Using ELP Repeats as a Scaffold for De Novo Construction of Gadolinium-Binding Domains within Multifunctional Recombinant Proteins for Targeted Delivery of Gadolinium to Tumour Cells

Three artificial proteins that bind the gadolinium ion (Gd³⁺) with tumour-specific ligands were de novo engineered and tested as candidate drugs for binary radiotherapy (BRT) and contrast agents for magnetic resonance imaging (MRI). Gd³⁺-binding modules were derived from calmodulin. They were joined with elastin-like polypeptide (ELP) repeats from human elastin to form the four-centre Gd³⁺-binding domain (4MBS-domain) that further was combined with F3 peptide (a ligand of nucleolin, a tumour marker) to form the F3-W4 block. The F3-W4 block was taken alone (E2-13W4 protein), as two repeats (E1-W8) and as three repeats (E1-W12). Each protein was supplemented with three copies of the RGD motif (a ligand of integrin αvβ3) and green fluorescent protein (GFP). In contrast to Magnevist (a Gd-containing contrast agent), the proteins exhibited three to four times higher accumulation in U87MG glioma and A375 melanoma cell lines than in normal fibroblasts. The proteins remained for >24 h in tumours induced by Ca755 adenocarcinoma in C57BL/6 mice. They exhibited stability towards blood proteases and only accumulated in the liver and kidney. The technological advantages of using the engineered proteins as a basis for developing efficient and non-toxic agents for early diagnosis of tumours by MRI as well as part of BRT were demonstrated.     

Hippocampal Over-Expression of Cyclooxygenase-2 (COX-2) Is Associated with Susceptibility to Stress-Induced Anhedonia in Mice

The phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature of depression, to investigate hippocampal expression of COX-2, a marker of microglial activation Iba-1, and the proliferation marker Ki67. Rat exposure, social defeat, restraints, and tail suspension were used as stressors. We compared the effects of treatment with either the selective COX-2 inhibitor celecoxib (30 mg/kg/day) or citalopram (15 mg/kg/day). For the celecoxib and vehicle-treated mice, the Porsolt test was used. Anhedonic (susceptible) but not non-anhedonic (resilient) animals exhibited elevated COX-2 mRNA levels, increased numbers of COX-2 and Iba-1-positive cells in the dentate gyrus and the CA1 area, and decreased numbers of Ki67-positive cells in the subgranular zone of the hippocampus. Drug treatment decreased the percentage of anhedonic mice, normalized swimming activity, reduced behavioral despair, and improved conditioned fear memory. Hippocampal over-expression of COX-2 is associated with susceptibility to stress-induced anhedonia, and its pharmacological inhibition with celecoxib has antidepressant effects that are similar in size to those of citalopram.     

High,in Contrast to Low Levels of Acute Stress Induce Depressive-like Behavior by Involving Astrocytic,in Addition to Microglial P2X7 Receptors in the Rodent Hippocampus

Extracellular adenosine 5′-triphosphate (ATP) in the brain is suggested to be an etiological factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also possess P2X7Rs. In order to elucidate the possible involvement of the MDD-relevant hippocampal astrocytes in the development of a depressive-like state, we used various behavioral tests (tail suspension test [TST], forced swim test [FST], restraint stress, inescapable foot shock, unpredictable chronic mild stress [UCMS]), as well as fluorescence immunohistochemistry, and patch-clamp electrophysiology in wild-type (WT) and genetically manipulated rodents. The TST and FST resulted in learned helplessness manifested as a prolongation of the immobility time, while inescapable foot shock caused lower sucrose consumption as a sign of anhedonia. We confirmed the participation of P2X7Rs in the development of the depressive-like behaviors in all forms of acute (TST, FST, foot shock) and chronic stress (UCMS) in the rodent models used. Further, pharmacological agonists and antagonists acted in a different manner in rats and mice due to their diverse potencies at the respective receptor orthologs. In hippocampal slices of mice and rats, only foot shock increased the current responses to locally applied dibenzoyl-ATP (Bz-ATP) in CA1 astrocytes; in contrast, TST and restraint depressed these responses. Following stressful stimuli, immunohistochemistry demonstrated an increased co-localization of P2X7Rs with a microglial marker, but no change in co-localization with an astroglial marker. Pharmacological damage to the microglia and astroglia has proven the significance of the microglia for mediating all types of depression-like behavioral reactions, while the astroglia participated only in reactions induced by strong stressors, such as foot shock. Because, in addition to acute stressors, their chronic counterparts induce a depressive-like state in rodents via P2X7R activation, we suggest that our data may have relevance for the etiology of MDD in humans.     

Mercury in the Arctic atmosphere: an analysis of eight years of measurements of GEM at Alert (Canada) and a comparison with observations at Amderma (Russia) and Kuujjuarapik (Canada)

Eight years of gaseous elemental mercury (GEM) concentration measurements from Alert, Nunavut, Canada (between 1995 and 2002) is presented. The annual time series shows a distinct repeating seasonal pattern with an overall annual median concentration for this time period of 1.58 (S.D.=0.04 ng m(-3)). Strong seasonal variation was observed throughout the years with springtime displaying strong variability in the GEM and overall lower median concentrations due to the so-called mercury depletion events (MDEs). Summer concentrations are higher than the annual average and show a decrease in variability. Fall and winter concentrations are distributed around the annual median concentrations and show little variability. The relationship between the springtime depression and the summer increase shows a change in the behaviour of mercury between 1995 and 2002. Preliminary results suggest that during this period an increasing amount of the mercury lost from the atmosphere in the spring is not returned to atmosphere in summer. A comparison of GEM concentration data from three sites--Alert (Canada), Amderma (Russia) and Kuujjuarapik (Canada)--demonstrated similar monthly distribution of GEM between Alert and Amderma, with the latter not showing as high summer concentrations. Monthly distribution of GEM at Kuujjuarapik varied considerably from the other two sites. MDEs were found to occur at each site in the spring yet displayed different characteristics. MDEs appear to start at Alert shortly after polar sunrise but in Amderma their initiation is delayed approximately 2 months following polar sunrise. MDEs occur in Kuujjuarapik in the springtime despite an incomplete development of the polar day-night cycle. In spring, as soon as air temperature attained temperatures consistently above 0 degrees C, MDEs ended immediately at all three sites. Continued studies into MDEs are warranted, but clearly an important component of future studies must focus on the origins of the variation of GEM behaviour at different sites.     

Absorbing photonic crystals for silicon thin-film solar cells: Design,fabrication and experimental investigation

In this paper, we present the integration of an absorbing photonic crystal within a thin-film photovoltaic solar cell. Optical simulations performed on a complete solar cell revealed that patterning the hydrogenated amorphous silicon active layer as a 2D photonic crystal membrane enabled to increase its integrated absorption by 28 % between 300 and 720 nm, comparing to a similar but unpatterned stack. In order to fabricate such promising cells, we developed a high throughput process based on holographic lithography and reactive ion etching. The influences of the parameters taking part in those processes on the obtained patterns are discussed. Optical measurements performed on the resulting “photonized” solar cell structures underline the regularity of the 2D pattern and a significant absorption increase above 550 nm, similarly to what is observed on the simulated absorption spectra. Moreover, our patterned cells are found to be robust with regards to the angle of incidence of the light.     

Matching Trajectories of Anatomical Landmarks Under Viewpoint,Anthropometric and Temporal Transforms

An approach is presented to match imaged trajectories of anatomical landmarks (e.g. hands, shoulders and feet) using semantic correspondences between human bodies. These correspondences are used to provide geometric constraints for matching actions observed from different viewpoints and performed at different rates by actors of differing anthropometric proportions. The fact that the human body has approximate anthropometric proportion allows innovative use of the machinery of epipolar geometry to provide constraints for analyzing actions performed by people of different sizes, while ensuring that changes in viewpoint do not affect matching. In addition, for linear time warps, a novel measure, constructed only from image measurements of the locations of anatomical landmarks across time, is proposed to ensure that similar actions performed at different rates are accurately matched as well. An additional feature of this new measure is that two actions from cameras moving at constant (and possibly different) velocities can also be matched. Finally, we describe how dynamic time warping can be used in conjunction with the proposed measure to match actions in the presence of nonlinear time warps. We demonstrate the versatility of our algorithm in a number of challenging sequences and applications, and report quantitative evaluation of the matching approach presented.     

BF<Subscript>3</Subscript>OEt<Subscript>2</Subscript>-coinitiated cationic polymerization of cyclopentadiene in the presence of water at room temperature

The cationic polymerization of cyclopentadiene (CPD) with 1-(4-methoxyphenyl)ethanol (1)/BF₃OEt₂ initiating system in CH₂Cl₂:CH₃CN 4:1 (v/v) mixture at room temperature and in the presence of water ([H₂O]/[BF₃OEt₂] up to 8) is reported. The number-average molecular weights of obtained polymers increased in direct proportion to monomer conversion or initial monomer concentration (M _n ≤ 4,000 g mol⁻¹) in agreement with calculated values, and were inversely proportional to initiator concentration. Polymer MWDs were relatively narrow (M _w/M _n = 1.4–1.7) up to 60% of monomer conversion. It was also shown that regioselectivity of CPD polymerization with 1/BF₃OEt₂ initiating system did not depend significantly on water, monomer, or initiator concentration (1,4-structures content was nearly 60% in all cases).     

Environmentally Benign Oxidation of Alkylphenols to p-Benzoquinones: A Comparative Study of Various Ti-Containing Catalysts

Catalytic properties of Ti-containing porous solids were compared in the oxidation of 2,3,6-trimethylphenol (TMP) with H₂O₂ to produce 2,3,5-trimethyl-1,4-benzoquinone (TMBQ, vitamin E key intermediate). Mesoporous titanium–silicates with di(oligo)nuclear Ti centers, metal–organic framework MIL-125 and amorphous TiO₂ demonstrated 100 % selectivity toward TMBQ. Titanium–silicates prepared by evaporation-induced self-assembly revealed superior performance in terms of product yield and catalyst reusability.

     

Radiative transfer code SHARM-3D for radiance simulations over a non-Lambertian nonhomogeneous surface: intercomparison study

Results of an extensive validation study of the new radiative transfer code SHARM-3D are described. The code is designed for modeling of unpolarized monochromatic radiative transfer in the visible and near-IR spectra in the laterally uniform atmosphere over an arbitrarily inhomogeneous anisotropic surface. The surface boundary condition is periodic. The algorithm is based on an exact solution derived with the Green's function method. Several parameterizations were introduced into the algorithm to achieve superior performance. As a result, SHARM-3D is 2-3 orders of magnitude faster than the rigorous code SHDOM. It can model radiances over large surface scenes for a number of incidence-view geometries simultaneously. Extensive comparisons against SHDOM indicate that SHARM-3D has an average accuracy of better than 1%, which along with the high speed of calculations makes it a unique tool for remote-sensing applications in land surface and related atmospheric radiation studies.