Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell-Integral-Diversity Criterion: A Proposal for Minimizing Cluster Artifact in Cell-Based Selections

Cell-based methods and the diversity integral criterion (a distance-based technique) are commonly used approaches for assessing the diversity of collections of compounds in terms of space coverage. The main deficiency with cell-based methods is the arbitrariness of cell boundaries which leads to edge effects or cluster artifacts, i.e., situations in which similar molecules separated by a cell boundary yield a higher diversity score than molecules falling within the same cell but which are less similar to each other. We describe a straightforward diversity metric based on quantifying the distance to the center of the bins resulting from partitioning the descriptor space which aims at bypassing these artifacts. The mentioned criteria are compared for the diversity assessment of a set of selections carried out on three combinatorial libraries of different cardinalities. For each method, the influence of its parameters (reference partition and number of points) on their efficacy is examined. Furthermore, the proposed diversity metric is also applied to designing diverse libraries for three test cases. We show that full arrays selected by minimizing the sum of distances to the center of the cells are formed by compounds spaced further apart than selections obtained by maximizing the degree of cell occupancy.
The development of new basal insulins: is there any clinical advantage with their use in type 2 diabetes?

Introduction: The basal insulin products currently on market do not optimally mimic endogenous insulin secretion. These unmet clinical needs have fueled the development of new basal insulin analogues for improving their pharmacokinetics/pharmacodynamics profile. Areas covered: We review the recent literature investigating the efficacy and safety of new basal insulin analogues in type 2 diabetes, as in the USA, insulin utilization accounted for 26% of treatment visits for these patients in 2012. Insulin degludec is a desB30 insulin acylated at the LysB29 residue with a glutamate linker and 16-carbon fatty diacyl side chain. Insulin lispro has been PEGylated at lysine B28, via a urethane bond, which increases the hydrodynamic size of the molecule and reduces its absorption and clearance following subcutaneous administration. Glargine U300 represents a new high-strength glargine formulation (300 U/ml): once injected, U300 forms a compact subcutaneous depot with a smaller surface area to produce a more gradual and prolonged release. Both PEG-lispro and glargine U300 are not yet on the market. Expert opinion: Ultra-long acting and high-strength formulations of new basal analogues have the potential for less glycemic variability, less (nocturnal) hypoglycemia and weight-loss advantage for PEG-lispro. However, these new basal insulin analogues need to be monitored closely for adverse signals.
Modeling the impact of declining sea ice on the Arctic marine planktonic ecosystem

[1] We have developed a coupled 3-D pan-Arctic biology/sea ice/ocean model to investigate the impact of declining Arctic sea ice on the marine planktonic ecosystem over 1988–2007. The biophysical model results agree with satellite observations of a generally downward trend in summer sea ice extent during 1988–2007, resulting in an increase in the simulated photosynthetically active radiation (PAR) at the ocean surface and marine primary productivity (PP) in the upper 100 m over open water areas of the Arctic Ocean. The simulated Arctic sea ice thickness has decreased steadily during 1988–2007, leading to an increase in PAR and PP in sea ice-covered areas. The simulated total PAR in all areas of the Arctic Ocean has increased by 43%, from 146 TW in 1988 to 209 TW in 2007; the corresponding total PP has increased by 50%, from 456 Tg C yr−1 in 1988 to 682 Tg C yr−1 in 2007. The simulated PAR and PP increases mainly occur in the seasonally and permanently ice-covered Arctic Ocean. In addition to increasing PAR, the decline in sea ice tends to increase the nutrient availability in the euphotic zone by enhancing air-sea momentum transfer, leading to strengthened upwelling and mixing in the water column and therefore increased nutrient input into the upper ocean layers from below. The increasing nutrient availability also contributes to the increase in the simulated PP, even though significant surface nutrient drawdown in summer is simulated. In conjunction with increasing surface absorption of solar radiation and rising surface air temperature, the increasing surface water temperature in the Arctic Ocean peripheral seas further contributes to the increase in PP. As PP has increased, so has the simulated biomass of phytoplankton and zooplankton.
COST 277 Nonlinear Processing of Speech 2 nd

Greece: Nonlinear methods in speech processing with applications to recognition: Modulations, fractals, chaos (Invited presentation) 10:00 Coffee break 10:30 WG 4 Session: Voice Analysis and Enhancement (Chair B. Petek) J. Schoentgen, Univ. Libre de Bruxelles, Belgium: Analysis and synthesis of the phonatory excitation signal by means of a polynomial waveshaper J. Rouat, Univ. Québecà Chicoutimi, Canada: Enhancement via nonlinear masking of a time-space representation of speech
Effects of calcium, calmodulin, protein kinase C and protein tyrosine kinases on volume‐activated taurine efflux in human erythroleukemia cells

The effects of calcium, calmodulin, protein kinase C (PKC) and protein tyrosine kinase (PTK) modulators were examined on the volume‐activated taurine efflux in the erythroleukemia cell line K562. Exposure to hypoosmotic solution significantly increased taurine efflux and intracellular calcium concentration ([Ca2+]i). The Ca2+ channel blockers La3+ (1 mM), verapamil (200 μM) and nifedipine (100 μM) inhibited the hypoosmotically‐induced [Ca2+]i increase by more than 90%, while the volume‐activated taurine efflux was inhibited by 61.3 ± 9.5, 74.1 ± 9.3 and 38.0 ± 1.5%, respectively. Furthermore, the calmodulin inhibitors W7 (50 μM) and trifluoperazine (10 μM) and the Ca2+/calmodulin‐dependent protein kinase II inhibitor KN‐62 (2 μM) significantly blocked the volume‐activated taurine efflux by 93.4 ± 2.7, 77.9 ± 3.5 and 61.3 ± 15.8%, respectively. In contrast, the PKC inhibitor staurosporine (200 nM) or the PKC activator phorbol 12‐myristate 13‐acetate (100 nM) did not have significant effects on the volume‐activated taurine efflux. However, pretreatment with PTK inhibitors genistein, tyrphostin A25, and tyrphostin A47 blocked the volume‐activated taurine efflux. These results suggest that the volume‐activated taurine efflux in K562 cells may not directly involve Ca2+, but may require the presence of calmodulin and/or PTK. © 2001 Wiley‐Liss, Inc.
System using hybrid LEO-GPS satellites for rapid resolution of integer cycle ambiguities

Resolution of integer cycle ambiguities is a critical requirement for centimeter-level carrier-phase positioning. This paper investigates the issue of GPS rapid resolution of integer cycle ambiguities, where a Low Earth orbit (LEO) ranging satellite is utilized to obtain large satellite geometry variations generated by its fast-moving property. We define a new system by adding the LEO ranging satellite transmitting signals on the L1 and/or L2 band to the GPS to improve the ability to estimate the integer cycle ambiguities rapidly, and analyse the performance using canonical metrics, such as gain in baseline precision, ambiguity precision and correlation, and ambiguity dilution of precision. Furthermore, in terms of success probability, we evaluate the performance of the proposed scheme compared with that of GPS. In addition, the impacts of the altitude of LEO satellite orbit, the number of visible satellites, the LEO satellite's L2 navigation frequency, and different locations of the receivers on the ambiguity resolution are further analysed. The performance of the proposed scheme is demonstrated through in-depth numerical simulations.
Number and topography of cones, rods and optic nerve axons in New and Old World primates

To better understand the evolution of spatial and color vision, the number and spatial distributions of cones, rods, and optic nerve axon numbers were assessed in seven New World primates (Cebus apella, Saimiri ustius, Saguinus midas niger, Alouatta caraya, Aotus azarae, Calllithrix jacchus, and Callicebus moloch). The spatial distribution and number of rods and cones was determined from counts of retinal whole mounts. Optic axon number was determined from optic nerve sections by electron microscopy. These data were amassed with existing data on retinal cell number and distribution in Old World primates, and the scaling of relative densities and numbers with respect to retinal area, eye and brain sizes, and foveal specializations were evaluated. Regular scaling of all cell types was observed, with the exceptionally large, rod-enriched retina of the nocturnal owl monkey Aotus azarae, and the unusually high cone density of the fovea of the trichromatic howler monkey Alouatta caraya presenting interesting variations on this basic plan. Over all species, the lawful scaling of rods, cones, and retinal ganglion cell number is hypothesized to result from a conserved sequence of cell generation that defends retinal acuity and sensitivity over a large range of eye sizes.
Predicting Ecological Roles in the Rhizosphere Using Metabolome and Transportome Modeling

The ability to obtain complete genome sequences from bacteria in environmental samples, such as soil samples from the rhizosphere, has highlighted the microbial diversity and complexity of environmental communities. However, new algorithms to analyze genome sequence information in the context of community structure are needed to enhance our understanding of the specific ecological roles of these organisms in soil environments. We present a machine learning approach using sequenced Pseudomonad genomes coupled with outputs of metabolic and transportomic computational models for identifying the most predictive molecular mechanisms indicative of a Pseudomonad’s ecological role in the rhizosphere: a biofilm, biocontrol agent, promoter of plant growth, or plant pathogen. Computational predictions of ecological niche were highly accurate overall with models trained on transportomic model output being the most accurate (Leave One Out Validation F-scores between 0.82 and 0.89). The strongest predictive molecular mechanism features for rhizosphere ecological niche overlap with many previously reported analyses of Pseudomonad interactions in the rhizosphere, suggesting that this approach successfully informs a system-scale level understanding of how Pseudomonads sense and interact with their environments. The observation that an organism’s transportome is highly predictive of its ecological niche is a novel discovery and may have implications in our understanding microbial ecology. The framework developed here can be generalized to the analysis of any bacteria across a wide range of environments and ecological niches making this approach a powerful tool for providing insights into functional predictions from bacterial genomic data.
Specific interactions of serpins in their native forms attenuate their conformational transitions

Plasminogen activator inhibitor‐1 (PAI‐1) belongs to the serine protease inhibitor (serpin) protein superfamily. Serpins are unique in that their native forms are not the most thermodynamically stable conformation; instead, a more stable, latent conformation exists. During the transition to the latent form, the first strand of β‐sheet C (s1C) in the serpin is peeled away from the β‐sheet, and the reactive center loop (RCL) is inserted into β‐sheet A, rendering the serpin inactive. To elucidate the contribution of specific interactions in the metastable native form to the latency transition, we examined the effect of mutations at the s1C of PAI‐1, specifically in positions P4′ through P10′. Several mutations strengthened the interactions between these residues and the core protein, and slowed the transition of the protein from the metastable native form to the latent form. In particular, anchoring of the strand to the protein's hydrophobic core at the beginning (P4′ site) and center of the strand (P8′ site) greatly retarded the latency transition. Mutations that weakened the interactions at the s1C region facilitated the conformational conversion of the protein to the latent form. PAI‐1's overall structural stability was largely unchanged by the mutations, as evaluated by urea‐induced equilibrium unfolding monitored via fluorescence emission. Therefore, the mutations likely exerted their effects by modulating the height of the energy barrier from the native to the latent form. Our results show that interactions found only in the metastable native form of serpins are important structural features that attenuate folding of the proteins into their latent forms.
School Consolidation and Notions of Progress: Why Community Actors Almost Always Lose the Fight to Keep Local Schools and How They Can Turn the Tables

Supported by a growing body of research, the idea that schools have an essential role to play in local community cohesion and development has gained currency among urban and rural school advocates alike. Yet moving theory into action often grinds to a halt in the face of a recalcitrant bureaucracy. To understand why, it is important to step back and examine the theoretical framework of progress that has driven school consolidation and bureaucratization over the past century. Knowing these underlying power dynamics will help community advocates understand where their power is weakest, and where it is strongest, leading to more effective community action in defence of local schools. Keywords: school consolitation; community action; community school
Characterization of metal and nucleotide liganded forms of adenylate kinase by electrospray ionization mass spectrometry.

Complexes of adenylate kinase from Escherichia coli, Bacillus subtilis, and Bacillus stearothermophilus with the bisubstrate nucleotide analog P1,P5-di(adenosine 5')-pentaphosphate and with metal ions (Zn2+ and/or Mg2+) were analyzed by electrospray ionization mass spectrometry. P1,P5-di(adenosine 5')-pentaphosphate. adenylate kinase complex was detected in the positive mode at pH as low as 3.8. Binding of nucleotide to adenylate kinase stabilizes the overall structure of the protein and preserves the Zn2+ chelated form of the enzyme from the gram-positive organisms. In this way, it is possible in a single mass spectrometry experiment to screen metal-chelating adenylate kinases, without use of radioactively labeled compounds. Binding of Mg2+ to enzyme via P1,P5-di(adenosine 5')-pentaphosphate was also demonstrated by mass spectrometry. Although no amino acid side chain in adenylate kinase is supposed to interact with Mg2+, Asp93 in porcine muscle cytosolic enzyme, equivalent to Asp84 in the E. coli adenylate kinase, was proposed to stabilize the nucleotide.Mg2+ complex via water molecules.
Learning Harmonic Progression Using Markov Models

In an effort to try to automate the learning of the structure of musical compositions, we recognize that music, like natural language, has a “deep structure” that is diff icult to represent. One barrier lies in our abili ty to even understand the semantics of music. The computer music society is interested in the generation and representation of music, and there are preliminary investigations in learning music that serve as motivation for this project.
Ethical Considerations in Adventure Therapy

The author addresses two major questions: (1) What ethical dilemmas exist in providing adventure therapy for women as it is commonly practiced? and, (2) Given what we know, how can adventure therapy be of the most therapeutic value to women? Research regarding the effectiveness of adventure therapy is mixed and inconclusive. A competing hypothesis for causation of the global changes people experience after a therapeutic experience is the impact of natural environment. Adventure therapy has its roots in a patriarchal society and was developed for boys and men. The same principles and practices now are being applied to women, thus creating a challenge for feminists in the field of adventure therapy to selectively employ those aspects of adventure therapy which increase women's mental and emotional health, and to discard or modify those aspects which are harmful. The author presents a model she believes recognizes women's strengths as well as needs. This model respects individual differences, recognizes and .
“It Gets You Away From Everyday Life”: Local Woodlands and Community Use—What Makes a Difference?

This paper explores who uses woodlands near their homes, why they visit, what benefits they believe they obtain and what makes the difference between them choosing to visit or not. In the research, supported by the Forestry Commission, a multi-method, user-led approach was used, based on focus groups, questionnaire surveys and on-site observation in relation to five different communities in the central belt of Scotland. The conclusions demonstrate the overriding importance of childhood woodland visits as predictors of adult patterns of use. Proximity of woodlands is important for regular woodland users and freedom from rubbish is the physical quality people care most about. The physical qualities that make a difference as to whether people visit woodlands or not include directional signs, good information boards, variety of trees and tidiness of appearance. Perceptions of woodlands differ according to age and sex but are predominantly positive across all groups sampled: most people feel at peace in a woodland.
Using a Painting Metaphor to Rate Large Numbers of Objects

When retrieving information from databases or search engines, or when configuring user profiles of information filtering systems, users have to describe what objects to retrieve. While some systems require users to describe their needs using textual input, other systems simplify the users’ task by proposing a set of items, so that the user’s task is reduced to picking or rating these items (e.g. relevance feedback (Haines 93)). This task is generally much simpler than writing queries from scratch. In interfaces of this type, users have to provide information of the type “does this item represent my information interest”, “do I like this item” or “how much do I like this item”. Similar problems are encountered in utility theory, when assessing the user’s value functions (Keeney and Raiffa 76). As an example, Figure 1 shows such a selection user interface. It allows users the selection of TV channels, e.g. to configure their user profile for a TV recommender system. The interface contains about sixty toggle switches.
Decentralized Multi-Period Economic Dispatch for Real-Time Flexible Demand Management

Emerging smart-grid-enabling technologies will allow an unprecedented degree of observability and control at all levels in a power system. Combined with flexible demand and storage, they could allow procuring energy at minimum cost and environmental impact. That however presupposes real-time coordination of demand of individual households and industries down at the distribution level, with generation at the transmission level. This is closely related with the balancing market economic dispatch (ED) problem, which currently does not take into account distribution network constraints and flexible demand characteristics. Still, assuming a suitably modified form of that problem was available, due to both computational and communications requirements, its centralized solution in its full detail would not be tractable. While there is currently a wealth of literature dealing with distributed optimization applications in power systems, it typically focuses on smaller parts of the overall energy management problem (e.g., transmission area synchronization or electric vehicles management) often without considering its full scale or establishing any association with energy market mechanisms. The target of this paper is twofold: 1) identify a flexible demand and distribution network inclusive formulation for ED and 2) propose a solution method.
Localized Temperature Variations in Laser-Irradiated Composites with Embedded Fiber Bragg Grating Sensors

Fiber Bragg grating (FBG) temperature sensors are embedded in composites to detect localized temperature gradients resulting from high energy infrared laser radiation. The goal is to detect the presence of radiation on a composite structure as rapidly as possible and to identify its location, much the same way human skin senses heat. A secondary goal is to determine how a network of sensors can be optimized to detect thermal damage in laser-irradiated composite materials or structures. Initial tests are conducted on polymer matrix composites reinforced with either carbon or glass fiber with a single optical fiber embedded into each specimen. As many as three sensors in each optical fiber measure the temporal and spatial thermal response of the composite to high energy radiation incident on the surface. Additional tests use a 2 × 2 × 3 array of 12 sensors embedded in a carbon fiber/epoxy composite to simultaneously measure temperature variations at locations on the composite surface and through the thickness. Results indicate that FBGs can be used to rapidly detect temperature gradients in a composite and their location, even for a direct strike of laser radiation on a sensor, when high temperatures can cause a non-uniform thermal response and FBG decay.
Using Nonverbal Communication in Efl Classes

This paper aims at providing information about nonverbal communication and to state its use in EFL classes. Briefly, this paper introduces the definition, aspects and importance of nonverbal communication. Especially, this study explains some ways of using nonverbal communication in EFL classes, in order to have good classroom management in the class. Based upon this assumption, we aimed to shed light on this area of research, by showing that teachers’ nonverbal behaviour plays a highly significant and essential role in foreign language classrooms for managing the students’ behaviour. This study was conducted in Lefke, Northern Cyprus. The participants were two female English language teachers who were working at the English Preparatory School of Lefke. The study was qualitative in design and the data was gathered through interviews and reflective reports. A triangulation technique was used to enhance confidence in the ensuing findings. Cross-case analysis was used to examine and identify common themes between the cases. The results showed that nonverbal communication has a pivotal role in classroom management. In EFL classes in Northern Cyprus, in order to guide teachers to use nonverbal communication before verbal communication, some seminars or workshops should be organized regarding the use of body language in classroom management to improve teachers professionally. Keywords: Nonverbal communication, classroom management, communication