Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

RAS proteins require membrane association for their biologic activity, making this association a logical target for anti-RAS therapeutics. Lipid modification of RAS proteins by a farnesyl isoprenoid is an obligate step in that association, and is an enzymatic process. Accordingly, farnesyltransferase inhibitors (FTI) were developed as potential anti-RAS drugs. The lack of efficacy of FTIs as anticancer drugs was widely seen as indicating that blocking RAS membrane association was a flawed approach to cancer treatment. However, a deeper understanding of RAS modification and trafficking has revealed that this was an erroneous conclusion. In the presence of FTIs, KRAS and NRAS, which are the RAS isoforms most frequently mutated in cancer, become substrates for alternative modification, can still associate with membranes, and can still function. Thus, FTIs failed not because blocking RAS membrane association is an ineffective approach, but because FTIs failed to accomplish that task. Recent findings regarding RAS isoform trafficking and the regulation of RAS subcellular localization have rekindled interest in efforts to target these processes. In particular, improved understanding of the palmitoylation/depalmitoylation cycle that regulates RAS interaction with the plasma membrane, endomembranes, and cytosol, and of the potential importance of RAS chaperones, have led to new approaches. Efforts to validate and target other enzymatically regulated posttranslational modifications are also ongoing. In this review, we revisit lessons learned, describe the current state of the art, and highlight challenging but promising directions to achieve the goal of disrupting RAS membrane association and subcellular localization for anti-RAS drug development. Clin Cancer Res; 21(8); 1819–27. ©2015 AACR. See all articles in this CCR Focus section, “Targeting RAS-Driven Cancers. ”
Are the discounts in UK open offers and placings due to inelastic demand

This paper investigates the large and diverse discounts in UK open offers and placings. Large discounts are a substantial cost to shareholders who do not buy new shares. The existing literature mainly examines US firm-commitment offers and private placements, but UK open offers and placings differ from both types of US offer. The paper presents evidence that inelastic demand, illiquidity of the issuer’s shares, and financial distress are key determinants of the discount. The effects of inelastic demand and distress are much more apparent in UK than in US SEOs. We argue that institutional features obscure the role of these variables in the US context.
Factitious increase in thyrotropin in a neonate caused by a maternally transmitted interfering substance.

Patient 1 was born at 41 weeks of gestation by normal delivery and had a normal birth weight of 3000 g. He had an increased thyrotropin (TSH) on day 3 after routine neonatal screening, using blood spots in the Elegance Neonatal TSH ELISA [TSH, 25.4 mIU/L; upper reference limit (URL), 13.0 mIU/L]. As per the standard newborn screening procedure (1)(2), the neonatal screening test was repeated on day 17, and although lower than the previous measurement, the TSH was again above the URL (TSH, 19.6 mIU/L; URL, 10.0 mIU/L). On day 21 of life, the child was euthyroid, had thrived since birth with a current weight of 3600 g, and was feeding well. No jaundice, palpable goiter, or other abnormalities were detectable. His mother had not been given iodine or other medications. She had no family history of thyroid disorder and was euthyroid on history and examination. However, both mother and child had markedly increased TSH values as measured by the laboratory Dade Behring Dimension TSH assay (mother’s TSH, 35.0 mIU/L; reference interval, 0.3–5.0 mIU/L; patient’s TSH, 60.9 mIU/L; URL, 13.0 mIU/L) but with normal free thyroxine (FT4) and free triiodothyronine (FT …
Identification of the source of androgen excess in hyperandrogenic type 1 diabetic patients.

We recently reported that the prevalence of hyperandrogenic disorders is markedly increased in women with type 1 diabetes (1). The polycystic ovary syndrome (PCOS) defined by endocrine criteria was found in 18.8% of the type 1 diabetic women who followed-up in our hospital (1), as compared with the 6.5% prevalence in nondiabetic women from similar ethnic and genetic backgrounds (2). The prevalence of hirsutism in type 1 diabetic women was 30.6% (1), which is markedly higher than the 7.1% prevalence of hirsutism found in nondiabetic women (2). In the present study, we evaluated the adrenal and ovarian steroidogenic profiles of hyperandrogenic and nonhyperandrogenic type 1 diabetic women and compared them with those of nondiabetic hyperandrogenic women and healthy control subjects. A total of 24 women with type 1 diabetes were recruited for the study (1). Fourteen diabetic patients (age [mean ± SD] 20.6 ± 4.0 years, BMI 24.8 ± 2.9 kg/m2) were considered to have hyperandrogenism. The other 10 women with type 1 diabetes (age 19.0 ± 3.0 years, BMI 23.3 ± 2.6 kg/m2) had no evidence of clinical or biochemical hyperandrogenism and had regular menstrual cycles. Both groups of type 1 diabetic patients had similar HbA1c levels (7.4 ± 1.2 vs 7.8 ± 1.2% in nonhyperandrogenic and hyperandrogenic diabetic patients, respectively, F = 0.591, P = 0.450), and there were no differences in the mean daily insulin dose used for their treatment (0.82 ± 0.27 vs. 0.66 ± 0.28 U · kg−1 body wt · day−1 in nonhyperandrogenic and hyperandrogenic diabetic patients, F = 1.875, P = 0.185). A total of 86 nondiabetic women were included as control subjects. Nondiabetic women were matched for BMI and age with the diabetic patients to avoid any influence of age and obesity on the results. Thirteen …
Dynamic Clustering and User Association in Wireless Small-Cell Networks With Social Considerations

In this paper, a novel social network-aware user association in wireless small cell networks with underlaid device-to-device (D2D) communication is investigated. The proposed approach exploits strategic social relationships between user equipments (UEs) and their physical proximity to optimize the overall network performance. This problem is formulated as a matching game between UEs and their serving nodes (SNs) in which, an SN can be a small cell base station (SCBS) or an <italic>important UE</italic> with D2D capabilities. The problem is cast as a many-to-one matching game in which UEs and SNs rank one another using preference relations that capture both the wireless aspects (i.e., received signal strength, traffic load, etc.) and users’ social ties (e.g., UE proximity and social distance). Due to the combinatorial nature of the network-wide UE–SN matching, the problem is decomposed into a dynamic clustering problem in which SCBSs are grouped into disjoint clusters based on mutual interference. Subsequently, an UE–SN matching game is carried out per cluster. The game under consideration is shown to belong to a class of matching games with <italic>externalities</italic> arising from interference and peer effects due to users social distance, enabling UEs and SNs to interact with one another until reaching a stable matching. Simulation results show that the proposed social-aware user association approach yields significant performance gains, reaching up to <inline-formula><tex-math notation="LaTeX">${\text{26}}\%$</tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">${\text{24}}\%$</tex-math></inline-formula>, and <inline-formula><tex-math notation="LaTeX"> ${\text{31}}\%$</tex-math></inline-formula> for 5th, 50th, and 95th percentiles for UE throughputs, respectively, as compared to the classical social-unaware baseline.
A Cloud-Based Transcoding Framework for Real-Time Mobile Video Conferencing System

High-definition video applications are often challenging for mobile devices due to their limited processing capability and bandwidth-constrained network connection. To deal with this issue, this paper proposes a cloud based transcoding framework to achieve scalable and efficient video adaption for mobile devices. This framework introduces a prediction-based scheduling algorithm to optimize both latency requirement and cloud utility cost for mobile clients. Following this framework, we developed a prototype system based on Windows Azure. Experiment results show that our system can effectively provide low-latency and cost-efficient video service to mobile clients.
Earning Trajectories of Highly Educated Immigrants: Does Place of Education Matter?

The author compares the earnings and earning trajectories of U.S. college-educated immigrants with those of similar immigrants who completed their education abroad using cross-sectional and longitudinal data from the 1993 and 2003 National Surveys of College Graduates. Adjusting for demographics, results based on cross-sectional data suggest that the annual earnings of college-educated, foreign-born men were 9% less than those of similar U.S.-born men whereas the annual earnings of college-educated foreign-born women were 3% less than those of similar U.S.-born women. After further adjusting for place of education, however, the gap narrowed by 42% for men and vanished for women. An analysis of longitudinal data reveals that in the first 15 years after arrival, U.S.-educated, foreign-born science and engineering (S&E) professionals had higher earnings growth (relative to native-born S&E professionals) than their foreign-educated counterparts. Evidence also indicates that attrition was associated with labor market performance. Of those in the sample, U.S.-educated S&E professionals who stayed had higher earnings than those who exited.
Calculation of key comparison reference values in the presence of non-zero-mean uncertainty distributions, using the maximum-likelihood technique

The international metrological community is involved in an ongoing series of comparisons of measurement standards. The calculation of differences from a "reference value", some form of weighted mean of the results, has been recommended as a convenient figure of merit for participating laboratories. In temperature metrology, the uncertainties of the defining reference points are dominated by the estimate of the purity of the metal sample used for the fixed-point determinations. As impurities result mainly in a depression of the apparent phase-transition temperature, the corresponding uncertainty has a non-zero mean, and the simple "least-squares" type of statistical technique for combination of uncertainties is inadequate. A robust solution based on the maximum-likelihood technique is proposed. The technique is applied to published data from a triple point of water cell comparison, and it is shown that when an exponential distribution is chosen, the calculated estimate is relatively insensitive to the magnitude of the estimated impurity uncertainty.
What is the Lowest Value of Left Ventricular Baseline Ejection Fraction that Predicts Response to Cardiac Resynchronization Therapy?

Background Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with refractory heart failure. However, many patients do not respond to therapy. Although it has been thought that there was no relation between response to CRT and baseline ejection fraction (EF), the response rate of patients with different baseline LVEF to CRT has not been evaluated in severe left ventricular systolic dysfunction. We aimed to investigate any difference in response to CRT between the severe heart failure patients with different baseline LVEF. Material/Methods In this study, 141 consecutive patients (mean age 59±13 years; 89 men) with severe heart failure and complete LBBB were included. Patients were divided into 3 groups according to their baseline LVEF: 5–15%, Group 1; 15–25%, Group 2, and 25–35%, Group 3. NYHA functional class, LVEF, LV volumes, and diameters were assessed at baseline and after 6 months of CRT. A response to CRT was defined as a decrease in LVSVi (left ventricular end-systolic volume index) ≥10% on echocardiography at 6 months. Results After 6 months, a significant increase of EF and a significant decrease of LVESVi and LVEDVi after 6 months of CRT were observed in all groups. Although the magnitude of improvement in EF was biggest in the first group, the percentage of decrease in LVESVi and LVEDVi was similar between the groups. The improvement in NYHA functional class was similar in all EF subgroups. At 6-month follow-up, 100 (71%) patients showed a reduction of >10% in LVESVi (mean reduction: −15.5±26.1 ml/m2) and were therefore classified as responders to CRT. Response rate to CRT was similar in all groups. It was 67%, 75%, and 70% in Group 1, 2, and 3, respectively, at 6-month follow-up (p>0.05). There was no statistically significant relation between the response rate to CRT and baseline LVEF, showing that the CRT has beneficial effects even in patients with very low LVEF. Conclusions It seems there is no lower limit for baseline LVEF to predict non-response to CRT in eligible patients according to current guidelines.
The Expressive Power of Word Embeddings

We seek to better understand the information encoded in word embeddings. We propose several tasks that help to distinguish the characteristics of different publicly released embeddings. Our evaluation shows that embeddings are able to capture surprisingly nuanced semantics even in the absence of sentence structure. Moreover, benchmarking the embeddings shows great variance in quality and characteristics of the semantics captured by the tested embeddings. Finally, we show the impact of varying the number of dimensions and the resolution of each dimension on the effective useful features captured by the embedding space. Our contributions highlight the importance of embeddings for NLP tasks and the effect of their quality on the final results.
Transaction-Cost Expenditures and the Relative Performance of Mutual Funds

We directly estimate annual trading costs for a sample of equity mutual funds and find that these costs are large and exhibit substantial cross sectional variation. Trading costs average 0.78% of fund assets per year and have an inter-quartile range of 0.59%. Trading costs, like expense ratios, are negatively related to fund returns and we find no evidence that on average trading costs are recovered in higher gross fund returns. We find that our direct estimates of trading costs have more explanatory power for fund returns than turnover. Finally, trading costs are associated with investment objectives. However, variation in trading costs within investment objectives is greater than the variation across objectives.
Students' Attitudes toward Using Innovative Information Technology for Learning Based on Theory of Planned Behavior

The main purpose of this study was to explore how IT is integrated into teaching and learning in German bachelor curriculum, and explore the university students' attitude toward the use of integration innovative information technology for learning in Germany. The data was collected by document collection and questionnaires. Multiple Regression Analysis was used to determine the three variables of behavioral intention. The results show that both attitude and subject norm are good predictors of IT for students' learning intention. Finally, results indicated TRA predicts the use innovative IT for learning intention well, though the impact of the TRA is greater than TPB.
Error Probability Analysis of Multi-Carrier Systems Impaired by Receiver I / Q Imbalance

I/Q imbalance has been identified as one of the most serious concerns in the practical implementation of the direct conversion receiver architecture. In particular, at the reception of multi-carrier signals the achievable error rate is strictly limited by the I/Q imbalance. Knowledge about the quantitative link between the hardware parameters and the resulting error rate is essential for a reasonable design of the receiver front-end. In this paper a framework for the analytical computation of the symbol error probability in multi-carrier systems is presented. We consider an arbitrary M-ary QAM modulated multi-carrier signal, which is corrupted by both a noisy frequency-selective Rayleigh fading channel and receiver I/Q imbalance. The theoretical results are validated exemplarily for the IEEE 802.11a WLAN standard.
Airborne Bacterial Communities in Residences: Similarities and Differences with Fungi

Genetic analysis of indoor air has uncovered a rich microbial presence, but rarely have both the bacterial and fungal components been examined in the same samples. Here we present a study that examined the bacterial component of passively settled microbes from both indoor and outdoor air over a discrete time period and for which the fungal component has already been reported. Dust was allowed to passively settle in five common locations around a home − living room, bedroom, bathroom, kitchen, and balcony − at different dwellings within a university-housing complex for a one-month period at two time points, once in summer and again in winter. We amplified the bacterial 16S rRNA gene in these samples and analyzed them with high-throughput sequencing. Like fungal OTU-richness, bacterial OTU-richness was higher outdoors then indoors and was invariant across different indoor room types. While fungal composition was structured largely by season and residential unit, bacterial composition varied by residential unit and room type. Bacteria from putative outdoor sources, such as Sphingomonas and Deinococcus, comprised a large percentage of the balcony samples, while human-associated taxa comprised a large percentage of the indoor samples. Abundant outdoor bacterial taxa were also observed indoors, but the reverse was not true; this is unlike fungi, in which the taxa abundant indoors were also well-represented outdoors. Moreover, there was a partial association of bacterial composition and geographic distance, such that samples separated by even a few hundred meters tended have greater compositional differences than samples closer together in space, a pattern also observed for fungi. These data show that while the outdoor source for indoor bacteria and fungi varies in both space and time, humans provide a strong and homogenizing effect on indoor bacterial bioaerosols, a pattern not observed in fungi.
Accountants' ethical sensitivity

O'Fallon and Butterfield (2005) in a review of the business ethics literature concluded that "ethical awareness" also called ethical sensitivity has received the least attention of the four steps in Rest's (1986) ethical decision making model. Available measures for ethical sensitivity are limited to specific contexts and suffer from several limitations. I extend the previous literature by creating a new measure for ethical sensitivity (AESS) that encompasses relevant dimensions for the accounting profession and is not specific to a particular setting. I also introduce a new individual differences variable to the accounting ethics literature. Specifically, I investigate the relationship between anti-intellectualism and ethical awareness. My findings support AESS as a measure of ethical sensitivity.
Teaching with Technology: Does Access to Computer Technology Increase Student Achievement?

This paper examines whether the use of computer technology as a supplemental study aid actually enhances student achievement in introductory economics. Data were collected for multiple sections over a four-semester period to test that hypothesis. The use of course web pages and online, multiple choice quizzes does not seem to increase student scores on common multiple-choice questions on the final or on the final itself.
Relationship of Urologic Complications With Health-Related Quality of Life and Perceived Value of Health in Men and Women With Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications (DCCT/EDIC) Cohort

OBJECTIVE Limited information exists about the influence of urologic complications on health-related quality of life (HRQOL) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS We studied 664 men and 580 women from the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications Study: mean ages were 51.6 ± 6.6 and 50.6 ± 7.2 years and duration of diabetes was 29.5 ± 4.8 and 29.8 ± 5.1 years, respectively. We assessed associations of sexual dysfunction, lower urinary tract symptoms (LUTS), and, in women, urinary incontinence (UI) with general quality of life (SF-36), perceived value of health (EuroQol-5), diabetes-related quality of life (Diabetes Quality of Life Scale [DQOL]), and psychiatric symptoms (Symptom Checklist 90-R). RESULTS In both men and women, urologic complications adversely affected HRQOL and psychiatric symptoms, even after accounting for history of depression leading to treatment. Multivariable analyses accounting for the presence of diabetic retinopathy, neuropathy, and nephropathy also revealed substantial independent effects. In men, for example, the odds (95% CI) of a low DQOL score (≤25th percentile) were 3.01 (1.90–4.75) times greater with erectile dysfunction and 2.65 (1.68–4.18) times greater with LUTS and in women, 2.04 (1.25–3.35) times greater with sexual dysfunction and 2.71 (1.72–4.27) times greater with UI/LUTS combined compared with men and women without such complications. Similar effects were observed for the other measures. CONCLUSIONS Sexual dysfunction and urinary complications with type 1 diabetes are associated with decreased quality of life and perceived value of health and with higher levels of psychiatric symptoms, even after accounting for other diabetes complications and depression treatment.
Ex-Ante Real Rates and Inflation Risk Premiums: A Consumption-Based Approach

This paper sets out to quantify, with the use of a consumption-based CAPM, the risk premiums inherent in the Israeli market for index-linked and non-index-linked bonds. In contrast to what has appeared in the macroeconomics literature, this study quantifies the size and dynamics of two such premiums: one is related to the inflation uncertainty in a nominal risk-free bond, and the other is related to the inflation uncertainty in an index-linked bond, caused by the indexation lag. This enables an approximation of the size and time-variation of the real ex-ante risk-free rate of return, and an evaluation of the accuracy of the method used by the Bank of Israel to measure inflation expectations. It is shown that the inflation risk premium term and the indexation-lag risk premium term depend heavily and positively on the degree of relative risk aversion, and that the latter is inconsequential. As a result, we claim that the bias caused due to overlooking both these risk premiums in the computation of inflation expectations depends on assumptions regarding the degree of relative risk aversion.