Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated in vivo and in vitro nascent chain profiling reveals widespread translational pausing

Significance The synthesis of a protein takes tens of seconds to a few minutes, in which amino acids are polymerized linearly. Nonuniform progression of this elongation process is thought to be important for the subsequent fates of newly synthesized proteins. However, there have been few attempts to profile elongation intermediates, polypeptidyl–tRNAs, directly. Here we attempted to detect systematically the accumulation of tRNA-linked nascent chain intermediates during the translation of Escherichia coli proteins in vivo and in vitro. The results revealed the widespread occurrence of translational pausing in a manner correlated with the subcellular localization and solubility properties of proteins. Our in vivo/in vitro integrated nascent chain profiling provides groundwork information for our understanding of genetic message translation into functional proteins. Although the importance of the nonuniform progression of elongation in translation is well recognized, there have been few attempts to explore this process by directly profiling nascent polypeptides, the relevant intermediates of translation. Such approaches will be essential to complement other approaches, including ribosome profiling, which is extremely powerful but indirect with respect to the actual translation processes. Here, we use the nascent polypeptide's chemical trait of having a covalently attached tRNA moiety to detect translation intermediates. In a case study, Escherichia coli SecA was shown to undergo nascent polypeptide-dependent translational pauses. We then carried out integrated in vivo and in vitro nascent chain profiling (iNP) to characterize 1,038 proteome members of E. coli that were encoded by the first quarter of the chromosome with respect to their propensities to accumulate polypeptidyl–tRNA intermediates. A majority of them indeed undergo single or multiple pauses, some occurring only in vitro, some occurring only in vivo, and some occurring both in vivo and in vitro. Thus, translational pausing can be intrinsically robust, subject to in vivo alleviation, or require in vivo reinforcement. Cytosolic and membrane proteins tend to experience different classes of pauses; membrane proteins often pause multiple times in vivo. We also note that the solubility of cytosolic proteins correlates with certain categories of pausing. Translational pausing is widespread and diverse in nature.
Analysis of Traffic and Meteorology on Airborne Particulate Matter in Münster, Northwest Germany

Abstract The importance of street traffic and meteorological conditions on the concentrations of particulate matter (PM) with an aerodynamic diameter smaller than 10 μm (PM10) was studied in the city of Münster in northwest Germany. The database consisted of meteorological data, data of PM10 mass concentrations and fine particle number (6–225 nm diameter) concentrations, and traffic intensity data as counted with tally hand counters at a four- to six-lane road. On working days, a significant correlation could be found between the diurnal mean PM10 mass concentration and vehicle number. The lower number of heavy-duty vehicles compared with passenger cars contributed more to the particle number concentration on working days than on weekend days. On weekends, when the vehicle number was very low, the correlation between PM10 mass concentration and vehicle number changed completely. Other sources of PM and the meteorology dominated the PM concentration. Independent of the weekday, by decreasing the traffic by approximately 99% during late-night hours, the PM10 concentration was reduced by 12% of the daily mean value. A correlation between PM10 and the particle number concentration was found for each weekday. In this study, meteorological parameters, including the atmospheric stability of the boundary layer, were also accounted for. The authors deployed artificial neural networks to achieve more information on the influence of various meteorological parameters, traffic, and the day of the week. A multilayer perceptron network showed the best results for predicting the PM10 concentration, with the correlation coefficient being 0.72. The influence of relative humidity, temperature, and wind was strong, whereas the influence of atmospheric stability and the traffic parameters was weak. Although traffic contributes a constant amount of particles in a daily and weekly cycle, it is the meteorology that drives most of the variability.
Stabilization of Nontoxic Aβ-Oligomers: Insights into the Mechanism of Action of Hydroxyquinolines in Alzheimer's Disease

The extracellular accumulation of amyloid β (Aβ) peptides is characteristic of Alzheimer's disease (AD). However, formation of diffusible, oligomeric forms of Aβ, both on and off pathways to amyloid fibrils, is thought to include neurotoxic species responsible for synaptic loss and neurodegeneration, rather than polymeric amyloid aggregates. The 8-hydroxyquinolines (8-HQ) clioquinol (CQ) and PBT2 were developed for their ability to inhibit metal-mediated generation of reactive oxygen species from Aβ:Cu complexes and have both undergone preclinical and Phase II clinical development for the treatment of AD. Their respective modes of action are not fully understood and may include both inhibition of Aβ fibrillar polymerization and direct depolymerization of existing Aβ fibrils. In the present study, we find that CQ and PBT2 can interact directly with Aβ and affect its propensity to aggregate. Using a combination of biophysical techniques, we demonstrate that, in the presence of these 8-HQs and in the absence of metal ions, Aβ associates with two 8-HQ molecules and forms a dimer. Furthermore, 8-HQ bind Aβ with an affinity of 1–10 μm and suppress the formation of large (>30 kDa) oligomers. The stabilized low molecular weight species are nontoxic. Treatment with 8-HQs also reduces the levels of in vivo soluble oligomers in a Caenorhabditis elegans model of Aβ toxicity. We propose that 8-HQs possess an additional mechanism of action that neutralizes neurotoxic Aβ oligomer formation through stabilization of small (dimeric) nontoxic Aβ conformers.
Simulated home delivery in hospital: a randomised controlled trial

Objectives To compare the outcome of two methods of maternity care during the antenatal period and at delivery. One was to be midwife‐led for both antenatal care and delivery, the latter taking place in rooms similar to those in one's own home to simulate home confinement. The other would be consultant‐led with the mothers labouring in the delivery suite rooms with resuscitation equipment for both mother and baby in evidence, monitors present and a delivery bed on which both anaesthetic and obstetric procedures could be easily and safely carried out.
Tooth Discoloration after Regenerative Endodontic Therapy

Introduction: The American Association of Endodontists clinical considerations for regenerative therapy (April 2015) advise of the risk of the possible adverse effect of staining of teeth. It is widely acknowledged that before these guidelines were developed there was no standardized protocol for regenerative therapy, and different approaches using different materials have been reported. The purpose of this review was to undertake a systematic review of published cases to determine the incidence of reported discoloration and examine whether there was any particular association with any material.Methods: A PubMed search was performed using key words for regenerative endodontic therapy consistent with prior published systematic reviews. Results: There were 80 studies identified with 379 teeth treated. Many of the studies did not report on the presence or absence of discoloration. It was noted that there was a strong association of discoloration with the use of triple antibiotic paste containing minocycline; however, discoloration was also noted when other materials were used. Unfortunately, bleaching of stained teeth was not predictably achieved in some studies. Conclusions: The use of triple antibiotic paste with minocycline as the intracanal medicament should be reconsidered. Either calcium hydroxide or the double antibiotic paste of metronidazole and ciprofloxacin may limit discoloration. Mineral trioxide aggregate was also associated with discoloration. However, there is little evidence of an alternative superior material as a coronal barrier. Because discoloration is a patientorientated outcome, further research should document and identify the incidence of discoloration in regenerative endodontic treatment. (J Endod 2016;42:563–569)
Impaired Itching Perception in Murine Models of Cholestasis Is Supported by Dysregulation of GPBAR1 Signaling

Background & Aims In cholestatic syndromes, body accumulation of bile acids is thought to cause itching. However, the mechanisms supporting this effect remain elusive. Recently, GPBAR1 (TGR5) a G-protein coupled receptor has been shown to mediate itching caused by intradermal administration of DCA and LCA. 6α-ethyl-3α, 7α-dihydroxy-24-nor-5β-cholan-23-ol (BAR502) is a non-bile acid dual ligand for FXR and GPBAR1. Methods Cholestasis was induced in wild type and GPBAR1-/- mice by administration of α-naphthyl-isothiocyanate (ANIT) or 17α-ethynylestradiol. Results. In naïve mice skin application of DCA, TLCA, 6-ECDCA, oleanolic and betulinic acid induces a GPBAR1 dependent pruritogenic response that could be desensitized by re-challenging the mice with the same GPBAR1 agonist. In wild type and GPBAR1-/- mice cholestasis induced by ANIT fails to induce spontaneous itching and abrogates scratching behavior caused by intradermal administration of DCA. In this model, co-treatment with BAR502 increases survival, attenuates serum alkaline phosphatase levels and robustly modulates the liver expression of canonical FXR target genes including OSTα, BSEP, SHP and MDR1, without inducing pruritus. Betulinic acid, a selective GPBAR1 ligand, failed to rescue wild type and GPBAR1-/- mice from ANIT cholestasis but did not induced itching. In the 17α-ethynylestradiol model BAR502 attenuates cholestasis and reshapes bile acid pool without inducing itching. Conclusions The itching response to intradermal injection of GPBAR1 agonists desensitizes rapidly and is deactivated in models of cholestasis, explain the lack of correlation between bile acids levels and itching severity in cholestatic syndromes. In models of non-obstructive cholestasis, BAR502 attenuates liver injury without causing itching.
Motor and Cognitive Sequelae of Unilateral Pallidotomy in Intractable Parkinson's Disease: Electronic Measurement of Motor Steadiness is a Useful Outcome Measure

This study examined the short-term motor and cognitive sequelae of unilateral posterolateral pallidotomy for patients with intractable Parkinson's Disease (PD). Unique to this study was the inclusion of electronic motor steadiness instrumentation among pre- and postsurgical assessment procedures. Fifteen PD patients underwent right-sided surgery and 10 underwent left-sided surgery; patients were evaluated 1 month presurgery and approximately 3 months postsurgery. Motorically, there were no significant changes in grooved pegboard or maze-drawing performances, but patients evidenced significantly improved steadiness, particularly in the hand contralateral to the side of surgery. Cognitively, there were no significant decrements on postsurgery composite variables comprised of well-known tests of attention, executive functioning, delayed memory or recognition memory; these findings were similar for patients with either left- or right-sided surgery. There was, however, a significant change in language abilities among a subset of patients. This change was evident in the decline in verbal fluency in PD patients who underwent left-sided pallidotomy, a finding that has consistently emerged in pallidotomy outcome studies. This decline is discussed in terms of evidence that suggests that the basal ganglia consist of several separate, but parallel circuits, some of which are important for cognition.
Genomic Comparison of Escherichia coli O104:H4 Isolates from 2009 and 2011 Reveals Plasmid, and Prophage Heterogeneity, Including Shiga Toxin Encoding Phage stx2

In May of 2011, an enteroaggregative Escherichia coli O104:H4 strain that had acquired a Shiga toxin 2-converting phage caused a large outbreak of bloody diarrhea in Europe which was notable for its high prevalence of hemolytic uremic syndrome cases. Several studies have described the genomic inventory and phylogenies of strains associated with the outbreak and a collection of historical E. coli O104:H4 isolates using draft genome assemblies. We present the complete, closed genome sequences of an isolate from the 2011 outbreak (2011C–3493) and two isolates from cases of bloody diarrhea that occurred in the Republic of Georgia in 2009 (2009EL–2050 and 2009EL–2071). Comparative genome analysis indicates that, while the Georgian strains are the nearest neighbors to the 2011 outbreak isolates sequenced to date, structural and nucleotide-level differences are evident in the Stx2 phage genomes, the mer/tet antibiotic resistance island, and in the prophage and plasmid profiles of the strains, including a previously undescribed plasmid with homology to the pMT virulence plasmid of Yersinia pestis. In addition, multiphenotype analysis showed that 2009EL–2071 possessed higher resistance to polymyxin and membrane-disrupting agents. Finally, we show evidence by electron microscopy of the presence of a common phage morphotype among the European and Georgian strains and a second phage morphotype among the Georgian strains. The presence of at least two stx2 phage genotypes in host genetic backgrounds that may derive from a recent common ancestor of the 2011 outbreak isolates indicates that the emergence of stx2 phage-containing E. coli O104:H4 strains probably occurred more than once, or that the current outbreak isolates may be the result of a recent transfer of a new stx2 phage element into a pre-existing stx2-positive genetic background.
The enumeration and transformation of dislocation dipoles II. The transformation of interstitial dipoles into vacancy dipoles in an open dislocation array

If the presence of crystal surfaces permits some of the dipole content of a dislocation array to leave the crystal to form intrusions or extrusions on the surface, then the dipole strength of the array, as defined in part I, can change by glide processes. It is confirmed that the energy difference between vacancy and interstitial dipoles of equal height due to nonlinear elasticity is a possible cause of the conversion of interstitial dipoles to vacancy dipoles by slip, with the consequent production of extrusions at the crystal surface. The energy difference increases with decreasing dipole height and may account for the observed preponderance of small vacancy dipoles. However, the gain in energy resulting from the conversion of interstitial dipoles to vacancy dipoles is offset by long-range elastic energy stored in the field of the ‘fibre stress’—the average tensile stress in the band resulting from the bias. This leads to an equilibrium bias in dipole population and causes the fibre stress to increase as cyclic straining reduces the height of the dipoles.
Concordance of risk factors in female spouses of male patients with coronary heart disease.

PURPOSE Shared environment may put marital partners at increased risk for coronary heart disease (CHD). In this study, the authors examined the degree of concordance of risk factors between men with CHD (n = 177) and their spouses, and described the risk profiles of both patients and spouses. Risk factors examined were smoking, hypertension, obesity, cholesterol level, diet, and exercise. METHODS Data were collected 2 months after the cardiac event using the Behavioral Risk Factor Surveillance System tool. Concordance between patient and spouse pairs was evaluated using Pearson correlation coefficients (r) for continuous data and phi coefficients (phi) for nominal data. RESULTS Significant concordance was found between patient and spouse pairs for body mass index, history of smoking, current smoking status, frequency of exercise, miles per exercise session, and the amount of fat and fiber in the diet. There was no significant spousal concordance in relation to the diagnosis of hypertension, systolic and diastolic blood pressure (BP), cholesterol level, history of high cholesterol, current exercise program, duration of exercise, and amount of salt in the diet. Thus, although the physiological indicators of risk (e.g., BP) were not significantly related among marital partners, behavioral indicators of risk (e.g., smoking) were significantly related. CONCLUSIONS The findings suggested that shared lifestyles of marital partners may result in greater risk of CHD for female partners of men with CHD. Furthermore, lifestyle interventions that specifically target the marital partners as a unit may be more efficacious than individual patient education strategies.
Feature Extraction by Non-Parametric Mutual Information Maximization

We present a method for learning discriminative feature transforms using as criterion the mutual information between class labels and transformed features. Instead of a commonly used mutual information measure based on Kullback-Leibler divergence, we use a quadratic divergence measure, which allows us to make an efficient non-parametric implementation and requires no prior assumptions about class densities. In addition to linear transforms, we also discuss nonlinear transforms that are implemented as radial basis function networks. Extensions to reduce the computational complexity are also presented, and a comparison to greedy feature selection is made.
The Price Impact of Rating Announcements: Which Announcements Matter?

Credit rating agencies make multiple announcements, some of which are intended to reflect the latest information available about a firm and others of which are intended to provide a stable signal of credit quality. Using data on CDS spreads, we examine which of these different types of rating announcements contains pricingrelevant information. We find that all types, including changes in outlook, have a significant impact on CDS spreads. Even rating announcements preceded by similar announcements have an impact. The price impact is greatest for firms with split ratings, smallcap firms and firms rated near the threshold of investment grade.
Secondary Structure Analysis of Genetically Modified Silk with Spider Fiber Protein

Secondary structure of silk fiber containing spider (Araneus ventricosus) fiber protein produced by transgenic silkworm (KH29) was analyzed by 13C CP/MAS NMR and compared with that of wild-type silk fiber. The NMR spectrum showed that the secondary structure of KH29 silk were the same as that of wild-type silkworm silk even though spider fiber protein existed in silk. In addition, since the peak signal around 15.7 ppm, indicating the α-helix of Ala Cβ, was not observed in the NMR spectrum of KH29 silk, in KH29 silk may form a β-sheet structure instead of an α-helix structure after spinning process of silkworm. These results indicate that physical properties of silk can be modified by the incorporation of foreign fiber proteins by the use of transgenic silkworm technology.
Performance analysis of time-hopping spread-spectrum multiple-access systems: uncoded and coded schemes

An ultra-wide bandwidth time-hopping spread-spectrum code division multiple-access system employing a binary PPM signaling has been introduced by Scholtz (1993), and its performance was obtained based on a Gaussian distribution assumption for the multiple-access interference. In this paper, we begin first by proposing to use a practical low-rate error correcting code in the system without any further required bandwidth expansion. We then present a more precise performance analysis of the system for both coded and uncoded schemes. Our analysis shows that the Gaussian assumption is not accurate for predicting bit error rates at high data transmission rates for the uncoded scheme. Furthermore, it indicates that the proposed coded scheme outperforms the uncoded scheme significantly, or more importantly, at a given bit error rate, the coding scheme increases the number of users by a factor which is logarithmic in the number of pulses used in time-hopping spread-spectrum systems.
Report on stage III Pig‐a mutation assays using N‐ethyl‐N‐nitrosourea – comparison with other in vivo genotoxicity endpoints

N‐Ethyl‐N‐nitrosourea (ENU) was evaluated as part of the Stage III trial for the rat Pig‐a gene mutation assay. Groups of six‐ to eight‐week‐old male Sprague Dawley (SD) or Fischer 344 (F344) rats were given 28 daily doses of the phosphate buffered saline vehicle, or 2.5, 5, or 10 mg/kg ENU, and evaluated for a variety of genotoxicity endpoints in peripheral blood, spleen, liver, and colon. Blood was sampled predose (Day‐1) and at various time points up to Day 57. Pig‐a mutant frequencies were determined in total red blood cells (RBCs) and reticulocytes (RETs) as RBCCD59− and RETCD59− frequencies. Consistent with the results from a reference laboratory, RBCCD59− and RETCD59− frequencies increased in a dose‐ and time‐dependent manner, producing significant increases at all doses by Day 15, with similar frequencies seen in both rat strains. ENU also induced small but significant increases in % micronucleated RETs on Days 4 and 29. No significant increases in micronuclei were seen in the liver or colon of the ENU‐treated SD rats. Hprt and Pig‐a lymphocyte mutation assays conducted on splenocytes from Day 56 F344 rats detected two‐ to fourfold stronger responses for Hprt than Pig‐a mutations. Results from the in vivo Comet assay in SD rats at Day 29 showed generally weak increases in DNA damage in all tissues evaluated. The results with ENU indicate that the Pig‐a RET and RBC assays are reproducible, transferable, and complement other genotoxicity endpoints that could potentially be integrated into 28‐day repeat‐dose rat studies. © Environ. Mol. Mutagen. 2011. Published 2011 Wiley‐Liss, Inc.
Bisphenol A Exposure during Oocyte Maturation in vitro Results in Spindle Abnormalities and Chromosome Misalignment in Bos taurus

Bisphenol A (BPA) exposure in humans is widespread, and BPA has been detected in a variety of samples including follicular fluid. BPA levels have been found to negatively correlate with the developmental potential of oocytes in women undergoing in vitro fertilization and to induce meiotic abnormalities experimentally in human and mouse models. BPA may detrimentally affect oocyte maturation, and different concentrations of exposure can cause various outcomes. Because of the importance of oocyte maturation on developmental potential, disturbances during this time can significantly impact oocyte viability. Here, bovine oocytes were matured in vitro with and without BPA treatment of the media. The levels of BPA taken up by the oocytes were much lower than the initial exposure. Medium treatment with 30 ng/ml resulted in an average of 2.48 ng/ml BPA measured in mature oocytes. These oocytes exhibited decreased maturation and increased incidence of spindle abnormalities. Only 57.4% of oocytes exposed to 30 ng/ml BPA reached maturity compared to 72.4% of controls (p < 0.05). Mature oocytes following BPA exposure displayed increased abnormal spindle morphology (67.9%) and chromosome dispersal (60%) compared to all other groups analyzed (p < 0.05). Thus, exposure to BPA during in vitro oocyte maturation has the potential to decrease oocyte quality.