Design techniques for radiation hardened-phase locked loops

Spacecrafts experience radiation in the course of their operation and all electronic equipment on board these spacecrafts has to be designed to withstand the effects of this radiation. This thesis describes the effects of total ionization dose (TID) and single event transients (SET) in phase-locked loops - an important circuit block for communication circuits and clock generation. The design of a digital phase-locked loop made tolerant to SET through redundancy and error correction techniques has been described. Digital phase-locked loops can also incorporate self-calibration techniques to compensate for the effects of TID. A linear analysis is presented for the design of digital phase-locked loops. This digital phase-locked loop was fabricated in the Honeywell 0.35 μm SOI CMOS process.Keywords: Phase-locked loops, Radiation hardene

Fermentation, Isolation, Structure, and antidiabetic activity of NFAT-133 produced by Streptomyces strain PM0324667

Type-2 diabetes is mediated by defects in either insulin secretion or insulin action. In an effort to identify extracts that may stimulate glucose uptake, similar to insulin, a high throughput-screening assay for measuring glucose uptake in skeletal muscle cells was established. During the screening studies to discover novel antidiabetic compounds from microbial resources a Streptomyces strain PM0324667 (MTCC 5543, the Strain accession number at Institute of Microbial Technology, Chandigarh, India), an isolate from arid soil was identified which expressed a secondary metabolite that induced glucose uptake in L6 skeletal muscle cells. By employing bioactivity guided fractionation techniques, a tri-substituted simple aromatic compound with anti-diabetic potential was isolated. It was characterized based on MS and 2D NMR spectral data and identified as NFAT-133 which is a known immunosuppressive agent that inhibits NFAT-dependent transcription in vitro. Our investigations revealed the antidiabetic potential of NFAT-133. The compound induced glucose uptake in differentiated L6 myotubes with an EC50 of 6.3 ± 1.8 μM without activating the peroxisome proliferator-activated receptor-γ. Further, NFAT-133 was also efficacious in vivo in diabetic animals and reduced systemic glucose levels. Thus it is a potential lead compound which can be considered for development as a therapeutic for the treatment of type-2 diabetes. We have reported herewith the isolation of the producer microbe, fermentation, purification, in vitro, and in vivo antidiabetic activity of the compound

TABLE OF CONTENTS

First and foremost, I would like to express my gratitude to my advisors Kartikeya Mayaram and Un-Ku Moon. The research work described in this thesis was performed under their supervision and guidance. Pavan was like a third mentor to me and has offered his advice on a number of issues during this project. I would like to thank him for his contributions towards this work. Then, I would like to acknowledge my teammates Kerem and Martin with whom I have worked together for a number of hours. Several members of PLL and Analog groups helped me during the last two years. My thanks to all of them

Cell proliferation and natural killer cell activity by polyherbal formulation, <span style="font-size:14.0pt;line-height:115%;font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";color:black;mso-ansi-language:EN-IN; mso-fareast-language:EN-IN;mso-bidi-language:HI" lang="EN-IN">Immu-21 in mice</span>

282-287Immunomodulatory activity of an Ayurvedic polyherbal formulation, Immu-21 containing extracts of Ocimum sanetum, Withania somnifera, Emblica officinalis and Tinospora cordifolia was studied on proliferative response of splenic leukocytes to T cell mitogens, concanavalin (Con)-A and phytohemagglutinin (PHA) and B cell mitogen, lipopolysaccharide (LPS) in vitro by [3H]-thymidine uptake assay in mice. The cytotoxic activity of Immu-21 was tested by measuring the splenic leukocyte natural killer (NK) cell activity against K 562 cells. Intraperitoneal (ip) treatment with Immu-21 (30 mg/kg) once a day for 14 and 21 days did not cause change in body weight and spleen weight, where as splenocytes/spleen count was increased. Treatment of Immu-21 (30 mg/kg, ip) for 14 days and 1 mg/kg for 21 days significantly increased LPS induced leukocyte proliferation. NK cell activity was significantly increased when mice were pretreated with Immu-21 (10 and 30 mg/kg, ip) once a day for 7 days. The results indicate that pretreatment with Immu-21 selectively increased the proliferation of splenic leukocyte to B cell mitogen, LPS and cytotoxic activity against K 562 cells in mice.</span

DESIGN TECHNIQUES FOR RADIATION HARDENED PHASE-LOCKED LOOPS

Reliable operation of electronic equipment onboard the spacecraft requires radiation hardening. This article presents the design and analysis of a radiation hardened digital phase-locked loop. The effects of radiation both single event and total ionization dose on the phase-locked loops are briefly described. The constituent parts of digital phase-locked loops (DPLLs) are described and their impact on the overall radiation tolerance is reviewed. Single event hardening design techniques were additionally introduced into the digital PLL to improve its radiation performance. This PLL was fabricated in the Honeywell 0.35µm SOI CMOS process. I

Prediction of volume of distribution in preclinical species and humans: application of simplified physiologically based algorithms

<p></p><p>The present study was aimed at developing simplified physiologically based semi-mechanistic algorithms to predict V_ss and interspecies scaling factors to predict tissue-K_ps which require minimum input parameters, diminish the computing complexity and have better predictability.</p><p>V_ss of 86 structurally diverse compounds in preclinical species and 27 compounds in humans were predicted using only lung- and muscle-K_p as inputs. Interspecies scaling factor (s) were developed based on fold-differences in individual tissue lipid contents, relative organ blood flow: relative organ weight ratio between two species. Tissue-K_ps were predicted for 34 compounds using the newly developed interspecies scaling factors.</p><p>The predicted-to-experimental V_ss values for all the 113 compounds was 1.3 ± 0.9 with 83% values being within a factor of two. The tissue-K_ps in rat, dog and human were predicted using experimental tissue-K_p data in rodents and interspecies scaling factors and here also, 83% of tissue-K_ps were within two-fold of the experimental values.</p><p>In conclusion, simplified physiologically based algorithms have been developed to predict both volume of distribution and tissue-K_ps, in which required input parameters as well as computing complexity have been noticeably reduced.</p><p></p> <p>The present study was aimed at developing simplified physiologically based semi-mechanistic algorithms to predict V_ss and interspecies scaling factors to predict tissue-K_ps which require minimum input parameters, diminish the computing complexity and have better predictability.</p> <p>V_ss of 86 structurally diverse compounds in preclinical species and 27 compounds in humans were predicted using only lung- and muscle-K_p as inputs. Interspecies scaling factor (s) were developed based on fold-differences in individual tissue lipid contents, relative organ blood flow: relative organ weight ratio between two species. Tissue-K_ps were predicted for 34 compounds using the newly developed interspecies scaling factors.</p> <p>The predicted-to-experimental V_ss values for all the 113 compounds was 1.3 ± 0.9 with 83% values being within a factor of two. The tissue-K_ps in rat, dog and human were predicted using experimental tissue-K_p data in rodents and interspecies scaling factors and here also, 83% of tissue-K_ps were within two-fold of the experimental values.</p> <p>In conclusion, simplified physiologically based algorithms have been developed to predict both volume of distribution and tissue-K_ps, in which required input parameters as well as computing complexity have been noticeably reduced.</p