Unified Pragmatic Models for Generating and Following Instructions

We show that explicit pragmatic inference aids in correctly generating and following natural language instructions for complex, sequential tasks. Our pragmatics-enabled models reason about why speakers produce certain instructions, and about how listeners will react upon hearing them. Like previous pragmatic models, we use learned base listener and speaker models to build a pragmatic speaker that uses the base listener to simulate the interpretation of candidate descriptions, and a pragmatic listener that reasons counterfactually about alternative descriptions. We extend these models to tasks with sequential structure. Evaluation of language generation and interpretation shows that pragmatic inference improves state-of-the-art listener models (at correctly interpreting human instructions) and speaker models (at producing instructions correctly interpreted by humans) in diverse settings.Comment: NAACL 2018, camera-ready versio

Efficacy of the DFT+U formalism for modeling hole polarons in perovskite oxides

We investigate the formation of self-trapped holes (STH) in three prototypical perovskites (SrTiO3, BaTiO3, PbTiO3) using a combination of density functional theory (DFT) calculations with local potentials and hybrid functionals. First we construct a local correction potential for polaronic configurations in SrTiO3 that is applied via the DFT+U method and matches the forces from hybrid calculations. We then use the DFT+U potential to search the configuration space and locate the lowest energy STH configuration. It is demonstrated that both the DFT+U potential and the hybrid functional yield a piece-wise linear dependence of the total energy on the occupation of the STH level suggesting that self-interaction effects have been properly removed. The DFT+U model is found to be transferable to BaTiO3 and PbTiO3, and formation energies from DFT+U and hybrid calculations are in close agreement for all three materials. STH formation is found to be energetically favorable in SrTiO3 and BaTiO3 but not in PbTiO3, which can be rationalized by considering the alignment of the valence band edges on an absolute energy scale. In the case of PbTiO3 the strong coupling between Pb 6s and O 2p states lifts the valence band minimum (VBM) compared to SrTiO3 and BaTiO3. This reduces the separation between VBM and STH level and renders the STH configuration metastable with respect to delocalization (band hole state). We expect that the present approach can be adapted to study STH formation also oxides with different crystal structures and chemical composition.Comment: 7 pages, 6 figure

Efficacy of the DFT + U formalism for modeling hole polarons in perovskite oxides

We investigate the formation of self-trapped holes (STH) in three prototypical perovskites (SrTiO₃, BaTiO₃, PbTiO₃) using a combination of density functional theory (DFT) calculations with local potentials and hybrid functionals. First we construct a local correction potential for polaronic configurations in SrTiO₃ that is applied via the DFT + U method and matches the forces from hybrid calculations. We then use the DFT + U potential to search the configuration space and locate the lowest energy STH configuration. It is demonstrated that both the DFT + U potential and the hybrid functional yield a piecewise linear dependence of the total energy on the occupation of the STH level, suggesting that self-interaction effects have been properly removed. The DFT + U model is found to be transferable to BaTiO₃ and PbTiO₃, and STH formation energies from DFT + U and hybrid calculations are in close agreement for all three materials. STH formation is found to be energetically favorable in SrTiO₃ and BaTiO₃ but not in PbTiO₃, which can be rationalized by considering the alignment of the valence band edges on an absolute energy scale. In the case of PbTiO₃ the strong coupling between Pb 6s and O 2p states lifts the valence band minimum (VBM) compared to SrTiO₃ and BaTiO₃. This reduces the separation between VBM and STH level and renders the STH configuration metastable with respect to delocalization (band hole state). We expect that the present approach can be adapted to study STH formation also in oxides with different crystal structures and chemical compositions

The Southern Brazilian shelf: general characteristics, quaternary evolution and sediment distribution

Extending from latitude 34ºS to 22ºS the Southern Brazilian shelf constitutes the only part of the Brazilian shelf with a subtropical to temperate environment. The studies on the different geological aspects of the area began in the 1960's and have recently been reassessed after studies related to the determination of the Economic Exclusive Zone. In terms of morphology, the Southern Brazilian shelf may be divided into three sectors, the São Paulo Bight, the Florianópolis-Mostardas Sector and the Rio Grande Cone, characterized by conspicuous differences in terms of geological determining factors, bathymetry, declivities and the presence of canyons and channels. Despite the existence of hundreds of radiocarbon datings the sea level changes curve of southern Brazil during the Last Glacial Cycle is still a matter of debate. A recent controversy on the Middle and late Holocene sea level changes curve raised the question of the amplitude of the oscillations which occurred in the period. Also, a few but relatively consistent radiocarbon datings suggest the occurrence of a high sea level during Isotope Stage 3. In terms of sedimentary cover the Southern Brazilian shelf exhibits a very strong hydrodynamic control, both latitudinal and bathymetrical. The sector southward from 25ºS is characterized by the influence of the plume of water carrying sediments originating from the Río de La Plata. Actually its presence is conspicuous up to 28ºS, with the area between this latitude and 25ºS constituting a transitional zone. In terms of bathymetry the outer shelf is marked by the "floor-polisher" effect of the Brazil Current, which is responsible for the maintenance of a relict facies in areas deeper than 100 meters.Estendendo-se entre as latitudes 34ºS e 22ºS, a plataforma continental sul-brasileira constitui o único setor que corresponde a um ambiente subtropical a temperado. Os estudos dos diferentes aspectos geológicos da área iniciaram-se na década de 1960 e foram recentemente retomados após os trabalhos relativos à delimitação da Zona Econômica Exclusiva. Em termos de morfologia, pode ser dividida em três setores: Embaiamento de São Paulo, Setor Florianópolis-Mostardas e o Cone do Rio Grande, cada qual definido com base em diferenças geológicas relativas a batimetria, declividade e a presença de cânions e canais. A despeito da existência de centenas de datações ao radiocarbono, a curva de variações relativas do nível do mar no Último Ciclo Glacial é ainda tema de debate. Controvérsia recente sobre as curvas de variação do nível do mar sobre as durante o Holoceno Médio e Tardio trouxe à tona a questão da amplitude das oscilações do nível do mar. Adicionalmente, poucas mas consistentes datações sugerem a ocorrência de um nível do mar elevado durante o Estágio Isotópico 3. Em termos de processos sedimentares atuais, a plataforma continental sul-brasileira exibe um controle hidrodinâmico muito forte, tanto latitudinal quanto batimétrico. O setor ao sul de 25ºS é caracterizado pela influência da pluma de água que carreia sedimentos originários do Rio da Prata, cuja presença é conspícua até 28ºS, havendo uma zona de transição entre essas duas latitudes. A plataforma externa é marcada pelo "efeito enceradeira" da Corrente do Brasil, relíquia responsável pela manutenção de uma fácies em áreas além da isóbata de 100 metros.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)(CNPq) Conselho de Desenvolvimento Científico e Tecnológic

Do-It-Yourself Preoperative High-Resolution Ultrasound-Guided Flap Design of the Superficial Circumflex Iliac Artery Perforator Flap (SCIP)

The superficial circumflex iliac artery perforator (SCIP) flap is a well-documented, thin, free tissue flap with a minimal donor site morbidity, and has the potential to become the new method for resurfacing moderate-size skin defects. The aim of this study is to describe an easy, reliable, systematic, and standardized approach for preoperative SCIP flap design and perforator characterization, using color-coded duplex sonography (CCDS). A list of customized settings and a straightforward algorithm are presented, which are easily applied by an operator with minimal experience. Specific settings for SCIP flap perforator evaluation were investigated and tested on 12 patients. Deep and superficial superficial circumflex iliac artery (SCIA) branches, along with their corresponding perforators and cutaneous veins, were marked individually with a permanent marker and the anatomy was verified intraoperatively. From this, a simplified procedure for preoperative flap design of the SCIP flap was developed. Branches could be localized and evaluated in all patients. A preoperative structured procedure for ultrasonically guided flap design of the SCIP flap is described. A 100% correlation between the number and emergence points of the branches detected by preoperative CCDS mapping and the intraoperative anatomy was found

LAMTOR2 (p14) Controls B Cell Differentiation by Orchestrating Endosomal BCR Trafficking

B-cell development and function depend on stage-specific signaling through the B-cell antigen receptor (BCR). Signaling and intracellular trafficking of the BCR are connected, but the molecular mechanisms of this link are incompletely understood. Here, we investigated the role of the endosomal adaptor protein and member of the LAMTOR/Ragulator complex LAMTOR2 (p14) in B-cell development. Efficient conditional deletion of LAMTOR2 at the pre-B1 stage using mb1-Cre mice resulted in complete developmental arrest. Deletion of LAMTOR2 using Cd19-Cre mice permitted analysis of residual B cells at later developmental stages, revealing that LAMTOR2 was critical for the generation and activation of mature B lymphocytes. Loss of LAMTOR2 resulted in aberrant BCR signaling due to delayed receptor internalization and endosomal trafficking. In conclusion, we identify LAMTOR2 as critical regulator of BCR trafficking and signaling that is essential for early B-cell development in mice

Haptoglobin improves shock, lung injury, and survival in canine pneumonia

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, mechanical ventilation, sedation, and continuous care are translatable to management in human intensive care units. We found, in this S. aureus pneumonia model inducing septic shock, that commercial human haptoglobin concentrate infusions over 48-hours bind canine CFH, increase CFH clearance, and lower circulating iron. Over the 96-hour study, this treatment was associated with an improved metabolic profile (pH, lactate), less lung injury, reversal of shock, and increased survival. Haptoglobin binding compartmentalized CFH to the intravascular space. This observation, in combination with increasing CFHs clearance, reduced available iron as a potential source of bacterial nutrition while decreasing the ability for CFH and iron to cause extravascular oxidative tissue injury. In contrast, haptoglobin therapy had no measurable antiinflammatory effect on elevations in proinflammatory C-reactive protein and cytokine levels. Haptoglobin therapy enhances normal host defense mechanisms in contrast to previously studied antiinflammatory sepsis therapies, making it a biologically plausible novel approach to treat septic shock

Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel–Lindau disease‐related tumours

Aims: Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours. Methods: Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis. Results: VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test). Conclusion: Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs