Miniaturized multisensor system with a thermal gradient: Performance beyond the calibration range

Two microchips, each with four identical microstructured sensors using SnO2 nanowires as sensing material (one chip decorated with Ag nanoparticles, the other with Pt nanoparticles), were used as a nano-electronic nose to distinguish five different gases and estimate their concentrations. This innovative approach uses identical sensors working at different operating temperatures thanks to the thermal gradient created by an integrated microheater. A system with in-house developed hardware and software was used to collect signals from the eight sensors and combine them into eight-dimensional data vectors. These vectors were processed with a support vector machine allowing for qualitative and quantitative discrimination of all gases after calibration. The system worked perfectly within the calibrated range (100% correct classification, 6.9% average error on concentration value). This work focuses on minimizing the number of points needed for calibration while maintaining good sensor performance, both for classification and error in estimating concentration. Therefore, the calibration range (in terms of gas concentration) was gradually reduced and further tests were performed with concentrations outside these new reduced limits. Although with only a few training points, down to just two per gas, the system performed well with 96% correct classifications and 31.7% average error for the gases at concentrations up to 25 times higher than its calibration range. At very low concentrations, down to 20 times lower than the calibration range, the system worked less well, with 93% correct classifications and 38.6% average error, probably due to proximity to the limit of detection of the sensors

Live 4D Imaging of the Embryonic Vertebrate Heart with Two-Photon Light Sheet Microscopy and Simultaneous Optical Phase Stamping

The developing vertebrate heart is a highly dynamic organ that starts to function early on during embryonic development, even as it continues to undergo dramatic morphological changes and cellular differentiation. Fast and high resolution three-dimensional (3D) imaging is needed to document the intrinsic cellular dynamics of the beating heart, as a critical step in understanding its development. To meet the challenges of obtaining sub-cellular resolution imaging of a dynamic 100-micron length scale 3D structure, which moves quasi-periodically at frequency of a few Hertz, over tens of microns amplitude, we have employed two-photon light sheet microscopy (2p-SPIM) and a novel independent optical phase stamping method to generate well-resolved 3D movies (4D) of the beating heart. Applying this 4D imaging modality to zebrafish embryos, we have found remarkable heterogeneity in cardiomyocyte morphology, gene expression, and behavior both during the cardiac cycle, and over the developmental time. The observed heterogeneity appears to play a key role in the maintenance of tissue geometry and cardiac output as the heart undergoes cycles of contraction and expansion. The variation in cellular morphology and behavior provide new insights into the tight link between cellular dynamics, mechanical environment exerted and felt by the beating heart, and the genetic program that governs not only the differentiation and construction but also the maintenance of this important organ

A case of hepatic cyst-induced internal jugular venous thrombosis

• Echocardiography can demonstrate hepatic cyst–induced right atrial compression. • Hepatic cyst–induced blood flow stasis can cause internal jugular venous thrombus. • Laparoscopic deroofing of hepatic cysts is a safe and effective treatment

The Crystal Structure of PPIL1 Bound to Cyclosporine A Suggests a Binding Mode for a Linear Epitope of the SKIP Protein

BACKGROUND: The removal of introns from pre-mRNA is carried out by a large macromolecular machine called the spliceosome. The peptidyl-prolyl cis/trans isomerase PPIL1 is a component of the human spliceosome and binds to the spliceosomal SKIP protein via a binding site distinct from its active site. PRINCIPAL FINDINGS: Here, we have studied the PPIL1 protein and its interaction with SKIP biochemically and by X-ray crystallography. A minimal linear binding epitope derived from the SKIP protein could be determined using a peptide array. A 36-residue region of SKIP centred on an eight-residue epitope suffices to bind PPIL1 in pull-down experiments. The crystal structure of PPIL1 in complex with the inhibitor cyclosporine A (CsA) was obtained at a resolution of 1.15 A and exhibited two bound Cd(2+) ions that enabled SAD phasing. PPIL1 residues that have previously been implicated in binding of SKIP are involved in the coordination of Cd(2+) ions in the present crystal structure. Employing the present crystal structure, the determined minimal binding epitope and previously published NMR data, a molecular docking study was performed. In the docked model of the PPIL1.SKIP interaction, a proline residue of SKIP is buried in a hydrophobic pocket of PPIL1. This hydrophobic contact is encircled by several hydrogen bonds between the SKIP peptide and PPIL1. CONCLUSION: We characterized a short, linear epitope of SKIP that is sufficient to bind the PPIL1 protein. Our data indicate that this SKIP peptide could function in recruiting PPIL1 into the core of the spliceosome. We present a molecular model for the binding mode of SKIP to PPIL1 which emphasizes the versatility of cyclophilin-type PPIases to engage in additional interactions with other proteins apart from active site contacts despite their limited surface area

Study on the effectivness of mutual and self-assessment methods of students’ tests

the article dealswith results of studying process at the department of pharmacy and chemistry using mutual and self-assessment methods and also the analysis of the questioning of students about this pedagogical method.в статье рассмотрены результаты проведения занятий на кафедре фармации и химии по методике само- и взаимооценивания результатов работы студентов, а также анализ анкетных ответов обучающихся относительно впечатлений о данном педагогическом приём

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study

Background Meta-analysis of patients with isoniazid-resistant tuberculosis given standard first-line anti-tuberculosis treatment indicated an increased risk of multi-drug resistant tuberculosis (MDR-TB) emerging (8%), compared to drug-sensitive tuberculosis (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with pre-existing isoniazid resistant disease with first-line anti-tuberculosis therapy risks selecting for rifampicin resistance, and hence MDR-TB. Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug-susceptibility testing was performed by Microscopic observation drug-susceptibility assay (MODS), Mycobacterial Growth Indicator Tube (MGIT) and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was five or fewer single nucleotide polymorphisms (SNPs) whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. Results 239 patients with isoniazid-resistant pulmonary tuberculosis were recruited. Fourteen (14/239, 5.9%) patients were diagnosed with a second episode of tuberculosis that was multi-drug resistant. Six (6/239, 2.5%) were identified as having evolved MDR-TB de novo and six as having been re-infected with a different strain. In two cases the genomic distance was between 5-10 SNPs and therefore indeterminate. Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment