Miracle-dz/UniFAR-FTUs huggingface dataset:
High-throughput pKa screening and prediction amenable for ADME profiling

Recent technological advances have made it possible for several new pKa assays to be used in drug screening. In this review, a critical overview is provided of current new methodologies for high-throughput screening and prediction of pKa. Typical applications of using pKa constants and charge state for absorption, distribution, metabolism and excretion (ADME) profiling and quantitative structureactivity relationship modelling complements the methodological comparisons and discussions. The experimental methods discussed include high-throughput screening of pKa by multiplexed capillary with ultraviolet absorbance detection on a 96-capillary format instrument, capillary electrophoresis and mass spectrometry (CEMS) based on sample pooling, determination of pKa by pH gradient high-performance liquid chromatography, and measurement of pKa by a mixed-buffer liner pH gradient system. Comparisons of the different experimental assays are made with emphasis on the newly developed CEMS method. The current status and recent progress in computational approaches to pKa prediction are also discussed. In particular, the accuracy limits of simple fragment-based approaches as well as quantum mechanical methods are addressed. Examples of pKa prediction from in-house drug candidates as well as commercially available drug molecules are shown and an outline is provided for how drug discovery companies can integrate experiments with computational approaches for increased applications for ADME profiling.
Citizenship and Collaboration: New Thrusts in Public Administration

In the broader context of governance intervention, humane governance, joined-up government, whole-of-government, democratic citizenship, empowered community, engaged citizens, organisational humanism, interpretive as well as critical analysis of bureaucracy and organisations, the diction shows a clear centripetal tendency towards a discourse that increasingly associates itself with a convergence that places citizens at the centre and their interests at the top. Discourse theory and post-modernism stressing the need for enhanced public dialogue reinforce the position of citizen as central in the whole scheme of things. This article is an attempt to furnish a review of recent and relevant developments in the field of governance and public administration with major emphasis on New Public Service and Collaborative Public Management, which advocate citizenship and collaboration for upholding citizens rights and ensuring better services.
Outer membrane protein 100, a versatile virulence factor of Actinobacillus actinomycetemcomitans

Actinobacillus actinomycetemcomitans (Aa) is one of the pathogenic bacteria involved in periodontal diseases. We have previously identified six major outer membrane proteins (Omps) of Aa Y4. Among them is an Omp with high molecular mass, designated Omp100, which has homology to a variety of virulence factors. Electron microscopic observation indicated that Omp100 is randomly localized on the cell surface of Aa. Aa Y4 has been shown to adhere and invade KB or normal human gingival keratinocytes. Anti‐Omp100 antibody inhibited 50% of adhesion and 70% of invasion of Aa Y4 to KB cells. An Omp100 knock‐out mutant had a decreased adhesion and invasion efficiency of 60%, compared with that of the wild type. Escherichia coli HB101 expressing Omp100 adhered twofold and invaded 10‐fold more than the wild‐type E. coli HB101. HB101 expressing Omp100 showed resistance to serum by trapping factor H, an inhibitor for C3b, with Omp100. Omp100 induced inflammatory cytokine responses of interleukin (IL)‐8, IL‐6 and tumour necrosis factor (TNF)α in epithelial cells, and induced IL‐1β and TNFα production in mouse macrophages. These results indicate that Omp100 is a versatile virulence factor that may demonstrate potential significance in the onset of periodontal diseases related to Aa.
A Trajectory Privacy-Preserving Algorithm Based on Road Networks in Continuous Location-Based Services

A major concern of the large-scale deployment of location based services (LBSs) is the safeguards of the user's location data collected by service providers, since person's location information may imply sensitive private information. Most existing techniques have addressed privacy protection mainly for snapshot queries. However, providing anonymity for continuous queries is important, since users' privacy information such as habits and customs is easy to be inferred by observing and mining a time-series sequence of query. In this paper, we present a novel l-diversity algorithm based on road networks for trajectory privacy protection, which preprocesses a set of similar trajectories to blur the actual trajectory of a user. Furthermore, we depersonalize a user's trajectory by ensuring that each location reported to LBS server is a cloaking region that contains other l-1 different trajectories, which are generated in advance from road maps. Therefore, both identity and location of the user remain anonymous from service providers in continuous queries. We evaluate our techniques under various conditions using location data synthetically generated based on real road maps, and the results show that our techniques can provide trajectory l-diversity protection using a minimum cloaking region.
Modeling of bistatic radar sea clutter returns based on IEM-B scattering model

Bistatic radar has received widespread attention for its potential advantages as it provides more degree of freedom than typical monostatic radar. However, the received signal from the marine bistatic radar is inevitably influenced by the sea clutter. In this paper, a new method of modeling bistatic radar sea clutter returns is presented. The method adopted the Bistatic Integral Equation Model (IEM-B) to calculate bistatic sea clutter reflectivity by formulating the bistatic geometrical relationship. Then a new formulation for the scale parameter of compound K-distribution in bistatic configuration is proposed according to the bistatic sea clutter reflectivity. Finally, the returns of the bistatic radar sea clutter following compound K-distribution are generated by the theory of Spherically Invariant Random Processes (SIRP). This study can be used to evaluate the bistatic radar signal model and predict system detection performance in a sea clutter environment. Simulation results show the efficiency of the proposed method.
[Effects of ethyl pyruvate on cell-mediated immune function in rats with delayed resuscitation after burn injury].

OBJECTIVE To investigate the effects of ethyl pyruvate (EP) on cell-mediated immune function in rats with delayed resuscitation after burn injury, and its potential regulatory mechanism. METHODS Wistar rats were subjected to 30% full-thickness scald injury with delayed resuscitation. One hundred and three male rats were randomly divided into normal controls (n=7), sham scald group (n=32), scald group (n=32) in which 40 ml/kg normal saline was infused peritoneally 6 hours after scald, and EP treatment group (n=32) in which 40 mg/kg EP was injected peritoneally 6 hours after scald. Animals were sacrificed on postburn day 1, 3, 5, and 7, and spleen was collected to determine splenocyte proliferation, IL-2 production and cell-surface IL-2 receptor (IL-2R) expression. RESULTS Splenic lymphocyte proliferation responses to T cell mitogen, concanavalin A (Con A), were depressed from 1 to 7 days after scald injury (all P<0.05). Meanwhile, in comparison with sham scald group, burn injury resulted in a significant decrease in splenic production of IL-2 on postburn day 1, 3, as well as 5, and a marked suppression of IL-2R expression on days 1 and 3 postburn (all P<0.05). Treatment with EP after burn injury showed a dramatic restoration of lymphocyte proliferation rate and increased production of IL-2 at various time points (all P<0.05). However, treatment with EP did not affect IL-2R expression compared with scalded rats (all P>0.05). CONCLUSION Treatment with EP could markedly elevate splenic T lymphocyte proliferation response and increase production of IL-2 following burn injury, thereby improving cell-mediated immunity in thermally injured rats with delayed resuscitation.
Childhood reactions to terrorism-induced trauma: a review of the past 10 years.

OBJECTIVE To summarize the literature about the clinical presentation and treatment interventions of childhood reactions to terrorism-induced trauma. METHOD The literature on children's responses to terrorist activities was reviewed. RESULTS Over the past 10 years, more research has emerged on the subject of terrorism in children. Many of the effects of terrorism-induced trauma are similar to the effects of natural and man-made trauma. Children's responses include acute stress disorder, posttraumatic stress disorder, anxiety, depression, regressive behaviors, separation problems, sleep difficulties, and behavioral problems. However, several aspects of terrorist attacks result in unique stressors and reactions and pose specific challenges for treatment. The unpredictable, indefinite threat of terrorist events, the profound effect on adults and communities, and the effect of extensive terrorist-related media coverage exacerbates underlying anxieties and contributes to a continuous state of stress and anxiety. Intervention strategies include early community-based interventions, screening of children at risk, triage and referral, and trauma-loss-focused treatment programs. CONCLUSIONS Advances have been made in the research of childhood reactions to terrorism-induced trauma. Further research is needed to identify children at risk and to determine the long-term impact on children's development. Although the preliminary results of interventions developed to help children are promising, outcome data have not been examined, and further research is needed to evaluate their effectiveness.
Model Predictive Control for Smart Grids With Multiple Electric-Vehicle Charging Stations

Next-generation power grids will likely enable concurrent service for residences and plug-in electric vehicles (PEVs). While the residence power demand profile is known and thus can be considered inelastic, the PEVs’ power demand is only known after random PEV arrivals. PEV charging scheduling aims at minimizing the potential impact of the massive integration of PEVs into power grids to save service costs to customers while power control aims at minimizing the cost of power generation subject to operating constraints and meeting demand. This paper develops a model predictive control-based approach to address joint PEV charging scheduling and power control to minimize both PEV charging cost and energy generation cost in meeting both residence and PEV power demands. Unlike in related works, no assumptions are made about the probability distribution of PEVs’ arrivals, knowledge of PEVs’ future demand, or unlimited charging capacity of PEVs. The proposed approach is shown to achieve a globally optimal solution. Numerical results for IEEE benchmark power grids serving Tesla model S PEVs show the merit of this approach.
Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis.

BACKGROUND Because the efficacy of carboplatin and cisplatin in the treatment of advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed. METHODS Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test (Q test) was used to test for heterogeneity among trials, and the I2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided. RESULTS Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P<.001). Carboplatin treatment was associated with a non-statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23 and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy. CONCLUSIONS Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.
Automated Classification of Multi-Labeled Patient Safety Reports: A Shift from Quantity to Quality Measure

Over the past two decades, there have seen an ever-increasing amount of patient safety reports yet the capacity of extracting useful information from the reports remains limited. Classification of patient safety reports is the first step of performing a downstream analysis. In practice, the manual review processes for classification are labor-intense. Studies have shown that the reports are often mislabeled or unclassifiable based on the pre-defined categories, which presents a notable data quality problem. In this study, we investigated the multi-labeled nature of patient safety reports. We argue that understanding multi-labeled nature of reports is a key to disclose the complex relations between many components during the courses and development of medical errors. Accordingly, we developed automated multi-label text classifiers to process patient safety reports. The experiments demonstrated feasibility and efficiency of a combination of multi-label algorithms in the benchmark comparison. Grounded on our experiments and results, we provided suggestions on how to implement automated classification of patient safety reports in the clinical settings.
Initiation of exemestane in two warfarin-treated patients leading to elevation and variability of INR

Aromatase inhibitors are sometimes chosen for adjuvant therapy in post-menopausal breast cancer patients with a history of venous thromboembolism over an antiestrogen due to the lower risk of venous thromboembolism associated with aromatase inhibitors compared to antiestrogens. We report two cases where patients on warfarin therapy had an increase in their international normalized ratio with the initiation of exemestane therapy. Initially, the patients also showed international normalized ratio variability possibly due to variable absorption of exemestane. We suggest patients being treated with warfarin and exemestane concomitantly need close monitoring and education in order to decrease the risk of adverse events that could be associated with this possible interaction. To our knowledge, there are no similar reported cases in the literature.
The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20–70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ∼ 6 × 10−9 Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of aP = (8.74 ± 1.33) × 10−10 m/s2. This apparent violation of the Newton’s gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.
Modified orthogonal pilot scheme for Carrier Frequency Offset estimation in 2×2 MIMO system

The emerging of OFDM technique applied on MIMO systems to improve signal quality and capacity has recently gained a lot of attention. The Carrier Frequency Offset (CFO) due to time-varying fading channel is the main cause of the loss of orthogonality among OFDM subcarriers which is linked to inter-carrier interference (ICI). Hence, it is necessary to precisely estimate and compensate the CFO. Especially for data-aid transmission, CFO also has to be correctly estimated in order to track the channel and frequency synchronization. In this paper, we present the new pilot scheme which reduces the effect of data-interference to pilot tone by modifying the orthogonal pilot pattern. The results show that our proposed scheme provides better system performance by reducing the variance of CFO error.
Effect of squamous metaplasia on infection of hamster trachea organ cultures with Mycoplasma pneumoniae

An organ culture system for hamster trachea was developed for maintenance of the ciliated respiratory epithelium during periods of extended cultivation (i.e., greater than 20 days). Evaluation of five serum types showed that horse serum and fetal calf serum were best for the maintenance of epithelial ciliary activity and morphology. Rings that were opened on one side ("split rings") had the best maintenance of the ciliated epithelium as judged by the retention of ciliary activity and normal histological appearance after 3 to 4 weeks in culture. The in vitro induction of squamous metaplasia was achieved by cultivating explants in Waymouth MAB 87/3 (vitamin A-free) medium, without serum. This system allowed a direct comparison of the effects of Mycoplasma pneumoniae infection in two epithelial types, ciliated pseudostratified columnar and keratinizing squamous. Attachment of 14C-labeled mycoplasmas was more than twofold greater in the normal epithelium. Pretreatment of explants with neuraminidase decreased attachment for both squamous and pseudostratified epithelial surfaces to a similar basal level. Recovery of viable organisms from infected tissue of both epithelial types indicated that the organism titer remained essentially constant during the infection period, but was significantly higher for the pseudostratified ciliated epithelium. These results suggest that specific receptor sites for M. pneumoniae are markedly reduced by the induction of squamous metaplasia and, hence, appear to be specific for the normal respiratory surface containing goblet cells and pseudostratified, ciliated epithelial cells.
Migration and career attainment of power couples: the roles of city size and human capital composition

Costa and Kahn [2000] documented that power couples tended to be located in large cities, postulating a need to solve a colocation problem peculiar to dual-career, highly-educated spouses. Using data from the 2008-2014 American Community Surveys, I find that while the point estimates indicate that young full-power couples are more likely to move to larger, better-educated cities than couples in which just the husband has a college degree, and wifeonly power couples more likely than couples in which neither spouse has a college degree, the differences are statistically significant only compared with medium-szie cities. Possession of an advanced degree by the wife matters more consistently for choice of city size. I also find that the wife’s degree matters with respect to the human capital composition of cities. Finally, I present new evidence that larger cities improve joint husband-and-wife career outcomes as measured by occupational attainment, and that the degree of improvement is greater when the wife has a college degree, holding constant whether the husband has a degree. 0This paper was presented at the 2013 NARSC meetings in Atlanta and 2014 NARSC meetings in Washington. I am grateful for the comments of my discussants Daniel Hartley and Dafeng Xu, Janice Madden, Tom Mroz, Jordan Rappaport, Will Strange, Robert Tamura, Tracy Turner, and John Winters. I am, of course, responsible for all errors and omissions.
miR‐124 Negatively Regulates Osteogenic Differentiation and In vivo Bone Formation of Mesenchymal Stem Cells

MicroRNAs are novel key regulators of cellular differentiation. Dlx transcription factors play an important role in osteoblast differentiation, and Dlx5 and Dlx2 are known targets of miR‐124. Therefore, in the present study, we investigated the regulatory effects of miR‐124 on the osteogenic differentiation and in vivo bone formation of mesenchymal stem cells (MSCs). During osteogenic induction by BMP2, the expression levels of miR‐124 were inversely correlated with those of osteogenic differentiation marker genes in human and mouse bone marrow‐derived MSCs, MC3T3‐E1 cells and C2C12 cells. The overexpression of a miR‐124 mimic significantly decreased the expression levels of Dlx5, Dlx3, and Dlx2, whereas the silencing of miR‐124 with hairpin inhibitors significantly increased the expression of these Dlx genes. Luciferase reporter assays demonstrated that miR‐124 directly targets the 3′UTRs of Dlx3, Dlx5, and Dlx2. The overexpression of a miR‐124 mimic suppressed the osteogenic marker gene expression levels, alkaline phosphatase activity and matrix mineralization, which were all significantly increased by the overexpression of a miR‐124 inhibitor. When ectopic bone formation was induced by the subcutaneous transplantation of human bone marrow‐derived MSCs in nude mice, MSCs overexpressing a miR‐124 inhibitor significantly enhanced woven bone formation compared with control MSCs. However, MSCs overexpressing a miR‐124 mimic exhibited increased adipocyte differentiation at the expense of ectopic bone formation. These results suggest that miR‐124 is a negative regulator of osteogenic differentiation and in vivo bone formation and that the targeting of Dlx5, Dlx3, and Dlx2 genes partly contributes to this inhibitory effect exerted by miR‐124. J. Cell. Biochem. 116: 730–742, 2015. © 2014 Wiley Periodicals, Inc.