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Knocking down disease: a progress report on siRNA therapeutics.

Small interfering RNAs (siRNAs), which downregulate gene expression guided by sequence complementarity, can be used therapeutically to block the synthesis of disease-causing proteins. The main obstacle to siRNA drugs - their delivery into the target cell cytosol - has been overcome to allow suppression of liver gene expression. Here, we review the results of recent clinical trials of siRNA therape

Transient Access to the Protein Interior: Simulation versus NMR.

Many proteins rely on rare structural fluctuations for their function, whereby solvent and other small molecules gain transient access to internal cavities. In magnetic relaxation dispersion (MRD) experiments, water molecules buried in such cavities are used as intrinsic probes of the intermittent protein motions that govern their exchange with external solvent. While this has allowed a detailed c

Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study

ObjectiveA subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). MethodsPatients received lenalidomide 10mg/d (days 1-21; n=47) or 5mg/d (days 1-28; n=43) on 28-d cycles or placebo (n=45). From the placebo and lenalid

Bleeding complications after central line insertions: relevance of pre-procedure coagulation tests and institutional transfusion policy.

BACKGROUND: The aim of this study was to map pre-procedural variables for insertion of a central venous catheter, prophylactic blood component use and to investigate whether any independent variable could be identified as an independent risk factor for associated bleeding complications in patients outside the intensive care unit. METHODS: In this retrospective study, we investigated 1737 consecuti

MicroRNAs are essential for stretch-induced vascular smooth muscle contractile differentiation via miR-145-dependent expression of L-type calcium channels.

Stretch of the vascular wall is an important stimulus to maintain smooth muscle contractile differentiation that is known to depend on L-type calcium influx, Rho-activation and actin polymerization. The role of microRNAs in this response was investigated using tamoxifen-inducible and smooth muscle specific Dicer KO mice. In the absence of Dicer, which is required for microRNA maturation, smooth mu

A reflection on Richard B. Saltman 'Structural patterns in Swedish health policy

Looking back over 30 years of Swedish health care, professor Saltman examines structural changes in the Swedish health care sector. This is a very welcome contribution to the literature, and it makes good sense – institutional change is often a slow process, and it may take considerable time before the effects can be fully appreciated. Saltman’s paper provides a useful analytical overview of thre

Process engineering for bioflavour production with metabolically active yeast - a minireview.

Flavours are biologically active molecules of large commercial interest in the food, cosmetics, detergent and pharmaceutical industry. The production of flavours can take place by either extraction from plant materials, chemical synthesis, through biological conversion of precursor molecules or through de novo biosynthesis. The latter alternatives are gaining importance through the rapidly growing

Hybrid Iterative Reconstruction Algorithm Improves Image Quality in Craniocervical CT Angiography.

OBJECTIVE. The purpose of this study was to evaluate the potential of a hybrid iterative reconstruction algorithm for improving image quality in craniocervical CT angiography (CTA) and to assess observer performance. SUBJECTS AND METHODS. Thirty patients (mean age, 58 years; range 16-80 years) underwent standard craniocervical CTA (volume CT dose index, 6.8 mGy, 2.8 mSv). Images were reconstructed

Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin.

Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. Genetic factors determining chemerin release from adipose tissue are yet unknown. We conducted a meta-analysis of genome-wide association studies (GWAS) for serum chemerin in three independent cohorts from Europe: Sorbs and KORA from Germany and PPP-Botnia from Finland (total N = 2,791). In addition, we m

Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load

Objective: To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Design: Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression i

Nocturnal passerine migration without tailwind assistance

Nocturnal passerine migrants could substantially reduce the amount of energy spent per distance covered if they fly with tailwind assistance and thus achieve ground speeds that exceed their airspeeds (the birds' speed in relation to the surrounding air). We analysed tracking radar data from two study sites in southern and northern Scandinavia and show that nocturnally migrating passerines, during

TraML: a standard format for exchange of selected reaction monitoring transition lists

Abstract in UndeterminedTargeted proteomics via selected reaction monitoring (SRM) is a powerful mass spectrometric technique affording higher dynamic range, increased specificity and lower limits of detection than other shotgun mass spectrometry methods when applied to proteome analyses. However, it involves selective measurement of predetermined analytes, which requires more preparation in the f

Third world list of cetrarioid lichens - in a new databased form, with amended phylogenetic and type information

The third, updated electronic version of the world list of cetrarioid lichens (http://esamba.bo.bg.ut.ee/checklist/cetrarioid/home.php) contains more than 570 names representing 149 accepted species. It is based on a FileMaker powered database, allowing users to view data in different sets and to perform searches. The list presents new information about the phylogenetic status of accepted taxa, an

Deoxygenation of the Baltic Sea during the last century

Deoxygenation is a global problem in coastal and open regions of the ocean, and has led to expanding areas of oxygen minimum zones and coastal hypoxia. The recent expansion of hypoxia in coastal ecosystems has been primarily attributed to global warming and enhanced nutrient input from land and atmosphere. The largest anthropogenically induced hypoxic area in the world is the Baltic Sea, where the

The components of the illiquidity premium: An empirical analysis of U.S. stocks 1927-2010

This paper implements a conditional version of the liquidity adjusted CAPM (LCAPM). The conditional LCAPM allows for a time-varying decomposition of the total illiquidity premium into a level component and three risk components. The estimated average annual total illiquidity premium for US stocks 1927-2010 is 1.74%-2.08%, which is substantially lower than in most previous studies. The contribution

Audio spectrum analysis of umbilical artery Doppler ultrasound signals applied to a clinical material.

Analysis of umbilical artery flow velocity waveforms characterized by pulsatility index (PI) is used to evaluate fetoplacental circulation in high-risk pregnancies. However, an experienced sonographer may be able to further differentiate between various timbres of Doppler audio signals. Recently, we have developed a method for objective audio signal characterization; the method has been tested in