Miracle-dz/UniFAR-FTUs huggingface dataset:
A small protein-protein interaction domain common to KlcB and global regulators KorA and TrbA of promiscuous IncP plasmids.

The kor regulon of broad host-range, incompatibility group P (IncP) plasmids uses the KorA, KorB, and KorC repressors to regulate expression of genes for replication, conjugation, segregation, and host range. One operon, kilC, encodes the KorC repressor and two genes of unknown function (klcA and klcB). The predicted sequences of the 51.1 kDa KlcB protein, the 11.3 kDa KorA repressor, and another small (13.5 kDa) regulatory protein, TrbA, show a highly related 35 amino acid residue segment (V-L-P domain). We found that induction of the klcB gene is toxic to Escherichia coli host cells harboring an IncP plasmid. We confirmed a model in which the V-L-P domain of KlcB interacts directly with the V-L-P domain of KorA to derepress KorA-regulated operons, thereby allowing expression of toxic genes. First, a lacZ reporter fused to the kleA promoter, which is regulated by KorA and KorC, revealed that klcB induction specifically releases KorA-repression but has no effect on KorC repression. Second, induced expression of the V-L-P domains from KorA or KlcB is sufficient to release KorA-repression at the kleA promoter. Third, purified GST-KlcB fusion protein interacts specifically with His-tagged KorA. Fourth, fusion of the V-L-P domains of KorA and TrbA and full-length KlcB polypeptide to the DNA-binding domain of bacteriophage lambda repressor leads to the formation of functional, dimeric repressors, and mutations that alter conserved residues of the V-L-P domain adversely affect dimerization. Fifth, crosslinking experiments demonstrated that the V-L-P domain of KorA is able to dimerize in solution and form heterodimers in mixtures with full-length KorA polypeptide. These findings show that the V-L-P domain is a protein-protein interaction module that is likely to be responsible for dimerization of KorA and TrbA, and important for KlcB dimerization. We speculate on the possible significance of KlcB-KorA heterodimers in IncP plasmid maintenance.
Economic Impact of Regulating the Use of Amalgam Restorations

Objective. This article estimates the financial impact of a ban on amalgam restorations for selected population groups: the entire population, children, and children and women of childbearing age. Methods. Using claim and enrollment data from Delta Dental of Michigan, Ohio, and Indiana and the American Dental Association Survey of Dental Services Rendered, we estimated the per capita use and annual rate of change in amalgam restorations for each age, gender, and socioeconomic subgroup. We used population projections to obtain national estimates of amalgam use, and the dental component of the Consumer Price Index to estimate the annual rate of change in fees. We then calculated the number of dental amalgams affected by the regulation, and the fees for each of the years 2005 to 2020. Results. If amalgam restorations are banned for the entire population, the average price of restorations before 2005 and after the ban would increase $52 from $278 to $330, and total expenditures for restorations would increase from $46.2 billion to $49.7 billion. As the price of restorations increases, there would be 15,444,021 fewer restorations inserted per year. The estimated first-year impact of banning dental amalgams in the entire population is an increase in expenditures of $8.2 billion. Conclusions. An amalgam ban would have a substantial short- and long-term impact on increasing expenditures for dental care, decreasing utilization, and increasing untreated disease. Based on the available evidence, we believe that state legislatures should seriously consider these effects when contemplating possible restrictions on the use of amalgam restorations.
Performance Limits of Nyquist-WDM and CO-OFDM in High-Speed PM-QPSK Systems

We compare by simulation the performance of two techniques for generating polarization-multiplexed quadrature phase-shift keying with a high spectral efficiency (SE). The first is based on coherent optical orthogonal frequency-division multiplexing (CO-OFDM). The second, which we call Nyquist wavelength-division multiplexing (N-WDM), is based on the use of optical pulses having an “almost” rectangular spectrum, with bandwidth ideally equal to the Baud-rate. We show that the two techniques have the same sensitivity and SE under idealized assumptions. However, we found that CO-OFDM requires a much larger receiver bandwidth and proportionally faster speed of the analog-to-digital converters. We also tested CO-OFDM and N-WDM over long-haul nonlinear links and found N-WDM to outperform CO-OFDM in this case, too.
Overexpression of FOXM1 is associated with metastases of nasopharyngeal carcinoma

Abstract Background. The forkhead box M1 (FOXM1) transcription factor plays an important role in the metastases of many cancers. Down-regulation of FOXM1 by its inhibitor, thiostrepton, can inhibit the metastatic potential of some cancers; however, there are few studies regarding the functional signiﬁcance of FOXM1 and thiostrepton in the metastases of nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods. Expression of FOXM1 in NPC, normal nasopharyngeal tissues, a NPC cell line (C666-1), and a nasopharyngeal epithelial cell line (NP69) was investigated by immunohistochemical staining, qRT-PCR, and Western blot. The correlation between FOXM1 expression and the clinical characteristics of patients was analyzed. Moreover, the effects of thiostrepton on expression of FOXM1 in C666-1 and NP69 cells, and the invasion and migration ability of C666-1 cells were examined. The expressions of MMP-2, MMP-9, fascin-1, ezrin, and paxillin were determined after treatment with thiostrepton. Results. FOXM1 was overexpressed in NPC and C666-1 cells compared with normal nasopharyngeal tissues and NP69 cells. Overexpression of FOXM1 was associated with lymph node metastasis and advanced tumor stage. Moreover, thiostrepton inhibited expression of FOXM1 in C666-1 cells in a dose-dependent manner, but had a minimal effect on NP69 cells. Thiostrepton inhibited the migration and invasion ability of C666-1 cells by down-regulating the expression of MMP-2, MMP-9, fascin-1, and paxillin. Conclusions. Overexpression of FOXM1 is associated with metastases of NPC patients. Thiostrepton inhibits the metastatic ability of NPC cells by down-regulating the expression of FOXM1, MMP-2, MMP-9, fascin-1, and paxillin.
Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.
Rewarding employee performance: line managers' values, beliefs and perspectives

This article explores managerial perceptions of the effectiveness and fairness of individual performance-related pay schemes. It draws upon findings from a two-part study of middle managers' interpretation and application of performance-related pay processes in a variety of organizational contexts. The analysis reveals that middle managers all too often do not share the principles or the stated objectives of the schemes they are required to operationalize. It concludes that the importance of managerial values and beliefs about rewarding individual contribution has been an overlooked and underestimated dimension in the design and application of individual performancerelated pay schemes (IPRP) despite the significance of the manager's role in their organizational effectiveness.
An unusually powerful mode of low-frequency sound interference due to defective hair bundles of the auditory outer hair cells

Significance We show that the submembrane scaffold protein Nherf1 is necessary for correct shaping of outer hair cells stereocilia bundles in the basal cochlea. The mild elevation of hearing thresholds (22–35 dB) of Nherf1−/− mice at high frequencies was inconsistent with the loss of outer hair cell functionality in the basal cochlea. Responses of Nherf1−/− mice to high-frequency test tones were masked by tones displaying inordinate characteristics in frequency, level, and growth response. We suggest that in Nherf1−/− mice, high-frequency vibrations are detected in the unaffected apical cochlea, thus accounting for the powerful masking effect of low-frequency sound. This source of misleading evaluation of high-frequency hearing thresholds and hypervulnerability to low-frequency sound interference should be systematically sought in hearing-impaired patients. A detrimental perceptive consequence of damaged auditory sensory hair cells consists in a pronounced masking effect exerted by low-frequency sounds, thought to occur when auditory threshold elevation substantially exceeds 40 dB. Here, we identified the submembrane scaffold protein Nherf1 as a hair-bundle component of the differentiating outer hair cells (OHCs). Nherf1−/− mice displayed OHC hair-bundle shape anomalies in the mid and basal cochlea, normally tuned to mid- and high-frequency tones, and mild (22–35 dB) hearing-threshold elevations restricted to midhigh sound frequencies. This mild decrease in hearing sensitivity was, however, discordant with almost nonresponding OHCs at the cochlear base as assessed by distortion-product otoacoustic emissions and cochlear microphonic potentials. Moreover, unlike wild-type mice, responses of Nherf1−/− mice to high-frequency (20–40 kHz) test tones were not masked by tones of neighboring frequencies. Instead, efficient maskers were characterized by their frequencies up to two octaves below the probe-tone frequency, unusually low intensities up to 25 dB below probe-tone level, and growth-of-masker slope (2.2 dB/dB) reflecting their compressive amplification. Together, these properties do not fit the current acknowledged features of a hypersensitivity of the basal cochlea to lower frequencies, but rather suggest a previously unidentified mechanism. Low-frequency maskers, we propose, may interact within the unaffected cochlear apical region with midhigh frequency sounds propagated there via a mode possibly using the persistent contact of misshaped OHC hair bundles with the tectorial membrane. Our findings thus reveal a source of misleading interpretations of hearing thresholds and of hypervulnerability to low-frequency sound interference.
Complementary Roles for Rpn11 and Ubp6 in Deubiquitination and Proteolysis by the Proteasome*

Substrates destined for degradation by the 26 S proteasome are labeled with polyubiquitin chains. These chains can be dismantled by deubiquitinating enzymes (DUBs). A number of reports have identified different DUBs that can hydrolyze ubiquitin from substrates bound to the proteasome. We measured deubiquitination by both isolated lid and base-core particle subcomplexes, suggesting that at least two different DUBs are intrinsic components of 26 S proteasome holoenzymes. In agreement, we find that highly purified proteasomes contain both Rpn11 and Ubp6, situated within the lid and base subcomplexes, respectively. To study their relative contributions, we purified proteasomes from a mutant in the putative metalloprotease domain of Rpn11 and from a ubp6 null. Interestingly, in both preparations we observed slower deubiquitination rates, suggesting that Rpn11 and Ubp6 serve complementary roles. In accord, the double mutant is synthetically lethal. In contrast to WT proteasomes, proteasomes lacking the lid subcomplex or those purified from the rpn11 mutant are less sensitive to metal chelators, supporting the prediction that Rpn11 may be a metalloprotein. Treatment of proteasomes with ubiquitin-aldehyde or with cysteine modifiers also inhibited deubiquitination but simultaneously promoted degradation of a monoubiquitinated substrate along with the ubiquitin tag. Degradation is unique to 26 S proteasome holoenzymes; we could not detect degradation of a ubiquitinated protein by “lidless” proteasomes, although they were competent for deubiquitination. The fascinating observation that a single ubiquitin moiety is sufficient for targeting an otherwise stable substrate to proteasomes exposes how rapid deubiquitination of poorly ubiquitinated substrates may counteract degradation.
Time to presentation and 12-month health outcomes in patients presenting to the emergency department with symptoms of possible acute coronary syndrome

Objective To define the association between time taken to present to the emergency department (ED) with symptoms of possible acute coronary syndrome (ACS) and 1-year outcomes. We also determined whether particular patient characteristics are associated with delays in seeking care after symptom onset. Methods We collected data, which included a customised case report form to record symptom onset, on adult patients presenting with suspected ACS to two EDs in Australia and New Zealand. Such patients were followed up prospectively for 1 year. The composite primary endpoint included death, acute myocardial infarction, unstable angina pectoris treated with revascularisation or readmission with heart failure occurring after discharge but within 12 months after the index presentation. Results ACS was diagnosed at presentation in 420 (16.8%) of 2515 patients recruited. Cox regression was conducted to assess the relationship between presentation time and the rate of primary endpoints after controlling for age, ethnicity, prior angina, prior coronary artery bypass graft and index diagnosis. Middle (2–6 h) and late presenters (>6 h postsymptom onset) developed the primary endpoint at a rate 1.22 (95% CI 0.80 to 1.85) and 1.57 (1.07 to 2.31) times higher than early presenters. Patients with known risk factors and cardiovascular disease were more likely to present late to the ED. Conclusions There is an independent association between time to presentation and 1-year cardiac outcomes following initial chest pain assessment for ED patients with possible cardiac chest pain in the Australian and New Zealand setting. This association occurred irrespective of the eventual diagnosis. Effective public health campaigns and other measures that facilitate early presentation with symptoms for patients with symptoms suggestive of ACS are justified and may improve prognosis. Trial registration number ACTRN12611001069943.
Measuring the Upstreamness of Production and Trade Flows

We propose two distinct approaches to the measurement of industry upstreamness (or average distance from final use) and show that they yield an equivalent measure. Furthermore, we provide two additional interpretations of this measure, one of them related to the concept of forward linkages in Input-Output analysis. On the empirical side, we construct this measure for 426 industries using the 2002 US Input-Output Tables. We also verify the stability of upstreamness across countries in the OECD STAN database, albeit with a more aggregated industry classification. Finally, we present an application that explores the determinants of the average upstreamness of exports at the country level using trade flows for 2002.
Sliding Mode Observer and Backstepping Control for a Quadrotor Unmanned Aerial Vehicles

In this paper, we propose a new approach of the backstepping control running parallel with a sliding mode observer for a quadrotor unmanned aerial vehicle. The sliding mode observer works as an observer of the quadrotor velocities and estimator of the external disturbances such as wind and parameter uncertainties. The controller objective is to achieve good tracking of desired (x,y,z) absolute positions and yaw angle while keeping the stability of the pitch and roll angles, in spite of the presence of bounded external disturbances. For this reason, the observer-controller is proposed to estimate the effect of external perturbations in order to compensate them. The design methodology is based on Lyapunov stability. Simulation results show the good performances and the robustness of the proposed observer-controller.
Sex, Ecology and the Brain: Evolutionary Correlates of Brain Structure Volumes in Tanganyikan Cichlids

Analyses of the macroevolutionary correlates of brain structure volumes allow pinpointing of selective pressures influencing specific structures. Here we use a multiple regression framework, including phylogenetic information, to analyze brain structure evolution in 43 Tanganyikan cichlid species. We analyzed the effect of ecological and sexually selected traits for species averages, the effect of ecological traits for each sex separately and the influence of sexual selection on structure dimorphism. Our results indicate that both ecological and sexually selected traits have influenced brain structure evolution. The patterns observed in males and females generally followed those observed at the species level. Interestingly, our results suggest that strong sexual selection is associated with reduced structure volumes, since all correlations between sexually selected traits and structure volumes were negative and the only statistically significant association between sexual selection and structure dimorphism was also negative. Finally, we previously found that monoparental female care was associated with increased brain size. However, here cerebellum and hypothalamus volumes, after controlling for brain size, associated negatively with female-only care. Thus, in accord with the mosaic model of brain evolution, brain structure volumes may not respond proportionately to changes in brain size. Indeed selection favoring larger brains can simultaneously lead to a reduction in relative structure volumes.
Predicting Factors for Retailers' Sale of Cigarettes to Adolescents in the Lower Part of Northern Region of Thailand.

BACKGROUND Thailand is one of the members of WHO FCTC and has paid so much attention to preventing adolescents' access to tobacco. However, Thai adolescents still have access to tobacco with ease. The aim of this research was to investigate the predicting factors for the cigarettes sale to adolescents by the retailers in Thailand. STUDY DESIGN A cross-sectional study. METHODS This cross sectional survey was conducted after a careful desk review of the relevant literature. Multistage random sampling technique was used to sample the survey participants (n = 675) who were retailers of tobacco in the lower northern region of Thailand. Data were collected by validated questionnaires and analyzed by descriptive analytic, chi-square test and binary logistic regression. RESULTS More than half (58.7%) of the participants sell cigarettes to adolescents. Factors such as open display of cigarette at the point of sale, selling cigarettes in sticks, selling cigarettes by self-service, and reluctant disregard of buyers' age by the seller significantly correlated with and predicted, at 95% level of confidence, the behavior of retailers selling cigarettes to adolescents. CONCLUSIONS Thai adolescent's access to tobacco continues to be a serious public health problem. Therefore, the Ministry of Public Health and other relevant stakeholders saddled with the responsibility of interventions to scale up measures that would reinforce the law of Tobacco Control Act.
(Gray) Mappings for Bit-Interleaved Coded Modulation

Mappings for square quadrature amplitude modulation (QAM) are investigated in terms of the achievable capacity in bit-interleaved coded modulation (BICM). In G. Caire et al. (1998) it is conjectured that Gray labelings maximize this capacity. However, Gray mappings are not unique and it can be shown that the conjecture cannot hold in general for QAM constellation sizes larger than 16. Based on the bit level capacities of mappings, structures determining capacity are analyzed. Construction guidelines leading to capacity maximizing Gray mappings are presented.
Real-time reconfigurable scheduling of aperiodic OS tasks on multiprocessor systems

The paper deals with the real-time scheduling of aperiodic OS tasks that composed multiprocessor embedded systems which can change their behaviors at run-time for each reconfiguration scenario. A reconfiguration scenario is assumed to be any run-time automatic addition, removal, or also update of OS tasks according to external events or also user requirements. We propose a new approach to check the system's feasibility of the tasks while minimizing their response times. An agent-based architecture is proposed to provide run-time technical solutions for users in order to reach again the system's feasibility after any reconfiguration scenario for the whole multiprocessor embedded systems. We discuss the paper's contribution by analyzing the experimental results that we did on a running example.
Streamlining DNA Barcoding Protocols: Automated DNA Extraction and a New cox1 Primer in Arachnid Systematics

Background DNA barcoding is a popular tool in taxonomic and phylogenetic studies, but for most animal lineages protocols for obtaining the barcoding sequences—mitochondrial cytochrome C oxidase subunit I (cox1 AKA CO1)—are not standardized. Our aim was to explore an optimal strategy for arachnids, focusing on the species-richest lineage, spiders by (1) improving an automated DNA extraction protocol, (2) testing the performance of commonly used primer combinations, and (3) developing a new cox1 primer suitable for more efficient alignment and phylogenetic analyses. Methodology We used exemplars of 15 species from all major spider clades, processed a range of spider tissues of varying size and quality, optimized genomic DNA extraction using the MagMAX Express magnetic particle processor—an automated high throughput DNA extraction system—and tested cox1 amplification protocols emphasizing the standard barcoding region using ten routinely employed primer pairs. Results The best results were obtained with the commonly used Folmer primers (LCO1490/HCO2198) that capture the standard barcode region, and with the C1-J-2183/C1-N-2776 primer pair that amplifies its extension. However, C1-J-2183 is designed too close to HCO2198 for well-interpreted, continuous sequence data, and in practice the resulting sequences from the two primer pairs rarely overlap. We therefore designed a new forward primer C1-J-2123 60 base pairs upstream of the C1-J-2183 binding site. The success rate of this new primer (93%) matched that of C1-J-2183. Conclusions The use of C1-J-2123 allows full, indel-free overlap of sequences obtained with the standard Folmer primers and with C1-J-2123 primer pair. Our preliminary tests suggest that in addition to spiders, C1-J-2123 will also perform in other arachnids and several other invertebrates. We provide optimal PCR protocols for these primer sets, and recommend using them for systematic efforts beyond DNA barcoding.