Separating Skill from Luck in REIT Mutual Funds

This study uses a bootstrap methodology to explicitly distinguish between skill and luck for 80 Real Estate Investment Trust Mutual Funds in the period January 1995 to May 2008. The methodology successfully captures non-normality in the idiosyncratic risk of the funds. Using unconditional, beta conditional and alpha-beta conditional estimation models, the results indicate that all but one fund demonstrates poor skill. Tests of robustness show that this finding is largely invariant to REIT market conditions and maturity.

Assessment of the direct and indirect effects of MPP+ and dopamine on the human proteasome: implications for Parkinson's disease aetiology

Mitochondrial impairment, glutathione depletion and oxidative stress have been implicated in the pathogenesis of Parkinson’s disease (PD), linked recently to proteasomal dysfunction. Our study analysed how these factors influence the various activities of the proteasome in human SH-SY5Y neuroblastoma cells treated with the PD mimetics MPP+ (a complex 1 inhibitor) or dopamine. Treatment with these toxins led to dose- and time-dependent reductions in ATP and glutathione and also chymotrypsin-like and post-acidic like activities; trypsin-like activity was unaffected. Antioxidants blocked the effects of dopamine, but not MPP+, suggesting that oxidative stress was more important in the dopamine-mediated effects. With MPP+, ATP depletion was a prerequisite for loss of proteasomal activity. Thus in a dopaminergic neuron with complex 1 dysfunction both oxidative stress and ATP depletion will contribute independently to loss of proteasomal function. We show for the first time that addition of MPP+ or dopamine to purified samples of the human 20S proteasome also reduced proteasomal activities; with dopamine being most damaging. As with toxin-treated cells, chymotrypsin-like activity was most sensitive and trypsin-like activity the least sensitive. The observed differential sensitivity of the various proteasomal activities to PD mimetics is novel and its significance needs further study in human cells

Strong direct exchange coupling and single-molecule magnetism in indigo-bridged lanthanide dimers

The synthesis, structure and magnetic properties of the indigo-bridged dilanthanide complexes [{(η5-Cp*)2Ln}2(μ-ind)]n− with Ln = Gd or Dy and n = 0, 1 or 2 are described. The gadolinium complexes with n = 0 and 2 show typically weak exchange coupling, whereas the complex bridged by the radical [ind]3− ligand shows an unusually large coupling constant of J = −11 cm−1 (−2J formalism). The dysprosium complexes with n = 0 and 1 are single-molecule magnets in zero applied field, whereas the complex with n = 2 does not show slow magnetic relaxation

The Failure of Correlation to Describe Out-of-Plane Carbon=Carbon Bending

Carbon-carbon multiply bonded systems are improperly described with standard correlation methods and basis sets. For computations of vibrational modes, the out-of- plane bends can be reported as imaginary at worst or simply too low at best. Utilizing the simplest of aromatic structures (cyclopropenylidene) and various levels of theory, this work diagnoses this known behavior for the first time. A combined 1-particle and n-particle basis set effect conspire to produce these non-physical results. When moving from sp2 to sp3 hybridization in the carbon atoms, the larger number of basis functions overcorrects the energy. This is exacerbated by correlation methods. These allow for occupation of the and orbitals in the expanded wave function that combine with the hydrogen s orbitals. As a result, the improperly described space can be further and non-physically stabilized by post-Hartree-Fock correlation. This represents a fundamental problem with at least Hartree-Fock based methods of all flavors in describing carbon. Beyond being a flaw in quantum chemical theory, other repercussions will be present in computations regarding spectroscopy as well as energy and environmental studies where highly-accurate hydrocabon vibrational transitions or thermochemical data are needed

Contribution of Ref(2)p to regulation of Drosophila notum epithelial cell apico-basal polarity and phenotype

Cell polarity impacts on the maintenance of cell shape, cell-cell junction integrity, and protrusion formation and dynamics. Further, polarity additionally regulates cell movement, proliferation and differentiation. Conversely when cells lose their polarity they may be susceptible to dysfunction that may underlie degenerative disorders. Cell polarity and polarity protein complexes are highly conserved between different organisms from unicellular to multi-cellular, and from invertebrates to vertebrates. The focus of this study is the apico-basal polarity that is established normally in epithelial cells. p62 is a multifunctional scaffold protein which acts as a signalling hub for different pathways, and through interactions with the polarity protein aPKC we hypothesise that it may regulate apico-basal polarity. Ref(2)p is the Drosophila homologue of p62 and using Drosophila as a model system we are investigating the effects of Ref(2)p mutation or expression levels on apico-basal polarity, cell shape and protrusion dynamics in the epithelial cells of the dorsal thorax. Our preliminary data suggest that Ref(2)p is required to maintain normal cell size, cell-cell junctions and protrusion dynamics. Mechanistically, these phenotypes may be due to Ref(2)p’s interaction with polarity proteins or broader changes in Ref(2)p-mediated autophagy

Boning up on autophagy: the role of autophagy in skeletal biology.

From an evolutionary perspective, the major function of bone is to provide stable sites for muscle attachment and affording protection of vital organs, especially the heart and lungs (ribs) and spinal cord (vertebrae and intervertebral discs). However, bone has a considerable number of other functions: serving as a store for mineral ions, providing a site for blood cell synthesis and participating in a complex system-wide endocrine system. Not surprisingly, bone and cartilage cell homeostasis is tightly controlled, as is the maintenance of tissue structure and mass. While a great deal of new information is accruing concerning skeletal cell homeostasis, one relatively new observation is that the cells of bone (osteoclasts osteoblasts and osteocytes) and cartilage (chondrocytes) exhibit autophagy. The focus of this review is to examine the significance of this process in terms of the functional demands of the skeleton in health and during growth and to provide evidence that dysregulation of the autophagic response is involved in the pathogenesis of diseases of bone (Paget disease of bone) and cartilage (osteoarthritis and the mucopolysaccharidoses). Delineation of molecular changes in the autophagic process is uncovering new approaches for the treatment of diseases that affect the axial and appendicular skeleton

Repurposing cancer drugs, batimastat and marimastat, to inhibit the activity of a group I metalloprotease from the venom of the Western Diamondback rattlesnake, Crotalus atrox

Snakebite envenomation causes over 140,000 deaths every year predominantly in developing countries. As a result, it is one of the most lethal neglected tropical diseases. It is associated with an incredibly complex pathophysiology due to the vast number of unique toxins/proteins found in the venoms of diverse snake species found worldwide. Here, we report the purification and functional characteristics of a group I metalloprotease (CAMP-2) from the venom of the western diamondback rattlesnake, Crotalus atrox. Its sensitivity to matrix metalloprotease inhibitors (batimastat and marimastat) was established using specific in vitro experiments and in silico molecular docking analysis. CAMP-2 shows high sequence homology to atroxase from the venom of Crotalus atrox and exhibits collagenolytic, fibrinogenolytic and mild haemolytic activities. It exerts a mild inhibitory effect on agonist-induced platelet aggregation in the absence of plasma proteins. Its collagenolytic activity was completely inhibited by batimastat and marimastat. Zinc chloride also inhibits the collagenolytic activity of CAMP-2 by around 75% at 50 M, while it is partially potentiated by calcium chloride. Molecular docking studies demonstrate that batimastat and marimastat are able to bind strongly to the active site residues of CAMP-2. This study demonstrates the impact of matrix metalloprotease inhibitors in the modulation of a purified, group I metalloprotease activities in comparison to the whole venom. By improving our understanding of snake venom metalloproteases and their sensitivity to small molecule inhibitors, we can begin to develop novel and improved treatment strategies for snakebites

Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration

Study question: Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). Summary answer: Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. What is known already: Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. Study design, size, duration: A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. Participants/materials, setting, methods: In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. Main results and the role of chance: Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen a, b and g chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. Limitations, reasons for caution: The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. Wider implications of the findings: This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen a, b and g chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital