Historical considerations and evolution of the forest policies for small woodlot owners of Quebec.

XVIII IUFRO World Congress, Ljubljana 1986.

Tumorigenesis in celiac disease

Celiac disease is life-long autoimmune disorder of the small intestine, which is caused by a reaction to gliadin found in wheat, rye and barley in genetically predisposed individuals. Proline- and glutamine -rich proteins cause villous atrophy and crypt hyperplasia with extensive inflammation in the epithelium and lamina propria. Symptoms of celiac disease vary considerably and elimination of gluten from diet is the only way to treat disease. In small intestine of celiac disease patient transglutaminase 2 (TG2) modifies gluten peptides, which causes T-cell activation and inflammation in the epithelium of mucosa. T-cell activation induces development of celiac disease specific antibodies. These celiac disease specific antibodies recognise TG2 and interfere in vitro and in vivo in angiogenesis. Abnormal angiogenesis is typical in many disorders, such in cancer, in which TG2 has a crucial role in the development and growth of tumor. Overexpression of TG2 has been shown to correlate with accelerated growth of tumor. TG2-specific antibodies are suggested to inhibit differentation of epithelial cell, increase their proliferation, decrease their barrier-function and increase the permeability of blood vessels. The aims of the pilot study were to establish whether celiac disease TG2 antibodies affect in vivo tumorigenesis and tumorangiogenesis as well as to try to clarify the mechanism behind the phenomenon. Tumor xenograft model was used in severe combined immunodeficient (SCID) mice. Human oesophageal carcinoma (OE-19) cancer cells were incubated with celiacs TG2 miniautoantibody (mini 2.8), non-celiac miniautoantibody (mini 6.2) or PBS before cancer cells were injected to mice subcutaneously. During the experiment mice were weighted and tumor size was measured couple of times per week. To estimate the volumes of tumors the following formula was used: π/6 * L* W* H. Experiment lasted for four weeks after which the mice were euthanized, cardiac blood and tissue samples taken and tumours were excised and weighted. Sections were made from tumors and immunohistochemical stainings were done to compare blood vessel areas and to study general tumors´morphology and other parameters. Western blot -analyse were performed to cancer cells. The masses and volumes were clearly smaller in mini 2.8-group compared to control groups and the necrotic area of tumor in mini 2.8 was smallest as percentage compared to control groups. Blood vessel area were smallest in mini 2.8 group. Results suggest that celiac disease anti-TG2-autoantibodies inhibit tumor growth, but the number of animals is insufficient to give an accurate outcome.

Polarization studies in electromagnetic scattering by small Solar-system particles

In remote-sensing studies, particles that are comparable to the wavelength exhibit characteristic features in electromagnetic scattering, especially in the degree of linear polarization. These features vary with the physical properties of the particles, such as shape, size, refractive index, and orientation. In the thesis, the direct problem of computing the unknown scattered quantities using the known properties of the particles and the incident radiation is solved at both optical and radar spectral regions in a unique way. The internal electromagnetic fields of wavelength-scale particles are analyzed by using both novel and established methods to show how the internal fields are related to the scattered fields in the far zone. This is achieved by using the tools and methods that were developed specifically to reveal the internal field structure of particles and to study the mechanisms that relate the structure to the scattering characteristics of those particles. It is shown that, for spherical particles, the internal field is a combination of a forward propagating wave with the apparent wavelength determined by the refractive index of the particle, and a standing wave pattern with the apparent wavelength the same as for the incident wave. Due to the surface curvature and dielectric nature of the particle, the incident wave front undergoes a phase shift, and the resulting internal wave is focused mostly at the forward part of the particle similar to an optical lens. This focusing is also seen for irregular particles. It is concluded that, for both spherical and nonspherical particles, the interference at the far field between the partial waves that originate from these concentrated areas in the particle interior, is responsible for the specific polarization features that are common for wavelength-scale particles, such as negative values and local extrema in the degree of linear polarization, asymmetry of the phase function, and enhancement of intensity near the backscattering direction. The papers presented in this thesis solve the direct problem for particles with both simple and irregular shapes to demonstrate that these interference mechanisms are common for all dielectric wavelength-scale particles. Furthermore, it is shown that these mechanisms can be applied to both regolith particles in the optical wavelengths and hydrometeors at microwave frequencies. An advantage from this kind of study is that it does not matter whether the observation is active (e.g., polarimetric radar) or passive (e.g., optical telescope). In both cases, the internal field is computed for two mutually perpendicular incident polarizations, so that the polarization characteristics can then be analyzed according to the relation between these fields and the scattered far field.

Poststroke survival and ischemic stroke recurrence : the cerebral small-vessel disease perspective

The aim of the present study was to investigate the influence of different manifestations of cerebral SVD on poststroke survival and ischemic stroke recurrence in long-term follow-up. The core imaging features of small-vessel disease (SVD) are confluent and extensive white matter changes (WMC) and lacunar infarcts. These are associated with minor motor deficits but a major negative influence on cognition, mood, and functioning in daily life, resulting from small-vessel lesions in the fronto-subcortical brain network. These sub-studies were conducted as part of the Helsinki Stroke Aging Memory (SAM) study. The SAM cohort consisted of 486 consecutive patients aged 55 to 85 years who were admitted to Helsinki University Central Hospital with acute ischemic stroke. The study included comprehensive clinical, neuropsychological, psychiatric and radiological assessment three months poststroke. The patients were followed up up for 12 years using extensive national registers. The effect of different manifestations of cerebral SVD on poststroke survival and stroke recurrence was analyzed controlling for factors such as age, education, and cardiovascular risk factors. Poststroke dementia and cognitive impairment relate to poor long-term survival. In particular, deficits in executive functions as well as visuospatial and constructional abilities predict poor outcome. The predictive value of cognitive deficits is further underlined by the finding that depression-executive dysfunction syndrome (DES), but not depression in itself, is associated with poor poststroke survival. Delirium is not independently associated with increased risk for long-term poststroke mortality, although it is associated with poststroke dementia. Furthermore, acute index stroke attributable to SVD is associated with poorer long-term survival and a higher risk for cardiac death than other stroke subtypes. Severe WMC, a surrogate of SVD, is independently related to an increased risk of stroke recurrence at five years. In summary, cognitive poststroke outcomes reflecting changes in the executive network brain, and the presence of cerebral SVD are important determinants of poststroke mortality and ischemic stroke recurrence, regardless of whether SVD is the cause of the index stroke or a condition concurrent to some other etiology.

Effects of gender, and SLCO1B1 and CYP7A1 polymorphisms on plasma bile acids in humans and the pharmacokinetics of therapeutic ursodeoxycholic acid

Bile acids are important steroid-derived molecules essential for fat absorption in the small intestine. They are produced in the liver and secreted into the bile. Bile acids are transported by bile flow to the small intestine, where they aid the digestion of lipids. Most bile acids are reabsorbed in the small intestine and return to the liver through the portal vein. The whole recycling process is referred to as the enterohepatic circulation, during which only a small amount of bile acids are removed from the body via faeces. The enterohepatic circulation of bile acids involves the delicate coordination of a number of bile acid transporters expressed in the liver and the small intestine. Organic anion transporting polypeptide 1B1 (OATP1B1), encoded by the solute carrier organic anion transporter family, member 1B1 (SLCO1B1) gene, mediates the sodium independent hepatocellular uptake of bile acids. Two common SNPs in the SLCO1B1 gene are well known to affect the transport activity of OATP1B1. Moreover, bile acid synthesis is an important elimination route for cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production. The aim of this thesis was to investigate the effects of SLCO1B1 polymorphism on the fasting plasma levels of individual endogenous bile acids and a bile acid synthesis marker, and the pharmacokinetics of exogenously administered ursodeoxycholic acid (UDCA). Furthermore, the effects of CYP7A1 genetic polymorphism and gender on the fasting plasma concentrations of individual endogenous bile acids and the bile acid synthesis marker were evaluated. Firstly, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of bile acids was developed (Study I). A retrospective study examined the effects of SLCO1B1 genetic polymorphism on the fasting plasma concentrations of individual bile acids and a bile acid synthesis marker in 65 healthy subjects (Study II). In another retrospective study with 143 healthy individuals, the effects of CYP7A1 genetic polymorphism and gender as well as SLCO1B1 polymorphism on the fasting plasma levels of individual bile acids and the bile acid synthesis marker were investigated (Study III). The effects of SLCO1B1 polymorphism on the pharmacokinetics of exogenously administered UDCA were evaluated in a prospective genotype panel study including 27 healthy volunteers (Study IV). A robust, sensitive and simple HPLC-MS/MS method was developed for the simultaneous determination of 16 individual bile acids in human plasma. The method validation parameters for all the analytes met the requirements of the FDA (Food and Drug Administration) bioanalytical guidelines. This HPLC-MS/MS method was applied in Studies II-IV. In Study II, the fasting plasma concentrations of several bile acids and the bile acid synthesis marker seemed to be affected by SLCO1B1 genetic polymorphism, but these findings were not replicated in Study III with a larger sample size. Moreover, SLCO1B1 polymorphism had no effect on the pharmacokinetic parameters of exogenously administered UDCA. Furthermore, no consistent association was observed between CYP7A1 genetic polymorphism and the fasting plasma concentrations of individual bile acids or the bile acid synthesis marker. In contrast, gender had a major effect on the fasting plasma concentrations of several bile acids and also total bile acids. In conclusion, gender, but not SLCO1B1 or CYP7A1 polymorphisms, has a major effect on the fasting plasma concentrations of individual bile acids. Moreover, the common genetic polymorphism of CYP7A1 is unlikely to influence the activity of CYP7A1 under normal physiological conditions. OATP1B1 does not play an important role in the in vivo disposition of exogenously administered UDCA.

Performance of a small solar pond in the tropics

The performance of the 240 m2 solar pond in Bangalore is discussed. The problems of erosion of gradient zone and formation of internal convective zones is highlighted. The technique of passive salt addition is shown to be a viable alternative for salt recycling. Different techniques of heat extraction are discussed and the use of an immersed copper heat exchanger is shown to be most convenient. A two-zone model for prediction of the seasonal structure of the solar pond performance is proposed. The model is shown to simulate the seasonal structure of the observed variation of the temperature in the storage zone.

Activation barriers for d.c. conductivity in ionic glasses: Classical calculations using the small-cluster approximation

A small-cluster approximation has been used to calculate the activation barriers for the d.c. conductivity in ionic glasses. The main emphasis of this approach is on the importance of the hitherto ignored polarization energy contribution to the total activation energy. For the first time it has been demonstrated that the d.c. conductivity activation energy can be calculated by considering ionic migration to a neighbouring vacancy in a smali cluster of ions consisting of face-sharing anion polyhedra. The activation energies from the model calculations have been compared with the experimental values in the case of highly modified lithium thioborate glasses.

An investigation of well-characterized small gold clusters by photoelectron spectroscopy, tunneling spectroscopy, and cognate techniques

After microscopic characterization of the size distributions of gold clusters, deposited on carbon substrates by vacuum evaporation or by soft landing, Au(4f') binding energy of the clusters has been measured as a function of the mean cluster size. Similar measurements have been carried out on Au clusters prepared from sols by chemical means and high-nuclearity cluster compounds. In general, small clusters with a mean diameter of $2 nm show significantly larger binding energies than the bulk metal value, due to the onset of nonmetallicity. Nonmetallicity manifests itself in terms of a tunneling conductance gap only in clusters of diameter ;5 1 nm containing 40 atoms or fewer.

A study of chemically prepared small metal clusters in the nonmetallic regime

Small gold clusters [mean diameter (d)[less, similar] 1.4 nm], unlike larger clusters, show a higher Au(4f) binding energy relative to the bulk value and the presence of a conductance gap in tunnelling measurements, just as the molecular cluster compound, Au55(PPh3)12Cl6; small platinum clusters show similar nonmetallic features.

The shear dynamo problem for small magnetic Reynolds numbers

We study large-scale kinematic dynamo action due to turbulence in the presence of a linear shear flow in the low-conductivity limit. Our treatment is non-perturbative in the shear strength and makes systematic use of both the shearing coordinate transformation and the Galilean invariance of the linear shear flow. The velocity fluctuations are assumed to have low magnetic Reynolds number (Re-m), but could have arbitrary fluid Reynolds number. The equation for the magnetic fluctuations is expanded perturbatively in the small quantity, Re-m. Our principal results are as follows: (i) the magnetic fluctuations are determined to the lowest order in Rem by explicit calculation of the resistive Green's function for the linear shear flow; (ii) the mean electromotive force is then calculated and an integro-differential equation is derived for the time evolution of the mean magnetic field. In this equation, velocity fluctuations contribute to two different kinds of terms, the 'C' and 'D' terms, respectively, in which first and second spatial derivatives of the mean magnetic field, respectively, appear inside the space-time integrals; (iii) the contribution of the D term is such that its contribution to the time evolution of the cross-shear components of the mean field does not depend on any other components except itself. Therefore, to the lowest order in Re-m, but to all orders in the shear strength, the D term cannot give rise to a shear-current-assisted dynamo effect; (iv) casting the integro-differential equation in Fourier space, we show that the normal modes of the theory are a set of shearing waves, labelled by their sheared wavevectors; (v) the integral kernels are expressed in terms of the velocity-spectrum tensor, which is the fundamental dynamical quantity that needs to be specified to complete the integro-differential equation description of the time evolution of the mean magnetic field; (vi) the C term couples different components of the mean magnetic field, so they can, in principle, give rise to a shear-current-type effect. We discuss the application to a slowly varying magnetic field, where it can be shown that forced non-helical velocity dynamics at low fluid Reynolds number does not result in a shear-current-assisted dynamo effect.

Taking Multiple Infections of Cells and Recombination into Account Leads to Small Within-Host Effective-Population-Size Estimates of HIV-1

Whether HIV-1 evolution in infected individuals is dominated by deterministic or stochastic effects remains unclear because current estimates of the effective population size of HIV-1 in vivo, N-e, are widely varying. Models assuming HIV-1 evolution to be neutral estimate N-e similar to 10(2)-10(4), smaller than the inverse mutation rate of HIV-1 (similar to 10(5)), implying the predominance of stochastic forces. In contrast, a model that includes selection estimates N-e>10(5), suggesting that deterministic forces would hold sway. The consequent uncertainty in the nature of HIV-1 evolution compromises our ability to describe disease progression and outcomes of therapy. We perform detailed bit-string simulations of viral evolution that consider large genome lengths and incorporate the key evolutionary processes underlying the genomic diversification of HIV-1 in infected individuals, namely, mutation, multiple infections of cells, recombination, selection, and epistatic interactions between multiple loci. Our simulations describe quantitatively the evolution of HIV-1 diversity and divergence in patients. From comparisons of our simulations with patient data, we estimate N-e similar to 10(3)-10(4), implying predominantly stochastic evolution. Interestingly, we find that N-e and the viral generation time are correlated with the disease progression time, presenting a route to a priori prediction of disease progression in patients. Further, we show that the previous estimate of N-e>10(5) reduces as the frequencies of multiple infections of cells and recombination assumed increase. Our simulations with N-e similar to 10(3)-10(4) may be employed to estimate markers of disease progression and outcomes of therapy that depend on the evolution of viral diversity and divergence.

Strong nonlocalization induced by small scale parameter on terahertz flexural wave dispersion characteristics of a monolayer graphene

This paper presents the strong nonlocal scale effect on the flexural wave propagation in a monolayer graphene sheet. The graphene is modeled as an isotropic plate of one atom thick. Nonlocal governing equation of motion is derived and wave propagation analysis is performed using spectral analysis. The present analysis shows that the flexural wave dispersion in graphene obtained by local and nonlocal elasticity theories is quite different. The nonlocal elasticity calculation shows that the wavenumber escapes to infinite at certain frequency and the corresponding wave velocity tends to zero at that frequency indicating localization and stationary behavior. This behavior is captured in the spectrum and dispersion curves. The cut-off frequency of flexural wave not only depend on the axial wavenumber but also on the nonlocal scaling parameter. The effect of axial wavenumber on the wave behavior in graphene is also discussed in the present manuscript. (C) 2010 Elsevier B.V. All rights reserved.