Shifting balance from neurodegeneration to regeneration of the brain: a novel therapeutic approach to Alzheimer's disease and related neurodegenerative conditions

Neurodegeneration is one of the biggest public health problems in modern society. Age-associated neurodegeneration, which is accelerated several-fold in Alzheimer＇s disease （AD） alone, is not only an enormous social and economic burden to the affected in- dividuals and their families, but is also a great scientific challenge. Currently 25-35 million people worldwide suffer from AD, the single largest cause of dementia in middle- to old-aged individuals. These numbers are projected to triple by 2050 if no treatment to prevent or reverse AD is developed.

Impacts of parameter uncertainties on deep chlorophyll maximum simulation revealed by the CNOP-P approach

Parameter uncertainty is a primary source of uncertainty in ocean ecosystem simulations.The deep chlorophyll maximum(DCM)is a ubiquitous ecological phenomenon in the ocean.Using a theoretical nutrients-phytoplankton model and the conditional nonlinear optimal perturbation approach related to parameters,we investigated the eff ects of parameter uncertainties on DCM simulations.First,the sensitivity of single parameter was analyzed.The sensitivity ranking of 10 parameters was obtained by analyzing the top four specifi cally.The most sensitive parameter(background turbidity)aff ects the light supply for DCM formation,whereas the other three parameters(nutrient content of phytoplankton,nutrient recycling coeffi cient,and vertical turbulent diff usivity)control nutrient supply.To explore the interactions among diff erent parameters,the sensitivity of multiple parameters was further studied by examining combinations of four parameters.The results show that background turbidity is replaced by the phytoplankton loss rate in the optimal parameter combination.In addition,we found that interactions among these parameters are responsible for such diff erences.Finally,we found that reducing the uncertainties of sensitive parameters could improve DCM simulations remarkably.Compared with the sensitive parameters identifi ed in the single parameter analysis,reducing parameter uncertainties in the optimal combination produced better model performance.This study shows the importance of nonlinear interactions among various parameters in identifying sensitive parameters.In the future,the conditional nonlinear optimal perturbation approach related to parameters,especially optimal parameter combinations,is expected to greatly improve DCM simulations in complex ecosystem models.

Ensemble Forecast for Tropical Cyclone Based on CNOP-P Method:A Case Study of WRF Model and Two Typhoons

In this paper,we set out to study the ensemble forecast for tropical cyclones.The case study is based on the Conditional Nonlinear Optimal Perturbation related to Parameter(CNOP-P)method and the WRF model to improve the prediction accuracy for track and intensity,and two different typhoons are selected as cases for analysis.We first select perturbed parameters in the YSU and WSM6 schemes,and then solve CNOP-Ps with simulated annealing algorithm for single parameters as well as the combination of multiple parameters.Finally,perturbations are imposed on default parameter values to generate the ensemble members.The whole proposed procedures are referred to as the PerturbedParameter Ensemble(PPE).We also conduct two experiments,which are control forecast and ensemble forecast,termed Ctrl and perturbed-physics ensemble(PPhyE)respectively,to demonstrate the performance for contrast.In the article,we compare the effects of three experiments on tropical cyclones in aspects of track and intensity,respectively.For track,the prediction errors of PPE are smaller.The ensemble mean of PPE filters the unpredictable situation and retains the reasonably predictable components of the ensemble members.As for intensity,ensemble mean values of the central minimum sea-level pressure and the central maximum wind speed are closer to CMA data during most of the simulation time.The predicted values of the PPE ensemble members included the intensity of CMA data when the typhoon made landfall.The PPE also shows uncertainty in the forecast.Moreover,we also analyze the track and intensity from physical variable fields of PPE.Experiment results show PPE outperforms the other two benchmarks in track and intensity prediction.