Photoreceptor types and distributions in the retinae of insectivores.

The retinae of insectivores have been rarely studied, and their photoreceptor arrangements and expression patterns of visual pigments are largely unknown. We have determined the presence and distribution of cones in three species of shrews (common shrew Sorex araneus, greater white-toothed shrew Crocidura russula, dark forest shrew Crocidura poensis; Soricidae) and in the lesser hedgehog tenrec Echinops telfairi (Tenrecidae). Special cone types were identified and quantified in flattened whole retinae by antisera/antibodies recognizing the middle-to-long-wavelength-sensitive (M/L-)cone opsin and the short-wavelength-sensitive (S-)cone opsin, respectively. A combination of immunocytochemistry with conventional histology was used to assess rod densities and cone/rod ratios. In all four species the rods dominate at densities of about 230,000-260,000/mm2. M/L- and S-cones are present, comprising between 2% of the photoreceptors in the nocturnal Echinops telfairi and 13% in Sorex araneus that has equal diurnal and nocturnal activity phases. This suggests dichromatic color vision like in many other mammals. A striking feature in all four species are dramatically higher S-cone proportions in ventral than in dorsal retina (0.5% vs. 2.5-12% in Sorex, 5-15% vs. 30-45% in Crocidura poensis, 3-12% vs. 20-50% in Crocidura russula, 10-30% vs. 40-70% in Echinops). The functional and comparative aspects of these structural findings are discussed.

Silicon quantum dots embedded in a SiO2 matrix: From structural study to carrier transport properties

We study the details of electronic transport related to the atomistic structure of silicon quantum dots embedded in a silicon dioxide matrix using ab initio calculations of the density of states. Several structural and composition features of quantum dots (QDs), such as diameter and amorphization level, are studied and correlated with transport under transfer Hamiltonian formalism. The current is strongly dependent on the QD density of states and on the conduction gap, both dependent on the dot diameter. In particular, as size increases, the available states inside the QD increase, while the QD band gap decreases due to relaxation of quantum confinement. Both effects contribute to increasing the current with the dot size. Besides, valence band offset between the band edges of the QD and the silica, and conduction band offset in a minor grade, increases with the QD diameter up to the theoretical value corresponding to planar heterostructures, thus decreasing the tunneling transmission probability and hence the total current. We discuss the influence of these parameters on electron and hole transport, evidencing a correlation between the electron (hole) barrier value and the electron (hole) current, and obtaining a general enhancement of the electron (hole) transport for larger (smaller) QD. Finally, we show that crystalline and amorphous structures exhibit enhanced probability of hole and electron current, respectively.

Development of stable cell lines for production or regulated expression using matrix attachment regions.

One of the major hurdles of isolating stable, inducible or constitutive high-level producer cell lines is the time-consuming selection procedure. Given the variation in the expression levels of the same construct in individual clones, hundreds of clones must be isolated and tested to identify one or more with the desired characteristics. Various boundary elements (BEs), matrix attachment regions, and locus control regions (LCRs) were screened for their ability to augment the expression of heterologous genes in Chinese hamster ovary (CHO) cells. Of the chromatin elements assayed, the chicken lysozyme matrix-attachment region (MAR) was the only element to significantly increase stable reporter expression. We found that the use of the MAR increases the proportion of high-producing clones, thus reducing the number of clones that need to be screened. These benefits are observed both for constructs with MARs flanking the transgene expression cassette, as well as when constructs are co-transfected with the MAR on a separate plasmid. Moreover, the MAR was co-transfected with a multicomponent regulatable beta-galactosidase expression system in C2C12 cells and several clones exhibiting regulated expression were identified. Hence, MARs are useful in the development of stable cell lines for production or regulated expression.

A developmental framework for endodermal differentiation and polarity.

The endodermis is a root cell layer common to higher plants and of fundamental importance for root function and nutrient uptake. The endodermis separates outer (peripheral) from inner (central) cell layers by virtue of its Casparian strips, precisely aligned bands of specialized wall material. Here we reveal that the membrane at the Casparian strip is a diffusional barrier between the central and peripheral regions of the plasma membrane and that it mediates attachment to the extracellular matrix. This membrane region thus functions like a tight junction in animal epithelia, although plants lack the molecular modules that establish tight junction in animals. We have also identified a pair of influx and efflux transporters that mark both central and peripheral domains of the plasma membrane. These transporters show opposite polar distributions already in meristems, but their localization becomes refined and restricted upon differentiation. This "central-peripheral" polarity coexists with the apical-basal polarity defined by PIN proteins within the same cells, but utilizes different polarity determinants. Central-peripheral polarity can be already observed in early embryogenesis, where it reveals a cellular polarity within the quiescent center precursor cell. A strict diffusion block between polar domains is common in animals, but had never been described in plants. Yet, its relevance to endodermal function is evident, as central and peripheral membranes of the endodermis face fundamentally different root compartments. Further analysis of endodermal transporter polarity and manipulation of its barrier function will greatly promote our understanding of plant nutrition and stress tolerance in roots.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry as an alternative to 16S rRNA gene sequencing for identification of difficult-to-identify bacterial strains.

Conventional methods are sometimes insufficient to identify human bacterial pathogens, and alternative techniques, often molecular, are required. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified with a valid score 45.9% of 410 clinical isolates from 207 different difficult-to-identify species having required 16S rRNA gene sequencing. MALDI-TOF MS might represent an alternative to 16S rRNA gene sequencing.

Degree of previous cutting in explaining the differences in diameter distributions between mature managed and natural Norway spruce forests

Abstract

A critical evaluation of secondary cancer risk models applied to Monte Carlo dose distributions of 2-dimensional, 3-dimensional conformal and hybrid intensity-modulated radiation therapy for breast cancer.

The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable approach to risk estimation would be to use organ-specific non-linear risk models applied to the dose distributions of organs within or near the treatment fields (lungs and contralateral breast in the case of breast radiotherapy) as the majority of radiation-induced secondary cancers are found in the beam-bordering regions.

Exhaled breath condensate as a matrix for combustion-based nanoparticle exposure and health effect evaluation

Health assessment and medical surveillance of workers exposed to combustion nanoparticles are challenging. The aim was to evaluate the feasibility of using exhaled breath condensate (EBC) from healthy volunteers for (1) assessing the lung deposited dose of combustion nanoparticles and (2) determining the resulting oxidative stress by measuring hydrogen peroxide (H2O2) and malondialdehyde (MDA). Methods: Fifteen healthy nonsmoker volunteers were exposed to three different levels of sidestream cigarette smoke under controlled conditions. EBC was repeatedly collected before, during, and 1 and 2 hr after exposure. Exposure variables were measured by direct reading instruments and by active sampling. The different EBC samples were analyzed for particle number concentration (light-scattering-based method) and for selected compounds considered oxidative stress markers. Results: Subjects were exposed to an average airborne concentration up to 4.3×10(5) particles/cm(3) (average geometric size ∼60-80 nm). Up to 10×10(8) particles/mL could be measured in the collected EBC with a broad size distribution (50(th) percentile ∼160 nm), but these biological concentrations were not related to the exposure level of cigarette smoke particles. Although H2O2 and MDA concentrations in EBC increased during exposure, only H2O2 showed a transient normalization 1 hr after exposure and increased afterward. In contrast, MDA levels stayed elevated during the 2 hr post exposure. Conclusions: The use of diffusion light scattering for particle counting proved to be sufficiently sensitive to detect objects in EBC, but lacked the specificity for carbonaceous tobacco smoke particles. Our results suggest two phases of oxidation markers in EBC: first, the initial deposition of particles and gases in the lung lining liquid, and later the start of oxidative stress with associated cell membrane damage. Future studies should extend the follow-up time and should remove gases or particles from the air to allow differentiation between the different sources of H2O2 and MDA.

Height distributions of Scots pine sapling stands affected by retained tree and edge stand competition

Abstract

Finite mixture analysis of beauty-contest data using generalised beta distributions

This paper introduces a mixture model based on the beta distribution, without preestablishedmeans and variances, to analyze a large set of Beauty-Contest data obtainedfrom diverse groups of experiments (Bosch-Domenech et al. 2002). This model gives a bettert of the experimental data, and more precision to the hypothesis that a large proportionof individuals follow a common pattern of reasoning, described as iterated best reply (degenerate),than mixture models based on the normal distribution. The analysis shows thatthe means of the distributions across the groups of experiments are pretty stable, while theproportions of choices at dierent levels of reasoning vary across groups.

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses.

Endothelial cells as key determinants of the tumor microenvironment: interaction with tumor cells, extracellular matrix and immune killer cells.

Besides tumor cells, the tumor microenvironment harbors a variety of host-derived cells, such as endothelial cells, fibroblasts, innate and adaptive immune cells. It is a complex and highly dynamic environment, providing very important cues to tumor development and progression. Tumor-associated endothelial cells play a key role in this process. On the one hand, they form tumor-associated (angiogenic) vessels through sprouting from locally preexisting vessels or recruitment of bone marrow-derived endothelial progenitor cells, to provide nutritional support to the growing tumor. On the other hand, they are the interface between circulating blood cells, tumor cells and the extracellular matrix, thereby playing a central role in controlling leukocyte recruitment, tumor cell behavior and metastasis formation. Hypoxia is a critical parameter modulating the tumor microenvironment and endothelial/tumor cell interactions. Under hypoxic stress, tumor cells produce factors that promote tumor angiogenesis, tumor cell motility and metastasis. Among these factors, VEGF, a main angiogenesis modulator, can also play a critical role in the control of immune tolerance. This review discusses some aspects of the role of endothelial cells within tumor microenvironment and emphasizes their interaction with tumor cells, the extracellular matrix and with immune killer cells. We will also address the role played by circulating endothelial progenitor cells and illustrate their features and mechanism of recruitment to the tumor microenvironment and their role in tumor angiogenesis.