Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts

DEFF Research Database (Denmark)

Boomsma, Wouter; Tian, Pengfei; Frellsen, J.

2014-01-01

recently been shown that using such information directly as input in molecular simulations based on the molecular fragment replacement strategy can help the process of protein structure determination. Here, we show how to implement this strategy to determine not only the structures of proteins but also...

Gravitational fragmentation caught in the act: the filamentary Musca molecular cloud

Science.gov (United States)

Kainulainen, J.; Hacar, A.; Alves, J.; Beuther, H.; Bouy, H.; Tafalla, M.

2016-02-01

Context. Filamentary structures are common in molecular clouds. Explaining how they fragment to dense cores is a missing step in understanding their role in star formation. Aims: We perform a case study of whether low-mass filaments are close to hydrostatic prior to their fragmentation, and whether their fragmentation agrees with gravitational fragmentation models. To accomplish this, we study the ~6.5 pc long Musca molecular cloud, which is an ideal candidate for a filament at an early stage of fragmentation. Methods: We employ dust extinction mapping, in conjunction with near-infrared JHKS-band data from the CTIO/NEWFIRM instrument, and 870 μm dust continuum emission data from the APEX/LABOCA instrument to estimate column densities in Musca. We use the data to identify fragments from the cloud and to determine the radial density distribution of its filamentary part. We compare the cloud's morphology with 13CO and C18O line emission observed with the APEX/SHeFI instrument. Results: The Musca cloud is pronouncedly fragmented at its ends, but harbors a remarkably well-defined, ~1.6 pc long filament in its center region. The line mass of the filament is 21-31 M⊙ pc-1 and the full width at half maximum (FWHM) 0.07 pc. The radial profile of the filament can be fitted with a Plummer profile, which has the power-index of 2.6 ± 11% and is flatter than that of an infinite hydrostatic filament. The profile can also be fitted with a hydrostatic cylinder truncated by external pressure. These models imply a central density of ~5-10 × 104 cm-3. The fragments in the cloud have a mean separation of ~0.4 pc, in agreement with gravitational fragmentation. These properties, together with the subsonic and velocity-coherent nature of the cloud, suggest a scenario in which an initially hydrostatic cloud is currently gravitationally fragmenting. The fragmentation started a few tenths of a Myr ago from the ends of the cloud, leaving its center still relatively nonfragmented

Interpreting closed-loop learning control of molecular fragmentation in terms of wave-packet dynamics and enhanced molecular ionization

International Nuclear Information System (INIS)

Cardoza, David; Baertschy, Mark; Weinacht, Thomas

2005-01-01

We interpret a molecular fragmentation experiment using shaped, ultrafast laser pulses in terms of enhanced molecular ionization during dissociation. A closed-loop learning control experiment was performed to maximize the CF 3 + /CH 3 + production ratio in the dissociative ionization of CH 3 COCF 3 . Using ab inito molecular structure calculations and quasistatic molecular ionization calculations along with data from pump-probe experiments, we identify the primary control mechanism which is quite general and should be applicable to a broad class of molecules

Spatial and energy distributions of the fragments resulting from the dissociation of swift molecular ions in solids

International Nuclear Information System (INIS)

Heredia-Avalos, Santiago; Garcia-Molina, Rafael; Abril, Isabel

2002-01-01

We have simulated the spatial evolution and energy loss of the fragments that result when swift molecular ions dissociate inside solid targets. In our calculations we have considered that these fragments undergo the following interactions: Coulomb repulsion (among like charged particles), stopping and wake forces (due to electronic excitations induced in the target), and nuclear scattering (with the target nuclei). We study the case of silicon targets irradiated with boron molecular or atomic ions; our results show that the main differences in the energy and spatial distributions of molecular fragments or atomic ions appear at shallow regions, and these tend to disappear at deeper depths

The thermodynamics of molecular cloud fragmentation : Star formation under non-Milky Way conditions

NARCIS (Netherlands)

Hocuk, S.; Spaans, M.

Context. Properties of candidate stars, forming out of molecular clouds, depend on the ambient conditions of the parent cloud. We present a series of 2D and 3D simulations of fragmentation of molecular clouds in starburst regions, as well as of clouds under conditions in dwarf galaxies, leading to

Ultrafast fragmentation dynamics of triply charged carbon dioxide: Vibrational-mode-dependent molecular bond breakage

Science.gov (United States)

Yang, HongJiang; Wang, Enliang; Dong, WenXiu; Gong, Maomao; Shen, Zhenjie; Tang, Yaguo; Shan, Xu; Chen, Xiangjun

2018-05-01

The a b i n i t i o molecular dynamics (MD) simulations using an atom-centered density matrix propagation method have been carried out to investigate the fragmentation of the ground-state triply charged carbon dioxide, CO23 +→C+ + Oa+ + Ob+ . Ten thousands of trajectories have been simulated. By analyzing the momentum correlation of the final fragments, it is demonstrated that the sequential fragmentation dominates in the three-body dissociation, consistent with our experimental observations which were performed by electron collision at impact energy of 1500 eV. Furthermore, the MD simulations allow us to have detailed insight into the ultrafast evolution of the molecular bond breakage at a very early stage, within several tens of femtoseconds, and the result shows that the initial nuclear vibrational mode plays a decisive role in switching the dissociation pathways.

Process of Fragment-Based Lead Discovery—A Perspective from NMR

Directory of Open Access Journals (Sweden)

Rongsheng Ma

2016-07-01

Full Text Available Fragment-based lead discovery (FBLD has proven fruitful during the past two decades for a variety of targets, even challenging protein–protein interaction (PPI systems. Nuclear magnetic resonance (NMR spectroscopy plays a vital role, from initial fragment-based screening to lead generation, because of its power to probe the intrinsically weak interactions between targets and low-molecular-weight fragments. Here, we review the NMR FBLD process from initial library construction to lead generation. We describe technical aspects regarding fragment library design, ligand- and protein-observed screening, and protein–ligand structure model generation. For weak binders, the initial hit-to-lead evolution can be guided by structural information retrieved from NMR spectroscopy, including chemical shift perturbation, transferred pseudocontact shifts, and paramagnetic relaxation enhancement. This perspective examines structure-guided optimization from weak fragment screening hits to potent leads for challenging PPI targets.

Collision induced fragmentation of fast molecular ions in solids and gases

International Nuclear Information System (INIS)

Gemmell, D.S.

1979-01-01

A brief review is given of recent high resolution measurements on fragments arising from the collision-induced dissociation of fast (MeV) molecular ions. For solid targets, strong wake effects are observed. For gaseous targets, excited electronic states of the projectile ions play an important role. Measurements of this type provide useful information on the charge states of fast ions traversing matter. The experimental techniques show promise as a unique method for determining the geometrical structures of the molecular-ion projectiles. 41 references

Linear and nonlinear relationships between biodegradation potential and molecular descriptors/fragments for organic pollutants and a theoretical interpretation

International Nuclear Information System (INIS)

He, Jia; Qin, Weichao; Zhang, Xujia; Wen, Yang; Su, Limin; Zhao, Yuanhui

2013-01-01

Prediction of the biodegradability of organic pollutants is an ecologically desirable and economically feasible tool for estimating the environmental fate of chemicals. In this paper, linear and nonlinear relationships between biological oxygen demand (BOD) and molecular descriptors/fragments have been investigated for 1130 organic chemicals. Significant relationships have been observed between the simple molecular descriptors and %BOD for some homologous compounds, but not for the whole set of compounds. Electronic parameters, such as E HOMO and E LUMO , are the dominant factors affecting the biodegradability for some homologous chemicals. However, other descriptors, such as molecular weight, acid dissociation constant and polarity still have a significant impact on the biodegradation. The best global model for %BOD prediction is that developed from a chain-based fragmentation scheme. At the same time, the theoretical relationship between %BOD and molecular descriptors/fragments has been investigated, based on a first-order kinetic process. The %BOD is nonlinearly, rather than linearly, related to the descriptors. The coefficients of determination can be significantly improved by using nonlinear models for the homologous compounds and the whole data set. After analysing 1130 ready and not ready biodegradable compounds using 23 simple descriptors and various fragmentation schemes, it was revealed that biodegradation could be well predicted from a chain-based fragmentation scheme, a decision tree and a %BOD model. The models were capable of separating NRB and RB with an overall accuracy of 87.2%, 83.0% and 82.5%, respectively. The best classification model developed was a chain-based model but it used 155 fragments. The simplest model was a decision tree which only used 10 structural fragments. The effect of structures on the biodegradation has been analysed and the biodegradation pathway and mechanisms have been discussed based on activating and inactivating

Molecular Dynamics Simulations of a Cyclic DP-240 Amylose Fragment in a Periodic Cell: Glass Transition Temperature and Water Diffusion

Science.gov (United States)

Molecular dynamics simulations using AMB06C, an in-house carbohydrate force field, (NPT ensembles, 1atm) were carried out on a periodic cell that contained a cyclic-DP-240 amylose fragment and TIP3P water molecules. Molecular conformation and movement of the amylose fragment and water molecules at ...

Molecular-Simulation-Driven Fragment Screening for the Discovery of New CXCL12 Inhibitors.

Science.gov (United States)

Martinez-Rosell, Gerard; Harvey, Matt J; De Fabritiis, Gianni

2018-03-26

Fragment-based drug discovery (FBDD) has become a mainstream approach in drug design because it allows the reduction of the chemical space and screening libraries while identifying fragments with high protein-ligand efficiency interactions that can later be grown into drug-like leads. In this work, we leverage high-throughput molecular dynamics (MD) simulations to screen a library of 129 fragments for a total of 5.85 ms against the CXCL12 monomer, a chemokine involved in inflammation and diseases such as cancer. Our in silico binding assay was able to recover binding poses, affinities, and kinetics for the selected library and was able to predict 8 mM-affinity fragments with ligand efficiencies higher than 0.3. All of the fragment hits present a similar chemical structure, with a hydrophobic core and a positively charged group, and bind to either sY7 or H1S68 pockets, where they share pharmacophoric properties with experimentally resolved natural binders. This work presents a large-scale screening assay using an exclusive combination of thousands of short MD adaptive simulations analyzed with a Markov state model (MSM) framework.

Effect of molecular structure on fragmentation of isolated organic molecules in solid rare gas matrices

International Nuclear Information System (INIS)

Kobrazenko, A.V.; Sukhov, F.F.; Orlov, A.Yu.; Kovalev, G.V.; Baranova, I.A.; Feldman, V.I.

2011-01-01

Complete text of publication follows. Elucidation of high-energy reaction pathways in the condensed phase is an important issue for basic understanding of the radiation stability of complex organic molecules. As was shown previously, organic radical cations (RC) may undergo fragmentation or rearrangement in solid matrices due to excess energy. The probability of this process depends on both ionization potential (IP) of the molecule and molecular structure. In the present work we have studied the role of 'hot' ionic reaction channels for RC of some bifunctional compounds and alkynes. The effect of excess energy was simulated by matrix isolation method as described in detail earlier. The formation of fragmentation products was monitored by EPR and FTIR spectroscopy. In the present work it was shown that the RC of bifunctional compounds (CH 3 OCH 2 COCH 3 , CH 3 CO(CH 2 ) n COCH 3 , n 0/2) dissociated efficiently producing · CH 3 radicals upon irradiation in solid argon matrix at T ≤ 16 K. The probability of fragmentation decreases with decrease of excess energy by switching from Ar to Xe. It is worth noting that acetone RC does not show fragmentation under these conditions. Thus, bifunctional molecules were found to be less stable to 'hot' ionic fragmentation in low-temperature solids in comparison with simple prototype carbonyl compounds. In the case of alkynes of the R-C ≡ CH type, a noticeable yield of fragmentation products was observed when R = -C(CH 3 ) 3 , but it was negligible for R = -CH 3 . It means that the presence of triple bond stabilizes the molecular skeleton of linear alkynes toward 'hot' fragmentation, similarly as it was shown for alkenes. The mechanisms of 'hot' reactions and excess energy relaxation are discussed. This work was supported by the Russian Foundation for Basic Research (project 09-03-00848a).

Density functional theory fragment descriptors to quantify the reactivity of a molecular family: application to amino acids.

Science.gov (United States)

Senet, P; Aparicio, F

2007-04-14

By using the exact density functional theory, one demonstrates that the value of the local electronic softness of a molecular fragment is directly related to the polarization charge (Coulomb hole) induced by a test electron removed (or added) from (at) the fragment. Our finding generalizes to a chemical group a formal relation between these molecular descriptors recently obtained for an atom in a molecule using an approximate atomistic model [P. Senet and M. Yang, J. Chem. Sci. 117, 411 (2005)]. In addition, a practical ab initio computational scheme of the Coulomb hole and related local descriptors of reactivity of a molecular family having in common a similar fragment is presented. As a blind test, the method is applied to the lateral chains of the 20 isolated amino acids. One demonstrates that the local softness of the lateral chain is a quantitative measure of the similarity of the amino acids. It predicts the separation of amino acids in different biochemical groups (aliphatic, basic, acidic, sulfur contained, and aromatic). The present approach may find applications in quantitative structure activity relationship methodology.

Vicinage forces between molecular and atomic fragments dissociated from small hydrogen clusters and their effects on energy distributions

International Nuclear Information System (INIS)

Barriga-Carrasco, Manuel D.; Garcia-Molina, Rafael

2003-01-01

In this paper we analyze the dynamic evolution of molecular and atomic fragments of small hydrogen clusters interacting with thin solid foils. We compare the vicinage forces, calculated within the dielectric formalism, for H + , H 0 , and H 2 + fragments. Using a molecular dynamics numerical code we determine the energy distribution of the fragments after interacting with the target. This distribution is compared to experimental results for protons coming from the fragmentation of v=2.02 a.u. H 2 + ions impinging on an aluminum foil; a fraction of neutral H 0 is needed to be included in the simulation to get a good agreement with the experimental results. The H 2 + energy spectra for v=5.42 a.u. H 3 + interacting with amorphous carbon is also determined. The asymmetry in the Coulomb peaks appearing in the energy spectra both experimentally and in our calculation is opposite for H 2 + than in H + ; kinematic effects and differences in the electronic stopping are enough to reproduce the difference in the alignment of H 2 + and H + fragments

Polysaccharides and their depolymerized fragments from Costaria costata: Molecular weight and sulfation-dependent anticoagulant and FGF/FGFR signal activating activities.

Science.gov (United States)

Hou, Ningning; Zhang, Meng; Xu, Yingjie; Sun, Zhongmin; Wang, Jing; Zhang, Lijuan; Zhang, Quanbin

2017-12-01

Crude polysaccharides from Costaria costata were extracted by hot water and further fractionated by anion exchange chromatography into three polysaccharide fractions. Three low molecular weight fragments were then prepared by degradation of the polysaccharides with hydrogen peroxide and ascorbic acid. The structural features of the polysaccharides and their low molecular weight fragments were elucidated for the first time based on the HGPC, FT-IR, NMR, MS, monosaccharide composition, and other chemical analyses. Their anticoagulant and FGF-1, -2, -7, -8, -9, -10/FGFR1c signaling activation activities in BaF3 cells were also examined. Our studies showed that the polysaccharides were sulfated at different positions of galactose and fucose residues. The APTT-, PT- and TT-based anticoagulant assay results indicated that a high molecular weight and a higher degree of sulfation were essential for their anticoagulant activities. In contrast, not only the polysaccharides but also the depolymerized fragments showed significant FGF/FGFR signal activating activities in a FGF-, molecular weight-, and sulfation-dependent manner. The results presented in current study demonstrated the potential use of the polysaccharides and their fragments as anticoagulants and FGF signal regulators. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of TensorFlow to recognition of visualized results of fragment molecular orbital (FMO) calculations

OpenAIRE

Saitou, Sona; Iijima, Jun; Fujimoto, Mayu; Mochizuki, Yuji; Okuwaki, Koji; Doi, Hideo; Komeiji, Yuto

2018-01-01

We have applied Google's TensorFlow deep learning toolkit to recognize the visualized results of the fragment molecular orbital (FMO) calculations. Typical protein structures of alpha-helix and beta-sheet provide some characteristic patterns in the two-dimensional map of inter-fragment interaction energy termed as IFIE-map (Kurisaki et al., Biophys. Chem. 130 (2007) 1). A thousand of IFIE-map images with labels depending on the existences of alpha-helix and beta-sheet were prepared by employi...

Missing Fragments: Detecting Cooperative Binding in Fragment-Based Drug Design

Science.gov (United States)

2012-01-01

The aim of fragment-based drug design (FBDD) is to identify molecular fragments that bind to alternate subsites within a given binding pocket leading to cooperative binding when linked. In this study, the binding of fragments to human phenylethanolamine N-methyltransferase is used to illustrate how (a) current protocols may fail to detect fragments that bind cooperatively, (b) theoretical approaches can be used to validate potential hits, and (c) apparent false positives obtained when screening against cocktails of fragments may in fact indicate promising leads. PMID:24900472

Propagating annotations of molecular networks using in silico fragmentation.

Science.gov (United States)

da Silva, Ricardo R; Wang, Mingxun; Nothias, Louis-Félix; van der Hooft, Justin J J; Caraballo-Rodríguez, Andrés Mauricio; Fox, Evan; Balunas, Marcy J; Klassen, Jonathan L; Lopes, Norberto Peporine; Dorrestein, Pieter C

2018-04-18

The annotation of small molecules is one of the most challenging and important steps in untargeted mass spectrometry analysis, as most of our biological interpretations rely on structural annotations. Molecular networking has emerged as a structured way to organize and mine data from untargeted tandem mass spectrometry (MS/MS) experiments and has been widely applied to propagate annotations. However, propagation is done through manual inspection of MS/MS spectra connected in the spectral networks and is only possible when a reference library spectrum is available. One of the alternative approaches used to annotate an unknown fragmentation mass spectrum is through the use of in silico predictions. One of the challenges of in silico annotation is the uncertainty around the correct structure among the predicted candidate lists. Here we show how molecular networking can be used to improve the accuracy of in silico predictions through propagation of structural annotations, even when there is no match to a MS/MS spectrum in spectral libraries. This is accomplished through creating a network consensus of re-ranked structural candidates using the molecular network topology and structural similarity to improve in silico annotations. The Network Annotation Propagation (NAP) tool is accessible through the GNPS web-platform https://gnps.ucsd.edu/ProteoSAFe/static/gnps-theoretical.jsp.

Adaptive frozen orbital treatment for the fragment molecular orbital method combined with density-functional tight-binding

Science.gov (United States)

Nishimoto, Yoshio; Fedorov, Dmitri G.

2018-02-01

The exactly analytic gradient is derived and implemented for the fragment molecular orbital (FMO) method combined with density-functional tight-binding (DFTB) using adaptive frozen orbitals. The response contributions which arise from freezing detached molecular orbitals on the border between fragments are computed by solving Z-vector equations. The accuracy of the energy, its gradient, and optimized structures is verified on a set of representative inorganic materials and polypeptides. FMO-DFTB is applied to optimize the structure of a silicon nano-wire, and the results are compared to those of density functional theory and experiment. FMO accelerates the DFTB calculation of a boron nitride nano-ring with 7872 atoms by a factor of 406. Molecular dynamics simulations using FMO-DFTB applied to a 10.7 μm chain of boron nitride nano-rings, consisting of about 1.2 × 106 atoms, reveal the rippling and twisting of nano-rings at room temperature.

A Force Balanced Fragmentation Method for ab Initio Molecular Dynamic Simulation of Protein

Directory of Open Access Journals (Sweden)

Mingyuan Xu

2018-05-01

Full Text Available A force balanced generalized molecular fractionation with conjugate caps (FB-GMFCC method is proposed for ab initio molecular dynamic simulation of proteins. In this approach, the energy of the protein is computed by a linear combination of the QM energies of individual residues and molecular fragments that account for the two-body interaction of hydrogen bond between backbone peptides. The atomic forces on the caped H atoms were corrected to conserve the total force of the protein. Using this approach, ab initio molecular dynamic simulation of an Ace-(ALA9-NME linear peptide showed the conservation of the total energy of the system throughout the simulation. Further a more robust 110 ps ab initio molecular dynamic simulation was performed for a protein with 56 residues and 862 atoms in explicit water. Compared with the classical force field, the ab initio molecular dynamic simulations gave better description of the geometry of peptide bonds. Although further development is still needed, the current approach is highly efficient, trivially parallel, and can be applied to ab initio molecular dynamic simulation study of large proteins.

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

Science.gov (United States)

Lau, Wan F.; Withka, Jane M.; Hepworth, David; Magee, Thomas V.; Du, Yuhua J.; Bakken, Gregory A.; Miller, Michael D.; Hendsch, Zachary S.; Thanabal, Venkataraman; Kolodziej, Steve A.; Xing, Li; Hu, Qiyue; Narasimhan, Lakshmi S.; Love, Robert; Charlton, Maura E.; Hughes, Samantha; van Hoorn, Willem P.; Mills, James E.

2011-07-01

Fragment Based Drug Discovery (FBDD) continues to advance as an efficient and alternative screening paradigm for the identification and optimization of novel chemical matter. To enable FBDD across a wide range of pharmaceutical targets, a fragment screening library is required to be chemically diverse and synthetically expandable to enable critical decision making for chemical follow-up and assessing new target druggability. In this manuscript, the Pfizer fragment library design strategy which utilized multiple and orthogonal metrics to incorporate structure, pharmacophore and pharmacological space diversity is described. Appropriate measures of molecular complexity were also employed to maximize the probability of detection of fragment hits using a variety of biophysical and biochemical screening methods. In addition, structural integrity, purity, solubility, fragment and analog availability as well as cost were important considerations in the selection process. Preliminary analysis of primary screening results for 13 targets using NMR Saturation Transfer Difference (STD) indicates the identification of uM-mM hits and the uniqueness of hits at weak binding affinities for these targets.

Electron-impact dissociation of molecular hydrogen into neutral fragments

Science.gov (United States)

Scarlett, Liam H.; Tapley, Jonathan K.; Fursa, Dmitry V.; Zammit, Mark C.; Savage, Jeremy S.; Bray, Igor

2018-02-01

We present convergent close-coupling calculations of electron-impact dissociation of the ground state of molecular hydrogen into neutral fragments over the range of impact energies from 6 to 300 eV. The calculations account for dissociative excitation, excitation radiative decay dissociation, and predissociation through all bound electronic triplet states, and singlet states up to the D' 1 Π u state. An estimate is given for the contribution from the remaining bound electronic singlet states. Our results are in agreement with the recommended data of Yoon et al. [J. Phys. Chem. Ref. Data 37, 913 (2008)] in the low (6-12 eV) and high (60-70 eV) energy regions, but somewhat lower at the intermediate energies.

IAEA technical meeting on 'Technical aspects of atomic and molecular data processing and exchange'. Summary report

International Nuclear Information System (INIS)

Humbert, Denis

2004-03-01

The proceedings of the IAEA Advisory Group Meeting on 'Technical Aspects of Atomic and Molecular Data Processing and Exchange' (17th Meeting of A+M Data Centres and ALADDIN Network), held on 6-7 October, 2003 in Vienna, Austria are briefly described. The meeting conclusions and recommendations on the priorities in A+M data compilation and evaluation, and on the technical aspects of data processing, exchange, and distribution are also presented. (author)

Mapping enzymatic catalysis using the effective fragment molecular orbital method

DEFF Research Database (Denmark)

Svendsen, Casper Steinmann; Fedorov, Dmitri G.; Jensen, Jan Halborg

2013-01-01

We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path...... of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We...

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

Science.gov (United States)

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.

A Novel Molecular Diagnostic of Glioblastomas: Detection of an Extracellular Fragment of Protein Tyrosine Phosphatase μ

Directory of Open Access Journals (Sweden)

Susan M. Burden-Gulley

2010-04-01

Full Text Available We recently found that normal human brain and low-grade astrocytomas express the receptor protein tyrosine phosphatase mu (PTPμ and that the more invasive astrocytomas, glioblastoma multiforme (GBM, downregulate full-length PTPμ expression. Loss of PTPμ expression in GBMs is due to proteolytic cleavage that generates an intracellular and potentially a cleaved and released extracellular fragment of PTPμ. Here, we identify that a cleaved extracellular fragment containing the domains required for PTPμ-mediated adhesion remains associated with GBM tumor tissue. We hypothesized that detection of this fragment would make an excellent diagnostic tool for the localization of tumor tissue within the brain. To this end, we generated a series of fluorescently tagged peptide probes that bind the PTPμ fragment. The peptide probes specifically recognize GBM cells in tissue sections of surgically resected human tumors. To test whether the peptide probes are able to detect GBM tumors in vivo, the PTPμ peptide probes were tested in both mouse flank and intracranial xenograft human glioblastoma tumor model systems. The glial tumors were molecularly labeled with the PTPμ peptide probes within minutes of tail vein injection using the Maestro FLEX In Vivo Imaging System. The label was stable for at least 3 hours. Together, these results indicate that peptide recognition of the PTPμ extracellular fragment provides a novel molecular diagnostic tool for detection of human glioblastomas. Such a tool has clear translational applications and may lead to improved surgical resections and prognosis for patients with this devastating disease.

A new apparatus for the study of electron impact fragmentation of molecular clusters

International Nuclear Information System (INIS)

Barrett, G; Burgt, P J M van der

2008-01-01

This paper reports on the development of a new experiment for the study of electron-impact induced dissociation and fragmentation of molecular clusters and biomolecules and other species solvated in water clusters. The purpose is to look at clusters that are of interest to biophysics, atmospheric physics, and other fields. The experiment consists of a differentially pumped vacuum system, with an expansion chamber to generate a pulsed supersonic beam of clusters, and a collision chamber where the cluster beam intersects with an electron beam. Water clusters can be seeded with biomolecules emerging from a resistively heated oven. Investigation will be possible into both ion yields and long-lived neutral metastable yields produced by electron-impact fragmentation of relevant clusters and biomolecules

Mapping Enzymatic Catalysis Using the Effective Fragment Molecular Orbital Method: Towards all ab initio Biochemistry

DEFF Research Database (Denmark)

Svendsen, Casper Steinmann; Jensen, Jan; Fedorov, Dmitri

2013-01-01

We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of ...

Direct determination of recoil ion detection efficiency for coincidence time-of-flight studies of molecular fragmentation

International Nuclear Information System (INIS)

Ben-Itzhak, I.; Carnes, K.D.; Ginther, S.G.; Johnson, D.T.; Norris, P.J.; Weaver, O.L.

1993-01-01

Molecular fragmentation of diatomic and small polyatomic molecules caused by fast ion impact has been studied. The evaluation of the cross sections of the different fragmentation channels depends strongly on the recoil ion detection efficiency, ε r (single ions proportional to ε r , and ion pairs to ε 2 r , etc.). A method is suggested for the direct determination of this detection efficiency. This method is based on the fact that fast H + + CH 4 collisions produce C 2+ fragments only in coincidence with H + and H + 2 fragments, that is, there is a negligible number of C 2+ singles, if any. The measured yield of C 2+ singles is therefore due to events in which the H + m of the H + m + C 2+ ion pair was not detected and thus is proportional to 1 - ε r . Methane fragmentation caused by 1 MeV proton impact is used to evaluate directly the recoil ion detection efficiency and to demonstrate the method of deriving the cross sections of all breakup channels. (orig.)

Fragment-based quantitative structure-activity relationship (FB-QSAR) for fragment-based drug design.

Science.gov (United States)

Du, Qi-Shi; Huang, Ri-Bo; Wei, Yu-Tuo; Pang, Zong-Wen; Du, Li-Qin; Chou, Kuo-Chen

2009-01-30

In cooperation with the fragment-based design a new drug design method, the so-called "fragment-based quantitative structure-activity relationship" (FB-QSAR) is proposed. The essence of the new method is that the molecular framework in a family of drug candidates are divided into several fragments according to their substitutes being investigated. The bioactivities of molecules are correlated with the physicochemical properties of the molecular fragments through two sets of coefficients in the linear free energy equations. One coefficient set is for the physicochemical properties and the other for the weight factors of the molecular fragments. Meanwhile, an iterative double least square (IDLS) technique is developed to solve the two sets of coefficients in a training data set alternately and iteratively. The IDLS technique is a feedback procedure with machine learning ability. The standard Two-dimensional quantitative structure-activity relationship (2D-QSAR) is a special case, in the FB-QSAR, when the whole molecule is treated as one entity. The FB-QSAR approach can remarkably enhance the predictive power and provide more structural insights into rational drug design. As an example, the FB-QSAR is applied to build a predictive model of neuraminidase inhibitors for drug development against H5N1 influenza virus. (c) 2008 Wiley Periodicals, Inc.

[Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment].

Science.gov (United States)

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2016-01-01

Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

Flow of nucleons and fragments in 40Ar+27Al collisions studied with antisymmetrized molecular dynamics

International Nuclear Information System (INIS)

Ono, A.; Horiuchi, H.

1995-01-01

Collective transverse momentum flow of nucleons and fragments in intermediate energy 40 Ar+ 27 Al collisions is calculated with the antisymmetrized molecular dynamics (AMD). The observed flow and its balance energy are reproduced well by calculation with the Gogny force which corresponds to the soft equation of state (EOS) of nuclear matter. The calculated absolute value of the fragment flow is larger than that of the nucleon flow in the negative flow region, which can be explained by the existence of two components of flow. In addition to many similarities, the difference in the deuteron flow is found between 12 C+ 12 C and 40 Ar+ 27 Al collisions, and its origin is investigated by studying the production mechanism of light fragments. We also investigate the dependence of the flow of nucleons and fragments on the stochastic collision cross section and the effective interaction, and conclude that the stiff EOS without momentum dependence of the mean field is not consistent with the experimental data

Fragment molecular orbital study on electron tunneling mechanisms in bacterial photosynthetic reaction center.

Science.gov (United States)

Kitoh-Nishioka, Hirotaka; Ando, Koji

2012-11-01

The tunneling mechanisms of electron transfers (ETs) in photosynthetic reaction center of Blastochloris viridis are studied by the ab initio fragment molecular orbital (FMO) method combined with the generalized Mulliken-Hush (GMH) and the bridge Green function (GF) calculations of the electronic coupling T(DA) and the tunneling current method for the ET pathway analysis at the fragment-based resolution. For the ET from batctriopheophytin (H(L)) to menaquinone (MQ), a major tunneling current through Trp M250 and a minor back flow via Ala M215, Ala M216, and His M217 are quantified. For the ET from MQ to ubiquinone, the major tunneling pathway via the nonheme Fe(2+) and His L190 is identified as well as minor pathway via His M217 and small back flows involving His L230, Glu M232, and His M264. At the given molecular structure from X-ray experiment, the spin state of the Fe(2+) ion, its replacement by Zn(2+), or its removal are found to affect the T(DA) value by factors within 2.2. The calculated T(DA) values, together with experimentally estimated values of the driving force and the reorganization energy, give the ET rates in reasonable agreement with experiments.

Fragment-orbital tunneling currents and electronic couplings for analysis of molecular charge-transfer systems.

Science.gov (United States)

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.

Effect of molecular structure on fragmentation of isolated organic molecules in solid rare gas matrices

International Nuclear Information System (INIS)

Kobzarenko, A.V.; Sukhov, F.F.; Orlov, A.Yu.; Kovalev, G.V.; Baranova, I.A.; Feldman, V.I.

2012-01-01

The effect of excess energy on the primary radical cations of bifunctional carbonyl compounds and aliphatic alkynes was simulated by matrix isolation method using rare gas matrices with various ionization potentials. The formation of fragmentation products was monitored by EPR and FTIR spectroscopy. It was shown that the radical cations of bifunctional compounds (CH 3 OCH 2 COCH 3 and CH 3 COCOCH 3 ) dissociated effectively yielding · CH 3 radicals upon irradiation in solid argon matrix at T≤16 K. In addition to isolated methyl radicals, the radical pairs consisting of two methyl radicals separated by two CO molecules were detected in the case of diacetyl. The probability of fragmentation decreases with the decreasing excess energy by switching from Ar to Xe. In general, bifunctional molecules were found to be less stable to “hot” ionic fragmentation in low-temperature solids in comparison with simple prototype compounds. In the case of alkynes of the R--C≡CH type, a noticeable yield of fragmentation products was observed when R=–C(CH 3 ) 3 , but it was negligible for R=–CH 3 . The mechanisms of “hot” reactions and excess energy relaxation are discussed. - Highlights: ► Radiolysis of bifunctional organic compounds and alkynes. ► Dependence of “hot” fragmentation probability from molecular structure. ► Ions of bifunctional compounds are less stable than those of monofunctional ones. ► Alkynes are rather stable to “hot” fragmentation.

De novo analysis of electron impact mass spectra using fragmentation trees

International Nuclear Information System (INIS)

Hufsky, Franziska; Rempt, Martin; Rasche, Florian; Pohnert, Georg; Böcker, Sebastian

2012-01-01

Highlights: ► We present a method for de novo analysis of accurate mass EI mass spectra of small molecules. ► This method identifies the molecular ion and thus the molecular formula where the molecular ion is present in the spectrum. ► Fragmentation trees are constructed by automated signal extraction and evaluation. ► These trees explain relevant fragmentation reactions. ► This method will be very helpful in the automated analysis of unknown metabolites. - Abstract: The automated fragmentation analysis of high resolution EI mass spectra based on a fragmentation tree algorithm is introduced. Fragmentation trees are constructed from EI spectra by automated signal extraction and evaluation. These trees explain relevant fragmentation reactions and assign molecular formulas to fragments. The method enables the identification of the molecular ion and the molecular formula of a metabolite if the molecular ion is present in the spectrum. These identifications are independent of existing library knowledge and, thus, support assignment and structural elucidation of unknown compounds. The method works even if the molecular ion is of very low abundance or hidden under contaminants with higher masses. We apply the algorithm to a selection of 50 derivatized and underivatized metabolites and demonstrate that in 78% of cases the molecular ion can be correctly assigned. The automatically constructed fragmentation trees correspond very well to published mechanisms and allow the assignment of specific relevant fragments and fragmentation pathways even in the most complex EI-spectra in our dataset. This method will be very helpful in the automated analysis of metabolites that are not included in common libraries and it thus has the potential to support the explorative character of metabolomics studies.

Jdpd: an open java simulation kernel for molecular fragment dissipative particle dynamics.

Science.gov (United States)

van den Broek, Karina; Kuhn, Hubert; Zielesny, Achim

2018-05-21

Jdpd is an open Java simulation kernel for Molecular Fragment Dissipative Particle Dynamics with parallelizable force calculation, efficient caching options and fast property calculations. It is characterized by an interface and factory-pattern driven design for simple code changes and may help to avoid problems of polyglot programming. Detailed input/output communication, parallelization and process control as well as internal logging capabilities for debugging purposes are supported. The new kernel may be utilized in different simulation environments ranging from flexible scripting solutions up to fully integrated "all-in-one" simulation systems.

Characterization of a half-molecular fragment obtained by reduction of human α2-macroglobulin with dithiothreitol

DEFF Research Database (Denmark)

Sjöberg, B.; Pap, S.; Kjems, Jørgen

1985-01-01

A half-molecular fragment of α2-macroglobulin has been prepared by reducing and alkylating the inter-subunit disulfide bonds in the tetrameric α2-macroglobulin molecule with 1 mM dithiothreitol (40 min) and 3 mM iodoacetamide (40 min). Further purification was made by gel chromatography...

Graph Theory. 1. Fragmentation of Structural Graphs

Directory of Open Access Journals (Sweden)

Lorentz JÄNTSCHI

2002-12-01

Full Text Available The investigation of structural graphs has many fields of applications in engineering, especially in applied sciences like as applied chemistry and physics, computer sciences and automation, electronics and telecommunication. The main subject of the paper is to express fragmentation criteria in graph using a new method of investigation: terminal paths. Using terminal paths are defined most of the fragmentation criteria that are in use in molecular topology, but the fields of applications are more generally than that, as I mentioned before. Graphical examples of fragmentation are given for every fragmentation criteria. Note that all fragmentation is made with a computer program that implements a routine for every criterion.[1] A web routine for tracing all terminal paths in graph can be found at the address: http://vl.academicdirect.ro/molecular_topology/tpaths/ [1] M. V. Diudea, I. Gutman, L. Jäntschi, Molecular Topology, Nova Science, Commack, New York, 2001, 2002.

Knowledge-based Fragment Binding Prediction

Science.gov (United States)

Tang, Grace W.; Altman, Russ B.

2014-01-01

Target-based drug discovery must assess many drug-like compounds for potential activity. Focusing on low-molecular-weight compounds (fragments) can dramatically reduce the chemical search space. However, approaches for determining protein-fragment interactions have limitations. Experimental assays are time-consuming, expensive, and not always applicable. At the same time, computational approaches using physics-based methods have limited accuracy. With increasing high-resolution structural data for protein-ligand complexes, there is now an opportunity for data-driven approaches to fragment binding prediction. We present FragFEATURE, a machine learning approach to predict small molecule fragments preferred by a target protein structure. We first create a knowledge base of protein structural environments annotated with the small molecule substructures they bind. These substructures have low-molecular weight and serve as a proxy for fragments. FragFEATURE then compares the structural environments within a target protein to those in the knowledge base to retrieve statistically preferred fragments. It merges information across diverse ligands with shared substructures to generate predictions. Our results demonstrate FragFEATURE's ability to rediscover fragments corresponding to the ligand bound with 74% precision and 82% recall on average. For many protein targets, it identifies high scoring fragments that are substructures of known inhibitors. FragFEATURE thus predicts fragments that can serve as inputs to fragment-based drug design or serve as refinement criteria for creating target-specific compound libraries for experimental or computational screening. PMID:24762971

Metabolite identification through multiple kernel learning on fragmentation trees.

Science.gov (United States)

Shen, Huibin; Dührkop, Kai; Böcker, Sebastian; Rousu, Juho

2014-06-15

Metabolite identification from tandem mass spectrometric data is a key task in metabolomics. Various computational methods have been proposed for the identification of metabolites from tandem mass spectra. Fragmentation tree methods explore the space of possible ways in which the metabolite can fragment, and base the metabolite identification on scoring of these fragmentation trees. Machine learning methods have been used to map mass spectra to molecular fingerprints; predicted fingerprints, in turn, can be used to score candidate molecular structures. Here, we combine fragmentation tree computations with kernel-based machine learning to predict molecular fingerprints and identify molecular structures. We introduce a family of kernels capturing the similarity of fragmentation trees, and combine these kernels using recently proposed multiple kernel learning approaches. Experiments on two large reference datasets show that the new methods significantly improve molecular fingerprint prediction accuracy. These improvements result in better metabolite identification, doubling the number of metabolites ranked at the top position of the candidates list. © The Author 2014. Published by Oxford University Press.

Fragment-based drug discovery and molecular docking in drug design.

Science.gov (United States)

Wang, Tao; Wu, Mian-Bin; Chen, Zheng-Jie; Chen, Hua; Lin, Jian-Ping; Yang, Li-Rong

2015-01-01

Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD. In particular, the computational strategies applied in the process of FBDD and molecular-docking programs are highlighted elaborately. In most cases, docking is used for predicting the ligand-receptor interaction modes and hit identification by structurebased virtual screening. The successful cases of typical significance and the hits identified most recently are discussed.

FRAGMENTATION OF MOLECULAR CLUMPS AND FORMATION OF A PROTOCLUSTER

International Nuclear Information System (INIS)

Zhang, Qizhou; Lu, Xing; Wang, Ke; Jiménez-Serra, Izaskun

2015-01-01

Sufficiently massive clumps of molecular gas collapse under self-gravity and fragment to spawn a cluster of stars that have a range of masses. We investigate observationally the early stages of formation of a stellar cluster in a massive filamentary infrared dark cloud, G28.34+0.06 P1, in the 1.3 mm continuum and spectral line emission using the Atacama Large Millimeter/Submillimeter Array. Sensitive continuum data reveal further fragmentation in five dusty cores at a resolution of several 10 3 AU. Spectral line emission from C 18 O, CH 3 OH, 13 CS, H 2 CO, and N 2 D + is detected for the first time toward these dense cores. We found that three cores are chemically more evolved as compared with the other two; interestingly, though, all of them are associated with collimated outflows as suggested by evidence from the CO, SiO, CH 3 OH, H 2 CO, and SO emission. The parsec-scale kinematics in exhibit velocity gradients along the filament, consistent with accretion flows toward the clumps and cores. The moderate luminosity and the chemical signatures indicate that the five cores harbor low- to intermediate-mass protostars that likely become massive ones at the end of the accretion. Despite the fact that the mass limit reached by the dust continuum sensitivity is 30 times lower than the thermal Jeans mass, there is a lack of a distributed low-mass protostellar population in the clump. Our observations indicate that in a protocluster, low-mass stars form at a later stage after the birth of more massive protostars

Extracellular matrix fragmentation in young, healthy cartilaginous tissues.

Science.gov (United States)

Craddock, R J; Hodson, N W; Ozols, M; Shearer, T; Hoyland, J A; Sherratt, M J

2018-02-09

Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC) and the nucleus pulposus (NP) of the intervertebral disc (IVD). Whilst structural heterogeneity of intact aggrecan ( containing three globular domains) is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months), bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 %) were fragmented (lacking one or more globular domains). Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa) comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis). As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2) as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2), it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally) and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

Application of the fragment molecular orbital method analysis to fragment-based drug discovery of BET (bromodomain and extra-terminal proteins) inhibitors.

Science.gov (United States)

Ozawa, Motoyasu; Ozawa, Tomonaga; Ueda, Kazuyoshi

2017-06-01

The molecular interactions of inhibitors of bromodomains (BRDs) were investigated. BRDs are protein interaction modules that recognizing ε-N-acetyl-lysine (εAc-Lys) motifs found in histone tails and are promising protein-protein interaction (PPI) targets. First, we analyzed a peptide ligand containing εAc-Lys to evaluate native PPIs. We then analyzed tetrahydroquinazoline-6-yl-benzensulfonamide derivatives found by fragment-based drug design (FBDD) and examined their interactions with the protein compared with the peptide ligand in terms of the inter-fragment interaction energy. In addition, we analyzed benzodiazepine derivatives that are high-affinity ligands for BRDs and examined differences in the CH/π interactions of the amino acid residues. We further surveyed changes in the charges of the amino acid residues among individual ligands, performed pair interaction energy decomposition analysis and estimated the water profile within the ligand binding site. Thus, useful insights for drug design were provided. Through these analyses and considerations, we show that the FMO method is a useful drug design tool to evaluate the process of FBDD and to explore PPI inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

Extracellular matrix fragmentation in young, healthy cartilaginous tissues

Directory of Open Access Journals (Sweden)

RJ Craddock

2018-02-01

Full Text Available Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC and the nucleus pulposus (NP of the intervertebral disc (IVD. Whilst structural heterogeneity of intact aggrecan ( containing three globular domains is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months, bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 % were fragmented (lacking one or more globular domains. Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p < 0.0001. In contrast, fibrillar collagen appeared structurally intact and tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis. As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2 as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2, it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

Fragment-based {sup 13}C nuclear magnetic resonance chemical shift predictions in molecular crystals: An alternative to planewave methods

Energy Technology Data Exchange (ETDEWEB)

Hartman, Joshua D.; Beran, Gregory J. O., E-mail: gregory.beran@ucr.edu [Department of Chemistry, University of California, Riverside, California 92521 (United States); Monaco, Stephen; Schatschneider, Bohdan [The Pennsylvania State University, The Eberly Campus, 2201 University Dr, Lemont Furnace, Pennsylvania 15456 (United States)

2015-09-14

We assess the quality of fragment-based ab initio isotropic {sup 13}C chemical shift predictions for a collection of 25 molecular crystals with eight different density functionals. We explore the relative performance of cluster, two-body fragment, combined cluster/fragment, and the planewave gauge-including projector augmented wave (GIPAW) models relative to experiment. When electrostatic embedding is employed to capture many-body polarization effects, the simple and computationally inexpensive two-body fragment model predicts both isotropic {sup 13}C chemical shifts and the chemical shielding tensors as well as both cluster models and the GIPAW approach. Unlike the GIPAW approach, hybrid density functionals can be used readily in a fragment model, and all four hybrid functionals tested here (PBE0, B3LYP, B3PW91, and B97-2) predict chemical shifts in noticeably better agreement with experiment than the four generalized gradient approximation (GGA) functionals considered (PBE, OPBE, BLYP, and BP86). A set of recommended linear regression parameters for mapping between calculated chemical shieldings and observed chemical shifts are provided based on these benchmark calculations. Statistical cross-validation procedures are used to demonstrate the robustness of these fits.

Gallstone fragmentation by control electrohydraulic lithotripsy

International Nuclear Information System (INIS)

Tung, G.A.; Mueller, P.R.; Brink, J.A.; Saini, S.; Picus, D.; Simeone, J.F.; Ferrucci, J.T.

1989-01-01

The authors have performed in vitro contact electrohydraulic lithotripsy (EHL) of 100 gallstones > 10 mm in diameter to identify physical and technical factors that affect fragmentation success. Ninety-one of 100 stones were fragmented with a 3-F electrode (average, seven shocks; range, 1--42); only 12 stones were fragmented with a single shock. Of the nine stones refractory to 50 shocks, four were > 30 mm in diameter and five stones were densely calcified. The most important variable determining power requirements for fragmentation was gallstone size (R = .58), but radiographic calcification of gallstones was also important (R = .47). Stones < 15 mm tended to produce fragments of left-angle 2 mm; stones right-angle 20 mm tended to produce two to five large discrete fragments (P , .05). In addition, lithotripsy could be conducted equally well in 1:1 dilute diatrizoate contrast agent as in 1:6 normal saline, suggesting that contact EHL could be performed under fluoroscopy

Fragment-based drug discovery using rational design.

Science.gov (United States)

Jhoti, H

2007-01-01

Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

Benchmark fragment-based 1H, 13C, 15N and 17O chemical shift predictions in molecular crystals†

Science.gov (United States)

Hartman, Joshua D.; Kudla, Ryan A.; Day, Graeme M.; Mueller, Leonard J.; Beran, Gregory J. O.

2016-01-01

The performance of fragment-based ab initio 1H, 13C, 15N and 17O chemical shift predictions is assessed against experimental NMR chemical shift data in four benchmark sets of molecular crystals. Employing a variety of commonly used density functionals (PBE0, B3LYP, TPSSh, OPBE, PBE, TPSS), we explore the relative performance of cluster, two-body fragment, and combined cluster/fragment models. The hybrid density functionals (PBE0, B3LYP and TPSSh) generally out-perform their generalized gradient approximation (GGA)-based counterparts. 1H, 13C, 15N, and 17O isotropic chemical shifts can be predicted with root-mean-square errors of 0.3, 1.5, 4.2, and 9.8 ppm, respectively, using a computationally inexpensive electrostatically embedded two-body PBE0 fragment model. Oxygen chemical shieldings prove particularly sensitive to local many-body effects, and using a combined cluster/fragment model instead of the simple two-body fragment model decreases the root-mean-square errors to 7.6 ppm. These fragment-based model errors compare favorably with GIPAW PBE ones of 0.4, 2.2, 5.4, and 7.2 ppm for the same 1H, 13C, 15N, and 17O test sets. Using these benchmark calculations, a set of recommended linear regression parameters for mapping between calculated chemical shieldings and observed chemical shifts are provided and their robustness assessed using statistical cross-validation. We demonstrate the utility of these approaches and the reported scaling parameters on applications to 9-tertbutyl anthracene, several histidine co-crystals, benzoic acid and the C-nitrosoarene SnCl2(CH3)2(NODMA)2. PMID:27431490

Benchmark fragment-based (1)H, (13)C, (15)N and (17)O chemical shift predictions in molecular crystals.

Science.gov (United States)

Hartman, Joshua D; Kudla, Ryan A; Day, Graeme M; Mueller, Leonard J; Beran, Gregory J O

2016-08-21

The performance of fragment-based ab initio(1)H, (13)C, (15)N and (17)O chemical shift predictions is assessed against experimental NMR chemical shift data in four benchmark sets of molecular crystals. Employing a variety of commonly used density functionals (PBE0, B3LYP, TPSSh, OPBE, PBE, TPSS), we explore the relative performance of cluster, two-body fragment, and combined cluster/fragment models. The hybrid density functionals (PBE0, B3LYP and TPSSh) generally out-perform their generalized gradient approximation (GGA)-based counterparts. (1)H, (13)C, (15)N, and (17)O isotropic chemical shifts can be predicted with root-mean-square errors of 0.3, 1.5, 4.2, and 9.8 ppm, respectively, using a computationally inexpensive electrostatically embedded two-body PBE0 fragment model. Oxygen chemical shieldings prove particularly sensitive to local many-body effects, and using a combined cluster/fragment model instead of the simple two-body fragment model decreases the root-mean-square errors to 7.6 ppm. These fragment-based model errors compare favorably with GIPAW PBE ones of 0.4, 2.2, 5.4, and 7.2 ppm for the same (1)H, (13)C, (15)N, and (17)O test sets. Using these benchmark calculations, a set of recommended linear regression parameters for mapping between calculated chemical shieldings and observed chemical shifts are provided and their robustness assessed using statistical cross-validation. We demonstrate the utility of these approaches and the reported scaling parameters on applications to 9-tert-butyl anthracene, several histidine co-crystals, benzoic acid and the C-nitrosoarene SnCl2(CH3)2(NODMA)2.

Fragmentation of atomic clusters: A theoretical study

International Nuclear Information System (INIS)

Lopez, M.J.; Jellinek, J.

1994-01-01

Collisionless fragmentation of nonrotating model n-atom metal clusters (n=12, 13, and 14) is studied using isoergic molecular-dynamics simulations. Minimum-energy paths for fragmentation are mapped out as functions of the distance between the centers of mass of the fragments. These paths provide information on the fragmentation energies for the different fragmentation channels. Fragmentation patterns (distributions of the fragmentation channel probabilities) and global and channel-specific fragmentation rate constants are computed and analyzed as functions of the internal energy and of the size of the clusters. The trends derived from the dynamics are compared with those obtained using the RRK and TST statistical approaches. The dynamics of the fragmentation process is analyzed in terms of characteristic quantities such as the distance between the centers of mass of the fragments, their relative translational energy, and their interaction energy, all considered as functions of time

A model for projectile fragmentation

International Nuclear Information System (INIS)

Chaudhuri, G; Mallik, S; Gupta, S Das

2013-01-01

A model for projectile fragmentation is developed whose origin can be traced back to the Bevalac era. The model positions itself between the phenomenological EPAX parametrization and transport models like 'Heavy Ion Phase Space Exploration' (HIPSE) model and antisymmetrised molecular dynamics (AMD) model. A very simple impact parameter dependence of input temperature is incorporated in the model which helps to analyze the more peripheral collisions. The model is applied to calculate the charge, isotopic distributions, average number of intermediate mass fragments and the average size of largest cluster at different Z bound of different projectile fragmentation reactions at different energies.

Origin of fragments in multifragmentation reactions

International Nuclear Information System (INIS)

Zbiri, K.; Aichelin, J.

2003-01-01

Using the quantum molecular dynamics approach we have started analyzing the results of the recent INDRA experiments at GSI facilities. For the first time we could identify a midrapidity source in which fragments are formed from an almost identical fraction of projectile and target nucleons. In smaller systems we have found this source. Nevertheless the fragment spectra at small and large angles is completely determined by the dynamics. We discuss how fragments are formed in the different regions of phase space and what they tell us about the reaction mechanism. (authors)

Origin of fragments in multifragmentation reactions

International Nuclear Information System (INIS)

Zbiri, K.; Aichelin, J.

2005-01-01

Using the quantum molecular dynamics approach we have started to analyze the results of the recent INDRA experiments at GSI experiments. For the first time we could identify a midrapidity source in which fragments are formed from a almost identical fraction of projectile and target nucleons. In smaller systems we have not found this source. Nevertheless the fragment spectra at small and large angles are completely determined by the dynamics. We discuss how fragments are formed in the different regions of phase space and what they tell us about the reaction mechanism. (author)

Molecular and FISH analyses of a 53-kbp intact DNA fragment inserted by biolistics in wheat (Triticum aestivum L.) genome.

Science.gov (United States)

Partier, A; Gay, G; Tassy, C; Beckert, M; Feuillet, C; Barret, P

2017-10-01

A large, 53-kbp, intact DNA fragment was inserted into the wheat ( Triticum aestivum L.) genome. FISH analyses of individual transgenic events revealed multiple insertions of intact fragments. Transferring large intact DNA fragments containing clusters of resistance genes or complete metabolic pathways into the wheat genome remains a challenge. In a previous work, we showed that the use of dephosphorylated cassettes for wheat transformation enabled the production of simple integration patterns. Here, we used the same technology to produce a cassette containing a 44-kb Arabidopsis thaliana BAC, flanked by one selection gene and one reporter gene. This 53-kb linear cassette was integrated in the bread wheat (Triticum aestivum L.) genome by biolistic transformation. Our results showed that transgenic plants harboring the entire cassette were generated. The inheritability of the cassette was demonstrated in the T1 and T2 generation. Surprisingly, FISH analysis performed on T1 progeny of independent events identified double genomic insertions of intact fragments in non-homoeologous positions. Inheritability of these double insertions was demonstrated by FISH analysis of the T1 generation. Relative conclusions that can be drawn from molecular or FISH analysis are discussed along with future prospects of the engineering of large fragments for wheat transformation or genome editing.

Technical aspects of atomic and molecular data processing and exchange. 19. meeting of the A+M Data Centres and ALADDIN Network. Summary report of an IAEA technical meeting

International Nuclear Information System (INIS)

Humbert, D.

2008-05-01

The proceedings of the IAEA Technical Meeting on Technical Aspects of Atomic and Molecular Data Processing and Exchange (19th Meeting of A+M Data Centres and ALADDIN Network), held on 3-5 October, 2007 in Vienna, Austria, are briefly described. Conclusions and recommendations are presented concerning various proposed projects and their priorities involving A+M data compilation and evaluation and technical aspects of data processing, exchange, and distribution. (author)

The multiple roles of computational chemistry in fragment-based drug design

Science.gov (United States)

Law, Richard; Barker, Oliver; Barker, John J.; Hesterkamp, Thomas; Godemann, Robert; Andersen, Ole; Fryatt, Tara; Courtney, Steve; Hallett, Dave; Whittaker, Mark

2009-08-01

Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.

Prediction of trypsin/molecular fragment binding affinities by free energy decomposition and empirical scores

Science.gov (United States)

Benson, Mark L.; Faver, John C.; Ucisik, Melek N.; Dashti, Danial S.; Zheng, Zheng; Merz, Kenneth M.

2012-05-01

Two families of binding affinity estimation methodologies are described which were utilized in the SAMPL3 trypsin/fragment binding affinity challenge. The first is a free energy decomposition scheme based on a thermodynamic cycle, which included separate contributions from enthalpy and entropy of binding as well as a solvent contribution. Enthalpic contributions were estimated with PM6-DH2 semiempirical quantum mechanical interaction energies, which were modified with a statistical error correction procedure. Entropic contributions were estimated with the rigid-rotor harmonic approximation, and solvent contributions to the free energy were estimated with several different methods. The second general methodology is the empirical score LISA, which contains several physics-based terms trained with the large PDBBind database of protein/ligand complexes. Here we also introduce LISA+, an updated version of LISA which, prior to scoring, classifies systems into one of four classes based on a ligand's hydrophobicity and molecular weight. Each version of the two methodologies (a total of 11 methods) was trained against a compiled set of known trypsin binders available in the Protein Data Bank to yield scaling parameters for linear regression models. Both raw and scaled scores were submitted to SAMPL3. Variants of LISA showed relatively low absolute errors but also low correlation with experiment, while the free energy decomposition methods had modest success when scaling factors were included. Nonetheless, re-scaled LISA yielded the best predictions in the challenge in terms of RMS error, and six of these models placed in the top ten best predictions by RMS error. This work highlights some of the difficulties of predicting binding affinities of small molecular fragments to protein receptors as well as the benefit of using training data.

Recovering Intrinsic Fragmental Vibrations Using the Generalized Subsystem Vibrational Analysis.

Science.gov (United States)

Tao, Yunwen; Tian, Chuan; Verma, Niraj; Zou, Wenli; Wang, Chao; Cremer, Dieter; Kraka, Elfi

2018-05-08

Normal vibrational modes are generally delocalized over the molecular system, which makes it difficult to assign certain vibrations to specific fragments or functional groups. We introduce a new approach, the Generalized Subsystem Vibrational Analysis (GSVA), to extract the intrinsic fragmental vibrations of any fragment/subsystem from the whole system via the evaluation of the corresponding effective Hessian matrix. The retention of the curvature information with regard to the potential energy surface for the effective Hessian matrix endows our approach with a concrete physical basis and enables the normal vibrational modes of different molecular systems to be legitimately comparable. Furthermore, the intrinsic fragmental vibrations act as a new link between the Konkoli-Cremer local vibrational modes and the normal vibrational modes.

NMR screening in fragment-based drug design: a practical guide.

Science.gov (United States)

Kim, Hai-Young; Wyss, Daniel F

2015-01-01

Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

Ionic fragmentation channels in electron collisions of small molecular ions

International Nuclear Information System (INIS)

Hoffmann, Jens

2009-01-01

Dissociative Recombination (DR) is one of the most important loss processes of molecular ions in the interstellar medium (IM). Ion storage rings allow to investigate these processes under realistic conditions. At the Heidelberg test storage ring TSR a new detector system was installed within the present work in order to study the DR sub-process of ion pair formation (IPF). The new detector expands the existing electron target setup by the possibility to measure strongly deflected negative ionic fragments. At the TSR such measurements can be performed with a uniquely high energy resolution by independently merging two electron beams with the ion beam. In this work IPF of HD + , H 3 + and HF + has been studied. In the case of HD + the result of the high resolution experiment shows quantum interferences. Analysis of the quantum oscillations leads to a new understanding of the reaction dynamics. For H 3 + it was for the first time possible to distinguish different IPF channels and to detect quantum interferences in the data. Finally the IPF of HF + was investigated in an energy range, where in previous experiments no conclusive results could be obtained. (orig.)

On the fragmentation of biomolecules: fragmentation of alanine dipeptide along the polypeptide chain

DEFF Research Database (Denmark)

Solov'yov, Ilia; Yakubovich, Alexander; Solov'yov, Andrey

2006-01-01

The interaction potential between amino acids in alanine dipeptide has been studied for the first time taking into account exact molecular geometry. Ab initio calculation has been performed in the framework of density functional theory taking into account all electrons in the system. The fragment...

Fragment profiling of low molecular weight heparins using reversed phase ion pair liquid chromatography-electrospray mass spectrometry.

Science.gov (United States)

Xu, Xiaohui; Li, Daoyuan; Chi, Lequan; Du, Xuzhao; Bai, Xue; Chi, Lianli

2015-04-30

Low molecular weight heparins (LMWHs) are linear and highly charged carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. Compared to unfractionated heparin (UFH), LMWHs are prevalently used as clinical anticoagulant drugs due to their lower side effects and better bioavailability. The work presented herein provides a rapid and powerful fragment mapping method for structural characterization of LMWHs. The chain fragments of two types of LMWHs, enoxaparin and nadroparin, were generated by controlled enzymatic digestion with each of heparinase I (Hep I, Enzyme Commission (EC) # 4.2.2.7), heparinase II (Hep II, no EC # assigned) and heparinase III (Hep III, EC # 4.2.2.8). Reversed phase ion pair high performance liquid chromatography (RPIP-HPLC) coupled with electrospray ion trap time-of-flight mass spectrometry (ESI-IT-TOF-MS) was used to profile the oligosaccharide chains ranging from disaccharides to decasaccharides. A database containing all theoretical structural compositions was established to assist the mass spectra interpretation. The six digests derived by three enzymes from two types of LMWHs exhibited distinguishable fingerprinting patterns. And a total of 94 enoxaparin fragments and 109 nadroparin fragments were detected and identified. Besides the common LMWH oligosaccharides, many components containing characteristic LMWH structures such as saturated L-idopyranosuronic acid, 2,5-anhydro-D-mannitol, 1,6-anhydro-D-aminopyranose, as well as odd number oligosaccharides were also revealed. Quantitative comparison of major components derived from innovator and generic nadroparin products was presented. This approach to profile LMWHs' fragments offers a highly reproducible, high resolution and information-rich tool for evaluating the quality of this category of anticoagulant drugs or comparing structural similarities among samples from various sources. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improved Barriers to Turbine Engine Fragments: Final Annual Report

National Research Council Canada - National Science Library

Shockey, Donald

2002-01-01

This final annual technical report describes the progress rnade during year 4 of the SPI International Phase II effort to develop a computational capability for designing lightweight fragment barriers...

Analysis of proton-induced fragment production cross sections by the Quantum Molecular Dynamics plus Statistical Decay Model

Energy Technology Data Exchange (ETDEWEB)

Chiba, Satoshi; Iwamoto, Osamu; Fukahori, Tokio; Niita, Koji; Maruyama, Toshiki; Maruyama, Tomoyuki; Iwamoto, Akira [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1997-03-01

The production cross sections of various fragments from proton-induced reactions on {sup 56}Fe and {sup 27}Al have been analyzed by the Quantum Molecular Dynamics (QMD) plus Statistical Decay Model (SDM). It was found that the mass and charge distributions calculated with and without the statistical decay have very different shapes. These results also depend strongly on the impact parameter, showing an importance of the dynamical treatment as realized by the QMD approach. The calculated results were compared with experimental data in the energy region from 50 MeV to 5 GeV. The QMD+SDM calculation could reproduce the production cross sections of the light clusters and intermediate-mass to heavy fragments in a good accuracy. The production cross section of {sup 7}Be was, however, underpredicted by approximately 2 orders of magnitude, showing the necessity of another reaction mechanism not taken into account in the present model. (author)

Paramecium putrinum (Ciliophora, Protozoa): the first insight into the variation of two DNA fragments - molecular support for the existence of cryptic species.

Science.gov (United States)

Tarcz, Sebastian; Rautian, Maria; Potekhin, Alexey; Sawka, Natalia; Beliavskaya, Alexandra; Kiselev, Andrey; Nekrasova, Irina; Przyboś, Ewa

2014-04-01

Paramecium putrinum (Claparede & Lachmann 1858) is one of the smallest (80-140 μm long) species of the genus Paramecium. Although it commonly occurs in freshwater reservoirs, no molecular studies of P. putrinum have been conducted to date. Herein we present an assessment of molecular variation in 27 strains collected from widely separated populations by using two selected DNA fragments (ITS1-5.8S-ITS2-5'LSU rDNA and COI mtDNA). Both the trees and haplotype networks reconstructed for both genome fragments show that the studied strains of P. putrinum form five main haplogroups. The mean distance between the studied strains is p-distance=0.007/0.068 (rDNA/COI) and exhibits similar variability as that between P. bursaria syngens. Based on these data, one could hypothesize that the clusters revealed in the present study may correspond to previously reported syngens and that there are at least five cryptic species within P. putrinum. Copyright © 2014 Elsevier Inc. All rights reserved.

The dynamics of fragment formation

International Nuclear Information System (INIS)

Keane, D.

1994-09-01

We demonstrate that in the Quantum Molecular Dynamics model, dynamical correlations can result in the production rate for final state nucleon clusters (and hence composite fragments) being higher than would be expected if statistics and the available phase space were dominant in determining composite formation. An intranuclear cascade or a Boltzmann-Uehling-Uhlenbeck model, combined with a statistical approach in the late stage of the collision to determine composites, provides an equivalent description only under limited conditions of centrality and beam energy. We use data on participant fragment production in Au + Au collisions in the Bevalac's BOS time projection chamber to map out the parameter space where statistical clustering provides a good description. In particular, we investigate momentum-space densities of fragments up to 4 He as a function of fragment transverse momentum, azimuth relative to the reaction plane, rapidity, multiplicity and beam energy

Summary report of IAEA technical meeting on technical aspects of atomic and molecular data processing and exchange - 18th meeting of the A+M Data Centres and ALADDIN Network

International Nuclear Information System (INIS)

Hubert, D.

2006-01-01

The IAEA Technical Meeting on 'Technical Aspects of Atomic and Molecular Data Processing and Exchange - 18th Meeting of A+M Data Centres and ALADDIN Network' was held on 10-11 October 2005, in Vienna, Austria. The discussions and presentations focused on the priorities in A+M data compilation and evaluation, and are summarized in this report. Conclusions and recommendations on the technical aspects of data processing, exchange and distribution are also presented. (author)

A new instrument of VUV laser desorption/ionization mass spectrometry imaging with micrometer spatial resolution and low level of molecular fragmentation.

Science.gov (United States)

Wang, Jia; Liu, Feng; Mo, Yuxiang; Wang, Zhaoying; Zhang, Sichun; Zhang, Xinrong

2017-11-01

Mass spectrometry imaging (MSI) has important applications in material research, biology, and medicine. The MSI method based on UV laser desorption/ionization (UVLDI) can obtain images of intact samples, but has a high level of molecular fragmentation. In this work, we report a new MSI instrument that uses a VUV laser (125.3 nm) as a desorption/ionization source to exploit its advantages of high single photon energy and small focus size. The new instrument was tested by the mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass spectrometric images of a fly brain section. For the tested samples, the VUVDI method offers lower levels of molecular fragmentations and higher sensitivities than those of the UVLDI method and second ion mass spectrometry imaging method using a Bi 3 + beam. The ablation crater produced by the focused VUV laser on a quartz plate has an area of 10 μm 2 . The VUV laser is prepared based on the four-wave mixing method using three collimated laser beams and a heated Hg cell.

A new instrument of VUV laser desorption/ionization mass spectrometry imaging with micrometer spatial resolution and low level of molecular fragmentation

Science.gov (United States)

Wang, Jia; Liu, Feng; Mo, Yuxiang; Wang, Zhaoying; Zhang, Sichun; Zhang, Xinrong

2017-11-01

Mass spectrometry imaging (MSI) has important applications in material research, biology, and medicine. The MSI method based on UV laser desorption/ionization (UVLDI) can obtain images of intact samples, but has a high level of molecular fragmentation. In this work, we report a new MSI instrument that uses a VUV laser (125.3 nm) as a desorption/ionization source to exploit its advantages of high single photon energy and small focus size. The new instrument was tested by the mass spectra of Nile red and FGB (Fibrinogen beta chain) samples and mass spectrometric images of a fly brain section. For the tested samples, the VUVDI method offers lower levels of molecular fragmentations and higher sensitivities than those of the UVLDI method and second ion mass spectrometry imaging method using a Bi3+ beam. The ablation crater produced by the focused VUV laser on a quartz plate has an area of 10 μm2. The VUV laser is prepared based on the four-wave mixing method using three collimated laser beams and a heated Hg cell.

A new assay based on terminal restriction fragment length polymorphism of homocitrate synthase gene fragments for Candida species identification.

Science.gov (United States)

Szemiako, Kasjan; Śledzińska, Anna; Krawczyk, Beata

2017-08-01

Candida sp. have been responsible for an increasing number of infections, especially in patients with immunodeficiency. Species-specific differentiation of Candida sp. is difficult in routine diagnosis. This identification can have a highly significant association in therapy and prophylaxis. This work has shown a new application of the terminal restriction fragment length polymorphism (t-RFLP) method in the molecular identification of six species of Candida, which are the most common causes of fungal infections. Specific for fungi homocitrate synthase gene was chosen as a molecular target for amplification. The use of three restriction enzymes, DraI, RsaI, and BglII, for amplicon digestion can generate species-specific fluorescence labeled DNA fragment profiles, which can be used to determine the diagnostic algorithm. The designed method can be a cost-efficient high-throughput molecular technique for the identification of six clinically important Candida species.

A probabilistic fragment-based protein structure prediction algorithm.

Directory of Open Access Journals (Sweden)

David Simoncini

Full Text Available Conformational sampling is one of the bottlenecks in fragment-based protein structure prediction approaches. They generally start with a coarse-grained optimization where mainchain atoms and centroids of side chains are considered, followed by a fine-grained optimization with an all-atom representation of proteins. It is during this coarse-grained phase that fragment-based methods sample intensely the conformational space. If the native-like region is sampled more, the accuracy of the final all-atom predictions may be improved accordingly. In this work we present EdaFold, a new method for fragment-based protein structure prediction based on an Estimation of Distribution Algorithm. Fragment-based approaches build protein models by assembling short fragments from known protein structures. Whereas the probability mass functions over the fragment libraries are uniform in the usual case, we propose an algorithm that learns from previously generated decoys and steers the search toward native-like regions. A comparison with Rosetta AbInitio protocol shows that EdaFold is able to generate models with lower energies and to enhance the percentage of near-native coarse-grained decoys on a benchmark of [Formula: see text] proteins. The best coarse-grained models produced by both methods were refined into all-atom models and used in molecular replacement. All atom decoys produced out of EdaFold's decoy set reach high enough accuracy to solve the crystallographic phase problem by molecular replacement for some test proteins. EdaFold showed a higher success rate in molecular replacement when compared to Rosetta. Our study suggests that improving low resolution coarse-grained decoys allows computational methods to avoid subsequent sampling issues during all-atom refinement and to produce better all-atom models. EdaFold can be downloaded from http://www.riken.jp/zhangiru/software.html [corrected].

Thermochemical Fragment Energy Method for Biomolecules: Application to a Collagen Model Peptide.

Science.gov (United States)

Suárez, Ernesto; Díaz, Natalia; Suárez, Dimas

2009-06-09

Herein, we first review different methodologies that have been proposed for computing the quantum mechanical (QM) energy and other molecular properties of large systems through a linear combination of subsystem (fragment) energies, which can be computed using conventional QM packages. Particularly, we emphasize the similarities among the different methods that can be considered as variants of the multibody expansion technique. Nevertheless, on the basis of thermochemical arguments, we propose yet another variant of the fragment energy methods, which could be useful for, and readily applicable to, biomolecules using either QM or hybrid quantum mechanical/molecular mechanics methods. The proposed computational scheme is applied to investigate the stability of a triple-helical collagen model peptide. To better address the actual applicability of the fragment QM method and to properly compare with experimental data, we compute average energies by carrying out single-point fragment QM calculations on structures generated by a classical molecular dynamics simulation. The QM calculations are done using a density functional level of theory combined with an implicit solvent model. Other free-energy terms such as attractive dispersion interactions or thermal contributions are included using molecular mechanics. The importance of correcting both the intermolecular and intramolecular basis set superposition error (BSSE) in the QM calculations is also discussed in detail. On the basis of the favorable comparison of our fragment-based energies with experimental data and former theoretical results, we conclude that the fragment QM energy strategy could be an interesting addition to the multimethod toolbox for biomolecular simulations in order to investigate those situations (e.g., interactions with metal clusters) that are beyond the range of applicability of common molecular mechanics methods.

Transforming fragments into candidates: small becomes big in medicinal chemistry.

Science.gov (United States)

de Kloe, Gerdien E; Bailey, David; Leurs, Rob; de Esch, Iwan J P

2009-07-01

Fragment-based drug discovery (FBDD) represents a logical and efficient approach to lead discovery and optimisation. It can draw on structural, biophysical and biochemical data, incorporating a wide range of inputs, from precise mode-of-binding information on specific fragments to wider ranging pharmacophoric screening surveys using traditional HTS approaches. It is truly an enabling technology for the imaginative medicinal chemist. In this review, we analyse a representative set of 23 published FBDD studies that describe how low molecular weight fragments are being identified and efficiently transformed into higher molecular weight drug candidates. FBDD is now becoming warmly endorsed by industry as well as academia and the focus on small interacting molecules is making a big scientific impact.

Fragmentation of the radiation degraded chitosan by centrifugal filter and application of the fragmented chitosan in cotton fabrics finishing

International Nuclear Information System (INIS)

Luu Thi Tho; Nguyen Van Thong; Vu Thi Hong Khanh; Tran Minh Quynh

2014-01-01

Three kind of Vietnamese chitosans with the same deacetylation degrees of about 75% and viscosity average molecular weights are 69.000, 187.000 and 345.000 Da, respectively, were produced from shrimp shells and cuttle-bone at the MTV chitosan company (Kien Giang). These chitosans were irradiated at 25, 50, 75, 100, 200 and 500 kGy under Cobalt-60 gamma source at Hanoi Irradiation Center in order to prepare a series of chitosan segments with wide distribution of molecular weights. Different chitosan samples of the predetermined average molecular weight from 3,000 to 50,000 Da were separated from the irradiated chitosans by ultrafiltration with series of filter membranes (Centriprep devices). Molecular properties of the fragmented chitosans were analysed with gel permeation chromatography, Fourier transfer infra red spectrometry, and the results suggested that principal characteristics of chitosan were not affected by gamma irradiation, even its deacetylation degrees was increased. Solubility of the fragmented chitosans were much improved by radiation processing, and the chitosans having molecular weights below 5.000 Da were water-soluble polymers, which can easily apply as the auxiliary agent in textile. (author)

Collision induced fragmentation dynamics of small metallic clusters; Dynamique de fragmentation induite par collision de petits agregats metalliques

Energy Technology Data Exchange (ETDEWEB)

Picard, Y

1999-04-15

The goal of this work is the complete analysis of the fragmentation of alkali clusters (Na{sub n}{sup +} (n < 10), NaK{sup +} and K{sub 2}{sup +}) induced by collision with light atomic (He) or molecular (H{sub 2}) targets. The main point is to study how the energy is transmitted to the cluster during the collision and how this energy is shared among the various degrees of freedom of the system and leads to its fragmentation. Two types of interactions govern the collision induced dissociation processes: on one hand, the electronic mechanisms where the target perturbs the electronic cloud and brings the molecule into a dissociative state, and on the other hand, the impulsive mechanisms where the momentum transferred to the atomic cores leads to the rotational-vibrational dissociation of the molecule. The experimental procedure is based on the measurement of the velocity vectors of the outgoing fragments detected in coincidence. This allows to reconstruct the full kinematics of the fragmentation and to separate and characterize for the first time the two types of interactions. The two basic mechanisms of collision induced dissociation are then clearly resolved for the diatomic molecule Na{sub 2}{sup +}. For the heteronuclear molecular ion NaK{sup +}, it is shown that the dissociation process is due to a combination of electronic and impulsive mechanisms in some of the dissociation pathways. The extension to the study of metallic clusters Na{sub n}{sup +} (n < 10) fragmentation shows the role and the relative importance of the electronic and impulsive mechanisms and their evolution with the cluster size. The complete analysis of Na{sub 3}{sup +} multi-fragmentation is also presented. (author)

Technical aspects of atomic and molecular data processing and exchange, 20. meeting of the A+M Data Centres and ALADDIN Network. Summary report of an IAEA technical meeting

International Nuclear Information System (INIS)

Humbert, D.; Braams, B.J.

2010-01-01

The proceedings of the IAEA Advisory Group Meeting on Technical Aspects of Atomic and Molecular Data Processing and Exchange (20th Meeting of A+M Data Centres Network), 7-9 September 2009 at IAEA Headquarters in Vienna, are summarized. The meeting conclusions and recommendations on priorities in A+M data compilation and evaluation and on technical aspects of data processing and exchange are also presented. (author)

Reducing the Flexibility of Type II Dehydroquinase for Inhibition: A Fragment-Based Approach and Molecular Dynamics Study.

Science.gov (United States)

Peón, Antonio; Robles, Adrián; Blanco, Beatriz; Convertino, Marino; Thompson, Paul; Hawkins, Alastair R; Caflisch, Amedeo; González-Bello, Concepción

2017-09-21

A multidisciplinary approach was used to identify and optimize a quinazolinedione-based ligand that would decrease the flexibility of the substrate-covering loop (catalytic loop) of the type II dehydroquinase from Helicobacter pylori. This enzyme, which is essential for the survival of this bacterium, is involved in the biosynthesis of aromatic amino acids. A computer-aided fragment-based protocol (ALTA) was first used to identify the aromatic fragments able to block the interface pocket that separates two neighboring enzyme subunits and is located at the active site entrance. Chemical modification of its non-aromatic moiety through an olefin cross-metathesis and Seebach's self-reproduction of chirality synthetic principle allowed the development of a quinazolinedione derivative that disables the catalytic loop plasticity, which is essential for the enzyme's catalytic cycle. Molecular dynamics simulations revealed that the ligand would force the catalytic loop into an inappropriate arrangement for catalysis by strong interactions with the catalytic tyrosine and by expelling the essential arginine out of the active site. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acute regulation of circulating parathyroid hormone (PTH) molecular forms by calcium: utility of PTH fragments/PTH(1-84) ratios derived from three generations of PTH assays.

Science.gov (United States)

D'Amour, Pierre; Räkel, Agnès; Brossard, Jean-Hugues; Rousseau, Louise; Albert, Caroline; Cantor, Tom

2006-01-01

The quantitative evaluation of circulating PTH peaks revealed by PTH assays after HPLC separation constitutes the best way to study the behavior of PTH molecular forms, but it is also impractical. The objective of the study was to investigate the regulation of circulating PTH molecular forms by calcium through the use of PTH fragments/PTH (1-84) ratios derived from PTH assays with different specificities before and after HPLC separation of circulating PTH. CaCl2 and Na citrate were infused in eight volunteers. PTH was measured in serum and HPLC fractions at different calcium concentrations in PTH assays reacting with regions 1-2 (CA), 12-18 (T), and 65-69 (C) of the PTH structure. From hypo- to hypercalcemia, the C/CA ratio had the highest range (1.92 to 9.75; P < 0.001), and the C/T ratio had a higher range (1.69 to 6.11; P < 0.01) than the T/CA ratio (1.15 to 1.86). Human (h) PTH (1-84) represented 32.7 and 4.3% of circulating PTH in hypo- and hypercalcemic HPLC profiles, respectively. These numbers were 5 and 0.9% for amino-terminal (N)-PTH, an amino-terminal form of PTH distinct from hPTH (1-84), 7.3 and 6.8% for non-(1-84) PTH or large C-PTH fragments with a partially preserved N structure, and 54.9 and 88.1% for C-PTH fragments missing a N structure. The HPLC C-PTH fragments to hPTH (1-84) ratio had the most extensive range (1.67 to 20.58). Despite their quantitative differences, all ratios identified identical behavior of PTH fragments relative to PTH (1-84). PTH assay ratios are an adequate tool to investigate the modulation of PTH molecular forms, even if all PTH assays show some undesirable cross-reactivity with certain circulating forms of PTH.

Molecular analysis of Leptospira spp. isolated from humans by restriction fragment length polymorphism, real-time PCR and pulsed-field gel electrophoresis.

Science.gov (United States)

Turk, Nenad; Milas, Zoran; Mojcec, Vesna; Ruzic-Sabljic, Eva; Staresina, Vilim; Stritof, Zrinka; Habus, Josipa; Postic, Daniele

2009-11-01

A total of 17 Leptospira clinical strains isolated from humans in Croatia were serologically and genetically analysed. For serovar identification, the microscopic agglutination test (MAT) and pulsed-field gel electrophoresis (PFGE) were used. To identify isolates on genomic species level, PCR-based restriction fragment length polymorphism (RFLP) and real-time PCR were performed. MAT revealed the following serogroup affinities: Grippotyphosa (seven isolates), Icterohaemorrhagiae (eight isolates) and Javanica (two isolates). RFLP of PCR products from a 331-bp-long fragment of rrs (16S rRNA gene) digested with endonucleases MnlI and DdeI and real-time PCR revealed three Leptospira genomic species. Grippotyphosa isolates belonged to Leptospira kirschneri, Icterohaemorrhagiae isolates to Leptospira interrogans and Javanica isolates to Leptospira borgpetersenii. Genomic DNA from 17 leptospiral isolates was digested with NotI and SgrAI restriction enzymes and analysed by PFGE. Results showed that seven isolates have the same binding pattern to serovar Grippotyphosa, eight isolates to serovar Icterohaemorrhagiae and two isolates to serovar Poi. Results demonstrate the diversity of leptospires circulating in Croatia. We point out the usefulness of a combination of PFGE, RFLP and real-time PCR as appropriate molecular methods in molecular analysis of leptospires.

Technical Aspects of Atomic and Molecular Data Processing and Exchange, 21. Meeting of the A+M Data Centres Network. Summary Report of an IAEA Technical Meeting

Energy Technology Data Exchange (ETDEWEB)

Chung, H.-K., E-mail: H.Chung@iaea.org [IAEA, Atomic and Molecular Data Unit, Vienna (Austria)

2011-11-15

This report summarizes the proceedings of the IAEA Technical Meeting on 'Technical Aspects of Atomic and Molecular Data Processing and Exchange' (21st Meeting of the A+M Data Centres Network) on 7-9 September 2011. Fourteen participants from 12 data centres of 7 Member States and 2 International Organizations attended the three-day meeting held at the IAEA Headquarters in Vienna. The report includes discussions on the data issues, meeting conclusions and recommendations and the abstracts of presentations presented in the meeting. (author)

Technical Aspects of Atomic and Molecular Data Processing and Exchange, 21. Meeting of the A+M Data Centres Network. Summary Report of an IAEA Technical Meeting

International Nuclear Information System (INIS)

Chung, H.-K.

2011-11-01

This report summarizes the proceedings of the IAEA Technical Meeting on 'Technical Aspects of Atomic and Molecular Data Processing and Exchange' (21st Meeting of the A+M Data Centres Network) on 7-9 September 2011. Fourteen participants from 12 data centres of 7 Member States and 2 International Organizations attended the three-day meeting held at the IAEA Headquarters in Vienna. The report includes discussions on the data issues, meeting conclusions and recommendations and the abstracts of presentations presented in the meeting. (author)

Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

Directory of Open Access Journals (Sweden)

Katerina T. Xenaki

2017-10-01

Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

Comparison by restriction fragment pattern analyses and molecular characterization of some European isolates of Suid herpesvirus 1: A contribution to strain differentiation of European isolates

DEFF Research Database (Denmark)

Christensen, Laurids Siig

1988-01-01

Eleven European isolates of Suid herpesvirus type 1 (SHV-1) were compared by restriction fragment pattern analyses and Southern blot hybridization using different genomic probes. The presence of strain discriminative 4 major genome types and several subtypes as well as the molecular distinctions...

Linkage map of the fragments of herpesvirus papio DNA.

Science.gov (United States)

Lee, Y S; Tanaka, A; Lau, R Y; Nonoyama, M; Rabin, H

1981-01-01

Herpesvirus papio (HVP), an Epstein-Barr-like virus, causes lymphoblastoid disease in baboons. The physical map of HVP DNA was constructed for the fragments produced by cleavage of HVP DNA with restriction endonucleases EcoRI, HindIII, SalI, and PvuI, which produced 12, 12, 10, and 4 fragments, respectively. The total molecular size of HVP DNA was calculated as close to 110 megadaltons. The following methods were used for construction of the map; (i) fragments near the ends of HVP DNA were identified by treating viral DNA with lambda exonuclease before restriction enzyme digestion; (ii) fragments containing nucleotide sequences in common with fragments from the second enzyme digest of HVP DNA were examined by Southern blot hybridization; and (iii) the location of some fragments was determined by isolating individual fragments from agarose gels and redigesting the isolated fragments with a second restriction enzyme. Terminal heterogeneity and internal repeats were found to be unique features of HVP DNA molecule. One to five repeats of 0.8 megadaltons were found at both terminal ends. Although the repeats of both ends shared a certain degree of homology, it was not determined whether they were identical repeats. The internal repeat sequence of HVP DNA was found in the EcoRI-C region, which extended from 8.4 to 23 megadaltons from the left end of the molecule. The average number of the repeats was calculated to be seven, and the molecular size was determined to be 1.8 megadaltons. Similar unique features have been reported in EBV DNA (D. Given and E. Kieff, J. Virol. 28:524-542, 1978). Images PMID:6261015

Technical Aspects of Atomic and Molecular Data Processing and Exchange, 22nd Meeting of the A+M Data Centres Network. Summary Report of an IAEA Technical Meeting

International Nuclear Information System (INIS)

Chung, Hyun-Kyung

2013-12-01

This report summarizes the proceedings of the IAEA Technical Meeting on ''Technical Aspects of Atomic and Molecular Data Processing and Exchange'' (22nd Meeting of the A+M Data Centres Network) on 4-6 September 2013. Twelve participants from 8 data centres of 6 Member States attended the three-day meeting held at the IAEA Headquarters in Vienna. The report includes discussions on the data issues, meeting conclusions and recommendations and the abstracts of presentations presented in the meeting. (author)

Isomeric signatures in the fragmentation of pyridazine and pyrimidine induced by fast ion impact

Energy Technology Data Exchange (ETDEWEB)

Wolff, Wania, E-mail: wania@if.ufrj.br; Luna, Hugo; Montenegro, Eduardo C. [Instituto de Física, Universidade Federal do Rio de Janeiro, 21941-972 Rio de Janeiro, RJ (Brazil)

2015-07-28

We present fast proton impact induced fragmentations of pyrimidine and pyridazine as an experimental resource to investigate isomeric signatures. Major isomeric imprints are identified for few fragment ions and differences of more than an order of magnitude for the cross sections of fragments of the same mass were measured. The observation of the molecular structure of these isomers gives no apparent indication for the reasons for such substantial differences. It is verified that the simple displacement of the position of one nitrogen atom strongly inhibits or favors the production of some ionic fragment species. The dependency of the fragmentation cross sections on the proton impact energy, investigated by means of time of flight mass spectroscopy and of a model calculation based in first order perturbation theory, allows us to disentangle the complex collision dynamics of the ionic fragments. The proton-induced fragmentation discriminates rather directly the association between a molecular orbital ionization and the fragment-ions creation and abundance, as well as how the redistribution of the energy imparted to the molecules takes place, triggering not only single but also double vacancy and leads to specific fragmentation pathways.

Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.

Science.gov (United States)

Han, Byeonggu; Ahn, Hee-Chul

2016-01-01

During the past decade fragment-based drug discovery (FBDD) has rapidly evolved and several drugs or drug candidates developed by FBDD approach are clinically in use or in clinical trials. For example, vemurafenib, a V600E mutated BRAF inhibitor, was developed by utilizing FBDD approach and approved by FDA in 2011. In FBDD, screening of fragments is the starting step for identification of hits and lead generation. Fragment screening usually relies on biophysical techniques by which the protein-bound small molecules can be detected. NMR spectroscopy has been extensively used to study the molecular interaction between the protein and the ligand, and has many advantages in fragment screening over other biophysical techniques. This chapter describes the practical aspects of fragment screening by saturation transfer difference NMR.

Bootstrap embedding: An internally consistent fragment-based method

Energy Technology Data Exchange (ETDEWEB)

Welborn, Matthew; Tsuchimochi, Takashi; Van Voorhis, Troy [Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 (United States)

2016-08-21

Strong correlation poses a difficult problem for electronic structure theory, with computational cost scaling quickly with system size. Fragment embedding is an attractive approach to this problem. By dividing a large complicated system into smaller manageable fragments “embedded” in an approximate description of the rest of the system, we can hope to ameliorate the steep cost of correlated calculations. While appealing, these methods often converge slowly with fragment size because of small errors at the boundary between fragment and bath. We describe a new electronic embedding method, dubbed “Bootstrap Embedding,” a self-consistent wavefunction-in-wavefunction embedding theory that uses overlapping fragments to improve the description of fragment edges. We apply this method to the one dimensional Hubbard model and a translationally asymmetric variant, and find that it performs very well for energies and populations. We find Bootstrap Embedding converges rapidly with embedded fragment size, overcoming the surface-area-to-volume-ratio error typical of many embedding methods. We anticipate that this method may lead to a low-scaling, high accuracy treatment of electron correlation in large molecular systems.

An improved algorithm for MFR fragment assembly

International Nuclear Information System (INIS)

Kontaxis, Georg

2012-01-01

A method for generating protein backbone models from backbone only NMR data is presented, which is based on molecular fragment replacement (MFR). In a first step, the PDB database is mined for homologous peptide fragments using experimental backbone-only data i.e. backbone chemical shifts (CS) and residual dipolar couplings (RDC). Second, this fragment library is refined against the experimental restraints. Finally, the fragments are assembled into a protein backbone fold using a rigid body docking algorithm using the RDCs as restraints. For improved performance, backbone nuclear Overhauser effects (NOEs) may be included at that stage. Compared to previous implementations of MFR-derived structure determination protocols this model-building algorithm offers improved stability and reliability. Furthermore, relative to CS-ROSETTA based methods, it provides faster performance and straightforward implementation with the option to easily include further types of restraints and additional energy terms.

Comparing the accuracy of high-dimensional neural network potentials and the systematic molecular fragmentation method: A benchmark study for all-trans alkanes

Energy Technology Data Exchange (ETDEWEB)

Gastegger, Michael; Kauffmann, Clemens; Marquetand, Philipp, E-mail: philipp.marquetand@univie.ac.at [Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 17, Vienna (Austria); Behler, Jörg [Lehrstuhl für Theoretische Chemie, Ruhr-Universität Bochum, Universitätsstraße 150, Bochum (Germany)

2016-05-21

Many approaches, which have been developed to express the potential energy of large systems, exploit the locality of the atomic interactions. A prominent example is the fragmentation methods in which the quantum chemical calculations are carried out for overlapping small fragments of a given molecule that are then combined in a second step to yield the system’s total energy. Here we compare the accuracy of the systematic molecular fragmentation approach with the performance of high-dimensional neural network (HDNN) potentials introduced by Behler and Parrinello. HDNN potentials are similar in spirit to the fragmentation approach in that the total energy is constructed as a sum of environment-dependent atomic energies, which are derived indirectly from electronic structure calculations. As a benchmark set, we use all-trans alkanes containing up to eleven carbon atoms at the coupled cluster level of theory. These molecules have been chosen because they allow to extrapolate reliable reference energies for very long chains, enabling an assessment of the energies obtained by both methods for alkanes including up to 10 000 carbon atoms. We find that both methods predict high-quality energies with the HDNN potentials yielding smaller errors with respect to the coupled cluster reference.

Comparing the accuracy of high-dimensional neural network potentials and the systematic molecular fragmentation method: A benchmark study for all-trans alkanes

International Nuclear Information System (INIS)

Gastegger, Michael; Kauffmann, Clemens; Marquetand, Philipp; Behler, Jörg

2016-01-01

Many approaches, which have been developed to express the potential energy of large systems, exploit the locality of the atomic interactions. A prominent example is the fragmentation methods in which the quantum chemical calculations are carried out for overlapping small fragments of a given molecule that are then combined in a second step to yield the system’s total energy. Here we compare the accuracy of the systematic molecular fragmentation approach with the performance of high-dimensional neural network (HDNN) potentials introduced by Behler and Parrinello. HDNN potentials are similar in spirit to the fragmentation approach in that the total energy is constructed as a sum of environment-dependent atomic energies, which are derived indirectly from electronic structure calculations. As a benchmark set, we use all-trans alkanes containing up to eleven carbon atoms at the coupled cluster level of theory. These molecules have been chosen because they allow to extrapolate reliable reference energies for very long chains, enabling an assessment of the energies obtained by both methods for alkanes including up to 10 000 carbon atoms. We find that both methods predict high-quality energies with the HDNN potentials yielding smaller errors with respect to the coupled cluster reference.

Identifying Interactions that Determine Fragment Binding at Protein Hotspots.

Science.gov (United States)

Radoux, Chris J; Olsson, Tjelvar S G; Pitt, Will R; Groom, Colin R; Blundell, Tom L

2016-05-12

Locating a ligand-binding site is an important first step in structure-guided drug discovery, but current methods do little to suggest which interactions within a pocket are the most important for binding. Here we illustrate a method that samples atomic hotspots with simple molecular probes to produce fragment hotspot maps. These maps specifically highlight fragment-binding sites and their corresponding pharmacophores. For ligand-bound structures, they provide an intuitive visual guide within the binding site, directing medicinal chemists where to grow the molecule and alerting them to suboptimal interactions within the original hit. The fragment hotspot map calculation is validated using experimental binding positions of 21 fragments and subsequent lead molecules. The ligands are found in high scoring areas of the fragment hotspot maps, with fragment atoms having a median percentage rank of 97%. Protein kinase B and pantothenate synthetase are examined in detail. In each case, the fragment hotspot maps are able to rationalize a Free-Wilson analysis of SAR data from a fragment-based drug design project.

Humidity Effects on Fragmentation in Plasma-Based Ambient Ionization Sources.

Science.gov (United States)

Newsome, G Asher; Ackerman, Luke K; Johnson, Kevin J

2016-01-01

Post-plasma ambient desorption/ionization (ADI) sources are fundamentally dependent on surrounding water vapor to produce protonated analyte ions. There are two reports of humidity effects on ADI spectra. However, it is unclear whether humidity will affect all ADI sources and analytes, and by what mechanism humidity affects spectra. Flowing atmospheric pressure afterglow (FAPA) ionization and direct analysis in real time (DART) mass spectra of various surface-deposited and gas-phase analytes were acquired at ambient temperature and pressure across a range of observed humidity values. A controlled humidity enclosure around the ion source and mass spectrometer inlet was used to create programmed humidity and temperatures. The relative abundance and fragmentation of molecular adduct ions for several compounds consistently varied with changing ambient humidity and also were controlled with the humidity enclosure. For several compounds, increasing humidity decreased protonated molecule and other molecular adduct ion fragmentation in both FAPA and DART spectra. For others, humidity increased fragment ion ratios. The effects of humidity on molecular adduct ion fragmentation were caused by changes in the relative abundances of different reagent protonated water clusters and, thus, a change in the average difference in proton affinity between an analyte and the population of water clusters. Control of humidity in ambient post-plasma ion sources is needed to create spectral stability and reproducibility.

Fragment formation in light-ion induced reactions

International Nuclear Information System (INIS)

Hirata, Yuichi

2001-01-01

The intermediate mass fragment (IMF) formation in the 12 GeV proton induced reaction on Au target is analyzed by the quantum molecular dynamics model combined with the JAM hadronic cascade model and the non-equilibrated percolation model. We show that the sideward peaked angular distribution of IMF occur in the multifragmentation at very short time scale around 20 fm/c where non-equilibrated features of the residual nucleus fluctuates the nucleon density and fragments in the repulsive Coulomb force are pushed for the sideward direction. (author)

Fragment-separator at the U-400 cyclotron. (The Technical proposal)

International Nuclear Information System (INIS)

Majdikov, V.Z.; Bashevoj, V.V.

1998-01-01

The ion-optical calculations together with graphical modeling show some possibility to create the low-energy fragment-separator for the RIB experiments performed at the Coulomb barrier of interactions at the U-400 cyclotron. Combination of two available magnetic dipoles SP-95 and SP-97 without any additional focussing elements at the cyclotron switchyard permits one to obtain the parameters of the RIB separator adequate for the modern experiments performance

COLLAPSE AND FRAGMENTATION OF MAGNETIC MOLECULAR CLOUD CORES WITH THE ENZO AMR MHD CODE. I. UNIFORM DENSITY SPHERES

International Nuclear Information System (INIS)

Boss, Alan P.; Keiser, Sandra A.

2013-01-01

Magnetic fields are important contributors to the dynamics of collapsing molecular cloud cores, and can have a major effect on whether collapse results in a single protostar or fragmentation into a binary or multiple protostar system. New models are presented of the collapse of magnetic cloud cores using the adaptive mesh refinement code Enzo2.0. The code was used to calculate the ideal magnetohydrodynamics (MHD) of initially spherical, uniform density, and rotation clouds with density perturbations, i.e., the Boss and Bodenheimer standard isothermal test case for three-dimensional (3D) hydrodynamics codes. After first verifying that Enzo reproduces the binary fragmentation expected for the non-magnetic test case, a large set of models was computed with varied initial magnetic field strengths and directions with respect to the cloud core axis of rotation (parallel or perpendicular), density perturbation amplitudes, and equations of state. Three significantly different outcomes resulted: (1) contraction without sustained collapse, forming a denser cloud core; (2) collapse to form a single protostar with significant spiral arms; and (3) collapse and fragmentation into binary or multiple protostar systems, with multiple spiral arms. Comparisons are also made with previous MHD calculations of similar clouds with a barotropic equations of state. These results for the collapse of initially uniform density spheres illustrate the central importance of both magnetic field direction and field strength for determining the outcome of dynamic protostellar collapse.

Structural features of Fab fragments of rheumatoid factor IgM-RF in solution

International Nuclear Information System (INIS)

Volkov, V. V.; Lapuk, V. A.; Shtykova, E. V.; Stepina, N. D.; Dembo, K. A.; Sokolova, A. V.; Amarantov, S. V.; Timofeev, V. P.; Ziganshin, R. Kh.; Varlamova, E. Yu.

2008-01-01

The structural features of the Fab fragments of monoclonal (Waldenstroem's disease) immunoglobulin M (IgM) and rheumatoid immunoglobulin M (IgM-RF) were studied by a complex of methods, including small-angle X-ray scattering (SAXS), electron spin resonance (ESR), and mass spectrometry (MS). The Fab-RF fragment was demonstrated to be much more flexible in the region of interdomain contacts, the molecular weights and the shapes of the Fab and Fab-RF macromolecules in solution being only slightly different. According to the ESR data, the rotational correlation time for a spin label introduced into the peptide sequence for Fab is twice as large as that for Fab-RF (21±2 and 11±1 ns, respectively), whereas the molecular weights of these fragments differ by only 0.5% (mass-spectrometric data), which correlates with the results of molecular-shape modeling by small-angle X-ray scattering. The conclusion about the higher flexibility of the Fab-RF fragment contributes to an understanding of the specificity of interactions between the rheumatoid factor and the antigens of the own organism.

Fragmentation of anthracene induced by collisions with 40 keV Ar8+ ions

International Nuclear Information System (INIS)

Brédy, R; Ortéga, C; Ji, M; Bernard, J; Chen, L; Montagne, G; Martin, S

2013-01-01

We report on the fragmentation of anthracene molecular ions C 14 H 10 r+ as a function of the parent ion initial charge r (= 1–4). Neutral anthracene molecules in the gas phase were ionized and excited in collisions with Ar 8+ ions at 40 keV and the mass-to-charge spectra of the parent ions C 14 H 10 r+ (1 ⩽ r ⩽ 4) were obtained. Stable molecular ions C 14 H 10 r+ (1 ⩽ r ⩽ 3) are observed. Branching ratios for the competitive evaporation (loss of neutral fragments) and fragmentation (charge separation) processes were measured for C 14 H 10 2+ parent ions. For C 14 H 10 3+ parent ions, the results indicate that fragmentation is the only dominant process and quasi-symmetric fission is observed. (paper)

The Y4-RNA fragment, a potential diagnostic marker, exists in saliva

Directory of Open Access Journals (Sweden)

Tatsuya Ishikawa

2017-06-01

Full Text Available The 94-nt full-length Y4-RNA is thought to have roles in the initiation of DNA replication and RNA quality control. Although its 31/32-nt fragment also exists abundantly in plasma, little is known about its physiological role. Since the 31/32-nt Y4-RNA fragment in sera is reported to be more abundant in patients with coronary artery disease than healthy persons, the fragment may have a potential for a diagnostic and/or prognostic biomarker for some diseases regardless of its functionality. As a step toward further investigation of its potential utility, we examined if the 31/32-nt Y4-RNA fragment also exists in saliva that can be obtained noninvasively, and showed that, in addition to the 31/32-nt fragment, 14- and 11-nt Y4-RNA fragments are present in all saliva RNA samples from four healthy persons. We established a PCR method to accurately quantitate the amount of the 31/32-nt Y4-RNA fragment, and estimated its amount in saliva of healthy persons to be 0.06 ± 0.04 fmol per nanogram of saliva RNA. We also tried to develop an easier quantitation method using a DNA molecular beacon. Keywords: Y4-RNA fragment, Saliva RNA, Diagnostic/prognostic marker, Next-generation sequencing, RT-PCR, Molecular beacon

Does the range of IMF affect rise and fall trend in fragmentation?

Science.gov (United States)

Sharma, Sakshi; Kumar, Rohit; Puri, Rajeev K.

2018-05-01

We study the rise and fall behavior in the multiplicity of intermediate mass fragments produced in the asymmetric reactions of 36S+ 198Pt using isospin-dependent quantum molecular dynamics model. We use different definitions of intermediate mass fragments according to various experimental studies. We find that the use of one or the other definition of intermediate mass fragments does not alter results significantly.

Fragmentation and structure of silicon microclusters

International Nuclear Information System (INIS)

Feuston, B.P.; Kalia, R.K.; Vashishta, P.

1987-01-01

It may be possible to determine the magic numbers and fragmentation spectra from the ground-state binding energies and structure, but the relationship between the lowest-energy zero-temperature configurations and the energetics of finite-temperature microclusters is not obvious. Recall fragmentation of Si clusters occurs at temperatures the order of the melting temperature (T∼2000 K). What is needed, a first-principles finite-temperature calculation, allowing the determination of all possible structures, their corresponding binding energies, and fragmentation spectra, is not presently possible. However, a molecular dynamics calculation does allow one to study the nature of fragmentation in addition to determination of the global ground-state structure and all mechanically stable configurations underlying the finite-temperature cluster, once given an interaction potential. The authors present results for such a calculation for Si/sub 2-14/ using the Stillinger-Weber 3-body potential. Their results indicate that the existence of magic numbers is determined by the topology and energetics of high-energy bound structures rather than the structure and ground-state energies at zero temperature

Fission fragment excited laser system

Science.gov (United States)

McArthur, David A.; Tollefsrud, Philip B.

1976-01-01

A laser system and method for exciting lasing action in a molecular gas lasing medium which includes cooling the lasing medium to a temperature below about 150 K and injecting fission fragments through the lasing medium so as to preferentially excite low lying vibrational levels of the medium and to cause population inversions therein. The cooled gas lasing medium should have a mass areal density of about 5 .times. 10.sup.-.sup.3 grams/square centimeter, relaxation times of greater than 50 microseconds, and a broad range of excitable vibrational levels which are excitable by molecular collisions.

Uncertainty Assessment for Theoretical Atomic and Molecular Scattering Data. Summary Report of a Joint IAEA-ITAMP Technical Meeting

International Nuclear Information System (INIS)

Chung, Hyun-Kyung; Bartschat, Klaus; Tennyson, Jonathan; Schultz, David R.

2014-10-01

This report summarizes the proceedings of the Joint IAEA-ITAMP Technical Meeting on “Uncertainty Assessment for Theoretical Atomic and Molecular Scattering Data” on 7-9 July 2014. Twenty-five participants from ten Member States and one from the IAEA attended the three-day meeting held at the Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts, USA and hosted by the Institute of Theoretical Atomic, Molecular and Optical Physics (ITAMP). The report includes discussions on the issues of uncertainty estimates for theoretical atomic and molecular scattering data. The abstracts of presentations presented in the meeting are attached in the Appendix. (author)

Baculovirus display of functional antibody Fab fragments.

Science.gov (United States)

Takada, Shinya; Ogawa, Takafumi; Matsui, Kazusa; Suzuki, Tasuku; Katsuda, Tomohisa; Yamaji, Hideki

2015-08-01

The generation of a recombinant baculovirus that displays antibody Fab fragments on the surface was investigated. A recombinant baculovirus was engineered so that the heavy chain (Hc; Fd fragment) of a mouse Fab fragment was expressed as a fusion to the N-terminus of baculovirus gp64, while the light chain of the Fab fragment was simultaneously expressed as a secretory protein. Following infection of Sf9 insect cells with the recombinant baculovirus, the culture supernatant was analyzed by enzyme-linked immunosorbent assay using antigen-coated microplates and either an anti-mouse IgG or an anti-gp64 antibody. A relatively strong signal was obtained in each case, showing antigen-binding activity in the culture supernatant. In western blot analysis of the culture supernatant using the anti-gp64 antibody, specific protein bands were detected at an electrophoretic mobility that coincided with the molecular weight of the Hc-gp64 fusion protein as well as that of gp64. Flow cytometry using a fluorescein isothiocyanate-conjugated antibody specific to mouse IgG successfully detected the Fab fragments on the surface of the Sf9 cells. These results suggest that immunologically functional antibody Fab fragments can be displayed on the surface of baculovirus particles, and that a fluorescence-activated cell sorter with a fluorescence-labeled antigen can isolate baculoviruses displaying specific Fab fragments. This successful baculovirus display of antibody Fab fragments may offer a novel approach for the efficient selection of specific antibodies.

Characterization of low molecular weight fragments from gamma irradiated κ-carrageenan used as plant growth promoter

Science.gov (United States)

Abad, Lucille V.; Aurigue, Fernando B.; Relleve, Lorna S.; Montefalcon, Djowel Recto V.; Lopez, Girlie Eunice P.

2016-01-01

Radiation degraded κ-carrageenan (1% solution at absorbed doses of 20 kGy and 30 kGy) were tested for its plant growth promoter (PGP) effect on pechay plants under hydroponics condition. Results revealed that higher PGP effects were found in κ-carrageenan irradiated at an absorbed dose of 30 kGy. Mw of irradiated κ-carrageenan as measured by GPC were determined to be 7362 Da and 6762 Da for 20 kGy and 30 kGy, respectively. Fractionation of the irradiated κ-carrageenan (30 kGy) was done to separate different Mw fractions using Mw cut-off filters of 1 kDa, 3 kDa, and 5 kDa. The PGP effect of the different retentates showed that biological activity in plants followed the order of 5 kDa>3 kDa>1 kDa using hydroponics condition but the reverse was observed in the order of 1 kDa>3 kDa>5 kDa when absorbed in plants by foliar spraying. GPC chromatogram indicated at least three (3) low molecular weight (LMW) fragments from radiation modified κ-carrageenan solution with an Mw<2000 Da. A fragment has also been identified with an Mw of as low as 160 Da which was produced under acidic (un-neutralized) condition. This may be attributed to the formation of 5-hydroxymethylfurfural (5-HMF).

[Analysis of Conformational Features of Watson-Crick Duplex Fragments by Molecular Mechanics and Quantum Mechanics Methods].

Science.gov (United States)

Poltev, V I; Anisimov, V M; Sanchez, C; Deriabina, A; Gonzalez, E; Garcia, D; Rivas, F; Polteva, N A

2016-01-01

It is generally accepted that the important characteristic features of the Watson-Crick duplex originate from the molecular structure of its subunits. However, it still remains to elucidate what properties of each subunit are responsible for the significant characteristic features of the DNA structure. The computations of desoxydinucleoside monophosphates complexes with Na-ions using density functional theory revealed a pivotal role of DNA conformational properties of single-chain minimal fragments in the development of unique features of the Watson-Crick duplex. We found that directionality of the sugar-phosphate backbone and the preferable ranges of its torsion angles, combined with the difference between purines and pyrimidines. in ring bases, define the dependence of three-dimensional structure of the Watson-Crick duplex on nucleotide base sequence. In this work, we extended these density functional theory computations to the minimal' fragments of DNA duplex, complementary desoxydinucleoside monophosphates complexes with Na-ions. Using several computational methods and various functionals, we performed a search for energy minima of BI-conformation for complementary desoxydinucleoside monophosphates complexes with different nucleoside sequences. Two sequences are optimized using ab initio method at the MP2/6-31++G** level of theory. The analysis of torsion angles, sugar ring puckering and mutual base positions of optimized structures demonstrates that the conformational characteristic features of complementary desoxydinucleoside monophosphates complexes with Na-ions remain within BI ranges and become closer to the corresponding characteristic features of the Watson-Crick duplex crystals. Qualitatively, the main characteristic features of each studied complementary desoxydinucleoside monophosphates complex remain invariant when different computational methods are used, although the quantitative values of some conformational parameters could vary lying within the

Fragment-based drug discovery and its application to challenging drug targets.

Science.gov (United States)

Price, Amanda J; Howard, Steven; Cons, Benjamin D

2017-11-08

Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of low molecular weight compounds (fragments). Although fragments bind to proteins with relatively low affinity, they form efficient, high quality binding interactions with the protein architecture as they have to overcome a significant entropy barrier to bind. Of the biophysical methods available for fragment screening, X-ray protein crystallography is one of the most sensitive and least prone to false positives. It also provides detailed structural information of the protein-fragment complex at the atomic level. Fragment-based screening using X-ray crystallography is therefore an efficient method for identifying binding hotspots on proteins, which can then be exploited by chemists and biologists for the discovery of new drugs. The use of FBDD is illustrated here with a recently published case study of a drug discovery programme targeting the challenging protein-protein interaction Kelch-like ECH-associated protein 1:nuclear factor erythroid 2-related factor 2. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

FragIt: a tool to prepare input files for fragment based quantum chemical calculations.

Directory of Open Access Journals (Sweden)

Casper Steinmann

Full Text Available Near linear scaling fragment based quantum chemical calculations are becoming increasingly popular for treating large systems with high accuracy and is an active field of research. However, it remains difficult to set up these calculations without expert knowledge. To facilitate the use of such methods, software tools need to be available to support these methods and help to set up reasonable input files which will lower the barrier of entry for usage by non-experts. Previous tools relies on specific annotations in structure files for automatic and successful fragmentation such as residues in PDB files. We present a general fragmentation methodology and accompanying tools called FragIt to help setup these calculations. FragIt uses the SMARTS language to locate chemically appropriate fragments in large structures and is applicable to fragmentation of any molecular system given suitable SMARTS patterns. We present SMARTS patterns of fragmentation for proteins, DNA and polysaccharides, specifically for D-galactopyranose for use in cyclodextrins. FragIt is used to prepare input files for the Fragment Molecular Orbital method in the GAMESS program package, but can be extended to other computational methods easily.

Improved production and function of llama heavy chain antibody fragments by molecular evolution

NARCIS (Netherlands)

Linden, van der R.H.; Geus, de B.; Frenken, G.J.; Peters, H.; Verrips, C.T.

2000-01-01

The aim of this study was to improve production level of llama heavy chain antibody fragments (V (HH)) in Saccharomyces cerevisiae while retaining functional characteristics. For this purpose, the DNA shuffling technique was used on llama V (HH) fragments specific for the azo-dye reactive red-6. In

Optimization long hole blast fragmentation techniques and detonating circuit underground uranium mine stope

International Nuclear Information System (INIS)

Li Qin; Yang Lizhi; Song Lixia; Qin De'en; Xue Yongshe; Wang Zhipeng

2012-01-01

Aim at high rate of large blast fragmentation, a big difficulty in long hole drilling and blasting underground uranium mine stope, it is pointed out at the same time of taking integrated technical management measures, the key is to optimize the drilling and blasting parameters and insure safety the act of one that primes, adopt 'minimum burden' blasting technique, renew the stope fragmentation process, and use new process of hole bottom indirect initiation fragmentation; optimize the detonating circuit and use safe, reliable and economically rational duplex non-electric detonating circuit. The production practice shows that under the guarantee of strictly controlled construction quality, the application of optimized blast fragmentation technique has enhanced the reliability of safety detonation and preferably solved the problem of high rate of large blast fragments. (authors)

A mechanism of gene amplification driven by small DNA fragments.

Directory of Open Access Journals (Sweden)

Kuntal Mukherjee

Full Text Available DNA amplification is a molecular process that increases the copy number of a chromosomal tract and often causes elevated expression of the amplified gene(s. Although gene amplification is frequently observed in cancer and other degenerative disorders, the molecular mechanisms involved in the process of DNA copy number increase remain largely unknown. We hypothesized that small DNA fragments could be the trigger of DNA amplification events. Following our findings that small fragments of DNA in the form of DNA oligonucleotides can be highly recombinogenic, we have developed a system in the yeast Saccharomyces cerevisiae to capture events of chromosomal DNA amplification initiated by small DNA fragments. Here we demonstrate that small DNAs can amplify a chromosomal region, generating either tandem duplications or acentric extrachromosomal DNA circles. Small fragment-driven DNA amplification (SFDA occurs with a frequency that increases with the length of homology between the small DNAs and the target chromosomal regions. SFDA events are triggered even by small single-stranded molecules with as little as 20-nt homology with the genomic target. A double-strand break (DSB external to the chromosomal amplicon region stimulates the amplification event up to a factor of 20 and favors formation of extrachromosomal circles. SFDA is dependent on Rad52 and Rad59, partially dependent on Rad1, Rad10, and Pol32, and independent of Rad51, suggesting a single-strand annealing mechanism. Our results reveal a novel molecular model for gene amplification, in which small DNA fragments drive DNA amplification and define the boundaries of the amplicon region. As DNA fragments are frequently found both inside cells and in the extracellular environment, such as the serum of patients with cancer or other degenerative disorders, we propose that SFDA may be a common mechanism for DNA amplification in cancer cells, as well as a more general cause of DNA copy number variation

Multiphoton above threshold effects in strong-field fragmentation

DEFF Research Database (Denmark)

B Madsen, C; Anis, F; B Madsen, L

2012-01-01

We present a study of multiphoton dissociative ionization from molecules. By solving the time-dependent Schrödinger equation for H2+ and projecting the solution onto double continuum scattering states, we observe the correlated electron-nuclear ionization dynamics in detail. We show—for the first...... time—how multiphoton structure prevails as long as one accounts for the energies of all the fragments. Our current work provides a new avenue to analyze strong-field fragmentation that leads to a deeper understanding of the correlated molecular dynamics....

Fragment-based approaches to the discovery of kinase inhibitors.

Science.gov (United States)

Mortenson, Paul N; Berdini, Valerio; O'Reilly, Marc

2014-01-01

Protein kinases are one of the most important families of drug targets, and aberrant kinase activity has been linked to a large number of disease areas. Although eminently targetable using small molecules, kinases present a number of challenges as drug targets, not least obtaining selectivity across such a large and relatively closely related target family. Fragment-based drug discovery involves screening simple, low-molecular weight compounds to generate initial hits against a target. These hits are then optimized to more potent compounds via medicinal chemistry, usually facilitated by structural biology. Here, we will present a number of recent examples of fragment-based approaches to the discovery of kinase inhibitors, detailing the construction of fragment-screening libraries, the identification and validation of fragment hits, and their optimization into potent and selective lead compounds. The advantages of fragment-based methodologies will be discussed, along with some of the challenges associated with using this route. Finally, we will present a number of key lessons derived both from our own experience running fragment screens against kinases and from a large number of published studies.

Densities and temperatures at fragment formation in heavy-ion collision

Energy Technology Data Exchange (ETDEWEB)

Ohnishi, Akira [Hokkaido Univ., Sapporo (Japan)

1998-07-01

In order to clarify whether the liquid-gas phase transition is relevant to the multi-fragment formation found in intermediate energy heavy-ion collisions, we estimate the densities and temperatures at fragment formation in Au+Au collisions at incident energies of 150 MeV/A and 400 MeV/A within the Quantum Molecular Dynamics (QMD) model with and without quantum fluctuations implemented according to the Quantal Langevin (QL) model. The calculated results show that the IMFs are mainly produced inside the unstable region of nuclear matter, which supports the idea of the fragment formation from supercooled nuclear matter. (author)

BcL-xL Conformational Changes upon Fragment Binding Revealed by NMR

Science.gov (United States)

Aguirre, Clémentine; ten Brink, Tim; Walker, Olivier; Guillière, Florence; Davesne, Dany; Krimm, Isabelle

2013-01-01

Protein-protein interactions represent difficult but increasingly important targets for the design of therapeutic compounds able to interfere with biological processes. Recently, fragment-based strategies have been proposed as attractive approaches for the elaboration of protein-protein surface inhibitors from fragment-like molecules. One major challenge in targeting protein-protein interactions is related to the structural adaptation of the protein surface upon molecular recognition. Methods capable of identifying subtle conformational changes of proteins upon fragment binding are therefore required at the early steps of the drug design process. In this report we present a fast NMR method able to probe subtle conformational changes upon fragment binding. The approach relies on the comparison of experimental fragment-induced Chemical Shift Perturbation (CSP) of amine protons to CSP simulated for a set of docked fragment poses, considering the ring-current effect from fragment binding. We illustrate the method by the retrospective analysis of the complex between the anti-apoptotic Bcl-xL protein and the fragment 4′-fluoro-[1,1′-biphenyl]-4-carboxylic acid that was previously shown to bind one of the Bcl-xL hot spots. The CSP-based approach shows that the protein undergoes a subtle conformational rearrangement upon interaction, for residues located in helices 2, 3 and the very beginning of 5. Our observations are corroborated by residual dipolar coupling measurements performed on the free and fragment-bound forms of the Bcl-xL protein. These NMR-based results are in total agreement with previous molecular dynamic calculations that evidenced a high flexibility of Bcl-xL around the binding site. Here we show that CSP of protein amine protons are useful and reliable structural probes. Therefore, we propose to use CSP simulation to assess protein conformational changes upon ligand binding in the fragment-based drug design approach. PMID:23717610

The use of many-body expansions and geometry optimizations in fragment-based methods.

Science.gov (United States)

Fedorov, Dmitri G; Asada, Naoya; Nakanishi, Isao; Kitaura, Kazuo

2014-09-16

Conspectus Chemists routinely work with complex molecular systems: solutions, biochemical molecules, and amorphous and composite materials provide some typical examples. The questions one often asks are what are the driving forces for a chemical phenomenon? How reasonable are our views of chemical systems in terms of subunits, such as functional groups and individual molecules? How can one quantify the difference in physicochemical properties of functional units found in a different chemical environment? Are various effects on functional units in molecular systems additive? Can they be represented by pairwise potentials? Are there effects that cannot be represented in a simple picture of pairwise interactions? How can we obtain quantitative values for these effects? Many of these questions can be formulated in the language of many-body effects. They quantify the properties of subunits (fragments), referred to as one-body properties, pairwise interactions (two-body properties), couplings of two-body interactions described by three-body properties, and so on. By introducing the notion of fragments in the framework of quantum chemistry, one obtains two immense benefits: (a) chemists can finally relate to quantum chemistry, which now speaks their language, by discussing chemically interesting subunits and their interactions and (b) calculations become much faster due to a reduced computational scaling. For instance, the somewhat academic sounding question of the importance of three-body effects in water clusters is actually another way of asking how two hydrogen bonds affect each other, when they involve three water molecules. One aspect of this is the many-body charge transfer (CT), because the charge transfers in the two hydrogen bonds are coupled to each other (not independent). In this work, we provide a generalized view on the use of many-body expansions in fragment-based methods, focusing on the general aspects of the property expansion and a contraction of a

Attosecond-recollision-controlled selective fragmentation of polyatomic molecules.

Science.gov (United States)

Xie, Xinhua; Doblhoff-Dier, Katharina; Roither, Stefan; Schöffler, Markus S; Kartashov, Daniil; Xu, Huailiang; Rathje, Tim; Paulus, Gerhard G; Baltuška, Andrius; Gräfe, Stefanie; Kitzler, Markus

2012-12-14

Control over various fragmentation reactions of a series of polyatomic molecules (acetylene, ethylene, 1,3-butadiene) by the optical waveform of intense few-cycle laser pulses is demonstrated experimentally. We show both experimentally and theoretically that the responsible mechanism is inelastic ionization from inner-valence molecular orbitals by recolliding electron wave packets, whose recollision energy in few-cycle ionizing laser pulses strongly depends on the optical waveform. Our work demonstrates an efficient and selective way of predetermining fragmentation and isomerization reactions in polyatomic molecules on subfemtosecond time scales.

Fragmentation of high-energy ionic hydrogen clusters by single collision with helium

International Nuclear Information System (INIS)

Ouaskit, S.; Farizon, B.; Farizon, M.; Gaillard, M.J.; Chevarier, A.; Chevarier, N.; Gerlic, E.; Stern, M.

1994-09-01

Fragmentation of mass-selected 60-keV/amu-H n + induced by single collision with helium has been studied for various cluster sizes n (9, 13,21, 25, and 31). The absolute cross sections of the charged fragments H p + are measured from p equal to n-2. The deduced mass distributions are strongly different from those obtained at lower collision energy (where molecular evaporation is mainly involved) due to a strong production of ionic fragments with a size of p/n -τ , where A is the normalized fragment mass (p/n) and τ an exponent close to 2.6. (authors)

Advances in fragment-based drug discovery platforms.

Science.gov (United States)

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

Evolutions in fragment-based drug design: the deconstruction–reconstruction approach

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Chen, Haijun; Zhou, Xiaobin; Wang, Ailan; Zheng, Yunquan; Gao, Yu; Zhou, Jia

2014-01-01

Recent advances in the understanding of molecular recognition and protein–ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction–reconstruction strategy by utilizing privileged fragments of reported ligands. PMID:25263697

Complete photo-fragmentation of the deuterium molecule

International Nuclear Information System (INIS)

Weber, Thorsten; Czasch, Achim O.; Jagutzki, Ottmar; Muller, Alkis K.; Mergel, Volker; Kheifets, A.; Rotenberg, Eli; Meigs, George; Prior, Mike H.; Daveau, Sebastian; Landers, Allen; Cocke, C.L.; Osipov, Timur; Diez Muino, Ricardo; Schmidt-Bocking, Horst; Dorner, Reinhard

2004-01-01

All properties of molecules, from binding and excitation energies to their geometry, are determined by the highly correlated initial state wavefunction of the electrons and nuclei. Perhaps surprisingly, details of these correlations can be revealed by studying the break-up of these systems into their constituents. The fragmentation might be initiated by the absorption of a single photon [1, 2, 3, 4, 5, 6], collision with a charged particle [7, 8] or exposure to a strong laser pulse [9, 10]. If the exciting interaction is sufficiently understood, one can use the fragmentation process as a tool to learn about the bound initial state [11, 12]. However, often the interaction and the fragment motions pose formidable challenges to quantum theory [13, 14, 15]. Here we report the coincident measurement of the momenta of both nuclei and both electrons from the single photon induced fragmentation of the deuterium molecule. The results reveal that the correlated motion of the electrons is strongly dependent on the inter-nuclear separation in the molecular ground state at the instant of photon absorption

Self-gravitational Hydrodynamics with Three-dimensional Adaptive Mesh Refinement: Methodology and Applications to Molecular Cloud Collapse and Fragmentation

International Nuclear Information System (INIS)

Truelove, J.K.; Klein, R.I.; McKee, C.F.; Holliman, J.H. II; Truelove, J.K.; McKee, C.F.; Truelove, J.K.; Holliman, J.H. II; Klein, R.I.; Woods, D.T.; McKee, C.F.; Woods, D.T.; Howell, L.H.; Greenough, J.A.

1998-01-01

We describe a new code for numerical solution of three-dimensional self-gravitational hydrodynamics problems. This code utilizes the technique of local adaptive mesh refinement (AMR), employing multiple grids at multiple levels of resolution and automatically and dynamically adding and removing these grids as necessary to maintain adequate resolution. This technology allows solution of problems that would be prohibitively expensive with a code using fixed resolution, and it is more versatile and efficient than competing methods of achieving variable resolution. In particular, we apply this technique to simulate the collapse and fragmentation of a molecular cloud, a key step in star formation. The simulation involves many orders of magnitude of variation in length scale as fragments form at positions that are not a priori discernible from general initial conditions. In this paper, we describe the methodology behind this new code and present several illustrative applications. The criterion that guides the degree of adaptive mesh refinement is critical to the success of the scheme, and, for the isothermal problems considered here, we employ the Jeans condition for this purpose. By maintaining resolution finer than the local Jeans length, we set new benchmarks of accuracy by which to measure other codes on each problem we consider, including the uniform collapse of a finite pressured cloud. We find that the uniformly rotating, spherical clouds treated here first collapse to disks in the equatorial plane and then, in the presence of applied perturbations, form filamentary singularities that do not fragment while isothermal. Our results provide numerical confirmation of recent work by Inutsuka ampersand Miyama on this scenario of isothermal filament formation. copyright copyright 1998. The American Astronomical Society

Determination of fragment orbitals and LCFO MO's in semiempirical methods with overlap matrices

International Nuclear Information System (INIS)

Konstantinavicius, K.V.; Lazauskas, V.M.

1988-01-01

We propose a technique for a fragment stage solution of the Roothaan equations, allowing us to obtain fragment orbitals (FO's) and to form molecular orbitals (LCFO MO'S) for the molecule from them. As an example, in the Mulliken-Wolfsberg-Helmholtz (MWH) approximation we obtain the orbitals for fragments of the simplest hydrocarbon molecules and we compare them with the FO's found in the CNDO/2 approximation. We discuss the possibilities in perturbation theory for joining the fragments and for study of the properties of the molecules in the FO basis

Cytological preparations for molecular analysis: A review of technical procedures, advantages and limitations for referring samples for testing.

Science.gov (United States)

da Cunha Santos, G; Saieg, M A; Troncone, G; Zeppa, P

2018-04-01

Minimally invasive procedures such as endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) must yield not only good quality and quantity of material for morphological assessment, but also an adequate sample for analysis of molecular markers to guide patients to appropriate targeted therapies. In this context, cytopathologists worldwide should be familiar with minimum requirements for refereeing cytological samples for testing. The present manuscript is a review with comprehensive description of the content of the workshop entitled Cytological preparations for molecular analysis: pre-analytical issues for EBUS TBNA, presented at the 40th European Congress of Cytopathology in Liverpool, UK. The present review emphasises the advantages and limitations of different types of cytology substrates used for molecular analysis such as archival smears, liquid-based preparations, archival cytospin preparations and FTA (Flinders Technology Associates) cards, as well as their technical requirements/features. These various types of cytological specimens can be successfully used for an extensive array of molecular studies, but the quality and quantity of extracted nucleic acids rely directly on adequate pre-analytical assessment of those samples. In this setting, cytopathologists must not only be familiar with the different types of specimens and associated technical procedures, but also correctly handle the material provided by minimally invasive procedures, ensuring that there is sufficient amount of material for a precise diagnosis and correct management of the patient through personalised care. © 2018 John Wiley & Sons Ltd.

Stathmin 1/2-triggered microtubule loss mediates Golgi fragmentation in mutant SOD1 motor neurons

NARCIS (Netherlands)

Bellouze, Sarah; Baillat, Gilbert; Buttigieg, Dorothée; de la Grange, Pierre; Rabouille, Catherine; Haase, Georg

2016-01-01

BACKGROUND: Pathological Golgi fragmentation represents a constant pre-clinical feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) but its molecular mechanisms remain hitherto unclear. RESULTS: Here, we show that the severe Golgi fragmentation in transgenic

Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors.

Science.gov (United States)

Kwiatkowski, Jacek; Liu, Boping; Tee, Doris Hui Ying; Chen, Guoying; Ahmad, Nur Huda Binte; Wong, Yun Xuan; Poh, Zhi Ying; Ang, Shi Hua; Tan, Eldwin Sum Wai; Ong, Esther Hq; Nurul Dinie; Poulsen, Anders; Pendharkar, Vishal; Sangthongpitag, Kanda; Lee, May Ann; Sepramaniam, Sugunavathi; Ho, Soo Yei; Cherian, Joseph; Hill, Jeffrey; Keller, Thomas H; Hung, Alvin W

2018-05-24

Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure-activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.

Fragmentation of small molecules induced by 46 keV/amu N+ and N2+ projectiles

International Nuclear Information System (INIS)

Kovacs, S.T.S.; Juhasz, Z.; Herczku, P.; Sulik, B.

2012-01-01

Complete text of publication follows. Collisional molecule fragmentation experiments has gain increasing attention in several research and applied fields. In order to understand the fundamental processes of molecule fragmentation one has to start with collisions of small few-atomic molecules. Moreover, fragments of small molecules such as water can cause damages of large molecules (DNA) very effectively in living tissues. In the last few years a new experimental setup was developed at Atomki. It was designed especially for molecule fragmentation experiments. Now the measurements using this system are running routinely. In 2012 the studied targets were water vapor, methane and nitrogen gases, injected into the collision area by an effusive molecular gas jet system. 650 keV N + and 1,3 MeV N 2 + ions were used as projectiles produced by the VdG-5 electrostatic accelerator. The velocity of the two types of projectiles was the same. Energy and angular distribution of the produced fragments was measured by an energy dispersive electrostatic spectrometer. For atomic ionization a symmetric, diatomic molecular projectile (e.g. N 2 + ) yields about twice more electrons compared to those of singly charged ion projectiles of the same atom (N + ) at the same velocity. In such cases the two atomic centers in the molecular ion can be considered as two individual atomic centers. For the fragmentation of molecular targets the picture is not so simple because in this case close collision of two extended systems is investigated. As figure 1 and 2 show, the measured yields for molecular projectile is not simply twice of the ones for atomic projectile. The shape of the energy spectra are different. The measured data are under evaluation. Acknowledgements. This work was supported by the Hungarian National Science Foundation OTKA (Grant: K73703) and by the TAMOP-4.2.2/B-10/1-2010-0024 project. The project is cofinanced by the European Union and the European Social Fund.

Fragmentation mechanism reflecting the cluster structure of {sup 19}B

Energy Technology Data Exchange (ETDEWEB)

Takemoto, H.; Horiuchi, H. [Kyoto Univ., Dept. of Physics, Kyoto (Japan); Ono, A.

1999-08-01

Clustering structure of neutron dripline nucleus {sup 19}B which was predicted theoritically is investigated by studying the fragmentation reaction of {sup 19}B. We compare {sup 19}B fragmentation with {sup 13}B fragmentation in {sup 19}B + {sup 14}N and {sup 13}B + {sup 14}N reactions by using antisymmetrized molecular dynamics, where {sup 13}B has no clustering feature in its structure. We find that the cluster structure of the {sup 19}B nucleus is reflected in its fragmentation as the simultaneous production of He and Li isotopes. Furthermore we investigate the dependence of the cluster decay of {sup 19}B on the incident energy, and find that the cluster structure of {sup 19}B in its ground state is more reflected in lower incident-energy reactions. (author)

Site Identification by Ligand Competitive Saturation (SILCS) simulations for fragment-based drug design.

Science.gov (United States)

Faller, Christina E; Raman, E Prabhu; MacKerell, Alexander D; Guvench, Olgun

2015-01-01

Fragment-based drug design (FBDD) involves screening low molecular weight molecules ("fragments") that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind nonoverlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR and X-ray crystallography, have proven very useful but can be expensive in terms of time, materials, and labor. Accordingly, a variety of computational FBDD approaches have been developed that provide different levels of detail and accuracy.The Site Identification by Ligand Competitive Saturation (SILCS) method of computational FBDD uses all-atom explicit-solvent molecular dynamics (MD) simulations to identify fragment binding. The target is "soaked" in an aqueous solution with multiple fragments having different identities. The resulting computational competition assay reveals what small molecule types are most likely to bind which regions of the target. From SILCS simulations, 3D probability maps of fragment binding called "FragMaps" can be produced. Based on the probabilities relative to bulk, SILCS FragMaps can be used to determine "Grid Free Energies (GFEs)," which provide per-atom contributions to fragment binding affinities. For essentially no additional computational overhead relative to the production of the FragMaps, GFEs can be used to compute Ligand Grid Free Energies (LGFEs) for arbitrarily complex molecules, and these LGFEs can be used to rank-order the molecules in accordance with binding affinities.

Site Identification by Ligand Competitive Saturation (SILCS) Simulations for Fragment-Based Drug Design

OpenAIRE

Faller, Christina E.; Raman, E. Prabhu; MacKerell, Alexander D.; Guvench, Olgun

2015-01-01

Fragment-based drug design (FBDD) involves screening low molecular weight molecules (“fragments”) that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind non-overlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR ...

Residue preference mapping of ligand fragments in the Protein Data Bank.

Science.gov (United States)

Wang, Lirong; Xie, Zhaojun; Wipf, Peter; Xie, Xiang-Qun

2011-04-25

The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables unprecedented possibilities for new insights. Herein, we applied molecule-fragmentation algorithms to split the ligands extracted from PDB crystal structures into small fragments. Subsequently, we have developed a ligand fragment and residue preference mapping (LigFrag-RPM) algorithm to map the profiles of the interactions between these fragments and the 20 proteinogenic amino acid residues. A total of 4032 fragments were generated from 71 798 PDB ligands by a ring cleavage (RC) algorithm. Among these ligand fragments, 315 unique fragments were characterized with the corresponding fragment-residue interaction profiles by counting residues close to these fragments. The interaction profiles revealed that these fragments have specific preferences for certain types of residues. The applications of these interaction profiles were also explored and evaluated in case studies, showing great potential for the study of protein-ligand interactions and drug design. Our studies demonstrated that the fragment-residue interaction profiles generated from the PDB ligand fragments can be used to detect whether these fragments are in their favorable or unfavorable environments. The algorithm for a ligand fragment and residue preference mapping (LigFrag-RPM) developed here also has the potential to guide lead chemistry modifications as well as binding residues predictions.

Fragment-based lead generation: identification of seed fragments by a highly efficient fragment screening technology

Science.gov (United States)

Neumann, Lars; Ritscher, Allegra; Müller, Gerhard; Hafenbradl, Doris

2009-08-01

For the detection of the precise and unambiguous binding of fragments to a specific binding site on the target protein, we have developed a novel reporter displacement binding assay technology. The application of this technology for the fragment screening as well as the fragment evolution process with a specific modelling based design strategy is demonstrated for inhibitors of the protein kinase p38alpha. In a fragment screening approach seed fragments were identified which were then used to build compounds from the deep-pocket towards the hinge binding area of the protein kinase p38alpha based on a modelling approach. BIRB796 was used as a blueprint for the alignment of the fragments. The fragment evolution of these deep-pocket binding fragments towards the fully optimized inhibitor BIRB796 included the modulation of the residence time as well as the affinity. The goal of our study was to evaluate the robustness and efficiency of our novel fragment screening technology at high fragment concentrations, compare the screening data with biochemical activity data and to demonstrate the evolution of the hit fragments with fast kinetics, into slow kinetic inhibitors in an in silico approach.

Distinctive and Complementary MS2 Fragmentation Characteristics for Identification of Sulfated Sialylated N-Glycopeptides by nanoLC-MS/MS Workflow

Science.gov (United States)

Kuo, Chu-Wei; Guu, Shih-Yun; Khoo, Kay-Hooi

2018-04-01

High sensitivity identification of sulfated glycans carried on specific sites of glycoproteins is an important requisite for investigation of molecular recognition events involved in diverse biological processes. However, aiming for resolving site-specific glycosylation of sulfated glycopeptides by direct LC-MS2 sequencing is technically most challenging. Other than the usual limiting factors such as lower abundance and ionization efficiency compared to analysis of non-glycosylated peptides, confident identification of sulfated glycopeptides among the more abundant non-sulfated glycopeptides requires additional considerations in the selective enrichment and detection strategies. Metal oxide has been applied to enrich phosphopeptides and sialylated glycopeptides, but its use to capture sulfated glycopeptides has not been investigated. Likewise, various complementary MS2 fragmentation modes have yet to be tested against sialylated and non-sialylated sulfoglycopeptides due to limited appropriate sample availability. In this study, we have investigated the feasibility of sequencing tryptic sulfated N-glycopeptide and its MS2 fragmentation characteristics by first optimizing the enrichment methods to allow efficient LC-MS detection and MS2 analysis by a combination of CID, HCD, ETD, and EThcD on hybrid and tribrid Orbitrap instruments. Characteristic sulfated glyco-oxonium ions and direct loss of sulfite from precursors were detected as evidences of sulfate modification. It is anticipated that the technical advances demonstrated in this study would allow a feasible extension of our sulfoglycomic analysis to sulfoglycoproteomics. [Figure not available: see fulltext.

Molecular identification of similar species of the genus Biomphalaria (Mollusca: Planorbidae determined by a polymerase chain reaction-restriction fragment length polymorphism

Directory of Open Access Journals (Sweden)

Caldeira Roberta Lima

1998-01-01

Full Text Available The freshwater snails Biomphalaria straminea, B. intermedia, B. kuhniana and B. peregrina, are morphologically similar; based on this similarity the first three species were therefore grouped in the complex B. straminea. The morphological identification of these species is based on characters such as vaginal wrinkling, relation between prepuce: penial sheath:deferens vas and number of muscle layers in the penis wall. In this study the polymerase chain reaction restriction fragment length polymorphism technique was used for molecular identification of these molluscs. This technique is based on the amplification of the internal transcribed spacer regions ITS1 e ITS2 of the ribosomal RNA gene and subsequent digestion of these fragments by restriction enzymes. Six enzymes were tested: Dde I, Mnl I, Hae III, Rsa I, Hpa II e Alu I. The restriction patterns obtained with DdeI presented the best profile for separation of the four species of Biomphalaria. The profiles obtained with all the enzymes were used to estimate the genetic distances among the species through analysis of common banding patterns.

Recent work with fast molecular-ion beams at Argonne National Laboratory

International Nuclear Information System (INIS)

Cooney, P.J.; Gemmell, D.S.; Groeneveld, K.O.; Kanter, E.P.; Pietsch, W.J.; Vager, Z.; Zabransky, B.J.

1979-01-01

Research in these areas during 1979 is summarized: (a) studies of molecular-ion dissociation in gaseous targets, (b) developing an understanding of the origins of central peaks and of the two phenomena of the transmission of fast molecular ions through thin foil targets and of the production of neutral fragments from collision-induced dissociation of fast molecular projectiles, (c) studies exploring the extent to which high-resolution measurements on dissociation fragments can be used to determine the stereochemical structures of the molecular ions in the incident beam, (d) extensive modifications to the beam-line and apparatus at the 4-MV Dynamitron so as to permit a wide variety of coincidence measurements on fragments from collision-induced molecular-ion dissociation

Developing a programme on molecular nuclear medicine. Proceedings of a technical meeting

International Nuclear Information System (INIS)

2007-07-01

been increasingly applied for revealing the different profiles of normal and affected cells or tissues and also for the following-up treatment of certain diseases like minimal residual disease (MRD). The detection of changes in the level of transcription of certain genes using this approach has been a useful tool for the early detection of disease, improving the patient survival. At the Technical Meeting on Developing a Medium to Long Term Programme on Molecular Nuclear Medicine, held in Vienna, 29 November - 1 December 2004, certain areas were selected as the best candidates to be included in the IAEA's programme in relation to their applicability and potential to improve human health. The IAEA will continue supporting training activities and fellowships, and encouraging developing Member States to take advantage of the use of isotopic advanced molecular techniques for the resolution of their health problems. This TECDOC contains useful information for health workers in the nuclear medicine and molecular biology fields. Previous IAEA publications, Nuclear Medicine Resources Manual (STI/PUB/1198), Radionuclides in Molecular Technology for Diagnosis of Communicable Diseases (IAEA-TECDOC-748), In Vitro Radionuclide Techniques in Medical Diagnosis (IAEA-TECDOC-1001) and Organization of a Radioisotope Based Molecular Biology Laboratory (IAEA-TECDOC-1528), are separately focused on nuclear medicine and molecular biology techniques applied to human diseases, while the present publication provides presentations on the advances of molecular nuclear medicine techniques

Dynamics of fragments and associated phenomena in heavy-ion collisions using a modified secondary algorithm

Energy Technology Data Exchange (ETDEWEB)

Kumar, Rohit [Department of Physics, Panjab University, Chandigarh-160014 (India)

2016-05-06

We discuss the stability of fragments identified by secondary algorithms used to construct fragments within quantum molecular dynamics model. For this purpose we employ three different algorithms for fragment identification. 1) The conventional minimum spanning tree (MST) method based on the spatial correlations, 2) an improved version of MST with additional binding energy constraints of cold nuclear matter, 3) and that of hot matter. We find significant role of thermal binding energies over cold matter binding energies. Significant role is observed for fragment multiplicities and stopping of fragments. Whereas insignificant effect is observed on fragment’s flow.

Virtual fragment preparation for computational fragment-based drug design.

Science.gov (United States)

Ludington, Jennifer L

2015-01-01

Fragment-based drug design (FBDD) has become an important component of the drug discovery process. The use of fragments can accelerate both the search for a hit molecule and the development of that hit into a lead molecule for clinical testing. In addition to experimental methodologies for FBDD such as NMR and X-ray Crystallography screens, computational techniques are playing an increasingly important role. The success of the computational simulations is due in large part to how the database of virtual fragments is prepared. In order to prepare the fragments appropriately it is necessary to understand how FBDD differs from other approaches and the issues inherent in building up molecules from smaller fragment pieces. The ultimate goal of these calculations is to link two or more simulated fragments into a molecule that has an experimental binding affinity consistent with the additive predicted binding affinities of the virtual fragments. Computationally predicting binding affinities is a complex process, with many opportunities for introducing error. Therefore, care should be taken with the fragment preparation procedure to avoid introducing additional inaccuracies.This chapter is focused on the preparation process used to create a virtual fragment database. Several key issues of fragment preparation which affect the accuracy of binding affinity predictions are discussed. The first issue is the selection of the two-dimensional atomic structure of the virtual fragment. Although the particular usage of the fragment can affect this choice (i.e., whether the fragment will be used for calibration, binding site characterization, hit identification, or lead optimization), general factors such as synthetic accessibility, size, and flexibility are major considerations in selecting the 2D structure. Other aspects of preparing the virtual fragments for simulation are the generation of three-dimensional conformations and the assignment of the associated atomic point charges.

Fragmentation of suddenly heated liquids in ICF reactors. Revision 1

International Nuclear Information System (INIS)

Blink, J.A.; Hoover, W.G.

1985-01-01

Fragmentation of free liquids in Inertial Confinement Fusion reactors could determine the upper bound on reactor pulse rate because increased surface area will enhance the cooling and condensation of coolant ablated by the fusion x rays. Relaxation from the suddenly (neutron) heated state will move a liquid into the negative pressure region under the liquid-vapor P-V dome. The resulting expansion in a diverging geometry will hydrodynamically force the liquid to fragment, with vapor then forming from the new surfaces to fill the cavities. An energy minimization model is used to determine the fragment size that produces the least amount of non-fragment-center-of-mass energy; i.e., the sum of the surface and dilational kinetic energies. This model predicts fragmentation dependence on original system size and amount of isochoric heating as well as liquid density, Grueneisen parameter, surface tension, and sound speed. A two dimensional molecular dynamics code was developed to test the model at a microscopic scale for the Lennard-Jones fluid with its two adjustable constants chosen to represent lithium

Cationization increases brain distribution of an amyloid-beta protofibril selective F(ab')2 fragment

OpenAIRE

Syvänen, Stina; Edén, Desireé; Sehlin, Dag

2017-01-01

Antibodies and fragments thereof are, because of high selectivity for their targets, considered as potential therapeutics and biomarkers for several neurological disorders. However, due to their large molecular size, antibodies/fragments do not easily penetrate into the brain. The aim of the present study was to improve the brain distribution via adsorptive-mediated transcytosis of an amyloid-beta (A beta) protofibril selective F(ab')2 fragment (F(ab')2-h158). F(ab')2-h158 was cationized to d...

Quantum molecular dynamics: Numerical methods and physical study of the structure, thermodynamics, stability and fragmentation of sodium metallic clusters

International Nuclear Information System (INIS)

Blaise, Philippe

1998-01-01

The aim of this thesis is to study metallic sodium clusters by numerical simulation. We have developed two ab initio molecular dynamics programs within the formalism of density functional theory. The first is based on the semi-classical extended Thomas-Fermi approach. We use a real-space grid and a Car-Parrinello-like scheme. The computational cost is O(N), and we have built a pseudopotential that speeds up the calculations. By neglecting quantum shell effects, we are able to study a very large set of clusters. We show that sodium cluster energies fit well a liquid drop formula, by adjusting a few parameters. We have investigated breathing modes, surface oscillations and the net charge density. We have shown that the surface energy varies strongly with temperature, and that clusters have a lower melting point than bulk material. We have calculated fission barriers by a constraint method. The second program is based on the quantum Kohn-Sham approach. We use a real-space grid, and combine a generalized Broyden scheme for assuring self-consistency with an iterative Davidson-Lanczos algorithm for solving the Eigen-problem. The cost of the method is much higher. First of all, we have calculated some stable structures for small clusters and their energetics. We obtained very good agreement with previous works. Then, we have investigated highly charged cluster dynamics. We have identified a chaotic fission process. For high fissility systems, we observe a multi-fragmentation dynamics and we find preferential emission of monomers on a characteristic time scale less than a pico-second. This has been simulated for the first time, with the help of our adaptive grid method which follows each fragment as they move apart during the fragmentation. (author)

Validation of Geant4 fragmentation for Heavy Ion Therapy

Science.gov (United States)

Bolst, David; Cirrone, Giuseppe A. P.; Cuttone, Giacomo; Folger, Gunter; Incerti, Sebastien; Ivanchenko, Vladimir; Koi, Tatsumi; Mancusi, Davide; Pandola, Luciano; Romano, Francesco; Rosenfeld, Anatoly B.; Guatelli, Susanna

2017-10-01

12C ion therapy has had growing interest in recent years for its excellent dose conformity. However at therapeutic energies, which can be as high as 400 MeV/u, carbon ions produce secondary fragments. For an incident 400 MeV/u 12C ion beam, ∼ 70 % of the beam will undergo fragmentation before the Bragg Peak. The dosimetric and radiobiological impact of these fragments must be accurately characterised, as it can result in increasing the risk of secondary cancer for the patient as well as altering the relative biological effectiveness. This work investigates the accuracy of three different nuclear fragmentation models available in the Monte Carlo Toolkit Geant4, the Binary Intranuclear Cascade (BIC), the Quantum Molecular Dynamics (QMD) and the Liege Intranuclear Cascade (INCL++). The models were benchmarked against experimental data for a pristine 400 MeV/u 12C beam incident upon a water phantom, including fragment yield, angular and energy distribution. For fragment yields the three alternative models agreed between ∼ 5 and ∼ 35 % with experimental measurements, the QMD using the "Frag" option gave the best agreement for lighter fragments but had reduced agreement for larger fragments. For angular distributions INCL++ was seen to provide the best agreement among the models for all elements with the exception of Hydrogen, while BIC and QMD was seen to produce broader distributions compared to experiment. BIC and QMD performed similar to one another for kinetic energy distributions while INCL++ suffered from producing lower energy distributions compared to the other models and experiment.

From small to powerful: the fragments universe and its "chem-appeal".

Science.gov (United States)

Sancineto, Luca; Massari, Serena; Iraci, Nunzio; Tabarrini, Oriana

2013-01-01

While increasing expertise in molecular biology and proteomics is markedly speeding up the target elucidation process, various strategies have been proposed that improve the chances of identifying active molecules. Among them, the Fragment Based Drug Design (FBDD) is surely worth noting. The FBDD entails the screening of a small number of low molecular weight compounds in the hopes of finding even low affine but high ligand efficient fragments that have high probability to became drug candidates. Since 1996, when the first paper on FBDD was reported, the potentialities of this strategy became progressively more apparent as testified by the growing number of publications. Many drug discovery projects started with the identification of fragments which after the optimization gave many molecules close to the approval and one marketed drug Vemurafenib, approved in 2011. A preamble that highlights the advantages of dealing with simple and "very small" molecules over conventional drug-like compounds will be herein given prior to discussing the canonical FBDD stages, from fragment library design, to the different screening methods concluding with the various optimization strategies, in an attempt to illustrate the whole FBDD workflow while discussing the most recent and successful applications. While this review is a tribute to the success achieved by the researchers in this field, it is particularly addressed to scientists who want to become aware of the versatility and potentiality of FBDD.

Applicability of effective fragment potential version 2 - Molecular dynamics (EFP2-MD) simulations for predicting excess properties of mixed solvents

Science.gov (United States)

Kuroki, Nahoko; Mori, Hirotoshi

2018-02-01

Effective fragment potential version 2 - molecular dynamics (EFP2-MD) simulations, where the EFP2 is a polarizable force field based on ab initio electronic structure calculations were applied to water-methanol binary mixture. Comparing EFP2s defined with (aug-)cc-pVXZ (X = D,T) basis sets, it was found that large sets are necessary to generate sufficiently accurate EFP2 for predicting mixture properties. It was shown that EFP2-MD could predict the excess molar volume. Since the computational cost of EFP2-MD are far less than ab initio MD, the results presented herein demonstrate that EFP2-MD is promising for predicting physicochemical properties of novel mixed solvents.

Quantum mechanical fragment methods based on partitioning atoms or partitioning coordinates.

Science.gov (United States)

Wang, Bo; Yang, Ke R; Xu, Xuefei; Isegawa, Miho; Leverentz, Hannah R; Truhlar, Donald G

2014-09-16

Conspectus The development of more efficient and more accurate ways to represent reactive potential energy surfaces is a requirement for extending the simulation of large systems to more complex systems, longer-time dynamical processes, and more complete statistical mechanical sampling. One way to treat large systems is by direct dynamics fragment methods. Another way is by fitting system-specific analytic potential energy functions with methods adapted to large systems. Here we consider both approaches. First we consider three fragment methods that allow a given monomer to appear in more than one fragment. The first two approaches are the electrostatically embedded many-body (EE-MB) expansion and the electrostatically embedded many-body expansion of the correlation energy (EE-MB-CE), which we have shown to yield quite accurate results even when one restricts the calculations to include only electrostatically embedded dimers. The third fragment method is the electrostatically embedded molecular tailoring approach (EE-MTA), which is more flexible than EE-MB and EE-MB-CE. We show that electrostatic embedding greatly improves the accuracy of these approaches compared with the original unembedded approaches. Quantum mechanical fragment methods share with combined quantum mechanical/molecular mechanical (QM/MM) methods the need to treat a quantum mechanical fragment in the presence of the rest of the system, which is especially challenging for those parts of the rest of the system that are close to the boundary of the quantum mechanical fragment. This is a delicate matter even for fragments that are not covalently bonded to the rest of the system, but it becomes even more difficult when the boundary of the quantum mechanical fragment cuts a bond. We have developed a suite of methods for more realistically treating interactions across such boundaries. These methods include redistributing and balancing the external partial atomic charges and the use of tuned fluorine

Fragment-based screening by protein crystallography: successes and pitfalls.

Science.gov (United States)

Chilingaryan, Zorik; Yin, Zhou; Oakley, Aaron J

2012-10-08

Fragment-based drug discovery (FBDD) concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS) will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.

Fragment-Based Screening by Protein Crystallography: Successes and Pitfalls

Directory of Open Access Journals (Sweden)

Aaron J. Oakley

2012-10-01

Full Text Available Fragment-based drug discovery (FBDD concerns the screening of low-molecular weight compounds against macromolecular targets of clinical relevance. These compounds act as starting points for the development of drugs. FBDD has evolved and grown in popularity over the past 15 years. In this paper, the rationale and technology behind the use of X-ray crystallography in fragment based screening (FBS will be described, including fragment library design and use of synchrotron radiation and robotics for high-throughput X-ray data collection. Some recent uses of crystallography in FBS will be described in detail, including interrogation of the drug targets β-secretase, phenylethanolamine N-methyltransferase, phosphodiesterase 4A and Hsp90. These examples provide illustrations of projects where crystallography is straightforward or difficult, and where other screening methods can help overcome the limitations of crystallography necessitated by diffraction quality.

An Efficient Method to Evaluate Intermolecular Interaction Energies in Large Systems Using Overlapping Multicenter ONIOM and the Fragment Molecular Orbital Method

Science.gov (United States)

Asada, Naoya; Fedorov, Dmitri G.; Kitaura, Kazuo; Nakanishi, Isao; Merz, Kenneth M.

2012-01-01

We propose an approach based on the overlapping multicenter ONIOM to evaluate intermolecular interaction energies in large systems and demonstrate its accuracy on several representative systems in the complete basis set limit at the MP2 and CCSD(T) level of theory. In the application to the intermolecular interaction energy between insulin dimer and 4′-hydroxyacetanilide at the MP2/CBS level, we use the fragment molecular orbital method for the calculation of the entire complex assigned to the lowest layer in three-layer ONIOM. The developed method is shown to be efficient and accurate in the evaluation of the protein-ligand interaction energies. PMID:23050059

The rise of fragment-based drug discovery.

Science.gov (United States)

Murray, Christopher W; Rees, David C

2009-06-01

The search for new drugs is plagued by high attrition rates at all stages in research and development. Chemists have an opportunity to tackle this problem because attrition can be traced back, in part, to the quality of the chemical leads. Fragment-based drug discovery (FBDD) is a new approach, increasingly used in the pharmaceutical industry, for reducing attrition and providing leads for previously intractable biological targets. FBDD identifies low-molecular-weight ligands (∼150 Da) that bind to biologically important macromolecules. The three-dimensional experimental binding mode of these fragments is determined using X-ray crystallography or NMR spectroscopy, and is used to facilitate their optimization into potent molecules with drug-like properties. Compared with high-throughput-screening, the fragment approach requires fewer compounds to be screened, and, despite the lower initial potency of the screening hits, offers more efficient and fruitful optimization campaigns. Here, we review the rise of FBDD, including its application to discovering clinical candidates against targets for which other chemistry approaches have struggled.

Fragment-based virtual screening approach and molecular dynamics simulation studies for identification of BACE1 inhibitor leads.

Science.gov (United States)

Manoharan, Prabu; Ghoshal, Nanda

2018-05-01

Traditional structure-based virtual screening method to identify drug-like small molecules for BACE1 is so far unsuccessful. Location of BACE1, poor Blood Brain Barrier permeability and P-glycoprotein (Pgp) susceptibility of the inhibitors make it even more difficult. Fragment-based drug design method is suitable for efficient optimization of initial hit molecules for target like BACE1. We have developed a fragment-based virtual screening approach to identify/optimize the fragment molecules as a starting point. This method combines the shape, electrostatic, and pharmacophoric features of known fragment molecules, bound to protein conjugate crystal structure, and aims to identify both chemically and energetically feasible small fragment ligands that bind to BACE1 active site. The two top-ranked fragment hits were subjected for a 53 ns MD simulation. Principle component analysis and free energy landscape analysis reveal that the new ligands show the characteristic features of established BACE1 inhibitors. The potent method employed in this study may serve for the development of potential lead molecules for BACE1-directed Alzheimer's disease therapeutics.

Incorporation of charge transfer into the explicit polarization fragment method by grand canonical density functional theory.

Science.gov (United States)

Isegawa, Miho; Gao, Jiali; Truhlar, Donald G

2011-08-28

Molecular fragmentation algorithms provide a powerful approach to extending electronic structure methods to very large systems. Here we present a method for including charge transfer between molecular fragments in the explicit polarization (X-Pol) fragment method for calculating potential energy surfaces. In the conventional X-Pol method, the total charge of each fragment is preserved, and charge transfer between fragments is not allowed. The description of charge transfer is made possible by treating each fragment as an open system with respect to the number of electrons. To achieve this, we applied Mermin's finite temperature method to the X-Pol wave function. In the application of this method to X-Pol, the fragments are open systems that partially equilibrate their number of electrons through a quasithermodynamics electron reservoir. The number of electrons in a given fragment can take a fractional value, and the electrons of each fragment obey the Fermi-Dirac distribution. The equilibrium state for the electrons is determined by electronegativity equalization with conservation of the total number of electrons. The amount of charge transfer is controlled by re-interpreting the temperature parameter in the Fermi-Dirac distribution function as a coupling strength parameter. We determined this coupling parameter so as to reproduce the charge transfer energy obtained by block localized energy decomposition analysis. We apply the new method to ten systems, and we show that it can yield reasonable approximations to potential energy profiles, to charge transfer stabilization energies, and to the direction and amount of charge transferred. © 2011 American Institute of Physics

Accommodating error analysis in comparison and clustering of molecular fingerprints.

Science.gov (United States)

Salamon, H; Segal, M R; Ponce de Leon, A; Small, P M

1998-01-01

Molecular epidemiologic studies of infectious diseases rely on pathogen genotype comparisons, which usually yield patterns comprising sets of DNA fragments (DNA fingerprints). We use a highly developed genotyping system, IS6110-based restriction fragment length polymorphism analysis of Mycobacterium tuberculosis, to develop a computational method that automates comparison of large numbers of fingerprints. Because error in fragment length measurements is proportional to fragment length and is positively correlated for fragments within a lane, an align-and-count method that compensates for relative scaling of lanes reliably counts matching fragments between lanes. Results of a two-step method we developed to cluster identical fingerprints agree closely with 5 years of computer-assisted visual matching among 1,335 M. tuberculosis fingerprints. Fully documented and validated methods of automated comparison and clustering will greatly expand the scope of molecular epidemiology.

Multiphoton ionization and fragmentation study of acetone using 308 nm laser radiation

Science.gov (United States)

Liu Houxiang, Li Shutao, Han Jingcheng, Zhu Rong, Guan Yifu, Wu Cunkai

1988-10-01

Multiphoton ionization and fragmentation (MPI-F) of acetone molecules using 308 nm laser radiation was studied by using a molecular beam and quadrupole mass spectrometer. The ion peaks of acetone molecule appear at m/e=15 and 43, corresponding to the two fragments CH3+ and CH3CO+. It is considered that these two ions are, respectively, formed by direct (2+1) and 2-photon ionization of methyl and acetyl radicals, generated by photodissociation of acetone molecule.

Photo fragmentation dynamics of small argon clusters and biological molecular: new tools by trapping and vectorial correlation

International Nuclear Information System (INIS)

Lepere, V.

2006-09-01

The present work concerns the building up of a complex set-up whose aim being the investigation of the photo fragmentation of ionised clusters and biological molecules. This new tool is based on the association of several techniques. Two ion sources are available: clusters produced in a supersonic beam are ionised by 70 eV electrons while ions of biological interest are produced in an 'electro-spray'. Ro-vibrational cooling is achieved in a 'Zajfman' electrostatic ion trap. The lifetime of ions can also be measured using the trap. Two types of lasers are used to excite the ionised species: the femtosecond laser available at the ELYSE facilities and a nanosecond laser. Both lasers have a repetition rate of 1 kHz. The neutral and ionised fragments are detected in coincidence using a sophisticated detection system allowing time and localisation of the various fragments to be determined. With such a tool, I was able to investigate in details the fragmentation dynamics of ionised clusters and bio-molecules. The first experiments deal with the measurement of the lifetime of the Ar 2+ dimer II(1/2)u metastable state. The relative population of this state was also determined. The Ar 2+ and Ar 3+ photo-fragmentation was then studied and electronic transitions responsible for their dissociation identified. The detailed analysis of our data allowed to distinguish the various fragmentation mechanisms. Finally, a preliminary investigation of the protonated tryptamine fragmentation is presented. (author)

Automated quantum chemistry based molecular dynamics simulations of electron ionization induced fragmentations of the nucleobases Uracil, Thymine, Cytosine, and Guanine.

Science.gov (United States)

Grimme, Stefan; Bauer, Christopher Alexander

2015-01-01

The gas-phase decomposition pathways of electron ionization (EI)-induced radical cations of the nucleobases uracil, thymine, cytosine, and guanine are investigated by means of mixed quantum-classical molecular dynamics. No preconceived fragmentation channels are used in the calculations. The results compare well to a plethora of experimental and theoretical data for these important biomolecules. With our combined stochastic and dynamic approach, one can access in an unbiased way the energetically available decomposition mechanisms. Additionally, we are able to separate the EI mass spectra of different tautomers of cytosine and guanine. Our method (previously termed quantum chemistry electron ionization mass spectra) reproduces free nucleobase experimental mass spectra well and provides detailed mechanistic in-sight into high-energy unimolecular decomposition processes.

Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy

DEFF Research Database (Denmark)

Sun, S; Henriksen, K; Karsdal, M A

2014-01-01

used to assess biological and clinical relevance. RESULTS: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy...... model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up...... at a 16.4 (±4.6) % increase at day 47. CONCLUSIONS: We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy....

Fragmentation of organic ions bearing fixed multiple charges observed in MALDI MS.

Science.gov (United States)

Lou, Xianwen; Li, Bao; de Waal, Bas F M; Schill, Jurgen; Baker, Matthew B; Bovee, Ralf A A; van Dongen, Joost L J; Milroy, Lech-Gustav; Meijer, E W

2018-01-01

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) was used to analyze a series of synthetic organic ions bearing fixed multiple charges. Despite the multiple intrinsic charges, only singly charged ions were recorded in each case. In addition to the pseudo-molecular ions formed by counterion adduction, deprotonation and electron capture, a number of fragment ions were also observed. Charge splitting by fragmentation was found to be a viable route for charge reduction leading to the formation of the observed singly charged fragment ions. Unlike multivalent metal ions, organic ions can rearrange and/or fragment during charge reduction. This fragmentation process will evidently complicate the interpretation of the MALDI MS spectrum. Because MALDI MS is usually considered as a soft ionization technique, the fragment ion peaks can easily be erroneously interpreted as impurities. Therefore, the awareness and understanding of the underlying MALDI-induced fragmentation pathways is essential for a proper interpretation of the corresponding mass spectra. Due to the fragment ions generated during charge reduction, special care should be taken in the MALDI MS analysis of multiply charged ions. In this work, the possible mechanisms by which the organic ions bearing fixed multiple charges fragment are investigated. With an improved understanding of the fragmentation mechanisms, MALDI TOF MS should still be a useful technique for the characterization of organic ions with fixed multiple charges. Copyright © 2017 John Wiley & Sons, Ltd.

Technical and operational assessment of molecular nanotechnology for space operations

Science.gov (United States)

McKendree, Thomas Lawrence

2001-07-01

This study assesses the performance of conventional technology and three levels of molecular nanotechnology (MNT) for space operations. The measures of effectiveness are technical performance parameters for five space transportation architectures, and the total logistics cost for an evaluation scenario with mining, market and factory locations on the Moon, Mars and asteroids. On these measures of effectiveness, improvements of 2--4 orders of magnitude are seen in chemical rockets, solar electric ion engines, solar sail accelerations (but not transit times), and in structural masses for planetary skyhooks and towers. Improvements in tether performance and logistics costs are nearer to 1 order of magnitude. Appendices suggest additional improvements may be possible in space mining, closed-environment life support, flexible operations, and with other space transportation architectures. In order to assess logistics cost, this research extends the facility location problem of location theory to orbital space. This extension supports optimal siting of a single facility serving circular, coplanar orbits, locations in elliptic planetary and moon orbits, and heuristic siting of multiple facilities. It focuses on conventional rocket transportation, and on high performance rockets supplying at least 1 m/s2 acceleration and 500,000 m/s exhaust velocity. Mathematica implementations are provided in appendices. Simple MNT allows diamond and buckytube construction. The main benefits are in chemical rocket performance, solar panel specific power, solar electric ion engine performance, and skyhook and tower structural masses. Complex MNT allows very small machinery, permitting large increases in solar panel specific power, which enables solar electric ion engines that are high performance rockets, and thus reduces total logistics costs an order of magnitude. Most Advance MNT allows molecular manufacturing, which enables self-repair, provides at least marginal improvements in nearly

Degradation of a field index by introduction of weakly ferromagnetic material fragment

International Nuclear Information System (INIS)

Pillet, E.

1957-06-01

After having recalled a problem met on chamber doors made of dural (eddy currents resulted in a too important index degradation) which lead to the replacement of dural by a magnetic stainless steel, this technical note report a study which aimed at determining whether the corresponding low magnetism would create a new degradation, but opposite to the previous one. The author first outlines why conventional methods are insufficient for this kind of assessment, and proposes a differential method to apply the superposition principle. This method results in the determination of the reduced magnetisation within the fragment, and in the study of the field created by this magnetisation. The author reports an approximate calculation, and then proposes another approximate method which is based on the determination of the rate between degradation due to fragment magnetisation and that due to eddy current induced in the same fragment

Jet fragmentation

International Nuclear Information System (INIS)

Saxon, D.H.

1985-10-01

The paper reviews studies on jet fragmentation. The subject is discussed under the topic headings: fragmentation models, charged particle multiplicity, bose-einstein correlations, identified hadrons in jets, heavy quark fragmentation, baryon production, gluon and quark jets compared, the string effect, and two successful models. (U.K.)

BARNARD 59: NO EVIDENCE FOR FURTHER FRAGMENTATION

Energy Technology Data Exchange (ETDEWEB)

Roman-Zuniga, C. G. [Instituto de Astronomia, Universidad Nacional Autonoma de Mexico, Km 103 Carr. Tijuana-Ensenada, Ensenada BC 22860 (Mexico); Frau, P.; Girart, J. M. [Institut de Ciencies de l' Espai (CSIC-IEEC), Campus UAB, Facultat de Ciencies, Torre C-5p, 08193 Bellaterra, Catalunya (Spain); Alves, Joao F., E-mail: croman@astrosen.unam.mx [Institute of Astronomy, University of Vienna, Tuerkenschanzstr. 17, 1180 Vienna (Austria)

2012-03-10

The dense molecular clump at the center of the Barnard 59 (B59) complex is the only region in the Pipe Nebula that has formed a small, stellar cluster. The previous analysis of a high-resolution near-IR dust extinction map revealed that the nuclear region in B59 is a massive, mostly quiescent clump of 18.9 M{sub Sun }. The clump shows a monolithic profile, possibly indicating that the clump is on the way to collapse, with no evident fragmentation that could lead to another group of star systems. In this paper, we present new analysis that compares the dust extinction map with a new dust emission radio-continuum map of higher spatial resolution. We confirm that the clump does not show any significant evidence for prestellar fragmentation at scales smaller than those probed previously.

BARNARD 59: NO EVIDENCE FOR FURTHER FRAGMENTATION

International Nuclear Information System (INIS)

Román-Zúñiga, C. G.; Frau, P.; Girart, J. M.; Alves, João F.

2012-01-01

The dense molecular clump at the center of the Barnard 59 (B59) complex is the only region in the Pipe Nebula that has formed a small, stellar cluster. The previous analysis of a high-resolution near-IR dust extinction map revealed that the nuclear region in B59 is a massive, mostly quiescent clump of 18.9 M ☉ . The clump shows a monolithic profile, possibly indicating that the clump is on the way to collapse, with no evident fragmentation that could lead to another group of star systems. In this paper, we present new analysis that compares the dust extinction map with a new dust emission radio-continuum map of higher spatial resolution. We confirm that the clump does not show any significant evidence for prestellar fragmentation at scales smaller than those probed previously.

Quantum Correlated Multi-Fragment Reaction Imaging

Energy Technology Data Exchange (ETDEWEB)

Feagin, James M. [California State Univ., Fullerton, CA (United States)

2017-06-30

This grant supported research in basic atomic, molecular and optical physics related to the interactions of atoms with particles and fields. This report will focus on the 12 year period from 2004 to 2017, although the DOE–BES has supported my research every year since 1986. All of the support from the grant was used to pay summer salaries of the PI and students and travel to conferences and meetings. The results were in the form of publications in peer reviewed journals as well as conference invited talks and colloquiums. There were 12 peer reviewed publications in these 12+ years. Innovations in few-body science at molecular and nano levels are a critical component of on- going efforts to establish sustainable environmental and energy resources. The varied research paths taken will require the development of basic science on broad fronts with increasing flexi- bility to crossover technologies. We thus worked to extract understanding and quantum control of few-body microscopic systems based on our long-time experience with more conventional studies of correlated electrons and ions. Given the enormous advances over the past 20 years to our understanding of quantum cor- relations with photon interferometry, AMO collision science generally is ready to move beyond the one-particle, single-port momentum detection that has dominated collision physics since Rutherford. Nevertheless, our familiar theoretical tools for collision theory need to be up- graded to incorporate these more generalized measurement formalisms and ultimately to give incentive for a new generation of experiments. Our interest in these topics remains motivated by the recent surge in and success of exper- iments involving few-body atomic and molecular fragmentation and the detection of all the fragments. The research described here thus involved two parallel efforts with (i) emphasis on reaction imaging while (ii) pursuing longtime work on quantum correlated collective excitations.

Activation energies for fragmentation channels of anthracene dications : Experiment and theory

NARCIS (Netherlands)

Reitsma, G.; Zettergren, H.; Martin, S.; Bredy, R.; Chen, L.; Bernard, J.; Hoekstra, R.; Schlathölter, Thomas

2012-01-01

We have studied the fragmentation of the polycyclic aromatic hydrocarbon anthracene (C14H10) after double electron transfer to a 5 keV proton. The excitation energies leading to the most relevant dissociation and fission channels of the resulting molecular dication were directly determined

Self-Attractive Hartree Decomposition: Partitioning Electron Density into Smooth Localized Fragments.

Science.gov (United States)

Zhu, Tianyu; de Silva, Piotr; Van Voorhis, Troy

2018-01-09

Chemical bonding plays a central role in the description and understanding of chemistry. Many methods have been proposed to extract information about bonding from quantum chemical calculations, the majority of them resorting to molecular orbitals as basic descriptors. Here, we present a method called self-attractive Hartree (SAH) decomposition to unravel pairs of electrons directly from the electron density, which unlike molecular orbitals is a well-defined observable that can be accessed experimentally. The key idea is to partition the density into a sum of one-electron fragments that simultaneously maximize the self-repulsion and maintain regular shapes. This leads to a set of rather unusual equations in which every electron experiences self-attractive Hartree potential in addition to an external potential common for all the electrons. The resulting symmetry breaking and localization are surprisingly consistent with chemical intuition. SAH decomposition is also shown to be effective in visualization of single/multiple bonds, lone pairs, and unusual bonds due to the smooth nature of fragment densities. Furthermore, we demonstrate that it can be used to identify specific chemical bonds in molecular complexes and provides a simple and accurate electrostatic model of hydrogen bonding.

Carboxyl-terminal parathyroid hormone fragments: role in parathyroid hormone physiopathology.

Science.gov (United States)

D'Amour, Pierre; Brossard, Jean-Hugues

2005-07-01

Carboxyl-terminal parathyroid hormone (C-PTH) fragments constitute 80% of circulating PTH. Since the first 34 amino acids of the PTH structure are sufficient to explain PTH classical biological effects on the type I PTH/PTHrP receptor and since C-PTH fragments do not bind to this receptor, they have long been considered inactive. Recent data suggest the existence of a C-PTH receptor through which C-PTH fragments exert biological effects opposite to those of human PTH(1-84) on the type I PTH/PTHrP receptor. This is why a lot of attention has been paid to these fragments recently. In vivo, synthetic C-PTH fragments are able to decrease calcium concentration, to antagonize the calcemic response to human PTH(1-34) and human PTH(1-84) and to decrease the high bone turnover rate induced by human PTH(1-84). In vitro, they inhibit bone resorption, promote osteocyte apoptosis and exert a variety of effects on bone and cartilaginous cells. These effects are opposite to those of human PTH(1-84) on the PTH/PTHrP type I receptor. This suggests that the molecular forms of circulating PTH may control bone participation in calcium homeostasis via two different receptors. Clinically, the accumulation of C-PTH fragments in renal failure patients may cause PTH resistance and may be associated with adynamic bone disease. Rare parathyroid tumors, without a set point error, overproduce C-PTH fragments. The implication of C-PTH fragments in osteoporosis is still to be explored. C-PTH fragments represent a new field of investigation in PTH biology. More studies are necessary to disclose their real importance in calcium and bone homeostasis in health and disease.

Designer genes. Recombinant antibody fragments for biological imaging

Energy Technology Data Exchange (ETDEWEB)

Wu, A.M.; Yazaki, P.J. [Beckman Research Institute of the City of Hope, Duarte, CA (United States). Dept. of Molecular Biology

2000-09-01

Monoclonal antibodies (MAbs), with high specificity and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C{sub H}3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering

Designer genes. Recombinant antibody fragments for biological imaging

International Nuclear Information System (INIS)

Wu, A.M.; Yazaki, P.J.

2000-01-01

Monoclonal antibodies (MAbs), with high specificy and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C H 3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering and

Analysis of Endonuclease R·EcoRI Fragments of DNA from Lambdoid Bacteriophages and Other Viruses by Agarose-Gel Electrophoresis

Science.gov (United States)

Helling, Robert B.; Goodman, Howard M.; Boyer, Herbert W.

1974-01-01

By means of agarose-gel electrophoresis, endonuclease R·EcoRI-generated fragments of DNA from various viruses were separated, their molecular weights were determined, and complete or partial fragment maps for lambda, φ80, and hybrid phages were constructed. Images PMID:4372397

Mass distribution and multiple fragmentation events in high energy cluster-cluster collisions: evidence for a predicted phase transition

International Nuclear Information System (INIS)

Farizon, B.; Farizon, M.; Gaillard, M.J.; Genre, R.; Louc, S.; Martin, J.; Senn, G.; Scheier, P.; Maerk, T.D.

1996-09-01

Fragment size distributions including multiple fragmentation events have been measured for high energy H 25 + cluster ions (60 keV/amu) colliding with a neutral C 60 target. In contrast to earlier collision experiments with a helium target the present studies do not show a U-shaped fragment mass distribution, but a single power-law falloff with increasing fragment mass. This behaviour is similar to what is known for the intermediate regime in nuclear collision physics and thus confirms a recently predicted scaling from nuclear to molecular collisions

Fragmentation study of iridoid glucosides through positive and negative electrospray ionization, collision-induced dissociation and tandem mass spectrometry.

Science.gov (United States)

Es-Safi, Nour-Eddine; Kerhoas, Lucien; Ducrot, Paul-Henri

2007-01-01

Mass spectrometric methodology based on the combined use of positive and negative electrospray ionization, collision-induced dissociation (CID) and tandem mass spectrometry (MS/MS) has been applied to the mass spectral study of a series of six naturally occurring iridoids through in-source fragmentation of the protonated [M+H]+, deprotonated [M--H]- and sodiated [M+Na]+ ions. This led to the unambiguous determination of the molecular masses of the studied compounds and allowed CID spectra of the molecular ions to be obtained. Valuable structural information regarding the nature of both the glycoside and the aglycone moiety was thus obtained. Glycosidic cleavage and ring cleavages of both aglycone and sugar moieties were the major fragmentation pathways observed during CID, where the losses of small molecules, the cinnamoyl and the cinnamate parts were also observed. The formation of the ionized aglycones, sugars and their product ions was thus obtained giving information on their basic skeleton. The protonated, i.e. [M+H]+ and deprotonated [M--H]-, ions were found to fragment mainly by glycosidic cleavages. MS/MS spectra of the [M+Na]+ ions gave complementary information for the structural characterization of the studied compounds. Unlike the dissociation of protonated molecular ions, that of sodiated molecules also provided sodiated sugar fragments where the C0+ fragment corresponding to the glucose ion was obtained as base peak for all the studied compounds. Copyright (c) 2007 John Wiley & Sons, Ltd.

Accommodating error analysis in comparison and clustering of molecular fingerprints.

OpenAIRE

Salamon, H.; Segal, M. R.; Ponce de Leon, A.; Small, P. M.

1998-01-01

Molecular epidemiologic studies of infectious diseases rely on pathogen genotype comparisons, which usually yield patterns comprising sets of DNA fragments (DNA fingerprints). We use a highly developed genotyping system, IS6110-based restriction fragment length polymorphism analysis of Mycobacterium tuberculosis, to develop a computational method that automates comparison of large numbers of fingerprints. Because error in fragment length measurements is proportional to fragment length and is ...

Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.

Science.gov (United States)

Huschmann, Franziska U; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S; Mueller, Uwe

2016-05-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity.

Structures of endothiapepsin–fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library

Science.gov (United States)

Huschmann, Franziska U.; Linnik, Janina; Sparta, Karine; Ühlein, Monika; Wang, Xiaojie; Metz, Alexander; Schiebel, Johannes; Heine, Andreas; Klebe, Gerhard; Weiss, Manfred S.; Mueller, Uwe

2016-01-01

Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein–ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin–fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity. PMID:27139825

The coordination between mechanical and chemical subsystems initiates locomotion of Physarum plasmodial fragments

Science.gov (United States)

Zhang, Shun; Guy, Robert; Del Alamo, Juan Carlos

2017-11-01

Physarum polycephalum is a multinucleated slime mold whose endoplasm flows periodically driven by the contraction of its ectoplasm, a dense shell of F-actin cross-linked by myosin molecular motors and attached to the cell membrane. We find that physarum fragments smaller than 100 microns remain round and stay in place. However, larger fragments break symmetry leading to sustained forward locomotion, in process that is reminiscent of an interfacial instability that seems to settle around two different limit cycles (traveling waves and standing waves). We use both theory and experiments to study how coordination emerges between the different mechanical and chemical subsystems of the fragment to initiate locomotion. The role of many involved factors, such as fragment size, substratum adhesiveness, rheological properties, actin polymerization and traction stresses are investigated, and we find they agree well with our predictive model.

Comparison of CHROMagar, polymerase chain reaction-restriction fragment length polymorphism, and polymerase chain reaction-fragment size for the identification of Candida species.

Science.gov (United States)

Jafari, Zahra; Motamedi, Marjan; Jalalizand, Nilufar; Shokoohi, Gholam R; Charsizadeh, Arezu; Mirhendi, Hossein

2017-09-01

The epidemiological alteration in the distribution of Candida species, as well as the significantly increasing trend of either intrinsic or acquired resistance of some of these fungi highlights the need for a reliable method for the identification of the species. Polymerase chain reaction (PCR) is one of the methods facilitating the quick and precise identification of Candida species. The aim of this study was to compare the efficiency of CHROMagar, PCR-restriction fragment length polymorphism (PCR-RFLP), and PCR-fragment size polymorphism (PCR-FSP) assays in the identification of Candida species to determine the benefits and limitations of these methods. This study was conducted on 107 Candida strains, including 20 standard strains and 87 clinical isolates. The identification of the isolates was accomplished by using CHROMagar as a conventional method. The PCR-RFLP assay was performed on the entire internal transcribed spacer (ITS) region of ribosomal DNA (rDNA), and the consequent enzymatic digestion was compared with PCR-FSP results in which ITS1 and ITS2 regions were separately PCR amplified. In both molecular assays, yeast identification was carried out through the specific electrophoretic profiles of the PCR products. According to the results, the utilization of CHROMagar resulted in the identification of 29 (33.3%) Candida isolates, while the PCR-RFLP and PCR-FSP facilitated the identification of 83 (95.4%) and 80 (91.9%) clinical isolates, respectively. The obtained concordances between CHROMagar and PCR-RFLP, between CHROMagar and PCR-FSP, as well as between PCR-RFLP and PCR-FSP were 0.23, 0.20, and 0.77, respectively. The recognition of the benefits and limitations of PCR methods allows for the selection of the most efficient technique for a fast and correct differentiation. The PCR-RFLP and PCR-FSP assays had satisfactory concordance. The PCR-FSP provides a rapid, technically simple, and cost-effective method for the identification of Candida species

Towards a population synthesis model of self-gravitating disc fragmentation and tidal downsizing II: the effect of fragment-fragment interactions

Science.gov (United States)

Forgan, D. H.; Hall, C.; Meru, F.; Rice, W. K. M.

2018-03-01

It is likely that most protostellar systems undergo a brief phase where the protostellar disc is self-gravitating. If these discs are prone to fragmentation, then they are able to rapidly form objects that are initially of several Jupiter masses and larger. The fate of these disc fragments (and the fate of planetary bodies formed afterwards via core accretion) depends sensitively not only on the fragment's interaction with the disc, but also with its neighbouring fragments. We return to and revise our population synthesis model of self-gravitating disc fragmentation and tidal downsizing. Amongst other improvements, the model now directly incorporates fragment-fragment interactions while the disc is still present. We find that fragment-fragment scattering dominates the orbital evolution, even when we enforce rapid migration and inefficient gap formation. Compared to our previous model, we see a small increase in the number of terrestrial-type objects being formed, although their survival under tidal evolution is at best unclear. We also see evidence for disrupted fragments with evolved grain populations - this is circumstantial evidence for the formation of planetesimal belts, a phenomenon not seen in runs where fragment-fragment interactions are ignored. In spite of intense dynamical evolution, our population is dominated by massive giant planets and brown dwarfs at large semimajor axis, which direct imaging surveys should, but only rarely, detect. Finally, disc fragmentation is shown to be an efficient manufacturer of free-floating planetary mass objects, and the typical multiplicity of systems formed via gravitational instability will be low.

Agarose gel electrophoresis for the separation of DNA fragments.

Science.gov (United States)

Lee, Pei Yun; Costumbrado, John; Hsu, Chih-Yuan; Kim, Yong Hoon

2012-04-20

Agarose gel electrophoresis is the most effective way of separating DNA fragments of varying sizes ranging from 100 bp to 25 kb(1). Agarose is isolated from the seaweed genera Gelidium and Gracilaria, and consists of repeated agarobiose (L- and D-galactose) subunits(2). During gelation, agarose polymers associate non-covalently and form a network of bundles whose pore sizes determine a gel's molecular sieving properties. The use of agarose gel electrophoresis revolutionized the separation of DNA. Prior to the adoption of agarose gels, DNA was primarily separated using sucrose density gradient centrifugation, which only provided an approximation of size. To separate DNA using agarose gel electrophoresis, the DNA is loaded into pre-cast wells in the gel and a current applied. The phosphate backbone of the DNA (and RNA) molecule is negatively charged, therefore when placed in an electric field, DNA fragments will migrate to the positively charged anode. Because DNA has a uniform mass/charge ratio, DNA molecules are separated by size within an agarose gel in a pattern such that the distance traveled is inversely proportional to the log of its molecular weight(3). The leading model for DNA movement through an agarose gel is "biased reptation", whereby the leading edge moves forward and pulls the rest of the molecule along(4). The rate of migration of a DNA molecule through a gel is determined by the following: 1) size of DNA molecule; 2) agarose concentration; 3) DNA conformation(5); 4) voltage applied, 5) presence of ethidium bromide, 6) type of agarose and 7) electrophoresis buffer. After separation, the DNA molecules can be visualized under uv light after staining with an appropriate dye. By following this protocol, students should be able to: Understand the mechanism by which DNA fragments are separated within a gel matrix Understand how conformation of the DNA molecule will determine its mobility through a gel matrix Identify an agarose solution of appropriate

Native Frames: Disentangling Sequential from Concerted Three-Body Fragmentation

Science.gov (United States)

Rajput, Jyoti; Severt, T.; Berry, Ben; Jochim, Bethany; Feizollah, Peyman; Kaderiya, Balram; Zohrabi, M.; Ablikim, U.; Ziaee, Farzaneh; Raju P., Kanaka; Rolles, D.; Rudenko, A.; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

2018-03-01

A key question concerning the three-body fragmentation of polyatomic molecules is the distinction of sequential and concerted mechanisms, i.e., the stepwise or simultaneous cleavage of bonds. Using laser-driven fragmentation of OCS into O++C++S+ and employing coincidence momentum imaging, we demonstrate a novel method that enables the clear separation of sequential and concerted breakup. The separation is accomplished by analyzing the three-body fragmentation in the native frame associated with each step and taking advantage of the rotation of the intermediate molecular fragment, CO2 + or CS2 + , before its unimolecular dissociation. This native-frame method works for any projectile (electrons, ions, or photons), provides details on each step of the sequential breakup, and enables the retrieval of the relevant spectra for sequential and concerted breakup separately. Specifically, this allows the determination of the branching ratio of all these processes in OCS3 + breakup. Moreover, we find that the first step of sequential breakup is tightly aligned along the laser polarization and identify the likely electronic states of the intermediate dication that undergo unimolecular dissociation in the second step. Finally, the separated concerted breakup spectra show clearly that the central carbon atom is preferentially ejected perpendicular to the laser field.

Universal elements of fragmentation

International Nuclear Information System (INIS)

Yanovsky, V. V.; Tur, A. V.; Kuklina, O. V.

2010-01-01

A fragmentation theory is proposed that explains the universal asymptotic behavior of the fragment-size distribution in the large-size range, based on simple physical principles. The basic principles of the theory are the total mass conservation in a fragmentation process and a balance condition for the energy expended in increasing the surface of fragments during their breakup. A flux-based approach is used that makes it possible to supplement the basic principles and develop a minimal theory of fragmentation. Such a supplementary principle is that of decreasing fragment-volume flux with increasing energy expended in fragmentation. It is shown that the behavior of the decreasing flux is directly related to the form of a power-law fragment-size distribution. The minimal theory is used to find universal asymptotic fragment-size distributions and to develop a natural physical classification of fragmentation models. A more general, nonlinear theory of strong fragmentation is also developed. It is demonstrated that solutions to a nonlinear kinetic equation consistent with both basic principles approach a universal asymptotic size distribution. Agreement between the predicted asymptotic fragment-size distributions and experimental observations is discussed.

Performances of Different Fragment Sizes for Reduced Representation Bisulfite Sequencing in Pigs.

Science.gov (United States)

Yuan, Xiao-Long; Zhang, Zhe; Pan, Rong-Yang; Gao, Ning; Deng, Xi; Li, Bin; Zhang, Hao; Sangild, Per Torp; Li, Jia-Qi

2017-01-01

Reduced representation bisulfite sequencing (RRBS) has been widely used to profile genome-scale DNA methylation in mammalian genomes. However, the applications and technical performances of RRBS with different fragment sizes have not been systematically reported in pigs, which serve as one of the important biomedical models for humans. The aims of this study were to evaluate capacities of RRBS libraries with different fragment sizes to characterize the porcine genome. We found that the Msp I-digested segments between 40 and 220 bp harbored a high distribution peak at 74 bp, which were highly overlapped with the repetitive elements and might reduce the unique mapping alignment. The RRBS library of 110-220 bp fragment size had the highest unique mapping alignment and the lowest multiple alignment. The cost-effectiveness of the 40-110 bp, 110-220 bp and 40-220 bp fragment sizes might decrease when the dataset size was more than 70, 50 and 110 million reads for these three fragment sizes, respectively. Given a 50-million dataset size, the average sequencing depth of the detected CpG sites in the 110-220 bp fragment size appeared to be deeper than in the 40-110 bp and 40-220 bp fragment sizes, and these detected CpG sties differently located in gene- and CpG island-related regions. In this study, our results demonstrated that selections of fragment sizes could affect the numbers and sequencing depth of detected CpG sites as well as the cost-efficiency. No single solution of RRBS is optimal in all circumstances for investigating genome-scale DNA methylation. This work provides the useful knowledge on designing and executing RRBS for investigating the genome-wide DNA methylation in tissues from pigs.

Non-ideal magnetohydrodynamic simulations of the two-stage fragmentation model for cluster formation

International Nuclear Information System (INIS)

Bailey, Nicole D.; Basu, Shantanu

2014-01-01

We model molecular cloud fragmentation with thin-disk, non-ideal magnetohydrodynamic simulations that include ambipolar diffusion and partial ionization that transitions from primarily ultraviolet-dominated to cosmic-ray-dominated regimes. These simulations are used to determine the conditions required for star clusters to form through a two-stage fragmentation scenario. Recent linear analyses have shown that the fragmentation length scales and timescales can undergo a dramatic drop across the column density boundary that separates the ultraviolet- and cosmic-ray-dominated ionization regimes. As found in earlier studies, the absence of an ionization drop and regular perturbations leads to a single-stage fragmentation on pc scales in transcritical clouds, so that the nonlinear evolution yields the same fragment sizes as predicted by linear theory. However, we find that a combination of initial transcritical mass-to-flux ratio, evolution through a column density regime in which the ionization drop takes place, and regular small perturbations to the mass-to-flux ratio is sufficient to cause a second stage of fragmentation during the nonlinear evolution. Cores of size ∼0.1 pc are formed within an initial fragment of ∼pc size. Regular perturbations to the mass-to-flux ratio also accelerate the onset of runaway collapse.

High-voltage pulsed generator for dynamic fragmentation of rocks.

Science.gov (United States)

Kovalchuk, B M; Kharlov, A V; Vizir, V A; Kumpyak, V V; Zorin, V B; Kiselev, V N

2010-10-01

A portable high-voltage (HV) pulsed generator has been designed for rock fragmentation experiments. The generator can be used also for other technological applications. The installation consists of low voltage block, HV block, coaxial transmission line, fragmentation chamber, and control system block. Low voltage block of the generator, consisting of a primary capacitor bank (300 μF) and a thyristor switch, stores pulse energy and transfers it to the HV block. The primary capacitor bank stores energy of 600 J at the maximum charging voltage of 2 kV. HV block includes HV pulsed step up transformer, HV capacitive storage, and two electrode gas switch. The following technical parameters of the generator were achieved: output voltage up to 300 kV, voltage rise time of ∼50 ns, current amplitude of ∼6 kA with the 40 Ω active load, and ∼20 kA in a rock fragmentation regime (with discharge in a rock-water mixture). Typical operation regime is a burst of 1000 pulses with a frequency of 10 Hz. The operation process can be controlled within a wide range of parameters. The entire installation (generator, transmission line, treatment chamber, and measuring probes) is designed like a continuous Faraday's cage (complete shielding) to exclude external electromagnetic perturbations.

High-voltage pulsed generator for dynamic fragmentation of rocks

Science.gov (United States)

Kovalchuk, B. M.; Kharlov, A. V.; Vizir, V. A.; Kumpyak, V. V.; Zorin, V. B.; Kiselev, V. N.

2010-10-01

A portable high-voltage (HV) pulsed generator has been designed for rock fragmentation experiments. The generator can be used also for other technological applications. The installation consists of low voltage block, HV block, coaxial transmission line, fragmentation chamber, and control system block. Low voltage block of the generator, consisting of a primary capacitor bank (300 μF) and a thyristor switch, stores pulse energy and transfers it to the HV block. The primary capacitor bank stores energy of 600 J at the maximum charging voltage of 2 kV. HV block includes HV pulsed step up transformer, HV capacitive storage, and two electrode gas switch. The following technical parameters of the generator were achieved: output voltage up to 300 kV, voltage rise time of ˜50 ns, current amplitude of ˜6 kA with the 40 Ω active load, and ˜20 kA in a rock fragmentation regime (with discharge in a rock-water mixture). Typical operation regime is a burst of 1000 pulses with a frequency of 10 Hz. The operation process can be controlled within a wide range of parameters. The entire installation (generator, transmission line, treatment chamber, and measuring probes) is designed like a continuous Faraday's cage (complete shielding) to exclude external electromagnetic perturbations.

Dimerized plasmin fragment D as a potential biomarker to predict successful catheter-directed thrombolysis therapy in acute deep vein thrombosis.

Science.gov (United States)

Luo, Chien-Ming; Wu, I-Hui; Chan, Chih-Yang; Chen, Yih-Sharng; Yang, Wei-Shiung; Wang, Shoei-Shen

2015-10-01

The value of dimerized plasmin fragment D in the clinical monitoring during the catheter-directed thrombolysis in patients with acute deep vein thrombosis is not known. Dimerized plasmin fragment D levels in 24 patients with acute deep vein thrombosis undergoing catheter-directed thrombolysis were prospectively evaluated. The plasma dimerized plasmin fragment D level was measured serially before and at every 12 h during catheter-directed thrombolysis for 24 h. Technical success was defined as restoration of patency and flow with less than 50% residual thrombus by surveillance rotational venography. Technical success was achieved in 79.2% (19 of 24) of the treated limbs after catheter-directed thrombolysis. In univariate analysis, there was significant elevation of the dimerized plasmin fragment D at 12th h after starting the catheter-directed thrombolysis (P fragment D to predict successful catheter-directed thrombolysis was determined as 18.4 µg/ml at the 12th h after starting the catheter-directed thrombolysis with sensitivity 0.8 and specificity 0.8 (P = 0.03). It was further validated in multivariate logistic regression analysis (odds ratio: 14.38; 95% CI: 1.22-169.20; P = 0.03). Catheter-directed thrombolysis is safe and effective for restoration of blood flow in patients with acute deep vein thrombosis. Dimerized plasmin fragment D value greater than 18.4 µg/ml at the 12th h after starting catheter-directed thrombolysis had a high predictive rate of greater than 50% lysis at the end of catheter-directed thrombolysis. © The Author(s) 2014.

Recombinant fragment of an antibody tailored for direct radioiodination

Czech Academy of Sciences Publication Activity Database

Sedláček, Juraj; Fábry, Milan; Sieglová, Irena; Král, Vlastimil; Uhnáková, Bronislava; Mudra, M.; Kronrád, L.; Sawicka, A.; Mikolajczak, R.; Řezáčová, Pavlína

2012-01-01

Roč. 55, č. 1 (2012), s. 52-56 ISSN 0362-4803 R&D Projects: GA MPO 2A-2TP1/076; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z50520514 Keywords : I125 labelling * single-chain antibody variable fragment * tyrosine-rich polypeptide segment * fusion protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.240, year: 2012

Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells

Czech Academy of Sciences Publication Activity Database

Ohradanova-Repic, A.; Nogueira, E.; Hartl, I.; Gomes, A.C.; Preto, A.; Steinhuber, E.; Muehlgrabner, V.; Repic, M.; Kuttke, M.; Zwirzitz, A.; Prouza, M.; Suchánek, M.; Wozniak-Knopp, G.; Hořejší, Václav; Schabbauer, G.; Cavaco-Paulo, A.; Stockinger, H.

2018-01-01

Roč. 14, č. 1 (2018), s. 123-130 ISSN 1549-9634 Institutional support: RVO:68378050 Keywords : Active targeting * Liposome functionalization * Immunoliposome * Antibody engineering * Recombinant Fab antibody fragment Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 5.720, year: 2016

Lower sperm DNA fragmentation after r-FSH administration in functional hypogonadotropic hypogonadism.

Science.gov (United States)

Ruvolo, Giovanni; Roccheri, Maria Carmela; Brucculeri, Anna Maria; Longobardi, Salvatore; Cittadini, Ettore; Bosco, Liana

2013-04-01

An observational clinical and molecular study was designed to evaluate the effects of the administration of recombinant human FSH on sperm DNA fragmentation in men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In the study were included 53 men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In all patients, sperm DNA fragmentation index (DFI), assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) in situ DNA nick end-labelling (TUNEL) assay, was evaluated before starting the treatment with 150 IU of recombinant human FSH, given three times a week for at least 3 months. Patients' semen analysis and DNA fragmentation index were re-evaluated after the 3-month treatment period. After recombinant human FSH therapy, we did not find any differences in terms of sperm count, motility and morphology. The average DNA fragmentation index was significantly reduced (21.15 vs 15.2, p15 %), while no significant variation occurred in the patients with DFI values ≤ 15 %. Recombinant human FSH administration improves sperm DNA integrity in hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia men with DNA fragmentation index value >15 % .

Automated building of organometallic complexes from 3D fragments.

Science.gov (United States)

Foscato, Marco; Venkatraman, Vishwesh; Occhipinti, Giovanni; Alsberg, Bjørn K; Jensen, Vidar R

2014-07-28

A method for the automated construction of three-dimensional (3D) molecular models of organometallic species in design studies is described. Molecular structure fragments derived from crystallographic structures and accurate molecular-level calculations are used as 3D building blocks in the construction of multiple molecular models of analogous compounds. The method allows for precise control of stereochemistry and geometrical features that may otherwise be very challenging, or even impossible, to achieve with commonly available generators of 3D chemical structures. The new method was tested in the construction of three sets of active or metastable organometallic species of catalytic reactions in the homogeneous phase. The performance of the method was compared with those of commonly available methods for automated generation of 3D models, demonstrating higher accuracy of the prepared 3D models in general, and, in particular, a much wider range with respect to the kind of chemical structures that can be built automatically, with capabilities far beyond standard organic and main-group chemistry.

Controlled fragmentation

International Nuclear Information System (INIS)

Arnold, Werner

2002-01-01

Contrary to natural fragmentation, controlled fragmentation offers the possibility to adapt fragment parameters like size and mass to the performance requirements in a very flexible way. Known mechanisms like grooves inside the casing, weaken the structure. This is, however, excluded for applications with high accelerations during launch or piercing requirements for example on a semi armor piercing penetrator. Another method to achieve controlled fragmentation with an additional grid layer is presented with which the required grooves are produced 'just in time' inside the casing during detonation of the high explosive. The process of generating the grooves aided by the grid layer was studied using the hydrocode HULL with respect to varying grid designs and material combinations. Subsequent to this, a large range of these theoretically investigated combinations was contemplated in substantial experimental tests. With an optimised grid design and a suitable material selection, the controlled fragment admits a very flexible adaptation to the set requirements. Additional advantages like the increase of perforation performance or incendiary amplification can be realized with the grid layer

Fragments detection of the Ar+ collision in air

International Nuclear Information System (INIS)

Chaparro V, F. J.; Fuentes M, B. E.; Yousif, F. B.; Roa N, J. A. E.

2012-10-01

The different components of a lineal accelerator of particles to low energy that will be used in experiments of atomic and molecular collisions are described. By means of the technique of flight time the fragments of the collision of positive ions were identified in gases. In this work values of some parameters are presented guided to optimize the operation of the accelerator, as well as preliminary data of the collision of argon ions in air. (Author)

Fragmentation cross sections outside the limiting-fragmentation regime

CERN Document Server

Sümmerer, K

2003-01-01

The empirical parametrization of fragmentation cross sections, EPAX, has been successfully applied to estimate fragment production cross sections in reactions of heavy ions at high incident energies. It is checked whether a similar parametrization can be found for proton-induced spallation around 1 GeV, the range of interest for ISOL-type RIB facilities. The validity of EPAX for medium-energy heavy-ion induced reactions is also checked. Only a few datasets are available, but in general EPAX predicts the cross sections rather well, except for fragments close to the projectile, where the experimental cross sections are found to be larger.

Universality of fragment shapes.

Science.gov (United States)

Domokos, Gábor; Kun, Ferenc; Sipos, András Árpád; Szabó, Tímea

2015-03-16

The shape of fragments generated by the breakup of solids is central to a wide variety of problems ranging from the geomorphic evolution of boulders to the accumulation of space debris orbiting Earth. Although the statistics of the mass of fragments has been found to show a universal scaling behavior, the comprehensive characterization of fragment shapes still remained a fundamental challenge. We performed a thorough experimental study of the problem fragmenting various types of materials by slowly proceeding weathering and by rapid breakup due to explosion and hammering. We demonstrate that the shape of fragments obeys an astonishing universality having the same generic evolution with the fragment size irrespective of materials details and loading conditions. There exists a cutoff size below which fragments have an isotropic shape, however, as the size increases an exponential convergence is obtained to a unique elongated form. We show that a discrete stochastic model of fragmentation reproduces both the size and shape of fragments tuning only a single parameter which strengthens the general validity of the scaling laws. The dependence of the probability of the crack plan orientation on the linear extension of fragments proved to be essential for the shape selection mechanism.

Anomalous nuclear fragments

International Nuclear Information System (INIS)

Karmanov, V.A.

1983-01-01

Experimental data are given, the status of anomalon problem is discussed, theoretical approaches to this problem are outlined. Anomalons are exotic objects formed following fragmentation of nuclei-targets under the effect of nuclei - a beam at the energy of several GeV/nucleon. These nuclear fragments have an anomalously large cross section of interaction and respectively, small free path, considerably shorter than primary nuclei have. The experimental daa are obtained in accelerators following irradiation of nuclear emulsions by 16 O, 56 Fe, 40 Ar beams, as well as propane by 12 C beams. The experimental data testify to dependence of fragment free path on the distance L from the point of the fragment formation. A decrease in the fragment free path is established more reliably than its dependence on L. The problem of the anomalon existence cannot be yet considered resolved. Theoretical models suggested for explanation of anomalously large cross sections of nuclear fragment interaction are variable and rather speculative

A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins.

Science.gov (United States)

Joshi, Priyanka; Chia, Sean; Habchi, Johnny; Knowles, Tuomas P J; Dobson, Christopher M; Vendruscolo, Michele

2016-03-14

The aggregation process of intrinsically disordered proteins (IDPs) has been associated with a wide range of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Currently, however, no drug in clinical use targets IDP aggregation. To facilitate drug discovery programs in this important and challenging area, we describe a fragment-based approach of generating small-molecule libraries that target specific IDPs. The method is based on the use of molecular fragments extracted from compounds reported in the literature to inhibit of the aggregation of IDPs. These fragments are used to screen existing large generic libraries of small molecules to form smaller libraries specific for given IDPs. We illustrate this approach by describing three distinct small-molecule libraries to target, Aβ, tau, and α-synuclein, which are three IDPs implicated in Alzheimer's and Parkinson's diseases. The strategy described here offers novel opportunities for the identification of effective molecular scaffolds for drug discovery for neurodegenerative disorders and to provide insights into the mechanism of small-molecule binding to IDPs.

The Wolff rearrangement of cyclic 2-diazo-1,3-diketones in electron impact - mass spectrometry - controlling the molecular fragmentation by means of low-energy electrons 18 to 70 eV

International Nuclear Information System (INIS)

Kuruc, J.; Kardosova, E.; Nikolaev, V. A.

2016-01-01

The electron-impact-induced fragmentations (the mass spectra, 17 - 70 eV) of cyclic 2-diazo-1,3-diketones were studied. As the suitable compounds were selected the following cyclic 2-diazo-1,3-diketones: 2-diazo-1,3-cyclohexanedione, Ia; 2-diazo-4,4-dimethyl-1,3-cyclohexanedione, Ib; 2-diazo-5,5-dimethyl-1,3-cyclohexanedione, Ic; 2-diazo-4,6-dioxa-5,5-dimethyl-1,3-cyclohexanedione, Id; and 2-diazo-5-phenyl-1,3-cyclohexanedione, Ie). The mass spectra were measured with Varian MAT 111 instrument with direct introduction of samples, with a source temperature of 120 grad C, energy of ionising electrons was in the range (17 - 70) eV. The elimination of the diazo group is the typical reaction of the fragmentation of the cyclic diazo-1,3-diketones after ionization of molecules by electron impact. All our studied cyclic diazo-1,3-diketones have a molecular ion with a relative intensity from 0.7 to 86.4%. Typical ions are [M]"+·, [M-N"_2]"+"·, [M-N_2-CO]"+"·, [M-N_2-CO-CH_2]"+"·, [M-N_2-CO-CH_3]"+"·. For all treatment cyclic diazo-1,3-diketones have been registered 3D mass spectra, for each cyclic diazo-1,3-diketone was proposed fragmentation scheme, including the general fragmentation scheme. The Wolff rearrangement is observed in all studied cyclic diazo-1,3-diketones after cleavage of nitrogen molecules. The energy of ionizing electrons ∼20 eV in the case of compounds Ib, Id - Ie dominating ions are fragments of the [M-N_2]"+"·, in the compound Ia at 18 and 20 eV is dominant fragment [M-N_2-CO-C_2H_2-H]"+"· and for the Ic at 30 eV becomes a dominant fragment [M-N_2-CH_3]"+"· (m/z = 123) but at (25 - 18) eV the most intensive ion is [M-N_2]"+"· (m/z = 138). (authors)

Fragmentation characteristics of hydroxycinnamic acids in ESI-MSn by density functional theory.

Science.gov (United States)

Yin, Zhi-Hui; Sun, Chang-Hai; Fang, Hong-Zhuang

2017-07-01

This work aims to analyze the electrospray ionization multistage mass spectrometry (ESI-MS n ) fragmentation characteristics of hydroxycinnamic acids (HCAs) in negative ion mode. The geometric parameters, energies, natural bond orbitals and frontier orbitals of fragments were calculated by density functional theory (DFT) to investigate mass spectral fragmentation mechanisms. The results showed that proton transfer always occurred during fragmentation of HCAs; their quasi-molecular ions ([M - H] - ) existed in more than one form and were mainly with the lowest energy. The fragmentation characteristics included the followings: (1) according to the different substitution position of phenolic hydroxyl group, the ring contraction reaction by CO elimination from benzene was in an increasingly difficult order: m-phenolic hydroxyl > p-phenolic hydroxyl > o-phenolic hydroxyl; and (2) ortho effect always occurred in o-dihydroxycinnamic acids (o-diHCAs), i.e. one phenolic hydroxyl group offered H + , which combined with the other one to lose H 2 O. In addition, there was a nucleophilic reaction during ring contraction in diHCAs that oxygen atom attacked the carbon atom binding with the other phenolic hydroxyl to lose CO 2 . The fragmentation characteristics and mechanism of HCAs could be used for analysis and identification of such compounds quickly and effectively, and as reference for structural analogues by ESI-MS. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen, produced by plasmin (fragments X)

NARCIS (Netherlands)

Nieuwenhuizen, W.; Gravesen, M.

1981-01-01

Early plasmin degradation products (X fragments) of human fibrinogen were prepared in the presence of calcium-ions or EGTA, and purified on Sepharose 6B-CL. X fragments were characterized with respect to amino-terminal amino acids, polypeptide-chain composition, anticlotting properties and

Fragmentation of C2H4 by charge-changing collisions of O2+ ions

International Nuclear Information System (INIS)

Sato, S.; Mizuno, T.; Yamada, T.; Imai, M.; Shibata, H.; Itoh, A.; Tsuchida, H.

2009-01-01

We investigated molecular fragmentation of C 2 H 4 in charge-changing collisions of 1.14MeV O 2+ ions. Branching ratios associated with decaying from temporary produced (C 2 H 4 ) r+ ions into various fragment channels were obtained. Dissociation via a C-C bond breaking is preferential in 1-electron loss collisions in comparison with 1-electron capture collisions. We confirmed that multiple ionization and dissociation rarely occur in electron capture collisions, while they occur rather strongly in electron loss collisions. (author)

Fragment E1 labeled with I-123 in the detection of venous thrombosis

International Nuclear Information System (INIS)

Knight, L.C.; Maurer, A.H.; Robbins, P.S.; Malmud, L.S.; Budzynski, A.Z.

1985-01-01

Fragment E1, which has been shown to have specific binding affinity for thrombi in an animal model, was investigated in humans for its safety and ability to bind to venous thrombi. Human Fragment E1 was labeled with I-123 and administered intravenously to patients with proved or suspected deep vein thrombosis. The vascular distribution of radioactivity was documented by obtaining gamma camera images of the patients' legs for 30 minutes following administration of I-123-Fragment E1. All patients (n = 5) with documented venous thrombi had rapid localization of labeled Fragment E1 in the area of thrombus. Patients without evidence of thrombi (n = 5) showed no focal localization, although two of these patients showed diffuse uptake along the length of the veins, due to superficial phlebitis. Analysis of blood samples in four patients indicated that disappearance of Fragment E1 from the circulation was more rapid in individuals with thrombosis (t 1/2 = 20 min) than in individuals without thrombosis (t 1/2 = 90 min), and a radiolabeled species of high molecular weight was found in patients with thrombosis but was absent from patients without thrombosis. These early results suggest that radiolabeled Fragment E1 is a safe and potentially valuable agent for the rapid detection of venous thrombosis

Does the Chemothermal Instability Have Any Role in the Fragmentation of Primordial Gas

Science.gov (United States)

Dutta, Jayanta

2015-10-01

The collapse of the primordial gas in the density regime ˜108-1010 cm-3 is controlled by the three-body H2 formation process, in which the gas can cool faster than free-fall time—a condition proposed as the chemothermal instability. We investigate how the heating and cooling rates are affected during the rapid transformation of atomic to molecular hydrogen. With a detailed study of the heating and cooling balance in a 3D simulation of Pop III collapse, we follow the chemical and thermal evolution of the primordial gas in two dark matter minihalos. The inclusion of sink particles in modified Gadget-2 smoothed particle hydrodynamics code allows us to investigate the long-term evolution of the disk that fragments into several clumps. We find that the sum of all the cooling rates is less than the total heating rate after including the contribution from the compressional heating (pdV). The increasing cooling rate during the rapid increase of the molecular fraction is offset by the unavoidable heating due to gas contraction. We conclude that fragmentation occurs because H2 cooling, the heating due to H2 formation and compressional heating together set a density and temperature structure in the disk that favors fragmentation, not the chemothermal instability.

DOES THE CHEMOTHERMAL INSTABILITY HAVE ANY ROLE IN THE FRAGMENTATION OF PRIMORDIAL GAS

International Nuclear Information System (INIS)

Dutta, Jayanta

2015-01-01

The collapse of the primordial gas in the density regime ∼10 8 −10 10 cm −3 is controlled by the three-body H 2 formation process, in which the gas can cool faster than free-fall time—a condition proposed as the chemothermal instability. We investigate how the heating and cooling rates are affected during the rapid transformation of atomic to molecular hydrogen. With a detailed study of the heating and cooling balance in a 3D simulation of Pop III collapse, we follow the chemical and thermal evolution of the primordial gas in two dark matter minihalos. The inclusion of sink particles in modified Gadget-2 smoothed particle hydrodynamics code allows us to investigate the long-term evolution of the disk that fragments into several clumps. We find that the sum of all the cooling rates is less than the total heating rate after including the contribution from the compressional heating (pdV). The increasing cooling rate during the rapid increase of the molecular fraction is offset by the unavoidable heating due to gas contraction. We conclude that fragmentation occurs because H 2 cooling, the heating due to H 2 formation and compressional heating together set a density and temperature structure in the disk that favors fragmentation, not the chemothermal instability

IAEA advisory group meeting on technical aspects of atomic and molecular data processing and exchange (16. meeting of the A+M Data Centres and ALADDIN network). Summary report

Energy Technology Data Exchange (ETDEWEB)

Stephens, J A [ed.

2001-12-01

The proceedings of the IAEA Advisory group meeting on technical aspects of atomic and molecular data processing and exchange (16. meeting of A+M Data centers and ALADDIN Network), held on September 10-11, 2001 in Vienna, Austria are briefly described. The meeting conclusions and recommendations on the priorities in A+M data compilation and evaluation, and on the technical aspects of data processing, exchange and distribution are also presented. (author)

Crossed molecular beams

International Nuclear Information System (INIS)

Lee, Y.T.

1976-01-01

Research activities with crossed molecular beams at Lawrence Berkeley Laboratory during 1976 are described. Topics covered include: scattering of Ar*, Kr*, with Xe; metastable rare gas interactions, He* + H 2 ; an atomic and molecular halogen beam source; a crossed molecular beam study of the Cl + Br 2 → BrCl + Br reaction; O( 3 P) reaction dynamics, development of the high pressure plasma beam source; energy randomization in the Cl + C 2 H 3 Br → Br + C 2 H 3 Cl reaction; high resolution photoionization studies of NO and ICl; photoionization of (H 2 O)/sub n/ and (NH 3 ) 2 ; photoionization mass spectroscopy of NH 3 + and O 3 + ; photo fragmentation of bromine; and construction of chemiluminescence-laser fluorescence crossed molecular beam machine

Fragmentation of molecular ions in differential mobility spectrometry as a method for identification of chemical warfare agents.

Science.gov (United States)

Maziejuk, M; Puton, J; Szyposzyńska, M; Witkiewicz, Z

2015-11-01

The subject of the work is the use of differential mobility spectrometry (DMS) for the detection of chemical warfare agents (CWA). Studies were performed for mustard gas, i.e., bis(2-chloroethyl)sulfide (HD), sarin, i.e., O-isopropyl methylphosphonofluoridate (GB) and methyl salicylate (MS) used as test compounds. Measurements were conducted with two ceramic DMS analyzers of different constructions allowing the generation of an electric field with an intensity of more than 120 Td. Detector signals were measured for positive and negative modes of operation in a temperature range from 0 to 80 °C. Fragmentations of ions containing analyte molecules were observed for all tested compounds. The effective temperatures of fragmentation estimated on the basis of dispersion plots were equal from about 148 °C for GB to 178 °C for MS. It was found that values of separation voltage (SV) and compensation voltage (CV) at which the fragmentation of sample ions is observed may be the parameters improving the certainty of detection for different analytes. The DMS analyzers enabling the observation of ion fragmentation can be successfully used for effective CWA detection. Copyright © 2015. Published by Elsevier B.V.

Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening

Energy Technology Data Exchange (ETDEWEB)

Begley, Darren W.; Davies, Douglas R.; Hartley, Robert C.; Hewitt, Stephen N.; Rychel, Amanda L.; Myler, Peter J.; Van Voorhis, Wesley C.; Staker, Bart L.; Stewart, Lance J. (Emerald)

2014-10-02

Glutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals.

Nuclear fragmentation

International Nuclear Information System (INIS)

Chung, K.C.

1989-01-01

An introduction to nuclear fragmentation, with emphasis in percolation ideas, is presented. The main theoretical models are discussed and as an application, the uniform expansion approximation is presented and the statistical multifragmentation model is used to calculate the fragment energy spectra. (L.C.)

Polarization dependent effects in photo-fragmentation dynamics of free molecules

International Nuclear Information System (INIS)

Mocellin, A.; Marinho, R.R.T.; Coutinho, L.H.; Burmeister, F.; Wiesner, K.; Naves de Brito, A.

2003-01-01

We present multicoincidence spectra of nitrogen, formic acid and methyl methacrylate. We demonstrate how to probe the local symmetry of molecular orbitals from molecules core excited with linearly polarized synchrotron radiation. The intensity distribution of the photoelectron photo-ion photo-ion coincidence (PEPIPICO) spectrum reflects the selectivity and localization of core excitation by polarized light. By simulating the spectra the angular dependence of the fragmentation is determined

Polarization dependent effects in photo-fragmentation dynamics of free molecules

Energy Technology Data Exchange (ETDEWEB)

Mocellin, A.; Marinho, R.R.T.; Coutinho, L.H.; Burmeister, F.; Wiesner, K.; Naves de Brito, A

2003-04-01

We present multicoincidence spectra of nitrogen, formic acid and methyl methacrylate. We demonstrate how to probe the local symmetry of molecular orbitals from molecules core excited with linearly polarized synchrotron radiation. The intensity distribution of the photoelectron photo-ion photo-ion coincidence (PEPIPICO) spectrum reflects the selectivity and localization of core excitation by polarized light. By simulating the spectra the angular dependence of the fragmentation is determined.

[Preparation of monoclonal antibody against 4-amylphenol and homology modeling of its Fv fragment].

Science.gov (United States)

Cheng, Lei; Wu, Haizhen; Fei, Jing; Zhang, Lujia; Ye, Jiang; Zhang, Huizhan

2017-03-01

Objective To prepare and characterize a monoclonal antibody (mAb) against 4-amylphenol (4-AP), clone its cDNA sequence and make homology modeling for its Fv fragment. Methods A high-affinity anti-4-AP mAb was generated from a hybridoma cell line F10 using electrofusion between splenocytes from APA-BSA-immunized mouse and Sp2/0 myeloma cells. Then we extracted the mRNA of F10 cells and cloned the cDNA of mAb. The homology modeling and molecular docking of its Fv fragment was conducted with biological software. Results Under the optimum conditions, the ic-ELISA equation was y=A 2 +(A 1 -A 2 )/(1+(x/x 0 ) p ) (A 1 =1.28; A 2 =-0.066; x 0 =12560.75; p=0.74) with a correlation coefficient (R 2 ) of 0.997. The lowest detectable limit was 0.65 μg/mL. The heavy and light chains of mAb respectively belonged to IgG1 and Kappa. The homology modeling and molecular docking studies revealed that the binding of 4-Ap and mAb was attributed to the hydrogen bond and hydrophobic interactions. Conclusion The study successfully established a stable 4-AP mAb-secreting hybridoma cell line. The study on spatial structure of Fv fragment using homology modeling provided a reference for the development and design of single chain variable fragments.

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

Directory of Open Access Journals (Sweden)

Hiroyoshi Takamura

2013-09-01

Full Text Available Symbiodinolide is a polyol marine natural product with a molecular weight of 2860. Herein, a streamlined synthesis of the C79–C97 fragment of symbiodinolide is described. In the synthetic route, a spiroacetalization, a Julia–Kocienski olefination, and a Sharpless asymmetric dihydroxylation were utilized as the key transformations.

IAEA advisory group meeting on technical aspects of atomic and molecular data processing and exchange (15. meeting of the A+M data centres and ALADDIN network). Summary report

International Nuclear Information System (INIS)

Stephens, J.A.

1999-12-01

The proceedings of the IAEA Advisory Group Meeting on 'Technical Aspects of Atomic and Molecular Data Processing and Exchange' (15th Meeting of A+M Data Centres and ALADDIN Network), held on September 13-14, 1999 in Vienna, Austria are briefly described. The meeting conclusions and recommendations on the priorities in A+M data compilation and evaluation, and on the technical aspects of data processing, exchange, and distribution are also presented. (author)

Impact of land fragmentation on rice producers' technical efficiency in South-East China

NARCIS (Netherlands)

Tan, S.; Heerink, N.; Kuyvenhoven, A.; Qu Futian, F.

2010-01-01

Rice farming is important for income generation in large parts of China and Asia. This paper uses detailed household, crop- and plot-level data to investigate the levels and determinants of rice producers’ technical efficiency for three villages with different characteristics in a major rice-growing

Molecular dynamics for irradiation driven chemistry

DEFF Research Database (Denmark)

Sushko, Gennady B.; Solov'yov, Ilia A.; Solov'yov, Andrey V.

2016-01-01

A new molecular dynamics (MD) approach for computer simulations of irradiation driven chemical transformations of complex molecular systems is suggested. The approach is based on the fact that irradiation induced quantum transformations can often be treated as random, fast and local processes...... that describe the classical MD of complex molecular systems under irradiation. The proposed irradiation driven molecular dynamics (IDMD) methodology is designed for the molecular level description of the irradiation driven chemistry. The IDMD approach is implemented into the MBN Explorer software package...... involving small molecules or molecular fragments. We advocate that the quantum transformations, such as molecular bond breaks, creation and annihilation of dangling bonds, electronic charge redistributions, changes in molecular topologies, etc., could be incorporated locally into the molecular force fields...

String fragmentation; La fragmentation des cordes

Energy Technology Data Exchange (ETDEWEB)

Drescher, H.J.; Werner, K. [Laboratoire de Physique Subatomique et des Technologies Associees - SUBATECH, Centre National de la Recherche Scientifique, 44 - Nantes (France)

1997-10-01

The classical string model is used in VENUS as a fragmentation model. For the soft domain simple 2-parton strings were sufficient, whereas for higher energies up to LHC, the perturbative regime of the QCD gives additional soft gluons, which are mapped on the string as so called kinks, energy singularities between the leading partons. The kinky string model is chosen to handle fragmentation of these strings by application of the Lorentz invariant area law. The `kinky strings` model, corresponding to the perturbative gluons coming from pQCD, takes into consideration this effect by treating the partons and gluons on the same footing. The decay law is always the Artru-Menessier area law which is the most realistic since it is invariant to the Lorentz and gauge transformations. For low mass strings a manipulation of the rupture point is necessary if the string corresponds already to an elementary particle determined by the mass and the flavor content. By means of the fragmentation model it will be possible to simulate the data from future experiments at LHC and RHIC 3 refs.

X-ray studies of recombinant anti-testosterone Fab fragments: the use of PEG 3350 in crystallization.

Science.gov (United States)

Valjakka, J; Hemminki, A; Teerinen, T; Takkinen, K; Rouvinen, J

2000-02-01

Recombinant anti-testosterone wild-type Fab fragment and mutant Fab fragments with high binding selectivity developed by protein engineering have been crystallized with and without ligands. Crystals of these Fab fragments were obtained by the vapour-diffusion technique at room temperature using solutions of PEG 3350 with various biological buffers and with a wide pH range. So far, five data sets have been collected from crystals of three Fab-antigen complexes and from two uncomplexed Fab fragments, with resolutions ranging from 2.10 to 3.1 A. Crystallization conditions for Fab fragments were found by using modifications of the low ionic strength PEG 3350 series. Suitable concentrations of PEG 400, MPD and glycerol solutions for use as cryoprotectants in PEG 3350 solutions have been determined. One useful observation was that PEG 3350 is able to work alone as a cryoprotectant. The screening protocol used requires a smaller amount of protein material to achieve auspicious pre-crystals than previously. Results support the claim that PEG 3350 is more suitable for the crystallization of Fab fragments than higher molecular weight PEGs.

A Comparison of Quantum and Molecular Mechanical Methods to Estimate Strain Energy in Druglike Fragments.

Science.gov (United States)

Sellers, Benjamin D; James, Natalie C; Gobbi, Alberto

2017-06-26

Reducing internal strain energy in small molecules is critical for designing potent drugs. Quantum mechanical (QM) and molecular mechanical (MM) methods are often used to estimate these energies. In an effort to determine which methods offer an optimal balance in accuracy and performance, we have carried out torsion scan analyses on 62 fragments. We compared nine QM and four MM methods to reference energies calculated at a higher level of theory: CCSD(T)/CBS single point energies (coupled cluster with single, double, and perturbative triple excitations at the complete basis set limit) calculated on optimized geometries using MP2/6-311+G**. The results show that both the more recent MP2.X perturbation method as well as MP2/CBS perform quite well. In addition, combining a Hartree-Fock geometry optimization with a MP2/CBS single point energy calculation offers a fast and accurate compromise when dispersion is not a key energy component. Among MM methods, the OPLS3 force field accurately reproduces CCSD(T)/CBS torsion energies on more test cases than the MMFF94s or Amber12:EHT force fields, which struggle with aryl-amide and aryl-aryl torsions. Using experimental conformations from the Cambridge Structural Database, we highlight three example structures for which OPLS3 significantly overestimates the strain. The energies and conformations presented should enable scientists to estimate the expected error for the methods described and we hope will spur further research into QM and MM methods.

Genetics of Euglossini bees (Hymenoptera in fragments of the Atlantic Forest in the region of Viçosa, MG

Directory of Open Access Journals (Sweden)

A. M. Waldschmidt

Full Text Available With uncontrolled deforestation, forest fragments remain, which in most cases are in different stages of regeneration and present isolated populations. In the present study we analyzed the genetic patterns of Eulaema nigrita populations in seven Atlantic Forest fragments of different sizes and successional stages in the region of Viçosa, MG. This was done by RAPD molecular markers. We observed that the area of the fragments had no effect on the genetic variability of E. nigrita in the direction predicted by meta-population models. Medium-sized well-preserved woods presented the lowest variability, whereas large and small woods were statistically identical. The evidence supports the notion that rural areas present greater dispersal among fragments, implying greater similarity between the populations of fragments located in rural areas when compared to fragments in urban areas.

Gas-phase structure and fragmentation pathways of singly protonated peptides with N-terminal arginine.

Science.gov (United States)

Bythell, Benjamin J; Csonka, István P; Suhai, Sándor; Barofsky, Douglas F; Paizs, Béla

2010-11-25

The gas-phase structures and fragmentation pathways of the singly protonated peptide arginylglycylaspartic acid (RGD) are investigated by means of collision-induced-dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. It is demonstrated that despite the ionizing proton being strongly sequestered at the guanidine group, protonated RGD can easily be fragmented on charge directed fragmentation pathways. This is due to facile mobilization of the C-terminal or aspartic acid COOH protons thereby generating salt-bridge (SB) stabilized structures. These SB intermediates can directly fragment to generate b(2) ions or facilely rearrange to form anhydrides from which both b(2) and b(2)+H(2)O fragments can be formed. The salt-bridge stabilized and anhydride transition structures (TSs) necessary to form b(2) and b(2)+H(2)O are much lower in energy than their traditional charge solvated counterparts. These mechanisms provide compelling evidence of the role of SB and anhydride structures in protonated peptide fragmentation which complements and supports our recent findings for tryptic systems (Bythell, B. J.; Suhai, S.; Somogyi, A.; Paizs, B. J. Am. Chem. Soc. 2009, 131, 14057-14065.). In addition to these findings we also report on the mechanisms for the formation of the b(1) ion, neutral loss (H(2)O, NH(3), guanidine) fragment ions, and the d(3) ion.

Peptide fragments induce a more rapid immune response than intact proteins in earthworms.

Science.gov (United States)

Hanusová, R; Tucková, L; Halada, P; Bezouska, K; Bilej, M

1999-01-01

The effect of in vivo proteolytic processing of protein antigen was studied in Eisenia foetida earthworms. Parenteral administration of the protein antigen induces elevated levels of an antigen-binding protein (ABP) which recognizes the protein used for stimulation. When the protein antigen is administered simultaneously with nontoxic serine proteinase inhibitor, ABP levels remain close to background. On the other hand, the in vivo adaptive response of earthworms to peptide fragments obtained by coelomic fluid digestion of the foreign antigen occurs even in the presence of proteinase inhibitor and, moreover, is significantly faster as compared to the response to intact antigen. These findings confirm the role of proteolytic processing in earthworms. MALDI mass spectrometric analysis of the fragments after coelomic fluid digestion has revealed the presence of the peptide fragments with molecular weights in the mass range 700-1100 Da.

Papain cleavage of the 38,000-dalton fragment inhibits the binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate to lys-539 on the 60,000-dalton fragment in human band 3.

Science.gov (United States)

Yamaguchi, Takeo; Kojima, Hideaki; Kawaguchi, Shiori; Shimada, Maiko; Aso, Haruka

2017-08-01

Human band 3 is a 98-kDa transmembrane (TM) protein comprising 14 TM segments. Papain cleavages band 3 into 38- and 60-kDa fragments. Under vigorous conditions, the cleavage of the loop region between the TM 7 of gate domain and the TM 8 of core domain in the 38-kDa fragment produces 7- and 31-kDa fragments. Conformational changes of the TM 5 segment containing Lys-539 by cleavage of the 38-kDa fragment remain unclear. Pressure-induced haemolysis of erythrocytes was suppressed by binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate (DIDS) to Lys-539. Such effect of DIDS was not observed upon cleavage of the 38-kDa fragment, because of inhibition of DIDS binding to Lys-539. Using fluorescence of DIDS labelled to Lys-539, conformational changes of band 3 were examined. Fluorescence spectra demonstrated that the molecular motion of DIDS is more restricted upon digestion of the 38-kDa fragment. Interestingly, the quenching of DIDS fluorescence showed that Hg2+ is less accessible to DIDS upon digestion of the 38-kDa fragment. Taken together, we propose that the conformational changes of the TM 5 segment characterized by the sequestration and restricted motion of Lys-539 are induced by the cleavage of the loop region between the TM 7 and the TM 8. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Fission fragment angular momentum

International Nuclear Information System (INIS)

Frenne, D. De

1991-01-01

Most of the energy released in fission is converted into translational kinetic energy of the fragments. The remaining excitation energy will be distributed among neutrons and gammas. An important parameter characterizing the scission configuration is the primary angular momentum of the nascent fragments. Neutron emission is not expected to decrease the spin of the fragments by more than one unit of angular momentum and is as such of less importance in the determination of the initial fragment spins. Gamma emission is a suitable tool in studying initial fragment spins because the emission time, number, energy, and multipolarity of the gammas strongly depend on the value of the primary angular momentum. The main conclusions of experiments on gamma emission were that the initial angular momentum of the fragments is large compared to the ground state spin and oriented perpendicular to the fission axis. Most of the recent information concerning initial fragment spin distributions comes from the measurement of isomeric ratios for isomeric pairs produced in fission. Although in nearly every mass chain isomers are known, only a small number are suitable for initial fission fragment spin studies. Yield and half-life considerations strongly limit the number of candidates. This has the advantage that the behavior of a specific isomeric pair can be investigated for a number of fissioning systems at different excitation energies of the fragments and fissioning nuclei. Because most of the recent information on primary angular momenta comes from measurements of isomeric ratios, the global deexcitation process of the fragments and the calculation of the initial fragment spin distribution from measured isomeric ratios are discussed here. The most important results on primary angular momentum determinations are reviewed and some theoretical approaches are given. 45 refs., 7 figs., 2 tabs

Fragmentation of DNA affects the accuracy of the DNA quantitation by the commonly used methods

Directory of Open Access Journals (Sweden)

Sedlackova Tatiana

2013-02-01

Full Text Available Abstract Background Specific applications and modern technologies, like non-invasive prenatal testing, non-invasive cancer diagnostic and next generation sequencing, are currently in the focus of researchers worldwide. These have common characteristics in use of highly fragmented DNA molecules for analysis. Hence, for the performance of molecular methods, DNA concentration is a crucial parameter; we compared the influence of different levels of DNA fragmentation on the accuracy of DNA concentration measurements. Results In our comparison, the performance of the currently most commonly used methods for DNA concentration measurement (spectrophotometric, fluorometric and qPCR based were tested on artificially fragmented DNA samples. In our comparison, unfragmented and three specifically fragmented DNA samples were used. According to our results, the level of fragmentation did not influence the accuracy of spectrophotometric measurements of DNA concentration, while other methods, fluorometric as well as qPCR-based, were significantly influenced and a decrease in measured concentration was observed with more intensive DNA fragmentation. Conclusions Our study has confirmed that the level of fragmentation of DNA has significant impact on accuracy of DNA concentration measurement with two of three mostly used methods (PicoGreen and qPCR. Only spectrophotometric measurement was not influenced by the level of fragmentation, but sensitivity of this method was lowest among the three tested. Therefore if it is possible the DNA quantification should be performed with use of equally fragmented control DNA.

The hierarchical structure of molecular clouds

International Nuclear Information System (INIS)

Chieze, J.P.

1987-01-01

The mass-radius-velocity dispersion relations observed among the members of cool molecular complexes is interpreted in terms of fragmentation at the gravitational instability threshold in a roughly constant pressure environment. The mass range of the self-similar fragmentation hierarchy is governed by the thermal instability thresholds. Using a realistic equation of state, the gravitational stability of thermally stable clumps is analysed as a function of both the local gas pressure and extinction of the mean interstellar radiation field

Azimuthal Anisotropies in Nuclear Fragmentation

International Nuclear Information System (INIS)

Dabrowska, A.; Szarska, M.; Trzupek, A.; Wolter, W.; Wosiek, B.

2002-01-01

The directed and elliptic flow of fragments emitted from the excited projectile nuclei has been observed for 158 AGeV Pb collisions with the lead and plastic targets. For comparison the flow analysis has been performed for 10.6 AGeV Au collisions with the emulsion target. The strong directed flow of heaviest fragments is found. Light fragments exhibit directed flow opposite to that of heavy fragments. The elliptic flow for all multiply charged fragments is positive and increases with the charge of the fragment. The observed flow patterns in the fragmentation of the projectile nucleus are practically independent of the mass of the target nucleus and the collision energy. Emission of fragments in nuclear multifragmentation shows similar, although weaker, flow effects. (author)

Formation and fragmentation of protostellar dense cores

International Nuclear Information System (INIS)

Maury, Anaelle

2009-01-01

Stars form in molecular clouds, when they collapse and fragment to produce protostellar dense cores. These dense cores are then likely to contract under their own gravity, and form young protostars, that further evolve while accreting their circumstellar mass, until they reach the main sequence. The main goal of this thesis was to study the formation and fragmentation of protostellar dense cores. To do so, two main studies, described in this manuscript, were carried out. First, we studied the formation of protostellar cores by quantifying the impact of protostellar outflows on clustered star formation. We carried out a study of the protostellar outflows powered by the young stellar objects currently formed in the NGc 2264-C proto-cluster, and we show that protostellar outflows seem to play a crucial role as turbulence progenitors in clustered star forming regions, although they seem unlikely to significantly modify the global infall processes at work on clump scales. Second, we investigated the formation of multiple systems by core fragmentation, by using high - resolution observations that allow to probe the multiplicity of young protostars on small scales. Our results suggest that the multiplicity rate of protostars on small scales increase while they evolve, and thus favor dynamical scenarios for the formation of multiple systems. Moreover, our results favor magnetized scenarios of core collapse to explain the small-scale properties of protostars at the earliest stages. (author) [fr

Fragmentation inside atomic cooling haloes exposed to Lyman-Werner radiation

Science.gov (United States)

Regan, John A.; Downes, Turlough P.

2018-04-01

Supermassive stars born in pristine environments in the early Universe hold the promise of being the seeds for the supermassive black holes observed as high redshift quasars shortly after the epoch of reionisation. H2 suppression is thought to be crucial in order to negate normal Population III star formation and allow high accretion rates to drive the formation of supermassive stars. Only in the cases where vigorous fragmentation is avoided will a monolithic collapse be successful, giving rise to a single massive central object. We investigate the number of fragmentation sites formed in collapsing atomic cooling haloes subject to various levels of background Lyman-Werner flux. The background Lyman-Werner flux manipulates the chemical properties of the gas in the collapsing halo by destroying H2. We find that only when the collapsing gas cloud shifts from the molecular to the atomic cooling regime is the degree of fragmentation suppressed. In our particular case, we find that this occurs above a critical Lyman-Werner background of J ˜ 10 J21. The important criterion being the transition to the atomic cooling regime rather than the actual value of J, which will vary locally. Once the temperature of the gas exceeds T ≳ 104 K and the gas transitions to atomic line cooling, then vigorous fragmentation is strongly suppressed.

Molecular Tools For Biodiversity Conservation

Indian Academy of Sciences (India)

... habits that make them difficultstudy subjects when using conventional field techniques.Molecular tools can be used to decipher distributions andpopulation connectedness in fragmented habitats and identifypopulations of immediate conservation concern. We discussthese with case studies on some cat species in India.

Analysis of fission-fragment mass distribution within the quantum-mechanical fragmentation theory

Energy Technology Data Exchange (ETDEWEB)

Singh, Pardeep; Kaur, Harjeet [Guru Nanak Dev University, Department of Physics, Amritsar (India)

2016-11-15

The fission-fragment mass distribution is analysed for the {sup 208}Pb({sup 18}O, f) reaction within the quantum-mechanical fragmentation theory (QMFT). The reaction potential has been calculated by taking the binding energies, Coulomb potential and proximity potential of all possible decay channels and a stationary Schroedinger equation has been solved numerically to calculate the fission-fragment yield. The overall results for mass distribution are compared with those obtained in experiment. Fine structure dips in yield, corresponding to fragment shell closures at Z = 50 and N=82, which are observed by Bogachev et al., are reproduced successfully in the present calculations. These calculations will help to estimate the formation probabilities of fission fragments and to understand many related phenomena occurring in the fission process. (orig.)

Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits.

Science.gov (United States)

Blaazer, Antoni R; Orrling, Kristina M; Shanmugham, Anitha; Jansen, Chimed; Maes, Louis; Edink, Ewald; Sterk, Geert Jan; Siderius, Marco; England, Paul; Bailey, David; de Esch, Iwan J P; Leurs, Rob

2015-01-01

Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint. Fragment-based drug discovery is a target-based approach that typically involves the screening of a relatively small number of fragment-like (molecular weight <300) molecules that efficiently cover chemical space. Here, we report a fragment screening on TbrPDEB1, an essential cyclic nucleotide phosphodiesterase (PDE) from Trypanosoma brucei, and human PDE4D, an off-target, in a workflow in which fragment hits and a series of close analogs are subsequently screened for antiparasitic activity in a phenotypic panel. The phenotypic panel contained T. brucei, Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum, the causative agents of human African trypanosomiasis (sleeping sickness), Chagas disease, leishmaniasis, and malaria, respectively, as well as MRC-5 human lung cells. This hybrid screening workflow has resulted in the discovery of various benzhydryl ethers with antiprotozoal activity and low toxicity, representing interesting starting points for further antiparasitic optimization. © 2014 Society for Laboratory Automation and Screening.

Transmission of tuberculosis in Havana, Cuba: a molecular epidemiological study by IS6110 restriction fragment length polymorphism typing

Directory of Open Access Journals (Sweden)

Diaz R

2001-01-01

Full Text Available The combination of molecular and conventional epidemiological methods has improved the knowledge about the transmission of tuberculosis in urban populations. To examine transmission of tuberculosis in Havana, Cuba, with DNA fingerprinting, we studied 51 out of 92 Mycobacterium tuberculosis strains isolated from tuberculosis patients who resided in Havana and whose infection was culture-confirmed in the period from September 1997 to March 1998. Isolates from 28 patients (55% had unique IS6110 restriction fragment length polymorphism (RFLP patterns, while isolates from 23 others (45% had identical patterns and belonged to 7 clusters. Three clusters consisting of six, five and two cases were each related to small outbreaks that occurred in a closed setting. Three other clustered cases were linked to a large outbreak that occurred in another institution. Younger patients were more correlated to clustering than older ones. The finding that 45% of the isolates had clustered RFLP patterns suggests that recent transmission is a key factor in the tuberculosis cases in Havana. The IS6110 RFLP typing made it possible to define the occurrence of outbreaks in two closed institutions.

Molecular Characterization of Yeast Strains Isolated from Different Sources by Restriction Fragment Length Polymorphism

International Nuclear Information System (INIS)

Ali, M. S.; Latif, Z.

2016-01-01

Various molecular techniques like analysis of the amplified rDNA internal transcribed spacers (ITS), intragenic spacers and total ITS region analysis by restriction fragment length polymorphism (RFLP) has been introduced for yeast identification but there are limited databases to identify yeast species on the basis of 5.8S rDNA. In this study, twenty nine yeast strains from various sources including spoiled fruits, vegetables, foodstuffs, and concentrated juices were characterized by PCR-RFLP. PCR-RFLP has been used to characterize yeasts present in different spoiled food samples after isolation of the yeasts. By using this technique, the isolated yeast strains were characterized by direct 5.8S-ITS rDNA region amplification. RFLP analysis was applied to each of the amplification products (varied from 400bp to 800bp) detected, and the corresponding yeast identifications were made according to each specific restriction patterns obtained after treatment with two endonucleases TaqI and HaeIII which yielded a specific banding pattern for each species. For further confirmation amplified products of eleven selected isolates were sequenced and blast on NCBI. Both RFLP and sequence analyses of the strains with accession nos. KF472163, KF472164, KF472165, KF472166, KF472167, KF472168, KF472169, KF472170, KF472171, KF472172, KF472173 gave significantly similar results. The isolates were found to belong five different yeast species including; Candida spp., Pichia spp., Kluyveromyces spp., Clavispora spp. and Hanseniaspora spp. This method provides a fast, easy, reliable and authentic way for determining yeast population present in different type of samples, as compared to traditional characterization technique. (author)

Correlations of intermediate mass fragments from Fe+Ta, Au, and Th collisions

International Nuclear Information System (INIS)

Sangster, T.C.; Begemann-Blaich, M.; Blaich, T.; Britt, H.C.; Hansen, L.F.; Namboodiri, M.N.; Peilert, G.

1995-01-01

Charge, velocity, and angular correlations between intermediate mass fragments (IMF) are presented for 50 and 100 MeV/nucleon Fe bombardments of Ta, Au, and Th targets. Correlation functions generated as a function of the relative velocity and the opening angle between two IMF's are qualitatively independent of the projectile energy and target mass and show a suppression at small relative velocities and opening angles due to the Coulomb repulsion between the fragments. The correlations are consistent with IMF's emitted primarily from a highly excited target residue following a rapid preequilibrium cascade. The correlation data are compared to model calculations using the event generator MENEKA and the quantum molecular dynamics (QMD) code with a statistical deexcitation of residual fragments utilizing the multifragmentation code SMM. All data are consistent with a simultaneous multifragmentation at a freeze-out density of 0.1--0.3 times normal nuclear matter density or a more sequential emission with time constant τ≤500 fm/c

Analysis for fragmentation products of proton-induced reactions on Pb with energy up to GeV

International Nuclear Information System (INIS)

Fan Sheng; Li Zhuxia; Zhao Zhixiang; Ding Dazhao

2002-01-01

The mass and charge distribution of residual products produced in the spallation reaction needs to be studied because it can provide useful information for the disposal of nuclear and the radiation damage in the spallation target. The mass and charge distribution of the spallation products is studied by using quantum molecular dynamic (QMD) models. The simulation results are well agreed with the experimental data of the spallation fragment and empirical formula. However, QMD model does not include the fission process; the calculations can not reproduce the fission fragment. The fission model is introduced into QMD model to investigate the fragment products from proton-induced reactions on Pb. The results are in good agreement with the experimental data

Wiring Techniques for the Fixation of Trochanteric Fragments during Bipolar Hemiarthroplasty for Femoral Intertrochanteric Fracture: Clinical Study and Technical Note.

Science.gov (United States)

Lee, Joong-Myung; Cho, Yongsuk; Kim, Junhyun; Kim, Dong-Won

2017-03-01

Femoral intertrochanteric fractures are common in the elderly. Appropriate surgical fixation of trochanteric fracture fragments can restore normal anatomical structure and ambulation, and can aid in the recovery of biomechanical function of the hip. We evaluated clinical outcomes of bipolar hemiarthroplasty using a wiring technique for trochanteric fracture fragment fixation. From September 2006 to February 2015, a total of 260 cases underwent simultaneous bipolar hemiarthroplasty and wire fixation. A total of 65 patients (69 hips) with an average age of 78 years and more than one year of follow-up was included in the study. Using pre-, postoperative and follow-up radiograms, we evaluated wire fixation failure and also assessed changes in walking ability. Loosening or osteolysis around the stem was not observed; however, we did observe bone growth around the stem (54 cases), cortical hypertrophy (6 cases), a wide range of sclerotic lines but no stem subsidence (1 case), wire breakage (9 cases), and fracture fragment migration with no significant functional deficiency (2 cases). Our study showed that additional wiring for trochanteric fracture fragment fixation following bipolar hemiarthroplasty can help restore normal anatomy. The added stability results in faster rehabilitation, and good clinical and radiographic outcomes. We recommend this procedure in this type of fracture.

Gene flow and pathogen transmission among bobcats (Lynx rufus) in a fragmented urban landscape

Science.gov (United States)

Lee, Justin S.; Ruell, Emily W.; Boydston, Erin E.; Lyren, Lisa M.; Alonso, Robert S.; Troyer, Jennifer L.; Crooks, Kevin R.; VandeWoude, Sue

2012-01-01

Urbanization can result in the fragmentation of once contiguous natural landscapes into a patchy habitat interspersed within a growing urban matrix. Animals living in fragmented landscapes often have reduced movement among habitat patches because of avoidance of intervening human development, which potentially leads to both reduced gene flow and pathogen transmission between patches. Mammalian carnivores with large home ranges, such as bobcats (Lynx rufus), may be particularly sensitive to habitat fragmentation. We performed genetic analyses on bobcats and their directly transmitted viral pathogen, feline immunodeficiency virus (FIV), to investigate the effects of urbanization on bobcat movement. We predicted that urban development, including major freeways, would limit bobcat movement and result in genetically structured host and pathogen populations. We analysed molecular markers from 106 bobcats and 19 FIV isolates from seropositive animals in urban southern California. Our findings indicate that reduced gene flow between two primary habitat patches has resulted in genetically distinct bobcat subpopulations separated by urban development including a major highway. However, the distribution of genetic diversity among FIV isolates determined through phylogenetic analyses indicates that pathogen genotypes are less spatially structured--exhibiting a more even distribution between habitat fragments. We conclude that the types of movement and contact sufficient for disease transmission occur with enough frequency to preclude structuring among the viral population, but that the bobcat population is structured owing to low levels of effective bobcat migration resulting in gene flow. We illustrate the utility in using multiple molecular markers that differentially detect movement and gene flow between subpopulations when assessing connectivity.

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

Science.gov (United States)

2018-01-01

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

Comparative study of BxNyCz nanojunctions fragments

International Nuclear Information System (INIS)

Batista, Fabiana Aparecida de Souza; Manzanares, Raquel Dastre; Carvalho, Ana Claudia Monteiro; Reis Junior, Magno dos; Custodio, Rogerio

2011-01-01

Theoretical analysis of formation energy and geometry was done to compare the relative stabilities of modified carbon nanostructures representative fragments. Structure and energies of formation were calculated at semiempirical level of theory. Depending of B-N pair localization on the molecular structures the formation enthalpy decreases. B-N substitution in tubular structures at low concentration decreases the energy when the tubes have small diameters. Our results are in according to experimental works which have shown that boron and nitrogen are met at region of defects in B X C Y N Z nanostructures. (author)

Hypervelocity Impact Test Fragment Modeling: Modifications to the Fragment Rotation Analysis and Lightcurve Code

Science.gov (United States)

Gouge, Michael F.

2011-01-01

Hypervelocity impact tests on test satellites are performed by members of the orbital debris scientific community in order to understand and typify the on-orbit collision breakup process. By analysis of these test satellite fragments, the fragment size and mass distributions are derived and incorporated into various orbital debris models. These same fragments are currently being put to new use using emerging technologies. Digital models of these fragments are created using a laser scanner. A group of computer programs referred to as the Fragment Rotation Analysis and Lightcurve code uses these digital representations in a multitude of ways that describe, measure, and model on-orbit fragments and fragment behavior. The Dynamic Rotation subroutine generates all of the possible reflected intensities from a scanned fragment as if it were observed to rotate dynamically while in orbit about the Earth. This calls an additional subroutine that graphically displays the intensities and the resulting frequency of those intensities as a range of solar phase angles in a Probability Density Function plot. This document reports the additions and modifications to the subset of the Fragment Rotation Analysis and Lightcurve concerned with the Dynamic Rotation and Probability Density Function plotting subroutines.

Optimizing virtual fragment screening for GPCRs: Identification of novel ligands for the histamine H3 receptor using ligand- and structure-based molecular fingerprints

NARCIS (Netherlands)

Sirci, F.; Istyastono, E.P.; Vischer, H.F.; Nijmeijer, S.; Kuijer, M.; Kooistra, A.J.; Wijtmans, M.; Mannhold, R.; Leurs, R.; de Esch, I.J.P.; de Graaf, C.

2012-01-01

Virtual fragment screening (VFS) is a promising new method that uses computer models to identify small, fragment-like biologically active molecules as useful starting points for fragment-based drug discovery (FBDD). Training sets of true active and inactive fragment-like molecules to construct and

Fragment capture device

Science.gov (United States)

Payne, Lloyd R.; Cole, David L.

2010-03-30

A fragment capture device for use in explosive containment. The device comprises an assembly of at least two rows of bars positioned to eliminate line-of-sight trajectories between the generation point of fragments and a surrounding containment vessel or asset. The device comprises an array of at least two rows of bars, wherein each row is staggered with respect to the adjacent row, and wherein a lateral dimension of each bar and a relative position of each bar in combination provides blockage of a straight-line passage of a solid fragment through the adjacent rows of bars, wherein a generation point of the solid fragment is located within a cavity at least partially enclosed by the array of bars.

Advantages of crystallographic fragment screening: functional and mechanistic insights from a powerful platform for efficient drug discovery.

Science.gov (United States)

Patel, Disha; Bauman, Joseph D; Arnold, Eddy

2014-01-01

X-ray crystallography has been an under-appreciated screening tool for fragment-based drug discovery due to the perception of low throughput and technical difficulty. Investigators in industry and academia have overcome these challenges by taking advantage of key factors that contribute to a successful crystallographic screening campaign. Efficient cocktail design and soaking methodologies have evolved to maximize throughput while minimizing false positives/negatives. In addition, technical improvements at synchrotron beamlines have dramatically increased data collection rates thus enabling screening on a timescale comparable to other techniques. The combination of available resources and efficient experimental design has resulted in many successful crystallographic screening campaigns. The three-dimensional crystal structure of the bound fragment complexed to its target, a direct result of the screening effort, enables structure-based drug design while revealing insights regarding protein dynamics and function not readily obtained through other experimental approaches. Furthermore, this "chemical interrogation" of the target protein crystals can lead to the identification of useful reagents for improving diffraction resolution or compound solubility. Copyright © 2014. Published by Elsevier Ltd.

Advantages of Crystallographic Fragment Screening: Functional and Mechanistic Insights from a Powerful Platform for Efficient Drug Discovery

Science.gov (United States)

Patel, Disha; Bauman, Joseph D.; Arnold, Eddy

2015-01-01

X-ray crystallography has been an under-appreciated screening tool for fragment-based drug discovery due to the perception of low throughput and technical difficulty. Investigators in industry and academia have overcome these challenges by taking advantage of key factors that contribute to a successful crystallographic screening campaign. Efficient cocktail design and soaking methodologies have evolved to maximize throughput while minimizing false positives/negatives. In addition, technical improvements at synchrotron beamlines have dramatically increased data collection rates thus enabling screening on a timescale comparable to other techniques. The combination of available resources and efficient experimental design has resulted in many successful crystallographic screening campaigns. The three-dimensional crystal structure of the bound fragment complexed to its target, a direct result of the screening effort, enables structure-based drug design while revealing insights regarding protein dynamics and function not readily obtained through other experimental approaches. Furthermore, this “chemical interrogation” of the target protein crystals can lead to the identification of useful reagents for improving diffraction resolution or compound solubility. PMID:25117499

Exact Solutions of Fragmentation Equations with General Fragmentation Rates and Separable Particles Distribution Kernels

Directory of Open Access Journals (Sweden)

S. C. Oukouomi Noutchie

2014-01-01

Full Text Available We make use of Laplace transform techniques and the method of characteristics to solve fragmentation equations explicitly. Our result is a breakthrough in the analysis of pure fragmentation equations as this is the first instance where an exact solution is provided for the fragmentation evolution equation with general fragmentation rates. This paper is the key for resolving most of the open problems in fragmentation theory including “shattering” and the sudden appearance of infinitely many particles in some systems with initial finite particles number.

Land fragmentation and production diversification

NARCIS (Netherlands)

Ciaian, Pavel; Guri, Fatmir; Rajcaniova, Miroslava; Drabik, Dusan; Paloma, Sergio Gomez Y.

2018-01-01

We analyze the impact of land fragmentation on production diversification in rural Albania. Albania represents a particularly interesting case for studying land fragmentation as the fragmentation is a direct outcome of land reforms. The results indicate that land fragmentation is an important driver

Fragmentation processes in nuclear reactions

International Nuclear Information System (INIS)

Legrain, R.

1984-08-01

Projectile and nuclear fragmentation are defined and processes referred to are recalled. The two different aspects of fragmentation are considered but the emphasis is also put on heavy ion induced reactions. The preliminary results of an experiment performed at GANIL to study peripheral heavy ions induced reactions at intermediate energy are presented. The results of this experiment will illustrate the characteristics of projectile fragmentation and this will also give the opportunity to study projectile fragmentation in the transition region. Then nuclear fragmentation is considered which is associated with more central collisions in the case of heavy ion induced reactions. This aspect of fragmentation is also ilustrated with two heavy ion experiments in which fragments emitted at large angle have been observed

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

International Nuclear Information System (INIS)

Zielinsky, A.; Hirsh, J.; Straumanis, G.; Carter, C.J.; Gent, M.; Sackett, D.L.; Hull, R.; Kelton, J.G.; Powers, P.; Turpie, A.G.

1982-01-01

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

International Nuclear Information System (INIS)

Zielinsky, A.; Hirsh, J.; Straumanis, G.; Carter, C.J.; Gent, M.; Sackett, D.L.; Hull, R.; Kelton, J.G.; Powers, P.

1982-01-01

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice

Observation of the dynamic movement of fragmentations by high-speed camera and high-speed video

Science.gov (United States)

Suk, Chul-Gi; Ogata, Yuji; Wada, Yuji; Katsuyama, Kunihisa

1995-05-01

The experiments of blastings using mortal concrete blocks and model concrete columns were carried out in order to obtain technical information on fragmentation caused by the blasting demolition. The dimensions of mortal concrete blocks were 1,000 X 1,000 X 1,000 mm. Six kinds of experimental blastings were carried out using mortal concrete blocks. In these experiments precision detonators and No. 6 electric detonators with 10 cm detonating fuse were used and discussed the control of fragmentation. As the results of experiment it was clear that the flying distance of fragmentation can be controlled using a precise blasting system. The reinforced concrete model columns for typical apartment houses in Japan were applied to the experiments. The dimension of concrete test column was 800 X 800 X 2400 mm and buried 400 mm in the ground. The specified design strength of the concrete was 210 kgf/cm2. These columns were exploded by the blasting with internal loading of dynamite. The fragmentation were observed by two kinds of high speed camera with 500 and 2000 FPS and a high speed video with 400 FPS. As one of the results in the experiments, the velocity of fragmentation, blasted 330 g of explosive with the minimum resisting length of 0.32 m, was measured as much as about 40 m/s.

Induced refolding of a temperature denatured llama heavy-chain antibody fragment by its antigen

NARCIS (Netherlands)

Dolk, E.; Vliet, C. van; Perez, J.M.J.; Vriend, G.; Darbon, H.; Ferrat, G.; Cambillau, C.; Frenken, L.G.J.; Verrips, T.

2005-01-01

In a previous study we have shown that llama VHH antibody fragments are able to bind their antigen after a heat shock of 90°C, in contrast to the murine monoclonal antibodies. However, the molecular mechanism by which antibody:antigen interaction occurs under these extreme conditions remains

IAEA advisory group meeting on 'Technical Aspects of Atomic and Molecular Data Processing and Exchange' (14th meeting of the A + M data centres and ALADDIN network). Summary report

International Nuclear Information System (INIS)

Stephens, A.

1998-01-01

The proceedings of the IAEA Advisory Group Meeting on ''Technical Aspects of Atomic and Molecular Data Processing and Exchange (14th Meeting of A + M Data Centres and ALADDIN Network)'', held on July 21-22, 1997 in Vienna, Austria are briefly described. The meeting conclusions and recommendations on the priorities in A + M data compilation and evaluation, and on the technical aspects of data processing and exchange are also presented. The document includes 15 reports from various Data Centres

Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy.

Science.gov (United States)

Sun, S; Henriksen, K; Karsdal, M A; Armbrecht, G; Belavý, D L; Felsenberg, D; Rittweger, J; Wang, Y; Zheng, Q; Nedergaard, A F

2014-10-01

In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass. Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competitive ELISA assay for measurement in serum. Rat tissue extractions in the presence or absence of a series of proteases of interest were used to identify its enzymatic origin. A rat model of dexamethasone (DEX) induced muscle atrophy and a human 56-day bed rest study with and without vibration therapy were used to assess biological and clinical relevance. A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up at a 16.4 (±4.6) % increase at day 47. We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy. Copyright © 2014 Elsevier Inc. All rights reserved.

Fragmentation of chromatin DNA in mouse thymus cells after whole body γ-irradiation

International Nuclear Information System (INIS)

Wei Kang; Liu Xueying; Zhu Xuefen

1984-01-01

The characteristics of soluble chromatin in mouse thymus nuclei after whole body γ-irradiation were investigated by means of polyacrylamide gel electrophoresis. After deproteinization and electrophoresis eight regular DNA bands were revealed. The molecular weights of these bands were estimated by comparing their migration rates with those of the standard fragments obtained from PBR 322 digested completely by restrictive endonuclease Hae III. The molecular weight of the first band was calculated to be 186 base pairs corresponding approximately to the size of DNA fragment from a single nucleosome, and those of other bands appeared to be its multiples. The results suggested that the disintegration of chromatin DNA after γ-irradiation might have occurred at the linkage regions of chromatin. The autolysis product of normal thymus chromatin under sterile condition were also analyzed and its electrophoretic pattern was found to be just the same as that of the postirradiation product. It seems, therefore, that the endonuclease existing in normal tissues might be responsible for the postirradiation chromatin degradation. The mechanism of this kind of enzymatic digestion remains to be elucidated in further investigation. (author)

Molecular growth in clusters of polycyclic aromatic hydrocarbons induced by collisions with ions

International Nuclear Information System (INIS)

Delaunay, Rudy

2016-01-01

This thesis concerns the experimental study of the interaction between low energy ions (keV range) and neutral isolated molecules or clusters of polycyclic aromatic hydrocarbons (PAH) in the gas phase. The use of ionising radiations on these complex molecular systems of astrophysical interest allowed to highlight processes of statistical fragmentation, corresponding to the redistribution of the energy through the degrees of freedom of the target, and non-statistical fragmentation, linked to binary collisions of the ions on the nuclei of the target. A mechanism of intermolecular growth in clusters of PAH is observed. It is associated to the ultrafast (≤ ps) formation of fragments inside the clusters following binary collisions. The presence of a molecular environment around the fragments formed during the interaction may initiate a process of reactivity between the fragments and the molecules of the clusters. More precisely, the study focusses on the importance of the electronic stopping power SE and the nuclear stopping power SN of the projectile ion. It shows that the molecular growth is enhanced when SN is higher than SE. This can be explained by the fact that the deposit of energy is mainly due to the interaction with the nuclei of the target. The process of growth has been observed for all the molecules of PAH studied during this thesis and also for nitrogenated analogues of the molecule of anthracene. This demonstrates that molecular growth may be efficiently induced by collisions of low energy ions with clusters of PAH. (author) [fr

PET/MRI: Technical challenges and recent advances

International Nuclear Information System (INIS)

Jung, Jin Ho; Choi, Yong; Im, Ki Chun

2016-01-01

Integrated positron emission tomography (PET)/magnetic resonance imaging (MRI), which can provide complementary functional and anatomical information about a specific organ or body system at the molecular level, has become a powerful imaging modality to understand the molecular biology details, disease mechanisms, and pharmacokinetics in animals and humans. Although the first experiment on the PET/MRI was performed in the early 1990s, its clinical application was accomplished in recent years because there were various technical challenges in integrating PET and MRI in a single system with minimum mutual interference between PET and MRI. This paper presents the technical challenges and recent advances in combining PET and MRI along with several approaches for improving PET image quality of the PET/MRI hybrid imaging system

Flexible bent rod model with a saturating induced dipole moment to study the electric linear dichroism of DNA fragments

Directory of Open Access Journals (Sweden)

Jorge A. Bertolotto

2016-06-01

Full Text Available In the present work we make a theoretical study of the steady state electric linear dichroism of DNA fragments in aqueous solution. The here developed theoretical approach considers a flexible bent rod model with a saturating induced dipole moment. The electric polarizability tensor of bent DNA fragments is calculated considering a phenomenological model which theoretical and experimental backgroung is presented here. The model has into account the electric polarizability longitudinal and transversal to the macroion. Molecular flexibility is described using an elastic potential. We consider DNA fragments originally bent with bending fluctuations around an average bending angle. The induced dipole moment is supposed constant once the electric field strength grows up at critical value. To calculate the reduced electric linear dichroism we determine the optical factor considering the basis of the bent DNA perpendicular to the molecular axis. The orientational distribution function has into account the anisotropic electric properties and the molecule flexibility. We applied the present theoretical background to fit electric dichroism experimental data of DNA fragments reported in the bibliography in a wide range of molecular weight and electric field. From these fits, values of DNA physical properties are estimated. We compare and discuss the results here obtained with the theoretical and experimental data presented by other authors. The original contributions of this work are: the inclusion of the transversal electric polarizability saturating with the electric field, the description of the electric properties with an electric polarizability tensor dependant on the bending angle and the use of an arc model originally bent.

Flexible bent rod model with a saturating induced dipole moment to study the electric linear dichroism of DNA fragments

Science.gov (United States)

Bertolotto, Jorge A.; Umazano, Juan P.

2016-06-01

In the present work we make a theoretical study of the steady state electric linear dichroism of DNA fragments in aqueous solution. The here developed theoretical approach considers a flexible bent rod model with a saturating induced dipole moment. The electric polarizability tensor of bent DNA fragments is calculated considering a phenomenological model which theoretical and experimental backgroung is presented here. The model has into account the electric polarizability longitudinal and transversal to the macroion. Molecular flexibility is described using an elastic potential. We consider DNA fragments originally bent with bending fluctuations around an average bending angle. The induced dipole moment is supposed constant once the electric field strength grows up at critical value. To calculate the reduced electric linear dichroism we determine the optical factor considering the basis of the bent DNA perpendicular to the molecular axis. The orientational distribution function has into account the anisotropic electric properties and the molecule flexibility. We applied the present theoretical background to fit electric dichroism experimental data of DNA fragments reported in the bibliography in a wide range of molecular weight and electric field. From these fits, values of DNA physical properties are estimated. We compare and discuss the results here obtained with the theoretical and experimental data presented by other authors. The original contributions of this work are: the inclusion of the transversal electric polarizability saturating with the electric field, the description of the electric properties with an electric polarizability tensor dependant on the bending angle and the use of an arc model originally bent.

A new in silico classification model for ready biodegradability, based on molecular fragments.

Science.gov (United States)

Lombardo, Anna; Pizzo, Fabiola; Benfenati, Emilio; Manganaro, Alberto; Ferrari, Thomas; Gini, Giuseppina

2014-08-01

Regulations such as the European REACH (Registration, Evaluation, Authorization and restriction of Chemicals) often require chemicals to be evaluated for ready biodegradability, to assess the potential risk for environmental and human health. Because not all chemicals can be tested, there is an increasing demand for tools for quick and inexpensive biodegradability screening, such as computer-based (in silico) theoretical models. We developed an in silico model starting from a dataset of 728 chemicals with ready biodegradability data (MITI-test Ministry of International Trade and Industry). We used the novel software SARpy to automatically extract, through a structural fragmentation process, a set of substructures statistically related to ready biodegradability. Then, we analysed these substructures in order to build some general rules. The model consists of a rule-set made up of the combination of the statistically relevant fragments and of the expert-based rules. The model gives good statistical performance with 92%, 82% and 76% accuracy on the training, test and external set respectively. These results are comparable with other in silico models like BIOWIN developed by the United States Environmental Protection Agency (EPA); moreover this new model includes an easily understandable explanation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Large scale meta-analysis of fragment-based screening campaigns: privileged fragments and complementary technologies.

Science.gov (United States)

Kutchukian, Peter S; Wassermann, Anne Mai; Lindvall, Mika K; Wright, S Kirk; Ottl, Johannes; Jacob, Jaison; Scheufler, Clemens; Marzinzik, Andreas; Brooijmans, Natasja; Glick, Meir

2015-06-01

A first step in fragment-based drug discovery (FBDD) often entails a fragment-based screen (FBS) to identify fragment "hits." However, the integration of conflicting results from orthogonal screens remains a challenge. Here we present a meta-analysis of 35 fragment-based campaigns at Novartis, which employed a generic 1400-fragment library against diverse target families using various biophysical and biochemical techniques. By statistically interrogating the multidimensional FBS data, we sought to investigate three questions: (1) What makes a fragment amenable for FBS? (2) How do hits from different fragment screening technologies and target classes compare with each other? (3) What is the best way to pair FBS assay technologies? In doing so, we identified substructures that were privileged for specific target classes, as well as fragments that were privileged for authentic activity against many targets. We also revealed some of the discrepancies between technologies. Finally, we uncovered a simple rule of thumb in screening strategy: when choosing two technologies for a campaign, pairing a biochemical and biophysical screen tends to yield the greatest coverage of authentic hits. © 2014 Society for Laboratory Automation and Screening.

High-resolution genomic fingerprinting of Campylobacter jejuni and Campylobacter coli by analysis of amplified fragment length polymorphisms

DEFF Research Database (Denmark)

Kokotovic, Branko; On, Stephen L.W.

1999-01-01

A method for high-resolution genomic fingerprinting of the enteric pathogens Campylobacter jejuni and Campylobacter coli, based on the determination of amplified fragment length polymorphism, is described. The potential of this method for molecular epidemiological studies of these species...... is evaluated with 50 type, reference, and well-characterised field strains. Amplified fragment length polymorphism fingerprints comprised over 60 bands detected in the size range 35-500 bp. Groups of outbreak strains, replicate subcultures, and 'genetically identical' strains from humans, poultry and cattle......, proved indistinguishable by amplified fragment length polymorphism fingerprinting, but were differentiated fi-om unrelated isolates. Previously unknown relationships between three hippurate-negative C. jejuni strains, and two C. coil var, hyoilei strains, were identified. These relationships corresponded...

Fragment-based drug design.

Science.gov (United States)

Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H

2011-01-01

Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process.

Assessing the lipophilicity of fragments and early hits

Science.gov (United States)

Mortenson, Paul N.; Murray, Christopher W.

2011-07-01

A key challenge in many drug discovery programs is to accurately assess the potential value of screening hits. This is particularly true in fragment-based drug design (FBDD), where the hits often bind relatively weakly, but are correspondingly small. Ligand efficiency (LE) considers both the potency and the size of the molecule, and enables us to estimate whether or not an initial hit is likely to be optimisable to a potent, druglike lead. While size is a key property that needs to be controlled in a small molecule drug, there are a number of additional properties that should also be considered. Lipophilicity is amongst the most important of these additional properties, and here we present a new efficiency index (LLEAT) that combines lipophilicity, size and potency. The index is intuitively defined, and has been designed to have the same target value and dynamic range as LE, making it easily interpretable by medicinal chemists. Monitoring both LE and LLEAT should help both in the selection of more promising fragment hits, and controlling molecular weight and lipophilicity during optimisation.

Fragment informatics and computational fragment-based drug design: an overview and update.

Science.gov (United States)

Sheng, Chunquan; Zhang, Wannian

2013-05-01

Fragment-based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment-based cheminformatics tools, high-throughput fragment docking, and fragment-based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research. © 2012 Wiley Periodicals, Inc.

A Semester-Long Project for Teaching Basic Techniques in Molecular Biology Such as Restriction Fragment Length Polymorphism Analysis to Undergraduate and Graduate Students

Science.gov (United States)

DiBartolomeis, Susan M.

2011-01-01

Several reports on science education suggest that students at all levels learn better if they are immersed in a project that is long term, yielding results that require analysis and interpretation. I describe a 12-wk laboratory project suitable for upper-level undergraduates and first-year graduate students, in which the students molecularly locate and map a gene from Drosophila melanogaster called dusky and one of dusky's mutant alleles. The mapping strategy uses restriction fragment length polymorphism analysis; hence, students perform most of the basic techniques of molecular biology (DNA isolation, restriction enzyme digestion and mapping, plasmid vector subcloning, agarose and polyacrylamide gel electrophoresis, DNA labeling, and Southern hybridization) toward the single goal of characterizing dusky and the mutant allele dusky73. Students work as individuals, pairs, or in groups of up to four students. Some exercises require multitasking and collaboration between groups. Finally, results from everyone in the class are required for the final analysis. Results of pre- and postquizzes and surveys indicate that student knowledge of appropriate topics and skills increased significantly, students felt more confident in the laboratory, and students found the laboratory project interesting and challenging. Former students report that the lab was useful in their careers. PMID:21364104

Molecular Networking As a Drug Discovery, Drug Metabolism, and Precision Medicine Strategy.

Science.gov (United States)

Quinn, Robert A; Nothias, Louis-Felix; Vining, Oliver; Meehan, Michael; Esquenazi, Eduardo; Dorrestein, Pieter C

2017-02-01

Molecular networking is a tandem mass spectrometry (MS/MS) data organizational approach that has been recently introduced in the drug discovery, metabolomics, and medical fields. The chemistry of molecules dictates how they will be fragmented by MS/MS in the gas phase and, therefore, two related molecules are likely to display similar fragment ion spectra. Molecular networking organizes the MS/MS data as a relational spectral network thereby mapping the chemistry that was detected in an MS/MS-based metabolomics experiment. Although the wider utility of molecular networking is just beginning to be recognized, in this review we highlight the principles behind molecular networking and its use for the discovery of therapeutic leads, monitoring drug metabolism, clinical diagnostics, and emerging applications in precision medicine. Copyright © 2016. Published by Elsevier Ltd.

Hydrodynamic characterization and molecular weight estimation of ultrasonically sheared DNA; Caracterizacion hidrodinamica y estimacion de pesos moleculares de DNA degradado por ultrasonidos

Energy Technology Data Exchange (ETDEWEB)

Casal, J I; Garces, F; Garcia-Sacristan, A

1981-07-01

The sedimentation coefficients and intrinsic viscosities of ultrasonically sheared calf thymus DNA have been determined. The molecular weight estimation according to this parameters have been compared with the ones obtained from the electrophoretic migration rates based on the calibration proposed using the known molecular weight restriction fragments of X-ENA. (Author) 35 refs.

Molecular cloning and restriction analysis of EcoRI-fragments of Vicia faba rDNA

International Nuclear Information System (INIS)

Yakura, Kimitaka; Tanifuji, Shigeyuki.

1983-01-01

EcoRI-fragments of Vicia faba rDNA were cloned in plasmid pBR325. Southern blot hybridization of BamHI-digests of these cloned plasmids and Vicia genomic DNA led to the determination of relative positions of BamHI sites in the rDNA and the physical map that had been tentatively made is corrected. (author)

PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration

Directory of Open Access Journals (Sweden)

Alexander Jonathan S

2010-12-01

Full Text Available Abstract The normal function of poly (ADP-ribose polymerase-1 (PARP-1 is the routine repair of DNA damage by adding poly (ADP ribose polymers in response to a variety of cellular stresses. Recently, it has become widely appreciated that PARP-1 also participates in diverse physiological and pathological functions from cell survival to several forms of cell death and has been implicated in gene transcription, immune responses, inflammation, learning, memory, synaptic functions, angiogenesis and aging. In the CNS, PARP inhibition attenuates injury in pathologies like cerebral ischemia, trauma and excitotoxicity demonstrating a central role of PARP-1 in these pathologies. PARP-1 is also a preferred substrate for several 'suicidal' proteases and the proteolytic action of suicidal proteases (caspases, calpains, cathepsins, granzymes and matrix metalloproteinases (MMPs on PARP-1 produces several specific proteolytic cleavage fragments with different molecular weights. These PARP-1 signature fragments are recognized biomarkers for specific patterns of protease activity in unique cell death programs. This review focuses on specific suicidal proteases active towards PARP-1 to generate signature PARP-1 fragments that can identify key proteases and particular forms of cell death involved in pathophysiology. The roles played by some of the PARP-1 fragments and their associated binding partners in the control of different forms of cell death are also discussed.

Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase.

Science.gov (United States)

Jordan, John B; Whittington, Douglas A; Bartberger, Michael D; Sickmier, E Allen; Chen, Kui; Cheng, Yuan; Judd, Ted

2016-04-28

Fragment-based drug discovery (FBDD) has become a widely used tool in small-molecule drug discovery efforts. One of the most commonly used biophysical methods in detecting weak binding of fragments is nuclear magnetic resonance (NMR) spectroscopy. In particular, FBDD performed with (19)F NMR-based methods has been shown to provide several advantages over (1)H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of (19)F-based fragment screening by detailing the identification of a second-site fragment through (19)F NMR screening that binds to a specific pocket of the aspartic acid protease, β-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a molecule exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallographic studies of the molecules demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and molecular modeling.

Assessment of fragment projection hazard: probability distributions for the initial direction of fragments.

Science.gov (United States)

Tugnoli, Alessandro; Gubinelli, Gianfilippo; Landucci, Gabriele; Cozzani, Valerio

2014-08-30

The evaluation of the initial direction and velocity of the fragments generated in the fragmentation of a vessel due to internal pressure is an important information in the assessment of damage caused by fragments, in particular within the quantitative risk assessment (QRA) of chemical and process plants. In the present study an approach is proposed to the identification and validation of probability density functions (pdfs) for the initial direction of the fragments. A detailed review of a large number of past accidents provided the background information for the validation procedure. A specific method was developed for the validation of the proposed pdfs. Validated pdfs were obtained for both the vertical and horizontal angles of projection and for the initial velocity of the fragments. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular Beacons in Diagnostics

OpenAIRE

Tyagi, Sanjay; Kramer, Fred Russell

2012-01-01

Recent technical advances have begun to realize the potential of molecular beacons to test for diverse infections in clinical diagnostic laboratories. These include the ability to test for, and quantify, multiple pathogens in the same clinical sample, and to detect antibiotic resistant strains within hours. The design principles of molecular beacons have also spawned a variety of allied technologies.

Fragmentation in the branching coral Acropora palmata (Lamarck): growth, survivorship, and reproduction of colonies and fragments.

Science.gov (United States)

Lirman

2000-08-23

Acropora palmata, a branching coral abundant on shallow reef environments throughout the Caribbean, is susceptible to physical disturbance caused by storms. Accordingly, the survivorship and propagation of this species are tied to its capability to recover after fragmentation. Fragments of A. palmata comprised 40% of ramets within populations that had experienced recent storms. While the survivorship of A. palmata fragments was not directly related to the size of fragments, removal of fragments from areas where they settled was influenced by size. Survivorship of fragments was also affected by type of substratum; the greatest mortality (58% loss within the first month) was observed on sand, whereas fragments placed on top of live colonies of A. palmata fused to the underlying tissue and did not experience any losses. Fragments created by Hurricane Andrew on a Florida reef in August 1992 began developing new growth (proto-branches) 7 months after the storm. The number of proto-branches on fragments was dependent on size, but growth was not affected by the size of fragments. Growth-rates of proto-branches increased exponentially with time (1.7 cm year(-1) for 1993-1994, 2.7 cm year(-1) for 1994-1995, 4.2 cm year(-1) for 1995-1996, and 6.5 cm year(-1) for 1996-1997), taking over 4 years for proto-branches to achieve rates comparable to those of adult colonies on the same reef (6.9 cm year(-1)). In addition to the initial mortality and reduced growth-rates, fragmentation resulted in a loss of reproductive potential. Neither colonies that experienced severe fragmentation nor fragments contained gametes until 4 years after the initial damage. Although A. palmata may survive periodic fragmentation, the long-term effects of this process will depend ultimately on the balance between the benefits and costs of this process.

Plasminogen fragments K 1-3 and K 5 bind to different sites in fibrin fragment DD.

Science.gov (United States)

Grinenko, T V; Kapustianenko, L G; Yatsenko, T A; Yusova, O I; Rybachuk, V N

2016-01-01

Specific plasminogen-binding sites of fibrin molecule are located in Аα148-160 regions of C-terminal domains. Plasminogen interaction with these sites initiates the activation process of proenzyme and subsequent fibrin lysis. In this study we investigated the binding of plasminogen fragments K 1-3 and K 5 with fibrin fragment DD and their effect on Glu-plasminogen interaction with DD. It was shown that the level of Glu-plasminogen binding to fibrin fragment DD is decreased by 50-60% in the presence of K 1-3 and K 5. Fragments K 1-3 and K 5 have high affinity to fibrin fragment DD (Kd is 0.02 for K 1-3 and 0.054 μМ for K 5). K 5 interaction is independent and K 1-3 is partly dependent on C-terminal lysine residues. K 1-3 interacts with complex of fragment DD-immobilized K 5 as well as K 5 with complex of fragment DD-immobilized K 1-3. The plasminogen fragments do not displace each other from binding sites located in fibrin fragment DD, but can compete for the interaction. The results indicate that fibrin fragment DD contains different binding sites for plasminogen kringle fragments K 1-3 and K 5, which can be located close to each other. The role of amino acid residues of fibrin molecule Аα148-160 region in interaction with fragments K 1-3 and K 5 is discussed.

Fractal statistics of brittle fragmentation

Directory of Open Access Journals (Sweden)

M. Davydova

2013-04-01

Full Text Available The study of fragmentation statistics of brittle materials that includes four types of experiments is presented. Data processing of the fragmentation of glass plates under quasi-static loading and the fragmentation of quartz cylindrical rods under dynamic loading shows that the size distribution of fragments (spatial quantity is fractal and can be described by a power law. The original experimental technique allows us to measure, apart from the spatial quantity, the temporal quantity - the size of time interval between the impulses of the light reflected from the newly created surfaces. The analysis of distributions of spatial (fragment size and temporal (time interval quantities provides evidence of obeying scaling laws, which suggests the possibility of self-organized criticality in fragmentation.

Yam ( Dioscorea spp.) molecular breeding

African Journals Online (AJOL)

Some progress has been made in recent years in germplasm characterization and the development of molecular markers for genome analysis. A genetic linkage map based on amplified fragment length polymorphism (AFLP) markers has been constructed for Guinea and water yams. These linkage maps were used to scan ...

Chemical Technology Division annual technical report, 1996

International Nuclear Information System (INIS)

1997-06-01

CMT is a diverse technical organization with principal emphases in environmental management and development of advanced energy sources. It conducts R ampersand D in 3 general areas: development of advanced power sources for stationary and transportation applications and for consumer electronics, management of high-level and low-level nuclear wastes and hazardous wastes, and electrometallurgical treatment of spent nuclear fuel. The Division also performs basic research in catalytic chemistry involving molecular energy resources, mechanisms of ion transport in lithium battery electrolytes, materials chemistry of electrified interfaces and molecular sieves, and the theory of materials properties. It also operates the Analytical Chemistry Laboratory, which conducts research in analytical chemistry and provides analytical services for programs at ANL and other organizations. Technical highlights of the Division's activities during 1996 are presented

Chemical Technology Division annual technical report, 1996

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-06-01

CMT is a diverse technical organization with principal emphases in environmental management and development of advanced energy sources. It conducts R&D in 3 general areas: development of advanced power sources for stationary and transportation applications and for consumer electronics, management of high-level and low-level nuclear wastes and hazardous wastes, and electrometallurgical treatment of spent nuclear fuel. The Division also performs basic research in catalytic chemistry involving molecular energy resources, mechanisms of ion transport in lithium battery electrolytes, materials chemistry of electrified interfaces and molecular sieves, and the theory of materials properties. It also operates the Analytical Chemistry Laboratory, which conducts research in analytical chemistry and provides analytical services for programs at ANL and other organizations. Technical highlights of the Division`s activities during 1996 are presented.

Mass spectrometry with ionization induced by 252Cf fission fragments

International Nuclear Information System (INIS)

Sysoev, A.A.; Artaev, V.B.

1991-01-01

The review deals with mass-spectrometry with ionization induced by 252 Cf fission fragments. Equipment and technique of the analysis, analytic possibilities of the method are considered. The method permits to determine molecular masses of large nonvolatile biological molecules. The method is practically nondestructive, it possesses a high resolution over the depth and surface, which permits to use it for the analysis of surface of semiconductors, dielectrics, catalysts, for the study of formation kinetics of complex unstable molecules on the surface

Chameleon fragmentation

Energy Technology Data Exchange (ETDEWEB)

Brax, Philippe [Institut de Physique Théorique, CEA, IPhT, CNRS, URA 2306, F-91191Gif/Yvette Cedex (France); Upadhye, Amol, E-mail: philippe.brax@cea.fr, E-mail: aupadhye@anl.gov [Institute for the Early Universe, Ewha University, International Education, Building #601, 11-1, Daehyun-Dong Seodaemun-Gu, Seoul 120-750 (Korea, Republic of)

2014-02-01

A scalar field dark energy candidate could couple to ordinary matter and photons, enabling its detection in laboratory experiments. Here we study the quantum properties of the chameleon field, one such dark energy candidate, in an ''afterglow'' experiment designed to produce, trap, and detect chameleon particles. In particular, we investigate the possible fragmentation of a beam of chameleon particles into multiple particle states due to the highly non-linear interaction terms in the chameleon Lagrangian. Fragmentation could weaken the constraints of an afterglow experiment by reducing the energy of the regenerated photons, but this energy reduction also provides a unique signature which could be detected by a properly-designed experiment. We show that constraints from the CHASE experiment are essentially unaffected by fragmentation for φ{sup 4} and 1/φ potentials, but are weakened for steeper potentials, and we discuss possible future afterglow experiments.

Chameleon fragmentation

International Nuclear Information System (INIS)

Brax, Philippe; Upadhye, Amol

2014-01-01

A scalar field dark energy candidate could couple to ordinary matter and photons, enabling its detection in laboratory experiments. Here we study the quantum properties of the chameleon field, one such dark energy candidate, in an ''afterglow'' experiment designed to produce, trap, and detect chameleon particles. In particular, we investigate the possible fragmentation of a beam of chameleon particles into multiple particle states due to the highly non-linear interaction terms in the chameleon Lagrangian. Fragmentation could weaken the constraints of an afterglow experiment by reducing the energy of the regenerated photons, but this energy reduction also provides a unique signature which could be detected by a properly-designed experiment. We show that constraints from the CHASE experiment are essentially unaffected by fragmentation for φ 4 and 1/φ potentials, but are weakened for steeper potentials, and we discuss possible future afterglow experiments

Pitfall in quantum mechanical/molecular mechanical molecular dynamics simulation of small solutes in solution.

Science.gov (United States)

Hu, Hao; Liu, Haiyan

2013-05-30

Developments in computing hardware and algorithms have made direct molecular dynamics simulation with the combined quantum mechanical/molecular mechanical methods affordable for small solute molecules in solution, in which much improved accuracy can be obtained via the quantum mechanical treatment of the solute molecule and even sometimes water molecules in the first solvation shell. However, unlike the conventional molecular mechanical simulations of large molecules, e.g., proteins, in solutions, special care must be taken in the technical details of the simulation, including the thermostat of the solute/solvent system, so that the conformational space of the solute molecules can be properly sampled. We show here that the common setup for classical molecular mechanical molecular dynamics simulations, such as the Berendsen or single Nose-Hoover thermostat, and/or rigid water models could lead to pathological sampling of the solutes' conformation. In the extreme example of a methanol molecule in aqueous solution, improper and sluggish setups could generate two peaks in the distribution of the O-H bond length. We discuss the factors responsible for this somewhat unexpected result and evoke a simple and ancient technical fix-up to resolve this problem.

Molecular diversity and genetic relationships in Secale

Indian Academy of Sciences (India)

2001); and molecular methods such as amplified fragment length polymorphism ... to the maintenance and rational use of germplasm resources in the improvement of ... study of diversity of ScMATE1 gene in different species of. Secale genus.

An unusual cysteine VL87 affects the antibody fragment conformations without interfering with the disulfide bond formation.

Science.gov (United States)

Attallah, Carolina; Aguilar, María Fernanda; Garay, A Sergio; Herrera, Fernando E; Etcheverrigaray, Marina; Oggero, Marcos; Rodrigues, Daniel E

2017-10-01

The Cys residues are almost perfectly conserved in all antibodies. They contribute significantly to the antibody fragment stability. The relevance of two natural contiguous Cys residues of an anti-recombinant human-follicle stimulation hormone (rhFSH) in a format of single-chain variable fragment (scFv) was studied. This scFv contains 5 Cys residues: V H 22 and V H 92 in the variable heavy chain (V H ) and V L 23, V L 87 and V L 88 in the variable light chain (V L ). The influence of two unusual contiguous Cys at positions V L 87 and V L 88 was studied by considering the wild type fragment and mutant variants: V L -C88S, V L -C87S, V L -C87Y. The analysis was carried out using antigen-binding ability measurement by indirect specific ELISA and a detailed molecular modeling that comprises homology methods, long molecular dynamics simulations and docking. We found that V L -C87 affected the antibody fragment stability without interfering with the disulfide bond formation. The effect of mutating the V L -C87 by a usual residue at this position like Tyr caused distant structural changes at the V H region that confers a higher mobility to the V H -CDR2 and V H -CDR3 loops improving the scFv binding to the antigen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Photo induced multiple fragmentation of atoms and molecules: Dynamics of Coulombic many-particle systems studied with the COLTRIMS reaction microscope

International Nuclear Information System (INIS)

Czasch, A.; Schmidt, L.Ph.H.; Jahnke, T.; Weber, Th.; Jagutzki, O.; Schoessler, S.; Schoeffler, M.S.; Doerner, R.; Schmidt-Boecking, H.

2005-01-01

Many-particle dynamics in atomic and molecular physics has been investigated by using the COLTRIMS reaction microscope. The COLTRIMS technique visualizes photon and ion induced many-particle fragmentation processes in the eV and milli-eV regime. It reveals the complete momentum pattern in atomic and molecular many-particle reactions comparable to the bubble chamber in nuclear physics

Occurrence of C-Terminal Residue Exclusion in Peptide Fragmentation by ESI and MALDI Tandem Mass Spectrometry

Science.gov (United States)

Dupré, Mathieu; Cantel, Sonia; Martinez, Jean; Enjalbal, Christine

2012-02-01

By screening a data set of 392 synthetic peptides MS/MS spectra, we found that a known C-terminal rearrangement was unexpectedly frequently occurring from monoprotonated molecular ions in both ESI and MALDI tandem mass spectrometry upon low and high energy collision activated dissociations with QqTOF and TOF/TOF mass analyzer configuration, respectively. Any residue localized at the C-terminal carboxylic acid end, even a basic one, was lost, provided that a basic amino acid such arginine and to a lesser extent histidine and lysine was present in the sequence leading to a fragment ion, usually depicted as (bn-1 + H2O) ion, corresponding to a shortened non-scrambled peptide chain. Far from being an epiphenomenon, such a residue exclusion from the peptide chain C-terminal extremity gave a fragment ion that was the base peak of the MS/MS spectrum in certain cases. Within the frame of the mobile proton model, the ionizing proton being sequestered onto the basic amino acid side chain, it is known that the charge directed fragmentation mechanism involved the C-terminal carboxylic acid function forming an anhydride intermediate structure. The same mechanism was also demonstrated from cationized peptides. To confirm such assessment, we have prepared some of the peptides that displayed such C-terminal residue exclusion as a C-terminal backbone amide. As expected in this peptide amide series, the production of truncated chains was completely suppressed. Besides, multiply charged molecular ions of all peptides recorded in ESI mass spectrometry did not undergo such fragmentation validating that any mobile ionizing proton will prevent such a competitive C-terminal backbone rearrangement. Among all well-known nondirect sequence fragment ions issued from non specific loss of neutral molecules (mainly H2O and NH3) and multiple backbone amide ruptures (b-type internal ions), the described C-terminal residue exclusion is highly identifiable giving raise to a single fragment ion in

Combining NMR and X-ray crystallography in fragment-based drug discovery: discovery of highly potent and selective BACE-1 inhibitors.

Science.gov (United States)

Wyss, Daniel F; Wang, Yu-Sen; Eaton, Hugh L; Strickland, Corey; Voigt, Johannes H; Zhu, Zhaoning; Stamford, Andrew W

2012-01-01

Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade. We review here how we have used highly structure-driven fragment-based approaches to complement more traditional lead discovery to tackle high priority targets and those struggling for leads. Combining biomolecular nuclear magnetic resonance (NMR), X-ray crystallography, and molecular modeling with structure-assisted chemistry and innovative biology as an integrated approach for FBDD can solve very difficult problems, as illustrated in this chapter. Here, a successful FBDD campaign is described that has allowed the development of a clinical candidate for BACE-1, a challenging CNS drug target. Crucial to this achievement were the initial identification of a ligand-efficient isothiourea fragment through target-based NMR screening and the determination of its X-ray crystal structure in complex with BACE-1, which revealed an extensive H-bond network with the two active site aspartate residues. This detailed 3D structural information then enabled the design and validation of novel, chemically stable and accessible heterocyclic acylguanidines as aspartic acid protease inhibitor cores. Structure-assisted fragment hit-to-lead optimization yielded iminoheterocyclic BACE-1 inhibitors that possess desirable molecular properties as potential therapeutic agents to test the amyloid hypothesis of Alzheimer's disease in a clinical setting.

Fragment library design: using cheminformatics and expert chemists to fill gaps in existing fragment libraries.

Science.gov (United States)

Kutchukian, Peter S; So, Sung-Sau; Fischer, Christian; Waller, Chris L

2015-01-01

Fragment based screening (FBS) has emerged as a mainstream lead discovery strategy in academia, biotechnology start-ups, and large pharma. As a prerequisite of FBS, a structurally diverse library of fragments is desirable in order to identify chemical matter that will interact with the range of diverse target classes that are prosecuted in contemporary screening campaigns. In addition, it is also desirable to offer synthetically amenable starting points to increase the probability of a successful fragment evolution through medicinal chemistry. Herein we describe a method to identify biologically relevant chemical substructures that are missing from an existing fragment library (chemical gaps), and organize these chemical gaps hierarchically so that medicinal chemists can efficiently navigate the prioritized chemical space and subsequently select purchasable fragments for inclusion in an enhanced fragment library.

Universality of projectile fragmentation model

International Nuclear Information System (INIS)

Chaudhuri, G.; Mallik, S.; Das Gupta, S.

2012-01-01

Presently projectile fragmentation reaction is an important area of research as it is used for the production of radioactive ion beams. In this work, the recently developed projectile fragmentation model with an universal temperature profile is used for studying the charge distributions of different projectile fragmentation reactions with different projectile target combinations at different incident energies. The model for projectile fragmentation consists of three stages: (i) abrasion, (ii) multifragmentation and (iii) evaporation

Piezoelectric sensors based on molecular imprinted polymers for detection of low molecular mass analytes.

Science.gov (United States)

Uludağ, Yildiz; Piletsky, Sergey A; Turner, Anthony P F; Cooper, Matthew A

2007-11-01

Biomimetic recognition elements employed for the detection of analytes are commonly based on proteinaceous affibodies, immunoglobulins, single-chain and single-domain antibody fragments or aptamers. The alternative supra-molecular approach using a molecularly imprinted polymer now has proven utility in numerous applications ranging from liquid chromatography to bioassays. Despite inherent advantages compared with biochemical/biological recognition (which include robustness, storage endurance and lower costs) there are few contributions that describe quantitative analytical applications of molecularly imprinted polymers for relevant small molecular mass compounds in real-world samples. There is, however, significant literature describing the use of low-power, portable piezoelectric transducers to detect analytes in environmental monitoring and other application areas. Here we review the combination of molecularly imprinted polymers as recognition elements with piezoelectric biosensors for quantitative detection of small molecules. Analytes are classified by type and sample matrix presentation and various molecularly imprinted polymer synthetic fabrication strategies are also reviewed.

Effective Fragment Potential Method for H-Bonding: How To Obtain Parameters for Nonrigid Fragments.

Science.gov (United States)

Dubinets, Nikita; Slipchenko, Lyudmila V

2017-07-20

Accuracy of the effective fragment potential (EFP) method was explored for describing intermolecular interaction energies in three dimers with strong H-bonded interactions, formic acid, formamide, and formamidine dimers, which are a part of HBC6 database of noncovalent interactions. Monomer geometries in these dimers change significantly as a function of intermonomer separation. Several EFP schemes were considered, in which fragment parameters were prepared for a fragment in its gas-phase geometry or recomputed for each unique fragment geometry. Additionally, a scheme in which gas-phase fragment parameters are shifted according to relaxed fragment geometries is introduced and tested. EFP data are compared against the coupled cluster with single, double, and perturbative triple excitations (CCSD(T)) method in a complete basis set (CBS) and the symmetry adapted perturbation theory (SAPT). All considered EFP schemes provide a good agreement with CCSD(T)/CBS for binding energies at equilibrium separations, with discrepancies not exceeding 2 kcal/mol. However, only the schemes that utilize relaxed fragment geometries remain qualitatively correct at shorter than equilibrium intermolecular distances. The EFP scheme with shifted parameters behaves quantitatively similar to the scheme in which parameters are recomputed for each monomer geometry and thus is recommended as a computationally efficient approach for large-scale EFP simulations of flexible systems.

Experimental study on the fragmentation of Adenine and Porphyrin molecules induced by low energy multicharged ion impact

International Nuclear Information System (INIS)

Li, B.

2010-01-01

Since the dissociation of small molecules might play key roles in the understanding of radiation induced damages of living tissues at the primary steps and at the molecular levels, fragmentation dynamics of small biomolecules have drawn much attention. The knowledge of the internal energy is of fundamental importance for understanding its fragmentation dynamics following external excitation. For a long time however, it was difficult to measure this parameter in coincidence with the fragmentation patterns until the development of CIDEC (Collision Induced Dissociation under Energy Control) method in 2007. In this work, the CIDEC method was extended to study the fragmentation of gas-phase biomolecules adenine (Ade: H 5 C 5 N 5 ) and porphyrin chloride FeTPPCl (C 44 H 28 N 4 FeCl). The population distribution for each dissociation channel as a function of the excitation energy of the parent molecular ions at a well-determined initial charge state has been experimentally determined, which could shed some light on the fragmentation dynamics of these molecules. In collisions between Cl + and Ade at 3 keV, the fragmentation pattern of Ade 2+ is dominated by the loss of H 2 CN + and the successive emission of HCN. The energy distribution of the parent dication confirms the successive emission dynamics. A specific decay channel is observed, i.e. the emission of a charged H 2 CN + followed by the emission of HC 2 N 2 . The measured mean excitation energies of this channel and other competitive channels are compared. In Kr 8+ - FeTPPCl collisions at 80 keV, parent ions FeTPPCL 1+,2+,3+ are observed, along with the corresponding decay patterns. It is found that, in the first step the dominant low-energy-cost decay channel is the emission of Cl 0 independent of the initial charge state of FeTPPCl r+ . For the resulted dication FeTPP 2+ , the dominant fragmentation channel is the neutral evaporation; for the tri-cation however, the dominant fragmentation channel is the

Robust Object Tracking Using Valid Fragments Selection.

Science.gov (United States)

Zheng, Jin; Li, Bo; Tian, Peng; Luo, Gang

Local features are widely used in visual tracking to improve robustness in cases of partial occlusion, deformation and rotation. This paper proposes a local fragment-based object tracking algorithm. Unlike many existing fragment-based algorithms that allocate the weights to each fragment, this method firstly defines discrimination and uniqueness for local fragment, and builds an automatic pre-selection of useful fragments for tracking. Then, a Harris-SIFT filter is used to choose the current valid fragments, excluding occluded or highly deformed fragments. Based on those valid fragments, fragment-based color histogram provides a structured and effective description for the object. Finally, the object is tracked using a valid fragment template combining the displacement constraint and similarity of each valid fragment. The object template is updated by fusing feature similarity and valid fragments, which is scale-adaptive and robust to partial occlusion. The experimental results show that the proposed algorithm is accurate and robust in challenging scenarios.

Sustained sleep fragmentation induces sleep homeostasis in mice

KAUST Repository

Baud, Maxime O.; Magistretti, Pierre J.; Petit, Jean Marie

2015-01-01

Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.

Sustained sleep fragmentation induces sleep homeostasis in mice

KAUST Repository

Baud, Maxime O.

2015-04-01

Study Objectives: Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes. Design: N/A. Setting: Animal sleep research laboratory. Participants : Sixty-six C57BL6/J adult mice. Interventions: Instrumental sleep disruption at a rate of 60/h during 14 days Measurements and Results: Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF. Conclusions: Chronic sleep fragmentation (SF) increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.

Occurrence and molecular characterization of Cryptosporidium spp. isolated from domestic animals in a rural area surrounding Atlantic dry forest fragments in Teodoro Sampaio municipality, State of São Paulo, Brazil.

Science.gov (United States)

Sevá, Anaiá da Paixão; Funada, Mikaela Renata; Souza, Sheila de Oliveira; Nava, Alessandra; Richtzenhain, Leonardo José; Soares, Rodrigo Martins

2010-01-01

The aim of this study was to assess the occurrence of Cryptosporidium in domestic animals in rural properties surrounding rain forest fragments within the municipality of Teodoro Sampaio, southeastern Brazil. Conventional sucrose flotation method followed by molecular characterization of the parasites by sequencing PCR products amplified from SSU rRNA gene were used. Stool samples were collected from domestic animals raised as pets and livestock in all rural properties surrounding three forest fragments. Samples from cattle (197), equine (63), pigs (25), sheep (11), and dogs (28) were collected from 98 rural properties. The frequency of occurrence of Cryptosporidium within each animal species was 3.0% (6/197) among cattle and 10.7% (3/28) among dogs. Cryptosporidium was not detected in stool samples from equine, sheep, and pigs. All sequences obtained from the six samples of calves showed molecular identity with Cryptosporidium andersoni while all sequences from dog samples were similar to C. canis. The frequency of occurrence of Cryptosporidium in these domestic animal species was low. The absence of C. parvum in the present study suggests that the zoonotic cycle of cryptosporidiosis may not be relevant in the region studied. The presence of Cryptosporidium species seldom described in humans may be, otherwise, important for the wild fauna as these animals are a source of infection and dissemination of this protozoan to other animal species. The impact and magnitude of infection by C. andersoni in wild ruminants and C. canis in wild canids have to be assessed in future studies to better understand the actual importance of these species in this region.

Self-organized criticality in fragmenting

DEFF Research Database (Denmark)

Oddershede, L.; Dimon, P.; Bohr, J.

1993-01-01

The measured mass distributions of fragments from 26 fractured objects of gypsum, soap, stearic paraffin, and potato show evidence of obeying scaling laws; this suggests the possibility of self-organized criticality in fragmenting. The probability of finding a fragment scales inversely to a power...

Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases

International Nuclear Information System (INIS)

Heljasvaara, Ritva; Nyberg, Pia; Luostarinen, Jani; Parikka, Mataleena; Heikkilae, Pia; Rehn, Marko; Sorsa, Timo; Salo, Tuula; Pihlajaniemi, Taina

2005-01-01

Endostatin, a potent inhibitor of endothelial cell proliferation, migration, angiogenesis and tumor growth, is proteolytically cleaved from the C-terminal noncollagenous NC1 domain of type XVIII collagen. We investigated the endostatin formation from human collagen XVIII by several MMPs in vitro. The generation of endostatin fragments differing in molecular size (24-30 kDa) and in N-terminal sequences was identified in the cases of MMP-3, -7, -9, -13 and -20. The cleavage sites were located in the protease-sensitive hinge region between the trimerization and endostatin domains of NC1. MMP-1, -2, -8 and -12 did not show any significant activity against the C-terminus of collagen XVIII. The anti-proliferative effect of the 20-kDa endostatin, three longer endostatin-containing fragments generated in vitro by distinct MMPs and the entire NC1 domain, on bFGF-stimulated human umbilical vein endothelial cells was established. The anti-migratory potential of some of these fragments was also studied. In addition, production of endostatin fragments between 24-30 kDa by human hepatoblastoma cells was shown to be due to MMP action on type XVIII collagen. Our results indicate that certain, especially cancer-related, MMP family members can generate biologically active endostatin-containing polypeptides from collagen XVIII and thus, by releasing endostatin fragments, may participate in the inhibition of endothelial cell proliferation, migration and angiogenesis

NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

Science.gov (United States)

Liu, Jiuyang; Gao, Jia; Li, Fudong; Ma, Rongsheng; Wei, Qingtao; Wang, Aidong; Wu, Jihui; Ruan, Ke

2017-01-01

The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled C α - and H α -based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

Ionic fragmentation of the isoprene molecule in the VUV energy range (12 to 310 eV)

Energy Technology Data Exchange (ETDEWEB)

Bernini, R.B., E-mail: rafael.bernini@ifrj.edu.br [Instituto Federal de Ciência e Tecnologia do Rio de Janeiro (IFRJ), 25050-100 Duque de Caxias, RJ (Brazil); Coutinho, L.H. [Instituto de Física, Universidade Federal do Rio De Janeiro (UFRJ), 21941-972 Rio de Janeiro, RJ (Brazil); Nunez, C.V. [Laboratório de Bioprospecção e Biotecnologia, Coordenação de Tecnologia e Inovação, Instituto Nacional de Pesquisas da Amazônia (INPA), 69060-001 Manaus, AM (Brazil); Castilho, R.B. de [Departamento de Química, Instituto de Ciências Exatas, Universidade Federal do Amazonas (UFAM), 69077-000 Manaus, AM (Brazil); Souza, G.G.B. de [Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), 21949-900 Rio de Janeiro, RJ (Brazil)

2015-07-15

Highlights: • Ionic fragmentation of isoprene following valence-shell and C 1s excitation. • Experimental observation of single and double ionization processes. • Large increase in fragmentation following core excitation. • Similar dissociation pattern bellow (270 eV) and above (310 eV) core edge. • Stable molecular ion observed at all photon energies. - Abstract: Isoprene, C{sub 5}H{sub 8}, is a biogenic volatile compound emitted from plants and animals, playing an important role in atmospheric chemistry. In this work, we have studied the ionic fragmentation of the isoprene molecule induced by high energy photons (synchrotron radiation), both at the valence (12.0, 14.0, 16.0, 18.0, and 21.0 eV) and carbon 1s edge (270 and 310 eV, respectively, below and above edge) energies. The ionic fragments were mass-analyzed using a Wiley–McLaren time-of-flight spectrometer (TOF) and single (PEPICO) and double ionization coincidence (PEPIPICO) spectra were obtained. As expected, the fragmentation degree increases with increasing energy. Below and above the carbon 1s edge, the fragmentation patterns are quite similar, and basically the same fragments are observed as compared to the spectra following valence-shell ionization. Stable doubly-charged ions were not observed. A PEPIPICO spectrum has shown that the main dissociation route for doubly-ionized species corresponds to the [CH{sub 3}]{sup +}/[C{sub 4}H{sub 2–5}]{sup +} ion pair. Intense fragmentation of the isoprene molecule has been observed following valence shell and core electron ionization. The observance of basically the same fragments when moving from valence to inner-shell suggests that basically the same fragmentation routes are present in both cases. All doubly (or multiply)-charged cations are unstable, at least on a microsecond scale.

Energy production using fission fragment rockets

International Nuclear Information System (INIS)

Chapline, G.; Matsuda, Y.

1991-08-01

Fission fragment rockets are nuclear reactors with a core consisting of thin fibers in a vacuum, and which use magnetic fields to extract the fission fragments from the reactor core. As an alternative to ordinary nuclear reactors, fission fragment rockets would have the following advantages: Approximately twice as efficient if one can directly convert the fission fragment energy into electricity; by reducing the buildup of a fission fragment inventory in the reactor one could avoid a Chernobyl type disaster; and collecting the fission fragments outside the reactor could simplify the waste disposal problem. 6 refs., 4 figs., 2 tabs

A Microchannel Inlet to Reduce High-Velocity Impact Fragmentation of Molecules in Orbital and Fly-by Mass Spectrometers

Science.gov (United States)

Turner, Brandon; Anupriya, Anupriya; Sevy, Eric; Austin, Daniel E.

2017-10-01

Closed source neutral mass spectrometers are often used on flyby missions to characterize the molecular components of planetary exospheres. In a typical closed source, neutrals are thermalized as they deflect off the walls within a spherical antechamber prior to ionization and mass analysis. However, the high kinetic energy of each molecule as it impacts the chamber can lead to fragmentation before the ionization region is reached. Due to this fragmentation, the original composition of the molecule can be altered, leading to ambiguous identification.Even knowing the fragmentation pathways that occur may not allow deconvolution of data to give the correct composition. Only stable, volatile fragments will be observed in the subsequent mass spectrometer and different organic compounds likely give similar fragmentation products. Simply detecting these products will not lead to unambiguous identication of the precursor molecules. Here, we present a hardware solution to this problem—an inlet that reduces the fragmentation of molecules that impact at high velocities.We present a microchannel inlet that reduces the impact fragmentation by allowing the molecules to dissipate kinetic energy faster than their respective dissociation lifetimes. Preliminary calculations indicate that impact-induced fragmentation will be reduced up to three orders of magnitude compared with conventional closed sources by using this inlet. The benefits of such an inlet apply to any orbital or flyby velocity. The microchannel inlet enables detection of semi-volatile molecules that were previously undetectable due to impact fragmentation.

Fragmentation of relativistic nuclei

International Nuclear Information System (INIS)

Cork, B.

1975-06-01

Nuclei with energies of several GeV/n interact with hadrons and produce fragments that encompass the fields of nuclear physics, meson physics, and particle physics. Experimental results are now available to explore problems in nuclear physics such as the validity of the shell model to explain the momentum distribution of fragments, the contribution of giant dipole resonances to fragment production cross sections, the effective Coulomb barrier, and nuclear temperatures. A new approach to meson physics is possible by exploring the nucleon charge-exchange process. Particle physics problems are explored by measuring the energy and target dependence of isotope production cross sections, thus determining if limiting fragmentation and target factorization are valid, and measuring total cross sections to determine if the factorization relation, sigma/sub AB/ 2 = sigma/sub AA/ . sigma/sub BB/, is violated. Also, new experiments have been done to measure the angular distribution of fragments that could be explained as nuclear shock waves, and to explore for ultradense matter produced by very heavy ions incident on heavy atoms. (12 figures, 2 tables)

Hydrodynamic characterization and molecular weight estimation of ultrasonically sheared DNA

International Nuclear Information System (INIS)

Casal, J. I.; Garces, F.; Garcia-Sacristan, A.

1981-01-01

The sedimentation coefficients and intrinsic viscosities of ultrasonically sheared calf thymus DNA have been determined. The molecular weight estimation according to this parameters have been compared with the ones obtained from the electrophoretic migration rates based on the calibration proposed using the known molecular weight restriction fragments of X-ENA. (Author) 35 refs

Hydrodynamic caracterization and molecular weight stimation of ultrasonically sheared DNA

International Nuclear Information System (INIS)

Garces, F.; Casal, J.I.; Garcia, A.

1981-01-01

The sedimentation coefficients and intrinsec viscosities of ultrasonically sheared calf thymus DNA have been determined. The molecular weight stimation according to this parameters have been compared with the ones obtained from the electrophoretic migration rates based on the calibration proposed using the known molecular weight restriction fragments of lambds-DNA. (author) [es

Detection of fission fragments by secondary emission; Detection des fragments de fission par emission secondaire

Energy Technology Data Exchange (ETDEWEB)

Audias, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1965-07-01

This fission fragment detecting apparatus is based on the principle that fragments traversing a thin foil will cause emission of secondary electrons. These electrons are then accelerated (10 kV) and directly detected by means of a plastic scintillator and associated photomultiplier. Some of the advantages of such a detector are, its rapidity, its discriminating power between alpha particles and fission fragments, its small energy loss in detecting the fragments and the relatively great amount of fissionable material which it can contain. This paper is subdivided as follows: a) theoretical considerations b) constructional details of apparatus and some experimental details and c) a study of the secondary emission effect itself. (author) [French] Le detecteur de fragments de fission que nous avons realise est base sur le principe de l'emission secondaire produite par les fragments de fission traversant une feuille mince: les electrons secondaires emis sont acceleres a des tensions telles (de l'ordre de 10 kV), qu'ils soient directement detectables par un scintillateur plastique associe a un photomultiplicateur. L'interet d'un tel detecteur reside: dans sa rapidite, sa tres bonne discrimination alpha, fission, la possibilite de detecter les fragments de fission avec une perte d'energie pouvant rester relativement faible, et la possibilite d'introduire des quantites de matiere fissile plus importantes que dans les autres types de detecteurs. Ce travail comporte: -) un apercu bibliographique de la theorie du phenomene, -) realisation et mise au point du detecteur avec etude experimentale de quelques parametres intervenant dans l'emission secondaire, -) etude de l'emission secondaire (sur la face d'emergence des fragments de fission) en fonction de l'energie du fragment et en fonction de l'epaisseur de matiere traversee avant emission secondaire, et -) une etude comparative de l'emission secondaire sur la face d'incidence et sur la face d'emergence des fragments de

Thermodynamics of the fuel fragmentation gas

International Nuclear Information System (INIS)

Perez, R.B.; Alsmiller, R.G. Jr.

1977-01-01

In the context of nuclear reactor safety studies, a program is in progress at ORNL whereby fuel-fragmentation situations are mocked up by the application of high-current capacitor discharges through solid UO 2 samples. The goal of the present work is to predict such quantities as the number of gas and liquid fragments and their energy distributions. The point of view adopted is that upon fragmentation, a cloud of UO 2 vapor is formed containing ''primeval'' liquid fragments which act as condensation centers. In the evolution of time, fragment growth is controlled by nucleation, coagulation and evaporation processes. Eventually, the vapor-droplet system will reach a situation in which clusters (fragments) of various sizes and UO 2 vapor will coexist in an ''association-disassociation'' equilibrium. Thus, the physical model considered here consists of the identification of the fragmentation gas with an ''imperfect'' vapor, made up of interacting UO 2 vapor and liquid fragments. The results of the study are presented

A role for fragment-based drug design in developing novel lead compounds for central nervous system targets

Directory of Open Access Journals (Sweden)

Michael J. Wasko

2015-09-01

Full Text Available Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacologic screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening, which employs computer models of the target protein to narrow the search for possible leads. A variant of virtual screening is fragment-based drug design, an emerging in silico lead discovery method that introduces low molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for growing the lead candidate. Current efforts in virtual fragment-based drug design within central nervous system (CNS targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor binding pocket using the fragment as a scaffold. This process places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

The dual role of fragments in fragment-assembly methods for de novo protein structure prediction

Science.gov (United States)

Handl, Julia; Knowles, Joshua; Vernon, Robert; Baker, David; Lovell, Simon C.

2013-01-01

In fragment-assembly techniques for protein structure prediction, models of protein structure are assembled from fragments of known protein structures. This process is typically guided by a knowledge-based energy function and uses a heuristic optimization method. The fragments play two important roles in this process: they define the set of structural parameters available, and they also assume the role of the main variation operators that are used by the optimiser. Previous analysis has typically focused on the first of these roles. In particular, the relationship between local amino acid sequence and local protein structure has been studied by a range of authors. The correlation between the two has been shown to vary with the window length considered, and the results of these analyses have informed directly the choice of fragment length in state-of-the-art prediction techniques. Here, we focus on the second role of fragments and aim to determine the effect of fragment length from an optimization perspective. We use theoretical analyses to reveal how the size and structure of the search space changes as a function of insertion length. Furthermore, empirical analyses are used to explore additional ways in which the size of the fragment insertion influences the search both in a simulation model and for the fragment-assembly technique, Rosetta. PMID:22095594

Lack of Population Genetic Structuring in Ocelots (Leopardus pardalis in a Fragmented Landscape

Directory of Open Access Journals (Sweden)

Marina G. Figueiredo

2015-07-01

Full Text Available Habitat fragmentation can promote patches of small and isolated populations, gene flow disruption between those populations, and reduction of local and total genetic variation. As a consequence, these small populations may go extinct in the long-term. The ocelot (Leopardus pardalis, originally distributed from Texas to southern Brazil and northern Argentina, has been impacted by habitat fragmentation throughout much of its range. To test whether habitat fragmentation has already induced genetic differentiation in an area where this process has been documented for a larger felid (jaguars, we analyzed molecular variation in ocelots inhabiting two Atlantic Forest fragments, Morro do Diabo (MD and Iguaçu Region (IR. Analyses using nine microsatellites revealed mean observed and expected heterozygosity of 0.68 and 0.70, respectively. The MD sampled population showed evidence of a genetic bottleneck under two mutational models (TPM = 0.03711 and SMM = 0.04883. Estimates of genetic structure (FST = 0.027; best fit of k = 1 with STRUCTURE revealed no meaningful differentiation between these populations. Thus, our results indicate that the ocelot populations sampled in these fragments are still not significantly different genetically, a pattern that strongly contrasts with that previously observed in jaguars for the same comparisons. This observation is likely due to a combination of two factors: (i larger effective population size of ocelots (relative to jaguars in each fragment, implying a slower effect of drift-induced differentiation; and (ii potentially some remaining permeability of the anthropogenic matrix for ocelots, as opposed to the observed lack of permeability for jaguars. The persistence of ocelot gene flow between these areas must be prioritized in long-term conservation planning on behalf of these felids.

Models of fragmentation with composite power laws

Science.gov (United States)

Tavassoli, Z.; Rodgers, G. J.

1999-06-01

Some models for binary fragmentation are introduced in which a time dependent transition size produces two regions of fragment sizes above and below the transition size. In the first model we assume a fixed rate of fragmentation for the largest fragment and two different rates of fragmentation in the two regions of sizes above and below the transition size. The model is solved exactly in the long time limit to reveal stable time-invariant solutions for the fragment size and mass distributions. These solutions exhibit composite power law behaviours; power laws with two different exponents for fragments in smaller and larger regions. A special case of the model with no fragmentation in the smaller size region is also examined. Another model is also introduced which have three regions of fragment sizes with different rates of fragmentation. The similarities between the stable distributions in our models and composite power law distributions from experimental work on shock fragmentation of long thin glass rods and thick clay plates are discussed.

Kinetics of fragmentation-annihilation processes

OpenAIRE

Filipe, JAN; Rodgers, GJ

1996-01-01

We investigate the kinetics of systems in which particles of one species undergo binary fragmentation and pair annihilation. In the latter, nonlinear process, fragments react at collision to produce an inert species, causing loss of mass. We analyze these systems in the reaction-limited regime by solving a continuous model within the mean-field approximation. The rate of fragmentation for a particle of mass x to break into fragments of masses y and x-y has the form x(lambda-1) (lambda > 0), a...

Fission fragment spins and spectroscopy

International Nuclear Information System (INIS)

Durell, J.L.

1988-01-01

Prompt γ-ray coincidence experiments have been carried out on γ-rays emitted from post-neutron emission fission fragments produced by the aup 19F + 197 Au and 18 O + 232 Th reactions. Decay schemes have been established for even-even nuclei ranging from 78 Se to 148 Nd. Many new states with spin up to ∼ 12h have been observed. Apart from providing a wealth of new information on the spectroscopy of neutron-rich nuclei, the data have been analyzed to determine the average spin of primary fission fragments as a function of fragment mass. The results suggest that the fragment spins are determined by the temperature and shape of the primary fragments at or near to scission

Vector properties in molecular photodissociation

International Nuclear Information System (INIS)

Underwood, J.

1999-12-01

The technique of resonance enhanced multi-photon ionization (REMPI) of atomic and molecular species produced from a photofragmentation event combined with time-of flight (TOF) detection is used to examine scalar and vector properties following photodissociation. This technique is applied to the study of methyl bromide dissociation in a product state specific manner. We report measurements of the angular distributions and kinetic energy releases of the resulting bromine atoms in the ground and first spin-orbit excited state. Additionally we report measurements of the angular distributions and kinetic energy releases of the methyl fragment in the ground vibrational state, and also the excited state with one quanta in the ν 2 vibrational modes. These studies were carried out in the red wing of the absorption band at several wavelengths. For these measurements we were able to resolve the spin orbit state of the partner bromine fragment. From our observations we find new evidence for enhanced nonadiabatic curve crossing active in methyl bromide dissociation in comparison with earlier studies of methyl iodide. The atomic polarization produced following photodissociation of a diatomic molecule was investigated both theoretically and experimentally. We develop theoretical expressions relating the lab frame and molecular frame atomic polarization to the photoexcitation and subsequent dissociation of a diatomic molecule. This treatment includes both incoherent, coherent and non-adiabatic processes which may be active in the photodissociation process. We treat the general case of a polarized diatomic molecule yielding two fragments with non zero angular momentum. Experimentally, an investigation of the polarization of atomic Cl( 2 P 3/2 ) photofragments from the ∼330 nm photolysis of molecular chlorine using the REMPI-TOF technique is reported. We present a theoretical framework in which to treat such experiments allowing the extraction of parameters with direct physical

Fragmentation study of isolated and nano-solvated biomolecules induced by collision with multiply charged ions and neutral particles

International Nuclear Information System (INIS)

Bernigaud, V.

2009-01-01

This thesis concerns a gas phase study of the fragmentation of bio-molecular systems induced by slow collisions with multiply charged ions (in the keV-region), alkali atoms and rare gases. The main objective was to study the physical processes involved in the dissociation of highly electronically excited systems. In order to elucidate the intrinsic properties of certain biomolecules (porphyrins and amino acids) we have performed experiments in the gas phase with isolated systems. The obtained results demonstrate the high stability of porphyrins after electron removal and attachment. Furthermore, a dependence of the fragmentation pattern produced by multiply charged ions on the isomeric structure of the alanine molecule has been shown. In a second part of the thesis, a strong influence of the environment of the biomolecule on the fragmentation channels, their modification and their new opening, has been clearly proven. This phenomenon occurs in the presence of other surrounding biomolecules (clusters of nucleobases) as well as for molecules of a solvent (molecules of water, methanol and acetonitrile) in which the biomolecule is embedded. In order to extend these studies to larger systems, a new experimental set-up, based on an electro-spray ion source combined with a quadrupole mass filter has been developed. Due to the successful tests and proposed improvements of the device future experiments will become available concerning the fragmentation of large charged and solvated bio-molecular systems induced by collision processes. (author) [fr

Molecular research on the genetic diversity of Tunisian date palm ...

African Journals Online (AJOL)

Molecular research on the genetic diversity of Tunisian date palm ( Phoenix dactylifera L.) using the random amplified microsatellite polymorphism (RAMPO) and amplified fragment length polymorphism (AFLP) methods.

Fragmentation of Protein Kinase N (PKN) in the Hydrocephalic Rat Brain

International Nuclear Information System (INIS)

Okii, Norifumi; Amano, Taku; Seki, Takahiro; Matsubayashi, Hiroaki; Mukai, Hideyuki; Ono, Yoshitaka; Kurisu, Kaoru; Sakai, Norio

2007-01-01

PKN (protein kinase N; also called protein kinase C-related kinase (PRK-1)), is a serine/threonine protein kinase that is ubiquitously expressed in several organs, including the brain. PKN has a molecular mass of 120 kDa and has two domains, a regulatory and a catalytic domain, in its amino-terminals and carboxyl-terminus, respectively. Although the role of PKN has not been fully elucidated, previous studies have revealed that PKN is cleaved to a constitutively active catalytic fragment of 55 kDa in response to apoptotic signals. Hydrocephalus is a pathological condition caused by insufficient cerebrospinal fluid (CSF) circulation and subsequent excess of CSF in the brain. In this study, in order to elucidate the role of PKN in the pathophysiology of hydrocephalus, we examined PKN fragmentation in hydrocephalic model rats. Hydrocephalus was induced in rats by injecting kaolin into the cisterna magna. Kaolin-induced rats (n=60) were divided into three groups according to the observation period after treatment (group 1: 3–6 weeks, group 2: 7–12 weeks, and group 3: 13–18 weeks). Sham-treated control rats, injected with sterile saline (n=20), were similarly divided into three groups. Spatial learning ability was estimated by a modified water maze test. Thereafter, brains were cut into slices and ventricular dilatation was estimated. Fragmentation of PKN was observed by Western blotting in samples collected from the parietal cortex, striatum, septal nucleus, hippocampus, and periaqueductal gray matter. All kaolin-induced rats showed ventricular dilatation. Most of them showed less spatial learning ability than those of sham-treated controls. In most regions, fragmentation of PKN had occurred in a biphasic manner more frequently than that in controls. The appearance of PKN fragmentation in periaqueductal gray matter was correlated with the extent of ventricular dilation and spatial learning disability. These results revealed that PKN fragmentation was observed in

Surface molecular imprinting onto fluorescein-coated magnetic nanoparticlesvia reversible addition fragmentation chain transfer polymerization: A facile three-in-one system for recognition and separation of endocrine disrupting chemicals

Science.gov (United States)

Li, Ying; Dong, Cunku; Chu, Jia; Qi, Jingyao; Li, Xin

2011-01-01

In this study, we present a general protocol for the making of surface-imprinted magnetic fluorescence beads viareversible addition-fragmentation chain transfer polymerization. The resulting composites were characterized by X-ray diffraction analysis, transmission electron microscopy, scanning electron microscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, and energy dispersive spectroscopy. The as-synthesized beads exhibited homogeneous polymer films (thickness of about 5.7 nm), spherical shape, high fluorescence intensity and magnetic property (Magnetization (Ms) = 3.67 emu g-1). The hybrids bind the original template 17β-estradiol with an appreciable selectivity over structurally related compounds. In addition, the resulting hybrids performed without obvious deterioration after five repeated cycles. This study therefore demonstrates the potential of molecularly imprinted polymers for the recognition and separation of endocrine disrupting chemicals.In this study, we present a general protocol for the making of surface-imprinted magnetic fluorescence beads viareversible addition-fragmentation chain transfer polymerization. The resulting composites were characterized by X-ray diffraction analysis, transmission electron microscopy, scanning electron microscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, and energy dispersive spectroscopy. The as-synthesized beads exhibited homogeneous polymer films (thickness of about 5.7 nm), spherical shape, high fluorescence intensity and magnetic property (Magnetization (Ms) = 3.67 emu g-1). The hybrids bind the original template 17β-estradiol with an appreciable selectivity over structurally related compounds. In addition, the resulting hybrids performed without obvious deterioration after five repeated cycles. This study therefore demonstrates the potential of molecularly imprinted polymers for the recognition and separation of endocrine disrupting chemicals. Electronic

Generating and Purifying Fab Fragments from Human and Mouse IgG Using the Bacterial Enzymes IdeS, SpeB and Kgp.

Science.gov (United States)

Sjögren, Jonathan; Andersson, Linda; Mejàre, Malin; Olsson, Fredrik

2017-01-01

Fab fragments are valuable research tools in various areas of science including applications in imaging, binding studies, removal of Fc-mediated effector functions, mass spectrometry, infection biology, and many others. The enzymatic tools for the generation of Fab fragments have been discovered through basic research within the field of molecular bacterial pathogenesis. Today, these enzymes are widely applied as research tools and in this chapter, we describe methodologies based on bacterial enzymes to generate Fab fragments from both human and mouse IgG. For all human IgG subclasses, the IdeS enzyme from Streptococcus pyogenes has been applied to generate F(ab')2 fragments that subsequently can be reduced under mild conditions to generate a homogenous pool of Fab' fragments. The enzyme Kgp from Porphyromonas gingivalis has been applied to generate intact Fab fragments from human IgG1 and the Fab fragments can be purified using a CH1-specific affinity resin. The SpeB protease, also from S. pyogenes, is able to digest mouse IgGs and has been applied to digest antibodies and Fab fragments can be purified on light chain affinity resins. In this chapter, we describe methodologies that can be used to obtain Fab fragments from human and mouse IgG using bacterial proteases.

Limiting Accretion onto Massive Stars by Fragmentation-Induced Starvation

Energy Technology Data Exchange (ETDEWEB)

Peters, Thomas; /ZAH, Heidelberg; Klessen, Ralf S.; /ZAH, Heidelberg /KIPAC, Menlo Park; Mac Low, Mordecai-Mark; /Amer. Museum Natural Hist.; Banerjee, Robi; /ZAH, Heidelberg

2010-08-25

Massive stars influence their surroundings through radiation, winds, and supernova explosions far out of proportion to their small numbers. However, the physical processes that initiate and govern the birth of massive stars remain poorly understood. Two widely discussed models are monolithic collapse of molecular cloud cores and competitive accretion. To learn more about massive star formation, we perform simulations of the collapse of rotating, massive, cloud cores including radiative heating by both non-ionizing and ionizing radiation using the FLASH adaptive mesh refinement code. These simulations show fragmentation from gravitational instability in the enormously dense accretion flows required to build up massive stars. Secondary stars form rapidly in these flows and accrete mass that would have otherwise been consumed by the massive star in the center, in a process that we term fragmentation-induced starvation. This explains why massive stars are usually found as members of high-order stellar systems that themselves belong to large clusters containing stars of all masses. The radiative heating does not prevent fragmentation, but does lead to a higher Jeans mass, resulting in fewer and more massive stars than would form without the heating. This mechanism reproduces the observed relation between the total stellar mass in the cluster and the mass of the largest star. It predicts strong clumping and filamentary structure in the center of collapsing cores, as has recently been observed. We speculate that a similar mechanism will act during primordial star formation.

Upper Caraş River (Danube watershed fish populations fragmentation – technical rehabilitation proposal

Directory of Open Access Journals (Sweden)

Voicu Răzvan

2018-01-01

Full Text Available We propose a technical solution for fish movement based on the flow of water over a spill threshold. Such barriers are common in the Danube system. The proposed system has a range of operating components which are easily detachable from the spill threshold, are resistant to corrosion and will not harm the fish. In fact, if designed to complement swimming abilities of target fish, it should provide adequate passage for both adults and juveniles. If implemented correctly, the design may offer a solution to help displaced fish recolonize upstream habitats.

Inner-shell excitation and site specific fragmentation of poly(methylmethacrylate) thin film

Science.gov (United States)

Tinone, Marcia C. K.; Tanaka, Kenichiro; Maruyama, Junya; Ueno, Nobuo; Imamura, Motoyasu; Matsubayashi, Nobuyuki

1994-04-01

Soft x-ray excitations in the 250-600 eV photon energy range on poly(methylmethacrylate) (PMMA) result in ionic fragmentation of the original polymer with the most intense ions corresponding to CH+3, H+, CH+2, CH+, CHO+, and COOCH+3. The photon energy dependence of ion desorption from thin films of PMMA was measured to investigate the primary steps in radiation induced decomposition following carbon and oxygen 1s electron excitations using monochromatic pulsed-synchrotron radiation. It was clearly found that the decomposition depends on the nature of the electronic states created in the excited species. The fragmentation pattern changes depending on the transitions of the 1s electron to a Rydberg orbital, an unoccupied molecular orbital or the ionization continuum. Moreover, the fragmentation occurs specifically around the site of the atom where the optical excitation takes place. Excitations from carbon and oxygen 1s to σ* states seem to be specially efficient for ion production as observed in the case of CH+3, CH+2, and CH+ at 288.7 and 535.6 eV, and in the case of CHO+ at 539.3 eV.

Polydopamine-Coated Magnetic Molecularly Imprinted Polymers with Fragment Template for Identification of Pulsatilla Saponin Metabolites in Rat Feces with UPLC-Q-TOF-MS.

Science.gov (United States)

Zhang, Yu-Zhen; Zhang, Jia-Wei; Wang, Chong-Zhi; Zhou, Lian-Di; Zhang, Qi-Hui; Yuan, Chun-Su

2018-01-24

In this work, a modified pretreatment method using magnetic molecularly imprinted polymers (MMIPs) was successfully applied to study the metabolites of an important botanical with ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The MMIPs for glucoside-specific adsorption was used to identify metabolites of Pulsatilla chinensis in rat feces. Polymers were prepared by using Fe 3 O 4 nanoparticles as the supporting matrix, d-glucose as fragment template, and dopamine as the functional monomer and cross-linker. Results showed that MMIPs exhibited excellent extraction performance, large adsorption capacity (5.65 mg/g), fast kinetics (60 min), and magnetic separation. Furthermore, the MMIPs coupled with UPLC-Q-TOF-MS were successfully utilized for the identification of 17 compounds including 15 metabolites from the Pulsatilla saponin metabolic pool. This study provides a reliable protocol for the separation and identification of saponin metabolites in a complex biological sample, including those from herbal medicines.

THE FRAGMENTATION OF MAGNETIZED, MASSIVE STAR-FORMING CORES WITH RADIATIVE FEEDBACK

Energy Technology Data Exchange (ETDEWEB)

Myers, Andrew T.; McKee, Christopher F. [Department of Physics, University of California, Berkeley, Berkeley, CA 94720 (United States); Cunningham, Andrew J. [Lawrence Livermore National Laboratory, P.O. Box 808, L-23, Livermore, CA 94550 (United States); Klein, Richard I. [Department of Astronomy, University of California, Berkeley, Berkeley, CA 94720 (United States); Krumholz, Mark R., E-mail: atmyers@berkeley.edu [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States)

2013-04-01

We present a set of three-dimensional, radiation-magnetohydrodynamic calculations of the gravitational collapse of massive (300 M{sub Sun }), star-forming molecular cloud cores. We show that the combined effects of magnetic fields and radiative feedback strongly suppress core fragmentation, leading to the production of single-star systems rather than small clusters. We find that the two processes are efficient at suppressing fragmentation in different regimes, with the feedback most effective in the dense, central region and the magnetic field most effective in more diffuse, outer regions. Thus, the combination of the two is much more effective at suppressing fragmentation than either one considered in isolation. Our work suggests that typical massive cores, which have mass-to-flux ratios of about 2 relative to critical, likely form a single-star system, but that cores with weaker fields may form a small star cluster. This result helps us understand why the observed relationship between the core mass function and the stellar initial mass function holds even for {approx}100 M{sub Sun} cores with many thermal Jeans masses of material. We also demonstrate that a {approx}40 AU Keplerian disk is able to form in our simulations, despite the braking effect caused by the strong magnetic field.

DNA fragmentation in spermatozoa

DEFF Research Database (Denmark)

Rex, A S; Aagaard, J.; Fedder, J

2017-01-01

Sperm DNA Fragmentation has been extensively studied for more than a decade. In the 1940s the uniqueness of the spermatozoa protein complex which stabilizes the DNA was discovered. In the fifties and sixties, the association between unstable chromatin structure and subfertility was investigated....... In the seventies, the impact of induced DNA damage was investigated. In the 1980s the concept of sperm DNA fragmentation as related to infertility was introduced as well as the first DNA fragmentation test: the Sperm Chromatin Structure Assay (SCSA). The terminal deoxynucleotidyl transferase nick end labelling...... (TUNEL) test followed by others was introduced in the nineties. The association between DNA fragmentation in spermatozoa and pregnancy loss has been extensively investigated spurring the need for a therapeutic tool for these patients. This gave rise to an increased interest in the aetiology of DNA damage...

Photon-hadron fragmentation: theoretical situation

International Nuclear Information System (INIS)

Peschanski, R.

1983-07-01

Using a selection of new experimental results models of hadronic fragmentation and their phenomenological comparison are presented. Indeed a convenient theory of hadronic fragmentation -for instance based on Q.C.D.- does not exist: low transverse momentum fragmentation involves the badly known hadronic long-range forces. Models should clarify the situation in the prospect of an eventual future theory

Anticoagulant and calcium-binding properties of high molecular weight derivatives of human fibrinogen (plasmin fragments Y)

NARCIS (Netherlands)

Nieuwenhuizen, W.; Voskuilen, M.; Hermans, J.

1982-01-01

The present study was undertaken as a step to delineate further the localization of the calcium-binding sites in fibrinogen and to assess the anticlotting properties of fibrinogen degradation products. To this purpose, fragments Y were prepared by plasmin digestion of human fibrinogen in the

Recent progress on perturbative QCD fragmentation functions

International Nuclear Information System (INIS)

Cheung, K.

1995-05-01

The recent development of perturbative QCD (PQCD) fragmentation functions has strong impact on quarkonium production. I shall summarize B c meson production based on these PQCD fragmentation functions, as well as, the highlights of some recent activities on applying these PQCD fragmentation functions to explain anomalous J/ψ and ψ' production at the Tevatron. Finally, I discuss a fragmentation model based on the PQCD fragmentation functions for heavy quarks fragmenting into heavy-light mesons

Molecular epidemiology of Blastocystis

Directory of Open Access Journals (Sweden)

Fadime Eroğlu

2015-12-01

Full Text Available Blastocystis pathogenicity and classification was newly illuminated with molecular genetic studies and recently the parasite was found in the focus of many researchers. Several molecular methods such as; polymerase chain reaction (PCR, PCR-restriction fragment length polymorphism, random amplified polymorphic DNA, real-time polymerase chain reaction and DNA sequencing analyses can be used in genotyping of Blastocystis. Blastocystis parasites may cause diarrhea, abdominal pain, bloating, gas, irritability, anorexia, cramps, vomiting, dehydration, insomnia, nausea, loss of appetite, weight loss, fatigue symptoms and also could be asymptomatic cases. In this review, it was aimed to summarize the associations between Blastocystis subtypes and pathogenicity.

From Protein Structure to Small-Molecules: Recent Advances and Applications to Fragment-Based Drug Discovery.

Science.gov (United States)

Ferreira, Leonardo G; Andricopulo, Adriano D

2017-01-01

Fragment-based drug discovery (FBDD) is a broadly used strategy in structure-guided ligand design, whereby low-molecular weight hits move from lead-like to drug-like compounds. Over the past 15 years, an increasingly important role of the integration of these strategies into industrial and academic research platforms has been successfully established, allowing outstanding contributions to drug discovery. One important factor for the current prominence of FBDD is the better coverage of the chemical space provided by fragment-like libraries. The development of the field relies on two features: (i) the growing number of structurally characterized drug targets and (ii) the enormous chemical diversity available for experimental and virtual screenings. Indeed, fragment-based campaigns have contributed to address major challenges in lead optimization, such as the appropriate physicochemical profile of clinical candidates. This perspective paper outlines the usefulness and applications of FBDD approaches in medicinal chemistry and drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fragmentation and flow in central collisions

International Nuclear Information System (INIS)

Jacak, B.V.; Doss, K.G.R.; Gustafsson, H.A.

1987-01-01

Investigation of the fragmentation mechanism requires the measurement of complicated observables. To identify what part of the reacting system gives rise to the fragments, it would be useful to tag them as participants or spectators. A large acceptance for all the reaction products and an event-by-event measurement of the fragment multiplicity is required to distinguish fragment formation via sequential emission from a large equilibrated system and multifragmentation. In order to address whether fragments are formed early or late in the collision, information about the dynamical evolution of the reaction is necessary. This can be provided by study of the global properties of the events. This paper discusses experimental techniques applicable to studying fragmentation processes. 25 refs., 8 figs

Long-term effects of fragmentation and fragment properties on bird species richness in Hawaiian forests

Science.gov (United States)

David J. Flaspohler; Christian P. Giardina; Gregory P. Asner; Patrick Hart; Jonathan Price; Cassie Ka’apu Lyons; Xeronimo. Castaneda

2010-01-01

Forest fragmentation is a common disturbance affecting biological diversity, yet the impacts of fragmentation on many forest processes remain poorly understood. Forest restoration is likely to be more successful when it proceeds with an understanding of how native and exotic vertebrates utilize forest patches of different size. We used a system of forest fragments...

Mass spectrometry for fragment screening.

Science.gov (United States)

Chan, Daniel Shiu-Hin; Whitehouse, Andrew J; Coyne, Anthony G; Abell, Chris

2017-11-08

Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography. In this context, MS is a relatively underutilized technique in fragment screening for drug discovery. MS-based techniques have the advantage of high sensitivity, low sample consumption and being label-free. This review highlights recent examples of the emerging use of MS-based techniques in fragment screening. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Universal odd-even staggering in isotopic fragmentation and spallation cross sections of neutron-rich fragments

Science.gov (United States)

Mei, B.; Tu, X. L.; Wang, M.

2018-04-01

An evident odd-even staggering (OES) in fragment cross sections has been experimentally observed in many fragmentation and spallation reactions. However, quantitative comparisons of this OES effect in different reaction systems are still scarce for neutron-rich nuclei near the neutron drip line. By employing a third-order difference formula, the magnitudes of this OES in extensive experimental cross sections are systematically investigated for many neutron-rich nuclei with (N -Z ) from 1 to 23 over a broad range of atomic numbers (Z ≈3 -50 ). A comparison of these magnitude values extracted from fragment cross sections measured in different fragmentation and spallation reactions with a large variety of projectile-target combinations over a wide energy range reveals that the OES magnitude is almost independent of the projectile-target combinations and the projectile energy. The weighted average of these OES magnitudes derived from cross sections accurately measured in different reaction systems is adopted as the evaluation value of the OES magnitude. These evaluated OES magnitudes are recommended to be used in fragmentation and spallation models to improve their predictions for fragment cross sections.

Isoschizomers and amplified fragment length polymorphism for the detection of specific cytosine methylation changes.

Science.gov (United States)

Ruiz-García, Leonor; Cabezas, Jose Antonio; de María, Nuria; Cervera, María-Teresa

2010-01-01

Different molecular techniques have been developed to study either the global level of methylated cytosines or methylation at specific gene sequences. One of them is a modification of the Amplified Fragment Length Polymorphism (AFLP) technique that has been used to study methylation of anonymous CCGG sequences in different fungi, plant and animal species. The main variation of this technique is based on the use of isoschizomers with different methylation sensitivity (such as HpaII and MspI) as a frequent cutter restriction enzyme. For each sample, AFLP analysis is performed using both EcoRI/HpaII and EcoRI/MspI digested samples. Comparative analysis between EcoRI/HpaII and EcoRI/MspI fragment patterns allows the identification of two types of polymorphisms: (1) "Methylation-insensitive polymorphisms" that show common EcoRI/HpaII and EcoRI/MspI patterns but are detected as polymorphic amplified fragments among samples; and (2) "Methylation-sensitive polymorphisms" that are associated with amplified fragments differing in their presence or absence or in their intensity between EcoRI/HpaII and EcoRI/MspI patterns. This chapter describes a detailed protocol of this technique and discusses modifications that can be applied to adjust the technology to different species of interest.

Molecular Identification of Date Palm Cultivars Using Random Amplified Polymorphic DNA (RAPD) Markers.

Science.gov (United States)

Al-Khalifah, Nasser S; Shanavaskhan, A E

2017-01-01

Ambiguity in the total number of date palm cultivars across the world is pointing toward the necessity for an enumerative study using standard morphological and molecular markers. Among molecular markers, DNA markers are more suitable and ubiquitous to most applications. They are highly polymorphic in nature, frequently occurring in genomes, easy to access, and highly reproducible. Various molecular markers such as restriction fragment length polymorphism (RFLP), amplified fragment length polymorphism (AFLP), simple sequence repeats (SSR), inter-simple sequence repeats (ISSR), and random amplified polymorphic DNA (RAPD) markers have been successfully used as efficient tools for analysis of genetic variation in date palm. This chapter explains a stepwise protocol for extracting total genomic DNA from date palm leaves. A user-friendly protocol for RAPD analysis and a table showing the primers used in different molecular techniques that produce polymorphisms in date palm are also provided.

The roles of family B and D DNA polymerases in Thermococcus species 9°N Okazaki fragment maturation.

Science.gov (United States)

Greenough, Lucia; Kelman, Zvi; Gardner, Andrew F

2015-05-15

During replication, Okazaki fragment maturation is a fundamental process that joins discontinuously synthesized DNA fragments into a contiguous lagging strand. Efficient maturation prevents repeat sequence expansions, small duplications, and generation of double-stranded DNA breaks. To address the components required for the process in Thermococcus, Okazaki fragment maturation was reconstituted in vitro using purified proteins from Thermococcus species 9°N or cell extracts. A dual color fluorescence assay was developed to monitor reaction substrates, intermediates, and products. DNA polymerase D (polD) was proposed to function as the replicative polymerase in Thermococcus replicating both the leading and the lagging strands. It is shown here, however, that it stops before the previous Okazaki fragments, failing to rapidly process them. Instead, Family B DNA polymerase (polB) was observed to rapidly fill the gaps left by polD and displaces the downstream Okazaki fragment to create a flap structure. This flap structure was cleaved by flap endonuclease 1 (Fen1) and the resultant nick was ligated by DNA ligase to form a mature lagging strand. The similarities to both bacterial and eukaryotic systems and evolutionary implications of archaeal Okazaki fragment maturation are discussed. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Anti-coagulation effect of Fc fragment against anti-β2-GP1 antibodies in mouse models with APS.

Science.gov (United States)

Xie, Weidong; Zhang, Yaou; Bu, Cunya; Sun, Shijing; Hu, Shaoliang; Cai, Guoping

2011-01-01

Anti-beta (2)-glycoprotein I (anti-β2-GP1) is one of the important pathogenesis factors responsible for thrombosis formation in patients with antiphospholipid syndrome (APS). Administration of intravenous immunoglobulin (IVIg) is a common method used to inhibit the abnormal antibody levels and decrease the mortality of APS in emergency situations. We hypothesize that the Fc fragment of IgG is the molecular structure responsible for these effects. The present study investigates the beneficial effects of both recombinant and natural human Fc fragments of heterogeneous IgG against human anti-β2-GP1 antibodies in mouse models with APS. Results showed that both recombinant and natural human Fc fragments moderately but significantly decreased the levels of serum anti-β2-GP1 antibodies and had anti-coagulation effects in human β2-GP1-immunized mice. Furthermore, both recombinant and natural human Fc fragments inhibited thrombosis formation and decreased mortality in mouse models infused intravenously with human anti-β2GP1 antibodies from patients with APS. Findings suggest that the Fc fragment might be one of the active structural units of heterogeneous IgG. Thus, recombinant human Fc fragment administration may be a useful treatment for individuals with APS. Copyright © 2010 Elsevier B.V. All rights reserved.

Physics of projectile fragments

International Nuclear Information System (INIS)

Minamisono, Tadanori

1982-01-01

This is a study report on the polarization phenomena of the projectile fragments produced by heavy ion reactions, and the beta decay of fragments. The experimental project by using heavy ions with the energy from 50 MeV/amu to 250 MeV/amu was designed. Construction of an angle-dispersion spectrograph for projectile fragments was proposed. This is a two-stage spectrograph. The first stage is a QQDQQ type separator, and the second stage is QDQD type. Estimation shows that Co-66 may be separated from the nuclei with mass of 65 and 67. The orientation of fragments can be measured by detecting beta-ray. The apparatus consists of a uniform field magnet, an energy absorber, a stopper, a RF coil and a beta-ray hodoscope. This system can be used for not only this purpose but also for the measurement of hyperfine structure. (Kato, T.)

Investigating the structure and fragmentation of a highly filamentary IRDC

Science.gov (United States)

Henshaw, J. D.; Caselli, P.; Fontani, F.; Jiménez-Serra, I.; Tan, J. C.; Longmore, S. N.; Pineda, J. E.; Parker, R. J.; Barnes, A. T.

2016-11-01

We present 3.7 arcsec (˜0.05 pc) resolution 3.2 mm dust continuum observations from the Institut de Radioastronomie Millimétrique Plateau de Bure Interferometer, with the aim of studying the structure and fragmentation of the filamentary infrared dark cloud (IRDC) G035.39-00.33. The continuum emission is segmented into a series of 13 quasi-regularly spaced (λobs ˜ 0.18 pc) cores, following the major axis of the IRDC. We compare the spatial distribution of the cores with that predicted by theoretical work describing the fragmentation of hydrodynamic fluid cylinders, finding a significant (a factor of ≳ 8) discrepancy between the two. Our observations are consistent with the picture emerging from kinematic studies of molecular clouds suggesting that the cores are harboured within a complex network of independent sub-filaments. This result emphasizes the importance of considering the underlying physical structure, and potentially, dynamically important magnetic fields, in any fragmentation analysis. The identified cores exhibit a range in (peak) beam-averaged column density (3.6 × 1023 cm-2 < NH, c < 8.0 × 1023 cm-2), mass (8.1 M⊙ < Mc < 26.1 M⊙), and number density (6.1 × 105 cm-3 < nH, c, eq < 14.7 × 105 cm-3). Two of these cores, dark in the mid-infrared, centrally concentrated, monolithic (with no traceable substructure at our PdBI resolution), and with estimated masses of the order ˜20-25 M⊙, are good candidates for the progenitors of intermediate-to-high-mass stars. Virial parameters span a range 0.2 < αvir < 1.3. Without additional support, possibly from dynamically important magnetic fields with strengths of the order of 230 μG < B < 670 μG, the cores are susceptible to gravitational collapse. These results may imply a multilayered fragmentation process, which incorporates the formation of sub-filaments, embedded cores, and the possibility of further fragmentation.

Quantum molecular dynamics: Numerical methods and physical study of the structure, thermodynamics, stability and fragmentation of sodium metallic clusters; Dynamique moleculaire quantique: Methodes numeriques et etude physique de la structure, de la thermodynamique, de la stabilite et de la fragmentation des agregats metalliques de sodium

Energy Technology Data Exchange (ETDEWEB)

Blaise, Philippe [Universite Joseph Fourier, Grenoble 1, 74 Annecy (France)

1998-09-29

The aim of this thesis is to study metallic sodium clusters by numerical simulation. We have developed two ab initio molecular dynamics programs within the formalism of density functional theory. The first is based on the semi-classical extended Thomas-Fermi approach. We use a real-space grid and a Car-Parrinello-like scheme. The computational cost is O(N), and we have built a pseudopotential that speeds up the calculations. By neglecting quantum shell effects, we are able to study a very large set of clusters. We show that sodium cluster energies fit well a liquid drop formula, by adjusting a few parameters. We have investigated breathing modes, surface oscillations and the net charge density. We have shown that the surface energy varies strongly with temperature, and that clusters have a lower melting point than bulk material. We have calculated fission barriers by a constraint method. The second program is based on the quantum Kohn-Sham approach. We use a real-space grid, and combine a generalized Broyden scheme for assuring self-consistency with an iterative Davidson-Lanczos algorithm for solving the Eigen-problem. The cost of the method is much higher. First of all, we have calculated some stable structures for small clusters and their energetics. We obtained very good agreement with previous works. Then, we have investigated highly charged cluster dynamics. We have identified a chaotic fission process. For high fissility systems, we observe a multi-fragmentation dynamics and we find preferential emission of monomers on a characteristic time scale less than a pico-second. This has been simulated for the first time, with the help of our adaptive grid method which follows each fragment as they move apart during the fragmentation. (author) 87 refs., 57 figs., 4 tabs.

Molecular dynamics for irradiation driven chemistry: application to the FEBID process*

Science.gov (United States)

Sushko, Gennady B.; Solov'yov, Ilia A.; Solov'yov, Andrey V.

2016-10-01

A new molecular dynamics (MD) approach for computer simulations of irradiation driven chemical transformations of complex molecular systems is suggested. The approach is based on the fact that irradiation induced quantum transformations can often be treated as random, fast and local processes involving small molecules or molecular fragments. We advocate that the quantum transformations, such as molecular bond breaks, creation and annihilation of dangling bonds, electronic charge redistributions, changes in molecular topologies, etc., could be incorporated locally into the molecular force fields that describe the classical MD of complex molecular systems under irradiation. The proposed irradiation driven molecular dynamics (IDMD) methodology is designed for the molecular level description of the irradiation driven chemistry. The IDMD approach is implemented into the MBN Explorer software package capable to operate with a large library of classical potentials, many-body force fields and their combinations. IDMD opens a broad range of possibilities for modelling of irradiation driven modifications and chemistry of complex molecular systems ranging from radiotherapy cancer treatments to the modern technologies such as focused electron beam deposition (FEBID). As an example, the new methodology is applied for studying the irradiation driven chemistry caused by FEBID of tungsten hexacarbonyl W(CO)6 precursor molecules on a hydroxylated SiO2 surface. It is demonstrated that knowing the interaction parameters for the fragments of the molecular system arising in the course of irradiation one can reproduce reasonably well experimental observations and make predictions about the morphology and molecular composition of nanostructures that emerge on the surface during the FEBID process.

Emission spectroscopic studies on dynamics of molecular excitation and dissociation by controlled electron impact

International Nuclear Information System (INIS)

Ogawa, Teiichiro

1986-01-01

Emission spectrum by controlled electron impact has been a successful technique for the investigation of molecular dynamics. (1) Molecular excitation. Aromatic molecules give an optical emission similar to fluorescence. However, as is shown by the vibrational structure and the electron energy dependence of benzene emission, its excitation process is not necessarily optical. Some aliphatic molecules also exhibit an emission band at the ultraviolet region. (2) Molecular dissociation. Analysis of the Doppler profile, the threshold energy, the excitation function and the isotope effect of the atomic emission produced in electron-molecule collisions has clarified the dynamics of the molecular dissociation. Especially the Doppler profile has given the translational energy distribution of the fragment atom, which is very useful to disclose the potential energy curve. Its angular dependence has recently found to allow determination of the symmetry of the intermediate excited state and the magnetic sublevel distribution of the fragment atom. These finding has revealed detailed state-to-state dynamics of the molecular dissociation. (author)

MRI of displaced meniscal fragments

International Nuclear Information System (INIS)

Dunoski, Brian; Zbojniewicz, Andrew M.; Laor, Tal

2012-01-01

A torn meniscus frequently requires surgical fixation or debridement as definitive treatment. Meniscal tears with associated fragment displacement, such as bucket handle and flap tears, can be difficult to recognize and accurately describe on MRI, and displaced fragments can be challenging to identify at surgery. A displaced meniscal fragment can be obscured by synovium or be in a location not usually evaluated at arthroscopy. We present a pictorial essay of meniscal tears with displaced fragments in patients referred to a pediatric hospital in order to increase recognition and accurate interpretation by the radiologist, who in turn can help assist the surgeon in planning appropriate therapy. (orig.)

MRI of displaced meniscal fragments

Energy Technology Data Exchange (ETDEWEB)

Dunoski, Brian [University of Cincinnati College of Medicine, Department of Radiology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Children' s Hospital of Michigan, Department of Radiology, Detroit, MI (United States); Zbojniewicz, Andrew M.; Laor, Tal [University of Cincinnati College of Medicine, Department of Radiology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States)

2012-01-15

A torn meniscus frequently requires surgical fixation or debridement as definitive treatment. Meniscal tears with associated fragment displacement, such as bucket handle and flap tears, can be difficult to recognize and accurately describe on MRI, and displaced fragments can be challenging to identify at surgery. A displaced meniscal fragment can be obscured by synovium or be in a location not usually evaluated at arthroscopy. We present a pictorial essay of meniscal tears with displaced fragments in patients referred to a pediatric hospital in order to increase recognition and accurate interpretation by the radiologist, who in turn can help assist the surgeon in planning appropriate therapy. (orig.)

Dimensional crossover in fragmentation

Science.gov (United States)

Sotolongo-Costa, Oscar; Rodriguez, Arezky H.; Rodgers, G. J.

2000-11-01

Experiments in which thick clay plates and glass rods are fractured have revealed different behavior of fragment mass distribution function in the small and large fragment regions. In this paper we explain this behavior using non-extensive Tsallis statistics and show how the crossover between the two regions is caused by the change in the fragments’ dimensionality during the fracture process. We obtain a physical criterion for the position of this crossover and an expression for the change in the power-law exponent between the small and large fragment regions. These predictions are in good agreement with the experiments on thick clay plates.

High molecular weight non-polar hydrocarbons as pure model substances and in motor oil samples can be ionized without fragmentation by atmospheric pressure chemical ionization mass spectrometry.

Science.gov (United States)

Hourani, Nadim; Kuhnert, Nikolai

2012-10-15

High molecular weight non-polar hydrocarbons are still difficult to detect by mass spectrometry. Although several studies have targeted this problem, lack of good self-ionization has limited the ability of mass spectrometry to examine these hydrocarbons. Failure to control ion generation in the atmospheric pressure chemical ionization (APCI) source hampers the detection of intact stable gas-phase ions of non-polar hydrocarbon in mass spectrometry. Seventeen non-volatile non-polar hydrocarbons, reported to be difficult to ionize, were examined by an optimized APCI methodology using nitrogen as the reagent gas. All these analytes were successfully ionized as abundant and intact stable [M-H](+) ions without the use of any derivatization or adduct chemistry and without significant fragmentation. Application of the method to real-life hydrocarbon mixtures like light shredder waste and car motor oil was demonstrated. Despite numerous reports to the contrary, it is possible to ionize high molecular weight non-polar hydrocarbons by APCI, omitting the use of additives. This finding represents a significant step towards extending the applicability of mass spectrometry to non-polar hydrocarbon analyses in crude oil, petrochemical products, waste or food. Copyright © 2012 John Wiley & Sons, Ltd.

Influence of turn (or fold) and local charge in fragmentation of the peptide analogue molecule CH3CO-Gly-NH2 following single-photon VUV (118.22 nm) ionization.

Science.gov (United States)

Bhattacharya, Atanu; Bernstein, Elliot R

2011-10-06

The radical cationic reactivity of the peptide analogue molecule CH(3)CO-Gly-NH(2) is addressed both experimentally and theoretically. The radical cation intermediate of CH(3)CO-Gly-NH(2) is created by single-photon ionization of this molecule at 118.22 nm (~10.5 eV). The two most stable conformers (C(7) and C(5)) of this molecule exhibit different folds along the backbone: the C(7) conformer has a γ-turn structure, and the C(5) conformer has a β-strand structure. The experimental results show that the radical cation intermediate of CH(3)CO-Gly-NH(2) dissociates and generates a fragment-ion signal at 73 amu that is observed through TOFMS. Theoretical results show how the fragment-ion signal at 73 amu is generated by only one conformer of CH(3)CO-Gly-NH(2) (C(7)) and how local charge and specific hydrogen bonding in the molecule influence fragmentation of the radical cation intermediate of CH(3)CO-Gly-NH(2). The specific fold of the molecule controls fragmentation of this reactive radical cation intermediate. Whereas the radical cation of the C(7) conformer dissociates through a hydrogen-transfer mechanism followed by HNCO elimination, the radical cation of the C(5) conformer does not dissociate at all. CASSCF calculations show that positive charge in the radical cationic C(7) conformer is localized at the NH(2)CO moiety of the molecular ion. This site-specific localization of the positive charge enhances the acidity of the terminal NH(2) group, facilitating hydrogen transfer from the NH(2) to the COCH(3) end of the molecular ion. Positive charge in the C(5) conformer of the CH(3)CO-Gly-NH(2) radical cation is, however, localized at the COCH(3) end of the molecular ion, and this conformer does not have enough energy to surmount the energy barrier to dissociation on the ion potential energy surface. CASSCF results show that conformation-specific localization of charge in the CH(3)CO-Gly-NH(2) molecular ion occurs as a result of the different hydrogen

Urban landscapes can change virus gene flow and evolution in a fragmentation-sensitive carnivore

Science.gov (United States)

Fountain-Jones, Nicholas M.; Craft, Meggan E.; Funk, W. Chris; Kozakiewicz, Chris; Trumbo, Daryl; Boydston, Erin E.; Lyren, Lisa M.; Crooks, Kevin R.; Lee, Justin S.; VandeWoude, Sue; Carver, Scott

2017-01-01

Urban expansion has widespread impacts on wildlife species globally, including the transmission and emergence of infectious diseases. However, there is almost no information about how urban landscapes shape transmission dynamics in wildlife. Using an innovative phylodynamic approach combining host and pathogen molecular data with landscape characteristics and host traits, we untangle the complex factors that drive transmission networks of Feline Immunodeficiency Virus (FIV) in bobcats (Lynx rufus). We found that the urban landscape played a significant role in shaping FIV transmission. Even though bobcats were often trapped within the urban matrix, FIV transmission events were more likely to occur in areas with more natural habitat elements. Urban fragmentation also resulted in lower rates of pathogen evolution, possibly owing to a narrower range of host genotypes in the fragmented area. Combined, our findings show that urban landscapes can have impacts on a pathogen and its evolution in a carnivore living in one of the most fragmented and urban systems in North America. The analytical approach used here can be broadly applied to other host-pathogen systems, including humans.

Liquid-vapor phase transition, collective flow and entropy determination from future measurements of intermediate mass fragments

International Nuclear Information System (INIS)

Coffin, J.P.

1991-01-01

Some global variables reflecting the highly collective character of nuclear matter produced in relativistic heavy-ion collisions are briefly reviewed on the basis of presently available experimental results and of Quantum Statistical Model and Quantum Molecular Dynamic Model predictions relative to intermediate mass fragments. Possible future measurements are suggested. (author) 27 refs., 8 figs

Analysis of multi-fragmentation reactions induced by relativistic heavy ions using the statistical multi-fragmentation model

Energy Technology Data Exchange (ETDEWEB)

Ogawa, T., E-mail: ogawa.tatsuhiko@jaea.go.jp [Research Group for Radiation Protection, Division of Environment and Radiation Sciences, Nuclear Science and Engineering Directorate, Japan Atomic Energy Agency, Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan); Sato, T.; Hashimoto, S. [Research Group for Radiation Protection, Division of Environment and Radiation Sciences, Nuclear Science and Engineering Directorate, Japan Atomic Energy Agency, Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan); Niita, K. [Research Organization for Information Science and Technology, Shirakata-shirane, Tokai, Ibaraki 319-1188 (Japan)

2013-09-21

The fragmentation cross-sections of relativistic energy nucleus–nucleus collisions were analyzed using the statistical multi-fragmentation model (SMM) incorporated with the Monte-Carlo radiation transport simulation code particle and heavy ion transport code system (PHITS). Comparison with the literature data showed that PHITS-SMM reproduces fragmentation cross-sections of heavy nuclei at relativistic energies better than the original PHITS by up to two orders of magnitude. It was also found that SMM does not degrade the neutron production cross-sections in heavy ion collisions or the fragmentation cross-sections of light nuclei, for which SMM has not been benchmarked. Therefore, SMM is a robust model that can supplement conventional nucleus–nucleus reaction models, enabling more accurate prediction of fragmentation cross-sections.

Analysis of multi-fragmentation reactions induced by relativistic heavy ions using the statistical multi-fragmentation model

International Nuclear Information System (INIS)

Ogawa, T.; Sato, T.; Hashimoto, S.; Niita, K.

2013-01-01

The fragmentation cross-sections of relativistic energy nucleus–nucleus collisions were analyzed using the statistical multi-fragmentation model (SMM) incorporated with the Monte-Carlo radiation transport simulation code particle and heavy ion transport code system (PHITS). Comparison with the literature data showed that PHITS-SMM reproduces fragmentation cross-sections of heavy nuclei at relativistic energies better than the original PHITS by up to two orders of magnitude. It was also found that SMM does not degrade the neutron production cross-sections in heavy ion collisions or the fragmentation cross-sections of light nuclei, for which SMM has not been benchmarked. Therefore, SMM is a robust model that can supplement conventional nucleus–nucleus reaction models, enabling more accurate prediction of fragmentation cross-sections

Molecular and morpho-anatomical characterization of some Egyptian durum wheat cultivars/lines

International Nuclear Information System (INIS)

Saleh, O.M.; Hamiedeldin, N.; Khafaga, A.

2016-01-01

Grains of eight durum wheat cultivars were tested for identification of genetic relationship among molecular, anatomical and morphological levels. On the molecular level, two techniques have been used; Randomly Amplified Polymorphic DNA (RAPD) and Inter Simple Sequence Repeats (ISSR). Amplification of RAPD primers showed different numbers of fragments ranged from six to thirteen fragments. Percentage of polymorphism ranged from 0% to 100%. The highest similarity value recorded was 91%, while the lowest similarity value was 69%. Amplification of ISSR primers showed different numbers of fragments ranged from six to twelve fragments. The highest similarity value recorded was 91%, while the lowest similarity value was 68%. The grain's coat morphology was reticulated in all taxa. There were variations with regard to the alignment and the shape of network and architecture of interspaces enclosed by raised line. Reticulate surface patterns appeared some variations ranged from weakly reticulate such as G 413 to strongly reticulate such as G 203. Stem cuticles of all cultivars were thick except cultivar; Benisweif 1. For leaf anatomy, all cultivars had epidermis composed of one layer of thick wall cells except cultivars; G 203 and Benisweif 1. (author)

Molecular Diagnostics for the Study of Hypersonic Flows

Science.gov (United States)

2000-04-01

UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADPO10744 TITLE: Molecular Diagnostics for the Study of Hypersonic Flows...following component part numbers comprise the compilation report: ADP010736 thru ADPO10751 UNCLASSIFIED 5-1 Molecular Diagnostics for the Study of

Dissociative Recombination of HD+ - State-to-State Experimental Investigation Using Fragment Imaging and Storage Ring Techniques

International Nuclear Information System (INIS)

Amitay, Z.; Baer, A.; Dahan, M.; Levin, J.; Vager, Z.; Zajfman, D.

1998-01-01

When a molecular ion collides with a free electron it can capture the electron and dissociate. The resulting process of Dissociative Recombination (DR) is a process of great significance in a wide variety of plasma environments. In this process, the capture of a free electron leads to the formation of an highly excited state of the neutral molecule, which then dissociates into neutral fragments with kinetic energy and, possibly, internal excitation depending on the energy balance of the reaction. Despite its importance, the DR process is still not yet completely understood theoretically. This is mainly due to the complexity of the nature and dynamics of highly excited molecular states, especially when several channels are involved, as is usually the situation in DR. from experimental point of view, for direct comparison between experiment and theory, this complexity requires detailed experimental data, including the knowledge of both the initial state of the molecular ion, to which DR is very sensitive, and of the final quantum states of the DR products. Inherent un- certainties in the initial vibrational excitation of the laboratory molecular ions was the main drawback of the experiments conducted over the years to, study DR. A substantial progress in the understanding of the DR process was achieved with the introduction (about five years ago) of a new experimental approach, which uses heavy-ion storage ring technique. In a storage ring, one can store many molecular ions for a time which is long enough to allow complete radiative deexcitation of tile initial electronic and vibrational excitation coming from the ion source. Those vibrationally cold ions are then merged with an intense electron beam to measure their DR cross section. Further experimental progress was the inclusion of two and three-dimensional molecular imaging techniques [1] for the measurement of the branching ratio to different final quantum states of the neutral DR fragments. This talk will

Monoclonal antibodies and Fc fragments for treating solid tumors

Directory of Open Access Journals (Sweden)

Eisenbeis AM

2012-01-01

Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

Trends in plant research using molecular markers.

Science.gov (United States)

Garrido-Cardenas, Jose Antonio; Mesa-Valle, Concepción; Manzano-Agugliaro, Francisco

2018-03-01

A deep bibliometric analysis has been carried out, obtaining valuable parameters that facilitate the understanding around the research in plant using molecular markers. The evolution of the improvement in the field of agronomy is fundamental for its adaptation to the new exigencies that the current world context raises. In addition, within these improvements, this article focuses on those related to the biotechnology sector. More specifically, the use of DNA markers that allow the researcher to know the set of genes associated with a particular quantitative trait or QTL. The use of molecular markers is widely extended, including: restriction fragment length polymorphism, random-amplified polymorphic DNA, amplified fragment length polymorphism, microsatellites, and single-nucleotide polymorphisms. In addition to classical methodology, new approaches based on the next generation sequencing are proving to be fundamental. In this article, a historical review of the molecular markers traditionally used in plants, since its birth and how the new molecular tools facilitate the work of plant breeders is carried out. The evolution of the most studied cultures from the point of view of molecular markers is also reviewed and other parameters whose prior knowledge can facilitate the approach of researchers to this field of research are analyzed. The bibliometric analysis of molecular markers in plants shows that top five countries in this research are: US, China, India, France, and Germany, and from 2013, this research is led by China. On the other hand, the basic research using Arabidopsis is deeper in France and Germany, while other countries focused its efforts in their main crops as the US for wheat or maize, while China and India for wheat and rice.

European Virtual Atomic And Molecular Data Center - VAMDC

Science.gov (United States)

Dimitrijevic, M. S.; Sahal-Brechot, S.; Kovacevic, A.; Jevremovic, D.; Popovic, L. C.

2010-07-01

Reliable atomic and molecular data are of great importance for different applications in astrophysics, atmospheric physics, fusion, environmental sciences, combustion chemistry, and in industrial applications from plasmas and lasers to lighting. Currently, very important resources of such data are highly fragmented, presented in different, nonstandardized ways, available through a variety of highly specialized and often poorly documented interfaces, so that the full exploitation of all their scientific worth is limited, hindering research in many topics like e.g. the characterization of extrasolar planets, understanding the chemistry of our local solar system and of the wider universe, the study of the terrestrial atmosphere and quantification of climate change; the development of the fusion rersearch, etc. The Virtual Atomic and Molecular Data Centre (http://www.vamdc.eu, VAMDC) is an European Union funded FP7 project aiming to build a secure, documented, flexible and interoperable e-science environment-based interface to existing atomic and molecular data. It will also provide a forum for training potential users and dissemination of expertise worldwide. Partners in the Consortium of the Project are: 1) Centre National de Recherche Scientifique - CNRS (Paris, Reims, Grenoble, Bordeaux, Dijon, Toulouse); 2) The Chancellor, Masters and Scholars of the University of Cambridge - CMSUC; 3) University College London - UCL; 4) Open University - OU; (Milton Keynes, England); 5) Universitaet Wien - UNIVIE; 6) Uppsala Universitet - UU; 7) Universitaet zu Koeln - KOLN; 8) Istituto Nazionale di Astrofisica - INAF (Catania, Cagliari); 9) Queen's University Belfast - QUB; 10) Astronomska Opservatorija - AOB (Belgrade, Serbia); 11) Institute of Spectroscopy RAS - ISRAN (Troitsk, Russia); 12) Russian Federal Nuclear Center - All-Russian Institute of Technical Physics - RFNC-VNIITF (Snezhinsk, Chelyabinsk Region, Russia; 13) Institute of Atmospheric Optics - IAO (Tomsk, Russia

19th Meeting of the IFRC Subcommittee on Atomic and Molecular Data for Fusion. Summary Report of an IAEA Technical Meeting

International Nuclear Information System (INIS)

Braams, Bastiaan J.

2014-07-01

The International Fusion Research Council (IFRC) Subcommittee on Atomic and Molecular Data met at IAEA Headquarters in Vienna on 28-29 April 2014 to review the work of the Atomic and Molecular Data Unit (AMDU) within the Nuclear Data Section. The subcommittee heard presentations on the Unit’s activities in the years 2012 and 2013 and discussed priorities for database development and evaluation, coordinated research projects and other meetings, and presentation on the web and elsewhere of the work of the Unit. The IFRC Subcommittee offers the following specific recommendations. • For Coordinated Research Projects in the area of plasma-material interaction highest priority goes to a CRP on erosion and tritium retention for steel surfaces, with emphasis on the kinds of low- or reduced-activation steels that may be used in a reactor. • In the area of atomic and molecular data it is recommended to initiate a new CRP on data for charge exchange processes related to neutral beams. The main topic of interest will be beam interaction with core plasma, but processes relevant to generation of the beam may also be included. • Data for plasma interaction with liquid metals gallium and tin, certain salts and possibly also aluminium, are needed in order to assess uses of these materials in a reactor environment. For a CRP this topic has lower priority than one on steel surfaces, but it is recommended as a good topic for a Technical Meeting. • The Unit should organize again, in 2014 or early 2015, a large “decennial” meeting on atomic, molecular and plasma-material interaction data for fusion science and technology to bring together fusion scientists users of A+M+PMI data and atomic, molecular and materials scientists data producers. • The Unit has the mission to provide internationally recommended and evaluated data for atomic, molecular and plasma-material interaction process and related materials structure properties for fusion science and technology; this is

Reframing landscape fragmentation's effects on ecosystem services.

Science.gov (United States)

Mitchell, Matthew G E; Suarez-Castro, Andrés F; Martinez-Harms, Maria; Maron, Martine; McAlpine, Clive; Gaston, Kevin J; Johansen, Kasper; Rhodes, Jonathan R

2015-04-01

Landscape structure and fragmentation have important effects on ecosystem services, with a common assumption being that fragmentation reduces service provision. This is based on fragmentation's expected effects on ecosystem service supply, but ignores how fragmentation influences the flow of services to people. Here we develop a new conceptual framework that explicitly considers the links between landscape fragmentation, the supply of services, and the flow of services to people. We argue that fragmentation's effects on ecosystem service flow can be positive or negative, and use our framework to construct testable hypotheses about the effects of fragmentation on final ecosystem service provision. Empirical efforts to apply and test this framework are critical to improving landscape management for multiple ecosystem services. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fragment Size Distribution of Blasted Rock Mass

Science.gov (United States)

Jug, Jasmin; Strelec, Stjepan; Gazdek, Mario; Kavur, Boris

2017-12-01

Rock mass is a heterogeneous material, and the heterogeneity of rock causes sizes distribution of fragmented rocks in blasting. Prediction of blasted rock mass fragmentation has a significant role in the overall economics of opencast mines. Blasting as primary fragmentation can significantly decrease the cost of loading, transport, crushing and milling operations. Blast fragmentation chiefly depends on the specific blast design (geometry of blast holes drilling, the quantity and class of explosive, the blasting form, the timing and partition, etc.) and on the properties of the rock mass (including the uniaxial compressive strength, the rock mass elastic Young modulus, the rock discontinuity characteristics and the rock density). Prediction and processing of blasting results researchers can accomplish by a variety of existing software’s and models, one of them is the Kuz-Ram model, which is possibly the most widely used approach to estimating fragmentation from blasting. This paper shows the estimation of fragmentation using the "SB" program, which was created by the authors. Mentioned program includes the Kuz-Ram model. Models of fragmentation are confirmed and calibrated by comparing the estimated fragmentation with actual post-blast fragmentation from image processing techniques. In this study, the Kuz-Ram fragmentation model has been used for an open-pit limestone quarry in Dalmatia, southern Croatia. The resulting calibrated value of the rock factor enables the quality prognosis of fragmentation in further blasting works, with changed drilling geometry and blast design parameters. It also facilitates simulation in the program to optimize blasting works and get the desired fragmentations of the blasted rock mass.

GPCR-SSFE 2.0-a fragment-based molecular modeling web tool for Class A G-protein coupled receptors.

Science.gov (United States)

Worth, Catherine L; Kreuchwig, Franziska; Tiemann, Johanna K S; Kreuchwig, Annika; Ritschel, Michele; Kleinau, Gunnar; Hildebrand, Peter W; Krause, Gerd

2017-07-03

G-protein coupled receptors (GPCRs) are key players in signal transduction and therefore a large proportion of pharmaceutical drugs target these receptors. Structural data of GPCRs are sparse yet important for elucidating the molecular basis of GPCR-related diseases and for performing structure-based drug design. To ameliorate this problem, GPCR-SSFE 2.0 (http://www.ssfa-7tmr.de/ssfe2/), an intuitive web server dedicated to providing three-dimensional Class A GPCR homology models has been developed. The updated web server includes 27 inactive template structures and incorporates various new functionalities. Uniquely, it uses a fingerprint correlation scoring strategy for identifying the optimal templates, which we demonstrate captures structural features that sequence similarity alone is unable to do. Template selection is carried out separately for each helix, allowing both single-template models and fragment-based models to be built. Additionally, GPCR-SSFE 2.0 stores a comprehensive set of pre-calculated and downloadable homology models and also incorporates interactive loop modeling using the tool SL2, allowing knowledge-based input by the user to guide the selection process. For visual analysis, the NGL viewer is embedded into the result pages. Finally, blind-testing using two recently published structures shows that GPCR-SSFE 2.0 performs comparably or better than other state-of-the art GPCR modeling web servers. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Construction and operation of an universal stopping equipment for the fragment separator of the GSI Darmstadt

International Nuclear Information System (INIS)

Weckenmann, J.; Hanelt, E.; Schmidt, K.H.

1990-07-01

The fragment separator is a magnetic spectrometer, in which an especially-shaped layer of matter is applied as ion-optical element. The energy loss occurring there is accompanied by a series of unwanted effects like nuclear reaction, elecromagnetic dissociation, energy and angle straggling. These effects reduce on the one hand the total resolution of the separator and on the other hand the number of the fragments, which reach the exit of the separator. In the present study it was stated that the influence of these effects exhibits in most of the cases only a weak dependence on the material of the stopper. The ideal stopper material has a mass number, which corresponds nearly to the mass number of the selected fragment. If only one single stopper material will be applied, a material with low mass number seems to be the best compromise. Therefore for the universal stopper equipment of the fragment separator aluminium was selected. A further object of this study was the profile of the stopper. In a symmetrically constructed magnet spectrometer as the fragment separator the highest resolution is then reached, when the required particles are stopped in the whole width of their momentum distribution by a constant factor. This requirement leads to a curved profile of the stopper. It was stated that the profile can be approached by a linear wedge shape without a disadvantageous change of the resolution of the separator. The technical realization of the universal stopping equipment for the fragment separator consists mainly of very accurately manufactured, shiftable, and rotatable wedge-shaped layers. By means of a step-motor guiding the profiles required for the isotope separation can thus be obtained in a wide range. (orig.) [de

A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets.

Science.gov (United States)

Wasko, Michael J; Pellegrene, Kendy A; Madura, Jeffry D; Surratt, Christopher K

2015-01-01

Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacological screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening (VS), which employs computer models of the target protein to narrow the search for possible leads. A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for "growing" the lead candidate. Current efforts in virtual FBDD within central nervous system (CNS) targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor-binding pocket using the fragment as a scaffold. This process not only places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

Medium-scale melt-sodium fragmentation experiments

International Nuclear Information System (INIS)

Chu, T.Y.; Beattie, A.G.; Drotning, W.D.; Powers, D.A.

1979-01-01

The results of a series of fragmentation experiments involving up to 20 Kg of thermitically produced high temperature melts and 23 Kg of sodium are presented. Except for one experiment where some centimeter size particles are observed, the fragment distributions seem to be in the range of previous data. Spatial distribution of the fragments in the debris bed appears to be stratified. Scanning electron micrographs of fragments indicate fragmentation to be occurring in the molten state for the more intense interactions observed. Interaction data obtained show quiescent periods of 0.5 to 1.5 second between pressure pulses. The force impulse values per unit mass of melt seems to be in the same range as previous experiments

Cloning and sequence analysis of chitin synthase gene fragments of Demodex mites*

OpenAIRE

Zhao, Ya-e; Wang, Zheng-hang; Xu, Yang; Xu, Ji-ru; Liu, Wen-yan; Wei, Meng; Wang, Chu-ying

2012-01-01

To our knowledge, few reports on Demodex studied at the molecular level are available at present. In this study our group, for the first time, cloned, sequenced and analyzed the chitin synthase (CHS) gene fragments of Demodex folliculorum, Demodex brevis, and Demodex canis (three isolates from each species) from Xi’an China, by designing specific primers based on the only partial sequence of the CHS gene of D. canis from Japan, retrieved from GenBank. Results show that amplification was succe...

Storage ion trap of an 'In-Flight Capture' type for precise mass measurement of radioactive nuclear reaction products and fission fragments

International Nuclear Information System (INIS)

Tarantin, N.I.

2001-01-01

Data on nuclear masses provide a basis for creating and testing various nuclear models. A tandem system of FLNR comprised of the U-400M cyclotron, the COMBAS magnetic separator and the mass-spectrometric ion trap of an 'in-flight capture' type is considered as a possible complex for producing of the short-lived nuclei in fragmentation reactions by heavy ions and for precise mass measurement of these nuclei. The plan of scientific and technical FLNR research includes a project DRIBs for producing beams of accelerated radioactive nuclear reaction products and photofission fragments. This project proposes also precise mass measurements of the fission fragment with the help of the ion trap. The in-flight entrance of the ions and their capture in the mass-spectrometric ion trap using the monochromatizing degrader, the static electric and magnetic fields and a new invention, a magnetic unidirectional transporting ventil, is considered

Identification of column edges of DNA fragments by using K-means clustering and mean algorithm on lane histograms of DNA agarose gel electrophoresis images

Science.gov (United States)

Turan, Muhammed K.; Sehirli, Eftal; Elen, Abdullah; Karas, Ismail R.

2015-07-01

Gel electrophoresis (GE) is one of the most used method to separate DNA, RNA, protein molecules according to size, weight and quantity parameters in many areas such as genetics, molecular biology, biochemistry, microbiology. The main way to separate each molecule is to find borders of each molecule fragment. This paper presents a software application that show columns edges of DNA fragments in 3 steps. In the first step the application obtains lane histograms of agarose gel electrophoresis images by doing projection based on x-axis. In the second step, it utilizes k-means clustering algorithm to classify point values of lane histogram such as left side values, right side values and undesired values. In the third step, column edges of DNA fragments is shown by using mean algorithm and mathematical processes to separate DNA fragments from the background in a fully automated way. In addition to this, the application presents locations of DNA fragments and how many DNA fragments exist on images captured by a scientific camera.

Dual Fragment Impact of PBX Charges

Science.gov (United States)

Haskins, Peter; Briggs, Richard; Leeming, David; White, Nathan; Cheese, Philip; DE&S MoD UK Team; Ordnance Test Solutions Ltd Team

2017-06-01

Fragment impact can pose a significant hazard to many systems containing explosives or propellants. Testing for this threat is most commonly carried out using a single fragment. However, it can be argued that an initial fragment strike (or strikes) could sensitise the energetic material to subsequent impacts, which may then lead to a more violent reaction than would have been predicted based upon single fragment studies. To explore this potential hazard we have developed the capability to launch 2 fragments from the same gun at a range of velocities, and achieve impacts on an acceptor charge with good control over the spatial and temporal separation of the strikes. In this paper we will describe in detail the experimental techniques we have used, both to achieve the dual fragment launch and observe the acceptor charge response. In addition, we will describe the results obtained against PBX filled explosive targets; discuss the mechanisms controlling the target response and their significance for vulnerability assessment. Results of these tests have clearly indicated the potential for detonation upon the second strike, at velocities well below those needed for shock initiation by a single fragment.

Fragmentation of massive dense cores down to ≲ 1000 AU: Relation between fragmentation and density structure

International Nuclear Information System (INIS)

Palau, Aina; Girart, Josep M.; Estalella, Robert; Fuente, Asunción; Fontani, Francesco; Sánchez-Monge, Álvaro; Commerçon, Benoit; Hennebelle, Patrick; Busquet, Gemma; Bontemps, Sylvain; Zapata, Luis A.; Zhang, Qizhou; Di Francesco, James

2014-01-01

In order to shed light on the main physical processes controlling fragmentation of massive dense cores, we present a uniform study of the density structure of 19 massive dense cores, selected to be at similar evolutionary stages, for which their relative fragmentation level was assessed in a previous work. We inferred the density structure of the 19 cores through a simultaneous fit of the radial intensity profiles at 450 and 850 μm (or 1.2 mm in two cases) and the spectral energy distribution, assuming spherical symmetry and that the density and temperature of the cores decrease with radius following power-laws. Even though the estimated fragmentation level is strictly speaking a lower limit, its relative value is significant and several trends could be explored with our data. We find a weak (inverse) trend of fragmentation level and density power-law index, with steeper density profiles tending to show lower fragmentation, and vice versa. In addition, we find a trend of fragmentation increasing with density within a given radius, which arises from a combination of flat density profile and high central density and is consistent with Jeans fragmentation. We considered the effects of rotational-to-gravitational energy ratio, non-thermal velocity dispersion, and turbulence mode on the density structure of the cores, and found that compressive turbulence seems to yield higher central densities. Finally, a possible explanation for the origin of cores with concentrated density profiles, which are the cores showing no fragmentation, could be related with a strong magnetic field, consistent with the outcome of radiation magnetohydrodynamic simulations.

Fragmentation of massive dense cores down to ≲ 1000 AU: Relation between fragmentation and density structure

Energy Technology Data Exchange (ETDEWEB)

Palau, Aina; Girart, Josep M. [Institut de Ciències de l' Espai (CSIC-IEEC), Campus UAB-Facultat de Ciències, Torre C5-parell 2, E-08193 Bellaterra, Catalunya (Spain); Estalella, Robert [Departament d' Astronomia i Meteorologia (IEEC-UB), Institut de Ciències del Cosmos, Universitat de Barcelona, Martí i Franquès, 1, E-08028 Barcelona (Spain); Fuente, Asunción [Observatorio Astronómico Nacional, P.O. Box 112, E-28803 Alcalá de Henares, Madrid (Spain); Fontani, Francesco; Sánchez-Monge, Álvaro [Osservatorio Astrofisico di Arcetri, INAF, Lago E. Fermi 5, I-50125 Firenze (Italy); Commerçon, Benoit; Hennebelle, Patrick [Laboratoire de Radioastronomie, UMR CNRS 8112, École Normale Supérieure et Observatoire de Paris, 24 rue Lhomond, F-75231 Paris Cedex 05 (France); Busquet, Gemma [INAF-Istituto di Astrofisica e Planetologia Spaziali, Area di Recerca di Tor Vergata, Via Fosso Cavaliere 100, I-00133 Roma (Italy); Bontemps, Sylvain [Université de Bordeaux, LAB, UMR 5804, F-33270 Floirac (France); Zapata, Luis A. [Centro de Radioastronomía y Astrofísica, Universidad Nacional Autónoma de México, P.O. Box 3-72, 58090 Morelia, Michoacán (Mexico); Zhang, Qizhou [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Di Francesco, James, E-mail: palau@ieec.uab.es [Department of Physics and Astronomy, University of Victoria, P.O. Box 355, STN CSC, Victoria, BC, V8W 3P6 (Canada)

2014-04-10

In order to shed light on the main physical processes controlling fragmentation of massive dense cores, we present a uniform study of the density structure of 19 massive dense cores, selected to be at similar evolutionary stages, for which their relative fragmentation level was assessed in a previous work. We inferred the density structure of the 19 cores through a simultaneous fit of the radial intensity profiles at 450 and 850 μm (or 1.2 mm in two cases) and the spectral energy distribution, assuming spherical symmetry and that the density and temperature of the cores decrease with radius following power-laws. Even though the estimated fragmentation level is strictly speaking a lower limit, its relative value is significant and several trends could be explored with our data. We find a weak (inverse) trend of fragmentation level and density power-law index, with steeper density profiles tending to show lower fragmentation, and vice versa. In addition, we find a trend of fragmentation increasing with density within a given radius, which arises from a combination of flat density profile and high central density and is consistent with Jeans fragmentation. We considered the effects of rotational-to-gravitational energy ratio, non-thermal velocity dispersion, and turbulence mode on the density structure of the cores, and found that compressive turbulence seems to yield higher central densities. Finally, a possible explanation for the origin of cores with concentrated density profiles, which are the cores showing no fragmentation, could be related with a strong magnetic field, consistent with the outcome of radiation magnetohydrodynamic simulations.

Fragmentation functions approach in pQCD fragmentation phenomena

International Nuclear Information System (INIS)

Rolli, S.

1996-07-01

Next-to-leading order parton fragmentation functions into light mesons are presented. They have been extracted from real and simulated e + e - data and used to predict inclusive single particle distributions at different machines

Synthesis of an A'B' Precursor to Angelmicin B: Product Diversification in the Suárez Lactol Fragmentation.

Science.gov (United States)

Li, Jialiang; Todaro, Louis; Mootoo, David R

2011-11-01

We describe a synthetic strategy for the angelimicin family of anthraquinoid natural products that involves converting a central highly oxygenated decalin intermediate to the AB and A'B' subunits. Herein, we report the synthesis of the bicyclic A'B' subunit that complements our earlier route to the tricyclic AB framework. The differentiating tact in the two syntheses focused on controlling the Suárez radical fragmentation of lactol precursors by modulating the substrate's structural rigidity. A more flexible lactol gave the tricyclic AB framework, whereas a more rigid substrate led to the bicyclic A'B' precursor, presumably through divergent pathways from the radical produced in the initial fragmentation step. These results establish a versatile advanced synthetic precursor for the angelimicins, and on a more general note, illustrate strategies for applying the Suárez fragmentation to diverse and complex molecular frameworks.

Molecular Analysis of Multi-Drug Resistance (MDR) in ...

African Journals Online (AJOL)

This review therefore brings to light some of the processes involved in molecular typing of Mycobacterium tuberculosis strains like the use of restriction fragment length polymorphism (RFLP) and spoligotyping, which have become valuable tools in the epidemiology of tuberculosis, identification of genotypes and ...

Fragmentation of neck-like structures

International Nuclear Information System (INIS)

Montoya, C.; Bowman, D.R.; Peaslee, G.F.; Michigan State Univ., East Lansing, MI

1994-01-01

Evidence for intermediate mass fragment emission from neck-like structures joining projectile- and target-like residues has been observed for peripheral 129 Xe+ nat Cu collisions at E/A=50 MeV. These framents are emitted primarily at velocities intermediate between those of the projectile and the target. Relative to the charge distribution for fragments evaporated from the projectile-like residue, the distribution for ''neck'' emission shows an enhanced emission for fragments with 4 f < 8. (orig.)

Multiple molecular forms of pyridinoline crosslinks generated by the ...

African Journals Online (AJOL)

molecular forms of pyridinoline crosslinks from insoluble bone type I collagen, and we studied ... resorbed in a dynamic process during ... proteins at 4 C for 24H in 4 mol/L .... fragments was merely due to interactions ... completely elucidated.

Forest Fragments Surrounded by Sugar Cane Are More Inhospitable to Terrestrial Amphibian Abundance Than Fragments Surrounded by Pasture

Directory of Open Access Journals (Sweden)

Paula Eveline Ribeiro D’Anunciação

2013-01-01

Full Text Available In recent years, there has been increasing interest in matrix-type influence on forest fragments. Terrestrial amphibians are good bioindicators for this kind of research because of low vagility and high philopatry. This study compared richness, abundance, and species composition of terrestrial amphibians through pitfall traps in two sets of semideciduous seasonal forest fragments in southeastern Brazil, according to the predominant surrounding matrix (sugar cane and pasture. There were no differences in richness, but fragments surrounded by sugar cane had the lowest abundance of amphibians, whereas fragments surrounded by pastures had greater abundance. The most abundant species, Rhinella ornata, showed no biometric differences between fragment groups but like many other amphibians sampled showed very low numbers of individuals in fragments dominated by sugar cane fields. Our data indicate that the sugar cane matrix negatively influences the community of amphibians present in fragments surrounded by this type of land use.

A Bioinorganic Approach to Fragment-Based Drug Discovery Targeting Metalloenzymes.

Science.gov (United States)

Cohen, Seth M

2017-08-15

Metal-dependent enzymes (i.e., metalloenzymes) make up a large fraction of all enzymes and are critically important in a wide range of biological processes, including DNA modification, protein homeostasis, antibiotic resistance, and many others. Consequently, metalloenzymes represent a vast and largely untapped space for drug development. The discovery of effective therapeutics that target metalloenzymes lies squarely at the interface of bioinorganic and medicinal chemistry and requires expertise, methods, and strategies from both fields to mount an effective campaign. In this Account, our research program that brings together the principles and methods of bioinorganic and medicinal chemistry are described, in an effort to bridge the gap between these fields and address an important class of medicinal targets. Fragment-based drug discovery (FBDD) is an important drug discovery approach that is particularly well suited for metalloenzyme inhibitor development. FBDD uses relatively small but diverse chemical structures that allow for the assembly of privileged molecular collections that focus on a specific feature of the target enzyme. For metalloenzyme inhibition, the specific feature is rather obvious, namely, a metal-dependent active site. Surprisingly, prior to our work, the exploration of diverse molecular fragments for binding the metal active sites of metalloenzymes was largely unexplored. By assembling a modest library of metal-binding pharmacophores (MBPs), we have been able to find lead hits for many metalloenzymes and, from these hits, develop inhibitors that act via novel mechanisms of action. A specific case study on the use of this strategy to identify a first-in-class inhibitor of zinc-dependent Rpn11 (a component of the proteasome) is highlighted. The application of FBDD for the development of metalloenzyme inhibitors has raised several other compelling questions, such as how the metalloenzyme active site influences the coordination chemistry of bound

Fragmentation of Ceramics in Rapid Expansion Mode

Science.gov (United States)

Maiti, Spandan; Geubelle, Philippe H.; Rangaswamy, Krishnan

The study of the fragmentation process goes back to more than a century, motivated primarily by problems related to mining and ore handling (Grady and Kipp, 1985). Various theories have been proposed to predict the fragmentation stress and the fragment size and distribution. But the investigations are generally case specific and relate to only a narrow set of fragmentation processes. A number of theoretical studies of dynamic fragmentation in a rapidly expanding body can be found in the literature. For example, the study summarized in (Grady, 1982) presents a model based on a simple energy balance concept between the surface energy released due to fracture and the kinetic energy of the fragments. Subsequent refinements of the energy balance model have been proposed by (Glenn and Chudnovsky, 1986), which take into account the strain energy of the fragments and specify a threshold stress below which no fragmentation occurs. These models assume that the fracture events are instantaneous and occur simultaneously. Evidently, these assumptions are quite restrictive and these models can not take into account the transient nature of the fragmentation process after the onset of fracture in the material. A more recent model proposed by (Miller et al., 1999) however takes into account this time-dependent nature of the fragmentation event and the distribution of flaws of various strengths in the original material.

Percolation versus microcanonical fragmentation - comparison of fragment size distribution: Where is the liquid-gas transition in nuclei?

International Nuclear Information System (INIS)

Jaqaman, H.R.; Birzeit Univ.; Papp, G.; Eoetvoes Lorand Tudomanyegyetem, Budapest; Gross, D.H.E.; Freie Univ. Berlin

1990-01-01

The distributions of fragments produced by microcanonical multifragmentation of hot nuclei are compared with the cluster distributions predicted by a bond percolation model on a finite lattice. The conditional moments of these distributions are used together with the correlations between the largest three fragments in each event. Whereas percolation and statistical nuclear fragmentation agree in many details as in the usual plots of the averaged moments of the fragment distributions which yield the critical exponents, they turn out to be essentially different when less averaged quantities or correlations are considered. The differences between the predictions of the two models are mainly due to the particularities of the nuclear problem, especially the effect of the long-range Coulomb force which favours the break-up of the highly excited nucleus into two large fragments (pseudo-fission) and, to a somewhat lesser extent, enhances the possibility for the cracking of the nucleus into more than two large fragments. The fission events are, however, clearly separated from a second branch of critical correlations which shows up clearly in both nuclear fragmentation and percolation. We think that this critical correlation branch is due to the liquid-gas phase transition in finite nuclei. (orig.)

Degree of Landscape Fragmentation Influences Genetic Isolation among Populations of a Gliding Mammal

Science.gov (United States)

Taylor, Andrea C.; Walker, Faith M.; Goldingay, Ross L.; Ball, Tina; van der Ree, Rodney

2011-01-01

Forests and woodlands are under continuing pressure from urban and agricultural development. Tree-dependent mammals that rarely venture to the ground are likely to be highly sensitive to forest fragmentation. The Australian squirrel glider (Petaurus norfolcensis) provides an excellent case study to examine genetic (functional) connectivity among populations. It has an extensive range that occurs in a wide band along the east coast. However, its forest and woodland habitat has become greatly reduced in area and is severely fragmented within the southern inland part of the species' range, where it is recognised as threatened. Within central and northern coastal regions, habitat is much more intact and we thus hypothesise that genetic connectivity will be greater in this region than in the south. To test this we employed microsatellite analysis in a molecular population biology approach. Most sampling locations in the highly modified south showed signatures of genetic isolation. In contrast, a high level of genetic connectivity was inferred among most sampled populations in the more intact habitat of the coastal region, with samples collected 1400 km apart having similar genetic cluster membership. Nonetheless, some coastal populations associated with urbanisation and agriculture are genetically isolated, suggesting the historic pattern observed in the south is emerging on the coast. Our study demonstrates that massive landscape changes following European settlement have had substantial impacts on levels of connectivity among squirrel glider populations, as predicted on the basis of the species' ecology. This suggests that landscape planning and management in the south should be focused on restoring habitat connectivity where feasible, while along the coast, existing habitat connectivity must be maintained and recent losses restored. Molecular population biology approaches provide a ready means for identifying fragmentation effects on a species at multiple scales

Degree of landscape fragmentation influences genetic isolation among populations of a gliding mammal.

Directory of Open Access Journals (Sweden)

Andrea C Taylor

Full Text Available Forests and woodlands are under continuing pressure from urban and agricultural development. Tree-dependent mammals that rarely venture to the ground are likely to be highly sensitive to forest fragmentation. The Australian squirrel glider (Petaurus norfolcensis provides an excellent case study to examine genetic (functional connectivity among populations. It has an extensive range that occurs in a wide band along the east coast. However, its forest and woodland habitat has become greatly reduced in area and is severely fragmented within the southern inland part of the species' range, where it is recognised as threatened. Within central and northern coastal regions, habitat is much more intact and we thus hypothesise that genetic connectivity will be greater in this region than in the south. To test this we employed microsatellite analysis in a molecular population biology approach. Most sampling locations in the highly modified south showed signatures of genetic isolation. In contrast, a high level of genetic connectivity was inferred among most sampled populations in the more intact habitat of the coastal region, with samples collected 1400 km apart having similar genetic cluster membership. Nonetheless, some coastal populations associated with urbanisation and agriculture are genetically isolated, suggesting the historic pattern observed in the south is emerging on the coast. Our study demonstrates that massive landscape changes following European settlement have had substantial impacts on levels of connectivity among squirrel glider populations, as predicted on the basis of the species' ecology. This suggests that landscape planning and management in the south should be focused on restoring habitat connectivity where feasible, while along the coast, existing habitat connectivity must be maintained and recent losses restored. Molecular population biology approaches provide a ready means for identifying fragmentation effects on a species at

The formation of planets by disc fragmentation

Directory of Open Access Journals (Sweden)

Stamatellos Dimitris

2013-04-01

Full Text Available I discuss the role that disc fragmentation plays in the formation of gas giant and terrestrial planets, and how this relates to the formation of brown dwarfs and low-mass stars, and ultimately to the process of star formation. Protostellar discs may fragment, if they are massive enough and can cool fast enough, but most of the objects that form by fragmentation are brown dwarfs. It may be possible that planets also form, if the mass growth of a proto-fragment is stopped (e.g. if this fragment is ejected from the disc, or suppressed and even reversed (e.g by tidal stripping. I will discuss if it is possible to distinguish whether a planet has formed by disc fragmentation or core accretion, and mention of a few examples of observed exoplanets that are suggestive of formation by disc fragmentation.

Extraction of 16th Century Calender Fragments

DEFF Research Database (Denmark)

Holck, Jakob Povl; Etheridge, Christian

at the Cultural Heritage & Archaeometric Research Team, SDU. Upon finding medieval manuscript fragments in the university library’s special collections, scholars at the Centre for Medieval Literature are consulted. In most cases, digital pictures of the finds will circulate in the international community...... fragments may require extensive use of Big Data and other forms of analysis in order to be identified. Usually, the university library prefers not to remove the fragments from their “fragment carriers”. In order to read fragments that are only partially visible or invisible, x-ray technology may be deployed...... of medieval scholars. Thousands of 16th and 17th Century books are stored in the University Library of Southern Denmark. One out of five of these books is expected to contain medieval manuscript fragments or fragments of rare prints, e.g. incunabula....

Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products.

Science.gov (United States)

Prescher, Horst; Koch, Guido; Schuhmann, Tim; Ertl, Peter; Bussenault, Alex; Glick, Meir; Dix, Ina; Petersen, Frank; Lizos, Dimitrios E

2017-02-01

A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD). Copyright © 2016 Elsevier Ltd. All rights reserved.

ANGULAR MOMENTUM TRANSFER AND LACK OF FRAGMENTATION IN SELF-GRAVITATING ACCRETION FLOWS

International Nuclear Information System (INIS)

Begelman, Mitchell C.; Shlosman, Isaac

2009-01-01

Rapid inflows associated with early galaxy formation lead to the accumulation of self-gravitating gas in the centers of proto-galaxies. Such gas accumulations are prone to nonaxisymmetric instabilities, as in the well known Maclaurin sequence of rotating ellipsoids, which are accompanied by a catastrophic loss of angular momentum (J). Self-gravitating gas is also intuitively associated with star formation. However, recent simulations of the infall process display highly turbulent continuous flows. We propose that J-transfer, which enables the inflow, also suppresses fragmentation. Inefficient J loss by the gas leads to decay of turbulence, triggering global instabilities and renewed turbulence driving. Flow regulated in this way is stable against fragmentation, while staying close to the instability threshold for bar formation-thick self-gravitating disks are prone to global instabilities before they become unstable locally. On smaller scales, the fraction of gravitationally unstable matter swept up by shocks in such a flow is a small and decreasing function of the Mach number. We conclude counterintuitively that gas able to cool down to a small fraction of its virial temperature will not fragment as it collapses. This provides a venue for supermassive black holes to form via direct infall, without the intermediary stage of forming a star cluster. Some black holes could have formed or grown in massive halos at low redshifts. Thus the fragmentation is intimately related to J redistribution within the system: it is less dependent on the molecular/metal cooling but is conditioned by the ability of the flow to develop virial, supersonic turbulence.

Fluctuations in the fragmentation process

International Nuclear Information System (INIS)

Botet, R.; Ploszajczak, M.

1993-01-01

Some general framework of sequential fragmentation is presented, as provided by the newly proposed Fragmentation - Inactivation - Binary model, and to study briefly its basic and universal features. This model includes as particular cases most of the previous kinetic fragmentation models. In particular it is discussed how one arrives in this framework to the critical behaviour, called the shattering transition. This model is then compared to recent data on gold multifragmentation at 600 MeV/nucl. (authors) 20 refs., 5 figs

The spectroscopy of fission fragments

International Nuclear Information System (INIS)

Phillips, W.R.

1998-01-01

High-resolution measurements on γ rays from fission fragments have provided a rich source of information, unobtainable at the moment in any other way, on the spectroscopy of neutron-rich nuclei. In recent years important data have been obtained on the yrast- and near yrast-structure of neutron-rich fission fragments. We discuss the scope of measurements which can be made on prompt gamma rays from secondary fission fragments, the techniques used in the experiments and some results recently obtained. (author)

[Fragment-based drug discovery: concept and aim].

Science.gov (United States)

Tanaka, Daisuke

2010-03-01

Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to "undruggable targets" (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.

Velocity distribution of fragments of catastrophic impacts

Science.gov (United States)

Takagi, Yasuhiko; Kato, Manabu; Mizutani, Hitoshi

1992-01-01

Three dimensional velocities of fragments produced by laboratory impact experiments were measured for basalts and pyrophyllites. The velocity distribution of fragments obtained shows that the velocity range of the major fragments is rather narrow, at most within a factor of 3 and that no clear dependence of velocity on the fragment mass is observed. The NonDimensional Impact Stress (NDIS) defined by Mizutani et al. (1990) is found to be an appropriate scaling parameter to describe the overall fragment velocity as well as the antipodal velocity.

Fragmentation in DNA double-strand breaks

International Nuclear Information System (INIS)

Wei Zhiyong; Suzhou Univ., Suzhou; Zhang Lihui; Li Ming; Fan Wo; Xu Yujie

2005-01-01

DNA double strand breaks are important lesions induced by irradiations. Random breakage model or quantification supported by this concept is suitable to analyze DNA double strand break data induced by low LET radiation, but deviation from random breakage model is more evident in high LET radiation data analysis. In this work we develop a new method, statistical fragmentation model, to analyze the fragmentation process of DNA double strand breaks. After charged particles enter the biological cell, they produce ionizations along their tracks, and transfer their energies to the cells and break the cellular DNA strands into fragments. The probable distribution of the fragments is obtained under the condition in which the entropy is maximum. Under the approximation E≅E 0 + E 1 l + E 2 l 2 , the distribution functions are obtained as exp(αl + βl 2 ). There are two components, the one proportional to exp(βl 2 ), mainly contributes to the low mass fragment yields, the other component, proportional to exp(αl), decreases slowly as the mass of the fragments increases. Numerical solution of the constraint equations provides parameters α and β. Experimental data, especially when the energy deposition is higher, support the statistical fragmentation model. (authors)

Effects of RAFT Agent on the Selective Approach of Molecularly Imprinted Polymers

OpenAIRE

Asman, Saliza; Mohamad, Sharifah; Sarih, Norazilawati

2015-01-01

Two types of reversible addition-fragmentation chain transfer molecularly imprinted polymers (RAFT-MIPs) were synthesized using different monomers, which were methacrylic acid functionalized β-cyclodextrin (MAA-β-CD) and 2-hydroxyethyl methacrylate functionalized β-cyclodextrin (HEMA-β-CD), via reversible addition-fragmentation chain transfer (RAFT) polymerization, and were represented as RAFT-MIP(MAA-β-CD) and RAFT-MIP(HEMA-β-CD), respectively. Both RAFT-MIPs were systematically characterize...

Fission fragment yields from heavy-ion-induced reactions measured with a fragment separator

Science.gov (United States)

Tarasov, O. B.; Delaune, O.; Farget, F.; Morrissey, D. J.; Amthor, A. M.; Bastin, B.; Bazin, D.; Blank, B.; Cacéres, L.; Chbihi, A.; Fernández-Dominguez, B.; Grévy, S.; Kamalou, O.; Lukyanov, S. M.; Mittig, W.; Pereira, J.; Perrot, L.; Saint-Laurent, M.-G.; Savajols, H.; Sherrill, B. M.; Stodel, C.; Thomas, J. C.; Villari, A. C.

2018-04-01

The systematic study of fission fragment yields under different initial conditions has provided valuable experimental data for benchmarking models of fission product yields. Nuclear reactions using inverse kinematics coupled to the use of a high-resolution spectrometer with good fragment identification are shown here to be a powerful tool to measure the inclusive isotopic yields of fission fragments. In-flight fusion-fission was used in this work to produce secondary beams of neutron-rich isotopes in the collisions of a 238U beam at 24 MeV/u with 9Be and 12C targets at GANIL using the LISE3 fragment separator. Unique identification of the A, Z, and atomic charge state, q, of fission products was attained with the Δ E- TKE-B ρ- ToF measurement technique. Mass, and atomic number distributions are reported for the two reactions. The results show the importance of different reaction mechanisms in the two cases. The optimal target material for higher yields of neutron-rich high- Z isotopes produced in fusion-fission reactions as a function of projectile energy is discussed.

Current fragmentation in deep inelastic scattering

International Nuclear Information System (INIS)

Hamer, C.J.

1975-04-01

It is argued that the current fragmentation products in deep inelastic electron scattering will not be distributed in a 'one-dimensional' rapidity plateau as in the parton model picture of Feynman and Bjorken. A reaction mechanism with a multiperipheral topology, but which the above configuration might have been achieved, does not in fact populate the current fragmentation plateau; and unless partons are actually observed in the final state, it cannot lead to Bjorken scaling. The basic reason for this failure is shown to be the fact that when a particle is produced in the current fragmentation plateau, the adjacent momentum transfer in the multiperipheral chain becomes large and negative: such processes are inevitably suppressed. Instead, the current fragmentation products are likely to be generated by a fragmentation, or sequential decay process. (author)

Molecular fingerprinting of the Egyptian medicinal plant Cocculus ...

African Journals Online (AJOL)

Since no information about the genome of C. pendulus is available, the current study deals with molecular investigation of C. pendulus expressed by DNA fingerprinting of the young leaves of this plant using amplified fragment length polymorphism (AFLP) technique with four primer combinations. The obtained results ...

Simulation of the molecular recombination yield for swift H2+ ions through thin carbon foils

International Nuclear Information System (INIS)

Garcia-Molina, Rafael; Barriga-Carrasco, Manuel D.

2003-01-01

We have calculated the recombination yield for swift H 2 + molecular ions at the exit of thin amorphous carbon foils, as a function of the dwell time and incident energy. Our results are based on a detailed simulation of the motion through the target of the H 2 + molecular ion (before dissociation takes place) and its constituent fragments (after dissociation), including the following effects: Coulomb repulsion, nuclear scattering, electron capture and loss, as well as self-retarding and wake forces, which provide the relative distance and velocity of the dissociated fragments at the foil exit. The recombination of an H 2 + ion at the exit of the foil depends on the interproton separation and internal energy of the dissociated fragments, and on their probability to capture an electron. Comparison of our results with the available experimental data shows a good agreement

Binary star formation: gravitational fragmentation followed by capture

Science.gov (United States)

Turner, J. A.; Chapman, S. J.; Bhattal, A. S.; Disney, M. J.; Pongracic, H.; Whitworth, A. P.

1995-11-01

We describe in detail one of a sequence of numerical simulations which realize the mechanism of binary star formation proposed by Pringle. In these simulations, collisions between stable molecular cloud clumps produce dense shocked layers, which cool radiatively and fragment gravitationally. The resulting fragments then condense to form protostellar discs, which at the same time fall together and, as a result of tidal and viscous interactions, capture one another to form binary systems. We refer to this mechanism as shock-induced gravitational fragmentation followed by capture, or SGF+C. When the initial clumps are sufficiently massive and/or the Mach number of the collision is sufficiently high, a large number (>~10) of protostellar discs is produced; under these circumstances, the layer fragments first into filaments, and then into beads along the filaments. The marriage of two protostellar discs in this way is `arranged' in the sense that the protostellar discs involved do not form independently. First, they both condense out of the same layer, and probably also out of the same filament within this layer; this significantly increases the likelihood of them interacting dynamically. Secondly, there tends to be alignment between the orbital and spin angular momenta of the interacting protostellar discs, reflecting the fact that these angular momenta derive mainly from the systematic global angular momentum of the off-axis collision which produced the layer; this alignment of the various angular momenta pre-disposes the discs to very dissipative interactions, thereby increasing the probability of producing a strongly bound, long-lasting union. It is a marriage because the binary orbit stabilizes itself rather quickly. Any subsequent orbit evolution, as the protostellar discs `mop up' the surrounding residual gas and interact tidally, tends to harden the orbit. Therefore, as long as a third body does not intervene, the union is binding. Even if a third body does

Fragment emission from modestly excited nuclear systems

Energy Technology Data Exchange (ETDEWEB)

Lou, Y. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Souza, R.T. de [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Chen, S.L. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Cornell, E.W. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Davin, B. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Fox, D. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Hamilton, T.M. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Mcdonald, K. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Tsang, M.B. [Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Glasmacher, T. [Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Dinius, J. [Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Gelbke, C.K. [Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Handzy, D.O. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility]|[Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Hsi, W.C.

1996-07-08

Fragment emission patterns occurring in nuclear systems of modest excitation are studied. Exclusive measurement of fragment emission in {sup 14}N+{sup 197}Au reactions at E/A=100, 130 and 156 MeV allows selection of central collisions where a single source dominates the decay. Low threshold measurement of IMF emission for these events allows investigation of the influence of detector threshold effects. The time scale of fragment emission is deduced using fragment-fragment velocity correlations. Comparisons are made to the predictions of a statistical decay model. (orig.).

The spectroscopy of fission fragments

Energy Technology Data Exchange (ETDEWEB)

Phillips, W.R. [Department of Physics and Astronomy, University of Manchester, Manchester, M13 9PL (United Kingdom); Collaboration: La Direction des Sciences de la Matiere du CEA (FR); Le Fonds National de la Recherche Scientifique de Belgique (BE)

1998-12-31

High-resolution measurements on {gamma} rays from fission fragments have provided a rich source of information, unobtainable at the moment in any other way, on the spectroscopy of neutron-rich nuclei. In recent years important data have been obtained on the yrast- and near yrast-structure of neutron-rich fission fragments. We discuss the scope of measurements which can be made on prompt gamma rays from secondary fission fragments, the techniques used in the experiments and some results recently obtained. (author) 24 refs., 8 figs., 1 tab.

Coulomb-explosion technique for determining geometrical structures of molecular ions

International Nuclear Information System (INIS)

Gemmell, D.S.

1981-01-01

Traditional experimental techniques (e.g. studies on photon absorption or emission) for determining the sterochemical structures of neutral molecules are extremeley difficult to apply to molecular ions because of problems in obtaining a sufficient spatial density of the ions to be studied. Recent high-resolution measurements on the energy and angle distributions of the fragments produced when fast (MeV) molecular-ion beams from an electrostatic accelerator dissociate (Coulomb explode) in thin foils and in gases, offer promising possibilities for deducing the sterochemical structures of the molecular ions constituting the incident beams. Bond lengths have been determined in this way for several diatomic projectiles (H 2+ , HeH + , CH + , NH + , OH + , N 2+ , O 2+ , etc.) with an accuracy of approx. 0.01 A. H 3+ has been demonstrated (for the first time) to be equilateral triangular and the interproton distance measured. Measurements on single fragments from CO 2+ , N 2 O + , C 3 H 3+ , and CH/sub n/ + have revealed the gross structures of the projectiles. An apparatus has recently been constructed at Argonne to permit precise measurements on fragments in coincidence. The apparatus has been tested on a known structure (OH 2+ ). The O-H bond length was found to be 1.0 +- 0.04 A and the H-O-H bond angle was measured as 110 --- 2 0 . These values are in excellent agreement with those found in optical experiments (0.999 A and 110.5 0 ). This Coulomb explosion technique can be expected to be refined in accuracy and to be extended to a wide range of molecular ions whose structures are inaccessible by other means

Endovascular Removal of Fractured Inferior Vena Cava Filter Fragments: 5-Year Registry Data with Prospective Outcomes on Retained Fragments.

Science.gov (United States)

Kesselman, Andrew J; Hoang, Nam Sao; Sheu, Alexander Y; Kuo, William T

2018-06-01

To evaluate the safety and efficacy of attempted percutaneous filter fragment removal during retrieval of fractured inferior vena cava (IVC) filters and to report outcomes associated with retained filter fragments. Over a 5-year period, 82 consecutive patients presenting with a fractured IVC filter were prospectively enrolled into an institutional review board-approved registry. There were 27 men and 55 women (mean, 47 y; range, 19-85 y). After main filter removal, percutaneous removal of fragments was attempted if they were deemed intravascular and accessible on preprocedural computed tomography (CT), cone-beam CT, and/or intravascular ultrasound; distal pulmonary artery (PA) fragments were left alone. A total of 185 fragments were identified (81 IVC, 33 PA, 16 cardiac, 2 hepatic vein, 1 renal vein, 1 aorta, 51 retroperitoneal). Mean filter dwell time was 2,183 days (range, 59-9,936 d). Eighty-seven of 185 fragments (47%) were deemed amenable to attempted removal: 65 IVC, 11 PA, 8 cardiac, 2 hepatic, and 1 aortic. Primary safety outcomes were major procedure-related complications. Fragment removal was successful in 78 of 87 cases (89.7%; 95% confidence interval [CI], 81.3-95.2). There were 6 minor complications with no consequence (6.9%; 95% CI, 2.6-14.4) involving intraprocedural fragment embolization and 1 major complication (1.1%; 95% CI, 0.0-6.2), a cardiac tamponade that was successfully treated. The complication rate from attempted cardiac fragment removal was 12.5% (1 of 8; 95% CI, 0.3-52.7). Among patients with retained cardiopulmonary fragments (n = 19), 81% remained asymptomatic during long-term clinical follow-up of 845 days (range, 386-2,071 d). Percutaneous removal of filter fragments from the IVC and proximal PAs is safe and effective overall, but attempted intracardiac fragment removal carries a higher risk of complication. Most residual filter fragments not amenable to percutaneous removal remain asymptomatic and may be monitored clinically

Physics with fast molecular-ion beams

International Nuclear Information System (INIS)

Kanter, E.P.

1980-01-01

Fast (MeV) molecular-ion beams provide a unique source of energetic projectile nuclei which are correlated in space and time. The recognition of this property has prompted several recent investigations of various aspects of the interactions of these ions with matter. High-resolution measurements on the fragments resulting from these interactions have already yielded a wealth of new information on such diverse topics as plasma oscillations in solids and stereochemical structures of molecular ions as well as a variety of atomic collision phenomena. The general features of several such experiments will be discussed and recent results will be presented

Dynameomics: Data-driven methods and models for utilizing large-scale protein structure repositories for improving fragment-based loop prediction

Science.gov (United States)

Rysavy, Steven J; Beck, David AC; Daggett, Valerie

2014-01-01

Protein function is intimately linked to protein structure and dynamics yet experimentally determined structures frequently omit regions within a protein due to indeterminate data, which is often due protein dynamics. We propose that atomistic molecular dynamics simulations provide a diverse sampling of biologically relevant structures for these missing segments (and beyond) to improve structural modeling and structure prediction. Here we make use of the Dynameomics data warehouse, which contains simulations of representatives of essentially all known protein folds. We developed novel computational methods to efficiently identify, rank and retrieve small peptide structures, or fragments, from this database. We also created a novel data model to analyze and compare large repositories of structural data, such as contained within the Protein Data Bank and the Dynameomics data warehouse. Our evaluation compares these structural repositories for improving loop predictions and analyzes the utility of our methods and models. Using a standard set of loop structures, containing 510 loops, 30 for each loop length from 4 to 20 residues, we find that the inclusion of Dynameomics structures in fragment-based methods improves the quality of the loop predictions without being dependent on sequence homology. Depending on loop length, ∼25–75% of the best predictions came from the Dynameomics set, resulting in lower main chain root-mean-square deviations for all fragment lengths using the combined fragment library. We also provide specific cases where Dynameomics fragments provide better predictions for NMR loop structures than fragments from crystal structures. Online access to these fragment libraries is available at http://www.dynameomics.org/fragments. PMID:25142412

Dynameomics: data-driven methods and models for utilizing large-scale protein structure repositories for improving fragment-based loop prediction.

Science.gov (United States)

Rysavy, Steven J; Beck, David A C; Daggett, Valerie

2014-11-01

Protein function is intimately linked to protein structure and dynamics yet experimentally determined structures frequently omit regions within a protein due to indeterminate data, which is often due protein dynamics. We propose that atomistic molecular dynamics simulations provide a diverse sampling of biologically relevant structures for these missing segments (and beyond) to improve structural modeling and structure prediction. Here we make use of the Dynameomics data warehouse, which contains simulations of representatives of essentially all known protein folds. We developed novel computational methods to efficiently identify, rank and retrieve small peptide structures, or fragments, from this database. We also created a novel data model to analyze and compare large repositories of structural data, such as contained within the Protein Data Bank and the Dynameomics data warehouse. Our evaluation compares these structural repositories for improving loop predictions and analyzes the utility of our methods and models. Using a standard set of loop structures, containing 510 loops, 30 for each loop length from 4 to 20 residues, we find that the inclusion of Dynameomics structures in fragment-based methods improves the quality of the loop predictions without being dependent on sequence homology. Depending on loop length, ∼ 25-75% of the best predictions came from the Dynameomics set, resulting in lower main chain root-mean-square deviations for all fragment lengths using the combined fragment library. We also provide specific cases where Dynameomics fragments provide better predictions for NMR loop structures than fragments from crystal structures. Online access to these fragment libraries is available at http://www.dynameomics.org/fragments. © 2014 The Protein Society.

Prospects of molecular markers in Fusarium species diversity

DEFF Research Database (Denmark)

Nayaka, S. Chandra; Wulff, Ednar Gadelha; Udayashankar, A.C.

2011-01-01

focuses of various molecular-based techniques employed to study the diversity of Fusarium species causing diseases in major food crops. An introduction of fusarial diseases and their mycotoxins and molecular-marker-based methods for detection introduce the concept of marker application. Various well...... for generation of probes and their use in phylogeny of Fusarium spp. are also presented. The concluding part emphasizes the value of molecular markers for assessing genetic variability and reveals that molecular tools are indispensable for providing information not only of one Fusarium species but on whole......-known molecular techniques such as random amplified polymorphic DNA, amplification fragment length polymorphism, etc. to more modern ones such as DNA microarrays, DNA barcoding, and pyrosequencing and their application form the core of the review. Target regions in the genome which can be potential candidates...

Fragment Length of Circulating Tumor DNA.

Science.gov (United States)

Underhill, Hunter R; Kitzman, Jacob O; Hellwig, Sabine; Welker, Noah C; Daza, Riza; Baker, Daniel N; Gligorich, Keith M; Rostomily, Robert C; Bronner, Mary P; Shendure, Jay

2016-07-01

Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.

Fragger: a protein fragment picker for structural queries.

Science.gov (United States)

Berenger, Francois; Simoncini, David; Voet, Arnout; Shrestha, Rojan; Zhang, Kam Y J

2017-01-01

Protein modeling and design activities often require querying the Protein Data Bank (PDB) with a structural fragment, possibly containing gaps. For some applications, it is preferable to work on a specific subset of the PDB or with unpublished structures. These requirements, along with specific user needs, motivated the creation of a new software to manage and query 3D protein fragments. Fragger is a protein fragment picker that allows protein fragment databases to be created and queried. All fragment lengths are supported and any set of PDB files can be used to create a database. Fragger can efficiently search a fragment database with a query fragment and a distance threshold. Matching fragments are ranked by distance to the query. The query fragment can have structural gaps and the allowed amino acid sequences matching a query can be constrained via a regular expression of one-letter amino acid codes. Fragger also incorporates a tool to compute the backbone RMSD of one versus many fragments in high throughput. Fragger should be useful for protein design, loop grafting and related structural bioinformatics tasks.

A fragment-based approach leading to the discovery of a novel binding site and the selective CK2 inhibitor CAM4066.

Science.gov (United States)

De Fusco, Claudia; Brear, Paul; Iegre, Jessica; Georgiou, Kathy Hadje; Sore, Hannah F; Hyvönen, Marko; Spring, David R

2017-07-01

Recently we reported the discovery of a potent and selective CK2α inhibitor CAM4066. This compound inhibits CK2 activity by exploiting a pocket located outside the ATP binding site (αD pocket). Here we describe in detail the journey that led to the discovery of CAM4066 using the challenging fragment linking strategy. Specifically, we aimed to develop inhibitors by linking a high-affinity fragment anchored in the αD site to a weakly binding warhead fragment occupying the ATP site. Moreover, we describe the remarkable impact that molecular modelling had on the development of this novel chemical tool. The work described herein shows potential for the development of a novel class of CK2 inhibitors. Copyright © 2017. Published by Elsevier Ltd.

Kaon fragmentation function from NJL-jet model

International Nuclear Information System (INIS)

Matevosyan, Hrayr H.; Thomas, Anthony W.; Bentz, Wolfgang

2010-01-01

The NJL-jet model provides a sound framework for calculating the fragmentation functions in an effective chiral quark theory, where the momentum and isospin sum rules are satisfied without the introduction of ad hoc parameters [1]. Earlier studies of the pion fragmentation functions using the Nambu-Jona-Lasinio (NJL) model within this framework showed good qualitative agreement with the empirical parameterizations. Here we extend the NJL-jet model by including the strange quark. The corrections to the pion fragmentation function and corresponding kaon fragmentation functions are calculated using the elementary quark to quark-meson fragmentation functions from NJL. The results for the kaon fragmentation function exhibit a qualitative agreement with the empirical parameterizations, while the unfavored strange quark fragmentation to pions is shown to be of the same order of magnitude as the unfavored light quark's. The results of these studies are expected to provide important guidance for the analysis of a large variety of semi-inclusive data.

Data Evaluation for Atomic, Molecular and Plasma Material Interaction Processes in Fusion. Summary Report of a Joint IAEA-NFRI Technical Meeting

International Nuclear Information System (INIS)

Chung, Hyun-Kyung

2012-12-01

This report summarizes the proceedings of the Joint IAEA-NFRI Technical Meeting on 'Data Evaluation for Atomic, Molecular and Plasma Material Interaction Processes in Fusion' on 4-7 September 2012. Twenty five participants from 10 Member States and two from the IAEA attended the four-day meeting held at the Daejeon Convention Center in Daejeon, Republic of Korea hosted by the National Fusion Research Institute (NFRI) in conjunction with the 8th International Symposium on Standard Reference Data. The report includes discussions on the issues of the critical assessment of fundamental data required for fusion and plasma applications, meeting conclusions and recommendations. The abstracts of presentations presented in the meeting are attached in the Appendix. (author)

Fragmentation of rotating protostellar clouds

International Nuclear Information System (INIS)

Tohline, J.E.

1980-01-01

We examine, with a three-dimensional hydrodynamic computer code, the behavior of rotating, isothermal gas clouds as they collapse from Jeans unstable configurations, in order to determine whether they are susceptible to fragmentation during the initial dynamic collapse phase of their evolution. We find that a gas cloud will not fragment unless (a) it begins collapsing from a radius much smaller than the Jeans radius (i.e., the cloud initially encloses many Jeans masses) and (b) irregularities in the cloud's initial structure (specifically, density inhomogeneities) enclose more than one Jeans mass of material. Gas pressure smooths out features that are not initially Jeans unstable while rotation plays no direct role in damping inhomogeneities. Instead of fragmenting, most of our models collapse to a ring configuration (as has been observed by other investigators in two-dimensional, axisymmetric models). The rings appear to be less susceptible to gragmentation from arbitrary perturbations in their structure than has previously been indicated in other work. Because our models, which include the effects of gas pressure, do not readily fragment during a phase of dynamic collapse, we suggest that gas clouds in the galactic disk undergo fragmentation only during quasi-equilibrium phases of their evolution

Fragment-based approaches to TB drugs.

Science.gov (United States)

Marchetti, Chiara; Chan, Daniel S H; Coyne, Anthony G; Abell, Chris

2018-02-01

Tuberculosis is an infectious disease associated with significant mortality and morbidity worldwide, particularly in developing countries. The rise of antibiotic resistance in Mycobacterium tuberculosis (Mtb) urgently demands the development of new drug leads to tackle resistant strains. Fragment-based methods have recently emerged at the forefront of pharmaceutical development as a means to generate more effective lead structures, via the identification of fragment molecules that form weak but high quality interactions with the target biomolecule and subsequent fragment optimization. This review highlights a number of novel inhibitors of Mtb targets that have been developed through fragment-based approaches in recent years.

Advances in molecular vibrations and collision dynamics molecular clusters

CERN Document Server

Bacic, Zatko

1998-01-01

This volume focuses on molecular clusters, bound by van der Waals interactions and hydrogen bonds. Twelve chapters review a wide range of recent theoretical and experimental advances in the areas of cluster vibrations, spectroscopy, and reaction dynamics. The authors are leading experts, who have made significant contributions to these topics.The first chapter describes exciting results and new insights in the solvent effects on the short-time photo fragmentation dynamics of small molecules, obtained by combining heteroclusters with femtosecond laser excitation. The second is on theoretical work on effects of single solvent (argon) atom on the photodissociation dynamics of the solute H2O molecule. The next two chapters cover experimental and theoretical aspects of the energetics and vibrations of small clusters. Chapter 5 describes diffusion quantum Monte Carlo calculations and non additive three-body potential terms in molecular clusters. The next six chapters deal with hydrogen-bonded clusters, refle...

The Zero-Degree Detector system for fragmentation studies

International Nuclear Information System (INIS)

Adams, J.H.; Christl, M.J.; Howell, L.W.; Kuznetsov, E.

2007-01-01

The measurement of nuclear fragmentation cross-sections requires the detection and identification of individual projectile fragments. If light and heavy fragments are recorded in the same detector, it may be impossible to distinguish the signal from the light fragment. To overcome this problem, we have developed the Zero-degree Detector System (ZDDS). The ZDDS enables the measurement of cross-sections for light fragment production by using pixelated detectors to separately measure the signals of each fragment. The system has been used to measure the fragmentation of beams as heavy as Fe at the NASA Space Radiation Laboratory at Brookhaven National Laboratory and the Heavy Ion Medical Accelerator in Chiba, Japan

Establishing molecular microbiology facilities in developing countries

Directory of Open Access Journals (Sweden)

Salman S. Ahmed

2015-11-01

Full Text Available Summary: Microbiology laboratories play an important role in epidemiology and infection control programs. Within microbiology laboratories, molecular microbiology techniques have revolutionized the identification and surveillance of infectious diseases. The combination of excellent sensitivity, specificity, low contamination levels and speed has made molecular techniques appealing methods for the diagnosis of many infectious diseases. In a well-equipped microbiology laboratory, the facility designated for molecular techniques remains indiscrete. However, in most developing countries, poor infrastructure and laboratory mismanagement have precipitated hazardous consequences. The establishment of a molecular microbiology facility within a microbiology laboratory remains fragmented. A high-quality laboratory should include both conventional microbiology methods and molecular microbiology techniques for exceptional performance. Furthermore, it should include appropriate laboratory administration, a well-designed facility, laboratory procedure standardization, a waste management system, a code of practice, equipment installation and laboratory personnel training. This manuscript lays out fundamental issues that need to be addressed when establishing a molecular microbiology facility in developing countries. Keywords: Developing country, Molecular technique, Molecular microbiology laboratory

Introduction to fragment-based drug discovery.

Science.gov (United States)

Erlanson, Daniel A

2012-01-01

Fragment-based drug discovery (FBDD) has emerged in the past decade as a powerful tool for discovering drug leads. The approach first identifies starting points: very small molecules (fragments) that are about half the size of typical drugs. These fragments are then expanded or linked together to generate drug leads. Although the origins of the technique date back some 30 years, it was only in the mid-1990s that experimental techniques became sufficiently sensitive and rapid for the concept to be become practical. Since that time, the field has exploded: FBDD has played a role in discovery of at least 18 drugs that have entered the clinic, and practitioners of FBDD can be found throughout the world in both academia and industry. Literally dozens of reviews have been published on various aspects of FBDD or on the field as a whole, as have three books (Jahnke and Erlanson, Fragment-based approaches in drug discovery, 2006; Zartler and Shapiro, Fragment-based drug discovery: a practical approach, 2008; Kuo, Fragment based drug design: tools, practical approaches, and examples, 2011). However, this chapter will assume that the reader is approaching the field with little prior knowledge. It will introduce some of the key concepts, set the stage for the chapters to follow, and demonstrate how X-ray crystallography plays a central role in fragment identification and advancement.

Habitat Fragmentation Differentially Affects Genetic Variation, Phenotypic Plasticity and Survival in Populations of a Gypsum Endemic

Directory of Open Access Journals (Sweden)

Silvia Matesanz

2017-05-01

Full Text Available Habitat fragmentation, i.e., fragment size and isolation, can differentially alter patterns of neutral and quantitative genetic variation, fitness and phenotypic plasticity of plant populations, but their effects have rarely been tested simultaneously. We assessed the combined effects of size and connectivity on these aspects of genetic and phenotypic variation in populations of Centaurea hyssopifolia, a narrow endemic gypsophile that previously showed performance differences associated with fragmentation. We grew 111 maternal families sampled from 10 populations that differed in their fragment size and connectivity in a common garden, and characterized quantitative genetic variation, phenotypic plasticity to drought for key functional traits, and plant survival, as a measure of population fitness. We also assessed neutral genetic variation within and among populations using eight microsatellite markers. Although C. hyssopifolia is a narrow endemic gypsophile, we found substantial neutral genetic variation and quantitative variation for key functional traits. The partition of genetic variance indicated that a higher proportion of variation was found within populations, which is also consistent with low population differentiation in molecular markers, functional traits and their plasticity. This, combined with the generally small effect of habitat fragmentation suggests that gene flow among populations is not restricted, despite large differences in fragment size and isolation. Importantly, population’s similarities in genetic variation and plasticity did not reflect the lower survival observed in isolated populations. Overall, our results indicate that, although the species consists of genetically variable populations able to express functional plasticity, such aspects of adaptive potential may not always reflect populations’ survival. Given the differential effects of habitat connectivity on functional traits, genetic variation and fitness

Resonant Auger electron-photoion coincidence study of the fragmentation dynamics of an acrylonitrile molecule

Energy Technology Data Exchange (ETDEWEB)

Kooser, K; Ha, D T; Granroth, S; Itaelae, E; Nommiste, E; Kukk, E [Department of Physics, University of Turku, FIN-20014 Turku (Finland); Partanen, L; Aksela, H, E-mail: kunkoo@utu.f [Department of Physics, University of Oulu, Box 3000, FIN-90014 Oulu (Finland)

2010-12-14

Monochromatic synchrotron radiation was used to promote K-shell electrons of nitrogen and carbon from the cyano group (C {identical_to} N) of gaseous acrylonitrile (C{sub 2}H{sub 3}-CN) to the unoccupied antibonding {pi}*{sub C} {sub {identical_to} N} orbital. Photofragmentation of acrylonitrile molecules following selective resonant core excitations of carbon and nitrogen core electrons to the {pi}*{sub C} {sub {identical_to} N} orbital was investigated using the electron-energy-resolved photoelecton-photoion coincidence technique. The fragment ion mass spectra were recorded in coincidence with the resonant Auger electrons, emitted in the decay process of the core-excited states. Singly and triply deuterated samples were used for fragment identification. The results showed the initial core-hole localization to be of minor importance in determining the dissociation pattern of the molecular cation. The participator and spectator Auger transitions produce entirely different fragmentation patterns and the latter indicates that complex nuclear rearrangements take place. It is suggested that the calculated kinetic energy releases are caused by the existence of metastable states, which appear with the opening of the spectator Auger channels.

Mechanisms Affecting Population Density in Fragmented Habitat

Directory of Open Access Journals (Sweden)

Lutz Tischendorf

2005-06-01

Full Text Available We conducted a factorial simulation experiment to analyze the relative importance of movement pattern, boundary-crossing probability, and mortality in habitat and matrix on population density, and its dependency on habitat fragmentation, as well as inter-patch distance. We also examined how the initial response of a species to a fragmentation event may affect our observations of population density in post-fragmentation experiments. We found that the boundary-crossing probability from habitat to matrix, which partly determines the emigration rate, is the most important determinant for population density within habitat patches. The probability of crossing a boundary from matrix to habitat had a weaker, but positive, effect on population density. Movement behavior in habitat had a stronger effect on population density than movement behavior in matrix. Habitat fragmentation and inter-patch distance may have a positive or negative effect on population density. The direction of both effects depends on two factors. First, when the boundary-crossing probability from habitat to matrix is high, population density may decline with increasing habitat fragmentation. Conversely, for species with a high matrix-to-habitat boundary-crossing probability, population density may increase with increasing habitat fragmentation. Second, the initial distribution of individuals across the landscape: we found that habitat fragmentation and inter-patch distance were positively correlated with population density when individuals were distributed across matrix and habitat at the beginning of our simulation experiments. The direction of these relationships changed to negative when individuals were initially distributed across habitat only. Our findings imply that the speed of the initial response of organisms to habitat fragmentation events may determine the direction of observed relationships between habitat fragmentation and population density. The time scale of post-fragmentation

Quark fragmentation in e+e- collisions

International Nuclear Information System (INIS)

Oddone, P.

1984-12-01

This brief review of new results in quark and gluon fragmentation observed in e + e - collisions concentrates mostly on PEP results and, within PEP, mostly on TPC results. The new PETRA results have been reported at this conference by M. Davier. It is restricted to results on light quark fragmentation since the results on heavy quark fragmentation have been reported by J. Chapman

Technical writing versus technical writing

Science.gov (United States)

Dillingham, J. W.

1981-01-01

Two terms, two job categories, 'technical writer' and 'technical author' are discussed in terms of industrial and business requirements and standards. A distinction between 'technical writing' and technical 'writing' is made. The term 'technical editor' is also considered. Problems inherent in the design of programs to prepare and train students for these jobs are discussed. A closer alliance between industry and academia is suggested as a means of preparing students with competent technical communication skills (especially writing and editing skills) and good technical skills.

[Recent advances of amplified fragment length polymorphism and its applications in forensic botany].

Science.gov (United States)

Li, Cheng-Tao; Li, Li

2008-10-01

Amplified fragment length polymorphism (AFLP) is a new molecular marker to detect genomic polymorphism. This new technology has advantages of high resolution, good stability, and reproducibility. Great achievements have been derived in recent years in AFLP related technologies with several AFLP expanded methodologies available. AFLP technology has been widely used in the fields of plant, animal, and microbes. It has become one of the hotspots in Forensic Botany. This review focuses on the recent advances of AFLP and its applications in forensic biology.

Fragmentation of a 500 MeV/nucleon 86Kr beam, investigated at the GSI projectile fragment separator