Optimization of a multielectrode array (MEA)-based approach to study the impact of Aβ on the SH-SY5Y cell line

The human brain stores, integrates, and transmits information recurring to millions of neurons, interconnected by countless synapses. Though neurons communicate through chemical signaling, information is coded and conducted in the form of electrical signals. Neuroelectrophysiology focus on the study of this type of signaling. Both intra and extracellular approaches are used in research, but none holds as much potential in high-throughput screening and drug discovery, as extracellular recordings using multielectrode arrays (MEAs). MEAs measure neuronal activity, both in vitro and in vivo. Their key advantage is the capability to record electrical activity at multiple sites simultaneously. Alzheimer’s disease (AD) is the most common neurodegenerative disease and one of the leading causes of death worldwide. It is characterized by neurofibrillar tangles and aggregates of amyloid-β (Aβ) peptides, which lead to the loss of synapses and ultimately neuronal death. Currently, there is no cure and the drugs available can only delay its progression. In vitro MEA assays enable rapid screening of neuroprotective and neuroharming compounds. Therefore, MEA recordings are of great use in both AD basic and clinical research. The main aim of this thesis was to optimize the formation of SH-SY5Y neuronal networks on MEAs. These can be extremely useful for facilities that do not have access to primary neuronal cultures, but can also save resources and facilitate obtaining faster high-throughput results to those that do. Adhesion-mediating compounds proved to impact cell morphology, viability and exhibition of spontaneous electrical activity. Moreover, SH-SY5Y cells were successfully differentiated and demonstrated acute effects on neuronal function after Aβ addition. This effect on electrical signaling was dependent on Aβ oligomers concentration. The results here presented allow us to conclude that the SH-SY5Y cell line can be successfully differentiated in properly coated MEAs and be used for assessing acute Aβ effects on neuronal signaling.

Consequences of big data on the individual: Interview

The speed with which data has moved from being scarce, expensive and valuable, thus justifying detailed and careful verification and analysis to a situation where the streams of detailed data are almost too large to handle has caused a series of shifts to occur. Legal systems already have severe problems keeping up with, or even in touch with, the rate at which unexpected outcomes flow from information technology. The capacity to harness massive quantities of existing data has driven Big Data applications until recently. Now the data flows in real time are rising swiftly, become more invasive and offer monitoring potential that is eagerly sought by commerce and government alike. The ambiguities as to who own this often quite remarkably intrusive personal data need to be resolved – and rapidly - but are likely to encounter rising resistance from industrial and commercial bodies who see this data flow as ‘theirs’. There have been many changes in ICT that has led to stresses in the resolution of the conflicts between IP exploiters and their customers, but this one is of a different scale due to the wide potential for individual customisation of pricing, identification and the rising commercial value of integrated streams of diverse personal data. A new reconciliation between the parties involved is needed. New business models, and a shift in the current confusions over who owns what data into alignments that are in better accord with the community expectations. After all they are the customers, and the emergence of information monopolies needs to be balanced by appropriate consumer/subject rights. This will be a difficult discussion, but one that is needed to realise the great benefits to all that are clearly available if these issues can be positively resolved. The customers need to make these data flow contestable in some form. These Big data flows are only going to grow and become ever more instructive. A better balance is necessary, For the first time these changes are directly affecting governance of democracies, as the very effective micro targeting tools deployed in recent elections have shown. Yet the data gathered is not available to the subjects. This is not a survivable social model. The Private Data Commons needs our help. Businesses and governments exploit big data without regard for issues of legality, data quality, disparate data meanings, and process quality. This often results in poor decisions, with individuals bearing the greatest risk. The threats harbored by big data extend far beyond the individual, however, and call for new legal structures, business processes, and concepts such as a Private Data Commons. This Web extra is the audio part of a video in which author Marcus Wigan expands on his article "Big Data's Big Unintended Consequences" and discusses how businesses and governments exploit big data without regard for issues of legality, data quality, disparate data meanings, and process quality. This often results in poor decisions, with individuals bearing the greatest risk. The threats harbored by big data extend far beyond the individual, however, and call for new legal structures, business processes, and concepts such as a Private Data Commons.

The Real-Quaternionic Indicator of Irreducible Self-Conjugate Representations of Real Reductive Algebraic Groups and A Comment on the Local Langlands Correspondence of GL(2, F )

The real-quaternionic indicator, also called the $\delta$ indicator, indicates if a self-conjugate representation is of real or quaternionic type. It is closely related to the Frobenius-Schur indicator, which we call the $\varepsilon$ indicator. The Frobenius-Schur indicator $\varepsilon(\pi)$ is known to be given by a particular value of the central character. We would like a similar result for the $\delta$ indicator. When $G$ is compact, $\delta(\pi)$ and $\varepsilon(\pi)$ coincide. In general, they are not necessarily the same. In this thesis, we will give a relation between the two indicators when $G$ is a real reductive algebraic group. This relation also leads to a formula for $\delta(\pi)$ in terms of the central character. For the second part, we consider the construction of the local Langlands correspondence of $GL(2,F)$ when $F$ is a non-Archimedean local field with odd residual characteristics. By re-examining the construction, we provide new proofs to some important properties of the correspondence. Namely, the construction is independent of the choice of additive character in the theta correspondence.

Leccinum vulpinum Watling induces DNA damage, decreases cell proliferation and induces apoptosis on the human MCF-7 breast cancer cell line

The current work aimed to study the antitumour activity of a phenolic extract of the edible mushroom Leccinum vulpinum Watling, rich essentially in hydroxybenzoic acids. In a first approach, the mushroom extract was tested against cancer cell growth by using four human tumour cell lines. Given the positive results obtained in these initial screening experiments and the evidence of some studies for an inverse relationship between mushroom consumption and breast cancer risk, a detailed study of the bioactivity of the extract was carried out on MCF-7 cells. Once the selected cell line to precede the work was the breast adenocarcinoma cell line, the human breast non-malignant cell line MCF-10A was used as control. Overall, the extract decreased cellular proliferation and induced apoptosis. Furthermore, the results also suggest that the extract causes cellular DNA damage. Data obtained highlight the potential of mushrooms as a source of biologically active compounds, particularly with antitumour activity.

Bodies on the Line: Violence, Disposable Subjects, and the US-Mexico Border Industrial Complex

Bodies On the Line: Violence, Disposable Subjects, and the Border Industrial Complex explores the construction of identity and notions of belonging within an increasingly privatized and militarized Border Industrial Complex. Specifically, the project interrogates how discourses of Mexican migrants as racialized, gendered, and hypersexualized “deviants” normalize violence against border crossers. Starting at Juárez/El Paso border, I follow the expanding border, interrogating the ways that Mexican migrants, regardless of sexual orientation, have been constructed and disciplined according to racialized notions of “sexual deviance." I engage a queer of color critique to argue that sexual deviance becomes a justification for targeting and containing migrant subjects. By focusing on the economic and racially motivated violence that the Border Industrial Complex does to Mexican migrant communities, I expand the critiques that feminists of color have long leveraged against systemic violence done to communities of color through the prison industrial system. Importantly, this project contributes to transnational feminist scholarship by contextualizing border violence within the global circuits of labor, capital, and ideology that shape perceptions of border insecurity. The project contributes an interdisciplinary perspective that uses a multi-method approach to understand how border violence is exercised against Mexicans at the Mexico-US border. I use archival methods to ask how historical records housed at the National Border Patrol Museum and Memorial Library serve as political instruments that reinforce the contemporary use of violence against Mexican migrants. I also use semi-structured interviews with nine frequent border crossers to consider the various ways crossers defined and aligned themselves at the border. Finally, I analyze the master narratives that come to surround specific cases of border violence. To that end, I consider the mainstream media’s coverage, legal proceedings, and policy to better understand the racialized, gendered, and sexualized logics of the violence.

Off-line and On-line Affective Recognition of a Computer User through A Biosignal Processing Approach

Physiological signals, which are controlled by the autonomic nervous system (ANS), could be used to detect the affective state of computer users and therefore find applications in medicine and engineering. The Pupil Diameter (PD) seems to provide a strong indication of the affective state, as found by previous research, but it has not been investigated fully yet. In this study, new approaches based on monitoring and processing the PD signal for off-line and on-line affective assessment (“relaxation” vs. “stress”) are proposed. Wavelet denoising and Kalman filtering methods are first used to remove abrupt changes in the raw Pupil Diameter (PD) signal. Then three features (PDmean, PDmax and PDWalsh) are extracted from the preprocessed PD signal for the affective state classification. In order to select more relevant and reliable physiological data for further analysis, two types of data selection methods are applied, which are based on the paired t-test and subject self-evaluation, respectively. In addition, five different kinds of the classifiers are implemented on the selected data, which achieve average accuracies up to 86.43% and 87.20%, respectively. Finally, the receiver operating characteristic (ROC) curve is utilized to investigate the discriminating potential of each individual feature by evaluation of the area under the ROC curve, which reaches values above 0.90. For the on-line affective assessment, a hard threshold is implemented first in order to remove the eye blinks from the PD signal and then a moving average window is utilized to obtain the representative value PDr for every one-second time interval of PD. There are three main steps for the on-line affective assessment algorithm, which are preparation, feature-based decision voting and affective determination. The final results show that the accuracies are 72.30% and 73.55% for the data subsets, which were respectively chosen using two types of data selection methods (paired t-test and subject self-evaluation). In order to further analyze the efficiency of affective recognition through the PD signal, the Galvanic Skin Response (GSR) was also monitored and processed. The highest affective assessment classification rate obtained from GSR processing is only 63.57% (based on the off-line processing algorithm). The overall results confirm that the PD signal should be considered as one of the most powerful physiological signals to involve in future automated real-time affective recognition systems, especially for detecting the “relaxation” vs. “stress” states.

A complexity-based diagnostic on the democratic unity roundtable mud: problems and alternatives (2008-2016)

Este trabajo exploratorio estudia al movimiento político Mesa de la Unidad Democrática (MUD), creada con el fin de oponerse la Gobierno socialista existente en venezuela. La crítica que este documento realiza, parte desde el punto de vista de la Ciencia de la Complejidad. Algunos conceptos clave de sistemas complejos han sido utilizados para explicar el funcionamiento y organización de la MUD, esto con el objetivo de generar un diagnóstico integral de los problemas que enfrenta, y evidenciar las nuevas percepciones sobre comportamientos perjudiciales que el partido tiene actualmente. Con el enfoque de la complejidad se pretende ayudar a comprender mejor el contexto que enmarca al partido y, para, finalmente aportar una serie de soluciones a los problemas de cohesión que presen

The Real-life Experience With Cardiovascular Complications In The First Dose Of Fingolimod For Multiple Sclerosis.

Fingolimod is a new and efficient treatment for multiple sclerosis (MS). The drug administration requires special attention to the first dose, since cardiovascular adverse events can be observed during the initial six hours of fingolimod ingestion. The present study consisted of a review of cardiovascular data on 180 patients with MS receiving the first dose of fingolimod. The rate of bradycardia in these patients was higher than that observed in clinical trials with very strict inclusion criteria for patients. There were less than 10% of cases requiring special attention, but no fatal cases. All but one patient continued the treatment after this initial dose. This is the first report on real-life administration of fingolimod to Brazilian patients with MS, and one of the few studies with these characteristics in the world.

Effect of propolis gel on the in vitro reduction of dentin permeability

OBJECTIVE: The aim of this study was to evaluate the capacity of potassium oxalate, fluoride gel and two kinds of propolis gel to reduce the hydraulic conductance of dentin, in vitro. MATERIAL AND METHODS: The methodology used for the measurement of hydraulic conductance of dentin in the present study was based on a model proposed in literature. Thirty-six 1-mm-thick dentin discs, obtained from extracted human third molars were divided into 4 groups (n=9). The groups corresponded to the following experimental materials: GI-10% propolis gel, pH 4.1; GII-30% propolis gel; GIII-3% potassium oxalate gel, pH 4,1; and GIV-1.23% fluoride gel, pH 4.1, applied to the dentin under the following surface conditions: after 37% phosphoric acid and before 6% citric acid application. The occluding capacity of the dentin tubules was evaluated using scanning electron microscopy (SEM) at ×500, ×1,000 and ×2,000 magnifications. Data were analyzed statistically by two-way ANOVA and Tukey's test at 5% significance level. RESULTS: Groups I, II, III, IV did not differ significantly from the others in any conditions by reducing in hydraulic conductance. The active agents reduced dentin permeability; however they produced the smallest reduction in hydraulic conductance when compared to the presence of smear layer (P<0.05). The effectiveness in reducing dentin permeability did not differ significantly from 10% or 30% propolis gels. SEM micrographs revealed that dentin tubules were partially occluded after treatment with propolis. CONCLUSIONS: Under the conditions of this study, the application of 10% and 30% propolis gels did not seem to reduce the hydraulic conductance of dentin in vitro, but it showed capacity of partially obliterating the dentin tubules. Propolis is used in the treatment of different oral problems without causing significant great collateral effects, and can be a good option in the treatment of patients with dentin sensitivity.

Influence of intrapulpal pressure simulation on the bond strength of adhesive systems to dentin

The purpose of this study was to evaluate the influence of intrapulpal pressure simulation on the bonding effectiveness of etch & rinse and self-etch adhesives to dentin. Eighty sound human molars were distributed into eight groups, according to the permeability level of each sample, measured by an apparatus to assess hydraulic conductance (Lp). Thus, a similar mean permeability was achieved in each group. Three etch & rinse adhesives (Prime & Bond NT - PB, Single Bond -SB, and Excite - EX) and one self-etch system (Clearfil SE Bond - SE) were employed, varying the presence or absence of an intrapulpal pressure (IPP) simulation of 15 cmH2O. After adhesive and restorative procedures were carried out, the samples were stored in distilled water for 24 hours at 37°C, and taken for tensile bond strength (TBS) testing. Fracture analysis was performed using a light microscope at 40 X magnification. The data, obtained in MPa, were then submitted to the Kruskal-Wallis test ( a = 0.05). The results revealed that the TBS of SB and EX was significantly reduced under IPP simulation, differing from the TBS of PB and SE. Moreover, SE obtained the highest bond strength values in the presence of IPP. It could be concluded that IPP simulation can influence the bond strength of certain adhesive systems to dentin and should be considered when in vitro studies are conducted.

Search for cytotoxic agents in multiple Laurencia complex seaweed species (Ceramiales, Rhodophyta) harvested from the Atlantic Ocean with emphasis on the Brazilian State of Espírito Santo

The development of new anti-cancer drugs of algal origin represents one of the least explored frontiers in medicinal chemistry. In this regard, the diversity of micro- and macroalgae found in Brazilian coastal waters can be viewed as a largely untapped natural resource. In this report, we describe a comparative study on the cytotoxic properties of extracts obtained from the Laurencia complex: Laurencia aldingensis, L. catarinensis, L. dendroidea, L. intricata, L. translucida, L. sp, and Palisada flagellifera. All of these species were collected in the coastal waters of the State of Espírito Santo, Brazil. Four out of the twelve samples initially investigated were found to show significant levels of toxicity towards a model tumor cell line (human uterine sarcoma, MES-SA). The highest levels of cytotoxicity were typically associated with non-polar (hexane) algal extracts, while the lowest levels of cytotoxicity were found with the corresponding polar (methanol) extracts. In this report, we also describe a biological model currently in development that will not only facilitate the search for new anti-cancer drug candidates of algal origin, but also permit the identification of compounds capable of inducing the destruction of multi-drug resistant tumors with greater efficiency than the pharmaceuticals currently in clinical use.

A new species of Trichogenes from the rio Itapemirim drainage, southeastern Brazil, with comments on the monophyly of the genus (Siluriformes: Trichomycteridae)

A new species of the formerly monotypic genus Trichogenes is described from a high-altitude stream of the rio Itapemirim system, an isolated Atlantic drainage in the State of Espírito Santo, southeastern Brazil. Trichogenes claviger, new species, differs from all other trichomycterids by the sexually dimorphic posterior process of the opercle, much elongated in males; the terminal mouth; the deeply bifurcated anterior neural spines and the presence of a large anterodorsal claw-like process on the neural arches of the anterior four free vertebrae. The new species also differs from its only congener, T. longipinnis, by a number of additional traits, including the the lack of branched anal-fin rays in specimens of any size; the broader than long posterior nostril; the deeper head (head depth 72.9-86.6% HL); the presence of a fine dark line along the base of the anal fin; the lack of dark spots on cheeks; the shape of the interopercle; the presence of odontodes on a bony expansion on the posterodorsal margin of the interopercle; the fewer vertebrae (35); the absence of an antorbital; and the fewer pleural ribs (eight). Small juveniles of the new species are also strikingly different from those of all other Trichomycteridae, including T. longipinnis, having a very large lateral eye, an upturned mouth, and compressed head. Trichogenes claviger occurs in shaded sectors of a blackwater sluggish stream with sandy substrate and patchy accumulations of vegetable debris, a habitat markedly different from the rocky torrential environment known for T. longipinnis. A comparison of the internal anatomy of the two species provides the basis for a hypothesis of a monophyletic Trichogenes. Data from the new species further support a sister-group relationship between Trichogeninae and Copionodontinae, as well as the position of that clade as sister group to all remaining Trichomycteridae.

Effects of Variations in Nonlinear Damping Coefficients on the Parametric Vibration of a Cantilever Beam with a Lumped Mass

Uncertainties in damping estimates can significantly affect the dynamic response of a given flexible structure. A common practice in linear structural dynamics is to consider a linear viscous damping model as the major energy dissipation mechanism. However, it is well known that different forms of energy dissipation can affect the structure's dynamic response. The major goal of this paper is to address the effects of the turbulent frictional damping force, also known as drag force on the dynamic behavior of a typical flexible structure composed of a slender cantilever beam carrying a lumped-mass on the tip. First, the system's analytical equation is obtained and solved by employing a perturbation technique. The solution process considers variations of the drag force coefficient and its effects on the system's response. Then, experimental results are presented to demonstrate the effects of the nonlinear quadratic damping due to the turbulent frictional force on the system's dynamic response. In particular, the effects of the quadratic damping on the frequency-response and amplitude-response curves are investigated. Numerically simulated as well as experimental results indicate that variations on the drag force coefficient significantly alter the dynamics of the structure under investigation. Copyright (c) 2008 D. G. Silva and P. S. Varoto.

Effect of zinc insertion and hydrophobicity on the membrane interactions and PDT activity of porphyrin photosensitizers

A series of photosensitizers (PS), which are meso-substituted tetra-cationic porphyrins, was synthesized in order to study the role of amphiphilicity and zinc insertion in photodynamic therapy (PDT) efficacy. Several properties of the PS were evaluated and compared within the series including photophysical properties (absorption spectra, fluorescence quantum yield Phi(f), and singlet oxygen quantum yield Phi(Delta)), uptake by vesicles, mitochondria and HeLa cells, dark and phototoxicity in HeLa cells. The photophysical properties of all compounds are quite similar (Phi(f) <= 0.02; Phi(Delta) similar to 0.8). An increase in lipophilicity and the presence of zinc in the porphyrin ring result in higher vesicle and cell uptake. Binding in mitochondria is dependent on the PS lipophilicity and on the electrochemical membrane potential, i.e., in uncoupled mitochondria PS binding decreases by up to 53%. The porphyrin substituted with octyl groups (TC8PyP) is the compound that is most enriched in mitochondria, and its zinc derivative (ZnTC8PyP) has the highest global uptake. The stronger membrane interaction of the zinc-substituted porphyrins is attributed to a complexing effect with phosphate groups of the phospholipids. Zinc insertion was also shown to decrease the interaction with isolated mitochondria and with the mitochondria of HeLa cells, an effect that has been explained by the particular characteristics of the mitochondrial internal membrane. Phototoxicity was shown to increase proportionally with membrane binding efficiency, which is attributed to favorable membrane interactions which allow more efficient membrane photooxidation. For this series of compounds, photodynamic efficiency is directly proportional to the membrane binding and cell uptake, but it is not totally related to mitochondrial targeting.