Phonemic fluency deficits in asymptomatic gene carriers for Huntington's disease.

The aim of the present study was to investigate verbal fluency in preclinical Huntington's disease (HD). Phonemic and semantic fluency and the rate of word production over time were assessed for 29 asymptomatic gene carriers and 34 noncarriers of HD. The relationship between fluency tasks and other cognitive domains was investigated. Compared to noncarriers, carriers produced fewer words and produced them more slowly in the phonemic fluency task but not in the semantic fluency task. When the carrier group was divided on the basis of Predicted-Years-To-Onset (PYTO), only carriers with     

In Vitro Treatment of Melanoma Brain Metastasis by Simultaneously Targeting the MAPK and PI3K Signaling Pathways

Malignant melanoma is the most lethal form of skin cancer, with a high propensity to metastasize to the brain. More than 60% of melanomas have the BRAF^V600E mutation, which activates the mitogen-activated protein kinase (MAPK) pathway [1]. In addition, increased PI3K (phosphoinositide 3-kinase) pathway activity has been demonstrated, through the loss of activity of the tumor suppressor gene, PTEN [2]. Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAF^V600E mutation and PTEN loss, and H3, harboring WT (wild-type) BRAF and PTEN loss, with the MAPK (BRAF) inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. Combined use of the drugs inhibited tumor cell growth and proliferation in vitro in H1_DL2 cells, compared to single drug treatment. Treatment was less effective in the H3 cells. Furthermore, a strong inhibitory effect on the viability of H1_DL2 cells, when grown as 3D multicellular spheroids, was seen. The treatment inhibited the expression of pERK1/2 and reduced the expression of pAKT and p-mTOR in H1_DL2 cells, confirming that the MAPK and PI3K pathways were inhibited after drug treatment. Microarray experiments followed by principal component analysis (PCA) mapping showed distinct gene clustering after treatment, and cell cycle checkpoint regulators were affected. Global gene analysis indicated that functions related to cell survival and invasion were influenced by combined treatment. In conclusion, we demonstrate for the first time that combined therapy with vemurafenib and temsirolimus is effective on melanoma brain metastasis cells in vitro. The presented results highlight the potential of combined treatment to overcome treatment resistance that may develop after vemurafenib treatment of melanomas.     

Production of enniatins A,A1, B,B1, B4, J1 by Fusarium tricinctum in solid corn culture: Structural analysis and effects on mitochondrial respiration

Enniatins (ENs) are secondary fungal metabolites with hexadepsipeptidic chemical structure and they possess a number of potent biological activities that can contaminate several kind of food and foodstuffs increasing the exposure risk for consumers. ENs are produced by several Fusariun strains including Fusarium subglutinans, Fusarium proliferatum and Fusarium tricinctum. Production of a mixture of ENs was performed by culturing F. tricinctum ITEM 9496 on white corn as substrate. The solid culture components were dried and subsequently extracted with water/methanol (50/50 v/v, 0.5% NaCl), homogenised, filtered, extracted by ethyl acetate and analysed by liquid chromatography with diode array detection (LC-DAD). The crude extract was first separated by low pressure liquid chromatography (LPLC) and then further purified by liquid chromatography (LC), resulting in six compounds with a purity higher than 95% as calculated by ¹H NMR, and with a yield of 30–300 mg per compound. The chemical structures of the ENs were determined by liquid chromatography coupled to mass spectrometry (LC–MS) and nuclear magnetic resonance (NMR). The biological activity of the resulting ENs was determined using a mitochondrial respiration test. We discovered that all the ENs studied induced an increase in the mitochondrial respiration resulting in uncoupling of the oxidative phosphorylation. This effect was most likely due to flux of K⁺ ions into the mitochondrial matrix. The order of potency of the ENs derivatives was: A₁ > B₁ > B > A > B₄ > J₁. These results suggest a correlation between the chemical structures and bioactivity and confirm the severe risks for human associated with consumption of enniatins.     

Simulation of sea surface wave influence on small target detection with airborne laser depth sounding.

A theoretical model for simulation of airborne depth-sounding lidar is presented with the purpose of analyzing the influence from water surface waves on the ability to detect 1-m(3) targets placed on the sea bottom. Although water clarity is the main limitation, sea surface waves can significantly affect the detectability. The detection probability for a target at a 9-m depth can be above 90% at 1-m/s wind and below 80% at 6-m/s wind for the same water clarity. The simulation model contains both numerical and analytical components. Simulated data are compared with measured data and give realistic results for bottom depths between 3 and 10 m.     

Magnetic Anomalies and Electronic Structure of Ce<Subscript>2</Subscript>Cu<Subscript>2</Subscript>Mg and Ce<Subscript>2</Subscript>Pd<Subscript>2</Subscript>Mg

The intermetallic compounds RE ₂Cu₂Mg and RE ₂Pd₂Mg (RE=La, Ce) were prepared and characterized by magnetic susceptibility and heat-capacity measurements. They crystallize with an ordered U₃Si₂ type structure (space group P4/mbm) and the cerium compounds contain stable trivalent cerium ions, which undergo antiferromagnetic ordering at ∼7.5 and ∼4 K, respectively. In high magnetic fields Ce₂Cu₂Mg exhibits spin reorientation with critical field strength of 40 kOe at 5 K. The data are compared to the non-magnetic isotypic compounds La₂ T ₂Mg (T=Cu, Ni, Pd) and to the already reported intermediate valent Ce₂Ni₂Mg.     

Sorption Equilibrium in Relation to the Spatial Distribution of Molecules – Application to Desorption of Potato

ABSTRACT

An analysis of desarption isotherms for potato shows the following probable qualities in the water-potato sysarn. in the natural staa the walcr is bound rather strongly due to loss of rotational degrees of freedom in the sorbed molecules, which is caused by small molecular voids in the cellulose structure. This strucmre therefore is formcd as a uniformly cross bound state of the OH-groups. This slate prevails up to a cenin temperature, above which a reaction sas in. whcre OH bonds are successively braken, giving passibility for a panial rotation of sorbed molecules. in the range of lower moisture conlcnt the cellulose strucmre is changed into n crystalline slate a in wood, although the dcgrcc of crystallinity is lower, which is thc     

Properties of Calanus finmarchicus biomass during frozen storage after heat inactivation of autolytic enzymes

Calanus finmarchicus is a marine zooplankton of interest for the aquaculture industry, as well as for nutraceuticals and the cosmetic industry. The chemical composition of C. finmarchicus rapidly changes postmortem due to autolytic processes; in particular phospholipids rapidly degrade to give free fatty acids. The aim of this study was to inactivate autolytic enzymes in C. finmarchicus by applying heat (72 °C, 5-30 min) through mixing with boiling, fresh water, and further to explore the effects of heat (70 °C, 15 min) combined with long time storage (−20 °C, 12 months) of treated and untreated material. Heat treatment (5 min) inactivated all tested enzymes and maintained the initial amount of phospholipids, total lipids and crude protein. Storage of untreated material led to complete degradation of all phospholipids, whereas heat treatment resulted in a stable product containing the initial amount of phospholipids and astaxanthin.     

Rational design methodology for fire exposed load bearing structures

The state-of-art of reliability studies in the area of fire-exposed structures or structural members is illustrated, taking examples from published papers concerning load-bearing building structures of steel, reinforced concrete, and wood. In parallel, trends are described in the present development of rational structural fire design methods, principally adapted to modern loading and safety philosophy for the non-fire state. Statistically derived results are presented for fire-exposed, insulated steel structures in office buildings, giving the breakdown of the total variance in maximum steel temperature and load-bearing capacity into component variances as a function of the insulation characteristics. The safety index and probability of failure are compared numerically for different fire design procedures. The data presented are examples of the information which is required as input in a qualified systems analysis of fire exposed load-bearing structures.