Miracle-dz/UniFAR-FTUs huggingface dataset:
STBins: Visual Tracking and Comparison of Multiple Data Sequences Using Temporal Binning

While analyzing multiple data sequences, the following questions typically arise: how does a single sequence change over time, how do multiple sequences compare within a period, and how does such comparison change over time. This paper presents a visual technique named STBins to answer these questions. STBins is designed for visual tracking of individual data sequences and also for comparison of sequences. The latter is done by showing the similarity of sequences within temporal windows. A perception study is conducted to examine the readability of alternative visual designs based on sequence tracking and comparison tasks. Also, two case studies based on real-world datasets are presented in detail to demonstrate usage of our technique.
Multiple channels of DEET repellency in Drosophila.

BACKGROUND DEET (N,N-diethyl-m-toluamide) is the most widely used prophylactic insect repellent to inhibit insect bites. Despite its use since 1944, the mechanism for DEET repellency remains controversial. Here, we revisited the role of smell and taste in DEET repellence using Drosophila as a model. RESULTS Analysis of the responses of individual olfactory receptor neuron (ORN) classes to DEET reveals that 11 ORNs are activated and 2 ORNs are inhibited by this compound. Blocking individual ORN classes in the antenna does not block DEET repellence. This argues against the existence of a single ORN mediating DEET repellence in Drosophila. Activation of all ORCO-expressing neurons using channelrhodopsin favors attraction, not repellence, in behavioral valence. We also demonstrate that gustatory neurons are highly sensitive to DEET. We used RNAi to screen candidate receptors encoded by gene families involved in the detection of bitter compounds, including 34 gustatory receptors (Grs), 14 ionotropic receptors (Irs), 5 pick-pocket subunits (PPKs), 3 transient receptor potential ion channels (TrpA, TrpL, Painless) and 1 metabotropic glutamate receptors gene (DmXR). We saw striking defects in DEET-mediated oviposition behavior when expression of either Gr32a or Gr33a were inhibited. CONCLUSION Our findings support a multimodal mechanism for DEET detection in fruit flies and indicate a prominent role for taste detection mediating DEET repellence. This article is protected by copyright. All rights reserved.
Keratins regulate Hsp70-mediated nuclear localization of p38 mitogen-activated protein kinase

ABSTRACT Intermediate filament protein keratin 8 (K8) binds to heat shock protein 70 (Hsp70) and p38 MAPK, and is phosphorylated at Ser74 by p38α (MAPK14, hereafter p38). However, a p38 binding site on K8 and the molecular mechanism of K8-p38 interaction related to Hsp70 are unknown. Here, we identify a p38 docking site on K8 (Arg148/149 and Leu159/161) that is highly conserved in other intermediate filaments. A docking-deficient K8 mutation caused increased p38-Hsp70 interaction and enhanced p38 nuclear localization, indicating that the p38 dissociated from mutant K8 makes a complex with Hsp70, which is known as a potential chaperone for p38 nuclear translocation. Comparison of p38 MAPK binding with keratin variants associated with liver disease showed that the K18 I150V variant dramatically reduced binding with p38, which is similar to the effect of the p38 docking-deficient mutation on K8. Because the p38 docking site on K8 (Arg148/149 and Leu159/161) and the K18 Ile150 residue are closely localized in the parallel K8/K18 heterodimer, the K18 I150V mutation might interfere with K8-p38 interaction. These findings show that keratins, functioning as cytoplasmic anchors for p38, modulate p38 nuclear localization and thereby might affect a number of p38-mediated signal transduction pathways. Summary: Keratin 8 interacts with p38 MAPK via a specific docking site and modulates formation of the p38-Hsp70 complex, which regulates the subcellular localization of p38 MAPK.
Conformational adaptation of UNCG loops upon crowding

If the A-form helix is the major structural motif found in RNA, the loops that cap them constitute the second most important family of motifs. Among those, two are overrepresented, GNRA and UNCG tetraloops. Recent surveys of RNA structures deposited in the PDB show that GNRA and UNCG tetraloops can adopt tertiary folds that are very different from their canonical conformations, characterized by the presence of a U-turn of a Z-turn, respectively. Crystallographic data from both a lariat-capping (LC) ribozyme and a group II intron ribozyme reveal that a given UUCG tetraloop can adopt a distinct fold depending on its structural environment. Specifically, when the crystal packing applies relaxed constraints on the loop, the canonical Z-turn conformation is observed. In contrast, a highly packed environment induces “squashing” of the tetraloop by distorting its sugar-phosphate backbone in a specific way that expels the first and fourth nucleobases out of the loop, and falls in van der Waals distance of the last base pair of the helix, taking the place of the pair formed between the first and fourth residues in Z-turn loops. The biological relevance of our observations is supported by the presence of similarly deformed loops in the highly packed environment of the ribosome and in a complex between a dsRNA and a RNase III. The finding that Z-turn loops change conformation under higher molecular packing suggests that, in addition to their demonstrated role in stabilizing RNA folding, they may contribute to the three-dimensional structure of RNA by mediating tertiary interactions with distal residues.
Lateral effects in pattern vision

There is a large literature on lateral effects in pattern vision but no consensus about them or comprehensive model of them. This paper reviews the literature with a focus on the effects of parallel context in the central fovea. It describes seven experiments that measure detection and discrimination thresholds in annular and Gabor-pattern contexts at different separations. It presents a model of these effects, which is an elaboration of Foley's (1994) model. The model describes the results well, and it shows that lateral context affects the response to the target by both multiplicative excitation and additive inhibition. Both lateral effects extend for several wavelengths beyond the target. They vary in relative strength, producing near suppression and far enhancement of the response to the target. The model describes the detection and discrimination results well, and it also describes the results of experiments on lateral effects on perceived contrast. The model is consistent with the physiology of V1 cells.
The Sensitivity to Initial Soil Moisture for Three Severe Cases of Heat Waves Over Eastern China

Using Weather Research and Forecasting model (WRF) simulations with different initial soil moisture (ISM) conditions, we investigate the sensitivity to ISM for the three severe heat wave events dominating eastern China in 2003, 2007 and 2013. The control simulations are able to reproduce the spatial distributions and the daily evolutions for each of the three heat waves but apparently underestimate their amplitudes, intensities and spatial extensions. The decreased ISM could cause an enhancement on heat waves with increased amplitudes, extents and intensities, while it has insignificant influence on the spatial distributions and temporal variations. The responses of heat waves are generally decreasing with the increasing ISM, controlled by different regimes in the surface soil moisture-temperature relationship. Through enhanced sensible flux as well as reduced latent cooling, the initial soil dryness locally strengthens the surface warming and the further drying of the soil. The three heat waves were all dominated by high-pressure systems in the mid-troposphere. The reduced ISM forces positive anomalies of geopotential height at mid-troposphere and negative anomalies at lower levels, leading to an enhanced thickness of the atmosphere. Such a thickened atmosphere can strengthen the anomalous high-pressure systems, favoring the maintenance of severe heat waves. This acts as a positive feedback between atmospheric circulation, surface warming and soil dryness.
Selective Carbon Material Engineering for Improved MEMS and NEMS

The development of micro and nano electromechanical systems and achievement of higher performances with increased quality and life time is confronted to searching and mastering of material with superior properties and quality. Those can affect many aspects of the MEMS, NEMS and MOMS design including geometric tolerances and reproducibility of many specific solid-state structures and properties. Among those: Mechanical, adhesion, thermal and chemical stability, electrical and heat conductance, optical, optoelectronic and semiconducting properties, porosity, bulk and surface properties. They can be affected by different kinds of phase transformations and degrading, which greatly depends on the conditions of use and the way the materials have been selected, elaborated, modified and assembled. Distribution of these properties cover several orders of magnitude and depend on the design, actually achieved structure, type and number of defects. It is then essential to be well aware about all these, and to distinguish and characterize all features that are able to affect the results. For this achievement, we point out and discuss the necessity to take into account several recently revisited fundamentals on carbon atomic rearrangement and revised carbon Raman spectroscopy characterizing in addition to several other aspects we will briefly describe. Correctly selected and implemented, these carbon materials can then open new routes for many new and more performing microsystems including improved energy generation, storage and conversion, 2D superconductivity, light switches, light pipes and quantum devices and with new improved sensor and mechanical functions and biomedical applications.
Revisiting the β-Lactams for Tuberculosis Therapy with a Compound-Compound Synthetic Lethality Approach

The suboptimal effectiveness of β-lactam antibiotics against Mycobacterium tuberculosis has hindered the utility of this compound class for tuberculosis treatment. However, the results of treatment with a second-line regimen containing meropenem plus a β-lactamase inhibitor were found to be encouraging in a case study of extensively drug-resistant tuberculosis (M. C. Payen, S. De Wit, C. Martin, R. ABSTRACT The suboptimal effectiveness of β-lactam antibiotics against Mycobacterium tuberculosis has hindered the utility of this compound class for tuberculosis treatment. However, the results of treatment with a second-line regimen containing meropenem plus a β-lactamase inhibitor were found to be encouraging in a case study of extensively drug-resistant tuberculosis (M. C. Payen, S. De Wit, C. Martin, R. Sergysels, et al., Int J Tuberc Lung Dis 16:558–560, 2012, https://doi.org/10.5588/ijtld.11.0414). We hypothesized that the innate resistance of M. tuberculosis to β-lactams is mediated in part by noncanonical accessory proteins that are not considered the classic targets of β-lactams and that small-molecule inhibitors of those accessory targets might sensitize M. tuberculosis to β-lactams. In this study, we screened an NIH small-molecule library for the ability to sensitize M. tuberculosis to meropenem. We identified six hit compounds, belonging to either the N-arylindole or benzothiophene chemotype. Verification studies confirmed the synthetic lethality phenotype for three of the N-arylindoles and one benzothiophene derivative. The latter was demonstrated to be partially bioavailable via oral administration in mice. Structure-activity relationship studies of both structural classes identified analogs with potent antitubercular activity, alone or in combination with meropenem. Transcriptional profiling revealed that oxidoreductases, MmpL family proteins, and a 27-kDa benzoquinone methyltransferase could be the targets of the N-arylindole potentiator. In conclusion, our compound-compound synthetic lethality screening revealed novel small molecules that were capable of potentiating the action of meropenem, presumably via inhibition of the innate resistance conferred by β-lactam accessory proteins. β-Lactam compound-compound synthetic lethality may be an alternative approach for drug-resistant tuberculosis.
Vibration‐induced depression in spinal loop excitability revisited

While it has been well described that prolonged vibration locally applied to a muscle or its tendon (up to 1 h) decreases spinal loop excitability between homonymous Ia afferents and motoneurons, the involved mechanisms are not fully understood. By combining electrophysiological methods, this study aimed to provide new insights into the mechanisms involved in soleus decreased spinal excitability after prolonged local vibration. We report that prolonged vibration induces a decrease in motoneuron excitability rather than an increase in presynaptic mechanisms (as commonly hypothesized in the current literature). The present results may help to design appropriate clinical intervention and could reinforce the interest in vibration as a treatment for spastic patients who are characterized by spinal hyper‐excitability responsible for spasms and long‐lasting reflexes.
Digital Health Apps in the Clinical Care of Inflammatory Bowel Disease: Scoping Review

Background Digital health is poised to transform health care and redefine personalized health. As Internet and mobile phone usage increases, as technology develops new ways to collect data, and as clinical guidelines change, all areas of medicine face new challenges and opportunities. Inflammatory bowel disease (IBD) is one of many chronic diseases that may benefit from these advances in digital health. This review intends to lay a foundation for clinicians and technologists to understand future directions and opportunities together. Objective This review covers mobile health apps that have been used in IBD, how they have fit into a clinical care framework, and the challenges that clinicians and technologists face in approaching future opportunities. Methods We searched PubMed, Scopus, and ClinicalTrials.gov to identify mobile apps that have been studied and were published in the literature from January 1, 2010, to April 19, 2019. The search terms were (“mobile health” OR “eHealth” OR “digital health” OR “smart phone” OR “mobile app” OR “mobile applications” OR “mHealth” OR “smartphones”) AND (“IBD” OR “Inflammatory bowel disease” OR “Crohn's Disease” (CD) OR “Ulcerative Colitis” (UC) OR “UC” OR “CD”), followed by further analysis of citations from the results. We searched the Apple iTunes app store to identify a limited selection of commercial apps to include for discussion. Results A total of 68 articles met the inclusion criteria. A total of 11 digital health apps were identified in the literature and 4 commercial apps were selected to be described in this review. While most apps have some educational component, the majority of apps focus on eliciting patient-reported outcomes related to disease activity, and a few are for treatment management. Significant benefits have been seen in trials relating to education, quality of life, quality of care, treatment adherence, and medication management. No studies have reported a negative impact on any of the above. There are mixed results in terms of effects on office visits and follow-up. Conclusions While studies have shown that digital health can fit into, complement, and improve the standard clinical care of patients with IBD, there is a need for further validation and improvement, from both a clinical and patient perspective. Exploring new research methods, like microrandomized trials, may allow for more implementation of technology and rapid advancement of knowledge. New technologies that can objectively and seamlessly capture remote data, as well as complement the clinical shift from symptom-based to inflammation-based care, will help the clinical and health technology communities to understand the full potential of digital health in the care of IBD and other chronic illnesses.
The “Grass-Fed” Milk Story: Understanding the Impact of Pasture Feeding on the Composition and Quality of Bovine Milk

Milk is a highly nutritious food that contains an array of macro and micro components, scientifically proven to be beneficial to human health. While the composition of milk is influenced by a variety of factors, such as genetics, health, lactation stage etc., the animal’s diet remains a key mechanism by which its nutrition and processing characteristics can be altered. Pasture feeding has been demonstrated to have a positive impact on the nutrient profile of milk, increasing the content of some beneficial nutrients such as Omega-3 polyunsaturated fatty acids, vaccenic acid, and conjugated linoleic acid (CLA), while reducing the levels of Omega-6 fatty acids and palmitic acid. These resultant alterations to the nutritional profile of “Grass-Fed” milk resonate with consumers that desire healthy, “natural”, and sustainable dairy products. This review provides a comprehensive comparison of the impact that pasture and non-pasture feeding systems have on bovine milk composition from a nutritional and functional (processability) perspective, highlighting factors that will be of interest to dairy farmers, processors, and consumers.
Genome-wide analysis of the transcriptional response to drought stress in root and leaf of common bean

Abstract Genes related to the response to drought stress in leaf and root tissue of drought-susceptible (DS) and tolerant (DT) genotypes were characterized by RNA-Seq. In total, 54,750 transcripts, representative of 28,590 genes, were identified; of these, 1,648 were of high-fidelity (merge of 12 libraries) and described for the first time in the Andean germplasm. From the 1,239 differentially expressed genes (DEGs), 458 were identified in DT, with a predominance of genes in categories of oxidative stress, response to stimulus and kinase activity. Most genes related to oxidation-reduction terms in roots were early triggered in DT (T75) compared to DS (T150) suggestive of a mechanism of tolerance by reducing the damage from ROS. Among the KEGG enriched by DEGs up-regulated in DT leaves, two related to the formation of Sulfur-containing compounds, which are known for their involvement in tolerance to abiotic stresses, were common to all treatments. Through qPCR, 88.64% of the DEGs were validated. A total of 151,283 variants were identified and functional effects estimated for 85,780. The raw data files were submitted to the NCBI database. A transcriptome map revealed new genes and isoforms under drought. These results supports a better understanding of the drought tolerance mechanisms in beans.
The South America Tomato Leafminer, Tuta absoluta (Lepidoptera: Gelechiidae), Spreads Its Wings in Eastern Africa: Distribution and Socioeconomic Impacts

Abstract Following the arrival of Tuta absoluta Meyrick in the eastern African subregion in 2012, several studies have shown numerous ecological aspects of its invasion. We investigated the impact of T. absoluta on people's livelihoods across four counties of Kenya. Here, 200 farmers in the country were interviewed in person using semistructured questionnaires. In addition to livelihood surveys, T. absoluta distribution was mapped between 2016 and 2018 to determine its current distribution across four countries (Kenya, Sudan, Tanzania, and Uganda) in the subregion. Albeit a recent invader, T. absoluta is abundant and distributed throughout the subregion and is viewed as the worst invasive alien species of agriculturally sustainable livelihoods by tomato farmers. The arrival of T. absoluta in the subregion has resulted in livelihood losses and increased both the cost of tomato production and frequency of pesticide application. We recommend the implementation of biological control along, with other control measures in an integrated approach, against T. absoluta in the subregion, where its impact on sustainable livelihoods is serious and long-term control strategies are required to curb its detrimental effects.
Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma

Purpose: Gastroesophageal adenocarcinoma (GEA) has a poor prognosis and few therapeutic options. Utilizing a 73-gene plasma-based next-generation sequencing (NGS) cell-free circulating tumor DNA (ctDNA-NGS) test, we sought to evaluate the role of ctDNA-NGS in guiding clinical decision-making in GEA. Experimental Design: We evaluated a large cohort (n = 2,140 tests; 1,630 patients) of ctDNA-NGS results (including 369 clinically annotated patients). Patients were assessed for genomic alteration (GA) distribution and correlation with clinicopathologic characteristics and outcomes. Results: Treatment history, tumor site, and disease burden dictated tumor-DNA shedding and consequent ctDNA-NGS maximum somatic variant allele frequency. Patients with locally advanced disease having detectable ctDNA postoperatively experienced inferior median disease-free survival (P = 0.03). The genomic landscape was similar but not identical to tissue-NGS, reflecting temporospatial molecular heterogeneity, with some targetable GAs identified at higher frequency via ctDNA-NGS compared with previous primary tumor-NGS cohorts. Patients with known microsatellite instability-high (MSI-High) tumors were robustly detected with ctDNA-NGS. Predictive biomarker assessment was optimized by incorporating tissue-NGS and ctDNA-NGS assessment in a complementary manner. HER2 inhibition demonstrated a profound survival benefit in HER2-amplified patients by ctDNA-NGS and/or tissue-NGS (median overall survival, 26.3 vs. 7.4 months; P = 0.002), as did EGFR inhibition in EGFR-amplified patients (median overall survival, 21.1 vs. 14.4 months; P = 0.01). Conclusions: ctDNA-NGS characterized GEA molecular heterogeneity and rendered important prognostic and predictive information, complementary to tissue-NGS. See related commentary by Frankell and Smyth, p. 6893