Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of Plasma Sample Pretreatment for Quantitative Analysis Using iTRAQ Labeling and LC-MALDI-TOF/TOF

Shotgun proteomic methods involving iTRAQ (isobaric tags for relative and absolute quantitation) peptide labeling facilitate quantitative analyses of proteomes and searches for useful biomarkers. However, the plasma proteome's complexity and the highly dynamic plasma protein concentration range limit the ability of conventional approaches to analyze and identify a large number of proteins, including useful biomarkers. The goal of this paper is to elucidate the best approach for plasma sample pretreatment for MS- and iTRAQ-based analyses. Here, we systematically compared four approaches, which include centrifugal ultrafiltration, SCX chromatography with fractionation, affinity depletion, and plasma without fractionation, to reduce plasma sample complexity. We generated an optimized protocol for quantitative protein analysis using iTRAQ reagents and an UltrafleXtreme (Bruker Daltonics) MALDI TOF/TOF mass spectrometer. Moreover, we used a simple, rapid, efficient, but inexpensive sample pretreatment technique that generated an optimal opportunity for biomarker discovery. We discuss the results from the four sample pretreatment approaches and conclude that SCX chromatography without affinity depletion is the best plasma sample preparation pretreatment method for proteome analysis. Using this technique, we identified 1,780 unique proteins, including 1,427 that were quantified by iTRAQ with high reproducibility and accuracy.
Hearing Safety From Single- and Double-Pulse Transcranial Magnetic Stimulation in Children and Young Adults

Purpose: Concerns regarding hearing safety have limited the number of studies using transcranial magnetic stimulation (TMS) in children and young adults. The objective of this study was to examine the safety of TMS with regards to hearing in a group of 16 children and young adults (17.3 ± 4.9 years) with and without brain injury. Methods: Pure-tone hearing thresholds and distortion-product otoacoustic emissions were measured before and after exposure to single- and paired-pulse TMS (1–2 sessions of 149–446 TMS pulses at a median of 49%–100% maximum stimulator output over a 2.2 hours period). Results: No mean change in hearing outcomes was noted. In addition, no clinically significant change in hearing threshold was observed in any participant, and participants did not experience a subjective change in hearing after TMS exposure. Conclusions: Single- and double-pulse TMS administered within the parameters used in this study, which included hearing protection, can be used in children and young adults without impacting hearing. This study provides further evidence for hearing safety after TMS exposure in children and young adults.
Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA

Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital SequencingTM is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient’s cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing.
Intimacy‐Anger and Insecure Attachment as Precursors of Abuse in Intimate Relationships

One hundred and twenty men referred for treatment for wife assault and forty demographic controls completed self-report questionnaires assessing attachment patterns, anger, jealousy, Borderline Personality Organization, and trauma symptoms. This constellation, with the exception of attachment, has been found to represent a profile related significantly to the frequency of both verbal and physical abuse. In the present study, attachment was found to correlate significantly with these other measures. A measure of secure attachment correlated significantly, but negatively, with the constellation measures. A measure of fearful attachment correlated significantly and positively. A preoccupied attachment pattern correlated with the other measures less strongly than did the fearful measure. A dismissing measure was not correlated with any constellation measures. The role of attachment anger is discussed; it is suggested that fearful attachment could also be described as angry attachment. The concept of intimacy anger is introduced from early studies in attachment and applied to the explanation of assaultiveness in adult relationships.
Household Financial Distress and Initial Endowments: Evidence from the 2008 Financial Crisis.

This paper studies in utero exposure to the 2008 financial crisis. Exploiting the sudden and unexpected collapse of the Icelandic economy, I find that first-trimester exposure to the crisis led to a sizable and significant reduction in birth weight, increased the probability of a low birth weight ( < 2500 g), and decreased the probability of a high birth weight ( > 4000 g). I also find evidence that the collapse reduced the sex ratio, indicating selection in utero due to maternal prenatal stress exposure. My results imply large welfare losses from financial distress that have hitherto been ignored - because children with worse health at birth can expect substantially lower lifetime earnings - and suggest that economic hardships may in general exacerbate income inequalities in the long run as low-income households are typically more exposed to financial distress. Copyright © 2016 John Wiley & Sons, Ltd.
Enhanced Mineralization of [U-14C]2,4-Dichlorophenoxyacetic Acid in Soil from the Rhizosphere of Trifolium pratense

ABSTRACT Enhanced biodegradation in the rhizosphere has been reported for many organic xenobiotic compounds, although the mechanisms are not fully understood. The purpose of this study was to discover whether rhizosphere-enhanced biodegradation is due to selective enrichment of degraders through growth on compounds produced by rhizodeposition. We monitored the mineralization of [U-14C]2,4-dichlorophenoxyacetic acid (2,4-D) in rhizosphere soil with no history of herbicide application collected over a period of 0 to 116 days after sowing of Lolium perenne and Trifolium pratense. The relationships between the mineralization kinetics, the number of 2,4-D degraders, and the diversity of genes encoding 2,4-D/α-ketoglutarate dioxygenase (tfdA) were investigated. The rhizosphere effect on [14C]2,4-D mineralization (50 μg g−1) was shown to be plant species and plant age specific. In comparison with nonplanted soil, there were significant (P < 0.05) reductions in the lag phase and enhancements of the maximum mineralization rate for 25- and 60-day T. pratense soil but not for 116-day T. pratense rhizosphere soil or for L. perenne rhizosphere soil of any age. Numbers of 2,4-D degraders in planted and nonplanted soil were low (most probable number, <100 g−1) and were not related to plant species or age. Single-strand conformational polymorphism analysis showed that plant species had no impact on the diversity of α-Proteobacteria tfdA-like genes, although an impact of 2,4-D application was recorded. Our results indicate that enhanced mineralization in T. pratense rhizosphere soil is not due to enrichment of 2,4-D-degrading microorganisms by rhizodeposits. We suggest an alternative mechanism in which one or more components of the rhizodeposits induce the 2,4-D pathway.
Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography: Findings From an Older Cohort With Mild Phenotype

Importance Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. Objective To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Design, Setting, and Participants Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra–wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. Main Outcomes and Measures The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra–wide-field FA. Results A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra–wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Conclusions and Relevance Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.
Nocturnal to Diurnal Switches with Spontaneous Suppression of Wheel-Running Behavior in a Subterranean Rodent

Several rodent species that are diurnal in the field become nocturnal in the lab. It has been suggested that the use of running-wheels in the lab might contribute to this timing switch. This proposition is based on studies that indicate feed-back of vigorous wheel-running on the period and phase of circadian clocks that time daily activity rhythms. Tuco-tucos (Ctenomys aff. knighti) are subterranean rodents that are diurnal in the field but are robustly nocturnal in laboratory, with or without access to running wheels. We assessed their energy metabolism by continuously and simultaneously monitoring rates of oxygen consumption, body temperature, general motor and wheel running activity for several days in the presence and absence of wheels. Surprisingly, some individuals spontaneously suppressed running-wheel activity and switched to diurnality in the respirometry chamber, whereas the remaining animals continued to be nocturnal even after wheel removal. This is the first report of timing switches that occur with spontaneous wheel-running suppression and which are not replicated by removal of the wheel.
Deep Eutectic Solvents as Convenient Media for Synthesis of Novel Coumarinyl Schiff Bases and Their QSAR Studies

Deep eutectic solvents, as green and environmentally friendly media, were utilized in the synthesis of novel coumarinyl Schiff bases. Novel derivatives were synthesized from 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetohydrazide and corresponding aldehyde in choline chloride:malonic acid (1:1) based deep eutectic solvent. In these reactions, deep eutectic solvent acted as a solvent and catalyst as well. Novel Schiff bases were synthesized in high yields (65–75%) with no need for further purification, and their structures were confirmed by mass spectra, 1H and 13C NMR. Furthermore, their antioxidant activity was determined and compared to antioxidant activity of previously synthesized derivatives, thus investigating their structure–activity relationship utilizing quantitative structure-activity relationship QSAR studies. Calculation of molecular descriptors has been performed by DRAGON software. The best QSAR model (Rtr = 0.636; Rext = 0.709) obtained with three descriptors (MATS3m, Mor22u, Hy) implies that the pairs of atoms higher mass at the path length 3, three-dimensional arrangement of atoms at scattering parameter s = 21 Å−1, and higher number of hydrophilic groups (-OH, -NH) enhanced antioxidant activity. Electrostatic potential surface of the most active compounds showed possible regions for donation of electrons to 1,1-diphenyl-2-picryhydrazyl (DPPH) radicals.
Searching for variable stars in the cores of five metal-rich globular clusters using EMCCD observations

Aims. In this paper, we present the analysis of time-series observations from 2013 and 2014 of five metal-rich ([Fe /H] > 1) globular clusters: NGC 6388, NGC 6441, NGC 6528, NGC 6638, and NGC 6652. The data have been used to perform a census of the variable stars in the central parts of these clusters. Methods. The observations were made with the electron-multiplying charge-couple device (EMCCD) camera at the Danish 1.54m Telescope at La Silla, Chile, and they were analysed using di ff erence image analysis to obtain high-precision light curves of the variable stars. Results. It was possible to identify and classify all of the previously known or suspected variable stars in the central regions of the five clusters. Furthermore, we were able to identify and, in most cases, classify 48, 49, 7, 8, and 2 previously unknown variables in NGC 6388, NGC 6441, NGC 6528, NGC 6638, and NGC 6652, respectively. Especially interesting is the case of NGC 6441, for which the variable star population of about 150 stars has been thoroughly examined by previous studies, including a Hubble Space Telescope study. In this paper we are able to present 49 new variable stars for this cluster, of which one (possibly two) are RR Lyrae stars, two areWVirginis stars, and the rest are long-period semi-regular or irregular variables on the red giant branch. We have also detected the first double-mode RR Lyrae in the cluster.
Atrial fibrillation detection using convolutional neural networks

As part of the PhysioNet/Computing in Cardiology Challenge 2017, this work focuses on the classification of a single channel short electrocardiogram (ECG) signal into normal, atrial fibrillation (AF), others and noise classes. To this end, we propose a shallow convolutional neural network architecture which learns suitable features pertaining to each class while eliminating the need to extract the traditionally used ad hoc features. In particular, we first developed a robust R-peak detector and stacked sequence of fixed number of detected beats with R-peaks aligned. These stack of beats corresponding to a segment of ECG record are classified into one of the four aforementioned classes. To improve the robustness, multiple classifiers were trained to classify these segments. Overall record classification was then generated using an voting scheme from the classification results of individual segments. Our best submission result during the official phase has a score of 71% with F1 scores of 86%, 73% and 56% respectively for normal, AF and other classes respectively.
Application of ozone during grape drying for the production of straw wine. Effects on the microbiota and compositive profile of grapes

Straw wine is a highly valuable oenological production, affected by relevant economical losses due to proliferation of spoilage micro‐organisms during drying grapes, after being harvested. In this work, ozone was evaluated as a tool to preserve grapes during drying, in terms of both qualitative and quantitative changes induced in the epiphytic microflora. In addition, the alteration exerted by ozone on grapes’ chemical composition was analysed.
Polypropylene–clay nanocomposites: Influence of low molecular weight polar additives on intercalation and exfoliation behavior

The influence of low molecular weight additives containing polar groups and modified polyolefin-based compatibilizers on polypropylene (PP)-clay nanocomposites (PPCN) has been studied, in terms of intercalation and degree of exfoliation achievable by melt-state mixing processes. PPCN were prepared by melt mixing two PP homopolymers with organically-modified montmorillonite type clay, in the presence of maleic anhydride-grafted polypropylene (PP-MA) compatibilizer. XRD analysis shows that interlayer spacing of clay has been increased dramatically, while TEM results show a significant improvement of clay dispersion in the PP matrix, when nanocomposites are prepared with commercial PP containing short-chain organic additives with polar end groups. Subsequent studies based upon customized PP formulations, with amide-type slip additive, confirm the intercalation of this additive into the clay galleries and its positive and significant impact on clay dispersion. Contact angle measurements suggest that these additives diffuse into the clay gallery space rather than migrating away from the bulk of the PPCN matrix. The interaction between polar group (NH 2 ) of this additive and the polar sites on the filler surface appears to be the driving force for the intercalation.
An experimental examination of alcohol consumption, alcohol expectancy, and self‐blame on willingness to report a hypothetical rape

This study experimentally examined the role of victim alcohol intoxication, and self‐blame in perceiving and reporting rape to the police using a hypothetical interactive rape scenario. Participants (N = 79) were randomly assigned to consume alcohol (mean BAC = 0.07%) or tonic water before they engaged in the scenario. Alcohol expectancy was manipulated, and participant beliefs about the beverage they thought they had consumed and their feelings of intoxication were measured. Alcohol consumption and expectancy did not affect the likelihood that the nonconsensual intercourse depicted in the scenario was perceived and would be reported as rape. Participants with higher levels of self‐blame were less likely to say they would report the hypothetical rape. Self‐blame levels were higher for participants who believed they had consumed alcohol, and were associated with increased feelings of intoxication. The implications are discussed.
APPROXIMATE INVERSION OF A LARGE SEMISEPARABLE POSITIVE MATRIX

Abstract. The inversion of a large (n × n) positive matrix is considered. We assume that the matrix has a semi-separable structure, which implies that all submatrices away from the main diagonal have rank less than q (the matrix itself may be full). In practice, a specified matrix will not exactly have low-rank submatrices. Given a threshold and a positive matrix T , the submatrices of T are rank truncated to this threshold (balanced model reduction) and the inverse of a Cholesky factor of T is computed using time-varying state-space techniques. The proposed algorithm requires O(nq) operations, where q is the average rank of the submatrices as detected by the algorithm.
Structural insights unravel the zymogenic mechanism of the virulence factor gingipain K from Porphyromonas gingivalis, a causative agent of gum disease from the human oral microbiome*

Skewing of the human oral microbiome causes dysbiosis and preponderance of bacteria such as Porphyromonas gingivalis, the main etiological agent of periodontitis. P. gingivalis secretes proteolytic gingipains (Kgp and RgpA/B) as zymogens inhibited by a pro-domain that is removed during extracellular activation. Unraveling the molecular mechanism of Kgp zymogenicity is essential to design inhibitors blocking its activity. Here, we found that the isolated 209-residue Kgp pro-domain is a boomerang-shaped all-β protein similar to the RgpB pro-domain. Using composite structural information of Kgp and RgpB, we derived a plausible homology model and mechanism of Kgp-regulating zymogenicity. Accordingly, the pro-domain would laterally attach to the catalytic moiety in Kgp and block the active site through an exposed inhibitory loop. This loop features a lysine (Lys129) likely occupying the S1 specificity pocket and exerting latency. Lys129 mutation to glutamate or arginine led to misfolded protein that was degraded in vivo. Mutation to alanine gave milder effects but still strongly diminished proteolytic activity, without affecting the subcellular location of the enzyme. Accordingly, the interactions of Lys129 within the S1 pocket are also essential for correct folding. Uniquely for gingipains, the isolated Kgp pro-domain dimerized through an interface, which partially overlapped with that between the catalytic moiety and the pro-domain within the zymogen, i.e. both complexes are mutually exclusive. Thus, pro-domain dimerization, together with partial rearrangement of the active site upon activation, explains the lack of inhibition of the pro-domain in trans. Our results reveal that the specific latency mechanism of Kgp differs from those of Rgps.
Dynamic frontotemporal systems process space and time in working memory

How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL–PFC interactions underlie working memory for everyday experiences.