Miracle-dz/UniFAR-FTUs huggingface dataset:
Absence of an Unusual “Densely Methylated Island” at the Hamster dhfr ori-β*

An unusual “densely methylated island” (DMI), in which all cytosine residues are methylated on both strands for 127-516 base pairs, has been reported at mammalian origins of DNA replication. This report had far-reaching implications in understanding of DNA methylation and DNA replication. For example, since this DMI appeared in about 90% of proliferating cells, but not in stationary cells, it may regulate origin activation. In an effort to confirm and extend these observations, the DMI at the well characterized ori-β locus 17 kilobases downstream of the dhfr gene in chromosomes of Chinese hamster ovary cells was checked for methylated cytosines in genomic DNA. The methylation status of this region was examined in randomly proliferating and stationary cells and in cell populations enriched in the G1, S, or G2 + M phases of their cell division cycle. DNA was subjected to 1) cleavage by methylation-sensitive restriction endonucleases, 2) hydrazine modification of cytosines followed by piperidine cleavage, and 3) permanganate modification of 5-methylcytosines (mC) followed by piperidine cleavage. The permanganate reaction is a novel method for direct detection of mC residues that complements the more commonly used hydrazine method. These methods were capable of detecting mC in 2% of the cells. At the region of the proposed DMI, only one mC at a CpG site was detected. However, the ori-β DMI was not detected in any of these cell populations using any of these methods.
Cooperative folding mechanism of a β‐hairpin peptide studied by a multicanonical replica‐exchange molecular dynamics simulation

G‐peptide is a 16‐residue peptide of the C‐terminal end of streptococcal protein G B1 domain, which is known to fold into a specific β‐hairpin within 6 μs. Here, we study molecular mechanism on the stability and folding of G‐peptide by performing a multicanonical replica‐exchange (MUCAREM) molecular dynamics simulation with explicit solvent. Unlike the preceding simulations of the same peptide, the simulation was started from an unfolded conformation without any experimental information on the native conformation. In the 278‐ns trajectory, we observed three independent folding events. Thus MUCAREM can be estimated to accelerate the folding reaction more than 60 times than the conventional molecular dynamics simulations. The free‐energy landscape of the peptide at room temperature shows that there are three essential subevents in the folding pathway to construct the native‐like β‐hairpin conformation: (i) a hydrophobic collapse of the peptide occurs with the side‐chain contacts between Tyr45 and Phe52, (ii) then, the native‐like turn is formed accompanying with the hydrogen‐bonded network around the turn region, and (iii) finally, the rest of the backbone hydrogen bonds are formed. A number of stable native hydrogen bonds are formed cooperatively during the second stage, suggesting the importance of the formation of the specific turn structure. This is also supported by the accumulation of the nonnative conformations only with the hydrophobic cluster around Tyr45 and Phe52. These simulation results are consistent with high ϕ‐values of the turn region observed by experiment. Proteins 2007. © 2006 Wiley‐Liss, Inc.
The effects of pictures, review credibility and personalization on users satisfaction of using restaurant recommender apps: Case study: Zomato dan qraved

This study aims to determine the effects of pictures, reviews credibility and personalization feature on users' satisfaction in accessing restaurant recommender apps. This study uses a quantitative approach with a total of 419 collected respondents. The data gathered within this study is being analyzed using multiple regressions using SPSS 22.0. The results of this study indicate that pictures and reviews credibility are affecting user satisfaction on using restaurant recommender apps. Additionally, providing personalization on a restaurant recommender apps may also improve its user satisfaction in accessing the apps.
Physical association between STAT1 and the interferon‐inducible protein kinase PKR and implications for interferon and double‐stranded RNA signaling pathways

The interferon‐inducible double‐stranded RNA protein kinase PKR controls protein synthesis through the phosphorylation of eukaryotic translation initiation factor (eIF)‐2. In addition to its demonstrated role in translational control, several reports have suggested a transcriptional role for PKR. Here we report that PKR is involved in IFN‐ and dsRNA‐signaling pathways by modulating the function of the signal transducer and activator of transcription STAT1. We also show that PKR associates with STAT1 in mouse and human cells. The association is not a kinase–substrate interaction since STAT1 phosphorylation is not modified by PKR in vitro or in vivo. In addition, the formation of the PKR–STAT1 complex is not dependent upon the enzymatic activity of PKR but does require the dsRNA‐binding domain of PKR. Moreover, there is a concomitant decrease in PKR–STAT1 interaction and increase in STAT1 DNA binding in response to IFNs or dsRNA. These findings suggest that PKR plays an important role in IFN and dsRNA‐signaling pathways by modulating the transcriptional function of STAT1.
Effects of tyrphostins, protein kinase inhibitors, on human immunodeficiency virus type 1 integrase.

Efficient replication of HIV-1 requires establishment of the proviral state, i.e., the integration of a DNA copy of the viral genome, synthesized by reverse transcriptase, into a chromosome of the host cell. Integration is catalyzed by the viral integrase protein. We have previously reported that phenolic moieties in compounds such as napthoquinones, flavones, caffeic acid phenethyl ester (CAPE), and curcumin confer inhibitory activity against HIV-1 integrase. We have extended these findings by examining the effects of tryphostins, tyrosine kinase inhibitors. The catalytic activities of HIV-1 integrase and the formation of enzyme-DNA complexes using photocross-linking were examined. Both steps of the integration reaction, 3'-processing and strand transfer, were inhibited by tyrphostins at micromolar concentrations. The DNA binding activity of integrase was inhibited at higher concentrations of tryphostins. Disintegration, an apparent reversal of the strand transfer reaction, catalyzed by an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA binding domains is also inhibited by tyrphostins, indicating that the binding site for these compounds resides in the central catalytic core of HIV-1 integrase. Binding of tyrphostins at or near the integrase catalytic site was also suggested by experiments showing a global inhibition of the choice of attacking nucleophile in the 3'-processing reaction. None of the tryphostins tested inhibited eukaryotic topoisomerase I, even at 100 microM, suggesting selectivity for integrase inhibition. Molecular-modeling studies have revealed that, after energy minimization, several tyrphostins may adopt folded conformations. The similarity of the tyrphostin family to other families of inhibitors is discussed. Tyrphostins may provide lead compounds for development of novel antiviral agents for the treatment of acquired immunodeficiency syndrome based upon inhibition of HIV-1 integrase.
A decade's experience with balloon catheter tamponade for the emergency control of hemorrhage.

BACKGROUND Balloon catheter tamponade is a valuable technique for arresting exsanguinating hemorrhage. Indications include (1) inaccessible major vascular injuries, (2) large cardiac injuries, and (3) deep solid organ parenchymal bleeding. Published literature is limited to small case series. The primary goal was to review a recent experience with balloon catheter use for emergency tamponade in a civilian trauma population. METHODS All patients requiring emergency use of a balloon catheter to tamponade exsanguinating hemorrhage (1998-2009) were included. Patient demographics, injury characteristics, technique, and outcomes were analyzed. RESULTS Of the 44 severely injured patients (82% presented with hemodynamic instability; mean base deficit=-20.4) who required balloon catheter tamponade, 23 of the balloons (52%) remained indwelling for more than 6 hours. Overall mortality depended on the site of injury/catheter placement and indwelling time (81% if <6 hours; 52% if ≥6 hours; p<0.05). Physiologic exhaustion was responsible for 76% of deaths in patients with short-term balloons. Mortality among patients with prolonged balloon catheter placement was 11%, 50%, and 88% for liver, abdominal vascular, and facial/pharyngeal injuries, respectively. Mean indwelling times for iliac, liver, and carotid injuries were 31 hours, 53 hours, and 78 hours, respectively. Overall survival rates were 67% (liver), 67% (extremity vascular), 50% (abdominal vascular), 38% (cardiac), and 8% (face). Techniques included Foley, Fogarty, Blakemore, and/or Penrose drains with concurrent red rubber Robinson catheters. Initial tamponade of bleeding structures was successful in 93% of patients. CONCLUSIONS Balloon catheter tamponade can be used in multiple anatomic regions and for variable patterns of injury to arrest ongoing hemorrhage. Placement for central hepatic gunshot wounds is particularly useful. This technique remains a valuable tool in a surgeon's armamentarium.
Agent based modeling for H1N1 influenza in artificial campus

Agent based artificial society is a new method to analyze and predict complex and emergency events. This artificial tried to use agent based method to build up an artificial campus with agents roles from the bottom up, and to study H1N1 influenza case in it. Firstly, a conceptual architecture of artificial society system was proposed which was divided into three meta models: environment, agent and region models. Secondly, an artificial campus was built up under the background of H1N1 influenza spreading rules, and five kinds of agents in campus were characterized. Finally, the interactions among agent with agent, and agents with environment were analyzed, characterized and modeled, and the social networks were also considered in this model.
Embodied Minds, Restless Spirits: Mid-Life Rural Women Speak of Their Health

ABSTRACT This manuscript explores mid-life women's views of corporeality and the links that these have to their health. Using ethnographic interview techniques, community based interviewers talked with 24 women from rural settings. Our findings suggest that mid-life women have an embodied view of their minds and spirits, and that dualism is generally reserved for thinking about and interacting with the bio-medical system. They have a sense of themselves as unique individuals who have a large role in caregiving, multiple other roles, and have luck but also agency in and control of their health and well-being. Motion was a strong theme throughout the interviews. Women embraced this mobility as a characteristic of their well-being as they coped with multiple changes associated with mid-life. In contrast to what some philosophers maintain, women seem to partner both corporeal changes and metaphor. While the sample was limited in scope, the findings support the importance to women's health of understanding the intersections between compositional and contextual variables in various settings.
Clinical interpretation of CNVs with cross-species phenotype data

Background Clinical evaluation of CNVs identified via techniques such as array comparative genome hybridisation (aCGH) involves the inspection of lists of known and unknown duplications and deletions with the goal of distinguishing pathogenic from benign CNVs. A key step in this process is the comparison of the individual's phenotypic abnormalities with those associated with Mendelian disorders of the genes affected by the CNV. However, because often there is not much known about these human genes, an additional source of data that could be used is model organism phenotype data. Currently, almost 6000 genes in mouse and zebrafish are, when knocked out, associated with a phenotype in the model organism, but no disease is known to be caused by mutations in the human ortholog. Yet, searching model organism databases and comparing model organism phenotypes with patient phenotypes for identifying novel disease genes and medical evaluation of CNVs is hindered by the difficulty in integrating phenotype information across species and the lack of appropriate software tools. Methods Here, we present an integrated ranking scheme based on phenotypic matching, degree of overlap with known benign or pathogenic CNVs and the haploinsufficiency score for the prioritisation of CNVs responsible for a patient's clinical findings. Results We show that this scheme leads to significant improvements compared with rankings that do not exploit phenotypic information. We provide a software tool called PhenogramViz, which supports phenotype-driven interpretation of aCGH findings based on multiple data sources, including the integrated cross-species phenotype ontology Uberpheno, in order to visualise gene-to-phenotype relations. Conclusions Integrating and visualising cross-species phenotype information on the affected genes may help in routine diagnostics of CNVs.
Hypertonic saline resuscitation prevents hydrostatically induced intestinal edema and ileus

Objective:We have shown that acute edema induced by mesenteric venous hypertension (MV-HTN) impairs intestinal transit and reduces the standardized engineering measures of intestinal stiffness (elastic modulus) and residual stress (opening angle). We hypothesized that hypertonic saline (7.5%) would reverse these detrimental effects of acute edema. Design:Laboratory study. Setting:University laboratory. Subjects:Male Sprague Dawley rats (270–330 g). Interventions:Rats were randomized to five groups: sham, MV-HTN alone, MV-HTN with 4 mL/kg normal saline resuscitation (equal volume), MV-HTN with 33 mL/kg normal saline resuscitation (equal salt), and MV-HTN with 4 mL/kg hypertonic saline. Intestinal edema was measured by wet to dry tissue weight ratio. A duodenal catheter was placed and, 30 mins before death, fluorescein isothiocyanate Dextran was injected. At death, dye concentrations were measured to determine intestinal transit. Segments of distal ileum were hung to a fixed point in a tissue bath and to a force displacement transducer and stretched in increments of 1 mm; we recorded the new length and the corresponding force from the force displacement transducer to determine elastic modulus. Next, two transverse cuts were made yielding a 1- to 2-mm thick ring-shaped segment of tissue which was then cut radially to open the ring. Then the opening angle was measured. Measurements and Main Results:MV-HTN, MV-HTN with 4 mL/kg normal saline, and MV-HTN with 33 mL/kg normal saline caused a significant increase in tissue edema and a significant decrease in intestinal transit, stiffness, and residual stress compared with sham. Hypertonic saline significantly lessened the effect of edema on intestinal transit and prevented the changes in stiffness and residual stress. Conclusions:Hypertonic saline prevented intestinal tissue edema. In addition, hypertonic saline improved intestinal transit, possibly through more efficient transmission of muscle force through stiffer intestinal tissue.
Effects of a problem-based learning rehabilitation program on physical activity in patients with coronary artery disease.

PURPOSE To evaluate the effects of a problem-based learning (PBL) rehabilitation program on physical activity. METHODS We randomized 207 consecutive patients younger than 70 years, with a recent event of coronary artery disease (CAD), to a PBL group (n = 104) or a control group (n = 103). In addition to standard treatment, the PBL patients participated in a 1-year program with 13 sessions in small groups, where learning needs and behavior change were focused upon. Physical activity was assessed by means of interviews with all patients and by an activity monitor in 69 patients at pretest and in 175 after 1 year. RESULTS Only small differences between groups were found at posttest. Interview data revealed significantly less activity at low-intensity level in the control group, whereas the activity monitor showed no significant differences. No changes were found in total physical activity during the year within the 2 groups. The self-reported physical activity indicating a level of brisk walking was markedly higher than that measured by the activity monitor, the latter indicating that only 35% of the patients achieved a 10-minute period of continued physical activity per day on an adequate level. CONCLUSIONS Our PBL program had no important impact on the physical activity pattern of patients with CAD. The activity monitor is a feasible way of measuring physical activity in these patients, indicating a lower level of physical activity than interview data.
Nucleosomes are positioned with base pair precision adjacent to the alpha 2 operator in Saccharomyces cerevisiae.

Analysis of the chromatin structure of minichromosomes containing the binding site for the yeast alpha 2 repressor protein by indirect end‐labeling has previously indicated that nucleosomes are stably positioned over sequences adjacent to the alpha 2 operator in the presence of the repressor. Development of a primer extension assay for nucleosome position now allows a more detailed examination of the location of these nucleosomes relative to the operator sequence, and indicates that nucleosomes are precisely and stably positioned both translationally and rotationally over sequences adjoining the operator. In addition, this assay enables analysis of the chromatin structure of single copy, genomic sequences. Chromatin structures determined for two genes regulated by alpha 2, STE6 and BAR1, are consistent with nucleosomes precisely positioned downstream of the operator sequence, incorporating promoter elements, in alpha cells but not in a‐cells. The location of these nucleosomes relative to the operator sequence is highly analogous to that observed in the minichromosome. The stability of the nucleosomes adjacent to the operator together with the precision of their location suggests that they may play a role in repression of a specific gene expression by alpha 2. Further, the primer extension assay allows a comparison of the structure of these positioned nucleosomes formed in vivo to that previously described for core particles reconstituted in vitro.
Artemisia tilesii Ledeb hairy roots establishment using Agrobacterium rhizogenes-mediated transformation

ABSTRACT An efficient and rapid protocol for the establishment of Artemisia tilesii “hairy” root culture is reported. Leaf explants of aseptically growing plants were cocultured with Agrobacterium rhizogenes A4 wild strain or A. rhizogenes carrying the plasmids with nptII and ifn-α2b genes. Root formation on the explants started in 5–6 days after their cocultivation with bacterial suspension. Prolongation of explant cultivation time on the medium without cefotaxime led to stimulation of root growth. The effects of sucrose concentration as well as of the levels of synthetic indole-3-butyric acid (IBA) and native growth regulator Emistim on the stimulation of A. tilesii “hairy” root growth were studied. Maximum stimulating effect both for the control and for transgenic roots was observed in case of root cultivation on the media supplemented with IBA—up to 7.95- and 9.1-fold biomass increase, respectively. Cultivation on the medium with 10 μl/L Emistime has also led to the control roots growth stimulation (up to 2.75-fold). Emistime at 5 μl/L concentration led to 5.46-fold mass increase in only one “hairy” root line. Higher sucrose content (40 g/L) stimulated growth of two hairy root lines but had no effect on growth of the control roots.
PKC-Dependent Stimulation of Exocytosis by Sulfonylureas in Pancreaticβ Cells

Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic β cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (KATP channels) in the β cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane KATP channels. This effect was dependent on protein kinase C (PKC) and was observed at therapeutic concentrations of sulfonylureas, which suggests that it contributes to their hypoglycemic action in diabetics.
Use of transthoracic bioimpedance to determine cardiac output in pediatric patients.

The use of a transthoracic bioimpedance monitor to determine cardiac output was evaluated in critically ill children. The children ranged in age from 10 months to 8 yr and their height and weight ranged from the third to the 97th percentile. Each child had a thermodilution catheter in place to monitor cardiac output. The bioimpedance monitor used in this study, the NCCOM-3, required the input of a constant (L), which was obtained for each individual patient by adjusting the L setting until cardiac output measured by bioimpedance (COBI) was within 10% of cardiac output measured by thermodilution (COTD). This method of determining L was superior to using either measured thoracic length or the manufacturer's guidelines to obtain L and resulted in an excellent correlation between COTD and COBI (r = .94; p less than .05; n = 59). In children less than 125 cm in height, measured thoracic length alone was inadequate to use for L but provided a good approximation of L when multiplied by 1.25. This study suggests that the use of transthoracic bioimpedance to determine cardiac output compares favorably with thermodilution techniques and it is noninvasive.
The evolution of micro-cursoriality in mammals

In this study we report on the evolution of micro-cursoriality, a unique case of cursoriality in mammals smaller than 1 kg. We obtained new running speed and limb morphology data for two species of elephant-shrews (Elephantulus spp., Macroscelidae) from Namaqualand, South Africa, which we compared with published data for other mammals. Elephantulus maximum running speeds were higher than those of most mammals smaller than 1 kg. Elephantulus also possess exceptionally high metatarsal:femur ratios (1.07) that are typically associated with fast unguligrade cursors. Cursoriality evolved in the Artiodactyla, Perissodactyla and Carnivora coincident with global cooling and the replacement of forests with open landscapes in the Oligocene and Miocene. The majority of mammal species, though, remained non-cursorial, plantigrade and small (<1 kg). The extraordinary running speed and digitigrady of elephant-shrews was established in the Early Eocene in the earliest macroscelid Prodiacodon, but was probably inherited from Paleocene, Holarctic stem macroscelids. Micro-cursoriality in macroscelids evolved from the plesiomorphic plantigrade foot of the possum-like ancestral mammal earlier than in other mammalian crown groups. Micro-cursoriality evolved first in forests, presumably in response to selection for rapid running speeds facilitated by local knowledge, in order to avoid predators. During the Miocene, micro-cursoriality was pre-adaptive to open, arid habitats, and became more derived in the newly evolved Elephantulus and Macroscelides elephant-shrews with trail running.