Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids

Abstract A unified strategy for enantioselective total synthesis of all stereoisomers of the [2+2] family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either meso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a meso precursor or controlling diastereoselectivity in elaborating C2-symmetric intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+)- or (-)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine

Building up spacetime with quantum entanglement

In this essay, we argue that the emergence of classically connected spacetimes is intimately related to the quantum entanglement of degrees of freedom in a non-perturbative description of quantum gravity. Disentangling the degrees of freedom associated with two regions of spacetime results in these regions pulling apart and pinching off from each other in a way that can be quantified by standard measures of entanglement.Comment: Gravity Research Foundation essay, 7 pages, LaTeX, 5 figure

Pairwise comparison matrices and the error-free property of the decision maker

Pairwise comparison is a popular assessment method either for deriving criteria-weights or for evaluating alternatives according to a given criterion. In real-world applications consistency of the comparisons rarely happens: intransitivity can occur. The aim of the paper is to discuss the relationship between the consistency of the decision maker—described with the error-free property—and the consistency of the pairwise comparison matrix (PCM). The concept of error-free matrix is used to demonstrate that consistency of the PCM is not a sufficient condition of the error-free property of the decision maker. Informed and uninformed decision makers are defined. In the first stage of an assessment method a consistent or near-consistent matrix should be achieved: detecting, measuring and improving consistency are part of any procedure with both types of decision makers. In the second stage additional information are needed to reveal the decision maker’s real preferences. Interactive questioning procedures are recommended to reach that goal

When a small self means manageable obstacles: Spontaneous self-distancing predicts divergent effects of awe during a subsequent performance stressor

The emotion of awe occurs when one feels small relative to something vaster than the self; it leads to benefits such as care for others. However, because awe elicits the experience of a “small self,” it is unclear to what extent awe positively versus negatively affects responses to subsequent stressors. If personal obstacles seem trivial in comparison to awe-inspiring stimuli, stressors should seem either manageable or unimportant, but if one's capabilities seem comparatively insignificant, stressors should seem unmanageable. We hypothesized that awe would have a generally positive effect on responses during a subsequent performance stressor, but that this would further depend on whether people tended to spontaneously take on a self-distanced versus self-immersed perspective. In the face of awe, focusing less on the self (self-distanced perspective) should make obstacles in particular seem trivial, whereas focusing more on the self (self-immersed) should lead one's capabilities to seem insignificant. Using the biopsychosocial model of challenge/threat, we found that spontaneous self-distancing significantly moderated awe's effects on responses during a subsequent performance stressor (speech task): For participants who self-distanced, the awe condition led to cardiovascular responses consistent with greater challenge than the neutral control condition (reflecting evaluating the stressor as more manageable); for participants who self-immersed, awe predicted relative threat (less manageable stressor). There was no support for awe making people care less about the stressor (as reflected in cardiovascular responses consistent with task engagement). This offers insight into how awe can have divergent effects on people's experiences during performance stressors

Bandit Models of Human Behavior: Reward Processing in Mental Disorders

Drawing an inspiration from behavioral studies of human decision making, we propose here a general parametric framework for multi-armed bandit problem, which extends the standard Thompson Sampling approach to incorporate reward processing biases associated with several neurological and psychiatric conditions, including Parkinson's and Alzheimer's diseases, attention-deficit/hyperactivity disorder (ADHD), addiction, and chronic pain. We demonstrate empirically that the proposed parametric approach can often outperform the baseline Thompson Sampling on a variety of datasets. Moreover, from the behavioral modeling perspective, our parametric framework can be viewed as a first step towards a unifying computational model capturing reward processing abnormalities across multiple mental conditions.Comment: Conference on Artificial General Intelligence, AGI-1

Numb regulates cell–cell adhesion and polarity in response to tyrosine kinase signalling

Epithelial-mesenchymal transition (EMT), which can be caused by aberrant tyrosine kinase signalling, marks epithelial tumour progression and metastasis, yet the underlying molecular mechanism is not fully understood. Here, we report that Numb interacts with E-cadherin (E-cad) through its phosphotyrosine-binding domain (PTB) and thereby regulates the localization of E-cad to the lateral domain of epithelial cell–cell junction. Moreover, Numb engages the polarity complex Par3–aPKC–Par6 by binding to Par3 in polarized Madin-Darby canine kidney cells. Intriguingly, after Src activation or hepatocyte growth factor (HGF) treatment, Numb decouples from E-cad and Par3 and associates preferably with aPKC–Par6. Binding of Numb to aPKC is necessary for sequestering the latter in the cytosol during HGF-induced EMT. Knockdown of Numb by small hairpin RNA caused a basolateral-to-apicolateral translocation of E-cad and β-catenin accompanied by elevated actin polymerization, accumulation of Par3 and aPKC in the nucleus, an enhanced sensitivity to HGF-induced cell scattering, a decrease in cell–cell adhesion, and an increase in cell migration. Our work identifies Numb as an important regulator of epithelial polarity and cell–cell adhesion and a sensor of HGF signalling or Src activity during EMT

A hybrid constructed wetland for organic-material and nutrient removal from sewage: Process performance and multi-kinetic models

© 2018 Elsevier Ltd A pilot-scale hybrid constructed wetland with vertical flow and horizontal flow in series was constructed and used to investigate organic material and nutrient removal rate constants for wastewater treatment and establish a practical predictive model for use. For this purpose, the performance of multiple parameters was statistically evaluated during the process and predictive models were suggested. The measurement of the kinetic rate constant was based on the use of the first-order derivation and Monod kinetic derivation (Monod) paired with a plug flow reactor (PFR) and a continuously stirred tank reactor (CSTR). Both the Lindeman, Merenda, and Gold (LMG) analysis and Bayesian model averaging (BMA) method were employed for identifying the relative importance of variables and their optimal multiple regression (MR). The results showed that the first-order–PFR (M2) model did not fit the data (P > 0.05, and R2 0.5). The pollutant removal rates in the case of M1 were 0.19 m/d (CODCr) and those for M3 were 25.2 g/m2∙d for CODCr and 2.63 g/m2∙d for NH4-N. By applying a multi-variable linear regression method, the optimal empirical models were established for predicting the final effluent concentration of five days' biochemical oxygen demand (BOD5) and NH4-N. In general, the hydraulic loading rate was considered an important variable having a high value of relative importance, which appeared in all the optimal predictive models

Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle

© 2013 Rakobowchuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP

Leveraging icebreaking tasks to facilitate uptake of voice communication in multiplayer games

Voice Communication (VC) is widely employed by developers as an essential component of online games. Typically, it is assumed that communications through this mechanism will be helpful and enjoyable, but existing literature suggests that the entry into VC can be problematic. In this paper, we present a study that attempts to mitigate player discomfort when first engaging with VC with strangers, through the use of traditional icebreaking tasks. We integrate these into the game RET, an online cooperative first person shooter which requires effective communication for players to succeed. An online user study with 18 participants suggests that icebreaking tasks can contribute to a positive VC experience, but their inclusion also creates further issues to be considered for successful integration