The Incomplete Rosetta Stone Problem: Identifiability Results for Multi-View Nonlinear ICA

We consider the problem of recovering a common latent source with independent components from multiple views. This applies to settings in which a variable is measured with multiple experimental modalities, and where the goal is to synthesize the disparate measurements into a single unified representation. We consider the case that the observed views are a nonlinear mixing of component-wise corruptions of the sources. When the views are considered separately, this reduces to nonlinear Independent Component Analysis (ICA) for which it is provably impossible to undo the mixing. We present novel identifiability proofs that this is possible when the multiple views are considered jointly, showing that the mixing can theoretically be undone using function approximators such as deep neural networks. In contrast to known identifiability results for nonlinear ICA, we prove that independent latent sources with arbitrary mixing can be recovered as long as multiple, sufficiently different noisy views are available

On Maximum Entropy and Inference

Maximum Entropy is a powerful concept that entails a sharp separation between relevant and irrelevant variables. It is typically invoked in inference, once an assumption is made on what the relevant variables are, in order to estimate a model from data, that affords predictions on all other (dependent) variables. Conversely, maximum entropy can be invoked to retrieve the relevant variables (sufficient statistics) directly from the data, once a model is identified by Bayesian model selection. We explore this approach in the case of spin models with interactions of arbitrary order, and we discuss how relevant interactions can be inferred. In this perspective, the dimensionality of the inference problem is not set by the number of parameters in the model, but by the frequency distribution of the data. We illustrate the method showing its ability to recover the correct model in a few prototype cases and discuss its application on a real dataset.Comment: 16 pages, 4 figure

Loss of matrix metalloproteinase 2 in platelets reduces arterial thrombosis in vivo

Platelet activation at a site of vascular injury is essential for the arrest of bleeding; however, excessive platelet activation at a site of arterial damage can result in the unwarranted formation of arterial thrombi, precipitating acute myocardial infarction, or ischemic stroke. Activation of platelets beyond the purpose of hemostasis may occur when substances facilitating thrombus growth and stability accumulate. Human platelets contain matrix metalloproteinase 2 (MMP-2) and release it upon activation. Active MMP-2 amplifies the platelet aggregation response to several agonists by potentiating phosphatidylinositol 3-kinase activation. Using several in vivo thrombosis models, we show that the inactivation of the MMP-2 gene prevented thrombosis induced by weak, but not strong, stimuli in mice but produced only a moderate prolongation of the bleeding time. Moreover, using cross-transfusion experiments and wild-type/MMP-2−/− chimeric mice, we show that it is platelet-derived MMP-2 that facilitates thrombus formation. Finally, we show that platelets activated by a mild vascular damage induce thrombus formation at a downstream arterial injury site by releasing MMP-2. Thus, platelet-derived MMP-2 plays a crucial role in thrombus formation by amplifying the response of platelets to weak activating stimuli. These findings open new possibilities for the prevention of thrombosis by the development of MMP-2 inhibitors

Hyperglycemia-Induced Platelet Activation in Type 2 Diabetes Is Resistant to Aspirin but Not to a Nitric Oxide–Donating Agent

OBJECTIVE: Acute, short-term hyperglycemia enhances high shear stress-induced platelet activation in type 2 diabetes. Several observations suggest that platelets in type 2 diabetes are resistant to inhibition by aspirin. Our aim was to assess comparatively the effect of aspirin, a nitric oxide-donating agent (NCX 4016), their combination, or placebo on platelet activation induced by acute hyperglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a double-blind, placebo-controlled, randomized trial, 40 type 2 diabetic patients were allocated to 100 mg aspirin once daily, 800 mg NCX 4016 b.i.d., both of them, or placebo for 15 days. On day 15, 1 h after the morning dose, a 4-h hyperglycemic clamp (plasma glucose 13.9 mmol/l) was performed, and blood samples were collected before and immediately after it for platelet activation and cyclooxygenase-1 (COX-1) inhibition studies. RESULTS Acute hyperglycemia enhanced shear stress-induced platelet activation in placebo-treated patients (basal closure time 63 +/- 7.1 s, after hyperglycemia 49.5 +/- 1.4 s, -13.5 +/- 6.3 s, P < 0.048). Pretreatment with aspirin, despite full inhibition of platelet COX-1, did not prevent it (-12.7 +/- 6.9 s, NS vs. placebo). On the contrary, pretreatment with the NO donor NCX 4016, alone or in combination with aspirin, suppressed platelet activation induced by acute hyperglycemia (NCX 4016 +10.5 +/- 8.3 s; NCX 4016 plus aspirin: +12.0 +/- 10.7 s, P < 0.05 vs. placebo for both). Other parameters of shear stress-dependent platelet activation were also more inhibited by NCX 4016 than by aspirin, despite lesser inhibition of COX-1. CONCLUSIONS: Acute hyperglycemia-induced enhancement of platelet activation is resistant to aspirin; a NO-donating agent suppresses it. Therapeutic approaches aiming at a wider platelet inhibitory action than that exerted by aspirin may prove useful in patients with type 2 diabetes

Laboratory diagnosis and monitoring of desmopressin treatment of von Willebrand's disease by flow cytometry.

Background and Objectives von Willebrand's disease (VWD) is a heterogeneous bleeding disorder caused by quantitative or qualitative defects in von Willebrand factor (VWF). The diagnosis of VWD requires several laboratory tests. The aim of our study was to validate a flow cytometric test for the diagnosis of VWD and for monitoring the effects of desmopressin therapy.Design and Methods Flow cytometric analysis of ristocetin-induced VWF binding to platelets was performed in platelet-rich plasma (PRP) samples from patients with VWD and from control subjects and in samples of formalin-fixed platelets in the presence of plasma from patients or controls. In 12 VWD patients the test was conducted before and 1 hour after desmopressin infusion. Results were compared with VWF:Ag, VWF:RCo, VWF:CB, RIPA, PFA-100® and the skin bleeding time.Results Ristocetin-induced VWF binding to platelets, evaluated by both flow cytometry-based assays, was significantly reduced in patients with type1, 2A and 2M VWD as compared with that in healthy subjects. Patients with type 2B VWD showed reduced binding of VWF to formalin-fixed platelets, but increased binding to autologous platelets in PRP, similar to RIPA. VWF binding to platelets assessed by both flow cytometric assays correlated significantly with VWF:Ag, VWF:RCo, VWF:CB, RIPA, PFA100® and bleeding time. VWF binding to platelets increased after desmopressin infusion.Interpretation and Conclusions The measurement of ristocetin-induced binding of VWF to platelets by flow cytometry is a sensitive, simple and rapid test for the diagnosis of VWD and for the monitoring of the effects of desmopressin therapy. The flow cytometric assay performed with autologous platelets is useful in the identification of type 2B VWD patients

Learning Identifiable Representations: Independent Influences and Multiple Views

Intelligent systems, whether biological or artificial, perceive unstructured information from the world around them: deep neural networks designed for object recognition receive collections of pixels as inputs; living beings capture visual stimuli through photoreceptors that convert incoming light into electrical signals. Sophisticated signal processing is required to extract meaningful features (e.g., the position, dimension, and colour of objects in an image) from these inputs: this motivates the field of representation learning. But what features should be deemed meaningful, and how to learn them? We will approach these questions based on two metaphors. The first one is the cocktail-party problem, where a number of conversations happen in parallel in a room, and the task is to recover (or separate) the voices of the individual speakers from recorded mixtures—also termed blind source separation. The second one is what we call the independent-listeners problem: given two listeners in front of some loudspeakers, the question is whether, when processing what they hear, they will make the same information explicit, identifying similar constitutive elements. The notion of identifiability is crucial when studying these problems, as it specifies suitable technical assumptions under which representations are uniquely determined, up to tolerable ambiguities like latent source reordering. A key result of this theory is that, when the mixing is nonlinear, the model is provably non-identifiable. A first question is, therefore, under what additional assumptions (ideally as mild as possible) the problem becomes identifiable; a second one is, what algorithms can be used to estimate the model. The contributions presented in this thesis address these questions and revolve around two main principles. The first principle is to learn representation where the latent components influence the observations independently. Here the term “independently” is used in a non-statistical sense—which can be loosely thought of as absence of fine-tuning between distinct elements of a generative process. The second principle is that representations can be learned from paired observations or views, where mixtures of the same latent variables are observed, and they (or a subset thereof) are perturbed in one of the views—also termed multi-view setting. I will present work characterizing these two problem settings, studying their identifiability and proposing suitable estimation algorithms. Moreover, I will discuss how the success of popular representation learning methods may be explained in terms of the principles above and describe an application of the second principle to the statistical analysis of group studies in neuroimaging

Identidade organizacional e construção de sentidos em tomadas de decisão : um estudo de caso na Cooperativa Agroindustrial Consolata (COPACOL)

Orientador : Profa. Dra. Yara Lúcia Mazziotti BulgacovDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Sociais Aplicadas, Programa de Pós-Graduação em Administração. Defesa: Curitiba, 23/09/2011Inclui referênciasÁrea de concentração: Estratégia e analise organizacionalResumo: O estudo parte da preocupação em analisar como seu deu a construção de sentidos e suas implicações para a identidade organizacional em tomadas de decisão na Cooperativa Agroindustrial Consolata (COPACOL). Como guia teórico adotamos os delineamentos sobre identidade organizacional desenvolvido por Albert e Whetten (1985), Ciampa (1998) e Weick (1995), e sobre construção de sentidos, nas concepções de Weick (1995). Com o quadro teórico sobre construção de sentidos buscamos ver a influência da identidade nas tomadas de decisões, mas também como a decisão influencia a identidade da organização (MILLS, 2003). Quanto às escolhas metodológicas o delineamento de estudo foi abordagem qualitativa, com estratégia de pesquisa de estudo de caso, natureza descritiva, com um corte de tempo retrospectivo, unidade de análise nas decisões estratégicas realizadas pelos praticantes e, por fim, o nível de análise foi organizacional. Como método de coleta de dados, utilizamos primeiramente documentos, posteriormente entrevistas semiestruturado, também consideramos as conversas informais, observação não participante e vídeos. Para a análise utilizamos a análise de narrativas descrito em Gibbs (2009) e a proposta metodológica de apreensão de sentidos desenvolvida por Aguiar e Ozella (2006). Já quanto aos resultados iniciamos com a apresentação do caso, compreendendo sua história, área de atuação, estrutura funcional e suas ações sociais. Os resultados apontaram que a identidade organizacional da Copacol – Cooperativa Agroindustrial Consolata, sediada na cidade de Cafelândia, Oeste do Paraná, é de uma cooperativa que busca uma diversificação e verticalização nos negócios como um meio de responder as dificuldades encontradas pelos produtores, buscando com isso resultados econômicos e sociais para associados e toda a comunidade, principalmente para os mini e pequenos agricultores. Os resultados também mostraram que as principais decisões estratégicas que envolveram a Cooperativa são: a decisão de fundação, de não incorporação à COOPAVEL, filiação a SUDCOOP e COTRIGUAÇU, implantação do Complexo Integrado Avícola, entrada no setor supermercadista e, por fim, a implantação do Complexo Integrado de Peixe. Vimos também, com ajuda do quadro teórico sobre construção de sentidos, que identidade da Copacol, que está em contínua construção (contínuo), foi pontuada por eventos (sinais) - tais como a necessidade de energia elétrica, comercialização de grãos e intempéries climáticas; fazendo com que as pessoas agissem (construção na ação) - fundando a Copacol e desenvolvendo atividades de diversificação, gerando uma maior interação das pessoas (social) - por meio de reuniões e assembléias; com decisões tomadas não sobre escolhas ótimas, mas sim sendo suficientes (plausível) para com seus objetivos, dos quais seus resultados só podem ser percebidos posteriormente (retrospectivo). Por fim, com base na identidade organizacional e na construção de sentidos, reconhecemos que as decisões tomadas vão ao encontro da identidade organizacional do caso em estudo, assim tanto a identidade organizacional condicionou suas decisões como as decisões ajudaram a manter sua identidade.Abstract: The study begins with a concern to analyze the how was the sensemaking process and its implications for organizational identity in decision making at the Cooperativa Agroindustrial Consolata (COPACOL). As a guide we adopted the theoretical designs on organizational identity, developed by Albert and Whetten (1985), Ciampa (1998) and Weick (1995), and on the sensemaking process, in the conceptions of Weick (1995). With the process of sensemaking, we seek to influence the identity in the process of decision making, but also how the decision affects the identity of the organization (Mills, 2003). The study design was a qualitative approach to research strategy case study, descriptive, with a retrospective look of time, analysis unit in the strategic decisions made by practitioners and, ultimately, the level of analysis was in the organizational. As a method of data collection used firstly documents, later semistructured interviews, we also consider the informal conversations, non-participant observation and videos. For the analysis we used the narrative analysis described in Gibbs (2009) and methodological proposal apprehension of meaning developed by Aguiar and Ozella (2006). We begin our results with the presentation of the case, including its history, industry, structure and its social actions. The results indicated that the Copacol – Cooperativa Agroindustrial Consolata, organizational identity’s, at Cafelândia, west State of Paraná, is a cooperative that seeks a business diversification and vertical integration as a way of responding to the difficulties encountered by producers, thereby seeking economic and social outcomes for members and the community, especially for the mini and small farmers. The results also showed that the major strategic decisions involving the Cooperative are: the decision of the foundation, not incorporation into COOPAVEL, join the SUDCOOP and COTRIGUAÇU, implementation of the Integrated Complex of Chicken, entry into the supermarket sector and, finally, the implementation of Integrated Complex of Fish. We also saw that Copacol identity’s, which is in continuous construction (ongoing), was punctuated by events (cues) - such as the need for energy, commercialization grain and bad weather, causing people to act (enactment) - founding and developing diversification activities, generating greater interaction between people (social) - through meetings and assemblies, with decisions wasn’t about optimal choices, but was sufficient (plausible) to their goals, which their results can only be seen later (retrospective). Finally, based on organizational identity and the sensemaking process, we recognize that decisions taken are in line with the organizational identity of the case study, and both, organizational identity conditioned their decisions and the decisions have helped to maintain their identity