Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer

Introduction Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. Materials and Methods A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments. Results Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively. Conclusions ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs.
Approaches to increase mechanistic understanding and aid in the selection of precipitation inhibitors for supersaturating formulations – a PEARRL review

Supersaturating formulations hold great promise for delivery of poorly soluble active pharmaceutical ingredients (APIs). To profit from supersaturating formulations, precipitation is hindered with precipitation inhibitors (PIs), maintaining drug concentrations for as long as possible. This review provides a brief overview of supersaturation and precipitation, focusing on precipitation inhibition. Trial‐and‐error PI selection will be examined alongside established PI screening techniques. Primarily, however, this review will focus on recent advances that utilise advanced analytical techniques to increase mechanistic understanding of PI action and systematic PI selection.
Protein delivery nanosystem of six-arm copolymer poly(ε-caprolactone)–poly(ethylene glycol) for long-term sustained release

Background To address the issue of delivery of proteins, a six-arm copolymer, six-arm poly (ε-caprolactone)–poly(ethylene glycol) (6S-PCL-PEG), was synthesized by a simple two-step reaction. Thereafter, the application of 6S-PCL-PEG as a protein carrier was evaluated. Materials and methods A six-arm copolymer, six-arm poly(ε-caprolactone) (6S-PCL), was synthesized by ring-opening polymerization, with stannous octoate as a catalyst and inositol as an initiator. Then, poly(ethylene glycol) (PEG) was linked with 6S-PCL by oxalyl chloride to obtain 6S-PCL-PEG. Hydrogen-1 nuclear magnetic resonance spectrum, Fourier-transform infrared spectroscopy, and gel-permeation chromatography were conducted to identify the structure of 6S-PCL-PEG. The biocompatibility of the 6S-PCL-PEG was evaluated by a cell counting kit-8 assay. Polymeric nanoparticles (NPs) were prepared by a water-in-oil-in-water double emulsion (W1/O/W2) solvent evaporation method. The size distribution and zeta potential of NPs were determined by dynamic light scattering. Transmission electron microscopy was used to observe the morphology of NPs. Drug-loading capacity, encapsulation efficiency, and the release behavior of ovalbumin (OVA)-loading NPs were tested by the bicinchoninic acid assay kit. The stability and activity of OVA released from NPs were detected and the uptake of NPs was evaluated by NIH-3T3 cells. Results All results indicated the successful synthesis of amphiphilic copolymer 6S-PCL-PEG, which possessed excellent biocompatibility and could formulate NPs easily. High drug-loading capacity and encapsulation efficiency of protein NPs were observed. In vitro, OVA was released slowly and the bioactivity of OVA was maintained for over 28 days. Conclusion 6S-PCL-PEG NPs prepared in this study show promising potential for use as a protein carrier.
Next‐generation sequencing (NGS)‐based identification of induced mutations in a doubly mutagenized tomato (Solanum lycopersicum) population

The identification of mutations in targeted genes has been significantly simplified by the advent of TILLING (Targeting Induced Local Lesions In Genomes), speeding up the functional genomic analysis of animals and plants. Next-generation sequencing (NGS) is gradually replacing classical TILLING for mutation detection, as it allows the analysis of a large number of amplicons in short durations. The NGS approach was used to identify mutations in a population of Solanum lycopersicum (tomato) that was doubly mutagenized by ethylmethane sulphonate (EMS). Twenty-five genes belonging to carotenoids and folate metabolism were PCR-amplified and screened to identify potentially beneficial alleles. To augment efficiency, the 600-bp amplicons were directly sequenced in a non-overlapping manner in Illumina MiSeq, obviating the need for a fragmentation step before library preparation. A comparison of the different pooling depths revealed that heterozygous mutations could be identified up to 128-fold pooling. An evaluation of six different software programs (camba, crisp, gatk unified genotyper, lofreq, snver and vipr) revealed that no software program was robust enough to predict mutations with high fidelity. Among these, crisp and camba predicted mutations with lower false discovery rates. The false positives were largely eliminated by considering only mutations commonly predicted by two different software programs. The screening of 23.47 Mb of tomato genome yielded 75 predicted mutations, 64 of which were confirmed by Sanger sequencing with an average mutation density of 1/367 Kb. Our results indicate that NGS combined with multiple variant detection tools can reduce false positives and significantly speed up the mutation discovery rate.
A new method for detecting and early-warning in-band interference of the GSM-R network

The Global System for Mobile Communications-Railway (GSM-R) network is currently used in railway systems of many countries. Interferences sensing and early-warning is an important problem to guarantee reliability and robustness of GSM-R network. This paper proposes a new method for inband interference detecting and early-warning of GSM-R network. The method is based on the statistical features of the instantaneous frequency histogram in time domain, which are obtained by a learning procedure. The simulation result shows that the new method can sense weaker interference than GMSK decoder and spectrum sensing; the experiment result prove validity of the method in practice.
Construction of English-French Multimodal Affective Conversational Corpus from TV Dramas

Recently, there has been an increase of interest in constructing corpora containing social-affective interactions. But the availability of multimodal, multilingual, and emotionally rich corpora remains limited. The tasks of recording and transcribing actual human-to-human affective conversations are also tedious and time-consuming. This paper describes construction of a multimodal affective conversational corpus based on TV dramas. The data contain parallel English-French languages in lexical, acoustic, and facial features. In addition, we annotated the part of the English data with speaker and emotion information. Our corpus can be utilized to develop and assess such tasks as speaker and emotion recognition, affective speech recognition and synthesis, linguistic, and paralinguistic speech-to-speech translation as well as a multimodal dialog system.
Refining the stress‐gradient hypothesis for competition and facilitation in plant communities

1 The stress‐gradient hypothesis (SGH) predicts that the frequency of facilitative and competitive interactions will vary inversely across abiotic stress gradients, with facilitation being more common in conditions of high abiotic stress relative to more benign abiotic conditions. With notable exceptions, most tests of the SGH have studied the interaction between a single pair or a few pairs of species, and thus have evaluated shifts in the magnitude and direction of pair‐wise interactions along stress gradients, rather than shifts in the general frequency of interactions. 2 The SGH has been supported by numerous studies in many ecosystems, has provided a crucial foundation for studying the interplay between facilitation and competition in plant communities, and has a high heuristic value. However, recent empirical research indicates that factors like the variation among species and the nature of the stress gradient studied add complexity not considered in the SGH, creating an opportunity to extend the SGH's general conceptual framework. 3 We suggest that one approach for extending the SGH framework is to differentiate between the original idea of how ‘common’ interactions might be along stress gradients and the ubiquitous empirical approach of studying shifts in the strength of pair‐wise interactions. Furthermore, by explicitly considering the life history of the interacting species (relative tolerance to stress vs. competitive ability) and the characteristics of the stress factor (resource vs. non‐resource) we may be able to greatly refine specific predictions relevant to the SGH. 4 We propose that the general pattern predicted by the SGH would hold more frequently for some combinations of life histories and stress factor, particularly when the benefactor and beneficiary species are mostly competitive and stress‐tolerant, respectively. However, we also predict that other combinations are likely to yield different results. For example, the effect of neighbours can be negative at both ends of the stress gradient when both interacting species have similar ‘competitive’ or ‘stress‐tolerant’ life histories and the abiotic stress gradient is driven by a resource (e.g. water). 5 Synthesis. The extension of the SGH presented here provides specific and testable hypotheses to foster research and helps to reconcile potential discrepancies among previous studies. It represents an important step in incorporating the complexity and species‐specificity of potential outcomes into models and theories addressing how plant–plant interactions change along stress gradients.
Neural Caption Generation for News Images

Automatic caption generation of images has gained signiﬁcant interest. It gives rise to a lot of interesting image-related applications. For example, it could help in image/video retrieval and management of vast amount of multimedia data available on the Internet. It could also help in development of tools that can aid visually impaired individuals in accessing multimedia content. In this paper, we particularly focus on news images and propose a methodology for automatically generating captions for news paper articles consisting of a text paragraph and an image. We propose several deep neural network architectures built upon Recurrent Neural Networks. Results on a BBC News dataset show that our proposed approach outperforms a traditional method based on Latent Dirichlet Allocation using both automatic evaluation based on BLEU scores and human evaluation.
Stylized Facts of Financial Markets and Modeling Volatility (The Case of Tehran Stock Exchange)

The financial markets stylized facts, volatility and its relationship with returns tested empirically in Tehran Stock Exchange (TSE). ARMA- ARCH type models including two symmetric conditional hetroscedastic models; ARMA (1, 1) - ARCH (1) and ARMA (1, 1) - GARCH (1, 1) and two asymmetric conditional hetroscedastic models; ARMA (1, 1) - GJR-GARCH (1, 1) and ARMA (1, 1) - EGARCH (1, 1) are used to determine the process of stock returns and volatility, and by applying ARCH(M) class models and out-of-sample methodology the relationship between stock return and volatility is examined. The key findings are as follows, In contrast to emerging markets which shows high volatility, TSE shows less volatility and it is due to unique features of TSE, Volatility Range, Basic Volume and Knot Event. Heavy tails, volatility clustering and mean reverting behavior are observed in TSE, however, the leverage effect is not observed. Estimates of model parameters suggest that the symmetric models explain the most process envisaged in the time series data, while the asymmetric models fail. TSE fails to confirm the weak form of efficient market hypothesis as returns have serial correlation, thus it supports the idea that controlling mechanism of Volatility Range and Basic Volume should be removed in TSE to attract foreign investment and finally we find no evidence of relationship between return and volatility.
Predictors of Human Papillomavirus Vaccine Follow-Through Among Privately Insured US Patients

Objectives To assess predictors of timely human papillomavirus (HPV) vaccine follow-through among privately insured individuals initiating the 3-dose series. Methods Using MarketScan Commercial claims data, we identified 1 332 217 privately insured US individuals aged 9 to 26 years who initiated the bivalent or quadrivalent HPV vaccine series from 2006 to 2014, with follow-up data extending through 2015. The study outcome was receipt of third HPV dose within 12 months of the first, compared by year of initiation. Control variables were age, region, insurance plan type, provider type, and seasonal influenza vaccination. Results Timely HPV vaccine follow-through fell over time. The trend was especially pronounced for females (from 67% in 2006 to 38% in 2014), but was also present for males (from 36% in 2011 to 33% in 2014). Similar patterns were present when we controlled for patient and provider characteristics or used alternative definitions of follow-through. Other positive predictors of timely follow-through included receipt of flu vaccine in the prior year and receipt of first HPV vaccine dose from an obstetrician/gynecologist. Conclusions HPV vaccine follow-through is low and has declined over time.
The ICoN Corpus of Academic Written Italian (L1 and L2)

This paper describes the ICoN corpus, a corpus of academic written Italian, some of the directions of research it could open, and some of the first outcomes of research conducted on it. The ICoN corpus includes 2,115,000 tokens written by students having Italian as L2 students (level B2 or higher) and 1,769,000 tokens written by students having Italian as L1; this makes it the largest corpus of its kind. The texts included in the corpus come from the online examinations taken by 787 different students for the ICoN Degree Program in Italian Language and Culture for foreign students and Italian citizens residing abroad. The texts were produced by students having 41 different L1s, and 18 different L1s are represented in the corpus by more than 20,000 tokens. The corpus is encoded in XML files; it can be freely queried online and it is available upon request for research purposes. The paper includes the discussion of preliminary research in the field of collocations, showing that, in the texts included in the corpus, while learners and natives do use multiword expressions in a similar way, learners can overuse relatively infrequent forms of multiword adverbials, or use some adverbials in a non-standard way.
Representation Mapping: A Novel Approach to Generate High-Quality Multi-Lingual Emotion Lexicons

In the past years, sentiment analysis has increasingly shifted attention to representational frameworks more expressive than semantic polarity (being positive, negative or neutral). However, these richer formats (like Basic Emotions or Valence-Arousal-Dominance, and variants therefrom), rooted in psychological research, tend to proliferate the number of representation schemes for emotion encoding. Thus, a large amount of representationally incompatible emotion lexicons has been developed by various research groups adopting one or the other emotion representation format. As a consequence, the reusability of these resources decreases as does the comparability of systems using them. In this paper, we propose to solve this dilemma by methods and tools which map different representation formats onto each other for the sake of mutual compatibility and interoperability of language resources. We present the first large-scale investigation of such representation mappings for four typologically diverse languages and find evidence that our approach produces (near-)gold quality emotion lexicons, even in cross-lingual settings. Finally, we use our models to create new lexicons for eight typologically diverse languages.
Evolutionary consequences of microhabitat: population‐genetic structuring in kelp‐ vs. rock‐associated chitons

Rafting has long been invoked as a key marine dispersal mechanism, but biologists have thus far produced little genetic evidence to support this hypothesis. We hypothesize that coastal species associated with buoyant seaweeds should experience enhanced population connectivity owing to rafting. In particular, invertebrates strongly associated with the buoyant bull‐kelp Durvillaea antarctica might be expected to have lower levels of population‐genetic differentiation than taxa mainly exploiting nonbuoyant substrates. We undertook a comparative genetic study of two codistributed, congeneric chiton species, assessing population connectivity at scales of 61–516 km, using ≥186 polymorphic AFLP loci per species. Consistent with predictions, population‐genetic differentiation was weaker in the kelp‐associated Sypharochiton sinclairi than in the rock‐associated S. pelliserpentis. Additionally, while we found a significant positive correlation between genetic and oceanographic distances in both chiton species, the correlation was stronger in S. pelliserpentis (R2 = 0.28) than in S. sinclairi (R2 = 0.18). These data support the hypothesis that epifaunal taxa can experience enhanced population‐genetic connectivity as a result of their rafting ability.
BioRead: A New Dataset for Biomedical Reading Comprehension

We present BioRead, a new publicly available cloze-style biomedical machine reading comprehension (MRC) dataset with approximately 16.4 million passage-question instances. BioRead was constructed in the same way as the widely used Children’s Book Test and its extension BookTest, but using biomedical journal articles and employing MetaMap to identify UMLS concepts. BioRead is one of the largest MRC datasets, and currently the largest one in the biomedical domain. We also provide a subset of BioRead, BioReadLite, for research groups with fewer computational resources. We re-implemented and tested on BioReadLite two well-known MRC methods, AS Reader and AOA Reader, along with four baselines, as a ﬁrst step towards a BioRead (and BioReadLite) leaderboard. AOA Reader is currently the best method on BioReadLite, with 51.19% test accuracy. Both AOA Reader and AS Reader outperform the baselines by a wide margin on the test subset of BioReadLite. Our re-implementations of the two MRC methods are also publicly available.
Support for the value 5/2 for the spin glass lower critical dimension at zero magnetic field

Significance Glassy systems at low temperature may stay in many equilibrium configurations quite different from one another. An important quantity is the (free) energy difference for going from an equilibrium configuration to another one: Its properties dominate the dynamics at large times. The analytic computation of these differences is notoriously difficult. For spin glasses a clean computation can be done, using uncontrolled approximations. Here we use numerical simulations to show that this theory predicts the correct properties of the differences in three and four dimensions. The same theory predicts also that the spin glass transition disappears at dimensions 5/2 and our verification of the predictions of the theory brings support to this result. We study numerically various properties of the free energy barriers in the Edwards–Anderson model of spin glasses in the low-temperature region in both three and four spatial dimensions. In particular, we investigated the dependence of height of free energy barriers on system size and on the distance between the initial and final states (i.e., the overlap distance). A related quantity is the distribution of large local fluctuations of the overlap in large 3D samples at equilibrium. Our results for both quantities (barriers and large deviations) are in agreement with the prediction obtained in the framework of mean-field theory. In addition, our result supports Dlc=2.5 as the lower critical dimension of the model.
Patterns of chromatin accessibility along the anterior-posterior axis in the early Drosophila embryo

As the Drosophila embryo transitions from the use of maternal RNAs to zygotic transcription, domains of open chromatin, with relatively low nucleosome density and specific histone marks, are established at promoters and enhancers involved in patterned embryonic transcription. However it remains unclear how regions of activity are established during early embryogenesis, and if they are the product of spatially restricted or ubiquitous processes. To shed light on this question, we probed chromatin accessibility across the anterior-posterior axis (A-P) of early Drosophila melanogaster embryos by applying a transposon based assay for chromatin accessibility (ATAC-seq) to anterior and posterior halves of hand-dissected, cellular blastoderm embryos. We find that genome-wide chromatin accessibility is highly similar between the two halves, with regions that manifest significant accessibility in one half of the embryo almost always accessible in the other half, even for promoters that are active in exclusively one half of the embryo. These data support previous studies that show that chromatin accessibility is not a direct result of activity, and point to a role for ubiquitous factors or processes in establishing chromatin accessibility at promoters in the early embryo. However, in concordance with similar works, we find that at enhancers active exclusively in one half of the embryo, we observe a significant skew towards greater accessibility in the region of their activity, highlighting the role of patterning factors such as Bicoid in this process.
Ranking the Skills of Golfers on the PGA TOUR using Gradient Boosting Machines and Network Analysis Other Sports

Until recently, ranking the skills of golfers on the PGA TOUR was best accomplished by using imprecise summary statistics such as Driving Accuracy and Average Putts Per Round. Since 2003, The PGA TOUR, through their ShotLink IntelligenceTM program, has collected detailed shot-level data, which provides coordinates of the locations of shots along with other information. Through the analysis of this data, more fine-grained and precise estimates of the skills of golfers on tour are now possible. The problem of estimating the skill of golfers in different aspects of the game given data from competitions is not simple. This work recognizes a wide array of statistical challenges associated with this problem, which a number of previous approaches to the problem have failed to adequately acknowledge. A brand new approach to the problem is presented which invokes comparisons of the quality of shots taken on the same hole during the same round. The comparisons are utilized in a Network Analysis technique, which is generalized to suit the needs of the problem. This approach is supported with empirical evidence of stronger correlations with the future success of the golfers than the system currently used by the PGA TOUR.