Monoclonal antibodies are essential biomedical research and clinical reagents that are produced by companies and research laboratories. The NIAID ImmPort (Immunology Database and Analysis Portal) resource provides a long-term, sustainable data warehouse for immunological data generated by NIAID, DAIT and DMID funded investigators for data archiving and re-use. A variety of immunological data is generated using techniques that rely upon monoclonal antibody reagents, including flow cytometry, immunofluorescence, and ELISA. In order to facilitate querying, integration, and reuse of data, standardized (...) terminology for describing monoclonal antibody reagents and their targets needs to be used for annotating data submitted to ImmPort. (shrink)

There is a popular and widely accepted version of the precautionary principle which may be expressed thus: “If you are in a hole—stop digging!”. Tom Baldwin, as Deputy Chair of the Human Fertilisation and Embryology Authority , may be excused for rushing to the defence of the indefensible,1 the HFEA’s sex selection report,2 but not surely for recklessly abandoning so prudent a principle. Baldwin has many complaints about my misrepresenting the HFEA and about my supposed elitist contempt for public opinion; (...) readers of this exchange will decide for themselves.REDRAFTING THE REPORTBaldwin begins with a piece of wishful thinking:"Harris objects that in this recommendation “an absurdly high standard of caution is employed”, since a theoretical risk is associated with almost all medical procedures. This objection is misplaced: as paragraph 142 of the report indicates, the phrase “theoretical risk” is to be understood here in the light of the earlier discussion of the risks arising from the fact that flow cytometry exposes sperm to laser energy, a procedure which is known to be liable to damage DNA."Paragraph 142 does not make that clear. It does indeed refer back to a set of earlier paragraphs but these give, if anything, an upbeat assessment of the safety of flow cytometry. Paragraph 121 states: “However whilst potentially less intrusive, and with potentially lower risk to the health of patients, flow cytometry …” .2 But even if the overall burden of the report does indicate unresolved fears, the standard is still absurdly high. However, so far from endorsing the report’s judgement that flow cytometry has “potentially lower risk to the health of patients”, Baldwin now regards the risk of flow cytometry as “serious”1:"Since the application of flow cytometry to humans is a new procedure, the risk of … ". (shrink)

In “Sex selection and regulated hatred”1 John Harris launches a vehement critique of the Human Fertilisation and Embryology Authority’s recent report Sex Selection: options for regulation, raising several issues that merit discussion.He begins by complaining about the recommendation that because of the theoretical risk associated with the use of flow cytometry as a method of sperm sorting, its use should be restricted for the moment to cases in which a clear medical benefit is to be gained from its use. (...) Harris objects that in this recommendation “an absurdly high standard of caution is employed”, since a theoretical risk is associated with almost all medical procedures. This objection is misplaced: as paragraph 142 of the report indicates, the phrase “theoretical risk” is to be understood here in the light of the earlier discussion of the risks arising from the fact that flow cytometry exposes sperm to laser energy, a procedure which is known to be liable to damage DNA. Since the application of flow cytometry to humans is a new procedure, the risk of human genetic defects caused this way is still only “theoretical”; nonetheless it is serious enough to warrant caution—hence the recommendation that at present flow cytometry should be available only when its use brings clear medical benefits. The HFEA has recently been criticised by some for not being cautious enough when permitting the use of intracytoplasmic sperm injection even though in that case there are clear medical benefits from its use. It is extraordinary that Harris should now criticise the HFEA for not throwing caution to the winds concerning flow cytometry.Harris’ next point concerns the justification for this suggestion that preimplantation sex selection should be available only where it is undertaken for medical reasons. The obvious way to justify this would appear …. (shrink)

The present study is an attempt to relate the multicomponent response of the cytoskeleton (CSK), evaluated in twisted living adherent cells, to the heterogeneity of the cytoskeletal structure - evaluated both experimentally by means of 3D reconstructions, and theoretically considering the predictions given by two tensegrity models composed of (four and six) compressive elements and (respectively 12 and 24) tensile elements. Using magnetic twisting cytometry in which beads are attached to integrin receptors linked to the actin CSK of living (...) adherent epithelial cells, we specifically measured the elastic CSK response at quasi equilibrium state and partitioned this response in terms of cortical and cytosolic contributions with a two-component model (i.e., a series of two Voigt bodies). These two CSK components were found to be prestressed and exhibited a stress-hardening response which both characterize tensegrity behaviour with however significant differences: compared to the cytosolic component, the cortical cytoskeleton appears to be a faster responding component, being a less prestressed and easily deformable structure. The discrepancies in elastic behaviour between the cortical and cytosolic CSK components may be understood on the basis of prestress tensegrity model predictions, given that the length and number of constitutive actin elements are taken into account. (shrink)

How environmental mechanical forces affect cellular functions is a central problem in cell biology. Theoretical models of cellular biomechanics provide relevant tools for understanding how the contributions of deformable intracellular components and specific adhesion conditions at the cell interface are integrated for determining the overall balance of mechanical forces within the cell. We investigate here the spatial distributions of intracellular stresses when adherent cells are probed by magnetic twisting cytometry. The influence of the cell nucleus stiffness on the simulated (...) nonlinear torque-bead rotation response is analyzed by considering a finite element multi-component cell model in which the cell and its nucleus are considered as different hyperelastic materials. We additionally take into account the mechanical properties of the basal cell cortex, which can be affected by the interaction of the basal cell membrane with the extracellular substrate. In agreement with data obtained on epithelial cells, the simulated behaviour of the cell model relates the hyperelastic response observed at the entire cell scale to the distribution of stresses and strains within the nucleus and the cytoskeleton, up to cell adhesion areas. These results, which indicate how mechanical forces are transmitted at distant points through the cytoskeleton, are compared to recent data imaging the highly localized distribution of intracellular stresses. (shrink)

The Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method to develop a (...) dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’. (shrink)

We present an algorithm to infer causal relations between a set of measured variables on the basis of experiments on these variables. The algorithm assumes that the causal relations are linear, but is otherwise completely general: It provides consistent estimates when the true causal structure contains feedback loops and latent variables, while the experiments can involve surgical or `soft' interventions on one or multiple variables at a time. The algorithm is `online' in the sense that it combines the results from (...) any set of available experiments, can incorporate background knowledge and resolves conflicts that arise from combining results from different experiments. In addition we provide a necessary and sufficient condition that determines when the algorithm can uniquely return the true graph, and can be used to select the next best experiment until this condition is satisfied. We demonstrate the method by applying it to simulated data and the flow cytometry data of Sachs et al. (shrink)

We present an algorithm to infer causal relations between a set of measured variables on the basis of experiments on these variables. The algorithm assumes that the causal relations are linear, but is otherwise completely general: It provides consistent estimates when the true causal structure contains feedback loops and latent variables, while the experiments can involve surgical or ‘soft’ interventions on one or multiple variables at a time. The algorithm is ‘online’ in the sense that it combines the results from (...) any set of available experiments, can incorporate background knowledge and resolves con- flicts that arise from combining results from different experiments. In addition we provide a necessary and sufficient condition that (i) determines when the algorithm can uniquely return the true graph, and (ii) can be used to select the next best experiment until this condition is satisfied. We demonstrate the method by applying it to simulated data and the flow cytometry data of Sachs et al (2005). (shrink)