WTI crude oil option implied VaR and CVaR: An empirical application

Using option market data we derive naturally forward‐looking, nonparametric and model‐free risk estimates, three desired characteristics hardly obtainable using historical returns. The option‐implied measures are only based on the first derivative of the option price with respect to the strike price, bypassing the difficult task of estimating the tail of the return distribution. We estimate and backtest the 1%, 2.5%, and 5% WTI crude oil futures option‐implied value at risk and conditional value at risk for the turbulent years 2011–2016 and for both tails of the distribution. Compared with risk estimations based on the filtered historical simulation methodology, our results show that the option‐implied risk metrics are valid alternatives to the statistically based historical models.     

Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice.

Pigmentary glaucoma is a significant cause of human blindness. Abnormally liberated iris pigment and cell debris enter the ocular drainage structures, leading to increased intraocular pressure (IOP) and glaucoma. DBA/2J (D2) mice develop a form of pigmentary glaucoma involving iris pigment dispersion (IPD) and iris stromal atrophy (ISA). Using high-resolution mapping techniques, sequencing and functional genetic tests, we show that IPD and ISA result from mutations in related genes encoding melanosomal proteins. IPD is caused by a premature stop codon mutation in the Gpnmb (GpnmbR150X) gene, as proved by the occurrence of IPD only in D2 mice that are homozygous with respect to GpnmbR150X; otherwise, similar D2 mice that are not homozygous for GpnmbR150X do not develop IPD. ISA is caused by the recessive Tyrp1b mutant allele and rescued by the transgenic introduction of wildtype Tyrp1. We hypothesize that IPD and ISA alter melanosomes, allowing toxic intermediates of pigment production to leak from melanosomes, causing iris disease and subsequent pigmentary glaucoma. This is supported by the rescue of IPD and ISA in D2 eyes with substantially decreased pigment production. These data indicate that pigment production and mutant melanosomal protein genes may contribute to human pigmentary glaucoma. The fact that hypopigmentation profoundly alleviates the D2 disease indicates that therapeutic strategies designed to decrease pigment production may be beneficial in human pigmentary glaucoma.     

Cell proliferation in mouse kidney by isoproterenol and the relationship with the thyroid function

Resumen En el presente trabajo se estudia el efecto del hipotiroidismo sobre la sintesis de DNA y proliferación celular renal estimuladas por isoproterenol. Se observa que la hormona tiroidea actúa como intermediario de las catecolaminas en el proceso de multiplicación celular. Se sugiere que la hormona tiroidea modula el efecto de catecolaminas aumentando la sensibilidad en el receptor. El aumento de la concentración de cAMP podría estar involucrado en este proceso.

---

---

This work was supported by a grant from the Consejo Nacional de Investigaciones Cientificas y Tecnicas, Rep. Argentina.     

<Emphasis Type="Bold">An Engineering View for Social Systems: Agency as an Operational Principle for Designing Higher Education Access Policies</Emphasis>

Access to higher education (HE) has been a persistent concern for governments, practitioners and researchers. Access to HE has been widely studied from scientific perspectives that have focussed on the factors that contribute to the problem; however, authors have highlighted the need for systemic and design perspectives on education systems. The need to connect research with policy remains one of the most challenging issues for education researchers. In view of this gap, this paper argues that engineering thinking and methods represent an opportunity for the design of HE access policies because engineering rationality (distinct from scientific rationalities) matches the concerns and goals of any policymaking attempt. Engineers design artefacts to meet particular goals. These artefacts are artificial systems, tangible or intangible, such as hammers, bridges or whole organizations, which are designed in particular contexts to meet precise goals. Policies for access to HE are good examples of artefacts that seek to fulfil specific needs under concrete constraints inherent to a country or region. More specifically, HE systems are social systems; in other words, they are created and recreated by the interactions and decisions of diverse actors. Hence, to change, redesign or improve such types of systems involves engineering their very interactions that are the outcomes of institutional and human actions. In particular, engineering design requires operational principles. Thus, we propose agency as a fundamental design concept for the improvement of HE systems, which opens new possibilities for a distinct type of policy-making that takes excellent advantage of what engineering can offer, while at the same time expanding on traditional expectations for engineering.     

Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells

Human induced pluripotent stem cells (iPSCs) represent a unique opportunity for regenerative medicine because they offer the prospect of generating unlimited quantities of cells for autologous transplantation, with potential application in treatments for a broad range of disorders. However, the use of human iPSCs in the context of genetically inherited human disease will require the correction of disease-causing mutations in a manner that is fully compatible with clinical applications. The methods currently available, such as homologous recombination, lack the necessary efficiency and also leave residual sequences in the targeted genome. Therefore, the development of new approaches to edit the mammalian genome is a prerequisite to delivering the clinical promise of human iPSCs. Here we show that a combination of zinc finger nucleases (ZFNs) and piggyBac technology in human iPSCs can achieve biallelic correction of a point mutation (Glu342Lys) in the α(1)-antitrypsin (A1AT, also known as SERPINA1) gene that is responsible for α(1)-antitrypsin deficiency. Genetic correction of human iPSCs restored the structure and function of A1AT in subsequently derived liver cells in vitro and in vivo. This approach is significantly more efficient than any other gene-targeting technology that is currently available and crucially prevents contamination of the host genome with residual non-human sequences. Our results provide the first proof of principle, to our knowledge, for the potential of combining human iPSCs with genetic correction to generate clinically relevant cells for autologous cell-based therapies.