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Many researchers have limited access to fully equipped laboratory-scale batch bioreactors and chemostats due to their relatively high cost. This becomes particularly prohibitive when multiple replicas of the same experiment are required, but not enough bioreactors are available to operate simultaneously. Additionally, experiments using shaken flasks are common but show significant limitations in terms of maintaining homogeneous conditions in liquid cultures or installing instrumentation for monitoring. Here, we proposed to tackle this significant hurdle by providing a route to make available the manufacture of low-cost, milliliter-scale bioreactors. This approach seems plausible for enabling proof-of-concept experiments before moving to a larger scale without significant investments. The conceptually designed systems were based on external-loop bioreactors due to their flexibility, simplicity, and ease of assembling and testing. Designs were initially evaluated in silico with the aid of COMSOL Multiphysics. The successfully evaluated systems were then constructed via additive manufacturing and assembled for hydrodynamics testing via tracer methods. This was enabled by a newly home-made optical absorbance sensor (OAS) for in-line and real-time measurements. Both the in silico and experimental results indicated close to ideal mixing conditions and low shear stress. Cell growth curves were prepared by culturing Escherichia coli and following its cell density in real-time. Our cell growth rate and maximum cell density were similar to those previously obtained in closely related systems. Therefore, the proposed bioreactors are an affordable alternative for batch and continuous cell growth studies rapidly and inexpensively., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study integrated accessibility and location-allocation models in geographic information systems as a proposed strategy to improve the spatial planning of public health services. To estimate the spatial accessibility, we modified the two-step floating catchment area (2SFCA) model with a different impedance function, a Gaussian weight for competition among service sites, a friction coefficient, distances along a street network based on the Dijkstra's algorithm and by performing a vectorial analysis. To check the accuracy of the strategy, we used the data from the public sterilization program for the dogs and cats of Bogot´a, Colombia. Since the proposed strategy is independent of the service, it could also be applied to any other public intervention when the capacity of the service is known. The results of the accessibility model were consistent with the sterilization program data, revealing that the western, central and northern zones are the most isolated areas under the sterilization program. Spatial accessibility improvement was sought by relocating the sterilization sites using the maximum coverage with finite demand and the p-median models. The relocation proposed by the maximum coverage model more effectively maximized the spatial accessibility to the sterilization service given the non-uniform distribution of the populations of dogs and cats throughout the city. The implementation of the proposed strategy would provide direct benefits by improving the effectiveness of different public health interventions and the use of financial and human resources.

IOR-T3, a mouse monoclonal antibody specific for human CD3, has been successfully used in the treatment of acute transplant rejection due to its potential as T-cell immunosuppressant. In the present work we report the construction of a human IgG1 chimeric variant of IOR-T3, named T3q. In order to reduce the T-cell activating capacity of the newly obtained chimeric molecule, the two leucine residues at positions 234 and 235 of the CH2 region were replaced by alanines, obtaining the T3q(Ala/Ala) molecule. In vitro evaluation of T3q and T3q(Ala/Ala) showed that there were no differences in the recognition of human CD3 in comparison with murine IOR-T3. However, the Fc-mutated version T3q(Ala/Ala) displayed a much weaker FcgammaR binding capacity than the unmutated chimeric molecule T3q, as well as a reduced ability to induce T-cell proliferation, proinflammatory cytokine release (TNFalpha and IL-6), and early activation surface marker expression (CD25 and CD69). We also found that, unlike treatment with T3q, the reduction in T-cell proliferation was less marked on CD8(+) cells compared to the CD4(+) cells after treatment with T3q(Ala/Ala). These properties make T3q(Ala/Ala) an attractive clinical alternative as an immunoregulatory agent endowed with reduced toxicity.

Neonatal natural antibodies (NAbs) are characterized by their high degree of idiotypic cross reactivity, together with some restrictions in the genetic mechanisms of variable region diversity. We report here the immunogenetic analysis of two anti-idiotype antibodies (B7 and 34B7 monoclonal antibodies [MAbs]), which are also polyreactive as NAbs. Evidence of a process of somatic mutations were found for heavy and light chain variable regions of both antibodies. A phylogenetic analysis of the V(H)J558 family showed that the immunoglobulin cross-reactivity displayed by B7 and 34B7 MAbs is not restricted to a particular subgroup of this family. Moreover, we identified amino acid motifs in the CDR H1 and H2 of B7 and 34B7 MAbs that are also present in high proportion in immunoglobulin cross-reactive antibodies (ICRA) reported in the Kabat database. We propose that these regions are involved in ICRA activity.