The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery

Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan–hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5 h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8 h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8 h to 24 h post-administration compared to the free NPs, due to a NP ‘guarding’ effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24 h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.

Fate of swallowed interleukin 8 and TNFα, and effect on the Wistar rat gut

To evaluate the passage of cytokines through the gastrointestinal tract, we investigated the digestion of interleukin-8 (IL-8) and tumour necrosis factor α (TNFα), in vitro and in vivo, and their propensity to induce intestinal inflammation. We serially immuno-assayed IL-8 and TNFα solutions co-incubated with each of three pancreatin preparations at pH 4.5 and pH 8. We gavaged IL-8, TNFα and marker into 15 Wistar rats, and measured their faecal cytokine concentrations by ELISA and histologically examined their guts. IL-8 immunoreactivity was extinguished by all pancreatin preparations after 1 h of incubation at 37 °C. TNFα concentration progressively fell from 1 to 4 h with all enzyme preparations. Buffer control samples maintained their cytokine concentrations throughout incubation. No IL-8 or TNFα was detected in any rat faecal pellets. There was no significant proinflammatory effect of the gavaged cytokines on rat intestine. IL-8 and TNFα in aqueous solution could well be fully digested in the CF gut when transit time is normal and exogenous enzymes are provided, although cytokines swallowed in viscous sputum may be protected from such digestion

Modern computed tomography techniques in stroke management

Technological development of fast multi-sectional, helical computed tomography (CT) scanners has allowed computed tomography perfusion (CTp) and angiography (CTA) in evaluating acute ischemic stroke. This study focuses on new multidetector computed tomography techniques, namely whole-brain and first-pass CT perfusion plus CTA of carotid arteries. Whole-brain CTp data is acquired during slow infusion of contrast material to achieve constant contrast concentration in the cerebral vasculature. From these data quantitative maps are constructed of perfused cerebral blood volume (pCBV). The probability curve of cerebral infarction as a function of normalized pCBV was determined in patients with acute ischemic stroke. Normalized pCBV, expressed as a percentage of contralateral normal brain pCBV, was determined in the infarction core and in regions just inside and outside the boundary between infarcted and noninfarcted brain. Corresponding probabilities of infarction were 0.99, 0.96, and 0.11, R² was 0.73, and differences in perfusion between core and inner and outer bands were highly significant. Thus a probability of infarction curve can help predict the likelihood of infarction as a function of percentage normalized pCBV. First-pass CT perfusion is based on continuous cine imaging over a selected brain area during a bolus injection of contrast. During its first passage, contrast material compartmentalizes in the intravascular space, resulting in transient tissue enhancement. Functional maps such as cerebral blood flow (CBF), and volume (CBV), and mean transit time (MTT) are then constructed. We compared the effects of three different iodine concentrations (300, 350, or 400 mg/mL) on peak enhancement of normal brain tissue and artery and vein, stratified by region-of-interest (ROI) location, in 102 patients within 3 hours of stroke onset. A monotonic increasing peak opacification was evident at all ROI locations, suggesting that CTp evaluation of patients with acute stroke is best performed with the highest available concentration of contrast agent. In another study we investigated whether lesion volumes on CBV, CBF, and MTT maps within 3 hours of stroke onset predict final infarct volume, and whether all these parameters are needed for triage to intravenous recombinant tissue plasminogen activator (IV-rtPA). The effect of IV-rtPA on the affected brain by measuring salvaged tissue volume in patients receiving IV-rtPA and in controls was investigated also. CBV lesion volume did not necessarily represent dead tissue. MTT lesion volume alone can serve to identify the upper size limit of the abnormally perfused brain, and those with IV-rtPA salvaged more brain than did controls. Carotid CTA was compared with carotid DSA in grading of stenosis in patients with stroke symptoms. In CTA, the grade of stenosis was determined by means of axial source and maximum intensity projection (MIP) images as well as a semiautomatic vessel analysis. CTA provides an adequate, less invasive alternative to conventional DSA, although tending to underestimate clinically relevant grades of stenosis.

Premixed flame response to equivalence ratio fluctuations: Comparison between reduced order modeling and detailed computations

Combustion instability events in lean premixed combustion systems can cause spatio-temporal variations in unburnt mixture fuel/air ratio. This provides a driving mechanism for heat-release oscillations when they interact with the flame. Several Reduced Order Modelling (ROM) approaches to predict the characteristics of these oscillations have been developed in the past. The present paper compares results for flame describing function characteristics determined from a ROM approach based on the level-set method, with corresponding results from detailed, fully compressible reacting flow computations for the same two dimensional slot flame configuration. The comparison between these results is seen to be sensitive to small geometric differences in the shape of the nominally steady flame used in the two computations. When the results are corrected to account for these differences, describing function magnitudes are well predicted for frequencies lesser than and greater than a lower and upper cutoff respectively due to amplification of flame surface wrinkling by the convective Darrieus-Landau (DL) instability. However, good agreement in describing function phase predictions is seen as the ROM captures the transit time of wrinkles through the flame correctly. Also, good agreement is seen for both magnitude and phase of the flame response, for large forcing amplitudes, at frequencies where the DL instability has a minimal influence. Thus, the present ROM can predict flame response as long as the DL instability, caused by gas expansion at the flame front, does not significantly alter flame front perturbation amplitudes as they traverse the flame. (C) 2012 The Combustion Institute. Published by Elsevier Inc. All rights reserved.

Narrowing of resonances in electromagnetically induced transparency and absorption using a Laguerre-Gaussian control beam

We study the phenomenon of electromagnetically induced transparency and absorption (EITA) using a control laser with a Laguerre-Gaussian (LG) profile instead of the usual Gaussian profile, and observe significant narrowing of the resonance widths. Aligning the probe beam to the central hole in the doughnut-shaped LG control beam allows simultaneously a strong control intensity required for high signal-to-noise ratio and a low intensity in the probe region required to get narrow resonances. Experiments with an expanded Gaussian control and a second-order LG control show that transit time and orbital angular momentum do not play a significant role. This explanation is borne out by a density-matrix analysis with a radially varying control Rabi frequency. We observe these resonances using degenerate two-level transitions in the D-2 line of Rb-87 in a room temperature vapor cell, and an EIA resonance with width up to 20 times below the natural linewidth for the F = 2 -> F' = 3 transition. Thus the use of LG beams should prove advantageous in all applications of EITA and other kinds of pump-probe spectroscopy as well.

Elastic Behaviour and Microstructural Characteristics of Nd60Al10Fe20Co10 Bulk Metallic Glass Investigated by Ultrasonic Measurement under Pressure

An ultrasonic pulse-echo method was used to measure the transit time of longitudinal and transverse (10 MHz) elastic waves in a Nd60Al10Fe20Co10 bulk metallic glass (BMG). The measurements were carried out under hydrostatic pressure up to 0.5 GPa at room temperature. On the basis of experimental data for the sound velocities and density, the elastic moduli and Debye temperature of the BMG were derived as a function of pressure. Murnaghan's equation of state is obtained. The normal behaviour of the positive pressure dependence of the ultrasonic velocities was observed for this glass. Moreover, the compression curve, the elastic constants, and the Debye temperature of the BMG are calculated on the basis of the similarity between their physical properties in the glassy state and those in corresponding crystalline state. These results confirm qualitatively the theoretical predictions concerning the features of the microstructure and interatomic bonding in the Nd60Al10Fe20Co10 BMG.

Heating, current drive and confinement regimes with the JET ICRH and lhcd systems

During its 1990 operation, 2 large RF systems were available on JET. The Ion Cyclotron Resonance Heating (ICRH) system was equipped with new beryllium screens and with feedback matching systems. Specific impurities generated by ICRH were reduced to negligible levels even in the most stringent H-mode conditions. A maximum power of 22 MW was coupled to L-mode plasmas. High quality H-modes (tau-E greater-than-or-equal-to 2.5 tau-EG) were achieved using dipole phasing. A new high confinement mode was discovered. It combines the properties of the H-mode regime to the low central diffusivities obtained by pellet injection. A value of n(d) tau-E T(i) = 7.8 x 10(20) m-3 s keV was obtained in this mode with T(e) approximately T(i) approximately 11 keV. In the L-mode regime, a regime, a record (140 kW) D-He-3 fusion power was generated with 10 - 14 MW of ICRH at the He-3 cyclotron frequency. Experiments were performed with the prototype launcher of the Lower Hybrid Current Drive (LHCD) systems with coupled power up to 1.6 MW with current drive efficiencies up to < n(e) > R I(CD)/P = 0.4 x 10(20) m-2 A/W. Fast electrons are driven by LHCD to tail temperatures of 100 keV with a hollow radial profile. Paradoxically, LHCD induces central heating particularly in combination with ICRH. Finally we present the first observations of the synergistic acceleration of fast electrons by Transit Time Magnetic Pumping (TTMP) (from ICRH) and Electron Landau Damping (ELD) (from LHCD). The synergism generates TTMP current drive even without phasing the ICRH antennae.

I. Electronic processes in α-sulfur. II. Polaron motion in a D.C. electric field

Part I: The mobilities of photo-generated electrons and holes in orthorhombic sulfur are determined by drift mobility techniques. At room temperature electron mobilities between 0.4 cm²/V-sec and 4.8 cm²/V-sec and hole mobilities of about 5.0 cm²/V-sec are reported. The temperature dependence of the electron mobility is attributed to a level of traps whose effective depth is about 0.12 eV. This value is further supported by both the voltage dependence of the space-charge-limited, D.C. photocurrents and the photocurrent versus photon energy measurements.

As the field is increased from 10 kV/cm to 30 kV/cm a second mechanism for electron transport becomes appreciable and eventually dominates. Evidence that this is due to impurity band conduction at an appreciably lower mobility (4.10^-4 cm²/V-sec) is presented. No low mobility hole current could be detected. When fields exceeding 30 kV/cm for electron transport and 35 kV/cm for hole transport are applied, avalanche phenomena are observed. The results obtained are consistent with recent energy gap studies in sulfur.

The theory of the transport of photo-generated carriers is modified to include the case of appreciable thermos-regeneration from the traps in one transit time.

Part II: An explicit formula for the electric field E necessary to accelerate an electron to a steady-state velocity v in a polarizable crystal at arbitrary temperature is determined via two methods utilizing Feynman Path Integrals. No approximation is made regarding the magnitude of the velocity or the strength of the field. However, the actual electron-lattice Coulombic interaction is approximated by a distribution of harmonic oscillator potentials. One may be able to find the “best possible” distribution of oscillators using a variational principle, but we have not been able to find the expected criterion. However, our result is relatively insensitive to the actual distribution of oscillators used, and our E-v relationship exhibits the physical behavior expected for the polaron. Threshold fields for ejecting the electron for the polaron state are calculated for several substances using numerical results for a simple oscillator distribution.

Estudo de pressão de poros a partir de dados de poços no Terciário da Bacia de Campos

O trabalho aqui apresentado teve como objetivo, avaliar o método de Eaton (1975) aplicado ao cálculo de pressão de poros das formações rochosas em subsuperfície, utilizando dados de perfis de poços no que diz respeito a porosidade, tais como, o Tempo de Transito da onda compressional, Resistividade, Densidade e Neutrão. Posteriormente foi avaliado o resultado alcançado por esta técnica e confrontado com o dado obtido pelo registro de pressão real da formação, adquirido pela ferramenta de perfilagem MDT. Distribuídos em 6 poços perfurados na porção sul da Bacia de Campos, o intervalo cronoestratigráfico estudado está compreendido no período geológico Terciário, e os registros de pressão real da formação foram adquiridos nos reservatórios turbidíticos da Formação Carapebus (Eoceno). Apesar de existir um mecanismo causador de anomalia de pressão na bacia (Desequilíbrio de Compactação Difícil migração dos fluidos ao longo do tempo geológico) devido ao forte aporte sedimentar sustentado pelo soerguimento da Serra do Mar no Eoceno, os resultados encontrados não apontaram qualquer tipo de alteração nas respostas dos perfis utilizados, onde a referência foi a assinatura do perfil sônico em um trend normal de compactação compreendido por rochas argilosas dentro do intervalo cronoestratigráfico estudado. O presente trabalho atesta que a boa calibração do trend de ompactação normal em rochas argilosas, juntamente com a similaridade entre o resultado obtido pelo cálculo da pressão de poros a partir do perfil sônico, e os valores reais registrados diretamente na formação, pela ferramenta de registro de pressões (MDT), comprovam a aplicabilidade do método de Eaton (1975) para o cálculo de geopressões a partir de um conjunto básico de perfis de poços tais como: Raios Gama, Resistividade, Velocidade Acústica, Densidade e Neutrão

Estudo do tempo de trânsito colônico em crianças e adolescentes com constipação intestinal crônica e disfunção do trato urinário inferior

A constipação intestinal e a disfunção do trato urinário inferior são condições associadas e bastante prevalentes na infância e adolescência. Existem múltiplas teorias para explicar essa associação, como: o efeito mecânico do reto cheio sobre a parede e o colo vesical; estimulo de reflexos sacrais a partir do reto distendido, e mais recentemente, a associação entre a bexiga e o reto no sistema nervoso central. Muitas destas crianças e adolescentes apresentam constipação refratária. Esse fato chama a atenção para a possibilidade de existência de uma desordem neuromuscular comum envolvendo o cólon e o trato urinário inferior. O objetivo desse estudo foi avaliar o trânsito colônico de crianças e adolescentes com constipação crônica refratária e sintomas do trato urinário inferior. Foi realizado um estudo observacional com análise transversal, no qual foram incluídos 16 indivíduos com constipação refratária e sintomas do trato urinário inferior, com idades entre sete e 14 anos (média de idade de 9,67 anos). Os participantes foram avaliados utilizando anamnese padrão; exame físico; diário miccional e das evacuações; escala de Bristol; Disfunctional Voiding Scoring System com versão validada para o português; ultrassonografia renal, de vias urinárias e medida de diâmetro retal; urodinâmica, estudo de trânsito colônico com marcadores radiopacos e manometria anorretal. O estudo de trânsito foi normal em três (18,75%) crianças, dez (62,5%) apresentaram constipação de trânsito lento e três (18,75%) obstrução de via de saída. A avaliação urodinâmica estava alterada em 14 das 16 crianças estudadas: dez (76,9%) apresentaram hiperatividade detrusora associada à disfunção miccional, três (23,1%) hiperatividade vesical isolada e um (6,25%) disfunção miccional sem hiperatividade vesical. Ao compararmos constipação de trânsito lento e disfunção do trato urinário inferior, dez (100%) sujeitos com constipação de trânsito lento e três (50%) sem constipação de trânsito lento apresentavam hiperatividade vesical (p=0,036). Sete (70%) sujeitos com constipação de trânsito lento e quatro (66,7%) sem constipação de trânsito lento apresentavam disfunção miccional (p=0,65). Ao compararmos constipação de trânsito lento e a presença de incontinência urinária, esta estava presente em nove (90%) participantes com constipação de trânsito lento e em um (16,7%) sem constipação de trânsito lento (p = 0,008). Quanto à urgência urinária, estava presente em 10 (100%) e três (50%) respectivamente (p = 0,036). O escore do Disfunctional Voiding Scoring System variou de 6 a 21. O subgrupo com constipação de trânsito lento mostrou um escore de Disfunctional Voiding Scoring System significativamente maior que o subgrupo sem constipação de trânsito lento. O presente estudo demonstrou alta prevalência de constipação de trânsito lento em crianças e adolescentes com constipação refratária e sintomas do trato urinário inferior. Este estudo foi pioneiro em demonstrar a associação entre hiperatividade vesical e constipação de trânsito lento e coloca em voga a possibilidade de uma desordem neuromuscular comum, responsável pela dismotilidade vesical e colônica. Futuros estudos envolvendo a motilidade intestinal e vesical são necessários para melhor compreensão do tema e desenvolvimento de novas modalidades terapêuticas.

A study of frequency response in silicon heterojunction bipolar transistors with amorphous silicon emitters

A detailed physical model of amorphous silicon (aSi:H) is incorporated into a twodimensional device simulator to examine the frequency response limits of silicon heterojunction bipolar transistors (HBT's) with aSi:H emitters. The cutoff frequency is severely limited by the transit time in the emitter space charge region, due to the low electron drift mobility in aSi:H, to 98 MHz which compares poorly with the 37 GHz obtained for a silicon homojunction bipolar transistor with the same device structure. The effects of the amorphous heteroemitter material parameters (doping, electron drift mobility, defect density and interface state density) on frequency response are then examined to find the requirements for an amorphous heteroemitter material such that the HBT has better frequency response than the equivalent homojunction bipolar transistor. We find that an electron drift mobility of at least 100 cnr'V"'"1 is required in the amorphous heteroemitter and at a heteroemitter drift mobility of 350 cm2 · V1· s1 and heteroemitter doping of 5×1017 cm3, a maximum cutoff frequency of 52 GHz can be expected. © 1996 IEEE.

Boat wakes and their influence on erosion in the Atlantic Intracoastal Waterway, North Carolina

Boat wakes in the Atlantic Intracoastal Waterway (AIWW) of North Carolina occur in environments not normally subjected to (wind) wave events, making sections of AIWW potentially vulnerable to extreme wave events generated by boat wakes. The Snow’s Cut area that links the Cape Fear River to the AIWW is an area identified by the Wilmington District of the U.S. Army Corps of Engineers as having significant erosion issues; it was hypothesized that this erosion could be being exacerbated by boat wakes. We compared the boat wakes for six combinations of boat length and speed with the top 5% wind events. We also computed the benthic shear stress associated with boat wakes and whether sediment would move (erode) under those conditions. Finally, we compared the transit time across Snow’s Cut for each speed. We focused on two size classes of V-hulled boats (7 and 16m) representative of AIWW traffic and on three boat speeds (3, 10 and 20 knots). We found that at 10 knots when the boat was plowing and not yet on plane, boat wake height and potential erosion was greatest. Wakes and forecast erosion were slightly mitigated at higher, planing speeds. Vessel speeds greater than 7 knots were forecast to generate wakes and sediment movement zones greatly exceeding that arising from natural wind events. We posit that vessels larger than 7m in length transiting Snow’s Cut (and likely many other fetch-restricted areas of the AIWW) frequently generate wakes of heights that result in sediment movement over large extents of the AIWW nearshore area, substantially in exceedance of natural wind wave events. If the speed, particularly of large V-hulled vessels (here represented by the 16m length class), were reduced to pre-plowing levels (~ 7 knots down from 20), transit times for Snow’s Cut would be increased approximately 10 minutes but based on our simulations would likely substantially reduce the creation of erosion-generating boat wakes. It is likely that boat wakes significantly exceed wind wave background for much of the AIWW and similar analyses may be useful in identifying management options.

How to achieve ultra high photoconductive gain for transparent oxide semiconductor image sensors

We present quantitative analysis of the ultra-high photoconductivity in amorphous oxide semiconductor (AOS) thin film transistors (TFTs), taking into account the sub-gap optical absorption in oxygen deficiency defects. We analyze the basis of photoconductivity in AOSs, explained in terms of the extended electron lifetime due to retarded recombination as a result of hole localization. Also, photoconductive gain in AOS photo-TFTs can be maximized by reducing the transit time associated with short channel lengths, making device scaling favourable for high sensitivity operation. © 2012 IEEE.

Echolocation range of captive and free-ranging baiji (Lipotes vexillifer), finless porpoise (Neophocaena phocaenoides), and bottlenose dolphin (Tursiops truncatus)

The interclick intervals of captive dolphins are known to be longer than the two-way transit time between the dolphin and a target. In the present study, the interclick intervals of free-ranging baiji, finless porpoises, and bottlenose dolphins in the wild and in captivity were compared. The click intervals in open waters ranged up to 100-200 ms, whereas the click intervals in captivity were in the order of 4-28 ms. Echolocation of free-ranging dolphins appears to adapt to various distance in navigation or ranging, sometimes up to 140 m. Additionally, the difference of waveform characteristics of clicks between species was recognized in the frequency of maximum energy and the click duration. (C) 1998 Acoustical Society of America. [S0001-4966(98)06609-0].

Characteristic analysis of the optical delay in frequency response of resonant cavity enhanced (RCE) photodetectors

With consideration of the modulation frequency of the input lightwave itself, we present a new model to calculate the quantum efficiency of RCE p-i-n photodetectors (PD) by superimposition of multiple reflected lightwaves. For the first time, the optical delay, another important factor limiting the electrical bandwidth of RCE p-i-n PD excluding the transit time of the carriers and RCd response of the photodetector, is analyzed and discussed in detail. The optical delay dominates the bandwidth of RCE p-i-n PD when its active layer is thinner than several 10 nm. These three limiting factors must be considered exactly for design of ultra-high-speed RCE p-i-n PD.