A simple paper test for isoniazid in urine

Tests for the presence of chemotherapeutic drugs or their metabolites in urine play an important part in the management of the treatment of tuberculosis (Dixon et al., 1957; Fox, 1958). A previous report from this Centre (Gangadharam et al., 1958) presented a comparison of a number of methods for detecting isoniazid in urine including the direct naphthoquinone-mercuric chloride (N-M) test (Short and Case, 1957), and also a modification of this test which employed alkaline hydrolysis to liberate isoniazid from its conjugated forms. The direct-and hydrolysis N-M tests have been employed in this Centre for the past four years to control the self-administration of isoniazid used in the domiciliary treatment of pulmonary tuberculosis. The effect of irregularity in taking isoniazid as detected by these tests on the response to treatment has been reported elsewhere (Tuberculosis Chemotherapy Centre, 1960). Since this method has the disadvantage that it requires a certain amount of equipment and trained personnel, it is not suitable for routine use in all chest clinics or under field conditions. An attempt was therefore made in this Centre to simplify the direct N-M test by incorporating the reagents in absorbent papers; Though impregnation of the paper with the pHl0 buffer and naphthoquinone reagent was successful, impregnation with the aqueous solution of the mercuric chloride was unsatisfactory. In 1960, Cattaneo, Fantoli and Belasio published details of a paper test modification of the N-M test in which this difficulty was overcome by impregnating absorbent papers with a solution of mercuric chloride in ether. Since then this modification has been adopted for the preparation of the test-paper developed in this Centre. Since a lower concentration of the naphthoquinone reagent and a shorter period of exposure was used in the preparation of the testpaper developed in this Centre than described by Cattaneo et al. (1960), both the paper tests have been compared with the direct and combined N-M tests described previously (Gangadharam et al., 1958). This paper presents the results of the comparison and of an of the specificity of the paper test

Design of e-shoe for Visually Impaired by Using RFID Technology

It is a known fact that blind people find it extremely difficult to detect their way through obstacles and stairs. Using a white stick to detect the obstacles had been an age old method, which cannot provide complete solution. In order to overcome this problem, an obstacle detecting shoe is developed. It senses the obstacle through ultrasonic sensors and alerts the user through the message. The ultrasonic waves transmitted are reflected by the obstacles and echo is received by the ultrasonic receiver, where the distance is calculated by using a microprocessor. The RFID system is used to assist the blind people. When the reader located on the shoe moves on to a specific tag, unique tag ID is sent to the reader. While in the case of walking in traffic, RF Link Transmitter/receiver is used for traffic signal detection and for passing instructions to the user through voice messages. A timer is used to detect the wet areas and helps the blind to avoid slippery.       

The cell polarity regulator hScrib controls ERK activation through a KIM site-dependent interaction

n/

Receptor Complementation and Mutagenesis Reveal SR-BI as an Essential HCV Entry Factor and Functionally Imply Its Intra- and Extra-Cellular Domains

HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI), a major receptor of high-density lipoprotein (HDL), the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection

Sphingomyelin Functions as a Novel Receptor for Helicobacter pylori VacA

The vacuolating cytotoxin (VacA) of the gastric pathogen Helicobacter pylori binds and enters epithelial cells, ultimately resulting in cellular vacuolation. Several host factors have been reported to be important for VacA function, but none of these have been demonstrated to be essential for toxin binding to the plasma membrane. Thus, the identity of cell surface receptors critical for both toxin binding and function has remained elusive. Here, we identify VacA as the first bacterial virulence factor that exploits the important plasma membrane sphingolipid, sphingomyelin (SM), as a cellular receptor. Depletion of plasma membrane SM with sphingomyelinase inhibited VacA-mediated vacuolation and significantly reduced the sensitivity of HeLa cells, as well as several other cell lines, to VacA. Further analysis revealed that SM is critical for VacA interactions with the plasma membrane. Restoring plasma membrane SM in cells previously depleted of SM was sufficient to rescue both toxin vacuolation activity and plasma membrane binding. VacA association with detergent-resistant membranes was inhibited in cells pretreated with SMase C, indicating the importance of SM for VacA association with lipid raft microdomains. Finally, VacA bound to SM in an in vitro ELISA assay in a manner competitively inhibited by lysenin, a known SM-binding protein. Our results suggest a model where VacA may exploit the capacity of SM to preferentially partition into lipid rafts in order to access the raft-associated cellular machinery previously shown to be required for toxin entry into host cells

Same data, different conclusions: Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis

In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists’ gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for organizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed