Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting the ERK signaling pathway in cancer therapy

The extracellular signal‐regulated kinase (ERK) signaling pathway is a major determinant in the control of diverse cellular processes such as proliferation, survival, differentiation and motility. This pathway is often up‐regulated in human tumors and as such represents an attractive target for the development of anticancer drugs. Because of its multiple roles in the acquisition of a complex malignant phenotype, specific blockade of the ERK pathway is expected to result in not only an anti‐proliferative effect but also in anti‐metastatic and anti‐angiogenic effects in tumor cells. Recently potent small‐molecule inhibitors targeting the components of the ERK pathway have been developed. Among them, BAY 43‐9006 (Raf inhibitor), and PD184352, PD0325901 and ARRY‐142886 (MEK1/2 inhibitors) have reached the clinical trial stage. We briefly discuss the possibility that combination of ERK pathway inhibitors (cytostatic agents) and conventional anticancer drugs (cytotoxic agents) provides an excellent basis for the development of new chemotherapeutic strategies against cancer.
Balancing Model Performance and Simplicity to Predict Postoperative Primary Care Blood Pressure Elevation

BACKGROUND:Because of uncertainty regarding the reliability of perioperative blood pressures and traditional notions downplaying the role of anesthesiologists in longitudinal patient care, there is no consensus for anesthesiologists to recommend postoperative primary care blood pressure follow-up for patients presenting for surgery with an increased blood pressure. The decision of whom to refer should ideally be based on a predictive model that balances performance with ease-of-use. If an acceptable decision rule was developed, a new practice paradigm integrating the surgical encounter into broader public health efforts could be tested, with the goal of reducing long-term morbidity from hypertension among surgical patients. METHODS:Using national data from US veterans receiving surgical care, we determined the prevalence of poorly controlled outpatient clinic blood pressures ≥140/90 mm Hg, based on the mean of up to 4 readings in the year after surgery. Four increasingly complex logistic regression models were assessed to predict this outcome. The first included the mean of 2 preoperative blood pressure readings; other models progressively added a broad array of demographic and clinical data. After internal validation, the C-statistics and the Net Reclassification Index between the simplest and most complex models were assessed. The performance characteristics of several simple blood pressure referral thresholds were then calculated. RESULTS:Among 215,621 patients, poorly controlled outpatient clinic blood pressure was present postoperatively in 25.7% (95% confidence interval [CI], 25.5%–25.9%) including 14.2% (95% CI, 13.9%–14.6%) of patients lacking a hypertension history. The most complex prediction model demonstrated statistically significant, but clinically marginal, improvement in discrimination over a model based on preoperative blood pressure alone (C-statistic, 0.736 [95% CI, 0.734–0.739] vs 0.721 [95% CI, 0.718–0.723]; P for difference <0.0001). The Net Reclassification Index was 0.088 (95% CI, 0.082–0.093); P < 0.0001. A preoperative blood pressure threshold ≥150/95 mm Hg, calculated as the mean of 2 readings, identified patients more likely than not to demonstrate outpatient clinic blood pressures in the hypertensive range. Four of 5 patients not meeting this criterion were indeed found to be normotensive during outpatient clinic follow-up (positive predictive value, 51.5%; 95% CI, 51.0–52.0; negative predictive value, 79.6%; 95% CI, 79.4–79.7). CONCLUSIONS:In a national cohort of surgical patients, poorly controlled postoperative clinic blood pressure was present in >1 of 4 patients (95% CI, 25.5%–25.9%). Predictive modeling based on the mean of 2 preoperative blood pressure measurements performed nearly as well as more complicated models and may provide acceptable predictive performance to guide postoperative referral decisions. Future studies of the feasibility and efficacy of such referrals are needed to assess possible beneficial effects on long-term cardiovascular morbidity.
Improving Risk Equalization Using Multiple-year High Cost as a Health Indicator

Background:More and more competitive health insurance markets use risk equalization to compensate health plans for the predictable high costs of chronically ill enrollees. In the presence of premium rate restrictions, an important goal of risk equalization is to reduce incentives for selection, while maintaining incentives for efficiency. The literature shows, however, that even the most sophisticated risk equalization models—which include both diagnoses-based and pharmacy-based indicators of health status—do not reduce incentives for selection sufficiently. Objectives:The goal of this study is to examine the extent to which a sophisticated risk-equalization model can be improved by using multiple-year high cost as a health indicator. The idea is that health plans receive an additional compensation for enrollees whose costs were in the top–15% in each of the 3 preceding years, assuming that this group contains a substantial overrepresentation of people with a chronic condition. Research design:We examine 3 types of additional compensation: (1) retrospective compensation, (2) fixed prospective compensation, and (3) continuous prospective compensation. Subjects:We use individual-level information on medical costs and risk characteristics from the period 2004 to 2007 for almost the entire Dutch population. Measures:The effect on selection incentives is measured by predictive ratios for subgroups of enrollees who were undercompensated in previous years. The effect on efficiency incentives is quantified by the relationship between cost and compensation. Results and conclusions:All 3 modalities substantially reduce incentives for selection, but—to some extent—also reduce incentives for efficiency. With respect to these criteria, the continuous prospective compensation outperforms the other 2 modalities.
Robust estimation of a global Gaussian mixture by decentralized aggregations of local models

Distributed data collections are now more and more common due to the emergence of cloud computing, to spatially decentralized businesses, or to the availability of various data sharing web services. Obtain knowledge in such a collection raises then the need of new data mining methods to apply in a decentralized architecture. In this paper, we explore a machine learning side of this work direction. We propose a novel technique for decentralized estimation of probabilistic mixture models, which are among the most versatile generative models for understanding data sets. More precisely, we demonstrate how to estimate a global mixture model from a set of local models. Our approach accommodates dynamic topology and data sources and is statistically robust, i.e. resilient to the presence of unreliable local models. Such outlier models may arise from local data which are outliers, compared to the global trend, or poor mixture estimation. We report experiments on synthetic data and real geo-location data from Flickr.
QSPR study of Setschenow constants of organic compounds using MLR, ANN, and SVM analyses

A quantitative structure‐property relationship (QSPR) study was performed for the prediction of the Setschenow constants (Ksalt) by sodium chloride of organic compounds. The entire set of 101 compounds was randomly divided into a training set of 71 compounds and a test set of 30 compounds. Multiple linear regression, artificial neural network (ANN), and support vector machine (SVM) were utilized to build the linear and nonlinear QSPR models, respectively. The obtained models with four descriptors involved show good predictive ability. The linear model fits the training set with R2 = 0.8680, while ANN and SVM higher values of R2 = 0.8898 and 0.9302, respectively. The validation results through the test set indicate that the proposed models are robust and satisfactory. The QSPR study suggests that the molecular lipophilicity is closely related to the Setschenow constants. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Increased hepcidin expression in colorectal carcinogenesis.

AIM To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anaemia and whether it might have a role in colorectal carcinogenesis. METHODS Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation was determined using immunohistochemistry. RESULTS We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was positively associated with increasing T-stage of colorectal cancer (P<0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repression. This was supported by hepcidin immunoreactivity in colorectal cancer tissue. CONCLUSION We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.
Intramolecular interaction in the tail of Acanthamoeba myosin IC between the SH3 domain and a putative pleckstrin homology domain

The 466-aa tail of the heavy chain of Acanthamoeba myosin IC (AMIC) comprises an N-terminal 220-residue basic region (BR) followed by a 56-residue Gly/Pro/Ala-rich region (GPA1), a 55-residue Src homology 3 (SH3) domain, and a C-terminal 135-residue Gly/Pro/Ala-rich region (GPA2). Cryo-electron microscopy of AMIC had shown previously that the AMIC tail is folded back on itself, suggesting the possibility of interactions between its N- and C-terminal regions. We now show specific differences between the NMR spectrum of bacterially expressed full-length tail and the sum of the spectra of individually expressed BR and GPA1-SH3-GPA2 (GSG) regions. These results are indicative of interactions between the two subdomains in the full-length tail. From the NMR data, we could assign many of the residues in BR and GSG that are involved in these interactions. By combining homology modeling with the NMR data, we identify a putative pleckstrin homology (PH) domain within BR, and show that the PH domain interacts with the SH3 domain.
THE STATUS OF GAMBUSIA AFFINIS (BAIRD & GIRARD) IN SOUTH-WESTERN AUSTRALIA

The truth is different, for actually Gambusia has been established in Western Australia for many years. Understandably, however, naturalists and zoologists are ,usually more interested in native fauna than in introduced exotic species and that is why in zoological literature little has been published on Gambusia in Western Australia. Whitley (1948) did not mention the species, but in the same year it was recorded from Lake Leschenaultia by Shipway (1948), who observed that in April 1948: 'No native fishes were found, the lake apparently containing only English Perch (Perca fluviatitis) and Gambusia affinis'. In later volumes of the Western Australian Naturalist I have traced four more references to Gambusia affinis, and perhaps it reflects the contempt in which this little fish is held that, although it has been recorded five times in five different volumes, its name is found in the index of only two. In chronological sequence the records are: Hyde Park Lake, Perth, where: 'An exotic fish, Gambusia affinis, has been introduced and no native fishes have been seen there' (Irene Shipway 1950, reporting on a visit made in 1949); Lake Cooloongup or White Lake (Robinson 1951); Ellendale Pool, Greenough River (Watson 1958) and Benger Swamp (Sedgwick 1973). In addition, the species is listed for Western Australia by Main and Edward (1968), but without particulars.
Effect of CPP-ACP Paste on Enamel Carious Lesion of Primary Upper Anterior Teeth Assessed by Quantitative Light-Induced Fluorescence: A One-Year Clinical Trial

The purpose of this clinical trial was to evaluate the effect of 1 year of daily application of 10% w/v CPP-ACP (casein phosphopeptide-amorphous calcium phosphate) paste in addition to regular toothbrushing with fluoridated toothpaste on the remineralization of enamel carious lesions in preschool children using quantitative light-induced fluorescence (QLF). A total of 103 Thai children (aged 21/2-31/2 years) with high caries risk who had at least 1 enamel carious lesion (ICDAS 1-3) on the labial surface of the upper anterior teeth were assigned to receive either CPP-ACP paste (n = 53) or placebo control (n = 50) following toothbrushing with fluoridated toothpaste after lunch at school. QLF measurement was performed at baseline, 6 months and 1 year. At 1 year, a significant reduction in fluorescence loss (ΔF), lesion area and lesion volume (ΔQ; p ≤ 0.001) of the lesions were found over time in both groups. However, no significant difference was observed between the groups (p = 0.79, 0.98 and 0.88, respectively). There was no statistically significant difference between the odds of ΔQ transition to a stage of regression or arrest compared with progression from baseline to 1 year between the two groups (OR = 1.03, 95% CI 0.31-3.39). The daily application of 10% w/v CPP-ACP paste on a school day for 1 year resulted in no improvement of enamel carious lesion remineralization in the primary upper anterior teeth as assessed by QLF. The lesion improvement was not superior to remineralization from regular toothbrushing with fluoridated toothpaste alone in these children.
MATLAB tool for predicting the global solar radiation in UAE

The prediction of the global solar radiation is of great importance for several engineering applications. Just to name few, solar radiation estimates are fundamental during the design phase of several technologies such as: flat plates and concentrating collectors, solar energy storage devices, solar heaters, and photovoltaic systems. The geographical location of the United Arab Emirates (UAE) (between 26° and 32° North Latitude and between 51° and 56° 25 East Latitude) favors the development and utilization of solar energy. A graphical user interface (GUI) was designed to assist solar energy planners, engineers, architectural scientists, and researchers to predict global solar radiation in different regions of the UAE. The predicted models are developed using Artificial Neural Network techniques.
Self-Perceptions of Life-Span Gender-Role Development

This article discusses two studies in which participants reported on self-perceptions of life-span gender-role variability based upon their expected or past performance in normative age-related developmental tasks. In Study 1, students rated themselves on the Personal Attributes Questionnaire (PAQ) at the present time and in two prospective tasks (parenthood and retirement). In Study 2, retired adults completed the PAQ at the present time and in two retrospective tasks (work-entry and parenthood). Both studies showed that participants perceived their masculine and feminine gender-role attributes as varying significantly as a result of the function of the three rating contexts, and both masculinity and femininity were perceived to increase from the chronologically earliest of these tasks to the latest.
Running head : SOCIAL BENEFITS BALANCING CREATIVITY IMITATION 1 The Social Benefits of Balancing Creativity and Imitation : Evidence from an Agent-based Model

Although creativity is encouraged in the abstract it is often discouraged in educational and workplace settings. Using an agent-based model of cultural evolution, we investigated the idea that tempering the novelty-generating effects of creativity with the novelty-preserving effects of imitation is beneficial for society. In Experiment One we systematically introduced individual differences in creativity, and observed a trade-off between the ratio of creators to imitators, and how creative the creators were. Excess creativity was detrimental because creators invested in unproven ideas at the expense of propagating proven ones. Experiment Two tested the hypothesis that society as a whole benefits if individuals adjust how creative they are in accordance with their creative success. When effective creators created more, and ineffective creators created less (social regulation), the agents segregated into creators and imitators, and the mean fitness of outputs was temporarily higher. We hypothesized that the temporary nature of the effect was due to a ceiling on output fitness. In Experiment Three we made the space of possible outputs open-ended by giving agents the capacity to chain simple outputs into arbitrarily complex ones such that fitter outputs were always possible. With the capacity for chained outputs, the effect of social regulation could indeed be maintained indefinitely. The results are discussed in light of empirical data.
The Impact of School Daily Schedule on Adolescent Sleep

Objectives. This study was initiated to examine the impact of starting school on adolescent sleep, to compare weekday and weekend sleep times, and to attempt to normalize the timing of the circadian sleep/wake cycle by administering bright light in the morning. This was a collaborative project involving high school students and their parents, as well as high school and university faculty members, for the purpose of contributing information to the scientific community while educating students about research processes and their own sleep/wake cycles and patterns. Methods. Sixty incoming high school seniors kept sleep/wake diaries beginning in August and continuing through 2 weeks after the start of school in September. Sleep diaries were also kept for 1 month in November and 1 month in February. Early-morning light treatments were given to 19 students in the last 2 weeks of November and the last 2 weeks of February. Neuropsychologic performance was measured with computer-administered tests. Paper-and-pencil tests were used for assessment of mood and vigor. A testing period consisted of 2 consecutive days at the beginning and end of November and at the beginning and end of February. Tests were given 3 times per day, ie, in the morning before school (6:30–8:00 am), during midday lunch periods (11:30 am to 1:00 pm), and in the afternoon (3:00–4:30 pm), on each of the test days. Results. Adolescents lost as much as 120 minutes of sleep per night during the week after the start of school, and weekend sleep time was also significantly longer (∼30 minutes) than that seen before the start of school (August). No significant differences were found between weekday sleep in the summer and weekend sleep during the school year. Early-morning light treatments did not modify total minutes of sleep per night, mood, or computer-administered vigilance test results. All students performed better in the afternoon than in the morning. Students in early morning classes reported being wearier, being less alert, and having to expend greater effort. Conclusions. The results of this study demonstrated that current high school start times contribute to sleep deprivation among adolescents. Consistent with a delay in circadian sleep phase, students performed better later in the day than in the early morning. However, exposure to bright light in the morning did not change the sleep/wake cycle or improve daytime performance during weekdays. Both short-term and long-term strategies that address the epidemic of sleep deprivation among adolescents will be necessary to improve health and maximize school performance.
An improved color-based tracking by particle filter

Color has proven an efficient visual feature for tracking non-linear objects in real time using Particle Filter (PF). However, the points generated by the Monte Carlo(MC)random sampling often form the possible gaps and clusters in sample set which affect the tracking accuracy and speed in PF. To solve these problems, we propose an improved method for tracking color objects with the points generated by Quasi-Monte Carlo(QMC) sampling to replace the MC points, which could break the correlation of the original ones, and use the robust color feature to model the object to improve the tracking accuracy and efficiency. Simulation shows that the proposed method is superior to the traditional one, and improves the tracking accuracy and speed.
Spindle Polarity in S. cerevisiae: MEN Can Tell

Spatial coordination between the axis of the spindle and the division plane is critical in asymmetric cell divisions. In the budding yeast S. cerevisiae, orientation of the mitotic spindle responds to two intertwined programs dictating the position of the spindle poles: one providing the blueprint for built-in pole asymmetry, the other sequentially confining microtubule-cortex interactions to the bud and the bud neck. The first program sets a temporal asymmetry to limit astral microtubules to a single pole prior to spindle pole separation. The second enforces this polarity by allowing these early formed microtubules to undergo capture at the bud cell cortex while stopping newly formed microtubules once cortical capture shifts to the bud neck. The remarkable precision of this integrated program results in an invariant pattern of spindle pole inheritance in which the "old" spindle pole is destined to the bud. An additional layer of asymmetry is superimposed to couple successful chromosomal segregation between the mother and the bud with mitotic exit. This is based on the asymmetric localization to the committed daughter-bound pole of signaling components of the mitotic exit network. This system operates irrespective of intrinsic spindle polarity to ensure that it is always the pole translocating into the bud that carries the signal to regulate mitotic exit. Key Words: Cell cycle, Polarity, checkpoint, Microtubule, Cortical cues
A Novel Silicon-Embedded Coreless Inductor for High-Frequency Power Management Applications

In this letter, a novel post-CMOS silicon-embedded coreless power inductor is proposed and demonstrated. The inductor is fabricated in the thick bottom layer of a silicon substrate and connected to the front side through vias opened in the thin top layer where control circuits can be fabricated for chip area saving. A 0.8- coreless inductor fabricated using this monolithic inductor technology shows a low dc resistance of 87 and an inductance of 13.1 nH with a quality factor of 3.9 at 100 MHz. A high inductor efficiency of 93% was estimated for 2.4-1.5-V 0.6-A power conversion at 100 MHz. This technology is very suitable for power-supply-on-chip applications.