Circadian effects on stroke outcome – did we not wake up in time for neuroprotection?

The occurrence of stroke in humans peaks in the morning. A recent study revealed that time of day mitigates the therapeutic impact of neuroprotective paradigms. These findings might not only explain the previous failure of translation of neuroprotective therapies but inspire new paradigms in stroke chronopathophysiology research. Taking chronotype into account may complement the many factors that influence efficacy of experimental therapies in stroke

On-Orbit Ephemeris Determination with Radio Doppler Validation

Multiple CubeSats are often released from the same host spacecraft into virtually the same orbit at nearly the same time. A satellite team needs the ability to identify and track its own satellites as soon as possible. However, this can be a difficult and confusing task with a large number of satellites. Los Alamos National Laboratory encountered this issue during a launch of LANL-designed CubeSats that were released with more than 20 other objects. A simple radio Doppler method used shortly after launch by the Los Alamos team to select its satellites of interest from the list of available tracked ephemerides is described. This method can also be used for automated real time ephemeris validation. For future efforts, each LANL-designed CubeSat will automatically perform orbit determination from the position, velocity, and covariance estimates provided by an added on-board GPS receiver. This self-determined ephemeris will be automatically downlinked by ground stations for mission planning, antenna tracking, Doppler-pre-correction, etc. A simple algorithm based on established theory and well suited for embedded on-board processing is presented. The trades examined in selecting the algorithm components and data formats are briefly discussed, as is the expected performance

Practical long-distance quantum key distribution system using decoy levels

Quantum key distribution (QKD) has the potential for widespread real-world applications. To date no secure long-distance experiment has demonstrated the truly practical operation needed to move QKD from the laboratory to the real world due largely to limitations in synchronization and poor detector performance. Here we report results obtained using a fully automated, robust QKD system based on the Bennett Brassard 1984 protocol (BB84) with low-noise superconducting nanowire single-photon detectors (SNSPDs) and decoy levels. Secret key is produced with unconditional security over a record 144.3 km of optical fibre, an increase of more than a factor of five compared to the previous record for unconditionally secure key generation in a practical QKD system.Comment: 9 page

Investigation of emitter homogeneity on laser doped emitters

The selective emitter formation by laser doping is a well known process to increase the efficiency of silicon solar cells [1], [2]. For the characterization of laser doped emitters, SIMS (Secondary Ion Mass Spectroscopy) and ECV (Electrochemical Capacitance Voltage Measurement) techniques are used to analyze the emitter profile [3]. It is very difficult to get acceptable result by SIMS on a textured surface, so only ECV can be used. It has been shown, that a charge carrier depth profile can be measured on a homogeneous emitter only by ECV. The use of laser doping results in a non-homogeneous emitter. We have shown that the emitter depth is not just a function of the pulse power, but in addition of the surface structure of the wafer. The texture seems responsible for a strong variability in the doping profile. It has been shown, that the ECV measurement is not applicable to characterize the emitter depth on laser doped areas, because of the microscopic inhomogeneities in the emitter on the macroscopic measurement area. The real emitter profiles are to complex to be characterized by SIMS or ECV. We have shown that the variation in the emitter profile is resulting from the texture in the laser-doped regions

Investigation of emitter homogeneity on laser doped emitters

The selective emitter formation by laser doping is a well known process to increase the efficiency of silicon solar cells [1], [2]. For the characterization of laser doped emitters, SIMS (Secondary Ion Mass Spectroscopy) and ECV (Electrochemical Capacitance Voltage Measurement) techniques are used to analyze the emitter profile [3]. It is very difficult to get acceptable result by SIMS on a textured surface, so only ECV can be used. It has been shown, that a charge carrier depth profile can be measured on a homogeneous emitter only by ECV. The use of laser doping results in a non-homogeneous emitter. We have shown that the emitter depth is not just a function of the pulse power, but in addition of the surface structure of the wafer. The texture seems responsible for a strong variability in the doping profile. It has been shown, that the ECV measurement is not applicable to characterize the emitter depth on laser doped areas, because of the microscopic inhomogeneities in the emitter on the macroscopic measurement area. The real emitter profiles are to complex to be characterized by SIMS or ECV. We have shown that the variation in the emitter profile is resulting from the texture in the laser-doped regions

Tissue-Specific Function of Period3 in Circadian Rhythmicity

The mammalian circadian system is composed of multiple central and peripheral clocks that are temporally coordinated to synchronize physiology and behavior with environmental cycles. Mammals have three homologs of the circadian Period gene (Per1, 2, 3). While numerous studies have demonstrated that Per1 and Per2 are necessary for molecular timekeeping and light responsiveness in the master circadian clock in the suprachiasmatic nuclei (SCN), the function of Per3 has been elusive. In the current study, we investigated the role of Per3 in circadian timekeeping in central and peripheral oscillators by analyzing PER2::LUCIFERASE expression in tissues explanted from C57BL/6J wild-type and Per3−/− mice. We observed shortening of the periods in some tissues from Per3−/− mice compared to wild-types. Importantly, the periods were not altered in other tissues, including the SCN, in Per3−/− mice. We also found that Per3-dependent shortening of endogenous periods resulted in advanced phases of those tissues, demonstrating that the in vitro phenotype is also present in vivo. Our data demonstrate that Per3 is important for endogenous timekeeping in specific tissues and those tissue-specific changes in endogenous periods result in internal misalignment of circadian clocks in Per3−/− mice. Taken together, our studies demonstrate that Per3 is a key player in the mammalian circadian system

Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1

International audiencePost-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP A1, an RBP implicated in many aspects of RNA processing, acts as an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a. Here, by using an integrative structural biology approach, we show that hnRNP A1 forms a 1:1 complex with pri-mir-18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence motifs in the terminal loop of pri-mir-18a. Terminal loop binding induces an allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes its downstream processing. Our results highlight terminal loop RNA recognition by RBPs as a potential general principle of miRNA biogenesis and regulation

Orally Available Selective Melanocortin-4 Receptor Antagonists Stimulate Food Intake and Reduce Cancer-Induced Cachexia in Mice

BACKGROUND: Cachexia is among the most debilitating and life-threatening aspects of cancer. It represents a metabolic syndrome affecting essential functional circuits involved in the regulation of homeostasis, and includes anorexia, fat and muscle tissue wasting. The anorexigenic peptide alpha-MSH is believed to be crucially involved in the normal and pathologic regulation of food intake. It was speculated that blockade of its central physiological target, the melanocortin (MC)-4 receptor, might provide a promising anti-cachexia treatment strategy. This idea is supported by the fact that in animal studies, agouti-related protein (AgRP), the endogenous inverse agonist at the MC-4 receptor, was found to affect two hallmark features of cachexia, i.e. to increase food intake and to reduce energy expenditure. METHODOLOGY/PRINCIPAL FINDINGS: SNT207707 and SNT209858 are two recently discovered, non peptidic, chemically unrelated, orally active MC-4 receptor antagonists penetrating the blood brain barrier. Both compounds were found to distinctly increase food intake in healthy mice. Moreover, in mice subcutaneously implanted with C26 adenocarcinoma cells, repeated oral administration (starting the day after tumor implantation) of each of the two compounds almost completely prevented tumor induced weight loss, and diminished loss of lean body mass and fat mass. CONCLUSIONS/SIGNIFICANCE: In contrast to the previously reported peptidic and small molecule MC-4 antagonists, the compounds described here work by the oral administration route. Orally active compounds might offer a considerable advantage for the treatment of cachexia patients