Miracle-dz/UniFAR-FTUs huggingface dataset:
A Rapid Luminescent Assay for Measuring Cytochrome P450 Activity in Individual Larval Culex Pipiens Complex Mosquitoes (Diptera: Culicidae)

ABSTRACT Multiple assays are available to measure P450 activity in insects, including mosquitoes; however, each of these assays has drawbacks in terms of the number of mosquitoes required, specificity, sensitivity, cost, and/or time required to prepare active enzyme homogenates. In this study, a commercially available luminescent assay, P450-Glo, was modified and evaluated to measure P450 activity from the gut of a single larva after removal of the gut contents. We also compared this assay to an earlier developed fluorescent assay. After optimization of assay conditions, the P450-Glo assay held considerable promise to be used as an effective, inexpensive, high-throughput, and sensitive screening assay to measure P450 activities in single mosquitoes. Furthermore, we tested the utility of the single gut assay using the pyrethroid resistant Marin strain of Culex pipiens pipiens form molestus and the pyrethroid sensitive CQ-1 strain of Cx. pipiens quinqefasciatus. We observed on average 1.8-fold higher levels of P450 activity in the resistant mosquitoes in comparison to the sensitive mosquitoes. Additionally, consistent with our previous findings, distribution plots of P450 activity showed 33% of individual Marin mosquitoes had higher P450 activities than the highest activity displayed by a CQ-1 mosquito. The assay platform is highly flexible in terms of choice of tissue, method of preparation, isozyme specificity, and sample quantity and thus could easily be adapted to be used for other arthropod species.
Genotypic variations in root traits of wheat varieties at phytomer level

The aims of this study were to investigate genotypic variations in root traits at phytomer level of wheat varieties and for recommending a few root traits as selection parameters in future breeding programs. Two separate experiments were conducted to measure their root traits for hydroponically grown wheat plants. In Experiment 1, main axis length, root hair density and diameter differed from phytomer to phytomer at 60 days after sowing for two varieties, Shotabdi and Sonalika. Density of first order laterals at their axis of origin, dry weights of roots and shoots and root:shoot ratio varied significantly among 8 varieties. In Experiment 2, number of root bearing phytomer, total number of adventitious roots, main axis length at root bearing phytomer 1 and 2 (youngest roots were the reference point and numbered as phytomer 1), length of first order laterals at phytomer 3, root hair density and dry weights of roots and shoots were significantly different among varieties. PC1 (principal component 1) resulted in significant variation among varieties for number of live leaves, new roots appeared, number of root bearing phytomer, total number of adventitious roots, root dry weight and shoot dry weight. PC2 yielded significant difference among varieties for live leaves, main axes length at phytomer 1 & 2, number of new roots, root hair density and diameter. Selection of varieties based on main axes length at the youngest phytomer & root hair density per unit surface area along with dry weights of roots and shoots could be recommended for future breeding program as these four parameters consistently resulted in significant variation among varieties.
Overlapping decentralized approach to automation generation control of multi-area power systems

An overlapping decentralized control scheme is presented and applied to automatic generation control (AGC) for multi-area power systems. Based on the inclusion principle, the system is first decomposed in the expanded space as a group of pair-wise subsystems (areas). Then, the decentralized controllers designed, by standard linear quadratic (LQ) control laws are implemented in each pair-wise subsystem. Finally, the overlapping decentralized controller is obtained by coordinating and contracting the pair-wise decentralized controllers from the expanded space to the original space, preserving the inclusion conditions. When applied to AGC of a four-area power system, the proposed methodology not only guarantees AGC qualities, but also increases the system reliability with respect to a wide variety of structured perturbations. Simulation results illustrate the effectiveness of the presented approach both in the general case of information structure constraints and in the cases when some pairs of subsystems are disconnected by unpredicted faults.
Smoking reduction, smoking cessation, and incidence of fatal and non-fatal myocardial infarction in Denmark 1976–1998: a pooled cohort study

Objective: To analyse the effects of smoking reduction and smoking cessation on incidence of myocardial infarction after adjustment for established cardiovascular risk factors. Design: Prospective cohort study with record linkage to mortality and hospital registers. The association of individual change in smoking with myocardial infarction was examined in Cox proportional hazard analyses with continuous heavy smokers (⩾5 cigarettes/day) as reference. Setting: Pooled data from three population studies conducted in Copenhagen, Denmark. Participants: 10 956 men and 8467 women with complete information on smoking habits at two examinations five to ten years apart were followed up from the second examination for a first hospital admission or death from myocardial infarction. Mean duration of follow up was 13.8 years. Main results: A total of 643 participants who were heavy smokers at baseline reduced their daily tobacco consumption by at least 50% without quitting between first and second examination, and 1379 participants stopped smoking. During follow up 1658 men and 521 women experienced a fatal or non-fatal myocardial infarction. After adjustment for cardiovascular risk factors, people who stopped smoking had a decreased risk of myocardial infarction, hazard ratio 0.71 (95% confidence intervals 0.59 to 0.85). Smoking reduction was not associated with reduced risk of myocardial infarction, hazard ratio 1.15 (95% confidence intervals 0.94 to 1.40). These associations remained unchanged after controlling for baseline illness in different ways. Conclusions: Smoking cessation in healthy people reduces the risk of a subsequent myocardial infarction, whereas this study provides no evidence of benefit from reduction in the amount smoked.
Anti-Fibrotic Actions of Interleukin-10 against Hypertrophic Scarring by Activation of PI3K/AKT and STAT3 Signaling Pathways in Scar-Forming Fibroblasts

Background The hypertrophic scar (HS) is a serious fibrotic skin condition and a major clinical problem. Interleukin-10 (IL-10) has been identified as a prospective scar-improving compound based on preclinical trials. Our previous work showed that IL-10 has anti-fibrotic effects in transforming growth factor (TGF)-β1-stimulated fibroblasts, as well as potential therapeutic benefits for the prevention and reduction of scar formation. However, relatively little is known about the mechanisms underlying IL-10-mediated anti-fibrotic and scar-improvement actions. Objective To explore the expression of the IL-10 receptor in human HS tissue and primary HS fibroblasts (HSFs), and the molecular mechanisms contributing to the anti-fibrotic and scar-improvement capabilities of IL-10. Methods Expression of the IL-10 receptor was assessed in HS tissue and HSFs by immunohistochemistry, immunofluorescence microscopy, and polymerase chain reaction analysis. Primary HSFs were treated with IL-10, a specific phosphatidylinositol 3 kinase (PI3K) inhibitor (LY294002) or a function-blocking antibody against the IL-10 receptor (IL-10RB). Next, Western blot analysis was used to evaluate changes in the phosphorylation status of AKT and signal transducers and activators of transcription (STAT) 3, as well as the expression levels of fibrosis-related proteins. Results HS tissue and primary HSFs were characterized by expression of the IL-10 receptor and by high expression of fibrotic markers relative to normal controls. Primary HSFs expressed the IL-10 receptor, while IL-10 induced AKT and STAT3 phosphorylation in these cells. In addition, LY294002 blocked AKT and STAT phosphorylation, and also up-regulated expression levels of type I and type III collagen (Col 1 and Col 3) and alpha-smooth muscle actin (α-SMA) in IL-10-treated cells. Similarly, IL-10RB reduced STAT3/AKT phosphorylation and blocked the IL-10-mediated mitigation of fibrosis in HSFs. Conclusion IL-10 apparently inhibits fibrosis by activating AKT and STAT3 phosphorylation downstream of the IL-10 receptor, and by facilitating crosstalk between the PI3K/AKT and STAT3 signal transduction pathways.
An experimental comparison of single-sided preference matching algorithms

We experimentally study the problem of assigning applicants to posts. Each applicant provides a preference list, which may contain ties, ranking a subset of the posts. Different optimization criteria may be defined, which depend on the desired solution properties. The main focus of this work is to assess the quality of matchings computed by rank-maximal and popular matching algorithms and compare this with the minimum weight matching algorithm, which is a standard matching algorithm that is used in practice. Both rank-maximal and popular matching algorithms use common algorithmic techniques, which makes them excellent candidates for a running time comparison. Since popular matchings do not always exist, we also study the unpopularity of matchings computed by the aforementioned algorithms. Finally, extra criteria like total weight and cardinality are included, due to their importance in practice. All experiments are performed using structured random instances as well as instances created using real-world datasets.
Time-reversal symmetry breaking and gapped surface states due to spontaneous emergence of new order in d-wave nanoislands

We solve the Bogoliubov-de Gennes equations self-consistently for the $d$-wave order parameter in nanoscale $d$-wave systems with [110] surfaces and show that spontaneous time-reversal symmetry (TRS) breaking occurs at low temperatures due to a spontaneously induced complex order parameter of extended $s$-wave symmetry. The Andreev surface bound states, which are protected by a one-dimensional (1D) topological invariant in the presence of TRS, are gapped by the emergence of this new order parameter. The extended $s$-wave order parameter is localized within a narrow region near the surfaces, which is consistent with the fact that topological protection of the gapless Andreev surface states is characterized by the 1D topological invariant. In this TRS-breaking phase, not only is the complex order parameter induced, but also the $d$-wave order parameter itself becomes complex. Furthermore, the disappearance of topological protection brings about novel vortex phenomena near the surfaces. We show that vortex-antivortex pairs are formed in the extended $s$-wave order parameter along the surfaces if the side length of a nanoisland or the width of an infinitely long nanoribbon is relatively large.
Differential contribution of plasmalemmal Na+/Ca2+ exchange isoforms to sodium‐dependent calcium influx and NMDA excitotoxicity in depolarized neurons

Inhibition of Na+,K+‐ATPase during NMDA applications greatly increased NMDA‐induced excitotoxicity in primary cultures of forebrain neurons (FNs), but not in cerebellar granule cells (CGCs). Because Na+,K+‐ATPase inhibition promotes reversal of plasmalemmal Na+/Ca2+ exchangers, we compared the activities of reversed K+‐independent (NCX) and K+‐dependent (NCKX) Na+/Ca2+ exchangers in these cultures. To this end, we measured gramicidin‐induced and Na+‐dependent elevation in cytosolic [Ca2+] ([Ca2+]c) that represents Ca2+ influx via reversed NCX and NCKX; NCX activity was dissected out by removing external K+. The [Ca2+]c elevations mediated by NCX alone, and NCX plus NCKX combined, were 17 and 6 times more rapid in FNs than in CGCs, respectively. Northern blot analysis showed that FNs preferentially express NCX1 whereas CGCs expressed NCX3. Differences in expression of other isoforms (NCX2, NCKX2, NCKX3 and NCKX4) were less pronounced. We tested whether the NCX or NCKX family of exchangers contributes most to the toxic NMDA‐induced Ca2+ influx in depolarized neurons. We found that in FNs, inhibition of NCX alone was sufficient to significantly limit NMDA excitotoxicity, whereas in CGCs, inhibition of both NCX and NCKX was required. The data suggest that the high activity of NCX isoforms expressed in FNs, possibly NCX1, sensitizes these neurons to NMDA excitotoxicity.
Heterogeneity of d-glucuronyl C5-epimerase expression and epigenetic regulation in prostate cancer

Heparansulfate proteoglycans (HSPG) play an important role in cell–cell and cell–matrix interactions and signaling, and one of the key enzymes in heparansulfate biosynthesis is d‐glucuronyl C5‐epimerase (GLCE). A tumor suppressor function has been demonstrated for GLCE in breast and lung carcinogenesis; however, no data are available as to the expression and regulation of the gene in prostate cancer. In this study, decreased GLCE expression was observed in 10% of benign prostate hyperplasia (BPH) tissues and 53% of prostate tumors, and increased GLCE mRNA levels were detected in 49% of BPH tissues and 21% of tumors. Statistical analysis showed a positive correlation between increased GLCE expression and Gleason score, TNM staging, and prostate‐specific antigen (PSA) level in the prostate tumors (Pearson correlation coefficients GLCE/Gleason = 0.56, P < 0.05; GLCE/TNM = 0.62, P < 0.05; and GLCE/PSA = 0.88, P < 0.01), suggesting GLCE as a candidate molecular marker for advanced prostate cancer. Immunohistochemical analysis revealed an intratumoral heterogeneity of GLCE protein levels both in BPH and prostate cancer cells, resulting in a mixed population of GLCE‐expressing and nonexpressing epithelial cells in vivo. A model experiment on normal (PNT2) and prostate cancer (LNCaP, PC3, DU145) cell lines in vitro showed a 1.5‐ to 2.5‐fold difference in GLCE expression levels between the cancer cell lines and an overall decrease in GLCE expression in cancer cells. Methyl‐specific polymerase chain reaction (PCR), bisulfite sequencing, and deoxy‐azacytidin (aza‐dC) treatment identified differential GLCE promoter methylation (LNCaP 70–72%, PC3 32–35%, DU145, and PNT2 no methylation), which seems to contribute to heterogeneous GLCE expression in prostate tumors. The obtained results reveal the complex deregulation of GLCE expression in prostatic diseases compared with normal prostate tissue and suggest that GLCE may be used as a potential model to study the functional role of intratumor cell heterogeneity in prostate cancer progression.
It's not a bug, it's a feature: How misclassification impacts bug prediction

In a manual examination of more than 7,000 issue reports from the bug databases of five open-source projects, we found 33.8% of all bug reports to be misclassified - that is, rather than referring to a code fix, they resulted in a new feature, an update to documentation, or an internal refactoring. This misclassification introduces bias in bug prediction models, confusing bugs and features: On average, 39% of files marked as defective actually never had a bug. We discuss the impact of this misclassification on earlier studies and recommend manual data validation for future studies.
A Review of the Measures Designed to Assess DSM-5 Personality Disorders

The definition, classification and assessment of personality disorders (PDs) have attracted considerable debate for nearly 50 years. This paper attempts a comprehensive review of the instruments to assess all, or specific, individual disorders as described in DSM-5, including structured interviews and inventories. The review should be helpful for clinicians, researchers and also industrial and organizational psychologists, to screen and assess the personality pathology spectrum from subclinical manifestations to full blown personality pathology. A decision tree helpful to choose among the different measures is also provided.
Loads Bias Genetic and Signaling Switches in Synthetic and Natural Systems

Biological protein interactions networks such as signal transduction or gene transcription networks are often treated as modular, allowing motifs to be analyzed in isolation from the rest of the network. Modularity is also a key assumption in synthetic biology, where it is similarly expected that when network motifs are combined together, they do not lose their essential characteristics. However, the interactions that a network module has with downstream elements change the dynamical equations describing the upstream module and thus may change the dynamic and static properties of the upstream circuit even without explicit feedback. In this work we analyze the behavior of a ubiquitous motif in gene transcription and signal transduction circuits: the switch. We show that adding an additional downstream component to the simple genetic toggle switch changes its dynamical properties by changing the underlying potential energy landscape, and skewing it in favor of the unloaded side, and in some situations adding loads to the genetic switch can also abrogate bistable behavior. We find that an additional positive feedback motif found in naturally occurring toggle switches could tune the potential energy landscape in a desirable manner. We also analyze autocatalytic signal transduction switches and show that a ubiquitous positive feedback switch can lose its switch-like properties when connected to a downstream load. Our analysis underscores the necessity of incorporating the effects of downstream components when understanding the physics of biochemical network motifs, and raises the question as to how these effects are managed in real biological systems. This analysis is particularly important when scaling synthetic networks to more complex organisms.
Information for Mandarin Tones in the Amplitude Contour and in Brief Segments

Abstract While the tones of Mandarin are conveyed mainly by the F₀ contour, they also differ consistently in duration and in amplitude contour. The contribution of these factors was examined by using signal-correlated noise stimuli, in which natural speech is manipulated so that it has no F₀ or formant structure but retains its original amplitude contour and duration. Tones 2, 3 and 4 were perceptible from just the amplitude contour, even when duration was not also a cue. In two further experiments, the location of the critical information for the tones during the course of the syllable was examined by extracting small segments from each part of the original syllable. Tones 2 and 3 were often confused with each other, and segments which did not have much F₀ change were most often heard as Tonel. There were, though, also cases in which a low, unchanging pitch was heard as Tone 3, indicating a partial effect of register even in Mandarin. F₀ was positively correlated with amplitude, even when both were computed on a pitch period basis. Taken together, the results show that Mandarin tones are realized in more than just the F₀ pattern, that amplitude contours can be used by listeners as cues for tone identification, and that not every portion of the F₀ pattern unambiguously indicates the original tone.
A versatile dataset for text entry evaluations based on genuine mobile emails

Mobile text entry methods are typically evaluated by having study participants copy phrases. However, currently there is no available phrase set that has been composed by mobile users. Instead researchers have resorted to using invented phrases that probably suffer from low external validity. Further, there is no available phrase set whose phrases have been verified to be memorable. In this paper we present a collection of mobile email sentences written by actual users on actual mobile devices. We obtained our sentences from emails written by Enron employees on their BlackBerry mobile devices. We provide empirical data on how easy the sentences were to remember and how quickly and accurately users could type these sentences on a full-sized keyboard. Using this empirical data, we construct a series of phrase sets we suggest for use in text entry evaluations.
Characterization of the Aspergillus fumigatus detoxification systems for reactive nitrogen intermediates and their impact on virulence

Aspergillus fumigatus is a saprophytic mold that can cause life-threatening infections in immunocompromised patients. In the lung, inhaled conidia are confronted with immune effector cells that attack the fungus by various mechanisms such as phagocytosis, production of antimicrobial proteins or generation of reactive oxygen intermediates. Macrophages and neutrophils can also form nitric oxide (NO) and other reactive nitrogen intermediates (RNI) that potentially also contribute to killing of the fungus. However, fungi can produce several enzymes involved in RNI detoxification. Based on genome analysis of A. fumigatus, we identified two genes encoding flavohemoglobins, FhpA, and FhpB, which have been shown to convert NO to nitrate in other fungi, and a gene encoding S-nitrosoglutathione reductase GnoA reducing S-nitrosoglutathione to ammonium and glutathione disulphide. To elucidate the role of these enzymes in detoxification of RNI, single and double deletion mutants of FhpA, FhpB, and GnoA encoding genes were generated. The analysis of mutant strains using the NO donor DETA-NO indicated that FhpA and GnoA play the major role in defense against RNI. By generating fusions with the green fluorescence protein, we showed that both FhpA-eGFP and GnoA-eGFP were located in the cytoplasm of all A. fumigatus morphotypes, from conidia to hyphae, whereas FhpB-eGFP was localized in mitochondria. Because fhpA and gnoA mRNA was also detected in the lungs of infected mice, we investigated the role of these genes in fungal pathogenicity by using a murine infection model for invasive pulmonary aspergillosis. Remarkably, all mutant strains tested displayed wild-type pathogenicity, indicating that the ability to detoxify host-derived RNI is not essential for virulence of A. fumigatus in the applied mouse infection model. Consistently, no significant differences in killing of ΔfhpA, ΔfhpB, or ΔgnoA conidia by cells of the macrophage cell line MH-S were observed when compared to the wild type.
Self-healing strategies for component integration faults

Software systems increasingly integrate Off-The-Shelf (OTS) components. However, due to the lack of knowledge about the reused OTS components, this integration is fragile and can cause in the field a lot of failures that result in dramatic consequences for users and service providers, e.g. loss of data, functionalities, money and reputation. As a consequence, dynamic and automatic fixing of integration problems in systems that include OTS components can be extremely beneficial to increase their reliability and mitigate these risks. In this paper, we present a technique for enhancing component-based systems with capabilities to self-heal common integration faults by using a predetermined set of healing strategies. The set of faults that can be healed has been determined from the analysis of the most frequent integration bugs experienced by users according to data in bug repositories available on Internet. An implementation based on AOP techniques shows the viability of this technique to heal faults in real case studies.