English clause-embedding verbs can be used in the evidential meaning (Simons, 2007; Murray, 2017), modulating the degree to which the speaker is committed to the truth of the proposition in the embedded clause. For example, an utterance like “I think the movie starts at 4” can signal that the speaker is uncertain whether the proposition the movie starts at 4 is true, and would like to attenuate their claim. Previous research has provided detailed accounts of lexical and contextual features that give rise to evidential meanings — however, less is known about how widespread these uses are, whether they are part of the verb’s lexical meaning, or emerge under certain pragmatic conditions. In this study, we addressed these questions by conducting two large-scale acceptability judgment experiments. In line with the observations in literature (Simons, 2007), we found that non-factive clause-embedding verbs are the most acceptable in evidential contexts. We also found, however, that even highly factive verbs can be acceptable as evidentials under favorable pragmatic conditions.

Verbs are widely analyzed as functions taking a discrete number of arguments (e.g., drink has two arguments but give has three). Recent studies, however, suggest that English verbs encode Instruments as more or less salient (e.g., the Instrument is more salient for slice, less salient for eat). We conducted a judgment task with adult speakers of Spanish and Mandarin and found that verbs in these languages also encode Instruments as having a relative degree of salience, inconsistent with the discrete model of participant encoding.

Introduction

Acute lymphoblastic leukemia (ALL) therapy confers risk for venous thromboembolism (VTE) and associated acute and long-term morbidity. Obesity increases VTE risk in the general population but its impact on ALL therapy-associated VTE is unknown.

Methods

In a retrospective cohort of children treated for ALL between 2008 and 2016 (n = 294), we analyzed obesity at diagnosis (body mass index [BMI] ≥95%) and subsequent development of VTE. A subset participated in two concurrent prospective ALL trials studying body composition via dual-energy X-ray absorptiometry (DXA) (n = 35) and hypercoagulability via thromboelastography (TEG) (n = 46). Secondary analyses explored whether precise measurement of body fat and/or global hemostasis ex vivo by TEG could further delineate VTE risk in the obese.

Results

Overall, we found 27/294 (9.2%) patients developed symptomatic VTE during therapy, 19/27 (70%) occurred during Induction. Study-defined "serious" VTE developed in 4/294 (1.4%) of patients. Obesity but not overweight was strongly predictive of symptomatic VTE (obesity odds ratio = 3.8, 95% confidence interval 1.5-9.6, p = 0.008). In the DXA subset, only 2/35 patients developed symptomatic VTE. However, within those prospectively screened during Induction, 30% (14/46) developed VTE; eight (17%) of these were asymptomatic and found only via screening.

Conclusions

In this pediatric ALL cohort, obesity conferred more than a three-fold increased risk for symptomatic VTE. In a subgroup of patients who underwent active screening, up to a third were noted to have VTE (symptomatic and asymptomatic). TEG did not predict VTE. Additional studies are necessary to validate these findings and to further refine a risk-stratified approach to thrombo-prevention during ALL therapy.

The balance between self-renewal and differentiation in human foetal lung epithelial progenitors controls the size and function of the adult organ. Moreover, progenitor cell gene regulation networks are employed by both regenerating and malignant lung cells, where modulators of their effects could potentially be of therapeutic value. Details of the molecular networks controlling human lung progenitor self-renewal remain unknown. We performed the first CRISPRi screen in primary human lung organoids to identify transcription factors controlling progenitor self-renewal. We show that SOX9 promotes proliferation of lung progenitors and inhibits precocious airway differentiation. Moreover, by identifying direct transcriptional targets using Targeted DamID, we place SOX9 at the centre of a transcriptional network, which amplifies WNT and RTK signalling to stabilise the progenitor cell state. In addition, the proof-of-principle CRISPRi screen and Targeted DamID tools establish a new workflow for using primary human organoids to elucidate detailed functional mechanisms underlying normal development and disease.

The Advanced Light Source (ALS) at Berkeley Lab remains one of the brightest sources for soft x-rays worldwide. A multiyear upgrade of the ALS is underway, which includes new and replacement x-ray beamlines, a replacement of many of the original insertion devices and many upgrades to the accelerator. The accelerator upgrade that affects the ALS performance most directly is the ALS brightness upgrade [1], which reduces the horizontal emittance from 6.3 to 2.0 nm (2.5 nm effective). Magnets for this upgrade were installed in late 2012 and early 2013 followed by user operation with the reduced emittance.

The Advanced Light Source (ALS) at Berkeley Lab remains one of the brightest sources for soft x-rays worldwide. A multiyear upgrade of the ALS is underway, which includes new and replacement x-ray beamlines, a replacement of many of the original insertion devices and many upgrades to the accelerator. The accelerator upgrade that affects the ALS performance most directly is the ALS brightness upgrade, which reduced the horizontal emittance from 6.3 to 2.0 nm (2.5 nm effective). Magnets for this upgrade were installed starting in 2012 followed by a transition to user operations with 2.0 nm emittance in spring 2013. Copyright © 2013 by JACoW.

The Advanced Light Source (ALS) is a thirdgeneration light source in operation since 1993. This light source is providing state-of-the-art performance to more than 40 beamlines and their users, due to the upgrades that have been completed over the last few years. The storage ring upgrade project that is developed here will allow the ALS to provide the 40 beamline users with higher photon beam brightness (factor of 2 or 3) by having its storage ring lattice modified. Forty-eight harmonic sextupole magnets with integrated dipole correctors and skew quadrupole coils will be introduced, which will require a level of installation activity not seen at the ALS since its original construction in 1991. Introducing new combined-function magnets in an existing storage ring is a challenge due to the limited space available and a balance had to be found between magnet performance and spatial constraints. After an introduction reviewing the characteristics of the three design families of the 48 combined-function magnets, the magnet fabrication and installation are developed along with analyses based on the magnetic measurements and the ALS storage ring commissioning results.

One gene can give rise to many functionally distinct proteoforms, each of which has a characteristic molecular mass. Top-down mass spectrometry enables the analysis of intact proteins and proteoforms. Here members of the Consortium for Top-Down Proteomics provide a decision tree that guides researchers to robust protocols for mass analysis of intact proteins (antibodies, membrane proteins and others) from mixtures of varying complexity. We also present cross-platform analytical benchmarks using a protein standard sample, to allow users to gauge their proficiency.

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development.