Generating recommendations for entity-oriented exploratory search

We introduce the task of recommendation set generation for entity-oriented exploratory search. Given an input search query which is open-ended or under-specified, the task is to present the user with an easily-understandable collection of query recommendations, with the goal of facilitating domain exploration or clarifying user intent. Traditional query recommendation systems select recommendations by identifying salient keywords in retrieved documents, or by querying an existing taxonomy or knowledge base for related concepts. In this work, we build a text-to-text model capable of generating a collection of recommendations directly, using the language model as a "soft" knowledge base capable of proposing new concepts not found in an existing taxonomy or set of retrieved documents. We train the model to generate recommendation sets which optimize a cost function designed to encourage comprehensiveness, interestingness, and non-redundancy. In thorough evaluations performed by crowd workers, we confirm the generalizability of our approach and the high quality of the generated recommendations

Transcriptional landscape of epithelial and immune cell populations revealed through FACS-seq of healthy human skin.

Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, CD4+ T effector cells, and CD8+ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant CD8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types

Threshold Tolerance of New Genotypes of Pennisetum glaucum (L.) R. Br. to Salinity and Drought

With continued population growth, increasing staple crop production is necessary. However, in dryland areas, this is negatively affected by various abiotic stresses, such as drought and salinity. The field screening of 10 improved genetic lines of pear millet originating from African dryland areas was conducted based on a set of agrobiological traits (i.e., germination rate, plant density, plant maturity rate, forage, and grain yields) in order to understand plant growth and its yield potential responses under saline environments. Our findings demonstrated that genotype had a significant impact on the accumulation of green biomass (64.4% based on two-way ANOVA), while salinity caused reduction in grain yield value. HHVBC Tall and IP 19586 were selected as the best-performing and high-yielding genotypes. HHVBC Tall is a dual purpose (i.e., forage and grain) line which produced high grain yields on marginal lands, with soil salinization up to electrical conductivity (EC) 6–8 dS m−1 (approximately 60–80 mM NaCl). Meanwhile, IP 19586, grown under similar conditions, showed a rapid accumulation of green biomass with a significant decrease in grain yield. Both lines were tolerant to drought and sensitive to high salinity (above 200 mM NaCl). The threshold salinity of HHVBC Tall calculated at the seedling stage was lower than that of IP 19586. Seedling viability of these lines was affected by oxidative stress and membrane peroxidation, and they had decreased chlorophyll and carotenoid biosynthesis. This study demonstrated that ionic stress is more detrimental for the accumulation of green and dry biomass, in combination with increasing the proline and malonic dialdehyde (MDA) contents of both best-performing pearl millet lines, as compared with osmotic stress

Properties of Parallel Tetramolecular G-Quadruplex Carrying N-Acetylgalactosamine as Potential Enhancer for Oligonucleotide Delivery to Hepatocytes

The development of oligonucleotide conjugates for in vivo targeting is one of the most exciting areas for oligonucleotide therapeutics. A major breakthrough in this field was the development of multifunctional GalNAc-oligonucleotides with high affinity to asialoglycoprotein receptors (ASGPR) that directed therapeutic oligonucleotides to hepatocytes. In the present study, we explore the use of G-rich sequences functionalized with one unit of GalNAc at the 3′-end for the formation of tetrameric GalNAc nanostructures upon formation of a parallel G-quadruplex. These compounds are expected to facilitate the synthetic protocols by providing the multifunctionality needed for the binding to ASGPR. To this end, several G-rich oligonucleotides carrying a TGGGGGGT sequence at the 3′-end functionalized with one molecule of N-acetylgalactosamine (GalNAc) were synthesized together with appropriate control sequences. The formation of a self-assembled parallel G-quadruplex was confirmed through various biophysical techniques such as circular dichroism, nuclear magnetic resonance, polyacrylamide electrophoresis and denaturation curves. Binding experiments to ASGPR show that the size and the relative position of the therapeutic cargo are critical for the binding of these nanostructures. The biological properties of the resulting parallel G-quadruplex were evaluated demonstrating the absence of the toxicity in cell lines. The internalization preferences of GalNAc-quadruplexes to hepatic cells were also demonstrated as well as the enhancement of the luciferase inhibition using the luciferase assay in HepG2 cell lines versus HeLa cells. All together, we demonstrate that tetramerization of G-rich oligonucleotide is a novel and simple route to obtain the beneficial effects of multivalent N-acetylgalactosamine functionalizatio

Advanced R744 solution for supermarkets, hotel chillers and maritime applications in India

R744 integrated systems can meet oscillating heating and cooling demands efficiently and become a game changer in countries such as India. The present work aims to develop and present R744 system designs and disseminate the knowledge under the framework of the INDEE+ project in India, with the focus on three vital sectors: supermarkets, hotels, and seafood industries. Ejector-supported R744 systems are observed to be an ideal solution to increase the R744 system efficiency at high ambient temperature operations as in tropical regions. The strategy is also to evaluate the system operations to deal with an individually proposed R744 system performances to fulfil the thermal load handling demand on both heating and cooling side. Furthermore, students, vendors and end-users are planned to train by utilizing the upcoming demonstration sites with R744 technology. Support is being provided to communicate and finalize the R744 system design specification for the various system configurations. Each development aspect will be evaluated critically to make the proposed R744 technology demo units a success and to become flagship developments supporting India to transfer towards clean cooling and heating technologies.Advanced R744 solution for supermarkets, hotel chillers and maritime applications in IndiaacceptedVersio

Effects of Two Different Catheter Ablation Techniques on Spectral Characteristics of Atrial Fibrillation

ObjectivesThe aim of this study was to determine the effects of circumferential pulmonary vein ablation (CPVA) and electrogram-guided ablation (EGA) on the spectral characteristics of atrial fibrillation (AF) and the relationship between changes in dominant frequency (DF) and clinical outcome.BackgroundCircumferential pulmonary vein ablation and EGA have been used to eliminate AF. Spectral analysis may identify high-frequency sources.MethodsIn 84 consecutive patients, CPVA (n = 42) or EGA (n = 42) was performed for paroxysmal (n = 49) or persistent (n = 35) AF. During EGA, complex electrograms were targeted. Lead V1and electrograms from the left atrium and coronary sinus were analyzed to determine the DF of AF before and after ablation.ResultsThe left atrial DF was higher in persistent (5.83 ± 0.86 Hz) than paroxysmal AF (5.33 ± 0.76 Hz, p = 0.03). There was a frequency gradient from the left atrium to the coronary sinus (p = 0.02). Circumferential pulmonary vein ablation and EGA resulted in a similar decrease in DF (18 ± 17% vs. 17 ± 15%, p = 0.8). During a mean follow-up of 9 ± 6 months, the change in DF after CPVA was similar among patients with and without recurrent AF. An acute decrease in DF after EGA was associated with freedom from recurrent AF only in patients with persistent AF (19 ± 14% vs. 3 ± 6%, p = 0.02).ConclusionsBoth CPVA and EGA decrease the DF of AF, consistent with elimination of high-frequency sources. Whereas the efficacy of EGA is associated with a decrease in DF in patients with persistent AF, the efficacy of CPVA is independent of changes in DF. This suggests that CPVA and EGA eliminate different mechanisms in the genesis of persistent AF

Colchicine Myopathy: A Case Series Including Muscle MRI and ABCB1 Polymorphism Data

Colchicine is a medication most commonly used in the treatment of gout and familial mediterannean fever. A rare complication of therapy is toxicity causing proximal myopathy and polyneuropathy. Colchicine myopathy has been associated with the coadministration of other medications with colchicine, such as statins or tacrolimus, and is more common in patients with renal impairment. Otherwise, it is unclear which patients are at greatest risk of developing this adverse drug reaction. ABCB1 is important to the metabolism of colchicine, so we speculated that it was possible that colchicine myopathy patients may have a particular genotype that is associated with this side effect. We describe two cases of colchicine myopathy which occurred with co-administration of rosuvastatin. From one case, we present the first published data on muscle MRI in this condition. We additionally present an analysis of four genetic polymorphisms in ABCB1 and transcript levels in muscle tissue, and demonstrate the descriptive finding of reduced ABCB1 transcript levels in the colchicine myopathy patients