Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of ground-state structure and Mg2+ binding on folding kinetics of the guanine-sensing riboswitch aptamer domain

Riboswitch RNAs fold into complex tertiary structures upon binding to their cognate ligand. Ligand recognition is accomplished by key residues in the binding pocket. In addition, it often crucially depends on the stability of peripheral structural elements. The ligand-bound complex of the guanine-sensing riboswitch from Bacillus subtilis, for example, is stabilized by extensive interactions between apical loop regions of the aptamer domain. Previously, we have shown that destabilization of this tertiary loop–loop interaction abrogates ligand binding of the G37A/C61U-mutant aptamer domain (Gswloop) in the absence of Mg2+. However, if Mg2+ is available, ligand-binding capability is restored by a population shift of the ground-state RNA ensemble toward RNA conformations with pre-formed loop–loop interactions. Here, we characterize the striking influence of long-range tertiary structure on RNA folding kinetics and on ligand-bound complex structure, both by X-ray crystallography and time-resolved NMR. The X-ray structure of the ligand-bound complex reveals that the global architecture is almost identical to the wild-type aptamer domain. The population of ligand-binding competent conformations in the ground-state ensemble of Gswloop is tunable through variation of the Mg2+ concentration. We quantitatively describe the influence of distinct Mg2+ concentrations on ligand-induced folding trajectories both by equilibrium and time-resolved NMR spectroscopy at single-residue resolution.
Plasmon resonances of novel monolayer and bilayer shell aggregate gold nanostructures

Various gold nanostructures have being investigated for medical and biological uses, such as surface enhanced-Raman spectroscopy (SERS) and photoacoustic imaging (PAI), each having its advantages and limitations depending on the specific application. For many imaging and spectroscopic applications, it would be beneficial to use near infrared (NIR) excitation as well as small gold nanospheres which can easily reach the cytoplasm and cell nucleus. For that purpose, we propose a novel nanostructure, the "shell aggregate," which consists of small nanospheres aggregated (mono/bi-layer) around a core such as an intracellular organelle. The extinction efficiency of such monolayer and bilayer shell aggregates is thoroughly investigated with appropriate simulations using the Discrete Dipole Approximation (DDA) method. The effect of parameters such as the overall radius of the nanostructure, the small nanosphere radius, and the distance between the nanospheres, on the extinction efficiency factor of the nanostructures was examined. The results indicate that the extinction spectra appear to depend heavily on the distance between the small nanospheres. Two distinct absorption peak wavelengths are observed for a specific nanostructure. The monolayer shell aggregate provides a reasonably tunable plasmon resonance wavelength while the small size of its components can be exploited for intracellular distribution.
Percolation and Survival of Escherichia coli O157:H7 and Salmonella enterica Serovar Typhimurium in Soil Amended with Contaminated Dairy Manure or Slurry

ABSTRACT The effect of cattle manure and slurry application on percolation and survival of Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium was investigated for different soil depths after the addition of water. Four treatments were chosen for the first set of experiments: (i) addition of inoculated farmyard manure on the soil surface, (ii) mixing of inoculated farmyard manure with the top 10 cm of soil, (iii) addition of inoculated slurry on the soil surface, and (iv) injection of inoculated slurry into the top 10 cm of the soil. Homogeneity of water distribution in the soil profile was confirmed by a nondestructive nuclear magnetic resonance method. Survival data were fitted to a modified logistic model, and estimated survival times were compared. In the second set of experiments, pathogen-inoculated farmyard manure or slurry was applied to soil columns with 1-month-old lettuce plants. More pathogen cells percolated to greater depths after slurry than after manure application. Survival of E. coli O157:H7 was significantly longer in soil with slurry than in that with manure, while survival of Salmonella serovar Typhimurium was equally high with manure and slurry. The densities of the pathogens were not different in the rhizosphere compared to the bulk soil with manure, while the densities were higher by 0.88 ± 0.11 and 0.71 ± 0.23 log CFU per g (dry weight), respectively, in the rhizosphere than in bulk soil after slurry application. Our results suggest that surface application of manure may decrease the risk of contamination of groundwater and lettuce roots compared to injection of slurry.
Procrastination, Deadlines, and Performance: Self-Control by Precommitment

Procrastination is all too familiar to most people. People delay writing up their research (so we hear! ), repeatedly declare they will start their diets tomorrow, or postpone until next week doing odd jobs around the house. Yet people also sometimes attempt to control their procrastination by setting deadlines for themselves. In this article, we pose three questions: (a) Are people willing to self-impose meaningful (i.e., costly) deadlines to overcome procrastination? (b) Are self-imposed deadlines effective in improving task performance? (c) When self-imposing deadlines, do people set them optimally, for maximum performance enhancement? A set of studies examined these issues experimentally, showing that the answer is “yes” to the first two questions, and “nO'’ to the third. People have self-control problems, they recognize them, and they try to control them by self-imposing costly deadlines. These deadlines help people control procrastination, but they are not as effective as some externally imposed deadlines in improving task performance.
Discovering personally meaningful places: An interactive clustering approach

The discovery of a person's meaningful places involves obtaining the physical locations and their labels for a person's places that matter to his daily life and routines. This problem is driven by the requirements from emerging location-aware applications, which allow a user to pose queries and obtain information in reference to places, for example, “home”, “work” or “Northwest Health Club”. It is a challenge to map from physical locations to personally meaningful places due to a lack of understanding of what constitutes the real users' personally meaningful places. Previous work has explored algorithms to discover personal places from location data. However, we know of no systematic empirical evaluations of these algorithms, leaving designers of location-aware applications in the dark about their choices. Our work remedies this situation. We extended a clustering algorithm to discover places. We also defined a set of essential evaluation metrics and an interactive evaluation framework. We then conducted a large-scale experiment that collected real users' location data and personally meaningful places, and illustrated the utility of our evaluation framework. Our results establish a baseline that future work can measure itself against. They also demonstrate that that our algorithm discovers places with reasonable accuracy and outperforms the well-known K-Means clustering algorithm for place discovery. Finally, we provide evidence that shapes more complex than “points” are required to represent the full range of people's everyday places.
News Shocks and Optimal Monetary Policy

This paper studies monetary policy in a model where output fluctuations are caused by shocks to public beliefs on the economy's fundamentals. I ask whether monetary policy can offset the effect of these shocks and whether this offsetting is socially desirable. I consider an environment with dispersed information and two aggregate shocks: a productivity shock and a "news shock" which affects aggregate beliefs. Neither the central bank nor individual agents can distinguish the two shocks when they hit the economy. The main results are: (1) despite the lack of superior information an appropriate monetary policy rule can change the economy's response to the two shocks; (2) monetary policy can achieve full aggregate stabilization, that is, it can induce a path for aggregate output that is identical to that which would arise under full information; (3) however, full aggregate stabilization is typically not optimal. The fact that monetary policy can tackle the two shocks separately is due to two crucial ingredients. First, agents are forward looking. Second, current fundamental shocks will become public information in the future and the central bank will be able to respond to them at that time. By announcing its response to future information, the central bank can influence the expected real interest rate faced by agents with different beliefs and, thus, induce an optimal use of the information dispersed in the economy.
Using YouTube to Disseminate Effective Vaccination Pain Treatment for Babies

Background Infant vaccinations are necessary for public health, but are painful, causing distress to the infant and caregivers. Breastfeeding and sucrose effectively reduce infants’ pain during vaccinations, and these strategies are recommended in health care provider (HCP)-targeted education and vaccination pain guidelines. However studies show these strategies are infrequently used. YouTube is a popular medium to publicly share and watch videos, and many consumer posted YouTube videos show distressed infants being vaccinated with no pain treatment. The aims of this study were to evaluate the reach and impact of a consumer-targeted YouTube video demonstrating use of effective pain reduction strategies during infant vaccinations. Methods A brief consumer-targeted video showing two infants being vaccinated was posted onto YouTube on October 2013. One infant was breastfed and another infant received sucrose by mouth before and during the injection. A link to a viewer survey was visible on a banner near the end of the video. An intensive strategically planned knowledge dissemination strategy using the media, social media and messages to professional organizations took place to promote the video. Data analysis of the viewer survey, YouTube analytics of the reach of the video in terms of number of views, country of viewers, and comments relating to the video took place 12 months after the video was posted. Results Twelve months after posting, the video had 65,478views, 68 comments, 245 likes, 17 dislikes, and 90 shares. Average duration of viewer time was 65% of the video. The viewer survey was completed by 156 (0.24%) viewers; 90 (58%) answered as HCPs and 66 (42%) as parents. Survey results showed that the video was persuasive; intent to use or support breastfeeding or sucrose was high in both parents and HCPs after viewing the video. Comments posted were often emotional in nature, and were related to anti-vaccination (n = 26, 38%); effectiveness or positive personal experiences (n = 21, 32%); research team comments or promotion (n = 12, 18%); pro-vaccination (n = 6, 8%) and barriers to using breastfeeding or sucrose during vaccinations (n = 3, 4%). Conclusion The video posted onto YouTube demonstrating effective pain treatment during infant vaccinations was viewed by large numbers of people around the world, however the response rate to the linked survey was extremely low. Using YouTube videos for knowledge dissemination has an extensive reach, however it is difficult to evaluate impact on behaviours and practices.
Down-regulation of Pkc1-mediated Signaling by the Deubiquitinating Enzyme Ubp3*

Regulated ubiquitination and degradation of signaling proteins have emerged as key mechanisms for modulating the strength and duration of signaling pathways. The reversible nature of the ubiquitination process as well as the large number and diversity of the deubiquitinating enzymes raise the possibility that signaling pathways might be modulated by specific deubiquitinating enzyme(s). Here we provide evidence that in the yeast Saccharomyces cerevisiae, the Pkc1-mediated signaling pathway that controls the cell wall integrity is negatively regulated by the deubiquitinating enzyme Ubp3. Disruption of the UBP3 gene leads to an enhanced activation of the cell wall integrity pathway MAPK Slt2 when cells are challenged with a variety of pathway activation agents such as pheromone and Congo red. The ubp3 deletion mutants accumulate high levels of Pkc1, suggesting potential regulation of Pkc1 by Ubp3. Consistent with this, Pkc1 and Ubp3 interact in vivo, and the stability of Pkc1 is markedly increased in the ubp3 deletion mutants. Moreover, disruption of the PKC1 gene, but not the genes that encode components downstream of Pkc1, completely suppresses other phenotypes displayed by the ubp3 deletion mutants such as hyperactivation of the pheromone-responsive MAPK Fus3 (Wang, Y., and Dohlman, H. G. (2002) J. Biol. Chem. 277, 15766–15772). These findings demonstrate that Ubp3 can regulate Pkc1 by facilitating its destruction and provide the initial evidence that Pkc1 plays a positive role in modulating the parallel pheromone-signaling pathway.
RESISTANCE CHANGEMENT OF COMPRESSION SENSIBLE CEMENT SPECIMENT UNDER DIFFERENT STRESSES

The resistivity of cement specimens mixedwith carbon fibres under different pressures is studied.Theresults reveal that when pressure becomes larger and larger,the resistivity of speciments changes.The process can be di-vided into three stages:reversible sensing period,balance pe-riod,and sharp increasing period.These three periods re-spectively show the closure and opening of raw flaw in speci-mens,germination of fresh cracks and cracks extending tofailure.The conducting mechanism is also analyzed.Ac-cording to the above characteristic of carbon fibre-cementspecimen,it can be used as an intrinsic smart material to be ap-plied in the non-destructive detection of concrete dams,ect.
Energy scaling and reduction in controlling complex networks

Recent works revealed that the energy required to control a complex network depends on the number of driving signals and the energy distribution follows an algebraic scaling law. If one implements control using a small number of drivers, e.g. as determined by the structural controllability theory, there is a high probability that the energy will diverge. We develop a physical theory to explain the scaling behaviour through identification of the fundamental structural elements, the longest control chains (LCCs), that dominate the control energy. Based on the LCCs, we articulate a strategy to drastically reduce the control energy (e.g. in a large number of real-world networks). Owing to their structural nature, the LCCs may shed light on energy issues associated with control of nonlinear dynamical networks.
Effects of Volatile Anesthetic Choice on Hospital Length-of-stay: A Retrospective Study and a Prospective Trial

Background:Volatile anesthetic prices differ substantially. But differences in drug-acquisition cost would be inconsequential if hospitalization were prolonged by more soluble anesthetics. The authors tested the hypothesis that the duration of hospitalization is prolonged with isoflurane anesthesia. Methods:Initially, the authors queried their electronic records and used propensity matching to generate homogeneous sets of adults having inpatient noncardiac surgery who were given desflurane, sevoflurane, and isoflurane. The authors then conducted a prospective alternating intervention trial in which adults (mostly having colorectal surgery) were assigned to isoflurane or sevoflurane, based on protocol. Results:In the retrospective analysis, 2,898 matched triplets were identified among 43,352 adults, each containing one patient receiving isoflurane, desflurane, and sevoflurane, respectively. The adjusted geometric mean (95% CI) hospital length-of-stay for the isoflurane cases was 2.85 days (2.78–2.93); this was longer than that observed for both desflurane (2.64 [2.57–2.72]; P < 0.001) and sevoflurane (2.55 [2.48–2.62]; P < 0.001). In the prospective trial (N = 1,584 operations), no difference was found; the adjusted ratio of means (95% CI) of hospital length-of-stay in patients receiving isoflurane versus sevoflurane was 0.98 (0.88–1.10), P = 0.77, with adjusted geometric means (95% CI) estimated at 4.1 (3.8–4.4) and 4.2 days (3.8–4.5), respectively. Conclusions:Results of the propensity-matched retrospective analysis suggested that avoiding isoflurane significantly reduced the duration of hospitalization. In contrast, length-of-stay was comparable in our prospective trial. Volatile anesthetic choice should not be based on concerns about the duration of hospitalization. These studies illustrate the importance of following even the best retrospective analysis with a prospective trial.
Hydrogen Storage in Microporous Metal-Organic Frameworks

Metal-organic framework-5 (MOF-5) of composition Zn4O(BDC)3 (BDC = 1,4-benzenedicarboxylate) with a cubic three-dimensional extended porous structure adsorbed hydrogen up to 4.5 weight percent (17.2 hydrogen molecules per formula unit) at 78 kelvin and 1.0 weight percent at room temperature and pressure of 20 bar. Inelastic neutron scattering spectroscopy of the rotational transitions of the adsorbed hydrogen molecules indicates the presence of two well-defined binding sites (termed I and II), which we associate with hydrogen binding to zinc and the BDC linker, respectively. Preliminary studies on topologically similar isoreticular metal-organic framework-6 and -8 (IRMOF-6 and -8) having cyclobutylbenzene and naphthalene linkers, respectively, gave approximately double and quadruple (2.0 weight percent) the uptake found for MOF-5 at room temperature and 10 bar.
Comparative Transcriptional Analysis of Homologous Pathogenic and Non-Pathogenic Lawsonia intracellularis Isolates in Infected Porcine Cells

Lawsonia intracellularis is the causative agent of proliferative enteropathy. This disease affects various animal species, including nonhuman primates, has been endemic in pigs, and is an emerging concern in horses. Non-pathogenic variants obtained through multiple passages in vitro do not induce disease, but bacterial isolates at low passage induce clinical and pathological changes. We hypothesize that genes differentially expressed between pathogenic (passage 10) and non-pathogenic (passage 60) L. intracellularis isolates encode potential bacterial virulence factors. The present study used high-throughput sequencing technology to characterize the transcriptional profiling of a pathogenic and a non-pathogenic homologous L. intracellularis variant during in vitro infection. A total of 401 genes were exclusively expressed by the pathogenic variant. Plasmid-encoded genes and those involved in membrane transporter (e.g. ATP-binding cassette), adaptation and stress response (e.g. transcriptional regulators) were the categories mostly responsible for this wider transcriptional landscape. The entire gene repertoire of plasmid A was repressed in the non-pathogenic variant suggesting its relevant role in the virulence phenotype of the pathogenic variant. Of the 319 genes which were commonly expressed in both pathogenic and non-pathogenic variants, no significant difference was observed by comparing their normalized transcription levels (fold change±2; p<0.05). Unexpectedly, these genes demonstrated a positive correlation (r2 = 0.81; p<0.05), indicating the involvement of gene silencing (switching off) mechanisms to attenuate virulence properties of the pathogenic variant during multiple cell passages. Following the validation of these results by reverse transcriptase-quantitative PCR using ten selected genes, the present study represents the first report characterizing the transcriptional profile of L. intracellularis. The complexity of the virulence phenotype was demonstrated by the diversity of genes exclusively expressed in the pathogenic isolate. The results support our hypothesis and provide the basis for prospective mechanistic studies regarding specific roles of target genes involved in the pathogenesis, diagnosis and control of proliferative enteropathy.
Repeatability, reproducibility, and effect of head position on central venous pressure measurement in standing adult horses.

BACKGROUND Central venous pressure (CVP) is a used as an estimation of intravascular volume status in various species. Techniques for measuring CVP in horses have been described, but the repeatability of these readings at a single time point or over time has not been established. HYPOTHESIS That CVP measurements in healthy adult horses would be repeatable at each time point, that these readings would be reproducible over time, and that alteration in head position relative to the heart would alter CVP. ANIMALS Ten healthy adult research horses. METHODS In an experimental study, horses were instrumented with a central venous catheter. Readings were taken in triplicate q6h for 2 days by water manometry, and twice daily with the head in neutral, elevated, and lowered positions by electronic manometry. RESULTS Variation in the "neutral" measurements obtained at each time point was <0.1 ± 1.0 cmH(2)O (P = .718). There was a significant decrease in CVP over time (P = .015), which was eliminated when results were controlled for acute decrease in body weight of -1.35% (presumed hypohydration because of lack of acclimatization and decreased water intake). Head height had a significant and directional effect on CVP in that the elevated head position decreased CVP -2.0 ± 6.5 cmH(2)O (P < .001) while the lowered head position increased CVP by 3.7 ± 5.5 cmH(2)O (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE CVP values obtained by water manometry were repeatable in adult horses, but were reproducible only when controlled for changes in hydration. Care should be taken to maintain consistency in head position to prevent erroneous readings.
Organochlorine pesticide exposure among agricultural workers in Colombian regions with illegal crops: an exploration in a hidden and dangerous world

A previous study suggested that banned organochlorine pesticides were being used to protect illegal crops from pests. The study herein explored the exposure of individuals living in a region with such crops. Samples from 99 individuals were collected during 2005 and 2006 and organochlorine pesticides were quantified using chromatography in serum samples. We detected heptachlor (72.73%), 4,4-DDE (19.19%), aldrin (15.15%), γ-chlordane (12.12%), dieldrin (11.11%), α-chlordane (10,10%), α-endosulfan (8.08%), endosulfan (6.06%), β-endosulfan (5.05%), oxychlordane (3.03%), 4,4-DDT (3.03%), and 2,4-DDT (2.02%). Heptachlor had a skewed and negative distribution (median: 8.69 ng/l and maximum: 43.8 ng/l). A two-dimensional biplot suggested that mixtures present were endosulfan/4,4-DDT, aldrin/γ-chlordane, and oxychlordane/β-endosulfan/dieldrin. We did not identify variables associated with exposure levels. These data suggest that banned organochlorine pesticides are used. This is an example of research in a war context, where the problems related with pesticides are complex, and their implications go beyond a toxicological or epidemiological viewpoint.