Muscarinic acetylcholine receptor down-regulation limits the extent of inhibition of cell cycle progression in Chinese hamster ovary cells.

Cellular desensitization is believed to be important for growth control but direct evidence is lacking. In the current study we compared effects of wild-type and down-regulation-resistant mutant m3 muscarinic receptors on Chinese hamster ovary (CHO-K1) cell desensitization, proliferation, and transformation. We found that down-regulation of m3 muscarinic acetylcholine receptors was the principal mechanism of desensitization of receptor-activated inositol phosphate phospholipid hydrolysis in these cells. Activation of wild-type and mutant receptors inhibited anchorage-independent growth as assayed by colony formation in agar. However, the potency for inhibition of anchorage-independent growth was greater for cells expressing the mutant receptor. Activation of either receptor also initially inhibited anchorage-dependent cell proliferation in randomly growing populations. Rates of DNA synthesis and cell division were profoundly reduced by carbachol in cells expressing either receptor at early time points. Analysis of cell cycle parameters indicated that cell cycle progression was inhibited at transitions from G1 to S and G2/M to G1 phases. However, mutant receptor effects on anchorage-dependent growth were sustained, whereas wild-type receptor effects were transient. Thus, receptor down-regulation restored cell cycle progression. In contrast, activation of either receptor blocked entry into the cell cycle from quiescence, and this response was not reduced by receptor down-regulation. Therefore, activation of m3 muscarinic acetylcholine receptors inhibited CHO cell anchorage-dependent and -independent growth. In anchored cells carbachol inhibited the cell cycle at three distinct points. Inhibitions at two of these points were eliminated by wild-type receptor down-regulation while the other was not. These results directly demonstrate that desensitization mechanisms can act as principal determinants of cellular growth responses.

Electrical investigation of p-type 4H-SiC heavily doped by ion implantation

In the last decades, an increasing interest in the research field of wide bandgap semiconductors was observed, mostly due to the progressive approaching of silicon-based devices to their theoretical limits. 4H-SiC is an example among these, and is a mature compound for applications. The main advantages offered 4H-SiC in comparison with silicon are an higher breakdown field, an higher thermal conductivity, a higher operating temperature, very high hardness and melting point, biocompatibility, but also low switching losses in high frequencies applications and lower on-resistances in unipolar devices. Then, 4H-SiC power devices offer great performance improvement; moreover, they can work in hostile environments where silicon power devices cannot function. Ion implantation technology is a key process in the fabrication of almost all kinds of SiC devices, owing to the advantage of a spatially selective doping. This work is dedicated to the electrical investigation of several differently-processed 4H-SiC ion- implanted samples, mainly through Hall effect and space charge spectroscopy experiments. It was also developed the automatic control (Labview) of several experiments. In the work, the effectiveness of high temperature post-implant thermal treatments (up to 2000°C) were studied and compared considering: (i) different methods, (ii) different temperatures and (iii) different duration of the annealing process. Preliminary p + /n and Schottky junctions were also investigated as simple test devices. 1) Heavy doping by ion implantation of single off-axis 4H-SiC layers The electrical investigation is one of the most important characterization of ion-implanted samples, which must be submitted to mandatory post-implant thermal treatment in order to both (i) recover the lattice after ion bombardment, and (ii) address the implanted impurities into lattice sites so that they can effectively act as dopants. Electrical investigation can give fundamental information on the efficiency of the electrical impurity activation. To understand the results of the research it should be noted that: (a) To realize good ohmic contacts it is necessary to obtain spatially defined highly doped regions, which must have conductivity as low as possible. (b) It has been shown that the electrical activation efficiency and the electrical conductivity increase with the annealing temperature increasing. (c) To maximize the layer conductivity, temperatures around 1700°C are generally used and implantation density high till to 10 21 cm -3 . In this work, an original approach, different from (c), is explored by the using very high annealing temperature, around 2000°C, on samples of Al + -implant concentration of the order of 10 20 cm -3 . Several Al + -implanted 4H-SiC samples, resulting of p-type conductivity, were investigated, with a nominal density varying in the range of about 1-5∙10 20 cm -3 and subjected to two different high temperature thermal treatments. One annealing method uses a radiofrequency heated furnace till to 1950°C (Conventional Annealing, CA), the other exploits a microwave field, providing a fast heating rate up to 2000°C (Micro-Wave Annealing, MWA). In this contest, mainly ion implanted p-type samples were investigated, both off-axis and on-axis <0001> semi-insulating 4H-SiC. Concerning p-type off-axis samples, a high electrical activation of implanted Al (50-70%) and a compensation ratio below 10% were estimated. In the work, the main sample processing parameters have been varied, as the implant temperature, CA annealing duration, and heating/cooling rates, and the best values assessed. MWA method leads to higher hole density and lower mobility than CA in equivalent ion implanted layers, resulting in lower resistivity, probably related to the 50°C higher annealing temperature. An optimal duration of the CA treatment was estimated in about 12-13 minutes. A RT resistivity on the lowest reported in literature for this kind of samples, has been obtained. 2) Low resistivity data: variable range hopping Notwithstanding the heavy p-type doping levels, the carrier density remained less than the critical one required for a semiconductor to metal transition. However, the high carrier densities obtained was enough to trigger a low temperature impurity band (IB) conduction. In the heaviest doped samples, such a conduction mechanism persists till to RT, without significantly prejudice the mobility values. This feature can have an interesting technological fall, because it guarantee a nearly temperature- independent carrier density, it being not affected by freeze-out effects. The usual transport mechanism occurring in the IB conduction is the nearest neighbor hopping: such a regime is effectively consistent with the resistivity temperature behavior of the lowest doped samples. In the heavier doped samples, however, a trend of the resistivity data compatible with a variable range hopping (VRH) conduction has been pointed out, here highlighted for the first time in p-type 4H-SiC. Even more: in the heaviest doped samples, and in particular, in those annealed by MWA, the temperature dependence of the resistivity data is consistent with a reduced dimensionality (2D) of the VRH conduction. In these samples, TEM investigation pointed out faulted dislocation loops in the basal plane, whose average spacing along the c-axis is comparable with the optimal length of the hops in the VRH transport. This result suggested the assignment of such a peculiar behavior to a kind of spatial confinement into a plane of the carrier hops. 3) Test device the p + -n junction In the last part of the work, the electrical properties of 4H-SiC diodes were also studied. In this case, a heavy Al + ion implantation was realized on n-type epilayers, according to the technological process applied for final devices. Good rectification properties was shown from these preliminary devices in their current-voltage characteristics. Admittance spectroscopy and deep level transient spectroscopy measurements showed the presence of electrically active defects other than the dopants ones, induced in the active region of the diodes by ion implantation. A critical comparison with the literature of these defects was performed. Preliminary to such an investigation, it was assessed the experimental set up for the admittance spectroscopy and current-voltage investigation and the automatic control of these measurements.

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV – the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.

Fragmentação florestal e prioridades para a conservação da biodiversidade

Um modelo dedicado ao planejamento da conservação e restauração de habitats deve incluir informações estratégicas para assegurar a eficácia e de fácil obtenção, para assegurar a agilidade necessária. Planos e estratégias para conservação usualmente são complexos e demandam informações detalhadas, difíceis de se obter, como inventários biológicos e certos tipos de mapeamento, o que traz limitações em termos de disponibilidade, qualidade e custo das informações. Assim, procurou-se testar a eficiência de métodos simples para a seleção, em escala local, de áreas prioritárias para conservação de habitats fortemente fragmentados e reduzidos, uma situação comum no sul do Brasil, usando dados de imagens LANDSAT e planos de informações disponíveis em mapeamentos comuns, e trabalho de campo. Inicialmente analisou-se a estrutura da paisagem e o padrão de fragmentação em parte da região norte do estado do Paraná, e testar se tamanho e forma são adequados para selecionar os fragmentos florestais mais importantes para a conservação, ou seja, as que contribuem para manter maior quantidade e melhor qualidade de habitats, bem como tenham maior impacto (positivo) na conectividade e em outras variáveis da paisagem. Os resultados mostram que a floresta madura cobre cerca de 3% da paisagem, e a cobertura florestal total atinge perto de 8%, consistindo principalmente de pequenos fragmentos (82% tem entre 1 e 10 ha). Fragmentos grandes (>100 ha) são apenas 1,4% dos remanescentes, mas somam 34% da área de floresta. Apesar de estarem sujeitos a efeitos de borda em toda ou quase toda a sua área, fragmentos pequenos mostraram ter um papel importante na conectividade da paisagem. Numa área maior, foi feita uma pré-seleção de áreas com potencial para estabelecimento de redes de conservação. A pré-seleção procurou responder às seguintes perguntas: 1-Quais são os sítios com maior potencial para a conservação da biodiversidade? 2-Quais são os sítios sob maior risco para objetivos de conservação? e 3-Quais sítios têm melhores oportunidades para o estabelecimento de zonas de conservação de uso múltiplo? Foi identificado um conjunto de 11 fragmentos pertencendo a 5 sub-regiões, sofrendo variados graus de pressão antrópica. Adicionalmente, usando medidas simples de estrutura da paisagem, relacionadas com tamanho, forma e conectividade dos fragmentos, procurou-se identificar tipos estruturais de fragmentos, como uma forma alternativa para auxiliar o estabelecimento de prioridades para conservação a partir do seu papel, efetivo ou potencial, na paisagem. Foram identificados 5 tipos de fragmentos, pequenos (ilhotas isoladas, trampolins), médios (núcleos auxiliares e corredores) e grandes (núcleos principais), que podem ser usados para subsidiar estratégias de conservação. Utilizando informações sobre a estrutura da paisagem, hidrografia e legislação ambiental, propõe-se aqui uma estratégia de conservação para o complexo das bacias dos ribeirões Apertados-Três Bocas (CATB), ordenando atividades de restauração e conservação de fragmentos florestais, criação e expansão de unidades de conservação, além da proposição de formas de uso do solo compatíveis com o entorno de unidades de conservação.

Representational Subversions and the Limits of Postcoloniality: Shahzia Sikander's Strategic Contemporaneity

Transnational artist Shahzia Sikander challenges the limitations of Edward Said's postcolonial emphasis on secular humanism by deploying the heterogeneous traditions of South Asian miniature painting while strategically drawing on tradition to critique contemporaneity. Through a palimpsest process of composition, Sikander reincorporates the unknown and silenced histories implicit in the tradition of miniature painting to create social imaginaries with motifs that draw on the diverse traditions of South Asian religions and aesthetics to create a subversive politics of remembering wherein alternative images of cosmopolitanism emerge. Through a sustained analysis, this dissertation demonstrates how these alternative traditions interrogate and critique the limitations of postcolonial theory. Particularly important to this critique are some recent approaches of Third World feminists that highlight the limitations of secular humanism implicit in much of postcolonial critique. Sikander's compositions mirror these approaches as her motifs of the feminine become an intervention into the spiritual emptiness and ethical confusions of contemporaneity. In effect, Sikander's work is an intervention, a warning, and a plea for the re-invention of positive alternatives as her images embody and facilitate a critical and daring consciousness that is necessary to both our social and spiritual well-being.

Uso do território e justiça: a Defensoria Pública do Estado de São Paulo e os limites à garantia constitucional do direito de defesa

Este trabalho investiga os limites à garantia constitucional do direito de defesa no Brasil, partindo de uma análise do uso do território paulista pela Defensoria Pública do Estado de São Paulo (DPESP), criada em 2006. Uma vez que as defensorias públicas oferecem assistência jurídica gratuita quase que exclusivamente aos pobres, o estudo de seus objetos e ações muito contribui para a compreensão destes limites. Assim, a pesquisa tem como objetivo testar a hipótese de que o uso do território paulista pela DPESP é expressão de como o sistema de justiça brasileiro não tem como prioridade a garantia constitucional do direito de defesa. Partindo de uma discussão teórica sobre a relação entre o território e o setor terciário, além da análise de uma série de mapas, o trabalho mostra como a localização das 41 unidades de atendimento da DPESP constitui um primeiro obstáculo ao acesso: na maior parte dos municípios atendidos, as unidades localizam-se nas áreas centrais enquanto os pobres habitam as periferias urbanas. Os deslocamentos representam um custo maior justamente para aqueles que mais necessitam dos serviços. A investigação em cada um dos municípios revela também a insuficiência no número de defensores. Ultrapassando a questão das localizações, a pesquisa analisa ainda os problemas estruturais, evidenciando que o sistema capitalista produz pobreza e concentração de renda, o Estado atende prioritariamente aos interesses empresariais e a justiça concentra seus esforços na garantia da ordem necessária aos negócios. Neste sentido, além de uma abordagem teórica a respeito do capitalismo, do Estado e da justiça, o trabalho recorre a dados empíricos do estado de São Paulo para evidenciar a produção estrutural de pobreza e a seletividade das ações estatais. Para teste da hipótese, são analisados igualmente os aspectos históricos da estruturação do direito na sociedade capitalista, destacando sua importância específica para a garantia dos interesses comerciais. Além disso, fundamentandose em pesquisa bibliográfica, a investigação sobre as origens dos serviços de assistência jurídica gratuita e da criação das defensorias públicas revela como estes são o resultado de difíceis embates políticos e que sua existência não é uma consequência natural do sistema legal pensado pelos ideólogos iluministas. A principal conclusão deste trabalho é que as dificuldades hoje enfrentadas pelas defensorias são, em grande medida, a expressão de uma estrutura social produtora de desigualdades e seletiva na aplicação da justiça. Neste sentido, a solução do problema do acesso à justiça aos mais pobres não se esgota na expansão dos serviços das defensorias. Este é apenas o começo, a partir do qual as desigualdades podem se tornar mais evidentes e as pessoas mais conscientes e exigentes de transformações sociais profundas.

Investigating evidence for different black hole accretion modes since redshift z ∼ 1

Chandra data in the COSMOS, AEGIS-XD and 4 Ms Chandra Deep Field South are combined with multiwavelength photometry available in those fields to determine the rest-frame U − V versus V − J colours of X-ray AGN hosts in the redshift intervals 0.1 < z < 0.6 (mean z¯=0.40) and 0.6 < z < 1.2 (mean z¯=0.85). This combination of colours provides an effective and least model-dependent means of separating quiescent from star-forming, including dust reddened, galaxies. Morphological information emphasizes differences between AGN populations split by their U − V versus V − J colours. AGN in quiescent galaxies consist almost exclusively of bulges, while star-forming hosts are equally split between early- and late-type hosts. The position of AGN hosts on the U − V versusV − J diagram is then used to set limits on the accretion density of the Universe associated with evolved and star-forming systems independent of dust induced biases. It is found that most of the black hole growth at z≈ 0.40 and 0.85 is associated with star-forming hosts. Nevertheless, a non-negligible fraction of the X-ray luminosity density, about 15–20 per cent, at both z¯=0.40 and 0.85, is taking place in galaxies in the quiescent region of the U − V versus V − J diagram. For the low-redshift sub-sample, 0.1 < z < 0.6, we also find tentative evidence, significant at the 2σ level, that AGN split by their U − V and V − J colours have different Eddington ratio distributions. AGN in blue star-forming hosts dominate at relatively high Eddington ratios. In contrast, AGN in red quiescent hosts become increasingly important as a fraction of the total population towards low Eddington ratios. At higher redshift, z > 0.6, such differences are significant at the 2σ level only for sources with Eddington ratios ≳ 10^− 3. These findings are consistent with scenarios in which diverse accretion modes are responsible for the build-up of supermassive black holes at the centres of galaxies. We compare these results with the predictions of theGALFORM semi-analytic model for the cosmological evolution of AGN and galaxies. This model postulates two black hole fuelling modes, the first is linked to star formation events and the second takes place in passive galaxies. GALFORM predicts that a substantial fraction of the black hole growth at z < 1 is associated with quiescent galaxies, in apparent conflict with the observations. Relaxing the strong assumption of the model that passive AGN hosts have zero star formation rate could bring those predictions in better agreement with the data.

The Limits of Marijuana Legalization in the States

Although some ingenious solutions have been proposed to the problems posed by Section 280E pf the federal tax code, the situation remains untenable. The only solution to this current conundrum is a change in federal law; so long as marijuana remains illegal under the Controlled Substances Act, state marijuana policy will inevitably be frustrated. This brief response to an article by Professor Leff identifies some of these frustrations and proposes a few modest federal solutions

Illinois Phosphorus Effluent Limits: Minimizing the Impacts Through the Use of Non-point Controls at the Springbrook Water Reclamation Center in Naperville, Illinois

Phosphorus pollution is a major concern in Illinois. Excessive amounts of phosphorus can be detrimental to water bodies. To help control phosphorus, the Illinois Pollution Control Board has proposed phosphorus limits on wastewater treatment facility discharges. If enacted, these limits will have negative impacts on the Springbrook Water Reclamation Center in Naperville, Illinois. To minimize these impacts, Naperville can utilize various non-point controls recommended in this paper to decrease the amount of phosphorus entering into the DuPage River and the Springbrook Water Reclamation Center. While these controls will not reduce levels low enough to totally satisfy limits on phosphorus discharges, they will significantly reduce the treatment costs Naperville will need to expend to meet them and be more environmentally effective.

Analysis of the colorimetric properties of goniochromatic colors using the MacAdam limits under different light sources

Technological innovation in all areas has led to the appearance in recent years of new metallic and pearlescent materials, yet no exhaustive studies have been conducted to assess their colorimetric capabilities. The chromatic variability of these special-effect pigments may largely be due to the three-dimensional effect of their curved shapes and orientations when they are directionally or diffusely illuminated. Our study examines goniochromatic colors using the optimal colors (MacAdam limits) associated with normal colors (photometric scale of relative spectral reflectance from 0 to 1) under certain conventional illuminants and other light sources. From a database of 91 metallic and interference samples and using a multi-gonio-spectrophotometer, we analyzed samples with lightness values of more than 100 and others with lightness values of less than 100, but with higher chromaticities than optimal colors, which places them beyond the MacAdam limits. Our study thus demonstrates the existence of chromatic perceptions beyond the normal solid color associated with these materials and independent of the light source. The challenge for future research, therefore, is to replicate and render these color appearances in current and future color reproduction technologies for computer graphics.

Number of discernible colors for color-deficient observers estimated from the MacAdam limits

We estimated the number of colors perceived by color normal and color-deficient observers when looking at the theoretic limits of object-color stimuli. These limits, the optimal color stimuli, were computed for a color normal observer and CIE standard illuminant D65, and the resultant colors were expressed in the CIELAB and DIN99d color spaces. The corresponding color volumes for abnormal color vision were computed using models simulating for normal trichromatic observers the appearance for dichromats and anomalous trichomats. The number of colors perceived in each case was then computed from the color volumes enclosed by the optimal colors also known as MacAdam limits. It was estimated that dichromats perceive less than 1% of the colors perceived by normal trichromats and that anomalous trichromats perceive 50%–60% for anomalies in the medium-wavelength-sensitive and 60%–70% for anomalies in the long-wavelength-sensitive cones. Complementary estimates obtained similarly for the spectral locus of monochromatic stimuli suggest less impairment for color-deficient observers, a fact that is explained by the two-dimensional nature of the locus.

Performance limits of graphene-ribbon field-effect transistors

The performance of field effect transistors based on an single graphene ribbon with a constriction and a single back gate are studied with the help of atomistic models. It is shown how this scheme, unlike that of traditional carbon-nanotube-based transistors, reduces the importance of the specifics of the chemical bonding to the metallic electrodes in favor of the carbon-based part of device. The ultimate performance limits are here studied for various constriction and metal-ribbon contact models. In particular, we show that, even for poorly contacting metals, properly tailored constrictions can give promising values for both the on conductance and the subthreshold swing.

Resolution limits to object tracking with subpixel accuracy

Subpixel methods increase the accuracy and efficiency of image detectors, processing units, and algorithms and provide very cost-effective systems for object tracking. Published methods achieve resolution increases up to three orders of magnitude. In this Letter, we demonstrate that this limit can be theoretically improved by several orders of magnitude, permitting micropixel and submicropixel accuracies. The necessary condition for movement detection is that one single pixel changes its status. We show that an appropriate target design increases the probability of a pixel change for arbitrarily small shifts, thus increasing the detection accuracy of a tracking system. The proposal does not impose severe restriction on the target nor on the sensor, thus allowing easy experimental implementation.

GRO J1008−57: an (almost) predictable transient X-ray binary

A study of archival RXTE, Swift, and Suzaku pointed observations of the transient high-mass X-ray binary GRO J1008−57 is presented. A new orbital ephemeris based on pulse arrival-timing shows the times of maximum luminosities during outbursts of GRO J1008−57 to be close to periastron at orbital phase − 0.03. This makes the source one of a few for which outburst dates can be predicted with very high precision. Spectra of the source in 2005, 2007, and 2011 can be well described by a simple power law with high-energy cutoff and an additional black body at lower energies. The photon index of the power law and the black-body flux only depend on the 15–50 keV source flux. No apparent hysteresis effects are seen. These correlations allow us to predict the evolution of the pulsar’s X-ray spectral shape over all outbursts as a function of just one parameter, the source’s flux. If modified by an additional soft component, this prediction even holds during GRO J1008−57’s 2012 type II outburst.

A highly resistive layer within the crust of X-ray pulsars limits their spin periods

The lack of isolated X-ray pulsars with spin periods longer than 12 s raises the question of where the population of evolved high-magnetic-field neutron stars has gone. Unlike canonical radiopulsars, X-ray pulsars are not subject to physical limits to the emission mechanism nor observational biases against the detection of sources with longer periods. Here we show that a highly resistive layer in the innermost part of the crust of neutron stars naturally limits the spin period to a maximum value of about 10–20 s. This highly resistive layer is expected if the inner crust is amorphous and heterogeneous in nuclear charge, possibly owing to the existence of a nuclear ‘pasta’ phase. Our findings suggest that the maximum period of isolated X-ray pulsars may be the first observational evidence for an amorphous inner crust, whose properties can be further constrained by future X-ray timing missions combined with more detailed models.