This article presents a novel representation-free model predictive control (RF-MPC) framework for controlling various dynamic motions of a quadrupedal robot in three-dimensional (3-D) space. Our ...formulation directly represents the rotational dynamics using the rotation matrix, which liberates us from the issues associated with the use of Euler angles and quaternion as the orientation representations. With a variation-based linearization scheme and a carefully constructed cost function, the MPC control law is transcribed to the standard quadratic program form. The MPC controller can operate at real-time rates of 250 Hz on a quadruped robot. Experimental results including periodic quadrupedal gaits and a controlled backflip validate that our control strategy could stabilize dynamic motions that involve singularity in 3-D maneuvers.
Cyclin‐dependent kinase 12 (CDK12) has emerged as an effective therapeutic target due to its ability to regulate DNA damage repair in human cancers, but little is known about the role of CDK12 in ...driving tumorigenesis. Here, we demonstrate that CDK12 promotes tumor initiation as a novel regulator of cancer stem cells (CSCs) and induces anti‐HER2 therapy resistance in human breast cancer. High CDK12 expression caused by concurrent amplification of CDK12 and HER2 in breast cancer patients is associated with disease recurrence and poor survival. CDK12 induces self‐renewal of breast CSCs and in vivo tumor‐initiating ability, and also reduces susceptibility to trastuzumab. Furthermore, CDK12 kinase activity inhibition facilitates anticancer efficacy of trastuzumab in HER2+ tumors, and mice bearing trastuzumab‐resistant HER2+ tumor show sensitivity to an inhibitor of CDK12. Mechanistically, the catalytic activity of CDK12 is required for the expression of genes involved in the activation of ErbB‐PI3K‐AKT or WNT‐signaling cascades. These results suggest that CDK12 is a major oncogenic driver and an actionable target for HER2+ breast cancer to replace or augment current anti‐HER2 therapies.
Synopsis
CDK12, a RNA polymerase II kinase, promotes breast cancer stem cell‐like properties mediated by WNT and ErbB‐PI3K signaling. Targeting CDK12 improves trastuzumab therapy in breast cancers characterised by HER2/CDK12 co‐amplification.
CDK12 amplification induces tumor initiation and progression, and mediates trastuzumab resistance.
CDK12 is required for transcriptional upregulation of genes involved in ErbB‐PI3K and WNT pathway activation.
CDK12 inhibition alone or in combination with trastuzumab therapy has anti‐tumor activity against HER2+ breast cancers.
CDK12, a RNA polymerase II kinase, promotes breast cancer stem cell‐like properties mediated by WNT and ErbB‐PI3K signaling. Targeting CDK12 improves trastuzumab therapy in breast cancers characterised by HER2/CDK12 co‐amplification.
The current goal in functional polymeric material research is the preparation of polymers with high-fidelity nanoscale self-assembled structures and advanced functionality. Thus, recent research ...efforts have focused on linking chemistry for the development of tailor-made polymers with desired properties. The design of α- or ω-functionalized telechelic polymers with strongly associative interactions is connected to their unique supramolecular self-assembly behavior in homopolymers and blends. In addition, the end-group modification of block copolymers has shown to alter the polymer morphology radically, resulting in unprecedented property changes arising from confinement effects. This is fascinating because the content of terminal moieties is small compared to that of macromolecular polymer backbones. As an emerging theme in polymer designs and end-group chemistry, the controlled synthesis of polymers with complex architectures and functional linkages has been performed extensively in the past few decades. However, the effects of this linkage on the resultant polymer properties remain elusive and thus will be an important research topic in polymer science in the near future.
The tight junctions (TJs) and barrier function of the intestinal epithelium are highly sensitive to radiation. However, polyphenols can be used to reverse the effects of radiation. Here, we ...investigated the effects of hesperidin (hesperetin-7-rhamnoglucoside) on X-ray-induced intestinal barrier dysfunction in human epithelial Caco-2 monolayers. To examine whether hesperidin mitigated the effects of X-ray exposure (2 Gy), cell survival was evaluated and intestinal barrier function was assessed by measuring the transepithelial flux, apparent permeability coefficient (Papp), and barrier integrity. Hesperidin improved the survival of Caco-2 cell monolayers and attenuated X-ray exposure-induced intestinal barrier dysfunction. For fluorescein transport experiments, transepithelial flux and Papp of fluorescein in control group were significantly elevated by X-ray, but were restored to near control by 10 μM hesperidin pretreatment. Further, X-ray exposure decreased the barrier integrity and TJ interruption by reducing TJ-related proteins occludin and claudin-4, whereas cell monolayers pretreated with hesperidin before X-ray exposure were reinstated to control level. It was concluded that hesperidin treatment before X-ray exposure alleviated X-ray-induced intestinal barrier dysfunction through regulation of TJ-related proteins. These results indicate that hesperidin prevents and mitigates X-ray-induced intestinal barrier dysfunction.
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Understanding the factors influencing infection management behavior related to Emerging Respiratory Infectious Diseases (ERIDs) among nursing students is important because nursing students play a ...vital role in preventing the spread of ERIDs. This study aimed to determine factors influencing infection management behavior related to ERIDs among nursing students in Korea. In this cross-sectional survey study, data were collected from May 3 to June 30, 2022, using a questionnaire. Data collected from 481 nursing students were analyzed using descriptive statistics, an independent t-test, a one-way analysis of variance, Pearson correlation coefficients, and hierarchical multiple regression using the SPSS program. The key factors influencing respondents' ERID-related infection management behavior were attitude (beta = 0.554, p<0.001) and knowledge (beta = 0.282, p<0.001). The explanatory power of this model was 40.2%, and the regression model was found to be statistically significant (F = 27.935, p<0.001). To improve nursing students' ERID-related infection management behavior, their knowledge of and attitudes toward ERIDs should be enhanced by repeatedly providing them with accurate professional information about ERIDs. Therefore, intensive efforts should be taken to develop a systematic educational program that can help nursing students better perform infection management.
To address the drug-resistance of bacterial pathogens without imposing a selective survival pressure, virulence and biofilms are highly attractive targets. Here, we show that terrein, which was ...isolated from Aspergillus terreus, reduced virulence factors (elastase, pyocyanin, and rhamnolipid) and biofilm formation via antagonizing quorum sensing (QS) receptors without affecting Pseudomonas aeruginosa cell growth. Additionally, the effects of terrein on the production of QS signaling molecules and expression of QS-related genes were verified. Interestingly, terrein also reduced intracellular 3,5-cyclic diguanylic acid (c-di-GMP) levels by decreasing the activity of a diguanylate cyclase (DGC). Importantly, the inhibition of c-di-GMP levels by terrein was reversed by exogenous QS ligands, suggesting a regulation of c-di-GMP levels by QS; this regulation was confirmed using P. aeruginosa QS mutants. This is the first report to demonstrate a connection between QS signaling and c-di-GMP metabolism in P. aeruginosa, and terrein was identified as the first dual inhibitor of QS and c-di-GMP signaling.
We investigated the effect of theaflavins (TFs) on membrane barrier of Caco-2 cells. For fluorescein-transport experiments, the apparent permeability (Papp) of fluorescein in Caco-2 cells pretreated ...with 20 μM TFs were significantly decreased compared with that in untreated cells. Although the respective monomeric catechins did not show any Papp reduction, purpurogallin pretreatment resulted in a significant Papp reduction similar to that of TF-3'-O-gallate (TF3'G) pretreatment. This indicates that the benzotropolone moiety may play a crucial role in the Papp reduction or tight junction (TJ)-closing effect induced by TFs. In TF-3'-O-gallate-pretreated Caco-2 cells, fluorescein transport was completely restored by compound C (AMPK inhibitor). In addition, TF3'G significantly increased both the mRNA and protein expression of TJ-related proteins (occludin, claudin-1, and ZO-1) as well as the phosphorylation of AMPK. It was, thus, concluded that TFs could enhance intestinal barrier function by increasing the expression of TJ-related proteins through the activation of AMPK in Caco-2 cells.
To gain the fundamental understanding of deformation mechanisms in an aluminum-containing austenitic high-Mn steel (Fe-32Mn-8.9Al-0.78 C (wt.%)), in-situ straining transmission electron microscopy ...(TEM) analysis is conducted. The in-situ observation during the deformation demonstrates that the plastic deformation is accommodated by the pronounced planar dislocation gliding followed by the formation of slip bands (SBs) and highly dense dislocation walls (HDDWs). Experimental evidences of the glide plane softening can be obtained from the interaction between the gliding perfect dislocations and the L'1
ordered precipitates in the austenite matrix. Furthermore, the observation of the localized cross-slip of dislocations at the slip band intersections enables to understand why slip bands are extensively developed without mutual obstructions between the slip bands. The enhanced strain hardening rate of the aluminum-containing austenitic high-Mn steels can be attributed to the pronounced planar dislocation glides followed by formation of extensive slip band which prevent premature failure by suppressing strain localization.
Several educational intervention programs have been designed and developed to improve osteoporosis diagnosis and treatment. However, most of the prior studies focused on how educational intervention ...programs affected diagnosis and treatment of condition of osteoporosis. The purpose of this prospective and educational intervention study was to evaluate the changes in osteoporosis knowledge, osteoporosis self-efficacy, fall self-efficacy, physical exercise and changes in dietary pattern of calcium and vitamin D intake after osteoporosis education.
From November 1, 2015 to August 31, 2016, 271 eligible candidates (who were over 50 years old and from 23 different community centers) were recruited through an announcement made by the public office, by two health care providers. The intervention involved an individualized education program to allow for differences in antecedent educational levels regarding several aspects of osteoporosis, including osteoporosis knowledge, osteoporosis self-efficacy, awareness of self-efficacy risk factors relating to an accidental fall and nutritional education (including the importance of sufficient calcium and vitamin D intake). The researchers revisited the community centers three months after the initial visit.
Of the 271 potential participants, 199 (73.4%; 43 men and 156 women) completed the education program and the second questionnaire. After education intervention, parameters including osteoporosis knowledge, osteoporosis self-efficacy and fall self-efficacy were improved (P < 0.0001). After education regarding percentage of calcium and vitamin D intake below recommended cut-offs, inadequate dietary calcium and vitamin D intake were decreased (P < 0.0001) from 89.4% (178/199) and 84.4% (168/199) to 79.9% (159/199) and 65.8% (131/199), respectively, at the three-month follow-up. (p = 0.038, p = 0.017).
This prospective intervention study demonstrated that education on osteoporosis knowledge and regular exercise programs could improve osteoporosis self- efficacy, fall self-efficacy and increase dietary calcium and vitamin D intake.
BACKGROUNDWe analyzed the International Classification of Diseases, 10th edition (ICD-10) diagnostic codes, procedure codes, and radiographic image codes for vertebral fracture (VF) used in the ...database of Health Insurance Review and Assessment Service (HIRA) of Korea to establish a validated operational definition for identifying patients with osteoporotic VF in claims data. METHODSWe developed three operational definitions for detecting VFs using 9 diagnostic codes, 5 procedure codes and 4 imaging codes. Medical records and radiographs of 2,819 patients, who had primary and subordinated codes of VF between January 2016 and December 2016 at two institutions, were reviewed to detect true vertebral fractures. We evaluated the sensitivity and positive predictive value (PPV) of the operational definition in detecting true osteoporotic VF and obtained the receiver operating characteristic (ROC) curve. RESULTSAmong the 2,819 patients who had primary or secondary diagnosis codes for VF, 995 patients satisfied at least one of the criteria for the operational definition of osteoporotic VF. Of these patients, 594 were judged as having true fractures based on medical records and radiographic examinations. The sensitivity and PPV were 62.5 (95% confidence interval CI, 59.4-65.6) and 59.7(95% CI, 56.6-62.8) respectively. In the receiver operating characteristic analysis, area under the curve (AUC) was 0.706 (95% CI, 0.688-0.724). CONCLUSIONOur findings demonstrate the validity of our operational definitions to identify VFs more accurately using claims data. This algorithm to identify VF is likely to be useful in future studies for diagnosing osteoporotic VF.
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