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Antagonizing L-type Ca2+ Channel Reduces Development of Abnormal Involuntary Movement in the Rat Model of L-3,4-Dihydroxyphenylalanine-Induced Dyskinesia

Background: Chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment of Parkinson's disease (PD) leads to debilitating involuntary movements, termed L-DOPA-induced dyskinesia. Striatofugal medium spiny neurons (MSN) lose their dendritic spines and cortico-striatal glutamatergic synapses in PD and in experimental models of DA depletion. This loss of connectivity is triggered by a dysregulation of in

Identification of low-risk tumours in histological high-grade soft tissue sarcomas

In more than one-third of patients with a histological high-grade malignant soft tissue sarcoma metastasis develops despite local control of the primary tumour. Hence, adjuvant chemotherapy is increasingly used for these relatively chemoresistant tumours which requires improved prognostication to exclude low-risk patients from overtreatment. We assessed the value of stepwise prognostication in a s

Hepatitis C virus RNA kinetics during the initial 12 weeks treatment with pegylated interferon-alpha 2a and ribavirin according to virological response

To optimize treatment of chronic hepatitis C early identification of patients who will not achieve a sustained virological response (SVR) is desirable. We investigated hepatitis C virus (HCV) RNA kinetics at day 1 (in 15 patients; genotypes 1 and non-1, 9 and 6 respectively) at weeks 1, 4 and 12 (in 53 patients; genotypes 1 and non-1, 19 and 34, respectively) during treatment with pegylated interf

Hydrolytically active tetranuclear nickel complexes with structural resemblance to the active site of urease

Reaction of the new asymmetric ligand 2-(N-isopropyl-N-((1-methylimidazolyl)methyl)aminomethyl)-6-(N-carboxylm ethyl-N-((1-methylimidazolyl)methyl) aminomethyl)-4-methylphenol (ICIMP) with nickel perchlorate and diphenylacetic acid leads to the formation of tetranuclear nickel complexes, whose crystal structures reveal that they consist of dimers of dimers in which each Ni-2 unit has a coordinatio

Of sheep and rain: large-scale population dynamics of the red kangaroo

1. We analysed time-series data from populations of red kangaroos (Macropus rufus, Desmarest) inhabiting four areas in the pastoral zone of South Australia. We formulated a set of a priori models to disentangle the relative effects of the covariates: rainfall, harvesting, intraspecific competition, and domestic herbivores, on kangaroo population-growth rate. 2. The statistical framework allowed fo

Oncostatin M signaling in human glioma cell lines

We have recently found that oncostatin M (OSM) is overexpressed in most human brain tumors. The effects of OSM are unclear with conflicting reports of growth stimulatory or inhibitory effects in various cell types. The aim of this study was to investigate the effects of OSM in 5 glioma cell lines and 7 short-term cultures of human gliomas and in normal cultured human astrocytes. None of the cell l

Pharmacokinetics of recombinant factor IX in relation to age of the patient: implications for dosing in prophylaxis

The aims of this study were to investigate possible age-related changes in the disposition of factor IX procoagulant activity (FIX:C) after administration of recombinant factor IX (rFIX) and to translate the pharmacokinetic findings into suggestions for dosing of rFIX during prophylactic treatment of haemophilia B. Pharmacokinetic data were available from a previous study on 56 patients, aged 4-56

Risk of lymphoma and leukaemia after bacille Calmette-Guerin and smallpox vaccination: A Danish case-cohort study

Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines. In a background cohort (N=47,622) from the Copenhagen School Health Records Register, cases of leukae

Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1.

Cell migration plays a central role in processes such as development, wound healing and cancer metastasis. Here we describe a novel interaction between DDR1, a receptor tyrosine kinase activated by collagen, and the phosphoprotein DARPP-32 in mammary epithelial cells. DARPP-32 expression was readily detected in non-transformed mammary cell lines, but was strongly reduced or even absent in breast t

Caspase-mediated death of newly formed neurons in the adult rat dentate gyrus following status epilepticus

A large proportion of cells that proliferate in the adult dentate gyrus under normal conditions or in response to brain insults exhibit only short-term survival. Here, we sought to determine which cell death pathways are involved in the degeneration of newly formed neurons in the rat dentate gyrus following 2 h of electrically induced status epilepticus. We investigated the role of three families

Can we beat the complexity of very large–scale requirements engineering?

Competitive development of complex embedded systems such as mobile phones requires management of massive amounts of complex requirements. This paper defines and discusses orders of magnitudes in RE and implications of the highest order of magnitude that we have experienced in industrial settings. Based on experiences from the mobile phone domain we propose research areas that, if ad-dressed succes

Comparison of waveforms in conventional 12-lead ECGs and those derived from EASI leads in children

To investigate the possibility of simplifying electrocardiogram (ECG) recording in children, we compared waveforms in conventional 12-lead ECGs to those derived from EASI leads in 221 children of various ages. The conventional 12-lead ECGs and the ECGs using EASI electrode positions were collected simultaneously. We developed and determined the value of age-specific transformation coefficients for

Analysis and design of modern stream ciphers

When designing symmetric ciphers, security and performance are of utmost importance. When selecting a symmetric encryption algorithm, the first choice is whether to choose a block cipher or a stream cipher. Most modern block ciphers offer a sufficient security and a reasonably good performance. But a block cipher must usually be used in a stream cipher mode of operation, which suggests that using

Comparison of food frequency questionnaires: the reduced Block and Willett questionnaires differ in ranking on nutrient intakes

Food frequency questionnaires, major tools in epidemiologic studies, are often criticized for biased and imprecise intake estimates. The aim of this study was to compare the performance of two widely used food frequency questionnaires, a reduced 60-item Block questionnaire and a 153-item Willett food frequency questionnaire, relative to three 24-hour recalls administered by telephone. The dietary

Mediator-modified electrodes for catalytic NADH oxidation: high rate constants at interesting overpotentials.

Carbon paste electrodes were modified with a nitrofluorenone derivative, 2,4,7-trinitro-9-fluorenone, adsorbed on zirconium phosphate (ZP). After electrochemical reduction of the fluorenone derivative, it turns into a very efficient mediator for electrocatalytic NADH oxidation, with a formal potential of about +250 mV vs. Ag/AgCl. The electrochemistry and the electrocatalytic properties of the med

Rat intestinal ceramidase: purification, properties and physiological relevance.

Neutral ceramidase activity has previously been identified in the intestinal mucosa and gut lumen and postulated to be important in the digestion of sphingolipids. It is found throughout the intestine but has never been fully characterized. We have purified rat intestinal neutral ceramidase from an eluate obtained by perfusing the intestinal lumen with 0.9% NaCl and 3 mM sodium taurodeoxycholate.

Operating charts for continuous sedimentation III: control of step inputs

The main purposes of a clarifier-thickener unit is that it should produce a high underflow concentration and a zero effluent concentration. The main difficulty in the control of the clarification-thickening process (by adjusting a volume flow) is that it is nonlinear with complex relations between concentrations and volume flows via the solution of a PDE - a conservation law with a source term and

Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer

Introduction We have previously reported that tumour-specific expression of the rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR), in the mevalonate pathway is associated with more favourable tumour parameters in breast cancer. In the present study, we examined the prognostic value of HMG-CoAR expression in a large cohort of primary breast cancer patients with long-

The development of global consensus guidelines on the management of the diabetic foot

The future for diabetes is grave. Now described as the global epidemic of the 21st century, the increasing incidence of diabetes (in 2007 over 246 million people affected by diabetes) will place considerable strain on resources and will bring suffering to many if the preventative measures promoted by the International Diabetes Federation (IDF), the International Working Group on the Diabetic Foot