Fifty years of spellchecking

A short history of spellchecking from the late 1950s to the present day, describing its development through dictionary lookup, affix stripping, correction, confusion sets, and edit distance to the use of gigantic databases

Internal transport barriers in the National Spherical Torus Experiment

In the National Spherical Torus Experiment [M. Ono , Nucl. Fusion 41, 1435 (2001)], internal transport barriers (ITBs) are observed in reversed (negative) shear discharges where diffusivities for electron and ion thermal channels and momentum are reduced. While neutral beam heating can produce ITBs in both electron and ion channels, high harmonic fast wave heating can also produce electron ITBs (e-ITBs) under reversed magnetic shear conditions without momentum input. Interestingly, the location of the e-ITB does not necessarily match that of the ion ITB (i-ITB). The e-ITB location correlates best with the magnetic shear minima location determined by motional Stark effect constrained equilibria, whereas the i-ITB location better correlates with the location of maximum ExB shearing rate. Measured electron temperature gradients in the e-ITB can exceed critical gradients for the onset of electron thermal gradient microinstabilities calculated by linear gyrokinetic codes. A high-k microwave scattering diagnostic shows locally reduced density fluctuations at wave numbers characteristic of electron turbulence for discharges with strongly negative magnetic shear versus weakly negative or positive magnetic shear. Reductions in fluctuation amplitude are found to be correlated with the local value of magnetic shear. These results are consistent with nonlinear gyrokinetic simulations predicting a reduction in electron turbulence under negative magnetic shear conditions despite exceeding critical gradients.X1128sciescopu

Creation of a multiple-use recombinant inbred line population for the development of molecular markers in soft white winter wheat

Tese de doutoramento em Física (Pré-Bolonha), especialidade de Física Experimental, apresentada à Faculdade de Ciências e Tecnologia da Universidade de CoimbraPositron emission tomography based on resistive plate chambers (RPC-PET) has been proposed for both preclinical and clinical applications. We firstly present imaging results of needle-like and planar 22Na sources obtained with a prototype of a high-acceptance small-animal RPC-PET. The two detector modules utilized in this experiment had an effective front face of 6.4 x 6.4 cm^2 and consisted of 5 gas gaps and 6 glass electrodes with a total thickness of 5 mm. The data included lines of response (LORs) inclined up to 58º, and the depth of interaction (DOI) was accurately measured, demonstrating the parallax-free property inherent to RPC-PET. The maximum likelihood expectation-maximization (MLEM) reconstruction of the acquired data yielded an excellent and stable resolution of 0.4 mm full width at half maximum (FWHM). Concurrently, we pursued studies of a suggested whole-body single-bed RPC-PET. It has been shown by simulation that RPC-PET with an axial field-of-view (AFOV) of 2.4 m is feasible and yields an absolute sensitivity at least one order of magnitude superior to that of typical crystal-based PET scanners. In addition, RPC-PET offers an important time-of-flight (TOF) advantage and provides a potentially very-high spatial resolution at the detector level. In the second part of this work, a fully three-dimensional reconstruction algorithm capable of processing the very inclined LORs from large AFOV systems such as RPC-PET is demonstrated. It relies on the application of a TOF-based-kernel into the MLEM algorithm. With the 300 ps FWHM time resolution, already experimentally demonstrated, a rejection of 63% of the body-scattered events is obtained. We present reconstructed results from blind simulations corresponding to the anthropomorphic phantom, NCAT, with oncological lesions introduced into different locations within the human body. A comparison between 300 and 600 ps FWHM TOF reconstructed images is performed, with an increasing detectability being observed for a better TOF resolution. We finally compare issues related to image convergence speed. An alternative new approach, which consists in dividing the full-body data into nine different image regions that are reconstructed independently with graphical processing unit (GPU) assistance, provides a six times faster reconstruction compared with a GPU-based whole-body reconstruction. For a 300 ps FWHM RPC-PET scanner, this allows reaching a reconstructed image, that results from 1.6 x 10^10 annihilations within 7 minutes and upon injection of 2 mCi, just 4 minutes after the end of data acquisition. We conclude that RPC-PET is well oriented to compete with other commercial PET scanners in the global market.A tomografia por emissão de positrões baseada em detectores do tipo câmaras de placas resistivas (RPC-PET) foi proposta para aplicação em ensaios com pequenos animais e na prática clínica. Neste trabalho, apresentamos primeiramente resultados experimentais obtidos a partir de um protótipo RPC-PET de alta aceitação para pequenos animais. Foram obtidas imagens de fontes do radioisótopo 22Na, uma quase pontual e outra planar. Usámos dois módulos de detectores RPC com uma área activa de 6.4 x 6.4 cm^2 e uma espessura de 5 mm, constituída por 6 vidros empilhados e 5 espaços gasosos definidos entre eles. Os dados adquiridos incluíram linhas de coincidência (LORs) inclinadas até um ângulo de 58º, tornando essencial a medida precisa da profundidade de interacção. A identificação dos espaços gasosos onde ocorreram as avalanches permitiu demonstrar a ausência de erro de paralaxe nas medidas realizadas com o RPC-PET para pequenos animais. A partir da reconstrução dos dados processados com o algoritmo maximum likelihood expectation-maximization (MLEM), obtivemos uma resolução espacial com largura a meia altura (FWHM) de 0.4 mm, excelente e estável. Em paralelo, continuámos a estudar as potencialidades de um protótipo RPC-PET de corpo inteiro e cama única, orientado para pessoas. Já foi anteriormente demonstrado por simulação que um scanner RPC-PET com 2.4 m de campo de visão axial (AFOV) é viável e permitirá o aumento de sensibilidade de pelo menos uma ordem de grandeza em relação aos scanners PET com cristais. Duas outras virtudes do RPC-PET são a sua capacidade de medição do tempo de voo (TOF) dos fotões e a elevada resolução espacial ao nível do detector. Na segunda parte deste trabalho apresentamos um algoritmo de reconstrução, totalmente tridimensional, capaz de processar LORs muito inclinadas em sistemas com um AFOV longo, como é o caso do RPC-PET. Este algoritmo acrescenta um kernel ao algoritmo MLEM, baseado na informação de TOF. Com uma resolução temporal de 300 ps FWHM, já experimentalmente comprovada, é possível rejeitar 63% dos eventos dispersados no corpo humano. Exibimos imagens reconstruídas obtidas a partir de simulações do fantoma antropomórfico, NCAT, com lesões oncológicas situadas em diferentes locais do corpo humano. A comparação entre imagens conseguidas com resoluções temporais de 300 ps e 600 ps FWHM, permite observar uma detectabilidade acrescida associada à melhor resolução de TOF. Por último, são estudados os tempos de convergência da reconstrução. Um método inovador e alternativo, que consiste na divisão dos dados do corpo humano em nove regiões e na reconstrução independente desses dados com recurso a unidades de processamento gráfico (GPUs), permite uma reconstrução seis vezes mais rápida do que a reconstrução de corpo inteiro também com o auxílio de GPUs. A partir de dados de 1.6 x 10^10 aniquilações ocorridas durante uma aquisição de 7 minutos e para uma actividade injectada de 2 mCi, um scanner RPC-PET com uma resolução temporal de 300 ps FWHM permitirá obter uma imagem reconstruída apenas 4 minutos após o fim da aquisição. Podemos assim concluir que o RPC-PET está bem colocado para competir no mercado dos scanners PET comerciais

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Reducing unscheduled hospital care for adults with diabetes following a hypoglycaemic event: which community-based interventions are most effective? A systematic review

AIM: To determine which community-based interventions are most effective at reducing unscheduled hospital care for hypoglycaemic events in adults with diabetes. METHODS: Medline Ovid, CINAHL Plus and ProQuest Health and Medical Collection were searched using both key search terms and medical subject heading terms (MeSH) to identify potentially relevant studies. Eligible studies were those that involved a community-based intervention to reduce unscheduled admissions in adults with diabetes. Papers were initially screened by the primary researcher and then a secondary reviewer. Relevant data were then extracted from papers that met the inclusion criteria. RESULTS: The search produced 2226 results, with 1360 duplicates. Of the remaining 866 papers, 198 were deemed appropriate based on titles, 90 were excluded following abstract review. A total of 108 full papers were screened with 19 full papers included in the review. The sample size of the 19 papers ranged from n = 25 to n = 104,000. The average ages within the studies ranged from 41 to 74 years with females comprising 57% of the participants. The following community-based interventions were identified that explored reducing unscheduled hospital care in people with diabetes; telemedicine, education, integrated care pathways, enhanced primary care and care management teams. CONCLUSIONS: This systematic review shows that a range of community-based interventions, requiring different levels of infrastructure, are effective in reducing unscheduled hospital care for hypoglycaemia in people with diabetes. Investment in effective community-based interventions such as integrated care and patient education must be a priority to shift the balance of care from secondary to primary care, thereby reducing hospital admissions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00817-z