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The aim of this study was to determine effects of parity (primiparous vs. multiparous), seasonal heat stress at calving (summer vs. winter), and time postpartum on some parameters associated with colostrum quality in Holstein cows reared in the Sonoran Desert ecosystem. Forty-seven cows (11 primiparous and 36 multiparous) expected to calve during summer, and 46 cows during winter (14 primiparous and 32 multiparous) were randomly selected. Management and feeding before and after parturition were similar for cows in both seasons. After parturition, colostrum from all cows was evaluated for volume, weight, temperature, density, and content of fat, protein, solids non-fat (SNF), and immunoglobulins (IGG). Data were analyzed with a model that included effects of parity status, calving season, and time postpartum, as well as all interactions. Colostrum produced in summer was warmer (P < 0.01) by almost 6 °C than winter colostrum, while colostrum from multiparous was warmer (P = 0.02) by 1.2 °C than that produced by primiparous cows. Colostrum volume and weight were not impacted by parity, calving season or time postpartum. Density, protein, and SNF content in colostrum were higher (P < 0.01) in multiparous vs. primiparous cows, as well as at parturition (0 h postpartum) than at 12 h postpartum (P < 0.01). At calving (0 h), spring colostrum had higher fat content (P < 0.01) and lower (P < 0.01) IGG concentration than that collected in summer, and no difference (P > 0.05) between seasons was observed for these components at 12 h postpartum. Multiparous cows produced colostrum with higher (P < 0.01) IGG concentrations than primiparous cows. In conclusion, only 0-h colostrum and that from multiparous cows was categorized as "Excellent," meanwhile the colostrum produced under summer heat stress was characterized as "Good" with reduced fat content. While the lacteal secretion collected at 12 post-partum still classified as colostrum, substantially lower contents of IGG, protein, fat, and SNF decreased its classification to "Poor" from the classification of "Excellent" at 0 h postpartum.
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Colostro , Lactação , Gravidez , Feminino , Humanos , Bovinos , Animais , Estações do Ano , Leite , Ecossistema , Período Pós-Parto , Imunoglobulina GRESUMO
Chenopodium quinoa Willd. it is an Andean cereal of great importance for human consumption due to its high nutritional value. In Colombia there is a high phenotypic and genotypic variability within quinoa crops, which has not been studied and has been maintained by the same farmers cycle after production cycle. The objective of this study was to carry out an interpopulation characterization of quinoa cultivated in different producing municipalities of the department of Boyacá, in Colombia, for which 19 morphological descriptors were used, which were evaluated in situ in nine municipalities and analyzed through descriptive statistics, principal component analysis, correlation and conglomerates. In the evaluation of the quantitative traits for all the populations, it was observed that the most variable descriptors were Number of teeth lower leaf (DHI), Lower leaf length (LHI), Width upper leaf (AHI) and Number of teeth upper leaf (DHS). Great segregation between and within individuals of Blanca de Jericó and Piartal was observed for panicle and leaf color and shape, stem color, presence of teeth, and axils on upper and lower leaves. A classification key is proposed that allows in the field to be able to morphologically differentiate the genotypes of Piartal and Blanca de Jericó. This research shows that among the most cultivated genotypes in the department of Boyacá, there is still an important phenotypic diversity given at the inter and intra-individual level, due to the phenological state and the agroclimatological conditions of the different producing regions.
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Chenopodium quinoa , Humanos , Chenopodium quinoa/genética , Colômbia , Grão Comestível , Fenótipo , GenótipoRESUMO
Inferring causal effects between variables when utilizing observational data is challenging due to confounding factors not controlled through a randomized experiment. Propensity score matching can decrease confounding in observational studies and offers insights about potential causal effects of prophylactic management interventions such as vaccinations. The objective of this study was to determine potential causality and impact of vaccination with an Escherichia coli J5 bacterin on the productive performance of dairy cows applying propensity score matching techniques to farm-recorded (e.g., observational) data. Traits of interest included 305-d milk yield (MY305), 305-d fat yield (FY305), 305-d protein yield (PY305), and somatic cell score (SCS). Records from 6,418 lactations generated by 5,121 animals were available for the analysis. Vaccination status of each animal was obtained from producer-recorded information. Confounding variables considered were herd-year-season groups (56 levels), parity (5 levels: 1, 2, 3, 4, and ≥5), and genetic quartile groups (4 levels: top 25% through bottom 25%) derived from genetic predictions for MY305, FY305, PY305, and SCS, as well as for the genetic susceptibility to mastitis. A logistic regression model was applied to estimate the propensity score (PS) for each cow. Subsequently, PS values were used to form pairs of animals (1 vaccinated with 1 unvaccinated control), depending on their PS similarities (difference in PS values of cows within a match required to be <20% of 1 standard deviation of the logit of PS). After the matching process, 2,091 pairs of animals (4,182 records) remained available to infer the causal effects of vaccinating dairy cows with the E. coli J5 bacterin. Causal effects estimation was performed using 2 approaches: simple matching and a bias-corrected matching. According to the PS methodology, causal effects of vaccinating dairy cows with a J5 bacterin on their productive performance were identified for MY305. The simple matched estimator suggested that vaccinated cows produced 163.89 kg more milk over an entire lactation when compared with nonvaccinated counterparts, whereas the bias-corrected estimator suggested that such increment in milk production was of 150.48 kg. Conversely, no causal effects of immunizing dairy cows with a J5 bacterin were identified for FY305, PY305, or SCS. In conclusion, the utilization of PS matching techniques applied to farm-recorded data was feasible and allowed us to identify that vaccination with an E. coli J5 bacterin relates to an overall milk production increment without compromising milk quality.
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Doenças dos Bovinos , Infecções por Escherichia coli , Mastite Bovina , Gravidez , Feminino , Bovinos , Animais , Escherichia coli , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Pontuação de Propensão , Mastite Bovina/prevenção & controle , Mastite Bovina/metabolismo , Lactação , Vacinação/veterinária , Leite/metabolismo , Vacinas Bacterianas , Doenças dos Bovinos/metabolismoRESUMO
Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between those cell types 1 . Neural cell types have previously been defined by morphology 2, 3 , electrophysiology 4, 5 , transcriptomic expression 6-8 , connectivity 9-13 , or even a combination of such modalities 14-16 . More recently, the Patch-seq technique has enabled the characterization of morphology (M), electrophysiology (E), and transcriptomic (T) properties from individual cells 17-20 . Using this technique, these properties were integrated to define 28, inhibitory multimodal, MET-types in mouse primary visual cortex 21 . It is unknown how these MET-types connect within the broader cortical circuitry however. Here we show that we can predict the MET-type identity of inhibitory cells within a large-scale electron microscopy (EM) dataset and these MET-types have distinct ultrastructural features and synapse connectivity patterns. We found that EM Martinotti cells, a well defined morphological cell type 22, 23 known to be Somatostatin positive (Sst+) 24, 25 , were successfully predicted to belong to Sst+ MET-types. Each identified MET-type had distinct axon myelination patterns and synapsed onto specific excitatory targets. Our results demonstrate that morphological features can be used to link cell type identities across imaging modalities, which enables further comparison of connectivity in relation to transcriptomic or electrophysiological properties. Furthermore, our results show that MET-types have distinct connectivity patterns, supporting the use of MET-types and connectivity to meaningfully define cell types.
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The hippocampus is a plastic brain area that shows functional segregation along its longitudinal axis, reflected by a higher level of long-term potentiation (LTP) in the CA1 region of the dorsal hippocampus (DH) compared to the ventral hippocampus (VH), but the mechanisms underlying this difference remain elusive. Numerous studies have highlighted the importance of microglia-neuronal communication in modulating synaptic transmission and hippocampal plasticity, although its role in physiological contexts is still largely unknown. We characterized in depth the features of microglia in the two hippocampal poles and investigated their contribution to CA1 plasticity under physiological conditions. We unveiled the influence of microglia in differentially modulating the amplitude of LTP in the DH and VH, showing that minocycline or PLX5622 treatment reduced LTP amplitude in the DH, while increasing it in the VH. This was recapitulated in Cx3cr1 knockout mice, indicating that microglia have a key role in setting the conditions for plasticity processes in a region-specific manner, and that the CX3CL1-CX3CR1 pathway is a key element in determining the basal level of CA1 LTP in the two regions. The observed LTP differences at the two poles were associated with transcriptional changes in the expression of genes encoding for Il-1, Tnf-α, Il-6, and Bdnf, essential players of neuronal plasticity. Furthermore, microglia in the CA1 SR region showed an increase in soma and a more extensive arborization, an increased prevalence of immature lysosomes accompanied by an elevation in mRNA expression of phagocytic markers Mertk and Cd68 and a surge in the expression of microglial outward K+ currents in the VH compared to DH, suggesting a distinct basal phenotypic state of microglia across the two hippocampal poles. Overall, we characterized the molecular, morphological, ultrastructural, and functional profile of microglia at the two poles, suggesting that modifications in hippocampal subregions related to different microglial statuses can contribute to dissect the phenotypical aspects of many diseases in which microglia are known to be involved.
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Plasticidade Neuronal , Masculino , Animais , CamundongosRESUMO
An array of spin torque nano-oscillators (STNOs), coupled by dipolar interaction and arranged on a ring, has been studied numerically and analytically. The phase patterns and locking ranges are extracted as a function of the number N, their separation, and the current density mismatch between selected subgroups of STNOs. If [Formula: see text] for identical current densities through all STNOs, two degenerated modes are identified an in-phase mode (all STNOs have the same phase) and a splay mode (the phase makes a 2[Formula: see text] turn along the ring). When inducing a current density mismatch between two subgroups, additional phase shifts occur. The locking range (maximum current density mismatch) of the in-phase mode is larger than the one for the splay mode and depends on the number N of STNOs on the ring as well as on the separation. These results can be used for the development of magnetic devices that are based on STNO arrays.
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The tayra Eira barbara is a Neotropical mustelid considered as an endangered species by Mexican environmental authorities. Despite the considerable information available on the biology and ecology of E. barbara, little is known about its helminth fauna. Here, we provided new records of nematodes from a road-killed tayra in Calakmul, Campeche, Mexico. The species identification of nematodes was based on morphological studies and molecular analysis of fragments of the 28S gene. The tayra specimen was infected by three nematodes: Molineus sp., Physalopterinae gen. sp. and Angiostrongylus vasosum. To our knowledge, this study is the first to report the natural infection of E. barbara with Molineus sp. and Physalopterinae gen. sp. Our study provides the first nucleotide sequences of nematodes parasitizing E. barbara providing a starting point against which future studies may be compared.
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A detailed analytic and numerical analysis of the interaction between two bubble skyrmions has been carried out. The results from the micromagnetic calculations show that when the skyrmions are in the same plane, the magnetic parameters vary weakly as a function of the separation between them. On the other hand, when the skyrmions are located in the same vertical axis, the magnetic parameters show a strong variation as a function of the separation of the skyrmions. In particular, when a magnetic disk is over another, there is a transition from a Bloch-like skyrmion configuration to a Néel-like skyrmion configuration as the distance between the disks decreases, as a consequence of the magnetostatic interaction. Therefore, it is possible to stabilize a bubble skyrmion with a Néel configuration without the Dzyaloshinskii-Moriya interaction. Thus, these results can be used for the control of the skyrmion parameters in magnetic spintronic devices that need to use these configurations.
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This study was performed to evaluate the linear and volumetric effects of a technique for reconstruction of the posterior atrophic mandible, including the final bone gain of the graft, by three-dimensional assessment. Thirteen individuals were recruited into the study and submitted to a total of 15 mandibular autogenous bone block surgeries. Cone beam computed tomography images were obtained at three different times. Bone graft length and thickness, and the volume, height, and width of the graft were measured. Data were compared statistically among the time points using the Friedman test, and cluster analysis was performed to identify the association between the study variables and the resorption rate (α = 0.05). Linear analysis of the width and height of the recipient area at the different time points revealed a statistically significant difference. The final average increase in height was 1.6 mm; all subjects showed an average volume gain of 3.412mm3, and 77% of the subjects showed an average graft resorption of 0.688mm3 construction of three-dimensional vertical defects of the posterior mandible resulted in good healing with minimal complications and minimal bone graft resorption, favouring vertical bone gain.
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Aumento do Rebordo Alveolar , Reabsorção Óssea , Transplante Ósseo , Tomografia Computadorizada de Feixe Cônico , Humanos , MandíbulaRESUMO
An increasing number of rare mutations linked to autism spectrum disorders have been reported in genes encoding for proteins involved in synapse formation and maintenance, such as the post-synaptic cell adhesion proteins neuroligins. Most of the autism-linked mutations in the neuroligin genes map on the extracellular protein domain. The autism-linked substitution R451C in Neuroligin3 (NLGN3) induces a local misfolding of the extracellular domain, causing defective trafficking and retention of the mutant protein in the endoplasmic reticulum (ER). The activation of the unfolded protein response (UPR), due to misfolded proteins accumulating in the ER, has been implicated in pathological and physiological conditions of the nervous system. It was previously shown that the over-expression of R451C NLGN3 in a cellular system leads to the activation of the UPR. Here, we have investigated whether this protective cellular response is detectable in the knock-in mouse model of autism endogenously expressing R451C NLGN3. Our data showed up-regulation of UPR markers uniquely in the cerebellum of the R451C mice compared to WT littermates, at both embryonic and adult stages, but not in other brain regions. Miniature excitatory currents in the Purkinje cells of the R451C mice showed higher frequency than in the WT, which was rescued inhibiting the PERK branch of UPR. Taken together, our data indicate that the R451C mutation in neuroligin3 elicits UPR in vivo, which appears to trigger alterations of synaptic function in the cerebellum of a mouse model expressing the R451C autism-linked mutation.
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Transtorno Autístico/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Cerebelo/metabolismo , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , Animais , Transtorno Autístico/genética , Moléculas de Adesão Celular Neuronais/genética , Cerebelo/patologia , Proteínas de Membrana/genética , Camundongos , Camundongos da Linhagem 129 , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Transmissão Sináptica/fisiologiaRESUMO
Ascorbic acid (Asc) is an antioxidant molecule essential for physiological functions. The concentration of extracellular Asc increases during synaptic transmission and renal reabsorption. These phenomena induce an increase of the Sodium-dependent-Vitamin-C-transporter 2 (SVCT2) at plasma membrane (PM) localization, as we previously demonstrated in neuronal and non-neuronal cells. Hence, the aim of this study was to evaluate intracellular SVCT2 trafficking kinetics in response to Asc. We observed two peaks of SVCT2 localization and function at the PM (at 5-10â¯min, "acute response", and 30-60â¯min, "post-acute response") when cells were incubated with Asc. We defined that the post-acute response was dependent on SVCT2 located in early secretory compartments, and its trafficking was abolished with Tunicamycin and Brefeldin A treatment. Moreover, using the RUSH system to retain and synchronize cargo secretion through the secretory pathway we demonstrated that the post-acute response increases SVCT2 trafficking kinetics from the ER to the PM suggesting the retention of SVCT2 at the early secretory pathway when Asc is absent. However, these observations do not explain the increased SVCT2 levels at the PM during the "acute" response, suggesting the involvement of a faster mechanism in close proximity with the PM. To investigate the possible role of endosomal compartments, we tested the effect of endocytosis inhibition. Expression of dominant-negative (DN) versions of the GTPase-dynamin II and clathrin-accessory protein AP180 showed a significant increase in SVCT2 levels at the PM. Moreover, expression of Rab11-DN, a GTPase implicated in cargo protein recycling from endosomes to the PM showed a similar outcome, strongly indicating that Asc impacts SVCT2 trafficking during the acute response. Therefore, our results revealed two mechanisms by which Asc modulates SVCT2 levels at the PM, one at the early secretory pathway and another at the endocytic compartments. We propose that these two mechanisms have key protective implications in the homeostasis of metabolically active and specialized tissues.
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Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/fisiologia , Transportadores de Sódio Acoplados à Vitamina C/metabolismo , Membrana Celular/metabolismo , Endocitose/efeitos dos fármacos , Endocitose/fisiologia , Células HEK293 , Células HeLa , HumanosRESUMO
OBJECTIVE: To simplify and optimize the ability of EuroSCORE I and II to predict early mortality after surgery for infective endocarditis (IE). METHODS: Multicentre retrospective study (n = 775). Simplified scores, eliminating irrelevant variables, and new specific scores, adding specific IE variables, were created. The performance of the original, recalibrated and specific EuroSCOREs was assessed by Brier score, C-statistic and calibration plot in bootstrap samples. The Net Reclassification Index was quantified. RESULTS: Recalibrated scores including age, previous cardiac surgery, critical preoperative state, New York Heart Association >I, and emergent surgery (EuroSCORE I and II); renal failure and pulmonary hypertension (EuroSCORE I); and urgent surgery (EuroSCORE II) performed better than the original EuroSCOREs (Brier original and recalibrated: EuroSCORE I: 0.1770 and 0.1667; EuroSCORE II: 0.2307 and 0.1680). Performance improved with the addition of fistula, staphylococci and mitral location (EuroSCORE I and II) (Brier specific: EuroSCORE I 0.1587, EuroSCORE II 0.1592). Discrimination improved in specific models (C-statistic original, recalibrated and specific: EuroSCORE I: 0.7340, 0.7471 and 0.7728; EuroSCORE II: 0.7442, 0.7423 and 0.7700). Calibration improved in both EuroSCORE I models (intercept 0.295, slope 0.829 (original); intercept -0.094, slope 0.888 (recalibrated); intercept -0.059, slope 0.925 (specific)) but only in specific EuroSCORE II model (intercept 2.554, slope 1.114 (original); intercept -0.260, slope 0.703 (recalibrated); intercept -0.053, slope 0.930 (specific)). Net Reclassification Index was 5.1% and 20.3% for the specific EuroSCORE I and II. CONCLUSIONS: The use of simplified EuroSCORE I and EuroSCORE II models in IE with the addition of specific variables may lead to simpler and more accurate models.
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Endocardite Bacteriana/mortalidade , Endocardite/mortalidade , Procedimentos Cirúrgicos Cardíacos/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de RiscoAssuntos
Crassostrea/microbiologia , Crassostrea/virologia , Herpesviridae/isolamento & purificação , Vibrio/isolamento & purificação , Animais , Brasil/epidemiologia , DNA Bacteriano , DNA Viral , Infecções por Herpesviridae/veterinária , Reação em Cadeia da Polimerase/veterinária , Vibrioses/veterináriaRESUMO
The house mouse (Mus musculus) and the black rat (Rattus rattus) are reservoir hosts for zoonotic pathogens, several of which cause neglected tropical diseases (NTDs). Studies of the prevalence of these NTD-causing zoonotic pathogens, in house mice and black rats from tropical residential areas are scarce. Three hundred and two house mice and 161 black rats were trapped in 2013 from two urban neighbourhoods and a rural village in Yucatan, Mexico, and subsequently tested for Trypanosoma cruzi, Hymenolepis diminuta and Leptospira interrogans. Using the polymerase chain reaction we detected T. cruzi DNA in the hearts of 4·9% (8/165) and 6·2% (7/113) of house mice and black rats, respectively. We applied the sedimentation technique to detect eggs of H. diminuta in 0·5% (1/182) and 14·2% (15/106) of house mice and black rats, respectively. Through the immunofluorescent imprint method, L. interrogans was identified in 0·9% (1/106) of rat kidney impressions. Our results suggest that the black rat could be an important reservoir for T. cruzi and H. diminuta in the studied sites. Further studies examining seasonal and geographical patterns could increase our knowledge on the epidemiology of these pathogens in Mexico and the risk to public health posed by rodents.
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Doença de Chagas/veterinária , Himenolepíase/veterinária , Leptospirose/veterinária , Camundongos , Ratos , Doenças dos Roedores/epidemiologia , Animais , Doença de Chagas/epidemiologia , Doença de Chagas/parasitologia , Reservatórios de Doenças/microbiologia , Reservatórios de Doenças/parasitologia , Meio Ambiente , Himenolepíase/epidemiologia , Himenolepíase/parasitologia , Hymenolepis diminuta/isolamento & purificação , Leptospira interrogans/isolamento & purificação , Leptospirose/epidemiologia , Leptospirose/microbiologia , México/epidemiologia , Prevalência , Doenças dos Roedores/microbiologia , Doenças dos Roedores/parasitologia , Roedores , Trypanosoma cruzi/isolamento & purificação , Zoonoses/epidemiologia , Zoonoses/microbiologia , Zoonoses/parasitologiaRESUMO
The presence of body posture changes among patients with temporomandibular disorders (TMD) has been a controversial topic in dentistry. Based on that, the aim of this study was to assess postural features of pain-free subjects with internal derangement of the temporomandibular joint (TMJ), viz. disc displacement, when compared to subjects with normal disc position. A total of 21 subjects with unilateral, pain-free TMJ disc displacement (DD) and 21 subjects without any TMD signs of symptoms were assessed for body posture changes by means of posturographic evaluation of several body segments and postural balance reactions through the centre of mass during jaw movements using a balance platform. Posturographic measurements showed the absence of any significant differences between the two groups in any of the outcome parameters. Similarly, all balance platform responses to mandibular movements were not different between groups. There are no significant differences in body posture between subjects with and without unilateral disc displacement in the temporomandibular joint. Such observations, indicating a well-preserved postural balance in the presence of TMJ internal derangement, put into serious question the potential influence of TMJ disorders on whole body posture and viceversa.
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Dor Facial/fisiopatologia , Cabeça/anatomia & histologia , Má Oclusão/fisiopatologia , Postura/fisiologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Análise de Variância , Estudos de Casos e Controles , Oclusão Dentária , Feminino , Humanos , Masculino , Côndilo Mandibular/fisiopatologia , Músculos da Mastigação/fisiopatologia , Reprodutibilidade dos Testes , Adulto JovemRESUMO
The release of cathepsin proteases from disrupted lysosomes results in lethal cellular autodigestion. Lysosomal disruption-related cell death is highly variable, showing both apoptotic and necrotic outcomes. As the substrate spectrum of lysosomal proteases encompasses the apoptosis-regulating proteins of the Bcl-2 family, their degradation could influence the cell death outcome upon lysosomal disruption. We used Förster resonance energy transfer (FRET)-based biosensors to image the real-time degradation of the Bcl-2-family members, Bcl-xl, Bax and Bid, in living cells undergoing lysosomal lysis and identified an early chain of proteolytic events, initiated by the release of cathepsin B, which directs cells toward apoptosis. In this apoptotic exit strategy, cathepsin B's proteolytic activity results in apoptosis-inducing Bid and removes apoptosis-preventing Bcl-xl. Cathepsin B furthermore appears to degrade a cystein protease that would otherwise have eliminated apoptosis-supporting Bax, indirectly keeping cellular levels of the Bax protein up. The concerted effort of these three early events shifts the balance of cell fate away from necrosis and toward apoptosis.
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This article presents the design of a sensor Fault Detection and Isolation (FDI) system for a condensation process based on a nonlinear model. The condenser is modeled by dynamic and thermodynamic equations. For this work, the dynamic equations are described by three pairs of differential equations which represent the energy balance between the fluids. The thermodynamic equations consist in algebraic heat transfer equations and empirical equations, that allow for the estimation of heat transfer coefficients. The FDI system consists of a bank of two nonlinear high-gain observers, in order to detect, estimate and to isolate the fault in any of both outlet temperature sensors. The main contributions of this work were the experimental validation of the condenser nonlinear model and the FDI system.
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Theoretical results for the absorption spectrum and electric properties of the enol and keto tautomeric forms of anil derivatives in the gas-phase and in solution are presented. The electronic properties in chloroform, acetonitrile, methanol, and water were determined by carrying out sequential Monte Carlo simulations and quantum mechanics calculations based on the time dependent density functional theory and on the second-order Møller-Plesset perturbation theory method. The results illustrate the role played by electrostatic interactions in the electronic properties of anil derivatives in a liquid environment. There is a significant increase of the dipole moment in solution (20%-100%) relative to the gas-phase value. Solvent effects are mild for the absorption spectrum and linear polarizability but they can be particularly important for first hyperpolarizability. A large first hyperpolarizability contrast between the enol and keto forms is observed when absorption spectra present intense lowest-energy absorption bands. Dynamic results for the first hyperpolarizability are in qualitative agreement with the available experimental results.
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Bipolar disorder (BD) is a severe mental illness with a strong genetic component. Despite its high degree of heritability, current genetic studies have failed to reveal individual loci of large effect size. In lieu of focusing on individual genes, we investigated regulatory units (regulons) in BD to identify candidate transcription factors (TFs) that regulate large groups of differentially expressed genes. Network-based approaches should elucidate the molecular pathways governing the pathophysiology of BD and reveal targets for potential therapeutic intervention. The data from a large-scale microarray study was used to reconstruct the transcriptional associations in the human prefrontal cortex, and results from two independent microarray data sets to obtain BD gene signatures. The regulatory network was derived by mapping the significant interactions between known TFs and all potential targets. Five regulons were identified in both transcriptional network models: early growth response 3 (EGR3), TSC22 domain family, member 4 (TSC22D4), interleukin enhancer-binding factor 2 (ILF2), Y-box binding protein 1 (YBX1) and MAP-kinase-activating death domain (MADD). With a high stringency threshold, the consensus across tests was achieved only for the EGR3 regulon. We identified EGR3 in the prefrontal cortex as a potential key target, robustly repressed in both BD signatures. Considering that EGR3 translates environmental stimuli into long-term changes in the brain, disruption in biological pathways involving EGR3 may induce an impaired response to stress and influence on risk for psychiatric disorders, particularly BD.