Cancer risk related to mammary gland structure and development

The breast undergoes dramatic changes in size, shape, and function in association with growth, reproduction, and post-menopausal regression. Those changes impact women's lifetime breast cancer risk. An early first full-term pregnancy exerts a protective effect, emphasizing the need for understanding the role of reproductive influences on breast development and on cancer initiation and progression, and providing a paradigm for developing preventive strategies based on physiological principles. Even though the cause of breast cancer and the ultimate mechanisms through which an early pregnancy protects from cancer development remain largely unknown, a likely explanation for this protection has been provided by experimental in vivo and in vitro models. These studies have led to the conclusions that cancer initiation requires the interaction of a carcinogen with an undifferentiated and highly proliferating mammary epithelium, whereas differentiation of the mammary gland inhibits carcinogenic initiation. The process of mammary gland differentiation is the result of complex interactions of ovarian, pituitary, and placental hormones, which in turn induce inhibition of cell proliferation, downregulation of estrogen and progesterone receptors, activation of specific genes, such as inhibin, mammary derived growth factor inhibitor and a serpin-like gene, and expression of extracellular matrix proteins in the normal breast. Cell immortalization and transformation are associated with the expression of ferritin H and S100P protein, which serve as markers of cancer initiation. Comparative studies of normal and neoplastic breast development have unraveled similarities with experimental models that validate the extrapolation of findings for testing hypotheses on the initiation and progression of breast cancer.     

Phospholipids as cancer biomarkers: Mass spectrometry‐based analysis

Lipids, particularly phospholipids (PLs), are key components of cellular membrane. PLs play important and diverse roles in cells such as chemical‐energy storage, cellular signaling, cell membranes, and cell–cell interactions in tissues. All these cellular processes are pertinent to cells that undergo transformation, cancer progression, and metastasis. Thus, there is a strong possibility that some classes of PLs are expected to present in cancer cells and tissues in cellular physiology. The mass spectrometric soft‐ionization techniques, electrospray ionization (ESI), and matrix‐assisted laser desorption/ionization (MALDI) are well‐established in the proteomics field, have been used for lipidomic analysis in cancer research. This review focused on the applications of mass spectrometry (MS) mainly on ESI‐MS and MALDI‐MS in the structural characterization, molecular composition and key roles of various PLs present in cancer cells, tissues, blood, and urine, and on their importance for cancer‐related problems as well as challenges for development of novel PL‐based biomarkers. The profiling of PLs helps to rationalize their functions in biological systems, and will also provide diagnostic information to elucidate mechanisms behind the control of cancer, diabetes, and neurodegenerative diseases. The investigation of cellular PLs with MS methods suggests new insights on various cancer diseases and clinical applications in the drug discovery and development of biomarkers for various PL‐related different cancer diseases. PL profiling in tissues, cells and body fluids also reflect the general condition of the whole organism and can indicate the existence of cancer and other diseases. PL profiling with MS opens new prospects to assess alterations of PLs in cancer, screening specific biomarkers and provide a basis for the development of novel therapeutic strategies. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:107‐138, 2018     

Tumor angiogenesis of non-small cell lung cancer

Lung cancer is one of the commonest causes of cancer death in developed countries. Recent evidence suggests that angoigenesis is related to poor prognosis in many solid tumors including non-small cell lung cancer (NSCLC). Angiogenesis is regulated by a complex interaction among growth factors and cytokines and influenced by proteolytic enzymes such as plasminogen activators and matrix metalloproteases, expression of adhesion molecules, and distribution of extracellular matrices. Fibroblasts, macrophages, mast cells, and endothelial cells themselves also affect angiogenesis. This review concentrates on angiogenic growth factors including vascular endothelial growth factor, angiopoietins, platelet derived endothelial growth factor, and basic fibroblast growth factor, proteases, adhesion molecules including vascular endothelial cadherin and integrins, osteopontin, and mast cell products in tumor angiogenesis of NSCLC.     

Note: Design of a novel ultraprecision in-plane XYθ positioning stage

This paper presents the design, fabrication, and experimental results of a novel ultraprecision in-plane XYθ positioning stage with kinematic decoupling between translational motion and rotational motion components. Two translational motions are guided by four cymbal mechanisms that have both motion guide and motion amplifier. Four leaf springs guide a rotational motion amplified by a Scott-Russell linkage mechanism. The proposed stage has advantages such as an in-plane symmetrical configuration as well as ease of design and control by serial kinematics. The experimental results demonstrate that the stage has a translational full motion range of 58 μm and a rotational full motion range of 1.05 mrad. The crosstalk experimental results show good agreement with the theoretical prediction of the decoupling between translational motion and rotational motion.     

Integrins as mediators of epithelial cell-matrix interactions in the human small intestinal mucosa

The intestinal epithelium is a highly dynamic tissue, which depends on a variety of factors for the regulation of its rapid renewal and expression of digestive functions. Over the last 10 years, it has become evident that among these factors are cell interactions with the extracellular matrix, more specifically with the underlying basement membrane, through a series of specific cell membrane receptors, many of which are integrins. Integrins regulate the assembly of adhesive junctions as well as the activation of various signaling pathways, leading to the modulation of gene expression. The analysis of the integrin repertoire along the crypt-villus axis in the human small intestinal epithelium identifies a number of beta1 and beta4 integrins, showing differential patterns of expression relative to its two functional compartments. Among them are the integrins alpha3beta1, alpha7Bbeta1 and the functional form of alpha6beta4 that appear to be related, in concert with the distribution of their ligands, to the process of intestinal cell differentiation, and the integrins alpha2beta1, alpha1beta1, alpha5beta1, and the non-functional form of alpha6beta4 that seem to be coupled with the undifferentiated/proliferative status of crypt cells. These observations delineate the potential complexity of the organization of epithelial cell-matrix interactions involved in the maintenance of the human intestinal crypt-villus axis.     

基于遗传算法的装载机工作装置优化设计研究

针对装载机工作装置设计要求满足平动性和较大掘起力等需求,采用标准遗传算法与惩罚函数相结合的优化方法,使得设计结果符合铲斗举升平动性这一目标,铲斗举升时位置角的变化均不超过10°,并满足高位卸载角度的要求。该方法解决了通常遗传算法面临的约束函数多、约束函数非线性的困难,通过各个控制参数的合理配置,快速得到一批最优稳定解,为装载机工作装置的设计提供动力性能更高并且工作性能优良的设计方案,提高了工程设计水平和设计效率,缩短了设计周期。     

Exact solutions for longitudinal vibration of rods coupled by translational springs

The objective of this paper is to present exact analytical solutions for longitudinal vibration of non-uniform rods with concentrated masses coupled by translational springs. Using appropriate transformation, the governing differential equation for longitudinal vibration of a rod with varying cross section is reduced to Bessel's equation or an ordinary differential equation with constant coefficients by selecting suitable expressions, such as power functions and exponential functions, for the area variation. The exact solutions for free longitudinal vibration of rods with varying cross-section are derived. The initial parameter method and the transfer matrix method are proposed to establish the frequency equation for the longitudinal vibration of two rods coupled by translational springs. The advantage of the proposed methods is that the frequency equation for two rods coupled by translational springs can be established in terms of a determinant of 2-order for any number of translational springs and concentrated masses. The proposed methods can be used to solve the problem of free longitudinal vibration of uniform and non-uniform rods with concentrated masses coupled by various translational springs, and thus to investigate the axial stiffness and mass distribution among the rods to alter the system's dynamic characteristics. A numerical example shows that the fundamental longitudinal natural frequency of two reaction towers coupled by a pipe calculated by the proposed methods is in good agreement with the full scale measured data, suggesting the proposed methods are applicable to engineering practices.     

MicroRNA-708 inhibits the proliferation and chemoresistance of pancreatic cancer cells

Pancreatic cancer is one of the most aggressive malignancies with poor prognosis and high mortality. Recent studies showed that microRNAs are dysregulated and involved in the initiation and progression of pancreatic cancer. In this study, we found that miR-708 was significantly downregulated in pancreatic cancer tissues and cell lines. Lentivirus-mediated overexpression of miR-708 could significantly inhibit the proliferation and invasion, while enhanced chemosensitivity to gemcitabine in both Panc-1 and SW1990 cells. Luciferase reporter assay showed that miR-708 bound the 3’-untranslated region of survivin and suppressed the expression of survivin in pancreatic cancer cells. In pancreatic cancer tissues, survivin protein was highly expressed and negatively correlated with miR-708 expression. Furthermore, the restoration of survivin expression could partially antagonize proliferation inhibition and apoptosis induction by miR-708 in pancreatic cancer cells. The Panc-1 cells with overexpression of miR-708 also showed decreased proliferation capability in nude mouse model compared with parental cells. In conclusion, our results suggest that miR-708 inhibits pancreatic cancer and could be a novel potential candidate to treat pancreatic cancer.     

The transmission of translational seat vibration to the head: the effect of measurement position at the head.

Head motion has been measured in six axes on twelve subjects exposed to vertical seat vibration in the frequency range 0.5-25 Hz. The subjects sat on a rigid flat seat in two postures: 'back-off' (no backrest) and 'back-on' (subject's back in contact with the seat backrest). Translational acceleration has been calculated for various locations on the head and transmissibilities between vertical seat vibration and translational head motion determined for each location and all axes. The translational motion of the head was most affected by pitch motion of the head. This caused variations in fore-and-aft motion with position along the vertical axis of the head and variations in vertical motion with position along the fore-and-aft axis of the head. These variations are illustrated for each subject in both postures. The individual data allow the identification of various modes of vibration and show that seat-to-head transmissibility is greatly affected by pitch modes of the head and neck. The magnitude of motion occurring in some modes is dependent on body posture.     

Distributed adaptive containment control of uncertain QUAV multiagents with time-varying payloads and multiple variable constraints

This paper considers the containment control problem for uncertain QUAV (Quadrotor Unmanned Aerial Vehicle) multiagents with time-varying payloads under a fixed topology graph, and a distributed adaptive containment control protocol with multiple variable constraints is proposed. Generally, the control framework is classified into two layers. In the first layer, the desired trajectories are determined for followers by the communication topology and initial values of leaders. For the second layer, the ith QUAV follower is required to track the desired trajectory by employing the information of itself and neighbors. Under the second layer, the system of the ith agent is decoupled into two subsystems: the translational subsystem and the rotational subsystem. For the translational subsystem, the distributed adaptive containment controller is designed via dynamic surface control method to track the desired position trajectory. With such method, the information requirement of ith agent for its neighbors can be reduced significantly. For the rotational subsystem, the adaptive tracking controller is constructed to track the desired attitudes derived from translational subsystem through commonly used attitudes extraction algorithms. In the end, the resulting closed-loop system is proved to be stable in the sense of uniformly ultimate boundness, and the effectiveness of the proposed approach is illustrated by numerical simulations.     

Glycoprotein analysis using protein microarrays and mass spectrometry

Protein glycosylation plays an important role in a multitude of biological processes such as cell–cell recognition, growth, differentiation, and cell death. It has been shown that specific glycosylation changes are key in disease progression and can have diagnostic value for a variety of disease types such as cancer and inflammation. The complexity of carbohydrate structures and their derivatives makes their study a real challenge. Improving the isolation, separation, and characterization of carbohydrates and their glycoproteins is a subject of increasing scientific interest. With the development of new stationary phases and molecules that have affinity properties for glycoproteins, the isolation and separation of these compounds have advanced significantly. In addition to detection with mass spectrometry, the microarray platform has become an essential tool to characterize glycan structure and to study glycosylation‐related biological interactions, by using probes as a means to interrogate the spotted or captured glycosylated molecules on the arrays. Furthermore, the high‐throughput and reproducible nature of microarray platforms have been highlighted by its extensive applications in the field of biomarker validation, where a large number of samples must be analyzed multiple times. This review covers a brief survey of the other experimental methodologies that are currently being developed and used to study glycosylation and emphasizes methodologies that involve the use of microarray platforms. This review describes recent advances in several options of microarray platforms used in glycoprotein analysis, including glycoprotein arrays, glycan arrays, lectin arrays, and antibody/lectin arrays. The translational use of these arrays in applications related to characterization of cells and biomarker discovery is also included. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 29:830–844, 2010     

Knockdown Wiskott-Aldrich syndrome protein family member 3 (WASF3) inhibits colorectal cancer metastasis and sensitizes to cisplatin through targeting ZNF471

Colorectal cancer (CRC) is a heterogeneous cancer, and many risk factors for colorectal cancer have been established. For CRC metastasis, tumor cell migration, adhesion as well as invasion are important processes. WiskottAldrich syndrome protein family member 3 (WASF3) is necessary for metastasis of various types of cancers. However, its role in CRC progression has not been fully elucidated. This study examined the in vitro functional roles of WASF3 in the CRC and explored the underlying molecular mechanisms. We used siRNA-WASF3 to gene silence WASF3 in colon cancer cell (HCT116) in vitro. The effects of WASF3 silencing on HCT116 cell apoptosis, proliferation, migration, as well as invasion were assessed by flow cytometry, CCK-8, and transwell assays. ZNF471 protein expressions were detected by immunofluorescence staining and RT-PCR. Moreover, the effects of ZNF471 were studied on a series of in vitro antitumor-promoting assays using HCT116. WASF3 knockdown expression using small interfering RNA (siRNA) ameliorated CRC cell proliferation, anchorage-independent growth, invasion, and metastasis. Furthermore, we observed that WASF3 contributed to upregulating the metastasis signaling pathway through inhibiting the expression of ZNF471. Our study suggests that targeting WASF3 signaling might be a novel therapeutic strategy for treating CRC.     

The expressional level of tankyrase-1 gene and its regulation in colorectal cancer in a Saudi population

Tankyrase1 plays an essential role in cancer progression by regulating telomere length. The study aimed to determine expression of TNKS1 and its regulation in colorectal cancer (CRC) in 20 samples from Saudi patients. mRNA expression of TNKS1 in CRC and paired normal tissues was measured by qRT-PCR. Epigenetic modification of TNKS1 promoter was determined by methylation-specific PCR while somatic mutation was analyzed by Sanger sequencing in exon 10 of the gene. All cancerous and normal tissues expressed TNKS1, but level of expression in CRC tissues was significantly associated with tumor stage though no other parameters; age, gender, and tumor location, showed any correlation. Expression of TNKS1 was markedly higher in earlier (I, II) than later (III, IV) stages of CRC development. Both cancerous and healthy tissues had unmethylated promoter. Sanger sequencing of exon 10 masked any somatic mutation in the samples. Our findings suggest that up-regulation of TNKS1 was inversely correlated with cancer progression in CRC, indicating that TNKS1 participates in the initiation of CRC by stabilizing telomere length in the first phase of cancer progression. Mechanisms other than TNKS1 might play a role in malignant tumor progression and telomere maintenance in the late stages of CRC.     

新型两平移一转动并联机器人机构精度分析与仿真

通过对一种新型两平移一转动并联机器人机构的分析,求出其运动学位置正解,利用微分理论,建立了该并联机器人机构的精度模型。通过计算机仿真,分析了主动副的移动误差、结构参数误差和位姿变化对机器人机构精度的影响。为该机器人机构实际误差补偿与控制提供理论依据。     

ISG15 and ISGylation: Emergence in the cytoskeleton dynamic and tumor microenvironment

Cytoskeletal remodeling affects the shape, adhesion, and motility of cells. Cytoskeletal dynamics are modulated by matrix proteins, integrins, and several cytokines in the tumor microenvironment. In this scenario, signaling is activated by integrins and interferons, which can induce ISG15 gene expression. This gene encodes a ubiquitin-like protein that functions as a protein modifier via the ISGylation system. Furthermore, non-conjugated ISG15 acts as a cytokine-like protein. In this viewpoint, the interplay between free ISG15, protein ISGylation, and cytoskeletal dynamics in the tumor microenvironment is discussed.     

Subcellular phosphoproteomics

Protein phosphorylation represents one of the most extensively studied post‐translational modifications, primarily due to the emergence of sensitive methods enabling the detection of this modification both in vitro and in vivo. The availability of enrichment methods combined with sensitive mass spectrometry instrumentation has played a crucial role in uncovering the dynamic changes and the large expanding repertoire of this reversible modification. The structural changes imparted by the phosphorylation of specific residues afford exquisite mechanisms for the regulation of protein functions by modulating new binding sites on scaffold proteins or by abrogating protein–protein interactions. However, the dynamic interplay of protein phosphorylation is not occurring randomly within the cell but is rather finely orchestrated by specific kinases and phosphatases that are unevenly distributed across subcellular compartments. This spatial separation not only regulates protein phosphorylation but can also control the activity of other enzymes and the transfer of other post‐translational modifications. While numerous large‐scale phosphoproteomics studies highlighted the extent and diversity of phosphoproteins present in total cell lysates, the further understanding of their regulation and biological activities require a spatio‐temporal resolution only achievable through subcellular fractionation. This review presents a first account of the emerging field of subcellular phosphoproteomics where cell fractionation approaches are combined with sensitive mass spectrometry methods to facilitate the identification of low abundance proteins and to unravel the intricate regulation of protein phosphorylation. © 2010 Wiley Periodicals, Inc. Mass Spec Rev 29:962–990, 2010