Visual pathways from the perspective of cost functions and multi-task deep neural networks

Vision research has been shaped by the seminal insight that we can understand the higher-tier visual cortex from the perspective of multiple functional pathways with different goals. In this paper, we try to give a computational account of the functional organization of this system by reasoning from the perspective of multi-task deep neural networks. Machine learning has shown that tasks become easier to solve when they are decomposed into subtasks with their own cost function. We hypothesize that the visual system optimizes multiple cost functions of unrelated tasks and this causes the emergence of a ventral pathway dedicated to vision for perception, and a dorsal pathway dedicated to vision for action. To evaluate the functional organization in multi-task deep neural networks, we propose a method that measures the contribution of a unit towards each task, applying it to two networks that have been trained on either two related or two unrelated tasks, using an identical stimulus set. Results show that the network trained on the unrelated tasks shows a decreasing degree of feature representation sharing towards higher-tier layers while the network trained on related tasks uniformly shows high degree of sharing. We conjecture that the method we propose can be used to analyze the anatomical and functional organization of the visual system and beyond. We predict that the degree to which tasks are related is a good descriptor of the degree to which they share downstream cortical-units.Comment: 16 pages, 5 figure

Treatment of phantom limb pain (PLP) based on augmented reality and gaming controlled by myoelectric pattern recognition: a case study of a chronic PLP patient

A variety of treatments have been historically used to alleviate phantom limb pain (PLP) with varying efficacy. Recently, virtual reality (VR) has been employed as a more sophisticated mirror therapy. Despite the advantages of VR over a conventional mirror, this approach has retained the use of the contralateral limb and is therefore restricted to unilateral amputees. Moreover, this strategy disregards the actual effort made by the patient to produce phantom motions. In this work, we investigate a treatment in which the virtual limb responds directly to myoelectric activity at the stump, while the illusion of a restored limb is enhanced through augmented reality (AR). Further, phantom motions are facilitated and encouraged through gaming. The proposed set of technologies was administered to a chronic PLP patient who has shown resistance to a variety of treatments (including mirror therapy) for 48 years. Individual and simultaneous phantom movements were predicted using myoelectric pattern recognition and were then used as input for VR and AR environments, as well as for a racing game. The sustained level of pain reported by the patient was gradually reduced to complete pain-free periods. The phantom posture initially reported as a strongly closed fist was gradually relaxed, interestingly resembling the neutral posture displayed by the virtual limb. The patient acquired the ability to freely move his phantom limb, and a telescopic effect was observed where the position of the phantom hand was restored to the anatomically correct distance. More importantly, the effect of the interventions was positively and noticeably perceived by the patient and his relatives. Despite the limitation of a single case study, the successful results of the proposed system in a patient for whom other medical and non-medical treatments have been ineffective justifies and motivates further investigation in a wider study

The molecular mechanisms underlying Inherited Growth Hormone Deficiency caused by cysteine mutation

Hintergrund: menschliches Wachstumshormon (hGH) enthält zwei Disulfidbrücken, die auch in anderen Spezies und in Prolaktin vorliegen. Es ist bekannt, dass hGH mit reduzierten und alkylierten Cysteinen, dadurch frei von Disulfidbrücken, fast die gleiche Bioaktivität wie Wildtyp hGH in Tiermodellen hat. Für diese Arbeit identifizierten wir Patienten mit angeborenem Wachstumshormonmangel und Mutationen der Cysteine im Wachstumshormonmolekül. Dann führten wir verschiedene Untersuchungen durch, um den jeweils zugrundeliegenden Mechanismus des Wachstumshormonmangels festzustellen. Zusätzlich untersuchten wir die Eigenschaften von Wachstumshormon ohne die Disulfidbrücken, ohne diese chemisch zu zerstören. Methoden: Plasmide mit hGH-cDNA, die der cDNA der betroffenen Individuen entspricht wurden mittels site-directed mutagenesis erzeugt. Um hGH frei von Cysteinen zu erzeugen ersetzten wir alle Cystein-codierenden Tripletts mit Alanin-codierenden Tripletts. Das mutierte Wachstumshormon wurde dann in Hypophysenzelllinien (AtT-20 und GC) exprimiert und analysiert mit Immunohistologie, Immunoassays und Western-Blots. hGH und hGH-Varianten exprimiert in CHO-K1 und HEK Zellen wurden aufgereinigt und die Bioaktivität in Zellproliferationsassays mit stabil mit dem Wachstumshormonrezeptor transfizierten Baf/B03 und einen trunkierten Prolaktinrezeptor exprimierenden Nb2 Zellen bestimmt. Rezeptorbindung der Mutanten wurde in Kompetitionsassays mit GHBP (growth-hormone binding protein) untersucht. Um die Stabilität der Mutanten zu untersuchen wurde die Resistenz gegen Trypsinverdau untersucht. Ergebnisse: Unsere umfangreiche Analyse identifizierte eine Vielzahl von Mechanismen, welche den Funktionsverlust durch die Cysteinmutationen bedingen. Manche hGH-Mutationen zeigten eine stark reduzierte Expression und Sekretion in Hypophysenzellen, andere hatten eine signifikant reduzierte Affinität zu dem Wachstumshormonrezeptor und eine reduzierte Bioaktivität. Bemerkenswerterweise bildet die hGH-C53S Variante disulfid-verbundene Dimere, die den Wachstumshormonrezeptor nicht binden oder aktivieren können. HGH ohne Disulfidbrücken hatte eine nur gering reduzierte Bioaktivität, allerdings eine deutliche verringerte Resistenz gegenüber Trypsinverdau. Schlussfolgerungen: Die Disulfidbrücken im Wachstumshormon sind nicht essentiell für die Bindung und Aktivierung des Wachstumshormonrezeptors, da die Bioaktivität ohne Disulfidbrücken nur gering reduziert ist. Sie sind allerdings entscheidend für die strukturelle Stabilisierung des Moleküls zum Schutz vor proteolytischen Abbau, was essentiell für die Aufrechterhaltung von ausreichenden hGH-Spiegeln in der Zirkulation im Organismus sein könnte. Die molekularen Mechanismen, die einen angeborenen Wachstumshormonmangel durch Cysteinmutationen im Wachstumshormon bedingen sind vielfältig und schließen die erstmals beschriebene Bildung eines bioinaktiven Wachstumshormondimers ein.Background: HGH contains two disulfide bridges, which are highly conserved among species and are also found in prolactin. It is well established, that hGH with reduced and alkylated cysteines, therefore devoid of disulfide bonds, has almost full wildtype bioactivity in animal models. For this study, we identified published cases of patients with Inherited Growth Hormone Deficiency and mutations of the cysteines in the hGH-molecule. We then conducted a number of studies to identify the underlying mechanisms. Additionally, we investigated the properties of hGH lacking all disulfide bonds, without disrupting them chemically. Methods: Plasmids containing hGH-cDNA matching the cDNA of the affected individuals were generated using site-directed mutagenesis. To generate hGH devoid of all disulfide bonds, we replaced all triplets encoding cysteine with triplets encoding alanine. Mutant growth hormone was then expressed in pituitary AtT20 as well as GC cells and analysed by immunohistology, immunoassay and western-blotting. hGH and hGH-variants generated in CHO-K1 and HEK cells were purified and used to examine their bioactivity in Baf-B03 cells stably expressing the GHR and Nb2 cells expressing a truncated prolactin receptor. Receptor binding of the mutants was studied in competition assays with GHBP (growth-hormone binding protein). To determine the stability of the mutants they were subjected to trypsin digestion. Results: Our extensive analysis revealed a variety of mechanisms which are responsible for the loss of biological function of the hGH variants. Some hGH-variants showed greatly reduced expression and secretion in pituitary cells, others showed significantly reduced affinity to the GHR and a reduction in bioactivity. Most strikingly, the hGH-C53S variant forms disulfide-linked dimers which are unable to bind and activate the GHR. HGH completely devoid of disulfide-bonds only had slightly diminished bioactivity compared to hGH-wt, however resistance to trypsin digestion was greatly reduced. Conclusions: The disulfide bonds in hGH are not essential to for binding to- and activate activation of the GHR, as the bioactivity of cysteine-free hGH is only moderately reduced. However, they these are structurally stabilizing the hormone by rescue from proteolytic cleavage, which might be essential for the maintainance of circulating hGH levels in vivo. The molecular mechanisms underlying Inherited Growth Hormone Deficiency caused by cysteine mutation are diverse and include the newly discovered formation of a bioinactive hGH-dimer

Pastagem de aveia e azevém na integraçao lavoura-pecuária : produçao de leite e características do solo

Orientador: Amadeu Bona FilhoDissertaçao (mestrado) - Universidade Federal do Paraná, Setor de Ciencias Agrárias, Programa de Pós-Graduaçao em Agronomia. Defesa: Curitiba, 2006Inclui bibliografiaÁrea de concentraçao: Produçao vegetalResumo: Com o objetivo de avaliar a viabilidade técnica da produção de leite pela substituição da ração a base de silagem e concentrado por pastagem, observando a quantidade e a qualidade do leite produzido, além de acompanhar o impacto que a presença dos animais teve sobre a densidade e a variação dos nutrientes fósforo, potássio e magnésio no solo, o presente trabalho foi conduzido no colégio agrícola Instituto Cristão, no município de Castro-PR., no período de 19/julho/2004 a 15/outubro/2004 em área de integração lavoura-pecuária, foi implantado no inverno pastagem de azevém e aveia (25 ha). Foram utilizadas 4 vacas "testers" por unidade experimental mais animais reguladores, com lotação contínua e utilização da metodologia "Put and Take". Os tratamentos foram: T1 - fornecimento de 100% da necessidade animal para mantença e produção de 28 Kg de leite por dia no cocho, na forma de silagem e concentrado, permitindo acesso a pastagem de aveia e azevém; T2 - fornecimento de 65% da necessidade animal para mantença e produção de 28 Kg de leite por dia no cocho, na forma de silagem e concentrado, mais acesso a área de pastagem de aveia e azevém; T3 - fornecimento de 45% da necessidade animal para mantença e produção de 28 Kg de leite por dia no cocho, na forma de silagem e concentrado, mais acesso a área de de pastagem de aveia e azevém; T4 - fornecimento de 25% da necessidade animal para mantença e produção de 28 Kg de leite por dia no cocho, na forma de silagem e concentrado, mais acesso a área de de pastagem de aveia e azevém, em um delineamento de blocos ao acaso com três repetições por tratamento, dividindo-se o tempo total do experimento em três períodos para análise das características animais e do leite. Não foi encontrado diferença estatística para a produção total de leite corrigida a 4% de gordura, assim como para o peso dos animais e os teores de gordura e de proteína e quantidade de gordura e proteína produzida. Houve melhoria da densidade do solo após pastejo, redução nos teores de fósforo e magnésio no solo e aumento nos teores de potássio no solo, sem, contudo, haver diferença entre os tratamentos.Abstract: The purpose of this dissertation is to evaluate the technical viability of milk production replacing ensilage and concentrated ration by range considering the quantity and quality of the produced milk and also following the impact that the presence of the animals had over the soil density and the phosphorus, potassium and magnesium variation on the soil. This work was conducted at the agricultural school "Instituto Cristão" in Castro-PR, from July 19th to October 15th 2004. It was used a farming-cattle raising integration area where 25 ha of oats and ryegrass were grown in winter. Four testers cows per experimental unit plus regulator animals were used with continuous capacity and Put and Take methodology. The treatments were: T1 - suply of 100% of the animal need for maintenance and production of 28 Kg of milk per day on feed trough, as ensilage and concentrate, plus the access to oats and ryegrass range; T2 - suply of 65% of the animal need for maintenance and production of 28 Kg of milk per day on feed trough, as ensilage and concentrate, plus the access to oats and ryegrass range; T3 - suply of 45% of the animal need for maintenance and production of 28 Kg of milk per day on feed trough, as ensilage and concentrate, plus the access to oats and ryegrass range; T4 - suply of 25% of the animal need for maintenance and production of 28 Kg of milk per day on feed trough, as ensilage and concentrate, plus the access to oats and ryegrass range. These treatments were submitted in casuality blocks design with three repetitions per treatment, dividing the total time of the experiment in three periods for analysing the caracteristics of the animals and the milk. There w asn't found any statistical difference of total production of the milk corrected per 4% of fat and also for the animals weight and levels of fat and protein and quantity of fat and produced protein. There was an improvement of the soil density after grazing, reduction of phosphorus and magnesium levels and increase of potassium levels on the soil, however, without diference between treatments

Pastagem de aveia e azevém na integraçăo lavoura-pecuária : produçăo de leite e características do solo /

Orientador: Amadeu Bona FilhoDissertaçăo (mestrado) - Universidade Federal do Paraná, Setor de Cięncias Agrárias, Programa de Pós-Graduaçăo em Agronomia. Defesa: Curitiba, 2006Inclui bibliografiaÁrea de concentraçăo: Produçăo vegeta

The Spectral Energy Distribution of Fermi bright blazars

(Abridged) We have conducted a detailed investigation of the broad-band spectral properties of the \gamma-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi gamma-ray spectra with Swift, radio, infra-red, optical and other hard X-ray/gamma-ray data, collected within three months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous Spectral Energy Distributions (SED) for 48 LBAS blazars.The SED of these gamma-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual Log $\nu$ - Log $\nu$ F$_\nu$ representation, the typical broad-band spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SEDs to characterize the peak intensity of both the low and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broad-band colors (i.e. the radio to optical and optical to X-ray spectral slopes) and from the gamma-ray spectral index. Our data show that the synchrotron peak frequency $\nu_p^S$ is positioned between 10$^{12.5}$ and 10$^{14.5}$ Hz in broad-lined FSRQs and between $10^{13}$ and $10^{17}$ Hz in featureless BL Lacertae objects.We find that the gamma-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron - inverse Compton scenarios. However, simple homogeneous, one-zone, Synchrotron Self Compton (SSC) models cannot explain most of our SEDs, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. (...)Comment: 85 pages, 38 figures, submitted to Ap

The Integration of Sustainability into the Risk Management Process and the Impact of the Energy Crisis and Green Transition: Insights from a Danish Energy Trading Company

The main purpose of the book chapter is twofold: it aims to analyze if and howsustainability has been integrated into the risk management process, and how the 2021 energy crisis and green transition have impacted the risk management process and practices of an Energy Trading company located in Denmark.The book chapter specifically answers the call made by Anton and Nucu (2020)and Lenssen et al. (2014) to explore the challenges of shifting to sustainability riskmanagement in the energy sector and in the context of the financial crisis, in thiscase, brought by the 2021 energy crisis, and political turbulence and effects of the Ukraine war