Molecular Modeling of Nucleic Acid Structure: Energy and Sampling

An overview of computer simulation techniques as applied to nucleic acid systems is presented. This unit expands an accompanying overview unit (UNIT ) by discussing methods used to treat the energy and sample representative configurations. Emphasis is placed on molecular mechanics and empirical force fields.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143698/1/cpnc0708.pd

Metabolic reconstruction of sulfur assimilation in the extremophile Acidithiobacillus ferrooxidans based on genome analysis

BACKGROUND: Acidithiobacillus ferrooxidans is a gamma-proteobacterium that lives at pH2 and obtains energy by the oxidation of sulfur and iron. It is used in the biomining industry for the recovery of metals and is one of the causative agents of acid mine drainage. Effective tools for the study of its genetics and physiology are not in widespread use and, despite considerable effort, an understanding of its unusual physiology remains at a rudimentary level. Nearly complete genome sequences of A. ferrooxidans are available from two public sources and we have exploited this information to reconstruct aspects of its sulfur metabolism. RESULTS: Two candidate mechanisms for sulfate uptake from the environment were detected but both belong to large paralogous families of membrane transporters and their identification remains tentative. Prospective genes, pathways and regulatory mechanisms were identified that are likely to be involved in the assimilation of sulfate into cysteine and in the formation of Fe-S centers. Genes and regulatory networks were also uncovered that may link sulfur assimilation with nitrogen fixation, hydrogen utilization and sulfur reduction. Potential pathways were identified for sulfation of extracellular metabolites that may possibly be involved in cellular attachment to pyrite, sulfur and other solid substrates. CONCLUSIONS: A bioinformatic analysis of the genome sequence of A. ferrooxidans has revealed candidate genes, metabolic process and control mechanisms potentially involved in aspects of sulfur metabolism. Metabolic modeling provides an important preliminary step in understanding the unusual physiology of this extremophile especially given the severe difficulties involved in its genetic manipulation and biochemical analysis

The Protein Data Bank: Present status and future plans

The Protein Data Bank (PDB) archival database of dimensional structures of biological macromolecules, an international resource facility, contains information on protein, DNA, RNA, virus and carbohydrate structures. While the vast majority of PDB entries represent crystal structures, results from NMR and theoretical modeling strudies also are included. PDB, which in July 1992 contained 957 atomic coordinate entries, currently is experiencing a time of explosive growth. The present deposition rate is ca. 50 structures per month, doubling in less than two years. Responding to the challenge posed by this. rising data flow, over the past 18 months PDB has attracted increased funding to implement important enhancements of the resource. A rapid pre-release of entries pending for input was inaugurated in April 1992, and a substantial fraction of the accumulated backlog of pending entries is now available via FTP and e-mail in prerelease form. Extrapolation of current data rates suggests that by the year 2000 PDB may contain over 25,000 structures. PDB`s plans, to manage this voluminous amount of data, include the development of PDB-AUTHORIN software to allow depositors to do most of the preparation and validation of their own entries, and a comprehensive upgrade of PDB contents to add new data items and convert the current interchange format to the Crystallographic Information File (CIF) standard established by the International Union of Crystallography (IUCr)

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62798/1/409860a0.pd

Experience in using workstations as hosts in an accelerator control environment

A new control system has been used for light ion acceleration at the Alternating Gradient Synchrotron (AGS). The control system uses Apollo workstations in the dual role of console hardware computer and controls system host. It has been found that having a powerful dedicated CPU with a demand paging virtual memory OS featuring strong interprocess communication, mapped memory shared files, shared code, and multi-window capabilities, allows us to provide an efficient operation environment in which users may view and manage several control processes simultaneously. The same features which make workstations good console computers also provide an outstanding platform for code development. The software for the system, consisting of about 30K lines of ''C'' code, was developed on schedule, ready for light ion commissioning. System development is continuing with work being done on applications programs

Burden of nonsteroidal anti-inflammatory and antiplatelet drug use in Asia: a multidisciplinary working party report

BACKGROUND & AIMS: We established a working group to examine the burden of atherothrombotic and musculoskeletal diseases in Asia and made recommendations for safer prescribing of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. METHODS: By using a modified Delphi process, consensus was reached among 12 multidisciplinary experts from Asia. Statements were developed by the steering committee after a literature review, modified, and then approved through 3 rounds of anonymous voting by using a 6-point scale from A+ (strongly agree) to D+ (strongly disagree). Agreement (A+/A) by >/= 80 of panelists was defined a priori as consensus. RESULTS: We identified unique aspects of atherothrombotic and musculoskeletal diseases in Asia. Asia has a lower prevalence of degenerative arthritis and coronary artery disease than Western countries. The age-adjusted mortality of coronary artery disease is lower in Asia; cerebrovascular accident has higher mortality than coronary artery disease. Ischemia has replaced hemorrhage as the predominant pattern of cerebrovascular accident. Low-dose aspirin use is less prevalent in Asia than in Western countries. Traditional Chinese medicine and mucoprotective agents are commonly used in Asia, but their efficacy is not established. For Asian populations, little is known about complications of the lower gastrointestinal tract from use of NSAIDs and underutilization of gastroprotective agents. Our recommendations for preventing ulcer bleeding among users of these drugs who are at high risk for these complications were largely derived from Asian studies and are similar to Western guidelines. CONCLUSIONS: By using an evidence-based, multidisciplinary approach, we have identified unique aspects of musculoskeletal and atherothrombotic diseases and strategies for preventing NSAID-related and low-dose aspirin-related gastrointestinal toxicity in Asia