selfsame

WordNet

the quality of being identical with itself

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English Journal

Measurements of Single Molecules in Solution and Live Cells Over Longer Observation Times Than Those Currently Possible: The Meaningful Time.

Földes-Papp Z.Author information Helios Clinical Center of Emergency Medicine, Department for Internal Medicine, Alte-Koelner-Strasse 9, D-51688 Koeln-Wipperfuerth, Germany. zeno.foldespapp@gmail.com.AbstractMonitoring translational diffusion of single molecules in solution or in a living cell, particularly DNA and proteins brings valuable information unperturbed by interaction with an artificial surface. The article derives theoretical relationships for time intervals during which just one molecule in the effective probe region can be studied, the time we call meaningful time. This time is greater than the transit time of the molecule through the detection volume, as a single molecule will likely reenter the detection volume several times during measurement. From the infinitely stretched molecular Poisson distribution of single molecules or particles, we select the contribution of the selfsame molecule or particle by applying rules for choosing appropriate statistics for the single-molecule trajectories. The results point to a useful and sensitive predictive power of the derived relationships. The meaningful time relationships are the criteria to check the experimental single molecule data measured under conditions of normal and anomalous Brownian diffusion of the molecules of interest. At femtomolar bulk concentration, it would be possible to observe an individual molecule over a second time interval or longer during which biological processes - and not conformational biophysical changes - are just starting.
Current pharmaceutical biotechnology.Curr Pharm Biotechnol.2013 Jan 29. [Epub ahead of print]
Monitoring translational diffusion of single molecules in solution or in a living cell, particularly DNA and proteins brings valuable information unperturbed by interaction with an artificial surface. The article derives theoretical relationships for time intervals during which just one molecule
PMID 23369193

Meaningful interpretation of subdiffusive measurements in living cells (crowded environment) by fluorescence fluctuation microscopy.

Baumann G, Place RF, Földes-Papp Z.Author information Mathematics Department, German University in Cairo. Gerd.Baumann@guc.edu.egAbstractIn living cell or its nucleus, the motions of molecules are complicated due to the large crowding and expected heterogeneity of the intracellular environment. Randomness in cellular systems can be either spatial (anomalous) or temporal (heterogeneous). In order to separate both processes, we introduce anomalous random walks on fractals that represented crowded environments. We report the use of numerical simulation and experimental data of single-molecule detection by fluorescence fluctuation microscopy for detecting resolution limits of different mobile fractions in crowded environment of living cells. We simulate the time scale behavior of diffusion times tau(D)(tau) for one component, e.g. the fast mobile fraction, and a second component, e.g. the slow mobile fraction. The less the anomalous exponent alpha the higher the geometric crowding of the underlying structure of motion that is quantified by the ratio of the Hausdorff dimension and the walk exponent d(f)/d(w) and specific for the type of crowding generator used. The simulated diffusion time decreases for smaller values of alpha # 1 but increases for a larger time scale tau at a given value of alpha # 1. The effect of translational anomalous motion is substantially greater if alpha differs much from 1. An alpha value close to 1 contributes little to the time dependence of subdiffusive motions. Thus, quantitative determination of molecular weights from measured diffusion times and apparent diffusion coefficients, respectively, in temporal auto- and crosscorrelation analyses and from time-dependent fluorescence imaging data are difficult to interpret and biased in crowded environments of living cells and their cellular compartments; anomalous dynamics on different time scales tau must be coupled with the quantitative analysis of how experimental parameters change with predictions from simulated subdiffusive dynamics of molecular motions and mechanistic models. We first demonstrate that the crowding exponent alpha also determines the resolution of differences in diffusion times between two components in addition to photophysical parameters well-known for normal motion in dilute solution. The resolution limit between two different kinds of single molecule species is also analyzed under translational anomalous motion with broken ergodicity. We apply our theoretical predictions of diffusion times and lower limits for the time resolution of two components to fluorescence images in human prostate cancer cells transfected with GFP-Ago2 and GFP-Ago1. In order to mimic heterogeneous behavior in crowded environments of living cells, we need to introduce so-called continuous time random walks (CTRW). CTRWs were originally performed on regular lattice. This purely stochastic molecule behavior leads to subdiffusive motion with broken ergodicity in our simulations. For the first time, we are able to quantitatively differentiate between anomalous motion without broken ergodicity and anomalous motion with broken ergodicity in time-dependent fluorescence microscopy data sets of living cells. Since the experimental conditions to measure a selfsame molecule over an extended period of time, at which biology is taken place, in living cells or even in dilute solution are very restrictive, we need to perform the time average over a subpopulation of different single molecules of the same kind. For time averages over subpopulations of single molecules, the temporal auto- and crosscorrelation functions are first found. Knowing the crowding parameter alpha for the cell type and cellular compartment type, respectively, the heterogeneous parameter gamma can be obtained from the measurements in the presence of the interacting reaction partner, e.g. ligand, with the same alpha value. The product alpha x gamma = gamma is not a simple fitting parameter in the temporal auto- and two-color crosscorrelation functions because it is related to the proper physical models of anomalous (spatial) and heterogeneous (temporal) randomness in cellular systems.We have already derived an analytical solution gamma for in the special case of gamma = 3/2. In the case of two-color crosscorrelation or/and two-color fluorescence imaging (co-localization experiments), the second component is also a two-color species gr, for example a different molecular complex with an additional ligand. Here, we first show that plausible biological mechanisms from FCS/ FCCS and fluorescence imaging in living cells are highly questionable without proper quantitative physical models of subdiffusive motion and temporal randomness. At best, such quantitative FCS/ FCCS and fluorescence imaging data are difficult to interpret under crowding and heterogeneous conditions. It is challenging to translate proper physical models of anomalous (spatial) and heterogeneous (temporal) randomness in living cells and their cellular compartments like the nucleus into biological models of the cell biological process under study testable by single-molecule approaches. Otherwise, quantitative FCS/FCCS and fluorescence imaging measurements in living cells are not well described and cannot be interpreted in a meaningful way.
Current pharmaceutical biotechnology.Curr Pharm Biotechnol.2010 Aug;11(5):527-43.
In living cell or its nucleus, the motions of molecules are complicated due to the large crowding and expected heterogeneity of the intracellular environment. Randomness in cellular systems can be either spatial (anomalous) or temporal (heterogeneous). In order to separate both processes, we introdu
PMID 20553227

Orthogonal predictions: follow-up questions for suggestive data.

Walker AM.Author information World Health Information Science Consultants, LLC, Newton, MA 02466, USA. Alec.Walker@WHISCON.comAbstractWhen a biological hypothesis of causal effect can be inferred, the hypothesis can sometimes be tested in the selfsame database that gave rise to the study data from which the hypothesis grew. Valid testing happens when the inferred biological hypothesis has scientific implications that predict new relations between observations already recorded. Testing for the existence of the new relations is a valid assessment of the biological hypothesis, so long as the newly predicted relations are not a logical correlate of the observations that stimulated the hypothesis in the first place. These predictions that lead to valid tests might be called 'orthogonal' predictions in the data, and stand in marked contrast to 'scrawny' hypotheses with no biological content, which predict simply that the same data relations will be seen in a new database. The Universal Data Warehouse will shortly render moot searches for new databases in which to test.
Pharmacoepidemiology and drug safety.Pharmacoepidemiol Drug Saf.2010 May;19(5):529-32. doi: 10.1002/pds.1929.
When a biological hypothesis of causal effect can be inferred, the hypothesis can sometimes be tested in the selfsame database that gave rise to the study data from which the hypothesis grew. Valid testing happens when the inferred biological hypothesis has scientific implications that predict new r
PMID 20309840

Japanese Journal

根本説一切有部律に引用されるMahadevasutra--テクストおよび訳注

八尾史
東洋文化研究所紀要 152, 380-321, 2007-12-00
… The Mūlasarvāstivāda-vinaya contains a huge number of quotations from sūtras in the Āgamas of the selfsame school. …
NAID 120000870371

メゾ蓚酸塩の抗糖尿病作用に関する研究-1-

小林芳人 [他],大橋茂,竹内節彌,明知愛子,池田良雄,磯野千冬
日本薬理学雑誌 48(5), 348-357, 1952
… If the administration of the drug was sustained, glycosuria reappeared from the selfsame day and the body weight, blood sugar content and other findings returned to their respective level prior to the drug was given. …
NAID 130000755383

膀胱結石並ニ尿道結石ニ就テ

小山正篤
日本泌尿器科學會雜誌 20(7), 359-378, i-ii, 1931-07-00
… If the radiation should be given from different directions, the selfsame calculus presents shades having different shapes. …
NAID 110003074523

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