On Metaeconomic Consensus in Global Management

The paper review the metaeconomic approaches in global management (MGM) which include social criteria and tasks arranged into consecutive conceptual system with account of changing normative (or minimax) functions and multicriteria approach detailing admitted hierarchies of those preferences. The systemic taxonomy of the MGM and its structurization are reviewed and conceptualized. The ranking of priorities in the multipurpose economic modelling of social preferences presupposes the weighed comparability of criteria functions on the qualitatively different levels-determining the alternatives of optimization, also multicriteria dynamic equilibrium and the preferable managerial strategies. The stochastic network modelling of universal sustainability for country’s economic development, disposable resources’ allocation a/o characteristics of complex adaptive systems can be recommended as a productive approach to intellectual management practice. The development of MGM would be more effective with more wide integration of multicriteria approaches, also more sophisticated statistical evaluations of intellectual potential in competitive management. The analytical review of the MGM revealed its significance at the stages of formulating the aim hierarchies, or choosing the optimization criteria, the restrictions on preferences and taxonomy of sustainable development

Water-in-oil-in-water emulsions of biopharmaceuticals for administration by injection

Tese de mestrado, Engenharia Farmacêutica 2021, Universidade de Lisboa, Faculdade de FarmáciaO crescimento do mercado biofarmacêutico, o interesse em formulações de liberação controlada (CR) combinado com a produção de micropartículas à base de polímero biodegradável, como o Poly(lactic-co-glycolic acid) (PLGA) têm sido amplamente estudado para o encapsulamento de biomoléculas. Neste trabalho, duas formulações para o encapsulamento da lisozima em microesferas PLGA foram desenvolvidas e otimizadas, bem como o processo de produção baseado na técnica dupla emulsão evaporação de solvente, água-em-óleo-em-água (W/O/W). Durante o desenvolvimento do processo, foi avaliado a morfologia, a eficiência de encapsulamento (EE), a atividade proteica e a liberação da proteína das microesferas. A produção da W/O/W consiste na emulsificação da primeira fase aquosa, que contém lisozima dissolvida, com a fase oleosa, solução de PLGA, e de seguida com a segunda fase aquosa. A tecnologia de produção utilizada foi um misturador de alto cisalhamento e um liofilizador. A combinação de PVA e NaCl na fase aquosa externa (W2) mostrou-se a melhor escolha como estabilizante da emulsão. As microesferas obtidas apresentam uma forma esférica, rígidas, o EE foi de ~ 100% e a atividade da proteína foi mantida. Durante as etapas de produção, a etapa de lavagem foi otimizada até a última etapa (stage 4) onde uma superfície limpa foi alcançada. A etapa de tempering, tempo necessário para a evaporação do solvente, é uma etapa crítica para a solidificação das microesferas, sem um tempo adequado nesta etapa as microesferas iram desfazer-se quando a etapa de lavagem fosse realizada. O desenvolvimento de uma nova formulação de libertação controlada requer meses de pesquisa e estudos de libertação in vitro (IVR) para atingir o perfil de liberação desejado do medicamento. Uma Wmaneira de reduzir esse tempo é tentar prever esses dados com o mínimo de tempo experimental usando modelos empíricos ou matemáticos. A equação de Weibull, modelo empírico, consegue prever o perfil de liberação do medicamento que é controlado pela erosão do polímero juntamente com uma explosão inicial de liberação mínima e uma liberação difusiva mínima, mas dados de IVR em tempo real e acelerados são necessários. O modelo matemático selecionado, uma framework analítica, para a previsão da libertação da substância ativa de microesferas de libertação controlada baseado em valores de parâmetros da matéria-prima e do produto final (microesferas). Com base em um artigo que descreve este modelo, a implementação foi tentada sem sucesso. Apesar deste modelo se encontrar amplamente estudado mais pesquisa é necessária para ajudar a construir um modelo robusto.The growth of the biopharmaceuticals market and the interest of controlled-release (CR) formulations combined with the production of microparticles based on biodegradable polymers such as Poly(lactic-co-glycolic acid) (PLGA) have been widely studied for encapsulation of biomolecules. In this work, two different formulations for Lysozyme encapsulations in PLGA microspheres have been developed and optimized as well as the production process based on the double emulsion water-in-oil-in-water (W/O/W) solvent evaporation technique. During the process development, morphology, encapsulation efficiency (EE), protein activity and release of the microspheres were assessed. The production of the W/O/W consist of the emulsification of the first aqueous phase, that contains dissolved lysozyme, with the oil phase, PLGA solution, and then with the second aqueous phase. The production technology used was the high shear mixer and the lyophilization. The combination of PVA and NaCl in the external aqueous phase (W2) proved to be the best choice in terms of surfactants. The microspheres obtained were spheric, rigid, the EE was close to 100% and the protein activity was maintained. During the production stages, the washing step was optimized until the last stage (stage 4) where the desired condition was achieved - a clean surface. The tempering process, time required for solvent evaporation, is critical for the solidification of the microspheres. Without proper time adjustment in this step, microspheres are not obtained in the subsequent washing step The development of a new formulation for control delivery requires months of research and in vitro release (IVR) studies to target the desired drug release profile. A way to shorten this time is to predict data with minimal experimental load using empirical or mathematical models. The Weibull Equation can predict the drug release profile controlled by polymer erosion linked with minimal initial burst release and minimal diffusive release but real-time and accelerated IVR data are needed. The selected mathematical model and analytical framework, for the prediction of CR from bulk biodegrading polymer microspheres is based on raw-materials and microspheres material attributes. The implementation of this model however require further research in order to increase its predictions robustness.Com o patrocínio da Empresa Hovione

Ecological Sustainability of Regional Development

In June 1987, an important international Workshop was held in Vilnius. Lithuanian SSR on the topic, "Ecological Sustainability of Regional Development". The number of participants was 65, coming from nine countries. Many of the papers dealt with ecological-economic assessment methods used in East European countries for regional development planning. Some of the ideas were quite new to environmental planners from Western Europe, and are of great interest to them. This is one kind of service that IIASA provides very well -- bringing people together and bridging language barriers in the East-West context. IIASA is pleased to be associated with the 1987 Workshop and with these Proceedings

Attention Reshapes Center-Surround Receptive Field Structure in Macaque Cortical Area MT

Directing spatial attention to a location inside the classical receptive field (cRF) of a neuron in macaque medial temporal area (MT) shifts the center of the cRF toward the attended location. Here we investigate the influence of spatial attention on the profile of the inhibitory surround present in many MT neurons. Two monkeys attended to the fixation point or to 1 of 2 random dot patterns (RDPs) placed inside or next to the cRF, whereas a third RDP (the probe) was briefly presented in quick succession across the cRF and surround. The probe presentation responses were used to compute a map of the excitatory receptive field and its inhibitory surround. Attention systematically reshapes the receptive field profile, independently shifting both center and surround toward the attended location. Furthermore, cRF size is changed as a function of relative distance to the attentional focus: attention inside the cRF shrinks it, whereas directing attention next to the cRF expands it. In addition, we find systematic changes in surround inhibition and cRF amplitude. This nonmultiplicative push–pull modulation of the receptive field's center-surround structure optimizes processing at and near the attentional focus to strengthen the representation of the attended stimulus while reducing influences from distractors

Variability Measures of Positive Random Variables

During the stationary part of neuronal spiking response, the stimulus can be encoded in the firing rate, but also in the statistical structure of the interspike intervals. We propose and discuss two information-based measures of statistical dispersion of the interspike interval distribution, the entropy-based dispersion and Fisher information-based dispersion. The measures are compared with the frequently used concept of standard deviation. It is shown, that standard deviation is not well suited to quantify some aspects of dispersion that are often expected intuitively, such as the degree of randomness. The proposed dispersion measures are not entirely independent, although each describes the interspike intervals from a different point of view. The new methods are applied to common models of neuronal firing and to both simulated and experimental data

Spike Timing Dependent Plasticity Finds the Start of Repeating Patterns in Continuous Spike Trains

Experimental studies have observed Long Term synaptic Potentiation (LTP) when a presynaptic neuron fires shortly before a postsynaptic neuron, and Long Term Depression (LTD) when the presynaptic neuron fires shortly after, a phenomenon known as Spike Timing Dependant Plasticity (STDP). When a neuron is presented successively with discrete volleys of input spikes STDP has been shown to learn ‘early spike patterns’, that is to concentrate synaptic weights on afferents that consistently fire early, with the result that the postsynaptic spike latency decreases, until it reaches a minimal and stable value. Here, we show that these results still stand in a continuous regime where afferents fire continuously with a constant population rate. As such, STDP is able to solve a very difficult computational problem: to localize a repeating spatio-temporal spike pattern embedded in equally dense ‘distractor’ spike trains. STDP thus enables some form of temporal coding, even in the absence of an explicit time reference. Given that the mechanism exposed here is simple and cheap it is hard to believe that the brain did not evolve to use it

No changes in parieto-occipital alpha during neural phase locking to visual quasi-periodic theta-, alpha-, and beta-band stimulation

Recent studies have probed the role of the parieto‐occipital alpha rhythm (8 – 12 Hz) in human visual perception through attempts to drive its neural generators. To that end, paradigms have used high‐intensity strictly‐periodic visual stimulation that created strong predictions about future stimulus occurrences and repeatedly demonstrated perceptual consequences in line with an entrainment of parieto‐occipital alpha. Our study, in turn, examined the case of alpha entrainment by non‐predictive low‐intensity quasi‐periodic visual stimulation within theta‐ (4 – 7 Hz), alpha‐ (8 – 13 Hz) and beta (14 – 20 Hz) frequency bands, i.e. a class of stimuli that resemble the temporal characteristics of naturally occurring visual input more closely. We have previously reported substantial neural phase‐locking in EEG recording during all three stimulation conditions. Here, we studied to what extent this phase‐locking reflected an entrainment of intrinsic alpha rhythms in the same dataset. Specifically, we tested whether quasi‐periodic visual stimulation affected several properties of parieto‐occipital alpha generators. Speaking against an entrainment of intrinsic alpha rhythms by non‐predictive low‐intensity quasi‐periodic visual stimulation, we found none of these properties to show differences between stimulation frequency bands. In particular, alpha band generators did not show increased sensitivity to alpha band stimulation and Bayesian inference corroborated evidence against an influence of stimulation frequency. Our results set boundary conditions for when and how to expect effects of entrainment of alpha generators and suggest that the parieto‐occipital alpha rhythm may be more inert to external influences than previously thought

STDP Allows Fast Rate-Modulated Coding with Poisson-Like Spike Trains

Spike timing-dependent plasticity (STDP) has been shown to enable single neurons to detect repeatedly presented spatiotemporal spike patterns. This holds even when such patterns are embedded in equally dense random spiking activity, that is, in the absence of external reference times such as a stimulus onset. Here we demonstrate, both analytically and numerically, that STDP can also learn repeating rate-modulated patterns, which have received more experimental evidence, for example, through post-stimulus time histograms (PSTHs). Each input spike train is generated from a rate function using a stochastic sampling mechanism, chosen to be an inhomogeneous Poisson process here. Learning is feasible provided significant covarying rate modulations occur within the typical timescale of STDP (∼10–20 ms) for sufficiently many inputs (∼100 among 1000 in our simulations), a condition that is met by many experimental PSTHs. Repeated pattern presentations induce spike-time correlations that are captured by STDP. Despite imprecise input spike times and even variable spike counts, a single trained neuron robustly detects the pattern just a few milliseconds after its presentation. Therefore, temporal imprecision and Poisson-like firing variability are not an obstacle to fast temporal coding. STDP provides an appealing mechanism to learn such rate patterns, which, beyond sensory processing, may also be involved in many cognitive tasks

Forward Masking Estimated by Signal Detection Theory Analysis of Neuronal Responses in Primary Auditory Cortex

Psychophysical forward masking is an increase in threshold of detection of a sound (probe) when it is preceded by another sound (masker). This is reminiscent of the reduction in neuronal responses to a sound following prior stimulation. Studies in the auditory nerve and cochlear nucleus using signal detection theory techniques to derive neuronal thresholds showed that in centrally projecting neurons, increases in masked thresholds were significantly smaller than the changes measured psychophysically. Larger threshold shifts have been reported in the inferior colliculus of awake marmoset. The present study investigated the magnitude of forward masking in primary auditory cortical neurons of anaesthetised guinea-pigs. Responses of cortical neurons to unmasked and forward masked tones were measured and probe detection thresholds estimated using signal detection theory methods. Threshold shifts were larger than in the auditory nerve, cochlear nucleus and inferior colliculus. The larger threshold shifts suggest that central, and probably cortical, processes contribute to forward masking. However, although methodological differences make comparisons difficult, the threshold shifts in cortical neurons were, in contrast to subcortical nuclei, actually larger than those observed psychophysically. Masking was largely attributable to a reduction in the responses to the probe, rather than either a persistence of the masker responses or an increase in the variability of probe responses