Desarrollo de controladores avanzados para sistemas multivariable en el entorno LabView

Este trabajo de fin de máster (TFM) consiste en el desarrollo de distintos algoritmos de control mediante la aplicación LabVIEW, además de una tarjeta de interfaz NI myRIO de National Instruments (NI) para el control en tiempo real de tres sistemas distintos: un sistema carro, un sistema péndulo Gantry (Grúa) y un sistema péndulo invertido. Los algoritmos están basados en controladores PID y de realimentación de estados, por asignación de polos y LQR. Así mismo, se crea una interfaz de usuario que permite interactuar con los sistemas y realizar pruebas con los algoritmos de control mencionados eligiendo los parámetros correspondientes, así como hacer simulaciones sobre sus modelos teóricos

Overexpression of wild-type human APP in mice causes cognitive déficits and pathological features unrelated to Abeta levels

Transgenic mice expressing mutant human amyloid precursor protein (APP) develop an age-dependent amyloid pathology and memory deficits, but no overt neuronal loss. Here, in mice overexpressing wild-type human APP (hAPPwt) we found an early memory impairment, particularly in the water maze and to a lesser extent in the object recognition task, but β-amyloid peptide (Aβ42) was barely detectable in the hippocampus. In these mice, hAPP processing was basically non-amyloidogenic, with high levels of APP carboxy-terminal fragments, C83 and APP intracellular domain. A tau pathology with an early increase in the levels of phosphorylated tau in the hippocampus, a likely consequence of enhanced ERK1/2 activation, was also observed. Furthermore, these mice presented a loss of synapse-associated proteins: PSD95, AMPA and NMDA receptor subunits and phosphorylated CaMKII. Importantly, signs of neurodegeneration were found in the hippocampal CA1 subfield and in the entorhinal cortex that were associated to a marked loss of MAP2 immunoreactivity. Conversely, in mice expressing mutant hAPP, high levels of Aβ42 were found in the hippocampus, but no signs of neurodegeneration were apparent. The results support the notion of Aβ- independent pathogenic pathways in Alzheimer's disease

Early Changes in Hippocampal Eph Receptors Precede the Onset of Memory Decline in Mouse Models of Alzheimer’s Disease

Abstract. Synapse loss occurs early in Alzheimer’s disease (AD) and is considered the best pathological correlate of cognitive decline. Ephrins and Eph receptors are involved in regulation of excitatory neurotransmission and play a role in cytoskeleton remodeling. We asked whether alterations in Eph receptors could underlie cognitive impairment in an AD mouse model overexpressing human amyloid-β protein precursor (hAβPP) with familial mutations (hAβPPswe-ind mice). We found that EphA4 and EphB2 receptors were reduced in the hippocampus before the development of impaired object recognition and spatial memory. Similar results were obtained in another line of transgenic AβPP mice, Tg2576. A reduction in Eph receptor levels was also found in postmortem hippocampal tissue from patients with incipient AD. At the time of onset of memory decline in hAβPPswe-ind mice, no change in surface expression of AMPA or NMDA receptor subunits was apparent, but we found changes in Eph-receptor downstream signaling, in particular a decrease in membrane-associated phospho-cofilin levels that may cause cytoskeletal changes and disrupted synaptic activity. Consistent with this finding, Eph receptor activation in cell culture increased phospho-cofilin levels. The results suggest that alterations in Eph receptors may play a role in synaptic dysfunction in the hippocampus leading to cognitive impairment in a model of AD

Rosiglitazone Rescues Memory Impairment in Alzheimer's Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology

Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARγ) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARγ, facilitated β-amyloid peptide (Aβ) clearance. Rosiglitazone not only reduced Aβ burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients

Dystocia in Friesian cows and its effects on postpartum reproductive performance and milk production

A total of 1,243 records for 585 dairy Friesian cows from 1997–2004 were used to study the factors affecting dystocia and its effects on reproductive performance and milk production. The overall incidence of dystocia was 6.9%. The percentage of dystocia decreased with increasing live body weight, age, and parity of cows (P < 0.05); however, it increased with increasing birth weight of calves (P < 0.05). The highest percentage of dystocia was detected in winter season, but the least percentage was in summer season (P < 0.05). The percentage of incidence of dystocia was significantly (P < 0.05) higher with winter feeding compared to summer ration (8.2% vs. 5.1%). The percentage of incidence of dystocia was significantly (P < 0.05) higher with twinning than single calving (15.5% vs. 6.5%), while not significantly affected by the sex of born calves. Incidence of dystocia had adverse effects on reproductive performance and milk yield. The service interval, service period, days open, and calving interval were significantly (P < 0.05) longer in cows afflicted with dystocia compared to normal cows. The conception rate was lower (P < 0.05), but the number of service per conception was higher (P < 0.05) in cows afflicted with dystocia compared to normal cows (60.5% vs. 73.0% and 3.4 vs. 2.7, respectively). Average daily milk yield was lower (P < 0.05) by 1 kg for cows with incidence of dystocia compared to normal cows

A new score for airway assessment using clinical and ultrasound parameters

BackgroundOver the last few years, ultrasonography has been introduced as the fifth pillar to patient’s bedside physical examination. Clinical assessments aim to screen and look for airway difficulties to predict difficult intubations, but none have demonstrated a significant predictive capacity. Recent systematic reviews have established a correlation between ultrasound imaging and difficult direct laryngoscopy. The primary objective of this study was to determine whether the utilization of ultrasonography to examine the upper airway could accurately predict difficult direct laryngoscopy.MethodsThis is a prospective observational study including 102 adult patients that required general anesthesia for elective surgery. Preoperatively, clinical airway assessments were performed. Data such as Mallampati-Samsoon grade (MS), upper lip bite test (ULBT), thyromental (TMD) and sternomental distance (SMD), cervical circumference (CC) and the Arné risk index were collected. Ultrasound evaluation was taken at five different levels in two planes, parasagittal and transverse. Therefore, the following measurements were registered: distance from skin to hyoid bone (DSHB), distance from skin to thyrohyoid membrane (DSTHM), distance from skin to epiglottis (DSE), distance from skin to thyroid cartilage (DSTC) and distance from hyoid bone and thyroid cartilage (DHBTC). Patients were divided into two groups based on the difficulty to perform direct laryngoscopy, according to Cormack-Lehane (C-L) classification. Grades I and II were classified as easy laryngoscopy and grades III or IV as difficult. Logistic regression models and the Receiver Operating Characteristic (ROC) curve was employed to determine the diagnostic precision of ultrasound measurements to distinguish difficult laryngoscopy (DL).ResultsThe following risk score for DL was obtained, DSTHM ≥ 1.60 cm (2 points), DSTC ≥ 0.78 cm (3 points) and gender (2 points for males). The score can range from 0 to 7 points, and showed and AUC (95% CI) of 0.84 (0.74–0.95). A score of 5 points or higher indicates a 34-fold increase in the risk of finding DL (p = 0.0010), sensitivity of 91.67, specificity of 75.56, positive predictive value of 33.33, and negative predictive value of 98.55.ConclusionThe use of ultrasonography combined with classic clinical screening tests are useful tools to predict difficult direct laryngoscopy

The active inference approach to ecological perception: general information dynamics for natural and artificial embodied cognition

The emerging neurocomputational vision of humans as embodied, ecologically embedded, social agents—who shape and are shaped by their environment—offers a golden opportunity to revisit and revise ideas about the physical and information-theoretic underpinnings of life, mind, and consciousness itself. In particular, the active inference framework (AIF) makes it possible to bridge connections from computational neuroscience and robotics/AI to ecological psychology and phenomenology, revealing common underpinnings and overcoming key limitations. AIF opposes the mechanistic to the reductive, while staying fully grounded in a naturalistic and information-theoretic foundation, using the principle of free energy minimization. The latter provides a theoretical basis for a unified treatment of particles, organisms, and interactive machines, spanning from the inorganic to organic, non-life to life, and natural to artificial agents. We provide a brief introduction to AIF, then explore its implications for evolutionary theory, ecological psychology, embodied phenomenology, and robotics/AI research. We conclude the paper by considering implications for machine consciousness

Distribution of GABAergic Interneurons and Dopaminergic Cells in the Functional Territories of the Human Striatum

BACKGROUND: The afferent projections of the striatum (caudate nucleus and putamen) are segregated in three territories: associative, sensorimotor and limbic. Striatal interneurons are in part responsible for the integration of these different types of information. Among them, GABAergic interneurons are the most abundant, and can be sorted in three populations according to their content in the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin (CB). Conversely, striatal dopaminergic cells (whose role as interneurons is still unclear) are scarce. This study aims to analyze the interneuron distribution in the striatal functional territories, as well as their organization regarding to the striosomal compartment. METHODOLOGY/PRINCIPAL FINDINGS: We used immunohistochemical methods to visualize CR, PV, CB and tyrosine hydroxylase (TH) positive striatal neurons. The interneuronal distribution was assessed by stereological methods applied to every striatal functional territory. Considering the four cell groups altogether, their density was higher in the associative (2120±91 cells/mm(3)) than in the sensorimotor (959±47 cells/mm(3)) or limbic (633±119 cells/mm(3)) territories. CB- and TH-immunoreactive(-ir) cells were distributed rather homogeneously in the three striatal territories. However, the density of CR and PV interneurons were more abundant in the associative and sensorimotor striatum, respectively. Regarding to their compartmental organization, CR-ir interneurons were frequently found in the border between compartments in the associative and sensorimotor territories, and CB-ir interneurons abounded at the striosome/matrix border in the sensorimotor domain. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that the architecture of the human striatum in terms of its interneuron composition varies in its three functional territories. Furthermore, our data highlight the importance of CR-ir striatal interneurons in the integration of associative information, and the selective role of PV-ir interneurons in the motor territory. On the other hand, the low density of dopaminergic cells casts doubts about their role in the normal human striatum

Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. RESULTS AND LIMITATIONS: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p \u3c 5 × 10 CONCLUSIONS: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. PATIENT SUMMARY: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer