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41.
The performance of an industrial pharmaceutical process (production of an active pharmaceutical ingredient by fermentation, API) was modeled by multiblock partial least squares (MBPLS). The most important process stages are inoculum production and API production fermentation. Thirty batches (runs) were produced according to an experimental planning. Rather than merging all these data into a single block of independent variables (as in ordinary PLS), four data blocks were used separately (manipulated and quality variables for each process stage). With the multiblock approach it was possible to calculate weights and scores for each independent block. It was found that the inoculum quality variables were highly correlated with API production for nominal fermentations. For the nonnominal fermentations, the manipulations of the fermentation stage explained the amount of API obtained (especially the pH and biomass concentration). Based on the above process analysis it was possible to select a smaller set of variables with which a new model was built. The amount of variance predicted of the final API concentration (cross-validation) for this model was 82.4%. The advantage of the multiblock model over the standard PLS model is that the contributions of the two main process stages to the API volumetric productivity were determined. 相似文献
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Beneficial effect of fluorocarbon emulsion media on the function of neuromuscular preparations in vitro
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The effects of liquid fluorocarbons as bathing media were determined by use of in vitro neuromuscular preparations. Rat hemidiaphragms were bathed in either oxygenated fluorocarbon (FC) emulsion or standard oxygenated Krebs solution. Contractile force in response to simple supramaximal nerve stimuli as well as to high frequency stimulation was greater, while twitch:tetanus ratio was smaller in FC emulsion. With such medium, post-tetanic potentiation of contraction was also more consistently observed. Indirectly stimulated diaphragms survived longer in FC emulsion. After cessation of oxygenation, oxygen tension (ρO(2)) of the medium declined more rapidly with Krebs than with FC emulsion; ρO(2) directly correlated with force of contraction. Similarly, in the chick biventer cervicis preparation, FC emulsion enhanced nerve-stimulated force of contraction; returning the preparation to standard Krebs solution reversed this phenomenon. Dose-resonse curves of muscle contraction in response to acetycholine and KCl administration were shifted upward during FC emulsion superfusion. Frequency of miniature endplate potentials was lower in FC emulsion than that observed in Krebs solution, measured from the same cell of the rat diaphragm. Resting membrane potentials were also greater in muscle cells sampled from FC emulsion-bathed preparations. These data suggest that FC emulsion is superior to standard Krebs solution as a bathing medium for in vitro neuromuscular preparations by virtue of the high solubility of oxygen in it. 相似文献
45.
Bob?JA?Schijvenaars Barend?Mons Marc?Weeber Martijn?J?Schuemie Erik?M?van Mulligen Hester?M?Wain Jan?A?KorsEmail author 《BMC bioinformatics》2005,6(1):149
Background
Massive text mining of the biological literature holds great promise of relating disparate information and discovering new knowledge. However, disambiguation of gene symbols is a major bottleneck. 相似文献46.
Miguel L Soares Seiki Haraguchi Maria-Elena Torres-Padilla Tibor Kalmar Lee Carpenter Graham Bell Alastair Morrison Christopher JA Ring Neil J Clarke David M Glover Magdalena Zernicka-Goetz 《BMC developmental biology》2005,5(1):1-11
Background
Studies of gene function in the mouse have relied mainly on gene targeting via homologous recombination. However, this approach is difficult to apply in specific windows of time, and to simultaneously knock-down multiple genes. Here we report an efficient method for dsRNA-mediated gene silencing in late cleavage-stage mouse embryos that permits examination of phenotypes at post-implantation stages.Results
We show that introduction of Bmp4 dsRNA into intact blastocysts by electroporation recapitulates the genetic Bmp4 null phenotype at gastrulation. It also reveals a novel role for Bmp4 in the regulation the anterior visceral endoderm specific gene expression and its positioning. We also show that RNAi can be used to simultaneously target several genes. When applied to the three murine isoforms of Dishevelled, it leads to earlier defects than previously observed in double knock-outs. These include severe delays in post-implantation development and defects in the anterior midline and neural folds at headfold stages.Conclusion
Our results indicate that the BMP4 signalling pathway contributes to the development of the anterior visceral endoderm, and reveal an early functional redundancy between the products of the murine Dishevelled genes. The proposed approach constitutes a powerful tool to screen the functions of genes that govern the development of the mouse embryo. 相似文献47.
A series of light-harvesting 1 (LH1) complexes was isolated by lithium dodecyl sulfate-polyacrylamide gel electrophoresis at 4 degrees C from Rhodobacter sphaeroides M21, which lacks the peripheral light-harvesting 2 (LH2) complex. This ladder of LH1 bands was also demonstrated in the wild type, partially superimposed upon a smaller number of LH2 complexes. An assessment of electrophoretic mobility vs acrylamide concentration, in which the reaction center LM particle and annular LH1 and LH2 complexes were used as standards of known structure, indicated that the LH1 gel bands 2 to 10 represent regular oligomers of an alpha beta heterodimeric unit, that vary in size from (alpha beta)(2-3) to (alpha beta)(10-11). The isolated LH1 complexes exhibited oligomeric state dependent optical properties, characterized by red shifts in near-IR absorption and emission maxima at 77 K of approximately 6 nm as aggregate sizes increased from approximately 3 to 7-8 alpha beta-heterodimers, accompanied by shifts in highly polarized fluorescence from the blue to the red side of the absorption band. This has been explained by the oligomerization of heterodimers to form a curvilinear array of excitonically coupled chromophores, with the anisotropic long-wavelength component, designated originally as B896, corresponding to low energy excitonic transitions arising from interactions within inhomogeneous BChl clusters [Westerhuis et al. (1999) J. Phys. Chem. B 103, 7733-7742]. Differences in electrophoretic profiles of LH1 bands between strains M21 and M2192, an LH1-only strain that also lacks PufX, further suggested that the more rapidly migrating bands represent arced fragments of the curvilinear array of LH1 complexes thought to exist as a large closed circular structure only in the latter strain. The electrophoretic banding pattern also indicated that the LH1 complex may be located at the peripheries of dimeric intramembrane particle arrays seen in freeze-fracture replicas of tubular M21 membranes; the possible role for the PufX protein in the assembly of these structures is discussed. 相似文献
48.
Ruis MA de Groot J te Brake JH Dinand Ekkel E van de Burgwal JA Erkens JH Engel B Buist WG Blokhuis HJ Koolhaas JM 《Applied animal behaviour science》2001,70(3):201-225
Endocrine, behavioural and immunologic processes, together with body growth, were evaluated in gilts that were defeated at 10 weeks of age in resident-intruder tests. Immediately after defeat, gilts were either separated from or reunited with a familiar conspecific (litter-mate; always a barrow). Gilts were assigned to one of four treatments: (a) DI: defeat, followed by isolation (separation from original litter-mate; n=8); (b) I: no defeat, isolation (control group; n=9); (c) DP; defeat, followed by pair-housing (reunion with original litter-mate; n=8); and (d) P: no defeat, pair-housing (control group; n=8). The following general conclusions were derived: (1) social defeat caused pronounced short-term elevations in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary activities, and of prolactin levels. Moreover, as soon as 1h after defeat, percentages of blood lymphocytes and neutrophilic granulocytes were, respectively, decreased and increased; (2) social defeat had some long-lasting influence on behaviour and physiology, but isolation predominantly determined responses in the longer term. Defeat, as well as isolation, resulted in increased cardiovascular activities compared to P controls, as observed in a novel object test (NOT: +7 days) and an aversion test (AVT: +14 days). Moreover, defeated as well as isolated gilts did not habituate to a repeated novel environment test (NET: -7, +2 and +7 days) in terms of frequencies of vocalising, whereas P controls did. Isolation, through the separation from any other pig, was responsible for the other observed long-term characteristics, which developed progressively. Isolated gilts showed high mobilities and high cortisol responses in the repeated NET (+7 days), not being habituated. This contrasted the reactions of pair-housed gilts, which were much reduced. In addition to their high cardiovascular activities in the NOT and the AVT, isolated gilts also displayed higher heart rates in the repeated NET and during human presence following the NOT, compared to pair-housed gilts. Finally, isolated gilts were more inhibited to approach a novel object (in the NOT) than pair-housed pigs; and (3) stress responses of defeated gilts were modulated by the subsequent social environment. Stimulation of the HPA-axis (plasma- and salivary cortisol) was prolonged in those defeated gilts which were isolated (observed in the first hour). Changes in leucocyte subsets were still observed after 3 days in DI, but were 'normalised' within 1 day in DP gilts. Two days after defeat, habituation to the repeated NET in terms of mobility and salivary cortisol responses occurred in control and DP gilts, but not in DI gilts. We argue that these effects of the social environment shortly after defeat were related to a stress-reducing effect of a stable social relationship, i.e. social support. 相似文献
49.
Davarzani Naser Diez-Simon Carmen Großmann Justus L. Jacobs Doris M. van Doorn Rudi van den Berg Marco A. Smilde Age K. Mumm Roland Hall Robert D. Westerhuis Johan A. 《Metabolomics : Official journal of the Metabolomic Society》2021,17(9):1-12
Metabolomics - To study metabolic signatures can be used to identify predictive biomarkers for a patient's therapeutic response. We hypothesized that the characterization of a patients’... 相似文献
50.
A. C. Ramalhinho J. Marques JA Fonseca-Moutinho L. Breitenfeld 《Molecular biology reports》2013,40(8):5093-5103
Estrogen receptor alpha (ERα), that mediates the biologic effects of estrogen in estrogen-sensitive tissues like breast, is genetically polymorphic. To evaluate the association between ?397 PvuII (T>C) and ?351 XbaI (A>G) restriction fragment length polymorphisms (RFLPs) in intron 1 of ERα gene and susceptibility of breast cancer, we undertook a case–control study in BRCA1 185delAG and 5382insC/BRCA2 6174delT negative Portuguese women. The study population consisted of 107 patients with histological diagnosis of breast cancer and 121 women with no history of breast cancer. Genomic DNA was extracted from blood samples and genotyping analyses were performed by PCR–RFLP. XbaI polymorphism was associated with a significant reduced risk of breast cancer for carriers of the x allele in homozygozity (OR 0.178; 95 % CI 0.070–0.456; P < 0.001) or heterozigozity (OR 0.223; 95 % CI 0.089–0.561; P = 0.001). The PvuII polymorphism was associated with a non-significantly reduced risk. The combined analysis of PvuII and XbaI polymorphisms revealed none synergistic effect of the two genotypes, except for simultaneous carriers of pp and xx genotypes, that have a reduced risk of breast cancer (OR 0.226; 95 % CI 0.049–1.035; P = 0.044). The combination of PvuII and XbaI genotypes into haplotypes showed that carriers of two copies of the px (ppxx) haplotype had a reduced risk of breast cancer (OR 0.405; 95 % CI 0.194–0.843; P = 0.014), compared with PX (PPXX + PPXx + PpXX + PpXx) haplotypes. PvuII and XbaI polymorphisms were in linkage disequilibrium both in cases (D = 0.044, r2 = 0.049, X2 = 5.216, P = 0.022) and controls (D = 0.090, r2 = 0.139, X2 = 16.819, P < 0.001), but not in the entire sample population analyzed as a whole (D = 0.087, r2 = 0.0076, X2 = 1.733, P = 0.188). In conclusion, in this case–control study we found that ERα gene XbaI polymorphism may modify individual susceptibility for breast cancer in this population. 相似文献