Clark-Ocone Formula for Generalized Functionals of Discrete-Time Normal Noises

The Clark-Ocone formula in the theory of discrete-time chaotic calculus holds only for square integrable functionals of discrete-time normal noises. In this paper, we aim at extending this formula to generalized functionals of discrete-time normal noises. Let $Z$ be a discrete-time normal noise that has the chaotic representation property. We first prove a result concerning the regularity of generalized functionals of $Z$. Then, we use the Fock transform to define some fundamental operators on generalized functionals of $Z$, and apply the above mentioned regularity result to prove the continuity of these operators. Finally, we establish the Clark-Ocone formula for generalized functionals of $Z$, and show its application results, which include the covariant identity result and the variant upper bound result for generalized functionals of $Z$

沈從文『邊城』論（四）

departmental bulletin pape

Genome-Wide Analysis of the PvHsp20 Family in Switchgrass: Motif, Genomic Organization, and Identification of Stress or Developmental-Related Hsp20s

Hsp20 proteins exist in all plant species and represent the most abundant small heat shock proteins (sHSPs) in plants. Hsp20s were known as chaperones maintaining cellular homeostasis during heat or other kinds of abiotic stresses. The objective of this study was to understand the phylogenetic relationship, genomic organization, diversification of motif modules, genome localization, expression profiles, and interaction networks of switchgrass (Panicum virgatum L.) Hsp20s (PvHsp20s). A total of 63 PvHsp20s were identified with their consensus as well as unique ACD motifs and gene structures analyzed. Most PvHsp20s (87%) were responsive to heat and other kinds of abiotic stresses. When under optimum growth condition, 38 of them displayed relative higher expression levels in inflorescence and seeds, suggesting their protective roles in the stress-sensitive reproductive organs. An in silico analysis of interaction network of PvHsp20 proteins further revealed potential interactive proteins, including stress-inducible ones in the network. Furthermore, PvHsp20 genes unevenly distributed in two sets of homeologous chromosomes, and only segmental duplication was found among the paralogous gene pairs, reflecting that the allotetraploidization of switchgrass allowed the accumulation of PvHsp20s that in turn facilitated its successful adaptation in hot and dry plateaus of North America. The present results provided an insight into PvHsp20s with an emphasis on the uniqueness of this gene family in switchgrass. Such information shall also be useful in functional studies of PvHsp20 genes and molecular breeding of switchgrass

Population pharmacokinetics of FCN-159, a MEK1/2 inhibitor, in adult patients with advanced melanoma and neurofibromatosis type 1 (NF1) and model informed dosing recommendations for NF1 pediatrics

Objective: FCN-159 is a highly active mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) inhibitor in patients with advanced melanoma and neurofibromatosis type 1 (NF1). We report a population pharmacokinetic (PopPK) model-based analysis of FCN-159 and its application to inform dose selection for NF1 pediatric trials.Methods: PK data collected from patients with advanced melanoma and NF1 in two clinical studies (NCT03932253 and NCT04954001) were analyzed using a non-linear mixed effects model. The adult model was adapted by incorporating allometric scaling for PK projection in 2–17 years old children. Pediatric exposure in different body surface area (BSA) bins was simulated to identify nominal doses (i.e., dose amounts given as integers) and BSA bin cutoffs to achieve exposure comparable to adults’ optimal exposure across the entire pediatric BSA range.Results: The final dataset consisted of 45 subjects with a total of 1030 PK samples. The PK of FCN-159 was well-described by a 2-compartment model with first-order linear elimination and delayed first-order absorption. Covariates, including BSA, age, sex, albumin, total protein, and cancer type, were identified as statistically significant predictors of FCN-159 disposition. Simulations based on the final model projected daily doses of 4 mg/m2 QD with optimized BSA bin cutoffs would allow fixed nominal doses within each bin and result in steady state exposure approximating the adult exposure observed at the recommended phase 2 dose (RP2D) in NF1, which is 8 mg QD.Conclusion: The developed population PK model adequately described the PK profile of FCN-159, which was adapted using allometric scaling to inform dose selection for NF1 pediatric trials

The role of gamma oscillations in central nervous system diseases: Mechanism and treatment

Gamma oscillation is the synchronization with a frequency of 30–90 Hz of neural oscillations, which are rhythmic electric processes of neuron groups in the brain. The inhibitory interneuron network is necessary for the production of gamma oscillations, but certain disruptions such as brain inflammation, oxidative stress, and metabolic imbalances can cause this network to malfunction. Gamma oscillations specifically control the connectivity between different brain regions, which is crucial for perception, movement, memory, and emotion. Studies have linked abnormal gamma oscillations to conditions of the central nervous system, including Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Evidence suggests that gamma entrainment using sensory stimuli (GENUS) provides significant neuroprotection. This review discusses the function of gamma oscillations in advanced brain activities from both a physiological and pathological standpoint, and it emphasizes gamma entrainment as a potential therapeutic approach for a range of neuropsychiatric diseases

Yap1 Hydroxylation Suppress Prostate Cancer Metastasis

View full abstracthttps://openworks.mdanderson.org/leading-edge/1031/thumbnail.jp

Associations between body mass index, weight control concerns and behaviors, and eating disorder symptoms among non-clinical Chinese adolescents

<p>Abstract</p> <p>Background</p> <p>Previous research with adolescents has shown associations of body weight, weight control concerns and behaviors with eating disorder symptoms, but it is unclear whether these associations are direct or whether a mediating effect exists. This study was conducted to investigate the prevalence of overweight and obesity, weight control concerns and behaviors, and eating disorder symptoms and to examine the mediating function of weight control concerns and behaviors on the relationship between body mass index (BMI) and eating disorder symptoms among non-clinical adolescents in China.</p> <p>Methods</p> <p>A cross-sectional survey among 2019 adolescent girls and 1525 adolescent boys in the 7th, 8th, 10th and 11th grades from seven cities in China was conducted. Information on weight control concerns and behaviors, and eating disorder symptoms (Eating Disorder Inventory-3) were collected from the adolescents using a self-administrated questionnaire.</p> <p>Results</p> <p>Weight control concerns and behaviors, and eating disorder symptoms were prevalent among the study population. A high proportion of adolescents scored at or above the threshold on the eating disorder inventory (EDI) subscale such as bulimia, interoceptive deficits, perfectionism, and maturity fears, which indicated eating disorder symptoms. High BMI was significantly associated with high score of drive for thinness, body dissatisfaction, bulimia, low self-esteem, interceptive deficits and maturity fears, so do perceived body weight status. Almost all weight control concerns and behaviors we investigated were significantly associated with high EDI subscale scores. When weight control concerns were added to the model, as shown in the model, the association between BMI and tendency of drive to thinness and bulimia was attenuated but still kept significant. The association between BMI and body dissatisfaction were no further significant. The association of BMI and drive for thinness, body dissatisfaction and bulimia was considerably weaker than when weight control behaviors were not included.</p> <p>Conclusions</p> <p>Weight control concerns and behaviors may be mediators of the association between BMI and eating disorder symptoms. Interpretation of these weight control problems is crucial to develop culturally appropriate educational and intervention programs for adolescents.</p