Optimization design for roadheader cutting head by orthogonal experiment and finite element analysis

U radu se istražuje optimizacija konstrukcije rezne glave stroja za bušenje. U tu su svrhu kao varijable optimizacije izabrani brzina rotacije, brzina oscilacije, rezni kutovi pijuka i kutovi nagiba pijuka, a kao ciljevi optimizacije izabrani su srednja vrijednost rezultirajuće sile i koeficijent varijacije reznog opterećenja. Učinci ovih parametara na indekse evaluacije analiziraju se ortogonalnim eksperimentom i analizom konačnih elemenata. Također je provedena analiza promjene trenda indeksa evaluacije s promjenama eksperimentalnih čimbenika. U usporedbi s originalnim projektom, dva indeksa evaluacije smanjila su se za 18,3 % i 5,5 % nakon optimizacije, čime je značajno poboljšana rezna performansa rezne glave stroja za bušenje.Optimization design for roadheader cutting head is investigated in this paper. For this purpose, the rotation velocity, the swing velocity, the cutting angles of picks, and the inclination angles of picks are chosen as the variable for the optimization, and the mean value of resultant force and variation coefficient of cutting load are chosen as optimization objective. The effects of these parameters on evaluation indexes are studied by orthogonal experiment and finite element analysis. The change trend of the evaluation indexes with the experimental factors is also carried out. Compared with the original design, the two evaluation indexes decreased by 18,3 % and 5,5 % after optimization design separately, which improves the cutting performance of roadheader cutting head efficiently

Case report of a Li-Fraumeni syndrome-like phenotype with a de novo mutation in <i>CHEK2</i>

BACKGROUND: Cases of multiple tumors are rarely reported in China. In our study, a 57-year-old female patient had concurrent squamous cell carcinoma, mucoepidermoid carcinoma, brain cancer, bone cancer, and thyroid cancer, which has rarely been reported to date. METHODS: To determine the relationship among these multiple cancers, available DNA samples from the thyroid, lung, and skin tumors and from normal thyroid tissue were sequenced using whole exome sequencing. RESULTS: The notable discrepancies of somatic mutations among the 3 tumor tissues indicated that they arose independently, rather than metastasizing from 1 tumor. A novel deleterious germline mutation (chr22:29091846, G->A, p.H371Y) was identified in CHEK2, a Li–Fraumeni syndrome causal gene. Examining the status of this novel mutation in the patient's healthy siblings revealed its de novo origin. CONCLUSION: Our study reports the first case of Li–Fraumeni syndrome-like in Chinese patients and demonstrates the important contribution of de novo mutations in this type of rare disease

Detection and analysis of human papillomavirus (HPV) DNA in breast cancer patients by an effective method of HPV capture

Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) and the risk of breast carcinoma, these studies remain inconclusive. Here we aim to detect HPV DNA in various tissues from patients with breast carcinoma using the method of HPV capture combined with massive paralleled sequencing (MPS). To validate the confidence of our methods, 15 cervical cancer samples were tested by PCR and the new method. Results showed that there was 100% consistence between the two methods.DNA from peripheral blood, tumor tissue, adjacent lymph nodes and adjacent normal tissue were collected from seven malignant breast cancer patients, and HPV type 16(HPV16) was detected in 1/7, 1/7, 1/7and 1/7 of patients respectively. Peripheral blood, tumor tissue and adjacent normal tissue were also collected from two patients with benign breast tumor, and 1/2, 2/2 and 2/2 was detected to have HPV16 DNA respectively. MPS metrics including mapping ratio, coverage, depth and SNVs were provided to characterize HPV in samples. The average coverage was 69% and 61.2% for malignant and benign samples respectively. 126 SNVs were identified in all 9 samples. The maximum number of SNVs was located in the gene of E2 and E4 among all samples. Our study not only provided an efficient method to capture HPV DNA, but detected the SNVS, coverage, SNV type and depth. The finding has provided further clue of association between HPV16 and breast cancer

Forced Notch Signaling Inhibits Commissural Axon Outgrowth in the Developing Chick Central Nerve System

BACKGROUND: A collection of in vitro evidence has demonstrated that Notch signaling plays a key role in the growth of neurites in differentiated neurons. However, the effects of Notch signaling on axon outgrowth in an in vivo condition remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the neural tubes of HH10-11 chick embryos were in ovo electroporated with various Notch transgenes of activating or inhibiting Notch signaling, and then their effects on commissural axon outgrowth across the floor plate midline in the chick developing central nerve system were investigated. Our results showed that forced expression of Notch intracellular domain, constitutively active form of RBPJ, or full-length Hes1 in the rostral hindbrain, diencephalon and spinal cord at stage HH10-11 significantly inhibited commissural axon outgrowth. On the other hand, inhibition of Notch signaling by ectopically expressing a dominant-negative form of RBPJ promoted commissural axonal growth along the circumferential axis. Further results revealed that these Notch signaling-mediated axon outgrowth defects may be not due to the alteration of axon guidance since commissural axon marker TAG1 was present in the axons in floor plate midline, and also not result from the changes in cell fate determination of commissural neurons since the expression of postmitotic neuron marker Tuj1 and specific commissural markers TAG1 and Pax7 was unchanged. CONCLUSIONS/SIGNIFICANCE: We first used an in vivo system to provide evidence that forced Notch signaling negatively regulates commissural axon outgrowth

Reconstructing Bone with Natural Bone Graft: A Review of In Vivo Studies in Bone Defect Animal Model

Bone defects caused by fracture, disease or congenital defect remains a medically important problem to be solved. Bone tissue engineering (BTE) is a promising approach by providing scaffolds to guide and support the treatment of bone defects. However, the autologous bone graft has many defects such as limited sources and long surgical procedures. Therefore, xenograft bone graft is considered as one of the best substitutions and has been effectively used in clinical practice. Due to better preserved natural bone structure, suitable mechanical properties, low immunogenicity, good osteoinductivity and osteoconductivity in natural bone graft, decellularized and demineralized bone matrix (DBM) scaffolds were selected and discussed in the present review. In vivo animal models provide a complex physiological environment for understanding and evaluating material properties and provide important reference data for clinical trials. The purpose of this review is to outline the in vivo bone regeneration and remodeling capabilities of decellularized and DBM scaffolds in bone defect models to better evaluate the potential of these two types of scaffolds in BTE. Taking into account the limitations of the state-of-the-art technology, the results of the animal bone defect model also provide important information for future design of natural bone composite scaffolds

Application of Collagen Scaffold in Tissue Engineering: Recent Advances and New Perspectives

Collagen is the main structural protein of most hard and soft tissues in animals and the human body, which plays an important role in maintaining the biological and structural integrity of the extracellular matrix (ECM) and provides physical support to tissues. Collagen can be extracted and purified from a variety of sources and offers low immunogenicity, a porous structure, good permeability, biocompatibility and biodegradability. Collagen scaffolds have been widely used in tissue engineering due to these excellent properties. However, the poor mechanical property of collagen scaffolds limits their applications to some extent. To overcome this shortcoming, collagen scaffolds can be cross-linked by chemical or physical methods or modified with natural/synthetic polymers or inorganic materials. Biochemical factors can also be introduced to the scaffold to further improve its biological activity. This review will summarize the structure and biological characteristics of collagen and introduce the preparation methods and modification strategies of collagen scaffolds. The typical application of a collagen scaffold in tissue engineering (including nerve, bone, cartilage, tendon, ligament, blood vessel and skin) will be further provided. The prospects and challenges about their future research and application will also be pointed out

Uninterrupted dynamic stiffening microenvironment enhances the paracrine function of mesenchymal stem cells for vascularization through chromatin remodeling

The stiffness of extracellular matrix is dynamically stiffened during bone formation. Paracrine of angiogenic factors in mesenchymal stem cells (MSCs) plays an essential role during tissue regeneration. Whether the paracrine of angiogenic factors in MSCs is influenced by the mechanical microenvironment of materials, especially dynamic matrix mechanics of materials largely remains unknown. A matrix dynamic stiffening material previous designed was used here to explore whether matrix dynamic stiffening could influence paracrine of angiogenic factors in MSCs. The cytoskeleton polymerization, chromatin remodeling and histone acetylation in MSCs were analyzed using phalloidin staining, chromatin condensation parameter analysis and immunofluorescent staining. The results found that the paracrine of MSCs cultured on dynamic stiffening material was higher than that on static stiffness materials. The cytoskeletal polymerization and nuclear deformation degrees of MSCs seeded on dynamic stiffening material were significantly higher than those seeded on materials with static stiffness. The dynamic stiffening substrate could promote the cytoskeletal polymerization to increase the nuclear deformation of MSCs and further induce the paracrine of MSCs. These findings will help to provide clinical guidelines for designing vascularized bone repair materials with appropriate mechanical properties

Suspension state promotes metastasis of breast cancer cells by up-regulating cyclooxygenase-2.

Hematogenous metastasis requires tumor cells to detach from primary tumor into blood/lymphatic circulation and extravasate. Tumor cells in the blood circulation system, named circulating tumor cells (CTCs), are in a suspension state, with unique cytoskeletal structure and molecular phenotype different from primary tumor cells. The aim of this study is to assess the impact of suspension state on the metastatic potential of breast cancer cells (BCCs) and study its underlying mechanism. Methods: BCCs were cultured on low-adhesion plates to mimic the suspension state. Conventional adherent culture BCCs were used as the control. This study examined the metastatic potential of adherent and suspension BCCs in vitro and in vivo. RNA sequencing analysis, siRNA, and inhibitors were used to determine the underlying molecular mechanism. Results: The suspension state significantly increased the metastatic potential of BCCs, but slightly suppressed their tumor growth. RNA sequencing analysis revealed that the suspension state resulted in an acquisition of unique molecular signature enriched in pro-metastatic and tumor-suppressive genes. Specifically, prostaglandin-endoperoxide synthase 2 (PTGS2), which encodes protein cyclooxygenase-2 (COX-2), was identified as a highly up-regulated gene in suspension state compared with adherent cultured BCCs. Inhibition of the catalytic activity of COX-2 by celecoxib markedly suppressed suspension-increased migration and invasion of BCCs. In addition, knock-down of COX-2 by siRNA reduced the experimental lung metastasis formation of suspension cultured BCCs, which was associated with a remarkable decrease in retention and survival of BCCs in lungs of mice in the early stage of metastasis. Activation of Ca2+/calcineurin (CaN)/nuclear factor of activated T cells (NFAT) pathway and disruption of cytoskeleton contributed to the COX-2 up-expression by suspension state. Conclusions: Our results demonstrate that suspension state plays an important role in the metastatic potential of CTCs, and suggest a potential application of COX-2 inhibitor for anti-metastasis