Indirect Inference for Time Series Using the Empirical Characteristic Function and Control Variates

We estimate the parameter of a stationary time series process by minimizing the integrated weighted mean squared error between the empirical and simulated characteristic function, when the true characteristic functions cannot be explicitly computed. Motivated by Indirect Inference, we use a Monte Carlo approximation of the characteristic function based on iid simulated blocks. As a classical variance reduction technique, we propose the use of control variates for reducing the variance of this Monte Carlo approximation. These two approximations yield two new estimators that are applicable to a large class of time series processes. We show consistency and asymptotic normality of the parameter estimators under strong mixing, moment conditions, and smoothness of the simulated blocks with respect to its parameter. In a simulation study we show the good performance of these new simulation based estimators, and the superiority of the control variates based estimator for Poisson driven time series of counts.Comment: 38 pages, 2 figure

Multi-criterion trade-offs and synergies for spatial conservation planning

1. Nature conservation policies need to deliver on multiple criteria, including genetic diversity, population viability and species richness as well as ecosystem services. The challenge of integrating these may be addressed by simulation modelling. 2. We used four models (MetaConnect, SPOMSIM, a community model and InVEST) to assess a variety of spatial habitat patterns with two levels of total habitat cover and realised at two spatial scales, exploring which landscape structures performed best according to five different criteria assessed for four functional types of organisms (approximately representing trees, butterflies, small mammals and birds). 3. The results display both synergies and trade-offs: population size and pollination services generally benefitted more from fragmentation than did genetic heterozygosity, and species richness more than allelic richness, although the latter two varied considerably among the functional types. 4. No single landscape performed best across all criteria, but averaging over criteria and functional types, overall performance improved with greater levels of habitat cover and intermediate fragmentation (or less fragmentation in cases with lower habitat cover). 5. Synthesis and applications. Different conservation objectives must be traded off, and considering only a single taxon or criterion may result in sub-optimal choices when planning reserve networks. Nevertheless, heterogeneous spatial patterns of habitat can provide reasonable compromises for multiple criteria

Hsc70 is a novel interactor of NF-kappaB p65 in living hippocampal neurons

Klenke C, Widera D, Engelen T, et al. Hsc70 is a novel interactor of NF-kappaB p65 in living hippocampal neurons. PLoS ONE. 2013;8(6): e65280.Signaling via NF-κB in neurons depends on complex formation with interactors such as dynein/dynactin motor complex and can be triggered by synaptic activation. However, so far a detailed interaction map for the neuronal NF-κB is missing. In this study we used mass spectrometry to identify novel interactors of NF-κB p65 within the brain. Hsc70 was identified as a novel neuronal interactor of NF-κB p65. In HEK293 cells, a direct physical interaction was shown by co-immunoprecipitation and verified via in situ proximity ligation in healthy rat neurons. Pharmacological blockade of Hsc70 by deoxyspergualin (DSG) strongly decreased nuclear translocation of NF-κB p65 and transcriptional activity shown by reporter gene assays in neurons after stimulation with glutamate. In addition, knock down of Hsc70 via siRNA significantly reduced neuronal NF-κB activity. Taken together these data provide evidence for Hsc70 as a novel neuronal interactor of NF-κB p65

Giant cell tumour of the distal radius/ulna: response to pre-operative treatment with short-term denosumab

Background Treatment of giant cell tumour of bone (GCTB) of the distal radius/ulna poses a surgical challenge, as complex reconstructive surgery may be required. This study evaluates the clinical, radiological and pathological findings in five cases of GCTB of the distal forearm where a 3 month course of denosumab was given prior to surgery. Methods Patients with biopsy proven distal forearm GCTB, treated for 3 months with denosumab, followed by salvage surgery (curettage and cementation) were included. Wrist pain and function were assessed using the modified Mayo Wrist Score (MMWS). Plain radiographs, MRI and PET/CT were performed pre-treatment and 2 months after initiation of denosumab therapy. Histological comparison was made between the original biopsy and surgical curettage specimens. Results Five patients with an average age of 25 years were included in the study. Improvement in wrist pain and function was seen in all patients with the average MMWS increasing from 30 pre-treatment to 85 at 3 months. Plain radiographs demonstrated marginal sclerosis in all cases with reconstitution of cortical and subarticular bone by 2 months; internal matrix sclerosis and osseous consolidation was more variable. Increased tumour heterogeneity and low signal were observed on T2-weighted MR images. PET/CT revealed a decrease in average SUV from 14.8 pre-treatment to 4.7 at 2 months. Histology showed disappearance of osteoclasts and increased fibro-osseous tissue. Denosumab treatment has the potential to facilitate salvage surgery, thus avoiding bone resection and graft reconstruction. A good outcome was achieved apart from local recurrence in one case. Follow up ranged from 17 to 54 months. Conclusion Distal forearm GCTB responds clinically, radiologically and histologically to a short course of pre-operative denosumab therapy, which has the potential to facilitate salvage surgery.</p