A dynamic look-ahead Monte Carlo algorithm for pricing Bermudan options

Under the assumption of no-arbitrage, the pricing of American and Bermudan options can be casted into optimal stopping problems. We propose a new adaptive simulation based algorithm for the numerical solution of optimal stopping problems in discrete time. Our approach is to recursively compute the so-called continuation values. They are defined as regression functions of the cash flow, which would occur over a series of subsequent time periods, if the approximated optimal exercise strategy is applied. We use nonparametric least squares regression estimates to approximate the continuation values from a set of sample paths which we simulate from the underlying stochastic process. The parameters of the regression estimates and the regression problems are chosen in a data-dependent manner. We present results concerning the consistency and rate of convergence of the new algorithm. Finally, we illustrate its performance by pricing high-dimensional Bermudan basket options with strangle-spread payoff based on the average of the underlying assets.Comment: Published in at http://dx.doi.org/10.1214/105051607000000249 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Psychosocial interventions for pain management in older adults with dementia: A systematic review of randomized controlled trials

Aim: To assess the effectiveness of psychosocial interventions on pain in older adults living with dementia. Design: A systematic review with meta-analysis of randomized controlled trials. Data sources: Scopus, ProQuest, EBSCO (CINAHL and MEDLINE), PubMed, OVID (PsycINFO), Web of Science, and Cochrane Library were searched from their inception up to 2 May 2018. Review Methods: Risk of bias assessment and meta-analysis were conducted according to the Cochrane methods using RevMan 5.3 and findings were generated using the GRADE profiler software. Results: Eight studies met the inclusion criteria, but the quality of the current evidence was low to moderate. Results showed that psychosocial interventions significantly reduced the observational pain score and pain medication. Subgroup analyses indicated that sensory stimulation and individual interventions showed a reduction in observational pain in people with dementia. Conclusion: Findings suggest that psychosocial interventions may be potentially effective alternatives for pain management in people with dementia. However, caution is needed in interpreting these results due to limited studies, risk of bias and heterogeneity across studies. Furthermore, well-designed research is needed on psychosocial interventions to strengthen quality of pain management in people with dementia. Impact: This review synthesized current evidence using psychosocial interventions to manage pain in people with dementia. Findings suggest that psychosocial interventions may lead to a potential reduction in pain and pain medication in people with dementia. Healthcare providers may wish to integrate psychosocial interventions as part of the multimodal approach to the management of pain in people living with dementia.No Full Tex

Nrf2 and Parkinson’s Disease

Parkinson’s disease (PD) results from a complex interaction of environmental and genetic influences on a background of aging. Regardless of etiology, significant clinical advances rely on identifying the common biological pathways that underpin neuronal degeneration. Oxidative stress is consistently reported as a hallmark feature of PD. Recently, it has been demonstrated that Nrf2 modulation can protect neurons from parkinsonian agents and, in some instances, reverse motor symptoms of animal models. Furthermore, baseline aberrations of Nrf2 and its associated pathway have been reported in PD patients, and genetic variability—within and around the Nrf2 gene—may modify PD susceptibility and onset. Overall, Nrf2 dysregulation has been tentatively implicated in the pathogenesis of PD and may prove to be an effective therapeutic target

Bayesian inference of atomistic structure in functional materials

Tailoring the functional properties of advanced organic/inorganic heterogeneous devices to their intended technological applications requires knowledge and control of the microscopic structure inside the device. Atomistic quantum mechanical simulation methods deliver accurate energies and properties for individual configurations, however, finding the most favourable configurations remains computationally prohibitive. We propose a 'building block'-based Bayesian Optimisation Structure Search (BOSS) approach for addressing extended organic/inorganic interface problems and demonstrate its feasibility in a molecular surface adsorption study. In BOSS, a Bayesian model identifies material energy landscapes in an accelerated fashion from atomistic configurations sampled during active learning. This allowed us to identify several most favourable molecular adsorption configurations for C-60 on the (101) surface of TiO2 anatase and clarify the key molecule-surface interactions governing structural assembly. Inferred structures were in good agreement with detailed experimental images of this surface adsorbate, demonstrating good predictive power of BOSS and opening the route towards large-scale surface adsorption studies of molecular aggregates and films.Peer reviewe

Neuron-glia crosstalk mediate the neurotoxic effects of ketamine via extracellular vesicles

Background: General anesthetics (GA) are associated with neurodevelopmental abnormalities including cell death, cognitive and behavioral changes. There is now powerful evidence for non-cell autonomous mechanisms in almost every pathological condition in the brain, especially relevant to glial cells, mainly astrocytes and microglia, that exhibit structural and functional contacts with neurons. These interactions were recently reported to occur via the secretion of extracellular vesicles (EVs). Here, we employed primary human neural cells to analyze ketamine effects focusing on the functions of glial cells and their polarization/differentiation state. We also explored the roles of extracellular vesicles (EVs) and different components of the BDNF pathway. Methods: Ketamine effects were analyzed on human neuronal and glial cell proliferation and apoptosis and astrocytic (A1/A2 ) and microglial (M1/M2) cell activation were analyzed. The impact of the neuron-glial cell interactions in the neurotoxic effects of ketamine was analyzed using transwell co-cultures. The role of the brainderived neurotrophic factor (BDNF) pathway, was analyzed using RT-PCR, ELISA western blot and gene silencing. EVs secreted by ketamine-treated cells were isolated, characterized and analyzed for their effects in neuron-glia cell interactions. Data were analyzed using analysis of variance or a Student\u27s t test with correction for data sets with unequal variances. Results: Ketamine induced neuronal and oligodendrocytic cell apoptosis and promoted the expression of proinflammatory astrocytes (A1) and microglia (M1) phenotypes. Astrocytes and microglia enhanced the neurotoxic effects of ketamine on neuronal cells, whereas neurons increased oligodendrocyte cell death. Ketamine modulated different components in the BDNF pathway: decreasing BDNF secretion in neurons and astrocytes while increasing the expression of p75 in neurons and oligodendrocytes. In addition, ketamine treatment increased the lncRNA BDNF-AS levels and the secretion of pro-BDNF secretion. We found an important role of EVs secreted by ketamine-treated astrocytes in neuronal cell death by delivering BDNF-AS. Conclusions: Ketamine neurotoxicity involves both autonomous and non-cell autonomous mechanisms andomponents of the BDNF pathway expressed by neurons and glial cells represent major regulators of ketamine effects. We demonstrated for the first time a role of EVs as important mediators of ketamine effects by the delivery of specific non-coding RNAs. These results may contribute to a better understanding of cellular and molecular mechanisms underlying ketamine neurotoxic effects in humans and to the development of potential approaches to decrease its neurodevelopmental impact

The human papillomavirus E7 proteins associate with p190RhoGAP and alter its function

Using mass spectrometry, we identified p190RhoGAP (p190) as a binding partner of human papillomavirus 16 (HPV16) E7. p190 belongs to the GTPase activating protein (GAP) family and is one of the primary GAPs for RhoA. GAPs stimulate the intrinsic GTPase activity of the Rho proteins, leading to Rho inactivation and influencing numerous biological processes. RhoA is one of the best-characterized Rho proteins and is specifically involved in formation of focal adhesions and stress fibers, thereby regulating cell migration and cell spreading. Since this is the first report that E7 associates with p190, we carried out detailed interaction studies. We show that E7 proteins from other HPV types also bind p190. Furthermore, we found that conserved region 3 (CR3) of E7 and the middle domain of p190 are important for this interaction. More specifically, we identified two residues in CR3 of E7 that are necessary for p190 binding and used mutants of E7 with mutations of these residues to determine the biological consequences of the E7-p190 interaction. Our data suggest that the interaction of E7 with p190 dysregulates this GAP and alters the actin cytoskeleton. We also found that this interaction negatively regulates cell spreading on a fibronectin substrate and therefore likely contributes to important aspects of the HPV life cycle or HPV-induced tumorigenesis. © 2014, American Society for Microbiology

JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JIP1 scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDA receptor currents, increased NMDA receptor-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDA receptor-mediated synaptic plasticity and learning. SIGNIFICANCE STATEMENT: The results of this study demonstrate that JNK activation induced by the JIP1 scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study reports the identification of JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDA receptor-dependent synaptic plasticity and memory

Impact of dissolved oxygen during UV-irradiation on the chemical composition and function of CHO cell culture media

Ultraviolet (UV) irradiation is advantageous as a sterilization technique in the biopharmaceutical industry since it is capable of targeting non-enveloped viruses that are typically challenging to destroy, as well as smaller viruses that can be difficult to remove via conventional separation techniques. In this work, we investigated the influence of oxygen in the media during UV irradiation and characterized the effect on chemical composition using NMR and LC-MS, as well as the ability of the irradiated media to support cell culture. Chemically defined Chinese hamster ovary cell growth media was irradiated at high fluences in a continuous-flow UV reactor. UV-irradiation caused the depletion of pyridoxamine, pyridoxine, pyruvate, riboflavin, tryptophan, and tyrosine; and accumulation of acetate, formate, kynurenine, lumichrome, and sarcosine. Pyridoxamine was the only compound to undergo complete degradation within the fluences considered; complete depletion of pyridoxamine was observed at 200 mJ/cm2. Although in both oxygen- and nitrogen-saturated media, the cell culture performance was affected at fluences above 200 mJ/cm2, there was less of an impact on cell culture performance in the nitrogen-saturated media. Based on these results, minimization of oxygen in cell culture media prior to UV treatment is recommended to minimize the negative impact on sensitive media. © 2016 Meunier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited