Honey, I shrunk the sample covariance matrix

The central message of this paper is that nobody should be using the samplecovariance matrix for the purpose of portfolio optimization. It containsestimation error of the kind most likely to perturb a mean-varianceoptimizer. In its place, we suggest using the matrix obtained from thesample covariance matrix through a transformation called shrinkage. Thistends to pull the most extreme coefficients towards more central values,thereby systematically reducing estimation error where it matters most.Statistically, the challenge is to know the optimal shrinkage intensity,and we give the formula for that. Without changing any other step in theportfolio optimization process, we show on actual stock market data thatshrinkage reduces tracking error relative to a benchmark index, andsubstantially increases the realized information ratio of the activeportfolio manager.

Improved estimation of the covariance matrix of stock returns with an application to portofolio selection

This paper proposes to estimate the covariance matrix of stock returnsby an optimally weighted average of two existing estimators: the samplecovariance matrix and single-index covariance matrix. This method isgenerally known as shrinkage, and it is standard in decision theory andin empirical Bayesian statistics. Our shrinkage estimator can be seenas a way to account for extra-market covariance without having to specifyan arbitrary multi-factor structure. For NYSE and AMEX stock returns from1972 to 1995, it can be used to select portfolios with significantly lowerout-of-sample variance than a set of existing estimators, includingmulti-factor models.

CRIMINAL JUSTICE, VICTIM SUPPORT CENTERS, AND THE EMOTIONAL WELLBEING OF CRIME VICTIMS

SUMMARY (Français au-dessous)After the Second World War, the role of the victim in criminal conflict became an objectof interest for academics. But it was only in the 1960s that the importance of providingprotection and assistance to crime victims was highlighted in particular by the victims'movement, which inaugurated a new era of criminal justice in systems throughout the world.Moving beyond just the role of controlling crime and punishing the offender, the criminaljustice system also began to contribute to the victims' rehabilitation and to help the victim tomove on from the event psychologically and emotionally.Although some criminological research has been conducted, to date the effect that thecriminal justice system and victim support services have on the well-being of crime victims isstill uncertain.The current study sought to understand better the healing process of victims of crime, thepotential consequences of their participation on the criminal justice system, and the supportof victim centers. Moreover, it aimed to find out whether the existence of a Victim SupportAct would change the treatment that the victim receives in the criminal justice system. Thusthis research was conducted based in two countries - Switzerland and Brazil - where theoutcome of the victims' movement on the criminal justice system was different, as was theparticipation of the victim in the criminal justice system and the government's provision ofsupport.In order to conduct this research we employed the qualitative method, which is the mostefficient to gather sensitive information. Interviews with crime victims were the main sourceof information. Hearing observation and document research were used as complementarysources.The results of this research show that victims who have contact with the criminal justicesystem and victim services are not more likely to recover than those who had no contact. Thisis to say, the support offered has no major effects; the influence of the criminal justice systemand the victim support services in the emotional well-being of crime victims is rather neutral.However, considering that the sample is not representative, findings are not expected to begeneralized. Instead, findings may give insight to practitioners or to future criminal justicepolicy makers, suggesting what may work to improve the emotional well-being of crimevictims, as well as suggesting further studies.________________________________________________________________________________RÉSUMÉAprès la deuxième guerre mondiale, le rôle de la victime est devenu un objet d'intérêtpour les académiciens. Par contre, c'est seulement dans les années 60 que l'importance defournir de la protection et de l'appui aux victimes d'infractions a été accentuée, en particulierpar un mouvement ― victims' mouvement ―, qui a inauguré un nouveau temps dans lajustice pénale des systèmes juridiques du monde entier. A part la fonction de contrôler lecrime et de punir le délinquant, le système de justice pénale joue également un rôle dans laréhabilitation des victimes.Malgré la réalisation de plusieurs recherches criminologiques sur ce sujet, les effets que lesystème de la justice pénale et les centres d'aides aux victimes ont sur le bien-être desvictimes d'infractions est encore incertain.Ainsi cette étude cherche à mieux comprendre le processus de réhabilitation des victimesd'infraction, les conséquences de leur participation dans le système de justice pénale ainsique la portée de l'appui des centres d'aide. De plus, l'étude vise à découvrir si l'existenced'une loi d'aide aux victimes, particulièrement la Loi d'Aide aux Victimes d'InfractionsLAVI, est susceptible de changer le traitement que la victime reçoit dans le système de lajustice pénale. Pour cela, elle a été conduite dans deux pays - la Suisse et le Brésil - où lesconséquences du mouvement des victimes sur le système de la justice pénale a eu undéveloppement différent; il en va de même pour la participation de la victime dans laprocédure pénale et pour l'appui offert par l'Etat.Cette étude utilise la méthode qualitative qui est la plus efficace pour le recueild'informations sensibles. La plus importante source des données sont les interviews avec lesvictimes. L'observation des audiences et l'analyse de documents ont été utilisés en tant quesources d'information complementáire.Les résultats de cette recherche montrent que les victimes qui ont porté plainte et qui ontreçu l'appui des centres d'aides ne sont pas mieux rétablies que celles qui n'ont rien fait. C'estainsi que nous avons conclu que les services offerts n'ont aucune influence dans ce processus.Cependant, considérant que notre échantillon n'est pas représentatif, il n'est pas possible degénéraliser nos résultats. Néanmoins, ceux-ci peuvent éclairer les praticiens ou les futursdécideurs politiques de la justice pénale, suggérant ce qui peut fonctionner pour lerétablissement des victimes d'infraction, aussi bien que suggérer d'autres études.

Patterns of calcium-binding proteins support parallel and hierarchical organization of human auditory areas.

The human primary auditory cortex (AI) is surrounded by several other auditory areas, which can be identified by cyto-, myelo- and chemoarchitectonic criteria. We report here on the pattern of calcium-binding protein immunoreactivity within these areas. The supratemporal regions of four normal human brains (eight hemispheres) were processed histologically, and serial sections were stained for parvalbumin, calretinin or calbindin. Each calcium-binding protein yielded a specific pattern of labelling, which differed between auditory areas. In AI, defined as area TC [see C. von Economo and L. Horn (1930) Z. Ges. Neurol. Psychiatr.,130, 678-757], parvalbumin labelling was dark in layer IV; several parvalbumin-positive multipolar neurons were distributed in layers III and IV. Calbindin yielded dark labelling in layers I-III and V; it revealed numerous multipolar and pyramidal neurons in layers II and III. Calretinin labelling was lighter than that of parvalbumin or calbindin in AI; calretinin-positive bipolar and bitufted neurons were present in supragranular layers. In non-primary auditory areas, the intensity of labelling tended to become progressively lighter while moving away from AI, with qualitative differences between the cytoarchitectonically defined areas. In analogy to non-human primates, our results suggest differences in intrinsic organization between auditory areas that are compatible with parallel and hierarchical processing of auditory information.

Institutional support of the firm: A theory of business registries

Registering originative business contracts allows entrepreneurs and creditors to choose, andcourts to enforce market-friendly contract rules that protect innocent third parties whenadjudicating disputes on subsequent contracts. This reduces information asymmetry for thirdparties, which enhances impersonal trade. It does so without seriously weakening property rights,because it is rightholders who choose or activate the legal rules and can, therefore, minimize thecost of any possible weakening. Registries are essential not only to make the chosen rules publicbut to ensure rightholders commitment and avoid rule-gaming, because independent registriesmake rightholders choices verifiable by courts. The theory is supported by comparative andhistorical analyses.

Cape Verde - Diagnostic Trade Inttegration study Update - 2013

This Report is an update of the Cape Verde Diagnostic Trade Integration Study, titled Cape Verde’s Insertion into the Global Economy, produced and validated by the Government of Cape Verde in December 2008. Like the previous 2008 study, this Cape Verde Diagnostic Trade Integration Study Update provides a critical examination of the major institutional and production constraints that hinder Cape Verde’s ability to capitalize fully on the growth and welfare gains from its integration into the world economy. As a policy report, this study offers a set of priority policies and measures that can be implemented by both the public and private sectors to mitigate and surmount these supply side and institutional constraints. These recommendations are summarized in an Action Matrix. The Report is fruit of the generous support of the multi-donor program the Enhanced Integrated Framework (EIF). In every crisis there is an opportunity. Four years after the validation of the country’s first Diagnostic Trade Integration Study in 2008, Cape Verde finds itself in a drastically altered external environment. Cape Verde faces a worsened external environment than four years ago, when it was also traversing years of crisis as global food and energy prices escalated. Just as the country was validating its first trade study in late 2008, and celebrating its graduation from the list of Least Developed Countries, the onset of the deepest global recession in recent memory triggered an even worse external situation as the country’s principal source of markets, investments, remittances and aid, the Eurozone, unraveled economically and politically. As the Eurozone crisis spread, it was Cape Verde’s misfortune that the crisis contaminated precisely its biggest Eurozone partners and donors, such as Portugal, Spain and Italy. For such a highly dependent and exposed economy like that of Cape Verde, the deteriorating external sector has had a substantial negative impact on its macroeconomic performance. At the time of the validation workshop and graduation in 2008, no one could have foreseen or predicted the severity of the global crisis that followed. Despite traversing these years of adversity and external shocks, and suffering palpable setbacks, Cape Verde’s economy had proven surprisingly resilient, especially its principal sector, tourism. To its great credit, the country’s economic fundamentals are solid, and have been carefully and prudently managed over the years. For this reason alone, the country has thus far weathered the global and Eurozone crisis. Yet the near and medium term future remains uncertain. The country’s margin for maneuver has narrowed, its options far more limited, and hard choices lie ahead. Thus, there is no better time than now to analyze Cape Verde’s position in the global economy, and to examine the many challenges and opportunities it faces. The first diagnostic trade study outlined an ambitious agenda and set of policy strategies to enhance Cape Verde’s participation in the global economy. Written prior to the global crisis, the study did not, and could not, anticipate the scope and depth of the subsequent global and Eurozone crises. A few short months before the validation of the first DTIS Cape Verde joined the World Trade Organization (WTO). It has spent these four years adjusting to this status and implementing its commitments. At the same time, the country seeks greater economic integration with the European Union. Since 2008 the government has been investing heavily in the country’s economic infrastructure, focusing especially on fostering transformation in key sectors like agriculture, fisheries, tourism and creative industries. For these and many other reasons, it is both timely and urgent to review the road traveled since 2008. It is an opportune moment to reassess the country’s options, to rethink strategies, and to chart a new way forward that it is practical, implementable, and that builds on the country’s competitive advantages and current successes.

Experimental support for the make-up hypothesis in nestling tawny owls (Strix aluco)

Body condition can affect coloration of traits used in sexual selection and parent-offspring communication by inducing rapid internal changes in pigment concentration or aggregation, thickness of collagen arrays, or blood flux. The recent "makeup hypothesis" proposes an alternative honesty-reinforcing mechanism, with behaviorally mediated deposition of substances on body surfaces ("cosmetics") generating covariation between body condition and coloration. In birds, the uropygial gland wax is actively spread on feathers using the bill and changes in its deposition rate may cause rapid changes in bill and plumage coloration. Using tawny owl nestlings, we tested 3 predictions of the makeup hypothesis, namely that 1) quantity of preen wax deposited accounts for variation in bill coloration, 2) an immune stimulation (induced by injection of a lipopolysaccharide [LPS]) impairs uropygial gland wax production, and 3) different intensities of immune stimulations (strong vs. weak stimulations induced by injections of either LPS or phytohemagglutinin [PHA], respectively) and high versus low food availabilities result in different bill colorations. We found that 1) preen wax reduced bill brightness, 2) a challenge with LPS impaired uropygial gland development, and 3) nestlings challenged with LPS had a brighter bill than PHA-injected nestlings, whereas diet manipulation had no significant effect. Altogether, these results suggest that a strong immune challenge may decrease preen wax deposition rate on the bill of nestling birds, at least by impairing gland wax production, which causes a change in bill coloration. Our study therefore highlights that cosmetic colors might signal short-term variation in immunological status.

Insects associated with exposed decomposing bodies in the Colombian Andean Coffee Region

In Colombia, mainly classic forensic medicine methods were used to clarify crimes until 2004. However, other disciplines, including forensic entomology, started to be considered only after the New Accusatory System introduction in Bogotá and the Coffee Region in 2005. In order to provide tools for obtaining evidentiary material elements in judicial trials, it is presented here the succession of insects throughout the decomposition process of an exposed carcass of Sus scrofa Linnaeus 1758 (Suidae) and the Occurrence Matrix of colonizing species. This process was evaluated under ambient conditions in the Andean rural area of the city of Pereira, in the Mundo Nuevo district, located in a pre-montane Wet Forest area, from October to November 2006. A sampling period of 27 days and 3198 individuals were collected. We found these colonizing species in the following stages of decomposition: Lucilia eximia (Wiedemann, 1819) fresh; Hemilucilia semidiaphana (Rondani, 1850), Oxelytrum discicolle (Brullé, 1840), and Cochliomyia macellaria (Fabricius 1775) bloated; Chrysomya albiceps (Wiedemann 1819), Compsomyiops verena (Walker, 1849), Ophyra aenescens (Wiedemann, 1830) and Musca domestica Linnaeus, 1758 active; Fannia sp. advanced and Stearibia nigriceps (Meigen, 1826) remains. This study provides support tools to define the Post Mortem Interval that may be used by experts from government institutions and laboratories officially accredited.

Distributional patterns of the Neotropical genus Thecomyia Perty (Diptera, Sciomyzidae) and phylogenetic support

Distributional patterns of the Neotropical genus Thecomyia Perty (Diptera, Sciomyzidae) and phylogenetic support. The distributional pattern of the genus Thecomyia Perty, 1833 was defined using panbiogeographic tools, and analyzed based on the phylogeny of the group. This study sought to establish biogeographical homologies in the Neotropical region between different species of the genus, based on their distribution pattern and later corroboration through its phylogeny. Eight individual tracks and 16 generalized tracks were identified, established along nearly the entire swath of the Neotropics. Individual tracks are the basic units of a panbiogeographic study, and correspond to the hypothesis of minimum distribution of the organisms involved. The generalized tracks, obtained from the spatial congruence between two or more individual tracks, are important in the identification of smaller areas of endemism. Thus, we found evidence from the generalized tracks in support of previous classification for the Neotropical region. The Amazon domain is indicated as an area of outstanding importance in the diversification of the group, by the confluence of generalized tracks and biogeographic nodes in the region. Most of the generalized tracks and biogeographical nodes were congruent with the phylogenetic hypothesis of the genus, indicating support of the primary biogeographical homologies originally defined by the track analysis.

Association of nuclear matrix proteins with granular and threaded nuclear bodies in cell lines undergoing apoptosis.

The granules which appear in the nucleolar area in apoptotic HL-60 cells after camptothecin administration (Zweyer et al., Exp. Cell Res. 221,27-40, 1995) were detected also in several other cell lines induced to undergo apoptosis by different stimuli, such as MOLT-4 treated with staurosporine, K-562 incubated with actinomycin D, P-815 exposed to temperature causing heat shock, Jurkat cells treated with EGTA, U-937 growing in the presence of cycloheximide and tumor necrosis factor-alpha, and HeLa cells treated with etoposide. Using immunoelectron microscopy techniques, we demonstrate that, besides the already described nuclear matrix proteins p125 and p160, these granules contain other nucleoskeletal polypeptides such as proliferating cell nuclear antigen, a component of ribonucleoprotein particles, a 105-kDa constituent of nuclear spliceosomes, and the 240-kDa nuclear mitotic apparatus-associated protein referred to as NuMA. Moreover, we also found in the granules SAF-A/hn-RNP-U and SATB1 proteins, two polypeptides that have been reported to bind scaffold-associated regions DNA sequences in vitro, thus mediating the formation of looped DNA structures in vivo. Fibrillarin and coilin are not present in these granules or the PML protein. Thus, the granules seen during the apoptotic process apparently are different from coiled bodies or other types of nuclear bodies. Furthermore, these granules do not contain chromatin components such as histones and DNA. Last, Western blotting analysis revealed that nuclear matrix proteins present in the granules are not proteolytically degraded except for the NuMA polypeptide. We propose that these granules might represent aggregates of nuclear matrix proteins forming during the apoptotic process. Moreover, since the granules are present in several cell lines undergoing apoptosis, they could be considered a previously unrecognized morphological hallmark of the apoptotic process.

Circulating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome.

BACKGROUND AND OBJECTIVES:  Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients. METHODS:  The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species. RESULTS:  We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated mgp levels. phosphorylated mgp was also found to be present in the first ks patient originally described. CONCLUSIONS:  Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.

The alternatively spliced domain TnFnIII A1A2 of the extracellular matrix protein tenascin-C suppresses activation-induced T lymphocyte proliferation and cytokine production.

Several lines of evidences have suggested that T cell activation could be impaired in the tumor environment, a condition referred to as tumor-induced immunosuppression. We have previously shown that tenascin-C, an extracellular matrix protein highly expressed in the tumor stroma, inhibits T lymphocyte activation in vitro, raising the possibility that this molecule might contribute to tumor-induced immunosuppression in vivo. However, the region of the protein mediating this effect has remained elusive. Here we report the identification of the minimal region of tenascin-C that can inhibit T cell activation. Recombinant fragments corresponding to defined regions of the molecule were tested for their ability to inhibit in vitro activation of human peripheral blood T cells induced by anti-CD3 mAbs in combination with fibronectin or IL-2. A recombinant protein encompassing the alternatively spliced fibronectin type III domains of tenascin-C (TnFnIII A-D) vigorously inhibited both early and late lymphocyte activation events including activation-induced TCR/CD8 down-modulation, cytokine production, and DNA synthesis. In agreement with this, full length recombinant tenascin-C containing the alternatively spliced region suppressed T cell activation, whereas tenascin-C lacking this region did not. Using a series of smaller fragments and deletion mutants issued from this region, we have identified the TnFnIII A1A2 domain as the minimal region suppressing T cell activation. Single TnFnIII A1 or A2 domains were no longer inhibitory, while maximal inhibition required the presence of the TnFnIII A3 domain. Altogether, these data demonstrate that the TnFnIII A1A2 domain mediate the ability of tenascin-C to inhibit in vitro T cell activation and provide insights into the immunosuppressive activity of tenascin-C in vivo.

Amelioration of Duchenne muscular dystrophy in mdx mice by elimination of matrix-associated fibrin-driven inflammation coupled to the αMβ2 leukocyte integrin receptor

In Duchenne muscular dystrophy (DMD), a persistently altered and reorganizing extracellular matrix (ECM) within inflamed muscle promotes damage and dysfunction. However, the molecular determinants of the ECM that mediate inflammatory changes and faulty tissue reorganization remain poorly defined. Here, we show that fibrin deposition is a conspicuous consequence of muscle-vascular damage in dystrophic muscles of DMD patients and mdx mice and that elimination of fibrin(ogen) attenuated dystrophy progression in mdx mice. These benefits appear to be tied to: (i) a decrease in leukocyte integrin α(M)β(2)-mediated proinflammatory programs, thereby attenuating counterproductive inflammation and muscle degeneration; and (ii) a release of satellite cells from persistent inhibitory signals, thereby promoting regeneration. Remarkably, Fib-gamma(390-396A) (Fibγ(390-396A)) mice expressing a mutant form of fibrinogen with normal clotting function, but lacking the α(M)β(2) binding motif, ameliorated dystrophic pathology. Delivery of a fibrinogen/α(M)β(2) blocking peptide was similarly beneficial. Conversely, intramuscular fibrinogen delivery sufficed to induce inflammation and degeneration in fibrinogen-null mice. Thus, local fibrin(ogen) deposition drives dystrophic muscle inflammation and dysfunction, and disruption of fibrin(ogen)-α(M)β(2) interactions may provide a novel strategy for DMD treatment.