49 Gbit/s Direct-Modulation and Direct-Detection Transmission over 80 km SMF-28 without Optical Amplification or Filtering

We demonstrate direct-modulation of a discrete mode laser using Discrete Multi-Tone modulation for transmission distances up to 100 km in the 1550 nm band. A large operational temperature range (0-65ºC) is also demonstrated

Exploring the role of fear in human decision making

This study explores the use of Convolutional Neural Networks (CNNs) to classify fear in the context of decision-making. The approach involves developing a CNN model that is trained using hyper-parameter tuning and K-fold cross-validation to accurately classify fear from video footage of participants’ facial expressions during an experiment. The videos are presented along with a map to show the location of the participants along the route. The study reports an overall accuracy of 95.05% for fear classification. The results show that the model can successfully predict fear levels in different conditions. For example, the most desolate route with the lowest light levels recorded an overall fear detected at 49.15%, while the safest route with the highest light levels in a densely populated area saw an overall fear detected at 2.69%. These findings demonstrate the potential for using CNNs to classify fear and provide insight into how fear can be taken into consideration for decision-making in realistic scenarios

In Vivo and In Vitro Pharmacological Studies of Methoxycarbonyl-Carboetomidate

Background—We previously developed two etomidate analogs that retain etomidate’s favorable hemodynamic properties, but whose adrenocortical effects are reduced in duration or magnitude. Methoxycarbonyl-etomidate (MOC-etomidate) is rapidly metabolized and ultra-short acting whereas (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) does not potently inhibit 11?-hydroxylase. We hypothesized that MOC-etomidate’s labile ester could be incorporated into carboetomidate to produce a new agent that possesses favorable properties individually found in each agent. We describe the synthesis and pharmacology of methoxycarbonyl-(R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (MOC-carboetomidate), a “soft” analog of carboetomidate. Methods—MOC-carboetomidate’s octanol:water partition coefficient was determined chromatographically and compared with those of etomidate, carboetomidate, and MOC-etomidate. MOC-carboetomidate’s EC50 and ED50 for loss of righting reflexes (LORR) were measured in tadpoles and rats, respectively. Its effect on gamma-aminobutyric acid A (GABAA) receptor function was assessed using two-microelectrode voltage clamp electrophysiological techniques and its metabolic stability was determined in pooled rat blood using high performance liquid chromatography. Its duration of action and effects on arterial blood pressure and adrenocortical function were assessed in rats. Results—MOC-carboetomidate’s octanol:water partition coefficient was 3300 ± 280, whereas those for etomidate, carboetomidate, and MOC-etomidate were 800 ± 180, 15000 ± 3700, and 190 ± 25, respectively. MOC-carboetomidate’s EC50 for LORR in tadpoles was 9 ± 1 µM and its EC50 for LORR in rats was 13 ± 5 mg/kg. At 13 µM, MOC-carboetomidate enhanced GABAA receptor currents by 400 ± 100%. Its metabolic half-life in pooled rat blood was 1.3 minutes. The slope of a plot of the duration of LORR in rats versus the logarithm of the hypnotic dose was significantly shallower for MOC-carboetomidate than for carboetomidate (4 ± 1 vs. 15 ± 3, respectively; p = 0. 0004123). At hypnotic doses, the effects of MOC-carboetomidate on arterial blood pressure and adrenocortical function were not significantly different from those of vehicle alone. Conclusions—MOC-carboetomidate is a GABAA receptor modulator with potent hypnotic activity that is more rapidly metabolized and cleared from the brain than carboetomidate, maintains hemodynamic stability similar to carboetomidate, and does not suppress adrenocortical function

Inhibition of activin/nodal signalling is necessary for pancreatic differentiation of human pluripotent stem cells

Peer reviewedPublisher PD

Impairment of Auditory-Motor Timing and Compensatory Reorganization after Ventral Premotor Cortex Stimulation

Integrating auditory and motor information often requires precise timing as in speech and music. In humans, the position of the ventral premotor cortex (PMv) in the dorsal auditory stream renders this area a node for auditory-motor integration. Yet, it remains unknown whether the PMv is critical for auditory-motor timing and which activity increases help to preserve task performance following its disruption. 16 healthy volunteers participated in two sessions with fMRI measured at baseline and following rTMS (rTMS) of either the left PMv or a control region. Subjects synchronized left or right finger tapping to sub-second beat rates of auditory rhythms in the experimental task, and produced self-paced tapping during spectrally matched auditory stimuli in the control task. Left PMv rTMS impaired auditory-motor synchronization accuracy in the first sub-block following stimulation (p<0.01, Bonferroni corrected), but spared motor timing and attention to task. Task-related activity increased in the homologue right PMv, but did not predict the behavioral effect of rTMS. In contrast, anterior midline cerebellum revealed most pronounced activity increase in less impaired subjects. The present findings suggest a critical role of the left PMv in feed-forward computations enabling accurate auditory-motor timing, which can be compensated by activity modulations in the cerebellum, but not in the homologue region contralateral to stimulation

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

Lignin biomarkers as tracers of mercury sources in lakes water column

This study presents the role of specific terrigenous organic compounds as important vectors of mercury (Hg) transported from watersheds to lakes of the Canadian boreal forest. In order to differentiate the autochthonous from the allochthonous organic matter (OM), lignin derived biomarker signatures [Lambda, S/V, C/V, P/(V ? S), 3,5-Bd/V and (Ad/Al)v] were used. Since lignin is exclusively produced by terrigenous plants, this approach can give a non equivocal picture of the watershed inputs to the lakes. Moreover, it allows a characterization of the source of OM and its state of degradation. The water column of six lakes from the Canadian Shield was sampled monthly between June and September 2005. Lake total dissolved Hg concentrations and Lambda were positively correlated, meaning that Hg and ligneous inputs are linked (dissolved OM r2 = 0.62, p\0.0001; particulate OM r2 = 0.76, p\0.0001). Ratios of P/(V ? S) and 3,5-Bd/V from both dissolved OM and particulate OM of the water column suggest an inverse relationship between the progressive state of pedogenesis and maturation of the OM in soil before entering the lake, and the Hg concentrations in the water column. No relation was found between Hg levels in the lakes and the watershed flora composition—angiosperm versus gymnosperm or woody versus non-woody compounds. This study has significant implications for watershed management of ecosystems since limiting fresh terrestrial OM inputs should reduce Hg inputs to the aquatic systems. This is particularly the case for largescale land-use impacts, such as deforestation, agriculture and urbanization, associated to large quantities of soil OM being transferred to aquatic systems

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

In Vivo MR Imaging of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Renal Ischemia

Objective: This study was designed to evaluate in vivo MR imaging for the depiction of intraarterially injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in an experimental rat model of renal ischemia. Materials and Methods: Left renal ischemia was induced in 12 male Sprague-Dawley rats by use of the catheter lodging method. In vivo MR signal intensity variations depicted on T2*-weighted sequences were evaluated in both the left and right kidneys prior to injection (n = 2), two hours (n = 4), 15 hours (n = 2), 30 hours (n = 2) and 72 hours (n = 2) after injection of SPIO-labeled MSCs in both kidneys. Signal intensity variations were correlated with the number of Prussian blue stain-positive cells as visualized in histological specimens. Results: In an in vivo study, it was determined that there was a significant difference in signal intensity variation for both the left and right cortex (40.8 +/- 4.12 and 26.4 +/- 7.92, respectively) and for both the left and right medulla (23.2 +/- 3.32 and 15.2 +/- 3.31, respectively) until two hours after injection (p < 0.05). In addition, signal intensity variation in the left renal cortex was well correlated with the number of Prussian blue stain-positive cells per high power field (r = 0.98, p < 0.05). Conclusion: Intraarterial injected SPIO-labeled MSCs in an experimental rat model of renal ischemia can be detected with the use of in vivo MR imaging immediately after injection.This study was partly supported by a grant from the Seoul Research and Business Development Program 10548 and by a grant (A062260) from the Innovative Research Institute for Cell Therapy, Republic of Korea.Ittrich H, 2007, J MAGN RESON IMAGING, V25, P1179, DOI 10.1002/jmri.20925Hauger O, 2006, RADIOLOGY, V238, P200, DOI 10.1148/radiol.2381041668Togel F, 2005, AM J PHYSIOL-RENAL, V289, pF31, DOI 10.1152/ajprenal.00007.2005Bos C, 2004, RADIOLOGY, V233, P781, DOI 10.1148/radiol.2333031714Bulte JWM, 2004, NMR BIOMED, V17, P484, DOI 10.1002/nbm.924Grove JE, 2004, STEM CELLS, V22, P487Herzog EL, 2003, BLOOD, V102, P3483, DOI 10.1182/blood-2003-05-1664Kalish H, 2003, MAGNET RESON MED, V50, P275, DOI 10.1002/mrm.10556Frank JA, 2003, RADIOLOGY, V228, P480, DOI 10.1148/radiol.2281020638Jo SK, 2003, KIDNEY INT, V64, P43Kale S, 2003, J CLIN INVEST, V112, P42, DOI 10.1172/JCI200317856Bulte JWM, 2003, MAGNET RESON MED, V50, P201, DOI 10.1002/mrm.10511Kraitchman DL, 2003, CIRCULATION, V107, P2290, DOI 10.1161/01.CIR.0000070931.62772.4EGupta S, 2002, KIDNEY INT, V62, P1285Krause DS, 2002, GENE THER, V9, P754Bulte JWM, 2001, NAT BIOTECHNOL, V19, P1141Lewin M, 2000, NAT BIOTECHNOL, V18, P410Kelly KJ, 2000, SEMIN NEPHROL, V20, P4Firbank MJ, 1999, PHYS MED BIOL, V44, pN261, DOI 10.1088/0031-9155/44/12/403Josephson L, 1999, BIOCONJUGATE CHEM, V10, P186Sutton TA, 1998, SEMIN NEPHROL, V18, P490Thadhani R, 1996, NEW ENGL J MED, V334, P1448SHANLEY PF, 1986, AM J PATHOL, V122, P462