Good rectifying characteristic in p–n junctions composed of La0.67Ca0.33MnO3-δ/Nb–0.7 wt %-doped SrTiO3

Simple p–n junctions have been fabricated using a simple heteroepitaxial structure of La0.67Ca0.33MnO3–/Nb-doped SrTiO3. In such junctions, the La0.67Ca0.33MnO3– exhibits semiconductor behavior due to oxygen deficiency, whereas the Nb–0.7 wt %-doped SrTiO3 shows a metal behavior. These junctions demonstrate good rectifying characteristic in a wide temperature range from 5 to 350 K. An intriguing observation is that the rectifying behavior is nearly independent of temperature. © 2003 American Institute of Physics.published_or_final_versio

Magnetoresistance in LaFe11.2Co0.7Si1.1 compound

Magnetoresistance has been studied in LaFe/sub 11.2/Co/sub 0.7/Si/sub 1.1/ compound. The ferromagnetic ordering at Curie temperature T/sub C/ of 274 K was found being accompanied by a drastic negative lattice expansion due to the strong structural and magnetic interplay. Such a simultaneous magnetic and lattice change would cause changes in transport properties. The measured transport properties indicate that the transition can be induced by temperature or applied magnetic field. The sample shows a metallic character below T/sub C/, whereas the electrical resistance decreases dramatically and then recovers the metal-like behavior above T/sub C/. Application of a magnetic field retains the transitions via increasing the ferromagnetic ordering temperature. An isothermal increase of field leads to an increase of resistance at temperatures near but above T/sub C/, which is a result of the field-induced metamagnetic transition from paramagnetic to ferromagnetic state.published_or_final_versio

Magnetocaloric effect in itinerant electron metamagnetic systems La(Fe1-xCox)11.9Si1.1

The NaZn13-type compounds La(Fe1–xCox)11.9Si1.1 (x=0.04, 0.06, 0.08) were successfully synthesized, in which the Si content is the limit that can be reached by arc-melting technique. TC is tunable from 243 to 301 K with Co doping from x=0.04 to 0.08. Great magnetic entropy change S in a wide temperature range from ~230 to ~320 K has been observed. The adiabatic temperature change Tad upon changing magnetic field was also directly measured. Tad of sample x=0.06 reaches ~2.4 K upon a field change from 0 to 1.1 T. The temperature hysteresis upon phase transition is small, ~1 K, for all samples. The influence of Co doping on itinerant electron metamagnetic transition and magnetic entropy change is discussed. ©2005 American Institute of Physics.published_or_final_versio

Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human α<inf>2</inf>-macroglobulin

Human α2-macroglobulin (hα2M) is a multidomain protein with a plethora of essential functions, including transport of signaling molecules and endopeptidase inhibition in innate immunity. Here, we dissected the molecular mechanism of the inhibitory function of the ∼720-kDa hα2M tetramer through eight cryo-electron microscopy (cryo-EM) structures of complexes from human plasma. In the native complex, the hα2M subunits are organized in two flexible modules in expanded conformation, which enclose a highly porous cavity in which the proteolytic activity of circulating plasma proteins is tested. Cleavage of bait regions exposed inside the cavity triggers rearrangement to a compact conformation, which closes openings and entraps the prey proteinase. After the expanded-to-compact transition, which occurs independently in the four subunits, the reactive thioester bond triggers covalent linking of the proteinase, and the receptor-binding domain is exposed on the tetramer surface for receptor-mediated clearance from circulation. These results depict the molecular mechanism of a unique suicidal inhibitory trap

Assessment of Surfactant Protein A (SP-A) dependent agglutination

Background: Monomers of the collectin surfactant associated protein-A (SP-A) are arranged in trimers and higher oligomers. The state of oligomerization differs between individuals and likely affects SP-A's functional properties. SP-A can form aggregates together with other SP-A molecules. Here we report and assess a test system for the aggregate forming properties of SP-A in serum and broncho-alveolar lavage samples. Methods: Anti-SP-A antibodies fixed to latex beads bound SP-A at its N-terminal end and allowed the interaction with other SP-A molecules in a given sample by their C-terminal carbohydrate recognition domain (CRD) to agglutinate the beads to aggregates, which were quantified by light microscopy. Results: SP-A aggregation was dependent on its concentration, the presence of calcium, and was dose-dependently inhibited by mannose. Unaffected by the presence of SP-D no aggregation was observed in absence of SP-A. The more complex the oligomeric structure of SP-A present in a particular sample, the better was its capability to induce aggregation at a given total concentration of SP-A. SP-A in serum agglutinated independently of the pulmonary disease; in contrast SP-A in lung lavage fluid was clearly inferior in patients with chronic bronchitis and particularly with cystic fibrosis compared to controls. Conclusions: The functional status of SP-A with respect to its aggregating properties in serum and lavage samples can be easily assessed. SP-A in lung lavage fluid in patients with severe neutrophilic bronchitis was inferior

Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?

<p>Abstract</p> <p>Background</p> <p>Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM.</p> <p>Methods</p> <p>Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 ± 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed.</p> <p>Results</p> <p>The mean loss of FEV₁was -2.30 ± 0.52 ml/day before therapy and a significant mean gain of FEV₁of 1.19 ± 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV₁and FVC at baseline were 1.12 ± 0.15 l (36.1 ± 4.5%pred.) and 2.47 ± 0.25 l (69.2 ± 6.5%pred.), respectively. At three and six months during follow-up a significant increase of FEV₁and FVC was demonstrated (3 months ΔFEV₁: 220 ± 82 ml, p = 0.024; 6 months ΔFEV₁: 345 ± 58 ml, p = 0.001); (3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy.</p> <p>Conclusions</p> <p>Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.</p

An analysis of temporal and generational trends in the incidence of anal and other HPV-related cancers in Southeast England

Patients diagnosed in 1960–2004 with cancer of the cervix, anus, vulva, vagina or penis were identified from the Thames Cancer Registry database, and age-standardised period (temporal) incidence rates calculated by direct standardisation. Age-cohort modelling techniques were used to estimate age-specific incidence rates in the earlier and later cohorts, enabling the calculation of age-standardised cohort (generational) rates. Incidence of anal cancer increased for both men and women over the period studied, mainly in those born from 1940 onwards. Similar generational patterns were seen for cancers of the vulva and vagina, but those for penile cancer were different. For cervix cancer, the steep downward trend in cohort rates due to screening levelled off in women born from 1940 onwards. Our findings are compatible with the hypothesis that changes in sexual practices were a major contributor to the increases of these cancers. Programmes of vaccination against HPV, aimed at reducing the burden of cervical cancer, may also help to reduce the incidence of cancer at other anogenital sites

Enhancement of carotenoids biosynthesis in Chlamydomonas reinhardtii by nuclear transformation using a phytoene synthase gene isolated from Chlorella zofingiensis

The isolation and characterization of the phytoene synthase gene from the green microalga Chlorella zofingiensis (CzPSY), involved in the first step of the carotenoids biosynthetic pathway, have been performed. CzPSY gene encodes a polypeptide of 420 amino acids. A single copy of CzPSY has been found in C. zofingiensis by Southern blot analysis. Heterologous genetic complementation in Escherichia coli showed the ability of the predicted protein to catalyze the condensation of two molecules of geranylgeranyl pyrophosphate (GGPP) to form phytoene. Phylogenetic analysis has shown that the deduced protein forms a cluster with the rest of the phytoene synthases (PSY) of the chlorophycean microalgae studied, being very closely related to PSY of plants. This new isolated gene has been adequately inserted in a vector and expressed in Chlamydomonas reinhardtii. The overexpression of CzPSY in C. reinhardtii, by nuclear transformation, has led to an increase in the corresponding CzPSY transcript level as well as in the content of the carotenoids violaxanthin and lutein which were 2.0- and 2.2-fold higher than in untransformed cells. This is an example of manipulation of the carotenogenic pathway in eukaryotic microalgae, which can open up the possibility of enhancing the productivity of commercial carotenoids by molecular engineering