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At least 1,063 records · Page 59Linked to original sources

Tissue-engineered bone for maxillary sinus augmentation.

PURPOSE: Autologous, allogenic, and alloplastic materials for bony reconstruction in the craniomaxillofacial region have specific drawbacks stimulating the ongoing search for new materials. Cultivated skin and mucosa grafts are in clinical routine use in head and neck reconstruction but so far, to the best of our knowledge, no successful clinical application has been described of periosteum-derived tissue-engineered bone for augmentation of the edentulous posterior maxilla. PATIENTS AND METHODS: In a clinical study, augmentation of the posterior maxilla was carried out using a bone matrix derived from mandibular periosteum cells on an Ethisorb (Ethicon, Norderstedt, Germany) fleece. In this report, we show the fabrication of the matrix, clinical application, and results in 27 patients. RESULTS: In 18 patients, an excellent clinical, radiologic, and histologic result could be proved 3 months after augmentation. Histologically, the bone biopsy samples from these patients revealed mineralized trabecular bone with remnants of the biomaterial. An unsuccessful result was found in 8 cases with a more extended augmentation procedure. The clinical inspection 3 months after augmentation showed almost no formation of new bone. In contrast, a replacement resorption with connective tissue was found. This may be the result of failure of the initial supply of the cells embedded within large cell-polymer constructs with sufficient oxygen and nutrients to sustain their survival and proliferation and allow for the integration of the developing tissue within the surrounding tissue. CONCLUSION: Our achieved results suggest that periosteum-derived osteoblasts on a suitable matrix can form lamellar bone within 3 months after transplantation and provide a reliable basis for simultaneous or secondary insertion of dental implants.

Alveolar Ridge Augmentation↗

Chitosan supports the expression of extracellular matrix proteins in human osteoblasts and chondrocytes.

The search for biocompatible materials that can support the growth and phenotypic expression of osteoblasts and chondrocytes is a major challenge in the application of tissue engineering techniques for the repair of bone and cartilage defects. Chitosan, a copolymer of glucosamine and N-acetylglucosamine, may provide an answer to this search. Chitosan is the deacetylated product of chitin, a ubiquitous biopolymer found in the exoskeleton of insects and marine invertebrates. Little is known about the utility of chitosan in propagating human osteoblasts and chondrocytes. In this study, we test the hypothesis that chitosan promotes the survival and function of osteoblasts and chondrocytes. Chitosan (4%, w/v in 2% HAc) was coated onto plastic coverslips that had been fitted into 24-well plates. Human osteoblasts and articular chondrocytes were seeded on either uncoated or chitosan-coated coverslips at 1 x 10(5)/cells per well. Cultures were incubated at 37 degrees C, 5% CO(2) for a period of 7 days. Cell viability was assessed at that time using a fluorescent molecular probe. The phenotypic expression of osteoblasts and chondrocytes was analyzed by reverse transcriptase-polymerase chain reaction and immunocytochemistry. Osteoblasts and chondrocytes appeared spherical and refractile on chitosan-coated coverslips. In contrast, greater than 90% of cells on plastic coverslips were elongated and spindle shaped after 7 days of culture. Similar to cells propagated on uncoated control wells, greater than 90% of human osteoblasts and chondrocytes propagated on chitosan remained viable. Human osteoblasts propagated on chitosan films continued to express collagen type I whereas chondrocytes expressed collagen type II and aggrecan, as shown by reverse transcriptase-polymerase chain reaction analysis and immunostaining. The present in vitro work demonstrates the biocompatibility of chitosan as a substrate for the growth and continued function of human osteoblasts and chondrocytes. Chitosan may have potential use as a tissue engineering tool for the repair of osseous and chondral defects.

Aggrecans↗

Engineering the serine/threonine protein kinase Raf-1 to utilise an orthogonal analogue of ATP substituted at the N6 position.

One key area of protein kinase research is the identification of cognate substrates. The search for substrates is hampered by problems in unambiguously assigning substrates to a particular kinase in vitro and in vivo. One solution to this impasse is to engineer the kinase of interest to accept an ATP analogue which is orthogonal (unable to fit into the ATP binding site) for the wild-type enzyme and the majority of other kinases. The acceptance of structurally modified, gamma-(32)P-labelled, nucleotide analogue by active site-modified kinase can provide a unique handle by which the direct substrates of any particular kinase can be displayed in crude mixtures or cell lysates. We have taken this approach with the serine/threonine kinase Raf-1, which plays an essential role in the transduction of stimuli through the Ras-->Raf-->MEK-->ERK/MAP kinase cascade. This cascade plays essential roles in proliferation, differentiation and apoptosis. Here we detail the mutagenesis strategy for the ATP binding pocket of Raf-1, such that it can utilise an N(6)-substituted ATP analogue. We show that these mutations do not alter the substrate specificity and signal transduction through Raf-1. We screen a library of analogues to identify which are orthogonal for Raf-1, and show that mutant Raf-1 can utilise the orthogonal analogue N(6)(2-phenethyl) ATP in vitro to phosphorylate its currently only accepted substrate MEK. Importantly we show that our approach can be used to tag putative direct substrates of Raf-1 kinase with (32)P-N(6)(2-phenethyl) ATP in cell lysates.

Adenosine Triphosphate↗

The case for a wet, warm climate on early Mars.

Theoretical arguments are presented in support of the idea that Mars possessed a dense CO2 atmosphere and a wet, warm climate early in its history. Calculations with a one-dimensional radiative-convective climate model indicate that CO2 pressures between 1 and 5 bars would have been required to keep the surface temperature above the freezing point of water early in the planet's history. The higher value corresponds to globally and orbitally averaged conditions and a 30% reduction in solar luminosity; the lower value corresponds to conditions at the equator during perihelion at times of high orbital eccentricity and the same reduced solar luminosity. The plausibility of such a CO2 greenhouse is tested by formulating a simple model of the CO2 geochemical cycle on early Mars. By appropriately scaling the rate of silicate weathering on present Earth, we estimate a weathering time constant of the order of several times 10(7) years for early Mars. Thus, a dense atmosphere could have persisted for a geologically significant time period (approximately 10(9) years) only if atmospheric CO2 was being continuously resupplied. The most likely mechanism by which this might have been accomplished is the thermal decomposition of carbonate rocks induced directly and indirectly (through burial) by intense, global-scale volcanism. For plausible values of the early heat flux, the recycling time constant is also of the order of several times 10(7) years. The amount of CO2 dissolved in standing bodies of water was probably small; thus, the total surficial CO2 inventory required to maintain these conditions was approximately 2 to 10 bars. The amount of CO2 in Mars' atmosphere would eventually have dwindled, and the climate cooled, as the planet's internal heat engine ran down. A test for this theory will be provided by spectroscopic searches for carbonates in Mars' crust.

Atmosphere↗

U.S. national response assets for radiological incidents.

The federal government has had the ability to respond to incidents of national significance for decades. Since 11 September 2001, there have been enhancements to existing federal assets and the creation of new federal assets. This presentation will provide an overview of the more significant federal assets. Pivotal to a response of national significance is the U.S. Department of Energy (DOE) Federal Radiological Monitoring and Assessment Center, which organizes and coordinates federal agency monitoring activities during an emergency. DOE manages the Federal Radiological Monitoring and Assessment Center during the emergency phase, and the Environmental Protection Agency (EPA) manages the response during the recovery phase once the emergency is terminated. EPA monitoring teams provide support during both the emergency and recovery phases of an emergency. Other DOE teams are available to respond to major nuclear power plant events, transportation accidents, or terrorism events involving the use of radiological materials, including the Radiological Assistance Program, the Aerial Measuring System, the National Atmospheric Release Advisory Center, and the Radiation Emergency Assistance Center/Training Site. For incidents involving a nuclear weapon, an improvised nuclear device, or a radiological dispersal device, DOE assets such as the Nuclear Emergency Support Team and the Accident Response Group could provide capabilities for weapon or device search, recovery, and removal. The Radiological Triage System harnesses the weapons scientists and engineers at the DOE national laboratories to provide gamma spectroscopy interpretation for agencies responding to an incident. In recent years, National Guard Weapons of Mass Destruction-Civil Support Teams have been created to support state and local response to terrorism events. The Civil Support Teams normally come under direct control of the state and can respond without requiring authorization from the U.S. Department of Defense (DoD). Changes brought about by the events of September 11 also extend to changing federal response policy and planning. Therefore, the Catastrophic Incident Response Annex to the National Response Plan is discussed. DoD also provides specifically designated radiological response capabilities that can be utilized within the guidelines of the National Response Plan. While optimally designed to support military missions, these resources also help provide for a well-equipped set of national assets to temporarily support and augment the local, state, and federal civil agencies that have primary authority and responsibility for domestic disaster assistance. The military's role in domestic emergencies is well defined in military regulations, as well as the national plan.

Civil Defense↗

[Database on natural and transgenic luminous microorganisms: "BiolumBase"].

The database "BiolumBase" is designed for the selection and systematization of available world information on microorganisms containing bioluminescent systems; it includes two sections: "natural" and "transgenic" luminous microorganisms. At present, logic schemes of divisions, classification of the objects, presentation of characteristics, and the inputs of relative information, as well as the necessary program modules including links to the database, are developed. The database is constructed on the basis of published data and our own experimental results; the subsequent linkage of the database to the Internet is envisaged. Users will be able to obtain not only the catalogues of strains but also information concerning the properties and functions of the known species of luminous bacteria, the structure, regulatory mechanisms, and application of bioluminescent systems and genetically engineered constructions with lux genes, as well as to find references and to search strains by using any set of attributes. The database will provide information that is of interest for the development of microbial ecology and biotechnology, in particular, for the prediction of biological hazard from the application of transgenic strains.

Bacteria↗

Soft tissue and hard tissue engineering in oral and maxillofacial surgery.

Autologous, allogenic and alloplastic materials for bony reconstruction in the cranio-maxillofacial area have specific drawbacks, thus stimulating the ongoing search for new (bio-) materials. Cultivated skin and mucosa grafts are in routine clinical use in head and neck reconstruction but so far, to the best of our knowledge, no successful clinical application has been described of periosteum-derived tissue-engineered bone for augmentation of the edentulous posterior maxilla. In a pilot clinical study, augmentation of the posterior maxilla was carried out using a bone matrix derived from mandibular periosteum cells on an Ethisorb fleece. In this paper we demonstrate the fabrication of the matrix, its clinical application, and histological results in two patients. Our results suggest that periosteum-derived osteoblasts on a suitable matrix can form lamellar bone within four months after transplantation and provide a reliable basis for implant insertion.

Alveolar Ridge Augmentation↗

Hybrid peptide-polyketide natural products: biosynthesis and prospects toward engineering novel molecules.

The structural and catalytic similarities between modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) inspired us to search for hybrid NRPS-PKS systems. By examining the biochemical and genetic data known to date for the biosynthesis of hybrid peptide-polyketide natural products, we show (1) that the same catalytic sites are conserved between the hybrid NRPS-PKS and normal NRPS or PKS systems, although the ketoacyl synthase domain in NRPS/PKS hybrids is unique, and (2) that specific interpolypeptide linkers exist at both the C- and N-termini of the NRPS and PKS proteins, which presumably play a critical role in facilitating the transfer of the growing peptide or polyketide intermediate between NRPS and PKS modules in hybrid NRPS-PKS systems. These findings provide new insights for intermodular communications in hybrid NRPS-PKS systems and should now be taken into consideration in engineering hybrid peptide-polyketide biosynthetic pathways for making novel "unnatural" natural products.

Amino Acid Sequence↗

In silico protein design by combinatorial assembly of protein building blocks.

Utilizing concepts of protein building blocks, we propose a de novo computational algorithm that is similar to combinatorial shuffling experiments. Our goal is to engineer new naturally occurring folds with low homology to existing proteins. A selected protein is first partitioned into its building blocks based on their compactness, degree of isolation from the rest of the structure, and hydrophobicity. Next, the protein building blocks are substituted by fragments taken from other proteins with overall low sequence identity, but with a similar hydrophobic/hydrophilic pattern and a high structural similarity. These criteria ensure that the designed protein has a similar fold, low sequence identity, and a good hydrophobic core compared with its native counterpart. Here, we have selected two proteins for engineering, protein G B1 domain and ubiquitin. The two engineered proteins share approximately 20% and approximately 25% amino acid sequence identities with their native counterparts, respectively. The stabilities of the engineered proteins are tested by explicit water molecular dynamics simulations. The algorithm implements a strategy of designing a protein using relatively stable fragments, with a high population time. Here, we have selected the fragments by searching for local minima along the polypeptide chain using the protein building block model. Such an approach provides a new method for engineering new proteins with similar folds and low homology.

Amino Acid Sequence↗

Oracle Database 10g: a platform for BLAST search and Regular Expression pattern matching in life sciences.

As database management systems expand their array of analytical functionality, they become powerful research engines for biomedical data analysis and drug discovery. Databases can hold most of the data types commonly required in life sciences and consequently can be used as flexible platforms for the implementation of knowledgebases. Performing data analysis in the database simplifies data management by minimizing the movement of data from disks to memory, allowing pre-filtering and post-processing of datasets, and enabling data to remain in a secure, highly available environment. This article describes the Oracle Database 10g implementation of BLAST and Regular Expression Searches and provides case studies of their usage in bioinformatics. http://www.oracle.com/technology/software/index.html.

Amino Acid Motifs↗

Research in physical medicine and rehabilitation X. Information resources.

Researchers in physical medicine and rehabilitation require access to information regarding possible interventions and programs, available services and technology, research (published, unpublished and in progress), statistics on incidence, prevalence and expected recovery, and funding sources. This paper provides an overview to the most readily available sources of information, including 16 abstracts and indexes, 6 sources of review articles, 9 population statistical databases and 84 journals specifically devoted to rehabilitation. Of these journals, 29 may be accessed through Medline and 32 through other sources. An additional 58 journals indexed in Medline publish more than 16 rehabilitation articles per year. The journals within Medline that publish the most rehabilitation articles are listed by topic area: geriatric rehabilitation, cardiac rehabilitation, pediatric rehabilitation, rehabilitation research, self-help devices, sports medicine and rheumatologic rehabilitation. Specific search strategies that may be used for any computer assisted search of Medline are given to locate articles in these topic areas and also the following areas: amputee rehabilitation, spinal cord injury rehabilitation, traumatic brain injury rehabilitation, cerebral palsy rehabilitation, stroke rehabilitation, decubitus care, electrodiagnosis, rehabilitation engineering, pain rehabilitation, pulmonary rehabilitation, sexual rehabilitation and urologic rehabilitation. The user friendly Grateful Med software is introduced for simplified online Medline searching. Exercises are provided for starting a journal club with the retrieved articles.

Humans↗

American pragmatism as a guide for professional ethical conduct for engineers.

The ethical choices faced by engineers today are increasingly complex. Competing and conflicting ethical demands from clients, communities, employees, and personal objectives combine to suggest that engineers employ ethical approaches that are adaptive yet grounded in three concrete professional circumstances: first, that engineers apply unique professional skills in the service of a client, subject to protecting the public interest; second, that engineers advance the state of knowledge of their professional field through reflection, research, and sharing experience in journals and conferences, and third, that they develop new professionals by active mentoring. This paper examines five features of American pragmatism and suggests that its emphasis on specific, context-based ethical decision making can assist engineers in a postmodern setting. In particular, it considers the venues of interpersonal ethical choices, institutional ethical conflicts, and social choices that have ethical components. Pragmatism suggests that in such a complex ethical climate, there is a need for the co-evolution of judgment and action, for individual reflective judgment in particular situations, and for ceasing to search for a single, immutable principle for ethical choice.

Engineering↗

Proline-dependent oligomerization with arm exchange.

BACKGROUND: Oligomerization is often necessary for protein activity or regulation and its efficiency is fundamental for the cell. The quaternary structure of a large number of oligomers consists of protomers tightly anchored to each other by exchanged arms or swapped domains. However, nothing is known about how the arms can be kept in a favourable conformation before such an oligomerization. RESULTS: Upon examination of such quaternary structures, we observe an extremely frequent occurrence of proline residues at the point where the arm leaves the protomer. Sequence alignment and site-directed mutagenesis confirm the importance of these prolines. The conservation of these residues at the hinge regions can be explained by the constraints that they impose on polypeptide conformation and dynamics: by rigidifying the mainchain, prolines favour extended conformations of arms thus favouring oligomerization, and may prevent interaction of the arms with the core of the protomer. CONCLUSIONS: Hinge prolines can be considered as 'quaternary structure helpers'. The presence of a proline should be considered when searching for a determinant of oligomerization with arm exchange and could be used to engineer synthetic oligomers or to displace a monomers to oligomers equilibrium by mutation of this proline residue.

Acetyltransferases↗

The SNP Consortium website: past, present and future.

The SNP Consortium website (http://snp.cshl.org) has undergone many changes since its initial conception three years ago. The database back end has been changed from the venerable ACeDB to the more scalable MySQL engine. Users can access the data via gene or single nucleotide polymorphism (SNP) keyword searches and browse or dump SNP data to textfiles. A graphical genome browsing interface shows SNPs mapped onto the genome assembly in the context of externally available gene predictions and other features. SNP allele frequency and genotype data are available via FTP-download and on individual SNP report web pages. SNP linkage maps are available for download and for browsing in a comparative map viewer. All software components of the data coordinating center (DCC) website (http://snp.cshl.org) are open source.

Chromosome Mapping↗

Biological data integration: wrapping data and tools.

Nowadays scientific data is inevitably digital and stored in a wide variety of formats in heterogeneous systems. Scientists need to access an integrated view of remote or local heterogeneous data sources with advanced data accessing, analyzing, and visualization tools. Building a digital library for scientific data requires accessing and manipulating data extracted from flat files or databases, documents retrieved from the Web as well as data generated by software. We present an approach to wrapping web data sources, databases, flat files, or data generated by tools through a database view mechanism. Generally, a wrapper has two tasks: it first sends a query to the source to retrieve data and, second builds the expected output with respect to the virtual structure. Our wrappers are composed of a retrieval component based on an intermediate object view mechanism called search views mapping the source capabilities to attributes, and an eXtensible Markup Language (XML) engine, respectively, to perform these two tasks. The originality of the approach consists of: 1) a generic view mechanism to access seamlessly data sources with limited capabilities and 2) the ability to wrap data sources as well as the useful specific tools they may provide. Our approach has been developed and demonstrated as part of the multidatabase system supporting queries via uniform object protocol model (OPM) interfaces.

Algorithms↗

Management of food allergy.

Our present options for the management of food allergy are avoidance and pharmacotherapy. There are, however, many promising perspectives for better future management such as the more extensive use of hydrolyzed and elemental formulas for therapy and prevention, or greater emphasis on diagnosis and treatment of accompanying diseases linked with increased gut permeability. In selected situations, specific immunotherapy might be helpful. Rapid progress is expected in the search for the conditions of induction of oral tolerance. The latest results in genetic engineering can give us very effective tools for mass production of less allergenic foods with high nutritional value--if all safety, stability, productivity, and antigenicity problems can be solved.

Food Hypersensitivity↗

Myoblast transplantation for inherited myopathies: a clinical approach.

Myoblast transplantation (MT) is an experimental strategy for the potential treatment of myopathies. MT has two properties that make it potentially beneficial: genetic complementation and myogenic potential. Preclinical experiments on monkeys have shown that promising results can be obtained with MT in large muscles of primates depending on two conditions: appropriate immunosuppression and cell delivery by a method of high-density injections. Preclinical work on MT is being, or may be, addressed to: develop efficient methods of donor cell delivery applicable to clinics; control or avoid acute rejection by methods with the fewest secondary effects; understand the factors that condition the early survival of donor cells following transplantation; increase the success of each individual injection; re-engineer a functional structure in muscles that degenerates to fibrosis and fat substitution; and search for precursor cells with potential advantages over myoblasts.

Animals↗