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The pathology of Alzheimer's disease (AD) is featured with extracellular amyloid-β (Aβ) plaques, whose impact on the mechanical properties of the surrounding brain tissues is unclear. Microglia sense and integrate biochemical cues of the microenvironment. However, whether the microglial mechanosensing pathways influence AD pathogenesis is unknown. Here, we surveyed the elevated stiffness of Aβ-plaque-associated tissues and observed the selective upregulation of the mechanosensitive ion channel Piezo1 in Aβ-plaque-associated microglia. Piezo1 sensed the stiffness stimuli of Aβ fibrils and subsequently induced Ca

Esta dissertação, desenvolvida dentro do contexto do projeto PRONEX do Centro Geotécnico de Meio Ambiente da PUC-Rio e através de um convênio com FURNAS - PUC-Rio, apresenta uma contribuição quanto à identificação e compreensão dos mecanismos envolvidos em processos de erosão, considerando seus aspectos geológico-geotécnicos bem como medidas preventivas de reparo no caso da formação de uma voçoroca específica. A evolução do processo erosivo estudado tem suas origens na remoção mecânica de uma camada com cerca de cinco metros de solo argiloso de uma área explorada na época da construção de uma barragem de terra homogênea pertencente ao complexo Hidrelétrico de Itumbiara. Os principais aspectos da área estudada, tais como sua localização, condições climáticas e tipos de solo e vegetação foram considerados no desenvolvimento do trabalho, além de aspectos geológicos regionais e características geológico-geotécnicas da área afetada pelos processos de erosão. Tomando como base o perfil de intemperismo identificado pela inspeção das paredes da formação da voçoroca, bem como amostras de furos de sondagens SPT (ensaio de penetração normal), quatro tipos de camadas de solo foram tomados como representantes das condições do local. Objetivando-se a identificação, classificação e definição do potencial de erosão de tais materiais, espécies de amostras indeformadas de bloco (bem como as amolgadas) foram submetidas a investigações laboratoriais abrangendo: ensaio convencional de caracterização de solo; ensaio de caracterização MCT (mini-MCV); Crumb Test; ensaio de Desagregação; Pinhole Test; e Inderbitzen; ensaios de permeabilidade (também desenvolvidos em campo); análise química da água intersticial; análise mineralógica (difração de raios - X); ensaio de Resistência a Tração (sob condições de saturações diferentes) e ensaio de papel filtro (para definição das curvas características da umidade). Baseado em testes de laboratório, observações e dados de pesquisas de campo advindos de um monitoramento de poro-pressão (através de piezômetros instalados no local), mecanismos de erosão que possam predominar na área foram definidos como: micro-ravinas, ravinas e voçorocas, dentre outros. Também, ao final do trabalho, são apresentadas sugestões para remediação do local, considerando-se medidas corretivas usadas dentro do contexto da prática geotécnica convencional, e uma metodologia a ser seguida em investigações futuras relacionadas à caracterização do local e desenvolvimento de processos de erosão. This dissertation, developed within the context of the PRONEX Project of the Environmental Geotechnical Center of PUC-Rio and through a FURNAS-PUC-Rio Convenium, presents a contribution towards the identification and comprehension of mechanisms involved in erosion processes, considering its geological and geotechnical aspects as well as preventive repairing measures in the case of a specific gully formation. The evolution of the studied erosive process has its origin in the mechanical removal of some five meters of a clayey soil layer from a borrow area exploited at the time of the construction of an homogeneous embankment dam belonging to the Itumbiara Hydroelectric Complex. The main aspects of the studied area, such as its location, climatic conditions and soil and vegetation types were considered in the development of the work, besides regional geological aspects and geological-geotechnical features of the area affected by the erosion processes. Taking as a basis the unsaturated weathering profile identified by inspection of the walls of the gully formation, as well as of samples from SPT (standard penetration test) boreholes, four types of soil layers were taken as representative of site conditions. Aiming the identification, classification and definition of the erodibility potential of such materials, specimens from undisturbed block samples (as well as remolded ones) were submitted to laboratory investigations comprising: conventional soil characterization tests; MCT characterization test (mini-MCV); crumb test; desegregation test; pinhole test; Inderbitzen test, permeability tests (also performed in the field); chemical analysis (both soil and voids -water); mineralogical analysis (Xrays diffraction); tensile strength test (under different saturation conditions) and filter paper test (for definition of soil-moisture characteristic curves). Based on the results of the laboratory tests, field observations and data from pore-pressure monitoring (through piezometers installed in the site), erosion mechanisms that may prevail in the area were defined as micro-rills, rill, gully and others. Also, at the end of the work, are presented suggestions for remediation of the site, considering corrective measures used within the context of conventional geotechnical practice, and a methodology to be followed in further investigations related to the characterization of the site and development of erosion processes.

This thesis addresses the observation, analysis and dynamics of waves as being trapped, generated and focused by sloping topography. ---Shelf waves with diurnal tidal frequency off Greenland--- Tidal analysis has been carried out on current measurements at a “cross-shelf” transect off Greenland at 71 N. The diurnal tides manifest themselves mainly as a barotropic continental shelf wave, travelling southward along the shelf slope. This follows from the amplitude distribution of the diurnal tidal components and from the rotation sense of the tidal ellipses at different cross-slope locations, as calculated with simple two-dimensional models. The well organized cross-slope pattern of the velocity amplitudes is absent in observations further north near 75 N. These observations suggest that the local vanishing of the group velocity, which is caused by topography, is of importance for the existence and local amplification of these continental shelf waves with diurnal tidal frequency. ---Tidal and residual currents near the shelf break in Biscay--- Internal-wave energy in continuously stratified fluids propagates in the vertical plane, at an angle set by the wave, buoyancy and Coriolis frequencies. Repeated Acoustic Doppler Current Profiler observations on three transects, crossing the shelf edge, now directly reveal this beam-wise propagation of internal tides in the Bay of Biscay. This confirms previous suggestions based on observations sampled more sparsely in space. The present observation is made by bin-wise harmonic analysis of horizontal currents, leading to the spatial resolution of barotropic and baroclinic semi-diurnal tidal and (time-averaged) residual flows. The observed baroclinic tide compares favourably to that produced by a two-dimensional numerical model. The observations reveal details of the internal tidal beam, including its spatial amplitude distribution, presence of amphidromes and direction of phase propagation. The cross-isobath structure of the along-slope barotropic mean flow shows a localized maximum near the shelf break. Over two transects it agrees in sign and magnitude with a theoretical tidally-rectified flow. The baroclinic, cross-isobath mean flow shows a strong near-bottom downwelling flow, compensated by an on-shelf directed flow in the upper part. The along-shelf mean flow displays subsurface-intensification attributed here to frictional modification of a tidally-rectified flow that is bottom-trapped due to stratification. ---Internal wave focusing revisited--- An experiment which discussed the appearance of an internal wave attractor in a uniformly-stratified, free-surface fluid (Maas et al. 1997) is revisited. This is done in order to give a more detailed and more accurate description of the underlying focusing process. Evolution of the attractor can now be quantified. For the tank with one sloping sidewall, and for the parameter regime (density stratification, forcing frequency) studied, the inverse exponential growth rate determined at several locations in the fluid turns out to be 122 seconds always. Only the start and duration of the growth differs: away from the attractor region it appears later and is of shorter duration. Here, these features are interpreted by employing a new theoretical basis that incorporates an external forcing via a surface boundary condition (an infinitesimal barotropic seiche) and that describes the solution in terms of propagating waves.

AbstractIn this study, the prevalence and prognostic significance of the early repolarization (ER) pattern in the inferolateral leads in patients with Brugada syndrome were investigated. Clinical, genetic, and electrophysiological data were collected and analyzed from 69 individuals with either a spontaneous or drug‐induced Brugada type 1 electrocardiogram (ECG) pattern. An ER pattern was defined as J‐point elevation at least 0.1 mV from the baseline in at least 2 inferior or lateral leads. The presence of late potentials and inducibility of ventricular fibrillation (VF) by programmed stimulation were compared between patients with and without a J wave. Follow‐up data, including outcome events, were obtained for all patients. An ER pattern was observed in the inferolateral leads in 6 patients with a spontaneous Brugada type 1 ECG pattern and in 1 patient with a drug‐induced Brugada type 1 ECG pattern. There was no significant intergroup difference in symptoms, family history of sudden cardiac death, prevalence of late potentials, or inducibility of VF. No patient with the ER pattern developed a cardiac event during the mean follow‐up period of 73.6±38.1 months. The ER pattern in the inferolateral leads is not uncommon in Brugada syndrome; however, the presence of a J wave does not appear to be associated with subsequent arrhythmic events in patients with Brugada syndrome.

The Ophiuchus stream is a short arc-like stellar feature of uncertain origin located $\sim 5$ kpc North of the Galactic centre. New proper motions from the second $Gaia$ data release reconcile the direction of motion of stream members with the stream arc, resolving a puzzling mismatch reported in earlier work. We use N-body simulations to show that the stream is likely only on its second pericentric passage, and thus was formed recently. The simulations suggest that the entire disrupted progenitor is visible in the observed stream today, and that little further tidal debris lies beyond the ends of the stream. The luminosity, length, width, and velocity dispersion of the stream suggest a globular cluster (GC) progenitor substantially fainter and of lower surface brightness than estimated in previous work, and unlike any other known globulars in the Galaxy. This result suggests the existence of clusters that would extend the known GC population to fainter and more weakly bound systems than hitherto known. How such a weakly-bound cluster of old stars survived until it was disrupted so recently, however, remains a mystery. Integrating backwards in time, we find that the orbits of Sagittarius and Ophiuchus passed within $\sim 5$ kpc of each other about $\sim 100$ Myrs ago, an interaction that might help resolve this puzzle. Comment: 11 pages, 7 figures, submitted to MNRAS

In this note we have revisited some of the results of Trachtenberg (On the cross-correlation functions of maximal linear sequences, Ph.D. thesis, University of Southern California, Los Angeles, 1970), which are directly related with the number of solutions of some special linearized polynomials over finite fields. In some cases we give improvements. Also, we give some results on the exact number of solutions of certain linearized equations depending on the coefficients of that equation.

1. The hypothermic effect on unanaesthetized cats of tetrodotoxin injected I.V. or into the lateral cerebral ventricle was examined.2. At an ambient temperature (T(a)) of 22 degrees C, tetrodotoxin given intraventricularly was over 400 times more potent in lowering body temperature (T(b)) than when given I.V. The magnitude of the hypothermia was dose-dependent for both routes. Decreases in T(b) as great as 6.8 degrees C were induced by infusions or multiple injections of tetrodotoxin into the ventricle.3. Tetrodotoxin also lowered T(b) at T(a) = 13, 30 or 35 degrees C. Tachypnoea, which lasted for longer durations and which became more intense the higher the T(a), accompanied development of hypothermia. Shivering was observed only during recovery from hypothermia at 13 degrees C.4. During the tetrodotoxin-induced hypothermia, animals were still able to regulate against environmental thermal stresses.5. EDTA disodium salt, leucocytic pyrogen and prostaglandin E(1) antagonized the hypothermic effect of tetrodotoxin when they were administered during recovery from tetrodotoxin.6. Activation of heat-loss mechanisms, and the absence of compensatory shivering during development of hypothermia after tetrodotoxin administration, plus lowering of T(b) by tetrodotoxin at T(a) above as well as below the thermoneutral temperature, indicate that lowering of the thermoregulatory set-point is the mechanism by which centrally or peripherally administered tetrodotoxin lowers T(b). Further evidence for set-point lowering after intraventricular administration of tetrodotoxin is provided by persistence of the ability to regulate against both heat and cold stresses during hypothermia. The possibility that the decrease in set-point could be due to the well known action of tetrodotoxin to block transient increases in membrane sodium ion conductance is discussed in terms of a recent hypothesis regarding ionic control of the thermoregulatory set-point.