123 research outputs found
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Temperature and concentration control of exothermic chemical processes in continuous stirred tank reactors
Exothermic chemical reaction taking place in continuous stirred tank reactor is considered. Heat release from the chemical reaction, non-linear dynamic behavior of the process and uncertainty in parameters are the main factors motivating the use of robust control design. Viewing temperature and molar concentration as variables both accessible in real time, PI and optimal state-feedback controllers driven by temperature and concentration error signals are proposed to regulate the system over reactorâs steady-state working points by counteracting undesired disturbances. Since access to concentration value has proved beneficial for the reactorâs performance, estimation techniques are examined to compensate for the problematic nature of the concentrationâs measurement. A linear reduced-order observer is first proposed to estimate the concentration value using temperature measurements. In addition, assuming concentration measurement is available with a relatively short delay via sample analysis, a linear and non-linear discrete-time predictor is constructed to estimate the concentrationâs real-time value. A linear combination of the two estimation schemes (observer, predictor) is proposed resulting in a combined estimator, in which the emphasis between the two individual schemes can be controlled via a scalar parameter. The work presented in this paper was supported by the GLOW project â New weather-stable low gloss powder coatings based on bifunctional acrylic solid resins and nanoadditives â as part of the development of novel and efficient processing technologies regarding the production of new families of powder coatings, responding to industrial requirements for quality improvement at lower cost and shorter development cycles
A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues
Expression database. Column A contains the names of the 1099 TFs in humans. Columns BâÂÂBC provide the expression of the TFs in FPKM (fragments per kilobase of transcript per million), as calculated by Analysis Pipeline 1, across the 40 cell-types (52 experiments). (CSV 553 kb
Effects of oxidation agents and metal ions on binding of p53 to supercoiled DNA
Wild type human full length (f.l.) tumor suppressor p53 protein binds preferentially to supercoiled (sc) DNA in vitro both in the presence and absence of the p53 consensus sequence (p53CON). This binding produces a ladder of retarded bands on the agarose gel. Bands revealed by immunoblotting with antibody DO-1 corresponded to the ethidium stained retarded bands. The intensity and the number of bands of p53-scDNA complex were decreased by physiological concentrations of unchelated zinc ions. Nickel and cobalt ions inhibited binding of p53 to scDNA and to p53CON in linear DNA fragments less efficiently than zinc. Compared to the intrinsic zinc strongly bound to Cys 176, Cys 238, Cys 242 and His 179 in the p53 core domain, binding of additional Zn2+ to p53 was much weaker as shown by an easy removal of the latter ions by low concentrations of EDTA. Oxidation of the protein with diamide resulted in a decrease of the number of the retarded bands. Under the same conditions, no binding of oxidized p53 to p53CON in a linear DNA fragment was observed. In agreement with the literature oxidation of f.l. p53 with diamide was irreversible and was not reverted by an excess of DTT. We showed that in the presence of 0.1 mM zinc ions, oxidation of p53 became reversible. Other divalent cations tested (cadmium, cobalt, nickel) exhibited no such effect. We suggested that the irreversibility of p53 oxidation was due, at least in part, to the removal of intrinsic zinc from its position in the DNA binding domain (after oxidation of the three cysteines to which the zinc ion is coordinated in the reduced protein) accompanied by a change in the p53 conformation. Binding of C-terminal anti-p53 antibody also protected bacterially expressed protein against irreversible loss of activity due to diamide oxidation. Binding the human p53 core domain (segment 94-312) to scDNA greatly differed from that observed with the full-length p53. The core domain did not posses the ability to bind strongly to many sites in scDNA regardless of the presence or absence of p53CON suggesting involvement of some other domain (probably C-terminal) in binding of the full-length p53 to scDNA. Supershift experiments using antibodies against p53 N- or C-terminus suggested that in oxidized p53, scDNA binding through the C-terminus gained importance
The effects of p53 gene inactivation on mutant proteome expression in a human melanoma cell model:Running Title : An isogenic p53-null melanoma cell model for use in mutant proteomics
HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells
Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong persistence. Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations. Among these, the deletion of the UL/bâ domain is associated with loss of virulence. In a screen of UL/bâ, we identified pUL135 as a protein responsible for the characteristic cytopathic effect of clinical HCMV strains that also protected from natural killer (NK) and TÂ cell attack. pUL135 interacted directly with abl interactor 1 (ABI1) and ABI2 to recruit the WAVE2 regulatory complex to the plasma membrane, remodel the actin cytoskeleton and dramatically reduce the efficiency of immune synapse (IS) formation. An intimate association between F-actin filaments in target cells and the IS was dispelled by pUL135 expression. Thus, F-actin in target cells plays a critical role in synaptogenesis, and this can be exploited by pathogens to protect against cytotoxic immune effector cells. An independent interaction between pUL135 and talin disrupted cell contacts with the extracellular matrix
The MDM2 ligand Nutlin-3 differentially alters expression of the immune blockade receptors PD-L1 and CD276
âNp63/p40 correlates with the location and phenotype of basal/mesenchymal cancer stem-like cells in human ER+ and HER2+ breast cancers
ÎNp63, also known as p40, regulates stemness of normal mammary gland epithelium and provides stem cell characteristics in basal and HER2âdriven murine breast cancer models. Whilst ÎNp63/p40 is a characteristic feature of normal basal cells and basalâtype tripleânegative breast cancer, some receptorâpositive breast cancers express ÎNp63/p40 and its overexpression imparts cancer stem cellâlike properties in ER+ cell lines. However, the incidence of ER+ and HER2+ tumours that express ÎNp63/p40 is unclear and the phenotype of ÎNp63/p40+ cells in these tumours remains uncertain. Using immunohistochemistry with p63 isoformâspecific antibodies, we identified a ÎNp63/p40+ tumour cell subpopulation in 100 of 173 (58%) nonâtriple negative breast cancers and the presence of this population associated with improved survival in patients with ERâ/HER2+ tumours (p = 0.006). Furthermore, 41% of ER+/PR+ and/or HER2+ locally metastatic breast cancers expressed ÎNp63/p40, and these cells commonly accounted for <1% of the metastatic tumour cell population that localised to the tumour/stroma interface, exhibited an undifferentiated phenotype and were CD44+/ALDHâ. In vitro studies revealed that MCF7 and T47D (ER+) and BTâ474 (HER2+) breast cancer cell lines similarly contained a small subpopulation of ÎNp63/p40+ cells that increased in mammospheres. In vivo, MCF7 xenografts contained ÎNp63/p40+ cells with a similar phenotype to primary ER+ cancers. Consistent with tumour samples, these cells also showed a distinct location at the tumour/stroma interface, suggesting a role for paracrine factors in the induction or maintenance of ÎNp63/p40. Thus, ÎNp63/p40 is commonly present in a small population of tumour cells with a distinct phenotype and location in ER+ and/or HER2+ human breast cancers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153532/1/cjp2149_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153532/2/cjp2149.pd
Hydrogen Deuterium Exchange Mass Spectrometry identifies the dominant paratope in CD20 antigen binding to the NCD1.2 monoclonal antibody
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