Impedance-Based Water-Quality Monitoring Using the Parallel-Plate Method

The application of electromagnetic (EM) waves to measure the electrical properties (dielectric constant and loss tangent) of materials is a well-known approach. The electrical properties can be used to indirectly measure several physical properties of solutions in water such as the concentration and chemical composition of contaminants in water, as a representative of the liquid phase in soil. A capacitive method of measuring dielectric properties of solutions is proposed to detect and determine low-concentration chemical and biological contaminations in water. The primary objective of this project is to design a low-cost sensor that would require small volumes of samples to detect low concentrations of dissolved contaminants in water. A forward model was developed using a finite-element method (FEM) to simulate the experimental setup (EXP). A calibration function was also developed to minimize deviations between FEM and EXP results for benchmark/reference solutions with known dielectric properties. The validated, calibrated forward model was then inverted to calculate the electrical properties of unknown solutions using the corresponding EXP results

Novel PCR primers to diagnose visceral leishmaniasis using peripheral blood, spleen or bone marrow aspirates

Objective To establish a suitable method of diagnosis of visceral leishmaniasis (VL) using peripheral blood, spleen or bone marrow aspirates. Methods Peripheral blood, bone marrow and spleen aspirate samples were collected from clinically suspected VL patients (n = 26). A new PCR primer pair (MK1F/R) was designed targeting kinetoplast mini circle DNA sequences of Leishmania donovani, and Leishmania infantum, and was used to diagnose VL along with some other established primers for VL in polymerase chain reactions. Test was validated by comparing with several other diagnostic methods. Results The designed primer set showed 100% specificity and 98% sensitivity in detecting VL using blood samples, when compared with more invasive samples: bone marrow or spleen aspirates. Conclusions The newly designed primer MK1F/R could be a better alternative for PCR based diagnosis of VL using less invasive sample, peripheral blood instead of bone marrow or spleen aspirates

Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy.

Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells <sup>1-14</sup> . The large HLA allele diversity and limiting clinical samples have restricted the study of the landscape of neoantigen-targeted T cell responses in patients over their treatment course. Here we applied recently developed technologies <sup>15-17</sup> to capture neoantigen-specific T cells from blood and tumours from patients with metastatic melanoma with or without response to anti-programmed death receptor 1 (PD-1) immunotherapy. We generated personalized libraries of neoantigen-HLA capture reagents to single-cell isolate the T cells and clone their T cell receptors (neoTCRs). Multiple T cells with different neoTCR sequences (T cell clonotypes) recognized a limited number of mutations in samples from seven patients with long-lasting clinical responses. These neoTCR clonotypes were recurrently detected over time in the blood and tumour. Samples from four patients with no response to anti-PD-1 also demonstrated neoantigen-specific T cell responses in the blood and tumour to a restricted number of mutations with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstitution of the neoTCRs in donor T cells using non-viral CRISPR-Cas9 gene editing demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines. Thus, effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8 <sup>+</sup> T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time