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Concepts Underlying Clinical Pharmacokinetics

Pharmacokinetics provides the scientific basis of dose selection, and the process of dose regimen design can be used to illustrate with a single-compartment model the basic concepts of apparent distribution volume (Vd), elimination half-life (tu2) and elimination clearance (CLE). A schematic diagram of this model is shown in Figure 2.4, along with the two primary phar-macokinetic parameters of distribution volume and elimination clearance that characterize it.

Polyamine Depletion Associated With Increase in JunDAP1 Activity

Schematic diagram depicting the regulation in expression of the p53 gene by cellular polyamines and the proposed role of p53 in growth inhibition of the small intestinal mucosa after polyamine depletion. Cellular polyamine levels are decreased by either inhibition of their biosynthesis by blocking ornithine decarboxylase activity, stimulation of the catabolism through the activation of spermidine spermine-N-acetyltransferase activity, or suppression of polyamine uptake. Decreased cellular polyamines stabilize p53 messenger RNA and result in the accumulation of p53 through the induction of newly synthesized p53 protein. Polyamine depletion also increases nucleophosmin that interacts with and stabilizes p53 protein. The resultant increases in p53 initiate or enhance transcription of cell-cycle arrest genes such as p21, inhibits cell proliferation, and suppresses mucosal growth of the small intestine. SPD, spermidine SPM, spermine Put, putrescine DFMO, a-difluoromethylornithine...

Action Spectra Relate Light Absorption to Photosynthetic Activity

FIGURE 7.9 Schematic diagram of the action spectrum measurements by T. W. Engelmann. Engelmann projected a spectrum of light onto the spiral chloroplast of the filamentous green alga Spirogyra and observed that oxygen-seeking bacteria introduced into the system collected in the region of the spectrum where chlorophyll pigments absorb. This action spectrum gave the first indication of the effectiveness of light absorbed by accessory pigments in driving photosynthesis.

Practical Preimplantation Genetic Diagnosis

PGD for 13-bp deletion in APC gene resulting in birth of a normal child. (Top) Schematic diagram of the mutation and linked markers on chromosome 5q21. (Middle) Restriction map for Rsa I and Ssp I restriction digestion in exon 1 and untranslated area of APC gene. (Bottom) Polyacrylamide gel electrophoresis of the PCR products of PB1 and PB2 from 11 oocytes in one of the cycles of PGD for FAP, showing mutation-free oocytes 1,2,8,10, and 12, evidenced by normal and mutant fragments in PB1 and a mutant fragment in PB2, in agreement with all two marker analyses.

Different Forms of Synaptic Plasticity

Figure 1 NMDA receptor-dependent LTP induced in vivo at hippocampal to PFC synapses. A. Schematic diagram representing the location of stimulating and recording electrodes in ventral hippocampus (S, subiculum) and prelimbic cortex (PL). B. Examples of pre- and posttetanus hippocampal-prefrontal synaptic responses characterized by a large negative component with a peak at around 18 ms latency. Measurements of the amplitude of the synaptic responses are taken by drawing a line from a tangent drawn between the negative onset and offset with the use of an A Dvance software. C. Hippocampal-prefrontal LTP is dependent on NMDA receptors and the activation of PKA. Each point represents mean SEM of averaged responses to four stimuli given at 30 sec intervals. Values are expressed as percentage changes relative to baseline. Tetanic stimulation (250 Hz, 200 ms, 2 series) is indicated by arrowheads. Left graph shows a blockade of LTP by the NMDA antagonist D-AP5 (adopted from Jay et al., 1995a)....

Preimplantation Genetic Diagnosis For Single Gene Disorders

PGD for SHH mutation involving confirmation of the presence of both maternal and paternal normal genes in preselected mutation-free embryo. (A) Schematic diagram of the mutation and D7S550 linked marker on chromosome 7 arrows demonstrate the positions of heminested primers. (B) Restriction map for Xbal digestion, showing the gain ofXbal site by the mutant allele (lower line). (C) Polyacrylamide gel electrophoresis of the XbaI digested PCR products of nine blastomeres from PGD cycle. (D) Follow-up DNA analysis of genomic DNA from five embryos predicted affected by blastomere testing. (E) Capillary electrophoregrams of fluorescently labelled PCR product of tightly linked marker D7S550. Paternally derived 156 bp dinucleotide C-A repeat linked to SHH mutation is shown by arrows (paternal affected) in blastomeres of embryos 2,9,10,17, and the genomic DNA of the whole embryo 17, in which ADO of mutant gene was seen (see panel C, embryo 17). Maternally derived 158 bp...

The Domain Structure of Bacterial IF2

Figure 7.1-3 The domain structure of E. coli initiation factor IF2. (A) Schematic diagram of the domain structure of E. coli IF2. There are two alternative initiation sites (arrowed) within subdomain II marked with IF2-2 and IF2-3. The structure of part of subdomain I of the N-terminal domain (NTD) of E. coli IF2 has been determined (pdb 1 euq 101 ) and the central (G domain) and CTD encompassing subdomains IV-VI have almost 50 similarity to the archeal IF2 homologue aIF5B, whose structure (pdb 1 g7t 102 ) is also shown. (B) Part of the NTD of IF2 (residues 2-50 subdomain I) has structural homology with the SC-fold domain of Gln (and Met) aminoacyl-tRNA synthetases (GlnRS-SC). Within the complex GlnRS structure, this region contacts the anti-codon stem of the tRNA (pdb1euq 101 ). The tRNA is colored yellow with the anticodon (red) and CCA end (green) highlighted for reference. The homologous region to domain I of IF2 in the GlnRS is colored purple. (C) Domain VI-2 of IF2 has...

The Biophase Compartment

Figure 19.2 is a schematic diagram of a pharmacokinetic-pharmacodynamic model in which a biophase compartment links drug concentrations in plasma to observed effects. The mathematical characteristics of this biophase compartment have been described in detail by Sheiner et al. (9) and by Holford and Sheiner (10). In Figure 19.2, the pharmacokinetics of drug distribution and elimination are characterized by a single compartment (V1). Since no drug actually passes from V1 to Vb, the amount of drug X in compartment V1 merely serves as a forcing function with respect to the biophase, and the differential equation for drug in V1 can be written as follows

Enzymatic Membrane Preparation

Schematic diagram of the enzymatic membrane device. Glass column dimensions diameter 1 cm, height 10 cm. The inset represents the enzyme linkage of the biotinylated enzyme to the electropolymerized polypyrrole-biotin by the avidin-biotin molecular recognition process Fig. 24. Schematic diagram of the enzymatic membrane device. Glass column dimensions diameter 1 cm, height 10 cm. The inset represents the enzyme linkage of the biotinylated enzyme to the electropolymerized polypyrrole-biotin by the avidin-biotin molecular recognition process

Experimental Facility and Methodology

Experiments on the pyrolysis of cellulose were carried out in a controlled mixing history reactor (CMHR), which is a plasma-operated drop-tube furnace capable of operating at temperatures up to 2500 K. A schematic diagram of the CMHR is shown in Figure 15.1. The graphite core reactor tube is 2 inches in diameter and 60 inches long. The central test section of the reactor has two 24-inch long Figure 15.1. A schematic diagram of controlled mixing history reactor (CMHR).

Water Activity Measurement Methods

Figure 5.2 shows a schematic diagram for this method. According to this method, a sample weighing 10 to 50 g is put into a sample flask and sealed on to the apparatus. The air space in the apparatus is evacuated. After the vacuum source is isolated and equilibration for 30 to 50 min, the pressure exerted by the sample is recorded as Ah 1. The level of oil in the manometer will change by the vapor pressure exerted by the sample. The sample flask is excluded from the system and the desiccant flask is opened. Water vapor is removed by sorption onto CaSO4 and the pressure exerted by volatiles and gases are indicated by Ah2 after equilibration. Then, water activity can be calculated using Eq. (5.85) Figure 5.2 Schematic diagram for vapor pressure manometric method. Figure 5.2 Schematic diagram for vapor pressure manometric method.

Calibration Of Infrared Thermometers

FIG. 24.3 Schematic diagram of infrared thermometer being calibrated either using (a) a controlled temperature bath, Bf, or (b) an aluminum block, B. Other abbrevations A, radiation thermometer To, controlled temperature S, spherical surface (black surface) S, anodized aluminum surface C, cone (reflecting surface) D, reference surface system. (From Perrier, A., Leaf temperature measurement. In Plant Photosynthetic Production. Manual of Methods, p. 632-671, 1971, Z. Sestak, J. Catsky, and P.G. Jarvis, Eds. Fig. 17.7c, p. 656. Dr W. Junk N.V. The Hague, The Netherlands. With kind permission of Kluwer Academic Publishers and Professor Alain Perrier.) FIG. 24.3 Schematic diagram of infrared thermometer being calibrated either using (a) a controlled temperature bath, Bf, or (b) an aluminum block, B. Other abbrevations A, radiation thermometer To, controlled temperature S, spherical surface (black surface) S, anodized aluminum surface C, cone (reflecting surface) D, reference surface...

Echinococcus granulosus

Fig. 22.2 Schematic diagram of the metacestodes of Echinococcus granulosus and E. multilocularis a, b, c and d are stages in the development of the brood capsule in E. granulosus. Redrawn and designed by Russ Hobbs after Thompson, 1995 Fig. 22.2 Schematic diagram of the metacestodes of Echinococcus granulosus and E. multilocularis a, b, c and d are stages in the development of the brood capsule in E. granulosus. Redrawn and designed by Russ Hobbs after Thompson, 1995

Equipment And Techniques

Schematic diagram to show typical method of crystal mounting for air-backed therapy transducers (A) metal housing (earthed) (B) piezoelectric crystal silvered on both faces (C) solder (D) spring-loaded contact to back face Figure 13.1. Schematic diagram to show typical method of crystal mounting for air-backed therapy transducers (A) metal housing (earthed) (B) piezoelectric crystal silvered on both faces (C) solder (D) spring-loaded contact to back face

Utility of Microfluidics for Crystallization

Fig. 11.7 Schematic diagram of the evolution of vapor diffusion, microbatch and FID experiments through a two-dimensional projection of phase space having protein concentration and precipitating agent concentration as variables. The phase space is divided into soluble (S), metastable (M), labile (L) and precipitation (P) regions. Microbatch and hanging-drop experiments start at point II where the target molecule is combined 1 1 with the precipitating agent. Microbatch experiments sample only a point in phase space since incubation under immiscible oil prevents subsequent concentration of reagents (green). In Fig. 11.7 Schematic diagram of the evolution of vapor diffusion, microbatch and FID experiments through a two-dimensional projection of phase space having protein concentration and precipitating agent concentration as variables. The phase space is divided into soluble (S), metastable (M), labile (L) and precipitation (P) regions. Microbatch and hanging-drop experiments start at...

U The Adrenal Medulla

FIGURE 10 Schematic diagram of the action of catecholamines, E and NE, in a target cell. Abbreviations E, epinephrine NE, norepinephrine ATP adenosine triphosphate cAMP cyclic adenosine monophosphate GTP guanosine triphosphate PO4. FIGURE 10 Schematic diagram of the action of catecholamines, E and NE, in a target cell. Abbreviations E, epinephrine NE, norepinephrine ATP adenosine triphosphate cAMP cyclic adenosine monophosphate GTP guanosine triphosphate PO4.

Scintillation Detectors in PET

Siemens Pet Block Detector Bgo Crystal

Schematic diagram of the energy levels in a scintillation crystal and the mechanism of light production after energy is absorbed. The photon energy is sufficient to move a valence band electron to the conduction band. In returning to the ground state, light photons are emitted. Figure 2.19. Schematic diagram of the energy levels in a scintillation crystal and the mechanism of light production after energy is absorbed. The photon energy is sufficient to move a valence band electron to the conduction band. In returning to the ground state, light photons are emitted. Figure 2.20. Schematic diagram of a photomultiplier tube and a photograph of a hexagonal 6 cm-diameter tube (inset). Light entering the PMT displaces a photoelectron which is electrostatically focused to the first-stage dynode. Each dynode has a positive voltage bias relative to the previous one, and so electrons are accelerated from one dynode to the next. The increase in kinetic energy acquired by this process...

Surface plasmon resonance biosensor analysis

Biacore Biosensor Flow Theory

Schematic diagram of a surface plasmon resonance biosensor. One of the binding partners is immobilized on the sensor surface. With the BIACORE instrument, the soluble molecule is allowed to flow over the immobilized molecule. Binding of the soluble molecule results in a change in the refractive index of the solvent near the surface of the sensor chip. The magnitude of the shift in refractive index is related quantitatively to the amount of the soluble molecule that is bound. Figure 7.9. Schematic diagram of a surface plasmon resonance biosensor. One of the binding partners is immobilized on the sensor surface. With the BIACORE instrument, the soluble molecule is allowed to flow over the immobilized molecule. Binding of the soluble molecule results in a change in the refractive index of the solvent near the surface of the sensor chip. The magnitude of the shift in refractive index is related quantitatively to the amount of the soluble molecule that is bound.

Gene Delivery Approaches Viral Methods

Gene Delivery Viral Method

Schematic diagrams showing basic differences of three major gene delivery approaches retrovirus (left), adenovirus (center) and liposome (right). Retrovirus, containing a RNA genome, attaches to a host cell by binding to a specific cell surface receptor and a double-stranded DNA is synthesized from the RNA genome by a process called reverse transcription. This DNA integrates into the host genome ensuring sustained expression of the transgene. Adenovirus is comprised of a double-stranded DNA genome. After entering the cell by a receptor mediated endocytosis process, the viral DNA is released within the cell, which then leads to a synthesis of proteins using host cell machinery. The DNA does not integrate into the host genome. In liposomal delivery the plasmid DNA containing the therapeutic gene is encased in a lipid bilayer, which upon reaching a host cell, gets fused with the cellular membrane and releases the DNA within the cell. This DNA then synthesizes its protein...

Smads are the Downstream Intracellular Effectors of Activated TGFbTGFb Receptors After Polyamine Depletion

Polyamines Dna

Schematic diagram depicting the proposed role of the TGF-b Smad signaling pathway in the inhibition of cell proliferation after polyamine depletion. In this model, polyamines are the negative regulators for expression of the TGF-b gene, whereas Smad proteins are the downstream intracellular effectors of activated T GF -b receptors. Decreased levels of cellular polyamines increase expression of T GF -b through stabilization of T GF -b mRNA, enhance the release of TGF-b, and subsequently phosphorylate TGF-b type II receptor (R-II). The phospho-rylated R-II activates T GF - b type I receptor (R-I), induces the formation of Smad3 Smad4 heteromeric complexes, and stimulates their nuclear translocation. The activated Smads in the nucleus bind to the specific DNA site and cooperate with Smad DNA-binding partners, such as some AP-1 proteins, to activate or repress transcription of specific target genes, thus leading to Fig. 6. Schematic diagram depicting the proposed role of the TGF-b...

Pore Volumes Based On Length Units

Soil Physics Material Picture

FIG. 12.12 Schematic diagram of a soil column outflow experiment, where solute is added at t 0. (From Jury, W.A., Gardner, W.R., and Gardner, W.H., Soil Physics, 5th ed., p. 224, 1991, John Wiley & Sons New York. This material is used by permission of John Wiley & Sons, Inc.) FIG. 12.12 Schematic diagram of a soil column outflow experiment, where solute is added at t 0. (From Jury, W.A., Gardner, W.R., and Gardner, W.H., Soil Physics, 5th ed., p. 224, 1991, John Wiley & Sons New York. This material is used by permission of John Wiley & Sons, Inc.)

Enhancing The Activity Of Tissuespecific Promoters

Schematic diagram of the two-step transcriptional amplification (TSTA) system. The first step consists of activation of the GAL4-VP16 transactivator by a tissue-specific promoter. This is followed by binding of the transactivator complex to five Gal4 binding sites placed upstream of the target gene and a minimal promoter. Transcription of the reporter gene leads to reporter protein, which, in turn, leads to a detectable signal in the presence of a reporter probe. (Reproduced with permission from ref. 122). Fig. 7. Schematic diagram of the two-step transcriptional amplification (TSTA) system. The first step consists of activation of the GAL4-VP16 transactivator by a tissue-specific promoter. This is followed by binding of the transactivator complex to five Gal4 binding sites placed upstream of the target gene and a minimal promoter. Transcription of the reporter gene leads to reporter protein, which, in turn, leads to a detectable signal in the presence of a reporter probe....

Indirect Imaging of a Therapeutic Gene via a Reporter Gene

Schematic diagram explaining different approaches to link a therapeutic gene and a reporter gene to achieve indirect imaging of therapeutic gene expression. In each approach the goal is to image reporter gene expression in order to infer therapeutic gene expression. P is a chosen promoter driving transcription, IRES is an internal ribosomal entry site, and TRE is a tetracycline responsive element. In all cases the gene constructs (Boxes and wide arrow) and the translational protein products (wavy line) are shown. (1) In the bicistronic approach an IRES is used to link the two genes. Transcription occurs under a single promoter to form a single mRNA molecule. Translation of a single mRNA leads to a therapeutic protein and a reporter protein. (2) In a fusion gene construct the two gene sequences are coupled together with a spacer sequence in between them which when transcribed under a single promoter, leads to one mRNA. Translation leads to a single fusion protein capable...

Regulation of Cytoskeletal Organization in Chemotaxis

A dramatic rise of the proportion of polymerized actin (F-actin) is one of the most striking changes after addition of extracellular cAMP to aggregation-competent Dictyostelium cells. A schematic diagram for the establishment of the leading edge by redistribution of actin filaments and components involved in the regulation of actin filaments is presented in Fig. 3. Localized actin assembly is required for the psuedo-pod formation during chemotaxis. Sites of actin filament assembly in the cell are regulated by the actin-binding proteins that control the localization, length, and stability of actin filaments. These actin-binding Immunofluorescence studies demonstrate that cytoskeletons composed of actin and myosin II rapidly reorganize in Dictyostelium cells that have been stimulated with the chemoattractant cAMP. The amounts of F-actin increase in the cortical region of cells after 5-10 s of stimulation by cAMP (the first peak). After a transient decrease in the amount of F-actin in...

Protein Orientation and Subsequent Activity Optimised Antibody Immobilisation Protocol

Schematic diagram of the immobilisation of IgG3 anticortisol to the sensor chip surface. GMBS N-(y-maleimidobutyryloxy)succinimide Fig. 5. Schematic diagram of the immobilisation of IgG3 anticortisol to the sensor chip surface. GMBS N-(y-maleimidobutyryloxy)succinimide

Tetrahydrobiopterin and Vascular Disease

Pulmonary Hypertension Vascular Changes

Schematic diagram of NOS structure and function. Active NOS is a dimmer, with each monomer consisting of a reductase domain linked to an oxigenase domain. Electron are donated by NADPH, and transferred to FAD and FMN from the reductase domain of one NOS monomer, to the heme group (Fe) in the oxygenase domain of the other monomer, resulting in NO and L-citrulline synthesis and molecular oxygen. BH4 is closely bound to the heme group, serving as an electron donor and also interacts with residues from both monomers. Figure 3. Schematic diagram of NOS structure and function. Active NOS is a dimmer, with each monomer consisting of a reductase domain linked to an oxigenase domain. Electron are donated by NADPH, and transferred to FAD and FMN from the reductase domain of one NOS monomer, to the heme group (Fe) in the oxygenase domain of the other monomer, resulting in NO and L-citrulline synthesis and molecular oxygen. BH4 is closely bound to the heme group, serving as an electron...

Subtilisin

Laundry detergent contains proteases such as subtilisin to enhance cleaning action. Genencor International manufactures subtilisin and holds patents on methods for its crystallization 18,30 . A schematic diagram of the process is shown in Figure 5.7. Fermentation of Bacillus subtilis followed by cell separation yields a clear solution containing subtilisin. This solution is concentrated by ultrafiltration to 45 to 52 g l subtilisin, adjusted to pH 4.8 to 5.4, and 15 to 40 g l of either sodium chloride or sodium sulfate added as the precipitant. Seed crystals are added and the solution is held at 22 to 30 C for about 5 to 24 h to allow for crystallization. Raising the temperature increases the rate of crystal growth, shortening the time for crystallization from days to as little as 5 h. Nevertheless,

Glass Support

Schematic diagram of the bacterial photosynthetic reaction center in a bilayer membrane. The three protein subunits (L, M, and H) and the relevant junctional components, the special pair primary electron donor, P, and the primary quinone acceptor QA are indicated. The RC is depicted in an orientation that is consistent with a mechanism in which the vesicles fuse to the glass support by opening out. Reprintedfrom Salafsky, J., Groves, J. T and Boxer, S.G. (1996) Biochemistry 35, 14773-14781 with permissionfrom American Chemical Society.

Bubble Motion

Schematic diagram showing non-inertial cavitation thresholds (B, C) and rectified diffusion threshold (A) for bubbles (see text for details) Figure 12.10. Schematic diagram showing non-inertial cavitation thresholds (B, C) and rectified diffusion threshold (A) for bubbles (see text for details)

Surgery

Schematic diagram of the principle of focused ultrasound surgery. The focus is placed within the target volume. T ssue overlying and surrounding the target is undamaged Figure 13.7. Schematic diagram of the principle of focused ultrasound surgery. The focus is placed within the target volume. T ssue overlying and surrounding the target is undamaged

Hydraulic Press

Diagram Hydraulic Press

FIG. 17.10 Schematic diagram of the hydraulic press. The piston of the jack is drilled and then welded to the top of the jack. The bolts that hold the head together are 3 8 inch (0.95 cm) diameter, and two, or preferably three, are used. The metal parts of the head are aluminum. (From Campbell, G.S., and Brewster, S.F., Leaf water potential, matric potential and soil water content measured with a simple hydraulic press. Paper presented at the Western Regional Research Project W-67 Quantification of Water-Soil Plant Relations for Efficient Water Use. Honolulu, Hawaii, January, 1975. 11 pp. Reprinted by permission of Gaylon S. Campbell.) FIG. 17.10 Schematic diagram of the hydraulic press. The piston of the jack is drilled and then welded to the top of the jack. The bolts that hold the head together are 3 8 inch (0.95 cm) diameter, and two, or preferably three, are used. The metal parts of the head are aluminum. (From Campbell, G.S., and Brewster, S.F., Leaf water potential, matric...

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