CytoGPS: a web-enabled karyotype analysis tool for cytogenetics.

SUMMARY: Karyotype data are the most common form of genetic data that is regularly used clinically. They are collected as part of the standard of care in many diseases, particularly in pediatric and cancer medicine contexts. Karyotypes are represented in a unique text-based format, with a syntax defined by the International System for human Cytogenetic Nomenclature (ISCN). While human-readable, ISCN is not intrinsically machine-readable. This limitation has prevented the full use of complex karyotype data in discovery science use cases. To enhance the utility and value of karyotype data, we developed a tool named CytoGPS. CytoGPS first parses ISCN karyotypes into a machine-readable format. It then converts the ISCN karyotype into a binary Loss-Gain-Fusion (LGF) model, which represents all cytogenetic abnormalities as combinations of loss, gain, or fusion events, in a format that is analyzable using modern computational methods. Such data is then made available for comprehensive 'downstream' analyses that previously were not feasible. AVAILABILITY AND IMPLEMENTATION: Freely available at http://cytogps.org.

Magnetically Actuated Fiber-Based Soft Robots.

Broad adoption of magnetic soft robotics is hampered by the sophisticated field paradigms for their manipulation and the complexities in controlling multiple devices. Furthermore, high-throughput fabrication of such devices across spatial scales remains challenging. Here, advances in fiber-based actuators and magnetic elastomer composites are leveraged to create 3D magnetic soft robots controlled by unidirectional fields. Thermally drawn elastomeric fibers are instrumented with a magnetic composite synthesized to withstand strains exceeding 600%. A combination of strain and magnetization engineering in these fibers enables programming of 3D robots capable of crawling or walking in magnetic fields orthogonal to the plane of motion. Magnetic robots act as cargo carriers, and multiple robots can be controlled simultaneously and in opposing directions using a single stationary electromagnet. The scalable approach to fabrication and control of magnetic soft robots invites their future applications in constrained environments where complex fields cannot be readily deployed.

Computational Modeling of a Low-Cost Fluidic Oscillator for Use in an Educational Respiratory Simulator.

Herein, the computational modeling of a fluidic oscillator for use in an educational respiratory simulator apparatus is presented. The design provides realistic visualization and tuning of respiratory biomechanics using a part that is (i) inexpensive, (ii) easily manufactured without the need for specialized equipment, (iii) simple to assemble and maintain, (iv) does not require any electronics, and (v) has no moving components that could be prone to failure. A computational fluid dynamics (CFD) model is used to assess flow characteristics of the system, and a prototype is developed and tested with a commercial benchtop respiratory simulator. The simulations show clinically relevant periodic oscillation with outlet pressures in the range of 8-20 cmH2O and end-user-tunable frequencies in the range of 3-6 s (respiratory rate [RR] of 10-20 breaths per minute). The fluidic oscillator presented here functions at physiologically relevant pressures and frequencies, demonstrating potential as a low cost, hands-on, and pedagogical tool. The model will serve as a realistic model for educating Science, Technology, Engineering, and Mathematics (STEM) students on the relationship between flow, pressure, compliance, and volume in respiratory biomechanics while simultaneously exposing them to basic manufacturing techniques.

The LC/MS analysis of glycation of IgG molecules in sucrose containing formulations.

Glycation of a recombinant monoclonal IgG2 molecule, in sucrose containing liquid formulations, was studied using reversed-phase LC/MS analysis of the intact IgG, the F(ab')2 fragments and after complete tryptic digestion. The extent of glycation in sucrose containing formulations was monitored at different temperatures over a period of 21 months using the Hexose index (Hex(I)). Hex(I) represents the average number of hexose molecules per molecule of IgG and was calculated by using the intensity values of peaks corresponding to hexose isoforms in the deconvoluted mass spectra. The rate of glycation in mildly acidic sucrose containing formulations was proportional to the incubation temperature. No glycation was observed in sucrose containing formulations incubated at 4 degrees C even after 18 months. However, when the same formulations were incubated at 37 degrees C glycation was observed after just 1 month. The glycation sites were mapped to 10 lysine residues distributed throughout the molecule. The amino terminal end of the light chain was also shown to contain glycation. The surface accessibility of the lysine side chain could influence its susceptibility to glycation.

Benthic injury dose-response models for polychlorinated biphenyl-contaminated sediment using equilibrium partitioning.

The study goal was to develop a sediment polychlorinated biphenyl (PCB) dose-response model based on benthic invertebrate effects to PCBs. The authors used an equilibrium partitioning (EqP) approach to generate predicted PCB sediment effect concentrations (largely Aroclor 1254) associated with a gradient of toxic effects in benthic organisms from effects observed in aquatic toxicity studies. The present study differs from all other EqP collective sediment investigations in that the authors examined a common dose-response gradient of effects for PCBs rather than a single, protective value. The authors reviewed the chronic aquatic toxicity literature to identify measured aqueous PCB concentrations and associated benthic invertebrate effects. The authors control-normalized the aquatic toxic effect data and expressed results from various studies as a common metric, percent injury. Then, they calculated organic carbon-normalized sediment PCB concentrations (mg/kg organic carbon) from the aqueous PCB toxicity data set using EqP theory based on the US Environmental Protection Agency's (EPIWEB 4.1) derivation of the water-organic carbon partition coefficient (KOC ). Lastly, the authors constructed a nonlinear dose-response numerical model for these synoptic sediment PCB concentrations and biological effects: Y = 100/1 + 10([logEC50-logX] × [Hill slope]) (EC50 = median effective concentration). These models were used to generate "look-up" tables reporting percent injury in benthic biota for a range of Aroclor-specific sediment concentrations. For example, the model using the EPIWEB KOC estimate predicts mean benthic injury of 23.3%, 46.0%, 70.6%, 87.1%, and 95% for hypothetical sediment concentrations of 1 mg/kg, 2 mg/kg, 4 mg/kg, 8 mg/kg, and 16 mg/kg dry weight of Aroclor 1254, respectively (at 1% organic carbon). The authors recommend the model presented for screening but suggest, when possible, determining a site-specific KOC that, along with the tables and equations, allows users to create their own protective dose-response sediment concentration. Environ Toxicol Chem 2017;36:1311-1329. © 2016 SETAC.

Approaches for linking whole-body fish tissue residues of mercury or DDT to biological effects thresholds.

A variety of methods have been used by numerous investigators attempting to link tissue concentrations with observed adverse biological effects. This paper is the first to evaluate in a systematic way different approaches for deriving protective (i.e., unlikely to have adverse effects) tissue residue-effect concentrations in fish using the same datasets. Guidelines for screening papers and a set of decision rules were formulated to provide guidance on selecting studies and obtaining data in a consistent manner. Paired no-effect (NER) and low-effect (LER) whole-body residue concentrations in fish were identified for mercury and DDT from the published literature. Four analytical approaches of increasing complexity were evaluated for deriving protective tissue residues. The four methods were: Simple ranking, empirical percentile, tissue threshold-effect level (t-TEL), and cumulative distribution function (CDF). The CDF approach did not yield reasonable tissue residue thresholds based on comparisons to synoptic control concentrations. Of the four methods evaluated, the t-TEL approach best represented the underlying data. A whole-body mercury t-TEL of 0.2 mg/kg wet weight, based largely on sublethal endpoints (growth, reproduction, development, behavior), was calculated to be protective of juvenile and adult fish. For DDT, protective whole-body concentrations of 0.6 mg/kg wet weight in juvenile and adult fish, and 0.7 mg/kg wet weight for early life-stage fish were calculated. However, these DDT concentrations are considered provisional for reasons discussed in this paper (e.g., paucity of sublethal studies).

Residue-based mercury dose-response in fish: an analysis using lethality-equivalent test endpoints.

Dose-response relationships for aquatic organisms have been developed for numerous contaminants using external media exposures (water and sediment). Dose-response relationships based on internal concentrations (tissue residues) are limited. The present study reports Hg dose-response curves for early life stage and juvenile or adult fish based on published tissue-residue toxicity studies. These curves rely primarily on endpoints that can be directly related to mortality, such as survival, reproductive success, and lethal developmental abnormalities. These lethality-equivalent endpoints were linked using the common metric of injury. Uncertainties and potential applications of this mercury dose-response curve are discussed. Major uncertainties include lab to field extrapolations, biological endpoints selected by investigators, interspecific extrapolations, and the paucity of published early life stage residue (dose)-response information. To the extent this curve is based exclusively on laboratory toxicity tests and does not consider other potentially sensitive and ecologically important biological endpoints (e.g., growth and behavior), the magnitude of the adverse effects predicted by the curve may be underestimated.