31 research outputs found

    PLA Microparticles for Pulmonary Delivery of AntiTB drugs: Biodistribution study

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    A dry powder inhalable (DPI) microparticles comprising anti-tuberculosis drugs incorporated in biodegradable polymers was developed for the treatment of pulmonary tuberculosis (P. Muttil _et al_. 2007). Poly L-lactic acid (PLA) microparticles incorporating a high payload of rifabutin and isoniazid were fabricated by spray drying (Buchi 190). Microparticles were composed of PLA and the drugs (rifabutin and isoniazid) at a 2:1:1 weight ratio. Microparticles of desired high encapsulation efficiency and sustained release characteristics were produced having a diameter range of 2-10 µm (Malvern Mastersizer 2000). Differential scanning calorimetry (DSC) was carried out to study drug polymer interaction. The time course of tissue biodistribution following a single inhalation dose of microparticles was evaluated. 
Thirty-two BALB/c mice were divided into groups of four and administered the DPI using an in-house (nose only) apparatus (Kaur _et al_. 2008; Verma _et al_. 2008). A validated HPLC method was used for determination of rifabutin and isoniazid in the lungs (target organ), liver and kidneys (major sites of toxicity) at different time-points after inhalation. A comparison was made with mice receiving free drugs (intravenous) at equivalent doses. Deposition of microparticles in lungs of mice following aerosolization was also evaluated. Pharmacokinetic parameters in different organs were calculated using WinNonlin software version 5.2. Area under the concentration-time curve observed (AUC~obs~), C~max~, half-life (t~½~) and clearance (CL) in lungs following inhalation /intravenous administration were:
*Rifabutin*: AUC~obs~-96h= 1697.39 ±154.67 (187.63 ±23.93) µg/ml^-1^hr^-1^; C~max~ = 33.42±3.80 (4.17±0.31) µg.ml^-1^; t~½~= 78.08±9.42 (34.00 ±3.31) and Cl= 1.16±.22 (0.68 ±0.45) ml.h^-1^.
*Isoniazid*: AUC~obs~-24h= 566.31±123.96 (99.85 ±14.24) µg/ml^-1^hr^-1^; Cmax= 24.02±1.71 (8.16±0.93) µg.ml^-1^; t~½~= 25.88±12.16 (6.45±3.24) h; and Cl= 5.47±1.30 (0.96±0.14) ml.h^-1^.
The relative bioavailability of both drugs incorporated in microparticles was significantly higher compared with free drugs. Peak levels of isoniazid and rifabutin in lungs (target organ) were much higher than those in the liver and kidney of mice in case of inhalation as compared to intravenous administration. Inhalation of microparticles resulted in targeting both drugs to the lungs, with the effect being more pronounced in the case of rifabutin than isoniazid. High and prolonged drug concentrations and increased AUC values (~9-fold and ~6 fold increase of rifabutin and isoniazid in case of lungs) with respect to free drugs were observed. Significant decrease in drug concentration was found in the liver and kidneys. Drug levels were maintained above the minimum inhibitory concentration (MIC) in organs through out the study after administration of encapsulated drugs. Based on favorable biodistribution kinetics, these microparticles hold great potential in reducing dosing frequency and toxicity of antituberculosis drugs.
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    State of fabric producing units in India

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    The estimates in the government funded survey of handloom and powerloom sectors of the number of units, looms and employment are not reliable since they are especially designed to identify units eligible for sector-specific schemes. The Unit-wise Annual survey of Industries and the NSSO 62nd round data for 2005-06 cover the entire manufacturing data, but the results derived for variables such as value added, output, fabric production etc are also not considered reliables as the small units have a tendency to under report their production in order to retain the benefits of small-scale sector tax incentives. This paper presents an analysis of the National Counicl of Applied Economic Research sample survey, which was designed to estimate the weighted per unit ratio for various size classess of units belonging to the handloom, powerloom mill and kitting sectors

    Not Minding the Gap: Intercultural Shakespeare in Britain

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    The article takes issue with the perceived space/gap between the multiple identities of mixed-heritage groups, as most of these people often pick and choose elements from all of their identities and amalgamate them into a cross-cultural whole. In recent years, such mixed-heritage groups in the U.K. have increasingly found cultural expression in Shakespeare. Focusing specifically on a number of recent Shakespearean productions, by what I term Brasian (my preferred term for British-Asians as it suggests a more fused identity) theatre companies, the article demonstrates how these productions employ hybrid aesthetic styles, stories, and theatre forms to present a layered Braisian identity. It argues that these productions not only provide a nuanced understanding of the intercultural map of Britain but are also a rich breeding ground for innovative Shakespeare productions in the U.K

    The CMS Outer Hadron Calorimeter

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    The CMS hadron calorimeter is a sampling calorimeter with brass absorber and plastic scintillator tiles with wavelength shifting fibres for carrying the light to the readout device. The barrel hadron calorimeter is complemented with a outer calorimeter to ensure high energy shower containment in CMS and thus working as a tail catcher. Fabrication, testing and calibrations of the outer hadron calorimeter are carried out keeping in mind its importance in the energy measurement of jets in view of linearity and resolution. It will provide a net improvement in missing \et measurements at LHC energies. The outer hadron calorimeter has a very good signal to background ratio even for a minimum ionising particle and can hence be used in coincidence with the Resistive Plate Chambers of the CMS detector for the muon trigger

    Design, Performance, and Calibration of CMS Hadron-Barrel Calorimeter Wedges

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    Extensive measurements have been made with pions, electrons and muons on four production wedges of the Compact Muon Solenoid (CMS) hadron barrel (HB) calorimeter in the H2 beam line at CERN with particle momenta varying from 20 to 300 GeV/c. Data were taken both with and without a prototype electromagnetic lead tungstate crystal calorimeter (EB) in front of the hadron calorimeter. The time structure of the events was measured with the full chain of preproduction front-end electronics running at 34 MHz. Moving-wire radioactive source data were also collected for all scintillator layers in the HB. These measurements set the absolute calibration of the HB prior to first pp collisions to approximately 4%

    Energy Response and Longitudinal Shower Profiles Measured in CMS HCAL and Comparison With Geant4

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    The response of the CMS combined electromagnetic and hadron calorimeter to beams of pions with momenta in the range 5-300 GeV/c has been measured in the H2 test beam at CERN. The raw response with the electromagnetic compartment calibrated to electrons and the hadron compartment calibrated to 300 GeV pions may be represented by sigma = (1.2) sqrt{E} oplus (0.095) E. The fraction of energy visible in the calorimeter ranges from 0.72 at 5 GeV to 0.95 at 300 GeV, indicating a substantial nonlinearity. The intrinsic electron to hadron ratios are fit as a function of energy and found to be in the range 1.3-2.7 for the electromagnetic compartment and 1.4-1.8 for the hadronic compartment. The fits are used to correct the non-linearity of the e pi response to 5% over the entire measured range resulting in a substantially improved resolution at low energy. Longitudinal shower profile have been measured in detail and compared to Geant4 models, LHEP-3.7 and QGSP-2.8. At energies below 30 GeV, the data, LHEP and QGSP are in agreement. Above 30 GeV, LHEP gives a more accurate simulation of the longitudinal shower profile

    Synchronization and Timing in CMS HCAL

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    The synchronization and timing of the hadron calorimeter (HCAL) for the Compact Muon Solenoid has been extensively studied with test beams at CERN during the period 2003-4, including runs with 40 MHz structured beam. The relative phases of the signals from different calorimeter segments are timed to 1 ns accuracy using a laser and equalized using programmable delay settings in the front-end electronics. The beam was used to verify the timing and to map out the entire range of pulse shapes over the 25 ns interval between beam crossings. These data were used to make detailed measurements of energy-dependent time slewing effects and to tune the electronics for optimal performance

    Design, Performance and Calibration of the CMS Forward Calorimeter Wedges

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    We report on the test beam results and calibration methods using charged particles of the CMS Forward Calorimeter (HF). The HF calorimeter covers a large pseudorapidity region (3\l |\eta| \le 5), and is essential for large number of physics channels with missing transverse energy. It is also expected to play a prominent role in the measurement of forward tagging jets in weak boson fusion channels. The HF calorimeter is based on steel absorber with embedded fused-silica-core optical fibers where Cherenkov radiation forms the basis of signal generation. Thus, the detector is essentially sensitive only to the electromagnetic shower core and is highly non-compensating (e/h \approx 5). This feature is also manifest in narrow and relatively short showers compared to similar calorimeters based on ionization. The choice of fused-silica optical fibers as active material is dictated by its exceptional radiation hardness. The electromagnetic energy resolution is dominated by photoelectron statistics and can be expressed in the customary form as a/\sqrt{E} + b. The stochastic term a is 198% and the constant term b is 9%. The hadronic energy resolution is largely determined by the fluctuations in the neutral pion production in showers, and when it is expressed as in the electromagnetic case, a = 280% and b = 11%

    Design, Performance, and Calibration of CMS Hadron Endcap Calorimeters

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    Detailed measurements have been made with the CMS hadron calorimeter endcaps (HE) in response to beams of muons, electrons, and pions. Readout of HE with custom electronics and hybrid photodiodes (HPDs) shows no change of performance compared to readout with commercial electronics and photomultipliers. When combined with lead-tungstenate crystals, an energy resolution of 8\% is achieved with 300 GeV/c pions. A laser calibration system is used to set the timing and monitor operation of the complete electronics chain. Data taken with radioactive sources in comparison with test beam pions provides an absolute initial calibration of HE to approximately 4\% to 5\%

    Design, Performance, and Calibration of the CMS Hadron-Outer Calorimeter

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    The CMS hadron calorimeter is a sampling calorimeter with brass absorber and plastic scintillator tiles with wavelength shifting fibres for carrying the light to the readout device. The barrel hadron calorimeter is complemented with an outer calorimeter to ensure high energy shower containment in the calorimeter. Fabrication, testing and calibration of the outer hadron calorimeter are carried out keeping in mind its importance in the energy measurement of jets in view of linearity and resolution. It will provide a net improvement in missing \et measurements at LHC energies. The outer hadron calorimeter will also be used for the muon trigger in coincidence with other muon chambers in CMS
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