Methadone maintenance treatment and drugs

The mental and physical capabilities of drivers in traffic are often seriously challenged these days. Not only do they need to concentrate on driving, predict connections between various phenomena, take appropriate judgements in current situations and foresee the sequence of measures to be taken, but they are also expected to be emotionally stable, etc. The problem with drugs in traffic is often encountered when assessing the actual safe driving capability of a person in a given moment, for example after a car accident or a police check, or medical check-ups that are required for a driving license. The Road Traffic Safety Law considers methadone a drug. Drug addicts do not meet the health standards required of drivers. This research program deals with the attitude of drivers who are in methadone maintenance treatment programs with respect to the driving ability as well as the effects of methadone use in combination with other drugs on driving. It has been established that drivers undergoing the methadone maintenance program, regularly drive not only under the influence of methadone but also under the influence of marijuana (20%) and heroin (18%) and sometimes under the influence of marijuana (58.6%), heroin (55.7%), and alcohol (48.6%). Certain initiatives have been taken by some therapists to give, under certain circumstances, a clean bill of health to responsible methadone maintenance patients who have an adequate level of responsibility for themselves and their deeds, in order to help them obtain a driving license. Since it has been established that methadone maintenance patients use methadone quite commonly in combination with illegal drugs and/or alcohol, the classification of this type of addicts among possible driving candidates remains disputable. Long term interdisciplinary research is still required to determine the basic principles required to asses and possibly admit this type of drivers to participate in traffic, as well as to determine which professional therapists can participate and evaluate the driving capabilities of these patients.     

Automation of conformational analysis and other molecular modeling calculations

A software system has been developed for facilitating modeling calculations on large numbers of molecules. Using the system, it is possible to subject one or more molecules to a series of calculations, each requiring use of a different computer program. No user intervention is required: where necessary, output from one program is used automatically as input to the next. Names are assigned to output files automatically and in a systematic manner. As an example, the system can be used to perform a succession of calculations aimed at identifying the major low-energy conformers of each of a set of molecules, starting only from their chemical connectivities. The reliability of the results has been tested by calculations on 40 molecules taken from the Cambridge Structural Database. The observed crystal structure geometry could be found for the majority of these molecules.     

The STRESS program: A computer program for the analysis of stresses in long bones

A computer program was developed to compute torsional and bending stresses in long bones. The input format for the program is designed to be as convenient to the user as possible, allowing him to transmit to the program only as many points as he feels are required to describe the cross-sectional geometry. The program permits the user to specify by which method torsional stresses are to be computed, what type of stresses are to be computed, and to what accuracy the results are desired. Computation times are of the order of 5 sec or less (on an IBM 360), making use of the program more economical than manual computations.     

One third of a million days of care at home, 1959 to 1975.

Although articles on studies of organized home care programs are numerous, reports of long-term effectiveness of these programs are scanty. While government spokesmen appear to advocate more widespread use of alternatives to hospitalization, there has been serious criticism of the efficiency and accomplishments of home care services. A medically oriented home care program in Saskatoon (population, less than 150 000) has grown steadily over a 16-year period and is now serving a daily average of 200 individuals. All patients have required "hospital-like care" at home and most have not ordinarily been sufficiently mobile during their time in the program to attend hospital outpatient services. Many have required "concentrated care" through daily visits of professional health personnel. The program is designed for the physically ill and disabled and is administered by the major teaching hospital in the city, although it provides services to the whole community. Over one third of the patients referred in recent years had been at home. Almost one half of the patients have undergone satisfactory rehabilitation at home. The program has also proven to be an acceptable alternative to long-term institutional care for the permanently seriously disabled, a large number of whom are elderly. The program has been able to operate at considerably less cost to the public than inpatient (hospital or institutional) services would have entailed.     

CheckShift: automatic correction of inconsistent chemical shift referencing

The construction of a consistent protein chemical shift database is an important step toward making more extensive use of this data in structural studies. Unfortunately, progress in this direction has been hampered by the quality of the available data, particularly with respect to chemical shift referencing, which is often either inaccurate or inconsistently annotated. Preprocessing of the data is therefore required to detect and correct referencing errors. We have developed a program for performing this task, based on the comparison of reported and expected chemical shift distributions. This program, named CheckShift, does not require additional data and is therefore applicable to data sets where structures are not available. Therefore CheckShift provides the possibility to re-reference chemical shifts prior to their use as structural constraints.     

HLA serum screening based on an heuristic solution of the set cover problem.

A computer program initially written by the Milwaukee Blood Bank has been modified to use a new algorithm for the assignment of HLA specificities to antisera. The assignment is based on the reactions of cells with known specificities. Specificities which are present only on cells which do not react are first ruled out. This step is followed by one or more steps in which the 'least reactive' specificities are ruled out. The rationale for the algorithm is discussed and an example is presented.     

Host-cell-determined methylation of specific Epstein-Barr virus promoters regulates the choice between distinct viral latency programs.

Epstein-Barr virus (EBV) is capable of adopting three distinct forms of latency: the type III latency program, in which six EBV-encoded nuclear antigens (EBNAs) are expressed, and the type I and type II latency programs, in which only a single viral nuclear protein, EBNA1, is produced. Several groups have reported heavy CpG methylation of the EBV genome in Burkitt's lymphoma cell lines which maintain type I latency, and loss of viral genome methylation in tumor cell lines has been correlated with a switch to type III latency. Here, evidence that the type III latency program must be inactivated by methylation to allow EBV to enter the type I or type II restricted latency program is provided. The data demonstrates that the EBNA1 gene promoter, Qp, active in types I and II latency, is encompassed by a CpG island which is protected from methylation. CpG methylation inactivates the type III latency program and consequently allows the type I or II latency program to operate by alleviating EBNA1-mediated repression of Qp. Methylation of the type III latency EBNA gene promoter, Cp, appears to be essential to prevent type III latency, since EBNA1 is expressed in all latently infected cells and, as shown here, is the only viral antigen required for activation of Cp. EBV is thus a pathogen which subverts host-cell-determined methylation to regulate distinct genetic programs.     

A computer program for selection of oligonucleotide primers for polymerase chain reactions.

We have designed a computer program which rapidly scans nucleic acid sequences to select all possible pairs of oligonucleotides suitable for use as primers to direct efficient DNA amplification by the polymerase chain reaction. This program is based on a set of rules which define in generic terms both the sequence composition of the primers and the amplified region of DNA. These rules (1) enhance primer-to-target sequence hybridization avidity at critical 3'-end extension initiation sites, (2) facilitate attainment of full length extension during the 72 degrees C phase, by minimizing generation of incomplete or nonspecific product and (3) limit primer losses occurring from primer-self or primer-primer homologies. Three examples of primer sets chosen by the program that correctly amplified the target regions starting from RNA are shown. This program should facilitate the rapid selection of effective and specific primers from long gene sequences while providing a flexible choice of various primers to focus study on particular regions of interest.     

Microcomputer simulation of steady-state enzyme kinetics for educational purposes

A BASIC program to assist the instruction of steady-state enzymekinetics has been developed for the IBM PC microcomputer. Itspurpose is to simulate laboratory experiments in order to minimizethe time required to obtain kinetic data from which studentsdeduce kinetic mechanisms and determine kinetic constants ofenzyme-catalyzed reactions. The program randomly selects a kineticscheme from various sequential, ping pong, and iso reactionsequences as well as values for the kinetic constants. The schemeand kinetic constants are unknown to the student at this time;the only thing he or she knows is the stoichiometry of the catalyzedreaction which can have two or three substrates and products.The student is prompted to enter values for concentrations ofsubstrates and products; several different concentrations foreach substrate and product can be entered in a single experiment.The program then calculates, displays and prints (if desired)the corresponding initial steadystate velocities. The studentcan perform as many experiments as desired until enough informationis obtained to determine the kinetic mechanism and to calculatevalues for the kinetic constants. Received on March 10, 1986; accepted on May 6, 1986     

siRNA pro 2.0：siRNA理性设计在线程序

siRNA作为基因功能研究和临床治疗的重要工具,已经引起了科学界的广泛关注,世界上许多学术和商业机构也开发了相应的siRNA设计程序.近年来,随着对siRNA机制研究的不断深入,尤其是2004年Reynolds提出siRNA理性设计规则之后,许多新的理论极大地推动了siRNA设计程序的发展.本文根据2003至2006年以来对siRNA机制的研究进展,在原有的设计程序siRNA pro的基础上进行了更新并推出了2.0版,为siRNA作用机制的研究和siRNA相关产品的开发提供更优质的理性设计服务.     

A nonlinear regression program for small computers

A BASIC computer program for performing weighted nonlinear regression is described and a listing of the program is given. The program, which is small and simple to use, has been designed to be run by users with little knowledge of mathematics or computers. Robust methods of analysis are described which may be applied to data in which experimental errors are not normally distributed, and the program incorporates one such method. It is shown that the program is useful for the analysis of data conforming to the Michaelis-Menten equation, a single exponential, and to binding equations, and other applications are discussed.     

Generation of density gradients. Approximations to equivolumetric gradients for zonal rotors

The use of a “density gradient generating function” allows the concentration profile of a density gradient to be written explicitly in terms of the required distribution of sedimentation coefficients in place of the previous implicit formulations. This function, which is easily implemented in a computer program, permits calculation of density gradients for a number of applications. This approach is applied to computation of a variety of equivolumetric gradients of sucrose for zonal rotors and yields a formula for the calibration of such gradients. An accurate approximation has been found which allows the generation of virtually all equivolumetric gradients of sucrose for a given rotor using a single program for the gradient generator employed; the adjustment for different particle densities and for different concentrations at the top of the gradient is made by varying only the initial and final concentrations of sucrose used.     

The Event Book System: A Community-based Natural Resource Monitoring System from Namibia

Namibia's Community Based Natural Resource Management program is a joint venture between government, national non-governmental organisations and rural communities. A component of the program involves communities in monitoring various aspects of their conservancy, ranging from wildlife numbers, through economic returns, to patrolling records and infringements of the rules. A main feature of community monitoring is the Event Book System, which differs from conventional monitoring in that the community dictates what needs to be monitored, and scientists only facilitate the design process and conservancy members undertake all data analysis. The system has been adopted with good results by more than 30 communal conservancies in Namibia, covering almost seven million ha, and is now also being piloted in six national parks. Continued emphasis is needed on enhancing community interpretation and use of data for active adaptive management, particularly where conservancy leaders are transient due to the democratic nature of local organizations. Moreover, because the system is driven by local priorities, it does not cover all aspects of a comprehensive biodiversity monitoring programme. Where society deems other biodiversity values worth monitoring, conservancies must either be willingly persuaded to act on this, or external systems must be established to cater for these needs. If a community already has a monitoring system of its own, a win–win solution might be for the community to be sub-contracted to undertake these ȁ8external modules' on behalf of national agencies.     

INTROnSPECTIVE and NORA: computerized compositional characterization of regions within introns and around start codons on the basis of non-randomness analysis

Non-randomness analysis has recently proven a valuable method in the characterization of chromosomes and genomes with respect to the nucleotides around start codons. This methodology has been implemented in a distributable program NORA, which is presented as freeware for users in academia. Moreover, because the current knowledge about introns is limited, another application, INTROnSPECTIVE, has been developed. This application analyzes introns in either direction (from 5' to 3' or from 3' to 5') and the user has the option to exclude introns on the basis of their size or intron number within the gene. Both programs are based on initial parsing of GenBank flatfiles, i.e., with these programs, entire genomes or chromosomes can be parsed and characterized within seconds. The programs run under 32-bit Windows operating systems and can be obtained via . They are the only ones available which perform non-randomness analysis, and INTROnSPECTIVE represents a comprehensive and novel methodology for the study of introns.     

Mathematical properties of neuronal TD-rules and differential Hebbian learning: a comparison

A confusingly wide variety of temporally asymmetric learning rules exists related to reinforcement learning and/or to spike-timing dependent plasticity, many of which look exceedingly similar, while displaying strongly different behavior. These rules often find their use in control tasks, for example in robotics and for this rigorous convergence and numerical stability is required. The goal of this article is to review these rules and compare them to provide a better overview over their different properties. Two main classes will be discussed: temporal difference (TD) rules and correlation based (differential hebbian) rules and some transition cases. In general we will focus on neuronal implementations with changeable synaptic weights and a time-continuous representation of activity. In a machine learning (non-neuronal) context, for TD-learning a solid mathematical theory has existed since several years. This can partly be transfered to a neuronal framework, too. On the other hand, only now a more complete theory has also emerged for differential Hebb rules. In general rules differ by their convergence conditions and their numerical stability, which can lead to very undesirable behavior, when wanting to apply them. For TD, convergence can be enforced with a certain output condition assuring that the δ-error drops on average to zero (output control). Correlation based rules, on the other hand, converge when one input drops to zero (input control). Temporally asymmetric learning rules treat situations where incoming stimuli follow each other in time. Thus, it is necessary to remember the first stimulus to be able to relate it to the later occurring second one. To this end different types of so-called eligibility traces are being used by these two different types of rules. This aspect leads again to different properties of TD and differential Hebbian learning as discussed here. Thus, this paper, while also presenting several novel mathematical results, is mainly meant to provide a road map through the different neuronally emulated temporal asymmetrical learning rules and their behavior to provide some guidance for possible applications.     

LINKER: a program to generate linker sequences for fusion proteins

The construction of functional fusion proteins often requires a linker sequence that adopts an extended conformation to allow for maximal flexibility. Linker sequences are generally selected based on intuition. Without a reliable selection criterion, the design of such linkers is often difficult, particularly in situations where longer linker sequences are required. Here we describe a program called LINKER which can automatically generate a set of linker sequences that are known to adopt extended conformations as determined by X-ray crystallography and NMR. The only required input to the program is the desired linker sequence length. The program is specifically designed to assist in fusion protein construction. A number of optional input parameters have been incorporated so that users are able to enhance sequence selection based on specific applications. The program output simply contains a set of sequences with a specified length. This program should be a useful tool in both the biotechnology industry and biomedical research. It can be accessed through the Web page http://www.fccc. edu/research/labs/feng/linker.html.     

A dedicated database program for cataloging recombinant clones and other laboratory products of molecular biology technology

A novel computer database program dedicated to storing, cataloging, and accessing information about recombinant clones and libraries has been developed for the IBM (or compatible) personal computer. This program, named CLONES, also stores information about bacterial strains and plasmid and bacteriophage vectors used in molecular biology. The advantages of this method are improved organization of data, fast and easy assimilation of new data, automatic association of new data with existing data, and rapid retrieval of desired records using search criteria specified by the user. Individual records are indexed in the database using B-trees, which automatically index new entries and expedite later access. The use of multiple windows, pull-down menus, scrolling pick-lists, and field-input techniques make the program intuitive to understand and easy to use. Daughter databases can be created to include all records of a particular type, or only those records matching user-specified search criteria. Separate databases can also be merged into a larger database. This computer program provides an easy-to-use and accurate means to organize, maintain, access, and share information about recombinant clones and other laboratory products of molecular biology technology.     

A program which automatically quantitates gel electrophoretic autoradiograms

The use of a computer-coupled film scanner to measure and analyze autoradiograms of gel electropherograms is described. A program has been written which fits Gaussian curves to the complex band pattern that constitutes a density profile without the need for estimated parameters in the input. The great majority of the fits are satisfactory. This program, which is written in FORTRAN, runs on a small, inexpensive computer. Another program which approximates a Gaussian least squares fit has been run for comparison; this procedure can also be used to refine occasional unsatisfactory fits. Finally, a program has been written which sums the density profile within specified limits, so that the integrated intensities of bands due to isolated protein components may be found.