Miracle-dz/UniFAR-FTUs huggingface dataset:
Brachyury as a potential modulator of androgen receptor activity and a key player in therapy resistance in prostate cancer

Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related deaths in men. Acquisition of resistance to conventional therapy is a major problem for PCa patient management. Several mechanisms have been described to promote therapy resistance in PCa, such as androgen receptor (AR) activation, epithelial-to-mesenchymal transition (EMT), acquisition of stem cell properties and neuroendocrine transdifferentiation (NEtD). Recently, we identified Brachyury as a new biomarker of PCa aggressiveness and poor prognosis. In the present study we aimed to assess the role of Brachyury in PCa therapy resistance. We showed that Brachyury overexpression in prostate cancer cells lines increased resistance to docetaxel and cabazitaxel drugs, whereas Brachyury abrogation induced decrease in therapy resistance. Through ChiP-qPCR assays we further demonstrated that Brachyury is a direct regulator of AR expression as well as of the biomarker AMACR and the mesenchymal markers Snail and Fibronectin. Furthermore, in vitro Brachyury was also able to increase EMT and stem properties. By in silico analysis, clinically human Brachyury-positive PCa samples were associated with biomarkers of PCa aggressiveness and therapy resistance, including PTEN loss, and expression of NEtD markers, ERG and Bcl-2. Taken together, our results indicate that Brachyury contributes to tumor chemotherapy resistance, constituting an attractive target for advanced PCa patients.
A new design technique for propagation delay and power reduction in the CML buffers

This paper introduces a method to determine the sizing of the buffers used in the driver of a differential transmission line on chip. Using this technique, the power and delay performance of the buffer is improved, compared with the conventional CML design method. Simulations show that for a differential transmission line with a 138.8fF capacitive and a 73Ω resistive load, the power-delay product and the rise-time are improved by 169.3% and 14.3%, respectively. The designs are performed in a typical 90nm CMOS technology with a 1.2V power supply.
SMEs and corporate social responsibility. The perspective from Spanish companies

Corporate social responsibility (CSR) can be understood as an instrument for the application of sustainability in business activity. Small and medium-sized enterprises (SMEs) have participated less in the development of CSR management than large corporations. However, many of these companies recognise that they are accountable for much of their impact, and they also perform actions that could be considered as CSR. This article presents the main findings of a study developed for SMEs with respect to their CSR practices and policies. The sample comprises companies located in a highly industrialised area of Valencia region, Spain. A general evaluation of these companies was made in terms of CSR practices and policies. Key aspects were identified that could easily be included in their strategy to improve sustainability performance. Results show that these companies are at an incipient stage of CSR strategy development and that the concept of CSR is not clearly understood.
Cortical ¹¹C-PIB uptake is associated with age, APOE genotype, and gender in "healthy aging".

BACKGROUND/OBJECTIVE Our aim was to elucidate factors that contribute to amyloid-β (Aβ) accumulation in the brains of the seemingly healthy elderly population, and whether there is interplay between those factors. METHODS We conducted a cross-sectional positron emission tomography (PET) study with the amyloid tracer 11C-PIB, in 64 cognitively healthy subjects (54-89 years). In addition to PET, magnetic resonance imaging, neuropsychological testing, and APOE genotyping was performed. The results were assessed with a statistical general linear model as well as with Statistical Parametric Mapping (SPM). RESULTS The effects of age (p < 0.001), APOE ε4 carrier status (p = 0.003), and gender (p = 0.001) on composite cortical 11C-PIB uptake were all significant. The effect of educational level was non-significant (p = 0.37). No significant interactions were found between any of the factors. Cortical 11C-PIB uptake increased, on the average, by 0.015 cortex/cerebellar cortical ratio unit, with every year of age. APOE ε4 positive subjects exhibited higher cortical 11C-PIB uptake than APOE ε4 negative subjects (unadjusted means 1.49 ± 0.34 versus 1.29 ± 0.26) and males had higher uptake than females (1.49 ± 0.39 versus 1.29 ± 0.22), irrespective of age. The results of the voxel-based (SPM) analysis were similar. In addition, SPM analysis showed that lower CERAD score was associated with higher 11C-PIB uptake in the frontal cortex. CONCLUSIONS Age and APOE ε4 genotype were associated with higher 11C-PIB uptake. In this sample of cognitively healthy elderly individuals, men exhibited higher 11C-PIB uptake than women. Possible gender differences in Aβ accumulation have not been addressed in detail in previous studies, and deeper evaluation in the future is warranted.
Identification of cell culture conditions to control N‐glycosylation site‐occupancy of recombinant glycoproteins expressed in CHO cells

The effect of different cell culture conditions on N‐glycosylation site‐occupancy has been elucidated for two different recombinant glycoproteins expressed in Chinese hamster ovary (CHO) cells, recombinant human tissue plasminogen activator (t‐PA) and a recombinant enzyme (glycoprotein 2—GP2). Both molecules contain a N‐glycosylation site that is variably occupied. Different environmental factors that affect the site‐occupancy (the degree of occupied sites) of these molecules were identified. Supplementing the culture medium with additional manganese or iron increased the fraction of fully occupied t‐PA (type I t‐PA) by approximately 2.5–4%. Decreasing the cultivation temperature from 37 to 33°C or 31°C gradually increased site‐occupancy of t‐PA up to 4%. The addition of a specific productivity enhancer, butyrate, further increased site‐occupancy by an additional 1% under each cultivation temperature tested. In addition, the thyroid hormones triiodothyronine and thyroxine increased site‐occupancy of t‐PA compared to control conditions by about 2%. In contrast, the addition of relevant nucleoside precursor molecules involved in N‐glycan biosynthesis (e.g., uridine, guanosine, mannose) either had no effect or slightly reduced site‐occupancy. For the recombinant enzyme (GP2), it was discovered that culture pH and the timing of butyrate addition can be used to control N‐glycan site‐occupancy within a specific range. An increase in culture pH correlated with a decrease in site‐occupancy. Similarly, delaying the timing for butyrate addition also decreased site‐occupancy of this molecule. These results highlight the importance of understanding how cell culture conditions and media components can affect the product quality of recombinant glycoproteins expressed in mammalian cell cultures. Furthermore, the identification of relevant factors will enable one to control product quality attributes, specifically N‐glycan site‐occupancy, within a specific range when applied appropriately. Biotechnol. Bioeng. 2009;103: 1164–1175. © 2009 Wiley Periodicals, Inc.
Multiperiod Models with Capacities in Competitive Supply Chain

This paper considers a supply chain setting where several capacitated suppliers compete for orders from a single retailer in a multiperiod environment. At each period, the retailer places orders to the suppliers in response to the prices they announce. Each supplier has a fixed capacity. We consider a make‐to‐stock setting where the retailer can carry inventory. The retailer faces exogenous, price‐dependent demand. We study the problem using ideas from fluid models. In particular, we (i) analyze when there are pure equilibrium policies in this setting and characterize the structure of these policies; (ii) consider coordination mechanisms; and (iii) present some preliminary computational results. We also consider a modified model that uses option contracts to coordinate the supply chain.
Fiscal Adjustment between 1991 and 2002: Stylised Facts and Policy Implications

This paper aims to assess whether the implementation of the European Union (EU) framework of fiscal rules has been successful in promoting budgetary consolidation in EU Member States. The paper focuses on the period 1991-2002. Stylised facts show that Member States implemented major budgetary adjustments in the 1990s marking clear structural breaks in the policy regimes compared with the previous decade. However, most progress was made via revenue-based adjustment, including temporary measures, with insufficient emphasis put on primary expenditure restraint. In recent years, "consolidation fatigue" has been evident in many Member States. Although an unfavourable economic environment has adversely affected nominal budget balances in recent years, budget indicators suggest that the process of budgetary adjustment, which started in the 1990s, is far from complete in many countries.
Optimal Mailing of Catalogs: a New Methodology Using Estimable Structural Dynamic Programming Models

We investigate the key determinants of the optimal direct mail policy in a dynamic environment where customers maximize utility and the direct mailer maximizes profits. We measure the sensitivity of the customers to receiving a catalog in the mail, while controlling for customer characteristics such as elapsed time in responses and number of purchases. We apply our model to a database from a national cataloger that markets nonseasonal products. We summarize the results of our model that are valid for these types of products. We find that the dynamic model significantly outperforms its single-period counterpart. We find that it is not optimal to mail to individuals at low recency levels because they are likely to buy anyway. It is better to save the mailing dollars for customers at higher recency levels. We find that it is optimal to mail to customers who have purchased only a small or a medium number of times to induce them to continue to buy from this catalog and not switch to others. It is not necessary to mail often to customers who have purchased many times before from the company unless they have high recency values. We find that under the optimal mailing policy the cataloguer enjoys higher profits than under the current mailing policy.
Cramer-Rao lower bound of Doppler stretch and delay in wideband signal model

Narrowband signal model, which approximates Doppler effect as a frequency shift, is inappropriate for some problems of radiolocation, hydroacoustics or passive location. In this case it is necessary to use Doppler stretch (time-scaling) as a signal parameter. In this paper Cramer-Rao lower bound of joint Doppler stretch and delay estimation for wideband signal model is derived. Maximum likelihood estimations in presence of nuisance parameters can be obtained by two ways. First method implies estimation of all unknown signal parameters and subsequent rejecting of nuisance. Second method involves averaging of conditional probability density function by nuisance parameters with considering it's priori probability density. Although Fisher information matrices of signal parameters are different for specified methods, estimation variances of Doppler stretch and delay are equal. In wideband signal model, the variance of time delay estimation depends on choice of reference axis. Varying the reference time leads to modifying of measurement moment with respect to signal. Since time delay is various parameter, its estimation variance is also variant. Appropriate choice of reference time results minimization of estimation variance and diagonalization of FIM. In the narrowband limit proposed consideration results in well-known CRLB of Doppler shift and delay estimation.
e-Government awareness among the techno-disadvantaged in the United States

This exploratory research focuses on awareness among techno-disadvantaged citizens in the United States. Specifically, we address whether awareness is associated with visitation and whether there are differences between those who are aware and those who are not aware. Following up on on a theory-based community initiative designed to improve computer literacy and access to information and communication technologies (ICT) for members of an underserved public housing community, a survey was undertaken. The results indicate that awareness is associated with visitation. Differences in demographic characterisitics, perceived ease of use (PEOU), and perceived access barriers between those who are aware of egovernment websites, and those who are not, were found. While nearly half of the respondents are neither aware of nor have visited e-government websites, a slight majority is partaking of egovernment services. We identify directions for future research and conclude by emphasizing the value of a theory-based community initiative to improve computer literacy, provide access to ICT, and advance e-government inclusion.
Nitrite Reductase Activity of Hemoglobin S (Sickle) Provides Insight into Contributions of Heme Redox Potential Versus Ligand Affinity*

Hemoglobin A (HbA) is an allosterically regulated nitrite reductase that reduces nitrite to NO under physiological hypoxia. The efficiency of this reaction is modulated by two intrinsic and opposing properties: availability of unliganded ferrous hemes and R-state character of the hemoglobin tetramer. Nitrite is reduced by deoxygenated ferrous hemes, such that heme deoxygenation increases the rate of NO generation. However, heme reactivity with nitrite, represented by its bimolecular rate constant, is greatest when the tetramer is in the R quaternary state. The mechanism underlying the higher reactivity of R-state hemes remains elusive. It can be due to the lower heme redox potential of R-state ferrous hemes or could reflect the high ligand affinity geometry of R-state tetramers that facilitates nitrite binding. We evaluated the nitrite reductase activity of unpolymerized sickle hemoglobin (HbS), whose oxygen affinity and cooperativity profile are equal to those of HbA, but whose heme iron has a lower redox potential. We now report that HbS exhibits allosteric nitrite reductase activity with competing proton and redox Bohr effects. In addition, we found that solution phase HbS reduces nitrite to NO significantly faster than HbA, supporting the thesis that heme electronics (i.e. redox potential) contributes to the high reactivity of R-state deoxy-hemes with nitrite. From a pathophysiological standpoint, under conditions where HbS polymers form, the rate of nitrite reduction is reduced compared with HbA and solution-phase HbS, indicating that HbS polymers reduce nitrite more slowly.
Testing the test—why pursue a better test for Huntington disease?

In 1993, the gene mutation for Huntington disease (HD) was identified and testing became possible with a reliability of >99%, without the need for co‐operation of relatives. In 1997, a systematic information program offered the mutation retest to individuals who had earlier received a linkage test result for HD, which has a residual uncertainty of 1–9%. The characteristics of 129 individuals tested by linkage analysis for HD are reported on, as well as the reasons for their reassessment by mutation testing. Three groups were compared: (1) people who were retested between 1993 and 1997, before this study had started, (2) people who were retested after we provided information, and (3) persons who refrained from retesting. Nearly half of the linkage‐tested individuals were retested, with the exception of noncarriers with a residual risk of 1 or 2%. Of them, less than one out of five were retested. Carriers with a hopeful view on the future (BHS) and a better sense of well‐being (GHQ) were more likely to have the retest. Female carriers were also more likely to have the retest before we contacted them. Noncarriers who were retested were more anxious (HADS) than noncarriers who refrained from the retest. Retestees were younger at the time of testing. No risk reversals were revealed by this study. © 2003 Wiley‐Liss, Inc.
A solution to the ecological inference problem: Reconstructing individual behavior from aggregate data

7. Page 4, footnote 2, Change the text to: “That is, given these aggregate numbers, a minimum of zero females in precinct 1 and 1/3 in precinct 2 (for an average of 1/6ths) could have opposed the referendum, whereas as maximum of 2/3rds and 100% of males (for an average of 5/6ths) in the two precincts could have opposed it. Chapter 5 provides easy graphical methods of making calculations like these. ” ∗All changes since the first printing are included here. An increasing subset of these have been incorporated in the successive reprint editions. †Littauer Center North Yard, Cambridge Massachusetts 02138, King@Harvard.Edu, http://GKing.Harvard.Edu, phone: (617) 495-2027.
A Comparative Study of Two Psychometric Approaches to Detect Risk Status for Dementia

This study results from an effort to examine the relationship between the diagnostic potentials for detecting risk status for dementia of a cognitive plasticity approach and a traditional status-oriented procedure (test battery) by Storandt et al. [Arch Neurol 1984;41:497–499]. The aim is to compare prediction accuracy for risk for developing dementia with these two approaches. A sample of 106 community-dwelling elderly adults were tested with both procedures, and their scores on the Structured Interview for the Diagnosis of Dementia used as external criterion for predicting risk status. The findings show that figural relations pretest and training gains account for a considerable amount of individual differences in mental status similar to that explained by the traditional test battery. In addition, the accuracy of discrimination between healthy and at-risk participants appears slightly higher when using the figural pretest and training gains. These results suggest the conclusion that use of figural relations tests and the cognitive plasticity approach represents a viable alternative to the traditional, status-oriented test battery as a means of early diagnosis of dementia in nonclinical populations.
The impact on annual earnings of adult upper secondary education in Sweden

The public supply of adult education is very different between countries, making it likely that there is scope for efficiency gains. The contribution of this paper is to provide an economic evaluation of the earnings impact of adult education at upper secondary level (AE) in Sweden, where the supply is plausibly larger than in any other country. The analysis is based on register data for 1990–2002 of the cohort born in 1970 on accomplished AE course credits and possibly subsequent higher education. Difference‐in‐differences estimates indicate that for AE enrolees in 1994–1996, a year of AE credits increased earnings in 2002 by 6% for males and by 4.5% for females. The estimates are reconciled with conflicting results from earlier studies. According to crude calculations, which disregard other societal benefits of AE, the earnings benefits are sufficient to cover the costs incurred by society within 17 years.
Resource-Efficient Mobile Multimedia Streaming With Adaptive Network Selection

From the advancements of mobile display and network infrastructure, mobile users can enjoy high quality mobile video streaming anywhere, anytime. However, most mobile users are still reluctant to use high quality video streaming when they are mobile due to costly cellular data and high energy consumption. In this work, we develop scheduling algorithms for resource-efficient mobile video streaming, which minimize the weighted sum objective of cellular cost and energy consumption. We first model the scheduling problem as a Markov decision process and propose an optimal scheduling algorithm based on dynamic programming. Then, we derive a heuristic algorithm that approximates the optimal algorithm. To evaluate the performance of proposed algorithms, we run simulation over YouTube video traces with audience retention graphs and mobility/connectivity traces in public transportation (e.g., commuting). Through extensive simulations, we show that our proposed scheduling algorithm has negligible performance loss compared to the optimal scheduling algorithm, where it saves 59% of cellular cost and 41% of energy compared to the YouTube default scheduler. We also implement our scheduling algorithm on an Android platform, and experimentally evaluate the performance compared to existing streaming policies.
The Determinants of Bank Capital Structure

The paper shows that mispriced deposit insurance and capital regulation were of second-order importance in determining the capital structure of large U.S. and European banks during 1991 to 2004. Instead, standard cross-sectional determinants of non-financial firms' leverage carry over to banks, except for banks whose capital ratio is close to the regulatory minimum. Consistent with a reduced role of deposit insurance, we document a shift in banks' liability structure away from deposits towards non-deposit liabilities. We find that unobserved time-invariant bank fixed-effects are ultimately the most important determinant of banks' capital structures and that banks' leverage converges to bank specific, time-invariant targets. Copyright 2010, Oxford University Press.
Web Experience and Growth

Corporate websites are often used to provide service to both external and internal clients (i.e., customers and employees). Thus, corporate websites have become an important communication channel, for which anywhere and anytime access with an outstanding user experience is simply expected. Because of this, designing positive web experiences can have a significant impact on reducing costs and increasing revenue in organizations. For example, a recent study shows %70 growth in online sales for an Internet Performance company, after the company improved the experience design of its e-commerce site (Djamasbi et. al 2014). The results of this previous study suggest that the ability to assess the business value of websites experience design can play a significant role in the company’s ability to plan and manage growth (Djamasbi 2014). One way to address this need is by using predictive models as a guide for planning the development process and budgets. Predictive models in IS research play a significant role in understanding user behavior. Such models can also serve as an invaluable tool for informing the planning and management of innovation that relies on user behavior. In order to address this need, we propose a basic step towards developing such a model for redesigning a live internal website in a Fortune 500 company.