Yield curve forecast combinations based on bond portfolio performance

We propose an economically motivated forecast combination strategy in which model weights are related to portfolio returns obtained by a given forecast model. An empirical application based on an optimal mean–variance bond portfolio problem is used to highlight the advantages of the proposed approach with respect to combination methods based on statistical measures of forecast accuracy. We compute average net excess returns, standard deviation, and the Sharpe ratio of bond portfolios obtained with nine alternative yield curve specifications, as well as with 12 different forecast combination strategies. Return‐based forecast combination schemes clearly outperformed approaches based on statistical measures of forecast accuracy in terms of economic criteria. Moreover, return‐based approaches that dynamically select only the model with highest weight each period and discard all other models delivered even better results, evidencing not only the advantages of trimming forecast combinations but also the ability of the proposed approach to detect best‐performing models. To analyze the robustness of our results, different levels of risk aversion and a different dataset are considered.     

Colloidal carbon as a multilevel marker for experimental lesions

Summary The use of colloidal carbon for the anatomical marking of experimental lesions is proposed. Visualization of the lesion site may be readily performed through this procedure at the macroscopic, light microscopic, and ultrastructural levels in the same specimen. The chemical inertness of the marker and its relative permanency greatly add to its usefulness.     

Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease

More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models.     

Standards of evidence and causality in regulatory science: Risk and benefit assessment

In this paper we analyze the Russo-Williamson Thesis (RWT) as a standard of evidence in regulatory science, in risk as well as benefit assessment. In our analysis we take account of the recent controversies that have taken place in regulation with respect to the evidentiary requirements necessary for regulatory decision making. RWT's main point is that not only probabilistic but also mechanistic evidence is necessary for being able to infer the existence of causal links. We ask in which way RWT could have an impact upon current decision making about subjecting to regulation (or, to the contrary, leaving them unregulated) certain chemical substances, food stuffs, health claims, and other typical objects of regulation. We show that the application of RWT resolves some of the problems posed by current standards of evidence. RWT makes it possible to determine with higher accuracy if a particular substance should be subjected to regulation or not, even though under certain circumstances RWT itself may turn into a source of regulatory error. The adequacy of RWT as a standard of evidence depends on the precise manner of its application to regulation (particularly the consideration of mechanistic evidence as a complementary or necessary requirement), as well as the assessment of its non-epistemic consequences.     

Orchid bees (Apidae: Euglossini) in Cerrado remnants in northeast Brazil

There is a general lack of information concerning the diversity of bees belonging to the Euglossini tribe in Cerrado areas closest to the Brazilian Amazon. The state of Maranhão is situated in the northeast Brazilian Cerrado and has become the agricultural frontier of the country due to the advancement of monoculture and cattle farming. These activities have suppressed animal and plant populations in large areas of the Cerrado remnants, for which we have not yet obtained adequate scientific knowledge of local species. The objective of this study was to conduct a survey of Euglossini fauna in the northeast Cerrado. We evaluated the variation in species richness, composition and abundance between two distinct vegetation types: Cerrado sensu stricto (s.s.) and gallery forest. Male bees were captured from 7:00 a.m. to 5:00 p.m. over two consecutive days. Captures were carried out once per month from July 2012 to December 2013, using a combination of passive and active collection techniques, including baited traps, as well as a collector with an entomological net to collect bees near traps. We collected a total of 766 Euglossini males belonging to 24 species and five genera. The most abundant species were Eulaema bombiformis, Eulaema nigrita and Eulaema cingulata for the gallery forest site, whereas Eulaema nigrita, Euglossa melanotricha and Euglossa cordata were more abundant in the Cerrado s.s. The gallery forest yielded a higher number of male Euglossini (n = 503, 21 species) compared with the Cerrado s.s. (n = 263, 16 species). The presence of seven exclusive species in the gallery forest and three in the Cerrado s.s. indicated that both environments are important for the maintenance of Euglossini species in this region and highlight the increasing need for conservation programmes for the protection of Cerrado environments.     

The tortoise caterpillar: carnivory and armoured larval morphology of the metalmark butterfly Pachythone xanthe (Lepidoptera: Riodinidae)

ABSTRACT

The natural history and morphology of the later instars and pupa of the metalmark butterfly Pachythone xanthe H. Bates are described and illustrated for the first time. The caterpillars are myrmecophilous and carnivorous, feeding on scale insects (Hemiptera: Coccoidea) tended by Azteca cf. chartifex Forel (Formicidae: Dolichoderinae) ants and appear to be physically shielded from potential ant attacks by a carapace-like body that protects the head and appendages. In addition, the larvae present several types of specialised setae and ant-organs such as perforated cupola organs, glandular openings and functional tentacle nectary organs that may be related to appeasement of aggressive ant behaviour. Our results reveal the first detailed life cycle data for the Pachythonina subtribe and record a new independent origin of carnivory in Riodinidae.     

Intracellular NAD(H) levels control motility and invasion of glioma cells

Oncogenic transformation involves reprogramming of cell metabolism, whereby steady-state levels of intracellular NAD⁺ and NADH can undergo dramatic changes while ATP concentration is generally well maintained. Altered expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD⁺-salvage, accompanies the changes in NAD(H) during tumorigenesis. Here, we show by genetic and pharmacological inhibition of NAMPT in glioma cells that fluctuation in intracellular [NAD(H)] differentially affects cell growth and morphodynamics, with motility/invasion capacity showing the highest sensitivity to [NAD(H)] decrease. Extracellular supplementation of NAD⁺ or re-expression of NAMPT abolished the effects. The effects of NAD(H) decrease on cell motility appeared parallel coupled with diminished pyruvate-lactate conversion by lactate dehydrogenase (LDH) and with changes in intracellular and extracellular pH. The addition of lactic acid rescued and knockdown of LDH-A replicated the effects of [NAD(H)] on motility. Combined, our observations demonstrate that [NAD(H)] is an important metabolic component of cancer cell motility. Nutrient or drug-mediated modulation of NAD(H) levels may therefore represent a new option for blocking the invasive behavior of tumors.     

Animal experiments, vital forces and courtrooms: Mateu Orfila, François Magendie and the study of poisons in nineteenth-century France

The paper follows the lives of Mateu Orfila and Fran?ois Magendie in early nineteenth-century Paris, focusing on their common interest in poisons. The first part deals with the striking similarities of their early careers: their medical training, their popular private lectures, and their first publications. The next section explores their experimental work on poisons by analyzing their views on physical and vital forces in living organisms and their ideas about the significance of animal experiments in medicine. The last part describes their contrasting research on the absorption of poisons and the divergences in their approaches, methods, aims, standards of proof, and intended audiences. The analysis highlights the connections between nineteenth-century courtrooms and experimental laboratories, and shows how forensic practice not only prompted animal experimentation but also provided a substantial body of information and new research methods for dealing with major theoretical issues like the absorption of poisons.     

Variation de la chaleur spécifique du caoutchouc en fonction de l'élongation

Summary The variation of the specific heat with extension was determined for several samples of rubber. Non-vulcanized rubber shows no change of the specific heat when extended between 0 and 300%. For vulcanized rubber, there is a very slight increase of the specific heat, proportional to the extension. For some samples a knee in the curve appears at about 200% (at room temperature), the linear increase of specific heat being about ten times higher for higher extensions. It is supposed that this sudden increase is related to the «heat of crystallization».     

Sur le rôle possible des deux acides nucléiques dans la cellule vivante

Summary According to the writer's theory a great number of different desoxyribonucleic and ribonucleic acids exist in each cell: desoxyribonucleic acids in the nucleus (genes) and ribonucleic acids in the cytoplasm (microsomes). Through catalytic actions the macromolecular desoxyribonucleic acids govern the building of macromolecular ribonucleic acids, and, in turn, these control the production of cytoplasmic enzymes. In truth, the enzymic equipment results simultaneously from the effect of ribonucleic acids (catalytic action) and from the effect of substrates (mass action). This hypothesis explains cellular differentiation (multicellular organism) through constitutional variations of cytoplasmic ribonucleic acids. The writer's fundamental arguments come from the study of bacterial biology, especially from the study of mutations directed by principles of desoxyribonucleic nature.