Miracle-dz/UniFAR-FTUs huggingface dataset:
Telomere biology: Rationale for diagnostics and therapeutics in cancer

The key step of carcinogenesis is the malignant transformation which is fundamentally a telomere biology dysfunction permitting cells to bypass the Hayflick limit and to divide indefinitely and uncontrollably. Thus all partners and structures involved in normal and abnormal telomere maintenance, protection and lengthening can be considered as potential anti-cancer therapeutic targets. In this Point of View we discuss, highlight and provide new perspectives from the current knowledge and understanding to position the different aspects of telomere biology and dysfunction as diagnostic, preventive and curative tools in the field of cancer.
Two Chemoreceptors Mediate Developmental Effects of Dauer Pheromone in C. elegans

Life Histories to Suit Nematode worms can profoundly manipulate their life histories in several ways. For example, Caenorhabditis elegans has two genders: males and hermaphrodites. Some clues for the evolution of this peculiar mating system have been revealed by Baldi et al. (p. 1002), who turned females of a related species, Caenorhabditis remanei, into hermaphrodites by modifying a gene involved in making sperm and another gene required for activating the spermatids. In most animals, the germ line is fully established during adulthood and a reproductive period is determined, at least in part, by aging of the germ line and the viability of oocytes. The reproductive longevity of hermaphrodite C. elegans can be increased at least 15-fold by starvation. Angelo and Van Gilst (p. 954, published online 27 August; see the Perspective by Ogawa and Sommer) found that in starved worms, the germline component of the reproductive system is actively killed, with the exception of a small set of preserved stem cells. When the worms are able to feed again, these cells regenerate into an entirely new and functional germ line. But this is not all. Kim et al. (p. 994, published online 1 October; see the Perspective by Ogawa and Sommer) show that subsets of the complex mixture of structurally related molecules in dauer pheromone act via distinct G protein–coupled receptors either to initiate longterm effects on development and physiology by modulating the neuroendocrine axis, or to trigger short-term acute effects on behavior by altering neuronal responses. Chemical signals that determine alternative nematode developmental programs act via two G protein–coupled receptors. Intraspecific chemical communication is mediated by signals called pheromones. Caenorhabditis elegans secretes a mixture of small molecules (collectively termed dauer pheromone) that regulates entry into the alternate dauer larval stage and also modulates adult behavior via as yet unknown receptors. Here, we identify two heterotrimeric GTP-binding protein (G protein)–coupled receptors (GPCRs) that mediate dauer formation in response to a subset of dauer pheromone components. The SRBC-64 and SRBC-66 GPCRs are members of the large Caenorhabditis-specific SRBC subfamily and are expressed in the ASK chemosensory neurons, which are required for pheromone-induced dauer formation. Expression of both, but not each receptor alone, confers pheromone-mediated effects on heterologous cells. Identification of dauer pheromone receptors will allow a better understanding of the signaling cascades that transduce the context-dependent effects of ecologically important chemical signals.
[3H]‐L‐2‐amino‐4‐phosphonobutyrate labels a metabotropic glutamate receptor, mGluR4a

1 The ligand binding site of subtype mGluR4a of the metabotropic glutamate receptor family was characterized by using [3H]‐L‐2‐amino‐4‐phosphonobutyrate ([3H]‐L‐AP4) binding. 2 Specific [3H]‐L‐AP4 binding to membranes prepared from baby hamster kidney (BHK) cells transfected with a vector encoding mGluR4a accounted for 60–70% of the total binding whereas no specific binding of [3H]‐L‐AP4 was observed to membranes prepared from BHK cells expressing the vector only. 3 Specific binding of [3H]‐L‐AP4 to mGluR4a was detectable at 0°C, was saturated within 10 min and enhanced by C1−ions but not by divalent cations (Mg2+, Ca2+, Mn2+). 4 [3H]‐L‐AP4 binding showed a maximal binding density (Bmax) of 3.0±0.5 pmol mg−1 protein and an affinity (KD) of 441 nM. A modest decrease in affinity was observed in the presence of 0.1 mM guanosine‐5′‐0‐(3‐thio)trisphosphate‐γ‐S, the KD being 761 nM and the Bmax 3.4±0.6 pmol mg−1 protein. 5 The following rank order of affinity for mGluR4a was observed: L‐AP4=L‐serine‐0‐phosphate > glutamate = (2S,1S,2S)‐2‐(carboxycyclopropyl)‐glycine > 1‐amino‐3‐(phosphonomethylene)cyclobitanecar‐boxylate> > (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylate = quisqualate > ibotenate. 6 A highly significant correlation was observed between the potencies of the compounds to inhibit forskolin‐stimulated cyclic AMP‐formation in BHK cells expressing mGluR4a and the affinity for displacement of [3H]‐L‐AP4 binding from mGluR4a suggesting that this binding site is functionally relevant. 7 In conclusion, [3H]‐L‐AP4 is a suitable radioligand for characterizing mGluR4a when expressed in BHK cells. Interestingly, a significant correlation was found between the ability of various compounds to displace [3H]‐L‐AP4 binding from mGluR4a and the previously observed potencies for inhibition of synaptic transmission via L‐AP4 sensitive glutamatergic pathways. These data support the hypothesis that the L‐AP4 receptor is contained within the mGluR family.
Access to Market and Growth of Micro and Small Scale Enterprises in Ethiopia: Evidence from Wolaita and Dawro Zones, Southern Ethiopia

Today in many developing countries like Ethiopia, micro and small scale enterprises (MSE) coupled with institutional supports such as good market access, grant a useful strategy to create jobs for jobless and reduce poverty. Access to market for the products of these MSE claimed to be the way and motivational factor in determining the achievement of the above stated goal. However, empirical evidence about access to market for the products of MSE are lacking and, if any, with so many challenges. Considering the case of access to market for products of MSEs in Wolaita and Dawro zones from Southern Ethiopia, this paper investigates whether there is good market access for their products to be revitalized as ensuring job creation and poverty reduction in the two zones. The study was based on primary data collected from 182 MSE operators selected from a total 7 districts (towns) of the two zones. The data was analyzed using descriptive statistics and probit regression model. Informed by relevant statistical tests, empirical model estimation was made using maximum likelihood estimation technique. The result shows the significant impact of access to credit, access to market information, experience in business, number of business development training attended, distance from the center of the market, age of the enterprise and the type of enterprise, on access to market reaffirming their role in promoting MSE development for income Original Research Article Gobena and Amare; BJEMT, 13(3): 1-9, 2016; Article no.BJEMT. 26232 2 poverty reduction and employment creation in the two zones. Further strengthening and expanding access to market for MSE's product is commendable in this case as MSEs need to be given special attention and support for their growth and development.
A disturbance-free read scheme and a compact stochastic-spin-dynamics-based MTJ circuit model for Gb-scale SPRAM

A magnetic-tunnel-junction (MTJ) circuit model, which considers spin dynamics under finite temperature, electrical bias, a stochastic process, and spin-transfer torque, was developed. Switching behaviors simulated by this model were verified by experimental measurements. Moreover, a disturbance-free read scheme for Gbit-scale spin-transfer torque RAM (SPRAM) was also developed. The feasibility of this scheme was confirmed by circuit simulation using the model and on-chip measurement of switching probability.
Ultrasound-enhanced extravasation of multifunctional nanodroplets from leaky vessel

Poorly organized vascular architecture of tumor tissue allows extravasation of drug-loaded nanoparticles through the large interendothelial gaps. Extravasated perfluorocarbon nanodroplets can convert into microbubbles under ultrasound irradiation to imaging or deliver drug for tumor treatment. However an increased interstitial fluid pressure in tumor tissue hinders convectional transport of drug carriers across blood vessel walls, thus extravasation of sufficient amounts of droplets remains a major challenge. In this paper, we propose an ultrasound-enhanced extravasation strategy using synergetic effect of acoustic radiation force and cavitation enhanced penetration.
CapitalizationofR&Dcostsandearningsmanagement: Evidence from Italian listed companies ☆

The capitalization of research and development (R&D) costs is a controversial accounting issue because of the contention that such capitalization is motivated by incentives to manipulate earnings. Based on a sample of Italian listed companies, this study examines whether companies' decisions to capitalize R&D costs are affected by earnings-management motivations. Italy provides a natural context for testing our hypothesized relationships because Italian GAAP allows for the capitalization of R&D costs. Using a Tobit regression model to test our hypotheses, we show that companies tend to use cost capitalization for earnings-smoothing purposes. The hypothesis that firms capitalize R&D costs to reduce the risk of violating debt covenants is not supported. © 2008 University of Illinois. All rights reserved.
The optimal supply of liquidity and the regulations of money substitutes: a Baumol-Tobin approach

I use the Baumol-Tobin approach to examine the following propositions: (a) The optimal supply of liquidity requires a government loan program in addition to paying interest on reserves held by banks, (b) The adoption of the optimal policy will crowd out private credit arrangement and will thus shrink the financial sector and (c) regulations aimed at eliminating money substitutes may be redundant if the optimal policy is adopted but otherwise may improve welfare.
The Effect of Buyer-Imposed Bidding Requirements and Bundle Structure on Purchase Performance

In industrial procurement the buying organization usually initiates and sets the stage for purchase negotiations by sending out a request for quotation (RFQ). The business tendered in the RFQ most often does not consist of just a single item, but of a group of different stockkeeping units (SKUs). How this order lot is structured, and whether suppliers are required to strictly adhere to its composition (i.e., quote on all items in the bundle versus a subset) may significantly impact the competitiveness of the bidding and the buyer’s perceived performance of the purchase. To better understand bundling practices and experiences, this study surveyed members of the Institute for Supply Management (ISM) that aggregate several SKUs into a single bundled RFQ. Within this context, respondent replies are categorized by buyer-imposed bidding requirements according to whether suppliers are either required to submit bids on all items in the bundle, merely encouraged, or free to bid on any item combination in the bundle. The resulting bundle structure is examined and its impact on purchase (bundle) performance, as perceived by the buying company, is explored. Results are discussed, with managerial insights provided for purchasing professionals.
Electronic government services in Europe: Strategies, projects and applications

In Europe, national electronic government incentives have made a significant contribution to the modernization of administration and its processes as well as its customer oriented services. In this study, European strategies and projects for electronic government as well as their implementation plans were analyzed, followed by an examination of the electronic services offered by the national governmental authorities in Austria, European pioneers in electronic government, the United Kingdom, the electronic government leader in Europe 2010, and Spain as a Southern European electronic government representative. The results revealed that Europe has developed hybrid electronic government strategies for the whole community, and has launched projects in that field, in which member countries have to participate, in order to offer electronic government services at a high level and in a competitive international environment. On a whole, offering a single gateway to governmental information and transactions generally offers higher attractiveness for conducting nationwide business and all incentives for electronic government focus on developing good practices in the area of efficient and effective electronic government. Nevertheless, strategies are transformed and implemented in different ways, and the intensity in the member countries and a union-wide electronic government is still in its infancy.
Preclinical Development Therapeutic Potential of AZD 1480 for the Treatment of Human Glioblastoma

Aberrant activationof the Januskinase (JAK)/signal transducer andactivatorof transcription (STAT)pathway has been implicated in glioblastoma (GBM) progression. To develop a therapeutic strategy to inhibit STAT-3 signaling, we have evaluated the effects of AZD1480, a pharmacologic inhibitor of JAK1 and JAK2. In this study, the in vitro efficacy ofAZD1480was tested inhumanandmurine glioma cell lines.AZD1480 treatment effectively blocks constitutive and stimulus-induced JAK1, JAK2, and STAT-3 phosphorylation in both human and murine glioma cells, and leads to a decrease in cell proliferation and induction of apoptosis. Furthermore, we used human xenograft GBM samples as models for the study of JAK/STAT-3 signaling in vivo, because human GBMsamplespropagatedasxenografts innudemice retainboth thehallmarkgenetic alterationsand the invasive phenotype seen in vivo. In these xenograft tumors, JAK2 and STAT-3 are constitutively active, but levels vary among tumors,which is consistentwith the heterogeneity ofGBMs.AZD1480 inhibits constitutive and stimulusinduced phosphorylation of JAK2 and STAT-3 in these GBM xenograft tumors in vitro, downstream gene expression, and inhibits cell proliferation. Furthermore, AZD1480 suppresses STAT-3 activation in the gliomainitiating cell population in GBM tumors. In vivo, AZD1480 inhibits the growth of subcutaneous tumors and increases survival of mice bearing intracranial GBM tumors by inhibiting STAT-3 activity, indicating that pharmacologic inhibition of the JAK/STAT-3 pathway by AZD1480 should be considered for study in the treatment of patients with GBM tumors. Mol Cancer Ther; 10(12); 2384–93. 2011 AACR.
Strategic Bundling of Products and Prices: A New Synthesis for Marketing

Bundling is pervasive in today's markets. However, the bundling literature contains inconsistencies in the use of terms and ambiguity about basic principles underlying the phenomenon. The literature also lacks an encompassing classification of the various strategies, clear rules to evaluate the legality of each strategy, and a unifying framework to indicate when each is optimal. Based on a review of the marketing, economics, and law literature, this article develops a new synthesis of the field of bundling, which provides three important benefits. First, the article clearly and consistently defines bundling terms and identifies two key dimensions that enable a comprehensive classification of bundling strategies. Second, it formulates clear rules for evaluating the legality of each of these strategies. Third, it proposes a framework of 12 propositions that suggest which bundling strategy is optimal in various contexts. The synthesis provides managers with a framework with which to understand and choose bundling strategies. It also provides researchers with promising avenues for further research.
When nutritional guidelines and life collide: family fruit and vegetable socialisation practices in low socioeconomic communities

Abstract Parents play a critical role in promoting fruit and vegetable consumption, for eating patterns established early in life tend to persist into adulthood. Despite this, the factors that facilitate or inhibit parents’ capacity to socialise fruit and vegetable consumption into their children’s daily diets remain poorly defined. Thirty-eight semi-structured interviews with residents, allied healthcare professionals, community leaders, community programme leaders and a local government leader living or working in two low socioeconomic suburbs were consequently conducted to ascertain factors exogenous and endogenous to the family unit that shaped parental food socialisation practices. Budgetary and time constraints emerged as exogenous factors that constrained fruit and vegetable socialisation. Constraining effects were also found for a range of endogenous factors, including commensal experiences, children’s food fussiness and the feeding styles employed by parents. As such, while many caregivers may wish to socialise fruit and vegetable consumption into their children’s daily diets, their capacity to do so is often inhibited by factors beyond their volitional control. Failure to take heed of these factors could therefore result in the development of social marketing campaigns that are ineffective at best or give rise to unintentionally harmful outcomes at worst.
Understanding Leaky-Wave Structures: A Special Form of Guided-Wave Structure

Guided-wave structures are the foundation for the design and development of RF and microwave circuits and systems. Whether it is planar or nonplanar, periodic or straight, a guided-wave structure, which consists of metallic and/or dielectric composite building blocks, is used to support signal propagation and processing. Except for free-space propagation, diffraction and scattering in an open medium or space, microwave energy is usually transferred by means of specially designed guided-wave structures with modal propagation behavior that are fundamentally characterized by a propagation constant and transmission loss with respect to specific guided-wave modes. Those modes are structure and frequency dependent, and satisfy the boundary conditions of a guided-wave structure. Guided-wave structures can be divided into two kinds, open and closed. The completely closed structures are known to support only the wave guided therein, while the open structure, including semi-open or partially open structures, are subject to a potential gradual wave leakage along the propagation path. Wave leakage is always related to wave guidance, which is very much dependent on a number of factors including structural geometry, fill materials, operating frequency and guided mode. Such leakage can be used positively to develop a leaky-wave structure called a leaky-wave antenna, which enjoys some distinctive properties such as beam-scanning with frequency. Leaky-wave radiating structures are easily fabricated at millimeter wave frequencies compared with other antennas. Although leaky-wave and guided-wave structures have similar characteristics and can be designed by common methods, the simulation and design of leaky-wave structures are usually much more complicated. This is because leaky-wave structures are not closed and their attenuation constant related to leakage needs to be considered. In this article, we focus on the presentation of basic operating principles and special features of positive leaky-wave structures (leaky-wave antennas) ranging from straight to periodic geometries.
Cultural Identities and Resolution of Social Dilemmas

An experiment is reported for payoff-equivalent public good and common pool games with high caste and low caste West Bengali villagers. Tests are reported for models of unconditional social preferences, models of reciprocity, and cultural identity. Results from the artefactual field experiment indicate that when information about caste is withheld no significant difference is observed in the efficiency of play between the villagers and student subjects at American universities in games with positive and negative externalities. In contrast, making the hereditary class structure salient induces different behavior among villagers. Providing caste information leads to: (i) the lowest level of efficiency when low caste first movers interact with a low caste second mover, and (ii) the highest level of efficiency when high caste first movers interact with a high caste second mover. Cross-caste play generates intermediate levels of efficiency.
Comparative performance analysis of neural networks architectures on H2O platform for various activation functions

Deep learning (deep structured learning, hierarchical learning or deep machine learning) is a branch of machine learning based on a set of algorithms that attempt to model high-level abstractions in data by using multiple processing layers with complex structures or otherwise composed of multiple non-linear transformations. In this paper, we present the results of testing neural networks architectures on H2O platform for various activation functions, stopping metrics, and other parameters of machine learning algorithm. It was demonstrated for the use case of MNIST database of handwritten digits in single-threaded mode that blind selection of these parameters can hugely increase (by 2–3 orders) the runtime without the significant increase of precision. This result can have crucial influence for opitmization of available and new machine learning methods, especially for image recognition problems.
MATHEMATICAL AND COMPUTER MODELLING REGULATORY MECHANISMS FOR PROGRAMMED CELL DEATH (APOPTOSIS)

The system for removing needless cells (programmed cell death apoptosis) is important in coordination of structural-functional organisation of large number of cells in an organism. Discovery of cells suicide phenomenon has allowed revising old notions about regulation mechanisms of cellular homeostasis and importance of this mechanisms disturbance during development of large number of diseases including cancer, auto-immune diseases and infection processes. Intuitive understanding activity of the regulatory system connected by means of complex interaction mechanisms between positive and negative feedback loops is very difficult. Here it is necessary formal mathematical methods and computer tools for modelling corresponding regulatory mechanisms. This work deals with some results of the quantitative analysis of simplest regulatory mechanisms for apoptosis process based on the methods for mathematical modeling and computer simulation.
Weight-measurement Based on Rank Ordering in Customer Satisfaction Survey

Ordinary measurement methods focus on absolute importance of factors,which makes the weights of factors no differences and it is ineffective for organizations to improve the quality of its customer satisfaction.Therefore,based on factors rank ordering,this paper puts up a new method of weight analysis that focuses on relative importance among factors and overcomes that imperfection effectively,and more effective quality improvement can be reached.