The Impact of Crumb-Rubber on the Mechanical Characteristics of Modified Asphalt Mixture

By following up on the effect of rubber, which has recently been widely used as a direct additive to the asphalt binder or to the concrete mix as a percentage of the weight of the aggregate. The success of the effect of this type of admixture on improving the modified asphalt binder in addition to the modified concrete mix has been investigated. As it was noted the importance of following the asphalt properties due to the increasing use of crumb rubber modifiers in asphalt mixtures, there is a more position to check their rheological and physical properties comprehensively. In general, the performance of the asphalt rubber binder is affected by the rubber crumb content and mixing conditions. This research used 40/50 asphalt grade and Crumb Rubber additives with contents (5, 10, 15, and 20%). The main objectives of this study were to investigate the physical and rheological properties of rubber-modified asphalt binder and mixture. These purposes were achieved by testing HMA samples using the Marshall test approach to determine (Marshall stability and flow and void properties) and measuring the retained Marshall stability and DSR and Viscosity test. Sample testing showed that when recycled rubber was used as modifiers for asphalt mixes, the mixture became more stable, had a higher bulk specific gravity, and had less flow value and air voids. This infers that using recycled rubber can enhance the rutting resistance of bituminous mix

Genetic Associations With Diabetic Retinopathy and Coronary Artery Disease in Emirati Patients With Type-2 Diabetes Mellitus

Aim: Type 2 Diabetes Mellitus (T2DM) is associated with both microvascular complications such as diabetic retinopathy (DR), and macrovascular complications like coronary artery disease (CAD). Genetic risk factors have a role in the development of these complications. In the present case-control study, we investigated genetic variations associated with DR and CAD in T2DM patients from the United Arab Emirates.Methods: A total of 407 Emirati patients with T2DM were recruited. Categorization of the study population was performed based on the presence or absence of DR and CAD. Seventeen Single Nucleotide Polymorphisms (SNPs), were selected for association analyses through search of publicly available databases, namely GWAS catalog, infinome genome interpretation platform and GWAS Central database. A multivariate logistic regression test was performed to evaluate the association between the 17 SNPs and DR, CAD, or both. To account for multiple testing, significance was set at p < 0.00294 using the Bonferroni correction.Results: The SNPs rs9362054 near the CEP162 gene and rs4462262 near the UBE2D1 gene were associated with DR (OR = 1.66, p = 0.001; OR = 1.37, p = 0.031; respectively), and rs12219125 near the PLXDC2 gene was associated (suggestive) with CAD (OR = 2.26, p = 0.034). Furthermore, rs9362054 near the CEP162 gene was significantly associated with both complications (OR = 2.27, p = 0.0021). The susceptibility genes for CAD (PLXDC2) and DR (UBE2D1) have a role in angiogenesis and neovascularization. Moreover, association between the ciliary gene CEP162 and DR was established in terms of retinal neural processing, confirming previous reports.Conclusions: The present study reports associations of different genetic loci with DR and CAD. We report new associations between CAD and PLXDC2, and DR with UBE2D1 using data from T2DM Emirati patients

Expression and Cellular Immunogenicity of a Transgenic Antigen Driven by Endogenous Poxviral Early Promoters at Their Authentic Loci in MVA

CD8+ T cell responses to vaccinia virus are directed almost exclusively against early gene products. The attenuated strain modified vaccinia virus Ankara (MVA) is under evaluation in clinical trials of new vaccines designed to elicit cellular immune responses against pathogens including Plasmodium spp., M. tuberculosis and HIV-1. All of these recombinant MVAs (rMVA) utilize the well-established method of linking the gene of interest to a cloned poxviral promoter prior to insertion into the viral genome at a suitable locus by homologous recombination in infected cells. Using BAC recombineering, we show that potent early promoters that drive expression of non-functional or non-essential MVA open reading frames (ORFs) can be harnessed for immunogenic expression of recombinant antigen. Precise replacement of the MVA orthologs of C11R, F11L, A44L and B8R with a model antigen positioned to use the same translation initiation codon allowed early transgene expression similar to or slightly greater than that achieved by the commonly-used p7.5 or short synthetic promoters. The frequency of antigen-specific CD8+ T cells induced in mice by single shot or adenovirus-prime, rMVA-boost vaccination were similarly equal or marginally enhanced using endogenous promoters at their authentic genomic loci compared to the traditional constructs. The enhancement in immunogenicity observed using the C11R or F11L promoters compared with p7.5 was similar to that obtained with the mH5 promoter compared with p7.5. Furthermore, the growth rates of the viruses were unimpaired and the insertions were genetically stable. Insertion of a transgenic ORF in place of a viral ORF by BAC recombineering can thus provide not only a potent promoter, but also, concomitantly, a suitable insertion site, potentially facilitating development of MVA vaccines expressing multiple recombinant antigens

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

The Impact of Crumb-Rubber on the Mechanical Characteristics of Modified Asphalt Mixture

By following up on the effect of rubber, which has recently been widely used as a direct additive to the asphalt binder or to the concrete mix as a percentage of the weight of the aggregate. The success of the effect of this type of admixture on improving the modified asphalt binder in addition to the modified concrete mix has been investigated. As it was noted the importance of following the asphalt properties due to the increasing use of crumb rubber modifiers in asphalt mixtures, there is a more position to check their rheological and physical properties comprehensively. In general, the performance of the asphalt rubber binder is affected by the rubber crumb content and mixing conditions. This research used 40/50 asphalt grade and Crumb Rubber additives with contents (5, 10, 15, and 20%). The main objectives of this study were to investigate the physical and rheological properties of rubber-modified asphalt binder and mixture. These purposes were achieved by testing HMA samples using the Marshall test approach to determine (Marshall stability and flow and void properties) and measuring the retained Marshall stability and DSR and Viscosity test. Sample testing showed that when recycled rubber was used as modifiers for asphalt mixes, the mixture became more stable, had a higher bulk specific gravity, and had less flow value and air voids. This infers that using recycled rubber can enhance the rutting resistance of bituminous mix

68Ga-PSMA PET/CT in Initial Diagnosis and Bone Metastasis Evaluation in Saudi Patients with High-Grade Prostate Cancer

We present the first study performed in Saudi Arabia to evaluate 68Ga-PSMA PET/CT in prostate cancer (PCa) initial diagnosis and its added value in bone metastases (BM) diagnosis in such patients. Twenty-six male patients underwent prostate histopathological examination and all imaging studies (68Ga-PSMA PET/CT and CT); all of them were confirmed with high-grade PCa. Patients' mean PSA levels and Gleason score were 5.12±1.12 and 7.0±0.9, respectively. 68Ga-PSMA PET/CT (20/26; sensitivity of 76.9%) was superior to traditional CT (18/26; sensitivity of 69.2%) in PCa detection. There was a non-significant association (P=0.206) between patients' age and BM. Based on bone scintigraphy (BS), in patients without BM (n=16), 68Ga-PSMA PET/CT detected metastasis-suspicious lesions in six patients (37.5%) and negative results in ten patients (62.5%). 68Ga-PSMA PET/CT showed no false-negative cases among patients with confirmed BM using BS. In conclusion, 68Ga-PSMA PET/CT performed well in PCa initial diagnosis in Saudi male patients with high-grade tumors. 68Ga-PSMA PET/CT also accurately detected BM in all PCa patients with confirmed BM by BS. Larger prospective studies are urgently required to compare 68Ga-PSMA PET/CT diagnostic performance with other standard modalities in PCa and BM diagnosis

Nf1+/− mast cells induce neurofibroma like phenotypes through secreted TGF-β signaling

Neurofibromas are common tumors found in neurofibromatosis type 1 (NF1) patients. These complex tumors are composed of Schwann cells, mast cells, fibroblasts and perineurial cells embedded in collagen that provide a lattice for tumor invasion. Genetic studies demonstrate that in neurofibromas, nullizygous loss of Nf1 in Schwann cells and haploinsufficiency of Nf1 in non-neuronal cells are required for tumorigenesis. Fibroblasts are a major cellular constituent in neurofibromas and are a source of collagen that constitutes ∼50% of the dry weight of the tumor. Here, we show that two of the prevalent heterozygous cells found in neurofibromas, mast cells and fibroblasts interact directly to contribute to tumor phenotype. Nf1+/− mast cells secrete elevated concentrations of the profibrotic transforming growth factor-beta (TGF-β). In response to TGF-β, both murine Nf1+/− fibroblasts and fibroblasts from human neurofibromas proliferate and synthesize excessive collagen, a hallmark of neurofibromas. We also establish that the TGF-β response occurs via hyperactivation of a novel Ras-c-abl signaling pathway. Genetic or pharmacological inhibition of c-abl reverses fibroblast proliferation and collagen synthesis to wild-type levels.These studies identify a novel molecular target to inhibit neurofibroma formation