Online real-time learning of dynamical systems from noisy streaming data.

Recent advancements in sensing and communication facilitate obtaining high-frequency real-time data from various physical systems like power networks, climate systems, biological networks, etc. However, since the data are recorded by physical sensors, it is natural that the obtained data is corrupted by measurement noise. In this paper, we present a novel algorithm for online real-time learning of dynamical systems from noisy time-series data, which employs the Robust Koopman operator framework to mitigate the effect of measurement noise. The proposed algorithm has three main advantages: (a) it allows for online real-time monitoring of a dynamical system; (b) it obtains a linear representation of the underlying dynamical system, thus enabling the user to use linear systems theory for analysis and control of the system; (c) it is computationally fast and less intensive than the popular extended dynamic mode decomposition (EDMD) algorithm. We illustrate the efficiency of the proposed algorithm by applying it to identify the Van der Pol oscillator, the chaotic attractor of the Henon map, the IEEE 68 bus system, and a ring network of Van der Pol oscillators.

Astrogliosis, neuritic microstructure, and sex effects: GFAP is an indicator of neuritic orientation in women.

BACKGROUND: Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life. METHODS: We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109). RESULTS: When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aß42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females. DISCUSSION: This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults.

The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 Down syndrome mice and improves learning/memory in wild-type mice.

Down syndrome (DS) is characterized by chronic neuroinflammation, peripheral inflammation, astrogliosis, imbalanced excitatory/inhibitory neuronal function, and cognitive deficits in both humans and mouse models. Suppression of inflammation has been proposed as a therapeutic approach to treating DS co-morbidities, including intellectual disability (DS/ID). Conversely, we discovered previously that treatment with the innate immune system stimulating cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which has both pro- and anti-inflammatory activities, improved cognition and reduced brain pathology in a mouse model of Alzheimer's disease (AD), another inflammatory disorder, and improved cognition and reduced biomarkers of brain pathology in a phase II trial of humans with mild-to-moderate AD. To investigate the effects of GM-CSF treatment on DS/ID in the absence of AD, we assessed behavior and brain pathology in 12-14 month-old DS mice (Dp[16]1Yey) and their wild-type (WT) littermates, neither of which develop amyloid, and found that subcutaneous GM-CSF treatment (5 µg/day, five days/week, for five weeks) improved performance in the radial arm water maze in both Dp16 and WT mice compared to placebo. Dp16 mice also showed abnormal astrocyte morphology, increased percent area of GFAP staining in the hippocampus, clustering of astrocytes in the hippocampus, and reduced numbers of calretinin-positive interneurons in the entorhinal cortex and subiculum, and all of these brain pathologies were improved by GM-CSF treatment. These findings suggest that stimulating and/or modulating inflammation and the innate immune system with GM-CSF treatment may enhance cognition in both people with DS/ID and in the typical aging population.

Astrogliosis and episodic memory in late life: higher GFAP is related to worse memory and white matter microstructure in healthy aging and Alzheimer's disease.

Astrocytes play a formative role in memory consolidation during physiological conditions; when dysregulated, astrocytes release glial fibrillary acidic protein (GFAP), which has been linked with negative memory outcomes in animal studies. We examined the association between blood GFAP, memory, and white matter (WM) integrity, accounting for blood markers of AD pathology (i.e., Aß42) and neurodegeneration (i.e., total tau; neurofilament light chain) in 114 older adults (asymptomatic, n = 69; MCI/AD dementia, n = 45). Higher levels of GFAP were associated with lower memory scores (p < 0.0001), such that for 1 SD increase in mean GFAP values, the memory composite score decreased on average by 0.49 (Standard error = 0.071). These results remained significant after controlling for diagnostic status and AD-related blood biomarkers. Higher GFAP was also related to lower WM integrity in regions vulnerable to AD pathology; however, WM integrity did not account for the association between GFAP and memory. Study findings suggest that higher blood levels of a marker of astrogliosis may reflect impoverished memory functions and white matter health, independent of markers of amyloid or neurodegeneration.

Industrial biotransformations in the synthesis of building blocks leading to enantiopure drugs.

Due to the growing demand of enantiomerically pure compounds, as well as the increasing strict safety, quality and environmentally requirements of industrial synthetic processes, the development of more sustainable, healthy and economically attractive strategies for the synthesis of chiral biologically active molecules is still an open challenge in the pharmaceutical industry. In this context, the biotransformations field has emerged as a real alternative to traditional synthetic routes, because of the exquisite chemo-, regio- and enantioselectivities commonly displayed by enzymes; thus, biocatalysis is becoming a widespread methodology for the synthesis of chiral compounds, not only at laboratory scale, but also at industrial scale. As hydrolases and oxido-reductases are the most employed enzymes, this review is focused on describing several industrial processes based on the use of these enzymes for obtaining chiral compounds useful for the pharmaceutical industry.

Policondritis recidivante: a propósito de un caso / Relapsing polychondritis: one case report

Presentamos un caso de policondritis recidivante que debutó con hipoacusia y cursó con ciertas peculiaridades. La paciente fue diagnosticada en un principio de otitis serosa. Investigando más detenidamente el caso se encontraron hallazgos que condujeron a la sospecha de policondritis recidivante. Se confirmó el diagnóstico mediante biopsia del cartílago nasal, realizándose a continuación un estudio sistémico exhaustivo. Como características peculiares del caso encontramos una hipoacusia mixta cuyo componente neurosensorial revirtió parcialmente con corticoides (AU)

We present a case of relapsing polychondritis which presented as hypoacusis and showed several peculiarities. The initial diagnosis was serous otitis. After a more careful study we found certain details which made us suspect a relapsing polychondritis. The diagnosis was confirmed by a biopsy of the nasal cartilage and a detailed systemic study was performed. As distinctive characteristics we found a mixed hypoacusis, in which the sensorineural component was partially recovered following corticoid treatment (AU)

[Recurrent polychondritis: apropos of a case]. / Policondritis recidivante: a propósito de un caso.

We present a case of relapsing polychondritis which presented as hypoacusis and showed several peculiarities. The initial diagnosis was serous otitis. After a more careful study we found certain details which made us suspect a relapsing polychondritis. The diagnosis was confirmed by a biopsy of the nasal cartilage and a detailed systemic study was performed. As distinctive characteristics we found a mixed hypoacusis, in which the sensorineural component was partially recovered following corticoid treatment.

Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1.

Calophyllum brasiliense, Lonchocarpus oaxacensis, and Lonchocarpus guatemalensis are used in Latin American folk medicine. Four natural xanthones, an acetylated derivative, and two coumarins were obtained from C. brasiliense. Two flavanones were extracted from L. oaxacensis and one chalcone from L guatemalensis. These compounds were tested as substrates and inhibitors for two recombinant sulfotransferases (SULTs) involved in the metabolism of many endogenous compounds and foreign chemicals. Assays were performed using recombinant phenolsulfotransferase (SULT1A1) and hydroxysteroidsulfotransferase (SULT2A1). Three of the five xanthones, one of the flavonoids and the coumarins tested were substrates for SULT1A1. None of the xanthones or the flavonoids were sulfonated by SULT2A1, whereas the coumarin mammea A/BA was a substrate for this enzyme. The natural xanthones reversibly inhibited SULT1A1 with IC50 values ranging from 1.6 to 7 microM whereas much higher amounts of these compounds were required to inhibit SULT2A1 (IC50 values of 26-204 microM). The flavonoids inhibited SULT1A1 with IC50 values ranging from 9.5 to 101 microM, which compared with amounts needed to inhibit SULT2A1 (IC50 values of 11 to 101 microM). Both coumarins inhibited SULT1A1 with IC50 values of 47 and 185 pM, and SULT2A1 with IC50 values of 16 and 31 microM. The acetylated xanthone did not inhibit either SULT1AI or SULT2A1 activity. Rotenone from a commercial source had potency comparable to that of the flavonoids isolated from Lonchocarpus for inhibiting both SULTs. The potency of this inhibition depends on the position and number of hydroxyls. The results indicate that SULT1A1, but not SULT2A1, is highly sensitive to inhibition by xanthones. Conversely, SULT2A1 is 3-6 times more sensitive to coumarins than SULT1A1. The flavonoids are non-specific inhibitors of the two SULTs. Collectively, the results suggest that these types of natural products have the potential for important pharmacological and toxicological interactions at the level of phase-II metabolism via sulfotransferases.

Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway.

Several lines of biochemical evidence correlate the presence of energy metabolic defects with the functional alterations associated with brain aging and with the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. Within this context we tested the ability of insulin to regulate the amyloid precursor protein (APP) processing in SH-SY5Y neuroblastoma cells. Our findings show that insulin promotes APP metabolism by a glucose-independent mechanism. We demonstrate a novel intracellular pathway that increases the rate of secretion of soluble APP through the activity of phosphatidyl-inositol 3 kinase (PI3-K). This pathway, downstream of insulin receptor tyrosine kinase activity, does not involve either the activation of protein kinase C or the mitogen-activated protein kinase (MAP-K) pathway. Because of the physiological role of PI3-K in the translocation of glucose transporter-containing vesicles, we speculate that PI3-K involvement in APP metabolism may act at the level of vesicular trafficking.

Flavanones and 3-hydroxyflavanones from Lonchocarpus oaxacensis.

The roots of the tropical tree Lonchocarpus oaxacensis afforded the 3-hydroxyflavanones jayacanol and mundulinol, as well as two flavanones, mundulin and minimiflorin. Flavonoids bearing 6,7-(dimethylpyran) and 8-(gammagamma-dimethyl allyl) substituents are characteristic for species grouped in the Minimiflori subsection. Therefore this subsection seems to be chemically and morphologically homogeneous. The antifungal activity of the four isolated compounds was tested against the wood rotting fungus Postia placenta, but only jayacanol was active.

Activity of alpha-secretase as the common final effector of protein kinase C-dependent and -independent modulation of amyloid precursor protein metabolism.

The metabolic fate of the amyloid precursor protein (APP) is one of the key factors in the pathogenesis of Alzheimer's disease (AD). A complex cellular mechanism regulates the rate at which the precursor is cleaved by alpha-secretase and released as soluble protein in the extracellular space. We show here that alpha-secretase constitutes the common final effector of several independent means of stimulation of soluble APP (sAPP) release. The release of sAPP by alpha-secretase resembles that of several other membrane-bound proteins with soluble counterparts, a process that is sensitive to matrix metalloprotease inhibitors. The hydroxamic acid-based compound KD-IX-73-4 inhibits phorbol ester-mediated sAPP release from COS cells with an IC50 of 8 microM, consistent with previous data for the same compound against leukocyte L-selectin shedding. Beyond direct protein kinase C (PKC) activation we show that KD-IX-73-4 inhibits also receptor-mediated sAPP release induced by carbachol in SH-SY5Y cells and by bradykinin in human skin fibroblasts, with the latter being a PKC-independent mechanism. Altogether these data suggest that all pharmacological means of stimulating sAPP release converge to a hydroxamic acid-based inhibitor-sensitive proteolytic enzyme. Moreover, because KD-IX-73-4 was effective in the inhibition of stimulated but not constitutive sAPP release, these data suggest the existence of different enzymes regulating the two metabolic pathways leading to sAPP secretion.

Fibroblasts from Alzheimer's disease donors do not differ from controls in response to heat shock.

We investigated HSPs mRNA expression in cultured fibroblasts from control and AD patients. Northern blot analysis using probes for HSP70 and HSC73 revealed that HS induced a several fold increase in both mRNA. Under these condition the extent of mRNA increase was similar in controls and AD. HS elicited also a modest increase in sAPP release that was similar in control and AD. The results suggest that the ability of AD fibroblasts to produce a defensive response to HS is preserved.

[Pulmonary epidermoid carcinoma in a 22-year-old patient with multiple cutaneous metastasis]. / Carcinoma epidermoide pulmonar en paciente de 22 años con metástasis cutáneas múltiples.

The authors present one clinical case of lung epidermoid carcinoma with several concurrent features which are uncommon in relation to this type of neoplasia. Consequently, the age of the patient (22), the lack of known risk factors, the histologic type (little differentiated squamous) and an aggressive biologic behaviour of the tumour, preceded of multiple cutaneous metastasis, are circumstances that make this clinical case exceptional. The more significative aspects present at lung carcinoma included in this age group respect to others are analyzed.

[Peritoneal pseudomyxoma secondary to mucinous cystadenoma of the ovary]. / Pseudomixoma peritoneal secundario a cistoadenoma mucinoso de ovario.

We present a new case of pseudomyxoma peritonei secondary to a mucinous cystadenoma of the ovary, whose presenting symptoms were abdominal distension and bilateral hernias. This is an uncommon entity and diagnosis tends to be casual. Each day, ultrasonography and computed tomography are more useful in suspicion. Aggressive surgical debulking followed by intraperitoneal chemotherapy seem to be the better treatment, even though controversies persist.

Antitermitic activity ofLonchocarpus castilloi flavonoids and heartwood extracts.

The heartwood of the tropical treeLonchocarpus castilloi Standley (Leguminosae) is highly resistant to attack by the drywood termitesCryptotermes brevis (Walker); nevertheless successive extraction with hexane, diethyl ether, acetone, methanol, and water reduced its resistance to these organisms. Antitermitic properties of the extracts were bioassayed using impregnated filter paper disks. Although the five extracts reduced both feeding and survival ofC. brevis, no significant differences among them were detected. Choice feeding tests showed that termites avoided eating the paper treated with the extracts. Two flavonoid compounds isolated from the heartwood, castillen D and castillen E, impregnated into filter paper showed concentration-dependent feeding deterrent activity, but were not toxic toC. brevis.

[Varicella pneumonia in the adult]. / Neumonía por varicela en el adulto.

In the adult, the primary infection by the varicella-zoster virus acquires an unusual severity due to several complications, the most frequent of them being pneumonia. The authors analyze the clinical, epidemiological, serological and radiological data of the only two cases of varicellous pneumonia in the adult at a general hospital during the past 5 years. They highlight as the main characteristics: easiness of diagnosis, dissociation between clinical and radiological signs and the excellent therapeutical response to the early administration of intravenous Aciclovir. They comment as well the risk factors of this complication and the criteria for hospitalization.