Theoretical and Numerical Analysis of an Optimal Execution Problem with Uncertain Market Impact

This paper is a continuation of Ishitani and Kato (2015), in which we derived a continuous-time value function corresponding to an optimal execution problem with uncertain market impact as the limit of a discrete-time value function. Here, we investigate some properties of the derived value function. In particular, we show that the function is continuous and has the semigroup property, which is strongly related to the Hamilton-Jacobi-Bellman quasi-variational inequality. Moreover, we show that noise in market impact causes risk-neutral assessment to underestimate the impact cost. We also study typical examples under a log-linear/quadratic market impact function with Gamma-distributed noise.Comment: 24 pages, 14 figures. Continuation of the paper arXiv:1301.648

Technologies, Policies, and Measures for Mitigating Climate Change

This Technical Paper provides an overview and analysis of technologies and measures to limit and reduce greenhouse gas (GHG) emissions and to enhance GHG sinks under the United Nations Framework Convention on Climate Change (FCCC). The paper focuses on technologies and measures for the countries listed in Annex I of the FCCC, while noting information as appropriate for use by non- Annex I countries. Technologies and measures are examined over three time periods -- with a focus on the short term (present to 2010) and the medium term (2010-2020), but also including discussion of longer-term (e.g., 2050) possibilities and opportunities. For this analysis, the authors draw on materials used to prepare the IPCC Second Assessment Report (SAR) and previous IPCC assessments and reports. The Technical Paper includes discussions of technologies and measures that can be adopted in three energy end-use sectors (commercial/residential/institutional buildings, transportation, and industry), as well as in the energy supply sector and the agriculture, forestry, and waste management sectors. Broader measures affecting national economies are discussed in a final section on economic instruments. A range of potential measures are analyzed, including market-based programs; voluntary agreements; regulatory measures; research, development, and demonstration (RD&D); taxes on GHG emissions; and emissions permits/quotas. It should be noted that the choice of instruments could have economic impacts on other countries. The paper identifies and evaluates different options on the basis of three criteria. Because of the difficulty of estimating the economic and market potential (see Box 1) of different technologies and the effectiveness of different measures in achieving emission reduction objectives, and because of the danger of double-counting the results achieved by measures that tap the same technical potentials, the paper does not estimate total global emissions reductions. Nor does the paper recommend adoption of any particular approaches

Recognition of the Major Histocompatibility Complex (MHC) class Ib molecule H2-Q10 by the natural killer cell receptor Ly49C

Murine natural killer (NK) cells are regulated by the interaction of Ly49 receptors with major histocompatibility complex class I molecules (MHC-I). Although the ligands for inhibitory Ly49 were considered to be restricted to classical MHC (MHC-Ia), we have shown that the non-classical MHC molecule (MHC-Ib) H2-M3 was a ligand for the inhibitory Ly49A. Here we establish that another MHC-Ib, H2-Q10, is a bona fide ligand for the inhibitory Ly49C receptor. H2-Q10 bound to Ly49C with a marginally lower affinity (∼5 μm) than that observed between Ly49C and MHC-Ia (H-2Kb/H-2Dd, both ∼1 μm), and this recognition could be prevented by cis interactions with H-2K in situ. To understand the molecular details underpinning Ly49·MHC-Ib recognition, we determined the crystal structures of H2-Q10 and Ly49C bound H2-Q10. Unliganded H2-Q10 adopted a classical MHC-I fold and possessed a peptide-binding groove that exhibited features similar to those found in MHC-Ia, explaining the diverse peptide binding repertoire of H2-Q10. Ly49C bound to H2-Q10 underneath the peptide binding platform to a region that encompassed residues from the α1, α2, and α3 domains, as well as the associated β2-microglobulin subunit. This docking mode was conserved with that previously observed for Ly49C·H-2Kb. Indeed, structure-guided mutation of Ly49C indicated that Ly49C·H2-Q10 and Ly49C·H-2Kb possess similar energetic footprints focused around residues located within the Ly49C β4-stand and L5 loop, which contact the underside of the peptide-binding platform floor. Our data provide a structural basis for Ly49·MHC-Ib recognition and demonstrate that MHC-Ib represent an extended family of ligands for Ly49 molecules

The role of hybrid ubiquitin chains in the MyD88 and other innate immune signalling pathways

The adaptor protein MyD88 is required for signal transmission by Toll-like Receptors (TLRs) and receptors of the interleukin 1 (IL-1) family of cytokines. MyD88 signalling triggers the formation of Lys63-linked and Met1-linked ubiquitin (K63-Ub, M1-Ub) chains within minutes. The K63-Ub chains, which are formed by the E3 ubiquitin ligases TRAF6, Pellino1 and Pellino2, activate TAK1, the master kinase that switches on mitogen-activated protein (MAP) kinase cascades and initiates activation of the canonical IκB kinase (IKK) complex. The M1-Ub chains, which are formed by the Linear Ubiquitin chain Assembly Complex (LUBAC), bind to the NEMO component of the IKK complex and are required for TAK1 to activate IKKs, but not MAP kinases. An essential E3 ligase-independent role of TRAF6 is to recruit LUBAC into the MyD88 signalling complex, where it recognises preformed K63-Ub chains attached to protein components of these complexes, such as IRAK1, producing ubiquitin chains containing both types of linkage, termed K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids, which is a feature of several innate immune signalling pathways, permits the co-recruitment of proteins that interact with either K63-Ub or M1-Ub chains. Two likely roles for K63/M1- Ub hybrids are to facilitate the TAK1-dependent activation of the IKK complex and to prevent the hyper-activation of these kinases by recruiting A20 and A20-binding inhibitor of NF-κB1 (ABIN1). These proteins restrict activation of the TAK1 and IKK complexes, probably by competing with them for binding to K63/M1-Ub hybrids. The formation of K63/M1-Ub hybrids may also regulate the rate at which the ubiquitin linkages in these chains are hydrolysed. The IKK-catalysed phosphorylation of some of its substrates permits their recognition by the E3 ligase SCFβ TRCP, leading to their Lys48-linked ubiquitylation and proteasomal degradation. Innate immune signalling is therefore controlled by the formation and destruction of three different types of ubiquitin linkage

A Single-Institution Review of Portosystemic Shunts in Children: An Ongoing Discussion

Purpose. Review the safety and long-term success with portosystemic shunts in children at a single institution. Methods. An IRB-approved, retrospective chart review of all children ages 19 and undergoing surgical portosystemic shunt from January 1990–September 2008. Results. Ten patients were identified, 8 females and 2 males, with a mean age of 15 years (range 5–19 years). Primary diagnoses were congenital hepatic fibrosis (5), hepatic vein thrombosis (2), portal vein thrombosis (2), and cystic fibrosis (1). Primary indications were repeated variceal bleeding (6), symptomatic hypersplenism (2), and significant liver dysfunction (2). Procedures performed were distal splenorenal bypass (4), side-to-side portocaval shunt (3), proximal splenorenal shunt (2), and an interposition H-graft portocaval shunt (1). There was no perioperative mortality and only minor morbidity. Seventy percent of patients had improvement of their symptoms. Eighty percent of shunts remained patent. Two were occluded at a median follow-up of 50 months (range 0.5–13.16 years). Two patients underwent subsequent liver transplantation. Two patients died at 0.5 and 12.8 years postoperatively, one from multisystem failure with cystic fibrosis and one from post-operative transplant complications. Conclusions. The need for portosystemic shunts in children is rare. However, in the era of liver transplantation, portosystemic shunts in selected patients with well-preserved liver function remains important. We conclude that portosystemic shunts are safe and efficacious in the control of variceal hemorrhage and symptoms related to hypersplenism

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060

Structural insights into RNA-dependent eukaryal and archaeal selenocysteine formation

The micronutrient selenium is present in proteins as selenocysteine (Sec). In eukaryotes and archaea, Sec is formed in a tRNA-dependent conversion of O-phosphoserine (Sep) by O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS). Here, we present the crystal structure of Methanococcus maripaludis SepSecS complexed with PLP at 2.5 Å resolution. SepSecS, a member of the Fold Type I PLP enzyme family, forms an (α2)2 homotetramer through its N-terminal extension. The active site lies on the dimer interface with each monomer contributing essential residues. In contrast to other Fold Type I PLP enzymes, Asn247 in SepSecS replaces the conserved Asp in binding the pyridinium nitrogen of PLP. A structural comparison with Escherichia coli selenocysteine lyase allowed construction of a model of Sep binding to the SepSecS catalytic site. Mutations of three conserved active site arginines (Arg72, Arg94, Arg307), protruding from the neighboring subunit, led to loss of in vivo and in vitro activity. The lack of active site cysteines demonstrates that a perselenide is not involved in SepSecS-catalyzed Sec formation; instead, the conserved arginines may facilitate the selenation reaction. Structural phylogeny shows that SepSecS evolved early in the history of PLP enzymes, and indicates that tRNA-dependent Sec formation is a primordial process

Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation

Members of the leucine-rich repeat-containing 8 (LRRC8) protein family, composed of the five LRRC8A-E isoforms, are pore-forming components of the volume-regulated anion channel (VRAC). LRRC8A and at least one of the other LRRC8 isoforms assemble into heteromers to generate VRAC transport activities. Despite the availability of the LRRC8A structures, the structural basis of how LRRC8 isoforms other than LRRC8A contribute to the functional diversity of VRAC has remained elusive. Here, we present the structure of the human LRRC8D isoform, which enables the permeation of organic substrates through VRAC. The LRRC8D homo-hexamer structure displays a two-fold symmetric arrangement, and together with a structure-based electrophysiological analysis, revealed two key features. The pore constriction on the extracellular side is wider than that in the LRRC8A structures, which may explain the increased permeability of organic substrates. Furthermore, an N-terminal helix protrudes into the pore from the intracellular side and may be critical for gating

Impact of Virologic Breakthrough and HBIG Regimen on Hepatitis B Recurrence After Liver Transplantation

The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre-OLT and HBIG regimens post-OLT. Data from the NIH HBV-OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1–81) post-OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log 10 copies/mL, 74% were receiving antiviral therapy. Twenty-five patients experienced virologic breakthrough before OLT. Post-OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high-dose, IV low-dose, intramuscular low-dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre-OLT as long as rescue therapy is administered pre- and post-OLT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79358/1/j.1600-6143.2010.03046.x.pd