcus; Schwartz, Russell

2017-01-01

Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally. PMID:28535149

Quantitative computational models of molecular self-assembly in systems biology.

PubMed

Thomas, Marcus; Schwartz, Russell

2017-05-23

Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

Dynamic combinatorial libraries: from exploring molecular recognition to systems chemistry.

PubMed

Li, Jianwei; Nowak, Piotr; Otto, Sijbren

2013-06-26

Dynamic combinatorial chemistry (DCC) is a subset of combinatorial chemistry where the library members interconvert continuously by exchanging building blocks with each other. Dynamic combinatorial libraries (DCLs) are powerful tools for discovering the unexpected and have given rise to many fascinating molecules, ranging from interlocked structures to self-replicators. Furthermore, dynamic combinatorial molecular networks can produce emergent properties at systems level, which provide exciting new opportunities in systems chemistry. In this perspective we will highlight some new methodologies in this field and analyze selected examples of DCLs that are under thermodynamic control, leading to synthetic receptors, catalytic systems, and complex self-assembled supramolecular architectures. Also reviewed are extensions of the principles of DCC to systems that are not at equilibrium and may therefore harbor richer functional behavior. Examples include self-replication and molecular machines.

Comets as a possible source of nanodust in the Solar System cloud and in planetary debris discs.

PubMed

Mann, Ingrid

2017-07-13

Comets, comet-like objects and their fragments are the most plausible source for the dust in both the inner heliosphere and planetary debris discs around other stars. The smallest size of dust particles in debris discs is not known and recent observational results suggest that the size distribution of the dust extends down to sizes of a few nanometres or a few tens of nanometres. In the Solar System, electric field measurements from spacecraft observe events that are explained with high-velocity impacts of nanometre-sized dust. In some planetary debris discs an observed mid- to near-infrared emission supposedly results from hot dust located in the vicinity of the star. And the observed emission is characteristic of dust of sizes a few tens of nanometres. Rosetta observations, on the other hand, provide little information on the presence of nanodust near comet 67P/Churyumov-Gerasimenko. This article describes why this is not in contradiction to the observations of nanodust in the heliosphere and in planetary debris discs. The direct ejection of nanodust from the nucleus of the comet would not contribute significantly to the observed nanodust fluxes. We discuss a scenario that nanodust forms in the interplanetary dust cloud through the high-velocity collision process in the interplanetary medium for which the production rates are highest near the Sun. Likewise, fragmentation by collisions occurs near the star in planetary debris discs. The collisional fragmentation process in the inner Solar System occurs at similar velocities to those of the collisional evolution in the interstellar medium. A question for future studies is whether there is a common magic size of the smallest collision fragments and what determines this size.This article is part of the themed issue 'Cometary science after Rosetta'. © 2017 The Author(s).

Comets as a possible source of nanodust in the Solar System cloud and in planetary debris discs

NASA Astrophysics Data System (ADS)

Mann, Ingrid

2017-05-01

Comets, comet-like objects and their fragments are the most plausible source for the dust in both the inner heliosphere and planetary debris discs around other stars. The smallest size of dust particles in debris discs is not known and recent observational results suggest that the size distribution of the dust extends down to sizes of a few nanometres or a few tens of nanometres. In the Solar System, electric field measurements from spacecraft observe events that are explained with high-velocity impacts of nanometre-sized dust. In some planetary debris discs an observed mid- to near-infrared emission supposedly results from hot dust located in the vicinity of the star. And the observed emission is characteristic of dust of sizes a few tens of nanometres. Rosetta observations, on the other hand, provide little information on the presence of nanodust near comet 67P/Churyumov-Gerasimenko. This article describes why this is not in contradiction to the observations of nanodust in the heliosphere and in planetary debris discs. The direct ejection of nanodust from the nucleus of the comet would not contribute significantly to the observed nanodust fluxes. We discuss a scenario that nanodust forms in the interplanetary dust cloud through the high-velocity collision process in the interplanetary medium for which the production rates are highest near the Sun. Likewise, fragmentation by collisions occurs near the star in planetary debris discs. The collisional fragmentation process in the inner Solar System occurs at similar velocities to those of the collisional evolution in the interstellar medium. A question for future studies is whether there is a common magic size of the smallest collision fragments and what determines this size. This article is part of the themed issue 'Cometary science after Rosetta'.

A high resolution water soluble fullerene molecular resist for electron beam lithography.

PubMed

Chen, X; Palmer, R E; Robinson, A P G

2008-07-09

Traditionally, many lithography resists have used hazardous, environmentally damaging or flammable chemicals as casting solvent and developer. There is now a strong drive towards processes that are safer and more environmentally friendly. We report nanometre-scale patterning of a fullerene molecular resist film with electron beam lithography, using water as casting solvent and developer. Negative tone behaviour is demonstrated after exposure and development. The sensitivity of this resist to 20 keV electrons is 1.5 × 10(-2) C cm(-2). Arrays of lines with a width of 30-35 nm and pitches of 200 and 400 nm, and arrays of dots with a diameter of 40 nm and a pitch of 200 nm have been patterned at 30 keV. The etch durability of this resist was found to be ∼2 times that of a standard novolac based resist. Initial results of the chemical amplification of this material for enhanced sensitivity are also presented.

Molecular helices as electron acceptors in high-performance bulk heterojunction solar cells

DOE PAGES

Yu M. Zhong; Nam, Chang -Yong; Trinh, M. Tuan; ...

2015-09-18

Despite numerous organic semiconducting materials synthesized for organic photovoltaics in the past decade, fullerenes are widely used as electron acceptors in highly efficient bulk-heterojunction solar cells. None of the non-fullerene bulk heterojunction solar cells have achieved efficiencies as high as fullerene-based solar cells. Design principles for fullerene-free acceptors remain unclear in the field. Here we report examples of helical molecular semiconductors as electron acceptors that are on par with fullerene derivatives in efficient solar cells. We achieved an 8.3% power conversion efficiency in a solar cell, which is a record high for non-fullerene bulk heterojunctions. Femtosecond transient absorption spectroscopy revealedmore » both electron and hole transfer processes at the donor–acceptor interfaces. Atomic force microscopy reveals a mesh-like network of acceptors with pores that are tens of nanometres in diameter for efficient exciton separation and charge transport. As a result, this study describes a new motif for designing highly efficient acceptors for organic solar cells.« less

Molecular helices as electron acceptors in high-performance bulk heterojunction solar cells.

PubMed

Zhong, Yu; Trinh, M Tuan; Chen, Rongsheng; Purdum, Geoffrey E; Khlyabich, Petr P; Sezen, Melda; Oh, Seokjoon; Zhu, Haiming; Fowler, Brandon; Zhang, Boyuan; Wang, Wei; Nam, Chang-Yong; Sfeir, Matthew Y; Black, Charles T; Steigerwald, Michael L; Loo, Yueh-Lin; Ng, Fay; Zhu, X-Y; Nuckolls, Colin

2015-09-18

Despite numerous organic semiconducting materials synthesized for organic photovoltaics in the past decade, fullerenes are widely used as electron acceptors in highly efficient bulk-heterojunction solar cells. None of the non-fullerene bulk heterojunction solar cells have achieved efficiencies as high as fullerene-based solar cells. Design principles for fullerene-free acceptors remain unclear in the field. Here we report examples of helical molecular semiconductors as electron acceptors that are on par with fullerene derivatives in efficient solar cells. We achieved an 8.3% power conversion efficiency in a solar cell, which is a record high for non-fullerene bulk heterojunctions. Femtosecond transient absorption spectroscopy revealed both electron and hole transfer processes at the donor-acceptor interfaces. Atomic force microscopy reveals a mesh-like network of acceptors with pores that are tens of nanometres in diameter for efficient exciton separation and charge transport. This study describes a new motif for designing highly efficient acceptors for organic solar cells.

Design theory and performance of cryogenic molecular adsorption refrigeration systems

NASA Technical Reports Server (NTRS)

Hartwig, W. H.; Woltman, A. W.; Masson, J. P.

1978-01-01

Closed-cycle operation of molecular adsorption refrigeration systems (MARS) has been demonstrated by using thermally cycled zeolites to adsorb and desorb various gases under pressures of 20-60 atm. This paper develops three aspects of the design theory: the physical theory of molecular adsorption of small molecules such as A, N2, N2O and NH3, the design relations for closed-cycle flow for three or more compressors, and the coefficient of performance. This work is intended to demonstrate nonmechanical gas compression for various cryogenic gases than can compete with mechanical systems with a different mix of advantages and disadvantages.

Molecular Mechanisms of Aging and Immune System Regulation in Drosophila

PubMed Central

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span. PMID:22949833

ANN expert system screening for illicit amphetamines using molecular descriptors

NASA Astrophysics Data System (ADS)

Gosav, S.; Praisler, M.; Dorohoi, D. O.

2007-05-01

The goal of this study was to develop and an artificial neural network (ANN) based on computed descriptors, which would be able to classify the molecular structures of potential illicit amphetamines and to derive their biological activity according to the similarity of their molecular structure with amphetamines of known toxicity. The system is necessary for testing new molecular structures for epidemiological, clinical, and forensic purposes. It was built using a database formed by 146 compounds representing drugs of abuse (mainly central stimulants, hallucinogens, sympathomimetic amines, narcotics and other potent analgesics), precursors, or derivatized counterparts. Their molecular structures were characterized by computing three types of descriptors: 38 constitutional descriptors (CDs), 69 topological descriptors (TDs) and 160 3D-MoRSE descriptors (3DDs). An ANN system was built for each category of variables. All three networks (CD-NN, TD-NN and 3DD-NN) were trained to distinguish between stimulant amphetamines, hallucinogenic amphetamines, and nonamphetamines. A selection of variables was performed when necessary. The efficiency with which each network identifies the class identity of an unknown sample was evaluated by calculating several figures of merit. The results of the comparative analysis are presented.

Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

NASA Astrophysics Data System (ADS)

Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

2010-07-01

Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

Density functional theory based study of molecular interactions, recognition, engineering, and quantum transport in π molecular systems.

PubMed

Cho, Yeonchoo; Cho, Woo Jong; Youn, Il Seung; Lee, Geunsik; Singh, N Jiten; Kim, Kwang S

2014-11-18

CONSPECTUS: In chemical and biological systems, various interactions that govern the chemical and physical properties of molecules, assembling phenomena, and electronic transport properties compete and control the microscopic structure of materials. The well-controlled manipulation of each component can allow researchers to design receptors or sensors, new molecular architectures, structures with novel morphology, and functional molecules or devices. In this Account, we describe the structures and electronic and spintronic properties of π-molecular systems that are important for controlling the architecture of a variety of carbon-based systems. Although DFT is an important tool for describing molecular interactions, the inability of DFT to accurately represent dispersion interactions has made it difficult to properly describe π-interactions. However, the recently developed dispersion corrections for DFT have allowed us to include these dispersion interactions cost-effectively. We have investigated noncovalent interactions of various π-systems including aromatic-π, aliphatic-π, and non-π systems based on dispersion-corrected DFT (DFT-D). In addition, we have addressed the validity of DFT-D compared with the complete basis set (CBS) limit values of coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)] and Møller-Plesset second order perturbation theory (MP2). The DFT-D methods are still unable to predict the correct ordering in binding energies within the benzene dimer and the cyclohexane dimer. Nevertheless, the overall DFT-D predicted binding energies are in reasonable agreement with the CCSD(T) results. In most cases, results using the B97-D3 method closely reproduce the CCSD(T) results with the optimized energy-fitting parameters. On the other hand, vdW-DF2 and PBE0-TS methods estimate the dispersion energies from the calculated electron density. In these approximations, the interaction energies around the equilibrium

Measurement of track structure parameters of low and medium energy helium and carbon ions in nanometric volumes

NASA Astrophysics Data System (ADS)

Hilgers, G.; Bug, M. U.; Rabus, H.

2017-10-01

Ionization cluster size distributions produced in the sensitive volume of an ion-counting wall-less nanodosimeter by monoenergetic carbon ions with energies between 45 MeV and 150 MeV were measured at the TANDEM-ALPI ion accelerator facility complex of the LNL-INFN in Legnaro. Those produced by monoenergetic helium ions with energies between 2 MeV and 20 MeV were measured at the accelerator facilities of PTB and with a 241Am alpha particle source. C3H8 was used as the target gas. The ionization cluster size distributions were measured in narrow beam geometry with the primary beam passing the target volume at specified distances from its centre, and in broad beam geometry with a fan-like primary beam. By applying a suitable drift time window, the effective size of the target volume was adjusted to match the size of a DNA segment. The measured data were compared with the results of simulations obtained with the PTB Monte Carlo code PTra. Before the comparison, the simulated cluster size distributions were corrected with respect to the background of additional ionizations produced in the transport system of the ionized target gas molecules. Measured and simulated characteristics of the particle track structure are in good agreement for both types of primary particles and for both types of the irradiation geometry. As the range in tissue of the ions investigated is within the typical extension of a spread-out Bragg peak, these data are useful for benchmarking not only ‘general purpose’ track structure simulation codes, but also treatment planning codes used in hadron therapy. Additionally, these data sets may serve as a data base for codes modelling the induction of radiation damages at the DNA-level as they almost completely characterize the ionization component of the nanometric track structure.

Subtle Monte Carlo Updates in Dense Molecular Systems.

PubMed

Bottaro, Sandro; Boomsma, Wouter; E Johansson, Kristoffer; Andreetta, Christian; Hamelryck, Thomas; Ferkinghoff-Borg, Jesper

2012-02-14

Although Markov chain Monte Carlo (MC) simulation is a potentially powerful approach for exploring conformational space, it has been unable to compete with molecular dynamics (MD) in the analysis of high density structural states, such as the native state of globular proteins. Here, we introduce a kinetic algorithm, CRISP, that greatly enhances the sampling efficiency in all-atom MC simulations of dense systems. The algorithm is based on an exact analytical solution to the classic chain-closure problem, making it possible to express the interdependencies among degrees of freedom in the molecule as correlations in a multivariate Gaussian distribution. We demonstrate that our method reproduces structural variation in proteins with greater efficiency than current state-of-the-art Monte Carlo methods and has real-time simulation performance on par with molecular dynamics simulations. The presented results suggest our method as a valuable tool in the study of molecules in atomic detail, offering a potential alternative to molecular dynamics for probing long time-scale conformational transitions.

A 3D visualization system for molecular structures

NASA Technical Reports Server (NTRS)

Green, Terry J.

1989-01-01

The properties of molecules derive in part from their structures. Because of the importance of understanding molecular structures various methodologies, ranging from first principles to empirical technique, were developed for computing the structure of molecules. For large molecules such as polymer model compounds, the structural information is difficult to comprehend by examining tabulated data. Therefore, a molecular graphics display system, called MOLDS, was developed to help interpret the data. MOLDS is a menu-driven program developed to run on the LADC SNS computer systems. This program can read a data file generated by the modeling programs or data can be entered using the keyboard. MOLDS has the following capabilities: draws the 3-D representation of a molecule using stick, ball and ball, or space filled model from Cartesian coordinates, draws different perspective views of the molecule; rotates the molecule on the X, Y, Z axis or about some arbitrary line in space, zooms in on a small area of the molecule in order to obtain a better view of a specific region; and makes hard copy representation of molecules on a graphic printer. In addition, MOLDS can be easily updated and readily adapted to run on most computer systems.

Evolution of complex adaptations in molecular systems

PubMed Central

Pál, Csaba; Papp, Balázs

2017-01-01

A central challenge in evolutionary biology concerns the mechanisms by which complex adaptations arise. Such adaptations depend on the fixation of multiple, highly specific mutations, where intermediate stages of evolution seemingly provide little or no benefit. It is generally assumed that the establishment of complex adaptations is very slow in nature, as evolution of such traits demands special population genetic or environmental circumstances. However, blueprints of complex adaptations in molecular systems are pervasive, indicating that they can readily evolve. We discuss the prospects and limitations of non-adaptive scenarios, which assume multiple neutral or deleterious steps in the evolution of complex adaptations. Next, we examine how complex adaptations can evolve by natural selection in changing environment. Finally, we argue that molecular ’springboards’, such as phenotypic heterogeneity and promiscuous interactions facilitate this process by providing access to new adaptive paths. PMID:28782044

Self-assembled three-dimensional chiral colloidal architecture

NASA Astrophysics Data System (ADS)

Ben Zion, Matan Yah; He, Xiaojin; Maass, Corinna C.; Sha, Ruojie; Seeman, Nadrian C.; Chaikin, Paul M.

2017-11-01

Although stereochemistry has been a central focus of the molecular sciences since Pasteur, its province has previously been restricted to the nanometric scale. We have programmed the self-assembly of micron-sized colloidal clusters with structural information stemming from a nanometric arrangement. This was done by combining DNA nanotechnology with colloidal science. Using the functional flexibility of DNA origami in conjunction with the structural rigidity of colloidal particles, we demonstrate the parallel self-assembly of three-dimensional microconstructs, evincing highly specific geometry that includes control over position, dihedral angles, and cluster chirality.

[Molecular genetics of familial tumour syndromes of the central nervous system].

PubMed

Murnyák, Balázs; Szepesi, Rita; Hortobágyi, Tibor

2015-02-01

Although most of the central nervous system tumours are sporadic, rarely they are associated with familial tumour syndromes. These disorders usually present with an autosomal dominant inheritance and neoplasia develops at younger age than in sporadic cases. Most of these tumours are bilateral, multiplex or multifocal. The causative mutations occur in genes involved in cell cycle regulation, cell growth, differentiation and DNA repair. Studying these hereditary cancer predisposition syndromes associated with nervous system tumours can facilitate the deeper understanding of the molecular background of sporadic tumours and the development of novel therapeutic agents. This review is an update on hereditary tumour syndromes with nervous system involvement with emphasis on molecular genetic characteristics and their clinical implications.

Molecular clocks and the early evolution of metazoan nervous systems.

PubMed

Wray, Gregory A

2015-12-19

The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation. © 2015 The Author(s).

Development of a hybrid molecular beam epitaxy deposition system for in situ surface x-ray studies

NASA Astrophysics Data System (ADS)

Andersen, Tassie K.; Cook, Seyoung; Benda, Erika; Hong, Hawoong; Marks, Laurence D.; Fong, Dillon D.

2018-03-01

A portable metalorganic gas delivery system designed and constructed to interface with an existing molecular beam epitaxy chamber at beamline 33-ID-E of the Advanced Photon Source is described. This system offers the ability to perform in situ X-ray measurements of complex oxide growth via hybrid molecular beam epitaxy. The performance of the hybrid molecular beam epitaxy system while delivering metalorganic source materials is described. The high-energy X-ray scattering capabilities of the hybrid molecular beam epitaxy system are demonstrated both on oxide films grown solely from the metalorganic source and ABO3 oxide perovskites containing elements from both the metalorganic source and a traditional effusion cell.

Structure and atomic correlations in molecular systems probed by XAS reverse Monte Carlo refinement

NASA Astrophysics Data System (ADS)

Di Cicco, Andrea; Iesari, Fabio; Trapananti, Angela; D'Angelo, Paola; Filipponi, Adriano

2018-03-01

The Reverse Monte Carlo (RMC) algorithm for structure refinement has been applied to x-ray absorption spectroscopy (XAS) multiple-edge data sets for six gas phase molecular systems (SnI2, CdI2, BBr3, GaI3, GeBr4, GeI4). Sets of thousands of molecular replicas were involved in the refinement process, driven by the XAS data and constrained by available electron diffraction results. The equilibrated configurations were analysed to determine the average tridimensional structure and obtain reliable bond and bond-angle distributions. Detectable deviations from Gaussian models were found in some cases. This work shows that a RMC refinement of XAS data is able to provide geometrical models for molecular structures compatible with present experimental evidence. The validation of this approach on simple molecular systems is particularly important in view of its possible simple extension to more complex and extended systems including metal-organic complexes, biomolecules, or nanocrystalline systems.

The Optical Bichromatic Force in Molecular Systems

NASA Astrophysics Data System (ADS)

Aldridge, Leland; Galica, Scott; Eyler, E. E.

2015-05-01

The optical bichromatic force has been demonstrated to be useful for slowing atomic beams much more rapidly than radiative forces. Through numerical simulations, we examine several aspects of applying the bichromatic force to molecular beams. One is the unavoidable existence of out-of-system radiative decay, requiring one or more repumping beams. We find that the average deceleration varies strongly with the repumping intensity, but when using optimal parameters, the force approaches the limiting value allowed by population statistics. Another consideration is the effect of fine and hyperfine structure. We examine a simplified multlevel model based on the B <--> X transition in calcium monofluoride. To circumvent optical pumping into coherent dark states, we include two possible schemes: (1) a skewed dc magnetic field, and (2) rapid optical polarization switching. Our results indicate that the bichromatic force remains a viable option for creating large forces in molecular beams, with a reduction in the peak force by approximately an order of magnitude compared to a two-level atom, but little effect on the velocity range over which the force is effective. We also describe our progress towards experimental tests of the bichromatic force on a molecular beam of CaF. Supported by the National Science Foundation.

Long-range energy transport in single supramolecular nanofibres at room temperature

NASA Astrophysics Data System (ADS)

Haedler, Andreas T.; Kreger, Klaus; Issac, Abey; Wittmann, Bernd; Kivala, Milan; Hammer, Natalie; Köhler, Jürgen; Schmidt, Hans-Werner; Hildner, Richard

2015-07-01

Efficient transport of excitation energy over long distances is a key process in light-harvesting systems, as well as in molecular electronics. However, in synthetic disordered organic materials, the exciton diffusion length is typically only around 10 nanometres (refs 4, 5), or about 50 nanometres in exceptional cases, a distance that is largely determined by the probability laws of incoherent exciton hopping. Only for highly ordered organic systems has the transport of excitation energy over macroscopic distances been reported--for example, for triplet excitons in anthracene single crystals at room temperature, as well as along single polydiacetylene chains embedded in their monomer crystalline matrix at cryogenic temperatures (at 10 kelvin, or -263 degrees Celsius). For supramolecular nanostructures, uniaxial long-range transport has not been demonstrated at room temperature. Here we show that individual self-assembled nanofibres with molecular-scale diameter efficiently transport singlet excitons at ambient conditions over more than four micrometres, a distance that is limited only by the fibre length. Our data suggest that this remarkable long-range transport is predominantly coherent. Such coherent long-range transport is achieved by one-dimensional self-assembly of supramolecular building blocks, based on carbonyl-bridged triarylamines, into well defined H-type aggregates (in which individual monomers are aligned cofacially) with substantial electronic interactions. These findings may facilitate the development of organic nanophotonic devices and quantum information technology.

A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

ERIC Educational Resources Information Center

Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

2011-01-01

Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

Development of a hybrid molecular beam epitaxy deposition system for in situ surface x-ray studies

DOE PAGES

Andersen, Tassie K.; Cook, Seyoung; Benda, Erika; ...

2018-03-08

A portable metalorganic gas delivery system designed and constructed to interface with an existing molecular beam epitaxy chamber at beamline 33-ID-E of the Advanced Photon Source is described. This system offers the ability to perform in situ X-ray measurements of complex oxide growth via hybrid molecular beam epitaxy. The performance of the hybrid molecular beam epitaxy system while delivering metalorganic source materials is described. In conclusion, the high-energy X-ray scattering capabilities of the hybrid molecular beam epitaxy system are demonstrated both on oxide films grown solely from the metalorganic source and ABO 3 oxide perovskites containing elements from both themore » metalorganic source and a traditional effusion cell.« less

Development of a hybrid molecular beam epitaxy deposition system for in situ surface x-ray studies

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

Andersen, Tassie K.; Cook, Seyoung; Benda, Erika

A portable metalorganic gas delivery system designed and constructed to interface with an existing molecular beam epitaxy chamber at beamline 33-ID-E of the Advanced Photon Source is described. This system offers the ability to perform in situ X-ray measurements of complex oxide growth via hybrid molecular beam epitaxy. The performance of the hybrid molecular beam epitaxy system while delivering metalorganic source materials is described. In conclusion, the high-energy X-ray scattering capabilities of the hybrid molecular beam epitaxy system are demonstrated both on oxide films grown solely from the metalorganic source and ABO 3 oxide perovskites containing elements from both themore » metalorganic source and a traditional effusion cell.« less

Elucidation of molecular kinetic schemes from macroscopic traces using system identification

PubMed Central

González-Maeso, Javier; Sealfon, Stuart C.; Galocha-Iragüen, Belén; Brezina, Vladimir

2017-01-01

Overall cellular responses to biologically-relevant stimuli are mediated by networks of simpler lower-level processes. Although information about some of these processes can now be obtained by visualizing and recording events at the molecular level, this is still possible only in especially favorable cases. Therefore the development of methods to extract the dynamics and relationships between the different lower-level (microscopic) processes from the overall (macroscopic) response remains a crucial challenge in the understanding of many aspects of physiology. Here we have devised a hybrid computational-analytical method to accomplish this task, the SYStems-based MOLecular kinetic scheme Extractor (SYSMOLE). SYSMOLE utilizes system-identification input-output analysis to obtain a transfer function between the stimulus and the overall cellular response in the Laplace-transformed domain. It then derives a Markov-chain state molecular kinetic scheme uniquely associated with the transfer function by means of a classification procedure and an analytical step that imposes general biological constraints. We first tested SYSMOLE with synthetic data and evaluated its performance in terms of its rate of convergence to the correct molecular kinetic scheme and its robustness to noise. We then examined its performance on real experimental traces by analyzing macroscopic calcium-current traces elicited by membrane depolarization. SYSMOLE derived the correct, previously known molecular kinetic scheme describing the activation and inactivation of the underlying calcium channels and correctly identified the accepted mechanism of action of nifedipine, a calcium-channel blocker clinically used in patients with cardiovascular disease. Finally, we applied SYSMOLE to study the pharmacology of a new class of glutamate antipsychotic drugs and their crosstalk mechanism through a heteromeric complex of G protein-coupled receptors. Our results indicate that our methodology can be successfully

Light-powered autonomous and directional molecular motion of a dissipative self-assembling system

NASA Astrophysics Data System (ADS)

Ragazzon, Giulio; Baroncini, Massimo; Silvi, Serena; Venturi, Margherita; Credi, Alberto

2015-01-01

Biomolecular motors convert energy into directed motion and operate away from thermal equilibrium. The development of dynamic chemical systems that exploit dissipative (non-equilibrium) processes is a challenge in supramolecular chemistry and a premise for the realization of artificial nanoscale motors. Here, we report the relative unidirectional transit of a non-symmetric molecular axle through a macrocycle powered solely by light. The molecular machine rectifies Brownian fluctuations by energy and information ratchet mechanisms and can repeat its working cycle under photostationary conditions. The system epitomizes the conceptual and practical elements forming the basis of autonomous light-powered directed motion with a minimalist molecular design.

Electronic properties of a molecular system with Platinum

NASA Astrophysics Data System (ADS)

Ojeda, J. H.; Medina, F. G.; Becerra-Alonso, David

2017-10-01

The electronic properties are studied using a finite homogeneous molecule called Trans-platinum-linked oligo(tetraethenylethenes). This system is composed of individual molecules such as benzene rings, platinum, Phosphore and Sulfur. The mechanism for the study of the electron transport through this system is based on placing the molecule between metal contacts to control the current through the molecular system. We study this molecule based on the tight-binding approach for the calculation of the transport properties using the Landauer-Büttiker formalism and the Fischer-Lee relationship, based on a semi-analytic Green's function method within a real-space renormalization approach. Our results show a significant agreement with experimental measurements.

Oriented nanometric aggregates of partially inverted zinc ferrite: One-step processing and tunable high-frequency magnetic properties

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

Sai, Ranajit, E-mail: ranajit@ecei.tohoku.ac.jp; Centre for Nano Science and Engineering, Indian Institute of Science, Bangalore; Endo, Yasushi

2015-05-07

In this work, it is demonstrated that the in situ growth of oriented nanometric aggregates of partially inverted zinc ferrite can potentially pave a way to alter and tune magnetocrystalline anisotropy that, in turn, dictates ferromagnetic resonance frequency (f{sub FMR}) by inducing strain due to aggregation. Furthermore, the influence of interparticle interaction on magnetic properties of the aggregates is investigated. Mono-dispersed zinc ferrite nanoparticles (<5 nm) with various degrees of aggregation were prepared through decomposition of metal-organic compounds of zinc (II) and iron (III) in an alcoholic solution under controlled microwave irradiation, below 200 °C. The nanocrystallites were found to possess highmore » degree of inversion (>0.5). With increasing order of aggregation in the samples, saturation magnetization (at 5 K) is found to decrease from 38 emu/g to 24 emu/g, while coercivity is found to increase gradually by up to 100% (525 Oe to 1040 Oe). Anisotropy-mediated shift of f{sub FMR} has also been measured and discussed. In essence, the result exhibits an easy way to control the magnetic characteristics of nanocrystalline zinc ferrite, boosted with significant degree of inversion, at GHz frequencies.« less

Preface - From molecules to molecular materials, biological molecular systems and nanostructures: A collection of contributions presented at the XIIIth International Conference on Molecular Spectroscopy

NASA Astrophysics Data System (ADS)

Ratajczak, Henryk; Drozd, Marek; Fausto, Rui

2016-12-01

This volume contains a series of selected contributions presented at the XIIIth International Conference on Molecular Spectroscopy (ICMS): "From Molecules to Molecular Materials, Biological Molecular Systems and Nanostructures" held in Wrocław, Poland, 9-12 September 2015, under the auspices of the Mayor of Wrocław and the European Academy of Sciences, Arts and Humanities. Wrocław was chosen not accidentally as venue for the conference. With more than a thousand years of history, Wrocław is the location of one of the oldest universities in Central Europe. Being a place where education and science play major roles in the daily life of its inhabitants, Wrocław is also a privileged center for spectroscopy in Poland.

Electron-correlated fragment-molecular-orbital calculations for biomolecular and nano systems.

PubMed

Tanaka, Shigenori; Mochizuki, Yuji; Komeiji, Yuto; Okiyama, Yoshio; Fukuzawa, Kaori

2014-06-14

Recent developments in the fragment molecular orbital (FMO) method for theoretical formulation, implementation, and application to nano and biomolecular systems are reviewed. The FMO method has enabled ab initio quantum-mechanical calculations for large molecular systems such as protein-ligand complexes at a reasonable computational cost in a parallelized way. There have been a wealth of application outcomes from the FMO method in the fields of biochemistry, medicinal chemistry and nanotechnology, in which the electron correlation effects play vital roles. With the aid of the advances in high-performance computing, the FMO method promises larger, faster, and more accurate simulations of biomolecular and related systems, including the descriptions of dynamical behaviors in solvent environments. The current status and future prospects of the FMO scheme are addressed in these contexts.

MDGRAPE-4: a special-purpose computer system for molecular dynamics simulations.

PubMed

Ohmura, Itta; Morimoto, Gentaro; Ohno, Yousuke; Hasegawa, Aki; Taiji, Makoto

2014-08-06

We are developing the MDGRAPE-4, a special-purpose computer system for molecular dynamics (MD) simulations. MDGRAPE-4 is designed to achieve strong scalability for protein MD simulations through the integration of general-purpose cores, dedicated pipelines, memory banks and network interfaces (NIFs) to create a system on chip (SoC). Each SoC has 64 dedicated pipelines that are used for non-bonded force calculations and run at 0.8 GHz. Additionally, it has 65 Tensilica Xtensa LX cores with single-precision floating-point units that are used for other calculations and run at 0.6 GHz. At peak performance levels, each SoC can evaluate 51.2 G interactions per second. It also has 1.8 MB of embedded shared memory banks and six network units with a peak bandwidth of 7.2 GB s(-1) for the three-dimensional torus network. The system consists of 512 (8×8×8) SoCs in total, which are mounted on 64 node modules with eight SoCs. The optical transmitters/receivers are used for internode communication. The expected maximum power consumption is 50 kW. While MDGRAPE-4 software has still been improved, we plan to run MD simulations on MDGRAPE-4 in 2014. The MDGRAPE-4 system will enable long-time molecular dynamics simulations of small systems. It is also useful for multiscale molecular simulations where the particle simulation parts often become bottlenecks.

MDGRAPE-4: a special-purpose computer system for molecular dynamics simulations

PubMed Central

Ohmura, Itta; Morimoto, Gentaro; Ohno, Yousuke; Hasegawa, Aki; Taiji, Makoto

2014-01-01

We are developing the MDGRAPE-4, a special-purpose computer system for molecular dynamics (MD) simulations. MDGRAPE-4 is designed to achieve strong scalability for protein MD simulations through the integration of general-purpose cores, dedicated pipelines, memory banks and network interfaces (NIFs) to create a system on chip (SoC). Each SoC has 64 dedicated pipelines that are used for non-bonded force calculations and run at 0.8 GHz. Additionally, it has 65 Tensilica Xtensa LX cores with single-precision floating-point units that are used for other calculations and run at 0.6 GHz. At peak performance levels, each SoC can evaluate 51.2 G interactions per second. It also has 1.8 MB of embedded shared memory banks and six network units with a peak bandwidth of 7.2 GB s−1 for the three-dimensional torus network. The system consists of 512 (8×8×8) SoCs in total, which are mounted on 64 node modules with eight SoCs. The optical transmitters/receivers are used for internode communication. The expected maximum power consumption is 50 kW. While MDGRAPE-4 software has still been improved, we plan to run MD simulations on MDGRAPE-4 in 2014. The MDGRAPE-4 system will enable long-time molecular dynamics simulations of small systems. It is also useful for multiscale molecular simulations where the particle simulation parts often become bottlenecks. PMID:24982255

[Motivation and Emotional States: Structural Systemic, Neurochemical, Molecular and Cellular Mechanisms].

PubMed

Bazyan, A S

2016-01-01

The structural, systemic, neurochemical, molecular and cellular mechanisms of organization and coding motivation and emotional states are describe. The GABA and glutamatergic synaptic systems of basal ganglia form a neural network and participate in the implementation of voluntary behavior. Neuropeptides, neurohormones and paracrine neuromodulators involved in the organization of motivation and emotional states, integrated with synaptic systems, controlled by neural networks and organizing goal-directed behavior. Structural centers for united and integrated of information in voluntary and goal-directed behavior are globus pallidus. Substantia nigra pars reticulata switches the information from corticobasal networks to thalamocortical networks, induces global dopaminergic (DA) signal and organize interaction of mesolimbic and nigostriatnoy DA systems controlled by prefrontal and motor cortex. Together with the motor cortex, substantia nigra displays information in the brainstem and spinal cord to implementation of behavior. Motivation states are formed in the interaction of neurohormonal and neuropeptide systems by monoaminergic systems of brain. Emotional states are formed by monoaminergic systems of the mid-brain, where the leading role belongs to the mesolimbic DA system. The emotional and motivation state of the encoded specific epigenetic molecular and chemical pattern of neuron.

Modeling and enhanced sampling of molecular systems with smooth and nonlinear data-driven collective variables.

PubMed

Hashemian, Behrooz; Millán, Daniel; Arroyo, Marino

2013-12-07

Collective variables (CVs) are low-dimensional representations of the state of a complex system, which help us rationalize molecular conformations and sample free energy landscapes with molecular dynamics simulations. Given their importance, there is need for systematic methods that effectively identify CVs for complex systems. In recent years, nonlinear manifold learning has shown its ability to automatically characterize molecular collective behavior. Unfortunately, these methods fail to provide a differentiable function mapping high-dimensional configurations to their low-dimensional representation, as required in enhanced sampling methods. We introduce a methodology that, starting from an ensemble representative of molecular flexibility, builds smooth and nonlinear data-driven collective variables (SandCV) from the output of nonlinear manifold learning algorithms. We demonstrate the method with a standard benchmark molecule, alanine dipeptide, and show how it can be non-intrusively combined with off-the-shelf enhanced sampling methods, here the adaptive biasing force method. We illustrate how enhanced sampling simulations with SandCV can explore regions that were poorly sampled in the original molecular ensemble. We further explore the transferability of SandCV from a simpler system, alanine dipeptide in vacuum, to a more complex system, alanine dipeptide in explicit water.

Modeling and enhanced sampling of molecular systems with smooth and nonlinear data-driven collective variables

NASA Astrophysics Data System (ADS)

Hashemian, Behrooz; Millán, Daniel; Arroyo, Marino

2013-12-01

Collective variables (CVs) are low-dimensional representations of the state of a complex system, which help us rationalize molecular conformations and sample free energy landscapes with molecular dynamics simulations. Given their importance, there is need for systematic methods that effectively identify CVs for complex systems. In recent years, nonlinear manifold learning has shown its ability to automatically characterize molecular collective behavior. Unfortunately, these methods fail to provide a differentiable function mapping high-dimensional configurations to their low-dimensional representation, as required in enhanced sampling methods. We introduce a methodology that, starting from an ensemble representative of molecular flexibility, builds smooth and nonlinear data-driven collective variables (SandCV) from the output of nonlinear manifold learning algorithms. We demonstrate the method with a standard benchmark molecule, alanine dipeptide, and show how it can be non-intrusively combined with off-the-shelf enhanced sampling methods, here the adaptive biasing force method. We illustrate how enhanced sampling simulations with SandCV can explore regions that were poorly sampled in the original molecular ensemble. We further explore the transferability of SandCV from a simpler system, alanine dipeptide in vacuum, to a more complex system, alanine dipeptide in explicit water.

Heat treatment influence on the superconducting properties of nanometric-scale Nb3Sn wires with Cu-Sn artificial pinning centers

NASA Astrophysics Data System (ADS)

Da Silva, L. B. S.; Rodrigues, C. A.; Oliveira, N. F., Jr.; Bormio-Nunes, C.; Rodrigues, D., Jr.

2010-11-01

Since the discovery of Nb3Sn superconductors many efforts have been expended to improve the transport properties in these materials. In this work, the heat treatment profiles for Nb3Sn superconductor wires with Cu(Sn) artificial pinning centers (APCs) with nanometric-scale sizes were analyzed in an attempt to improve the critical current densities and upper critical magnetic field. The methodology to optimize the heat treatment profiles in respect to the diffusion, reaction and formation of the superconducting phases is described. Microstructural characterization, transport and magnetic measurements were performed in an attempt to relate the microstructure to the pinning mechanisms acting in the samples. It was concluded that the maximum current densities occur due to normal phases (APCs) that act as the main pinning centers in the global behavior of the Nb3Sn superconducting wire. The APC technique was shown to be very powerful because it permitted mixing of the pinning mechanism. This achievement was not possible in other studies in Nb3Sn wires reported up to now.

Optical detection of nanometric thermal fluctuations to measure the stiffness of rigid superparamagnetic microrods

PubMed Central

Wang, Yuan

2017-01-01

The rigidity of numerous biological filaments and crafted microrods has been conveniently deduced from the analysis of their thermal fluctuations. However, the difficulty of measuring nanometric displacements with an optical microscope has so far limited such studies to sufficiently flexible rods, of which the persistence length (Lp) rarely exceeds 1 m at room temperature. Here, we demonstrate the possibility to probe 10-fold stiffer rods by a combination of superresolutive optical methods and a statistical analysis of the data based on a recent theoretical model that predicts the amplitude of the fluctuations at any location of the rod [Benetatos P, Frey E (2003) Phys Rev E Stat Nonlin Soft Matter Phys 67(5):051108]. Using this approach, we report measures of Lp up to 0.5 km. We obtained these measurements on recently designed superparamagnetic ∼40-μm-long microrods containing iron-oxide nanoparticles connected by a polymer mesh. Using their magnetic properties, we provide an alternative proof of validity of these thermal measurements: For each individual studied rod, we performed a second measure of its rigidity by deflecting it with a uniform magnetic field. The agreement between the thermal and the magnetoelastic measures was realized with more than a decade of values of Lp from 5.1 m to 129 m, corresponding to a bending modulus ranging from 2.2 to 54 (×10−20 Jm). Despite the apparent homogeneity of the analyzed microrods, their Young modulus follows a broad distribution from 1.9 MPa to 59 MPa and up to 200 MPa, depending on the size of the nanoparticles. PMID:28228530

Insights into structural and dynamical features of water at halloysite interfaces probed by DFT and classical molecular dynamics simulations.

PubMed

Presti, Davide; Pedone, Alfonso; Mancini, Giordano; Duce, Celia; Tiné, Maria Rosaria; Barone, Vincenzo

2016-01-21

Density functional theory calculations and classical molecular dynamics simulations have been used to investigate the structure and dynamics of water molecules on kaolinite surfaces and confined in the interlayer of a halloysite model of nanometric dimension. The first technique allowed us to accurately describe the structure of the tetrahedral-octahedral slab of kaolinite in vacuum and in interaction with water molecules and to assess the performance of two widely employed empirical force fields to model water/clay interfaces. Classical molecular dynamics simulations were used to study the hydrogen bond network structure and dynamics of water adsorbed on kaolinite surfaces and confined in the halloysite interlayer. The results are in nice agreement with the few experimental data available in the literature, showing a pronounced ordering and reduced mobility of water molecules at the hydrophilic octahedral surfaces of kaolinite and confined in the halloysite interlayer, with respect to water interacting with the hydrophobic tetrahedral surfaces and in the bulk. Finally, this investigation provides new atomistic insights into the structural and dynamical properties of water-clay interfaces, which are of fundamental importance for both natural processes and industrial applications.

Stable and solubilized active Au atom clusters for selective epoxidation of cis-cyclooctene with molecular oxygen

DOE PAGES

Qian, Linping; Wang, Zhen; Beletskiy, Evgeny V.; ...

2017-03-28

Here, the ability of Au catalysts to effect the challenging task of utilizing molecular oxygen for the selective epoxidation of cyclooctene is fascinating. Although supported nanometre-size Au particles are poorly active, here we show that solubilized atomic Au clusters, present in ng ml –1 concentrations and stabilized by ligands derived from the oxidized hydrocarbon products, are active. They can be formed from various Au sources. They generate initiators and propagators to trigger the onset of the auto-oxidation reaction with an apparent turnover frequency of 440 s –1, and continue to generate additional initiators throughout the auto-oxidation cycle without direct participationmore » in the cycle. Spectroscopic characterization suggests that 7–8 atom clusters are effective catalytically. Extension of work based on these understandings leads to the demonstration that these Au clusters are also effective in selective oxidation of cyclohexene, and that solubilized Pt clusters are also capable of generating initiators for cyclooctene epoxidation.« less

Stable and solubilized active Au atom clusters for selective epoxidation of cis-cyclooctene with molecular oxygen

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

Qian, Linping; Wang, Zhen; Beletskiy, Evgeny V.

Here, the ability of Au catalysts to effect the challenging task of utilizing molecular oxygen for the selective epoxidation of cyclooctene is fascinating. Although supported nanometre-size Au particles are poorly active, here we show that solubilized atomic Au clusters, present in ng ml –1 concentrations and stabilized by ligands derived from the oxidized hydrocarbon products, are active. They can be formed from various Au sources. They generate initiators and propagators to trigger the onset of the auto-oxidation reaction with an apparent turnover frequency of 440 s –1, and continue to generate additional initiators throughout the auto-oxidation cycle without direct participationmore » in the cycle. Spectroscopic characterization suggests that 7–8 atom clusters are effective catalytically. Extension of work based on these understandings leads to the demonstration that these Au clusters are also effective in selective oxidation of cyclohexene, and that solubilized Pt clusters are also capable of generating initiators for cyclooctene epoxidation.« less

EUV-angle resolved scatter (EUV-ARS): a new tool for the characterization of nanometre structures

NASA Astrophysics Data System (ADS)

Fernández Herrero, Analía.; Mentzel, Heiko; Soltwisch, Victor; Jaroslawzew, Sina; Laubis, Christian; Scholze, Frank

2018-03-01

The advance of the semiconductor industry requires new metrology methods, which can deal with smaller and more complex nanostructures. Particularly for inline metrology a rapid, sensitive and non destructive method is needed. Small angle X-ray scattering under grazing incidence has already been investigated for this application and delivers significant statistical information which tracks the profile parameters as well as their variations, i.e. roughness. However, it suffers from the elongated footprint at the sample. The advantage of EUV radiation, with its longer wavelengths, is that larger incidence angles can be used, resulting in a significant reduction of the beam footprint. Targets with field sizes of 100 μm and smaller are accessible with our experimental set-up. We present a new experimental tool for the measurement of small structures based on the capabilities of soft X-ray and EUV scatterometry at the PTB soft X-ray beamline at the electron storage ring BESSY II. PTB's soft X-ray radiometry beamline uses a plane grating monochromator, which covers the spectral range from 0.7 nm to 25 nm and was especially designed to provide highly collimated radiation. An area detector covers the scattered radiation from a grazing exit angle up to an angle of 30° above the sample horizon and the fluorescence emission can be detected with an energy dispersive X-ray silicon drift detector. In addition, the sample can be rotated and linearly moved in vacuum. This new set-up will be used to explore the capabilities of EUV-scatterometry for the characterization of nanometre-sized structures.

The nanometre-scale physiology of bone: steric modelling and scanning transmission electron microscopy of collagen–mineral structure

PubMed Central

Alexander, Benjamin; Daulton, Tyrone L.; Genin, Guy M.; Lipner, Justin; Pasteris, Jill D.; Wopenka, Brigitte; Thomopoulos, Stavros

2012-01-01

The nanometre-scale structure of collagen and bioapatite within bone establishes bone's physical properties, including strength and toughness. However, the nanostructural organization within bone is not well known and is debated. Widely accepted models hypothesize that apatite mineral (‘bioapatite’) is present predominantly inside collagen fibrils: in ‘gap channels’ between abutting collagen molecules, and in ‘intermolecular spaces’ between adjacent collagen molecules. However, recent studies report evidence of substantial extrafibrillar bioapatite, challenging this hypothesis. We studied the nanostructure of bioapatite and collagen in mouse bones by scanning transmission electron microscopy (STEM) using electron energy loss spectroscopy and high-angle annular dark-field imaging. Additionally, we developed a steric model to estimate the packing density of bioapatite within gap channels. Our steric model and STEM results constrain the fraction of total bioapatite in bone that is distributed within fibrils at less than or equal to 0.42 inside gap channels and less than or equal to 0.28 inside intermolecular overlap regions. Therefore, a significant fraction of bone's bioapatite (greater than or equal to 0.3) must be external to the fibrils. Furthermore, we observe extrafibrillar bioapatite between non-mineralized collagen fibrils, suggesting that initial bioapatite nucleation and growth are not confined to the gap channels as hypothesized in some models. These results have important implications for the mechanics of partially mineralized and developing tissues. PMID:22345156

Development of design information for molecular-sieve type regenerative CO2-removal systems

NASA Technical Reports Server (NTRS)

Wright, R. M.; Ruder, J. M.; Dunn, V. B.; Hwang, K. C.

1973-01-01

Experimental and analytic studies were conducted with molecular sieve sorbents to provide basic design information, and to develop a system design technique for regenerable CO2-removal systems for manned spacecraft. Single sorbate equilibrium data were obtained over a wide range of conditions for CO2, water, nitrogen, and oxygen on several molecular sieve and silica gel sorbents. The coadsorption of CO2 with water preloads, and with oxygen and nitrogen was experimentally evaluated. Mass-transfer, and some limited heat-transfer performance evaluations were accomplished under representative operating conditions, including the coadsorption of CO2 and water. CO2-removal system performance prediction capability was derived.

The generation of meaningful information in molecular systems.

PubMed

Wills, Peter R

2016-03-13

The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. The origin and evolution of genetic information (nucleic acid sequences) is reasonably well understood, but scant attention has been paid to the origin and evolution of the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. We take the origin of genetic coding as a paradigm of the emergence of computation in natural systems, focusing on the requirement that the molecular components of an interpreter be synthesized autocatalytically. Within this context, it is seen that interpreters of increasing complexity are generated by series of transitions through stepped dynamic instabilities (non-equilibrium phase transitions). The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it. © 2016 The Author(s).

Molecular ion battery: a rechargeable system without using any elemental ions as a charge carrier

PubMed Central

Yao, Masaru; Sano, Hikaru; Ando, Hisanori; Kiyobayashi, Tetsu

2015-01-01

Is it possible to exceed the lithium redox potential in electrochemical systems? It seems impossible to exceed the lithium potential because the redox potential of the elemental lithium is the lowest among all the elements, which contributes to the high voltage characteristics of the widely used lithium ion battery. However, it should be possible when we use a molecule-based ion which is not reduced even at the lithium potential in principle. Here we propose a new model system using a molecular electrolyte salt with polymer-based active materials in order to verify whether a molecular ion species serves as a charge carrier. Although the potential of the negative-electrode is not yet lower than that of lithium at present, this study reveals that a molecular ion can work as a charge carrier in a battery and the system is certainly a molecular ion-based “rocking chair” type battery. PMID:26043147

A Hadoop-based Molecular Docking System

NASA Astrophysics Data System (ADS)

Dong, Yueli; Guo, Quan; Sun, Bin

2017-10-01

Molecular docking always faces the challenge of managing tens of TB datasets. It is necessary to improve the efficiency of the storage and docking. We proposed the molecular docking platform based on Hadoop for virtual screening, it provides the preprocessing of ligand datasets and the analysis function of the docking results. A molecular cloud database that supports mass data management is constructed. Through this platform, the docking time is reduced, the data storage is efficient, and the management of the ligand datasets is convenient.

Chapter 5 Multiple, Localized, and Delocalized/Conjugated Bonds in the Orbital Communication Theory of Molecular Systems

NASA Astrophysics Data System (ADS)

Nalewajski, Roman F.

Information theory (IT) probe of the molecular electronic structure, within the communication theory of chemical bonds (CTCB), uses the standard entropy/information descriptors of the Shannon theory of communication to characterize a scattering of the electronic probabilities and their information content throughout the system chemical bonds generated by the occupied molecular orbitals (MO). These "communications" between the basis-set orbitals are determined by the two-orbital conditional probabilities: one- and two-electron in character. They define the molecular information system, in which the electron-allocation "signals" are transmitted between various orbital "inputs" and "outputs". It is argued, using the quantum mechanical superposition principle, that the one-electron conditional probabilities are proportional to the squares of corresponding elements of the charge and bond-order (CBO) matrix of the standard LCAO MO theory. Therefore, the probability of the interorbital connections in the molecular communication system is directly related to Wiberg's quadratic covalency indices of chemical bonds. The conditional-entropy (communication "noise") and mutual-information (information capacity) descriptors of these molecular channels generate the IT-covalent and IT-ionic bond components, respectively. The former reflects the electron delocalization (indeterminacy) due to the orbital mixing, throughout all chemical bonds in the system under consideration. The latter characterizes the localization (determinacy) in the probability scattering in the molecule. These two IT indices, respectively, indicate a fraction of the input information lost in the channel output, due to the communication noise, and its surviving part, due to deterministic elements in probability scattering in the molecular network. Together, these two components generate the system overall bond index. By a straightforward output reduction (condensation) of the molecular channel, the IT indices of

Supramolecular assembly/reassembly processes: molecular motors and dynamers operating at surfaces.

PubMed

Ciesielski, Artur; Samorì, Paolo

2011-04-01

Among the many significant advances within the field of supramolecular chemistry over the past decades, the development of the so-called "dynamers" features a direct relevance to materials science. Defined as "combinatorial dynamic polymers", dynamers are constitutional dynamic systems and materials resulting from the application of the principles of supramolecular chemistry to polymer science. Like supramolecular materials in general, dynamers are reversible dynamic multifunctional architectures, capable of modifying their constitution by exchanging, recombining, incorporating components. They may exhibit a variety of novel properties and behave as adaptive materials. In this review we focus on the design of responsive switchable monolayers, i.e. monolayers capable to undergo significant changes in their physical or chemical properties as a result of external stimuli. Scanning tunneling microscopy studies provide direct evidence with a sub-nanometre resolution, on the formation and dynamic response of these self-assembled systems featuring controlled geometries and properties.

A high performance system for molecular dynamics simulation of biomolecules using a special-purpose computer.

PubMed

Komeiji, Y; Yokoyama, H; Uebayasi, M; Taiji, M; Fukushige, T; Sugimoto, D; Takata, R; Shimizu, A; Itsukashi, K

1996-01-01

GRAPE (GRavity PipE) processors are special purpose computers for simulation of classical particles. The performance of MD-GRAPE, one of the GRAPEs developed for molecular dynamics, was investigated. The effective speed of MD-GRAPE was equivalent to approximately 6 Gflops. The precision of MD-GRAPE was good judging from the acceptable fluctuation of the total energy. Then a software named PEACH (Program for Energetic Analysis of bioCHemical molecules) was developed for molecular dynamics of biomolecules in combination with MD-GRAPE. Molecular dynamics simulation was performed for several protein-solvent systems with different sizes. Simulation of the largest system investigated (27,000 atoms) took only 5 sec/step. Thus, the PEACH-GRAPE system is expected to be useful in accurate and reliable simulation of large biomolecules.

Discovering disease-disease associations by fusing systems-level molecular data

PubMed Central

Žitnik, Marinka; Janjić, Vuk; Larminie, Chris; Zupan, Blaž; Pržulj, Nataša

2013-01-01

The advent of genome-scale genetic and genomic studies allows new insight into disease classification. Recently, a shift was made from linking diseases simply based on their shared genes towards systems-level integration of molecular data. Here, we aim to find relationships between diseases based on evidence from fusing all available molecular interaction and ontology data. We propose a multi-level hierarchy of disease classes that significantly overlaps with existing disease classification. In it, we find 14 disease-disease associations currently not present in Disease Ontology and provide evidence for their relationships through comorbidity data and literature curation. Interestingly, even though the number of known human genetic interactions is currently very small, we find they are the most important predictor of a link between diseases. Finally, we show that omission of any one of the included data sources reduces prediction quality, further highlighting the importance in the paradigm shift towards systems-level data fusion. PMID:24232732

Discovering disease-disease associations by fusing systems-level molecular data.

PubMed

Žitnik, Marinka; Janjić, Vuk; Larminie, Chris; Zupan, Blaž; Pržulj, Nataša

2013-11-15

The advent of genome-scale genetic and genomic studies allows new insight into disease classification. Recently, a shift was made from linking diseases simply based on their shared genes towards systems-level integration of molecular data. Here, we aim to find relationships between diseases based on evidence from fusing all available molecular interaction and ontology data. We propose a multi-level hierarchy of disease classes that significantly overlaps with existing disease classification. In it, we find 14 disease-disease associations currently not present in Disease Ontology and provide evidence for their relationships through comorbidity data and literature curation. Interestingly, even though the number of known human genetic interactions is currently very small, we find they are the most important predictor of a link between diseases. Finally, we show that omission of any one of the included data sources reduces prediction quality, further highlighting the importance in the paradigm shift towards systems-level data fusion.

Glassy dynamics of polymethylphenylsiloxane in one- and two-dimensional nanometric confinement—A comparison

NASA Astrophysics Data System (ADS)

Kipnusu, Wycliffe K.; Elsayed, Mohamed; Krause-Rehberg, Reinhard; Kremer, Friedrich

2017-05-01

Glassy dynamics of polymethylphenylsiloxane (PMPS) is studied by broadband dielectric spectroscopy in one-dimensional (1D) and two-dimensional (2D) nanometric confinement; the former is realized in thin polymer layers having thicknesses down to 5 nm, and the latter in unidirectional (thickness 50 μm) nanopores with diameters varying between 4 and 8 nm. Based on the dielectric measurements carried out in a broad spectral range at widely varying temperatures, glassy dynamics is analyzed in detail in 1D and in 2D confinements with the following results: (i) the segmental dynamics (dynamic glass transition) of PMPS in 1D confinement down to thicknesses of 5 nm is identical to the bulk in the mean relaxation rate and the width of the relaxation time distribution function; (ii) additionally a well separated surface induced relaxation is observed, being assigned to adsorption and desorption processes of polymer segments with the solid interface; (iii) in 2D confinement with native inner pore walls, the segmental dynamics shows a confinement effect, i.e., the smaller the pores are, the faster the segmental dynamics; on silanization, this dependence on the pore diameter vanishes, but the mean relaxation rate is still faster than in 1D confinement; (iv) in a 2D confinement, a pronounced surface induced relaxation process is found, the strength of which increases with the decreasing pore diameter; it can be fully removed by silanization of the inner pore walls; (v) the surface induced relaxation depends on its spectral position only negligibly on the pore diameter; (vi) comparing 1D and 2D confinements, the segmental dynamics in the latter is by about two orders of magnitude faster. All these findings can be comprehended by considering the density of the polymer; in 1D it is assumed to be the same as in the bulk, hence the dynamic glass transition is not altered; in 2D it is reduced due to a frustration of packaging resulting in a higher free volume, as proven by ortho

Advances of Molecular Imaging for Monitoring the Anatomical and Functional Architecture of the Olfactory System.

PubMed

Zhang, Xintong; Bi, Anyao; Gao, Quansheng; Zhang, Shuai; Huang, Kunzhu; Liu, Zhiguo; Gao, Tang; Zeng, Wenbin

2016-01-20

The olfactory system of organisms serves as a genetically and anatomically model for studying how sensory input can be translated into behavior output. Some neurologic diseases are considered to be related to olfactory disturbance, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis, and so forth. However, it is still unclear how the olfactory system affects disease generation processes and olfaction delivery processes. Molecular imaging, a modern multidisciplinary technology, can provide valid tools for the early detection and characterization of diseases, evaluation of treatment, and study of biological processes in living subjects, since molecular imaging applies specific molecular probes as a novel approach to produce special data to study biological processes in cellular and subcellular levels. Recently, molecular imaging plays a key role in studying the activation of olfactory system, thus it could help to prevent or delay some diseases. Herein, we present a comprehensive review on the research progress of the imaging probes for visualizing olfactory system, which is classified on different imaging modalities, including PET, MRI, and optical imaging. Additionally, the probes' design, sensing mechanism, and biological application are discussed. Finally, we provide an outlook for future studies in this field.

Resolution of identity approximation for the Coulomb term in molecular and periodic systems.

PubMed

Burow, Asbjörn M; Sierka, Marek; Mohamed, Fawzi

2009-12-07

A new formulation of resolution of identity approximation for the Coulomb term is presented, which uses atom-centered basis and auxiliary basis functions and treats molecular and periodic systems of any dimensionality on an equal footing. It relies on the decomposition of an auxiliary charge density into charged and chargeless components. Applying the Coulomb metric under periodic boundary conditions constrains the explicit form of the charged part. The chargeless component is determined variationally and converged Coulomb lattice sums needed for its determination are obtained using chargeless linear combinations of auxiliary basis functions. The lattice sums are partitioned in near- and far-field portions which are treated through an analytical integration scheme employing two- and three-center electron repulsion integrals and multipole expansions, respectively, operating exclusively in real space. Our preliminary implementation within the TURBOMOLE program package demonstrates consistent accuracy of the method across molecular and periodic systems. Using common auxiliary basis sets the errors of the approximation are small, in average about 20 muhartree per atom, for both molecular and periodic systems.

Resolution of identity approximation for the Coulomb term in molecular and periodic systems

NASA Astrophysics Data System (ADS)

Burow, Asbjörn M.; Sierka, Marek; Mohamed, Fawzi

2009-12-01

A new formulation of resolution of identity approximation for the Coulomb term is presented, which uses atom-centered basis and auxiliary basis functions and treats molecular and periodic systems of any dimensionality on an equal footing. It relies on the decomposition of an auxiliary charge density into charged and chargeless components. Applying the Coulomb metric under periodic boundary conditions constrains the explicit form of the charged part. The chargeless component is determined variationally and converged Coulomb lattice sums needed for its determination are obtained using chargeless linear combinations of auxiliary basis functions. The lattice sums are partitioned in near- and far-field portions which are treated through an analytical integration scheme employing two- and three-center electron repulsion integrals and multipole expansions, respectively, operating exclusively in real space. Our preliminary implementation within the TURBOMOLE program package demonstrates consistent accuracy of the method across molecular and periodic systems. Using common auxiliary basis sets the errors of the approximation are small, in average about 20 μhartree per atom, for both molecular and periodic systems.

MacSyFinder: A Program to Mine Genomes for Molecular Systems with an Application to CRISPR-Cas Systems

PubMed Central

Abby, Sophie S.; Néron, Bertrand; Ménager, Hervé; Touchon, Marie; Rocha, Eduardo P. C.

2014-01-01

Motivation Biologists often wish to use their knowledge on a few experimental models of a given molecular system to identify homologs in genomic data. We developed a generic tool for this purpose. Results Macromolecular System Finder (MacSyFinder) provides a flexible framework to model the properties of molecular systems (cellular machinery or pathway) including their components, evolutionary associations with other systems and genetic architecture. Modelled features also include functional analogs, and the multiple uses of a same component by different systems. Models are used to search for molecular systems in complete genomes or in unstructured data like metagenomes. The components of the systems are searched by sequence similarity using Hidden Markov model (HMM) protein profiles. The assignment of hits to a given system is decided based on compliance with the content and organization of the system model. A graphical interface, MacSyView, facilitates the analysis of the results by showing overviews of component content and genomic context. To exemplify the use of MacSyFinder we built models to detect and class CRISPR-Cas systems following a previously established classification. We show that MacSyFinder allows to easily define an accurate “Cas-finder” using publicly available protein profiles. Availability and Implementation MacSyFinder is a standalone application implemented in Python. It requires Python 2.7, Hmmer and makeblastdb (version 2.2.28 or higher). It is freely available with its source code under a GPLv3 license at https://github.com/gem-pasteur/macsyfinder. It is compatible with all platforms supporting Python and Hmmer/makeblastdb. The “Cas-finder” (models and HMM profiles) is distributed as a compressed tarball archive as Supporting Information. PMID:25330359

Nanometre-scale investigations by atomic force microscopy into the effect of different treatments on the surface structure of hair.

PubMed

Durkan, C; Wang, N

2014-12-01

To investigate the effect of different washing regimes on the surface of human hair at the nanometre scale - comparable to the size of typical deposits left behind by commercial products. Atomic force microscopy (AFM) and related techniques. It can be directly seen that washing hair using commercial hair care products removes deposits that naturally form on the shaft, revealing the underlying structure of the hair, whereas in many cases leaving new deposits behind. The spatial distribution of these deposits is explored and quantified. The spatial distribution of the surface charge of pristine hair is mapped, and the electrical screening effect of deposits is directly observed. We also show that the roughness of the treated hair depends directly on the type of product used, with a marked difference between shampoo and conditioner. Some products leave isolated deposits behind, whereas others leave layers of material behind which wet the hair surface. Atomic force microscopy and the related techniques we have employed in a forensic approach is able to distinguish between different hair care products on the basis of the deposits they leave behind. This opens up the capability of further analysis tools to complement already existing techniques. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Interactive display of molecular models using a microcomputer system

NASA Technical Reports Server (NTRS)

Egan, J. T.; Macelroy, R. D.

1980-01-01

A simple, microcomputer-based, interactive graphics display system has been developed for the presentation of perspective views of wire frame molecular models. The display system is based on a TERAK 8510a graphics computer system with a display unit consisting of microprocessor, television display and keyboard subsystems. The operating system includes a screen editor, file manager, PASCAL and BASIC compilers and command options for linking and executing programs. The graphics program, written in USCD PASCAL, involves the centering of the coordinate system, the transformation of centered model coordinates into homogeneous coordinates, the construction of a viewing transformation matrix to operate on the coordinates, clipping invisible points, perspective transformation and scaling to screen coordinates; commands available include ZOOM, ROTATE, RESET, and CHANGEVIEW. Data file structure was chosen to minimize the amount of disk storage space. Despite the inherent slowness of the system, its low cost and flexibility suggests general applicability.

Variational path integral molecular dynamics and hybrid Monte Carlo algorithms using a fourth order propagator with applications to molecular systems

NASA Astrophysics Data System (ADS)

Kamibayashi, Yuki; Miura, Shinichi

2016-08-01

In the present study, variational path integral molecular dynamics and associated hybrid Monte Carlo (HMC) methods have been developed on the basis of a fourth order approximation of a density operator. To reveal various parameter dependence of physical quantities, we analytically solve one dimensional harmonic oscillators by the variational path integral; as a byproduct, we obtain the analytical expression of the discretized density matrix using the fourth order approximation for the oscillators. Then, we apply our methods to realistic systems like a water molecule and a para-hydrogen cluster. In the HMC, we adopt two level description to avoid the time consuming Hessian evaluation. For the systems examined in this paper, the HMC method is found to be about three times more efficient than the molecular dynamics method if appropriate HMC parameters are adopted; the advantage of the HMC method is suggested to be more evident for systems described by many body interaction.

Highly sensitive detection of molecular interactions with plasmonic optical fiber grating sensors.

PubMed

Voisin, Valérie; Pilate, Julie; Damman, Pascal; Mégret, Patrice; Caucheteur, Christophe

2014-01-15

Surface Plasmon resonance (SPR) optical fiber biosensors constitute a miniaturized counterpart to the bulky prism configuration and offer remote operation in very small volumes of analyte. They are a cost-effective and relatively straightforward technique to yield in situ (or even possibly in vivo) molecular detection. The biosensor configuration reported in this work uses nanometric-scale gold-coated tilted fiber Bragg gratings (TFBGs) interrogated by light polarized radially to the optical fiber outer surface, so as to maximize the optical coupling with the SPR. These gratings were recently associated to aptamers to assess their label-free biorecognition capability in buffer and serum solutions. In this work, using the well-acknowledged biotin-streptavidin pair as a benchmark, we go forward in the demonstration of their unique sensitivity. In addition to the monitoring of the self-assembled monolayer (SAM) in real time, we report an unprecedented limit of detection (LOD) as low as 2 pM. Finally, an immunosensing experiment is realized with human transferrin (dissociation constant Kd~10(-8) M(-1)). It allows to assess both the reversibility and the robustness of the SPR-TFBG biosensors and to confirm their high sensitivity. © 2013 Published by Elsevier B.V.

Theoretical study of ANTO molecular systems: Causes of insensitivity of the energetic compound NTO

NASA Astrophysics Data System (ADS)

Liu, Min-Hsien; Chen, Cheng; Hong, Yaw-Shun

The ANTO molecular system, which comprises the energetic compound 3-nitro-1,2,4-triazole-5-one (NTO, with its two lowest-energy conformers L1 and L2), ammonia (NH3), and water (H2O) molecules, is introduced for a theoretical survey of corresponding geometrical structure and localized bonding character. With the medium (or solvent) of H2O and NH3, three intermolecular hydrogen bonds formed in the NTO + NH3 + H2O system would lower the overall molecular energy and stabilize.

A grass molecular identification system for forensic botany: a critical evaluation of the strengths and limitations.

PubMed

Ward, Jodie; Gilmore, Simon R; Robertson, James; Peakall, Rod

2009-11-01

Plant material is frequently encountered in criminal investigations but often overlooked as potential evidence. We designed a DNA-based molecular identification system for 100 Australian grasses that consisted of a series of polymerase chain reaction assays that enabled the progressive identification of grasses to different taxonomic levels. The identification system was based on DNA sequence variation at four chloroplast and two mitochondrial loci. Seventeen informative indels and 68 single-nucleotide polymorphisms were utilized as molecular markers for subfamily to species-level identification. To identify an unknown sample to subfamily level required a minimum of four markers or nine markers for species identification. The accuracy of the system was confirmed by blind tests. We have demonstrated "proof of concept" of a molecular identification system for trace botanical samples. Our evaluation suggests that the adoption of a system that combines this approach with DNA sequencing could assist the morphological identification of grasses found as forensic evidence.

Time-dependent theoretical treatments of the dynamics of electrons and nuclei in molecular systems

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

Deumens, E.; Diz, A.; Longo, R.

1994-07-01

An overview is presented of methods for time-dependent treatments of molecules as systems of electrons and nuclei. The theoretical details of these methods are reviewed and contrasted in the light of a recently developed time-dependent method called electron-nuclear dynamics. Electron-nuclear dynamics (END) is a formulation of the complete dynamics of electrons and nuclei of a molecular system that eliminates the necessity of constructing potential-energy surfaces. Because of its general formulation, it encompasses many aspects found in other formulations and can serve as a didactic device for clarifying many of the principles and approximations relevant in time-dependent treatments of molecular systems.more » The END equations are derived from the time-dependent variational principle applied to a chosen family of efficiently parametrized approximate state vectors. A detailed analysis of the END equations is given for the case of a single-determinantal state for the electrons and a classical treatment of the nuclei. The approach leads to a simple formulation of the fully nonlinear time-dependent Hartree-Fock theory including nuclear dynamics. The nonlinear END equations with the [ital ab] [ital initio] Coulomb Hamiltonian have been implemented at this level of theory in a computer program, ENDyne, and have been shown feasible for the study of small molecular systems. Implementation of the Austin Model 1 semiempirical Hamiltonian is discussed as a route to large molecular systems. The linearized END equations at this level of theory are shown to lead to the random-phase approximation for the coupled system of electrons and nuclei. The qualitative features of the general nonlinear solution are analyzed using the results of the linearized equations as a first approximation. Some specific applications of END are presented, and the comparison with experiment and other theoretical approaches is discussed.« less

A quantum-mechanics molecular-mechanics scheme for extended systems

NASA Astrophysics Data System (ADS)

Hunt, Diego; Sanchez, Veronica M.; Scherlis, Damián A.

2016-08-01

We introduce and discuss a hybrid quantum-mechanics molecular-mechanics (QM-MM) approach for Car-Parrinello DFT simulations with pseudopotentials and planewaves basis, designed for the treatment of periodic systems. In this implementation the MM atoms are considered as additional QM ions having fractional charges of either sign, which provides conceptual and computational simplicity by exploiting the machinery already existing in planewave codes to deal with electrostatics in periodic boundary conditions. With this strategy, both the QM and MM regions are contained in the same supercell, which determines the periodicity for the whole system. Thus, while this method is not meant to compete with non-periodic QM-MM schemes able to handle extremely large but finite MM regions, it is shown that for periodic systems of a few hundred atoms, our approach provides substantial savings in computational times by treating classically a fraction of the particles. The performance and accuracy of the method is assessed through the study of energetic, structural, and dynamical aspects of the water dimer and of the aqueous bulk phase. Finally, the QM-MM scheme is applied to the computation of the vibrational spectra of water layers adsorbed at the TiO2 anatase (1 0 1) solid-liquid interface. This investigation suggests that the inclusion of a second monolayer of H2O molecules is sufficient to induce on the first adsorbed layer, a vibrational dynamics similar to that taking place in the presence of an aqueous environment. The present QM-MM scheme appears as a very interesting tool to efficiently perform molecular dynamics simulations of complex condensed matter systems, from solutions to nanoconfined fluids to different kind of interfaces.

A quantum-mechanics molecular-mechanics scheme for extended systems.

PubMed

Hunt, Diego; Sanchez, Veronica M; Scherlis, Damián A

2016-08-24

We introduce and discuss a hybrid quantum-mechanics molecular-mechanics (QM-MM) approach for Car-Parrinello DFT simulations with pseudopotentials and planewaves basis, designed for the treatment of periodic systems. In this implementation the MM atoms are considered as additional QM ions having fractional charges of either sign, which provides conceptual and computational simplicity by exploiting the machinery already existing in planewave codes to deal with electrostatics in periodic boundary conditions. With this strategy, both the QM and MM regions are contained in the same supercell, which determines the periodicity for the whole system. Thus, while this method is not meant to compete with non-periodic QM-MM schemes able to handle extremely large but finite MM regions, it is shown that for periodic systems of a few hundred atoms, our approach provides substantial savings in computational times by treating classically a fraction of the particles. The performance and accuracy of the method is assessed through the study of energetic, structural, and dynamical aspects of the water dimer and of the aqueous bulk phase. Finally, the QM-MM scheme is applied to the computation of the vibrational spectra of water layers adsorbed at the TiO2 anatase (1 0 1) solid-liquid interface. This investigation suggests that the inclusion of a second monolayer of H2O molecules is sufficient to induce on the first adsorbed layer, a vibrational dynamics similar to that taking place in the presence of an aqueous environment. The present QM-MM scheme appears as a very interesting tool to efficiently perform molecular dynamics simulations of complex condensed matter systems, from solutions to nanoconfined fluids to different kind of interfaces.

TopoMS: Comprehensive topological exploration for molecular and condensed-matter systems.

PubMed

Bhatia, Harsh; Gyulassy, Attila G; Lordi, Vincenzo; Pask, John E; Pascucci, Valerio; Bremer, Peer-Timo

2018-06-15

We introduce TopoMS, a computational tool enabling detailed topological analysis of molecular and condensed-matter systems, including the computation of atomic volumes and charges through the quantum theory of atoms in molecules, as well as the complete molecular graph. With roots in techniques from computational topology, and using a shared-memory parallel approach, TopoMS provides scalable, numerically robust, and topologically consistent analysis. TopoMS can be used as a command-line tool or with a GUI (graphical user interface), where the latter also enables an interactive exploration of the molecular graph. This paper presents algorithmic details of TopoMS and compares it with state-of-the-art tools: Bader charge analysis v1.0 (Arnaldsson et al., 01/11/17) and molecular graph extraction using Critic2 (Otero-de-la-Roza et al., Comput. Phys. Commun. 2014, 185, 1007). TopoMS not only combines the functionality of these individual codes but also demonstrates up to 4× performance gain on a standard laptop, faster convergence to fine-grid solution, robustness against lattice bias, and topological consistency. TopoMS is released publicly under BSD License. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Study of lnter-Molecular Dynamics within Alkylsiloxane Self-Assembled Monolayer and Elastomer Systems

NASA Astrophysics Data System (ADS)

Roman, Michael

In this work, molecular motion, and in particular, glassy relaxations are studied in two novel experimental systems. Both experimental systems offer a significant degree of control over molecule-molecule, or group-group (where group refers to a portion of a molecule), interactions by controlling density and the type of inter-molecular interaction. Both systems have rigid elements that decrease the tendency of bulk materials to spontaneously change their density with temperature. Thus, density can be maintained and controlled and the effect of density and temperature can be (at least in part) de-convolved. The goal of this work is to experimentally observe the transition from simple, local relaxations to glassy dynamics as density is increased and to understand how this transition differs as the inter-molecular interactions are altered. In both approaches, the system is fabricated from individual parts where the nature, spacing, and particular arrangement of the parts can be controlled and the resultant changes in molecular motion can be observed. Building up a custom system from parts enables fundamental investigation into the glass transition (as discussed above) and also makes possible the development of materials that have engineered responses as a function of temperature. As a short-hand, we refer to the two systems as the monolayer or SAM (short for Self-Assembled Monolayer) and elastomer approaches. In Chapters 4-7 we discuss results from the monolayer approach. Chapter 8 summarizes results from the elastomer approach. In particular, Chapter 4 introduces you to dielectric spectroscopy and briefly summarizes the previous work by former students in the Clarke group which identified the local and glass relaxations in silane monolayers of substituted alkyl chains as analogous to the local and glassy relaxations in polymeric systems containing phase segregated alkyl chains, and similar to the local and glass modes in poly(ethylene). The remainder of Chapter 4

Cellular and Molecular Mechanisms of Sexual Differentiation in the Mammalian Nervous System

PubMed Central

Forger, Nancy G.; Strahan, J. Alex; Castillo-Ruiz, Alexandra

2016-01-01

Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to rethink often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain. PMID:26790970

Path integral molecular dynamic simulation of flexible molecular systems in their ground state: Application to the water dimer

NASA Astrophysics Data System (ADS)

Schmidt, Matthew; Roy, Pierre-Nicholas

2018-03-01

We extend the Langevin equation Path Integral Ground State (LePIGS), a ground state quantum molecular dynamics method, to simulate flexible molecular systems and calculate both energetic and structural properties. We test the approach with the H2O and D2O monomers and dimers. We systematically optimize all simulation parameters and use a unity trial wavefunction. We report ground state energies, dissociation energies, and structural properties using three different water models, two of which are empirically based, q-TIP4P/F and q-SPC/Fw, and one which is ab initio, MB-pol. We demonstrate that our energies calculated from LePIGS can be merged seamlessly with low temperature path integral molecular dynamics calculations and note the similarities between the two methods. We also benchmark our energies against previous diffusion Monte Carlo calculations using the same potentials and compare to experimental results. We further demonstrate that accurate vibrational energies of the H2O and D2O monomer can be calculated from imaginary time correlation functions generated from the LePIGS simulations using solely the unity trial wavefunction.

Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

PubMed

Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

2017-05-01

In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. © 2016 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Self-assembled three-dimensional chiral colloidal architecture.

PubMed

Ben Zion, Matan Yah; He, Xiaojin; Maass, Corinna C; Sha, Ruojie; Seeman, Nadrian C; Chaikin, Paul M

2017-11-03

Although stereochemistry has been a central focus of the molecular sciences since Pasteur, its province has previously been restricted to the nanometric scale. We have programmed the self-assembly of micron-sized colloidal clusters with structural information stemming from a nanometric arrangement. This was done by combining DNA nanotechnology with colloidal science. Using the functional flexibility of DNA origami in conjunction with the structural rigidity of colloidal particles, we demonstrate the parallel self-assembly of three-dimensional microconstructs, evincing highly specific geometry that includes control over position, dihedral angles, and cluster chirality. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Gene expression-based molecular diagnostic system for malignant gliomas is superior to histological diagnosis.

PubMed

Shirahata, Mitsuaki; Iwao-Koizumi, Kyoko; Saito, Sakae; Ueno, Noriko; Oda, Masashi; Hashimoto, Nobuo; Takahashi, Jun A; Kato, Kikuya

2007-12-15

Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling. The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study. Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival. Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.

In vivo assessing of nanometric changes on the surface of whole tomatoes that have been inoculated with Candida guilliermondii yeast.

PubMed

Infante, Esperanza Del Pilar

2014-08-01

The cuticle of plants that covers the epidermis of cells, an interface between the fruit and the environment, has an important role to play in fruit quality because it prevents water loss and mechanical damage while simultaneously forming a barrier as it prevents phytopathogens from entering the fruit. All these factors give rise to flaws in the appearance of the fruit, thus contributing to marketing problems in the form of financial loss. In the search for solutions to some of these problems, certain biocontrolling yeasts have been introduced in the last few years. In the study described here, the changes observed on the surface of the whole tomato were evaluated in vivo during the first 72 h after inoculation by spraying Candida guilliermondii yeast onto the fruit's surface. The measurements were taken on a nanometric scale using atomic force microscopy; images were created in both contact and tapping modes. The results showed diminished roughness of the surface, which could contribute to reduced phytopathogen adherence due to the thinner contact area. These results furthermore showed that a yeast biofilm was formed on the fruit which probably helps to improve water retention inside the fruit. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Structural insight into RNA recognition motifs: versatile molecular Lego building blocks for biological systems.

PubMed

Muto, Yutaka; Yokoyama, Shigeyuki

2012-01-01

'RNA recognition motifs (RRMs)' are common domain-folds composed of 80-90 amino-acid residues in eukaryotes, and have been identified in many cellular proteins. At first they were known as RNA binding domains. Through discoveries over the past 20 years, however, the RRMs have been shown to exhibit versatile molecular recognition activities and to behave as molecular Lego building blocks to construct biological systems. Novel RNA/protein recognition modes by RRMs are being identified, and more information about the molecular recognition by RRMs is becoming available. These RNA/protein recognition modes are strongly correlated with their biological significance. In this review, we would like to survey the recent progress on these versatile molecular recognition modules. Copyright © 2012 John Wiley & Sons, Ltd.

Solid-solid collapse transition in a two dimensional model molecular system.

PubMed

Singh, Rakesh S; Bagchi, Biman

2013-11-21

Solid-solid collapse transition in open framework structures is ubiquitous in nature. The real difficulty in understanding detailed microscopic aspects of such transitions in molecular systems arises from the interplay between different energy and length scales involved in molecular systems, often mediated through a solvent. In this work we employ Monte-Carlo simulation to study the collapse transition in a model molecular system interacting via both isotropic as well as anisotropic interactions having different length and energy scales. The model we use is known as Mercedes-Benz (MB), which, for a specific set of parameters, sustains two solid phases: honeycomb and oblique. In order to study the temperature induced collapse transition, we start with a metastable honeycomb solid and induce transition by increasing temperature. High density oblique solid so formed has two characteristic length scales corresponding to isotropic and anisotropic parts of interaction potential. Contrary to the common belief and classical nucleation theory, interestingly, we find linear strip-like nucleating clusters having significantly different order and average coordination number than the bulk stable phase. In the early stage of growth, the cluster grows as a linear strip, followed by branched and ring-like strips. The geometry of growing cluster is a consequence of the delicate balance between two types of interactions, which enables the dominance of stabilizing energy over destabilizing surface energy. The nucleus of stable oblique phase is wetted by intermediate order particles, which minimizes the surface free energy. In the case of pressure induced transition at low temperature the collapsed state is a disordered solid. The disordered solid phase has diverse local quasi-stable structures along with oblique-solid like domains.

Solid-solid collapse transition in a two dimensional model molecular system

NASA Astrophysics Data System (ADS)

Singh, Rakesh S.; Bagchi, Biman

2013-11-01

Solid-solid collapse transition in open framework structures is ubiquitous in nature. The real difficulty in understanding detailed microscopic aspects of such transitions in molecular systems arises from the interplay between different energy and length scales involved in molecular systems, often mediated through a solvent. In this work we employ Monte-Carlo simulation to study the collapse transition in a model molecular system interacting via both isotropic as well as anisotropic interactions having different length and energy scales. The model we use is known as Mercedes-Benz (MB), which, for a specific set of parameters, sustains two solid phases: honeycomb and oblique. In order to study the temperature induced collapse transition, we start with a metastable honeycomb solid and induce transition by increasing temperature. High density oblique solid so formed has two characteristic length scales corresponding to isotropic and anisotropic parts of interaction potential. Contrary to the common belief and classical nucleation theory, interestingly, we find linear strip-like nucleating clusters having significantly different order and average coordination number than the bulk stable phase. In the early stage of growth, the cluster grows as a linear strip, followed by branched and ring-like strips. The geometry of growing cluster is a consequence of the delicate balance between two types of interactions, which enables the dominance of stabilizing energy over destabilizing surface energy. The nucleus of stable oblique phase is wetted by intermediate order particles, which minimizes the surface free energy. In the case of pressure induced transition at low temperature the collapsed state is a disordered solid. The disordered solid phase has diverse local quasi-stable structures along with oblique-solid like domains.

Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems

PubMed Central

Lü, Jian-Ming; Lin, Peter H; Yao, Qizhi; Chen, Changyi

2010-01-01

Abstract Free radicals derived from oxygen, nitrogen and sulphur molecules in the biological system are highly active to react with other molecules due to their unpaired electrons. These radicals are important part of groups of molecules called reactive oxygen/nitrogen species (ROS/RNS), which are produced during cellular metabolism and functional activities and have important roles in cell signalling, apoptosis, gene expression and ion transportation. However, excessive ROS attack bases in nucleic acids, amino acid side chains in proteins and double bonds in unsaturated fatty acids, and cause oxidative stress, which can damage DNA, RNA, proteins and lipids resulting in an increased risk for cardiovascular disease, cancer, autism and other diseases. Intracellular antioxidant enzymes and intake of dietary antioxidants may help to maintain an adequate antioxidant status in the body. In the past decades, new molecular techniques, cell cultures and animal models have been established to study the effects and mechanisms of antioxidants on ROS. The chemical and molecular approaches have been used to study the mechanism and kinetics of antioxidants and to identify new potent antioxidants. Antioxidants can decrease the oxidative damage directly via reacting with free radicals or indirectly by inhibiting the activity or expression of free radical generating enzymes or enhancing the activity or expression of intracellular antioxidant enzymes. The new chemical and cell-free biological system has been applied in dissecting the molecular action of antioxidants. This review focuses on the research approaches that have been used to study oxidative stress and antioxidants in lipid peroxidation, DNA damage, protein modification as well as enzyme activity, with emphasis on the chemical and cell-free biological system. PMID:19754673

DCMS: A data analytics and management system for molecular simulation.

PubMed

Kumar, Anand; Grupcev, Vladimir; Berrada, Meryem; Fogarty, Joseph C; Tu, Yi-Cheng; Zhu, Xingquan; Pandit, Sagar A; Xia, Yuni

Molecular Simulation (MS) is a powerful tool for studying physical/chemical features of large systems and has seen applications in many scientific and engineering domains. During the simulation process, the experiments generate a very large number of atoms and intend to observe their spatial and temporal relationships for scientific analysis. The sheer data volumes and their intensive interactions impose significant challenges for data accessing, managing, and analysis. To date, existing MS software systems fall short on storage and handling of MS data, mainly because of the missing of a platform to support applications that involve intensive data access and analytical process. In this paper, we present the database-centric molecular simulation (DCMS) system our team developed in the past few years. The main idea behind DCMS is to store MS data in a relational database management system (DBMS) to take advantage of the declarative query interface ( i.e. , SQL), data access methods, query processing, and optimization mechanisms of modern DBMSs. A unique challenge is to handle the analytical queries that are often compute-intensive. For that, we developed novel indexing and query processing strategies (including algorithms running on modern co-processors) as integrated components of the DBMS. As a result, researchers can upload and analyze their data using efficient functions implemented inside the DBMS. Index structures are generated to store analysis results that may be interesting to other users, so that the results are readily available without duplicating the analysis. We have developed a prototype of DCMS based on the PostgreSQL system and experiments using real MS data and workload show that DCMS significantly outperforms existing MS software systems. We also used it as a platform to test other data management issues such as security and compression.

EDITORIAL: 18th European Conference on Dynamics of Molecular Systems 18th European Conference on Dynamics of Molecular Systems

NASA Astrophysics Data System (ADS)

Varandas, A. J. C.

2011-08-01

This special section of Comments on Atomic, Molecular and Optical Physics (CAMOP) in Physica Scripta collects some of the papers that have been presented at the 18th European Conference on Dynamics of Molecular Systems MOLEC 2010 held in September 2010 in Curia, Portugal, as part of a series of biennial MOLEC conferences. This started in 1976 in Trento, Italy, and has continued, visiting 17 cities in 11 countries, namely Denmark, The Netherlands, Israel, France, Italy, Germany, Czech Republic, Spain, United Kingdom, Turkey and Russia. Following the MOLEC tradition, the scientific programme of the Curia meeting focused on experimental and theoretical studies of molecular interactions, collision dynamics, spectroscopy, and related fields. It included invited speakers from 22 countries, who were asked to summarize the problems reported in their presentations with the objective of revealing the current thinking of leading researchers in atomic, molecular and optical physics. It is hoped that their authoritative contributions presented in this CAMOP special section will also appeal to non-specialists through their clear and broad introductions to the field as well as references to the accessible literature. This CAMOP special section comprises ten contributions, which cover theoretical studies on the electronic structure of molecules and clusters as well as dynamics of elastic, inelastic and reactive encounters between atoms, molecules, ions, clusters and surfaces. Specifically, it includes electronic structure calculations using the traditional coupled-cluster method (Barreto et al 028111), the electron-attached equation-of-motion coupled cluster method (Hansen et al 028110), the diffusion Monte Carlo method (López-Durán et al 028107) and the path-integral Monte Carlo method (Barragán et al 028109). The contributions on molecular dynamics include on-the-fly quasi-classical trajectories on a five-atom molecule (Yu 028104), quantum reaction dynamics on triatomics

Molecular Dynamics Study of Polystyrene-b-poly(ethylene oxide) Asymmetric Diblock Copolymer Systems.

PubMed

Dobies, M; Makrocka-Rydzyk, M; Jenczyk, J; Jarek, M; Spontak, R J; Jurga, S

2017-09-12

Two polystyrene-b-poly(ethylene oxide) (PS-b-PEO) diblock copolymers differing in molecular mass (49 and 78 kDa) but possessing the same PEO cylindrical morphology are examined to elucidate their molecular dynamics. Of particular interest here is the molecular motion of the PEO blocks involved in the rigid amorphous fraction (RAF). An analysis of complementary thermal calorimetry and X-ray scattering data confirms the presence of microphase-separated morphology as well as semicrystalline structure in each copolymer. Molecular motion within the copolymer systems is monitored by dielectric and nuclear magnetic resonance spectroscopies. The results reported herein reveal the existence of two local Arrhenius-type processes attributed to the noncooperative local motion of PEO segments involved in fully amorphous and rigid amorphous PEO microphases. In both systems, two structural relaxations governed by glass-transition phenomena are identified and assigned to cooperative segmental motion in the fully amorphous phase (the α process) and the RAF (the α c process). We measure the temperature dependence of the dynamics associated with all of the processes mentioned above and propose that these local processes are associated with corresponding cooperative segmental motion in both copolymer systems. In marked contrast to the thermal activation of the α process as discerned in both copolymers, the α c process appears to be a sensitive probe of the copolymer nanostructure. That is, the copolymer with shorter PEO blocks exhibits more highly restricted cooperative dynamics of PEO segments in the RAF, which can be explained in terms of the greater constraint imposed by the glassy PS matrix on the PEO blocks comprising smaller cylindrical microdomains.

Thermodynamic Modeling of Ag-Ni System Combining Experiments and Molecular Dynamic Simulation

NASA Astrophysics Data System (ADS)

Rajkumar, V. B.; Chen, Sinn-wen

2017-04-01

Ag-Ni is a simple and important system with immiscible liquids and (Ag,Ni) phases. Previously, this system has been thermodynamically modeled utilizing certain thermochemical and phase equilibria information based on conjecture. An attempt is made in this study to determine the missing information which are difficult to measure experimentally. The boundaries of the liquid miscibility gap at high temperatures are determined using a pyrometer. The temperature of the liquid ⇌ (Ag) + (Ni) eutectic reaction is measured using differential thermal analysis. Tie-lines of the Ag-Ni system at 1023 K and 1473 K are measured using a conventional metallurgical method. The enthalpy of mixing of the liquid at 1773 K and the (Ag,Ni) at 973 K is calculated by molecular dynamics simulation using a large-scale atomic/molecular massively parallel simulator. These results along with literature information are used to model the Gibbs energy of the liquid and (Ag,Ni) by a calculation of phase diagrams approach, and the Ag-Ni phase diagram is then calculated.

Capillary levelling as a probe of rheology in polymer thin films

NASA Astrophysics Data System (ADS)

McGraw, Joshua D.; Jago, Nick M.; Dalnoki-Veress, Kari

2011-03-01

While measuring the rheology of bulk polymer systems is routine, when the size of a system becomes comparable to the molecular size, flow properties are poorly understood and hard to measure. Here, we present the results of experiments that are easily performed and can probe the rheological properties of polymer films that are mere tens of nanometres in thickness. We prepare glassy bilayer polymer films with height profiles well approximated by a step function. Upon annealing above the glass transition, broadening of the height profiles due to gradients in the Laplace pressure is observed. By validating the technique as a probe of the rheology with a range of molecular weights, we will show that this robust technique can be used to investigate the effects of confinement and interfaces on the rheology of ultrathin polymer films. Financial support from NSERC of Canada is gratefully acknowledged.

Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

PubMed

Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

2018-01-01

Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

DEMONSTRATION BULLETIN: MOLECULAR BONDING SYSTEM FOR HEAVY METALS STABILIZATION - SOLUCORP INDUSTRIES LTD.

EPA Science Inventory

This document presents an evaluation of the Molecular Bonding System (MBS) and its ability to chemically stabilize three metals-contaminated wstes/soils during a SITe demo. The MBS process treated approximately 500 tons each of soil/Fill, Slag, and Miscellaneous Smelter Waste wit...

Studying chemical reactions in biological systems with MBN Explorer: implementation of molecular mechanics with dynamical topology

NASA Astrophysics Data System (ADS)

Sushko, Gennady B.; Solov'yov, Ilia A.; Verkhovtsev, Alexey V.; Volkov, Sergey N.; Solov'yov, Andrey V.

2016-01-01

The concept of molecular mechanics force field has been widely accepted nowadays for studying various processes in biomolecular systems. In this paper, we suggest a modification for the standard CHARMM force field that permits simulations of systems with dynamically changing molecular topologies. The implementation of the modified force field was carried out in the popular program MBN Explorer, and, to support the development, we provide several illustrative case studies where dynamical topology is necessary. In particular, it is shown that the modified molecular mechanics force field can be applied for studying processes where rupture of chemical bonds plays an essential role, e.g., in irradiation- or collision-induced damage, and also in transformation and fragmentation processes involving biomolecular systems. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey V. Solov'yov, Nigel Mason, Gustavo Garcia and Eugene Surdutovich.

Diseno de puertas moleculares controladas a nivel nanoscopico

NASA Astrophysics Data System (ADS)

Casasus Lis, Rosa

would give one observable and easy signal such as change of colour and even more the only way to occur was if the studied species came inside the nanometric porous. In second place it was reported a complete study of the behaviour of a pH-driven and anion-controlled nano-supramolecular gate-like ensemble obtained by anchoring suitable polyamines on the pore outlets of mesoporous materials of the type MCM-41. The release of an entrapped dye (Ru(bipy)3 2+) from the pore voids into the bulk solution allows us to study the gating effect. This study was carried out by monitoring the dye released from the pore voids of the solid at a certain pH in the presence of a range of anions with different structural dimensions and charges, including chloride, sulphate, phosphate, and ATP. The choice of a certain anionic guest results in a different gate-like ensemble behaviour, ranging from basically no action (chloride) to complete (ATP) or partial pore blockage, depending on the pH (sulphate and phosphate). Molecular dynamics simulations using force field methods have been carried out to explain the pH-driven open/close mechanism and selectivity patterns have been discussed in terms of kinetic rates of the liberation of the dye. Furthermore, it has been applied the potential use of molecular gatelike systems as a new strategy for the chromogenic signalling of the target anions in aqueous solutions. The idea involves molecular-recognition events coupled with the control of dye transport. It entails the use of solids with nanoscopic 3D organized surfaces (mesoporous solids) that have been functionalized at the outer surface with certain binding moieties (for example amines) and additionally the pores have been loaded with a suitable dye. In absence of any species to detect there is an opened gatelike system that is able to deliver the enclosed dye to the solution. The addition of a target anionic guest capable of forming a suitable complex with the binding site might "close the gate

High Molecular Weight Isoforms of Growth Hormone In Cells of the Immune System

PubMed Central

Weigent, Douglas A.

2013-01-01

A substantial body of research exists to support the idea that cells of the immune system produce growth hormone (GH). However, the structure and mechanism of action of lymphocyte-derived GH continues to remain largely unknown. Here we present the results of Western analysis of whole cell extracts showing that different molecular weight isoforms of GH of approximately 100 kDa, 65 kDa, and 48 kDa can be detected in primary mouse cells of the immune system and in the mouse EL4 cell line. The identity of the 65 kDa and 48 kDa isoforms of GH were confirmed by mass spectrometry. The various isoforms were detected in both enriched T and B spleen cell populations. The large molecular weight isoform appears to reside primarily in the cytoplasm whereas the lower molecular weight 65 kDa and 48 kDa isoforms were detected primarily in the nucleus. These results also suggest that GH isoforms are induced by oxidative stress. In EL4 cells overexpressing GH, the expression of luciferase controlled by a promoter containing the antioxidant response element is increased almost three-fold above control. The data suggest that the induction of isoforms of the GH molecule in cells of the immune system may be an important mechanism of adaptation and/or protection of lymphoid cells under conditions of oxidative stress. PMID:21741628

Automation and Preclinical Evaluation of a Dedicated Emission Mammotomography System for Fully 3-D Molecular Breast Imaging

DTIC Science & Technology

2009-10-01

molecular breast imaging, with the ability to dynamically contour any sized breast, will improve detection and potentially in vivo characterization of...Having flexible 3D positioning about the breast yielded minimal RMSD differences, which is important for high resolution molecular emission imaging. This...TITLE: Automation and Preclinical Evaluation of a Dedicated Emission Mammotomography System for Fully 3-D Molecular Breast Imaging PRINCIPAL

Bicanonical ab Initio Molecular Dynamics for Open Systems.

PubMed

Frenzel, Johannes; Meyer, Bernd; Marx, Dominik

2017-08-08

Performing ab initio molecular dynamics simulations of open systems, where the chemical potential rather than the number of both nuclei and electrons is fixed, still is a challenge. Here, drawing on bicanonical sampling ideas introduced two decades ago by Swope and Andersen [ J. Chem. Phys. 1995 , 102 , 2851 - 2863 ] to calculate chemical potentials of liquids and solids, an ab initio simulation technique is devised, which introduces a fictitious dynamics of two superimposed but otherwise independent periodic systems including full electronic structure, such that either the chemical potential or the average fractional particle number of a specific chemical species can be kept constant. As proof of concept, we demonstrate that solvation free energies can be computed from these bicanonical ab initio simulations upon directly superimposing pure bulk water and the respective aqueous solution being the two limiting systems. The method is useful in many circumstances, for instance for studying heterogeneous catalytic processes taking place on surfaces where the chemical potential of reactants rather than their number is controlled and opens a pathway toward ab initio simulations at constant electrochemical potential.

Tailor-made Molecular Cobalt Catalyst System for the Selective Transformation of Carbon Dioxide to Dialkoxymethane Ethers.

PubMed

Schieweck, Benjamin G; Klankermayer, Jürgen

2017-08-28

Herein a non-precious transition-metal catalyst system for the selective synthesis of dialkoxymethane ethers from carbon dioxide and molecular hydrogen is presented. The development of a tailored catalyst system based on cobalt salts in combination with selected Triphos ligands and acidic co-catalysts enabled a synthetic pathway, avoiding the oxidation of methanol to attain the formaldehyde level of the central CH 2 unit. This unprecedented productivity based on the molecular cobalt catalyst is the first example of a non-precious transition-metal system for this transformation utilizing renewable carbon dioxide sources. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular transformation, gene cloning, and gene expression systems for filamentous fungi

USGS Publications Warehouse

Gold, Scott E.; Duick, John W.; Redman, Regina S.; Rodriguez, Rusty J.

2001-01-01

This chapter discusses the molecular transformation, gene cloning, and gene expression systems for filamentous fungi. Molecular transformation involves the movement of discrete amounts of DNA into cells, the expression of genes on the transported DNA, and the sustainable replication of the transforming DNA. The ability to transform fungi is dependent on the stable replication and expression of genes located on the transforming DNA. Three phenomena observed in bacteria, that is, competence, plasmids, and restriction enzymes to facilitate cloning, were responsible for the development of molecular transformation in fungi. Initial transformation success with filamentous fungi, involving the complementation of auxotrophic mutants by exposure to sheared genomic DNA or RNA from wt isolates, occurred with low transformation efficiencies. In addition, it was difficult to retrieve complementing DNA fragments and isolate genes of interest. This prompted the development of transformation vectors and methods to increase efficiencies. The physiological studies performed with fungi indicated that the cell wall could be removed to generate protoplasts. It was evident that protoplasts could be transformed with significantly greater efficiencies than walled cells.

DNA barcode-based molecular identification system for fish species.

PubMed

Kim, Sungmin; Eo, Hae-Seok; Koo, Hyeyoung; Choi, Jun-Kil; Kim, Won

2010-12-01

In this study, we applied DNA barcoding to identify species using short DNA sequence analysis. We examined the utility of DNA barcoding by identifying 53 Korean freshwater fish species, 233 other freshwater fish species, and 1339 saltwater fish species. We successfully developed a web-based molecular identification system for fish (MISF) using a profile hidden Markov model. MISF facilitates efficient and reliable species identification, overcoming the limitations of conventional taxonomic approaches. MISF is freely accessible at http://bioinfosys.snu.ac.kr:8080/MISF/misf.jsp .

Magnetic hysteresis in a lanthanide molecular magnet dimer system

NASA Astrophysics Data System (ADS)

Atkinson, James; Cebulka, Rebecca; Del Barco, Enrique; Roubeau, Olivier; Velasco, Veronica; Barrios, Leo; Aromi, Guillem

Molecular magnets present a wonderful means for studying the dynamics of spin. Often synthesized as a crystal lattice of identical systems, ensemble measurements enable thorough detailing of the internal degrees of freedom. Here we present the results of characterization performed on a dimer system, CeTm(HL)2(H2L)NO3pyH2O (L = ligand, C45H31O15N3), consisting of two lanthanide spins (Cerium and Thulium) with expected local axial anisotropies tilted with respect to each other. Microwave EPR spectroscopy at low temperature reveals hysteresis in observed absorption features, with angle dependence studies indicating the presence of several ``easy axis'' orientations. We attempt to understand this system through modelling via a spin Hamiltonian, and to determine the strength and nature of the coupling between the lanthanide centers. This research was funded through NSF Grant # 24086159.

All-organic microelectromechanical systems integrating specific molecular recognition--a new generation of chemical sensors.

PubMed

Ayela, Cédric; Dubourg, Georges; Pellet, Claude; Haupt, Karsten

2014-09-03

Cantilever-type all-organic microelectromechanical systems based on molecularly imprinted polymers for specific analyte recognition are used as chemical sensors. They are produced by a simple spray-coating-shadow-masking process. Analyte binding to the cantilever generates a measurable change in its resonance frequency. This allows label-free detection by direct mass sensing of low-molecular-weight analytes at nanomolar concentrations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

System geometry optimization for molecular breast tomosynthesis with focusing multi-pinhole collimators

NASA Astrophysics Data System (ADS)

van Roosmalen, Jarno; Beekman, Freek J.; Goorden, Marlies C.

2018-01-01

Imaging of 99mTc-labelled tracers is gaining popularity for detecting breast tumours. Recently, we proposed a novel design for molecular breast tomosynthesis (MBT) based on two sliding focusing multi-pinhole collimators that scan a modestly compressed breast. Simulation studies indicate that MBT has the potential to improve the tumour-to-background contrast-to-noise ratio significantly over state-of-the-art planar molecular breast imaging. The aim of the present paper is to optimize the collimator-detector geometry of MBT. Using analytical models, we first optimized sensitivity at different fixed system resolutions (ranging from 5 to 12 mm) by tuning the pinhole diameters and the distance between breast and detector for a whole series of automatically generated multi-pinhole designs. We evaluated both MBT with a conventional continuous crystal detector with 3.2 mm intrinsic resolution and with a pixelated detector with 1.6 mm pixels. Subsequently, full system simulations of a breast phantom containing several lesions were performed for the optimized geometry at each system resolution for both types of detector. From these simulations, we found that tumour-to-background contrast-to-noise ratio was highest for systems in the 7 mm-10 mm system resolution range over which it hardly varied. No significant differences between the two detector types were found.

Molecular Genetics Information System (MOLGENIS): alternatives in developing local experimental genomics databases.

PubMed

Swertz, Morris A; De Brock, E O; Van Hijum, Sacha A F T; De Jong, Anne; Buist, Girbe; Baerends, Richard J S; Kok, Jan; Kuipers, Oscar P; Jansen, Ritsert C

2004-09-01

Genomic research laboratories need adequate infrastructure to support management of their data production and research workflow. But what makes infrastructure adequate? A lack of appropriate criteria makes any decision on buying or developing a system difficult. Here, we report on the decision process for the case of a molecular genetics group establishing a microarray laboratory. Five typical requirements for experimental genomics database systems were identified: (i) evolution ability to keep up with the fast developing genomics field; (ii) a suitable data model to deal with local diversity; (iii) suitable storage of data files in the system; (iv) easy exchange with other software; and (v) low maintenance costs. The computer scientists and the researchers of the local microarray laboratory considered alternative solutions for these five requirements and chose the following options: (i) use of automatic code generation; (ii) a customized data model based on standards; (iii) storage of datasets as black boxes instead of decomposing them in database tables; (iv) loosely linking to other programs for improved flexibility; and (v) a low-maintenance web-based user interface. Our team evaluated existing microarray databases and then decided to build a new system, Molecular Genetics Information System (MOLGENIS), implemented using code generation in a period of three months. This case can provide valuable insights and lessons to both software developers and a user community embarking on large-scale genomic projects. http://www.molgenis.nl

Local and systemic vasodilatory effects of low molecular weight S-nitrosothiols.

PubMed

Liu, Taiming; Schroeder, Hobe J; Wilson, Sean M; Terry, Michael H; Romero, Monica; Longo, Lawrence D; Power, Gordon G; Blood, Arlin B

2016-02-01

S-nitrosothiols (SNOs) such as S-nitroso-L-cysteine (L-cysNO) are endogenous compounds with potent vasodilatory activity. During circulation in the blood, the NO moiety can be exchanged among various thiol-containing compounds by S-transnitrosylation, resulting in SNOs with differing capacities to enter the cell (membrane permeability). To determine whether the vasodilating potency of SNOs is dependent upon membrane permeability, membrane-permeable L-cysNO and impermeable S-nitroso-D-cysteine (D-cysNO) and S-nitroso-glutathione (GSNO) were infused into one femoral artery of anesthetized adult sheep while measuring bilateral femoral and systemic vascular conductances. L-cysNO induced vasodilation in the infused hind limb, whereas D-cysNO and GSNO did not. L-cysNO also increased intracellular NO in isolated arterial smooth muscle cells, whereas GSNO did not. The infused SNOs remained predominantly in a low molecular weight form during first-passage through the hind limb vasculature, but were converted into high molecular weight SNOs upon systemic recirculation. At systemic concentrations of ~0.6 μmol/L, all three SNOs reduced mean arterial blood pressure by ~50%, with pronounced vasodilation in the mesenteric bed. Pharmacokinetics of L-cysNO and GSNO were measured in vitro and in vivo and correlated with their hemodynamic effects, membrane permeability, and S-transnitrosylation. These results suggest local vasodilation by SNOs in the hind limb requires membrane permeation, whereas systemic vasodilation does not. The systemic hemodynamic effects of SNOs occur after equilibration of the NO moiety amongst the plasma thiols via S-transnitrosylation. Copyright © 2015 Elsevier Inc. All rights reserved.

Hybrid particle-field molecular dynamics simulation for polyelectrolyte systems.

PubMed

Zhu, You-Liang; Lu, Zhong-Yuan; Milano, Giuseppe; Shi, An-Chang; Sun, Zhao-Yan

2016-04-14

To achieve simulations on large spatial and temporal scales with high molecular chemical specificity, a hybrid particle-field method was proposed recently. This method is developed by combining molecular dynamics and self-consistent field theory (MD-SCF). The MD-SCF method has been validated by successfully predicting the experimentally observable properties of several systems. Here we propose an efficient scheme for the inclusion of electrostatic interactions in the MD-SCF framework. In this scheme, charged molecules are interacting with the external fields that are self-consistently determined from the charge densities. This method is validated by comparing the structural properties of polyelectrolytes in solution obtained from the MD-SCF and particle-based simulations. Moreover, taking PMMA-b-PEO and LiCF3SO3 as examples, the enhancement of immiscibility between the ion-dissolving block and the inert block by doping lithium salts into the copolymer is examined by using the MD-SCF method. By employing GPU-acceleration, the high performance of the MD-SCF method with explicit treatment of electrostatics facilitates the simulation study of many problems involving polyelectrolytes.

On the quantification of the dissolved hydroxyl radicals in the plasma-liquid system using the molecular probe method

NASA Astrophysics Data System (ADS)

Ma, Yupengxue; Gong, Xinning; He, Bangbang; Li, Xiaofei; Cao, Dianyu; Li, Junshuai; Xiong, Qing; Chen, Qiang; Chen, Bing Hui; Huo Liu, Qing

2018-04-01

Hydroxyl (OH) radical is one of the most important reactive species produced by plasma-liquid interactions, and the OH in liquid phase (dissolved OH radical, OHdis) takes effect in many plasma-based applications due to its high reactivity. Therefore, the quantification of the OHdis in a plasma-liquid system is of great importance, and a molecular probe method usually used for the OHdis detection might be applied. Herein, we investigate the validity of using the molecular probe method to estimate the [OHdis] in the plasma-liquid system. Dimethyl sulfoxide is used as the molecular probe to estimate the [OHdis] in an air plasma-liquid system, and usually the estimation of [OHdis] is deduced by quantifying the OHdis-induced derivative, the formaldehyde (HCHO). The analysis indicates that the true concentration of the OHdis should be estimated from the sum of three terms: the formed HCHO, the existing OH scavengers, and the H2O2 formed from the OHdis. The results show that the measured [HCHO] needs to be corrected since the HCHO consumption is not negligible in the plasma-liquid system. We conclude from the results and the analysis that the molecular probe method generally underestimates the [OHdis] in the plasma-liquid system. If one wants to obtain the true concentration of the OHdis in the plasma-liquid system, one needs to know the consumption behavior of the OHdis-induced derivatives, the information of the OH scavengers (such as hydrated electron, atomic hydrogen besides the molecular probe), and also the knowledge of the H2O2 formed from the OHdis.

Nucleocytoplasmic Transport: A Paradigm for Molecular Logistics in Artificial Systems.

PubMed

Vujica, Suncica; Zelmer, Christina; Panatala, Radhakrishnan; Lim, Roderick Y H

2016-01-01

Artificial organelles, molecular factories and nanoreactors are membrane-bound systems envisaged to exhibit cell-like functionality. These constitute liposomes, polymersomes or hybrid lipo-polymersomes that display different membrane-spanning channels and/or enclose molecular modules. To achieve more complex functionality, an artificial organelle should ideally sustain a continuous influx of essential macromolecular modules (i.e. cargoes) and metabolites against an outflow of reaction products. This would benefit from the incorporation of selective nanopores as well as specific trafficking factors that facilitate cargo selectivity, translocation efficiency, and directionality. Towards this goal, we describe how proteinaceous cargoes are transported between the nucleus and cytoplasm by nuclear pore complexes and the biological trafficking machinery in living cells (i.e. nucleocytoplasmic transport). On this basis, we discuss how biomimetic control may be implemented to selectively import, compartmentalize and accumulate diverse macromolecular modules against concentration gradients in artificial organelles.

Charge migration and charge transfer in molecular systems

PubMed Central

Wörner, Hans Jakob; Arrell, Christopher A.; Banerji, Natalie; Cannizzo, Andrea; Chergui, Majed; Das, Akshaya K.; Hamm, Peter; Keller, Ursula; Kraus, Peter M.; Liberatore, Elisa; Lopez-Tarifa, Pablo; Lucchini, Matteo; Meuwly, Markus; Milne, Chris; Moser, Jacques-E.; Rothlisberger, Ursula; Smolentsev, Grigory; Teuscher, Joël; van Bokhoven, Jeroen A.; Wenger, Oliver

2017-01-01

The transfer of charge at the molecular level plays a fundamental role in many areas of chemistry, physics, biology and materials science. Today, more than 60 years after the seminal work of R. A. Marcus, charge transfer is still a very active field of research. An important recent impetus comes from the ability to resolve ever faster temporal events, down to the attosecond time scale. Such a high temporal resolution now offers the possibility to unravel the most elementary quantum dynamics of both electrons and nuclei that participate in the complex process of charge transfer. This review covers recent research that addresses the following questions. Can we reconstruct the migration of charge across a molecule on the atomic length and electronic time scales? Can we use strong laser fields to control charge migration? Can we temporally resolve and understand intramolecular charge transfer in dissociative ionization of small molecules, in transition-metal complexes and in conjugated polymers? Can we tailor molecular systems towards specific charge-transfer processes? What are the time scales of the elementary steps of charge transfer in liquids and nanoparticles? Important new insights into each of these topics, obtained from state-of-the-art ultrafast spectroscopy and/or theoretical methods, are summarized in this review. PMID:29333473

Teaching Applied Genetics and Molecular Biology to Agriculture Engineers. Application of the European Credit Transfer System

ERIC Educational Resources Information Center

Weiss, J.; Egea-Cortines, M.

2008-01-01

We have been teaching applied molecular genetics to engineers and adapted the teaching methodology to the European Credit Transfer System. We teach core principles of genetics that are universal and form the conceptual basis of most molecular technologies. The course then teaches widely used techniques and finally shows how different techniques…

The display of molecular models with the Ames Interactive Modeling System (AIMS)

NASA Technical Reports Server (NTRS)

Egan, J. T.; Hart, J.; Burt, S. K.; Macelroy, R. D.

1982-01-01

A visualization of molecular models can lead to a clearer understanding of the models. Sophisticated graphics devices supported by minicomputers make it possible for the chemist to interact with the display of a very large model, altering its structure. In addition to user interaction, the need arises also for other ways of displaying information. These include the production of viewgraphs, film presentation, as well as publication quality prints of various models. To satisfy these needs, the display capability of the Ames Interactive Modeling System (AIMS) has been enhanced to provide a wide range of graphics and plotting capabilities. Attention is given to an overview of the AIMS system, graphics hardware used by the AIMS display subsystem, a comparison of graphics hardware, the representation of molecular models, graphics software used by the AIMS display subsystem, the display of a model obtained from data stored in molecule data base, a graphics feature for obtaining single frame permanent copy displays, and a feature for producing multiple frame displays.

A field-deployable mobile molecular diagnostic system for malaria at the point of need.

PubMed

Choi, Gihoon; Song, Daniel; Shrestha, Sony; Miao, Jun; Cui, Liwang; Guan, Weihua

2016-11-01

In response to the urgent need of a field-deployable and highly sensitive malaria diagnosis, we developed a standalone, "sample-in-answer-out" molecular diagnostic system (AnyMDx) to enable quantitative molecular analysis of blood-borne malaria in low resource areas. The system consists of a durable battery-powered analyzer and a disposable microfluidic compact disc loaded with reagents ready for use. A low power thermal module and a novel fluorescence-sensing module are integrated into the analyzer for real-time monitoring of loop-mediated isothermal nucleic acid amplification (LAMP) of target parasite DNA. With 10 μL of raw blood sample, the AnyMDx system automates the nucleic acid sample preparation and subsequent LAMP and real-time detection. Under laboratory conditions with whole-blood samples spiked with cultured Plasmodium falciparum, we achieved a detection limit of ∼0.6 parasite per μL, much lower than those for the conventional microscopy and rapid diagnostic tests (∼50-100 parasites per μL). The turnaround time from sample to answer is less than 40 minutes. The AnyMDx is user-friendly requiring minimal technological training. The analyzer and the disposable reagent compact discs are cost-effective, making AnyMDx a potential tool for malaria molecular diagnosis under field settings for malaria elimination.

[Metastasis tumors of the central nervous system: molecular biology].

PubMed

Bello, M Josefa; González-Gómez, P; Rey, J A

2004-12-01

Metastases in the nervous system represent an important and growing problem in the clinical practice, being the cause of a great mortality in the developed countries. This article reviews the few data available on the molecular mechanisms involved in the pathogenesis of these tumours, leading to oncogene activation, inactivation of tumour suppressor genes, not only by the classical mechanisms, but also by the tumour cell epigenetic balance alteration. We conclude that all this knowledge will lead in the future to a better diagnosis, treatment and clinic evolution of these patients.

In vivo targeted peripheral nerve imaging with a nerve-specific nanoscale magnetic resonance probe.

PubMed

Zheng, Linfeng; Li, Kangan; Han, Yuedong; Wei, Wei; Zheng, Sujuan; Zhang, Guixiang

2014-11-01

Neuroimaging plays a pivotal role in clinical practice. Currently, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography (PET) are applied in the clinical setting as neuroimaging modalities. There is no optimal imaging modality for clinical peripheral nerve imaging even though fluorescence/bioluminescence imaging has been used for preclinical studies on the nervous system. Some studies have shown that molecular and cellular MRI (MCMRI) can be used to visualize and image the cellular and molecular level of the nervous system. Other studies revealed that there are different pathological/molecular changes in the proximal and distal sites after peripheral nerve injury (PNI). Therefore, we hypothesized that in vivo peripheral nerve targets can be imaged using MCMRI with specific MRI probes. Specific probes should have higher penetrability for the blood-nerve barrier (BNB) in vivo. Here, a functional nanometre MRI probe that is based on nerve-specific proteins as targets, specifically, using a molecular antibody (mAb) fragment conjugated to iron nanoparticles as an MRI probe, was constructed for further study. The MRI probe allows for imaging the peripheral nerve targets in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

MolabIS--an integrated information system for storing and managing molecular genetics data.

PubMed

Truong, Cong V C; Groeneveld, Linn F; Morgenstern, Burkhard; Groeneveld, Eildert

2011-10-31

Long-term sample storage, tracing of data flow and data export for subsequent analyses are of great importance in genetics studies. Therefore, molecular labs do need a proper information system to handle an increasing amount of data from different projects. We have developed a molecular labs information management system (MolabIS). It was implemented as a web-based system allowing the users to capture original data at each step of their workflow. MolabIS provides essential functionality for managing information on individuals, tracking samples and storage locations, capturing raw files, importing final data from external files, searching results, accessing and modifying data. Further important features are options to generate ready-to-print reports and convert sequence and microsatellite data into various data formats, which can be used as input files in subsequent analyses. Moreover, MolabIS also provides a tool for data migration. MolabIS is designed for small-to-medium sized labs conducting Sanger sequencing and microsatellite genotyping to store and efficiently handle a relative large amount of data. MolabIS not only helps to avoid time consuming tasks but also ensures the availability of data for further analyses. The software is packaged as a virtual appliance which can run on different platforms (e.g. Linux, Windows). MolabIS can be distributed to a wide range of molecular genetics labs since it was developed according to a general data model. Released under GPL, MolabIS is freely available at http://www.molabis.org.

Theoretical modeling of large molecular systems. Advances in the local self consistent field method for mixed quantum mechanics/molecular mechanics calculations.

PubMed

Monari, Antonio; Rivail, Jean-Louis; Assfeld, Xavier

2013-02-19

Molecular mechanics methods can efficiently compute the macroscopic properties of a large molecular system but cannot represent the electronic changes that occur during a chemical reaction or an electronic transition. Quantum mechanical methods can accurately simulate these processes, but they require considerably greater computational resources. Because electronic changes typically occur in a limited part of the system, such as the solute in a molecular solution or the substrate within the active site of enzymatic reactions, researchers can limit the quantum computation to this part of the system. Researchers take into account the influence of the surroundings by embedding this quantum computation into a calculation of the whole system described at the molecular mechanical level, a strategy known as the mixed quantum mechanics/molecular mechanics (QM/MM) approach. The accuracy of this embedding varies according to the types of interactions included, whether they are purely mechanical or classically electrostatic. This embedding can also introduce the induced polarization of the surroundings. The difficulty in QM/MM calculations comes from the splitting of the system into two parts, which requires severing the chemical bonds that link the quantum mechanical subsystem to the classical subsystem. Typically, researchers replace the quantoclassical atoms, those at the boundary between the subsystems, with a monovalent link atom. For example, researchers might add a hydrogen atom when a C-C bond is cut. This Account describes another approach, the Local Self Consistent Field (LSCF), which was developed in our laboratory. LSCF links the quantum mechanical portion of the molecule to the classical portion using a strictly localized bond orbital extracted from a small model molecule for each bond. In this scenario, the quantoclassical atom has an apparent nuclear charge of +1. To achieve correct bond lengths and force constants, we must take into account the inner shell of

A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

PubMed

Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

2015-02-01

The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Background-Free 3D Nanometric Localization and Sub-nm Asymmetry Detection of Single Plasmonic Nanoparticles by Four-Wave Mixing Interferometry with Optical Vortices

NASA Astrophysics Data System (ADS)

Zoriniants, George; Masia, Francesco; Giannakopoulou, Naya; Langbein, Wolfgang; Borri, Paola

2017-10-01

Single nanoparticle tracking using optical microscopy is a powerful technique with many applications in biology, chemistry, and material sciences. Despite significant advances, localizing objects with nanometric position precision in a scattering environment remains challenging. Applied methods to achieve contrast are dominantly fluorescence based, with fundamental limits in the emitted photon fluxes arising from the excited-state lifetime as well as photobleaching. Here, we show a new four-wave-mixing interferometry technique, whereby the position of a single nonfluorescing gold nanoparticle of 25-nm radius is determined with 16 nm precision in plane and 3 nm axially from rapid single-point measurements at 1-ms acquisition time by exploiting optical vortices. The precision in plane is consistent with the photon shot-noise, while axially it is limited by the nano-positioning sample stage, with an estimated photon shot-noise limit of 0.5 nm. The detection is background-free even inside biological cells. The technique is also uniquely sensitive to particle asymmetries of only 0.5% ellipticity, corresponding to a single atomic layer of gold, as well as particle orientation. This method opens new ways of unraveling single-particle trafficking within complex 3D architectures.

Logic circuits based on molecular spider systems.

PubMed

Mo, Dandan; Lakin, Matthew R; Stefanovic, Darko

2016-08-01

Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized reactions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi-spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Molecular biomimetics: utilizing nature's molecular ways in practical engineering.

PubMed

Tamerler, Candan; Sarikaya, Mehmet

2007-05-01

In nature, proteins are the machinery that accomplish many functions through their specific recognition and interactions in biological systems from single-celled to multicellular organisms. Biomolecule-material interaction is accomplished via molecular specificity, leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, molecular recognition and, consequently, functions developed through successive cycles of mutation and selection. Using biology as a guide, we can now understand, engineer and control peptide-material interactions and exploit these to tailor novel materials and systems for practical applications. We adapted combinatorial biology protocols to display peptide libraries, either on the cell surface or on phages, to select short peptides specific to a variety of practical materials systems. Following the selection step, we determined the kinetics and stability of peptide binding experimentally to understand the bound peptide structure via modeling and its assembly via atomic force microscopy. The peptides were further engineered to have multiple repeats or their amino acid sequences varied to tailor their function. Both nanoparticles and flat inorganic substrates containing multimaterials patterned at the nano- and microscales were used for self-directed immobilization of molecular constructs. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems with wide ranging applications, from tissue engineering, drug delivery and biosensors, to nanotechnology and bioremediation. Here we give examples of protein-mediated functional materials in biology, peptide selection and engineering with affinity to inorganics, demonstrate potential utilizations in materials science, engineering and medicine, and describe future prospects.

Non-linear optical techniques and optical properties of condensed molecular systems

NASA Astrophysics Data System (ADS)

Citroni, Margherita

2013-06-01

Structure, dynamics, and optical properties of molecular systems can be largely modified by the applied pressure, with remarkable consequences on their chemical stability. Several examples of selective reactions yielding technologically attractive products can be cited, which are particularly efficient when photochemical effects are exploited in conjunction with the structural conditions attained at high density. Non-linear optical techniques are a basic tool to unveil key aspects of the chemical reactivity and dynamic properties of molecules. Their application to high-pressure samples is experimentally challenging, mainly because of the small sample dimensions and of the non-linear effects generated in the anvil materials. In this talk I will present results on the electronic spectra of several aromatic crystals obtained through two-photon induced fluorescence and two-photon excitation profiles measured as a function of pressure (typically up to about 25 GPa), and discuss the relationship between the pressure-induced modifications of the electronic structure and the chemical reactivity at high pressure. I will also present the first successful pump-probe infrared measurement performed as a function of pressure on a condensed molecular system. The system under examination is liquid water, in a sapphire anvil cell, up to 1 GPa along isotherms at 298 and 363 K. These measurements give a new enlightening insight into the dynamical properties of low- and high-density water allowing a definition of the two structures.

Preventing iron(ii) precipitation in aqueous systems using polyacrylic acid: some molecular insights.

PubMed

Artola, Pierre-Arnaud; Rousseau, Bernard; Clavaguéra, Carine; Roy, Marion; You, Dominique; Plancque, Gabriel

2018-06-22

We present molecular dynamics simulations of aqueous iron(ii) systems in the presence of polyacrylic acid (PAA) under the extreme conditions that take place in the secondary coolant circuit of a nuclear power plant. The aim of this work is to understand how the oligomer can prevent iron(ii) deposits, and to provide molecular interpretation. We show how, to this end, not only the complexant ability is necessary, but also the chain length compared to iron(ii) concentration. When the chain is long enough, a hyper-complexation phenomenon occurs that can explain the specific capacity of the polymer to prevent iron(ii) precipitation.

Electronic structure, transport, and collective effects in molecular layered systems.

PubMed

Hahn, Torsten; Ludwig, Tim; Timm, Carsten; Kortus, Jens

2017-01-01

The great potential of organic heterostructures for organic device applications is exemplified by the targeted engineering of the electronic properties of phthalocyanine-based systems. The transport properties of two different phthalocyanine systems, a pure copper phthalocyanine (CoPc) and a flourinated copper phthalocyanine-manganese phthalocyanine (F 16 CoPc/MnPc) heterostructure, are investigated by means of density functional theory (DFT) and the non-equilibrium Green's function (NEGF) approach. Furthermore, a master-equation-based approach is used to include electronic correlations beyond the mean-field-type approximation of DFT. We describe the essential theoretical tools to obtain the parameters needed for the master equation from DFT results. Finally, an interacting molecular monolayer is considered within a master-equation approach.

Conductance oscillations in molecularly linked Au nanoparticle film-superconductor systems.

PubMed

Dunford, Jeffrey L; Dhirani, Al-Amin

2008-01-16

Charge transport across a disordered normal-superconductor (DN-S) interface was studied using a macroscopic, molecularly linked Au nanoparticle film as the DN component. Low-temperature conductance versus voltage and magnetic field exhibit zero-bias and zero-field peaks, respectively. Importantly, the latter typically exhibit superimposed oscillations. Such oscillations are rarely seen in other DN-S systems and are remarkable given their robustness in these macroscopic films and interfaces. A number of observations indicate that conductance peaks and oscillations arise due to a 'reflectionless tunnelling' process. Scattering length scales extracted from the data using a reflectionless tunnelling picture are consistent with literature values. Factors resulting in the observation of oscillations in this system are discussed.

International Conference on Intelligent Systems for Molecular Biology (ISMB)

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

Goldberg, Debra; Hibbs, Matthew; Kall, Lukas

The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference hasmore » resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.« less

Molecular features determining different partitioning patterns of papain and bromelain in aqueous two-phase systems.

PubMed

Rocha, Maria Victoria; Nerli, Bibiana Beatriz

2013-10-01

The partitioning patterns of papain (PAP) and bromelain (BR), two well-known cysteine-proteases, in polyethyleneglycol/sodium citrate aqueous two-phase systems (ATPSs) were determined. Polyethyleneglycols of different molecular weight (600, 1000, 2000, 4600 and 8000) were assayed. Thermodynamic characterization of partitioning process, spectroscopy measurements and computational calculations of protein surface properties were also carried out in order to explain their differential partitioning behavior. PAP was observed to be displaced to the salt-enriched phase in all the assayed systems with partition coefficients (KpPAP) values between 0.2 and 0.9, while BR exhibited a high affinity for the polymer phase in systems formed by PEGs of low molecular weight (600 and 1000) with partition coefficients (KpBR) values close to 3. KpBR values resulted higher than KpPAP in all the cases. This difference could be assigned neither to the charge nor to the size of the partitioned biomolecules since PAP and BR possess similar molecular weight (23,000) and isoelectric point (9.60). The presence of highly exposed tryptophans and positively charged residues (Lys, Arg and His) in BR molecule would be responsible for a charge transfer interaction between PEG and the protein and, therefore, the uneven distribution of BR in these systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Multiscale Molecular Dynamics Model for Heterogeneous Charged Systems

NASA Astrophysics Data System (ADS)

Stanton, L. G.; Glosli, J. N.; Murillo, M. S.

2018-04-01

Modeling matter across large length scales and timescales using molecular dynamics simulations poses significant challenges. These challenges are typically addressed through the use of precomputed pair potentials that depend on thermodynamic properties like temperature and density; however, many scenarios of interest involve spatiotemporal variations in these properties, and such variations can violate assumptions made in constructing these potentials, thus precluding their use. In particular, when a system is strongly heterogeneous, most of the usual simplifying assumptions (e.g., spherical potentials) do not apply. Here, we present a multiscale approach to orbital-free density functional theory molecular dynamics (OFDFT-MD) simulations that bridges atomic, interionic, and continuum length scales to allow for variations in hydrodynamic quantities in a consistent way. Our multiscale approach enables simulations on the order of micron length scales and 10's of picosecond timescales, which exceeds current OFDFT-MD simulations by many orders of magnitude. This new capability is then used to study the heterogeneous, nonequilibrium dynamics of a heated interface characteristic of an inertial-confinement-fusion capsule containing a plastic ablator near a fuel layer composed of deuterium-tritium ice. At these scales, fundamental assumptions of continuum models are explored; features such as the separation of the momentum fields among the species and strong hydrogen jetting from the plastic into the fuel region are observed, which had previously not been seen in hydrodynamic simulations.

Optical/MRI Multimodality Molecular Imaging

NASA Astrophysics Data System (ADS)

Ma, Lixin; Smith, Charles; Yu, Ping

2007-03-01

Multimodality molecular imaging that combines anatomical and functional information has shown promise in development of tumor-targeted pharmaceuticals for cancer detection or therapy. We present a new multimodality imaging technique that combines fluorescence molecular tomography (FMT) and magnetic resonance imaging (MRI) for in vivo molecular imaging of preclinical tumor models. Unlike other optical/MRI systems, the new molecular imaging system uses parallel phase acquisition based on heterodyne principle. The system has a higher accuracy of phase measurements, reduced noise bandwidth, and an efficient modulation of the fluorescence diffuse density waves. Fluorescent Bombesin probes were developed for targeting breast cancer cells and prostate cancer cells. Tissue phantom and small animal experiments were performed for calibration of the imaging system and validation of the targeting probes.

MolabIS - An integrated information system for storing and managing molecular genetics data

PubMed Central

2011-01-01

Background Long-term sample storage, tracing of data flow and data export for subsequent analyses are of great importance in genetics studies. Therefore, molecular labs do need a proper information system to handle an increasing amount of data from different projects. Results We have developed a molecular labs information management system (MolabIS). It was implemented as a web-based system allowing the users to capture original data at each step of their workflow. MolabIS provides essential functionality for managing information on individuals, tracking samples and storage locations, capturing raw files, importing final data from external files, searching results, accessing and modifying data. Further important features are options to generate ready-to-print reports and convert sequence and microsatellite data into various data formats, which can be used as input files in subsequent analyses. Moreover, MolabIS also provides a tool for data migration. Conclusions MolabIS is designed for small-to-medium sized labs conducting Sanger sequencing and microsatellite genotyping to store and efficiently handle a relative large amount of data. MolabIS not only helps to avoid time consuming tasks but also ensures the availability of data for further analyses. The software is packaged as a virtual appliance which can run on different platforms (e.g. Linux, Windows). MolabIS can be distributed to a wide range of molecular genetics labs since it was developed according to a general data model. Released under GPL, MolabIS is freely available at http://www.molabis.org. PMID:22040322

DEVELOPMENT OF SEPARATION SYSTEMS FOR POLYNUCLEAR AROMATIC HYDROCARBON ENVIRONMENTAL CONTAMINANTS USING MICELLAR ELECTROKINETIC CHROMATOGRAPHY WITH MOLECULAR MICELLES AND FREE ZONE ELECTROPHORESIS

EPA Science Inventory

Of four systems available from the literature, based on cyclodextrins, dioctylsulfosuccinate, bile salts, and molecular micelles consisting of oligomers of undecylenic acid, the most successful separation system in our hands is based on the molecular micelles, oligomers of sodiu...

A Unique Large-Scale Undergraduate Research Experience in Molecular Systems Biology for Non-Mathematics Majors

ERIC Educational Resources Information Center

Kappler, Ulrike; Rowland, Susan L.; Pedwell, Rhianna K.

2017-01-01

Systems biology is frequently taught with an emphasis on mathematical modeling approaches. This focus effectively excludes most biology, biochemistry, and molecular biology students, who are not mathematics majors. The mathematical focus can also present a misleading picture of systems biology, which is a multi-disciplinary pursuit requiring…

Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data.

PubMed

Martyanov, Viktor; Whitfield, Michael L

2016-01-01

The goal of this review is to summarize recent advances into the pathogenesis and treatment of systemic sclerosis (SSc) from genomic and proteomic studies. Intrinsic gene expression-driven molecular subtypes of SSc are reproducible across three independent datasets. These subsets are a consistent feature of SSc and are found in multiple end-target tissues, such as skin and esophagus. Intrinsic subsets as well as baseline levels of molecular target pathways are potentially predictive of clinical response to specific therapeutics, based on three recent clinical trials. A gene expression-based biomarker of modified Rodnan skin score, a measure of SSc skin severity, can be used as a surrogate outcome metric and has been validated in a recent trial. Proteome analyses have identified novel biomarkers of SSc that correlate with SSc clinical phenotypes. Integrating intrinsic gene expression subset data, baseline molecular pathway information, and serum biomarkers along with surrogate measures of modified Rodnan skin score provides molecular context in SSc clinical trials. With validation, these approaches could be used to match patients with the therapies from which they are most likely to benefit and thus increase the likelihood of clinical improvement.

Supramolecular Systems Behavior at the Air-Water Interface. Molecular Dynamic Simulation Study.

NASA Astrophysics Data System (ADS)

Sandoval, C.; Saavedra, M.; Gargallo, L.; Radić, D.

2008-08-01

Atomistic molecular dynamics simulation (MDS) was development to investigate the structural and dynamic properties of a monolayer of supramolecular systems. The simulations were performed at room temperature, on inclusion complexes (ICs) of α-cyclodextrin (CD) with poly(ethylene-oxide)(PEO), poly(ɛ-caprolactone)(PEC) and poly(tetrahydrofuran)(PTHF). The simulations were carried out for a surface area of 30Å. The trajectories of the MDS show that the system more stable was IC-PEC, being the less stable IC-PEO. The disordered monolayer for the systems was proved by the orientation correlation function and the radial distribution function between the polar groups of ICs and the water molecules. We found that the system IC-PEC was more stable that the systems IC-PTHF and IC-PEO.

A Fast Algorithm for Massively Parallel, Long-Term, Simulation of Complex Molecular Dynamics Systems

NASA Technical Reports Server (NTRS)

Jaramillo-Botero, Andres; Goddard, William A, III; Fijany, Amir

1997-01-01

The advances in theory and computing technology over the last decade have led to enormous progress in applying atomistic molecular dynamics (MD) methods to the characterization, prediction, and design of chemical, biological, and material systems,.

Molecular phenology in plants: in natura systems biology for the comprehensive understanding of seasonal responses under natural environments.

PubMed

Kudoh, Hiroshi

2016-04-01

Phenology refers to the study of seasonal schedules of organisms. Molecular phenology is defined here as the study of the seasonal patterns of organisms captured by molecular biology techniques. The history of molecular phenology is reviewed briefly in relation to advances in the quantification technology of gene expression. High-resolution molecular phenology (HMP) data have enabled us to study phenology with an approach of in natura systems biology. I review recent analyses of FLOWERING LOCUS C (FLC), a temperature-responsive repressor of flowering, along the six steps in the typical flow of in natura systems biology. The extensive studies of the regulation of FLC have made this example a successful case in which a comprehensive understanding of gene functions has been progressing. The FLC-mediated long-term memory of past temperatures creates time lags with other seasonal signals, such as photoperiod and short-term temperature. Major signals that control flowering time have a phase lag between them under natural conditions, and hypothetical phase lag calendars are proposed as mechanisms of season detection in plants. Transcriptomic HMP brings a novel strategy to the study of molecular phenology, because it provides a comprehensive representation of plant functions. I discuss future perspectives of molecular phenology from the standpoints of molecular biology, evolutionary biology and ecology. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

Programmable disorder in random DNA tilings

NASA Astrophysics Data System (ADS)

Tikhomirov, Grigory; Petersen, Philip; Qian, Lulu

2017-03-01

Scaling up the complexity and diversity of synthetic molecular structures will require strategies that exploit the inherent stochasticity of molecular systems in a controlled fashion. Here we demonstrate a framework for programming random DNA tilings and show how to control the properties of global patterns through simple, local rules. We constructed three general forms of planar network—random loops, mazes and trees—on the surface of self-assembled DNA origami arrays on the micrometre scale with nanometre resolution. Using simple molecular building blocks and robust experimental conditions, we demonstrate control of a wide range of properties of the random networks, including the branching rules, the growth directions, the proximity between adjacent networks and the size distribution. Much as combinatorial approaches for generating random one-dimensional chains of polymers have been used to revolutionize chemical synthesis and the selection of functional nucleic acids, our strategy extends these principles to random two-dimensional networks of molecules and creates new opportunities for fabricating more complex molecular devices that are organized by DNA nanostructures.

Identification and super-resolution imaging of ligand-activated receptor dimers in live cells

NASA Astrophysics Data System (ADS)

Winckler, Pascale; Lartigue, Lydia; Giannone, Gregory; de Giorgi, Francesca; Ichas, François; Sibarita, Jean-Baptiste; Lounis, Brahim; Cognet, Laurent

2013-08-01

Molecular interactions are key to many chemical and biological processes like protein function. In many signaling processes they occur in sub-cellular areas displaying nanoscale organizations and involving molecular assemblies. The nanometric dimensions and the dynamic nature of the interactions make their investigations complex in live cells. While super-resolution fluorescence microscopies offer live-cell molecular imaging with sub-wavelength resolutions, they lack specificity for distinguishing interacting molecule populations. Here we combine super-resolution microscopy and single-molecule Förster Resonance Energy Transfer (FRET) to identify dimers of receptors induced by ligand binding and provide super-resolved images of their membrane distribution in live cells. By developing a two-color universal-Point-Accumulation-In-the-Nanoscale-Topography (uPAINT) method, dimers of epidermal growth factor receptors (EGFR) activated by EGF are studied at ultra-high densities, revealing preferential cell-edge sub-localization. This methodology which is specifically devoted to the study of molecules in interaction, may find other applications in biological systems where understanding of molecular organization is crucial.

Structural and molecular interrogation of intact biological systems

PubMed Central

Chung, Kwanghun; Wallace, Jenelle; Kim, Sung-Yon; Kalyanasundaram, Sandhiya; Andalman, Aaron S.; Davidson, Thomas J.; Mirzabekov, Julie J.; Zalocusky, Kelly A.; Mattis, Joanna; Denisin, Aleksandra K.; Pak, Sally; Bernstein, Hannah; Ramakrishnan, Charu; Grosenick, Logan; Gradinaru, Viviana; Deisseroth, Karl

2014-01-01

Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease. PMID:23575631

Engineering molecular machines

NASA Astrophysics Data System (ADS)

Erman, Burak

2016-04-01

Biological molecular motors use chemical energy, mostly in the form of ATP hydrolysis, and convert it to mechanical energy. Correlated thermal fluctuations are essential for the function of a molecular machine and it is the hydrolysis of ATP that modifies the correlated fluctuations of the system. Correlations are consequences of the molecular architecture of the protein. The idea that synthetic molecular machines may be constructed by designing the proper molecular architecture is challenging. In their paper, Sarkar et al (2016 New J. Phys. 18 043006) propose a synthetic molecular motor based on the coarse grained elastic network model of proteins and show by numerical simulations that motor function is realized, ranging from deterministic to thermal, depending on temperature. This work opens up a new range of possibilities of molecular architecture based engine design.

Positron annihilation lifetime spectroscopy (PALS): a probe for molecular organisation in self-assembled biomimetic systems.

PubMed

Fong, Celesta; Dong, Aurelia W; Hill, Anita J; Boyd, Ben J; Drummond, Calum J

2015-07-21

Positron annihilation lifetime spectroscopy (PALS) has been shown to be highly sensitive to conformational, structural and microenvironmental transformations arising from subtle geometric changes in molecular geometry in self-assembling biomimetic systems. The ortho-positronium (oPs) may be considered an active probe that can provide information on intrinsic packing and mobility within low molecular weight solids, viscous liquids, and soft matter systems. In this perspective we provide a critical overview of the literature in this field, including the evolution of analysis software and experimental protocols with commentary upon the practical utility of PALS. In particular, we discuss how PALS can provide unique insight into the macroscopic transport properties of several porous biomembrane-like nanostructures and suggest how this insight may provide information on the release of drugs from these matrices to aid in developing therapeutic interventions. We discuss the potentially exciting and fruitful application of this technique to membrane dynamics, diffusion and permeability. We propose that PALS can provide novel molecular level information that is complementary to conventional characterisation techniques.

Photon Upconversion and Molecular Solar Energy Storage by Maximizing the Potential of Molecular Self-Assembly.

PubMed

Kimizuka, Nobuo; Yanai, Nobuhiro; Morikawa, Masa-Aki

2016-11-29

The self-assembly of functional molecules into ordered molecular assemblies and the fulfillment of potentials unique to their nanotomesoscopic structures have been one of the central challenges in chemistry. This Feature Article provides an overview of recent progress in the field of molecular self-assembly with the focus on the triplet-triplet annihilation-based photon upconversion (TTA-UC) and supramolecular storage of photon energy. On the basis of the integration of molecular self-assembly and photon energy harvesting, triplet energy migration-based TTA-UC has been achieved in varied molecular systems. Interestingly, some molecular self-assemblies dispersed in solution or organogels revealed oxygen barrier properties, which allowed TTA-UC even under aerated conditions. The elements of molecular self-assembly were also introduced to the field of molecular solar thermal fuel, where reversible photoliquefaction of ionic crystals to ionic liquids was found to double the molecular storage capacity with the simultaneous pursuit of switching ionic conductivity. A future prospect in terms of innovating molecular self-assembly toward molecular systems chemistry is also discussed.

Molecular Physiology of Root System Architecture in Model Grasses

NASA Astrophysics Data System (ADS)

Hixson, K.; Ahkami, A. H.; Anderton, C.; Veličković, D.; Myers, G. L.; Chrisler, W.; Lindenmaier, R.; Fang, Y.; Yabusaki, S.; Rosnow, J. J.; Farris, Y.; Khan, N. E.; Bernstein, H. C.; Jansson, C.

2017-12-01

Unraveling the molecular and physiological mechanisms involved in responses of Root System Architecture (RSA) to abiotic stresses and shifts in microbiome structure is critical to understand and engineer plant-microbe-soil interactions in the rhizosphere. In this study, accessions of Brachypodium distachyon Bd21 (C3 model grass) and Setaria viridis A10.1 (C4 model grass) were grown in phytotron chambers under current and elevated CO2 levels. Detailed growth stage-based phenotypic analysis revealed different above- and below-ground morphological and physiological responses in C3 and C4 grasses to enhanced CO2 levels. Based on our preliminary results and by screening values of total biomass, water use efficiency, root to shoot ratio, RSA parameters and net assimilation rates, we postulated a three-phase physiological mechanism, i.e. RootPlus, BiomassPlus and YieldPlus phases, for grass growth under elevated CO2 conditions. Moreover, this comprehensive set of morphological and process-based observations are currently in use to develop, test, and calibrate biophysical whole-plant models and in particular to simulate leaf-level photosynthesis at various developmental stages of C3 and C4 using the model BioCro. To further link the observed phenotypic traits at the organismal level to tissue and molecular levels, and to spatially resolve the origin and fate of key metabolites involved in primary carbohydrate metabolism in different root sections, we complement root phenotypic observations with spatial metabolomics data using mass spectrometry imaging (MSI) methods. Focusing on plant-microbe interactions in the rhizosphere, six bacterial strains with plant growth promoting features are currently in use in both gel-based and soil systems to screen root growth and development in Brachypodium. Using confocal microscopy, GFP-tagged bacterial systems are utilized to study the initiation of different root types of RSA, including primary root (PR), coleoptile node axile root (CNR

GIDL: a rule based expert system for GenBank Intelligent Data Loading into the Molecular Biodiversity database

PubMed Central

2012-01-01

Background In the scientific biodiversity community, it is increasingly perceived the need to build a bridge between molecular and traditional biodiversity studies. We believe that the information technology could have a preeminent role in integrating the information generated by these studies with the large amount of molecular data we can find in bioinformatics public databases. This work is primarily aimed at building a bioinformatic infrastructure for the integration of public and private biodiversity data through the development of GIDL, an Intelligent Data Loader coupled with the Molecular Biodiversity Database. The system presented here organizes in an ontological way and locally stores the sequence and annotation data contained in the GenBank primary database. Methods The GIDL architecture consists of a relational database and of an intelligent data loader software. The relational database schema is designed to manage biodiversity information (Molecular Biodiversity Database) and it is organized in four areas: MolecularData, Experiment, Collection and Taxonomy. The MolecularData area is inspired to an established standard in Generic Model Organism Databases, the Chado relational schema. The peculiarity of Chado, and also its strength, is the adoption of an ontological schema which makes use of the Sequence Ontology. The Intelligent Data Loader (IDL) component of GIDL is an Extract, Transform and Load software able to parse data, to discover hidden information in the GenBank entries and to populate the Molecular Biodiversity Database. The IDL is composed by three main modules: the Parser, able to parse GenBank flat files; the Reasoner, which automatically builds CLIPS facts mapping the biological knowledge expressed by the Sequence Ontology; the DBFiller, which translates the CLIPS facts into ordered SQL statements used to populate the database. In GIDL Semantic Web technologies have been adopted due to their advantages in data representation, integration and

[Low-grade systemic inflammation and the development of metabolic diseases: from the molecular evidence to the clinical practice].

PubMed

León-Pedroza, José Israel; González-Tapia, Luis Alonso; del Olmo-Gil, Esteban; Castellanos-Rodríguez, Diana; Escobedo, Galileo; González-Chávez, Antonio

2015-01-01

Systemic inflammation is characterised by high circulating levels of inflammatory cytokines and increased macrophage infiltration in peripheral tissues. Most importantly, this inflammatory state does not involve damage or loss of function of the infiltrated tissue, which is a distinctive feature of the low-grade systemic inflammation. The term "meta-inflammation" has also been used to refer to the low-grade systemic inflammation due to its strong relationship with the development of cardio-metabolic diseases in obesity. A review is presented on the recent clinical and experimental evidence concerning the role of adipose tissue inflammation as a key mediator of low-grade systemic inflammation. Furthermore, the main molecular mechanisms involved in the inflammatory polarization of macrophages with the ability to infiltrate both the adipose tissue and the vascular endothelium via activation of toll-like receptors by metabolic damage-associated molecular patterns, such as advanced glycation-end products and oxidized lipoproteins, is discussed. Finally, a review is made of the pathogenic mechanisms through which the low-grade systemic inflammation contributes to develop insulin resistance, dyslipidaemia, atherogenesis, type 2 diabetes, and hypertension in obese individuals. A better understanding of the molecular mechanisms of low-grade systemic inflammation in promoting cardio-metabolic diseases is necessary, in order to further design novel anti-inflammatory therapies that take into consideration clinical data, as well as the circulating levels of cytokines, immune cells, and metabolic damage-associated molecular patterns in each patient. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

System for Informatics in the Molecular Pathology Laboratory: An Open-Source End-to-End Solution for Next-Generation Sequencing Clinical Data Management.

PubMed

Kang, Wenjun; Kadri, Sabah; Puranik, Rutika; Wurst, Michelle N; Patil, Sushant A; Mujacic, Ibro; Benhamed, Sonia; Niu, Nifang; Zhen, Chao Jie; Ameti, Bekim; Long, Bradley C; Galbo, Filipo; Montes, David; Iracheta, Crystal; Gamboa, Venessa L; Lopez, Daisy; Yourshaw, Michael; Lawrence, Carolyn A; Aisner, Dara L; Fitzpatrick, Carrie; McNerney, Megan E; Wang, Y Lynn; Andrade, Jorge; Volchenboum, Samuel L; Furtado, Larissa V; Ritterhouse, Lauren L; Segal, Jeremy P

2018-04-24

Next-generation sequencing (NGS) diagnostic assays increasingly are becoming the standard of care in oncology practice. As the scale of an NGS laboratory grows, management of these assays requires organizing large amounts of information, including patient data, laboratory processes, genomic data, as well as variant interpretation and reporting. Although several Laboratory Information Systems and/or Laboratory Information Management Systems are commercially available, they may not meet all of the needs of a given laboratory, in addition to being frequently cost-prohibitive. Herein, we present the System for Informatics in the Molecular Pathology Laboratory, a free and open-source Laboratory Information System/Laboratory Information Management System for academic and nonprofit molecular pathology NGS laboratories, developed at the Genomic and Molecular Pathology Division at the University of Chicago Medicine. The System for Informatics in the Molecular Pathology Laboratory was designed as a modular end-to-end information system to handle all stages of the NGS laboratory workload from test order to reporting. We describe the features of the system, its clinical validation at the Genomic and Molecular Pathology Division at the University of Chicago Medicine, and its installation and testing within a different academic center laboratory (University of Colorado), and we propose a platform for future community co-development and interlaboratory data sharing. Copyright © 2018. Published by Elsevier Inc.

Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments.

PubMed

Renard, Justine; Norris, Christopher; Rushlow, Walter; Laviolette, Steven R

2017-04-01

Growing clinical and pre-clinical evidence points to a critical role for cannabidiol (CBD), the largest phytochemical component of cannabis, as a potential pharmacotherapy for various neuropsychiatric disorders. In contrast to delta-9-tetrahydrocannabinol (THC), which is associated with acute and neurodevelopmental pro-psychotic side-effects, CBD possesses no known psychoactive or dependence-producing properties. However, evidence has demonstrated that CBD strongly modulates the mesolimbic dopamine (DA) system and may possess promising anti-psychotic properties. Despite the psychotropic differences between CBD and THC, little is known regarding their molecular and neuronal effects on the mesolimbic DA system, nor how these differential effects may relate to their potential pro vs. anti-psychotic properties. This review summarizes clinical and pre-clinical evidence demonstrating CBD's modulatory effects on DA activity states within the mesolimbic pathway, functional interactions with the serotonin 5-HT 1A receptor system, and their downstream molecular signaling effects. Together with clinical evidence showing that CBD may normalize affective and cognitive deficits associated with schizophrenia, CBD may represent a promising treatment for schizophrenia, acting through novel molecular and neuronal mesolimbic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resistance of Type 5 chemical protective clothing against nanometric airborne particles: Behavior of seams and zipper.

PubMed

Vinches, Ludwig; Hallé, Stéphane

2017-12-01

In the field of dermal protection, the use of chemical protective clothing (CPC) (including coveralls) are considered as the last barrier against airborne engineered nanomaterials (ENM). In the majority of cases, Type 5 CPC, used against solid particles (ISO 13982-1), perform well against ENM. But in a recent study, a penetration level (PL) of up to 8.5% of polydisperse sodium chloride airborne nanoparticles has been measured. Moreover, in all the previous studies, tests were performed on a sample of protective clothing material without seams or zippers. Thus, the potential for permeation through a zipper or seams has not yet been determined, even though these areas would be privileged entry points for airborne ENM. This work was designed to evaluate the PL of airborne ENM through coveralls and specifically the PL through the seams on different parts of the CPC and the zipper. Eight current models of CPC (Type 5) were selected. The samples were taken from places with and without seams and with a zipper. In some cases, a cover strip can be added to the zipper to enhance its sealing. Polydisperse nanoparticles were generated by nebulization of a sodium chloride solution. A penetration cell was developed to expose the sample to airborne nanometric particles. The NaCl particle concentration in number was measured with an ultrafine particle counter and the PL was defined as the downstream concentration divided by the upstream concentration. The results obtained show that the PL increased significantly in the presence of seams and could reach up to 90% depending on the seam's design. Moreover, this study classifies the different types of seams by their resistance against airborne ENM. As for the penetration of airborne NaCl particles through the zipper, the PL was greatly attenuated by the presence of a cover strip, but only for certain models of coveralls. Finally, the values of the pressure drop were directly linked to the type of seam. All of these conclusions provide

Technical Note: Nanometric organic photovoltaic thin film detectors for dose monitoring in diagnostic x-ray imaging

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

Elshahat, Bassem; Gill, Hardeep Singh; Kumar, Jayant

2015-07-15

Purpose: To fabricate organic photovoltaic (OPV) cells with nanometric active layers sensitive to ionizing radiation and measure their dosimetric characteristics in clinical x-ray beams in the diagnostic tube potential range of 60–150 kVp. Methods: Experiments were designed to optimize the detector’s x-ray response and find the best parameter combination by changing the active layer thickness and the area of the electrode. The OPV cell consisted of poly (3-hexylthiophene-2,5-diyl): [6,6]-phenyl C{sub 61} butyric acid methyl ester photoactive donor and acceptor semiconducting organic materials sandwiched between an aluminum electrode as an anode and an indium tin oxide electrode as a cathode. Themore » authors measured the radiation-induced electric current at zero bias voltage in all fabricated OPV cells. Results: The net OPV current as a function of beam potential (kVp) was proportional to kVp{sup −0.5} when normalized to x-ray tube output, which varies with kVp. Of the tested configurations, the best combination of parameters was 270 nm active layer thicknesses with 0.7 cm{sup 2} electrode area, which provided the highest signal per electrode area. For this cell, the measured current ranged from approximately 0.7 to 2.4 nA/cm{sup 2} for 60–150 kVp, corresponding to about 0.09 nA–0.06 nA/mGy air kerma, respectively. When compared to commercial amorphous silicon thin film photovoltaic cells irradiated under the same conditions, this represents 2.5 times greater sensitivity. An additional 40% signal enhancement was observed when a 1 mm layer of plastic scintillator was attached to the cells’ beam-facing side. Conclusions: Since both OPVs can be produced as flexible devices and they do not require external bias voltage, they open the possibility for use as thin film in vivo detectors for dose monitoring in diagnostic x-ray imaging.« less

Library of molecular associations: curating the complex molecular basis of liver diseases.

PubMed

Buchkremer, Stefan; Hendel, Jasmin; Krupp, Markus; Weinmann, Arndt; Schlamp, Kai; Maass, Thorsten; Staib, Frank; Galle, Peter R; Teufel, Andreas

2010-03-20

Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases.

Molecular interactions in a surfactant-water-polyacrylamide system, according to densimetry, viscometry, conductometry, and spectroscopy data

NASA Astrophysics Data System (ADS)

Harutyunyan, R. S.

2013-08-01

Molecular interactions in a surfactant-polyacrylamide-water system are investigated. It is established that the interactions affect such physicochemical parameters of the system as viscosity, density, surface tension, conductivity, and critical micelle concentration. It is shown that in a polyacrylamide-water system, raising the polyacrylamide concentration to 0.02% causes conformational changes in its macromolecule.

The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies.

PubMed

Vegting, Yosta; Reneman, Liesbeth; Booij, Jan

2016-10-01

Ecstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems. The objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans. A search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied. Thirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use. Preclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.

A research project-based and self-determined teaching system of molecular biology techniques for undergraduates.

PubMed

Zhang, Shuping

2008-05-01

Molecular biology techniques play a very important role in understanding the biological activity. Students who major in biology should know not only how to perform experiments, but also the reasons for performing them. Having the concept of conducting research by integrating various techniques is especially important. This paper introduces a research project-based and self-determined teaching system of molecular biology techniques for undergraduates. Its aim is to create an environment mimicking real research programs and to help students build up confidence in their research skills. The students are allowed to explore a set of commonly used molecular biology techniques to solve some fundamental problems about genes on their own. They find a gene of interest, write a mini-proposal, and give an oral presentation. This course provides students a foundation before entering the research laboratory and allows them to adapt easily to real research programs. Copyright © 2008 International Union of Biochemistry and Molecular Biology, Inc.

Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System

NASA Astrophysics Data System (ADS)

Ouyang, Mengxing; Hill, Winfield; Lee, Jung Hyun; Hur, Soojung Claire

2017-03-01

Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages.

A unique large-scale undergraduate research experience in molecular systems biology for non-mathematics majors.

PubMed

Kappler, Ulrike; Rowland, Susan L; Pedwell, Rhianna K

2017-05-01

Systems biology is frequently taught with an emphasis on mathematical modeling approaches. This focus effectively excludes most biology, biochemistry, and molecular biology students, who are not mathematics majors. The mathematical focus can also present a misleading picture of systems biology, which is a multi-disciplinary pursuit requiring collaboration between biochemists, bioinformaticians, and mathematicians. This article describes an authentic large-scale undergraduate research experience (ALURE) in systems biology that incorporates proteomics, bacterial genomics, and bioinformatics in the one exercise. This project is designed to engage students who have a basic grounding in protein chemistry and metabolism and no mathematical modeling skills. The pedagogy around the research experience is designed to help students attack complex datasets and use their emergent metabolic knowledge to make meaning from large amounts of raw data. On completing the ALURE, participants reported a significant increase in their confidence around analyzing large datasets, while the majority of the cohort reported good or great gains in a variety of skills including "analysing data for patterns" and "conducting database or internet searches." An environmental scan shows that this ALURE is the only undergraduate-level system-biology research project offered on a large-scale in Australia; this speaks to the perceived difficulty of implementing such an opportunity for students. We argue however, that based on the student feedback, allowing undergraduate students to complete a systems-biology project is both feasible and desirable, even if the students are not maths and computing majors. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(3):235-248, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

Cellular and Molecular Actions of Methylene Blue in the Nervous System

PubMed Central

Oz, Murat; Lorke, Dietrich E.; Hasan, Mohammed; Petroianu, George A.

2010-01-01

Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide-induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. PMID:19760660

Mobile-bearing knee systems: ultra-high molecular weight polyethylene wear and design issues.

PubMed

Greenwald, A Seth; Heim, Christine S

2005-01-01

In June 2004, the U.S. Food and Drug Administration Orthopaedic Advisory Panel recommended the reclassification of mobile-bearing knee systems for general use. This reflects the increasing use of mobile-bearing knee systems internationally, which is currently limited in the United States by regulatory requirement. Mobile-bearing knee systems are distinguished from conventional, fixed-plateau systems in that they allow dual-surface articulation between an ultra-high molecular weight polyethylene insert and metallic femoral and tibial tray components. Their in vivo success is dependent on patient selection, design, and material choice, as well as surgical precision during implantation. Laboratory and clinical experience extending over 25 years with individual systems suggests that mobile-bearing knee systems represent a viable treatment option for patients with knee arthrosis.

Molecular architecture of the fruit fly's airway epithelial immune system.

PubMed

Wagner, Christina; Isermann, Kerstin; Fehrenbach, Heinz; Roeder, Thomas

2008-09-29

Airway epithelial cells not only constitute a physical barrier, but also the first line of defence against airborne pathogens. At the same time, they are constantly exposed to reactive oxygen species. Therefore, airway epithelia cells have to possess a sophisticated innate immune system and a molecular armamentarium to detoxify reactive oxygen species. It has become apparent that deregulation of epithelial innate immunity is a major reason for the development of chronic inflammatory lung diseases. To elucidate the molecular architecture of the innate immune system of airway epithelial cells, we choose the fruit fly Drosophila melanogaster as a model, because it has the simplest type of airways, consisting of epithelial cells only. Elucidating the structure of the innate immune system of this "airway epithelial cell culture" might enable us to understand why deregulatory processes in innate immune signalling cascades lead to long lasting inflammatory events. All airway epithelial cells of the fruit fly are able to launch an immune response. They contain only one functional signal transduction pathway that converges onto NF-kappaB factors, namely the IMD-pathway, which is homologous to the TNF-alpha receptor pathway. Although vital parts of the Toll-pathway are missing, dorsal and dif, the NF-kappaB factors dedicated to this signalling system, are present. Other pathways involved in immune regulation, such as the JNK- and the JAK/STAT-pathway, are completely functional in these cells. In addition, most peptidoglycan recognition proteins, representing the almost complete collection of pattern recognition receptors, are part of the epithelial cells equipment. Potential effector molecules are different antimicrobial peptides and lysozymes, but also transferrin that can inhibit bacterial growth through iron-depletion. Reactive oxygen species can be inactivated through the almost complete armamentarium of enzymatic antioxidants that has the fly to its disposal. The innate

Origami: A Versatile Modeling System for Visualising Chemical Structure and Exploring Molecular Function

ERIC Educational Resources Information Center

Davis, James; Leslie, Ray; Billington, Susan; Slater, Peter R.

2010-01-01

The use of "Origami" is presented as an accessible and transferable modeling system through which to convey the intricacies of molecular shape and highlight structure-function relationships. The implementation of origami has been found to be a versatile alternative to conventional ball-and-stick models, possessing the key advantages of being both…

Online molecular image repository and analysis system: A multicenter collaborative open-source infrastructure for molecular imaging research and application.

PubMed

Rahman, Mahabubur; Watabe, Hiroshi

2018-05-01

Molecular imaging serves as an important tool for researchers and clinicians to visualize and investigate complex biochemical phenomena using specialized instruments; these instruments are either used individually or in combination with targeted imaging agents to obtain images related to specific diseases with high sensitivity, specificity, and signal-to-noise ratios. However, molecular imaging, which is a multidisciplinary research field, faces several challenges, including the integration of imaging informatics with bioinformatics and medical informatics, requirement of reliable and robust image analysis algorithms, effective quality control of imaging facilities, and those related to individualized disease mapping, data sharing, software architecture, and knowledge management. As a cost-effective and open-source approach to address these challenges related to molecular imaging, we develop a flexible, transparent, and secure infrastructure, named MIRA, which stands for Molecular Imaging Repository and Analysis, primarily using the Python programming language, and a MySQL relational database system deployed on a Linux server. MIRA is designed with a centralized image archiving infrastructure and information database so that a multicenter collaborative informatics platform can be built. The capability of dealing with metadata, image file format normalization, and storing and viewing different types of documents and multimedia files make MIRA considerably flexible. With features like logging, auditing, commenting, sharing, and searching, MIRA is useful as an Electronic Laboratory Notebook for effective knowledge management. In addition, the centralized approach for MIRA facilitates on-the-fly access to all its features remotely through any web browser. Furthermore, the open-source approach provides the opportunity for sustainable continued development. MIRA offers an infrastructure that can be used as cross-boundary collaborative MI research platform for the rapid

Cellular and Molecular Underpinnings of Neuronal Assembly in the Central Auditory System during Mouse Development

PubMed Central

Di Bonito, Maria; Studer, Michèle

2017-01-01

During development, the organization of the auditory system into distinct functional subcircuits depends on the spatially and temporally ordered sequence of neuronal specification, differentiation, migration and connectivity. Regional patterning along the antero-posterior axis and neuronal subtype specification along the dorso-ventral axis intersect to determine proper neuronal fate and assembly of rhombomere-specific auditory subcircuits. By taking advantage of the increasing number of transgenic mouse lines, recent studies have expanded the knowledge of developmental mechanisms involved in the formation and refinement of the auditory system. Here, we summarize several findings dealing with the molecular and cellular mechanisms that underlie the assembly of central auditory subcircuits during mouse development, focusing primarily on the rhombomeric and dorso-ventral origin of auditory nuclei and their associated molecular genetic pathways. PMID:28469562

Molecular simulations of lipid systems: Edge stability and structure in pure and mixed bilayers

NASA Astrophysics Data System (ADS)

Jiang, Yong

2007-12-01

Understanding the structural, mechanical and dynamical properties of lipid self-assembled systems is fundamental to understand the behavior of the cell membrane. This thesis has investigated the equilibrium properties of lipid systems with edge defects through various molecular simulation techniques. The overall goal of this study is to understand the free energy terms of the edges and to develop efficient methods to sample equilibrium distributions of mixed-lipid systems. In the first main part of my thesis, an atomistic molecular model is used to study lipid ribbon which has two edges on both sides. Details of the edge structures, such as area per lipid and tail torsional statistics are presented. Line tension, calculated from pressure tensor in MD simulation has good agreement with result from other sources. To further investigate edge properties on a longer timescale and larger length scale, we have applied a coarse-grained forcefield on mixed lipid systems and try to interpret the edge fluctuations in terms of free energy parameters such as line tension and bending modulus. We have identified two regimes with quite different edge behavior: a high line tension regime and a low line tension regime. The last part of this thesis focuses on a hybrid Molecular dynamics and Configurational-bias Monte Carlo (MCMD) simulation method in which molecules can change their type by growing and shrinking the terminal acyl united carbon atoms. A two-step extension of the MCMD method has been developed to allow for a larger difference in the components' tail lengths. Results agreed well with previous one-step mutation results for a mixture with a length difference of four carbons. The current method can efficiently sample mixtures with a length difference of eight carbons, with a small portion of lipids of intermediate tail length. Preliminary results are obtained for "bicelle"-type (DMPC/DHPC) ribbons.

Evaluation of 3M molecular detection system and ANSR pathogen detection system for rapid detection of salmonella from egg products

USDA-ARS?s Scientific Manuscript database

Loop-mediated isothermal amplification (LAMP) is a novel simple detection technology that amplifies DNA with high speed, efficiency, and specificity under isothermal conditions. The objective of this study was to evaluate the effectiveness of 3M Molecular Detection System (MDS) and ANSR Pathogen Det...

Molecular robots with sensors and intelligence.

PubMed

Hagiya, Masami; Konagaya, Akihiko; Kobayashi, Satoshi; Saito, Hirohide; Murata, Satoshi

2014-06-17

CONSPECTUS: What we can call a molecular robot is a set of molecular devices such as sensors, logic gates, and actuators integrated into a consistent system. The molecular robot is supposed to react autonomously to its environment by receiving molecular signals and making decisions by molecular computation. Building such a system has long been a dream of scientists; however, despite extensive efforts, systems having all three functions (sensing, computation, and actuation) have not been realized yet. This Account introduces an ongoing research project that focuses on the development of molecular robotics funded by MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan). This 5 year project started in July 2012 and is titled "Development of Molecular Robots Equipped with Sensors and Intelligence". The major issues in the field of molecular robotics all correspond to a feedback (i.e., plan-do-see) cycle of a robotic system. More specifically, these issues are (1) developing molecular sensors capable of handling a wide array of signals, (2) developing amplification methods of signals to drive molecular computing devices, (3) accelerating molecular computing, (4) developing actuators that are controllable by molecular computers, and (5) providing bodies of molecular robots encapsulating the above molecular devices, which implement the conformational changes and locomotion of the robots. In this Account, the latest contributions to the project are reported. There are four research teams in the project that specialize on sensing, intelligence, amoeba-like actuation, and slime-like actuation, respectively. The molecular sensor team is focusing on the development of molecular sensors that can handle a variety of signals. This team is also investigating methods to amplify signals from the molecular sensors. The molecular intelligence team is developing molecular computers and is currently focusing on a new photochemical technology for accelerating DNA

Molecular implementation of simple logic programs.

PubMed

Ran, Tom; Kaplan, Shai; Shapiro, Ehud

2009-10-01

Autonomous programmable computing devices made of biomolecules could interact with a biological environment and be used in future biological and medical applications. Biomolecular implementations of finite automata and logic gates have already been developed. Here, we report an autonomous programmable molecular system based on the manipulation of DNA strands that is capable of performing simple logical deductions. Using molecular representations of facts such as Man(Socrates) and rules such as Mortal(X) <-- Man(X) (Every Man is Mortal), the system can answer molecular queries such as Mortal(Socrates)? (Is Socrates Mortal?) and Mortal(X)? (Who is Mortal?). This biomolecular computing system compares favourably with previous approaches in terms of expressive power, performance and precision. A compiler translates facts, rules and queries into their molecular representations and subsequently operates a robotic system that assembles the logical deductions and delivers the result. This prototype is the first simple programming language with a molecular-scale implementation.

Concept of a Cloud Service for Data Preparation and Computational Control on Custom HPC Systems in Application to Molecular Dynamics

NASA Astrophysics Data System (ADS)

Puzyrkov, Dmitry; Polyakov, Sergey; Podryga, Viktoriia; Markizov, Sergey

2018-02-01

At the present stage of computer technology development it is possible to study the properties and processes in complex systems at molecular and even atomic levels, for example, by means of molecular dynamics methods. The most interesting are problems related with the study of complex processes under real physical conditions. Solving such problems requires the use of high performance computing systems of various types, for example, GRID systems and HPC clusters. Considering the time consuming computational tasks, the need arises of software for automatic and unified monitoring of such computations. A complex computational task can be performed over different HPC systems. It requires output data synchronization between the storage chosen by a scientist and the HPC system used for computations. The design of the computational domain is also quite a problem. It requires complex software tools and algorithms for proper atomistic data generation on HPC systems. The paper describes the prototype of a cloud service, intended for design of atomistic systems of large volume for further detailed molecular dynamic calculations and computational management for this calculations, and presents the part of its concept aimed at initial data generation on the HPC systems.

Molecular dynamics simulation of melting of 2D glassy monatomic system

NASA Astrophysics Data System (ADS)

Nhu Tranh, Duong Thi; Van Hoang, Vo; Thu Hanh, Tran Thi

2018-01-01

The melting of two-dimensional (2D) glassy monatomic systems is studied using the molecular dynamics simulation with Lennard-Jones-Gauss interaction potential. The temperature dependence of various structural and dynamical properties of the systems during heating is analyzed and discussed via the radial distribution functions, the coordination number distributions, the ring statistics, the mobility of atoms and their clustering. Atomic mechanism of melting is also analyzed via tendency to increase mobility and breaking clusters of atoms upon heating. We found that melting of a 2D glass does not follow any theory of the melting of 2D crystals proposed in the past. The melting exhibits a homogeneous nature, i.e. liquid-like atoms occur homogeneously throughout the system and melting proceeds further leading to the formation of an entire liquid phase. In addition, we found a defined transition temperature region in which structural and dynamical properties of systems strongly change with increasing temperature.

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

PubMed Central

Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

2015-01-01

Background/Objectives: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. Methods: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. Results: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. Conclusions: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions. PMID:28725458

Effective Brownian ratchet separation by a combination of molecular filtering and a self-spreading lipid bilayer system.

PubMed

Motegi, Toshinori; Nabika, Hideki; Fu, Yingqiang; Chen, Lili; Sun, Yinlu; Zhao, Jianwei; Murakoshi, Kei

2014-07-01

A new molecular manipulation method in the self-spreading lipid bilayer membrane by combining Brownian ratchet and molecular filtering effects is reported. The newly designed ratchet obstacle was developed to effectively separate dye-lipid molecules. The self-spreading lipid bilayer acted as both a molecular transport system and a manipulation medium. By controlling the size and shape of ratchet obstacles, we achieved a significant increase in the separation angle for dye-lipid molecules compared to that with the previous ratchet obstacle. A clear difference was observed between the experimental results and the simple random walk simulation that takes into consideration only the geometrical effect of the ratchet obstacles. This difference was explained by considering an obstacle-dependent local decrease in molecular diffusivity near the obstacles, known as the molecular filtering effect at nanospace. Our experimental findings open up a novel controlling factor in the Brownian ratchet manipulation that allow the efficient separation of molecules in the lipid bilayer based on the combination of Brownian ratchet and molecular filtering effects.

Low Molecular Weight Norbornadiene Derivatives for Molecular Solar‐Thermal Energy Storage

PubMed Central

Quant, Maria; Lennartson, Anders; Dreos, Ambra; Kuisma, Mikael; Erhart, Paul; Börjesson, Karl

2016-01-01

Abstract Molecular solar‐thermal energy storage systems are based on molecular switches that reversibly convert solar energy into chemical energy. Herein, we report the synthesis, characterization, and computational evaluation of a series of low molecular weight (193–260 g mol−1) norbornadiene–quadricyclane systems. The molecules feature cyano acceptor and ethynyl‐substituted aromatic donor groups, leading to a good match with solar irradiation, quantitative photo‐thermal conversion between the norbornadiene and quadricyclane, as well as high energy storage densities (396–629 kJ kg−1). The spectroscopic properties and energy storage capability have been further evaluated through density functional theory calculations, which indicate that the ethynyl moiety plays a critical role in obtaining the high oscillator strengths seen for these molecules. PMID:27492997

WF/PC internal molecular contamination during system thermal-vacuum test

NASA Technical Reports Server (NTRS)

Taylor, Daniel M.; Barengoltz, J.; Jenkins, T.; Leschly, K.; Triolo, J.

1988-01-01

During the recent system thermal vacuum test of the Wide-Field/Planetary Camera (WF/PC), instrumentation was added to the WF/PC to characterize the internal molecular contamination and verify the instrument throughput down to 1470 angstroms. Analysis of data elements revealed two contaminants affecting the far-ultraviolet (FUV) performance of the WF/PC. The one contaminant (heavy volatile) is correlated with the electronic and housing temperature, and the contamination is significantly reduced when the electronics are operated below plus 8 degrees to plus 10 degrees C. The other contaminant (light volatile) is controlled by the heat pipe temperature, and the contamination is significantly reduced when the Thermal Electric Cooler (TEC) hot-junction temperature is below minus 40 degrees to minus 50 degrees C. The utility of contamination sensors located behind instruments during system tests was demonstrated.

Molecular Force Spectroscopy on Cells

NASA Astrophysics Data System (ADS)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

Boolean logic tree of graphene-based chemical system for molecular computation and intelligent molecular search query.

PubMed

Huang, Wei Tao; Luo, Hong Qun; Li, Nian Bing

2014-05-06

The most serious, and yet unsolved, problem of constructing molecular computing devices consists in connecting all of these molecular events into a usable device. This report demonstrates the use of Boolean logic tree for analyzing the chemical event network based on graphene, organic dye, thrombin aptamer, and Fenton reaction, organizing and connecting these basic chemical events. And this chemical event network can be utilized to implement fluorescent combinatorial logic (including basic logic gates and complex integrated logic circuits) and fuzzy logic computing. On the basis of the Boolean logic tree analysis and logic computing, these basic chemical events can be considered as programmable "words" and chemical interactions as "syntax" logic rules to construct molecular search engine for performing intelligent molecular search query. Our approach is helpful in developing the advanced logic program based on molecules for application in biosensing, nanotechnology, and drug delivery.

Nanoscale studies link amyloid maturity with polyglutamine diseases onset

NASA Astrophysics Data System (ADS)

Ruggeri, F. S.; Vieweg, S.; Cendrowska, U.; Longo, G.; Chiki, A.; Lashuel, H. A.; Dietler, G.

2016-08-01

The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington’s disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.

Kinetics of propagation of the lattice excitation in a swift heavy ion track

NASA Astrophysics Data System (ADS)

Lipp, V. P.; Volkov, A. E.; Sorokin, M. V.; Rethfeld, B.

2011-05-01

In this research we verify the applicability of the temperature and heat diffusion conceptions for the description of subpicosecond lattice excitations in nanometric tracks of swift heavy ions (SHI) decelerated in solids in the electronic stopping regime. The method is based on the molecular dynamics (MD) analysis of temporal evolutions of the local kinetic and configurational temperatures of a lattice. We used solid argon as the model system. MD simulations demonstrated that in a SHI track (a) thermalization of lattice excitations takes time of several picoseconds, and (b) application of the parabolic heat diffusion equations for the description of spatial and temporal propagation of lattice excitations is questionable at least up to 10 ps after the ion passage.

Molecular dewetting on insulators.

PubMed

Burke, S A; Topple, J M; Grütter, P

2009-10-21

Recent attention given to the growth and morphology of organic thin films with regard to organic electronics has led to the observation of dewetting (a transition from layer(s) to islands) of molecular deposits in many of these systems. Dewetting is a much studied phenomenon in the formation of polymer and liquid films, but its observation in thin films of the 'small' molecules typical of organic electronics requires additional consideration of the structure of the interface between the molecular film and the substrate. This review covers some key concepts related to dewetting and molecular film growth. In particular, the origins of different growth modes and the thickness dependent interactions which give rise to dewetting are discussed in terms of surface energies and the disjoining pressure. Characteristics of molecular systems which may lead to these conditions, including the formation of metastable interface structures and commensurate-incommensurate phase transitions, are also discussed. Brief descriptions of some experimental techniques which have been used to study molecular dewetting are given as well. Examples of molecule-on-insulator systems which undergo dewetting are described in some detail, specifically perylene derivatives on alkali halides, C(60) on alkali halides, and the technologically important system of pentacene on SiO(2). These examples point to some possible predicting factors for the occurrence of dewetting, most importantly the formation of an interface layer which differs from the bulk crystal structure.

Molecular hydrogen absorption systems in Sloan Digital Sky Survey

NASA Astrophysics Data System (ADS)

Balashev, S. A.; Klimenko, V. V.; Ivanchik, A. V.; Varshalovich, D. A.; Petitjean, P.; Noterdaeme, P.

2014-05-01

We present a systematic search for molecular hydrogen absorption systems at high redshift in quasar spectra from the Sloan Digital Sky Survey (SDSS)-II Data Release 7 and SDSS-III Data Release 9. We have selected candidates using a modified profile fitting technique taking into account that the Lyα forest can effectively mimic H2 absorption systems at the resolution of SDSS data. To estimate the confidence level of the detections, we use two methods: a Monte Carlo sampling and an analysis of control samples. The analysis of control samples allows us to define regions of the spectral quality parameter space where H2 absorption systems can be confidently identified. We find that H2 absorption systems with column densities log NH2 > 19 can be detected in only less than 3 per cent of SDSS quasar spectra. We estimate the upper limit on the detection rate of saturated H2 absorption systems (NH2 > 19) in damped Lyα (DLA) systems to be about 7 per cent. We provide a sample of 23 confident H2 absorption system candidates that would be interesting to follow up with high-resolution spectrographs. There is a 1σ r - i colour excess and non-significant AV extinction excess in quasar spectra with an H2 candidate compared to standard DLA-bearing quasar spectra. The equivalent widths of C II, Si II and Al III (but not Fe II) absorptions associated with H2 candidate DLAs are larger compared to standard DLAs. This is probably related to a larger spread in velocity of the absorption lines in the H2-bearing sample.

Molecular Magnetic Resonance Imaging of Endothelial Activation in the Central Nervous System

PubMed Central

Gauberti, Maxime; Fournier, Antoine P.; Docagne, Fabian; Vivien, Denis; Martinez de Lizarrondo, Sara

2018-01-01

Endothelial cells of the central nervous system over-express surface proteins during neurological disorders, either as a cause, or a consequence, of the disease. Since the cerebral vasculature is easily accessible by large contrast-carrying particles, it constitutes a target of choice for molecular magnetic resonance imaging (MRI). In this review, we highlight the most recent advances in molecular MRI of brain endothelial activation and focus on the development of micro-sized particles of iron oxide (MPIO) targeting adhesion molecules including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P-Selectin and E-Selectin. We also discuss the perspectives and challenges for the clinical application of this technology in neurovascular disorders (ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage, diabetes mellitus), neuroinflammatory disorders (multiple sclerosis, brain infectious diseases, sepsis), neurodegenerative disorders (Alzheimer's disease, vascular dementia, aging) and brain cancers (primitive neoplasms, metastasis). PMID:29507614

Engineering a new class of thermal spray nano-based microstructures from agglomerated nanostructured particles, suspensions and solutions: an invited review

NASA Astrophysics Data System (ADS)

Fauchais, P.; Montavon, G.; Lima, R. S.; Marple, B. R.

2011-03-01

From the pioneering works of McPherson in 1973 who identified nanometre-sized features in thermal spray conventional alumina coatings (using sprayed particles in the tens of micrometres size range) to the most recent and most advanced work aimed at manufacturing nanostructured coatings from nanometre-sized feedstock particles, the thermal spray community has been involved with nanometre-sized features and feedstock for more than 30 years. Both the development of feedstock (especially through cryo-milling, and processes able to manufacture coatings structured at the sub-micrometre or nanometre sizes, such as micrometre-sized agglomerates made of nanometre-sized particles for feedstock) and the emergence of thermal spray processes such as suspension and liquid precursor thermal spray techniques have been driven by the need to manufacture coatings with enhanced properties. These techniques result in two different types of coatings: on the one hand, those with a so-called bimodal structure having nanometre-sized zones embedded within micrometre ones, for which the spray process is similar to that of conventional coatings and on the other hand, sub-micrometre or nanostructured coatings achieved by suspension or solution spraying. Compared with suspension spraying, solution precursor spraying uses molecularly mixed precursors as liquids, avoiding a separate processing route for the preparation of powders and enabling the synthesis of a wide range of oxide powders and coatings. Such coatings are intended for use in various applications ranging from improved thermal barrier layers and wear-resistant surfaces to thin solid electrolytes for solid oxide fuel cell systems, among other numerous applications. Meanwhile these processes are more complex to operate since they are more sensitive to parameter variations compared with conventional thermal spray processes. Progress in this area has resulted from the unique combination of modelling activities, the evolution of

A high pressure modulated molecular beam mass spectrometric sampling system

NASA Technical Reports Server (NTRS)

Stearns, C. A.; Kohl, F. J.; Fryburg, G. C.; Miller, R. A.

1977-01-01

The current state of understanding of free-jet high pressure sampling is critically reviewed and modifications of certain theoretical and empirical considerations are presented. A high pressure, free-jet expansion, modulated molecular beam, mass spectrometric sampling apparatus was constructed and this apparatus is described in detail. Experimental studies have demonstrated that the apparatus can be used to sample high temperature systems at pressures up to one atmosphere. Condensible high temperature gaseous species have been routinely sampled and the mass spectrometric detector has provided direct identification of sampled species. System sensitivity is better than one tenth of a part per million. Experimental results obtained with argon and nitrogen beams are presented and compared to theoretical predictions. These results and the respective comparison are taken to indicate acceptable performance of the sampling apparatus. Results are also given for two groups of experiments related to hot corrosion studies. The formation of gaseous sodium sulfate in doped methane-oxygen flames was characterized and the oxidative vaporization of metals was studied in an atmospheric pressure flowing gas system to which gaseous salt partial pressures were added.

SU-E-CAMPUS-I-01: Nanometric Organic Photovoltaic Thin Film X-Ray Detectors for Clinical KVp Beams

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

Elshahat, Bassem; Gill, Hardeep; Kumar, Jayant

2014-06-15

Purpose: To fabricate and test nanometric organic photovoltaic (OPV) cells made of various active-layer/electrode thicknesses and sizes; to determine the optimal material combinations and geometries suitable for dose measurements in clinical kilovoltage x-ray beams. Methods: The OPV consisted of P3HT:PCBM photoactive materials sandwiched between aluminum and Indium Tin Oxide (ITO) electrodes. Direct conversion of xrays in the active layer composed of donor and acceptor semiconducting organic materials generated signal in photovoltaic mode (without external voltage bias). OPV cells were fabricated with different active layer thicknesses (150, 270, 370 nm) and electrode areas (0.4, 0.7, 0.9, 1.4, 2.6 cm{sup 2}). Amore » series of experiments were preformed in the energy range of 60–150 kVp. The net current per unit area (nA/cm{sup 2}) was measured using 200 mAs time-integrated beam current. Results: The net OPV current as function of beam energy (kVp) was proportional to ∼E{sup 0,4} {sup 5} when adjusted for beam output. The best combination of parameters for these cells was 270 nm active layer thicknesses for 0.7 cm{sup 2} electrode area. The measured current ranged from 0.69 to 2.43 nA/cm{sup 2} as a function of x-ray energy between 60 and 150 kVp, corresponding to 0.09 – 0.06 nA/cm{sup 2}/mGy, respectively, when adjusted for the beam output. Conclusion: The experiments indicate that OPV detectors possessing 270 nm active layer and 0.7 cm{sup 2} Al electrode areas have sensitivity by a factor of 2.5 greater than commercial aSi thin film PV. Because OPV can be made flexible and they do not require highvoltage bias supply, they open the possibility for using as in-vivo detectors in radiation safety in x-ray imaging beams.« less

Markov state models and molecular alchemy

NASA Astrophysics Data System (ADS)

Schütte, Christof; Nielsen, Adam; Weber, Marcus

2015-01-01

In recent years, Markov state models (MSMs) have attracted a considerable amount of attention with regard to modelling conformation changes and associated function of biomolecular systems. They have been used successfully, e.g. for peptides including time-resolved spectroscopic experiments, protein function and protein folding , DNA and RNA, and ligand-receptor interaction in drug design and more complicated multivalent scenarios. In this article, a novel reweighting scheme is introduced that allows to construct an MSM for certain molecular system out of an MSM for a similar system. This permits studying how molecular properties on long timescales differ between similar molecular systems without performing full molecular dynamics simulations for each system under consideration. The performance of the reweighting scheme is illustrated for simple test cases, including one where the main wells of the respective energy landscapes are located differently and an alchemical transformation of butane to pentane where the dimension of the state space is changed.

Efficient calculation of many-body induced electrostatics in molecular systems

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

McLaughlin, Keith, E-mail: kmclaugh@mail.usf.edu; Cioce, Christian R.; Pham, Tony

Potential energy functions including many-body polarization are in widespread use in simulations of aqueous and biological systems, metal-organics, molecular clusters, and other systems where electronically induced redistribution of charge among local atomic sites is of importance. The polarization interactions, treated here via the methods of Thole and Applequist, while long-ranged, can be computed for moderate-sized periodic systems with extremely high accuracy by extending Ewald summation to the induced fields as demonstrated by Nymand, Sala, and others. These full Ewald polarization calculations, however, are expensive and often limited to very small systems, particularly in Monte Carlo simulations, which may require energymore » evaluation over several hundred-thousand configurations. For such situations, it shall be shown that sufficiently accurate computation of the polarization energy can be produced in a fraction of the central processing unit (CPU) time by neglecting the long-range extension to the induced fields while applying the long-range treatments of Ewald or Wolf to the static fields; these methods, denoted Ewald E-Static and Wolf E-Static (WES), respectively, provide an effective means to obtain polarization energies for intermediate and large systems including those with several thousand polarizable sites in a fraction of the CPU time. Furthermore, we shall demonstrate a means to optimize the damping for WES calculations via extrapolation from smaller trial systems.« less

Spectroscopic Studies of Molecular Systems relevant in Astrobiology

NASA Astrophysics Data System (ADS)

Fornaro, Teresa

2016-01-01

In the Astrobiology context, the study of the physico-chemical interactions involving "building blocks of life" in plausible prebiotic and space-like conditions is fundamental to shed light on the processes that led to emergence of life on Earth as well as to molecular chemical evolution in space. In this PhD Thesis, such issues have been addressed both experimentally and computationally by employing vibrational spectroscopy, which has shown to be an effective tool to investigate the variety of intermolecular interactions that play a key role in self-assembling mechanisms of nucleic acid components and their binding to mineral surfaces. In particular, in order to dissect the contributions of the different interactions to the overall spectroscopic signals and shed light on the intricate experimental data, feasible computational protocols have been developed for the characterization of the spectroscopic properties of such complex systems. This study has been carried out through a multi-step strategy, starting the investigation from the spectroscopic properties of the isolated nucleobases, then studying the perturbation induced by the interaction with another molecule (molecular dimers), towards condensed phases like the molecular solid, up to the case of nucleic acid components adsorbed on minerals. A proper modeling of these weakly bound molecular systems has required, firstly, a validation of dispersion-corrected Density Functional Theory methods for simulating anharmonic vibrational properties. The isolated nucleobases and some of their dimers have been used as benchmark set for identifying a general, reliable and effective computational procedure based on fully anharmonic quantum mechanical computations of the vibrational wavenumbers and infrared intensities within the generalized second order vibrational perturbation theory (GVPT2) approach, combined with the cost-effective dispersion-corrected density functional B3LYP-D3, in conjunction with basis sets of

Enamel: Molecular identity of its transepithelial ion transport system.

PubMed

Lacruz, Rodrigo S

2017-07-01

Enamel is the most calcified tissue in vertebrates. It differs from bone in a number of characteristics including its origin from ectodermal epithelium, lack of remodeling capacity by the enamel forming cells, and absence of collagen. The enamel-forming cells known as ameloblasts, choreograph first the synthesis of a unique protein-rich matrix, followed by the mineralization of this matrix into a tissue that is ∼95% mineral. To do this, ameloblasts arrange the coordinated movement of ions across a cell barrier while removing matrix proteins and monitoring extracellular pH using a variety of buffering systems to enable the growth of carbonated apatite crystals. Although our knowledge of these processes and the molecular identity of the proteins involved in transepithelial ion transport has increased in the last decade, it remains limited compared to other cells. Here we present an overview of the evolution and development of enamel, its differences with bone, and describe the ion transport systems associated with ameloblasts. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

Force loading explains spatial sensing of ligands by cells

NASA Astrophysics Data System (ADS)

Oria, Roger; Wiegand, Tina; Escribano, Jorge; Elosegui-Artola, Alberto; Uriarte, Juan Jose; Moreno-Pulido, Cristian; Platzman, Ilia; Delcanale, Pietro; Albertazzi, Lorenzo; Navajas, Daniel; Trepat, Xavier; García-Aznar, José Manuel; Cavalcanti-Adam, Elisabetta Ada; Roca-Cusachs, Pere

2017-12-01

Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin-ligand bonds are separated by more than a few tens of nanometres. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model, in which individual integrin-ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds

Investigations into the mechanism of material removal and surface modification at atomic scale on stainless steel using molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Ranjan, Prabhat; Balasubramaniam, R.; Jain, V. K.

2018-06-01

A molecular dynamics simulation (MDS) has been carried out to investigate the material removal phenomenon of chemo-mechanical magnetorheological finishing (CMMRF) process. To understand the role of chemical assisted mechanical abrasion in CMMRF process, material removal phenomenon is subdivided into three different stages. In the first stage, new atomic bonds viz. Fe-O-Si is created on the surface of the workpiece (stainless steel). The second stage deals with the rupture of parent bonds like Fe-Fe on the workpiece. In the final stage, removal of material from the surface in the form of dislodged debris (cluster of atoms) takes place. Effects of process parameters like abrasive particles, depth of penetration and initial surface condition on finishing force, potential energy (towards secondary phenomenon such as chemical instability of the finished surface) and material removal at atomic scale have been investigated. It was observed that the type of abrasive particle is one of the important parameters to produce atomically smooth surface. Experiments were also conducted as per the MDS to generate defect-free and sub-nanometre-level finished surface (Ra value better than 0.2 nm). The experimental results reasonably agree well with the simulation results.

Fluorescence-Raman Dual Modal Endoscopic System for Multiplexed Molecular Diagnostics

NASA Astrophysics Data System (ADS)

Jeong, Sinyoung; Kim, Yong-Il; Kang, Homan; Kim, Gunsung; Cha, Myeong Geun; Chang, Hyejin; Jung, Kyung Oh; Kim, Young-Hwa; Jun, Bong-Hyun; Hwang, Do Won; Lee, Yun-Sang; Youn, Hyewon; Lee, Yoon-Sik; Kang, Keon Wook; Lee, Dong Soo; Jeong, Dae Hong

2015-03-01

Optical endoscopic imaging, which was recently equipped with bioluminescence, fluorescence, and Raman scattering, allows minimally invasive real-time detection of pathologies on the surface of hollow organs. To characterize pathologic lesions in a multiplexed way, we developed a dual modal fluorescence-Raman endomicroscopic system (FRES), which used fluorescence and surface-enhanced Raman scattering nanoprobes (F-SERS dots). Real-time, in vivo, and multiple target detection of a specific cancer was successful, based on the fast imaging capability of fluorescence signals and the multiplex capability of simultaneously detected SERS signals using an optical fiber bundle for intraoperative endoscopic system. Human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) on the breast cancer xenografts in a mouse orthotopic model were successfully detected in a multiplexed way, illustrating the potential of FRES as a molecular diagnostic instrument that enables real-time tumor characterization of receptors during routine endoscopic procedures.

Integrating open-source software applications to build molecular dynamics systems.

PubMed

Allen, Bruce M; Predecki, Paul K; Kumosa, Maciej

2014-04-05

Three open-source applications, NanoEngineer-1, packmol, and mis2lmp are integrated using an open-source file format to quickly create molecular dynamics (MD) cells for simulation. The three software applications collectively make up the open-source software (OSS) suite known as MD Studio (MDS). The software is validated through software engineering practices and is verified through simulation of the diglycidyl ether of bisphenol-a and isophorone diamine (DGEBA/IPD) system. Multiple simulations are run using the MDS software to create MD cells, and the data generated are used to calculate density, bulk modulus, and glass transition temperature of the DGEBA/IPD system. Simulation results compare well with published experimental and numerical results. The MDS software prototype confirms that OSS applications can be analyzed against real-world research requirements and integrated to create a new capability. Copyright © 2014 Wiley Periodicals, Inc.

Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis.

PubMed

Álvarez-Twose, Iván; Jara-Acevedo, María; Morgado, José Mário; García-Montero, Andrés; Sánchez-Muñoz, Laura; Teodósio, Cristina; Matito, Almudena; Mayado, Andrea; Caldas, Carolina; Mollejo, Manuela; Orfao, Alberto; Escribano, Luis

2016-01-01

Well-differentiated systemic mastocytosis (WDSM) is a rare variant of systemic mastocytosis (SM) characterized by bone marrow (BM) infiltration by mature-appearing mast cells (MCs) often lacking exon 17 KIT mutations. Because of its rarity, the clinical and biological features of WDSM remain poorly defined. We sought to determine the clinical, biological, and molecular features of a cohort of 33 patients with mastocytosis in the skin in association with BM infiltration by well-differentiated MCs and to establish potential diagnostic criteria for WDSM. Thirty-three patients with mastocytosis in the skin plus BM aggregates of round, fully granulated MCs lacking strong CD25 and CD2 expression in association with clonal MC features were studied. Our cohort of patients showed female predominance (female/male ratio, 4:1) and childhood onset of the disease (91%) with frequent familial aggregation (39%). Skin involvement was heterogeneous, including maculopapular (82%), nodular (6%), and diffuse cutaneous (12%) mastocytosis. KIT mutations were detected in only 10 (30%) of 33 patients, including the KIT D816V (n = 5), K509I (n = 3), N819Y (n = 1), and I817V (n = 1) mutations. BM MCs displayed a unique immunophenotypic pattern consisting of increased light scatter features, overexpression of cytoplasmic carboxypeptidase, and aberrant expression of CD30, together with absent (79%) or low (21%) positivity for CD25, CD2, or both. Despite only 9 (27%) of 33 patients fulfilling the World Health Organization criteria for SM, our findings allowed us to establish the systemic nature of the disease, which fit with the definition of WDSM. WDSM represents a rare clinically and molecularly heterogeneous variant of SM that requires unique diagnostic criteria to avoid a misdiagnosis of cutaneous mastocytosis per current World Health Organization criteria. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

[The action of high-molecular linear polymers on the circulatory system].

PubMed

Grigorian, S S; Sokolova, I A; Shakhnazarov, A A

1995-01-01

An analysis of the hemodynamic consequences of the injections of long linear polymers with high molecular weight is introduced. These injections lead to an increase of the cardiac output, to a decrease of the blood pressure, and hence cause a reduction of the resistance to blood flow. It follows that such kind of polymers is able to normalize hemodynamics under some pathophysiological conditions, e.g., during experimental atherosclerosis, ischemic state, hemorrhagic shock. An addition of drag-reducing polymers into the blood system is associated with a modification of the blood flow microstructure itself.

Instrumentation in molecular imaging.

PubMed

Wells, R Glenn

2016-12-01

In vivo molecular imaging is a challenging task and no single type of imaging system provides an ideal solution. Nuclear medicine techniques like SPECT and PET provide excellent sensitivity but have poor spatial resolution. Optical imaging has excellent sensitivity and spatial resolution, but light photons interact strongly with tissues and so only small animals and targets near the surface can be accurately visualized. CT and MRI have exquisite spatial resolution, but greatly reduced sensitivity. To overcome the limitations of individual modalities, molecular imaging systems often combine individual cameras together, for example, merging nuclear medicine cameras with CT or MRI to allow the visualization of molecular processes with both high sensitivity and high spatial resolution.

Dynamical Localization in Molecular Systems.

NASA Astrophysics Data System (ADS)

Wang, Xidi

In the first four chapters of this thesis we concentrate on the Davydov model which describes the vibrational energy quanta of Amide I bonds (C=O bonds on the alpha -helix) coupled to the acoustic phonon modes of the alpha-helix backbone in the form of a Frohlich Hamiltonian. Following a brief introduction in chapter one, in chapter two we formulate the dynamics of vibrational quanta at finite temperature by using coherent state products. The fluctuation-dissipation relation is derived. At zero temperature, in the continuum limit, we recover the original results of Davydov. We also achieve good agreement with numerical simulations. In chapter three, the net contraction of the lattice is calculated exactly at any temperature, and its relation to the so -call "topological stability" of the Davydov soliton is discussed. In the second section of the chapter three we calculate the overtone spectra of crystalline acetanilide (according to some opinions ACN provides experimental evidence for the existence of Davydov solitons). Good agreement with experimental data has been obtained. In chapter four we study the self-trapped vibrational excitations by the Quantum Monte Carlo technique. For a single excitation, the temperature dependence of different physical observables is calculated. The quasi-particle which resembles the Davydov soliton has been found to be fairly narrow using the most commonly used data for the alpha -helix; at temperatures above a few Kelvin, the quasi-particle reaches its smallest limit (extends over three sites), which implies diffusive motion of the small polaron-like quasi-particle at high temperatures. For the multi-excitation case, bound pairs and clusters of excitations are found at low temperatures; they gradually dissociate when the temperature of the system is increased as calculated from the density-density correlation function. In the last chapter of this thesis, we study a more general model of dynamical local modes in molecular systems

A computational kinetic model of diffusion for molecular systems.

PubMed

Teo, Ivan; Schulten, Klaus

2013-09-28

Regulation of biomolecular transport in cells involves intra-protein steps like gating and passage through channels, but these steps are preceded by extra-protein steps, namely, diffusive approach and admittance of solutes. The extra-protein steps develop over a 10-100 nm length scale typically in a highly particular environment, characterized through the protein's geometry, surrounding electrostatic field, and location. In order to account for solute energetics and mobility of solutes in this environment at a relevant resolution, we propose a particle-based kinetic model of diffusion based on a Markov State Model framework. Prerequisite input data consist of diffusion coefficient and potential of mean force maps generated from extensive molecular dynamics simulations of proteins and their environment that sample multi-nanosecond durations. The suggested diffusion model can describe transport processes beyond microsecond duration, relevant for biological function and beyond the realm of molecular dynamics simulation. For this purpose the systems are represented by a discrete set of states specified by the positions, volumes, and surface elements of Voronoi grid cells distributed according to a density function resolving the often intricate relevant diffusion space. Validation tests carried out for generic diffusion spaces show that the model and the associated Brownian motion algorithm are viable over a large range of parameter values such as time step, diffusion coefficient, and grid density. A concrete application of the method is demonstrated for ion diffusion around and through the Eschericia coli mechanosensitive channel of small conductance ecMscS.

Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics

PubMed Central

Haenisch, Britta; Nöthen, Markus M; Molderings, Gerhard J

2012-01-01

Despite increasing understanding of its pathophysiology, the aetiology of systemic mast cell activation disease (MCAD) remains largely unknown. Research has shown that somatic mutations in kinases are necessary for the establishment of a clonal mast cell population, in particular mutations in the tyrosine kinase Kit and in enzymes and receptors with crucial involvement in the regulation of mast cell activity. However, other, as yet undetermined, abnormalities are necessary for the manifestation of clinical disease. The present article reviews molecular genetic research into the identification of disease-associated genes and their mutational alterations. The authors also present novel data on familial systemic MCAD and review the associated literature. Finally, the importance of understanding the molecular basis of inherited mutations in terms of diagnostics and therapy is emphasized. PMID:22957768

Comparison of Computed Condon Loci with Franck-Condon Factors in Deslandres Tables of Molecular Band Systems

NASA Astrophysics Data System (ADS)

Hefferlin, R.; Clark, B.; Tatum, J.

2012-06-01

The literature often shows a Condon parabola not quite tracking the Franck-Condon factors for the strongest bands in the Deslandres table for a diatomic molecular band system; often the parabola appears to have been hand-drawn. We have calculated Condon loci, assuming originally that the lower and upper electronic potentials are simple harmonic potentials, and assuming now that they are Morse potentials. In the harmonic case the Condon loci are parabolas. These calculations are for small vibrational quantum numbers, where the Morse loci also begin as parabolas. We will present these loci for representative molecular band systems and discuss the extent to which the loci track the strongest Franck-Condon factors. In the event that neither does, calculations for arbitrary potentials are available. The importance of this study is that we have previously calculated the latera recta and the symmetry-axis angles of the harmonic oscillator parabolas in Deslandres tables appropriate to molecules in several isoelectronic sequences. We have found that the angle increases along the sequence until the species one proton-shift away from “rare-gas” molecules, such as LiNe, is reached. This phenomenon is a suggestion that diatomic molecules are periodic with respect to each of their two atoms. G. Herzberg, Molecular Spectra and Molecular Structure, 1950, pg. 197 D. J. Flynn, R. J. Spindler; S. Fifer; M. Kelly, J. Quant. Spectr. Radiat. Transfer 4, 271-282, (1964) R. W. Nicholls, J. Quant. Spectr. Radiat. Transfer 28, 481-492, (1982).

Building New Bridges between In Vitro and In Vivo in Early Drug Discovery: Where Molecular Modeling Meets Systems Biology.

PubMed

Pearlstein, Robert A; McKay, Daniel J J; Hornak, Viktor; Dickson, Callum; Golosov, Andrei; Harrison, Tyler; Velez-Vega, Camilo; Duca, José

2017-01-01

Cellular drug targets exist within networked function-generating systems whose constituent molecular species undergo dynamic interdependent non-equilibrium state transitions in response to specific perturbations (i.e.. inputs). Cellular phenotypic behaviors are manifested through the integrated behaviors of such networks. However, in vitro data are frequently measured and/or interpreted with empirical equilibrium or steady state models (e.g. Hill, Michaelis-Menten, Briggs-Haldane) relevant to isolated target populations. We propose that cells act as analog computers, "solving" sets of coupled "molecular differential equations" (i.e. represented by populations of interacting species)via "integration" of the dynamic state probability distributions among those populations. Disconnects between biochemical and functional/phenotypic assays (cellular/in vivo) may arise with targetcontaining systems that operate far from equilibrium, and/or when coupled contributions (including target-cognate partner binding and drug pharmacokinetics) are neglected in the analysis of biochemical results. The transformation of drug discovery from a trial-and-error endeavor to one based on reliable design criteria depends on improved understanding of the dynamic mechanisms powering cellular function/dysfunction at the systems level. Here, we address the general mechanisms of molecular and cellular function and pharmacological modulation thereof. We outline a first principles theory on the mechanisms by which free energy is stored and transduced into biological function, and by which biological function is modulated by drug-target binding. We propose that cellular function depends on dynamic counter-balanced molecular systems necessitated by the exponential behavior of molecular state transitions under non-equilibrium conditions, including positive versus negative mass action kinetics and solute-induced perturbations to the hydrogen bonds of solvating water versus kT. Copyright© Bentham

Low Molecular Weight Norbornadiene Derivatives for Molecular Solar-Thermal Energy Storage.

PubMed

Quant, Maria; Lennartson, Anders; Dreos, Ambra; Kuisma, Mikael; Erhart, Paul; Börjesson, Karl; Moth-Poulsen, Kasper

2016-09-05

Molecular solar-thermal energy storage systems are based on molecular switches that reversibly convert solar energy into chemical energy. Herein, we report the synthesis, characterization, and computational evaluation of a series of low molecular weight (193-260 g mol(-1) ) norbornadiene-quadricyclane systems. The molecules feature cyano acceptor and ethynyl-substituted aromatic donor groups, leading to a good match with solar irradiation, quantitative photo-thermal conversion between the norbornadiene and quadricyclane, as well as high energy storage densities (396-629 kJ kg(-1) ). The spectroscopic properties and energy storage capability have been further evaluated through density functional theory calculations, which indicate that the ethynyl moiety plays a critical role in obtaining the high oscillator strengths seen for these molecules. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Frequency Domain Fluorescent Molecular Tomography and Molecular Probes for Small Animal Imaging

NASA Astrophysics Data System (ADS)

Kujala, Naresh Gandhi

Fluorescent molecular tomography (FMT) is a noninvasive biomedical optical imaging that enables 3-dimensional quantitative determination of fluorochromes distributed in biological tissues. There are three methods for imaging large volume tissues based on different light sources: (a) using a light source of constant intensity, through a continuous or constant wave, (b) using a light source that is intensity modulated with a radio frequency (RF), and (c) using ultrafast pulses in the femtosecond range. In this study, we have developed a frequency domain fluorescent molecular tomographic system based on the heterodyne technique, using a single source and detector pair that can be used for small animal imaging. In our system, the intensity of the laser source is modulated with a RF frequency to produce a diffuse photon density wave in the tissue. The phase of the diffuse photon density wave is measured by comparing the reference signal with the signal from the tissue using a phasemeter. The data acquisition was performed by using a Labview program. The results suggest that we can measure the phase change from the heterogeneous inside tissue. Combined with fiber optics and filter sets, the system can be used to sensitively image the targeted fluorescent molecular probes, allowing the detection of cancer at an early stage. We used the system to detect the tumor-targeting molecular probe Alexa Fluor 680 and Alexa Fluor 750 bombesin peptide conjugates in phantoms as well as mouse tissues. We also developed and evaluated fluorescent Bombesin (BBN) probes to target gastrin-releasing peptide (GRP) receptors for optical molecular imaging. GRP receptors are over-expressed in several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. BBN is a 14 amino acid peptide that is an analogue to human gastrin-releasing peptide that binds specifically to GRPr receptors. BBN conjugates are significant in cancer detection and therapy. The

Solar fuels generation and molecular systems: is it homogeneous or heterogeneous catalysis?

PubMed

Artero, Vincent; Fontecave, Marc

2013-03-21

Catalysis is a key enabling technology for solar fuel generation. A number of catalytic systems, either molecular/homogeneous or solid/heterogeneous, have been developed during the last few decades for both the reductive and oxidative multi-electron reactions required for fuel production from water or CO(2) as renewable raw materials. While allowing for a fine tuning of the catalytic properties through ligand design, molecular approaches are frequently criticized because of the inherent fragility of the resulting catalysts, when exposed to extreme redox potentials. In a number of cases, it has been clearly established that the true catalytic species is heterogeneous in nature, arising from the transformation of the initial molecular species, which should rather be considered as a pre-catalyst. Whether such a situation is general or not is a matter of debate in the community. In this review, covering water oxidation and reduction catalysts, involving noble and non-noble metal ions, we limit our discussion to the cases in which this issue has been directly and properly addressed as well as those requiring more confirmation. The methodologies proposed for discriminating homogeneous and heterogeneous catalysis are inspired in part by those previously discussed by Finke in the case of homogeneous hydrogenation reaction in organometallic chemistry [J. A. Widegren and R. G. Finke, J. Mol. Catal. A, 2003, 198, 317-341].

Endogenous Molecular-Cellular Network Cancer Theory: A Systems Biology Approach.

PubMed

Wang, Gaowei; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

2018-01-01

In light of ever apparent limitation of the current dominant cancer mutation theory, a quantitative hypothesis for cancer genesis and progression, endogenous molecular-cellular network hypothesis has been proposed from the systems biology perspective, now for more than 10 years. It was intended to include both the genetic and epigenetic causes to understand cancer. Its development enters the stage of meaningful interaction with experimental and clinical data and the limitation of the traditional cancer mutation theory becomes more evident. Under this endogenous network hypothesis, we established a core working network of hepatocellular carcinoma (HCC) according to the hypothesis and quantified the working network by a nonlinear dynamical system. We showed that the two stable states of the working network reproduce the main known features of normal liver and HCC at both the modular and molecular levels. Using endogenous network hypothesis and validated working network, we explored genetic mutation pattern in cancer and potential strategies to cure or relieve HCC from a totally new perspective. Patterns of genetic mutations have been traditionally analyzed by posteriori statistical association approaches in light of traditional cancer mutation theory. One may wonder the possibility of a priori determination of any mutation regularity. Here, we found that based on the endogenous network theory the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. Normal hepatocyte and cancerous hepatocyte stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable

A portable molecular-sieve-based CO2 sampling system for radiocarbon measurements

NASA Astrophysics Data System (ADS)

Palonen, V.

2015-12-01

We have developed a field-capable sampling system for the collection of CO2 samples for radiocarbon-concentration measurements. Most target systems in environmental research are limited in volume and CO2 concentration, making conventional flask sampling hard or impossible for radiocarbon studies. The present system captures the CO2 selectively to cartridges containing 13X molecular sieve material. The sampling does not introduce significant under-pressures or significant losses of moisture to the target system, making it suitable for most environmental targets. The system also incorporates a significantly larger sieve container for the removal of CO2 from chambers prior to the CO2 build-up phase and sampling. In addition, both the CO2 and H2O content of the sample gas are measured continuously. This enables in situ estimation of the amount of collected CO2 and the determination of CO2 flux to a chamber. The portable sampling system is described in detail and tests for the reliability of the method are presented.

A portable molecular-sieve-based CO2 sampling system for radiocarbon measurements.

PubMed

Palonen, V

2015-12-01

We have developed a field-capable sampling system for the collection of CO2 samples for radiocarbon-concentration measurements. Most target systems in environmental research are limited in volume and CO2 concentration, making conventional flask sampling hard or impossible for radiocarbon studies. The present system captures the CO2 selectively to cartridges containing 13X molecular sieve material. The sampling does not introduce significant under-pressures or significant losses of moisture to the target system, making it suitable for most environmental targets. The system also incorporates a significantly larger sieve container for the removal of CO2 from chambers prior to the CO2 build-up phase and sampling. In addition, both the CO2 and H2O content of the sample gas are measured continuously. This enables in situ estimation of the amount of collected CO2 and the determination of CO2 flux to a chamber. The portable sampling system is described in detail and tests for the reliability of the method are presented.

Organic-based molecular switches for molecular electronics.

PubMed

Fuentes, Noelia; Martín-Lasanta, Ana; Alvarez de Cienfuegos, Luis; Ribagorda, Maria; Parra, Andres; Cuerva, Juan M

2011-10-05

In a general sense, molecular electronics (ME) is the branch of nanotechnology which studies the application of molecular building blocks for the fabrication of electronic components. Among the different types of molecules, organic compounds have been revealed as promising candidates for ME, due to the easy access, great structural diversity and suitable electronic and mechanical properties. Thanks to these useful capabilities, organic molecules have been used to emulate electronic devices at the nanoscopic scale. In this feature article, we present the diverse strategies used to develop organic switches towards ME with special attention to non-volatile systems.

Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

PubMed Central

Leung, Maxwell C.K.; Phuong, Jimmy; Baker, Nancy C.; Sipes, Nisha S.; Klinefelter, Gary R.; Martin, Matthew T.; McLaurin, Keith W.; Setzer, R. Woodrow; Darney, Sally Perreault; Judson, Richard S.; Knudsen, Thomas B.

2015-01-01

Background: Trends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies. Objective: In the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system. Methods: We used U.S. EPA’s animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features. Results: A phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network. Conclusion: Computational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarchy across animal studies consistent with the human TDS hypothesis. We confirmed the known role of estrogen and androgen signaling pathways in rodent TDS, and importantly, broadened the list of molecular targets to include retinoic acid signaling, vascular remodeling proteins, G-protein coupled receptors (GPCRs), and cytochrome P450s. Citation: Leung MC, Phuong J, Baker NC, Sipes NS, Klinefelter GR, Martin MT, McLaurin KW, Setzer RW, Darney SP, Judson RS, Knudsen TB. 2016. Systems toxicology of male

A versatile electrophoresis system for the analysis of high- and low-molecular-weight proteins

PubMed Central

Tastet, Christophe; Lescuyer, Pierre; Diemer, Hélène; Luche, Sylvie; van Dorsselaer, Alain; Rabilloud, Thierry

2003-01-01

A new, versatile, multiphasic buffer system for high resolution sodium dodecyl sulfatepolyacrylamide gel electrophoresis of proteins in the relative molecular weight Mw range of 300,000-3000 Da is described. The system, based on the theory of multiphasic zone electrophoresis, allows complete stacking and destacking of proteins in the above Mw range. The buffer system uses taurine and chloride as trailing and leading ion, respectively, and Tris, at a pH close to its pKa, as the buffering counter ion. Coupled with limited variation in the acrylamide concentration, this electrophoresis system allows to tailor the resolution in the 6–200 kDa Mw range, with minimal difficulties in the post electrophoretic identification processes. PMID:12783456

3M™ Molecular detection system versus MALDI-TOF mass spectrometry and molecular techniques for the identification of Escherichia coli 0157:H7, Salmonella spp. &Listeria spp.

PubMed

Loff, Marché; Mare, Louise; de Kwaadsteniet, Michele; Khan, Wesaal

2014-06-01

The aim of this study was to compare standard selective plating, conventional PCR (16S rRNA and species specific primers), MALDI-TOF MS and the 3M™ Molecular Detection System for the routine detection of the pathogens Listeria, Salmonella and Escherichia coli 0157:H7 in wastewater and river water samples. MALDI-TOF MS was able to positively identify 20/21 (95%) of the E. coli isolates obtained at genus and species level, while 16S rRNA sequencing only correctly identified 6/21 (28%) as E. coli strains. None of the presumptive positive Listeria spp. and Salmonella spp. isolates obtained by culturing on selective media were positively identified by MALDI-TOF and 16S rRNA analysis. The species-specific E. coli 0157:H7 PCR described in this present study, was not able to detect any E. coli 0157:H7 strains in the wastewater and river water samples analysed. However, E. coli strains, Listeria spp., L. monocytogenes and Salmonella spp. were detected using species specific PCR. Escherichia coli 0157:H7, Listeria spp. and Salmonella spp. were also sporadically detected throughout the sampling period in the wastewater and river water samples analysed by the 3M™ Molecular Detection System. MALDI-TOF MS, which is a simple, accurate and cost-effective detection method, efficiently identified the culturable organisms, while in the current study both species specific PCR (Listeria spp. and Salmonella spp.) and 3M™ Molecular Detection System could be utilised for the direct routine analysis of pathogens in water sources. Copyright © 2014 Elsevier B.V. All rights reserved.

epiPATH: an information system for the storage and management of molecular epidemiology data from infectious pathogens.

PubMed

Amadoz, Alicia; González-Candelas, Fernando

2007-04-20

Most research scientists working in the fields of molecular epidemiology, population and evolutionary genetics are confronted with the management of large volumes of data. Moreover, the data used in studies of infectious diseases are complex and usually derive from different institutions such as hospitals or laboratories. Since no public database scheme incorporating clinical and epidemiological information about patients and molecular information about pathogens is currently available, we have developed an information system, composed by a main database and a web-based interface, which integrates both types of data and satisfies requirements of good organization, simple accessibility, data security and multi-user support. From the moment a patient arrives to a hospital or health centre until the processing and analysis of molecular sequences obtained from infectious pathogens in the laboratory, lots of information is collected from different sources. We have divided the most relevant data into 12 conceptual modules around which we have organized the database schema. Our schema is very complete and it covers many aspects of sample sources, samples, laboratory processes, molecular sequences, phylogenetics results, clinical tests and results, clinical information, treatments, pathogens, transmissions, outbreaks and bibliographic information. Communication between end-users and the selected Relational Database Management System (RDMS) is carried out by default through a command-line window or through a user-friendly, web-based interface which provides access and management tools for the data. epiPATH is an information system for managing clinical and molecular information from infectious diseases. It facilitates daily work related to infectious pathogens and sequences obtained from them. This software is intended for local installation in order to safeguard private data and provides advanced SQL-users the flexibility to adapt it to their needs. The database schema

Super-resolution photon-efficient imaging by nanometric double-helix point spread function localization of emitters (SPINDLE)

PubMed Central

Grover, Ginni; DeLuca, Keith; Quirin, Sean; DeLuca, Jennifer; Piestun, Rafael

2012-01-01

Super-resolution imaging with photo-activatable or photo-switchable probes is a promising tool in biological applications to reveal previously unresolved intra-cellular details with visible light. This field benefits from developments in the areas of molecular probes, optical systems, and computational post-processing of the data. The joint design of optics and reconstruction processes using double-helix point spread functions (DH-PSF) provides high resolution three-dimensional (3D) imaging over a long depth-of-field. We demonstrate for the first time a method integrating a Fisher information efficient DH-PSF design, a surface relief optical phase mask, and an optimal 3D localization estimator. 3D super-resolution imaging using photo-switchable dyes reveals the 3D microtubule network in mammalian cells with localization precision approaching the information theoretical limit over a depth of 1.2 µm. PMID:23187521

Fragment-orbital tunneling currents and electronic couplings for analysis of molecular charge-transfer systems.

PubMed

Hwang, Sang-Yeon; Kim, Jaewook; Kim, Woo Youn

2018-04-04

In theoretical charge-transfer research, calculation of the electronic coupling element is crucial for examining the degree of the electronic donor-acceptor interaction. The tunneling current (TC), representing the magnitudes and directions of electron flow, provides a way of evaluating electronic couplings, along with the ability of visualizing how electrons flow in systems. Here, we applied the TC theory to π-conjugated organic dimer systems, in the form of our fragment-orbital tunneling current (FOTC) method, which uses the frontier molecular-orbitals of system fragments as diabatic states. For a comprehensive test of FOTC, we assessed how reasonable the computed electronic couplings and the corresponding TC densities are for the hole- and electron-transfer databases HAB11 and HAB7. FOTC gave 12.5% mean relative unsigned error with regard to the high-level ab initio reference. The shown performance is comparable with that of fragment-orbital density functional theory, which gave the same error by 20.6% or 13.9% depending on the formulation. In the test of a set of nucleobase π stacks, we showed that the original TC expression is also applicable to nondegenerate cases under the condition that the overlap between the charge distributions of diabatic states is small enough to offset the energy difference. Lastly, we carried out visual analysis on the FOTC densities of thiophene dimers with different intermolecular alignments. The result depicts an intimate topological connection between the system geometry and electron flow. Our work provides quantitative and qualitative grounds for FOTC, showing it to be a versatile tool in characterization of molecular charge-transfer systems.

A molecular beam/quadrupole mass spectrometer system with synchronized beam modulation and digital waveform analysis

NASA Technical Reports Server (NTRS)

Pellett, G. L.; Adams, B. R.

1983-01-01

A performance evaluation is conducted for a molecular beam/mass spectrometer (MB/MS) system, as applied to a 1-30 torr microwave-discharge flow reactor (MWFR) used in the formation of the methylperoxy radical and a study of its subsequent destruction in the presence or absence of NO(x). The modulated MB/MS system is four-staged and differentially pumped. The results obtained by the MWFR study is illustrative of overall system performance, including digital waveform analysis; significant improvements over previous designs are noted in attainable S/N ratio, detection limit, and accuracy.

Studying the Impact of Spaceflight Environment on Immune Functions Using New Molecular Diagnostics System

NASA Astrophysics Data System (ADS)

Cohen, Luchino

Immune functions are altered during space flights. Latent virus reactivation, reduction in the number of immune cells, decreased cell activation and increased sensitivity of astronauts to infections following their return on Earth demonstrate that the immune system is less efficient during space flight. The causes of this immune deficiency are not fully understood and this dysfunction during long-term missions could result in the appearance of opportunistic infections or a decrease in the immuno-surveillance mechanisms that eradicate cancer cells. Therefore, the immune functions of astronauts will have to be monitored continuously during long-term missions in space, using miniature and semi-automated diagnostic systems. The objectives of this project are to study the causes of space-related immunodeficiency, to develop countermeasures to maintain an optimal immune function and to improve our capacity to detect infectious diseases during space missions through the monitoring of astronauts' immune system. In order to achieve these objectives, an Immune Function Diagnostic System (IFDS) will be designed to perform a set of immunological assays on board spacecrafts or on planet-bound bases. Through flow cytometric assays and molecular biology analyses, this diagnostic system could improve medical surveillance of astronauts and could be used to test countermeasures aimed at preventing immune deficiency during space missions. The capacity of the instrument to assess cellular fluorescence and to quantify the presence of soluble molecules in biological samples would support advanced molecular studies in space life sciences. Finally, such diagnostic system could also be used on Earth in remote areas or in mobile hospitals following natural disasters to fight against infectious diseases and other pathologies.

New Tools and New Biology: Recent Miniaturized Systems for Molecular and Cellular Biology

PubMed Central

Hamon, Morgan; Hong, Jong Wook

2013-01-01

Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology. PMID:24305843

Workflow Management Systems for Molecular Dynamics on Leadership Computers

NASA Astrophysics Data System (ADS)

Wells, Jack; Panitkin, Sergey; Oleynik, Danila; Jha, Shantenu

Molecular Dynamics (MD) simulations play an important role in a range of disciplines from Material Science to Biophysical systems and account for a large fraction of cycles consumed on computing resources. Increasingly science problems require the successful execution of ''many'' MD simulations as opposed to a single MD simulation. There is a need to provide scalable and flexible approaches to the execution of the workload. We present preliminary results on the Titan computer at the Oak Ridge Leadership Computing Facility that demonstrate a general capability to manage workload execution agnostic of a specific MD simulation kernel or execution pattern, and in a manner that integrates disparate grid-based and supercomputing resources. Our results build upon our extensive experience of distributed workload management in the high-energy physics ATLAS project using PanDA (Production and Distributed Analysis System), coupled with recent conceptual advances in our understanding of workload management on heterogeneous resources. We will discuss how we will generalize these initial capabilities towards a more production level service on DOE leadership resources. This research is sponsored by US DOE/ASCR and used resources of the OLCF computing facility.

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

Hu, Qing; Jin, Dafei; Xiao, Jun

Two-dimensional molecular aggregate (2DMA), a thin sheet of strongly interacting dipole molecules self-assembled at close distance on an ordered lattice, is a fascinating fluorescent material. It is distinctively different from the conventional (single or colloidal) dye molecules and quantum dots. Here, in this paper, we verify that when a 2DMA is placed at a nanometric distance from a metallic substrate, the strong and coherent interaction between the dipoles inside the 2DMA dominates its fluorescent decay at a picosecond timescale. Our streak-camera lifetime measurement and interacting lattice–dipole calculation reveal that the metal-mediated dipole–dipole interaction shortens the fluorescent lifetime to about one-halfmore » and increases the energy dissipation rate by 10 times that expected from the noninteracting single-dipole picture. In conclusion, our finding can enrich our understanding of nanoscale energy transfer in molecular excitonic systems and may designate a unique direction for developing fast and efficient optoelectronic devices.« less

Controlling electron localization in H2 + by intense plasmon-enhanced laser fields

NASA Astrophysics Data System (ADS)

Yavuz, I.; Ciappina, M. F.; Chacón, A.; Altun, Z.; Kling, M. F.; Lewenstein, M.

2016-03-01

We present a theoretical study of the H2 + molecular ion wave-packet dynamics in plasmon-enhanced laser fields. These fields may be produced, for instance, when metallic nanostructures are illuminated by a laser pulse of moderated intensity. Their main property is that they vary in space on a nanometric scale. We demonstrate that the spatial inhomogeneous character of the plasmonic fields leads to an enhancement of electron localization (EL), an instrumental phenomenon to control molecular fragmentation. We suggest that the charge imbalance induced by the surface-plasmon resonance near the metallic nanostructure is the origin of the increase in the EL.

Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology (Final Report)

EPA Science Inventory

EPA announced the release of the final report, Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology. This report describes new approaches that are faster, less resource intensive, and more robust that can help ...

Ferrocene-containing non-interlocked molecular machines.

PubMed

Scottwell, Synøve Ø; Crowley, James D

2016-02-11

Ferrocene is the prototypical organometallic sandwich complex and despite over 60 years passing since the discovery and elucidation of ferrocene's structure, research into ferrocene-containing compounds continues to grow as potential new applications in catalysis, biology and the material sciences are found. Ferrocene is chemically robust and readily functionalized which enables its facile incorporation into more complex molecular systems. This coupled with ferrocene's reversible redox properties and ability function as a "molecular ball bearing" has led to the use of ferrocene as a component in wide range of interlocked and non-interlocked synthetic molecular machine systems. This review will focus on the exploitation of ferrocene (and related sandwich complexes) for the development of non-interlocked synthetic molecular machines.

Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System

PubMed Central

Adelson, David; Brown, Fred; Chaudhri, Naeem

2017-01-01

The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient's genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice. PMID:28812013

Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System.

PubMed

Banjar, Haneen; Adelson, David; Brown, Fred; Chaudhri, Naeem

2017-01-01

The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient's genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.

Enhanced Molecular Sieve CO2 Removal Evaluation

NASA Technical Reports Server (NTRS)

Rose, Susan; ElSherif, Dina; MacKnight, Allen

1996-01-01

The objective of this research is to quantitatively characterize the performance of two major types of molecular sieves for two-bed regenerative carbon dioxide removal at the conditions compatible with both a spacesuit and station application. One sorbent is a zeolite-based molecular sieve that has been substantially improved over the materials used in Skylab. The second sorbent is a recently developed carbon-based molecular sieve. Both molecular sieves offer the potential of high payoff for future manned missions by reducing system complexity, weight (including consumables), and power consumption in comparison with competing concepts. The research reported here provides the technical data required to improve CO2 removal systems for regenerative life support systems for future IVA and EVA missions.

A 99 percent purity molecular sieve oxygen generator

NASA Technical Reports Server (NTRS)

Miller, G. W.

1991-01-01

Molecular sieve oxygen generating systems (MSOGS) have become the accepted method for the production of breathable oxygen on military aircraft. These systems separate oxygen for aircraft engine bleed air by application of pressure swing adsorption (PSA) technology. Oxygen is concentrated by preferential adsorption in nitrogen in a zeolite molecular sieve. However, the inability of current zeolite molecular sieves to discriminate between oxygen and argon results in an oxygen purity limitations of 93-95 percent (both oxygen and argon concentrate). The goal was to develop a new PSA process capable of exceeding the present oxygen purity limitations. A novel molecular sieve oxygen concentrator was developed which is capable of generating oxygen concentrations of up to 99.7 percent directly from air. The process is comprised of four absorbent beds, two containing a zeolite molecular sieve and two containing a carbon molecular sieve. This new process may find use in aircraft and medical breathing systems, and industrial air separation systems. The commercial potential of the process is currently being evaluated.

Advanced systemic mastocytosis: from molecular and genetic progress to clinical practice.

PubMed

Ustun, Celalettin; Arock, Michel; Kluin-Nelemans, Hanneke C; Reiter, Andreas; Sperr, Wolfgang R; George, Tracy; Horny, Hans-Peter; Hartmann, Karin; Sotlar, Karl; Damaj, Gandhi; Hermine, Olivier; Verstovsek, Srdan; Metcalfe, Dean D; Gotlib, Jason; Akin, Cem; Valent, Peter

2016-10-01

Systemic mastocytosis is a heterogeneous disease characterized by the accumulation of neoplastic mast cells in the bone marrow and other organ organs/tissues. Mutations in KIT, most frequently KIT D816V, are detected in over 80% of all systemic mastocytosis patients. While most systemic mastocytosis patients suffer from an indolent disease variant, some present with more aggressive variants, collectively called "advanced systemic mastocytosis", which include aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic, clonal non mast cell-lineage disease, and mast cell leukemia. Whereas patients with indolent systemic mastocytosis have a near normal life expectancy, patients with advanced systemic mastocytosis have a reduced life expectancy. Although cladribine and interferon-alpha are of benefit in a group of patients with advanced systemic mastocytosis, no curative therapy is available for these patients except possible allogeneic hematopoietic stem cell transplantation. Recent studies have also revealed additional somatic defects (apart from mutations in KIT) in a majority of patients with advanced systemic mastocytosis. These include TET2, SRSF2, ASXL1, RUNX1, JAK2, and/or RAS mutations, which may adversely impact prognosis and survival in particular systemic mastocytosis with an associated hematological neoplasm. In addition, several additional signaling molecules involved in the abnormal proliferation of mast cells in systemic mastocytosis have been identified. These advances have led to a better understanding of the biology of advanced systemic mastocytosis and to the development of new targeted treatment concepts. Herein, we review the biology and pathogenesis of advanced systemic mastocytosis, with a special focus on novel molecular findings as well as current and evolving therapeutic options. Copyright© Ferrata Storti Foundation.

Molecular replication

NASA Technical Reports Server (NTRS)

Orgel, Leslie E.

1992-01-01

Recent experiments demonstrating nonenzymatic replication in molecular systems are reviewed. The difficulties facing nonenzymatic replication are discussed along with specificity, fidelity, and mutation in nonenzymatic replication. The prospects for research in this area are considered.

Novel insights into systemic autoimmune rheumatic diseases using shared molecular signatures and an integrative analysis.

PubMed

Hudson, Marie; Bernatsky, Sasha; Colmegna, Ines; Lora, Maximilien; Pastinen, Tomi; Klein Oros, Kathleen; Greenwood, Celia M T

2017-06-03

We undertook this study to identify DNA methylation signatures of three systemic autoimmune rheumatic diseases (SARDs), namely rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, compared to healthy controls. Using a careful design to minimize confounding, we restricted our study to subjects with incident disease and performed our analyses on purified CD4 + T cells, key effector cells in SARD. We identified differentially methylated (using the Illumina Infinium HumanMethylation450 BeadChip array) and expressed (using the Illumina TruSeq stranded RNA-seq protocol) sites between cases and controls, and investigated the biological significance of this SARD signature using gene annotation databases. We recruited 13 seropositive rheumatoid arthritis, 19 systemic sclerosis, 12 systemic lupus erythematosus subjects, and 8 healthy controls. We identified 33 genes that were both differentially methylated and expressed (26 over- and 7 under-expressed) in SARD cases versus controls. The most highly overexpressed gene was CD1C (log fold change in expression = 1.85, adjusted P value = 0.009). In functional analysis (Ingenuity Pathway Analysis), the top network identified was lipid metabolism, molecular transport, small molecule biochemistry. The top canonical pathways included the mitochondrial L-carnitine shuttle pathway (P = 5E-03) and PTEN signaling (P = 8E-03). The top upstream regulator was HNF4A (P = 3E-05). This novel SARD signature contributes to ongoing work to further our understanding of the molecular mechanisms underlying SARD and provides novel targets of interest.

A CRISPR/molecular beacon hybrid system for live-cell genomic imaging.

PubMed

Wu, Xiaotian; Mao, Shiqi; Yang, Yantao; Rushdi, Muaz N; Krueger, Christopher J; Chen, Antony K

2018-04-30

The clustered regularly interspersed short palindromic repeat (CRISPR) gene-editing system has been repurposed for live-cell genomic imaging, but existing approaches rely on fluorescent protein reporters, making sensitive and continuous imaging difficult. Here, we present a fluorophore-based live-cell genomic imaging system that consists of a nuclease-deactivated mutant of the Cas9 protein (dCas9), a molecular beacon (MB), and an engineered single-guide RNA (sgRNA) harboring a unique MB target sequence (sgRNA-MTS), termed CRISPR/MB. Specifically, dCas9 and sgRNA-MTS are first co-expressed to target a specific locus in cells, followed by delivery of MBs that can then hybridize to MTS to illuminate the target locus. We demonstrated the feasibility of this approach for quantifying genomic loci, for monitoring chromatin dynamics, and for dual-color imaging when using two orthogonal MB/MTS pairs. With flexibility in selecting different combinations of fluorophore/quencher pairs and MB/MTS sequences, our CRISPR/MB hybrid system could be a promising platform for investigating chromatin activities.

Reinforced dynamics for enhanced sampling in large atomic and molecular systems

NASA Astrophysics Data System (ADS)

Zhang, Linfeng; Wang, Han; E, Weinan

2018-03-01

A new approach for efficiently exploring the configuration space and computing the free energy of large atomic and molecular systems is proposed, motivated by an analogy with reinforcement learning. There are two major components in this new approach. Like metadynamics, it allows for an efficient exploration of the configuration space by adding an adaptively computed biasing potential to the original dynamics. Like deep reinforcement learning, this biasing potential is trained on the fly using deep neural networks, with data collected judiciously from the exploration and an uncertainty indicator from the neural network model playing the role of the reward function. Parameterization using neural networks makes it feasible to handle cases with a large set of collective variables. This has the potential advantage that selecting precisely the right set of collective variables has now become less critical for capturing the structural transformations of the system. The method is illustrated by studying the full-atom explicit solvent models of alanine dipeptide and tripeptide, as well as the system of a polyalanine-10 molecule with 20 collective variables.

A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

PubMed

Turan, Nil; Kalko, Susana; Stincone, Anna; Clarke, Kim; Sabah, Ayesha; Howlett, Katherine; Curnow, S John; Rodriguez, Diego A; Cascante, Marta; O'Neill, Laura; Egginton, Stuart; Roca, Josep; Falciani, Francesco

2011-09-01

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

Microstructural homogeneity of support silk spun by Eriophora fuliginea (C.L. Koch) determined by scanning X-ray microdiffraction

NASA Astrophysics Data System (ADS)

Riekel, C.; Craig, C. L.; Burghammer, M.; Müller, M.

2001-01-01

Scanning X-ray microdiffraction (SXD) permits the 'imaging' in-situ of crystalline phases, crystallinity and texture in whole biopolymer samples on the micrometre scale. SXD complements transmission electron microscopy (TEM) techniques, which reach sub-nanometre lateral resolution but require thin sections and a vacuum environment. This is demonstrated using a support thread from a web spun by the orb-weaving spider Eriophora fuliginea (C.L. Koch). Scanning electron microscopy (SEM) shows a central thread composed of two fibres to which thinner fibres are loosely attached. SXD of a piece of support thread approximately 60 µm long shows in addition the presence of nanometre-sized crystallites with the β-poly(L-alanine) structure in all fibres. The crystallinity of the thin fibres appears to be higher than that of the central thread, which probably reflects a higher polyalanine content of the fibroins. The molecular axis of the polymer chains in the central thread is orientated parallel to the macroscopic fibre axis, but in the thin fibres the molecular axis is tilted by about 71° to the macroscopic fibre axis. A helical model is tentatively proposed to describe this morphology. The central thread has a homogeneous distribution of crystallinity along the macroscopic fibre axis.

Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective

PubMed Central

van Heeswijk, Wally C.; Westerhoff, Hans V.

2013-01-01

SUMMARY We present a comprehensive overview of the hierarchical network of intracellular processes revolving around central nitrogen metabolism in Escherichia coli. The hierarchy intertwines transport, metabolism, signaling leading to posttranslational modification, and transcription. The protein components of the network include an ammonium transporter (AmtB), a glutamine transporter (GlnHPQ), two ammonium assimilation pathways (glutamine synthetase [GS]-glutamate synthase [glutamine 2-oxoglutarate amidotransferase {GOGAT}] and glutamate dehydrogenase [GDH]), the two bifunctional enzymes adenylyl transferase/adenylyl-removing enzyme (ATase) and uridylyl transferase/uridylyl-removing enzyme (UTase), the two trimeric signal transduction proteins (GlnB and GlnK), the two-component regulatory system composed of the histidine protein kinase nitrogen regulator II (NRII) and the response nitrogen regulator I (NRI), three global transcriptional regulators called nitrogen assimilation control (Nac) protein, leucine-responsive regulatory protein (Lrp), and cyclic AMP (cAMP) receptor protein (Crp), the glutaminases, and the nitrogen-phosphotransferase system. First, the structural and molecular knowledge on these proteins is reviewed. Thereafter, the activities of the components as they engage together in transport, metabolism, signal transduction, and transcription and their regulation are discussed. Next, old and new molecular data and physiological data are put into a common perspective on integral cellular functioning, especially with the aim of resolving counterintuitive or paradoxical processes featured in nitrogen assimilation. Finally, we articulate what still remains to be discovered and what general lessons can be learned from the vast amounts of data that are available now. PMID:24296575

Systems biology meets stress ecology: linking molecular and organismal stress responses in Daphnia magna

PubMed Central

Heckmann, Lars-Henrik; Sibly, Richard M; Connon, Richard; Hooper, Helen L; Hutchinson, Thomas H; Maund, Steve J; Hill, Christopher J; Bouetard, Anthony; Callaghan, Amanda

2008-01-01

Background Ibuprofen and other nonsteroidal anti-inflammatory drugs have been designed to interrupt eicosanoid metabolism in mammals, but little is known of how they affect nontarget organisms. Here we report a systems biology study that simultaneously describes the transcriptomic and phenotypic stress responses of the model crustacean Daphnia magna after exposure to ibuprofen. Results Our findings reveal intriguing similarities in the mode of action of ibuprofen between vertebrates and invertebrates, and they suggest that ibuprofen has a targeted impact on reproduction at the molecular, organismal, and population level in daphnids. Microarray expression and temporal real-time quantitative PCR profiles of key genes suggest early ibuprofen interruption of crustacean eicosanoid metabolism, which appears to disrupt signal transduction affecting juvenile hormone metabolism and oogenesis. Conclusion Combining molecular and organismal stress responses provides a guide to possible chronic consequences of environmental stress for population health. This could improve current environmental risk assessment by providing an early indication of the need for higher tier testing. Our study demonstrates the advantages of a systems approach to stress ecology, in which Daphnia will probably play a major role. PMID:18291039

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

PubMed

Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

2016-07-01

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

Preparation of Low Molecular Weight Gelatin Using Microwave Discharge Electrodeless Lamp/TiO2 Photocatalyst Hybrid System.

PubMed

Lee, Do-Jin; Kim, Hangun; Park, Young-Kwon; Kim, Byung Hoon; Lee, Heon; Jungf, Sana-Chul

2016-02-01

In this study, an MDEL/TiO2 photocatalyst hybrid system was applied to the production of low molecular weight gelatin. The molecular weight of produed gelatin decreased with increasing microwave intensity and increasing treatment time. The abscission of the chemical bonds between the con- stituents of gelatin by photocatalytic reaction did not alter the characteristics of gelatin. Formation of any by-products due to side reaction was not observed. It is suggested that gelatin was depolymerized by hydroxyl radicals produced during the MDEL/TiO2 photochemical reaction.

Crystalline molecular machines: Encoding supramolecular dynamics into molecular structure

PubMed Central

Garcia-Garibay, Miguel A.

2005-01-01

Crystalline molecular machines represent an exciting new branch of crystal engineering and materials science with important implications to nanotechnology. Crystalline molecular machines are crystals built with molecules that are structurally programmed to respond collectively to mechanic, electric, magnetic, or photonic stimuli to fulfill specific functions. One of the main challenges in their construction derives from the picometric precision required for their mechanic operation within the close-packed, self-assembled environment of crystalline solids. In this article, we outline some of the general guidelines for their design and apply them for the construction of molecular crystals with units intended to emulate macroscopic gyroscopes and compasses. Recent advances in the preparation, crystallization, and dynamic characterization of these interesting systems offer a foothold to the possibilities and help highlight some avenues for future experimentation. PMID:16046543

Effect of molecular weight of starch on the properties of cassava starch microspheres prepared in aqueous two-phase system.

PubMed

Xia, Huiping; Li, Bing-Zheng; Gao, Qunyu

2017-12-01

Starch microspheres (SMs) were fabricated in an aqueous two-phase system (ATPS). A series of starch samples with different molecular weight were prepared by acid hydrolysis, and the effect of molecular weight of starch on the fabrication of SMs were investigated. Scanning electron microscopy (SEM) showed that the morphologies of SMs varied with starch molecular weight, and spherical SMs with sharp contours were obtained while using starch samples with weight-average molecular weight (M¯w)≤1.057×10 5 g/mol. X-ray diffraction (XRD) results revealed that crystalline structure of SMs were different from that of native cassava starch, and the relative crystallinity of SMs increased with the molecular weight of starch decreasing. Differential scanning calorimetry (DSC) results showed peak gelatinization temperature (T p ) and enthalpy of gelatinization (ΔH) of SMs increased with decreased M¯wof starch. Stability tests indicated that the SMs were stable under acid environment, but not stable under α-amylase hydrolysis. Copyright © 2017. Published by Elsevier Ltd.

Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

DOE PAGES

Radak, Brian K.; Chipot, Christophe; Suh, Donghyuk; ...

2017-11-07

We report that an increasingly important endeavor is to develop computational strategies that enable molecular dynamics (MD) simulations of biomolecular systems with spontaneous changes in protonation states under conditions of constant pH. The present work describes our efforts to implement the powerful constant-pH MD simulation method, based on a hybrid nonequilibrium MD/Monte Carlo (neMD/MC) technique within the highly scalable program NAMD. The constant-pH hybrid neMD/MC method has several appealing features; it samples the correct semigrand canonical ensemble rigorously, the computational cost increases linearly with the number of titratable sites, and it is applicable to explicit solvent simulations. The present implementationmore » of the constant-pH hybrid neMD/MC in NAMD is designed to handle a wide range of biomolecular systems with no constraints on the choice of force field. Furthermore, the sampling efficiency can be adaptively improved on-the-fly by adjusting algorithmic parameters during the simulation. Finally, illustrative examples emphasizing medium- and large-scale applications on next-generation supercomputing architectures are provided.« less

Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

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

Radak, Brian K.; Chipot, Christophe; Suh, Donghyuk

We report that an increasingly important endeavor is to develop computational strategies that enable molecular dynamics (MD) simulations of biomolecular systems with spontaneous changes in protonation states under conditions of constant pH. The present work describes our efforts to implement the powerful constant-pH MD simulation method, based on a hybrid nonequilibrium MD/Monte Carlo (neMD/MC) technique within the highly scalable program NAMD. The constant-pH hybrid neMD/MC method has several appealing features; it samples the correct semigrand canonical ensemble rigorously, the computational cost increases linearly with the number of titratable sites, and it is applicable to explicit solvent simulations. The present implementationmore » of the constant-pH hybrid neMD/MC in NAMD is designed to handle a wide range of biomolecular systems with no constraints on the choice of force field. Furthermore, the sampling efficiency can be adaptively improved on-the-fly by adjusting algorithmic parameters during the simulation. Finally, illustrative examples emphasizing medium- and large-scale applications on next-generation supercomputing architectures are provided.« less

Molecular mechanisms of autophagy in the cardiovascular system.

PubMed

Gatica, Damián; Chiong, Mario; Lavandero, Sergio; Klionsky, Daniel J

2015-01-30

Autophagy is a catabolic recycling pathway triggered by various intra- or extracellular stimuli that is conserved from yeast to mammals. During autophagy, diverse cytosolic constituents are enveloped by double-membrane vesicles, autophagosomes, which later fuse with lysosomes or the vacuole to degrade their cargo. Dysregulation in autophagy is associated with a diverse range of pathologies including cardiovascular disease, the leading cause of death in the world. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been characterized widely in cardiomyocytes, cardiac fibroblasts, endothelial cells, and vascular smooth muscle cells. In all cases, a window of optimal autophagic activity seems to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. Here, we review the molecular mechanisms that govern autophagosome formation and analyze the link between autophagy and cardiovascular disease. © 2015 American Heart Association, Inc.

Self-consistent continuum solvation for optical absorption of complex molecular systems in solution

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

Timrov, Iurii; Biancardi, Alessandro; Andreussi, Oliviero

2015-01-21

We introduce a new method to compute the optical absorption spectra of complex molecular systems in solution, based on the Liouville approach to time-dependent density-functional perturbation theory and the revised self-consistent continuum solvation model. The former allows one to obtain the absorption spectrum over a whole wide frequency range, using a recently proposed Lanczos-based technique, or selected excitation energies, using the Casida equation, without having to ever compute any unoccupied molecular orbitals. The latter is conceptually similar to the polarizable continuum model and offers the further advantages of allowing an easy computation of atomic forces via the Hellmann-Feynman theorem andmore » a ready implementation in periodic-boundary conditions. The new method has been implemented using pseudopotentials and plane-wave basis sets, benchmarked against polarizable continuum model calculations on 4-aminophthalimide, alizarin, and cyanin and made available through the QUANTUM ESPRESSO distribution of open-source codes.« less

Using vibrational molecular spectroscopy to reveal association of steam-flaking induced carbohydrates molecular structural changes with grain fractionation, biodigestion and biodegradation

NASA Astrophysics Data System (ADS)

Xu, Ningning; Liu, Jianxin; Yu, Peiqiang

2018-04-01

Advanced vibrational molecular spectroscopy has been developed as a rapid and non-destructive tool to reveal intrinsic molecular structure conformation of biological tissues. However, this technique has not been used to systematically study flaking induced structure changes at a molecular level. The objective of this study was to use vibrational molecular spectroscopy to reveal association between steam flaking induced CHO molecular structural changes in relation to grain CHO fractionation, predicted CHO biodegradation and biodigestion in ruminant system. The Attenuate Total Reflectance Fourier-transform Vibrational Molecular Spectroscopy (ATR-Ft/VMS) at SRP Key Lab of Molecular Structure and Molecular Nutrition, Ministry of Agriculture Strategic Research Chair Program (SRP, University of Saskatchewan) was applied in this study. The fractionation, predicted biodegradation and biodigestion were evaluated using the Cornell Net Carbohydrate Protein System. The results show that: (1) The steam flaking induced significant changes in CHO subfractions, CHO biodegradation and biodigestion in ruminant system. There were significant differences between non-processed (raw) and steam flaked grain corn (P < .01); (2) The ATR-Ft/VMS molecular technique was able to detect the processing induced CHO molecular structure changes; (3) Induced CHO molecular structure spectral features are significantly correlated (P < .05) to CHO subfractions, CHO biodegradation and biodigestion and could be applied to potentially predict CHO biodegradation (R2 = 0.87, RSD = 0.74, P < .01) and intestinal digestible undegraded CHO (R2 = 0.87, RSD = 0.24, P < .01). In summary, the processing induced molecular CHO structure changes in grain corn could be revealed by the ATR-Ft/VMS vibrational molecular spectroscopy. These molecular structure changes in grain were potentially associated with CHO biodegradation and biodigestion.

Molecular finite-size effects in stochastic models of equilibrium chemical systems.

PubMed

Cianci, Claudia; Smith, Stephen; Grima, Ramon

2016-02-28

The reaction-diffusion master equation (RDME) is a standard modelling approach for understanding stochastic and spatial chemical kinetics. An inherent assumption is that molecules are point-like. Here, we introduce the excluded volume reaction-diffusion master equation (vRDME) which takes into account volume exclusion effects on stochastic kinetics due to a finite molecular radius. We obtain an exact closed form solution of the RDME and of the vRDME for a general chemical system in equilibrium conditions. The difference between the two solutions increases with the ratio of molecular diameter to the compartment length scale. We show that an increase in the fraction of excluded space can (i) lead to deviations from the classical inverse square root law for the noise-strength, (ii) flip the skewness of the probability distribution from right to left-skewed, (iii) shift the equilibrium of bimolecular reactions so that more product molecules are formed, and (iv) strongly modulate the Fano factors and coefficients of variation. These volume exclusion effects are found to be particularly pronounced for chemical species not involved in chemical conservation laws. Finally, we show that statistics obtained using the vRDME are in good agreement with those obtained from Brownian dynamics with excluded volume interactions.

Toward the identification of molecular cogs.

PubMed

Dziubiński, Maciej; Lesyng, Bogdan

2016-04-05

Computer simulations of molecular systems allow determination of microscopic interactions between individual atoms or groups of atoms, as well as studies of intramolecular motions. Nevertheless, description of structural transformations at the mezoscopic level and identification of causal relations associated with these transformations is very difficult. Structural and functional properties are related to free energy changes. Therefore, to better understand structural and functional properties of molecular systems, it is required to deepen our knowledge of free energy contributions arising from molecular subsystems in the course of structural transformations. The method presented in this work quantifies the energetic contribution of each pair of atoms to the total free energy change along a given collective variable. Next, with the help of a genetic clustering algorithm, the method proposes a division of the system into two groups of atoms referred to as molecular cogs. Atoms which cooperate to push the system forward along a collective variable are referred to as forward cogs, and those which work in the opposite direction as reverse cogs. The procedure was tested on several small molecules for which the genetic clustering algorithm successfully found optimal partitionings into molecular cogs. The primary result of the method is a plot depicting the energetic contributions of the identified molecular cogs to the total Potential of Mean Force (PMF) change. Case-studies presented in this work should help better understand the implications of our approach, and were intended to pave the way to a future, publicly available implementation. © 2015 Wiley Periodicals, Inc.

Molecular piracy: manipulation of the ubiquitin system by Kaposi's sarcoma-associated herpesvirus.

PubMed

Fujimuro, Masahiro; Hayward, S Diane; Yokosawa, Hideyoshi

2007-01-01

Ubiquitination, one of several post-translational protein modifications, plays a key role in the regulation of cellular events, including protein degradation, signal transduction, endocytosis, protein trafficking, apoptosis and immune responses. Ubiquitin attachment at the lysine residue of cellular factors acts as a signal for endocytosis and rapid degradation by the 26S proteasome. It has recently been observed that viruses, especially oncogenic herpesviruses, utilise molecular piracy by encoding their own proteins to interfere with regulation of cell signalling. Kaposi's sarcoma- associated herpesvirus (KSHV) manipulates the ubiquitin system to facilitate cell proliferation, anti-apoptosis and evasion from immunity. In this review, we will describe the strategies used by KSHV at distinct stages of the viral life-cycle to control the ubiquitin system and promote oncogenesis and viral persistence. (c) 2007 John Wiley & Sons, Ltd.

PPARγ: A Molecular Link between systemic metabolic disease and benign prostate hyperplasia

PubMed Central

Jiang, Ming; Strand, Douglas W.; Franco, Omar E.; Clark, Peter E.; Hayward, Simon W.

2011-01-01

The emergent epidemic of metabolic syndrome and its complex list of sequelae mandate a more thorough understanding of benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) in the context of systemic metabolic disease. Here we discuss the nature and origins of BPH, examine its role as a component of LUTS and review retrospective clinical studies that have drawn associations between BPH/LUTS and type II diabetes, inflammation and dyslipidemia. PPARγ signaling, which sits at the nexus of systemic metabolic disease and BPH/LUTS through its regulation of inflammation and insulin resistance is proposed as a candidate for molecular manipulation in regard to BPH/LUTS. Finally, we introduce new cell and animal models that are being used to study the consequences of obesity, diabetes and inflammation on benign prostatic growth. PMID:21645960

A portable molecular-sieve-based CO{sub 2} sampling system for radiocarbon measurements

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

Palonen, V., E-mail: vesa.palonen@helsinki.fi

We have developed a field-capable sampling system for the collection of CO{sub 2} samples for radiocarbon-concentration measurements. Most target systems in environmental research are limited in volume and CO{sub 2} concentration, making conventional flask sampling hard or impossible for radiocarbon studies. The present system captures the CO{sub 2} selectively to cartridges containing 13X molecular sieve material. The sampling does not introduce significant under-pressures or significant losses of moisture to the target system, making it suitable for most environmental targets. The system also incorporates a significantly larger sieve container for the removal of CO{sub 2} from chambers prior to the CO{submore » 2} build-up phase and sampling. In addition, both the CO{sub 2} and H{sub 2}O content of the sample gas are measured continuously. This enables in situ estimation of the amount of collected CO{sub 2} and the determination of CO{sub 2} flux to a chamber. The portable sampling system is described in detail and tests for the reliability of the method are presented.« less

Molecular Regulation of Phosphate Metabolism by Fibroblast Growth Factor-23–Klotho System

PubMed Central

Cheng, Chung-Yi; Kuro-o, Makoto; Razzaque, Mohammed S.

2011-01-01

Phosphorus is an essential nutrient and is routinely assimilated through consumption of food. The body’s need of phosphate is usually fulfilled by intestinal absorption of this element from the consumed food, whereas its serum level is tightly regulated by renal excretion or reabsorption. Sodium-dependent phosphate transporters, located in the luminal side of the proximal tubular epithelial cells, have a molecular control on renal phosphate excretion and reabsorption. The systemic regulation of phosphate metabolism is a complex multiorgan process, and the identification of fibroblast growth factor-23 (FGF23)–Klotho system as a potent phosphatonin has provided new mechanistic insights into the homeostatic control of phosphate. Hypophosphatemia as a result of an increase in urinary phosphate wasting after activation of the FGF23–Klotho system is a common phenomenon, observed in both animal and human studies, whereas suppression of the FGF23–Klotho system leads to the development of hyperphosphatemia. This article will briefly summarize how delicate interactions of the FGF23–Klotho system can regulate systemic phosphate homeostasis. PMID:21406293

The Renormalization Group and Its Applications to Generating Coarse-Grained Models of Large Biological Molecular Systems.

PubMed

Koehl, Patrice; Poitevin, Frédéric; Navaza, Rafael; Delarue, Marc

2017-03-14

Understanding the dynamics of biomolecules is the key to understanding their biological activities. Computational methods ranging from all-atom molecular dynamics simulations to coarse-grained normal-mode analyses based on simplified elastic networks provide a general framework to studying these dynamics. Despite recent successes in studying very large systems with up to a 100,000,000 atoms, those methods are currently limited to studying small- to medium-sized molecular systems due to computational limitations. One solution to circumvent these limitations is to reduce the size of the system under study. In this paper, we argue that coarse-graining, the standard approach to such size reduction, must define a hierarchy of models of decreasing sizes that are consistent with each other, i.e., that each model contains the information of the dynamics of its predecessor. We propose a new method, Decimate, for generating such a hierarchy within the context of elastic networks for normal-mode analysis. This method is based on the concept of the renormalization group developed in statistical physics. We highlight the details of its implementation, with a special focus on its scalability to large systems of up to millions of atoms. We illustrate its application on two large systems, the capsid of a virus and the ribosome translation complex. We show that highly decimated representations of those systems, containing down to 1% of their original number of atoms, still capture qualitatively and quantitatively their dynamics. Decimate is available as an OpenSource resource.

Molecular characterization of a functional type VI secretion system from a clinical isolate of Aeromonas hydrophila

EPA Science Inventory

Our laboratory recently molecularly characterized the type II secretion system (T2SS)-associated cytotoxic enterotoxin (Act) and the T3SS-secreted AexU effector from a diarrheal isolate SSU of Aeromonas hydrophila. The role of these toxin proteins in the pathogenesis of A. hydrop...

Molecular Characterization of a Functional Type VI Secretion System from a Clinical Isolate of Aeromonas hydrophilia

EPA Science Inventory

Our laboratory recently molecularly characterized the type II secretion system (T2SS)-associated cytotoxic enterotoxin (Act) and the T3SS-secreted AexU effector from a diarrheal isolate SSU of Aeromonas hydrophila. The role of these toxin proteins in the pathogenesis of A. hydrop...

A simple molecular orbital treatment of current distributions in quantum transport through molecular junctions

NASA Astrophysics Data System (ADS)

Jhan, Sin-Mu; Jin, Bih-Yaw

2017-11-01

A simple molecular orbital treatment of local current distributions inside single molecular junctions is developed in this paper. Using the first-order perturbation theory and nonequilibrium Green's function techniques in the framework of Hückel theory, we show that the leading contributions to local current distributions are directly proportional to the off-diagonal elements of transition density matrices. Under the orbital approximation, the major contributions to local currents come from a few dominant molecular orbital pairs which are mixed by the interactions between the molecule and electrodes. A few simple molecular junctions consisting of single- and multi-ring conjugated systems are used to demonstrate that local current distributions inside molecular junctions can be decomposed by partial sums of a few leading contributing transition density matrices.

Molecular optoelectronics: the interaction of molecular conduction junctions with light.

PubMed

Galperin, Michael; Nitzan, Abraham

2012-07-14

The interaction of light with molecular conduction junctions is attracting growing interest as a challenging experimental and theoretical problem on one hand, and because of its potential application as a characterization and control tool on the other. It stands at the interface between two important fields, molecular electronics and molecular plasmonics and has attracted attention as a challenging scientific problem with potentially important technological consequences. Here we review the present state of the art of this field, focusing on several key phenomena and applications: using light as a switching device, using light to control junction transport in the adiabatic and non-adiabatic regimes, light generation in biased junctions and Raman scattering from such systems. This field has seen remarkable progress in the past decade, and the growing availability of scanning tip configurations that can combine optical and electrical probes suggests that further progress towards the goal of realizing molecular optoelectronics on the nanoscale is imminent.

Hierarchical Time-Lagged Independent Component Analysis: Computing Slow Modes and Reaction Coordinates for Large Molecular Systems.

PubMed

Pérez-Hernández, Guillermo; Noé, Frank

2016-12-13

Analysis of molecular dynamics, for example using Markov models, often requires the identification of order parameters that are good indicators of the rare events, i.e. good reaction coordinates. Recently, it has been shown that the time-lagged independent component analysis (TICA) finds the linear combinations of input coordinates that optimally represent the slow kinetic modes and may serve in order to define reaction coordinates between the metastable states of the molecular system. A limitation of the method is that both computing time and memory requirements scale with the square of the number of input features. For large protein systems, this exacerbates the use of extensive feature sets such as the distances between all pairs of residues or even heavy atoms. Here we derive a hierarchical TICA (hTICA) method that approximates the full TICA solution by a hierarchical, divide-and-conquer calculation. By using hTICA on distances between heavy atoms we identify previously unknown relaxation processes in the bovine pancreatic trypsin inhibitor.

A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease

PubMed Central

Turan, Nil; Kalko, Susana; Stincone, Anna; Clarke, Kim; Sabah, Ayesha; Howlett, Katherine; Curnow, S. John; Rodriguez, Diego A.; Cascante, Marta; O'Neill, Laura; Egginton, Stuart; Roca, Josep; Falciani, Francesco

2011-01-01

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients. PMID:21909251

Molecular – genetic variance of RH blood group system within human population of Bosnia and Herzegovina

PubMed Central

Lasić, Lejla; Lojo-Kadrić, Naida; Silajdžić, Elma; Pojskić, Lejla; Hadžiselimović, Rifat; Pojskić, Naris

2013-01-01

There are two major theories for inheritance of Rh blood group system: Fisher – Race theory and Wiener theory. Aim of this study was identifying frequency of RHDCE alleles in Bosnian – Herzegovinian population and introduction of this method in screening for Rh phenotype in B&H since this type of analysis was not used for blood typing in B&H before. Rh blood group was typed by Polymerase Chain Reaction, using the protocols and primers previously established by other authors, then carrying out electrophoresis in 2-3% agarose gel. Percentage of Rh positive individuals in our sample is 84.48%, while the percentage of Rh negative individuals is 15.52%. Inter-rater agreement statistic showed perfect agreement (K=1) between the results of Rh blood system detection based on serological and molecular-genetics methods. In conclusion, molecular – genetic methods are suitable for prenatal genotyping and specific cases while standard serological method is suitable for high-throughput of samples. PMID:23448604

Optical spectroscopy and system-bath interactions in molecular aggregates with full configuration interaction Frenkel exciton model

NASA Astrophysics Data System (ADS)

Seibt, Joachim; Sláma, Vladislav; Mančal, Tomáš

2016-12-01

Standard application of the Frenkel exciton model neglects resonance coupling between collective molecular aggregate states with different number of excitations. These inter-band coupling terms are, however, of the same magnitude as the intra-band coupling between singly excited states. We systematically derive the Frenkel exciton model from quantum chemical considerations, and identify it as a variant of the configuration interaction method. We discuss all non-negligible couplings between collective aggregate states, and provide compact formulae for their calculation. We calculate absorption spectra of molecular aggregate of carotenoids and identify significant band shifts as a result of inter-band coupling. The presence of inter-band coupling terms requires renormalization of the system-bath coupling with respect to standard formulation, but renormalization effects are found to be weak. We present detailed discussion of molecular dimer and calculate its time-resolved two-dimensional Fourier transformed spectra to find weak but noticeable effects of peak amplitude redistribution due to inter-band coupling.

Harnessing Reversible Electronic Energy Transfer: From Molecular Dyads to Molecular Machines.

PubMed

Denisov, Sergey A; Yu, Shinlin; Pozzo, Jean-Luc; Jonusauskas, Gediminas; McClenaghan, Nathan D

2016-06-17

Reversible electronic energy transfer (REET) may be instilled in bi-/multichromophoric molecule-based systems, following photoexcitation, upon judicious structural integration of matched chromophores. This leads to a new set of photophysical properties for the ensemble, which can be fully characterized by steady-state and time-resolved spectroscopic methods. Herein, we take a comprehensive look at progress in the development of this type of supermolecule in the last five years, which has seen systems evolve from covalently tethered dyads to synthetic molecular machines, exemplified by two different pseudorotaxanes. Indeed, REET holds promise in the control of movement in molecular machines, their assembly/disassembly, as well as in charge separation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular environmental geochemistry

NASA Astrophysics Data System (ADS)

O'Day, Peggy A.

1999-05-01

The chemistry, mobility, and bioavailability of contaminant species in the natural environment are controlled by reactions that occur in and among solid, aqueous, and gas phases. These reactions are varied and complex, involving changes in chemical form and mass transfer among inorganic, organic, and biochemical species. The field of molecular environmental geochemistry seeks to apply spectroscopic and microscopic probes to the mechanistic understanding of environmentally relevant chemical processes, particularly those involving contaminants and Earth materials. In general, empirical geochemical models have been shown to lack uniqueness and adequate predictive capability, even in relatively simple systems. Molecular geochemical tools, when coupled with macroscopic measurements, can provide the level of chemical detail required for the credible extrapolation of contaminant reactivity and bioavailability over ranges of temperature, pressure, and composition. This review focuses on recent advances in the understanding of molecular chemistry and reaction mechanisms at mineral surfaces and mineral-fluid interfaces spurred by the application of new spectroscopies and microscopies. These methods, such as synchrotron X-ray absorption and scattering techniques, vibrational and resonance spectroscopies, and scanning probe microscopies, provide direct chemical information that can elucidate molecular mechanisms, including element speciation, ligand coordination and oxidation state, structural arrangement and crystallinity on different scales, and physical morphology and topography of surfaces. Nonvacuum techniques that allow examination of reactions in situ (i.e., with water or fluids present) and in real time provide direct links between molecular structure and reactivity and measurements of kinetic rates or thermodynamic properties. Applications of these diverse probes to laboratory model systems have provided fundamental insight into inorganic and organic reactions at

EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

NASA Astrophysics Data System (ADS)

Weinelt, Martin; von Oppen, Felix

2012-10-01

In nature, molecules exploit interaction with their environment to realize complex functionalities on the nanometer length scale. Physical, chemical and/or biological specificity is frequently achieved by the switching of molecules between microscopically different states. Paradigmatic examples are the energy production in proton pumps of bacteria or the signal conversion in human vision, which rely on switching molecules between different configurations or conformations by external stimuli. The remarkable reproducibility and unparalleled fatigue resistance of these natural processes makes it highly desirable to emulate nature and develop artificial systems with molecular functionalities. A promising avenue towards this goal is to anchor the molecular switches at surfaces, offering new pathways to control their functional properties, to apply electrical contacts, or to integrate switches into larger systems. Anchoring at surfaces allows one to access the full range from individual molecular switches to self-assembled monolayers of well-defined geometry and to customize the coupling between molecules and substrate or between adsorbed molecules. Progress in this field requires both synthesis and preparation of appropriate molecular systems and control over suitable external stimuli, such as light, heat, or electrical currents. To optimize switching and generate function, it is essential to unravel the geometric structure, the electronic properties and the dynamic interactions of the molecular switches on surfaces. This special section, Molecular Switches at Surfaces, collects 17 contributions describing different aspects of this research field. They analyze elementary processes, both in single molecules and in ensembles of molecules, which involve molecular switching and concomitant changes of optical, electronic, or magnetic properties. Two topical reviews summarize the current status, including both challenges and achievements in the field of molecular switches on

Molecular tailoring of interfaces for thin film on substrate systems

NASA Astrophysics Data System (ADS)

Grady, Martha Elizabeth

Thin film on substrate systems appear most prevalently within the microelectronics industry, which demands that devices operate in smaller and smaller packages with greater reliability. The reliability of these multilayer film systems is strongly influenced by the adhesion of each of the bimaterial interfaces. During use, microelectronic components undergo thermo-mechanical cycling, which induces interfacial delaminations leading to failure of the overall device. The ability to tailor interfacial properties at the molecular level provides a mechanism to improve thin film adhesion, reliability and performance. This dissertation presents the investigation of molecular level control of interface properties in three thin film-substrate systems: photodefinable polyimide films on passivated silicon substrates, self-assembled monolayers at the interface of Au films and dielectric substrates, and mechanochemically active materials on rigid substrates. For all three materials systems, the effect of interfacial modifications on adhesion is assessed using a laser-spallation technique. Laser-induced stress waves are chosen because they dynamically load the thin film interface in a precise, noncontacting manner at high strain rates and are suitable for both weak and strong interfaces. Photodefinable polyimide films are used as dielectrics in flip chip integrated circuit packages to reduce the stress between silicon passivation layers and mold compound. The influence of processing parameters on adhesion is examined for photodefinable polyimide films on silicon (Si) substrates with three different passivation layers: silicon nitride (SiNx), silicon oxynitride (SiOxNy), and the native silicon oxide (SiO2). Interfacial strength increases when films are processed with an exposure step as well as a longer cure cycle. Additionally, the interfacial fracture energy is assessed using a dynamic delamination protocol. The high toughness of this interface (ca. 100 J/m2) makes it difficult

A Silicon SPECT System for Molecular Imaging of the Mouse Brain.

PubMed

Shokouhi, Sepideh; Fritz, Mark A; McDonald, Benjamin S; Durko, Heather L; Furenlid, Lars R; Wilson, Donald W; Peterson, Todd E

2007-01-01

We previously demonstrated the feasibility of using silicon double-sided strip detectors (DSSDs) for SPECT imaging of the activity distribution of iodine-125 using a 300-micrometer thick detector. Based on this experience, we now have developed fully customized silicon DSSDs and associated readout electronics with the intent of developing a multi-pinhole SPECT system. Each DSSD has a 60.4 mm × 60.4 mm active area and is 1 mm thick. The strip pitch is 59 micrometers, and the readout of the 1024 strips on each side gives rise to a detector with over one million pixels. Combining four high-resolution DSSDs into a SPECT system offers an unprecedented space-bandwidth product for the imaging of single-photon emitters. The system consists of two camera heads with two silicon detectors stacked one behind the other in each head. The collimator has a focused pinhole system with cylindrical-shaped pinholes that are laser-drilled in a 250 μm tungsten plate. The unique ability to collect projection data at two magnifications simultaneously allows for multiplexed data at high resolution to be combined with lower magnification data with little or no multiplexing. With the current multi-pinhole collimator design, our SPECT system will be capable of offering high spatial resolution, sensitivity and angular sampling for small field-of-view applications, such as molecular imaging of the mouse brain.

Molecular Thermometry

PubMed Central

McCabe, Kevin M.; Hernandez, Mark

2010-01-01

Conventional temperature measurements rely on material responses to heat, which can be detected visually. When Galileo developed an air expansion based device to detect temperature changes, Santorio, a contemporary physician, added a scale to create the first thermometer. With this instrument, patients’ temperatures could be measured, recorded and related to changing health conditions. Today, advances in materials science and bioengineering provide new ways to report temperature at the molecular level in real time. In this review the scientific foundations and history of thermometry underpin a discussion of the discoveries emerging from the field of molecular thermometry. Intracellular nanogels and heat sensing biomolecules have been shown to accurately report temperature changes at the nano-scale. Various systems will soon provide the ability to accurately measure temperature changes at the tissue, cellular, and even sub-cellular level, allowing for detection and monitoring of very small changes in local temperature. In the clinic this will lead to enhanced detection of tumors and localized infection, and accurate and precise monitoring of hyperthermia based therapies. Some nanomaterial systems have even demonstrated a theranostic capacity for heat-sensitive, local delivery of chemotherapeutics. Just as early thermometry moved into the clinic, so too will these molecular thermometers. PMID:20139796

A tunable pH-sensing system based on Ag nanoclusters capped by hyperbranched polyethyleneimine with different molecular weights.

PubMed

Qu, Fei; Zou, Xuan; Kong, Rongmei; You, Jinmao

2016-01-01

In this assay, a tunable pH sensing system was developed based on Ag nanoclusters (Ag NCs) capped by hyperbranched polyethyleneimine (PEI) with different molecular weights (abbreviated as Ag NC-PEIs). For instance, when the molecular weight of PEI was 600 or 1800, the fluorescence intensities of Ag NCs exhibited a linear fashion over the pH range 4.10-7.96; when the molecular weight of PEI was 25,000, the pH linear range was from 4.78 to 7.96; when the molecular weight of PEI was 70,000, the pH linear range was 6.09-8.95. According to the molecular weight of PEI 600/1800, 25,000, and 70,000, the color change point was pH 4.10-4.78, 5.33-6.09, and 6.09-6.80, respectively. Therefore, Ag NC-PEI 600 and 1800 were proper to acid conditions; Ag NC-PEI 25,000 was sensitive to weak acid media; while Ag NC-PEI 70,000 was adapted to neutral solution. The tunable and selective color change points brought an excellent feature of Ag NC-PEIs as visual pH indicators, which was flexible and applicable to a variety of environments. Besides, the ratios of absorbance at 415 nm and 268 nm of Ag NCs also showed linear relationships with pH variations. Therefore, there were three ways of this system for sensing pH values, including fluorescence assay, ultraviolet-visible measurement, and visual detection, suggesting that this tunable pH-sensing platform was more feasible, reliable, and accurate. Copyright © 2015 Elsevier B.V. All rights reserved.

Mass-velocity and size-velocity distributions of ejecta cloud from shock-loaded tin surface using large scale molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Durand, Olivier; Soulard, Laurent

2015-06-01

The mass (volume and areal densities) versus velocity as well as the size versus velocity distributions of a shock-induced cloud of particles are investigated using large scale molecular dynamics (MD) simulations. A generic 3D tin crystal with a sinusoidal free surface roughness is set in contact with vacuum and shock-loaded so that it melts directly on shock. At the reflection of the shock wave onto the perturbations of the free surface, 2D sheets/jets of liquid metal are ejected. The simulations show that the distributions may be described by an analytical model based on the propagation of a fragmentation zone, from the tip of the sheets to the free surface, within which the kinetic energy of the atoms decreases as this zone comes closer to the free surface on late times. As this kinetic energy drives (i) the (self-similar) expansion of the zone once it has broken away from the sheet and (ii) the average size of the particles which result from fragmentation in the zone, the ejected mass and the average size of the particles progressively increase in the cloud as fragmentation occurs closer to the free surface. Though relative to nanometric scales, our model reproduces quantitatively experimental profiles and may help in their analysis.

Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

NASA Astrophysics Data System (ADS)

Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

2016-12-01

A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

Computing molecular fluctuations in biochemical reaction systems based on a mechanistic, statistical theory of irreversible processes.

PubMed

Kulasiri, Don

2011-01-01

We discuss the quantification of molecular fluctuations in the biochemical reaction systems within the context of intracellular processes associated with gene expression. We take the molecular reactions pertaining to circadian rhythms to develop models of molecular fluctuations in this chapter. There are a significant number of studies on stochastic fluctuations in intracellular genetic regulatory networks based on single cell-level experiments. In order to understand the fluctuations associated with the gene expression in circadian rhythm networks, it is important to model the interactions of transcriptional factors with the E-boxes in the promoter regions of some of the genes. The pertinent aspects of a near-equilibrium theory that would integrate the thermodynamical and particle dynamic characteristics of intracellular molecular fluctuations would be discussed, and the theory is extended by using the theory of stochastic differential equations. We then model the fluctuations associated with the promoter regions using general mathematical settings. We implemented ubiquitous Gillespie's algorithms, which are used to simulate stochasticity in biochemical networks, for each of the motifs. Both the theory and the Gillespie's algorithms gave the same results in terms of the time evolution of means and variances of molecular numbers. As biochemical reactions occur far away from equilibrium-hence the use of the Gillespie algorithm-these results suggest that the near-equilibrium theory should be a good approximation for some of the biochemical reactions. © 2011 Elsevier Inc. All rights reserved.

Information engineering for molecular diagnostics.

PubMed Central

Sorace, J. M.; Ritondo, M.; Canfield, K.

1994-01-01

Clinical laboratories are beginning to apply the recent advances in molecular biology to the testing of patient samples. The emerging field of Molecular Diagnostics will require a new Molecular Diagnostics Laboratory Information System which handles the data types, samples and test methods found in this field. The system must be very flexible in regards to supporting ad-hoc queries. The requirements which are shaping the developments in this field are reviewed and a data model developed. Several queries which demonstrate the data models ability to support the information needs of this area have been developed and run. These results demonstrate the ability of the purposed data model to meet the current and projected needs of this rapidly expanding field. PMID:7949937

The Effect of Two Receivers on Broadcast Molecular Communication Systems.

PubMed

Lu, Yi; Higgins, Matthew D; Noel, Adam; Leeson, Mark S; Chen, Yunfei

2016-12-01

Molecular communication is a paradigm that utilizes molecules to exchange information between nano-machines. When considering such systems where multiple receivers are present, prior work has assumed for simplicity that they do not interfere with each other. This paper aims to address this issue and shows to what extent an interfering receiver, [Formula: see text], will have an impact on the target receiver, [Formula: see text], with respect to Bit Error Rate (BER) and capacity. Furthermore, approximations of the Binomial distribution are applied to reduce the complexity of calculations. Results show the sensitivity in communication performance due to the relative location of the interfering receiver. Critically, placing [Formula: see text] between the transmitter [Formula: see text] and [Formula: see text] causes a significant increase in BER or decrease in capacity.

Full Quantum Dynamics Simulation of a Realistic Molecular System Using the Adaptive Time-Dependent Density Matrix Renormalization Group Method.

PubMed

Yao, Yao; Sun, Ke-Wei; Luo, Zhen; Ma, Haibo

2018-01-18

The accurate theoretical interpretation of ultrafast time-resolved spectroscopy experiments relies on full quantum dynamics simulations for the investigated system, which is nevertheless computationally prohibitive for realistic molecular systems with a large number of electronic and/or vibrational degrees of freedom. In this work, we propose a unitary transformation approach for realistic vibronic Hamiltonians, which can be coped with using the adaptive time-dependent density matrix renormalization group (t-DMRG) method to efficiently evolve the nonadiabatic dynamics of a large molecular system. We demonstrate the accuracy and efficiency of this approach with an example of simulating the exciton dissociation process within an oligothiophene/fullerene heterojunction, indicating that t-DMRG can be a promising method for full quantum dynamics simulation in large chemical systems. Moreover, it is also shown that the proper vibronic features in the ultrafast electronic process can be obtained by simulating the two-dimensional (2D) electronic spectrum by virtue of the high computational efficiency of the t-DMRG method.

Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

PubMed Central

Algieri, Catia; Drioli, Enrico; Guzzo, Laura; Donato, Laura

2014-01-01

An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template) was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported. PMID:25196110

Effects of the Shuttle Orbiter fuselage and elevon on the molecular distribution of water vapor from the flash evaporator system

NASA Technical Reports Server (NTRS)

Richmond, R. G.; Kelso, R. M.

1980-01-01

A concern has arisen regarding the emissive distribution of water molecules from the shuttle orbiter flash evaporator system (FES). The role of the orbiter fuselage and elevon in affecting molecular scattering distributions was nuclear. The effect of these components were evaluated. Molecular distributions of the water vapor effluents from the FE were measured. These data were compared with analytically predicted values and the resulting implications were calculated.

Light-operated machines based on threaded molecular structures.

PubMed

Credi, Alberto; Silvi, Serena; Venturi, Margherita

2014-01-01

Rotaxanes and related species represent the most common implementation of the concept of artificial molecular machines, because the supramolecular nature of the interactions between the components and their interlocked architecture allow a precise control on the position and movement of the molecular units. The use of light to power artificial molecular machines is particularly valuable because it can play the dual role of "writing" and "reading" the system. Moreover, light-driven machines can operate without accumulation of waste products, and photons are the ideal inputs to enable autonomous operation mechanisms. In appropriately designed molecular machines, light can be used to control not only the stability of the system, which affects the relative position of the molecular components but also the kinetics of the mechanical processes, thereby enabling control on the direction of the movements. This step forward is necessary in order to make a leap from molecular machines to molecular motors.

Topology, localization, and quantum information in atomic, molecular and optical systems

NASA Astrophysics Data System (ADS)

Yao, Norman Ying

The scientific interface between atomic, molecular and optical (AMO) physics, condensed matter, and quantum information science has recently led to the development of new insights and tools that bridge the gap between macroscopic quantum behavior and detailed microscopic intuition. While the dialogue between these fields has sharpened our understanding of quantum theory, it has also raised a bevy of new questions regarding the out-of-equilibrium dynamics and control of many-body systems. This thesis is motivated by experimental advances that make it possible to produce and probe isolated, strongly interacting ensembles of disordered particles, as found in systems ranging from trapped ions and Rydberg atoms to ultracold polar molecules and spin defects in the solid state. The presence of strong interactions in these systems underlies their potential for exploring correlated many-body physics and this thesis presents recent results on realizing fractionalization and localization. From a complementary perspective, the controlled manipulation of individual quanta can also enable the bottom-up construction of quantum devices. To this end, this thesis also describes blueprints for a room-temperature quantum computer, quantum credit cards and nanoscale quantum thermometry.

Molecular and Cellular Designs of Insect Taste Receptor System

PubMed Central

Isono, Kunio; Morita, Hiromi

2010-01-01

The insect gustatory receptors (GRs) are members of a large G-protein coupled receptor family distantly related to the insect olfactory receptors. They are phylogenetically different from taste receptors of most other animals. GRs are often coexpressed with other GRs in single receptor neurons. Taste receptors other than GRs are also expressed in some neurons. Recent molecular studies in the fruitfly Drosophila revealed that the insect taste receptor system not only covers a wide ligand spectrum of sugars, bitter substances or salts that are common to mammals but also includes reception of pheromone and somatosensory stimulants. However, the central mechanism to perceive and discriminate taste information is not yet elucidated. Analysis of the primary projection of taste neurons to the brain shows that the projection profiles depend basically on the peripheral locations of the neurons as well as the GRs that they express. These results suggest that both peripheral and central design principles of insect taste perception are different from those of olfactory perception. PMID:20617187

A Molecular Code for Identity in the Vomeronasal System.

PubMed

Fu, Xiaoyan; Yan, Yuetian; Xu, Pei S; Geerlof-Vidavsky, Ilan; Chong, Wongi; Gross, Michael L; Holy, Timothy E

2015-10-08

In social interactions among mammals, individuals are recognized by olfactory cues, but identifying the key signals among thousands of compounds remains a major challenge. To address this need, we developed a new technique, component-activity matching (CAM), to select candidate ligands that "explain" patterns of bioactivity across diverse complex mixtures. Using mouse urine from eight different sexes and strains, we identified 23 components to explain firing rates in seven of eight functional classes of vomeronasal sensory neurons. Focusing on a class of neurons selective for females, we identified a novel family of vomeronasal ligands, steroid carboxylic acids. These ligands accounted for much of the neuronal activity of urine from some female strains, were necessary for normal levels of male investigatory behavior of female scents, and were sufficient to trigger mounting behavior. CAM represents the first step toward an exhaustive characterization of the molecular cues for natural behavior in a mammalian olfactory system. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiplexed Molecular Diagnostics for Respiratory, Gastrointestinal, and Central Nervous System Infections.

PubMed

Hanson, Kimberly E; Couturier, Marc Roger

2016-11-15

The development and implementation of highly multiplexed molecular diagnostic tests have allowed clinical microbiology laboratories to more rapidly and sensitively detect a variety of pathogens directly in clinical specimens. Current US Food and Drug Administration-approved multiplex panels target multiple different organisms simultaneously and can identify the most common pathogens implicated in respiratory viral, gastrointestinal, or central nervous system infections. This review summarizes the test characteristics of available assays, highlights the advantages and limitations of multiplex technology for infectious diseases, and discusses potential utilization of these new tests in clinical practice. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Molecular Modeling of Lipid Aggregates: Theory and Application

NASA Astrophysics Data System (ADS)

Fenner, Joel Stewart

The ability of cell membranes to perform a wide variety of biological functions stems from the organization and composition of its molecular constituents. There are many engineering applications, such as liposome drug delivery carriers, whose functionality takes advantage of the structure to function relationship of lipid membranes. The fundamental understanding of the relationship between the thermodynamic behavior and structure of lipid membranes and the molecular properties of their lipid constituents is crucial to the successful design of lipid related applications. However, information about how the local microscopic composition of lipid membranes responds to the presence of proteins and nanomaterials is challenging given the intrinsic experimental and theoretical difficulties of studying such small-scale systems. The present work generalizes a self consistent mean field theory for the study of the thermodynamic and structural behavior of lipid bilayers as a function of its molecular composition and physicochemical environments. This novel molecular theory provides with the ability of performing systematic thermodynamic calculations at relatively low computational costs while considering a detailed molecular description of the system under study. The competition of all relevant molecular interactions, such as electrostatics, vdW and chemical equilibria, in the membrane system is described. The developed molecular theory is applied to study how the protonation state of pH-sensitive amphiphiles in a membrane system affects the membrane's morphology. The molecular theory results demonstrate that the protonation state of ionizable groups within amphiphilic membranes shows a highly complex non-monotonic dependence on bulk salt concentration and pH strength. This result suggests that information about the pKa of the molecules is not sufficient to predict the protonation state of the ionizable groups in the membrane system. The molecular theory is also applied to

Molecular microenvironments: Solvent interactions with nucleic acid bases and ions

NASA Technical Reports Server (NTRS)

Macelroy, R. D.; Pohorille, A.

1986-01-01

The possibility of reconstructing plausible sequences of events in prebiotic molecular evolution is limited by the lack of fossil remains. However, with hindsight, one goal of molecular evolution was obvious: the development of molecular systems that became constituents of living systems. By understanding the interactions among molecules that are likely to have been present in the prebiotic environment, and that could have served as components in protobiotic molecular systems, plausible evolutionary sequences can be suggested. When stable aggregations of molecules form, a net decrease in free energy is observed in the system. Such changes occur when solvent molecules interact among themselves, as well as when they interact with organic species. A significant decrease in free energy, in systems of solvent and organic molecules, is due to entropy changes in the solvent. Entropy-driven interactioins played a major role in the organization of prebiotic systems, and understanding the energetics of them is essential to understanding molecular evolution.

Design of Molecular Materials: Supramolecular Engineering

NASA Astrophysics Data System (ADS)

Simon, Jacques; Bassoul, Pierre

2001-02-01

This timely and fascinating book is destined to be recognised as THE book on supramolecular engineering protocols. It covers this sometimes difficult subject in an approachable form, gathering together information from many sources. Supramolecular chemistry, which links organic chemistry to materials science, is one of the fastest growth areas of chemistry research. This book creates a correlation between the structure of single molecules and the physical and chemical properties of the resulting materials. By making systematic changes to the component molecules, the resulting solid can be engineered for optimum performance. There is a clearly written development from synthesis of designer molecules to properties of solids and further on to devices and complex materials systems, providing guidelines for mastering the organisation of these systems. Topics covered include: Systemic chemistry Molecular assemblies Notions of symmetry Supramolecular engineering Principe de Curie Organisation in molecular media Molecular semiconductors Industrial applications of molecular materials This superb book will be invaluable to researchers in the field of supramolecular materials and also to students and teachers of the subject.

Modeling convection-diffusion-reaction systems for microfluidic molecular communications with surface-based receivers in Internet of Bio-Nano Things

PubMed Central

Akan, Ozgur B.

2018-01-01

We consider a microfluidic molecular communication (MC) system, where the concentration-encoded molecular messages are transported via fluid flow-induced convection and diffusion, and detected by a surface-based MC receiver with ligand receptors placed at the bottom of the microfluidic channel. The overall system is a convection-diffusion-reaction system that can only be solved by numerical methods, e.g., finite element analysis (FEA). However, analytical models are key for the information and communication technology (ICT), as they enable an optimisation framework to develop advanced communication techniques, such as optimum detection methods and reliable transmission schemes. In this direction, we develop an analytical model to approximate the expected time course of bound receptor concentration, i.e., the received signal used to decode the transmitted messages. The model obviates the need for computationally expensive numerical methods by capturing the nonlinearities caused by laminar flow resulting in parabolic velocity profile, and finite number of ligand receptors leading to receiver saturation. The model also captures the effects of reactive surface depletion layer resulting from the mass transport limitations and moving reaction boundary originated from the passage of finite-duration molecular concentration pulse over the receiver surface. Based on the proposed model, we derive closed form analytical expressions that approximate the received pulse width, pulse delay and pulse amplitude, which can be used to optimize the system from an ICT perspective. We evaluate the accuracy of the proposed model by comparing model-based analytical results to the numerical results obtained by solving the exact system model with COMSOL Multiphysics. PMID:29415019

Modeling convection-diffusion-reaction systems for microfluidic molecular communications with surface-based receivers in Internet of Bio-Nano Things.

PubMed

Kuscu, Murat; Akan, Ozgur B

2018-01-01

We consider a microfluidic molecular communication (MC) system, where the concentration-encoded molecular messages are transported via fluid flow-induced convection and diffusion, and detected by a surface-based MC receiver with ligand receptors placed at the bottom of the microfluidic channel. The overall system is a convection-diffusion-reaction system that can only be solved by numerical methods, e.g., finite element analysis (FEA). However, analytical models are key for the information and communication technology (ICT), as they enable an optimisation framework to develop advanced communication techniques, such as optimum detection methods and reliable transmission schemes. In this direction, we develop an analytical model to approximate the expected time course of bound receptor concentration, i.e., the received signal used to decode the transmitted messages. The model obviates the need for computationally expensive numerical methods by capturing the nonlinearities caused by laminar flow resulting in parabolic velocity profile, and finite number of ligand receptors leading to receiver saturation. The model also captures the effects of reactive surface depletion layer resulting from the mass transport limitations and moving reaction boundary originated from the passage of finite-duration molecular concentration pulse over the receiver surface. Based on the proposed model, we derive closed form analytical expressions that approximate the received pulse width, pulse delay and pulse amplitude, which can be used to optimize the system from an ICT perspective. We evaluate the accuracy of the proposed model by comparing model-based analytical results to the numerical results obtained by solving the exact system model with COMSOL Multiphysics.

Molecular Adsorber Coating

NASA Technical Reports Server (NTRS)

Straka, Sharon; Peters, Wanda; Hasegawa, Mark; Hedgeland, Randy; Petro, John; Novo-Gradac, Kevin; Wong, Alfred; Triolo, Jack; Miller, Cory

2011-01-01

A document discusses a zeolite-based sprayable molecular adsorber coating that has been developed to alleviate the size and weight issues of current ceramic puck-based technology, while providing a configuration that more projects can use to protect against degradation from outgassed materials within a spacecraft, particularly contamination-sensitive instruments. This coating system demonstrates five times the adsorption capacity of previously developed adsorber coating slurries. The molecular adsorber formulation was developed and refined, and a procedure for spray application was developed. Samples were spray-coated and tested for capacity, thermal optical/radiative properties, coating adhesion, and thermal cycling. Work performed during this study indicates that the molecular adsorber formulation can be applied to aluminum, stainless steel, or other metal substrates that can accept silicate-based coatings. The coating can also function as a thermal- control coating. This adsorber will dramatically reduce the mass and volume restrictions, and is less expensive than the currently used molecular adsorber puck design.

Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces

NASA Astrophysics Data System (ADS)

Poloni, Laura N.

-cystine surfaces. Collectively, these findings identify the key structural factors responsible for molecular recognition between molecular imposters and L-cystine crystal step sites, thereby articulating a strategy for stone prevention based on molecular design. The second part of this thesis describes the crystal growth and inhibition of a P2X3 receptor antagonist, denoted as DAPSA, recently reported as a non-opioid treatment of chronic pain. The low solubility of this compound results in the formation of drug-induced renal calculi (a.k.a. xenostones). in situ AFM of the morphologically significant (011) DAPSA surface revealed dislocation-actuated growth spirals with an anisotropic morphology, behavior that can be attributed to the non-uniform rate of solute attachment to eight crystallographically unique steps of the spiral, a direct consequence of the dissymmetry of this crystal surface. Eighteen molecular imposters were selected from the screening library to systematically investigate the roles of imposter substitute position, size, and functionality on the step velocities along the eight unique crystallographic directions. A non-uniform reduction in step velocities was observed, signaling site discrimination of imposter binding that can be attributed to stereochemical recognition of the imposters at specific crystal sites. The anisotropy of growth inhibition observed in the presence of the various imposters is consistent with binding energies calculated for the thirty-two crystallographically unique kink sites on steps advancing along predominant growth directions. These results provide insight to the design of growth inhibitors for molecular crystalline solids with complex and dissymmetric surfaces, while also suggesting a strategy for formulations containing congeners that can prevent harmful crystal growth in human renal structures. The last two crystalline systems discussed in this thesis are two isomorphous crystal systems that are ideal for the study of impurity

Forensic molecular pathology of violent deaths.

PubMed

Maeda, Hitoshi; Zhu, Bao-li; Ishikawa, Takaki; Michiue, Tomomi

2010-12-15

In forensic pathology, while classical morphology remains a core procedure to investigate deaths, a spectrum of ancillary procedures has been developed and incorporated to detail the pathology. Among them, postmortem biochemistry is important to investigate the systemic pathophysiological changes involved in the dying process that cannot be detected by morphology. In addition, recent advances in molecular biology have provided a procedure to investigate genetic bases of diseases that might present with sudden death, which is called 'molecular autopsy'. Meanwhile, the practical application of RNA analyses to postmortem investigation has not been accepted due to rapid decay after death; however, recent experimental and practical studies using real-time reverse transcription-PCR have suggested that the relative quantification of mRNA transcripts can be applied in molecular pathology for postmortem investigation of deaths, which may be called 'advanced molecular autopsy'. In a broad sense, forensic molecular pathology implies applied medical sciences to investigate the genetic basis of diseases, and the pathophysiology of diseases and traumas leading to death at a biological molecular level in the context of forensic pathology. The possible applications include analyses of local pathology, including tissue injury, ischemia/hypoxia and inflammation at the site of insult or specific tissue damage from intoxication, systemic responses to violence or environmental hazards, disorders due to intoxication, and systemic pathophysiology of fatal process involving major life-support organs. A review of previous studies suggests that systematic postmortem quantitative analysis of mRNA transcripts can be established from multi-faceted aspects of molecular biology and incorporated into death investigations in forensic pathology, to support and reinforce morphological evidence. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Stimuli Responsive Systems Constructed Using Cucurbit[n]uril-Type Molecular Containers

PubMed Central

2015-01-01

Conspectus This Account focuses on stimuli responsive systems that function in aqueous solution using examples drawn from the work of the Isaacs group using cucurbit[n]uril (CB[n]) molecular containers as key recognition elements. Our entry into the area of stimuli responsive systems began with the preparation of glycoluril derived molecular clips that efficiently distinguish between self and nonself by H-bonds and π–π interactions even within complex mixtures and therefore undergo self-sorting. We concluded that the selectivity of a wide variety of H-bonded supramolecular assemblies was higher than previously appreciated and that self-sorting is not exceptional behavior. This lead us to examine self-sorting within the context of CB[n] host–guest chemistry in water. We discovered that CB[n] homologues (CB[7] and CB[8]) display remarkably high binding affinity (Ka up to 1017 M–1) and selectivity (ΔΔG) toward their guests, which renders CB[n]s prime components for the construction of stimuli responsive host–guest systems. The CB[7]·adamantaneammonium ion complex, which is particularly privileged (Ka = 4.2 × 1012 M–1), was introduced by us as a stimulus to trigger constitutional changes in multicomponent self-sorting systems. For example, we describe how the free energy associated with the formation of host–guest complexes of CB[n]-type receptors can drive conformational changes of included guests like triazene–arylene foldamers and cationic calix[4]arenes, as well as induced conformational changes (e.g., ammonium guest size dependent homotropic allostery, metal ion triggered folding, and heterochiral dimerization) of the hosts themselves. Many guests display large pKa shifts within their CB[n]–guest complexes, which we used to promote pH controlled guest swapping and thermal trans-to-cis isomerization of azobenzene derivatives. We also used the high affinity and selectivity of CB[7] toward its guests to outcompete an enzyme (bovine carbonic

Molecular Diagnosis of Tuberculosis.

PubMed

Nurwidya, Fariz; Handayani, Diah; Burhan, Erlina; Yunus, Faisal

2018-01-01

Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.

Local structure in anisotropic systems determined by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Komolkin, Andrei V.; Maliniak, Arnold

In the present communication we describe the investigation of local structure using a new visualization technique. The approach is based on two-dimensional pair correlation functions derived from a molecular dynamics computer simulation. We have used this method to analyse a trajectory produced in a simulation of a nematic liquid crystal of 4-n-pentyl-4'-cyanobiphenyl (5CB) (Komolkin et al., 1994, J. chem. Phys., 101, 4103). The molecule is assumed to have cylindrical symmetry, and the liquid crystalline phase is treated as uniaxial. The pair correlation functions or cylindrical distribution functions (CDFs) are calculated in the molecular (m) and laboratory (l) frames, gm2(z1 2, d1 2) and g12(Z1 2, D1 2). Anisotropic molecular organization in the liquid crystal is reflected in laboratory frame CDFs. The molecular excluded volume is determined and the effect of the fast motion in the alkyl chain is observed. The intramolecular distributions are included in the CDFs and indicate the size of the motional amplitude in the chain. Absence of long range order was confirmed, a feature typical for a nematic liquid crystal.

Bacterial Translocation Ratchets: Shared Physical Principles with Different Molecular Implementations: How bacterial secretion systems bias Brownian motion for efficient translocation of macromolecules.

PubMed

Hepp, Christof; Maier, Berenike

2017-10-01

Secretion systems enable bacteria to import and secrete large macromolecules including DNA and proteins. While most components of these systems have been identified, the molecular mechanisms of macromolecular transport remain poorly understood. Recent findings suggest that various bacterial secretion systems make use of the translocation ratchet mechanism for transporting polymers across the cell envelope. Translocation ratchets are powered by chemical potential differences generated by concentration gradients of ions or molecules that are specific to the respective secretion systems. Bacteria employ these potential differences for biasing Brownian motion of the macromolecules within the conduits of the secretion systems. Candidates for this mechanism include DNA import by the type II secretion/type IV pilus system, DNA export by the type IV secretion system, and protein export by the type I secretion system. Here, we propose that these three secretion systems employ different molecular implementations of the translocation ratchet mechanism. © 2017 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Architectonics: Design of Molecular Architecture for Functional Applications.

PubMed

Avinash, M B; Govindaraju, Thimmaiah

2018-02-20

The term architectonics has its roots in the architectural and philosophical (as early as 1600s) literature that refers to "the theory of structure" and "the structure of theory", respectively. The concept of architectonics has been adapted to advance the field of molecular self-assembly and termed as molecular architectonics. In essence, the methodology of organizing molecular units in the required and controlled configurations to develop advanced functional systems for materials and biological applications comprises the field of molecular architectonics. This concept of designing noncovalent systems enables to focus on different functional aspects of designer molecules for biological and nonbiological applications and also strengthens our efforts toward the mastery over the art of controlled molecular self-assemblies. Programming complex molecular interactions and assemblies for specific functions has been one of the most challenging tasks in the modern era. Meticulously ordered molecular assemblies can impart remarkable developments in several areas spanning energy, health, and environment. For example, the well-defined nano-, micro-, and macroarchitectures of functional molecules with specific molecular ordering possess potential applications in flexible electronics, photovoltaics, photonic crystals, microreactors, sensors, drug delivery, biomedicine, and superhydrophobic coatings, among others. The functional molecular architectures having unparalleled properties are widely evident in various designs of Nature. By drawing inspirations from Nature, intended molecular architectures can be designed and developed to harvest various functions, as there is an inexhaustible resource and scope. In this Account, we present exquisite designer molecules developed by our group and others with an objective to master the art of molecular recognition and self-assembly for functional applications. We demonstrate the tailor-ability of molecular self-assemblies by employing

Stand-off molecular composition analysis

NASA Astrophysics Data System (ADS)

Hughes, Gary B.; Lubin, Philip; Meinhold, Peter; O'Neill, Hugh; Brashears, Travis; Zhang, Qicheng; Griswold, Janelle; Riley, Jordan; Motta, Caio

2015-09-01

Molecular composition of distant stars is explored by observing absorption spectra. The star produces blackbody radiation that passes through the molecular cloud of vaporized material surrounding the star. Characteristic absorption lines are discernible with a spectrometer, and molecular composition is investigated by comparing spectral observations with known material profiles. Most objects in the solar system—asteroids, comets, planets, moons—are too cold to be interrogated in this manner. Molecular clouds around cold objects consist primarily of volatiles, so bulk composition cannot be probed. Additionally, low volatile density does not produce discernible absorption lines in the faint signal generated by low blackbody temperatures. This paper describes a system for probing the molecular composition of cold solar system targets from a distant vantage. The concept utilizes a directed energy beam to melt and vaporize a spot on a distant target, such as from a spacecraft orbiting the object. With sufficient flux (~10 MW/m2), the spot temperature rises rapidly (to ~2 500 K), and evaporation of all materials on the target surface occurs. The melted spot creates a high-temperature blackbody source, and ejected material creates a molecular plume in front of the spot. Bulk composition is investigated by using a spectrometer to view the heated spot through the ejected material. Spatial composition maps could be created by scanning the surface. Applying the beam to a single spot continuously produces a borehole, and shallow sub-surface composition profiling is also possible. Initial simulations of absorption profiles with laser heating show great promise for molecular composition analysis.

The Challenges of Recombinant Endostatin in Clinical Application: Focus on the Different Expression Systems and Molecular Bioengineering

PubMed Central

Mohajeri, Abbas; Sanaei, Sarvin; Kiafar, Farhad; Fattahi, Amir; Khalili, Majid; Zarghami, Nosratollah

2017-01-01

Angiogenesis plays an essential role in rapid growing and metastasis of the tumors. Inhibition of angiogenesis is a putative strategy for cancer therapy. Endostatin (Es) is an attractive anti-angiogenesis protein with some clinical application challenges including; short half-life, instability in serum and requirement to high dosage. Therefore, production of recombinant endostatin (rEs) is necessary in large scale. The production of rEs is difficult because of its structural properties and is high-cost. Therefore, this review focused on the different expression systems that involved in rEs production including; mammalian, baculovirus, yeast, and Escherichia coli (E. coli) expression systems. The evaluating of the results of different expression systems declared that none of the mentioned systems can be considered to be generally superior to the other. Meanwhile with considering the advantages and disadvantage of E. coli expression system compared with other systems beside the molecular properties of Es, E. coli expression system can be a preferred expression system for expressing of the Es in large scale. Also, the molecular bioengineering and sustained release formulations that lead to improving of its stability and bioactivity will be discussed. Point mutation (P125A) of Es, addition of RGD moiety or an additional zinc biding site to N-terminal of Es , fusing of Es to anti-HER2 IgG or heavy-chain of IgG, and finally loading of the endostar by PLGA and PEG- PLGA nanoparticles and gold nano-shell particles are the effective bioengineering methods to overcome to clinical changes of endostatin. PMID:28507934

MIDG-Emerging grid technologies for multi-site preclinical molecular imaging research communities.

PubMed

Lee, Jasper; Documet, Jorge; Liu, Brent; Park, Ryan; Tank, Archana; Huang, H K

2011-03-01

Molecular imaging is the visualization and identification of specific molecules in anatomy for insight into metabolic pathways, tissue consistency, and tracing of solute transport mechanisms. This paper presents the Molecular Imaging Data Grid (MIDG) which utilizes emerging grid technologies in preclinical molecular imaging to facilitate data sharing and discovery between preclinical molecular imaging facilities and their collaborating investigator institutions to expedite translational sciences research. Grid-enabled archiving, management, and distribution of animal-model imaging datasets help preclinical investigators to monitor, access and share their imaging data remotely, and promote preclinical imaging facilities to share published imaging datasets as resources for new investigators. The system architecture of the Molecular Imaging Data Grid is described in a four layer diagram. A data model for preclinical molecular imaging datasets is also presented based on imaging modalities currently used in a molecular imaging center. The MIDG system components and connectivity are presented. And finally, the workflow steps for grid-based archiving, management, and retrieval of preclincial molecular imaging data are described. Initial performance tests of the Molecular Imaging Data Grid system have been conducted at the USC IPILab using dedicated VMware servers. System connectivity, evaluated datasets, and preliminary results are presented. The results show the system's feasibility, limitations, direction of future research. Translational and interdisciplinary research in medicine is increasingly interested in cellular and molecular biology activity at the preclinical levels, utilizing molecular imaging methods on animal models. The task of integrated archiving, management, and distribution of these preclinical molecular imaging datasets at preclinical molecular imaging facilities is challenging due to disparate imaging systems and multiple off-site investigators. A

Modeling Molecular Hydrogen Emission in M-Dwarf Exoplanetary Systems

NASA Astrophysics Data System (ADS)

Evonosky, W. R.; France, K.; Kruczek, N.; Youngblood, A.

2016-12-01

Exoplanets orbiting low-mass stars are prime candidates for atmospheric characterization due to their astronomical abundance and short orbital periods. These planets orbit stars that are often more active than main sequence solar-type stars. They are exposed to differing levels of ultraviolet radiation which can cause traditional "biosignature" gases to be generated abiotically, potentially causing false-positive identifications of life. We modeled the recently discovered molecular hydrogen emission in the ultraviolet spectra (1350 - 1650 Å) as arising from the stellar surface, excited by radiation generated in the upper chromosphere. The model was compared with observed hydrogen emission from the "Measurements of the Ultraviolet Spectral Characteristics of Low-mass Exoplanet host Stars" (MUSCLES) survey by conducting a grid search and implementing a chi-squared minimization routine. We considered only progressions from the [1, 4] and [1, 7] first excited electronic levels. Our modeling procedure varied the atomic hydrogen column density (in the chromosphere) as well as the photospheric molecular hydrogen column density and temperature. The model required as an input a reconstructed intrinsic Lyman α profile which served as the pumping radiation for the molecular hydrogen. We found that an atomic hydrogen column density of log10N(H I) = 14.13 ± 0.16 cm-2 represents a breaking point above which there is not enough Lyman α flux available to excite a significant molecular hydrogen population into the [1, 7] state. We also present H2 temperatures which may suggest that star spots on low mass stars persist longer, and encompass more area than star spots on solar-type stars.

Dealing with chemical reaction pathways and electronic excitations in molecular systems via renormalized and active-space coupled-cluster methods

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

Piecuch, Piotr; Li, Wei; Lutz, Jesse J.

Coupled-cluster (CC) theory has become the de facto standard for high-accuracy molecular calculations, but the widely used CC and equation-of-motion (EOM) CC approaches, such as CCSD(T) and EOMCCSD, have difficulties with capturing stronger electron correlations that characterize multi-reference molecular problems. This presentation demonstrates that many of these difficulties can be addressed by exploiting the completely renormalized (CR) CC and EOMCC approaches, such as CR-CC(2,3), CR-EOMCCSD(T), and CR-EOMCC(2,3), and their local correlation counterparts applicable to systems with hundreds of atoms, and the active-space CC/EOMCC approaches, such as CCSDt and EOMCCSDt, and their extensions to valence systems via the electron-attached and ionizedmore » formalisms.« less

Molecular networks related to the immune system and mitochondria are targets for the pesticide dieldrin in the zebrafish (Danio rerio) central nervous system.

PubMed

Cowie, Andrew M; Sarty, Kathleena I; Mercer, Angella; Koh, Jin; Kidd, Karen A; Martyniuk, Christopher J

2017-03-22

The objectives of this study were to determine the behavioral and molecular responses in the adult zebrafish (Danio rerio) central nervous system (CNS) following a dietary exposure to the pesticide dieldrin. Zebrafish were fed pellets spiked with 0.03, 0.15, or 1.8μg/g dieldrin for 21days. Behavioral analysis revealed no difference in exploratory behaviors or those related to anxiety. Transcriptional networks for T-cell aggregation and selection were decreased in expression suggesting an immunosuppressive effect of dieldrin, consistent with other studies investigating organochlorine pesticides. Processes related to oxidative phosphorylation were also differentially affected by dieldrin. Quantitative proteomics (iTRAQ) using a hybrid quadrupole-Orbitrap identified 226 proteins that were different following one or more doses. These proteins included ATP synthase subunits (mitochondrial) and hypoxia up-regulated protein 1 which were decreased and NADH dehydrogenases (mitochondrial) and signal recognition particle 9 which were up-regulated. Thus, proteins affected were functionally associated with the mitochondria and a protein network analysis implicated Parkinson's disease (PD) and Huntington's disease as diseases associated with altered proteins. Molecular networks related to mitochondrial dysfunction and T-cell regulation are hypothesized to underlie the association between dieldrin and PD. These data contribute to a comprehensive transcriptomic and proteomic biomarker framework for pesticide exposures and neurodegenerative diseases. Dieldrin is a persistent organochlorine pesticide that has been associated with human neurodegenerative disease such as Parkinson's disease. Dieldrin is ranked 18th on the 2015 U.S. Agency for Toxic Substances and Disease Registry and continues to be a pesticide of concern for human health. Transcriptomics and quantitative proteomics (ITRAQ) were employed to characterize the molecular networks in the central nervous system that are

Molecular Mechanisms of RNA-Targeting by Cas13-containing Type VI CRISPR-Cas Systems.

PubMed

O'Connell, Mitchell

2018-06-22

Prokaryotic adaptive immune systems use CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR associated (Cas) proteins for RNA-guided cleavage of foreign genetic elements. The focus of this review, Type VI CRISPR-Cas systems, include a single protein known as Cas13 (formerly C2c2), that when assembled with a crRNA forms a crRNA-guided RNA-targeting effector complex. Type VI CRISPR-Cas systems can be divided into four subtypes (A-D) based on Cas13 phylogeny. All Cas13 proteins studied to date possess two enzymatically distinct ribonuclease activities that are required for optimal interference. One RNase is responsible for pre-crRNA processing to form mature Type VI interference complexes, while the other RNase activity provided by the two HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding) domains, is required for degradation of target RNA during viral interference. In this review, I will compare and contrast what is known about the molecular architecture and behavior of Type VI (A-D) CRISPR-Cas13 interference complexes, how this allows them to carry out their RNA-targeting function, how Type VI accessory proteins are able to modulate Cas13 activity, and how together all of these features have led to the rapid development of a range of RNA-targeting applications. Throughout I will also discuss some of the outstanding questions regarding Cas13's molecular behavior, and its role in bacterial adaptive immunity and RNA-targeting applications. Copyright © 2018. Published by Elsevier Ltd.

The effects of moisture on molecular sieve oxygen concentrators.

PubMed

Ikels, K G; Theis, C F

1985-01-01

Molecular sieve oxygen generating systems are receiving extensive laboratory and flight evaluation. Assessment of the molecular system has generally been conducted in the laboratory using clean dry air. In aircraft, however, the molecular sieve generator is supplied with engine bleed air which may not always be totally free of contaminants and water. Recent studies using bed washout technics have shown that the molecular sieve units, with 50% of the beds deactivated with water, still function normally with respect to product gas flow and O2 concentration. By utilizing the technics described in this paper, the moisture content or state of hydration of the molecular sieve can readily be determined.

The cobas® 6800/8800 System: a new era of automation in molecular diagnostics.

PubMed

Cobb, Bryan; Simon, Christian O; Stramer, Susan L; Body, Barbara; Mitchell, P Shawn; Reisch, Natasa; Stevens, Wendy; Carmona, Sergio; Katz, Louis; Will, Stephen; Liesenfeld, Oliver

2017-02-01

Molecular diagnostics is a key component of laboratory medicine. Here, the authors review key triggers of ever-increasing automation in nucleic acid amplification testing (NAAT) with a focus on specific automated Polymerase Chain Reaction (PCR) testing and platforms such as the recently launched cobas® 6800 and cobas® 8800 Systems. The benefits of such automation for different stakeholders including patients, clinicians, laboratory personnel, hospital administrators, payers, and manufacturers are described. Areas Covered: The authors describe how molecular diagnostics has achieved total laboratory automation over time, rivaling clinical chemistry to significantly improve testing efficiency. Finally, the authors discuss how advances in automation decrease the development time for new tests enabling clinicians to more readily provide test results. Expert Commentary: The advancements described enable complete diagnostic solutions whereby specific test results can be combined with relevant patient data sets to allow healthcare providers to deliver comprehensive clinical recommendations in multiple fields ranging from infectious disease to outbreak management and blood safety solutions.

Monte Carlo treatment planning for molecular targeted radiotherapy within the MINERVA system

NASA Astrophysics Data System (ADS)

Lehmann, Joerg; Hartmann Siantar, Christine; Wessol, Daniel E.; Wemple, Charles A.; Nigg, David; Cogliati, Josh; Daly, Tom; Descalle, Marie-Anne; Flickinger, Terry; Pletcher, David; DeNardo, Gerald

2005-03-01

The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU) and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (modality inclusive environment for radiotherapeutic variable analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plugin architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4—2%, MCNP—10%) (Descalle et al 2003 Cancer Biother. Radiopharm. 18 71-9). The code is currently being benchmarked against experimental data. The interpatient variability of

GraphSAW: a web-based system for graphical analysis of drug interactions and side effects using pharmaceutical and molecular data.

PubMed

Shoshi, Alban; Hoppe, Tobias; Kormeier, Benjamin; Ogultarhan, Venus; Hofestädt, Ralf

2015-02-28

Adverse drug reactions are one of the most common causes of death in industrialized Western countries. Nowadays, empirical data from clinical studies for the approval and monitoring of drugs and molecular databases is available. The integration of database information is a promising method for providing well-based knowledge to avoid adverse drug reactions. This paper presents our web-based decision support system GraphSAW which analyzes and evaluates drug interactions and side effects based on data from two commercial and two freely available molecular databases. The system is able to analyze single and combined drug-drug interactions, drug-molecule interactions as well as single and cumulative side effects. In addition, it allows exploring associative networks of drugs, molecules, metabolic pathways, and diseases in an intuitive way. The molecular medication analysis includes the capabilities of the upper features. A statistical evaluation of the integrated data and top 20 drugs concerning drug interactions and side effects is performed. The results of the data analysis give an overview of all theoretically possible drug interactions and side effects. The evaluation shows a mismatch between pharmaceutical and molecular databases. The concordance of drug interactions was about 12% and 9% of drug side effects. An application case with prescribed data of 11 patients is presented in order to demonstrate the functionality of the system under real conditions. For each patient at least two interactions occured in every medication and about 8% of total diseases were possibly induced by drug therapy. GraphSAW (http://tunicata.techfak.uni-bielefeld.de/graphsaw/) is meant to be a web-based system for health professionals and researchers. GraphSAW provides comprehensive drug-related knowledge and an improved medication analysis which may support efforts to reduce the risk of medication errors and numerous drastic side effects.

Analysis of A Drug Target-based Classification System using Molecular Descriptors.

PubMed

Lu, Jing; Zhang, Pin; Bi, Yi; Luo, Xiaomin

2016-01-01

Drug-target interaction is an important topic in drug discovery and drug repositioning. KEGG database offers a drug annotation and classification using a target-based classification system. In this study, we gave an investigation on five target-based classes: (I) G protein-coupled receptors; (II) Nuclear receptors; (III) Ion channels; (IV) Enzymes; (V) Pathogens, using molecular descriptors to represent each drug compound. Two popular feature selection methods, maximum relevance minimum redundancy and incremental feature selection, were adopted to extract the important descriptors. Meanwhile, an optimal prediction model based on nearest neighbor algorithm was constructed, which got the best result in identifying drug target-based classes. Finally, some key descriptors were discussed to uncover their important roles in the identification of drug-target classes.

Cell and molecular mechanics of biological materials

NASA Astrophysics Data System (ADS)

Bao, G.; Suresh, S.

2003-11-01

Living cells can sense mechanical forces and convert them into biological responses. Similarly, biological and biochemical signals are known to influence the abilities of cells to sense, generate and bear mechanical forces. Studies into the mechanics of single cells, subcellular components and biological molecules have rapidly evolved during the past decade with significant implications for biotechnology and human health. This progress has been facilitated by new capabilities for measuring forces and displacements with piconewton and nanometre resolutions, respectively, and by improvements in bio-imaging. Details of mechanical, chemical and biological interactions in cells remain elusive. However, the mechanical deformation of proteins and nucleic acids may provide key insights for understanding the changes in cellular structure, response and function under force, and offer new opportunities for the diagnosis and treatment of disease. This review discusses some basic features of the deformation of single cells and biomolecules, and examines opportunities for further research.

Ames interactive molecular model building system - A 3-D computer modelling system applied to the study of the origin of life

NASA Technical Reports Server (NTRS)

Coeckelenbergh, Y.; Macelroy, R. D.; Rein, R.

1978-01-01

The investigation of specific interactions among biological molecules must take into consideration the stereochemistry of the structures. Thus, models of the molecules are essential for describing the spatial organization of potentially interacting groups, and estimations of conformation are required for a description of spatial organization. Both the function of visualizing molecules, and that of estimating conformation through calculations of energy, are part of the molecular modeling system described in the present paper. The potential uses of the system in investigating some aspects of the origin of life rest on the assumption that translation of conformation from genetic elements to catalytic elements would have been required for the development of the first replicating systems subject to the process of biological evolution.

Interrogating selectivity in catalysis using molecular vibrations

NASA Astrophysics Data System (ADS)

Milo, Anat; Bess, Elizabeth N.; Sigman, Matthew S.

2014-03-01

The delineation of molecular properties that underlie reactivity and selectivity is at the core of physical organic chemistry, and this knowledge can be used to inform the design of improved synthetic methods or identify new chemical transformations. For this reason, the mathematical representation of properties affecting reactivity and selectivity trends, that is, molecular parameters, is paramount. Correlations produced by equating these molecular parameters with experimental outcomes are often defined as free-energy relationships and can be used to evaluate the origin of selectivity and to generate new, experimentally testable hypotheses. The premise behind successful correlations of this type is that a systematically perturbed molecular property affects a transition-state interaction between the catalyst, substrate and any reaction components involved in the determination of selectivity. Classic physical organic molecular descriptors, such as Hammett, Taft or Charton parameters, seek to independently probe isolated electronic or steric effects. However, these parameters cannot address simultaneous, non-additive variations to more than one molecular property, which limits their utility. Here we report a parameter system based on the vibrational response of a molecule to infrared radiation that can be used to mathematically model and predict selectivity trends for reactions with interlinked steric and electronic effects at positions of interest. The disclosed parameter system is mechanistically derived and should find broad use in the study of chemical and biological systems.

Interfacial Molecular Packing Determines Exciton Dynamics in Molecular Heterostructures: The Case of Pentacene-Perfluoropentacene.

PubMed

Rinn, Andre; Breuer, Tobias; Wiegand, Julia; Beck, Michael; Hübner, Jens; Döring, Robin C; Oestreich, Michael; Heimbrodt, Wolfram; Witte, Gregor; Chatterjee, Sangam

2017-12-06

The great majority of electronic and optoelectronic devices depend on interfaces between p-type and n-type semiconductors. Finding matching donor-acceptor systems in molecular semiconductors remains a challenging endeavor because structurally compatible molecules may not necessarily be suitable with respect to their optical and electronic properties, and the large exciton binding energy in these materials may favor bound electron-hole pairs rather than free carriers or charge transfer at an interface. Regardless, interfacial charge-transfer exciton states are commonly considered as an intermediate step to achieve exciton dissociation. The formation efficiency and decay dynamics of such states will strongly depend on the molecular makeup of the interface, especially the relative alignment of donor and acceptor molecules. Structurally well-defined pentacene-perfluoropentacene heterostructures of different molecular orientations are virtually ideal model systems to study the interrelation between molecular packing motifs at the interface and their electronic properties. Comparing the emission dynamics of the heterosystems and the corresponding unitary films enables accurate assignment of every observable emission signal in the heterosystems. These heterosystems feature two characteristic interface-specific luminescence channels at around 1.4 and 1.5 eV that are not observed in the unitary samples. Their emission strength strongly depends on the molecular alignment of the respective donor and acceptor molecules, emphasizing the importance of structural control for device construction.

Molecular theory of smectic ordering in liquid crystals with nanoscale segregation of different molecular fragments

NASA Astrophysics Data System (ADS)

Gorkunov, M. V.; Osipov, M. A.; Kapernaum, N.; Nonnenmacher, D.; Giesselmann, F.

2011-11-01

A molecular statistical theory of the smectic A phase is developed taking into account specific interactions between different molecular fragments which enables one to describe different microscopic scenario of the transition into the smectic phase. The effects of nanoscale segregation are described using molecular models with different combinations of attractive and repulsive sites. These models have been used to calculate numerically coefficients in the mean filed potential as functions of molecular model parameters and the period of the smectic structure. The same coefficients are calculated also for a conventional smectic with standard Gay-Berne interaction potential which does not promote the segregation. The free energy is minimized numerically to calculate the order parameters of the smectic A phases and to study the nature of the smectic transition in both systems. It has been found that in conventional materials the smectic order can be stabilized only when the orientational order is sufficiently high, In contrast, in materials with nanosegregation the smectic order develops mainly in the form of the orientational-translational wave while the nematic order parameter remains relatively small. Microscopic mechanisms of smectic ordering in both systems are discussed in detail, and the results for smectic order parameters are compared with experimental data for materials of various molecular structure.