The works of William E. Channing.

Contiene: T. I (XXX, 387 p.) -- T. II (411 p.) -- T. III (398 p.) -- T. IV (407 p.) -- T. V (440 p.) -- T.VI (420 p.)

A voyage of discovery to the North Pacific Ocean, and round the world : in which the coast of north-west America has been carefully examined and accurately surveyed : Undertaken by His Majesty's command, principally with a view to ascertain the existence of any navigable communication between the North Pacific and North Atlantic Oceans, and performed in the years 1790, 1791, 1792, 1793, 1794, and 1795, in the Discovery sloop of war, and armed tender Chatham, under the command of Captain George Vancouver : in three volumes, Vol. III.

Mode of access: Internet.

Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.

Crystal Coulomb energies: I. Organic donor-acceptor complexes--a review. II. Classical Ewald calculations of the Coulomb binding energy of four donor-acceptor crystals and Wurster's blue perchlorate. III. A rapid-convergence quantum-mechanical formalism for crystal electronic energies

<p>Chapter Ip> <p>Theories for organic donor-acceptor (DA) complexes in solution and in the solid state are reviewed, and compared with the available experimental data. As shown by McConnell et al. (Proc. Natl. Acad. Sci. U.S., 53, 46-50 (1965)), the DA crystals fall into two classes, the holoionic class with a fully or almost fully ionic ground state, and the nonionic class with little or no ionic character. If the total lattice binding energy 2ε₁ (per DA pair) gained in ionizing a DA lattice exceeds the cost 2ε_o of ionizing each DA pair, ε₁ + ε_o less than 0, then the lattice is holoionic. The charge-transfer (CT) band in crystals and in solution can be explained, following Mulliken, by a second-order mixing of states, or by any theory that makes the CT transition strongly allowed, and yet due to a small change in the ground state of the non-interacting components D and A (or Dp>+p> and Ap>-p>). The magnetic properties of the DA crystals are discussed.p> <p>Chapter IIp> <p>A computer program, EWALD, was written to calculate by the Ewald fast-convergence method the crystal Coulomb binding energy E_C due to classical monopole-monopole interactions for crystals of any symmetry. The precision of E_C values obtained is high: the uncertainties, estimated by the effect on E_C of changing the Ewald convergence parameter η, ranged from ± 0.00002 eV to ± 0.01 eV in the worst case. The charge distribution for organic ions was idealized as fractional point charges localized at the crystallographic atomic positions: these charges were chosen from available theoretical and experimental estimates. The uncertainty in E_C due to different charge distribution models is typically ± 0.1 eV (± 3%): thus, even the simple Hückel model can give decent results.p> <p>E_C for Wurster's Blue Perchl orate is -4.1 eV/molecule: the crystal is stable under the binding provided by direct Coulomb interactions. E_C for N-Methylphenazinium Tetracyanoquino- dimethanide is 0.1 eV: exchange Coulomb interactions, which cannot be estimated classically, must provide the necessary binding.p> <p>EWALD was also used to test the McConnell classification of DA crystals. For the holoionic (1:1)-(N,N,N',N'-Tetramethyl-para- phenylenediamine: 7,7,8,8-Tetracyanoquinodimethan) E_C = -4.0 eV while 2ε_o = 4.6₅ eV: clearly, exchange forces must provide the balance. For the holoionic (1:1)-(N,N,N',N'-Tetramethyl-para- phenylenediamine:para-Chloranil) E_C = -4.4 eV, while 2ε_o = 5.0 eV: again EC falls short of 2ε₁. As a Gedankenexperiment, two nonionic crystals were assumed to be ionized: for (1:1)-(Hexamethyl- benzene:para-Chloranil) E_C = -4.5 eV, 2ε_o = 6.6 eV; for (1:1)- (Napthalene:Tetracyanoethylene) E_C = -4.3 eV, 2ε_o = 6.5 eV. Thus, exchange energies in these nonionic crystals must not exceed 1 eV.p> <p>Chapter IIIp> <p>A rapid-convergence quantum-mechanical formalism is derived to calculate the electronic energy of an arbitrary molecular (or molecular-ion) crystal: this provides estimates of crystal binding energies which include the exchange Coulomb inter- actions. Previously obtained LCAO-MO wavefunctions for the isolated molecule(s) ("unit cell spin-orbitals") provide the starting-point. Bloch's theorem is used to construct "crystal spin-orbitals". Overlap between the unit cell orbitals localized in different unit cells is neglected, or is eliminated by Löwdin orthogonalization. Then simple formulas for the total kinetic energy Q^(XT)_λ, nuclear attraction [λ/λ]p>XTp>, direct Coulomb [λλ/λ'λ']p>XTp> and exchange Coulomb [λλ'/λ'λ]p>XTp> integrals are obtained, and direct-space brute-force expansions in atomic wavefunctions are given. Fourier series are obtained for [λ/λ]p>XTp>, [λλ/λ'λ']p>XTp>, and [λλ/λ'λ]p>XTp> with the help of the convolution theorem; the Fourier coefficients require the evaluation of Silverstone's two-center Fourier transform integrals. If the short-range interactions are calculated by brute-force integrations in direct space, and the long-range effects are summed in Fourier space, then rapid convergence is possible for [λ/λ]p>XTp>, [λλ/λ'λ']p>XTp> and [λλ'/λ'λ]p>XTp>. This is achieved, as in the Ewald method, by modifying each atomic wavefunction by a "Gaussian convergence acceleration factor", and evaluating separately in direct and in Fourier space appropriate portions of [λ/λ]p>XTp>, etc., where some of the portions contain the Gaussian factor.p>

I. Spectroscopic observation of discrete sites in simple liquids. II. Infrared intensity perturbations of hydrogen halide fundamentals in liquid xenon. III. Rotation of HCl in solid rare gases.

<p>Part Ip> <p>The spectrum of dissolved mercury atoms in simple liquids has been shown to be capable of revealing information concerning local structures in these liquids.p> <p>Part IIp> <p>Infrared intensity perturbations in simple solutions have been shown to involve more detailed interaction than just dielectric polarization. No correlation has been found between frequency shifts and intensity enhancements.p> <p>Part IIIp> <p>Evidence for perturbed rotation of HCl in rare gas matrices has been found. The magnitude of the barrier to rotation is concluded to be of order of 30 cm^(-1).p>

I. The crystal structure of potassium bis(tricyanovinyl)amine. II. Nuclear magnetic resonance studies of alkali halide solutions. III. Elucidation of the intramolecular hydrogen bond in acetylacetone by the deuterium isotope effect on the chemical shift of the bridge hydrogen

<p>Part Ip> <p>Potassium bis-(tricyanovinyl) amine, Kp>+p>N[C(CN)=C(CN)₂]₂p>-p>, crystallizes in the monoclinic system with the space group Cc and lattice constants, a = 13.346 ± 0.003 Ã…, c = 8.992 ± 0.003 Ã…, B = 114.42 ± 0.02°, and Z = 4. Three dimensional intensity data were collected by layers perpendicular to b* and c* axes. The crystal structure was refined by the least squares method with anisotropic temperature factor to an R value of 0.064. p> <p>The average carbon-carbon and carbon-nitrogen bond distances in –C-CΞN are 1.441 ± 0.016 Ã… and 1.146 ± 0.014 Ã… respectively. The bis-(tricyanovinyl) amine anion is approximately planar. The coordination number of the potassium ion is eight with bond distances from 2.890 Ã… to 3.408 Ã…. The bond angle C-N-C of the amine nitrogen is 132.4 ± 1.9°. Among six cyano groups in the molecule, two of them are bent by what appear to be significant amounts (5.0° and 7.2°). The remaining four are linear within the experimental error. The bending can probably be explained by molecular packing forces in the crystals.p> <p>Part IIp> <p>The nuclear magnetic resonance of p>81p>Br and p>127p>I in aqueous solutions were studied. The cation-halide ion interactions were studied by studying the effect of the Lip>+p>, Nap>+p>, Kp>+p>, Mgp>++p>, Csp>+p> upon the line width of the halide ions. The solvent-halide ion interactions were studied by studying the effects of methanol, acetonitrile, and acetone upon the line width of p>81p>Br and p>127p>I in the aqueous solutions. It was found that the viscosity plays a very important role upon the halide ions line width. There is no specific cation-halide ion interaction for those ions such as Mgp>++p>, Dip>+p>, Nap>+p>, and Kp>+p>, whereas the Csp>+p> - halide ion interaction is strong. The effect of organic solvents upon the halide ion line width in aqueous solutions is in the order acetone ˃ acetonitrile ˃ methanol. It is suggested that halide ions do form some stable complex with the solvent molecules and the reason Csp>+p> can replace one of the ligands in the solvent-halide ion complex.p> <p>Part IIIp> <p>An unusually large isotope effect on the bridge hydrogen chemical shift of the enol form of pentanedione-2, 4(acetylacetone) and 3-methylpentanedione-2, 4 has been observed. An attempt has been made to interpret this effect. It is suggested from the deuterium isotope effect studies, temperature dependence of the bridge hydrogen chemical shift studies, IR studies in the OH, OD, and C=O stretch regions, and the HMO calculations, that there may probably be two structures for the enol form of acetylacetone. The difference between these two structures arises mainly from the electronic structure of the Ï€-system. The relative population of these two structures at various temperatures for normal acetylacetone and at room temperature for the deuterated acetylacetone were calculated. p>

I. Fundamental limitations in microelectronics. II. Power Schottky diode design and comparison with the junction diode. III. Permittivity of strontium titanate

<p>Part Ip> <p>The physical phenomena which will ultimately limit the packing density of planar bipolar and MOS integrated circuits are examined. The maximum packing density is obtained by minimizing the supply voltage and the size of the devices. The minimum size of a bipolar transistor is determined by junction breakdown, punch-through and doping fluctuations. The minimum size of a MOS transistor is determined by gate oxide breakdown and drain-source punch-through. The packing density of fully active bipolar or static non-complementary MOS circuits becomes limited by power dissipation. The packing density of circuits which are not fully active such as read-only memories, becomes limited by the area occupied by the devices, and the frequency is limited by the circuit time constants and by metal migration. The packing density of fully active dynamic or complementary MOS circuits is limited by the area occupied by the devices, and the frequency is limited by power dissipation and metal migration. It is concluded that read-only memories will reach approximately the same performance and packing density with MOS and bipolar technologies, while fully active circuits will reach the highest levels of integration with dynamic MOS or complementary MOS technologies.p> <p>Part IIp> <p>Because the Schottky diode is a one-carrier device, it has both advantages and disadvantages with respect to the junction diode which is a two-carrier device. The advantage is that there are practically no excess minority carriers which must be swept out before the diode blocks current in the reverse direction, i.e. a much faster recovery time. The disadvantage of the Schottky diode is that for a high voltage device it is not possible to use conductivity modulation as in the p i n diode; since charge carriers are of one sign, no charge cancellation can occur and current becomes space charge limited. The Schottky diode design is developed in Section 2 and the characteristics of an optimally designed silicon Schottky diode are summarized in Fig. 9. Design criteria and quantitative comparison of junction and Schottky diodes is given in Table 1 and Fig. 10. Although somewhat approximate, the treatment allows a systematic quantitative comparison of the devices for any given application.p> <p>Part IIIp> <p>We interpret measurements of permittivity of perovskite strontium titanate as a function of orientation, temperature, electric field and frequency performed by Dr. Richard Neville. The free energy of the crystal is calculated as a function of polarization. The Curie-Weiss law and the LST relation are verified. A generalized LST relation is used to calculate the permittivity of strontium titanate from zero to optic frequencies. Two active optic modes are important. The lower frequency mode is attributed mainly to motion of the strontium ions with respect to the rest of the lattice, while the higher frequency active mode is attributed to motion of the titanium ions with respect to the oxygen lattice. An anomalous resonance which multi-domain strontium titanate crystals exhibit below 65°K is described and a plausible mechanism which explains the phenomenon is presented.p>

Artefact detection and removal algorithms for EEG diagnostic systems

The electroencephalogram (EEG) is a medical technology that is used in the monitoring of the brain and in the diagnosis of many neurological illnesses. Although coarse in its precision, the EEG is a non-invasive tool that requires minimal set-up times, and is suitably unobtrusive and mobile to allow continuous monitoring of the patient, either in clinical or domestic environments. Consequently, the EEG is the current tool-of-choice with which to continuously monitor the brain where temporal resolution, ease-of- use and mobility are important. Traditionally, EEG data are examined by a trained clinician who identifies neurological events of interest. However, recent advances in signal processing and machine learning techniques have allowed the automated detection of neurological events for many medical applications. In doing so, the burden of work on the clinician has been significantly reduced, improving the response time to illness, and allowing the relevant medical treatment to be administered within minutes rather than hours. However, as typical EEG signals are of the order of microvolts (μV ), contamination by signals arising from sources other than the brain is frequent. These extra-cerebral sources, known as artefacts, can significantly distort the EEG signal, making its interpretation difficult, and can dramatically disimprove automatic neurological event detection classification performance. This thesis therefore, contributes to the further improvement of auto- mated neurological event detection systems, by identifying some of the major obstacles in deploying these EEG systems in ambulatory and clinical environments so that the EEG technologies can emerge from the laboratory towards real-world settings, where they can have a real-impact on the lives of patients. In this context, the thesis tackles three major problems in EEG monitoring, namely: (i) the problem of head-movement artefacts in ambulatory EEG, (ii) the high numbers of false detections in state-of-the-art, automated, epileptiform activity detection systems and (iii) false detections in state-of-the-art, automated neonatal seizure detection systems. To accomplish this, the thesis employs a wide range of statistical, signal processing and machine learning techniques drawn from mathematics, engineering and computer science. The first body of work outlined in this thesis proposes a system to automatically detect head-movement artefacts in ambulatory EEG and utilises supervised machine learning classifiers to do so. The resulting head-movement artefact detection system is the first of its kind and offers accurate detection of head-movement artefacts in ambulatory EEG. Subsequently, addtional physiological signals, in the form of gyroscopes, are used to detect head-movements and in doing so, bring additional information to the head- movement artefact detection task. A framework for combining EEG and gyroscope signals is then developed, offering improved head-movement arte- fact detection. The artefact detection methods developed for ambulatory EEG are subsequently adapted for use in an automated epileptiform activity detection system. Information from support vector machines classifiers used to detect epileptiform activity is fused with information from artefact-specific detection classifiers in order to significantly reduce the number of false detections in the epileptiform activity detection system. By this means, epileptiform activity detection which compares favourably with other state-of-the-art systems is achieved. Finally, the problem of false detections in automated neonatal seizure detection is approached in an alternative manner; blind source separation techniques, complimented with information from additional physiological signals are used to remove respiration artefact from the EEG. In utilising these methods, some encouraging advances have been made in detecting and removing respiration artefacts from the neonatal EEG, and in doing so, the performance of the underlying diagnostic technology is improved, bringing its deployment in the real-world, clinical domain one step closer.

Analysis of UDP-galactose 4'-epimerase mutations associated with the intermediate form of type III galactosaemia

<p>Type III galactosaemia is a hereditary disease caused by reduced activity in the Leloir pathway enzyme, UDP-galactose 4'-epimerase (GALE). Traditionally, the condition has been divided into two forms-a mild, or peripheral, form and a severe, or generalized, form. Recently it has become apparent that there are disease states which are intermediate between these two extremes. Three mutations associated with this intermediate form (S81R, T150M and P293L) were analysed for their kinetic and structural properties in vitro and their effects on galactose-sensitivity of Saccharomyces cerevisiae cells that were deleted for the yeast GALE homologue Gal10p. All three mutations result in impairment of the kinetic parameters (principally the turnover number, k(cat)) compared with the wild-type enzyme. However, the degree of impairment was mild compared with that seen with the mutation (V94M) associated with the generalized form of epimerase deficiency galactosaemia. None of the three mutations tested affected the ability of the protein to dimerize in solution or its susceptibility to limited proteolysis in vitro. Finally, in the yeast model, each of the mutated patient alleles was able to complement the galactose-sensitivity of gal10 Delta cells as fully as was the wild-type human allele. Furthermore, there was no difference from control in metabolite profile following galactose exposure for any of these strains. Thus we conclude that the subtle biochemical and metabolic abnormalities detected in patients expressing these GALE alleles likely reflect, at least in part, the reduced enzymatic activity of the encoded GALE proteins.p>

Lumbar estrecho: experiencia de 10 años en la fundación santa fé de Bogotá

El canal lumbar estrecho de tipo degenerativo, es una enfermedad que se presenta en pacientes entre la quinta y la sexta década de vida; es la causa más común de cirugía lumbar después de los 65 años. Este trabajo busca determinar cuáles son los factores asociados a la presentación de eventos adversos o re-intervención en cirugía de canal lumbar estrecho en la Fundación Santa Fe de Bogotá en los años comprendidos entre 2003 y 2013. Métodos: se realizó un estudio de prevalencia de tipo analítico, en donde se analizaron 249 pacientes sometidos a intervención quirúrgica por cirugía de canal lumbar estrecho.

Transcriptional regulators of the GAD acid stress island are carried by effector protein-encoding prophages and indirectly control type III secretion in enterohemorrhagic Escherichia coli O157:H7

P>Type III secretion (T3S) plays a pivotal role in the colonization of ruminant hosts by Enterohemorrhagic Escherichia coli (EHEC). The T3S system translocates effector proteins into host cells to promote bacterial attachment and persistence. The repertoire and variation in prophage regions underpins differences in the pathogenesis and epidemiology of EHEC strains. In this study, we have used a collection of deletions in cryptic prophages and EHEC O157 O-islands to screen for novel regulators of T3S. Using this approach we have identified a family of homologous AraC-like regulators that indirectly repress T3S. These prophage-encoded secretion regulator genes (psr) are found exclusively on prophages and are associated with effector loci and the T3S activating Pch family of regulators. Transcriptional profiling, mutagenesis and DNA binding studies were used to show that these regulators usurp the conserved GAD acid stress resistance system to regulate T3S by increasing the expression of GadE (YhiE) and YhiF and that this regulation follows attachment to bovine epithelial cells. We further demonstrate that PsrA and effectors encoded within cryptic prophage CP933-N are required for persistence in a ruminant model of colonization.

Custos posturais nos posicionamentos em pé, em pé/sentado e sentado nos postos de trabalho do setor costura na indústria calçadista

Este trabalho de pesquisa é de natureza experimental e tem como objetivo analisar os custos posturais nos postos de trabalho do setor costura da indústria calçadista do Vale do Paranhana (RGS). Foram avaliados os custos metabólicos (freqüência cardíaca e nível de lactato), as sensações subjetivas de desconforto e dor (pelo Diagrama de Corlett e Bishop, 1976) e a produtividade nos posicionamentos em (I) pé e sentado (pela altemância postural), em (11)pé e (III) sentado em cadeira de palha e em (IV) cadeira ergonômica (conforme denominação do mercado). Foram realizados quatro estudos de caso, tendo fixado as seguintes variáveis dependentes: a percepção de desconforto e dor, os fatores metabólicos (freqüência cardíaca e nível de lactato no sangue) e a produtividade, e variável independente, a temperatura ambiente. Obteve-se como resultados que a postura em pé sempre apresenta o maior índice de desconforto e dor quando comparada com as demais posturas. Não foi encontrada diferença significativa de produtividade nas quatro condições. As variáveis metabólicas não foram indicadores de carga de trabalho nas diversas posturas.

Geochemical composition of olivine, spinel and amphibole in ODP Hole 209-1271B

Dunite and gabbroic materials recovered from Hole 1271B, Ocean Drilling Program (ODP) Leg 209, were examined for mineral chemistry to understand melt flow and melt-mantle reactions in the shallowest upper mantle of the Mid-Atlantic Ridge near the 15°20' Fracture Zone. Hole 1271B was drilled to 103.8 meters below seafloor on the inner corner high along the south wall of the 15°20' Fracture Zone. The total length of core collected was 15.9 m (recovery = ~15%). The dominant rock type in Hole 1271B is dunite, followed by brown amphibole gabbro, olivine gabbro, and troctolite, along with minor amounts of harzburgite and olivine gabbronorite. A large proportion of the dunite is associated with gabbroic rocks in Hole 1271B, similar to those observed in the Mohorovicic (Moho) transition zone of the Oman ophiolite, indicating significant magmatic activity in this region near the 15°20' Fracture Zone. Olivine Fo content varies from 89.2 to 91.2 in impregnated dunite and from 85.6 to 88.6 in troctolite, olivine gabbro, and olivine gabbronorite. Spinel Cr# (= 100 x Cr/[Cr + Al] molar ratio) ranges from 38.9 to 62.7 in dunite and from 46.3 to 57.6 in troctolites, olivine gabbro, and olivine gabbronorite. Compositional trends for spinel from dunite through troctolite toward olivine gabbro/gabbronorite are characterized by increases in TiO2, Cr#, and Fe3+#, very similar to those reported from Hess Deep Site 895. Olivine gabbro, olivine gabbronorite, and troctolite in Hole 1271B are considered to have formed as hybrid rocks between dunite and an evolved melt in the walls of a melt channel in the shallowest upper mantle that is tens of meters wide. The melt trapped in the wall rock crystallized plagioclase and clinopyroxene. On the other hand, dunite in the center of the melt channel became more refractory by melt-mantle reactions, increasing spinel Cr# to 62.5.