The Way to Spray: Modeling Nasal Spray Deposition

Intranasal drug delivery is an alternative method in addition to traditional oral and intravenous doses. Nasal drug delivery has proven to be a very effective technique for nicotine cessation (Hjalmarson et al., 1994), the influenza vaccine (Jackson et al. 1999), and drugs that need to be take continuously, such as insulin (Dondeti et al., 1995). Studies have found that for effective fast-acting body response, the drug needs to be deposited in the highly vascularized mucosal tissue lining the bony turbinates in the nasal cavity. Commercial nasal sprays are continuously optimizing parameters to develop the most effective deposition patterns. In this project, drug deposition is modeled using a simplified 2D depiction of the nasal passageway with uniformly-shaped, spherical spray particles. This problem is implemented in COMSOL by using 2D Navier Stokes fluid flow equations to model the airflow through the nose, and the Particle Tracing module to model the spray trajectory and deposition. The model output was validated by determining the percentages of particles in each region of the nasal passage - anterior, turbinate, posterior, and outlet - and comparing with published experimental data by Cheng et al (2001). A sensitivity analysis was done on the following parameters: particle density, particle size, nozzle spray angle, and nozzle penetration depth. It was found that this model was sensitive to only penetration depth. As penetration depth through the nostril increased, there was a decrease in the particle deposition in the anterior region of the nasal cavity and an increase in the percentage of particles that exited through the outlet. Deposition in the middle and posterior regions was not affected by variation in penetration depth. Our sensitivity analysis demonstrated that variations in spray angle, particle size, and density of the nasal spray fluid do not significantly affect deposition pattern. Therefore, when designing nasal sprays, as long as these parameters remain within the specified ranges, consistent deposition patterns will be achieved. This result also allows for further research on creating sprays that are more concentrated and have encapsulated drugs

Towards Omni-supervised Referring Expression Segmentation

Referring Expression Segmentation (RES) is an emerging task in computer vision, which segments the target instances in images based on text descriptions. However, its development is plagued by the expensive segmentation labels. To address this issue, we propose a new learning task for RES called Omni-supervised Referring Expression Segmentation (Omni-RES), which aims to make full use of unlabeled, fully labeled and weakly labeled data, e.g., referring points or grounding boxes, for efficient RES training. To accomplish this task, we also propose a novel yet strong baseline method for Omni-RES based on the recently popular teacher-student learning, where the weak labels are not directly transformed into supervision signals but used as a yardstick to select and refine high-quality pseudo-masks for teacher-student learning. To validate the proposed Omni-RES method, we apply it to a set of state-of-the-art RES models and conduct extensive experiments on a bunch of RES datasets. The experimental results yield the obvious merits of Omni-RES than the fully-supervised and semi-supervised training schemes. For instance, with only 10% fully labeled data, Omni-RES can help the base model achieve 100% fully supervised performance, and it also outperform the semi-supervised alternative by a large margin, e.g., +14.93% on RefCOCO and +14.95% on RefCOCO+, respectively. More importantly, Omni-RES also enable the use of large-scale vision-langauges like Visual Genome to facilitate low-cost RES training, and achieve new SOTA performance of RES, e.g., 80.66 on RefCOCO

Data for the gene expression profiling and alternative splicing events during the chondrogenic differentiation of human cartilage endplate-derived stem cells under hypoxia

AbstractThis article contains relevant data of the research article titled Global profiling of the gene expression and alternative splicing events during the hypoxia-regulated chondrogenic differentiation in human cartilage endplate-derived stem cells (Yao et al., 2016) [1]. The data show global profiling of the DEGs (Differentially expressed genes) and AS (Alternative splicing) events during the hypoxia-regulated chondrogenesis of CESCs (human cartilage endplate-derived stem cells) by using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0) system. In addition, the enriched GO (Gene Ontology) functions and signaling pathways are listed. The information presented here includes the information of patients from which the clinical samples are obtained, the list of primers used for validation, the identification, GO and KEGG analysis of DEG and AS events

DRIVE: Dockerfile Rule Mining and Violation Detection

A Dockerfile defines a set of instructions to build Docker images, which can then be instantiated to support containerized applications. Recent studies have revealed a considerable amount of quality issues with Dockerfiles. In this paper, we propose a novel approach DRIVE (Dockerfiles Rule mIning and Violation dEtection) to mine implicit rules and detect potential violations of such rules in Dockerfiles. DRIVE firstly parses Dockerfiles and transforms them to an intermediate representation. It then leverages an efficient sequential pattern mining algorithm to extract potential patterns. With heuristic-based reduction and moderate human intervention, potential rules are identified, which can then be utilized to detect potential violations of Dockerfiles. DRIVE identifies 34 semantic rules and 19 syntactic rules including 9 new semantic rules which have not been reported elsewhere. Extensive experiments on real-world Dockerfiles demonstrate the efficacy of our approach

Sno/scaRNAbase: a curated database for small nucleolar RNAs and cajal body-specific RNAs

Small nucleolar RNAs (snoRNAs) and Cajal body-specific RNAs (scaRNAs) are named for their subcellular localization within nucleoli and Cajal bodies (conserved subnuclear organelles present in the nucleoplasm), respectively. They have been found to play important roles in rRNA, tRNA, snRNAs, and even mRNA modification and processing. All snoRNAs fall in two categories, box C/D snoRNAs and box H/ACA snoRNAs, according to their distinct sequence and secondary structure features. Box C/D snoRNAs and box H/ACA snoRNAs mainly function in guiding 2′-O-ribose methylation and pseudouridilation, respectively. ScaRNAs possess both box C/D snoRNA and box H/ACA snoRNA sequence motif features, but guide snRNA modifications that are transcribed by RNA polymerase II. Here we present a Web-based sno/scaRNA database, called sno/scaRNAbase, to facilitate the sno/scaRNA research in terms of providing a more comprehensive knowledge base. Covering 1979 records derived from 85 organisms for the first time, sno/scaRNAbase is not only dedicated to filling gaps between existing organism-specific sno/scaRNA databases that are focused on different sno/scaRNA aspects, but also provides sno/scaRNA scientists with an opportunity to adopt a unified nomenclature for sno/scaRNAs. Derived from a systematic literature curation and annotation effort, the sno/scaRNAbase provides an easy-to-use gateway to important sno/scaRNA features such as sequence motifs, possible functions, homologues, secondary structures, genomics organization, sno/scaRNA gene's chromosome location, and more. Approximate searches, in addition to accurate and straightforward searches, make the database search more flexible. A BLAST search engine is implemented to enable blast of query sequences against all sno/scaRNAbase sequences. Thus our sno/scaRNAbase serves as a more uniform and friendly platform for sno/scaRNA research. The database is free available at

Association of MDR1 Gene SNPs and Haplotypes with the Tacrolimus Dose Requirements in Han Chinese Liver Transplant Recipients

BACKGROUND: This work seeks to evaluate the association between the C/D ratios (plasma concentration of tacrolimus divided by daily dose of tacrolimus per body weight) of tacrolimus and the haplotypes of MDR1 gene combined by C1236T (rs1128503), G2677A/T (rs2032582) and C3435T (rs1045642), and to further determine the functional significance of haplotypes in the clinical pharmacokinetics of oral tacrolimus in Han Chinese liver transplant recipients. METHODOLOGY/PRINCIPAL FINDINGS: The tacrolimus blood concentrations were continuously recorded for one month after initial administration, and the peripheral blood DNA from a total of 62 liver transplant recipients was extracted. Genotyping of C1236T, G2677A/T and C3435T was performed, and SNP frequency, Hardy-Weinberg equilibrium, linkage disequilibrium, haplotypes analysis and multiple testing were achieved by software PLINK. C/D ratios of different SNP groups or haplotype groups were compared, with a p value<0.05 considered statistically significant. Linkage studies revealed that C1236T, G2677A/T and C3435T are genetically associated with each other. Patients carrying T-T haplotype combined by C1236T and G2677A/T, and an additional T/T homozygote at either position would require higher dose of tacrolimus. Tacrolimus C/D ratios of liver transplant recipients varied significantly among different haplotype groups of MDR1 gene. CONCLUSIONS: Our studies suggest that the genetic polymorphism could be used as a valuable molecular marker for the prediction of tacrolimus C/D ratios of liver transplant recipients

Safety and Efficacy of Exclusive Enteral Nutrition for Percutaneously Undrainable Abdominal Abscesses in Crohn’s Disease

Background. The percutaneously undrainable abdominal abscesses in Crohn’s disease (CD) are not uncommon. The treatment protocol is still under debate. This study was conducted to assess the safety and efficacy of exclusive enteral nutrition (EEN) for percutaneously undrainable abscesses in CD. Methods. A consecutive cohort of 83 CD patients with percutaneously undrainable abdominal abscesses between January 2011 and June 2015 was retrospectively analyzed. They were divided into the EEN group and the non-EEN group. Results. The cumulative surgical rate was significantly lower in the EEN group than in the non-EEN group (P=0.001). Fifteen percent patients treated with EEN avoided surgery. EEN (P=0.002) was associated with a decreased need for surgery. Previous abdominal surgery (P=0.009) and abscess diameter > 3 cm (P=0.022) were associated with an increased need for operation. EEN increased the albumin level, while decreased ESR and CRP significantly for patients requiring surgery. The risk of postoperative intra-abdominal septic complications (P=0.036) was significantly lower in the EEN group compared with the non-EEN group. Conclusions. EEN is feasible in CD patients presenting with percutaneously undrainable abdominal abscesses. It is associated with a reduction in surgical rate, optimized preoperative condition, and improved postoperative outcomes in these specific groups of patients

Photopolymerized maleilated chitosan/methacrylated silk fibroin micro/nanocomposite hydrogels as potential scaffolds for cartilage tissue engineering

Hydrogels composed of natural materials exhibit great application potential in artificial scaffolds for cartilage repair as they can resemble the extracellular matrices of cartilage tissues comprised of various glycosaminoglycan and collagen. Herein, the natural polymers with vinyl groups, i.e. maleilated chitosan (MCS) and methacrylated silk fibroin (MSF) micro/nanoparticles, were firstly synthesized. The chemical structures of MCS and MSF micro/nanoparticles were investigated using Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). Then MCS/MSF micro/nanocomposite hydrogels were prepared by the photocrosslinking of MCS and MSF micro/nanoparticles in aqueous solutions in the presence of the photoinitiator Darocur 2959 under UV light irradiation. A series of properties of the MCS/MSF micro/nanocomposite hydrogels including rheological property, equilibrium swelling, sol content, compressive modulus, and morphology were examined. The results showed that these behaviors could be tunable via the control of MSF content. When the MSF content was 0.1%, the hydrogel had the compressive modulus of 0.32±0.07MPa, which was in the range of that of articular cartilage. The in vitro cytotoxic evaluation and cell culture of the micro/nanocomposite hydrogels in combination with mouse articular chondrocytes were also investigated. The results demonstrated that the micro/nanocomposite hydrogels with TGF-β1 was biocompatible to mouse articular chondrocytes and could support cells attachment well, indicating their potential as tissue engineering scaffolds for cartilage repair.This study was supported by National Natural Science Foundation of China (Grant No. 51203123, 51403165, 51503161) and the National Key Research and Development Program of China (No.2016YFA0101102)