Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular pharmacokinetics and cytotoxicity of camptothecin and topotecan at normal and acidic pH.

pH-mediated conversions in the structure of the topoisomerase (topo) I inhibitors camptothecin (CPT) and its analogues have strong implications for the pharmacokinetics and pharmacodynamics of these novel anticancer agents. Because the cell-penetrating and biologically active lactone isomers predominate at acidic conditions, we have tested if low pH potentiates the cytotoxic and antitumor effects of CPT and its water-soluble derivative topotecan (TPT). In L1210 leukemia cells, rapid initial uptake of radiolabeled CPT and TPT was followed by a gradual release from cells at physiological pH 7.4, whereas high drug levels were maintained in cells at pH 6.2. Steady-state uptake levels of CPT increased proportionally, up to 5-fold, with decreasing pH of the incubating medium (from 7.4 to 6.0). With TPT, a maximum 3-fold increase was observed at pH 6.8 to 6.4. By contrast, the cellular pharmacokinetics of the topoisomerase II inhibitor etoposide (ETP) were independent of the ambient pH. The large increases in intracellular CPT and TPT levels caused only moderate potentiation of cytotoxicity in short-term incubations. Conditions of very low pH < or =6.2 even antagonized the cytotoxicity of the topo I and topo II inhibitors, due to inhibition of DNA synthesis by intracellular acidification. However, in clinically relevant schedules of prolonged exposures at low drug concentration, low pH potentiated the cytotoxicity of CPT and TPT by 2-3-fold. To investigate the effect of local pH in vivo, the basal interstitial pH of 6.8 of RIF-1 tumors was selectively lowered by i.p. injection of the host animals with the mitochondrial inhibitor meta-iodobenzylguanidine (32 mg/kg) and glucose (1.5 g/kg). In accordance with the pH optimum for TPT uptake at pH 6.8 to 6.4, tumor acidification had no effect on the antitumor effect of this analogue. By contrast, the intervention significantly potentiated the response of tumors to CPT. The results indicate that local pH is an important determinant of the cellular pharmacokinetics and the antitumor activity of CPT and analogues.
Tourism and the Economic Valuation of Cultural Heritage

world. Many countries depend on income generated by the tourism sector and related businesses. The sector’s total contribution in 2011 to world GDP (taking direct, indirect and induced impacts into account) was €4.8 trillion (9.1% of world GDP). In every region of the world, travel and tourism directly sustains more jobs than most of the other important worldwide industries like financial services, communication and mining. Of the many tourism market niches, cultural tourism is one of the most important. This cultural tourism is strongly related to the cultural heritage of destinations. This dissertation investigates the economic value of certain types of cultural heritage with respect to the destination choices of holidaymakers in the Netherlands. Cultural heritage is considered as an important tourist attractor, and contributes to the identity of a destination. The more important a heritage object is, and the more widespread its reputation is (like that of UNESCO World Heritage sites), the greater are the possible benefits for the tourism sector and for the local economy as a whole. The challenge for policy makers is to balance decisions in order to increase the economic return for all the stakeholders and to preserve the cultural heritage for future generations in a sustainable way. In this dissertation we have found evidence that cultural heritage is a key factor associated with the attractiveness of a location. We showed that cultural heritage is an important factor that drives the destination choices of Dutch holidaymakers and recreationists. And we showed that cultural heritage is of importance to retail dynamics. This evidence we found helps policymakers to make the balanced decisions that benefit all stakeholders.
OPERADS AS POLYNOMIAL 2-MONADS

In this article we give a construction of a polynomial 2-monad from an operad and describe the algebras of the 2-monads which then arise. This construction is dierent from the standard construction of a monad from an operad in that the algebras of our associated 2-monad are the categoried algebras of the original operad. Moreover it enables us to characterise operads as categorical polynomial monads in a canonical way. This point of view reveals categorical polynomial monads as a unifying environment for operads, Cat-operads and clubs. We recover the standard construction of a monad from an operad in a 2-categorical way from our associated 2-monad as a coidentier of 2-monads, and understand the algebras of both as weak morphisms of operads into a Cat-operad of categories. Algebras of operads within general symmetric monoidal categories arise from our new associated 2-monad in a canonical way. When the operad is sigma-free, we establish a Quillen equivalence, with respect to the model structures on algebras of 2-monads found by Lack, between the strict algebras of our associated 2-monad, and those of the standard one.
Infall of substructures on to a Milky Way-like dark halo

We analyse the dynamical properties of substructures in a high-resolution dark matter simulation of the formation of a Milky Way-like halo in a Lambda cold dark matter cosmology. Our goal is to shed light on the dynamical peculiarities of the Milky Way satellites. Our simulations show that about one-third of the subhaloes have been accreted in groups. We quantify this clustering by measuring the alignment of the angular momentum of subhaloes in a group. We find that this signal is visible even for objects accreted up to z similar to 1, i.e. 8 Gyr ago, and long after the spatial coherence of the groups has been lost due the host tidal field. This group infall may well explain the ghostly streams proposed by Lynden-Bell & Lynden-Bell to orbit the Milky Way. Our analyses also show that if most satellites originate in a few groups, the disc-like distribution of the Milky Way satellites would be almost inevitable. This non-random assignment of satellites to subhaloes implies an environmental dependence on whether these low-mass objects are able to form stars, possibly related to the nature of reionization in the early Universe. With this picture, both the 'ghostly streams' and the 'disc-like configuration' are manifestations of the same phenomenon: the hierarchical growth of structure down to the smallest scales.
Large-Scale Sensor Networks Simulation with GTSNetS

This paper presents a highly scalable sensor network simulation environment that allows users to evaluate the effects of different architectural choices and strategies on the lifetime and performance of a sensor network. This tool can also be used to evaluate new approaches (e.g., routing protocols, cooperation algorithms), and compare them with the ones already in place. The simulator incorporates models for the different functional units composing a sensor node and characterizes the energy consumption of each. GTSNetS is designed in a modular and efficient way favoring the ease of use and extension. The simulator also allows the user to choose from different implementations of energy models, accuracy models, communication protocols, application classes and types of sensors. New models can be easily added if necessary. Simulation results from a set of tests are reported to demonstrate some of the capabilities of the simulator. We present a case study using our tool to measure the performance of an existing algorithm that provides fault-tolerance for distributed detection using a wireless sensor network. The simulator gives results that are in accordance with the ones reported in the original paper describing the simulated algorithm. Tests were also performed to evaluate the simulator scalability as the network size increases. In particular, it was found that this tool could simulate sensor networks of several hundred thousand nodes while using less than 2 GB of memory, which exceeds the capabilities of existing simulators by an order of magnitude. The simulation execution time also scales well with the network size.
Critical success factors of public private partnership (PPP) implementation in Malaysia

Purpose – This paper aims to examine the importance of the success factors as perceived by the overall respondents. Also, the study intends to identify the differences concerning the importance of the success factors between the public and private sectors.Design/methodology/approach – A questionnaire survey was used to elicit the perceptions of public and private sectors on the key success factors of a PPP project in Malaysia. In total, 179 usable responses were obtained and analysed using SPSS to rank the importance of the success factors and to examine the differences in the perceptions between the government and the private sector.Findings – The overall results show that “good governance”, “commitment of the public and private sectors”, “favourable legal framework”, “sound economic policy” and “availability of finance market” are the top five success factors of PPP implementation in Malaysia. Although the rankings of many factors were different between the public and private sectors, there were no sign.
Towards combination HIV prevention for injection drug users: addressing addictophobia, apathy and inattention

Purpose of reviewRecent breakthroughs in HIV-prevention science led us to evaluate the current state of combination HIV prevention for injection drug users (IDUs). We review the recent literature focusing on possible reasons why coverage of prevention interventions for HIV, hepatitis C virus (HCV) and tuberculosis among IDUs remains dismal. We make recommendations for future HIV research and policy. Recent findingsIDUs disproportionately under-utilize voluntary HIV counseling and testing (VCT), primary care and antiretroviral therapy (ART), especially in countries that have the largest burden of HIV among IDUs. IDUs present later in the course of HIV infection and experience greater morbidity and mortality. Why are IDUs under-represented in HIV-prevention research, access to treatment for both HIV and addiction, and access to HIV combination prevention? Possible explanations include addictophobia, apathy, and inattention, which we describe in the context of recent literature and events. SummaryThis commentary discusses the current state of HIV-prevention interventions for IDUs including VCT, needle and syringe program (NSP), opioid substitution therapy (OST), ART and pre-exposure chemoprophylaxis (PrEP), and discusses ways to work towards true combination HIV prevention for IDU populations. Communities need to overcome tacit assumptions that IDUs can navigate through systems that are maintained as separate silos, and begin to take a rights-based approach to HIV prevention to ensure that IDUs have equitable access to life-saving prevention and treatments.
Effect of Pre-ovulatory Single Dose GnRH agonist Therapy on IVF Outcome in GnRH Antagonist Cycles; A Prospective Study

Background The purpose of present study was to evaluate the role of pre-ovulatory GnRH agonist therapy on IVF outcomes in GnRH antagonist cycles. Methods In this prospective study we recruited 100 infertile women undergoing IVF cycles with GnRH antagonists. The patients were assigned to two groups: Group A (the study group, n = 42) were assigned for receiving hCG + triptorelin for the final oocyte maturation and group B (the control group, n = 58) were assigned for only hCG. The t-test, chi-square (χ2), and Fisher's exact test were used for data analysis. A p < 0.05 was taken as statistically significant. The results are presented by mean± SD, and in percents (%). Results LH levels significantly (p < 0.001) increased in the study group on the day of oocyte retrieval. All embryological parameters including the number of mature oocytes, fertilization and cleavage rates, number of high quality embryos and number of cases whose embryos were frozen were non-significantly higher in the study group. There were small but non-significant improvements in the clinical pregnancy, ongoing pregnancy, live birth and implantation rates in the study group. Conclusion Administering a single dose of GnRH agonist before oocyte retrieval in antagonist cycles may be helpful in improving the pregnancy rate but the results need to be verified in a larger trials.
Examples are not enough, learn to criticize! Criticism for Interpretability

Example-based explanations are widely used in the effort to improve the interpretability of highly complex distributions. However, prototypes alone are rarely sufficient to represent the gist of the complexity. In order for users to construct better mental models and understand complex data distributions, we also need {\em criticism} to explain what are \textit{not} captured by prototypes. Motivated by the Bayesian model criticism framework, we develop \texttt{MMD-critic} which efficiently learns prototypes and criticism, designed to aid human interpretability. A human subject pilot study shows that the \texttt{MMD-critic} selects prototypes and criticism that are useful to facilitate human understanding and reasoning. We also evaluate the prototypes selected by \texttt{MMD-critic} via a nearest prototype classifier, showing competitive performance compared to baselines.
New ways to measure well-being? A first joint analysis of subjective and objective measures

Our study is, to our knowledge, the first joint analysis of subjective and objective measures of well-being. Using a rich longitudinal data from the mothers pregnancy until adulthood for a birth cohort of children who attended school in Orebro during the 1960s, we analyse in a first step how subjective (self-assessed) and objective (cortisol-based) measures of well-being are related to each other. In a second step, life-course models for these two measures are estimated and compared with each other. Despite the fact that our analysis is largely exploratory, our results suggest interesting possibilities to use objective measures to measure well-being, even though this may imply a greater degree of complexity.
Learning communities today - who benefits?

This paper examines the benefits of learning communities today and introspects the risks and dilemmas that confront communities of learners as they embark on school/university partnerships designed to integrate research, theory and excellent teaching practice. Building from case studies of two separate pre-service teacher education programs at Griffith University (Gold Coast Campus) and James Cook University (Cairns Campus), we identify some of the differences that exist between schools and universities. We discuss the conflicts that arise when they attempt to collaborate in the area of teacher preparation (early childhood, primary, middle years of schooling and secondary). We contend that when such conflicts are acknowledged and worked on in a positive manner by the relevant stakeholders, they become crucial to the development of robust partnerships, innovative approaches to teacher preparation and provision of interesting professional learning development to a wide range of recipients in diverse communities.
Discovery of facial motions using deep machine perception

Deep, intuitive understanding of facial motions has the potential to provide an intelligent facial expression system as well as a unique encoding of the dynamics of facial actions. The most promising existing approaches rely on extracting hand crafted features; and existing approaches typically work best in constrained conditions and do not generalise well to varying environmental conditions which make them poorly suited to applications such as real-time human robot interactions. In this paper, we propose a multi-label deep learning based facial action detector, which along with a linear SVM classifier outperforms state of the art approaches such as HOG and LBP. We show that our approach can be generalized to other datasets by learning inner data structure, encoding facial actions, and providing a hierarchical representation of facial features. Our experimental results also demonstrate the efficiency of using image patches, which results in faster learning convergence while outperforms holistic approaches. We evaluate our proposed frame-work on the DISFA and CK+ datasets.
Postweaning Exposure to Aflatoxin Results in Impaired Child Growth: A Longitudinal Study in Benin, West Africa

Aflatoxins are dietary contaminants that are hepatocarcinogenic and immunotoxic and cause growth retardation in animals, but there is little evidence concerning the latter two parameters in exposed human populations. Aflatoxin exposure of West African children is known to be high, so we conducted a longitudinal study over an 8-month period in Benin to assess the effects of exposure on growth. Two hundred children 16–37 months of age were recruited from four villages, two with high and two with low aflatoxin exposure (50 children per village). Serum aflatoxin–albumin (AF-alb) adducts, anthropometric parameters, information on food consumption, and various demographic data were measured at recruitment (February) and at two subsequent time points (June and October). Plasma levels of vitamin A and zinc were also measured. AF-alb adducts increased markedly between February and October in three of the four villages, with the largest increases in the villages with higher exposures. Children who were fully weaned at recruitment had higher AF-alb than did those still partially breast-fed (p < 0.0001); the major weaning food was a maize-based porridge. There was no association between AF-alb and micronutrient levels, suggesting that aflatoxin exposure was not accompanied by a general nutritional deficiency. There was, however, a strong negative correlation (p < 0.0001) between AF-alb and height increase over the 8-month follow-up after adjustment for age, sex, height at recruitment, socioeconomic status, village, and weaning status; the highest quartile of AF-alb was associated with a mean 1.7 cm reduction in growth over 8 months compared with the lowest quartile. This study emphasizes the association between aflatoxin and stunting, although the underlying mechanisms remain unclear. Aflatoxin exposure during the weaning period may be critical in terms of adverse health effects in West African children, and intervention measures to reduce exposure merit investigation.
Efficient coding and the neural representation of value

To survive in a dynamic environment, an organism must be able to effectively learn, store, and recall the expected benefits and costs of potential actions. The nature of the valuation and decision processes is thus of fundamental interest to researchers at the intersection of psychology, neuroscience, and economics. Although normative theories of choice have outlined the theoretical structure of these valuations, recent experiments have begun to reveal how value is instantiated in the activity of neurons and neural circuits. Here, we review the various forms of value coding that have been observed in different brain systems and examine the implications of these value representations for both neural circuits and behavior. In particular, we focus on emerging evidence that value coding in a number of brain areas is context dependent, varying as a function of both the current choice set and previously experienced values. Similar contextual modulation occurs widely in the sensory system, and efficient coding principles derived in the sensory domain suggest a new framework for understanding the neural coding of value.
INNOVATIONS IN TEACHER EDUCATION IN DEVELOPING COUNTRIES: A CASE STUDY

Innovations in Teacher Education in Developing Countries: A Case Study Margaret Lynn Maxwell, B.A., Wilson College M.A. , State University of New York at Albany Ed.D. , University of Massachusetts Directed by: Professor Robert Miltz Current research findings indicate 1) that the impact of innovations on educational settings is minimal, if any, and 2) that few innovations are being institutionalized. This study examined issues surrounding the institutionalization of innovations, particularly within teacher education programs in developing countries. The study first examined literature on the types of innovations within teacher training institutions in developing countries and on representati ve innovation research models and theories. Subsequently, based on this literature, a Wholistic Innovation Model was proposed in which four aspects of innovation were identified as "sensitizing concepts. " These aspects were 1) innovation characteristics, 2) adopter characteri sti cs , 3) innovation process strategies, and 4) social system constraints and resources As sensitizing concepts, these four aspects guided the researcher in developing a case-study research design which bothquantitatively and qualitatively evaluated the innovation of self-instructional materials (SIMs) at the National Teacher Training College (N.T.T.C.) of Lesotho. Personnel involved currently and historically with SIMs as well as documents were used as sources in evaluating 1) the institutionalization level of the innovation, and 2) the factors influencing
Why Doesn't Capital Flow from Rich to Poor Countries? An Empirical Investigation

We examine the empirical role of different explanations for the lack of capital flows from rich to poor countriesthe Lucas Paradox. The theoretical explanations include cross-country differences in fundamentals affecting productivity, and capital market imperfections. We show that during 19702000, low institutional quality is the leading explanation. Improving Peru's institutional quality to Australia's level implies a quadrupling of foreign investment. Recent studies emphasize the role of institutions for achieving higher levels of income but remain silent on the specific mechanisms. Our results indicate that foreign investment might be a channel through which institutions affect long-run development.
Fuzzy multi-objective optimization for network design of integrated e-supply chains

Worldwide competition originated the development of integrated e-supply chains (IESC) that are distributed manufacturing systems integrating international logistics and information technologies with production. This work builds upon an IESC network design methodology previously proposed to select partners in the different IESC stages and the links connecting them. In order to rank the Pareto optimal solutions obtained by such a method, the paper proposes a second level IESC optimization performed using fuzzy logic. Indeed, fuzzy multi-criteria optimization is particularly suitable for choosing, on the basis of the subjective and qualitative knowledge provided by the decision makers, the IESC configuration from the set of Pareto optimal alternatives. Two fuzzification techniques and two different multi-criteria methods are considered. Moreover, a discussion on the different advantages and limitations of the proposed techniques is provided. Finally, the effectiveness of the methodology is illustrated by way of a case study.