DIGITAL TWINS – THE NEXT STAGE IN THE DEVELOPMENT OF AUTOMATED CONTROL SYSTEMS?

В настоящей статье рассматривается как технология цифровых двойников может повлиять на развитие систем управления технологическими процессам. Описываются преимущества и особенности использования теории управления на примере сравнения АСУТП и цифрового двойника.This article discusses how digital twin technology can influence the development of process control systems. The advantages and features of using control theory are described using the example of a comparison of process control systems and a digital twin

[Introduction] Toward an anthropology of the just price: history, ethnography, critique

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Lateral orbitofrontal cortex anticipates choices and integrates prior with current information

Adaptive behavior requires integrating prior with current information to anticipate upcoming events. Brain structures related to this computation should bring relevant signals from the recent past into the present. Here we report that rats can integrate the most recent prior information with sensory information, thereby improving behavior on a perceptual decision-making task with outcome-dependent past trial history. We find that anticipatory signals in the orbitofrontal cortex about upcoming choice increase over time and are even present before stimulus onset. These neuronal signals also represent the stimulus and relevant second-order combinations of past state variables. The encoding of choice, stimulus and second-order past state variables resides, up to movement onset, in overlapping populations. The neuronal representation of choice before stimulus onset and its build-up once the stimulus is presented suggest that orbitofrontal cortex plays a role in transforming immediate prior and stimulus information into choices using a compact state-space representation

Genome of <i>Leptomonas pyrrhocoris</i>:a high-quality reference for monoxenous trypanosomatids and new insights into evolution of <i>Leishmania</i>

Many high-quality genomes are available for dixenous (two hosts) trypanosomatid species of the genera Trypanosoma, Leishmania, and Phytomonas, but only fragmentary information is available for monoxenous (single-host) trypanosomatids. In trypanosomatids, monoxeny is ancestral to dixeny, thus it is anticipated that the genome sequences of the key monoxenous parasites will be instrumental for both understanding the origin of parasitism and the evolution of dixeny. Here, we present a high-quality genome for Leptomonas pyrrhocoris, which is closely related to the dixenous genus Leishmania. The L. pyrrhocoris genome (30.4 Mbp in 60 scaffolds) encodes 10,148 genes. Using the L. pyrrhocoris genome, we pinpointed genes gained in Leishmania. Among those genes, 20 genes with unknown function had expression patterns in the Leishmania mexicana life cycle suggesting their involvement in virulence. By combining differential expression data for L. mexicana, L. major and Leptomonas seymouri, we have identified several additional proteins potentially involved in virulence, including SpoU methylase and U3 small nucleolar ribonucleoprotein IMP3. The population genetics of L. pyrrhocoris was also addressed by sequencing thirteen strains of different geographic origin, allowing the identification of 1,318 genes under positive selection. This set of genes was significantly enriched in components of the cytoskeleton and the flagellum

Nanotools for Neuroscience and Brain Activity Mapping

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function

Ewing sarcoma of the bone. Multidisciplinary approach and oncological results in 88 patients

El sarcoma de Ewing óseo es un tumor poco frecuente, agresivo, que afecta principalmente a niñosy adultos jóvenes. Existe ausencia de registros en nuestro país respecto de la prevalencia de estaenfermedad, los esquemas de tratamiento utilizados y sus resultados. El objetivo fue analizar, en un grupode pacientes con sarcoma de Ewing óseo tratados con quimioterapia y cirugía de conservación de miembro,las tasas de supervivencia global, de recurrencia local y los factores de riesgo oncológicos. Se incluyó a 88pacientes. La edad media de la serie fue de 14.5 años y el seguimiento promedio de 8.8 años. La tasa de supervivencia global fue de 79.5% a los 2 años, de 69% a 5 años y de 64% a 10 años. Los factores pronósticosnegativos asociados a menor supervivencia fueron: mala respuesta a la quimioterapia, edad ≥ de 16 años,localización central, y recurrencia local. En el análisis multivariable únicamente la respuesta a la quimioterapiatuvo significancia estadística. La tasa libre de recurrencia local a 2 y 5 años fue del 87%. La mala respuesta ala quimioterapia fue el único factor significativo para la recurrencia local. Consideramos que la cirugía de conservación de miembro asociada a quimioterapia pre y postoperatoria debe ser el tratamiento para el sarcomade Ewing óseo, alcanzando de esta manera una supervivencia global a 5 años del 69%. En nuestra serie, larespuesta a la quimioterapia ha sido el factor pronóstico más relevante para supervivencia y recurrencia local.Ewing sarcoma of the bone is a rare, highly aggressive tumor that typically affects children and young adults. In Argentina, the lack of Ewing’s sarcoma registries reflects in the absence of information regarding prevalence, treatment protocols and patient´s outcome. The purpose of this study was to analyze, in a group of patients diagnosed with Ewing sarcoma of the bone, treated with chemotherapy and limb-conserving surgery, their overall survival rate, local recurrence rate, and oncological risk factors. A retrospective research was conducted between 1990 and 2017. Eighty-eight patients with Ewing sarcoma of the bone matched the inclusion criteria. Median age was 14.5 years and median follow-up was 8.8 years. Overall survival rate was 79.5%, 69% and 64% at 2, 5 and 10 years respectively. Negative prognostic factors, associated with less survival rate after univariate analysis, were: bad response to chemotherapy (tumoral necrosis 0-89%), age > 16 years-old, central tumor localization and local recurrence. Gender and tumor size were not significant prognostic factors. After multivariate analysis, response to chemotherapy remained statistical significant. Local recurrence-free survival rate at 2 and 5 years was 87%. Tumor response to chemotherapy (0-89%) was the only significant factor for local recurrence. We consider that limb-salvage surgery, with neoadjuvant and adjuvant chemotherapy, are the mainstays of treatment for Ewing’s sarcoma, with an overall survival rate, at 5 years, of 69%. In this population, response to chemotherapy is the most relevant prognostic factor, being associated with both local recurrence and overall survival.Fil: Sanchez Saba, Javier E.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Abrego, Mariano O.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Albergo, José I.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Farfalli, Germán Luis. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Aponte Tinao, Luis A.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Ayerza, Miguel A.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Cayol, Federico. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Streitenberger, Patricia. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Risk, Marcelo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Roitman, Pablo Daniel. Instituto Universidad Escuela de Medicina del Hospital Italiano; Argentin

Norms, Networks, Power, and Control: Understanding Informal Payments and Brokerage in Cross-Border Trade in Sierra Leone

Recent research has cast light on the variety of informal payments and practices that govern the day-to-day interactions between traders and customs agents at border posts in low-income countries. Building on this literature, this paper draws on survey and qualitative evidence in an effort to explore which groups are most advantaged and disadvantaged by the largely informal processes and norms governing cross-border trade. We find that understanding variation in strategies and outcomes across traders can only be effectively understood with reference to the importance of norms, networks, power, and the logic of control.Department for International DevelopmentBill and Melinda Gates Foundatio

Force-Field Compensation in a Manual Tracking Task

This study addresses force/movement control in a dynamic “hybrid” task: the master sub-task is continuous manual tracking of a target moving along an eight-shaped Lissajous figure, with the tracking error as the primary performance index; the slave sub-task is compensation of a disturbing curl viscous field, compatibly with the primary performance index. The two sub-tasks are correlated because the lateral force the subject must exert on the eight-shape must be proportional to the longitudinal movement speed in order to perform a good tracking. The results confirm that visuo-manual tracking is characterized by an intermittent control mechanism, in agreement with previous work; the novel finding is that the overall control patterns are not altered by the presence of a large deviating force field, if compared with the undisturbed condition. It is also found that the control of interaction-forces is achieved by a combination of arm stiffness properties and direct force control, as suggested by the systematic lateral deviation of the trajectories from the nominal path and the comparison between perturbed trials and catch trials. The coordination of the two sub-tasks is quickly learnt after the activation of the deviating force field and is achieved by a combination of force and the stiffness components (about 80% vs. 20%), which is a function of the implicit accuracy of the tracking task

High Cooperativity of the SV40 Major Capsid Protein VP1 in Virus Assembly

SV40 is a small, non enveloped DNA virus with an icosahedral capsid of 45 nm. The outer shell is composed of pentamers of the major capsid protein, VP1, linked via their flexible carboxy-terminal arms. Its morphogenesis occurs by assembly of capsomers around the viral minichromosome. However the steps leading to the formation of mature virus are poorly understood. Intermediates of the assembly reaction could not be isolated from cells infected with wt SV40. Here we have used recombinant VP1 produced in insect cells for in vitro assembly studies around supercoiled heterologous plasmid DNA carrying a reporter gene. This strategy yields infective nanoparticles, affording a simple quantitative transduction assay. We show that VP1 assembles under physiological conditions into uniform nanoparticles of the same shape, size and CsCl density as the wild type virus. The stoichiometry is one DNA molecule per capsid. VP1 deleted in the C-arm, which is unable to assemble but can bind DNA, was inactive indicating genuine assembly rather than non-specific DNA-binding. The reaction requires host enzymatic activities, consistent with the participation of chaperones, as recently shown. Our results demonstrate dramatic cooperativity of VP1, with a Hill coefficient of ∼6. These findings suggest that assembly may be a concerted reaction. We propose that concerted assembly is facilitated by simultaneous binding of multiple capsomers to a single DNA molecule, as we have recently reported, thus increasing their local concentration. Emerging principles of SV40 assembly may help understanding assembly of other complex systems. In addition, the SV40-based nanoparticles described here are potential gene therapy vectors that combine efficient gene delivery with safety and flexibility

NF-κB-dependent synergistic regulation of CXCL10 gene expression by IL-1β and IFN-γ in human intestinal epithelial cell lines

Background and aims Little is known about the intestinal epithelial expression and secretion of CXCL10 (IP-10), a chemokine involved in recruiting T cells and monocytes. We aimed to study CXCL10 gene expression and regulation by the pro-inflammatory cytokines interleukin (IL)-1 beta, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in intestinal epithelial cell lines. Materials and methods CXCL10 expression and secretion kinetics were assessed in Caco-2, HT-29 and DLD1 human colon epithelial cells, treated with IL-1 beta, TNF-alpha, IFN-gamma alone or in combination with each other by real-time polymerase chain reaction (PCR), Northern blotting and enzyme-linked immunoabsorbent assay (ELISA). Transient transfections with TGL-IP10 (CXCL10 promoter) and TGL-IP10-kappa B2 mutant promoter and gelshifts and supershifts for nuclear factor (NF)-kappa B were also performed. Results Real-time PCRs and ELISA experiments revealed that IL-1 beta was the strongest and earliest inducer of CXCL10 messenger ribonucleic acid (mRNA) expression and protein secretion in Caco-2 cell line, whereas INF-gamma had a delayed kinetics. There was a strong synergistic effect of either TNF-alpha or IL-1 beta with IFN-gamma both on CXCL10 mRNA expression and protein secretion in all three cell lines. Real-time PCR and ELISA experiments using a specific NF-kappa B inhibitor and transfection experiments with a NF-kappa B-binding defective CXCL10 promoter construct revealed that the induction of CXCL10 by IL-1 beta and its synergism with IFN-gamma is NF-kappa B dependent. Conclusion These data demonstrate that in colonic epithelial cells, depending on the cellular context and utilizing the NF-kappa B pathway, IL-1 beta alone and/or in synergism with IFN-gamma may play a major role in the induction of CXCL10