Altered expression of the cyclin D1 and retinoblastoma genes in human esophageal cancer.

We have examined DNA from four human esophageal carcinoma cell lines and 50 primary esophageal carcinomas obtained from China, Italy, and France for amplification of the cyclin D1 gene. We also examined 36 of these 50 carcinomas for expression of the cyclin D1 and retinoblastoma (RB) proteins by immunohistochemistry. We found a 3- to 10-fold amplification of the cyclin D1 gene in 16 of the 50 (32%) tumors and in two of the four cell lines. Cyclin D1 protein was overexpressed in 12 of 13 tumors and the two cell lines that showed gene amplification when compared to normal controls. Studies on RB protein expression indicated that 6 of the 36 (17%) tumor samples examined and one cell line did not show detectable expression of this protein. The tumors and cell lines that had cyclin D1 gene amplification and overexpression exhibited normal levels of expression of RB protein. By contrast, the tumors and cell line that did not appear to express the RB protein did not show amplification of the cyclin D1 gene and expressed only low levels of the cyclin D1 protein (P = 0.03). These results suggest that the inhibitory effect of RB on cell cycle progression can be abrogated during tumor development either by loss of expression of the RB gene or by increased expression of the cyclin D1 gene.     

Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand

We evolved muscarinic receptors in yeast to generate a family of G protein-coupled receptors (GPCRs) that are activated solely by a pharmacologically inert drug-like and bioavailable compound (clozapine-N-oxide). Subsequent screening in human cell lines facilitated the creation of a family of muscarinic acetylcholine GPCRs suitable for in vitro and in situ studies. We subsequently created lines of telomerase-immortalized human pulmonary artery smooth muscle cells stably expressing all five family members and found that each one faithfully recapitulated the signaling phenotype of the parent receptor. We also expressed a G(i)-coupled designer receptor in hippocampal neurons (hM(4)D) and demonstrated its ability to induce membrane hyperpolarization and neuronal silencing. We have thus devised a facile approach for designing families of GPCRs with engineered ligand specificities. Such reverse-engineered GPCRs will prove to be powerful tools for selectively modulating signal-transduction pathways in vitro and in vivo.     

Design and development of a novel body scanning system for healthcare applications

This paper presents a novel instant 3D whole body scanner for healthcare applications. It is based on photogrammetry, a digital technology which allows to reconstruct the surface of objects starting from multiple pictures. The motivation behind this work is the development of minimally invasive procedures for instant data acquisitions of anatomical structure. The scanner provides several features of interests in 3D body scanning technologies for the healthcare domains: (i) instant capture of human body models; (ii) magnitude of accuracy in the order of 1 mm; (iii) simplicity of use; (iv) possibility to scan using different settings; (v) possibility to reconstruct the texture. The system is built upon a modular and distributed architecture. In this paper we highlight its key concepts and the methodology which has led to the current product. We illustrate its potential through one of the most promising 3D scanning healthcare applications: the data acquisition and processing of human body models for the digital manufacturing process of prostheses and orthoses. We validate the overall system in terms of conformity with the the initial requirements.     

Technical aspects of internet-based knowledge presentation in radiotherapy.

Three-dimensional radiotherapy planning is a complex and time-consuming optimization process which requires much experience. To simplify and to speed up the process of treatment planning as well as to exchange experience and therapeutic knowledge, the department of Medical Physics at the German Cancer Research Centre (DKFZ) in Heidelberg is developing an Internet-based 3D Radiotherapy planning and Information System (IRIS). IRIS designed internet-based client-server application, implemented using Java, CORBA and PVM. The concept of IRIS combines the functionality of an interactive tutorial with a discussion forum, teleconferencing tool and an atlas of dose distributions. Furthermore an integral knowledge-based system provides automatically generated, preoptimized treatment plans. This paper explains the technical design of the system and gives an overview of experiences gained by the technical realization of a first prototype using currently available internet technology. The prototype is currently running for testing in the intranet of DKFZ.     

Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma

The development of three-dimensional environments to mimic the in vivo cellular response is a problem in the building of disease models. This study aimed to synthesize and validate three-dimensional support for culturing monoclonal plasma cells (mPCs) as a disease model for multiple myeloma. The three-dimensional environment is a biomimetic microgel formed by alginate microspheres and produced on a microfluidic device whose surface has been functionalized by a layer-by-layer process with components of the bone marrow’s extracellular matrix, which will interact with mPC. As a proof of concept, RPMI 8226 cell line cells were cultured in our 3D culture platform. We proved that hyaluronic acid significantly increased cell proliferation and corroborated its role in inducing resistance to dexamethasone. Despite collagen type I having no effect on proliferation, it generated significant resistance to dexamethasone. Additionally, it was evidenced that both biomolecules were unable to induce resistance to bortezomib. These results validate the functionalized microgels as a 3D culture system that emulates the interaction between tumoral cells and the bone marrow extracellular matrix. This 3D environment could be a valuable culture system to test antitumoral drugs efficiency in multiple myeloma.     

Automatic generation of glomerular capillary topological organization.

Glomerular structural changes are conventionally investigated by optical or electron microscopy on two-dimensional (2D) sections. To understand the relationship between functional and structural changes of glomerular capillary networks in more detail, three-dimensional (3D) investigation of the capillary tufts is required. Since confocal microscopy and scanning electron microscopy cannot completely show the 3D topological organization of the capillary tuft, we have developed an automatic method to obtain a 3D model of the glomerular capillary lumen structure and to derive its topological organization. Serial semithin sections of a glomerular tuft, from rat kidney tissue, were digitized at high resolution. Capillary lumens were digitally outlined and segmented images were automatically aligned. A 3D model of the capillary tuft was automatically generated using the Visualization Toolkit library and the Marching Cubes algorithm. We then developed an original algorithm for automatic 3D skeletonization of capillary lumen volume to identify capillary segments and bifurcations and to obtain the topological organization of the network and geometric parameters of capillary segments (length, radius, and spatial configuration). Capillary segment connectivity was graphically presented in a 2D layout with an automatic procedure, revealing the lobular organization of the network. This technique, successfully applied to serial sections of a glomerular capillary, can be used to study a population of glomerular capillaries to disclose the structural effects of pathological conditions. The methodology can be extended to other vascular structures, such as the microcirculation of neoplastic tissues.     

PLM and early stages collaboration in interactive design,a case study in the glass industry

Product design activity is traditionally presented as a succession of four to six stages. In the early stages of design, during the search for concepts, multi-disciplinary teams are working together, sometimes on the fringe of the digital design chain. But it is during these stages, that most of the product development cost is committed. Therefore, collaboration should be emphasized, and PLM software should contribute to it strongly. This paper first defines the boundaries of the early stages of design. Then, we analyze designer collaboration in this stage and describe the knowledge necessary for efficient collaboration. Finally, we propose and test a concept for a tool to assist the early stages of design, to be integrated in a continuum with other existing digital design tools. A case study is presented in Verallia, specialized in the design and manufacturing of glassware.     

Advanced computer aided technologies for design automation in footwear industry

In the footwear industry there is growing methodological research linking advanced computer-based technologies to the traditional manufacturing process. This paper deals with the automation of shoe design phases and describes a computer aided design system that brings together theories and tools from geometric modeling, image processing, and reverse engineering. At first, the paper reviews the current technologies used for creating new shoe models. Then the paper presents an approach based on shoe 3D virtual modeling in order to overcome the traditional time-consuming manual operations. The approach is concretized into dedicated tools able to automatically perform design of the last shape model and flattening of the shoe styling curves represented in the virtual prototype. The modeling tool uses 3D geometric rules derived from the analysis of strategies adopted by skilled manual operators, while the styling curves recognition and flattening are based on specific image processing algorithms and geometrical deformation rules. Experimental results show a good compromise between quality results and modeling time.     

Clinical assessment of a new method for pacing pulse detection using a hybrid circuit in digital Holter monitoring

Holter monitoring is widely used for the detection of arrhythmia and ischemic episodes. Traditionally, analog amplitude-modulated Holter devices have been used for detecting arrhythmia, but they produce signal distortion due to contour effects and phase distortion caused by the tape recorders. A digital Holter device without these disadvantages has been developed and can reproduce clinically accurate electrocardiographic waveforms useful for assessment of arrhythmia and ST segments. However, their reliability is questionable when detecting pacing pulses in pacemaker patients. Because electrocardiographic signals are digitized based on sampling rate, pacing pulses are occasionally missed. Therefore, the FM-300 was developed, a new device for detecting pacing pulses on digital recordings that has both digital and analog circuits in one system and indicates pacing pulse timing with arrows. This device can automatically detect and recognize pacing pulses from various artifacts and pacing modalities, making it easy to identify pacing pulses on digitally recorded electrocardiograms. The FM-300 is useful in the diagnosis and assessment of pacemaker function and has improved the reliability of pulse detection in digital Holter monitoring.     

Anatomical M-mode: an old-new technique

The M-mode (motion mode) technique has improved the diagnostic possibilities of echocardiography due to its high temporal resolution. The use of a two-dimensional (2D) image as a basis for M-mode analysis at a defined line, independent of the transducer orientation, namely the anatomic M-mode (AMM), has been proposed from the beginning of 2D echocardiography. For several years, however, this could not be accomplished due to several reasons including the limited digital memory, the relatively rough pixels of 2D images, and the low temporal resolution of the screen. The AMM has been improved by the "fully digital" machines. These are able to provide a series of digital data (direction, position, and timing) relative to any single echo received from any point of the tissue. AMM analysis, thus, can be performed in any direction, as a "normal" monodimensional echocardiogram. With respect to traditional M-mode, AMM permits a more detailed analysis of cardiac chambers diameters obtained by linear measurements, regional wall motion of the left ventricle (both at rest and during stress), and location of accessory pathways. In particular, the assessment of left ventricular regional wall motion represents the most important goal of this new technique, which results in marked reduction or even elimination of the limitations due to the subjective character of wall motion evaluation with 2D echocardiography.     

Tangible digital master for product lifecycle management in augmented reality

We present a novel approach, called tangible digital master (TaDiMa), based on a flexible access to Product Lifecycle Management (PLM) database using a tangible/graphical user interface and augmented reality. We developed and tested a technical drawing template with automatically embedded markers for augmentation. We embedded the Mozilla FireFox engine into our annotation system for the integration of web 2.0 applications in the AR environment. We also extended the concept of web feed to PLM for notification of technical contents. We implemented a dynamic labelling management with view-driven filtering and placement. We also present a tangible management for layers visualization and users access by marked tokens. We validated the TaDiMa approach in a selection of possible scenarios for different PLM applications. The main benefit of the TaDiMa system is the easy and low-cost integration in the product lifecycle process.     

Optimally sparse representation in general (nonorthogonal) dictionaries via l minimization

Given a dictionary D = {d(k)} of vectors d(k), we seek to represent a signal S as a linear combination S = summation operator(k) gamma(k)d(k), with scalar coefficients gamma(k). In particular, we aim for the sparsest representation possible. In general, this requires a combinatorial optimization process. Previous work considered the special case where D is an overcomplete system consisting of exactly two orthobases and has shown that, under a condition of mutual incoherence of the two bases, and assuming that S has a sufficiently sparse representation, this representation is unique and can be found by solving a convex optimization problem: specifically, minimizing the l(1) norm of the coefficients gamma. In this article, we obtain parallel results in a more general setting, where the dictionary D can arise from two or several bases, frames, or even less structured systems. We sketch three applications: separating linear features from planar ones in 3D data, noncooperative multiuser encoding, and identification of over-complete independent component models.     

人工智能技术在结肠镜退镜速度实时监控中的应用

目的构建一种基于计算机视觉的结肠镜退镜速度实时监控系统,并验证其可行性和性能。方法从武汉大学人民医院消化内镜中心数据库选取2018年5—10月期间的35938张肠镜图片和63个结肠镜检查视频。肠镜图片分成体外/体内/不合格和回盲部/非盲肠两个数据集,分别从第一个、第二个数据集中选取3594张和2000张图片用于深度学习模型的测试,其余图片用于训练模型;选取3个结肠镜检查视频资料评价实时监控系统自动监控退镜速度的可行性,剩余60个结肠镜检查视频资料用于评估实时监控系统的性能。结果深度学习模型对于结肠镜检查图片分类识别体外/体内/不合格图片的准确率分别为90.79%(897/988)、99.92%(1300/1301)、99.08%(1293/1305),总体准确率为97.11%(3490/3594);分类识别回盲部/非盲肠图片的准确率分别为96.70%(967/1000)、94.90%(949/1000),总体准确率为95.80%(1916/2000)。在其可行性评价方面,3个结肠镜视频资料显示退镜速度与图片处理间隔时间呈线性关系,提示该监控系统可在结肠镜退出过程中自动监控退镜速度。在其性能评价方面,结肠镜退镜速度实时监控系统正确预测了所有60个肠镜检查的开始时间和结束时间,分析显示结肠镜平均退镜速度和退镜时间呈明显负相关(R=-0.661,P<0.001),退镜时间不足5 min、5~6 min和超过6 min视频的平均退镜速度的95%置信区间分别为43.90~49.74、40.19~45.43和34.89~39.11,故将39.11设为安全退镜速度,将45.43设为预警退镜速度。结论构建的结肠镜退镜速度实时监控系统可用于实时监控结肠镜退镜速度,可在结肠镜检查中辅助内镜医师进行实时监测,以提高结肠镜检查质量。     

Association between the expression of the c-myc oncogene mRNA and the expression of the receptor protein for 1,25-dihydroxyvitamin D3

Studies in lymphocytes have indicated similarities in the state of activation, the time kinetics, and the pathologic states associated with the expression of the c-myc oncogene, and the expression of the 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptor protein. Here, we have sought evidence for an association between c-myc and the 1,25-(OH)2D3 receptor protein in mammalian cells other than lymphocytes. Comparing two rat osteogenic sarcoma cell lines, one that produces constitutively relatively high levels of the 1,25-(OH)2D3 receptor protein (ROS 17/2.8) and one in which the 1,25-(OH)2D3 receptor protein is practically undetectable (ROS 2/3), we found that the 1,25-(OH)2D3 receptor-expressing cell line also expressed c-myc mRNA. In contrast, the cell line in which the 1,25-(OH)2D3 receptor was undetectable did not express c-myc mRNA. Furthermore, we transfected mouse skin fibroblasts (NIH 3T3) with a recombinant plasmid carrying the human c-myc oncogene. We found a dramatic increase in the 1,25-(OH)2D3 receptor concentration in five separate clonal lines of NIH 3T3 cells transfected with the c-myc-carrying plasmid compared to their nontransfected counterparts or to NIH 3T3 fibroblasts transfected with the vector plasmid alone. The receptor protein of the transfected cells exhibited biochemical characteristics indistinguishable from those of classical receptors for 1,25-(OH)2D3. The increased expression in the transfected cells appeared specific for the receptor for 1,25-(OH)2D3; receptors for sex steroids were not detected in the nontransfected NIH 3T3 cells and remained undetectable after transfection with c-myc. Moreover, the level of the glucocorticoid receptor protein, which was expressed in the nontransfected cells, did not change upon transfection with c-myc.     

A system for determination of 3D vessel tree centerlines from biplane images

With the increasing number and complexity of therapeutic coronary interventions, there is an increasing need for accurate quantitative measurements. These interventions and measurements may be facilitated by accurate and reproducible magnifications and orientations of the vessel structures, specifically by accurate 3D vascular tree centerlines. A number of methods have been proposed to calculate 3D vascular tree centerlines from biplane images. In general, the calculated magnifications and orientations are accurate to within approximately 1–3% and 2–5°, respectively. Here, we present a complete system for determination of the 3D vessel centerlines from biplane angiograms without the use of a calibration object. Subsequent to indication of the vessel centerlines, the imaging geometry and 3D centerlines are calculated automatically and within approximately 2 min. The system was evaluated in terms of the intra- and inter-user variations of the various calculated quantities. The reproducibilities obtained with this system are comparable to or better than the accuracies and reproducibilities quoted for other proposed methods. Based on these results and those reported in earlier studies, we believe that this system will provide accurate and reproducible vascular tree centerlines from biplane images while the patient is still on the table, and thereby will facilitate interventions and associated quantitative analyses of the vasculature.     

The process of designing a rotating platform artificial knee prosthesis with posterior stabilizers by finite element analysis

The purpose of this paper is to design a rotating platform knee prosthesis with posterior stabilizers. This design is based on reverse engineering and interactive acquisition and reconstruction of 3D models combined with the finite element method. A 3D geometric model of a healthy knee joint was created from an anatomical knee model by using an active acquisition system based on a 3D scanner. This healthy model comprises a portion of the long bones (femur, tibia and fibula), as well as the transverse ligament, medial collateral ligament, posterior cruciate ligament, anterior cruciate ligament, medial meniscus and cartilage. The digital model that was obtained was repaired and converted to an engineering drawing format by use of CATIA© software. Also, based on the foregoing format, a rotating platform knee prosthesis was designed and assembled by this software. Once the healthy and artificial models were repaired, the Mentat Marc© software was used to develop the healthy and artificial knee FE models. From the anthropometry of the human body, a combination of loads and positions were obtained by use of 3D Static Strength Prediction software. The normal stresses, Von Mises stresses and all relative displacements of the healthy and artificial knee FE model were determined. The Von Mises stresses on both the cortical and the trabecular bone of the artificial and healthy knee FE model were analyzed and compared. The prosthesis was designed for the knee of a male patient of height and body weight of 190 cm and 120 kg, respectively.     

Myeloma cells upregulate interleukin-6 secretion in osteoblastic cells through cell-to-cell contact but downregulate osteocalcin

Previous studies have shown that bone marrow, especially the bone microenvironment, may play an important role in the pathogenesis of multiple myeloma (MM). To elucidate the relationship between myeloma cells and bone cells, mainly osteoblasts, we have established a coculture system between two interleukin-6 (IL-6)-dependent myeloma cell lines, XG1 and XG6, and the osteosarcoma cell lines Saos-2 and MG63. Both osteosarcoma cell lines have retained major functions of normal osteoblasts; principally, the capacity to produce hematopoietic growth factors (including IL-6) and osteocalcin, a noncollagenic protein essential in the bone formation process. Because IL-6 is a critical growth factor in MM, we have examined the IL-6 osteoblastic cell production in our coculture system. XG1 cells strongly upregulate IL-6 production by MG63 and Saos-2 cells. Of major interest, the triggering of IL-6 is totally dependent on the physical contact between myeloma cells and osteoblastic cells, contact that is partly mediated by CD44, CD56, and fibronectin interactions. Osteocalcin production by MG63 and Saos-2 cells has previously been shown to be dependent on 1,25- (OH)2D3. We demonstrate that XG1 and XG6 cells reduced the amount of osteocalcin in MG63 coculture cell supernatants, a reduction that is partly mediated by a soluble factor and by cell-to-cell contact. Notably, whereas one of the myeloma cell lines, XG6, has lost its capacity to stimulate IL-6 production by osteoblastic cell lines, both XG1 and XG6 cell lines remain able to reduce the osteocalcin amount, indicating that IL-6 and osteocalcin levels are regulated by two different pathways. In conclusion, these data strongly support the concept that the bone microenvironment is directly modified by contact with myeloma cells and are consistent with the characteristics observed in vivo in patients with MM patients, ie, abnormally high IL-6 and low osteocalcin levels, respectively.     

What is ‘social integration of the elderly’ in small-scale society?

Social integration of the elderly is a key analytical concept in both Western social and cross-cultural gerontology. While generally understood to describe the fit between the elderly and society in industrial nations, this construct should have utility for Third World societies as well. I argue that the concept is useful insofar as we clarify several antecedent considerations. These are, specification of (1) the model of integration being used; (2) other social distinctions besides age which affect the elderly; (3) the analytical level used; (4) underlying values leading to or away from integration; and, (5) the referent moment of time for society. These notions are discussed with reference to old age in one small-scale Melanesian society, Malo, Vanuatu.