Miracle-dz/UniFAR-FTUs huggingface dataset:
Imaging surface and submembranous structures with the atomic force microscope: a study on living cancer cells, fibroblasts and macrophages

Atomic force microscopy (AFM) has been used to image a wide variety of cells. Fixed and dried‐coated, wet‐fixed or living cells were investigated. The major advantage of AFM over SEM is the avoidance of vacuum and electrons, whereas imaging can be done at environmental pressure and in aqueous conditions. Evidence of the successful application of AFM in biological imaging is provided by comparing results of AFM with SEM and/or TEM. In this study, we investigated surface and submembranous structures of living and glutaraldehyde‐fixed colon carcinoma cells, skin fibroblasts and liver macrophages by AFM. Special attention was paid to the correct conditions for the acquisition of images of the surface of these cells, because quality SEM examinations have already been abundantly presented.
Opportunities for Promoting Physical Activity in Rural Communities by Understanding the Interests and Values of Community Members

Purpose Physical activity (PA) has well-established health benefits, but most Americans do not meet national guidelines. In southeastern Missouri, trails have been developed to increase rates of PA. Although this has had success, broad-scale interventions will be needed to improve rates further. In this study, we surveyed residents of southeastern Missouri to identify ways to improve rates of PA. Methods We conducted a telephone survey in 2015 of adults (n = 524) from eight rural Missouri towns that had walking trails, regarding their activities and interests. Findings Forty percent of respondents reported both walking and meeting PA recommendations, 29% reported walking but not meeting PA recommendations, and the remainder did not walk or did not answer. Respondents who used the trails were significantly more likely to meet PA recommendations (odds ratio = 2.7; 95% confidence interval = 1.7, 4.5). Certain values and interests that may encourage PA or draw people to trails were common. Conclusions The group that walked but did not meet PA recommendations would be the ideal group to target for intervention, which could focus on their reported values and interests (e.g., personal relationships, being outdoors). Use of walking trails was associated with meeting PA recommendations.
Stated Preference Models for Airport and Airline Choice with Conditioning on Observed Choices

This paper describes how researchers are increasingly making use of random coefficients structures, such as mixed logit, in the analysis of air travel choice behavior. These models have the advantage of being able to retrieve random variations in sensitivities across travelers, leading to very significant gains in modeling accuracy. However, an important issue arises in the computation of willingness to pay indicators, such as the valuation of travel time savings (VTTS), on the basis of randomly distributed coefficients. Indeed, with the standard approach of using simulation of the ratios across random draws, major problems can be caused by outliers, leading to biased trade-offs, which in turn lead to major issues in policy analyses. This paper explores a different approach, making use of individual-specific draws from the random distributions, conditioned on the observed sequence of choices for each respondent. An analysis making use of Stated Preference data for airport and airline choice confirms the advantages of the approach using conditional draws, producing much more realistic distributional patterns for a range of willingness to pay indicators, including but not limited to the VTTS.
Gaining and maintaining commitment to large-scale change in healthcare organizations

Healthcare administrators have sought to improve the quality of healthcare services by using organizational change as a lever. Unfortunately, evaluations of organizational change efforts in areas such as total quality management (TQM), continuous quality improvement (CQI), and organizational restructuring have indicated that these change programmes have not fulfilled their promise in improving service delivery. Furthermore, there are no easy answers as to why so many large-scale change programmes are unsuccessful. The aim of this analysis is to provide insights into practices that may be utilized to improve the chances of successful change management. It is proposed that in order to effect change, implementers must first gain commitment to the change. This is done by ensuring organizational readiness for change, surfacing dissatisfaction with the present state, communicating a clear vision of the proposed change, promoting participation in the change effort, and developing a clear and consistent communication plan. However gaining commitment is not enough. Many change programmes have been initially perceived as being successful but long-term success has been elusive. Therefore, maintaining commitment during the uncertainty associated with the transition period is imperative. This can be done by successfully managing the transition using action steps such as consolidating change using feedback mechanisms and making the change a permanent part of the organization's culture.
Tuning DNA binding affinity and cleavage specificity of an engineered gene-targeting nuclease via surface display, flow cytometry and cellular analyses

The combination of yeast surface display and flow cytometric analyses and selections is being used with increasing frequency to alter specificity of macromolecular recognition, including both protein-protein and protein-nucleic acid interactions. Here we describe the use of yeast surface display and cleavage-dependent flow cytometric assays to increase the specificity of an engineered meganuclease. The re-engineered meganuclease displays a significantly tightened specificity profile, while binding its cognate target site with a slightly lower, but still sub-nanomolar affinity. When incorporated into otherwise identical megaTAL protein scaffolds, these two nucleases display significantly different activity and toxicity profiles in cellulo. The structural basis for reprogrammed DNA cleavage specificity was further examined via high-resolution X-ray crystal structures of both enzymes. This analysis illustrated the altered protein-DNA contacts produced by mutagenesis and selection, that resulted both in altered readout of those based and a necessary reduction in DNA binding affinity that were necessary to improve specificity across the target site. The results of this study provide an illustrative example of the potential (and the challenges) associated with the use of surface display and flow cytometry for the retargeting and optimization of enzymes that act on nucleic acid substrates in a sequence-specific manner.
Acute stress disrupts paired pulse facilitation and long‐term potentiation in rat dorsal hippocampus through activation of glucocorticoid receptors

Cognitive functions such as learning and memory are widely believed to depend on patterns of short‐ and long‐term synaptic plasticity. Factors, such as acute stress, which affect learning and memory, may do so by altering patterns of synaptic plasticity in distinct neural circuits. Numerous studies have examined the effects of acute stress on long‐term synaptic plasticity; however, few have examined its influence on short‐term plasticity. The present experiments directly assessed the effects of acute stress on short‐term synaptic plasticity as measured by paired pulse facilitation (PPF) of excitatory postsynaptic potentials recorded from rat dorsal hippocampus (dHip) in vivo. Long‐term potentiation (LTP) was also examined. Acute stress induced by exposure to an elevated platform impaired PPF and LTP in the dHip. Pretreatment of rats exposed to stress with mifepristone (RU38486; 10 mg kg−1) blocked the stress‐induced impairment of both PPF and LTP. These data demonstrate that activation of glucocorticoid receptors during acute stress disrupts normal patterns of both PPF and LTP in the dHip. © 2009 Wiley‐Liss, Inc.
MicroRNA‐375 promotes 3T3‐L1 adipocyte differentiation through modulation of extracellular signal‐regulated kinase signalling

1. Adipocyte hypertrophy and hyperplasia are important processes in the development of obesity. To understand obesity and its associated diseases, it is important to elucidate the molecular mechanisms governing adipogenesis. MicroRNA‐375 has been shown to inhibit differentiation of neurites, and participate in the regulation of insulin secretion and blood homeostasis. However, it is unknown whether miR‐375 plays a role in adipocyte differentiation.
Whole-Grain Fiber Composition Influences Site of Nutrient Digestion, Standardized Ileal Digestibility of Amino Acids, and Whole-Body Energy Utilization in Grower Pigs.

BACKGROUND Variant chemical composition and physical structure of whole grains may change the site of energy digestion from the small to the large intestine. OBJECTIVE We determined the site of nutrient digestion, standardized ileal digestibility (SID) of amino acids (AAs), and net energy (NE) value of barley cultivars that vary in nutrient composition compared with wheat. METHODS Ileal-cannulated barrows (27.7 kg initial body weight) were fed diets containing 800 g whole grains/kg alongside a basal and nitrogen-free diet for calculations in a 6 (period) × 7 (diet) Youden square. Diets included 1 of 5 whole grains-1) high-fermentable, high-β-glucan, hull-less barley (HFB); 2) high-fermentable, high-amylose, hull-less barley (HFA); 3) moderate-fermentable, hull-less barley (MFB); 4) low-fermentable, hulled barley (LFB); and 5) low-fermentable, hard red spring wheat (LFW). Intestine nutrient flow and whole-body energy utilization were tested and explained by using whole-grain and digesta confocal laser scanning. RESULTS Starch apparent ileal digestibility was 14-29% lower (P < 0.05) in HFB and HFA than in MFB, LFB, and LFW due to the unique embedding of starch within the protein-fiber matrix of HFB and the high amylose content in HFA. Starch hindgut fermentation was 50-130% higher (P < 0.05) in HFB and HFA than in MFB, LFB, and LFW. The SID of indispensable AAs was lower (P < 0.05) in HFB and HFA than in MFB, LFB, and LFW. NE value was 18% higher (P < 0.05) for HFB than for HFA and was not different from MFB, LFB, and LFW. CONCLUSIONS Whole grains high in fermentable carbohydrates shifted digestion from the small intestine to the hindgut. NE value depended on the concentration of fermentable fiber and starch and digestible protein, ranging from 2.12-1.76 Mcal/kg in barley to 1.94 Mcal/kg in wheat. High-fiber whole grains may be used as energy substrates for pigs; however, the reduced SID of AAs requires titration of indispensable AAs to maintain growth.
Tetrahydrobiopterin regulates monoamine neurotransmitter sulfonation

Significance Human cytosolic sulfotransferases (SULTs) regulate hundreds of signaling small molecules, yet little is known regarding their small-molecule regulation. Members of the SULT1 family harbor a conserved allosteric site that we hypothesize allows independent regulation of sulfonation in the 11 metabolic areas in which these isoforms operate. This hypothesis is validated using SULT1A3, which sulfonates and inactivates monoamine neurotransmitters. During validation it was discovered that tetrahydrobiopterin (THB), an essential cofactor in monoamine neurotransmitter biosynthesis, allosterically inhibits SULT1A3 with high affinity (Ki, 23 nM) and isozyme selectivity. Monoamine neurotransmitter metabolism shapes human behavior and social interactions and is a therapeutic target. These findings provide a paradigm for regulating sulfonation and a target for controlling neurotransmitter activity. Monoamine neurotransmitters are among the hundreds of signaling small molecules whose target interactions are switched “on” and “off” via transfer of the sulfuryl-moiety (–SO3) from PAPS (3′-phosphoadenosine 5′-phosphosulfate) to the hydroxyls and amines of their scaffolds. These transfer reactions are catalyzed by a small family of broad-specificity enzymes—the human cytosolic sulfotransferases (SULTs). The first structure of a SULT allosteric-binding site (that of SULT1A1) has recently come to light. The site is conserved among SULT1 family members and is promiscuous—it binds catechins, a naturally occurring family of flavanols. Here, the catechin-binding site of SULT1A3, which sulfonates monoamine neurotransmitters, is modeled on that of 1A1 and used to screen in silico for endogenous metabolite 1A3 allosteres. Screening predicted a single high-affinity allostere, tetrahydrobiopterin (THB), an essential cofactor in monoamine neurotransmitter biosynthesis. THB is shown to bind and inhibit SULT1A3 with high affinity, 23 (±2) nM, and to bind weakly, if at all, to the four other major SULTs found in brain and liver. The structure of the THB-bound binding site is determined and confirms that THB binds the catechin site. A structural comparison of SULT1A3 with SULT1A1 (its immediate evolutionary progenitor) reveals how SULT1A3 acquired high affinity for THB and that the majority of residue changes needed to transform 1A1 into 1A3 are clustered at the allosteric and active sites. Finally, sequence records reveal that the coevolution of these sites played an essential role in the evolution of simian neurotransmitter metabolism.
Assembly of U 7 Small Nuclear Ribonucleoprotein Particle and Histone RNA 3 * Processing in Xenopus Egg Extracts *

From the ‡Abteilung Entwicklungsbiologie, Zoologisches Institut, Universität Bern, Baltzerstrasse 4, CH 3012 Bern, Switzerland, the §Department of Molecular and Cell Biology, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, United Kingdom, and the iMedical Research Council Protein Phosphorylation Unit, Department of Biochemistry, The University of Dundee, Medical Sciences Institute, Dundee DD1 4HN, Scotland, United Kingdom
Risk Attitudes and Choice under Uncertainty: Experimental Evidence from Russia

This paper presents the results of one of the first experimental studies of individual choice in transitional Russia. The study is based on two standard types of experimental design: on risk attitudes via individual preferences over two-outcome lotteries, and on public good provision under voluntary contribution mechanism. By comparing preferences exhibited by 186 Moscow students to those observed elsewhere in the world, the author attempted to test claims that the Russian national character and/or years of socialist experience causes individual behavior to deviate from "normal" patterns. Both series of results turned out to be remarkably similar to the basic patterns exhibited in analogous studies abroad. However, public choice experiments showed that contribution rates typically increased in proportion to the share of female bidders in a group, a pattern that hasn't been observed in similar experiments in the other countries.
Interaction of Dietary and Genetic Factors Influencing Body Iron Status and Risk of Type 2 Diabetes Within the EPIC-InterAct Study

OBJECTIVE Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS The case-cohort comprised 9,347 case subjects and 12,301 subcohort participants from eight European countries. Single nucleotide polymorphisms (SNPs) were selected from genome-wide association studies on iron status biomarkers and candidate gene studies. A ferritin-related gene score was constructed. Multiplicative and additive interactions of heme iron and SNPs as well as the gene score were evaluated using Cox proportional hazards regression. RESULTS Higher heme iron intake (per 1 SD) was associated with higher ferritin levels (β = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (−0.019 [−0.043; 0.006]) or transferrin saturation (0.016 [−0.006; 0.037]). Five SNPs located in four genes (rs1799945 [HFE H63D], rs1800562 [HFE C282Y], rs236918 [PCK7], rs744653 [SLC40A1], and rs855791 [TMPRSS6 V736A]) were associated with ferritin. We did not detect an interaction of heme iron and the gene score on the risk of diabetes in the overall study population (Padd = 0.16, Pmult = 0.21) but did detect a trend toward a negative interaction in men (Padd = 0.04, Pmult = 0.03). CONCLUSIONS We found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.
Security technologies go phishing

In the computer industry, that usually means that when a problem arises, somebody figures out how to solve it and make money in the process. One of the latest computer-related problems to arise is phishing, in which e-mails lure unsuspecting victims into giving up user names, passwords, social security numbers, and account information after linking to counterfeit bank, credit card, and e-commerce Web sites. Organized crime frequently uses phishing. So far, phishers have hit only a small percentage of financial institutions $150 of 9,000 in the US - but the number is rising and attackers are targeting other industries, such as e-commerce. Nonetheless, major phishing incidents have already eroded consumer confidence in online banking. Banks and many other affected organizations are fighting phishing via public education. Some companies are using litigation. However, the focus for numerous companies is on antiphishing technology.
Supplementary Note S3 – Directional effects of translation differences within and between yeast species

For example, the authors of the two comparisons of the S. cerevisiae and S. paradoxus yeast species [1,2] examined the subset of TE genes that also had an mRNA difference. Within this subset, they compared the number of reinforced genes to the sum of the buffered, completely buffered and inverted genes, i.e. all cases where the translation difference opposes the mRNA difference (“opposing” genes). These analyses leave out “FP only” genes, although “FP only” genes and reinforced genes both increase the footprint difference relative to the mRNA difference (we call these two groups “increasing” genes). Further, it is not necessarily obvious that inverted genes should be grouped with the two “buffered” categories, because the absolute magnitude of the resulting difference in protein synthesis need not be smaller than the mRNA difference. Indeed, McManus et al. only included inverted genes in their set of opposing genes if the absolute footprint difference was smaller than the absolute mRNA difference [1].
What Do Patients Want from Otolaryngologists? A Discrete Choice Experiment

Objectives Patient preferences are crucial for the delivery of patient-centered care. Discrete choice experiments (DCEs) are an emerging quantitative methodology used for understanding these preferences. In this study, we employed DCE techniques to understand the preferences of patients presenting for an ear, nose, and throat clinic visit. Study Design DCE. Setting Decision science laboratory. Methods A DCE survey of 5 attributes—wait time, physician experience, physician personality, utilization of visit time, and cost/copayment—was constructed with structured qualitative interviews with patients. The DCE was administered to participants from the general population, who chose among hypothetical scenarios that varied across these attributes. A conditional logit model was used to determine relative attribute importance, with a separate logit model for determining subject effects. Results A total of 161 participants were included. Cost/copayment had the greatest impact on decision making (importance, 32.2%), followed by wait time and physician experience (26.5% and 24.7%, respectively). Physician personality mattered least (4.7%), although all attributes were significantly correlated to decision making. Participants preferred doctors who spent more time performing physical examination than listening or explaining. Participants were willing to pay $52 extra to avoid a 4-week delay in appointment time; $87 extra for a physician with 10 years of experience (vs 0 years); and $9 extra for a caring, friendly, and compassionate doctor (vs formal, efficient, and business-like). Conclusion DCEs allow for powerful economic analyses that may help physicians understand patient preferences. Our model showed that cost is an important factor to patients and that patients are willing to pay extra for timely appointments, experience, and thorough physical examination.
Understanding the term structure of interest rates: the expectations theory

nil S. HE INTERES’r RATES on loans and securities provide basic summary measures of their attractiveness to lenders. The role played by interest rates in allocating funds across financial markets is very similar to the role played by prices in allocating resources in markets for goods and services. Just as a relatively high price of a particular good tends to draw physical resources into its production, a relatively high interest rate on a particular type of security tends to draw funds into the activities that type of security is issued to finance. And just as identifying the factors that help determine prices is a key area of inquiry among economists who study goods markets, identifying the factors that help determine interest rates is a key area of inquiry for those who study financial markets.
Contingent Valuation Methods: Possibilities and Problems

Valuation of external costs created from transport is important to undertake in order to improve the decision-making basis for transport policy. In particular, this information could be utilised with respect to policy measures for the internalisation of external costs as well as with respect to appraisal of specific transport investment projects. A number of methods towards the valuation of external costs have appeared in recent years in parallel with the increased awareness about the environmental problems created by transport. These methods include approaches based on assessing the resources required to reduce the costs as well as utility-based approaches. In particular, the so-called contingent valuation method has been put forward as a way to determine the willingness to pay for various environmental goods/functions for a sample of individuals. This method has been applied in a wide range of empirical context in the last two decades. This paper will provide a critical assessment of contingent valuation methods. In particular, the paper will consider the theoretical and empirical possibilities and problems provided by this method. The paper will include the following sections. Section 1 will identify the need to valuate external costs. In section 2 an overview of contingent valuation methods will be given. This will be followed in section 3 by an examination of the possibilities and problems involved in this method. Section 4 concludes with final remarks and suggestions for further research to improve the method.
An improved software reliability model incorporating detection process and the total number of faults

Software reliability growth models base on the NHPP are quite successful tools that have been proposed to assess the software reliability. Various NHPP-SRGMs have been built upon various assumptions such as the number of remaining faults, software failure rate, and software reliability. But in realistic, the number of faults and the detection rate are not constants. They are time functions. In this paper, we aim to incorportate total number function of faults and detection rate function into conditional SRGMs. Experimental results indicate that the new model which proposed in this paper has a fairly accurate prediction capability.