julilili42/papers huggingface dataset:
Exploiting Transient Protein States for the Design of Small-Molecule Stabilizers of Mutant p53
2015-12-01

The destabilizing p53 cancer mutation Y220C creates an extended crevice on the surface of the protein that can be targeted by small-molecule stabilizers. Here, we identify different classes of small molecules that bind to this crevice and determine their binding modes by X-ray crystallography. These structures reveal two major conformational states of the pocket and a cryptic, transiently open hydrophobic subpocket that is modulated by Cys220. In one instance, specifically targeting this transient protein state by a pyrrole moiety resulted in a 40-fold increase in binding affinity. Molecular dynamics simulations showed that both open and closed states of this subsite were populated at comparable frequencies along the trajectories. Our data extend the framework for the design of high-affinity Y220C mutant binders for use in personalized anticancer therapy and, more generally, highlight the importance of implementing protein dynamics and hydration patterns in the drug-discovery process.
Electronically Excited States of Higher Acenes up to Nonacene: A Density Functional Theory/Multireference Configuration Interaction Study
2015-12-01

While the optical spectra of the acene series up to pentacene provide textbook examples for the annulation principle, the spectra of the larger members are much less understood. The present work provides an investigation of the optically allowed excited states of the acene series from pentacene to nonacene, the largest acene observed experimentally, using the density functional based multireference configuration method (DFT/MRCI). For this purpose, the ten lowest energy states of the B2u and B3u irreducible representations were computed. In agreement with previous computational investigations, the electronic wave functions of the acenes acquire significant multireference character with increasing acene size. The HOMO → LUMO excitation is the major contributor to the (1)La state (p band, B2u) also for the larger acenes. The oscillator strength decreases with increasing length. The (1)Lb state (α band, B3u), so far difficult to assign for the larger acenes due to overlap with photoprecursor bands, becomes almost insensitive to acene length. The (1)Bb state (β band, B3u) also moves only moderately to lower energy with increasing acene size. Excited states of B3u symmetry that formally result from double excitations involving HOMO, HOMO-1, LUMO, and LUMO+1 decrease in energy much faster with system size. One of them (D1) has very small oscillator strength but becomes almost isoenergetic with the (1)La state for nonacene. The other (D2) also has low oscillator strength as long as it is higher in energy than (1)Bb. Once it is lower in energy than the (1)Bb state, both states interact strongly resulting in two states with large oscillator strengths. The emergence of two strongly absorbing states is in agreement with experimental observations. The DFT/MRCI computations reproduce experimental excitation energies very well for pentacene and hexacene (within 0.1 eV). For the larger acenes deviations are larger (up to 0.2 eV), but qualitative agreement is observed.
Ultraviolet Keratitis: From the Pathophysiological Basis to Prevention and Clinical Management
2015-12-01

Ultraviolet keratitis is caused by the toxic effects of acute high-dose ultraviolet radiation (UVR) reflecting the sensitivity of the ocular surface to photochemical injury. The clinical syndrome presents with ocular pain, tearing, conjunctival chemosis, blepharospasm, and deterioration of vision typically several hours after exposure, lasting up to 3 days. Mountaineers, skiers, and beach recreationalists are particularly at risk to suffer from ultraviolet (UV) keratitis as the reflectivity of UVR in these environments is extremely high. The aim of this review is to raise awareness about the potential of UV damage on the eye with an emphasis on UV keratitis, to highlight the pathophysiological basis of corneal phototoxicity, and to provide practical guidance for the prevention and clinical management of UV keratitis commonly known as snow blindness.
Impulsivity-focused group intervention to reduce binge eating episodes in patients with binge eating disorder: study protocol of the randomised controlled IMPULS trial
2015-12-01

Introduction The core symptom of binge eating disorder (BED) is recurrent binge eating that is accompanied by a sense of loss of control. BED is frequently associated with obesity, one of the main public health challenges today. Experimental studies deliver evidence that general trait impulsivity and disorder-specific food-related impulsivity constitute risk factors for BED. Cognitive-behavioural treatment (CBT) is deemed to be the most effective intervention concerning BED. We developed a group intervention based on CBT and especially focusing on impulsivity. We hypothesise that such an impulsivity-focused group intervention is able to increase control over impulsive eating behaviour, that is, reduce binge eating episodes, further eating pathology and impulsivity. Body weight might also be influenced in the long term. Methods and analysis The present randomised controlled trial investigates the feasibility, acceptance and efficacy of this impulsivity-focused group intervention in patients with BED. We compare 39 patients with BED in the experimental group to 39 patients with BED in the control group at three appointments: before and after the group intervention and in a 3-month follow-up. Patients with BED in the experimental group receive 8 weekly sessions of the impulsivity-focused group intervention with 5-6 patients per group. Patients with BED in the control group receive no group intervention. The primary outcome is the binge eating frequency over the past 4 weeks. Secondary outcomes comprise further eating pathology, general impulsivity and food-related impulsivity assessed by eye tracking methodology, and body weight. Additionally, we assess binge eating and other impulsive behaviour weekly in process analyses during the time period of the group intervention. Ethics and dissemination This study has been approved by the ethics committee of the medical faculty of Eberhard Karls University Tübingen and the University Hospital Tübingen. Data are monitored by the Centre of Clinical Studies, University Hospital Tübingen. Trial registration number German Clinical Trials Register, DRKS00007689, 14/01/2015, version from 11/06/2015, pre-results.
The Perception of Cooperativeness Without Any Visual or Auditory Communication
2015-12-01

Perceiving social information such as the cooperativeness of another person is an important part of human interaction. But can people perceive the cooperativeness of others even without any visual or auditory information? In a novel experimental setup, we connected two people with a rope and made them accomplish a point-collecting task together while they could not see or hear each other. We observed a consistently emerging turn-taking behavior in the interactions and installed a confederate in a subsequent experiment who either minimized or maximized this behavior. Participants experienced this only through the haptic force-feedback of the rope and made evaluations about the confederate after each interaction. We found that perception of cooperativeness was significantly affected only by the manipulation of this turn-taking behavior. Gender- and size-related judgments also significantly differed. Our results suggest that people can perceive social information such as the cooperativeness of other people even in situations where possibilities for communication are minimal.
Orbital and epicyclic frequencies around neutron and strange stars in $$R^2$$ R 2 gravity
2015-12-01

\\n According to various models, the orbital and the epicyclic frequencies of particles moving on a circular orbit around compact objects are related to the quasi-periodic oscillations observed in the X-ray flux of some pulsars or black hole candidates. It is expected that they originate from the inner edge of the accretion discs, deep into the gravitational field of the compact objects. Considering the planned new generation X-ray timing observatories with large collective areas, the quasi-periodic oscillations might be an excellent tool for testing gravity in strong field regime and, respectively, alternative gravitational theories. We examine the orbital and the epicyclic frequencies of a particle moving on a circular orbit around neutron or strange stars in gravity. The case of slow rotation is considered too. The gravity results are compared to the general relativistic case. We comment on the deviations from general relativity, as well as the deviations due to rotation in both theories.\\n
A Putative Association of COMT Val(108/158)Met with Impulsivity in Binge Eating Disorder
2015-12-01

Abstract Objective This study aims to investigate the influence of the COMT Val(108/158)Met polymorphism on trait and behavioural impulsivity in binge eating disorder (BED). COMT Val(108/158)Met has been related to impulsivity in previous studies, but so far no study has investigated the role of this polymorphism in the context of BED. Method Impulsivity was assessed via a questionnaire (trait) and on a behavioural level via the antisaccade task in a sample of 69 participants classified into one out of three age‐matched groups: (1) obese individuals with BED according to DMS‐IV (BED+); (2) obese individuals without BED, matched with the BED+ sample according to body weight (OBED–); and (3) normal‐weight healthy controls (NWC). The COMT Val(108/158)Met polymorphism was genotyped in all samples. Results As expected, the BED+ sample showed higher trait and behavioural impulsivity. Furthermore, within the BED+ group, COMT Met/Met homozygous individuals showed stronger deficits in inhibitory control. Discussion COMT Met/Met homozygous individuals with BED might represent a specific group in the BED spectrum, which shows a higher behavioural impulsivity. The association between COMT Val(108/158)Met with inhibitory control should be interpreted with caution because of the small sample size. Larger replication studies are needed to further elucidate the role of the COMT Val(108/158)Met polymorphism in the regulation of disordered eating behaviour.
Individual Uncertainty and the Uncertainty of Science: The Impact of Perceived Conflict and General Self-Efficacy on the Perception of Tentativeness and Credibility of Scientific Information
2015-12-01

We examined in two empirical studies how situational and personal aspects of uncertainty influence laypeople's understanding of the uncertainty of scientific information, with focus on the detection of tentativeness and perception of scientific credibility. In the first study (N = 48), we investigated the impact of a perceived conflict due to contradicting information as a situational, text-inherent aspect of uncertainty. The aim of the second study (N = 61) was to explore the role of general self-efficacy as an intra-personal uncertainty factor. In Study 1, participants read one of two versions of an introductory text in a between-group design. This text provided them with an overview about the neurosurgical procedure of deep brain stimulation (DBS). The text expressed a positive attitude toward DBS in one experimental condition or focused on the negative aspects of this method in the other condition. Then participants in both conditions read the same text that dealt with a study about DBS as experimental treatment in a small sample of patients with major depression. Perceived conflict between the two texts was found to increase the perception of tentativeness and to decrease the perception of scientific credibility, implicating that text-inherent aspects have significant effects on critical appraisal. The results of Study 2 demonstrated that participants with higher general self-efficacy detected the tentativeness to a lesser degree and assumed a higher level of scientific credibility, indicating a more naïve understanding of scientific information. This appears to be contradictory to large parts of previous findings that showed positive effects of high self-efficacy on learning. Both studies showed that perceived tentativeness and perceived scientific credibility of medical information contradicted each other. We conclude that there is a need for supporting laypeople in understanding the uncertainty of scientific information and that scientific writers should consider how to present scientific results when compiling pertinent texts.
Level dependence of the nonlinear-distortion component of distortion-product otoacoustic emissions in humans
2015-12-01

Distortion-product otoacoustic emissions (DPOAEs) emerge when presenting two primary tones with different frequencies f1 and f2 to the cochlea and are commonly used in diagnosis and research to evaluate the functional state of the cochlea. Optimal primary-tone stimulus levels accounting for the different level dependencies of the traveling-wave amplitudes of the two primary tones near the f2-tonotopic place on the basilar membrane are often used to maximize DPOAE amplitudes. However, parameters defining the optimal levels can be affected by wave interference between the nonlinear-distortion and coherent-reflection components of the DPOAE. Here, the components were separated in the time domain using a pulsed stimulus paradigm and optimal levels determined. Based on the amplitude dependence of the nonlinear-distortion components on primary-tone stimulus levels, level parameters yielding maximum DPOAE amplitudes were derived for six normal-hearing adults and compared to data recorded with continuous two-tone stimulation. The level parameters resulting from analysis of the nonlinear-distortion components show dependence on stimulus frequency and small standard deviations. DPOAE input/output functions derived for optimal levels exhibit larger slopes, wider dynamic range and less variability across subjects than those derived for conventional stimulus and analysis conditions, potentially increasing their reliability and sensitivity for assessing cochlea function.
Improving Indoor Mobility of the Visually Impaired with Depth-Based Spatial Sound
2015-12-01

We present a novel system to help visually impaired people to move efficiently and safely in indoor environments by mapping input from a depth camera to spatially localized auditory cues. We propose a set of context-specific cues which are suitable for use in systems that provide minimal audio feedback and hence reduce masking of natural sounds compared to the audio provided by general-purpose sense substitution devices. Using simple but effective heuristics for detecting the floor and the side walls, we propose auditory cues that encode information about the distances to walls, obstacles, the orientation of the corridor or room, and openings into corridors or rooms. But the key to our system is the use of a spatial sound engine that localizes the generated sounds in 3D. We evaluate our system, comparing with MeloSee. Our preliminary pilot study with ten blindfolded participants suggests that our system was more helpful for spotting smaller obstacles on the floor, though neither system had a significant edge in terms of walking speed or safety.
Rapid thyroid nodule growth is not a marker for well-differentiated thyroid cancer
2015-12-01

Thyroid nodule growth alone and especially a rapid growth pattern during follow-up for thyroid nodular disease is not a marker for well-differentiated thyroid cancer and should not be used as a stand-alone argument for thyroid surgery.
Learning from brain control: clinical application of brain–computer interfaces
2015-12-01

Abstract Brain-computer interfaces (BCI) use neuroelectric and metabolic brain activity to activate peripheral devices and computers without mediation of the motor system. In order to activate the BCI patients have to learn a certain amount of brain control. Self-regulation of brain activity was found to follow the principles of skill learning and instrumental conditioning. This review focuses on the clinical application of brain-computer interfaces in paralyzed patients with locked-in syndrome and completely locked-in syndrome (CLIS). It was shown that electroencephalogram (EEG)-based brain-computer interfaces allow selection of letters and words in a computer menu with different types of EEG signals. However, in patients with CLIS without any muscular control, particularly of eye movements, classical EEG-based brain-computer interfaces were not successful. Even after implantation of electrodes in the human brain, CLIS patients were unable to communicate. We developed a theoretical model explaining this fundamental deficit in instrumental learning of brain control and voluntary communication: patients in complete paralysis extinguish goal-directed responseoriented thinking and intentions. Therefore, a reflexive classical conditioning procedure was developed and metabolic brain signals measured with near infrared spectroscopy were used in CLIS patients to answer simple questions with a “yes” or “no”-brain response. The data collected so far are promising and show that for the first time CLIS patients communicate with such a BCI system using metabolic brain signals and simple reflexive learning tasks. Finally, brain machine interfaces and rehabilitation in chronic stroke are described demonstrating in chronic stroke patients without any residual upper limb movement a surprising recovery of motor function on the motor level as well as on the brain level. After extensive combined BCI training with behaviorally oriented physiotherapy, significant improvement in motor function was shown in this previously intractable paralysis. In conclusion, clinical application of brain machine interfaces in well-defined and circumscribed neurological disorders have demonstrated surprisingly positive effects. The application of BCIs to psychiatric and clinical-psychological problems, however, at present did not result in substantial improvement of complex behavioral disorders.
“Enemies at the Gate:” The West German Greens and Their Arrival at the Bundestag—Between Old Ideals and New Challenges
2015-12-01

The West German Green Party's 1983 entrance into the Bundestag marked a major break, both in the history of this young political force and the parliamentary system of the Bonn Republic. The Greens had been founded in opposition to the guiding principles of the West German postwar consensus and conceived of themselves as an “anti-parliamentary party.” Although they had gained parliamentary experience in some regional chambers, their entrance onto the national parliamentary stage juxtaposed old ideals and new challenges—for the Greens themselves as well as for German political culture. Taking this singular historic moment as a starting point, this article summarizes the formation of the Greens in the context of the changing political and ideological landscape of the 1970s. It also contrasts the party's formation with the transformations in terms of program and personnel that it undertook during the 1980s. The focus lies less on the specific activities of the green parliamentary group than on the broader developments in green politics and thinking.
Superpixel segmentation based gradient maps on RGB-D dataset
2015-12-01

Superpixels aim to group homogenous pixels by a series of characteristics in an image. They decimate redundancy that may be utilized later by more computationally expensive algorithms. The most popular algorithms obtain superpixels based on an energy function on a graph. However, these graph-based methods have a high computational time consumption. This study presents a fast and high quality over-segmentation method by a watershed transform based on computing the dissimilarity of pixels among RGB(D) cues and gradient maps. Specifically, we first capture a gradient map based on an image to enhance and explain directional variations in the image scene. A distance function then measures the similarity among adjacent pixels, which is calculated according to RGB(D) values. A fast marker-controlled watershed (MCW) algorithm traverses the entire image based on the distance function. Finally, we acquire all watersheds consisting of superpixel contours. Experimental results compare state-of-the-art algorithms and highlight the effectiveness of the proposed method. As an application, the proposed superpixel algorithm can be used in applications aiming for real-time, like mobile robot saliency detection and segmentation.
“Astrophel” and Spenser’s 1595 Quarto
2015-12-01

Edmund Spenser’s “Astrophel” tends to be regarded as a minor poem that is inadequate as an elegy for Sidney and is further overshadowed by “Colin Clouts Come Home Againe.” Originally, both poems were published in the same volume in 1595, along with works by four other poets. Nonetheless, modern readings of “Astrophel” have been substantially shaped by modern editing practice, which has separated it from the rest of the volume’s contents. This article examines the original published context of “Astrophel” in detail and argues that all of the contents of the 1595 quarto — including those not written by Spenser himself — were intended to (and should) be read as a unit.
Piece Rates vs. Contests in Product Market Competition
2015-12-01

Abstract We study product market competition between firm owners (principals) where workers (agents) decide on their efforts and, hence, on output levels. Various worker compensation schemes are compared: a piece-rate compensation as a benchmark when workers’ output performance is verifiable, and different contest-based compensation schemes with fixed and variable prizes when it is only verifiable who the best performing worker is. Without rivalry between firms, all considered compensation schemes lead to the same outcome. In case of product market competition, however, a contest-based compensation scheme with revenue-dependent prizes leads to more employment, more production, and lower firm profits. The reason is that strategic interaction between the firm owners leads to an aggressive overinvestment in worker employment as well as in the revenue shares offered to the contest winners.
Schelling und der Selbstrepräsentationalismus über phänomenales Bewusstsein
2015-12-01

Abstract This paper explores Schelling’s theory of phenomenal consciousness in the System of Transcendental Idealism. It is shown that Schelling’s description and explanation of phenomenal consciousness is in accord with contemporary self-representationalist accounts of phenomenal consciousness. Thus, it is argued that Schelling develops a self-representationalist approach of phenomenal consciousness. Furthermore, it is demonstrated on the basis of Schelling’s account that analytic self-representationalism fails to completely explain phenomenal consciousness. Finally, however, a fundamental critique of Schelling’s theory of phenomenal consciousness is presented. Thus the central theses of the paper are, on the one hand, that Schelling is of systematic importance for contemporary debates, on the other hand, that his account is not convincing.
The Myth of Profit-Shifting Trade Policies
2015-12-01

Since Dixit (1984), it is well accepted that a home country's best policy is &#13;\\nto ban imports in an oligopolistic market if the resulting monopoly has a cost advantage over imports. &#13;\\nThis note (i) provides a formal proof and (ii) extends this result to symmetric firms. When domestic &#13;\\ninstruments are available, the optimal policy in a non-cooperative game is to subsidize local production &#13;\\nsuch that it completely replaces imports. This policy is also globally first-best.