449 research outputs found
Observação introspectiva de uma tarefa do voleibol em ambiente escolar
Parece ser já um lugar comum dizer-se que os professores de educação física e os treinadores desportivos tentam ajudar os praticantes (alunos e atletas) no sentido de melhorar as suas prestações e que, para atingirem tal objectivo, têm de observar criteriosamente as suas execuções motoras de modo a poderem fornecer "feedbacks" apropriados que as facilitem e melhorem. Por outro lado há uma constante necessidade de controlar o envolvimento onde estão inseridos de forma a permitir-lhes uma eficaz intervenção pedagógica. Esse controle é efectuado pela sua competência de observação.
Estas são as razões primordiais que nos levam a dizer que a observação é uma tarefa inerente ao ensino e ao treino das habilidades físicas e desportivas, tendo em conta a sua necessidade para supervisionar os mais diversificados aspectos do comportamento dos seus alunos (atenção, disciplina, comportamentos apropriados e inapropriados, fora da tarefa, etc.), como também o desenvolvimento dos comportamentos técnicos, possibilitando corrigir erros de execução e, consequentemente, aperfeiçoá-los
The impact of realistic models of mass segregation on the event rate of extreme-mass ratio inspirals and cusp re-growth
One of the most interesting sources of gravitational waves (GWs) for LISA is
the inspiral of compact objects on to a massive black hole (MBH), commonly
referred to as an "extreme-mass ratio inspiral" (EMRI). The small object,
typically a stellar black hole (bh), emits significant amounts of GW along each
orbit in the detector bandwidth. The slowly, adiabatic inspiral of these
sources will allow us to map space-time around MBHs in detail, as well as to
test our current conception of gravitation in the strong regime. The event rate
of this kind of source has been addressed many times in the literature and the
numbers reported fluctuate by orders of magnitude. On the other hand, recent
observations of the Galactic center revealed a dearth of giant stars inside the
inner parsec relative to the numbers theoretically expected for a fully relaxed
stellar cusp. The possibility of unrelaxed nuclei (or, equivalently, with no or
only a very shallow cusp) adds substantial uncertainty to the estimates. Having
this timely question in mind, we run a significant number of direct-summation
body simulations with up to half a million particles to calibrate a much
faster orbit-averaged Fokker-Planck code. We then investigate the regime of
strong mass segregation (SMS) for models with two different stellar mass
components. We show that, under quite generic initial conditions, the time
required for the growth of a relaxed, mass segregated stellar cusp is shorter
than a Hubble time for MBHs with
(i.e. nuclei in the range of LISA). SMS has a significant impact boosting the
EMRI rates by a factor of for our fiducial models of Milky Way type
galactic nuclei.Comment: Accepted by CQG, minor changes, a bit expande
Total phallic construction techniques in transgender men: An updated narrative review
From 2012, the World Professional Association Transgender Health defined a structured therapeutic path and standards of care for transgender patients undergoing genital gender affirming surgery (GGAS). The main goal of GGAS in transgender males is to provide patients with an aesthetically appealing appearance of the neophallus that should allow standing micturition and enabling penetrative intercourse along with erogenous and tactile sensitivity. The optimal procedure should be safe, reproducible and performed in the fewest number of surgical stages. The ideal technique for total phallic construction (TPC) has not yet been demonstrated; TPC remains challenging and, from a functional point of view, it is also make more demanding as yet there are no perfect replacement materials for erectile and urethral tissues. Several procedures and different type of flaps (pedicled and free-flaps) have been proposed and investigated over time to address TPC with significant advances over the years especially after microsurgical procedures introduction. Due to its high complexity TPC is not free from complications. Local tissue ischaemic complications, complete and partial flap loss, donor site morbidity and urethral complications (fistulae and strictures) are reported. This narrative review aims to provide the readers with a contemporary overview of surgical procedures for TPC in transgender males focusing on key surgical steps, as well as surgical and functional outcomes
Formation and Evolution of Black Holes in Galactic Nuclei and Star Clusters
We study the formation, growth, and co-evolution of single and multiple supermassive black holes (SMBHs) and compact objects like neutron stars, white dwarfs, and stellar mass black holes in galactic nuclei and star clusters, focusing on the role of stellar dynamics. In this paper we focus on one exemplary topic out of a wider range of work done, the study of orbital parameters of binary black holes in galactic nuclei (binding energy, eccentricity, relativistic coalescence) as a function of initial parameters. In some cases the classical evolution of black hole binaries in dense stellar systems drives them to surprisingly high eccentricities, which is very exciting for the emission of gravitational waves and relativistic orbit shrinkage. Such results are interesting to the emerging field of gravitational wave astronomy, in relation to a number of ground and space based instruments designed to measure gravitational waves from astrophysical sources (VIRGO, Geo600, LIGO, LISA). Our models self-consistently cover the entire range from Newtonian dynamics to the relativistic coalescence of SMBH binaries
New synthetic raloxifen-like di(hetero)arylamines induce apoptosis and inhibit the estrogen receptor in breast cancer cells
Breast cancer is the most common form of cancer in women in the western world, and in spite of some decline in death rates in recent years it is still the second most common cause of death from cancer, in women (1).
For more than three decades, the estrogen receptor (ER) has been the most important biomarker of breast cancer, largely due to the substantial benefit that endocrine therapy provides in the treatment of ER positive tumors, in women of all ages (2). Endocrine therapies currently available include selective estrogen receptor modulators (SERMs), like tamoxifen and raloxifene (3). Raloxifene acts as an estrogen antagonist in the breast by competitive binding to the ER, inhibiting estrogen-induced breast tissue proliferation and preventing the growth of mammary tumors. In addition, it shows no increase in incidence of endometrial cancer, which is an advantage compared to tamoxifen (4). The successes of these endocrine therapies, however, are often limited. So, it is important to continue searching for new strategies and/or drugs that overcome resistance problems and that can be potent enough with fewer adverse effects.
In this work, we studied the effect of two new synthetic di(hetero)arylamines, named MJQ2 and MJQ3 (which have in common with raloxifene a benzothiophene ring), in cell proliferation and apoptosis of two different cell lines from breast cancer: MCF-7 (ER positive) and MDA-MB-231 (ER negative).
Our results showed that both diarylamines induce apoptosis without significant necrosis (evaluated by Hoechst-PI staining), at the IC50 concentration that inhibits cell proliferation (evaluated by the SRB assay). The results obtained with TMRM, a marker of mitochondrial membrane potential, suggest that mitochondrial disruption can be involved in this apoptotic process. These effects are more pronounced in the MCF-7 cell line (ER positive), suggesting that the presence of the ER might be important in the response to these compounds. Confirmation of their interaction with the ER was obtained in the E-Screen assay, where a clear antagonism of the proliferative effects of the hormone 17β-estradiol was observed with both compounds, at non-toxic concentrations.
The overall results suggest that these new synthetic “raloxifene-like” drugs might have potential to be further developed as alternative hormonal or adjuvant therapies for breast cancer.Fundação para a Ciência e a Tecnologia (FCT) research project PTDC/QUI/68382/2006 (FCOMP-01-0124-FEDER 007441)
Dynamic simulations of potential methane release from East Siberian continental slope sediments
Sediments deposited along continental margins of the Arctic Ocean presumably host large amounts of methane (CH4) in gas hydrates. Here we apply numerical simulations to assess the potential of gas hydrate dissociation and methane release from the East Siberian slope over the next 100 years. Simulations are based on a hypothesized bottom water warming of 3°C, and an assumed starting distribution of gas hydrate. The simulation results show that gas hydrate dissociation in these sediments is relatively slow, and that CH4 fluxes toward the seafloor are limited by low sediment permeability. The latter is true even when sediment fractures are permitted to form in response to overpressure in pore space. With an initial gas hydrate distribution dictated by present-day pressure and temperature conditions, nominally 0.35 Gt of CH4 are released from the East Siberian slope during the first 100 years of the simulation. However, this CH4 discharge becomes significantly smaller (~0.05 Gt) if glacial sea level changes in the Arctic Ocean are considered. This is because a lower sea level during the last glacial maximum (LGM) must result in depleted gas hydrate abundance within the most sensitive region of the modern gas hydrate stability zone. Even if all released CH4 reached the atmosphere, the amount coming from East Siberian slopes would be trivial compared to present-day atmospheric CH4 inputs from other sources
N-Body Growth of a Bahcall-Wolf Cusp Around a Black Hole
We present a clear N-body realization of the growth of a Bahcall-Wolf f ~
E^0.25 (rho ~ 1/r^1.75) density cusp around a massive object ("black hole") at
the center of a stellar system. Our N-body algorithm incorporates a novel
implementation of Mikkola-Aarseth chain regularization to handle close
interactions between star and black hole particles. Forces outside the chain
were integrated on a GRAPE-6A/8 special-purpose computer with particle numbers
up to N=0.25 x 10^6. We compare our N-body results with predictions of the
isotropic Fokker-Planck equation and verify that the time dependence of the
density (both configuration and phase-space) predicted by the Fokker-Planck
equation is well reproduced by the N-body algorithm, for various choices of N
and of the black hole mass. Our results demonstrate the feasibility of
direct-force integration techniques for simulating the evolution of galactic
nuclei on relaxation time scales.Comment: 4 pages, 3 figure
Luteolin, quercetin and ursolic acid are potent inhibitors of proliferation and inducers of apoptosis in both KRAS and BRAF mutated human colorectal cancer cells
KRAS and BRAF mutations are frequent in colorectal carcinoma (CRC) and have the potential to activate proliferation and survival through MAPK/ERK and/or PI3K signalling pathways. Because diet is one of the most important determinants of CRC incidence and progression, we studied the effects of the dietary phytochemicals quercetin (Q), luteolin (L) and ursolic acid (UA) on cell proliferation and apoptosis in two human CRC derived cell lines, HCT15 and CO115, harboring KRAS and BRAF activating mutations, respectively. In KRAS mutated HCT15 cells, Q and L significantly decreased ERK phosphorylation, whereas in BRAF mutated CO115 cells the three compounds decreased Akt phosphorylation but had no effect on phospho-ERK. Our findings show that these natural compounds have antiproliferative and proapoptotic effects and simultaneously seem to act on KRAS and PI3K but not on BRAF. These results shed light on the molecular mechanisms of action of Q, L and UA and emphasize the potential of dietary choices for the control of CRC progression.This work was supported by the Foundation for Science and Technology, Portugal, by the research Grant POCI/AGR/62040/2004. CPRX and CFL were supported by the Foundation for Science and Technology, Portugal, through the Grants SFRH/BD/ 27524/2006 and SFRH/BPD/26316/2006, respectively
Monocarboxylate transport inhibition potentiates the cytotoxic effect of 5-fluorouracil in colorectal cancer cells
Cancer cells rely mostly on glycolysis to meet their energetic demands, producing large amounts of lactate that are extruded to the tumour microenvironment by monocarboxylate transporters (MCTs). The role of MCTs in the survival of colorectal cancer (CRC) cells is scarce and poorly understood. In this study, we aimed to better understand this issue and exploit these transporters as novel therapeutic targets alone or in combination with the CRC classical chemotherapeutic drug 5-Fluorouracil. For that purpose, we characterized the effects of MCT activity inhibition in normal and CRC derived cell lines and assessed the effect of MCT inhibition in combination with 5-FU. Here, we demonstrated that MCT inhibition using CHC (a-cyano-4-hydroxycinnamic acid), DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and quercetin decreased cell viability, disrupted the glycolytic phenotype, inhibited proliferation and enhanced cell death in CRC cells. These results were confirmed by specific inhibition of MCT1/4 by RNA interference. Notably, we showed that 5-FU cytotoxicity was potentiated by lactate transport inhibition in CRC cells, either by activity inhibition or expression silencing. These findings provide novel evidence for the pivotal role of MCTs in CRC maintenance and survival, as well as for the use of these transporters as potential new therapeutic targets in combination with CRC conventional therapy.Ricardo Amorim was recipient of the fellowships SFRH/BI/51118/
2010 and SFRH/BD/98002/2013, from Fundação para a Ciência e
Tecnologia (FCT, Portugal). This study was supported by the FCT
grant ref. PTDC/SAU-FCF/104347/2008, under the scope of “Programa
Operacional Temático Factores de Competitividade” (COMPETE) of
“Quadro Comunitário de Apoio III” and co-financed by Fundo
Comunitário Europeu FEDER. This work was also supported
by FEDER through POFC – COMPETE and by FCT through project
PEst-OE/BIA/UI4050/2014 and Helena Pereira’s fellowship
(SFRH/BD/73139/2010)
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