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We report on the development of a simple-architecture fiber-based frequency distribution system used to transfer high frequency stability 100 MHz signals. This work is focused on the emitter and the receiver performances that allow the transmission of the radio-frequency signal over an optical fiber. The system exhibits a residual fractional frequency stability of 1 × 10−14 at 1 s integration time and in the low 10−16 range after 100 s. These performances are suitable to transfer the signal of frequency references such as those of a state-of-the-art hydrogen maser without any phase noise compensation scheme. As an application, we demonstrate the dissemination of such a signal through a 100 m long optical fiber without any degradation. The proposed setup could be easily extended for operating frequencies in the 10 MHz–1 GHz range. [ABSTRACT FROM AUTHOR]

In this paper, we propose technical solutions to solve the issue of the thermal stabilization of a room-temperature high-Q whispering gallery mode microwave sapphire resonator. This technology enables the design of very low phase noise microwave sources which can be used as references for phase noise measurements or for high sensitivity radar systems. Nevertheless, the sapphire resonator presents at the ambient temperature a high sensitivity to thermal fluctuations of the order of -70 ppm/K limiting the oscillator stability in the long term. An original resonator thermal configuration has been designed and optimized thanks to finite difference technique simulations. The symmetry of the proposed thermal structure increases the temperature control efficiency. Coupled to a high-resolution electronic temperature controller directly embedded on the microwave cavity, this structure presents a very low sensitivity to the environment thermal fluctuations. This sensitivity is better than -0.05 ppm/K. [ABSTRACT FROM AUTHOR]

Interleukine-1β converting enzyme (ICE) was the first identified member of a growing family of cysteine proteases that now includes ten mammalian homologs. Within this large family, two functional proteins, denoted TX and TY share 60% amino-acid identity with ICE in the mature protein and, together with ICE, constitute the ICE subfamily. The present study describes the identification of five new gene sequences, denoted S1-S5, closely related to ICE and TX and belonging to this subfamily. Sequences were identified using genomic Southern-blot analysis of human DNA with probes corresponding to ICE and TX exon 6. Using PCR amplification and cloning, the complete exon-6 sequence of these new genes was identified; three exhibit around 90% identity with Ice within exon 6, whereas the two others share about 70% identity with Ice. Examination of open reading frames and of amino acids essential for ICE activity indicate that none of these genes encodes for a functional protease. In conclusion, extensive analysis of the genes closely related to Ice shows that the Ice subfamily is constituted of eight members. Three of them encode for functional proteases (ICE, TX and TY) whereas the remaining members probably correspond to pseudogenes. [ABSTRACT FROM AUTHOR]

Hookworm-related cutaneous larva migrans is a zoonotic disease prevalent in tropical regions. Infection occurs through direct contact with hookworm larvae that is defecated by dogs or cats, in sandy, moist and warm places. Any body part can be affected, but it predominates in feet, buttocks, thighs and hands. Itching is the main symptom and bacterial infections are sometimes added. The diagnosis is mainly clinical supported by the medical history, focusing on recent trips. It is treated with ivermectin having the symptoms disappearing, on average, in three days. Preventive measures are aimed to wear shoes when walking on the sand and to prohibit the passage of dogs and cats to the beaches. [ABSTRACT FROM AUTHOR]

Previous reports demonstrate that metformin, an anti-diabetic drug, can decrease the risk of cancer and inhibit cancer cell growth. However, its mechanism in cancer cells is still unknown. Metformin significantly blocks cell cycle and inhibits cell proliferation and colony formation of leukemic cells. However, the apoptotic response to metformin varies. Furthermore, daily treatment with metformin induces apoptosis and reduces tumor growth in vivo. While metformin induces early and transient activation of AMPK, inhibition of AMPKα1/2 does not abrogate anti-proliferative or pro-apoptotic effects of metformin. Metformin decreases electron transport chain complex I activity, oxygen consumption and mitochondrial ATP synthesis, while stimulating glycolysis for ATP and lactate production, pentose phosphate pathway for purine biosynthesis, fatty acid metabolism, as well as anaplerotic and mitochondrial gene expression. Importantly, leukemic cells with high basal AKT phosphorylation, glucose consumption or glycolysis exhibit a markedly reduced induction of the Pasteur effect in response to metformin and are resistant to metformin-induced apoptosis. Accordingly, glucose starvation or treatment with deoxyglucose or an AKT inhibitor induces sensitivity to metformin. Overall, metformin elicits reprogramming of intermediary metabolism leading to inhibition of cell proliferation in all leukemic cells and apoptosis only in leukemic cells responding to metformin with AKT phosphorylation and a strong Pasteur effect. [ABSTRACT FROM AUTHOR]

Abstract: Activity defects in respiratory chain complexes are responsible for a large variety of pathological situations, including neuromuscular diseases and multisystemic disorders. Their impact on energy production is highly variable and disproportional. The same biochemical or genetic defect can lead to large differences in clinical symptoms and severity between tissues and patients, making the pathophysiological analysis of mitochondrial diseases difficult. The existence of compensatory mechanisms operating at the level of the respiratory chain might be an explanation for the biochemical complexity observed for respiratory defects. Here, we analyzed the role of cytochrome c and coenzyme Q in the attenuation of complex III and complex IV pharmacological inhibition on the respiratory flux. Spectrophotometry, HPLC–EC, polarography and enzymology permitted the calculation of molar ratios between respiratory chain components, giving values of 0.8:61:3:12:6.8 in muscle and 1:131:3:9:6.5 in liver, for CII:CoQ:CIII:Cyt c:CIV. The results demonstrate the dynamic functional compartmentalization of respiratory chain substrates, with the existence of a substrate pool that can be recruited to maintain energy production at normal levels when respiratory chain complexes are inhibited. The size of this reserve was different between muscle and liver, and in proportion to the magnitude of attenuation of each respiratory defect. Such functional compartmentalization could result from the recently observed physical compartmentalization of respiratory chain substrates. The dynamic nature of the mitochondrial network may modulate this compartmentalization and could play a new role in the control of mitochondrial respiration as well as apoptosis. [Copyright &y& Elsevier]

To investigate the physiological diversity in the regulation and control of mitochondrial oxidative phosphorylation, we determined the composition and functional features of the respiratory chain in muscle, heart, liver, kidney, and brain. First, we observed important variations in mitochondrial content and infrastructure via electron micrographs of the different tissue sections. Analyses of respiratory chain enzyme content by Western blot also showed large differences between tissues, in good correlation with the expression level of mitochondrial transcription factor A and the activity of citrate synthase. On the isolated mitochondria, we observed a conserved molar ratio between the respiratory chain complexes and a variable stoichiometry for coenzyme Q and cytochrome c, with typical values of [l-1.5]:[30- 1351: [31: [9-35]: [6.5-7.5] for complex II:coenzyme Q:complex III: cytochrome c:complex IV in the different tissues. The functional analysis revealed important differences in maximal velocities of respiratory chain complexes, with higher values in heart. However, calculation of the catalytic constants showed that brain contained the more active enzyme complexes. Hence, our study demonstrates that, in tissues, oxidative phosphorylation capacity is highly variable and diverse, as determined by different combinations of 1) the mitochondrial content, 2) the amount of respiratory chain complexes, and 3) their intrinsic activity. In all tissues, there was a large excess of enzyme capacity and intermediate substrate concentration, compared with what is required for state 3 respiration. To conclude, we submitted our data to a principal component analysis that revealed three groups of tissues: muscle and heart, brain, and liver and kidney. [ABSTRACT FROM AUTHOR]