Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequence determinants of nucleotide binding in Sucrose Synthase: improving the affinity of a bacterial Sucrose Synthase for UDP by introducing plant residues

Sucrose Synthase (SuSy) catalyzes the reversible conversion of sucrose and a nucleoside diphosphate (NDP) into NDP-glucose and fructose. Biochemical characterization of several plant and bacterial SuSys has revealed that the eukaryotic enzymes preferentially use UDP whereas prokaryotic SuSys prefer ADP as acceptor. In this study, SuSy from the bacterium Acidithiobacillus caldus, which has a higher affinity for ADP as reflected by the 25-fold lower Km value compared to UDP, was used as a test case to scrutinize the effect of introducing plant residues at positions in a putative nucleotide binding motif surrounding the nucleobase ring of NDP. All eight single to sextuple mutants had similar activities as the wild-type enzyme but significantly reduced Km values for UDP (up to 60 times). In addition, we recognized that substrate inhibition by UDP is introduced by a methionine at position 637. The affinity for ADP also increased for all but one variant, although the improvement was much smaller compared to UDP. Further characterization of a double mutant also revealed more than 2-fold reduction in Km values for CDP and GDP. This demonstrates the general impact of the motif on nucleotide binding. Furthermore, this research also led to the establishment of a bacterial SuSy variant that is suitable for the recycling of UDP during glycosylation reactions. The latter was successfully demonstrated by combining this variant with a glycosyltransferase in a one-pot reaction for the production of the C-glucoside nothofagin, a health-promoting flavonoid naturally found in rooibos (tea).
Cortex Is Driven by Weak but Synchronously Active Thalamocortical Synapses

Sensory stimuli reach the brain via the thalamocortical projection, a group of axons thought to be among the most powerful in the neocortex. Surprisingly, these axons account for only ∼15% of synapses onto cortical neurons. The thalamocortical pathway might thus achieve its effectiveness via high-efficacy thalamocortical synapses or via amplification within cortical layer 4. In rat somatosensory cortex, we measured in vivo the excitatory postsynaptic potential evoked by a single synaptic connection and found that thalamocortical synapses have low efficacy. Convergent inputs, however, are both numerous and synchronous, and intracortical amplification is not required. Our results suggest a mechanism of cortical activation by which thalamic input alone can drive cortex.
Comply or explain in corporate governance codes: in need of greater regulatory oversight?

At the heart of the voluntary corporate governance code in the UK and elsewhere is the concept of ‘comply or explain’. It provides that a company is to comply with a code's provision; but if it does not do so, then it is to state that it does not and explain why it does not. There is no provision in the UK for any statements by companies to be assessed by any regulatory body. It is incumbent on the markets generally and the company's shareholders specifically to determine whether the response of the company to code provisions does enough, and then to take some action if they do not. The aim of comply or explain is to empower shareholders to make an informed evaluation as to whether non-compliance is justified, given the company's circumstances. This paper assesses whether the present scheme, which relies on the stewardship of shareholders and the efficiency of the markets, should continue, or whether a regulatory body should be empowered to determine whether companies are in fact complying with code provisions or, if not, whether they are providing adequate explanations for not complying.
The Golden Section Hypothesis—Its Last Funeral

Since the very beginning of experimental aesthetics with Fechner's investigation of the Holbein Madonna (1872) and the aesthetic pleasingness of the golden section (1865, 1871a, 1876/1925/1978) there have been reports with widely differing results on this hypothesis (to quote only a few: Benjafield, 1976; Boselie, 1992; Davis, 1933; Godkewitsch, 1974; Haines & Davies, 1904; Lalo, 1908; Piehl, 1976; Plug, 1980; Svensson, 1977; Thompson, 1946; see also the reviews of Green, 1995 and Höge, 1995). Thus, as there are so many results on the golden section hypothesis showing contradictory outcomes it seemed necessary to replicate Fechner's original study as far as possible: giving the same proportions, using white cards on black ground. Other specifics could not be kept constant because Fechner's report on the experiment is not very precise (cf. Fechner, 1876/1925/1997). As a complete replication is not possible, three experiments were carried out, each of them being slightly different in methodology. However, regardless of the conditions under which the choices were made, the golden section did not turn out to be the preferred proportion. The comparison with Fechner's results makes this research only quasi-experimental in character and, hence, inevitably there are some restrictions with respect to the strength of the conclusions to be drawn. But, nevertheless, the nice peak of preference Fechner reported for the golden section seems to be either an artifact or it is an effect of still unknown factors. Two possible hypotheses (change-of-taste and color-of-paper) are discussed. It is concluded that the golden section hypothesis is a myth.
Number Matters: The Multimodality of Internet Use as an Indicator of the Digital Inequalities

This study explores the multimodality of Internet use as a critical indicator of digital inequalities. Rather than relying on traditional measures of user/nonuser and information/entertainment uses, this study focuses on a broad scope of online activities and investigates them collectively. Results show that the more modes of Internet activities people are engaged in, the more advanced uses they will add to their online behaviors. Female, older, poorer, and less educated only use the Internet for very limited basic applications, which are associated with fewer political communication and participation. While previous research concludes that the type of Internet activities matters, this study suggests that it is the number of types that matters in examining potential inequalities and their social consequences. © 2012 Wiley Periodicals, Inc.
Low-Frequency Radio Observations of X-Ray Ghost Bubbles in A2597: A History of Radio Activity in the Core

A previous analysis of the Chandra X-ray image of the center of the cooling core cluster A2597 showed two "ghost holes" in the X-ray emission to the west and northeast of the central radio galaxy PKS 2322-123. Previous radio observations did not detect any radio emission coming from the interior of the X-ray holes. We present new low-frequency radio observations of A2597. At 330 MHz, radio emission extends into the interior of the western ghost bubble, but not the northeast one. Our reanalysis of the archival Chandra data shows evidence for an X-ray tunnel (elongated region of reduced X-ray emission) extending from near the center of the cD galaxy out to the west ghost bubble. We also detect a smaller X-ray hole to the northeast of the center of the cD and closer than the outer ghost bubbles. Radio observations at 1.3 GHz show extensions to the west along the X-ray tunnel toward the west ghost bubble, to the northeast into the new X-ray hole, and to the northwest. All of these structures are much larger than the two inner radio lobes seen previously at 8 GHz. The X-ray tunnel suggests that the west ghost bubble is part of a continuous flow of radio plasma out from the active galactic nucleus, rather than a detached buoyant old radio lobe, and thus it may be an intermediate case between an active radio galaxy and a buoyant lobe.
Human Immunodeficiency Virus Type 1 Escape from RNA Interference

ABSTRACT Sequence-specific degradation of mRNA by short interfering RNA (siRNA) allows the selective inhibition of viral proteins that are critical for human immunodeficiency virus type 1 (HIV-1) replication. The aim of this study was to characterize the potency and durability of virus-specific RNA interference (RNAi) in cell lines that stably express short hairpin RNA (shRNA) targeting the HIV-1 transactivator protein gene tat. We found that the antiviral activity of tat shRNA was abolished due to the emergence of viral quasispecies harboring a point mutation in the shRNA target region. Our results suggest that, in order for RNAi to durably suppress HIV-1 replication, it may be necessary to target highly conserved regions of the viral genome. Alternatively, similar to present antiviral drug therapy paradigms, DNA constructs expressing multiple siRNAs need to be developed that target different regions of the viral genome, thereby reducing the probability of generating escape mutants.
Reaching Accessibility

VOL. 40, NO. 3, JANUARY 2005 (PP. 171–176) 171 from 3% in 1994, to 77% in 2000, and 92% in 2002 (U.S. Department of Education, 2003). The same survey indicated that nationwide, 86% of public schools with access to the Internet had a Web site or Web page in 2002. As students move into postsecondary education, the role of technology grows. According to the U.S. Department of Education’s National Center for Education Statistics (Waits & Lewis, 2003), 89% of public, 4-year institutions offered distance education courses during the 2000–2001 academic year. Of those offering distance education courses, 90% offered Internet courses. The same report indicated less than encouraging efforts at making Internet offerings accessible to individuals with disabilities:
Comparison of two methods for automatic brain morphometry analysis

The methods of computational neuroanatomy are widely used; the data on their individual strengths and limitations from direct comparisons are, however, scarce. The aim of the present study was direct comparison of deformation-based morphometry (DBM) based on highresolution spatial transforms with widely used voxel-based morphometry (VBM) analysis based on segmented highresolution images. We performed DBM and VBM analyses on simulated volume changes in a set of 20 3-D MR images, compared to 30 MR images, where only random spatial transforms were introduced. The ability of the two methods to detect regions with the simulated volume changes was determined using overlay index together with the ground truth regions of the simulations; the precision of the detection in space was determined using the distance measures between the centers of detected and simulated regions. DBM was able to detect all the regions with simulated local volume changes with high spatial precision. On the other hand, VBM detected only changes in vicinity of the largest simulated change, with a poor overlap of the detected changes and the ground truth. Taken together we suggest that the analysis of high-resolution deformation fields is more convenient, sensitive, and precise than voxel-wise analysis of tissue-segmented images.
Accurate Foreground Segmentation without Pre-learning

Foreground segmentation has been widely used in many computer vision applications. However, most of the existing methods rely on a pre-learned motion or background model, which will increase the burden of users. In this paper, we present an automatic algorithm without pre-learning for segmenting foreground from background based on the fusion of motion, color and contrast information. Motion information is enhanced by a novel method called support edges diffusion (SED), which is built upon a key observation that edges of the difference image of two adjacent frames only appear in moving regions in most of the cases. Contrasts in background are attenuated while those in foreground are enhanced using gradient of the previous frame and that of the temporal difference. Experiments on many video sequences demonstrate the effectiveness and accuracy of the proposed algorithm. The segmentation results are comparable to those obtained by other state-of-the-art methods that depend on a pre-learned background or a stereo setup.
Undergraduate Mathematics for the Life Sciences: Computational Systems Biology: Discrete Models of Gene Regulation Networks

This article describes a 2-3 day workshop offered at regional undergraduate teaching institutions and high schools. Its goal is to use discrete dynamic models, in particular Boolean networks, to illustrate mathematical modeling of biological networks, such as gene regulatory networks, to a broad audience that can include undergraduate faculty, undergraduate students, high school teachers, and even high school students. The workshop covers the basics of biology, mathematical modeling, and model analysis, using the wellknown lac operon network in E coli as a model system. The workshop materials can be used independently or as one or several modules in a college or high school class. Supplementary materials are available at admg.vbi. vt.edu/home/Outreach/Workshops/2.
Bankruptcy Without Borders

Review Essay on Terrence Halliday and Bruce Carruthers, Bankrupt: Global Lawmaking and Systemic Financial Crisis.In 1998, Bruce Carruthers and Terence Halliday published a magisterial 600-page tome on the reform of bankruptcy law in the United States (1978) and Britain (1985). Rescuing Business was really two books in one. It detailed how institutional differences, and power differentials among interested players, translated a shared concern about corporate bankruptcy into quite different policy changes in the two countries. The shared concern was that bankruptcy conventions were not Pareto optimal.
Impaired Interoceptive Accuracy in Semantic Variant Primary Progressive Aphasia

Background Interoception (the perception of internal bodily sensations) is strongly linked to emotional experience and sensitivity to the emotions of others in healthy subjects. Interoceptive impairment may contribute to the profound socioemotional symptoms that characterize frontotemporal dementia (FTD) syndromes, but remains poorly defined. Methods Patients representing all major FTD syndromes and healthy age-matched controls performed a heartbeat counting task as a measure of interoceptive accuracy. In addition, patients had volumetric MRI for voxel-based morphometric analysis, and their caregivers completed a questionnaire assessing patients’ daily-life sensitivity to the emotions of others. Results Interoceptive accuracy was impaired in patients with semantic variant primary progressive aphasia relative to healthy age-matched individuals, but not in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Impaired interoceptive accuracy correlated with reduced daily-life emotional sensitivity across the patient cohort, and with atrophy of right insula, cingulate, and amygdala on voxel-based morphometry in the impaired semantic variant group, delineating a network previously shown to support interoceptive processing in the healthy brain. Conclusion Interoception is a promising novel paradigm for defining mechanisms of reduced emotional reactivity, empathy, and self-awareness in neurodegenerative syndromes and may yield objective measures for these complex symptoms.
Perceptualization: Techniques for Efffective Image Generation Visualization and Communication of Information

Abstract Most scientists, doctors, analysts, and even com-puter animators are faced with a data deluge. Theymust analyze, extract meaningful information, andcreate solutions from huge quantities of data whosesize is increasing at an enormous rate. However,screen resolution, image generation techniques, andvisualization techniques are only making modestimprovements. This has led us to take a differentapproach to image generation and visualization thatwe call perceptualization. We describe our initialwork in perceptualization, the main challenges, andour current research directions. 1 Introduction Throughout history, man has tried to effectivelyconvey important information through the use ofimages, using techniques such as illustrations, pho-tographs, and detailed technical drawings. Thesetechniques harness the enormous bandwidth andpre-attentive processing of the human visual sys-tem. Many disciplines of study have evolved toto further these techniques, including photography,technical and medical illustration, and now visual-ization. While illustration and photography bothare successful at capturing and conveying informa-tion, they utilize different techniques and character-istics of the human visual system to convey infor-mation. Photography concentrates on conveying in-formation with light and color variation, while illus-trations additionally tries to effectively convey in-formation by omitting unimportant details, enhanc-ing the most signiﬁcant components of the image,simplifying complex features, and exposing hiddenfeatures [8]. Scientiﬁc illustrations have been usedfor centuries because of their effective communica-tive ability [4]. The effectiveness of illustration techniques, theamazing power of the human perceptual system,and the enormous data deluge facing informationanalysts, medical and scientiﬁc researchers havemotivated our work on extending visualizationtech-niques to
A quantitative and qualitative evaluation of the British Columbia Take Home Naloxone program.

BACKGROUND In August 2012, the British Columbia Take Home Naloxone (BCTHN) program was introduced to help to reduce opioid overdose and its consequences. This study evaluates the BCTHN program, identifying the successes and challenges of implementing a provincial program in Canada. METHODS In this cross-sectional study, we reviewed the records of the BCTHN administrative program to report on program outcomes (participation and overdose reversals). Focus groups and individual interviews were conducted with 40 clients in Vancouver; 12 individual interviews were completed with service providers, police officers and parents of people who use opioids from both the Vancouver and Interior regions of British Columbia. Qualitative data were analyzed using content analysis and a qualitative descriptive approach. RESULTS As of March 13, 2014, the BCTHN program had been implemented at 40 sites, trained 1318 participants in overdose prevention, recognition and response, distributed 836 kits to clients and received reports of 85 overdose reversals. Stakeholders were supportive of the program, and clients reported greater confidence in response to overdose. Service providers found the program training materials easy to use and that training increased client engagement. Some of the challenges included difficulty in identifying physician willing to prescribe, recruitment of some at-risk populations (e.g., long-term opioid users and patients with chronic pain), and clients' reluctance to call 911. We also found that the police had some misconceptions about BCTHN. INTERPRETATION The BCTHN program was easy to implement, empowering for clients and was responsible for reversing 85 overdoses in its first 20 months. We suggest communities across Canada should consider implementing take-home naloxone programs and evaluate their findings.
Validity and Reliability of Ventilatory and Blood Lactate Thresholds in Well-Trained Cyclists

Purpose The purpose of this study was to determine, i) the reliability of blood lactate and ventilatory-based thresholds, ii) the lactate threshold that corresponds with each ventilatory threshold (VT1 and VT2) and with maximal lactate steady state test (MLSS) as a proxy of cycling performance. Methods Fourteen aerobically-trained male cyclists (V˙O2max 62.1±4.6 ml·kg-1·min-1) performed two graded exercise tests (50 W warm-up followed by 25 W·min-1) to exhaustion. Blood lactate, V˙O2 and V˙CO2 data were collected at every stage. Workloads at VT1 (rise in V˙E/V˙O2;) and VT2 (rise in V˙E/V˙CO2) were compared with workloads at lactate thresholds. Several continuous tests were needed to detect the MLSS workload. Agreement and differences among tests were assessed with ANOVA, ICC and Bland-Altman. Reliability of each test was evaluated using ICC, CV and Bland-Altman plots. Results Workloads at lactate threshold (LT) and LT+2.0 mMol·L-1 matched the ones for VT1 and VT2, respectively (p = 0.147 and 0.539; r = 0.72 and 0.80; Bias = -13.6 and 2.8, respectively). Furthermore, workload at LT+0.5 mMol·L-1 coincided with MLSS workload (p = 0.449; r = 0.78; Bias = -4.5). Lactate threshold tests had high reliability (CV = 3.4–3.7%; r = 0.85–0.89; Bias = -2.1–3.0) except for DMAX method (CV = 10.3%; r = 0.57; Bias = 15.4). Ventilatory thresholds show high reliability (CV = 1.6%–3.5%; r = 0.90–0.96; Bias = -1.8–2.9) except for RER = 1 and V-Slope (CV = 5.0–6.4%; r = 0.79; Bias = -5.6–12.4). Conclusions Lactate threshold tests can be a valid and reliable alternative to ventilatory thresholds to identify the workloads at the transition from aerobic to anaerobic metabolism.
Cuckoo sampling: Robust collection of flow aggregates under a fixed memory budget

Collecting per-flow aggregates in high-speed links is challenging and usually requires traffic sampling to handle peak rates and extreme traffic mixes. Static selection of sampling rates is problematic, since worst-case resource usage is orders of magnitude higher than the average. To address this issue, adaptive schemes have been proposed in the last few years that periodically adjust packet sampling rates to network conditions. However, such proposals rely on complex algorithms and data structures of costly maintenance. As a consequence, adaptive sampling is still not widely implemented in routers.
Case Report: Injuries Associated with Interactive Game Consoles: Preliminary Data

Abstract The use of motion-sensing video game software has provided users with the ability to mimic movements in many sports such as baseball, tennis, and boxing. Epidemiology on injuries and overuse of motion-sensing video game systems is minimal because the systems have only been available for 2 years. This case series report presents preliminary data on injuries related to the game systems from the first full year of use. Methods included the use of secondary data from the National Electronic Injury Surveillance System for 2007. The query found 21 cases of injury related to the use of the “Wii” video game system (Nintendo of America Inc., Redmond, WA). Results indicated that females were more prone to injuries, and the mean age was 16 years. Most injuries were soft tissue in nature and located in the shoulders, hands and fingers, and the face and neck region. Our discussion includes prevention strategies for reducing injury risk when playing motion-sensing video games.
Assessing Uncertainties in X-ray Single-particle Three-dimensional reconstructions

Modern technology for producing extremely bright and coherent x-ray laser pulses provides the possibility to acquire a large number of diffraction patterns from individual biological nanoparticles, including proteins, viruses, and DNA. These two-dimensional diffraction patterns can be practically reconstructed and retrieved down to a resolution of a few angstroms. In principle, a sufficiently large collection of diffraction patterns will contain the required information for a full three-dimensional reconstruction of the biomolecule. The computational methodology for this reconstruction task is still under development and highly resolved reconstructions have not yet been produced. We analyze the expansion-maximization-compression scheme, the current state of the art approach for this very challenging application, by isolating different sources of resolution-limiting factors. Through numerical experiments on synthetic data we evaluate their respective impact. We reach conclusions of relevance for handling actual experimental data, and we also point out certain improvements to the underlying estimation algorithm. We also introduce a practically applicable computational methodology in the form of bootstrap procedures for assessing reconstruction uncertainty in the real data case. We evaluate the sharpness of this approach and argue that this type of procedure will be critical in the near future when handling the increasing amount of data.