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Carver Egeberg posted an update 6 months, 3 weeks ago
In the era of technology and digitalization, the process industries are undergoing a digital transformation. The available process models, advance sensor technologies, enhanced computational power and a broad set of data analytical techniques enable solid bases for digital transformation in the biopharmaceutical industry.Among various data analytical techniques, the Kalman filter and its non-linear extensions are powerful tools for prediction of reliable process information. The combination of the Kalman filter with a virtual representation of the bioprocess, called digital twin, can provide real-time available process information. Incorporation of such variables in process operation can provide improved control performance with enhanced productivity.In this chapter the linear discrete Kalman filter, the extended Kalman filter and the unscented Kalman filters are described and a brief overview of applications of the Kalman filter and its non-linear extensions to bioreactors are presented. Furthermore, in a case study an example of the digital twin of the backer’s yeast batch cultivation process is presented. A digital twin of a bioreactor mirrors the processes of the real bioreactor. It contains the physical parts, the process model and prediction algorithm to predict the bioprocess variables. These values could be used for optimization and control of the process.The kappa opioid receptor (KOR) and its primary cognate ligands, the dynorphin peptides, are involved in diverse physiological processes. Disruptions to the KOR/dynorphin system have been found to likely play a role in multiple neuropsychological disorders, and hence KOR has emerged as a potential therapeutic target. Targeting KOR is complicated by close homology to the mu and delta opioid receptors (MOR and DOR), and many KOR ligands have at least moderate affinity to MOR and/or DOR. Animal models utilizing primarily very long-lasting selective KOR antagonists (>3 weeks following a single dose) have demonstrated that KOR antagonism attenuates certain anxiety-like and depression-like behaviors and blocks stress- and cue-induced reinstatement to drug seeking. Recently, relatively selective KOR antagonists with medication-like pharmacokinetic and pharmacodynamic properties and durations of action have been developed. One of these, JNJ-67953964 (also referred to as CERC-501, LY2456302, OpraKappa or Aticaprant) has been studied in humans, and shown to be safe, relatively KOR selective, and able to substantially attenuate binding of a KOR PET tracer to CNS localized KOR for greater than 24 h. While animal studies have indicated that compounds of this structural class are capable of normalizing withdrawal signs in animal models of cocaine and alcohol dependence and reducing cocaine and alcohol intake/seeking, additional studies are needed to determine the value of these second generation KOR antagonists in treating mood disorders and substance use disorders in humans.An in situ zeolite imidazole metal organic framework-90 (ZIF-90) modified capillary was prepared via the method of solvothermal synthesis. The coating of ZIF-90 was characterized by scanning electron microscopy, energy-dispersive X-ray spectrometry, and EOF. Capillary electrochromatography-based enantioseparation of the basic drugs propranolol (PRO), metoprolol (MET), atenolol (ATE), bisoprolol (BIS), and sotalol (SOT) was performed using lactobionic acid (LA) as the chiral selector. Compared with an uncoated silica capillary, the resolutions are greatly improved (PRO 1.40 → 3.23; MET 1.07 → 3.19; ATE 1.07 → 3.15; BIS 1.16 → 3.41; SOT 1.00 → 2.79). Effects of buffer pH values, proportion of organic additives, concentration of lactobionic acid, and applied voltage were investigated. Graphical abstract Schematic presentation of the preparation of zeolitic imidazolate framework-90 (ZIF-90) modified capillary (ZIF-90@capillary) for enantioseparation of drug enantiomers. The capillary was applied to construct capillary electrochromatography system with lactobionic acid for enantioseparation of basic chiral drugs.Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is caused by autoantibodies against the NR1 subunit of NMDAR. Recurrent cases combined with systemic lupus erythematosus (SLE) during pregnancy have not been reported. We report the case of a 23-year-old woman with a past history of SLE who presented with the characteristic features of anti-NMDAR encephalitis during both of her two pregnancies.Telomeric repeat binding factor 1 (TERF1) has been identified as a tumor suppressor gene in numerous types of human cancer. However, the expression of TERF1 and its mechanism in prostate cancer (PCa) remains unclear. The present study aimed to explore the expression and functions of TERF1 in PCa. The UALCAN database was used to analyze the differential expression of TERF1 between normal prostate tissue and primary PCa tissue. Cell apoptosis was analyzed by Annexin V/propidium iodide staining, and wound healing and Transwell assays were used to detect the cell migration and invasion abilities, respectively. click here The cell viability was analyzed using an MTT assay. Reverse transcription‑quantitative PCR and western blotting were used to analyze the mRNA and protein expression levels, respectively, of epithelial‑mesenchymal transition (EMT) markers following TERF1 knockdown in the PC3 cell line. A dual luciferase reporter assay was used to verify the association between TERF1 and microRNA (miR)‑155 predicted by bioinff the downregulated miR‑155 expression levels on the cellular behaviors of PC3 cells. In conclusion, TERF1, as a direct target of miR‑155, was discovered to be significantly downregulated in PCa, which was suggested to promote the migration and invasion of PCa via the EMT pathway.Oxyresveratrol (ORES) is a natural phenolic compound with multiple biological functions including antioxidation, anti‑inflammation and neuroprotection; however, the inhibitory effect of ORES on osteosarcoma remains largely unknown. The present study aimed to determine the effects of ORES on osteosarcoma cell Saos‑2. Cell Counting Kit‑8 assay was performed to detect Soas‑2 cell viability. Annexin‑FITC/PI staining and JC‑1 staining were used to measure cell apoptosis and the change of mitochondrial membrane potential. In addition, western blotting was conducted to determine the expression levels of apoptotic proteins and the phosphorylation of STAT3. It was found that ORES inhibited cell viability and induced apoptosis of osteosarcoma Saos‑2 cells in a concentration‑dependent manner. In addition, ORES increased the expression levels of apoptotic proteases caspase‑9 and caspase‑3 and reduced mitochondrial membrane potential. In response to ORES treatment, the expression levels of pro‑apoptotic proteins, Bad and Bax, were enhanced, whereas those of anti‑apoptotic proteins, Bcl‑2 and Bcl‑xL, were reduced.