1,353 research outputs found
Priming Effects on Commitment to Help and on Real Helping Behavior
Years of research on bystander apathy have demonstrated that the physical presence of
others can reduce the tendency to help individuals needing assistance. Recent research
on the implicit bystander effect has suggested that simply imagining the presence of
others can lead to less helping behavior on a subsequent unrelated task. The present
study was designed to contribute to previous findings on the implicit bystander effect
by demonstrating these effects on commitment to help and on real helping behavior,
rather than simply on intentions to help. Studies 1a and 1b demonstrate that merely
priming participants with the construct of being in a group at Time 1 created significantly
less commitment to future helping on a subsequent task at Time 2. Study 2 aimed
to extend this effect to behavioral measures and verified that participants exposed to a
group prime helped less than those who were exposed to a single-person prime. The
implications of these findings for the literature on the bystander effect are discussed
A 1-acetamido derivative of 6-epi-valienamine: an inhibitor of a diverse group of β-N-acetylglucosaminidases
The synthesis of an analogue of 6-epi-valienamine bearing an acetamido group and its characterisation as an inhibitor of β-N-acetylglucosaminidases are described. The compound is a good inhibitor of both human O-GlcNAcase and human β-hexosaminidase, as well as two bacterial β-N-acetylglucosaminidases. A 3-D structure of the complex of Bacteroides thetaiotaomicron BtGH84 with the inhibitor shows the unsaturated ring is surprisingly distorted away from its favoured solution phase conformation and reveals potential for improved inhibitor potency
A Minimal Model of Signaling Network Elucidates Cell-to-Cell Stochastic Variability in Apoptosis
Signaling networks are designed to sense an environmental stimulus and adapt
to it. We propose and study a minimal model of signaling network that can sense
and respond to external stimuli of varying strength in an adaptive manner. The
structure of this minimal network is derived based on some simple assumptions
on its differential response to external stimuli. We employ stochastic
differential equations and probability distributions obtained from stochastic
simulations to characterize differential signaling response in our minimal
network model. We show that the proposed minimal signaling network displays two
distinct types of response as the strength of the stimulus is decreased. The
signaling network has a deterministic part that undergoes rapid activation by a
strong stimulus in which case cell-to-cell fluctuations can be ignored. As the
strength of the stimulus decreases, the stochastic part of the network begins
dominating the signaling response where slow activation is observed with
characteristic large cell-to-cell stochastic variability. Interestingly, this
proposed stochastic signaling network can capture some of the essential
signaling behaviors of a complex apoptotic cell death signaling network that
has been studied through experiments and large-scale computer simulations. Thus
we claim that the proposed signaling network is an appropriate minimal model of
apoptosis signaling. Elucidating the fundamental design principles of complex
cellular signaling pathways such as apoptosis signaling remains a challenging
task. We demonstrate how our proposed minimal model can help elucidate the
effect of a specific apoptotic inhibitor Bcl-2 on apoptotic signaling in a
cell-type independent manner. We also discuss the implications of our study in
elucidating the adaptive strategy of cell death signaling pathways.Comment: 9 pages, 6 figure
Visualizing Poiseuille flow of hydrodynamic electrons
Hydrodynamics is a general description for the flow of a fluid, and is
expected to hold even for fundamental particles such as electrons when
inter-particle interactions dominate. While various aspects of electron
hydrodynamics were revealed in recent experiments, the fundamental spatial
structure of hydrodynamic electrons, the Poiseuille flow profile, has remained
elusive. In this work, we provide the first real-space imaging of Poiseuille
flow of an electronic fluid, as well as visualization of its evolution from
ballistic flow. Utilizing a scanning nanotube single electron transistor, we
image the Hall voltage of electronic flow through channels of high-mobility
graphene. We find that the profile of the Hall field across the channel is a
key physical quantity for distinguishing ballistic from hydrodynamic flow. We
image the transition from flat, ballistic field profiles at low temperature
into parabolic field profiles at elevated temperatures, which is the hallmark
of Poiseuille flow. The curvature of the imaged profiles is qualitatively
reproduced by Boltzmann calculations, which allow us to create a 'phase
diagram' that characterizes the electron flow regimes. Our results provide
long-sought, direct confirmation of Poiseuille flow in the solid state, and
enable a new approach for exploring the rich physics of interacting electrons
in real space
Time-dependent rate of multicomponent dark matter: reproducing the DAMA/LIBRA phase-2 results
The current paradigm for dark matter direct detection is to assume that the dark sector is solely composed of a single particle species. In this short paper, we make the observation that dark matter comprising both a light and a heavy component that modulate out of phase leads to interesting phenomenology in annual modulation experiments. For an illustrative example, we use the recently released DAMA/LIBRA phase-2 results with a lower energy threshold. Immediately after, it was argued that a one-component spin-independent dark matter explanation of the observed annual modulation is strongly disfavored or excluded unless isospin-violating couplings are invoked. We show that a simple two-component extension can reproduce the observed spectrum without the need to invoke fine-tuned couplings. Using the publicly available DAMA/LIBRA data, we perform a fit of the DAMA/LIBRA energy spectrum of the annual modulation amplitude to a scenario with two dark matter components. We also take into account how gravitational focusing affects the phases of the light and a heavy components differently, which leads to nontrivial effects in the total time-dependent rate. Our results show that there exists a unique solution in agreement with the data in the simplest case of isospin-conserving couplings with equal cross sections. The distinctive features found in this work are crucial for a dark matter interpretation of any observed annual modulation.Juan Herrero-Garcia, Andre Scaffidi, Martin White and Anthony G. William
Global trends in training and credentialing guidelines for gastrointestinal endoscopy: a systematic review
Background and study aims Credentialing, the process through which an institution assesses and validates an endoscopist’s qualifications to independently perform a procedure, can vary by region and country. Little is known about these inter-societal and geographic differences. We aimed to systematically characterize credentialing recommendations and requirements worldwide.
Methods We conducted a systematic review of credentialing practices among gastrointestinal and endoscopy societies worldwide. An electronic search as well as hand-search of World Endoscopy Organization members’ websites was performed for credentialing documents. Abstracts were screened in duplicate and independently. Data were collected on procedures included in each document (e. g. colonoscopy, ERCP) and types of credentialing statements (procedural volume, key performance indicators (KPIs), and competency assessments). The primary objective was to qualitatively describe and compare the available credentialing recommendations and requirements from the included studies. Descriptive statistics were used to summarize data when appropriate.
Results We screened 653 records and included 20 credentialing documents from 12 societies. Guidelines most commonly included credentialing statements for colonoscopy, esophagogastroduodenoscopy (EGD), and ERCP. For colonoscopy, minimum procedural volumes ranged from 150 to 275 and adenoma detection rate (ADR) from 20 % to 30%. For EGD, minimum procedural volumes ranged from 130 to 1000, and duodenal intubation rate of 95 % to 100%. For ERCP, minimum procedural volumes ranged from 100 to 300 with selective duct cannulation success rate of 80 % to 90 %. Guidelines also reported on flexible sigmoidoscopy, capsule endoscopy, and endoscopic ultrasound.
Conclusions While some metrics such as ADR were relatively consistent among societies, there was substantial variation among societies with respect to procedural volume and KPI statements
Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities
E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities
Modulation of the CD95-Induced Apoptosis: The Role of CD95 N-Glycosylation
Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems
Bending modes, elastic constants and mechanical stability of graphitic systems
The thermodynamic and mechanical properties of graphitic systems are strongly
dependent on the shear elastic constant C44. Using state-of-the-art density
functional calculations, we provide the first complete determination of their
elastic constants and exfoliation energies. We show that stacking
misorientations lead to a severe lowering of C44 of at least one order of
magnitude. The lower exfoliation energy and the lower C44 (more bending modes)
suggest that flakes with random stacking should be easier to exfoliate than the
ones with perfect or rhombohedral stacking. We also predict ultralow friction
behaviour in turbostratic graphitic systems.Comment: 7 pages, 6 figure
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