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PubMed2006

Mouse models for human head and neck squamous cell carcinomas.

Mouse models of human cancer play an important role in understanding the mechanisms of carcinogenesis and have accelerated the search for finding new molecular targets for cancer therapy. However, genetically engineered mouse models for head and neck squamous cell carcinoma (HNSCC) have only recently overcome major technical obstacles and begun to be explored. Here we review the current progress in the development of mouse models for human HNSCC, with emphasis on conditional transgenic and knockout mouse models. These new models faithfully recapitulate human HNSCC at both the pathologic and molecular levels. These animal models will not only be useful to define the roles of specific genes in HNSCC development and progression but will also provide a unique tool for developing and testing new therapeutic approaches.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

Hirudin as alternative anticoagulant--a historical review.

Advances in separation techniques and biotechnology have contributed to the development of anticoagulant agents from hematophagous animals. The most potent known natural thrombin inhibitor from blood-sucking leeches ( Hirudo medicinalis), hirudin has served as a standard for designing the natural coagulation inhibitors as an anticoagulant drug. The search for the development of hirudin from leech extract to genetically engineered products as an alternative anticoagulant has been resumed. The pharmacological profiling of the isolated thrombin inhibitor has shown that native hirudin is an antithrombotic agent of high quality. However, its clinical use has remained limited, because the substance has not been available in adequate amounts. The progress in molecular biology has stimulated the interest in the structure and function of hirudin. This development resulted in the production of recombinant hirudins (r-hirudins) through gene technology. The biological properties of hirudin combined with the ready availability of recombinant forms make the specific thrombin inhibitor well-suited for use as an antithrombotic drug. Its use should lead to a decisive progress in the management of thromboembolic diseases of both arterial and venous origin. Clinical trials, especially in diseases in which thrombin plays a crucial role, are in progress.

Amino Acid Sequence↗

PubMed1996

Rapid construction in yeast of complex targeting vectors for gene manipulation in the mouse.

Targeting vectors for embryonic stem (ES) cells typically contain a mouse gene segment of >7 kb with the neo gene inserted for positive selection of the targeting event. More complex targeting vectors carry additional genetic elements (e.g. lacZ, loxP, point mutations). Here we use homologous recombination in yeast to construct targeting vectors for the incorporation of genetic elements (GEs) into mouse genes. The precise insertion of GEs into any position of a mouse gene segment cloned in an Escherichia coli/yeast shuttle vector is directed by short recombinogenic arms (RAs) flanking the GEs. In this way, complex targeting vectors can be engineered with considerable ease and speed, obviating extensive gene mapping in search for suitable restriction sites.

Animals↗

PubMedDate not supplied

Sources of clinical engineering employment information.

Information regarding Clinical Engineering employment opportunities is scattered among many sources. There are many paths that can be followed in searching for employment. This article contains a collection and discussion of these sources, and paths to employment, written from the viewpoint of a student or a recent graduate looking for a Clinical Engineering position.

Biomedical Engineering↗

PubMed2002

Interaction of chondrocytes, extracellular matrix and growth factors: relevance for articular cartilage tissue engineering.

UNLABELLED: The abundant extracellular matrix of articular cartilage has to be maintained by a limited number of chondrocytes. Vice versa, the extracellular matrix has an important role in the regulation of chondrocyte function. OBJECTIVE: In this review we discuss the role of the extracellular matrix in the regulation of chondrocyte function and the relevance for cartilage tissue engineering. To reach this goal the international literature on this subject has been searched with a major focus on the last 5 years. RESULTS: Structural matrix macromolecules (e.g. collagen, hyaluronate), but also growth factors (e.g. IGF-I, TGF beta) entrapped in the matrix and released under specific conditions affect chondrocyte behavior. These factors communicate with the chondrocyte via specific membrane receptors. In this way there is a close interaction between the extracellular and intracellular milieu. Articular cartilage has a limited capacity of intrinsic repair, which has resulted in the development of tissue engineering approaches to repair damaged cartilage. Successful application of scaffolds has to take into account the important role of both soluble and insoluble matrix-derived factors in cartilage homeostasis. CONCLUSION: Functional tissue engineering will only be realized when the scaffolds used will provide cartilage cells with the correct extracellular signals.

Annexins↗

PubMed2004

Recent advances in liver-directed gene transfer vectors.

BACKGROUND: Gene therapy as part of modern molecular medicine holds great promise for the treatment of hepatocellular carcinoma (HCC) and has the potential to bring a revolutionary era to cancer treatment. For the past decade various viral and non-viral vectors have been engineered for improved liver gene therapy. DATA RESOURCES: An English-language literature search using MEDLINE (2004), Index Medicus (2004) and bibliographic reviews of books and review articles. Liver-directed gene transfer vectors and their history and recent clinical applications. RESULTS: The ultimate goal of liver-directed gene therapy for HCC is the stable expression of a therapeutic transgene in a significant proportion of hepatocytes. The design of a vector system providing efficient and stable gene engraftment and expression in human hepatocytes is still a challenging issue. The advantages and disadvantages of the genetically engineered vector of viral or non-viral origin are discussed with respect to their essential relevance. CONCLUSION: Liver gene therapy has a long way to go and efficient and innocuous liver-directed gene transfer vectors are therefore urgently required.

Animals↗

PubMed1997

Application of a deductive database system to search for topological and similar three-dimensional structures in protein.

A deductive database system PACADE (Protein Atomic Coordinate Analyzer with Deductive Engine) has been developed for protein structure analysis. With this system, super-secondary structures described in logical and declarative rules can be retrieved effectively. For protein structure analysis, comparison of local structures in different proteins is a necessary mean. A function to search for similar structures has, therefore, been added to the PACADE system. We describe herein the result of searches for the same topological structures and three-dimensionally similar ones. A user of PACADE can select these two levels of similarity by changing parameters. This function enables the inference system to retrieve similar structures, according to the restraints of variables defined by the user. Similar super-secondary structures among proteins can be searched for automatically, which is useful for protein structure analysis. The retrieved similar super-secondary structures can serve as criteria for protein spatial alignment.

Algorithms↗

PubMed2003

The space elevator: a new tool for space studies.

The objective has been to develop a viable scenario for the construction, deployment and operation of a space elevator using current or near future technology. This effort has been primarily a paper study with several experimental tests of specific systems. Computer simulations, engineering designs, literature studies and inclusion of existing programs have been utilized to produce a design for the first space elevator. The results from this effort illustrate a viable design using current and near-term technology for the construction of the first space elevator. The timeline for possible construction is within the coming decades and estimated costs are less than $10 B. The initial elevator would have a 5 ton/day capacity and operating costs near $100/lb for payloads going to any Earth orbit or traveling to the Moon, Mars, Venus or the asteroids. An operational space elevator would allow for larger and much longer-term biological space studies at selectable gravity levels. The high-capacity and low operational cost of this system would also allow for inexpensive searches for life throughout our solar system and the first tests of environmental engineering. This work is supported by a grant from the NASA Institute for Advanced Concepts (NIAC).

Acceleration↗

PubMed2002

Fulfilling the promise of biotechnology.

Genetic engineering has produced pharmaceuticals, disease-resistant plants, cloned animals and research and industrial products. While the comparably mature field of medical biotechnology now reveals its true potential, marine biotechnology is still in the realm of the future. As we explore the earth for new sources of natural chemicals, we now search the waters. Myriad organisms, most unknown to us, live there. Many produce compounds that can be commercialized, or the organisms themselves may be commercialized, through genetic engineering methods. For decades, scientists studied the ocean depths searching for unique molecules and organisms. But not until the early 1980s was there a synthesis uniting marine natural products, ecology, aquaculture and bioremediation research under the heading of marine biotechnology. As harvesting enough products from marine sources to produce sufficient amounts, even for study, is nearly impossible, we need to use genomics techniques to identify biologically active compounds. As we damage our oceanic ecosystems through pollution, overfishing and destructive fishing methods, opportunities to learn more about marine organisms and their commercial potential may be limited. Although governments and intergovernmental agencies are committed to funding and expanding oceanic research, more funding is needed to discover and study the ocean's vast, unplumbed resources.

Journal Article↗

PubMed1986

Radioimmunotherapy of malignancy using antibody targeted radionuclides.

Antibodies directed against tumour associated antigens provide a means for delivering preferentially cytotoxic radionuclides to the cells of primary and secondary tumours. The factors that influence the effectiveness of the radiation in the tumour compared with its effect on the radiosensitive normal tissues include the specificity of the antibody, the distribution of targeted energy within the tumour and the host's response to the injected foreign antibody. Recently some encouraging results from clinical trials of radioimmunotherapy have been reported in the literature. There is a continual search for more avid and specific antibodies, and the techniques of genetic engineering are being applied to the problem of reducing the antigenicity and mass of the carrier antibody. The improved efficiency of the labelled antibody needs to be supplemented by an identification of those tumours most likely to respond to this form of therapy.

Animals↗

PubMed2000

HELM: searching for helix motifs within protein sequences.

SUMMARY: HELM is a web tool designed to automate the analysis of protein sequences searching for alpha helix motifs. This analysis can be useful in protein engineering studies, aimed at the identification of regions to be modified in order to obtain more suitable features of local and/or global stability. AVAILABILITY: The tool is available to academic and commercial institutions at the URL http://crisceb.area.na.cnr.it/angelo/ PROTEIN_TOOLS/HELM/ CONTACT: angelo@crisceb.area.na.cnr.it

Amino Acid Motifs↗

PubMed2025

Phylogeny, chromosomal mapping and expression analyses of wheat CLAVATA pathway components suggest differential selection on receptor-like kinases, CLEs and T3 WOXes.

Ensuring continuous global food security is a major challenge of the 21st century. Wheat contributes approximately 20% of the total calories consumed by humans, and an estimated 60% increase in production will be required by 2050 to meet forecast global demand. In cereals like wheat, inflorescence (ear) size and branching patterns determine the number of flowers (florets) and grains produced, and these aspects of plant architecture are regulated by the activity of stem cells in the growing shoot tips. CLAVATA peptide and receptor-like kinase signalling regulates angiosperm stem cell activity, and as changes in CLAVATA function can improve crop yields, CLAVATA is a key target for reverse engineering. Here, we identify components of the wheat CLAVATA pathway using genome searches against Triticum aestivum and its wild relatives Triticum turgidum ssp. durum, Triticum turgidum ssp. dicoccoides, Triticum urartu and Aegilops tauschii. Using phylogenetic and synteny analysis, we determine the relationship between homoeologues and infer patterns of gene family evolution. Whilst CLAVATA1, BARELY ANY MERISTEM, RECEPTOR-LIKE PROTEIN KINASE 2, CORYNE and CLAVATA2 receptor-like kinase homologues are mainly present as single genome copies as in other grasses, CLAVATA3-like but not TRACHEARY ELEMENT DIFFERENTIATION FACTOR (TDIF)-like peptide encoding genes and WUSCHEL-LIKE HOMEOBOX (WOX) genes have expanded copy numbers with many gene gains and losses during evolution. Our results highlight wheat CLAVATA pathway components for reverse genetic analysis and indicate potential differential selection on wheat receptor-like kinases, their peptide ligands and WOXes.

Triticum↗

PubMed2002

[Tissue-engineered auricled cartilage: an experimental study].

OBJECTIVE: To study the feasibility of engineering auricled neocartilage with chitosan/polylacticacid-polycrylactone (PLA-PCL) network scaffolds and to search the difference between dynamic and silent chondrocytal culture techniques. METHODS: Chondrocytes from auricled cartilage of 4 weeks old New Zealand White rabbit were seeded onto chitosan/PLA-PCL network. Ten cell-polymer scaffolds were divided into two groups: dynamic group (n1 = 5) with rotating bioreactors and silent group (n2 = 5) with ordinary dishes to culture. Using scan electroscope, grossly histological and immunohistological techniques, the morphological evaluation was done individually at 1st week in vitro, 4th and 8th week in vivo. RESULTS: Chondrocytes adhered and grew up well on the network, but more quantities of chondrocytes, Glycoaminoglygan (GAG) and type II collagen were found in dynamic group. There was an obvious difference between dynamic and silent group (P < 0.05). CONCLUSION: Chitosan/PLA-PCL network scaffold is good for adhesions and growth of chondrocytes. Furthermore, dynamic cell culture method is better than silent method for formation of neocartilage.

Animals↗

PubMed1994

Artificial intelligence within the chemical laboratory.

Various techniques within the area of artificial intelligence such as expert systems and neural networks may play a role during the problem-solving processes within the clinical biochemical laboratory. Neural network analysis provides a non-algorithmic approach to information processing, which results in the ability of the computer to form associations and to recognize patterns or classes among data. It belongs to the machine learning techniques which also include probabilistic techniques such as discriminant function analysis and logistic regression and information theoretical techniques. These techniques may be used to extract knowledge from example patients to optimize decision limits and identify clinically important laboratory quantities. An expert system may be defined as a computer program that can give advice in a well-defined area of expertise and is able to explain its reasoning. Declarative knowledge consists of statements about logical or empirical relationships between things. Expert systems typically separate declarative knowledge residing in a knowledge base from the inference engine: an algorithm that dynamically directs and controls the system when it searches its knowledge base. A tool is an expert system without a knowledge base. The developer of an expert system uses a tool by entering knowledge into the system. Many, if not the majority of problems encountered at the laboratory level are procedural. A problem is procedural if it is possible to write up a step-by-step description of the expert's work or if it can be represented by a decision tree. To solve problems of this type only small expert system tools and/or conventional programming are required.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial Intelligence↗

PubMed1996

Palingol: a declarative programming language to describe nucleic acids' secondary structures and to scan sequence database.

At the DNA/RNA level, biological signals are defined by a combination of spatial structures and sequence motifs. Until now, few attempts had been made in writing general purpose search programs that take into account both sequence and structure criteria. Indeed, the most successful structure scanning programs are usually dedicated to particular structures and are written using general purpose programming languages through a complex and time consuming process where the biological problem of defining the structure and the computer engineering problem of looking for it are intimately intertwined. In this paper, we describe a general representation of structures, suitable for database scanning, together with a programming language, Palingol, designed to manipulate it. Palingol has specific data types, corresponding to structural elements-basically helices-that can be arranged in any way to form a complex structure. As a consequence of the declarative approach used in Palingol, the user should only focus on 'what to search for' while the language engine takes care of 'how to look for it'. Therefore, it becomes simpler to write a scanning program and the structural constraints that define the required structure are more clearly identified.

Base Sequence↗

PubMed2006

Spatial confidentiality and GIS: re-engineering mortality locations from published maps about Hurricane Katrina.

BACKGROUND: Geographic Information Systems (GIS) can provide valuable insight into patterns of human activity. Online spatial display applications, such as Google Earth, can democratise this information by disseminating it to the general public. Although this is a generally positive advance for society, there is a legitimate concern involving the disclosure of confidential information through spatial display. Although guidelines exist for aggregated data, little has been written concerning the display of point level information. The concern is that a map containing points representing cases of cancer or an infectious disease, could be re-engineered back to identify an actual residence. This risk is investigated using point mortality locations from Hurricane Katrina re-engineered from a map published in the Baton Rouge Advocate newspaper, and a field team validating these residences using search and rescue building markings. RESULTS: We show that the residence of an individual, visualized as a generalized point covering approximately one and half city blocks on a map, can be re-engineered back to identify the actual house location, or at least a close neighbour, even if the map contains little spatial reference information. The degree of re-engineering success is also shown to depend on the urban characteristic of the neighborhood. CONCLUSION: The results in this paper suggest a need to re-evaluate current guidelines for the display of point (address level) data. Examples of other point maps displaying health data extracted from the academic literature are presented where a similar re-engineering approach might cause concern with respect to violating confidentiality. More research is also needed into the role urban structure plays in the accuracy of re-engineering. We suggest that health and spatial scientists should be proactive and suggest a series of point level spatial confidentiality guidelines before governmental decisions are made which may be reactionary toward the threat of revealing confidential information, thereby imposing draconian limits on research using a GIS.

Confidentiality↗

PubMed2002

Bacterial alkaline proteases: molecular approaches and industrial applications.

Proteolytic enzymes are ubiquitous in occurrence, being found in all living organisms, and are essential for cell growth and differentiation. The extracellular proteases are of commercial value and find multiple applications in various industrial sectors. Although there are many microbial sources available for producing proteases, only a few are recognized as commercial producers. A good number of bacterial alkaline proteases are commercially available, such as subtilisin Carlsberg, subtilisin BPN' and Savinase, with their major application as detergent enzymes. However, mutations have led to newer protease preparations with improved catalytic efficiency and better stability towards temperature, oxidizing agents and changing wash conditions. Many newer preparations, such as Durazym, Maxapem and Purafect, have been produced, using techniques of site-directed mutagenesis and/or random mutagenesis. Directed evolution has also paved the way to a great variety of subtilisin variants with better specificities and stability. Molecular imprinting through conditional lyophilization is coming up to match molecular approaches in protein engineering. There are many possibilities for modifying biocatalysts through molecular approaches. However, the search for microbial sources of novel alkaline proteases in natural diversity through the "metagenome" approach is targeting a hitherto undiscovered wealth of molecular diversity. This fascinating development will allow the biotechnological exploitation of uncultured microorganisms, which by far outnumber the species accessible by cultivation, regardless of the habitat. In this review, we discuss the types and sources of proteases, protease yield-improvement methods, the use of new methods for developing novel proteases and applications of alkaline proteases in industrial sectors, with an overview on the use of alkaline proteases in the detergent industry.

Amino Acid Sequence↗

PubMed2004

Geotechnical engineering properties of incinerator ash mixes.

The incineration of solid waste produces large quantities of bottom and fly ash. Landfilling has been the primary mode of disposal of these waste materials. Shortage in landfill space and the high cost of treatment have, however, prompted the search for alternative uses of these waste materials. This study presents an experimental program that was conducted to determine the engineering properties of incinerator ash mixes for use as construction materials. Incinerator ash mixes were tested as received and around optimum compacted conditions. Compaction curves, shear strength, and permeability values of fly ash, bottom ash, and their various blends were investigated. Bottom ash tends to achieve maximum dry density at much lower water content than does fly ash. The mixes displayed a change in their cohesion and friction angle values when one of the two mix components was altered or as a result of the addition of water. The permeability of bottom ash is quite comparable to that of sand. The permeability of fly ash lies in the range of those values obtained for silts and clays. A 100% bottom ash compacted at the optimum water content has a lower density value and yields a higher friction angle and cohesion values than most construction fills. This would encourage the use of bottom ash as a fill or embankment material because free drainage of water will prevent the buildup of pore water pressures.

Carbon↗