共查询到20条相似文献,搜索用时 31 毫秒
1.
Woltosz WS 《Journal of computer-aided molecular design》2012,26(1):159-163
In the early days, airplanes were put together with parts designed for other purposes (bicycles, farm equipment, textiles,
automotive equipment, etc.). They were then flown by their brave designers to see if the design would work—often with disastrous
results. Today, airplanes, helicopters, missiles, and rockets are designed in computers in a process that involves iterating
through enormous numbers of designs before anything is made. Until very recently, novel drug-like molecules were nearly always
made first like early airplanes, then tested to see if they were any good (although usually not on the brave scientists who
created them!). The resulting extremely high failure rate is legendary. This article describes some of the evolution of computer-based
design in the aerospace industry and compares it with the progress made to date in computer-aided drug design. Software development
for pharmaceutical research has been largely entrepreneurial, with only relatively limited support from government and industry
end-user organizations. The pharmaceutical industry is still about 30 years behind aerospace and other industries in fully
recognizing the value of simulation and modeling and funding the development of the tools needed to catch up. 相似文献
2.
Douglas J. Van Cleef 《Journal of Radioanalytical and Nuclear Chemistry》2009,282(3):837-840
Until recently, high-purity germanium (HPGe) was used only by small, select teams of specialists in field applications for
nuclear materials detection in national defense, treaty verification, and interdiction applications. Recent advances in technology
of hardware and software has enabled widespread deployment of HPGe-based tools which dramatically expand the envelope of information
available to personnel previously outside the ‘circle’ of nuclear measurement experts. This paper describes the technological
advances as well as the practical implications of these new tools for counter-terrorism, non-proliferation, homeland security,
and post-accident triage applications. 相似文献
3.
Y. Eden 《Journal of Radioanalytical and Nuclear Chemistry》1970,6(1):165-175
The usual method of the neutron activation analysis is performed by the measurement of the characteristic nuclear radiations
of the produced radioactive isotope by neutron irradiation. An advance in this field has recently been proposed in which the
prompt capture γ-rays are observed in addition to the nuclear radiation of the produced nucleus. The characteristic energy
spectra of these two kinds of γ-radiations are the main basis for the combined activation analysis method. The experimental
setup consists of a γ-radiation pulse height energy spectrum system which is synchronized with a pulsing neutron generator
of ‘D—T’ or ‘D—D’ reaction. The present results indicate that a qualitative and semi-quantitative determination of a number
of elements is feasible, with an overall error of 10–15%. 相似文献
4.
Playing tag with quantitative proteomics 总被引:1,自引:0,他引:1
There is steady need for new proteomic strategies on quantitative measurements that provide essential components for detailing
dynamic changes in many cellular functions and processes. Stable isotope labeling is a rapidly evolving field, which can be
used either after protein extraction with chemical labeling, or in cell culture with metabolic incorporation. In this review,
we explore the most frequently utilized quantitation techniques with particular attention paid to chemical labeling using
different isotopic tags, including a recent labeling strategy—soluble polymer-based isotopic labeling (SoPIL)—that achieves
efficient labeling in homogeneous conditions. Special care should be devoted to the selection of appropriate quantitation
approaches according to the needs of the sample and overall experimental design. We evaluate recent advances in quantitative
proteomics using stable isotope labeling and their applications to current insightful biological inquiries.
Figure Chemical modules of isotopic tags for quantitative proteomics. 相似文献
5.
Molecular dynamics simulations can now track rapid processes—those occurring in less than about a millisecond—at atomic resolution
for many biologically relevant systems. These simulations appear poised to exert a significant impact on how new drugs are
found, perhaps even transforming the very process of drug discovery. We predict here future results we can expect from, and
enhancements we need to make in, molecular dynamics simulations over the coming 25 years, and in so doing set out several
Grand Challenges for the field. In the context of the problems now facing the pharmaceutical industry, we ask how we can best
address drug discovery needs of the next quarter century using molecular dynamics simulations, and we suggest some possible
approaches. 相似文献
6.
Xu Y Jang K Yamashita T Tanaka Y Mawatari K Kitamori T 《Analytical and bioanalytical chemistry》2012,402(1):99-107
By combining cell technology and microchip technology, innovative cellular biochemical tools can be created from the microscale
to the nanoscale for both practical applications and fundamental research. On the microscale level, novel practical applications
taking advantage of the unique capabilities of microfluidics have been accelerated in clinical diagnosis, food safety, environmental
monitoring, and drug discovery. On the other hand, one important trend of this field is further downscaling of feature size
to the 101–103 nm scale, which we call extended-nano space. Extended-nano space technology is leading to the creation of innovative nanofluidic
cellular and biochemical tools for analysis of single cells at the single-molecule level. As a pioneering group in this field,
we focus not only on the development of practical applications of cellular microchip devices but also on fundamental research
to initiate new possibilities in the field. In this paper, we review our recent progress on tissue reconstruction, routine
cell-based assays on microchip systems, and preliminary fundamental method for single-cell analysis at the single-molecule
level with integration of the burgeoning technologies of extended-nano space. 相似文献
7.
Samira Zeroual Nathalie Bouet Fabien Tuyèras Cyril Peltier Nadia Ouddai Philippe Ochsenbein Carlo Adamo Philippe P. Lainé Ilaria Ciofini 《Theoretical chemistry accounts》2012,131(2):1107-10
With the aim of designing new inorganic photosensitizers for photovoltaic applications, the structural and electronic properties
of two Ru(II) complexes containing terpyridine-based ligands derived from expanded pyridiniums both branched—polyphenyl—and
fused—polycyclic—were investigated by the means of density functional theory (DFT) and time-dependent DFT (TD-DFT). In particular,
the structure and electronic absorption of the fused architectures—including the isolated ligand and its complex—were compared
with those of their respective branched precursors with the aim to account for the their enhanced electronic features in the
visible spectral region. The theoretical insights gained into the “large-surface” ligand and its associated complex open the
route for a joint experimental and theoretical design of new inorganic photosensitizers based on fused expanded pyridiniums. 相似文献
8.
Mobley DL 《Journal of computer-aided molecular design》2012,26(1):93-95
Molecular simulations see widespread and increasing use in computation and molecular design, especially within the area of
molecular simulations applied to biomolecular binding and interactions, our focus here. However, force field accuracy remains
a concern for many practitioners, and it is often not clear what level of accuracy is really needed for payoffs in a discovery
setting. Here, I argue that despite limitations of today’s force fields, current simulation tools and force fields now provide
the potential for real benefits in a variety of applications. However, these same tools also provide irreproducible results
which are often poorly interpreted. Continued progress in the field requires more honesty in assessment and care in evaluation
of simulation results, especially with respect to convergence. 相似文献
9.
Martin Egginger Siegfried Bauer Reinhard Schw?diauer Helmut Neugebauer Niyazi Serdar Sariciftci 《Monatshefte für Chemie / Chemical Monthly》2009,95(1):735-750
Abstract
Research into organic field effect transistors (OFETs) has made significant advances—both scientifically and technologically—during the last decade, and the first products will soon enter the market. Printed electronic circuits using organic resistors, diodes and transistors may become cheap alternatives to silicon-based systems, especially in large-area applications. A key parameter for device operation, besides long term stability, is the reproducibility of the current–voltage behavior, which may be affected by hysteresis phenomena. Hysteresis effects are often observed in organic transistors during sweeps of the gate voltage (V GS). This hysteresis can originate in various ways, but comparative scientific investigations are rare and a comprehensive picture of “hysteresis phenomena” in OFETs is still missing. This review provides an overview of the physical effects that cause hysteresis and discusses the importance of such effects in OFETs in a comparative manner. 相似文献10.
J. F. A. Soltero J. E. Puig P. C. Schulz 《Journal of Thermal Analysis and Calorimetry》1998,51(1):105-114
The state of water and several transitions were examined in the systemsn-decanephosphonic acid (DPA)—water and the sodium salts of DPA—water. Temperature — composition phase diagrams are reported.
The results show that several liquid crystalline phases plus isotropic liquid, and two solid phases (a waxy solid phase and
a crystalline phase) are formed. Several types of water were detected: bulk-like water, interfacial water and hydration water.
This work was supported by the Consejo Nacional de Ciencia y Technología de México (grant # 3319-E) and by the Consejo Nacional
de Investigaciones Científicas y Técnicas de la República de Argentina. 相似文献
11.
Michael F. Santillo Andrew G. Ewing Michael L. Heien 《Analytical and bioanalytical chemistry》2011,399(1):183-190
Computational modeling and theoretical simulations have recently become important tools for the development, characterization,
and validation of microfluidic devices. The recent proliferation of commercial user-friendly software has allowed researchers
in the microfluidics community, who might not be familiar with computer programming or fluid mechanics, to acquire important
information on microsystems used for sensors, velocimetry, detection for microchannel separations, and microfluidic fuel cells.
We discuss the most popular computational technique for modeling these systems—the finite element method—and how it can be
applied to model electrochemical processes coupled with hydrodynamic flow in microchannels. Furthermore, some of the limitations
and challenges of these computational models are also discussed. 相似文献
12.
Kamphausen S Höltge N Wirsching F Morys-Wortmann C Riester D Goetz R Thürk M Schwienhorst A 《Journal of computer-aided molecular design》2002,16(8-9):551-567
The design of molecules with desired properties is still a challenge because of the largely unpredictable end results. Computational methods can be used to assist and speed up this process. In particular, genetic algorithms have proved to be powerful tools with a wide range of applications, e.g. in the field of drug development. Here, we propose a new genetic algorithm that has been tailored to meet the demands of de novo drug design, i.e. efficient optimization based on small training sets that are analyzed in only a small number of design cycles. The efficiency of the design algorithm was demonstrated in the context of several different applications. First, RNA molecules were optimized with respect to folding energy. Second, a spinglass was optimized as a model system for the optimization of multiletter alphabet biopolymers such as peptides. Finally, the feasibility of the computer-assisted molecular design approach was demonstrated for the de novo construction of peptidic thrombin inhibitors using an iterative process of 4 design cycles of computer-guided optimization. Synthesis and experimental fitness determination of only 600 different compounds from a virtual library of more than 1017 molecules was necessary to achieve this goal.These authors contributed equally to the results presentedThese authors contributed equally to the results presentedThese authors contributed equally to the results presentedThese authors contributed equally to the results presented 相似文献
13.
V. Jánošová M. Sýkorová O. Štroffeková E. Havránek 《Journal of Analytical Chemistry》2010,65(1):56-63
Preconcentration performance characteristics of precipitation of Mn, Fe, Co, Cu, Zn, Pb, Hg, and Cd and with subsequent filtration
through cellulose nitrate membrane were investigated for the X-ray spectrometry identification and determination of trace
metal ions in drug samples. The method was optimised for several parameters, including pH and amount of thioacetamide. The
investigated analyte ions were collected on cellulose nitrate membrane filter (Pragopor 4) as sulphides after the reaction
with thioacetamide. Optimal reaction conditions were found out (pH 8.5 for Fe, Zn, Hg, and Cd and pH 11.5 for Mn, Co, Cu,
and Pb; 1.2 mL of added thioacetamide). Thereafter, the content of these elements was determined in the samples of drugs—NaCl,
glucose and dextrane. The rapidity of this method, its polycomponent character and low detection limits (for filters: Mn—1.09
μg, Fe—1.08 μg, Co—0.82 μg, Cu—0.42 μg, Zn—0.61 μg, Pb—0.45 μg, Hg—0.42 μg, and Cd—0.99 μg) have proved this method to be
very promising in rapid screening used in quality control of drugs. 相似文献
14.
Roman F. Nalewajski 《Journal of mathematical chemistry》2008,44(3):802-815
Within the fragment resolution of molecular systems the conceptual and interpretative advantages of using the separate eigenvalue
problems for the internal and external part of the Hermitian matrix representing a physical quantity in quantum mechanics are examined. By definition, these two
parts accordingly combine only the diagonal and off-diagonal subsystem-resolved blocks of matrix elements. These two partial eigenvalue problems bring about the matrix internal or external
decouplings, respectively, which have recently been used in several interpretations of the molecular electronic structure.
A character and structure of the external eigensolutions is examined in some detail and their recent applications in the Charge
Sensitivity Analysis—to extract the most important electron-transfer effects between constituent atoms of model chemisorption
systems, and in the Molecular-Orbital theory—to precisely identify the inter-orbital flows of electrons, are summarized and
commented upon. The grouping relation, for combining the external/internal eigensolutions into those for the whole matrix,
is derived in the context of the complementary “rotations” of the basis set vectors. 相似文献
15.
Rational drug design involves finding solutions to large combinatorial problems for which an exhaustive search is impractical. Genetic algorithms provide a novel tool for the investigation of such problems. These are a class of algorithms that mimic some of the major characteristics of Darwinian evolution. LEA has been designed in order to conceive novel small organic molecules which satisfy quantitative structure-activity relationship based rules (fitness). The fitness consists of a sum of constraints that are range properties. The algorithm takes an initial set of fragments and iteratively improves them by means of crossover and mutation operators that are related to those involved in Darwinian evolution. The basis of the algorithm, its implementation and parameterization, are described together with an application in de novo molecular design of new retinoids. The results may be promising for chemical synthesis and show that this tool may find extensive applications in de novo drug design projects. 相似文献
16.
Martin Egginger Siegfried Bauer Reinhard Schwödiauer Helmut Neugebauer Niyazi Serdar Sariciftci 《Monatshefte für Chemie / Chemical Monthly》2009,140(7):735-750
Abstract Research into organic field effect transistors (OFETs) has made significant advances—both scientifically and technologically—during
the last decade, and the first products will soon enter the market. Printed electronic circuits using organic resistors, diodes
and transistors may become cheap alternatives to silicon-based systems, especially in large-area applications. A key parameter
for device operation, besides long term stability, is the reproducibility of the current–voltage behavior, which may be affected
by hysteresis phenomena. Hysteresis effects are often observed in organic transistors during sweeps of the gate voltage (V
GS). This hysteresis can originate in various ways, but comparative scientific investigations are rare and a comprehensive picture
of “hysteresis phenomena” in OFETs is still missing. This review provides an overview of the physical effects that cause hysteresis
and discusses the importance of such effects in OFETs in a comparative manner.
Graphical abstract
相似文献
17.
A tremendous growth in the field of carbon nanomaterials has led to the emergence of carbon nanotubes, fullerenes, mesoporous carbon and more recently graphene. Some of these materials have found applications in electronics, sensors, catalysis, drug delivery, composites, and so forth. The high temperatures and hydrocarbon precursors involved in their synthesis usually yield highly inert graphitic surfaces. As some of the applications require functionalization of their inert graphitic surface with groups like ? COOH, ? OH, and ? NH2, treatment of these materials in oxidizing agents and concentrated acids become inevitable. More recent works have involved using precursors like carbohydrates to produce carbon nanostructures rich in functional groups in a single‐step under hydrothermal conditions. These carbon nanostructures have already found many applications in composites, drug delivery, materials synthesis, and Li ion batteries. The review aims to highlight some of the recent developments in the application of carbohydrate derived carbon nanostructures and also provide an outlook of their future prospects. 相似文献
18.
The development of an accurate aqueous thermodynamic model is described for oxalate species in the Na—Ba—Ca—Mn—Sr—Cl—NO3—PO4—SO4—H2O system at 25 °C. The model is valid to high ionic strength (as high as 10 mol·kg−1) and from very acid (10 mol·kg−1 H2SO4) to neutral and basic conditions. The model is based upon the equations of Pitzer and co-workers. The necessary ion-interaction
parameters are determined by comparison with experimental data taken from the literature or determined in this study. The
proposed aqueous activity and solubility model is valid for a range of applications from interpretation of studies on mineral
dissolution at circumneutral pH to the dissolution of high-level waste tank sludges under acidic conditions. 相似文献
19.
V. Koprda 《Journal of Radioanalytical and Nuclear Chemistry》1976,30(1):103-118
The diffusion of chlorocomplexes of some corrosion and fission products in anion exchange beads has been studied in mixed
solvent media. The effects of variables on the kinetics of the exchange process by the batch and flow technique were examined.
The strongly basic anion exchanger Dowex 2X8 in its Cl− form was used in organic solvent—water—hydrochloric acid solutions. The dependence of the exchange rate on temperature, the
viscosity of the solution, the mean resin particle diameter and the composition of the solution was studied. Film and particle
diffusion coefficients were calculated from the experimental data. The results provide valuable data for the design of separation
procedures. 相似文献
20.
Forensic applications of ambient ionization mass spectrometry 总被引:1,自引:0,他引:1
Demian R. Ifa Ayanna U. Jackson Giuseppe Paglia R. Graham Cooks 《Analytical and bioanalytical chemistry》2009,394(8):1995-2008
This review highlights and critically assesses forensic applications in the developing field of ambient ionization mass spectrometry.
Ambient ionization methods permit the ionization of samples outside the mass spectrometer in the ordinary atmosphere, with
minimal sample preparation. Several ambient ionization methods have been created since 2004 and they utilize different mechanisms
to create ions for mass-spectrometric analysis. Forensic applications of these techniques—to the analysis of toxic industrial
compounds, chemical warfare agents, illicit drugs and formulations, explosives, foodstuff, inks, fingerprints, and skin—are
reviewed. The minimal sample pretreatment needed is illustrated with examples of analysis from complex matrices (e.g., food)
on various substrates (e.g., paper). The low limits of detection achieved by most of the ambient ionization methods for compounds
of forensic interest readily offer qualitative confirmation of chemical identity; in some cases quantitative data are also
available. The forensic applications of ambient ionization methods are a growing research field and there are still many types
of applications which remain to be explored, particularly those involving on-site analysis. Aspects of ambient ionization
currently undergoing rapid development include molecular imaging and increased detection specificity through simultaneous
chemical reaction and ionization by addition of appropriate chemical reagents. 相似文献