Cytotoxicity of triorganophosphinegold(i) complexes of thiobenzoate

The preparation and characterization of two triorganophosphinegold(I) complexes containing the anion derived from thiobenzoic acid are described. The cytotoxicity of these complexes has been investigated along with that of triphenylphosphinegold(I) mercaptopurinate, a known anti-tumor compound, against a variety of human cell lines. The complexes showed moderate to high cytotoxicity (ID(50) 250 - 2500 ng/ml).     

Is there the potential for an epidemic of variant Creutzfeldt–Jakob disease via blood transfusion in the UK?

The discovery of three individuals suspected to have contracted variant Creutzfeldt-Jakob disease (vCJD) through blood transfusions has heightened concerns that a secondary epidemic via human-to-human transmission could occur in the UK. The Department of Health responded immediately to this threat by banning those who had received blood transfusions since 1980 from donating blood. In this paper, we conduct a sensitivity analysis to explore the potential size of a blood-borne vCJD epidemic and investigate the effectiveness of public health interventions. A mathematical model was developed together with an expression for the basic reproduction number (R0). The sensitivity of model predictions to unknown parameters determining the transmission of vCJD via infected blood was assessed under pessimistic modelling assumptions. We found that the size of the epidemic (up until 2080) was bounded above by 900 cases, with self-sustaining epidemics (R0>1) also possible; but the scenarios under which such epidemics could arise were found to be biologically implausible. Under optimistic assumptions, public health interventions reduced the upper bound to 250 and further still when only biologically plausible scenarios were considered. Our results support the belief that scenarios leading to large or self-sustaining epidemics are possible but unlikely, and that public health interventions were effective.     

Impact of query intent and search context on clickthrough behavior in sponsored search

Implicit feedback techniques may be used for query intent detection, taking advantage of user behavior to understand their interests and preferences. In sponsored search, a primary concern is the user’s interest in purchasing or utilizing a commercial service, or what is called online commercial intent. In this paper, we develop a methodology for employing the content of search engine result pages (SERPs), along with the information obtained from query strings, to study characteristics of query intent, with a particular focus on sponsored search. Our work represents a step toward the development and evaluation of an ontology for commercial search, considering queries that reference specific products, brands, and retailers. Characteristics of query categories are studied with respect to aggregated user clickthrough behavior on advertising links. We present a model for clickthrough behavior that considers the influence of such factors as the location of ads and the rank of ads, along with query category. We evaluate our work using a large corpus of clickthrough data obtained from a major commercial search engine. In addition, the impact of query intent is studied on clickthrough rate, where a baseline model and the query intent model are compared for the purpose of calculating an expected ad clickthrough rate. Our findings suggest that query-based features, along with the content of SERPs, are effective in detecting query intent. Factors such as query category, the rank of an ad, and the total number of ads displayed on a result page relate to the context of the ad, rather than its content. We demonstrate that these context-related factors can have a major influence on expected clickthrough rate, suggesting that these factors should be taken into consideration when the performance of an ad is evaluated.     

The use of LiDAR in applied interpretive landform mapping for natural resource management,Murray River alluvial plain,Australia

High resolution Light Detection and Ranging (LiDAR) Digital Elevation Models (DEMs) have proved an invaluable tool for landform mapping along the alluvium of the Murray River in southern Australia. They are a key part of an integrated approach to addressing salinity, land management and groundwater resource issues on the Murray River alluvial plain when used in conjunction with satellite imagery, airborne and ground geophysics, and surface and borehole information on soils and sediments. This article describes the processing and application of LiDAR DEMs to the Murray River alluvial plain and how this has informed concepts of landform architecture in the region and confirmed and elaborated on earlier studies. In particular the LiDAR data show how the landform architecture of the Murray River alluvial plain changes dramatically downstream, from the unconfined depositional landscapes of the Riverine Plain to being increasingly confined to an incised valley downstream.     

Quantum-confined stark effect and ultrafast absorption dynamics in bilayer inas quantum dot waveguide

A Stark shift of 40 nm at 1340 nm in a bilayer InAs/GaAs quantum dot ridge waveguide is reported. Time-resolved measurements indicate absorption recovery times of 7 ps at -8 V. Such favourable properties are desirable for intensity and phase modulators     

Bulge-Forming miRNases Cleave Oncogenic miRNAs at the Central Loop Region in a Sequence-Specific Manner

The selective degradation of disease-associated microRNA is promising for the development of new therapeutic approaches. In this study, we engineered a series of bulge-loop-forming oligonucleotides conjugated with catalytic peptide [(LeuArg)₂Gly]₂ (BC–miRNases) capable of recognizing and destroying oncogenic miR-17 and miR-21. The principle behind the design of BC–miRNase is the cleavage of miRNA at a three-nucleotide bulge loop that forms in the central loop region, which is essential for the biological competence of miRNA. A thorough study of mono- and bis-BC–miRNases (containing one or two catalytic peptides, respectively) revealed that: (i) the sequence of miRNA bulge loops and neighbouring motifs are of fundamental importance for efficient miRNA cleavage (i.e., motifs containing repeating pyrimidine–A bonds are more susceptible to cleavage); (ii) the incorporation of the second catalytic peptide in the same molecular scaffold increases the potency of BC–miRNase, providing a complete degradation of miR-17 within 72 h; (iii) the synergetic co-operation of BC–miRNases with RNase H accelerates the rate of miRNA catalytic cleavage by both the conjugate and the enzyme. Such synergy allows the rapid destruction of constantly emerging miRNA to maintain sufficient knockdown and achieve a desired therapeutic effect.     

Prenatal cocaine delays astroglial maturation: immunodensitometry shows increased markers of immaturity (vimentin and GAP-43) and decreased proliferation and production of the growth factor S-100

Exposure to cocaine during fetal development has been demonstrated to produce a variety of brain and behavioral changes. Cocaine is a potent releaser of a variety of neurotransmitters, such as serotonin, which act as developmental signals. Since serotonin plays an important role in astroglial maturation, migration, and growth factor production (e.g. S-100 beta), we proposed that these properties of astroglial cells will be altered in a brain prenatally exposed to cocaine. To observe cocaine's effects on astroglial development, we performed immunocytochemical analyses of a variety of developmental protein makers including BrdU, Gap-43, vimentin, and S100 beta. Our results demonstrate that prenatal cocaine administration produces decreased cell proliferation as measured by BrdU staining, retarded neurite outgrowth as ascertained by increased Gap-43 immunoreactivity, increased density of vimentin-positive radial glial cells, and diminished tissue S100 beta immunoreactivity. Overall, these results suggest that cocaine delays astroglial development. This delay would have profound effects on neuronal development and outgrowth and, thus, development of the entire brain.     

Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe

Sinus pericranii is an anomalous extracranial vascular malformation that is in continuity with the intracranial dural venous sinuses. Five case reports, three congenital and two traumatic, are described. Clinical management, including evaluation, diagnosis, and treatment, is discussed. Awareness of this entity by plastic surgeons will allow for earlier diagnosis and appropriate surgical management, resulting in decreased risk of complications.     

Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode Caenorhabditis elegans

The NMR solution structure of an immunoglobulin superfamily module of twitchin (Ig 18') has been determined and the kinetic and equilibrium folding behaviour characterised. Thirty molecular coordinates were calculated using a hybrid distance geometry-simulated annealing protocol based on 1207 distance and 48 dihedral restraints. The atomic rms distributions about the mean coordinate for the ensemble of structures is 0.55( +/- 0.09) A for backbone atoms and 1.10( +/- 0.08) A for all heavy atoms. The protein has a topology very similar to that of telokin and the titin Ig domains and thus it falls into the I set of the immunoglobulin superfamily. The close agreement between the predicted and observed structures of Ig 18' demonstrates clearly that the I set profile can be applied in the structure prediction of immunoglobulin-like domains of diverse modular proteins. Folding studies reveal that the protein has relatively low thermodynamic stability, deltaG(H2O)U-F = 4.0 kcal mol(-1) at physiological pH. Unfolding studies suggest that the protein has considerable kinetic stability, the half life of the unfolding is greater than 40 minutes in the absence of denaturant.