Globally distributed object identification for biological knowledgebases

The World-Wide Web provides a globally distributed communication framework that is essential for almost all scientific collaboration, including bioinformatics. However, several limits and inadequacies have become apparent, one of which is the inability to programmatically identify locally named objects that may be widely distributed over the network. This shortcoming limits our ability to integrate multiple knowledgebases, each of which gives partial information of a shared domain, as is commonly seen in bioinformatics. The Life Science Identifier (LSID) and LSID Resolution System (LSRS) provide simple and elegant solutions to this problem, based on the extension of existing internet technologies. LSID and LSRS are consistent with next-generation semantic web and semantic grid approaches. This article describes the syntax, operations, infrastructure compatibility considerations, use cases and potential future applications of LSID and LSRS. We see the adoption of these methods as important steps toward simpler, more elegant and more reliable integration of the world's biological knowledgebases, and as facilitating stronger global collaboration in biology.     

Fluid flow in a spiral device used for irradiation of biological fluids

The manufacture of plasma‐derived therapeutics includes dedicated viral inactivation steps to minimize the risk of infection. Traditional viral inactivation methods are effective for the removal and inactivation of enveloped viruses, but less effective against small nonenveloped viruses. UV‐C irradiation has been demonstrated to be an effective means of inactivating such viruses. The UVivatec lab system consists of a spiral tube around an UV‐C irradiation source. Flow of a solution through the chamber generates and ensures controlled mixing and uniform exposure to irradiation. A detailed assessment of the effect of flow rate, alternate cross sectional design and scale up of the irradiation chamber on Dean vortices was performed using the smoothed particle hydrodynamics method. The aim was to provide a basis for setting flow rate limits and using a laboratory scale apparatus to model viral inactivation in larger manufacturing scale equipment. The effect of flow rate related changes on the fluence rate was also investigated through chemical actinometry studies. The data were consistent with the simulations indicating that Dean vortices were present at low flow rates, but dissipated at higher flow rates through the spiral chamber. Importantly, this work also allowed a correlation between the small system and large scale system to be established. This will greatly facilitate process development and viral validation studies. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 359–367, 2013     

A triaxial-measurement shear-test device for soft biological tissues

A novel shear-test device for soft biological tissue, capable of applying simple shear deformations simultaneously in two orthogonal directions while measuring the resulting forces generated in three axes, is described. We validated the device using a synthetic gel, the properties of which were ascertained from independent tensile and rotational shear tests. Material parameters for the gel were fitted using neo-Hookean analytical solutions to the independent test data, and these matched the results from the device. Preliminary results obtained with rat septal myocardium are also presented to demonstrate the feasibility of the apparatus in determining the shear characteristics of living tissue.     

A simple device for harvesting biological fluids at the microscopic level

A simple aspirating device is described which permits repeated samples of biological materials to be taken near or at the microscopic level. It features an inner coaxial tube which delivers a harvesting fluid into the very tip of the collecting needle, permitting metabolic activity in the sample to be quenched immediately. The device is easily constructed from common laboratory material.     

Mechanical device for morphological and orientation analysis of biological structures

A simple mechanical device for different kinds of morphological analysis is suggested. It consists of a binocular microscope, a luminiscent illuminator, a coordination table with a disc-chuck (0-360 degrees) and a nest for disposing the test systems and the light or electronmicroscopic negatives (6 x 9 and 9 x 12). The analysis is performed by means of visual scanning of the negatives, by counting the number of crossings of the structure with the test system knots and by registration of the measurements by a key recorder. For orientation analysis the microscope is supplied with a goniometer (0-360 degrees) and an oculometer with a cross of filaments.     

The Search for a Biological Energy Transducer

Muscle can be thought of as an engine—an assembly of devicescapable of performing useful work at the expense of degradingfuel. Among the devices the most distinctive is the transducer,wherein energy of one form (chemical) is converted into energyof another form (mechanical). The author contends that untilrecently muscle research has examined the auxiliary devices,and that only currently is the transducer under study.     

Application of a directed conformational search for generating 3-D coordinates for protein structures from alpha-carbon coordinates.

A directed conformational search algorithm using the program CONGEN (ref. 3), which samples backbone conformers, is described. The search technique uses information from the partially built structures to direct the search process and is tested on the problem of generating a full set of backbone Cartesian coordinates given only alpha-carbon coordinates. The method has been tested on six proteins of known structure, varying in size and classification, and was able to generate the original backbone coordinates with RMSs ranging from 0.30-0.87A for the alpha-carbons and 0.5-0.99A RMSs for the backbone atoms. Cis peptide linkages were also correctly identified. The procedure was also applied to two proteins available with only alpha-carbon coordinates in the Brookhaven Protein Data Bank; thioredoxin (SRX) and triacylglycerol acylhydrolase (TGL). All-atom models are proposed for the backbone of both these proteins. In addition, the technique was applied to randomized coordinates of flavodoxin to assess the effects of irregularities in the data on the final RMS. This study represents the first time a deterministic conformational search was used on such a large scale.     

Controlling the freezing process: a robotic device for rapidly freezing biological tissues with millisecond time resolution

A robotic cryogenic device was developed which allows freezing of thick biological tissues with millisecond time resolution. The device consists of two horizontally oriented hammers (pre-cooled with liquid N(2)) driven by two linear servo-motors. The tissue sample is bathed in Ringers contained in a chamber which drops rapidly out of the way just as the hammers approach. A third linear motor is vertically oriented, and permits the rapidly dropping chamber to smoothly decelerate. All movements were performed by the three motors and four solenoids controlled by a PC. Mechanical adjustments, that change the size of the gap between the hammers at the end position, permit the final thickness of the frozen tissue to be varied. Here we show that the freezing time increased with the square of the final thickness of the frozen bundle. However, when bundles of different original thicknesses (up to at least 1mm) were compressed to the same final thickness (e.g., 0.2mm), they exhibited nearly equal freezing times. Hence, by being able to adjust the final thickness of the frozen bundles, the device not only speeds the rate of freezing, but standardizes the freezing time for different diameter samples. This permits the use of freezing for accurate determination of the kinetics of cellular processes in biological tissue.     

A PVC-based electrode sensitive to DDA+ as a device for monitoring the membrane potential in biological systems

A polyvinyl chloride (PVC)-based membrane electrode sensitive to dibenzyldimethyl ammonium cation (DDA⁺) was constructed, and operational parameters such as the selectivity coefficients, the detection limit, and the response time were obtained. In comparison with the selectivity coefficients obtained with the previous liquid-membrane electrode, significant improvement was not obtained, but the response time became pronouncedly shorter. Furthermore, the electrode lifetime was remarkably prolonged. With the electrode developed, the change in the membrane potential of liposomes containing dibutyl ferrocene which separated oxidizing and reducing agent solutions was measured. The DDA⁺ uptake, U, and the membrane potential estimated from U changed in accordance with the redox potential in the medium when the concentration of internal ferricyanide was kept constant. The membrane potential collapsed when the uncoupler of oxidative phosphorylation was added. The ANS fluorescence measurement indicated that negative charges appeared on energization with oxidizing-reducing agent. The change in membrane potential of mitochondria during energization was also measured. It was found that the liposome described above is a good model for the generation of membrane potentials in mitochondria.     

A device for immobilizing small biological objects under light optical study

A device constructed on the base of a slide and a coverslip is proposed for immobilisation of small biological objects. The device permits performance of gradual and reversible squeezing of live micro-objects. Using the above device it is possible to watch one and the same living object, (for example, a ciliate) repeatedly within a prolonged period of time.     

A device for testing mechanical properties of biological materials--the "Biodyne".

An electromechanical servo-controlled device has been developed. This device can be used to test the mechanical behavior of a wide variety of biological soft tissues. Control and execution of material testing procedures such as stress-strain, vibration, relaxation, creep etc. can be performed by manual operation of the device or by interfacing it with a laboratory type minicomputer. Experiments on excitable tissues such as muscle can also be executed. The design details and system performance are discussed.     

Investigating the status of biological stimuli as objects of attention in multiple object tracking

Background

Humans are able to track multiple simultaneously moving objects. A number of factors have been identified that can influence the ease with which objects can be attended and tracked. Here, we explored the possibility that object tracking abilities may be specialized for tracking biological targets such as people.

Methodology/Principal Findings

We used the Multiple Object Tracking (MOT) paradigm to explore whether the high-level biological status of the targets affects the efficiency of attentional selection and tracking. In Experiment 1, we assessed the tracking of point-light biological motion figures. As controls, we used either the same stimuli or point-light letters, presented in upright, inverted or scrambled configurations. While scrambling significantly affected performance for both letters and point-light figures, there was an effect of inversion restricted to biological motion, inverted figures being harder to track. In Experiment 2, we found that tracking performance was equivalent for natural point-light walkers and ‘moon-walkers’, whose implied direction was incongruent with their actual direction of motion. In Experiment 3, we found higher tracking accuracy for inverted faces compared with upright faces. Thus, there was a double dissociation between inversion effects for biological motion and faces, with no inversion effect for our non-biological stimuli (letters, houses).

Conclusions/Significance

MOT is sensitive to some, but not all naturalistic aspects of biological stimuli. There does not appear to be a highly specialized role for tracking people. However, MOT appears constrained by principles of object segmentation and grouping, where effectively grouped, coherent objects, but not necessarily biological objects, are tracked most successfully.