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Model averaging has attracted increasing attention in recent years for the analysis of high-dimensional data. By weighting several competing statistical models suitably, model averaging attempts to achieve stable and improved prediction. In this paper, we develop a two-stage model averaging procedure to enhance accuracy and stability in prediction for high-dimensional linear regression. First we employ a high-dimensional variable selection method such as LASSO to screen redundant predictors and construct a class of candidate models, then we apply the jackknife cross-validation to optimize model weights for averaging.

In simulation studies, the proposed technique outperforms commonly used alternative methods under high-dimensional regression setting, in terms of minimizing the mean of the squared prediction error. We apply the proposed method to a riboflavin data, the result show that such method is quite efficient in forecasting the riboflavin production rate, when there are thousands of genes and only ter predictive performance (1) More suitable methods are applied for model constructing and weighting. (2) Computational flexibility is retained since each candidate model and its corresponding weight are determined in the low-dimensional setting and the quadratic programming is utilized in the cross-validation. (3) Model selection and averaging are combined in the procedure thus it makes full use of the strengths of both techniques. As a consequence, the proposed method can achieve stable and accurate predictions in high-dimensional linear models, and can greatly help practical researchers analyze genetic data in medical research.
Lipopolysaccharide (LPS) is an endotoxin and a vital component of gram-negative bacteria's outer membrane. During gram-negative bacterial sepsis, LPS regulates osteoclast differentiation and activity, in addition to increasing inflammation. This study aimed to investigate how LPS regulates osteoclast differentiation of RAW 264.7 cells in vitro.

Herein, we revealed that RAW cells failed to differentiate into mature osteoclasts in vitro in the presence of LPS. selleckchem However, differentiation occurred in cells primed with receptor activator of nuclear factor-kappa-Β ligand (RANKL) for 24 h and then treated with LPS for 48 h (henceforth, denoted as LPS-treated cells). In cells treated with either RANKL or LPS, an increase in membrane levels of toll-like receptor 4 (TLR4) receptor was observed. Mechanistically, an inhibitor of TLR4 (TAK-242) reduced the number of osteoclasts as well as the secretion of tumor necrosis factor (TNF)-α in LPS-treated cells. RANKL-induced RAW cells secreted a very basal level TNF-α. TAK-2 that TLR4/TNF-α might be a potential target to suppress bone loss associated with inflammatory bone diseases, including periodontitis, rheumatoid arthritis, and osteoporosis.
Bowman-Birk inhibitors (BBI) are a family of serine-type protease inhibitors that modulate endogenous plant proteolytic activities during different phases of development. They also inhibit exogenous proteases as a component of plant defense mechanisms, and their overexpression can confer resistance to phytophagous herbivores and multiple fungal and bacterial pathogens. Dicot BBIs are multifunctional, with a "double-headed" structure containing two separate inhibitory loops that can bind and inhibit trypsin and chymotrypsin proteases simultaneously. By contrast, monocot BBIs have a non-functional chymotrypsin inhibitory loop, although they have undergone internal duplication events giving rise to proteins with multiple BBI domains.

We used a Hidden Markov Model (HMM) profile-based search to identify 57 BBI genes in the common wheat (Triticum aestivum L.) genome. The BBI genes are unevenly distributed, with large gene clusters in the telomeric regions of homoeologous group 1 and 3 chromosomes that likely arhigh rate of homologous tandem duplication and deletion events, giving rise to a diverse set of encoded proteins. This information will facilitate the functional characterization of individual wheat BBI genes to determine their role in wheat development and stress responses, and their potential application in breeding.
Genome-wide characterization reveals that the BBI gene family in wheat is subject to a high rate of homologous tandem duplication and deletion events, giving rise to a diverse set of encoded proteins. This information will facilitate the functional characterization of individual wheat BBI genes to determine their role in wheat development and stress responses, and their potential application in breeding.
Atherosclerotic plaques are often present in regions of arterieswith complicated flow patterns. Vascular morphology plays importantrole in hemodynamics. In this study, we investigated the relationship between the geometry of the vertebrobasilar artery system and presence ofbasilar artery (BA) plaque.

We enrolled 290 patients with posterior circulation ischemic stroke. We distinguished four configurations of the vertebrobasilar artery Walking, Tuning Fork, Lambda, and No Confluence. Patients were divided into multi-bending (≥ 3 bends) and oligo-bending (< 3 bends) VA groups.The diameter of the vertebral artery (VA) and the number of bends in the intracranial VA segment wereassessed using three-dimensional time-of-flight magnetic resonance angiography. High-resolution magnetic resonance imaging was used to evaluate BA plaques. Logistic regression models were used to determine the relationship between the geometry type and BA plaque prevalence.

After adjusting for sex, age, body mass index ≥ 28, hypertension, and diabetes mellitus, the Walking, Lambda, and No Confluence geometries were associated with the presence of BA plaque(all p < 0.05). Patients with multi-bending VAs in both the Walking (20/28, 71.43%vs. 6/21, 28.57%, p = 0.003) and Lambda group (19/47, 40.43%vs. 21/97, 21.65%, p = 0.018) had more plaques compared to patients with oligo-bending VAs in these groups. In the Lambda group, the difference in diameter of bilateral VAs was larger in patients with BA plaques than that in patients without BA plaques (1.4mm [IQR 0.9-1.6mm] vs. 0.9mm [IQR 0.6-1.3mm], p < 0.001).

The Walking, Lambda, and No Confluence geometry, ≥ 3 bends in the VAs, and a large diameter difference between bilateral VAs are associated with the presence of BA plaque.
The Walking, Lambda, and No Confluence geometry, ≥ 3 bends in the VAs, and a large diameter difference between bilateral VAs are associated with the presence of BA plaque.
Synthetic long reads (SLR) with long-range co-barcoding information are now widely applied in genomics research. Although several tools have been developed for each specific SLR technique, a robust standalone scaffolder with high efficiency is warranted for hybrid genome assembly.

In this work, we developed a standalone scaffolding tool, SLR-superscaffolder, to link together contigs in draft assemblies using co-barcoding and paired-end read information. Our top-to-bottom scheme first builds a global scaffold graph based on Jaccard Similarity to determine the order and orientation of contigs, and then locally improves the scaffolds with the aid of paired-end information. We also exploited a screening algorithm to reduce the negative effect of misassembled contigs in the input assembly. We applied SLR-superscaffolder to a human single tube long fragment read sequencing dataset and increased the scaffold NG50 of its corresponding draft assembly 1349 fold. Moreover, benchmarking on different input contigs showed that this approach overall outperformed existing SLR scaffolders, providing longer contiguity and fewer misassemblies, especially for short contigs assembled by next-generation sequencing data. The open-source code of SLR-superscaffolder is available at https//github.com/BGI-Qingdao/SLR-superscaffolder .

SLR-superscaffolder can dramatically improve the contiguity of a draft assembly by integrating a hybrid assembly strategy.
SLR-superscaffolder can dramatically improve the contiguity of a draft assembly by integrating a hybrid assembly strategy.
Acetosyringone (3,5-dimethoxy-4-hydroxyacetophenone, AS) is a syringyl-type phenolic compound rarely found in plants in free form. It has been shown earlier to inhibit the growth of Pseudomonas bacteria in the presence of hydrogen peroxide and peroxidase (AS mix).

We detected elevated levels of free AS in Nicotiana tabacum and N. benthamiana plants after inducing pattern-triggered immunity (PTI) by injecting bacterial elicitor flg22, or pathogenicity-mutant Pseudomonas syringae pv. syringae 61 hrcC- bacteria; but not after inoculations with compatible or incompatible pathogens at the time of PTI onset. In this study, we demonstrate that the antibacterial effect of the AS mix is general, as growth of several Gram-negative and -positive phytopathogenic bacteria was characteristically inhibited. The inhibition of bacterial metabolism by the AS mix was rapid, shown by the immediate drop of luminescence intensity of P. link2 syringae pv. tomato DC3000 lx strain after addition of AS mix. The mechanism of the bacterioing PTI.
Level of free acetosyringone is elevated during plant PTI responses in tobacco leaves (N. tabacum and N. benthamiana). When combined with hydrogen peroxide and peroxidase (AS mix), components of the mix act synergistically to inhibit bacterial metabolism and proliferation rapidly in a wide range of plant pathogens. This effect is related to depolarization rather than to permeabilization of the bacterial cell membrane. Similar AS mixture to the in vivo model might form locally at sites of invading bacterial attachment to the plant cells and the presence of acetosyringone might have an important role in the inhibition of bacterial proliferation during PTI.
The spread of a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in China and other countries is of great concern worldwide with no effective vaccine. This study aimed to design a novel vaccine construct against SARS-CoV-2 from the spike S protein and orf1ab polyprotein using immunoinformatics tools. The vaccine was designed from conserved epitopes interacted against B and T lymphocytes by the combination of highly immunogenic epitopes with suitable adjuvant and linkers.

The proposed vaccine composed of 526 amino acids and was shown to be antigenic in Vaxigen server (0.6194) and nonallergenic in Allertop server. The physiochemical properties of the vaccine showed isoelectric point of 10.19. The instability index (II) was 31.25 classifying the vaccine as stable. Aliphatic index was 84.39 and the grand average of hydropathicity (GRAVY) was - 0.049 classifying the vaccine as hydrophilic. Vaccine tertiary structure was predicted, refined and validated to assess the stabiliist in developing a suitable therapeutics protocol to combat SARSCoV-2 infection.
A unique vaccine construct from spike S protein and orf1ab polyprotein against B and T lymphocytes was generated with potential protection against the pandemic. The present study might assist in developing a suitable therapeutics protocol to combat SARSCoV-2 infection.
It is recommended that difficult airway predictors be evaluated before emergency airway management. link3 However, little is known about how patients with difficult airway predictors are managed in emergency departments. We aimed to explore the incidence, management and outcomes of patients with difficult airway predictors in an emergency department.

We conducted a retrospective study using intubation data collected by a prospective registry in an academic emergency department from November 2017 to October 2018. Records with complete assessment of difficult airway predictors were included. Two categories of predictors were analyzed predicted difficult intubation by direct laryngoscopy and predicted difficult bag-mask ventilation. The former was evaluated based on difficult external appearance, mouth opening and thyromental distance, Mallampati score, obstruction, and limited neck mobility as in the mnemonic "LEMON". The latter was evaluated based on difficult mask sealing, obstruction or obesity, absence of teeth, advanced age and reduced pulmonary compliance as in the mnemonic "MOANS".
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