Data Assimilation Based on Sequential Monte Carlo Methods for Dynamic Data Driven Simulation

Simulation models are widely used for studying and predicting dynamic behaviors of complex systems. Inaccurate simulation results are often inevitable due to imperfect model and inaccurate inputs. With the advances of sensor technology, it is possible to collect large amount of real time observation data from real systems during simulations. This gives rise to a new paradigm of Dynamic Data Driven Simulation (DDDS) where a simulation system dynamically assimilates real time observation data into a running model to improve simulation results. Data assimilation for DDDS is a challenging task because sophisticated simulation models often have: 1) nonlinear non-Gaussian behavior 2) non-analytical expressions of involved probability density functions 3) high dimensional state space 4) high computation cost. Due to these properties, most existing data assimilation methods fail to effectively support data assimilation for DDDS in one way or another. This work develops algorithms and software to perform data assimilation for dynamic data driven simulation through non-parametric statistic inference based on sequential Monte Carlo (SMC) methods (also called particle filters). A bootstrap particle filter based data assimilation framework is firstly developed, where the proposal distribution is constructed from simulation models and statistical cores of noises. The bootstrap particle filter-based framework is relatively easy to implement. However, it is ineffective when the uncertainty of simulation models is much larger than the observation model (i.e. peaked likelihood) or when rare events happen. To improve the effectiveness of data assimilation, a new data assimilation framework, named as the SenSim framework, is then proposed, which has a more advanced proposal distribution that uses knowledge from both simulation models and sensor readings. Both the bootstrap particle filter-based framework and the SenSim framework are applied and evaluated in two case studies: wildfire spread simulation, and lane-based traffic simulation. Experimental results demonstrate the effectiveness of the proposed data assimilation methods. A software package is also created to encapsulate the different components of SMC methods for supporting data assimilation of general simulation models

Status of treatment strategies for Hutchinson-Gilford progeria syndrome with a focus on prelamin: A posttranslational modification.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature ageing and early death at a mean age of 14.7 years. At the molecular level, HGPS is caused by a de novo heterozygous mutation in LMNA, the gene encoding A-type lamins (mainly lamin A and C) and nuclear proteins, which have important cellular functions related to structure of the nuclear envelope. The LMNA mutation leads to the synthesis of a truncated prelamin A protein (called progerin), which cannot undergo normal processing to mature lamin A. In normal cells, prelamin A processing involves four posttranslational processing steps catalysed by four different enzymes. In HGPS cells, progerin accumulates as a farnesylated and methylated intermediate in the nuclear envelope where it is toxic and causes nuclear shape abnormalities and senescence. Numerous efforts have been made to target and reduce the toxicity of progerin, eliminate its synthesis and enhance its degradation, but as of today, only the use of farnesyltransferase inhibitors is approved for clinical use in HGPS patients. Here, we review the main current strategies that are being evaluated for treating HGPS, and we focus on efforts to target the posttranslational processing of progerin.Medicinska Forskningsrådet; Spanish Ministerio de Ciencia e Innovacion/ Agencia Estatal de Investigacion (AEI), Grant/Award Number: PID2019-108489RB-I00; Asociación Progeria Alexandra Peraut; Fundació la Marató TV3; European Regional Development Fund, Grant/Award Number: 202033; Swedish Medical Research Council; Progeria Research Foundation, Grant/Award Number: PRF 2019-77.S

Distribution and expression of SLC45A2 in the skin of sheep with different coat colors

Introduction. To investigate whether the membrane-associated transporter protein SLC45A2 is differentially expressed in the skin of sheep with different coat colors and to determine its correlation with coat color establishment in sheep. Material and methods. The expression of SLC45A2 in sheep skin samples with different coat colors was qualitatively and quantitatively analyzed by PCR amplification, RT-PCR, immunohistochemical staining and Western blotting. Results. A 193-bp SLC45A2 CDS sequence was successfully amplified from sheep skin samples with diverse coat colors. RT-PCR analysis revealed that SLC45A2 mRNA was expressed in all sheep skin samples tested, with relative expression levels of 512.74 ± 121.51 in black skin, 143.38 ± 119.31 and 1.36 ± 0.09 in black dots and white dots of piebald skin, respectively, and 1.02 ± 0.23 in white skin (p < 0.01**). Positive SLC45A2 protein bands were also detected in all skin samples by Western blot analysis, with relative expression levels of 0.85 ± ± 0.17** in black skin, 0.60 ± 0.05** and 0.34 ± 0.07 in black dots and white dots of piebald skin, respectively, and 0.20 ± 0.05 in white skin (p < 0.01**). Immunohistochemical assays revealed that SLC45A2 was expressed in the hair follicle matrix, the inner and outer root sheath, and the dermal papilla in the skin tissues with different coat colors. These patterns were quantified by optical density (OD) analysis, which yielded relative expression levels of 0.23 ± 0.11 in black skin, 0.19 ± 0.09 and 0.10 ± 0.03 in black dots and white dots of piebald skin, respectively, and 0.08 ± 0.01 in white skin (p < 0.05*). Conclusion. SLC45A2 is detectably expressed in sheep skin of all coat colors, though at significantly different levels. SLC45A2 may participate in the establishment of coat color by regulating the synthesis and trafficking of melanin.

Effect of dietary soy isoflavones on bone loss in ovariectomized rats

Purpose: To determine the effect of dietary soy isoflavone supplementation on bone loss in ovariectomized (OVX) rats.Methods: Forty-eight rats were assigned randomly to groups of OVX rats receiving soy isoflavones (20, 30, or 40 mg/kg of body weight daily), untreated OVX rats, or untreated intact rats. After 8 weeks, bone mineral density (BMD), mineral (Ca, P, Mn, Mg, and Zn) concentrations, and the expression of osteoblast-related genes were measured in femur tissue samples.Results: Eight weeks after OVX, there was a significant decrease in body weight, serum levels of osteocalcin, alkaline phosphatase, and oestradiol, BMD and mineral elements, as well as the expressions of Ctnnb1, Runx2, and Sp7 (all p < 0.05). These decreases were accompanied by reduced maximum load capacity of lumbar vertebrae. Daily supplementation with soy isoflavones dosedependently ameliorated these effects (all p < 0.05). Western blotting revealed that these effects were likely due to the reversal of the OVX-induced decrease in Notch1 proteins in bone and muscle.Conclusion: Soy isoflavone treatment represents a potential therapy for preventing postmenopausal bone loss by stimulating the Notch signalling.Keywords: Mineral elements, Alkaline phosphatase, Isoflavones, Bone loss, Notch pathwa

Analysis of appearance and active substances of Cordyceps militaris stromata on Antheraea pernyi pupae after optimization

Abstract Cordyceps militaris stromata on Antheraea pernyi pupae contain various active components, including cordycepin, adenosine, polysaccharides, and amino acids. Response surface methodology (RSM) was used to optimize the liquid culture conditions for C. militaris before its injection into A. pernyi pupae. A pH of 7.56 ± 0.02, a culture temperature of 20.5 ± 0.1 °C, a culture time of 110.5 ± 0.5 h, and a KH2PO4 concentration of 1.11 ± 0.01 g l−1 resulted in a C. militaris dry weight of 1.0226 g l−1. Experimental and predicted values were similar. The RSM optimization increased the number of fruiting bodies (17 to 22) and the average fruiting body length (6.9 cm to 7.9 cm), while also deepening the yellow colouration of the fruiting bodies. The adenosine, cordycepin, polysaccharide, carotenoid, and cordycepic acid contents increased by 12.52%, 7.67%, 3.03%, 14.93%, and 0.02%, respectively, after the optimization. However, the optimization did not alter the number of different amino acids (18) or the total amino acid content, even though the contents of certain amino acids changed somewhat. These finding may be useful for increasing the yield of C. militaris stromata on A. pernyi pupae, which will increase the profitability of C. militaris production

Skin transcriptome profiles associated with coat color in sheep

Background Previous molecular genetic studies of physiology and pigmentation of sheep skin have focused primarily on a limited number of genes and proteins. To identify additional genes that may play important roles in coat color regulation, Illumina sequencing technology was used to catalog global gene expression profiles in skin of sheep with white versus black coat color. Results There were 90,006 and 74,533 unigenes assembled from the reads obtained from white and black sheep skin, respectively. Genes encoding for the ribosomal proteins and keratin associated proteins were most highly expressed. A total of 2,235 known genes were differentially expressed in black versus white sheep skin, with 479 genes up-regulated and 1,756 genes down-regulated. A total of 845 novel genes were differentially expressed in black versus white sheep skin, consisting of 107 genes which were up-regulated (including 2 highly expressed genes exclusively expressed in black sheep skin) and 738 genes that were down-regulated. There was also a total of 49 known coat color genes expressed in sheep skin, from which 13 genes showed higher expression in black sheep skin. Many of these up-regulated genes, such as DCT, MATP, TYR and TYRP1, are members of the components of melanosomes and their precursor ontology category. Conclusion The white and black sheep skin transcriptome profiles obtained provide a valuable resource for future research to understand the network of gene expression controlling skin physiology and melanogenesis in sheep

A novel fusion protein consisting of anti-ANGPTL3 antibody and interleukin-22 ameliorates diabetic nephropathy in mice

IntroductionThe pathogenic mechanisms of diabetic nephropathy (DN) include podocyte injury, inflammatory responses and metabolic disorders. Although the antagonism of Angiopoietin-like protein 3 (ANGPTL3) can alleviate proteinuria symptoms by inhibiting the activation of integrin αvβ3 on the surface of podocytes, it can not impede other pathological processes, such as inflammatory responses and metabolic dysfunction of glucolipid. Interleukin-22 (IL-22) is considered to be a pivotal molecule involved in suppressing inflammatory responses, initiating regenerative repair, and regulating glucolipid metabolism.MethodsGenes encoding the mIL22IgG2aFc and two chains of anti-ANGPTL3 antibody and bifunctional protein were synthesized. Then, the DN mice were treated with intraperitoneal injection of normal saline, anti-ANGPTL3 (20 mg/kg), mIL22Fc (12 mg/kg) or anti-ANGPTL3 /IL22 (25.3 mg/kg) and irrigation of positive drug losartan (20mg/kg/d) twice a week for 8 weeks.ResultsIn this research, a novel bifunctional fusion protein (anti-ANGPTL3/IL22) formed by the fusion of IL-22 with the C-terminus of anti-ANGPTL3 antibody exhibited favorable stability and maintained the biological activity of anti-ANGPTL3 and IL-22, respectively. The fusion protein showed a more pronounced attenuation of proteinuria and improved dysfunction of glucolipid metabolism compared with mIL22Fc or anti-ANGPTL3. Our results also indicated that anti-ANGPTL3/IL22 intervention significantly alleviated renal fibrosis via inhibiting the expression of the inflammatory response-related protein nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) p65 and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Moreover, transcriptome analysis revealed the downregulation of signaling pathways associated with injury and dysfunction of the renal parenchymal cell indicating the possible protective mechanisms of anti-ANGPTL3/IL22 in DN.ConclusionCollectively, anti-ANGPTL3/IL22 bifunctional fusion protein can be a promising novel therapeutic strategy for DN by reducing podocyte injury, ameliorating inflammatory response, and enhancing renal tissue recovery

Exploiting Sensor Spatial Correlation for Dynamic Data Driven Simulation of Wildfire

Abstract—Dynamic data driven simulation based on Particle Filter (PF) has been shown to increase the accuracy of wildfire spread simulation by assimilating real time sensor data into the simulation. An important issue in dynamic data driven simulation is to utilize the sensor data in an efficient and effective manner. In our previous work, all sensor readings are treated as independent from each other; however, when sensors are randomly deployed, measurement data from nearby sensors could be correlated and thus biased observation could be incurred. This paper presents a spatial correlation model to exploit sensor correlations from sensor spatial locations and inter-distance, and integrate it as part of the PF measurement model. Experiment results show that with the information of sensor correlation simulation accuracy is further increased. Keywords-data assimilation; sensor spatial correlation; wildfir