Developing novel explanatory models for electronics education

This paper explores how representations of technological concepts may be designed to help students with visual learning styles achieve successful comprehension in the field of electronics. The work accepts a wide definition of what is understood by the visualisation of a model in that it can take different external forms, but also include an internal representation in a person’s mind. We are of the opinion that to acquire scientific or technological knowledge there is a requirement for abstract models to exhibit particular features that complement the nature of their fields, and that their effectiveness is dependent on the context in question. This work reports on the development of experimental materials which are novel teaching aids in the context of electronics education. It proposes design principles based on congruent, schematised, symmetrical spatial metaphors of circuits incorporating interactivity by the use of gesture, scaffolding, learning by topological, analogical and conceptual resemblances. We conclude that qualitative methods may be employed with a significant measure of success even for a field such as electronics that is often considered to be difficult due to the necessity of abstract explanations

Investigating the diversity of the 18S SSU rRNA hyper-variable region of Theileria in cattle and Cape buffalo (Syncerus caffer) from southern Africa using a next generation sequencing approach

Molecular classification and systematics of the Theileria is based on the analysis of the 18S rRNA gene. Reverse line blot or conventional sequencing approaches have disadvantages in the study of 18S rRNA diversity and a next-generation 454 sequencing approach was investigated. The 18S rRNA gene was amplified using RLB primers coupled to 96 unique sequence identifiers (MIDs). Theileria positive samples from African buffalo (672) and cattle (480) from southern Africa were combined in batches of 96 and sequenced using the GS Junior 454 sequencer to produce 825711 informative sequences. Sequences were extracted based on MIDs and analysed to identify Theileria genotypes. Genotypes observed in buffalo and cattle were confirmed in the current study, while no new genotypes were discovered. Genotypes showed specific geographic distributions, most probably linked with vector distributions. Host specificity of buffalo and cattle specific genotypes were confirmed and prevalence data as well as relative parasitemia trends indicate preference for different hosts. Mixed infections are common with African buffalo carrying more genotypes compared to cattle. Associative or exclusion co-infection profiles were observed between genotypes that may have implications for speciation and systematics: specifically that more Theileria species may exist in cattle and buffalo than currently recognized. Analysis of primers used for Theileria parva diagnostics indicate that no new genotypes will be amplified by the current primer sets confirming their specificity. T. parva SNP variants that occur in the 18S rRNA hypervariable region were confirmed. A next generation sequencing approach is useful in obtaining comprehensive knowledge regarding 18S rRNA diversity and prevalence for the Theileria, allowing for the assessment of systematics and diagnostic assays based on the 18S gene.The Theileria diagnostics project ARC-OVI (OV15/08/1P01) and the Department of Agriculture, Forestry and Fisheries (OV21/03/C148).http://www.elsevier.com/locate/ttbdis2017-07-31hb2016Veterinary Tropical Disease

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target. Here we demonstrate specificity redirection by rational design using structure-guided computational biology to generate a TRBC2-specific antibody (KFN), complementing the antibody previously described by our laboratory with unique TRBC1 specificity (Jovi-1) in targeting broader spectrum of T cell malignancies clonally expressing either of the two chains. This permits generation of paired reagents (chimeric antigen receptor-T cells) specific for TRBC1 and TRBC2, with preclinical evidence to support their efficacy in T cell malignancies

In situ fluorescence measurements of dissolved organic matter: a review

YesThere is a need for an inexpensive, reliable and fast monitoring tool to detect contaminants in a short time, for quick mitigation of pollution sources and site remediation, and for characterization of natural dissolved organic matter (DOM). Fluorescence spectroscopy has proven to be an excellent technique in quantifying aquatic DOM, from autochthonous, allochthonous or anthropogenic sources. This paper reviews the advances in in situ fluorescence measurements of DOM and pollutants in various water environments. Studies have demonstrated, using high temporal-frequency DOM fluorescence data, that marine autochthonous production of DOM is highly complex and that the allochthonous input of DOM from freshwater to marine water can be predicted. Furthermore, river measurement studies found a delayed fluorescence response of DOM following precipitation compared to turbidity and discharge, with various lags, depending on season, site and input of dissolved organic carbon (DOC) concentration. In addition, research has shown that blue light fluorescence (λemission = 430–500 nm) can be a good proxy for DOC, in environments with terrestrial inputs, and ultraviolet fluorescence (λemission = UVA–320–400 nm) for biochemical oxygen demand, and also E. coli in environments with sanitation issues. The correction of raw fluorescence data improves the relationship between fluorescence intensity and these parameters. This review also presents the specific steps and parameters that must be considered before and during in situ fluorescence measurement session for a harmonized qualitative and quantitative protocol. Finally, the strengths and weaknesses of the research on in situ fluorescence are identified.Authors, E.M. Carstea and C.L. Popa, acknowledge the support of the Ministry of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1.1-TE-2016-0646, within PNCDI III, project number 18N/2019, under the Core Program OPTRONICA VI, project number 19PFE/17.10.2018 and project number 152/2016, SMIS 108109

Background Radioactivity in the North West Province

MSc (Arts), North-West University, Mahikeng CampusThe unavailability of the background radioactivity baseline data of the North West province for the various geological units is a problem from the radiation protection point of view. The regulation of the nuclear industry and the protection of members of the public against the harmful effects of ionising radiation requires this baseline data for appropriate regulating standards to be set. Hence this study has mainly focused on determining background radioactivity in various geological formations in terms of specific activity (Bq/kg) and dose rate (μSv/h) due to the external gamma radiation in order to make a contribution for regulatory purpose. The focus of this study was on the U-238 series due to its contribution on background, and thus the Ra-226 specific• activity was determined in Bqlkg. Gamma spectrometry units coupled to Nal(Tl) detectors were used both in-situ and in the laboratory to measure the gamma rays emitted from soil and dose rate was measured in-situ with electra G.M dose rate meter. The average background radioactivity from the measurements is high in granites, intermediate in shale and low in gabbro, norite anorthosites, quartzite calcrete with limestone, hybrid rocks, diabase and epidiorite and this pattern agreed with literature. The average radioactivity for the surveyed areas range from 26 Bq/kg to 150 Bq/kgfor various rocks types. The dose rate range from 0.15 μSv/h to 0.35 μSvlhfor various geological structures. The average specific activity is 150 Bq/kg and 82 Bq/kg in course grained and mixed granites, 72 Bq/kg and 61 Bq/kg in shale, polo and shale slate respectively. The average specific activity in norite, sandy soil, gabbro, norite anorthosite, brick clay and limestone is 37 Bq/kg, 25 Bq/kg, 28 Bq/kg, 26 Bq/kg and 27 Bq/kg respectively. The average dose rate range from 0.15 μSvlh to 0.35 μSv/h for various geological structures. There is a correlation of the results of this study with the studied geology in the North West Province. The results are also comparable with data from the previous international studies. There was a parallel study for Gauteng by the other worker. The geological formations that were surveyed in the North West Province are different from those surveyed in Gauteng Province. As a result the background radioactivity tends to be generally higher in Gauteng than the North West Province. The background radioactivity in most studied areas for both provinces should only be associated with NORM due to their distance from all TENO RM operations. Inferential statistics using student t-test indicate that there is 95 % probability that the background radioactivity mean for the North West Province lies in the interval 5 0. 048 Bq/kg to 61. 7./ Bq/kg. The average specific activity for the province is 55. 9 Bq/kg. The student t-value and the p-value, indicate that there is enough evidence to infer that the average specific activity for the whole North West Province is below 200 Bq/kg. The Nuclear Energy Act no. 131 of the CNS 1993 in South Africa, specifies the entry level into regulation of 200 Bq/kg for background specific activity. Any activity handling radioactivity material below 200 Bq/kg is not amenable for regulation because that is regarded to be background. From statistical analysis, all the areas that were covered by this study have a specific activity below a value of 200 Bq/kg. Hence the results suggest suggests that the entry level into regulation of 200 Bq/kg is appropriate because it does not bring areas at background level into regulation.Master

Removal of FcR binding motifs in IgG1 spacer.

<p>(a) amino acid sequence of the wild type (top) and mutated (PVAA) CH2 regions responsible for FcγR binding. (b) flow staining with anti-Fc antibody to show comparable level of expression of receptor with or without the PVAA mutation. Identical CARs with and without PVAA were compared side by side in terms of cytotoxicity against GD2 engineered SupT1 and GD2 negative wild type SipT1 cells (c), cytotoxicity against GD2 positive Lan1 cells and FcRγ positive THP-1 cells (d), and IL-1β release on culture with THP-1 cells (e). Data shown as means +/-SEM from 4 independent experiments with different donors.</p

Consequence and function of iCasp9.

<p>The SAR codon-optimized cassette was taken further and compared with the original cassette without iCasp9. (a) Expression of the CAR was unchanged. Depletion is shown by facs after addition of CID. The function of cassettes with and without iCasp9 were assessed by (b) Killing (c) IFN-γ release and (d) IL-2 release. Data shown as means +/-SEM from 4 independent experiments with different donors.</p