Development and establishment of a parallel plate ionization chamber as a transfer standard for measurement of dose to tissue in beta radiation fields.

A parallel-plate ionization chamber (PPC) with a nominal volume of 8.16 cm³ was developed based on theoretically simulated design parameters. Its purpose is to serve as a transfer standard for dosimetry in a beta radiation field. The entrance window of the PPC consists of an aluminized Mylar sheet with a thickness of 1.4 mg/cm2. The collecting and guard electrodes are created by applying a graphite coating on a Poly Methyl Methacrylate (PMMA) substrate with a thickness of 5 mm. The nominal sheet resistance of the graphite-coated PMMA substrate was measured using a four-probe technique and found to be approximately 800 Ω per square (Ω/□). Dosimetric characterization of the PPC was performed in the ISO 6980 reference beta radiation field, utilizing 90Sr-90Y and 85Kr beta radiation sources. The assessment included studies on short-term stability, linearity, current-to-voltage characteristics, stabilization time, and leakage current. The PPC was calibrated and established as a transfer standard using the 'Extrapolation Ionization Chamber,' recognized as an absolute standard for dose to tissue in 90Sr-90Y and 85Kr beta sources within the laboratory. The calibration coefficient of the PPC indicates an energy dependence of 0.6 % for 90Sr-90Y and 85Kr beta sources.

Effect of electrode separation and electrode backscatter thickness of a parallel plate ionization chamber on the measurement of dose to tissue in beta radiation fields.

Plane parallel plate ionization chamber (PPC) is used in dosimetry especially for beta particles and low energy electron beam. The response of the PPC is affected by the electrode separation, thickness and material of backscatterer. The effect of electrode separation arises due to the well-known inscattering effect of electron which causes fluence perturbation inside the chamber cavity. The perturbation is caused due to reduced electron scattering in the chamber cavity compared to an ideal phantom material and it depends on the thickness of the cavity. Furthermore, the response of PPC also gets affected by the material behind the air cavity. Variation in the response depends on the thickness and the atomic number of the material behind collecting electrode of the PPC. The theoretical studies on the effect of collecting electrode backscatter thickness and electrode separation on the response of a PPC used as a transfer standard in ISO 6980 reference beta radiation field from 85Kr, 90Sr-90Y and 106Ru-106Rh radionuclides are presented. Multi-particle transport code FLUKA is used for the studies. The Polymethyl Methacrylate (PMMA) plate having 3.5 mm thickness is found to provide full backscatter for the above beta radionuclides. It is also observed that even for a well-guarded PPC, as the chamber electrode separation increases, the measured depth dose curve deviates from the ideal depth dose curve and the effective point of measurement (EPOM) of the PPC shifts towards downward direction from chamber reference point. It is also observed that the deviation between ideal and measured depth dose curve (related to EPOM shift) depends on the cavity thickness of the PPC. In the present work, optimization of design parameters of a PPC is carried out to establish it as a transfer standard in compliance with ISO 6980 for the standardization of reference beta radiation fields from 85Kr, 90Sr-90Y and 106Ru-106Rh radionuclide.

Assessing Transporter-Mediated Natural Product-Drug Interactions Via In vitro-In Vivo Extrapolation: Clinical Evaluation With a Probe Cocktail.

The botanical natural product goldenseal can precipitate clinical drug interactions by inhibiting cytochrome P450 (CYP) 3A and CYP2D6. Besides P-glycoprotein, effects of goldenseal on other clinically relevant transporters remain unknown. Established transporter-expressing cell systems were used to determine the inhibitory effects of a goldenseal extract, standardized to the major alkaloid berberine, on transporter activity. Using recommended basic models, the extract was predicted to inhibit the efflux transporter BCRP and uptake transporters OATP1B1/3. Using a cocktail approach, effects of the goldenseal product on BCRP, OATP1B1/3, OATs, OCTs, MATEs, and CYP3A were next evaluated in 16 healthy volunteers. As expected, goldenseal increased the area under the plasma concentration-time curve (AUC0-inf ) of midazolam (CYP3A; positive control), with a geometric mean ratio (GMR) (90% confidence interval (CI)) of 1.43 (1.35-1.53). However, goldenseal had no effects on the pharmacokinetics of rosuvastatin (BCRP and OATP1B1/3) and furosemide (OAT1/3); decreased metformin (OCT1/2, MATE1/2-K) AUC0-inf (GMR, 0.77 (0.71-0.83)); and had no effect on metformin half-life and renal clearance. Results indicated that goldenseal altered intestinal permeability, transport, and/or other processes involved in metformin absorption, which may have unfavorable effects on glucose control. Inconsistencies between model predictions and pharmacokinetic outcomes prompt further refinement of current basic models to include differential transporter expression in relevant organs and intestinal degradation/metabolism of the precipitant(s). Such refinement should improve in vitro-in vivo prediction accuracy, contributing to a standard approach for studying transporter-mediated natural product-drug interactions.

Structural basis of the strong cell-cell junction formed by cadherin-23.

Cadherin-23, a giant atypical cadherin, forms homophilic interactions at the cell-cell junction of epithelial cells and heterophilic interactions with protocadherin-15 at the tip-links of neuroepithelial cells. While the molecular structure of the heterodimer is solved, the homodimer structure is yet to be resolved. The homodimers play an essential role in cell-cell adhesion as the downregulation of cadherin-23 in cancers loosen the intercellular junction resulting in faster-migration of cancer cells and a significant drop in patient survival. In vitro studies have measured a stronger aggregation-propensity of cadherin-23 compared to typical E-cadherin. Here, we deciphered the unique trans-homodimer structure of cadherin-23 in solution, and show that it consists of two electrostatic-based interfaces extended up to two terminal domains. The interface is robust, with a low off-rate of ~8x10-4 s-1 that supports its strong aggregation-propensity. We identified a point-mutation, E78K, that disrupts this binding. Interestingly, a mutation at the interface was reported in skin cancer. Overall, the structural basis of the strong cadherin-23 adhesion may have far-reaching applications in the fields of mechanobiology and cancer.

Tobacco-related cancers in India: A review of incidence reported from population-based cancer registries.

BACKGROUND: Tobacco related cancers (TRC) account for major share of all cancers and updated of incidence data are helpful in policy changes. The aim was to present an update of TRCs on age-adjusted incidence data and corresponding lifetime risk of developing TRC for different regions of the country. METHODS: The data for this study were obtained from published reports of 25 population-based cancer registries (PBCRs) in India. The PBCRs in different parts of India were divided into seven regions such as North, South, Central, Northeast, West, Rural West, and East. Data indicators such as age-adjusted rates (AARs) of incidence and the cumulative risks of TRCs up to the age of 64 years for each of the 10 TRC sites of either sex in each of 25 registries were obtained from the National Cancer Registry Programme reports. RESULTS: Among all TRCs, esophagus, lung, hypopharynx, and mouth are the leading sites for both males and females. Males in Northeast region had the highest risk 1 in 27 of developing esophageal cancer, 1 in 67 for cancer of lungs and hypopharynx, followed by 1 in 143 for both mouth and tongue cancers. Females also had the highest risk of esophagus and lungs (1 in 63 female) and cancer of mouth (1 in 250) in Northeast region. Proportion of TRC in comparison of all cancer ranged from 11-25% for men and 3-18% for women. CONCLUSIONS: Proportion of TRC in relation to all cancers was still high in different registries of India including the Northeast region.

Effect of cataract surgery and pupil dilation on iris pattern recognition for personal authentication.

PURPOSE: The purpose of this study was to investigate the effect of cataract surgery and pupil dilation on iris pattern recognition for personal authentication. METHODS: Prospective non-comparative cohort study. Images of 15 subjects were captured before (enrolment), and 5, 10, and 15 min after instillation of mydriatics before routine cataract surgery. After cataract surgery, images were captured 2 weeks thereafter. Enrolled and test images (after pupillary dilation and after cataract surgery) were segmented to extract the iris. This was then unwrapped onto a rectangular format for normalization and a novel method using the Discrete Cosine Transform was applied to encode the image into binary bits. The numerical difference between two iris codes (Hamming distance, HD) was calculated. The HD between identification and enrolment codes was used as a score and was compared with a confidence threshold for specific equipment, giving a match or non-match result. The Correct Recognition Rate (CRR) and Equal Error Rates (EERs) were calculated to analyse overall system performance. RESULTS: After cataract surgery, perfect identification and verification was achieved, with zero false acceptance rate, zero false rejection rate, and zero EER. After pupillary dilation, non-elastic deformation occurs and a CRR of 86.67% and EER of 9.33% were obtained. CONCLUSIONS: Conventional circle-based localization methods are inadequate. Matching reliability decreases considerably with increase in pupillary dilation. Cataract surgery has no effect on iris pattern recognition, whereas pupil dilation may be used to defeat an iris-based authentication system.

Reduction of copper(II) by iron(II).

Laboratory and field investigations have clearly demonstrated the important role of reduced iron (Fe(II)) in reductive transformations of first-row transition metal species. However, interactions of Fe(II) and copper (Cu) are not clearly understood. This study examined the reduction of Cu(II) by Fe(II) in stirred-batch experiments at pH 5.2 and 5.5 as influenced by chloride (Cl-) concentration (0.002-0.1 M), initial metal concentration (0.1-9.1 mM), and reaction time (1-60 min) under anoxic conditions. Reduction of Cu(II) to Cu(I) by dissolved Fe(II) was rapid under all experimental conditions and the stability of the products explains the driving force for the redox reaction. Under conditions of low [Cl-] and high initial metal concentration, >40% of total Cu and Fe were removed from solution after 1 min, which accompanied formation of a brownish-red precipitate. X-ray diffraction (XRD) patterns of the precipitates revealed the presence of cuprite (Cu2O), a Cu(I) mineral, based on d-spacings located at 0.248, 0.215, 0.151, and 0.129 nm. Fourier transform infrared (FTIR) spectroscopy corroborated XRD data for the presence of Cu2O, with features located at 518, 625, and 698 cm(-1). Increasing [Cl-] stabilized the dissolved Cu(I) product against Cu2O precipitation and resulted in more Fe precipitated from solution (relative to Cu) that appears to be present as poorly crystalline lepidocrocite (gamma-FeOOH). This process may be important in anoxic soil environments, where dissolved Fe(II) levels can accumulate.

Camptothecin induced mitochondrial dysfunction leading to programmed cell death in unicellular hemoflagellate Leishmania donovani.

The parasites of the order kinetoplastidae including Leishmania spp. emerge from most ancient phylogenic branches of unicellular eukaryotic lineages. In their life cycle, topoisomerase I plays a significant role in carrying out vital cellular processes. Camptothecin (CPT), an inhibitor of DNA topoisomerase I, induces programmed cell death (PCD) both in the amastigotes and promastigotes form of L. donovani parasites. CPT-induced cellular dysfunction in L. donovani promastigotes is characterized by several cytoplasmic and nuclear features of apoptosis. CPT inhibits cellular respiration that results in mitochondrial hyperpolarization taking place by oligomycin-sensitive F0-F1 ATPase-like protein in leishmanial cells. During the early phase of activation, there is an increase in reactive oxygen species (ROS) inside cells, which causes subsequent elevation in the level of lipid peroxidation and decrease in reducing equivalents like GSH. Endogenous ROS formation and lipid peroxidation cause eventual loss of mitochondrial membrane potential. Furthermore, cytochrome c is released into the cytosol in a manner independent of involvement of CED3/CPP32 group of proteases and unlike mammalian cells it is insensitive to cyclosporin A. These events are followed by activation of both CED3/CPP32 and ICE group of proteases in PCD of Leishmania. Taken together, our study indicates that different biochemical events leading to apoptosis in leishmanial cells provide information that could be exploited to develop newer potential therapeutic targets.