In 1967, Grünbaum conjectured that any
d
-dimensional polytope with
d
+ s ≤ 2
d
vertices has at least
ϕ
k
(
d
+
s
,
d
)
=
(
d
+
1
k
+
1
)
+
(
d
k
+
1
)
−
(
d
+
1
−
s
k
+
1
)
k
-faces. We prove this ...conjecture and also characterize the cases in which equality holds.
Abstract
Geometric and topological properties of protein structures, including surface pockets, interior cavities and cross channels, are of fundamental importance for proteins to carry out their ...functions. Computed Atlas of Surface Topography of proteins (CASTp) is a web server that provides online services for locating, delineating and measuring these geometric and topological properties of protein structures. It has been widely used since its inception in 2003. In this article, we present the latest version of the web server, CASTp 3.0. CASTp 3.0 continues to provide reliable and comprehensive identifications and quantifications of protein topography. In addition, it now provides: (i) imprints of the negative volumes of pockets, cavities and channels, (ii) topographic features of biological assemblies in the Protein Data Bank, (iii) improved visualization of protein structures and pockets, and (iv) more intuitive structural and annotated information, including information of secondary structure, functional sites, variant sites and other annotations of protein residues. The CASTp 3.0 web server is freely accessible at http://sts.bioe.uic.edu/castp/.
The chemokine receptor CXCR2 and its ligands are implicated in the progression of tumours and various inflammatory diseases. Activation of the CXCLs/CXCR2 axis activates multiple signalling pathways, ...including the PI3K, p38/ERK, and JAK pathways, and regulates cell survival and migration. The CXCLs/CXCR2 axis plays a vital role in the tumour microenvironment and in recruiting neutrophils to inflammatory sites. Extensive infiltration of neutrophils during chronic inflammation is one of the most important pathogenic factors in various inflammatory diseases. Chronic inflammation is considered to be closely correlated with initiation of cancer. In addition, immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) against T cells attenuate the anti-tumour effects of T cells and promote tumour invasion and metastasis. Over the last several decades, many therapeutic strategies targeting CXCR2 have shown promising results and entered clinical trials. In this review, we focus on the features and functions of the CXCLs/CXCR2 axis and highlight its role in cancer and inflammatory diseases. We also discuss its potential use in targeted therapies.
Mass shootings are horrific events that annually take scores of innocent lives in the United States. Federal, state, and local governments as well as educational, religious, and private-sector ...organizations propose and enact polices and strategies to protect people from and during active shooter situations. A probabilistic risk assessment of a mass shooting for a specific organization, jurisdiction, or location can be the first step toward evaluating the effectiveness of risk mitigation strategies and determining which strategies might be most appropriate for a location. This article proposes a novel hierarchical method to assess the probability of a mass shooting at specific locations based on available historical data. First, the method generates a probability distribution over the annual number of mass shootings in the United States. Second, the article uses this national number of mass shootings to determine the risk for each state. Third, the state risk assessment is decomposed to calculate the probability of a mass shooting in a specific location such as a school. Multiple ways to assess the risk are presented, leading to slightly different probability assessments for a location. Results indicate that annual probability of a mass shooting in the largest high school in California is on the order of
, and the annual probability of a mass shooting in the largest high school in Iowa is about half as likely as in the California school.
Intestinal organoids derived from single cells undergo complex crypt-villus patterning and morphogenesis. However, the nature and coordination of the underlying forces remains poorly characterized. ...Here, using light-sheet microscopy and large-scale imaging quantification, we demonstrate that crypt formation coincides with a stark reduction in lumen volume. We develop a 3D biophysical model to computationally screen different mechanical scenarios of crypt morphogenesis. Combining this with live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven crypt apical contraction and villus basal tension work synergistically with lumen volume reduction to drive crypt morphogenesis, and demonstrate the existence of a critical point in differential tensions above which crypt morphology becomes robust to volume changes. Finally, we identified a sodium/glucose cotransporter that is specific to differentiated enterocytes that modulates lumen volume reduction through cell swelling in the villus region. Together, our study uncovers the cellular basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust morphogenesis.
Recurrence rates of diabetic foot ulcers vary widely in the published literature. The aim of this systematic review is to estimate recurrence rates of diabetic foot ulcers. We did a PubMed search and ...performed a review of reference lists for studies reporting recurrence of diabetic foot ulcers. The weighted relative risk (RR) and corresponding 95% confidence interval (CI) for recurrence was estimated. Forty‐nine studies reporting recurrence of diabetic foot ulcers were included. A pooled estimate for recurrence rate was 22.1% per person‐year (py) (95% CI, 19.0‐25.2%). Recurrence rate was 24.9% per py in Europe (95% CI, 20.0%‐29.7%), 17.8% per py in North America (95% CI, 12.7%‐22.9%), 16.9% per py in Africa (95% CI, 4.7%‐29.0%), and 17.0% per py in Asia (95% CI, 11.1%‐23.0%). Turkey had the highest recurrence rate of 44.4% per py (95% CI, 24.9%‐63.9%), and Bangladesh had the lowest of 4.3% per py (95% CI, 2.3%‐6.3%). Recurrence rates of diabetic foot ulcers before 2002, between 2002 and 2008, and after 2008 were 22.2% per py (95% CI, 17.6%‐26.8%), 21.9% per py (95% CI, 17.0%‐26.8%), and 21.8% per py (95% CI, 16.3%‐27.2%), respectively. Recurrence rates of diabetic foot ulcers are high. Recurrence rates vary widely in different regions and have decreased recently. More attention towards recurrence of diabetic foot ulcers is urgently required.
Senescence of renal tubular epithelial cells plays an important role in diabetic nephropathy, but the mechanism is unknown. Metformin may alleviate diabetic nephropathy by reducing this senescence. ...This study is aimed at clarifying the effects and mechanism of metformin on the senescence of renal tubular epithelial cells in diabetic nephropathy. We found that metformin reduced the expression of senescence-associated gene P21 in high-glucose-induced (30 mmol/L) renal tubular epithelial cells and decreased the β-galactosidase positive staining rate (decreased 16%, p<0.01). Metformin was able to reduce senescence by upregulating the expression of RNA-binding protein MBNL1 and miR-130a-3p and reducing STAT3 expression. MBNL1 prolonged the half-life of miR-130a-3p, and miR-130a-3p could negatively regulate STAT3 by binding to its mRNA 3′UTR. In db/db diabetic mice, we found an enhanced senescence level combined with low expression of MBNL1 and miR-130a-3p and high expression of STAT3 compared with db/m control mice during nephropathy development. Meanwhile, metformin (200 mg/kg/day) could increase the expression of MBNL1 and miR-130a-3p and decreased STAT3 expression, thus reducing this senescence in db/db mice. Our results suggest that metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway, which provided new ideas for the therapy of this disease.
The objective of this work was to elucidate the influence of shear rates on the properties of polyamide 6/multiwalled carbon nanotube (PA6/CNT) composites which was realized by adopting different ...types of processing methods that feature different orders of magnitude in shear rates, such as compression molding (CM, ~0 s−1), conventional injection molding (CIM, ~102 s−1) and microinjection molding (μIM, ~105 s−1). Electrical conductivity (σ) results indicated that the prevailing high shearing conditions in injection molding was unfavorable for the formation of intact filler network, thereby resulting in a much lower σ than CM counterparts. Moreover, the σ of PA6/CNT microparts was higher than that of CIM macroparts when the filler content was less than 5 wt%, otherwise the σ of CIM macroparts prevailed over that of μIM counterparts. A better filler distribution was observed when PA6/CNT composites were processed under higher shearing conditions, as corroborated by SEM. In addition, CNTs were preferentially aligned along flow direction and a higher degree of CNT orientation was expected with increasing shear rates, as confirmed by Raman spectral analysis. The tensile strength of injection molded PA6/CNT samples increased with increasing filler concentrations, and the more preferential orientation and better distribution of CNT were considered to be the contributing factors. The comparative study of the properties of PA6/CNT composites that processed using different methods was important for their practical applications in industrial sectors.
The morphology of PA6/CNT composites was different when they were processed using different methods, thereby resulting in a dfferent trend of electrical conductivity vs the filler concentration.
With the deepening of the concept of sustainable development, the academic community has paid more and more attention to how enterprises can achieve value co-creation for multiple stakeholders from ...the perspective of corporate innovation. ESG is a new concept concerned with how to achieve sustainable development in enterprises in terms of environment, society, and corporate governance. However, there is still a lack of research on how to reshape the innovation processes of enterprises based on the new concept of sustainability and bring competitive value to corporate value. Based on this, we took the listed companies on the main board of the Shanghai and Shenzhen A-shares from 2010 to 2020 as the research object and empirically tested the impact effect of corporate ESG on corporate value, as well as the mediating effect of corporate innovation between corporate ESG and corporate value. At the same time, the institutional environment was incorporated as a moderating variable to further explore its influence mechanism. Finally, the heterogeneity of corporate ESG on corporate value was analyzed at both an enterprise level and a regional level. The results show that corporate ESG and its three sub-dimensions can significantly improve corporate value and innovation level; the internal mechanism shows that corporate innovation plays a mediating role between corporate ESG and its three sub-dimensions, while institutional environment play a moderating effect; non-state-owned enterprises’ ESG has a higher impact on corporate value than state-owned enterprises, especially in eastern China, where the value enhancement effect of ESG is more significant.
PDF
