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21.
The dose-response of an individual organism can be described by a step functions if the organism survives when the dose is
below a certain lethal level and dies when this level is exceeded. If, in a population of organism, the lethal dose for an
individual has a unimodal distribution, the latter's properties will determine the shape of the population's response in the
following manner. If the distribution is symmetric the dose-response curve has a symmetric sigmoid shape when plotted on linear
coordinates. The location of the inflection point and the curve's slope around it are determined by the distribution's mode
and variance. When the distribution is skewed, the dose-response curve has an asymmetric sigmoid shape which becomes reminiscent
of an exponential decay when the distribution is strongly skewed to the right. The population's dose-response curve can be
constructed by integration of the step changes over the distribution range. The step function representing the dose-response
of an individual organism can be approximate by a Fermi function, and the distribution of an lethal doses can be represented
by the Weibull distribution function. When the two functions are combined, the resulting dose-response of the populationS(X)), which is the fraction of survivors after exposure to a doseX, is given by:S(X)=∫
0
1
[1/{+exp{(X-X
c
(φ))/a
i
]}]dω whereX
c
(ω)={(1/b)[-ln(1-ω)]}(1/n),n andb being the constants of the Weibull distribution anda
i
an arbitrarily small number, i.e.a
i
≪[X−X
c
(ϕ)], whose actual magnitude is of little significance. This model can be used to determine the underlying distributions of
experimental dose-response relationship. It was applied to published survival data of microorganisms exposed to pulsed electric
field, X-ray radiation and ozone to show that the different observed shapes of the dose-response curve, and shifts between
them, can be expressed in terms of the correponding distribution parameters, namely the mode, variance and skewness. 相似文献
22.
Emmie Dornez Evi Croes Kurt Gebruers Sebastien Carpentier Rony Swennen Kris Laukens Erwin Witters Martin Urban Jan A. Delcour Christophe M. Courtin 《Proteomics》2010,10(12):2303-2319
Wheat contains three different classes of proteinaceous xylanase inhibitors (XIs), i.e. Triticum aestivum xylanase inhibitors (TAXIs) xylanase‐inhibiting proteins (XIPs), and thaumatin‐like xylanase inhibitors (TLXIs) which are believed to act as a defensive barrier against phytopathogenic attack. In the absence of relevant data in wheat kernels, we here examined the response of the different members of the XI protein population to infection with a ΔTri5 mutant of Fusarium graminearum, the wild type of which is one of the most important wheat ear pathogens, in early developing wheat grain. Wheat ears were inoculated at anthesis, analyzed using 2‐D DIGE and multivariate analysis at 5, 15, and 25 days post anthesis (DPA), and compared with control samples. Distinct abundance patterns could be distinguished for different XI forms in response to infection with F. graminearum ΔTri5. Some (iso)forms were up‐regulated, whereas others were down‐regulated. This pathogen‐specific regulation of proteins was mostly visible at five DPA and levelled off in the samples situated further from the inoculation point. Furthermore, it was shown that most identified TAXI‐ and XIP‐type XI (iso)forms significantly increased in abundance from the milky (15 DPA) to the soft dough stages (25 DPA) on a per kernel basis, although the extent of increase differed greatly. Non‐glycosylated XIP forms increased more strongly than their glycosylated counterparts. 相似文献
23.
Tyan L Sopjani M Dërmaku-Sopjani M Schmid E Yang W Xuan NT Shumilina E Lang F 《American journal of physiology. Cell physiology》2010,299(6):C1379-C1385
Rapamycin, an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR), is a widely used immunosuppressive drug. Rapamycin affects the function of dendritic cells (DCs), antigen-presenting cells participating in the initiation of primary immune responses and the establishment of immunological memory. Voltage-gated K(+) (Kv) channels are expressed in and impact on the function of DCs. The present study explored whether rapamycin influences Kv channels in DCs. To this end, DCs were isolated from murine bone marrow and ion channel activity was determined by whole cell patch clamp. To more directly analyze an effect of mTOR on Kv channel activity, Kv1.3 and Kv1.5 were expressed in Xenopus oocytes with or without the additional expression of mTOR and voltage-gated currents were determined by dual-electrode voltage clamp. As a result, preincubation with rapamycin (0-50 nM) led to a gradual decline of Kv currents in DCs, reaching statistical significance within 6 h and 50 nM of rapamycin. Rapamycin accelerated Kv channel inactivation. Coexpression of mTOR upregulated Kv1.3 and Kv1.5 currents in Xenopus oocytes. Furthermore, mTOR accelerated Kv1.3 channel activation and slowed down Kv1.3 channel inactivation. In conclusion, mTOR stimulates Kv channels, an effect contributing to the immunomodulating properties of rapamycin in DCs. 相似文献
24.
Manalo DJ Baek JH Buehler PW Struble E Abraham B Alayash AI 《Biochemical and biophysical research communications》2011,416(3-4):421-426
25.
26.
Soutoglou E Dorn JF Sengupta K Jasin M Nussenzweig A Ried T Danuser G Misteli T 《Nature cell biology》2007,9(6):675-682
Formation of cancerous translocations requires the illegitimate joining of chromosomes containing double-strand breaks (DSBs). It is unknown how broken chromosome ends find their translocation partners within the cell nucleus. Here, we have visualized and quantitatively analysed the dynamics of single DSBs in living mammalian cells. We demonstrate that broken ends are positionally stable and unable to roam the cell nucleus. Immobilization of broken chromosome ends requires the DNA-end binding protein Ku80, but is independent of DNA repair factors, H2AX, the MRN complex and the cohesion complex. DSBs preferentially undergo translocations with neighbouring chromosomes and loss of local positional constraint correlates with elevated genomic instability. These results support a contact-first model in which chromosome translocations predominantly form among spatially proximal DSBs. 相似文献
27.
28.
Øystein Rist Marie Grimstrup Jean-Marie Receveur Thomas M. Frimurer Trond Ulven Evi Kostenis Thomas Högberg 《Bioorganic & medicinal chemistry letters》2010,20(3):1177-1180
Structure–activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7 nM and functional antagonistic effect of 66 nM in a BRET and 12 nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27 μM in cAMP). 相似文献
29.
Archaeobotanical research, ethnographic observations and laboratory experiments are put together to create model sequences
of olive processing, which are developed, presented and explored as an aid for the interpretation of rich archaeobotanical
assemblages of Olea. We conclude that the remains of different processing stages are reasonably distinctive in the archaeobotanical record and
assist in the identification of different types of olive remains, such as fragmented olive stones, the inner kernels, and
fruit flesh 相似文献
30.