Miracle-dz/UniFAR-FTUs huggingface dataset:
IS 200 / IS 605 family single-strand transposition : mechanism of IS 608 strand transfer

Transposase, TnpA, of the IS200/IS605 family member IS608, catalyses single-strand DNA transposition and is dimeric with hybrid catalytic sites composed of an HUH motif from one monomer and a catalytic Y127 present in an a-helix (aD) from the other (trans configuration). aD is attached to the main body by a flexible loop. Although the reactions leading to excision of a transposition intermediate are well characterized, little is known about the dynamic behaviour of the transpososome that drives this process. We provide evidence strongly supporting a strand transfer model involving rotation of both aD helices from the trans to the cis configuration (HUH and Y residues from the same monomer). Studies with TnpA heterodimers suggest that TnpA cleaves DNA in the trans configuration, and that the catalytic tyrosines linked to the 50-phosphates exchange positions to allow rejoining of the cleaved strands (strand transfer) in the cis configuration. They further imply that, after excision of the transposon junction, TnpA should be reset to a trans configuration before the cleavage required for integration. Analysis also suggests that this mechanism is conserved among members of the IS200/IS605 family.
Assessing Fatigability in the Lab and in Daily Life in Older Adults With Osteoarthritis Using Perceived, Performance, and Ecological Measures

Background: Fatigue in older adults is associated with functional decline and reduced participation in daily life; however, it is not well characterized. Examining fatigue within activity performance, or “fatigability,” is a recommended approach to begin to understand fatigue and its underlying mechanisms. This study examined the construct validity of lab-based measures of fatigability and compared these measures with fatigability in daily life (termed ecological fatigability). Methods: Participants with osteoarthritis and fatigue (n = 163) underwent laboratory assessments, completed questionnaires, and wore accelerometers for 7 days while tracking symptoms and behaviors. Lab-based fatigability measures were quantified using the 6-minute walk test. Perceived fatigability was assessed by asking participants before and after the test to report: (i) fatigue severity and (ii) perceived exertion. Performance fatigability was calculated using change in walking speed divided by total distance walked. Ecological fatigability was calculated from the 7-day assessment in which fatigue severity was reported five times a day and physical activity was continuously measured. Additional ecological measures (eg, self-pacing) were examined. Results: Lab-based perceived and performance fatigability measures were highly inter-correlated, moderately correlated with gait speed and metabolic measures, and weakly correlated with physical activity. Although ecological fatigability was weakly correlated with lab-based measures, participants with high fatigability on lab-based measures demonstrated more self-pacing behaviors than participants with low fatigability. Conclusion: Lab-based fatigability measures are related to physical capacity measured both in the lab and daily life. Lab-based fatigability measures provide important information regarding daily life fatigability useful for future intervention development.
Slab-waveguide irradiation of UV laser light for photosensitive phase error compensation of arrayed-waveguide gratings

The photosensitive refractive index change in a slab waveguide was utilized to compensate for the phase error of an arrayed-waveguide grating. The UV laser irradiation of a slab waveguide has certain advantages. The irradiation of several different parts of the waveguide can compensate for a large phase error of the order of ten radians. Phase error compensation can be achieved even when there is no space on the arrayed-waveguide part to place a mask for irradiation.
Heritability Estimated Using 50K SNPs Indicates Missing Heritability Problem in Holstein Breeding

Previous studies in Holstein have shown 35% to 51.8% heritability in milk production traits, such as milk yield, fat, and protein, using pedigree data. Other studies in complex human traits could be captured by common single-nucleotide polymorphisms (SNPs), and their genetic variations, attributed to chromosomes, are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analyzed three quantitative Holstein traits relevant to milk production in Korean Holstein data harvested from 462 individuals genotyped for 54,609 SNPs. For all three traits (milk yield, fat, and protein), we estimated a nominally significant (p = 0.1) proportion of variance explained by all SNPs on the Illumina BovineSNP50 Beadchip (h2G). These common SNPs explained approximately most of the narrow-sense heritability. Longer genomic regions tended to provide more phenotypic variation information, with a correlation of 0.46~0.53 between the estimate of variance explained by individual chromosomes and their physical length. These results suggested that polygenicity was ubiquitous for Holstein milk production traits. These results will expand our knowledge on recent animal breeding, such as genomic selection in Holstein.
Saccharomicins, Novel Heptadecaglycoside Antibiotics Produced by Saccharothrix espanaensis: Antibacterial and Mechanistic Activities

ABSTRACT Saccharomicins A and B, two new heptadecaglycoside antibiotics, were isolated from the fermentation broth of the rare actinomyceteSaccharothrix espanaensis. They represent a novel class of bactericidal antibiotics that are active both in vitro and in vivo against bacteria and yeast (MICs: Staphylococcus aureus, <0.12 to 0.5; vancomycin-resistant enterococci, 0.25 to 16; gram-negative bacteria, 0.25 to >128; and yeast, >128 μg/ml), including multiply resistant strains. Saccharomicins protected mice from lethal challenges by staphylococci (subcutaneous 50% effective dose range of 0.06 to 2.6 mg/kg of body weight, depending on theS. aureus strain). The 50% lethal dose by the subcutaneous route was 16 mg/kg. Mechanistic studies with Escherichia coli imp and Bacillus subtilis suggested complete, nonspecific inhibition of DNA, RNA, and protein biosynthesis within 10 min of drug treatment. Microscopic examination of drug-treated cells also suggested cell lysis. These data are consistent with a strong membrane-disruptive activity. The antibacterial activities of the saccharomicins against gram-positive bacteria were unaffected by the presence of Ca2+ or Mg2+, but activity against gram-negative bacteria was substantially reduced.
A drop array culture for patterning adherent mouse embryonic stem cell‐derived neurospheres

New therapeutic approaches for repairing an injured or degenerating nervous system have accelerated the development of methods to generate populations of neurons derived from various stem cell sources efficiently. Many of these methods require the generation of neurospheres. Here a simple technique is described for creating an array of adherent mouse embryonic stem cell (mESC)‐derived neurospheres using a conventional plastic culture dish and a patterning template. mESC‐derived neurospheres are confined to circular (4‐mm diameter), gel‐coated regions within an array. The adherent neurosphere arrays require 3 days to prepare from an mESC source; they can be maintained in 15 μl drops of medium, and exhibit extensive neurite elaboration after 8 days of cultivation. Additionally, the potential of treating the adherent neurospheres in selected drops of an array is demonstrated with a variety of differentiation‐inducing reagents and subsequently individually analysing such neurospheres for gene expression, protein levels and morphological development. Copyright © 2016 John Wiley & Sons, Ltd.
Constrained binary classification using ensemble learning: an application to cost‐efficient targeted PrEP strategies

Binary classification problems are ubiquitous in health and social sciences. In many cases, one wishes to balance two competing optimality considerations for a binary classifier. For instance, in resource‐limited settings, an human immunodeficiency virus prevention program based on offering pre‐exposure prophylaxis (PrEP) to select high‐risk individuals must balance the sensitivity of the binary classifier in detecting future seroconverters (and hence offering them PrEP regimens) with the total number of PrEP regimens that is financially and logistically feasible for the program. In this article, we consider a general class of constrained binary classification problems wherein the objective function and the constraint are both monotonic with respect to a threshold. These include the minimization of the rate of positive predictions subject to a minimum sensitivity, the maximization of sensitivity subject to a maximum rate of positive predictions, and the Neyman–Pearson paradigm, which minimizes the type II error subject to an upper bound on the type I error. We propose an ensemble approach to these binary classification problems based on the Super Learner methodology. This approach linearly combines a user‐supplied library of scoring algorithms, with combination weights and a discriminating threshold chosen to minimize the constrained optimality criterion. We then illustrate the application of the proposed classifier to develop an individualized PrEP targeting strategy in a resource‐limited setting, with the goal of minimizing the number of PrEP offerings while achieving a minimum required sensitivity. This proof of concept data analysis uses baseline data from the ongoing Sustainable East Africa Research in Community Health study. Copyright © 2017 John Wiley & Sons, Ltd.
TCP-path: Improving load balance by network exploration

Bridging is widely used in Ethernet networks, but the spanning tree protocol blocks all redundant links to prevent loops, and therefore it cannot take advantage of multipath topologies to balance traffic load. Several multipath routing proposals use link-state protocols and Equal Cost Multi-Path routing (ECMP) to distribute the load over multiple paths. However, these proposals are complex and prone to flow collisions that may degrade performance. This paper proposes the new TCP-Path protocol, which selects the fastest available path to a destination host on the fly when a new flow is established. TCP-Path is a new multilayer switching paradigm based on exploring all network paths triggered by TCP-SYN packets, instead of link-state based route computation. Here, we evaluate TCP-Path on ns-3 and Mininet and compare its performance. TCP-Path improves on ECMP by up to 25% in terms of throughput and up to 60% in terms of flow completion time. Thus, TCP-Path offers a better, yet simple alternative to ECMP-based solutions for multipath topologies.
A comparative study of odor identification and odor discrimination deficits in Parkinson's disease

The aim of this study was to compare the characteristics of odor discrimination and odor identification deficits in a large population of patients with Parkinson's disease (PD) and to determine which of these olfactory tests best distinguishes between patients with PD and control subjects. Olfactory performance was assessed in 404 patients with PD and 150 controls, using the odor identification and discrimination parts of the Sniffin' Sticks battery. Mean identification and discrimination scores in patients with PD were significantly lower than in controls. Linear regression analysis using a 95% confidence interval revealed that, relative to the performance of controls, 65.0% of patients with PD had an impairment in odor identification, whereas 42.1% of patients were impaired on the odor discrimination task. ROC curves revealed a higher sensitivity and specificity for odor identification than for odor discrimination in separating patients from controls. In patients with PD, odor discrimination performance decreased with increasing disease duration, whereas odor identification was not correlated with disease stage or duration. In PD, odor identification is more frequently impaired than odor discrimination and allows a better discrimination between patients and controls. Although an odor identification deficit is generally believed to be independent of disease progression, the impairment in odor discrimination appears to increase with disease duration. © 2008 Movement Disorder Society
Signal identification for emerging intelligent radios: classical problems and new challenges

Signal identification, which initially found applications in electronic warfare and spectrum monitoring and surveillance, has been recently considered for commercial communications in the context of software defined and cognitive radios. In this article, I present a snapshot of the status of signal identification algorithms, starting from a general description of maximum likelihood (ML) and feature based (FB) approaches to a more detailed discussion of a practical methodology using cyclostationarity-based features. I discuss the cyclostationarity-based features of various signals and the criteria of decision for their identification, while considering classical problems of identifying single carrier linearly digitally (SCLD) modulated signals, as well as new challenges posed by the identification of orthogonal frequency division multiplexing (OFDM), SC frequency domain equalization (SC-FDE), and multiple-transmit antenna signals. I conclude the article with remarks on practical solutions to signal identification and open research issues.
Inhibitory effect of deferoxamine or macrophage activation on transformation of Paracoccidioides brasiliensis conidia ingested by macrophages: reversal by holotransferrin

Conidia of P. brasiliensis ingested by murine macrophages at 37 degrees C showed enhanced transformation to yeast cells and further intracellular growth compared with conidia in culture medium alone. Treatment of macrophages with the iron chelator deferoxamine inhibited the intracellular conidium-to-yeast transformation. Cytokine-activated macrophages could also exert this inhibitory effect. Holotransferrin reversed the inhibitory effect of either deferoxamine or activated macrophages on intracellular conidium-to-yeast transformation. These results indicate that iron restriction is one of the mechanisms by which activated macrophages control the intracellular transformation of ingested conidia and growth of yeast cells.
A Comparison of Histomorphometric Data Collection Methods *

Abstract: Although many variables that skeletal biologists examine have been standardized, the actual techniques used to collect these data from bone thin sections vary. This project compares different methods of obtaining data (relative cortical area values) for histomorphometric research. One visual and three digital methods of histomorphometric data collection are compared: (i) Merz microscopic eyepiece counting reticule, (ii) flatbed scanner, (iii) overlaying multiple images of a thin section, and (iv) digital SLR camera with macro settings. The discussion includes a comparison of usability factors such as cost, time, user‐experience, and ease‐of‐use, which vary for each method. Values from the different methods are compared using ANOVA tests to evaluate inter‐method, inter‐observer, and intra‐observer variability. Intra‐observer error was greater for the microscopic method, although the error values are concomitant with experience. We found no statistically significant differences between the four methods examined, but certain caveats must be addressed when these methods are used.
Cytotoxic T lymphocytes as immune‐therapy in haematological practice

Viral infections are a significant cause of morbidity and mortality, particularly in pediatric allogeneic haematopoietic stem cell transplant recipients. Effective therapies are limited and often associated with significant side effects. Adoptive transfer of virus‐reactive T cells offers a means of reconstituting antiviral immunity and this approach has been successfully used to prevent and treat cytomegalovirus, Epstein‐Barr virus, and adenovirus infections in vivo. This review outlines the clinical trials that have been performed to date, and will describe future initiatives to (a) develop strategies that can increase the breadth of the viruses that can be targeted, and (b) simplify the process to extend this technology to more centers so that cellular therapy to reconstitute immunity can be more widely applied.
Amygdala and insula response to emotional images in patients with generalized social anxiety disorder.

BACKGROUND Functional brain imaging studies have demonstrated amygdala and insula hyper-reactivity to probes of social threat in participants with generalized social anxiety disorder (gSAD). The amygdala and insula are known to serve broad functions in emotional processing, including integration of affective information. However, few studies have examined brain responses in socially anxious participants during general emotional processing. We examined brain response to emotionally evocative images in patients with gSAD and matched healthy controls. METHODS Eleven patients with gSAD who were not taking psychotropic medications and did not have psychiatric comorbidities and 11 matched healthy controls underwent functional magnetic resonance imaging while viewing blocks of emotionally salient (positive, negative, neutral) pictures. RESULTS Participants with gSAD exhibited enhanced bilateral amygdala and insula reactivity to negative (v. neutral) images compared with healthy controls who did not exhibit enhanced reactivity. Within the gSAD group, the extent of amygdala activation was correlated with social anxiety severity, whereas the extent of insula activation was correlated with trait anxiety. LIMITATIONS The small sample size may have limited our ability to detect group differences in other relevant brain regions and in behavioural measures. CONCLUSION In addition to prior findings of probes of social information processing, our findings suggest that the amygdala and insula responses are hyper-reactive to general emotional images with negative emotional content and that these brain regions may play divergent roles in their representation of different phenotypes.
A silver stain protocol for proteins yielding high resolution and transparent background in sodium dodecyl sulfate‐polyacrylamide gels

A simple, sensitive silver staining method for sodium dodecyl sulfate polyacrylamide gel electrophoresis has been developed which yields high resolution of proteins with a transparent background. The method includes the incorporation of a water wash after a short fixation step in ethanol/acetic acid and prior to glutaraldehyde cross‐linking, which appears to be necessary for the high resolution staining of protein bands and the low background staining.
The quantitative measurement of DNA hybridization from renaturation rates.

A new method is proposed to measure relatedness amongst bacteria, based on renaturation rate determinations of DNA types and their mixture. The equations, relating the degree of binding with renaturation rates, are calculated for several cases. The optimal conditions for measurements are given. The method was checked in several ways. The advantages are summarized.
Studies on the inactivation of human parvovirus 4

Human parvovirus 4 (PARV4) is a novel parvovirus, which like parvovirus B19 (B19V) can be a contaminant of plasma pools used to prepare plasma‐derived medicinal products. Inactivation studies of B19V have shown that it is more sensitive to virus inactivation strategies than animal parvoviruses. However, inactivation of PARV4 has not yet been specifically addressed.
Characterization and comparison of adipose tissue‐derived cells from human subcutaneous and omental adipose tissues

Different fat depots contribute differently to disease and function. These differences may be due to the regional variation in cell types and inherent properties of fat cell progenitors. To address the differences of cell types in the adipose tissue from different depots, the phenotypes of freshly isolated adipose tissue‐derived cells (ATDCs) from subcutaneous (SC) and omental (OM) adipose tissues were compared using flow cytometry. Our results showed that CD31−CD34+CD45−CD90‐CD105−CD146+ population, containing vascular smooth muscle cells and pericytes, was specifically defined in the SC adipose tissue while no such population was observed in OM adipose tissue. On the other hand, CD31−CD34+CD45−CD90−CD105−CD146− population, which is an undefined cell population, were found solely in OM adipose tissue. Overall, the SC adipose tissue contained more ATDCs than OM adipose tissue, while OM adipose tissue contained more blood‐derived cells. Regarding to the inherent properties of fat cell progenitors from the two depots, adipose‐derived stem cells (ADSCs) from SC had higher capacity to differentiate into both adipogenic and osteogenic lineages than those from OM, regardless of that the proliferation rates of ADSCs from both depots were similar. The higher differentiation capacity of ADSCs from SC adipose tissue suggests that SC tissue is more suitable cell source for regenerative medicine than OM adipose tissue. Copyright © 2009 John Wiley & Sons, Ltd.
Blunted day-night changes in luteinizing hormone pulse frequency in girls with obesity: the potential role of hyperandrogenemia.

CONTEXT Puberty is marked by sleep-associated changes in LH pulse frequency and amplitude. Early pubertal girls with obesity exhibit blunted day-to-night changes in LH secretion; whether this occurs in late pubertal obese girls is unknown. OBJECTIVE The objective of the study was to test two hypotheses: 1) blunted day-to-night changes in LH secretion occur in both early and late pubertal obese girls, and 2) such alterations are specifically associated with hyperandrogenemia. DESIGN This was a cross-sectional analysis. SETTING The study was conducted at a clinical research center. PATIENTS OR OTHER PARTICIPANTS Twenty-seven early pubertal, premenarcheal girls (12 of whom were obese) and 63 late pubertal (postmenarcheal) girls (27 of whom were obese) participated in the study. INTERVENTION Blood samples were taken every 10 minutes from 7:00 pm to 7:00 am. MAIN OUTCOME MEASURE Change in LH pulse frequency [LH interpulse interval (IPI)] from daytime hours (7:00 pm-11:00 pm, while awake) to nighttime hours (11:00 pm to 7:00 am, while generally asleep). RESULTS Both nonobese and obese postmenarcheal girls demonstrated significant day-to-night decreases in LH pulse frequency (IPI increases of 33% and 16%, respectively), but day-to-night changes were blunted in obese girls (P = .004, obese vs nonobese). Day-to-night LH pulse frequency decreased significantly in postmenarcheal obese subjects with normal T concentrations (26% IPI increase) but not in those with hyperandrogenemia. Similar differences were evident for LH pulse amplitude. Nonobese and obese early pubertal girls exhibited nonsignificant differences in day-night LH pulse frequency (day to night IPI increase of 26% vs decrease of 1%, respectively). CONCLUSIONS Day-to-night changes in LH pulse secretion are blunted in postmenarcheal obese adolescent girls. This phenomenon may in part reflect hyperandrogenemia.