Miracle-dz/UniFAR-FTUs huggingface dataset:
Design of a Genetically Stable High Fidelity Coxsackievirus B3 Polymerase That Attenuates Virus Growth in Vivo*

Positive strand RNA viruses replicate via a virally encoded RNA-dependent RNA polymerase (RdRP) that uses a unique palm domain active site closure mechanism to establish the canonical two-metal geometry needed for catalysis. This mechanism allows these viruses to evolutionarily fine-tune their replication fidelity to create an appropriate distribution of genetic variants known as a quasispecies. Prior work has shown that mutations in conserved motif A drastically alter RdRP fidelity, which can be either increased or decreased depending on the viral polymerase background. In the work presented here, we extend these studies to motif D, a region that forms the outer edge of the NTP entry channel where it may act as a nucleotide sensor to trigger active site closure. Crystallography, stopped-flow kinetics, quench-flow reactions, and infectious virus studies were used to characterize 15 engineered mutations in coxsackievirus B3 polymerase. Mutations that interfere with the transport of the metal A Mg2+ ion into the active site had only minor effects on RdRP function, but the stacking interaction between Phe364 and Pro357, which is absolutely conserved in enteroviral polymerases, was found to be critical for processive elongation and virus growth. Mutating Phe364 to tryptophan resulted in a genetically stable high fidelity virus variant with significantly reduced pathogenesis in mice. The data further illustrate the importance of the palm domain movement for RdRP active site closure and demonstrate that protein engineering can be used to alter viral polymerase function and attenuate virus growth and pathogenesis.
The Inhibitor of Death Receptor Signaling, Flice-Inhibitory Protein Defines a New Class of Tumor Progression Factors

Death receptor–mediated apoptosis can be modulated by several antiapoptotic proteins, such as the FLICE (FADD [Fas-associated death domain]-like IL-1β–converting enzyme)-inhibitory proteins (FLIPs). The FLIP family includes both cellular and viral members. The Kaposi's sarcoma–associated herpesvirus protein (KSHV)-FLIP is expressed by human herpesvirus 8 (HHV-8), which is associated with malignancies such as Kaposi's sarcoma and certain lymphomas. In this paper, we demonstrate that KSHV-FLIP protects cells from Fas-mediated apoptosis by inhibiting caspase activation and permits clonal growth in the presence of death stimuli in vitro. Furthermore, we show that KSHV-FLIP can act as a tumor progression factor by promoting tumor establishment and growth in vivo. When injected into immunocompetent recipient mouse strains, murine B lymphoma cells (A20) transduced with KSHV-FLIP rapidly develop into aggressive tumors showing a high rate of survival and growth. The tumor-progressive activity of KSHV-FLIP is mediated by prevention of death receptor–induced apoptosis triggered by conventional T cells. Consequently, inhibitors of death receptor signaling can be regarded as a new class of tumor progression factors, and HHV-8–associated tumors may represent naturally occurring examples of the tumorigenic effect of such inhibitors.
Inside-out or outside-in: the topology of reionization in the photon-starved regime suggested by Lyα forest data

We use a set of seminumerical simulations based on the Zel'dovich approximation, the friends-of-friends algorithm and excursion set formalism to generate reionization maps of high dynamic range with a range of assumptions regarding the distribution and luminosity of ionizing sources and the spatial distribution of sinks for the ionizing radiation. We find that ignoring the inhomogeneous spatial distribution of regions of high gas density where recombinations are important - as is often done in studies of this kind - can lead to misleading conclusions regarding the topology of reionization, especially if reionization occurs in the photon-starved regime suggested by Lya forest data. The inhomogeneous spatial distribution of recombinations significantly reduces the mean-free path of ionizing photons and the typical size of coherently ionized regions. Reionization proceeds then much more as an outside-in process. Low-density regions far from ionizing sources become ionized before regions of high gas density not hosting sources of ionizing radiation. The spatial distribution of sinks of ionization radiation also significantly affects the shape and amplitude of the power spectrum of fluctuations of 21 cm emission. The slope of the 21 cm power spectrum as measured by upcoming 21 cm experiments should be able to distinguish to what extent the topology of reionization proceeds outside-in or inside-out, while the evolution of the amplitude of the power spectrum with increasing ionized mass fraction should be sensitive to the spatial distribution and the luminosity of ionizing sources.
Towards Automatized Studioless Audio Recording : A Smart Lecture Recorder

Webcasting and recording of university lectures has become common practice. While much effort has been put into the development and improvement of formats and codecs, few computer scientist have studied how to improve the quality of the signal before it is digitized. A Lecture hall or a seminar room is not a professional recording studio. Good quality recordings require full-time technicians to setup and monitor the signals. Although often advertised, most current systems cannot yield professional quality recordings just by plugging a microphone into a sound card and starting the lecture. This paper describes a lecture broadcasting system that eases studioless voice recording by automatizing several tasks usually handled by professional audio technicians. The software described here measures the quality of the sound hardware used, monitors possible hardware malfunctions, prevents common user mistakes, and provides gain control and filter mechanisms.
Designing emergency management services by ontology driven social simulation ∗

There are numerous attempts to assess emergency plans by simulations, and excellent contributions have been proposed. Simulations have allowed emergency committees and emergency experts to improve the performance and efficiency of many emergency plans while decreasing the limitations of regular drills. However, there is no “most complete” tool, and most of the time, it is not possible to reuse and combine components of different frameworks. As a result, without a true interest in sharing and interconnecting works, researchers in this domain are constantly damned to reinvent the wheel. To improve this situation, this paper proposes a general model for designing emergency management services in indoor environments. The core of this model is EinSim, an ontology which gathers the most relevant concepts for the design of these services and which, in the spirit of the Liked Data methods, links a number of external and well-referenced data. The paper supports the hypothesis that semantic web technologies are a powerful tool to reuse, extend, and combine different simulation components. Moreover, the use of semantic reasoners allows providing developers with automatic verification in the emergency management service development.
Parity and disparity among three measures of fear of crime: A research note

Research on fear of crime often concerns problems associated with measuring fear of crime. Most of the literature in this area critiques “global measures,” which are the most commonly used, and suggests movement to more specific measures of fear of crime. Although much has been said about the use of alternative measures of fear, seldom has research provided comparative analyses of the alternative measures. Using a conceptual model based on previous research, the present study illustrates the differences among findings using three measures of fear of crime: global fear, fear of property crime, and fear of violent crime. This is achieved by employing each of the three measures of fear as the dependent variable in identical models. Comparing the results, the parity and disparity of these measures are demonstrated. The results suggest that conflicting findings from previous research may be a consequence of the types of measures used in the analyses. Thus, it is theoretically important to understand what dimen.
Licklider Transmission Protocol - Security Extensions

The Licklider Transmission Protocol (LTP), is intended to serve as a reliable convergence layer over single hop deep-space RF links. LTP does ARQ of data transmissions by soliciting selective-acknowledgment reception reports. It is stateful and has no negotiation or handshakes. LTP is designed to provide retransmission-based reliability over links characterized by extremely long message round- trip times (RTTs) and/or frequent interruptions in connectivity. Since communication across interplanetary space is the most prominent example of this sort of environment, LTP is principally aimed at supporting "long- haul" reliable transmission in interplanetary space, but has applications in other environments as well. This document describes security extensions to LTP, and is part of a series of related documents describing LTP. Other documents in this series cover the motivation for LTP and the main protocol specification. We recommend reading all the documents in the series before writing code based on this document. This document is a product of the Delay Tolerant Networking Research Group and has been reviewed by that group. No objections to its publication as an RFC were raised.
Restoring large-scale brain networks in PTSD and related disorders: a proposal for neuroscientifically-informed treatment interventions

Background Three intrinsic connectivity networks in the brain, namely the central executive, salience, and default mode networks, have been identified as crucial to the understanding of higher cognitive functioning, and the functioning of these networks has been suggested to be impaired in psychopathology, including posttraumatic stress disorder (PTSD). Objective 1) To describe three main large-scale networks of the human brain; 2) to discuss the functioning of these neural networks in PTSD and related symptoms; and 3) to offer hypotheses for neuroscientifically-informed interventions based on treating the abnormalities observed in these neural networks in PTSD and related disorders. Method Literature relevant to this commentary was reviewed. Results Increasing evidence for altered functioning of the central executive, salience, and default mode networks in PTSD has been demonstrated. We suggest that each network is associated with specific clinical symptoms observed in PTSD, including cognitive dysfunction (central executive network), increased and decreased arousal/interoception (salience network), and an altered sense of self (default mode network). Specific testable neuroscientifically-informed treatments aimed to restore each of these neural networks and related clinical dysfunction are proposed. Conclusions Neuroscientifically-informed treatment interventions will be essential to future research agendas aimed at targeting specific PTSD and related symptoms.
A multi-resolution approach for adapting close character interaction

Synthesizing close interactions such as dancing and fighting between characters is a challenging problem in computer animation. While encouraging results are presented in [Ho et al. 2010], the high computation cost makes the method unsuitable for interactive motion editing and synthesis. In this paper, we propose an efficient multiresolution approach in the temporal domain for editing and adapting close character interactions based on the Interaction Mesh framework. In particular, we divide the original large spacetime optimization problem into multiple smaller problems such that the user can observe the adapted motion while playing-back the movements during run-time. Our approach is highly parallelizable, and achieves high performance by making use of multi-core architectures. The method can be applied to a wide range of applications including motion editing systems for animators and motion retargeting systems for humanoid robots.
Palliative Medicine Consultation Reduces Length of Stay, Improves Symptom Management, and Clarifies Advance Directives in the Geriatric Trauma Population

The impact of Palliative Medicine Consultation (PMC) on geriatric trauma patients' outcomes was evaluated. It was hypothesized that patients with PMC would have a shorter length of stay. Patients aged 65 years or older and admitted to trauma services were analyzed. Patients with a PMC were more likely to have a documented advance directive discussion (P < .001) and a code status update (P < .001). Length of stay was reduced for patients with a PMC on or before trauma day 2 compared to those with a PMC after trauma day 2. Palliative Medicine should be consulted early into a geriatric patient's hospital stay.
Multimodal Information Fusion for Semantic Video Analysis

Multimedia data by its very nature contains multimodal information in it. For a successful analysis of multimedia content, all available multimodal information should be utilized. Additionally, since concepts can contain valuable cues about other concepts, concept interaction is a crucial source of multimedia information and helps to increase the fusion performance. The aim of this study is to show that integrating existing modalities along with the concept interactions can yield a better performance in detecting semantic concepts. Therefore, in this paper, the authors present a multimodal fusion approach that integrates semantic information obtained from various modalities along with additional semantic cues. The experiments conducted on TRECVID 2007 and CCV Database datasets validates the superiority of such combination over best single modality and alternative modality combinations. The results show that the proposed fusion approach provides 16.7% relative performance gain on TRECVID dataset and 47.7% relative performance improvement on CCV database over the results of best unimodal approaches.
Evolutionary rescue by compensatory mutations is constrained by genomic and environmental backgrounds

Since deleterious mutations may be rescued by secondary mutations during evolution, compensatory evolution could identify genetic solutions leading to therapeutic targets. Here, we tested this hypothesis and examined whether these solutions would be universal or would need to be adapted to one's genetic and environmental makeups. We performed experimental evolutionary rescue in a yeast disease model for the Wiskott–Aldrich syndrome in two genetic backgrounds and carbon sources. We found that multiple aspects of the evolutionary rescue outcome depend on the genotype, the environment, or a combination thereof. Specifically, the compensatory mutation rate and type, the molecular rescue mechanism, the genetic target, and the associated fitness cost varied across contexts. The course of compensatory evolution is therefore highly contingent on the initial conditions in which the deleterious mutation occurs. In addition, these results reveal biologically favored therapeutic targets for the Wiskott–Aldrich syndrome, including the target of an unrelated clinically approved drug. Our results experimentally illustrate the importance of epistasis and environmental evolutionary constraints that shape the adaptive landscape and evolutionary rate of molecular networks.
Keep Your Eyes on Development: The Behavioral and Neurophysiological Development of Visual Mechanisms Underlying Form Processing

Visual form perception is essential for correct interpretation of, and interaction with, our environment. Form perception depends on visual acuity and processing of specific form characteristics, such as luminance contrast, spatial frequency, color, orientation, depth, and even motion information. As other cognitive processes, form perception matures with age. This paper aims at providing a concise overview of our current understanding of the typical development, from birth to adulthood, of form-characteristic processing, as measured both behaviorally and neurophysiologically. Two main conclusions can be drawn. First, the current literature conveys that for most reviewed characteristics a developmental pattern is apparent. These trajectories are discussed in relation to the organization of the visual system. The second conclusion is that significant gaps in the literature exist for several age-ranges. To complete our understanding of the typical and, by consequence, atypical development of visual mechanisms underlying form processing, future research should uncover these missing segments.
Weighted ensemble based automatic detection of exudates in fundus photographs

Diabetic retinopathy (DR) is a visual complication of diabetes, which has become one of the leading causes of preventable blindness in the world. Exudate detection is an important problem in automatic screening systems for detection of diabetic retinopathy using color fundus photographs. In this paper, we present a method for detection of exudates in color fundus photographs, which combines several preprocessing and candidate extraction algorithms to increase the exudate detection accuracy. The first stage of the method consists of an ensemble of several exudate candidate extraction algorithms. In the learning phase, simulated annealing is used to determine weights for combining the results of the ensemble candidate extraction algorithms. The second stage of the method uses a machine learning-based classification for detection of exudate regions. The experimental validation was performed using the DRiDB color fundus image set. The validation has demonstrated that the proposed method achieved higher accuracy in comparison to state-of-the art methods.
PROFESSIONAL DEVELOPMENT AND THE IMPROVEMENT OF INSTRUCTION El desarrollo profesional y el mejoramiento de la enseñanza

This chapter describes the underlying philosophy and research base of a program of professional development designed to support teachers in low-performing schools in Santiago, Chile. Scientific teaching methods in literacy learning combined with intensive training for teachers and long-term follow-up were used to improve the achievement of elementary students in reading and writing. The major components of effective professional development and their impact on school change and student performance are identified and discussed. The application of these various standards in the AILEM program (Reading, Writing and Mathematics Early Learning) a collaborative project with the Foundation for Comprehensive Early Literacy Learning, is also reviewed.
Inventing a collaborative full dome production course

Beginning in the spring semester of 2006, ARTS Lab at the University of New Mexico began offering the world’s first full semester course in “Full Dome Production. ” Students from Fine Arts as well as Science and Engineering backgrounds are required to work in collaborative teams to create and produce 1 to 3 minute large format digital video works designed to be projected in an immersive full dome multi-projection system.
Conflict and Agreement in Sex Attitudes of Hispanic Male and Female College Students

Research by Eisenman and Dantzker (2003, 2006) has suggested that male and female Hispanic college students may have sex attitudes that lead to conflict between the sexes. Findings are presented here from 330 university students which show possible areas of conflict and also areas of agreement. The results mostly supported evolutionary psychology theory, with 23 of the 38 sex attitude items showing statistically significant sex differences, and mostly in the expected direction. In addition, 19 of the 38 items showed statistically significant differences between Hispanics and non-Hispanics. However, for both comparisons, all of the differences were relatively small. Overall, there was more agreement than disagreement with the sex attitude items. Implications are discussed.
String phase in phase-separating fluids under shear flow.

Transmission light micrographs show that domains in spinodal decomposition are elongated into extremely long strings in steady states of a polymer solution under strong shear flow. The shear flow stabilizes the string against their intrinsic surface tension instabilities. The string diameter decreases with increase in the shear rate and ultimately becomes of the order of the interface thickness, resulting in shear-induced homogenization.
Romantic Cosmopolitanism: Novalis’s “Christianity or Europe”

German Romanticism is commonly associated with nationalism rather than cosmopolitanism. Against this standard picture, I argue that the early German romantic author, Novalis (Georg Philipp Friedrich von Hardenberg, 1772–1801) holds a decidedly cosmopolitan view. Novalis’s essay “Christianity or Europe” has been the subject of much dispute and puzzlement ever since he presented it to the Jena romantic circle in the fall of 1799. On the basis of an account of the philosophical background of Novalis’s romanticism, I show that the image of the Middle Ages sketched in “Christianity or Europe” plays a symbolic role and should not be taken as a literal description of the historical past or as a blueprint for the future. Rather, the romantic picture of medieval Europe serves to evoke poetically the ideal of a cosmopolitan re-unification of humanity.
Dorsal-ventral midline signaling in the developing Drosophila eye

Boundaries between different cell types play key roles in many developmental patterning processes. They can be established by various mechanisms, and signaling between the different cell types can occur in a number of ways. One mechanism of crossboundary signaling is controlled by the Notch (N)-modifying protein Fringe (Fng). At the Drosophila wing dorsal-ventral (D-V) border, the mechanism by which an Fng+-Fng- interface controls local N activation has been well characterized. A similar N-activating Fng+-Fng- interface has also been described at the D-V border of the fly eye, but the mechanisms that establish and regulate it are different from those in the wing. Here we describe the ventral role of the Sloppy-paired (Slp) transcription factor, and its interactions with dorsally expressed Iroquois (Iro) transcription factors in the regulation of signaling about the Fng+-Fng- interface in the developing eye. The two transcription factors are mutually repressive and initially abut at the D-V midline. However, N signaling at the interface downregulates Slp expression, and a gap opens between the two expression domains in which Serrate (Ser, an N ligand) is upregulated.
Can one see the shape of a network?

Traditionally, network analysis is based on local properties of vertices, like their degree or clustering, and their statistical behavior across the network in question. This paper develops an approach which is different in two respects. We investigate edge-based properties, and we define global characteristics of networks directly. The latter will provide our affirmative answer to the question raised in the title. More concretely, we start with Forman's notion of the Ricci curvature of a graph, or more generally, a polyhedral complex. This will allow us to pass from a graph as representing a network to a polyhedral complex for instance by filling in triangles into connected triples of edges and to investigate the resulting effect on the curvature. This is insightful for two reasons: First, we can define a curvature flow in order to asymptotically simplify a network and reduce it to its essentials. Second, using a construction of Bloch, which yields a discrete Gauss-Bonnet theorem, we have the Euler characteristic of a network as a global characteristic. These two aspects beautifully merge in the sense that the asymptotic properties of the curvature flow are indicated by that Euler characteristic.