Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Repair Excision Nuclease Attacks Undamaged DNA

Nucleotide excision repair is a general repair system that eliminates many dissimilar lesions from DNA. In an effort to understand substrate determinants of this repair system, we tested DNAs with minor backbone modifications using the ultrasensitive excision assay. We found that a phosphorothioate and a methylphosphonate were excised with low efficiency. Surprisingly, we also found that fragments of 23–28 nucleotides and of 12–13 nucleotides characteristic of human and Escherichia coliexcision repair, respectively, were removed from undamaged DNA at a significant rate. Considering the relative abundance of undamaged DNA in comparison to damaged DNA in the course of the life of an organism, we conclude that, in general, excision from and resynthesis of undamaged DNA may exceed the excision and resynthesis caused by DNA damage. As resynthesis is invariably associated with mutations, we propose that gratuitous repair may be an important source of spontaneous mutations.
Sensing Lipids with Mincle: Structure and Function

Mincle is a C-type lectin receptor that has emerged as an important player in innate immunity through its capacity to recognize a wide range of lipidic species derived from damaged/altered self and foreign microorganisms. Self-ligands include sterols (e.g., cholesterol), and β-glucosylceramides, and the protein SAP130, which is released upon cell death. Foreign lipids comprise those from both microbial pathogens and commensals and include glycerol, glucose and trehalose mycolates, and glycosyl diglycerides. A large effort has focused on structural variation of these ligands to illuminate the structure–activity relationships required for the agonism of signaling though Mincle and has helped identify key differences in ligand recognition between human and rodent Mincle. These studies in turn have helped identify new Mincle ligands, further broadening our understanding of the diversity of organisms and lipidic species recognized by Mincle. Finally, progress toward the development of Mincle agonists as vaccine adjuvants providing humoral and cell-mediated immunity with reduced toxicity is discussed.
Further Developments and Tests of a Progressive Algorithm for Multiple Criteria Decision Making

P. Korhonen, H. Moskowitz, and J. Wallenius 1986 developed a progressive algorithm and the supporting theory for modeling and solving multiple criteria decision problems with discrete alternatives. A special feature of the algorithm is that it relaxes the usual assumption of a fixed set of available decision alternatives and complete knowledge of a decision maker's DM's preference structure or value function. The algorithm is based on progressively sampling the decision space, obtaining preference information from the DM, determining the likelihood of finding possibly/surely better alternatives, and based on this information, continuing the search or terminating it by making the final choice. We describe a computerized implementation and extensive computational tests of the algorithm, as well as some of our experiences in applying and field testing it in practice. We also consider several improvements and developments of the algorithm to further facilitate its use in practice.
Hamiltonian of tensionless strings with tensor central charge coordinates

A new class of twistor-like string models in four-dimensional space-time extended by the addition of six tensorial central charge (TCC) coordinates zmn is studied. The hamiltonian of tensionless string in the extended space-time is derived and its symmetries are investigated. We establish that the string constraints reduce the number of independent TCC coordinates zmn to one real effective coordinate which composes an effective 5-dimensional target space together with the xm coordinates. We construct the P.B. algebra of the first class constraints and discover that it coincides with the P.B. algebra of tensionless strings. The Lorentz covariant antisymmetric Dirac -matrix of the P.B. of the second class constraints is constructed and its algebraic structure is further presented.
Light-controlled flavonoid biosynthesis in fruits

Light is one of the most important environmental factors affecting flavonoid biosynthesis in plants. The absolute dependency of light to the plant development has driven evolvement of sophisticated mechanisms to sense and transduce multiple aspects of the light signal. Light effects can be categorized in photoperiod (duration), intensity (quantity), direction and quality (wavelength) including UV-light. Recently, new information has been achieved on the regulation of light-controlled flavonoid biosynthesis in fruits, in which flavonoids have a major contribution on quality. This review focuses on the effects of the different light conditions on the control of flavonoid biosynthesis in fruit producing plants. An overview of the currently known mechanisms of the light-controlled flavonoid accumulation is provided. R2R3 MYB transcription factors are known to regulate by differential expression the biosynthesis of distinct flavonoids in response to specific light wavelengths. Despite recent advances, many gaps remain to be understood in the mechanisms of the transduction pathway of light-controlled flavonoid biosynthesis. A better knowledge on these regulatory mechanisms is likely to be useful for breeding programs aiming to modify fruit flavonoid pattern.
BSA dosing and suboptimal 5-FU exposure among colorectal cancer patients of varying gender and age.

579 Background: 5-Fluorouracil (5-FU) remains the cornerstone of colorectal cancer (CRC) therapy and its dosing is based on body surface area (BSA). Although convenient, BSA dosing disregards factors that impact 5-FU PK such as genotype, age, gender, etc. Thus, patients receiving the same BSA based dose show a wide range of 5-FU plasma levels (measured as AUC in mg·h/L), resulting in ineffective or toxic doses affecting therapy outcome. An optimal therapeutic AUC target range of 20-30 mg·h/L has been proposed. METHODS Plasma samples from the initial treatment cycle of 927 CRC patients who received 2400 mg/m2 continuous infusion of 5-FU over 44-48 hours, with or without bevacizumab, were tested for 5-FU exposure using an immune-based assay (OnDose). AUC results were analyzed to evaluate gender and age effects. RESULTS There are 391 (42.2%) female and 536 (57.8%) male patients with age ranging from 17-93 years (mean/SD: 58.5/11.8). These analyses indicate that in comparison to the proposed optimal AUC target range of 20-30 mg·h/L, females receive supra-optimal doses compared to males (p=0.0083). Age also affects the 5-FU AUC (p=0.0002), with younger patients more likely to receive sub-optimal doses than older patients. CONCLUSIONS BSA dosing is an unreliable indicator of exposure and may lead to under dosing in males and younger patients, and overdosing in females and older patients, potentially resulting in corresponding diminished efficacy or increased toxicity. Data suggest that therapy could be optimized by 5-FU dose adjustment in subsequent cycles based on PK monitoring so that AUC values will converge towards the target range irrespective of gender or age. A large clinical trial is in progress to validate these findings.
Optical Mode Splitting in Ring-Shaped Hollow Bragg Cavity

We investigate the optical modes of hollow ring resonator with omnidirectional reflector cladding by numerical method. We demonstrate that each TM0ml mode (or TE0ml mode) can split into two modes whose wavelengths are very close. The doublet effect is caused by the symmetry breaking at circular cross section when a straight waveguide is curled into a ring shape. The ring-shaped hollow Bragg cavity provides a platform to research the interaction of Rydberg atoms and light mode.
Modelling asphalt mastic stiffness using discrete element analysis and micromechanics-based models

This study uses the discrete element method (DEM) to simulate the dynamic mechanical behaviour of asphalt mastics. Asphalt mastics are defined as dispersions of aggregate fillers within a medium of asphalt binder. The fillers refer to the fraction of mineral aggregate passing the 200-mesh sieve, (i.e. smaller than 75 μm). Mastic measurements obtained using the dynamic shear rheometer were compared to DEM predictions and available micromechanics-based models. Three asphalt binders (ABD-1, AAM-1 and ABM-1) and four mineral fillers (glacial gravel, granite, limestone and greywacke) were used to prepare the mastics in this study. The stiffening effect of the mineral fillers was investigated at different filler volume fractions. The DEM results captured the stiffening behaviour of asphalt mastics as a function of the volumetric concentration of mineral fillers. The DEM results exhibited a high rate of stiffening that is typically observed in experimental measurements of mastics at relatively low volume concentrations of fillers. Compared to the DEM results, the micromechanics-based models were not sensitive to the dynamic shear modulus of the asphalt binder, and they underestimated the stiffening effect of the mineral fillers.
Rankings of Directed Graphs

A ranking of a graph is a coloring of the vertex set with positive integers such that on every path connecting two vertices of the same color there is a vertex of larger color. We consider the directed variant of this problem, where the above condition is imposed only on those paths in which all edges are oriented in the same direction. We show that the ranking number of a directed tree is bounded by that of its longest directed path plus one, and that it can be computed in polynomial time. Unlike the undirected case, however, deciding whether the ranking number of a directed (and even of an acyclic directed) graph is bounded by a constant is NP-complete. In fact, the 3-ranking of planar bipartite acyclic digraphs is already hard.
GABA Concentration in Posterior Cingulate Cortex Predicts Putamen Response during Resting State fMRI

The role of neurotransmitters in the activity of resting state networks has been gaining attention and has become a field of research with magnetic resonance spectroscopy (MRS) being one of the key techniques. MRS permits the measurement of γ-aminobutyric acid (GABA) and glutamate levels, the central biochemical constituents of the excitation-inhibition balance in vivo. The inhibitory effects of GABA in the brain have been largely investigated in relation to the activity of resting state networks in functional magnetic resonance imaging (fMRI). In this study GABA concentration in the posterior cingulate cortex (PCC) was measured using single voxel spectra acquired with standard point resolved spectroscopy (PRESS) from 20 healthy male volunteers at 3 T. Resting state fMRI was consecutively measured and the values of GABA/Creatine+Phosphocreatine ratio (GABA ratio) were included in a general linear model matrix as a step of dual regression analysis in order to identify voxels whose neuroimaging metrics during rest were related to individual levels of the GABA ratio. Our data show that the connection strength of putamen to the default-mode network during resting state has a negative linear relationship with the GABA ratio measured in the PCC. These findings highlight the role of PCC and GABA in segregation of the motor input, which is an inherent condition that characterises resting state.
The Main Aeromonas Pathogenic Factors

The members of the Aeromonas genus are ubiquitous, water-borne bacteria. They have been isolated from marine waters, rivers, lakes, swamps, sediments, chlorine water, water distribution systems, drinking water and residual waters; different types of food, such as meat, fish, seafood, vegetables, and processed foods. Aeromonas strains are predominantly pathogenic to poikilothermic animals, and the mesophilic strains are emerging as important pathogens in humans, causing a variety of extraintestinal and systemic infections as well as gastrointestinal infections. The most commonly described disease caused by Aeromonas is the gastroenteritis; however, no adequate animal model is available to reproduce this illness caused by Aeromonas. The main pathogenic factors associated with Aeromonas are: surface polysaccharides (capsule, lipopolysaccharide, and glucan), S-layers, iron-binding systems, exotoxins and extracellular enzymes, secretion systems, fimbriae and other nonfilamentous adhesins, motility and flagella.
BMS-204352: a potassium channel opener developed for the treatment of stroke.

During ischemic stroke, a fatal biochemical cascade that results in neuronal hyperexcitability is initiated when neurons at risk are exposed to excessive excitatory amino acids and pathologically high levels of intracellular calcium (Ca(2+)). Therefore, neuroprotectants including NMDA-antagonists and blockers of voltage-gated Ca(2+) channels have been proposed as novel strategies for stroke treatment. Since potassium channels are key players in the control of neuronal excitability, and activation of neuronal potassium channels decrease excitability and neurotransmitter release, a novel approach for targeting acute ischemic stroke has been to develop openers of neuronal potassium channels. Bristol-Myers Squibb is developing BMS-204352, a fluoro-oxindole potassium channel opener, as a potential neuroprotectant for the treatment of acute ischemic stroke. BMS-203252 is a potent and effective opener of two important subtypes of neuronal potassium channels, the calcium-activated, big-conductance potassium channels (K(Ca) channels) and voltage-dependent, non-inactivating potassium channels known as KCNQ channels. BMS-204352 (0.3 mg/kg, i.v.) significantly reduced cortical infarct volume in a model of permanent occlusion of the middle cerebral artery (MCA) in spontaneous hypertensive rats (SHR), as compared to vehicle when administered 2 h post-occlusion. At doses from 1 microg/kg to 1 mg/kg i.v. , BMS-204352 produced a significant reduction in cortical infarct volume in normotensive Wistar rats. In healthy humans, single and multiple i.v. doses of BMS-204352 (0.001 to 0.2 mg/kg) were safe, well-tolerated and without psychomotor function effects. Multiple doses of BMS-204352 (0.1-2 mg/kg i.v.) administered within 48 h after stroke onset were well tolerated in patients in Phase II studies, designed to evaluate safety, tolerability and pharmacokinetics. No clinically significant differences in organ toxicity or adverse effects were found, and total clearance and volume of distribution were independent of dose. BMS-204352 failed to show superior efficacy in acute stroke patients compared to placebo in a Phase III study that included 1978 patients at 200 centers worldwide.
Reforme na tržištu rada u kontekstu teorije političkih procesa: Analiza Slovenije

The rigidity of labour market has several important negative economic consequences: it stifles job creation, increases discrimination of those it is actually aimed at protecting (young, women and low skilled), hurts the unemployed, slows down economic restructuring and damages its global competitiveness. But reforms are slow and often marked with disputes among partners in the collective bargaining process. Afraid of social security loss, unions usually oppose the reform, while governments usually give in to the union pressures and negative image of reform consequences created by unions and assisted by media. The characteristics of the labour market and labour market reform with respect to bargaining among power groups are examined both theoretically and empirically in the case of Slovenia.
Learning with Mean-Variance Filtering, SVM and Gradient-based Optimization

We consider several models, which employ gradient-based method as a core optimization tool. Experimental results were obtained in a real time environment during WCCI-2006 Performance Prediction Challenge. None of the models were proved to be absolutely best against all five datasets. Furthermore, we can exploit the actual difference between different models and create an ensemble system as a complex of the base models where the balances may be regulated using special parameters or confidence levels. Overfitting is a usual problem in the situation when dimension is comparable with the sample size or even higher. Using mean-variance filtering we can reduce the difference between training and test results significantly considering some features as a noise.
Adaptation-Based Programming in Haskell

We present an embedded DSL to support adaptation-based programming (ABP) in Haskell. ABP is an abstract model for defining adaptive values, called adaptives, which adapt in response to some associated feedback. We show how our design choices in Haskell motivate higher-level combinators and constructs and help us derive more complicated compositional adaptives. We also show an important specialization of ABP is in support of reinforcement learning constructs, which optimize adaptive values based on a programmer-specified objective function. This permits ABP users to easily define adaptive values that express uncertainty anywhere in their programs. Over repeated executions, these adaptive values adjust to more efficient ones and enable the user's programs to self optimize. The design of our DSL depends significantly on the use of type classes. We will illustrate, along with presenting our DSL, how the use of type classes can support the gradual evolution of DSLs.
2 O ct 2 00 7 The diagonal of the Stasheff polytope

We construct an A-infinity structure on the tensor product of two Ainfinity algebras by using the simplicial decomposition of the Stasheff polytope. The key point is the construction of an operad AA-infinity based on the simplicial Stasheff polytope. The operad AA-infinity admits a coassociative diagonal and the operad A-infinity is a retract by deformation of it. We compare these constructions with analogous constructions due to Saneblidze-Umble and Markl-Shnider based on the Boardman-Vogt cubical decomposition of the Stasheff polytope.
Glaucoma drainage implants: a critical comparison of types

Purpose of review The purpose of this review is to critically compare the various glaucoma drainage implants in popular use. Recent findings Glaucoma drainage implants are being increasingly utilized in the surgical management of glaucoma. Comparisons between the various drainage implants are difficult because most clinical data are derived from retrospective studies with different study populations, follow-up periods, and criteria defining success. The type of glaucoma under treatment is a major factor influencing surgical outcomes. The resistance to aqueous flow through glaucoma drainage implants occurs across the fibrous capsule around the end plate, and the major determinants of the final intraocular pressure are capsular thickness and filtration surface area. The use of antifibrotic agents as adjuncts to drainage implant surgery has not proven effective in modulating capsular thickness. Valved implants appear to reduce, but do not eliminate, the risk of hypotony. Bleb encapsulation is more frequently seen with the Ahmed valve implant than other drainage implants. Diplopia was a common complication with the Baerveldt glaucoma implant after its introduction, but design modifications have markedly reduced the incidence of this complication. Summary There are several glaucoma drainage implants that are currently available, and all have been shown to be safe and effective in reducing intraocular pressure. Greater pressure reduction may be achieved with implants with larger end plates, and valved implants appear to reduce the risk of postoperative hypotony.
Relative safety profiles of high dose statin regimens

Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.
Locating the source of spreading in complex networks

Locating the source that triggers a dynamical process is a fundamental but challenging problem in complex networks, ranging from epidemic spreading in society and on the Internet to cancer metastasis in the human body. An accurate localization of the source is inherently limited by our ability to simultaneously access the information of all nodes in a large-scale complex network. This thus raises two critical questions: how do we locate the source from incomplete information and can we achieve full localization of sources at any possible location from a given set of observable nodes. Here we develop a time-reversal backward spreading algorithm to locate the source of a diffusion-like process efficiently and propose a general locatability condition. We test the algorithm by employing epidemic spreading and consensus dynamics as typical dynamical processes and apply it to the H1N1 pandemic in China. We find that the sources can be precisely located in arbitrary networks insofar as the locatability condition is assured. Our tools greatly improve our ability to locate the source of diffusion in complex networks based on limited accessibility of nodal information. Moreover, they have implications for controlling a variety of dynamical processes taking place on complex networks, such as inhibiting epidemics, slowing the spread of rumors, pollution control, and environmental protection.
Learning Hierarchical Task Networks for Nondeterministic Planning Domains

This paper describes how to learn Hierarchical Task Networks (HTNs) in nondeterministic planning domains, where actions may have multiple possible outcomes. We discuss several desired properties that guarantee that the resulting HTNs will correctly handle the nondeterminism in the domain. We developed a new learning algorithm, called HTN-MAKERND, that exploits these properties. We implemented HTN-MAKERND in the recently-proposed HTN-MAKER system, a goal-regression based HTN learning approach. In our theoretical study, we show that HTN-MAKERND soundly produces HTN planning knowledge in low-order polynomial times, despite the nondeterminism. In our experiments with two nondeterministic planning domains, ND-SHOP2, a well-known HTN planning algorithm for nondeterministic domains, significantly outperformed (in some cases, by about 3 orders of magnitude) the well-known planner MBP using the learned HTNs.
Static generation and dissipation of polyester continuous filament yarn

The effect of environmental conditions (temperature and relative humidity) and contact conditions (yarn tension and speed) on static generation and dissipation of polyester flat continuous filament yarn, when rubbed against stainless steel was analyzed. A newly developed device, housed in an environmental room, was used to charge the yarn while moving under desired tension. The charge potentials were measured at two different positions in real time. These measurements and previously established exponential relationship permitted the calculation of the initial potential (at the generation point) and a ‘characteristic decay time’, which is a measure of static dissipation. Experimental data showed that temperature, humidity, yarn tension, and yarn speed have significant effects on static generation; while temperature, humidity, and yarn speed yielded statistically significant changes on static dissipation. Anomalous behavior of static charge when measured at a temperature of 35°C, provided a meaningful clue to control the environmental conditions in the textile industry.