Privacy-Preserving Domain Adaptation of Semantic Parsers

Task-oriented dialogue systems often assist users with personal or confidential matters. For this reason, the developers of such a system are generally prohibited from observing actual usage. So how can they know where the system is failing and needs more training data or new functionality? In this work, we study ways in which realistic user utterances can be generated synthetically, to help increase the linguistic and functional coverage of the system, without compromising the privacy of actual users. To this end, we propose a two-stage Differentially Private (DP) generation method which first generates latent semantic parses, and then generates utterances based on the parses. Our proposed approach improves MAUVE by 2.5$\times$ and parse tree function type overlap by 1.3$\times$ relative to current approaches for private synthetic data generation, improving both on fluency and semantic coverage. We further validate our approach on a realistic domain adaptation task of adding new functionality from private user data to a semantic parser, and show overall gains of 8.5% points in accuracy with the new feature.Comment: ACL 202

ENERGY FLOW AND GROUND REACTION FORCE PREDICTORS OF BAT SWING SPEED DURING PITCHED BALL BATTING IN PROFESSIONAL BASEBALL PLAYERS

The purposes of this study are to determine how mechanical energy is absorbed, generated, and transferred during baseball hitting for professional athletes. This study also aims to identify which ground reaction force and energy flow variables influence bat speed. The findings of this study suggest that energy flows from the trunk to the lead leg as the pelvis rotates towards the pitcher. The results of this study emphasize the crucial role of the back leg and trunk during acceleration as well as eccentric contraction of muscles in the lead leg and trunk to decelerate during follow-through. Training strategies that improve muscular strength and mobility of the trunk and hips can be implemented to potentially increase bat speed

Measuring the Pharmacodynamic Effects of a Novel Hsp90 Inhibitor on HER2/neu Expression in Mice Using 89Zr-DFO-Trastuzumab

The positron-emitting radionuclide (89)Zr (t(1/2) = 3.17 days) was used to prepare (89)Zr-radiolabeled trastuzumab for use as a radiotracer for characterizing HER2/neu-positive breast tumors. In addition, pharmacodynamic studies on HER2/neu expression levels in response to therapeutic doses of PU-H71 (a specific inhibitor of heat-shock protein 90 [Hsp90]) were conducted.Trastuzumab was functionalized with desferrioxamine B (DFO) and radiolabeled with [(89)Zr]Zr-oxalate at room temperature using modified literature methods. ImmunoPET and biodistribution experiments in female, athymic nu/nu mice bearing sub-cutaneous BT-474 (HER2/neu positive) and/or MDA-MB-468 (HER2/neu negative) tumor xenografts were conducted. The change in (89)Zr-DFO-trastuzumab tissue uptake in response to high- and low-specific-activity formulations and co-administration of PU-H71 was evaluated by biodistribution studies, Western blot analysis and immunoPET. (89)Zr-DFO-trastuzumab radiolabeling proceeded in high radiochemical yield and specific-activity 104.3+/-2.1 MBq/mg (2.82+/-0.05 mCi/mg of mAb). In vitro assays demonstrated >99% radiochemical purity with an immunoreactive fraction of 0.87+/-0.07. In vivo biodistribution experiments revealed high specific BT-474 uptake after 24, 48 and 72 h (64.68+/-13.06%ID/g; 71.71+/-10.35%ID/g and 85.18+/-11.10%ID/g, respectively) with retention of activity for over 120 h. Pre-treatment with PU-H71 was followed by biodistribution studies and immunoPET of (89)Zr-DFO-trastuzumab. Expression levels of HER2/neu were modulated during the first 24 and 48 h post-administration (29.75+/-4.43%ID/g and 41.42+/-3.64%ID/g, respectively). By 72 h radiotracer uptake (73.64+/-12.17%ID/g) and Western blot analysis demonstrated that HER2/neu expression recovered to baseline levels.The results indicate that (89)Zr-DFO-trastuzumab provides quantitative and highly-specific delineation of HER2/neu positive tumors, and has potential to be used to measure the efficacy of long-term treatment with Hsp90 inhibitors, like PU-H71, which display extended pharmacodynamic profiles

Contrastive Decoding: Open-ended Text Generation as Optimization

Likelihood, although useful as a training loss, is a poor search objective for guiding open-ended generation from language models (LMs). Existing generation algorithms must avoid both unlikely strings, which are incoherent, and highly likely ones, which are short and repetitive. We propose contrastive decoding (CD), a more reliable search objective that returns the difference between likelihood under a large LM (called the expert, e.g. OPT-13b) and a small LM (called the amateur, e.g. OPT-125m). CD is inspired by the fact that the failures of larger LMs are even more prevalent in smaller LMs, and that this difference signals exactly which texts should be preferred. CD requires zero training, and produces higher quality text than decoding from the larger LM alone. It also generalizes across model types (OPT and GPT2) and significantly outperforms four strong decoding algorithms in automatic and human evaluations

Growth and characterization of α\alpha-Sn thin films on In- and Sb-rich reconstructions of InSb(001)

$\alpha$-Sn thin films can exhibit a variety of topologically non-trivial phases. Both studying the transitions between these phases and making use of these phases in eventual applications requires good control over the electronic and structural quality of $\alpha$-Sn thin films. $\alpha$-Sn growth on InSb often results in out-diffusion of indium, a p-type dopant. By growing $\alpha$-Sn via molecular beam epitaxy on the Sb-rich c(4$\times$4) surface reconstruction of InSb(001) rather than the In-rich c(8$\times$2), we demonstrate a route to substantially decrease and minimize this indium incorporation. The reduction in indium concentration allows for the study of the surface and bulk Dirac nodes in $\alpha$-Sn via angle-resolved photoelectron spectroscopy without the common approaches of bulk doping or surface dosing, simplifying topological phase identification. The lack of indium incorporation is verified in angle-resolved and -integrated ultraviolet photoelectron spectroscopy as well as in clear changes in the Hall response

Safety and efficacy of endoscopic submucosal dissection for rectal neoplasia: a multicenter North American experience.

Background and aims  Rectal lesions traditionally represent the first lesions approached during endoscopic submucosal dissection (ESD) training in the West. We evaluated the safety and efficacy of rectal ESD in North America. Methods  This is a multicenter retrospective analysis of rectal ESD between January 2010 and September 2018 in 15 centers. End points included: rates of en bloc resection, R0 resection, adverse events, comparison of pre- and post-ESD histology, and factors associated with failed resection. Results  In total, 171 patients (median age 63 years; 56 % men) underwent rectal ESD (median size 43 mm). En bloc resection was achieved in 141 cases (82.5 %; 95 %CI 76.8-88.2), including 24 of 27 (88.9 %) with prior failed endoscopic mucosal resection (EMR). R0 resection rate was 74.9 % (95 %CI 68.4-81.4). Post-ESD bleeding and perforation occurred in 4 (2.3 %) and 7 (4.1 %), respectively. Covert submucosal invasive cancer (SMIC) was identified in 8.6 % of post-ESD specimens. There was one case (1/120; 0.8 %) of recurrence at a median follow-up of 31 weeks; IQR: 19-76 weeks). Older age and higher body mass index (BMI) were predictors of failed R0 resection, whereas submucosal fibrosis was associated with a higher likelihood of both failed en bloc and R0 resection. Conclusion  Rectal ESD in North America is safe and is associated with high en bloc and R0 resection rates. The presence of submucosal fibrosis was the main predictor of failed en bloc and R0 resection. ESD can be considered for select rectal lesions, and serves not only to establish a definitive tissue diagnosis but also to provide curative resection for lesions with covert advanced disease

Epitaxial growth, magnetoresistance, and electronic band structure of GdSb magnetic semimetal films

Motivated by observations of extreme magnetoresistance (XMR) in bulk crystals of rare-earth monopnictide (RE-V) compounds and emerging applications in novel spintronic and plasmonic devices based on thin-film semimetals, we have investigated the electronic band structure and transport behavior of epitaxial GdSb thin films grown on III-V semiconductor surfaces. The Gd3+ ion in GdSb has a high spin S=7/2 and no orbital angular momentum, serving as a model system for studying the effects of antiferromagnetic order and strong exchange coupling on the resulting Fermi surface and magnetotransport properties of RE-Vs. We present a surface and structural characterization study mapping the optimal synthesis window of thin epitaxial GdSb films grown on III-V lattice-matched buffer layers via molecular beam epitaxy. To determine the factors limiting XMR in RE-V thin films and provide a benchmark for band structure predictions of topological phases of RE-Vs, the electronic band structure of GdSb thin films is studied, comparing carrier densities extracted from magnetotransport, angle-resolved photoemission spectroscopy (ARPES), and density functional theory (DFT) calculations. ARPES shows hole-carrier rich topologically-trivial semi-metallic band structure close to complete electron-hole compensation, with quantum confinement effects in the thin films observed through the presence of quantum well states. DFT predicted Fermi wavevectors are in excellent agreement with values obtained from quantum oscillations observed in magnetic field-dependent resistivity measurements. An electron-rich Hall coefficient is measured despite the higher hole carrier density, attributed to the higher electron Hall mobility. The carrier mobilities are limited by surface and interface scattering, resulting in lower magnetoresistance than that measured for bulk crystals

Design and development of a field-deployable single-molecule detector (SMD) for the analysis of molecular markers

Single-molecule detection (SMD) has demonstrated some attractive benefits for many types of biomolecular analyses including enhanced processing speed by eliminating processing steps, elimination of ensemble averaging and single-molecule sensitivity. However, it's wide spread use has been hampered by the complex instrumentation required for its implementation when using fluorescence as the readout modality. We report herein a simple and compact fluorescence single-molecule instrument that is straightforward to operate and consisted of fiber optics directly coupled to a microfluidic device. The integrated fiber optics served as waveguides to deliver the laser excitation light to the sample and collecting the resulting emission, simplifying the optical requirements associated with traditional SMD instruments by eliminating the need for optical alignment and simplification of the optical train. Additionally, the use of a vertical cavity surface emitting laser and a single photon avalanche diode serving as the excitation source and photon transducer, respectively, as well as a field programmable gate array (FPGA) integrated into the processing electronics assisted in reducing the instrument footprint. This small footprint SMD platform was tested using fluorescent microspheres and single AlexaFluor 660 molecules to determine the optimal operating parameters and system performance. As a demonstration of the utility of this instrument for biomolecular analyses, molecular beacons (MBs) were designed to probe bacterial cells for the gene encoding Gram-positive species. The ability to monitor biomarkers using this simple and portable instrument will have a number of important applications, such as strain-specific detection of pathogenic bacteria or the molecular diagnosis of diseases requiring rapid turn-around-times directly at the point-of-use.close5

Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions

Abstract: Background and aims: Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone-marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. Methods and results: Here we show using intravital microscopy, morphometric analysis and gene expression profiling that bone marrow derived “KCs” accumulating as a result of genotoxic injury resemble, but are not identical to their yolk-sac (YS) counterparts. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allows discrimination between these two KC populations. Reflecting the differential expression of scavenger receptors, YS-derived KCs were more effective at accumulating Ac-LDL, whereas surprisingly they were poorer than BM-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to LPS challenge, ii) phagocytosis of effete RBCs and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite. Conclusions: BM-derived KCs differentiate locally to resemble YS-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology

Chemokine (C-C motif) ligand 2 mediates direct and indirect fibrotic responses in human and murine cultured fibrocytes

<p>Abstract</p> <p>Background</p> <p>Fibrocytes are a population of circulating bone-marrow-derived cells that express surface markers for leukocytes and mesenchymal cells, and are capable of differentiating into myofibroblasts. They have been observed at sites of active fibrosis and increased circulating numbers correlate with mortality in idiopathic pulmonary fibrosis (IPF). Inhibition of chemokine (C-C motif) receptor 2 (CCR2) during experimental models of lung fibrosis reduces lung collagen deposition, as well as reducing lung fibrocyte accumulation. The aim of the present study was to determine whether human and mouse fibrocytes express functional CCR2.</p> <p>Results</p> <p>Following optimized and identical human and murine fibrocyte isolation, both cell sources were shown to be positive for CCR2 by flow cytometry and this expression colocalized with collagen I and CD45. Human blood fibrocytes stimulated with the CCR2 ligand chemokine (C-C motif) ligand 2 (CCL2), demonstrated increased proliferation (<it>P </it>< 0.005) and differentiation into myofibroblasts (<it>P </it>< 0.001), as well as a chemotactic response (<it>P </it>< 0.05). Murine fibrocytes also responded to CCR2 stimulation, with CCL12 being more potent than CCL2.</p> <p>Conclusions</p> <p>This study directly compares the functional responses of human and murine fibrocytes to CCR2 ligands, and following comparable isolation techniques. We have shown comparable biological effects, strengthening the translatability of the murine models to human disease with respect to targeting the CCR2 axis to ameliorate disease in IPF patients.</p