Miracle-dz/UniFAR-FTUs huggingface dataset:
Palindrome‐Mediated and Replication‐Dependent Pathogenic Structural Rearrangements within the NF1 Gene

Palindromic sequences can form hairpin structures or cruciform extrusions, which render them susceptible to genomic rearrangements. A 197‐bp long palindromic AT‐rich repeat (PATRR17) is located within intron 40 of the neurofibromatosis type 1 (NF1) gene (17q11.2). Through comprehensive NF1 analysis, we identified six unrelated patients with a rearrangement involving intron 40 (five deletions and one reciprocal translocation t(14;17)(q32;q11.2)). We hypothesized that PATRR17 may be involved in these rearrangements thereby causing NF1. Breakpoint cloning revealed that PATRR17 was indeed involved in all of the rearrangements. As microhomology was present at all breakpoint junctions of the deletions identified, and PATRR17 partner breakpoints were located within 7.1 kb upstream of PATRR17, fork stalling and template switching/microhomology‐mediated break‐induced replication was the most likely rearrangement mechanism. For the reciprocal translocation case, a 51 bp insertion at the translocation breakpoints mapped to a short sequence within PATRR17, proximal to the breakpoint, suggesting a multiple stalling and rereplication process, in contrast to previous studies indicating a purely replication‐independent mechanism for PATRR‐mediated translocations. In conclusion, we show evidence that PATRR17 is a hotspot for pathogenic intragenic deletions within the NF1 gene and suggest a novel replication‐dependent mechanism for PATRR‐mediated translocation.
Reproductive and Developmental Risks from Ethylene Oxide: A Probabilistic Characterization of Possible Regulatory Thresholds

Ethylene oxide is a gas produced in large quantities in the United States that is used primarily as a chemical intermediate in the production of ethylene glycol, propylene glycol, nonionic surfactants, ethanolamines, glycol ethers, and other chemicals. It has been well established that ethylene oxide can induce cancer, genetic, reproductive and developmental, and acute health effects in animals. The U.S. Environmental Protection Agency is currently developing both a cancer potency factor and a reference concentration (RfC) for ethylene oxide. This study used the rich database on the reproductive and developmental effects of ethylene oxide to develop a probabilistic characterization of possible regulatory thresholds for ethylene oxide. This analysis was based on the standard regulatory approach for noncancer risk assessment, but involved several innovative elements, such as: (1) the use of advanced statistical methods to account for correlations in developmental outcomes among littermates and allow for simultaneous control of covariates (such as litter size); (2) the application of a probabilistic approach for characterizing the uncertainty in extrapolating the animal results to humans; and (3) the use of a quantitative approach to account for the variation in heterogeneity among the human population. This article presents several classes of results, including: (1) probabilistic characterizations of ED10s for two quantal reproductive outcomes—resorption and fetal death, (2) probabilistic characterizations of one developmental outcome—the dose expected to yield a 5% reduction in fetal (or pup) weight, (3) estimates of the RfCs that would result from using these values in the standard regulatory approach for noncancer risk assessment, and (4) a probabilistic characterization of the level of ethylene oxide exposure that would be expected to yield a 1/1000 increase in the risk of reproductive or developmental outcomes in exposed human populations.
What is a Neural Correlate of Consciousness

The search for neural correlates of consciousness (or NCCs) is arguably the cornerstone in the recent resurgence of the science of consciousness. The search poses many difficult empirical problems, but it seems to be tractable in principle, and some ingenious studies in recent years have led to considerable progress. A number of proposals have been put forward concerning the nature and location of neural correlates of consciousness. A few of these include: • 40-hertz oscillations in the cerebral cortex (Crick and Koch 1990) • Intralaminar nuclei in the thalamus (Bogen 1995) • Re-entrant loops in thalamocortical systems (Edelman 1989) • 40-hertz rhythmic activity in thalamocortical systems (Llinas et al 1994) • Extended reticular-thalamic activation system (Newman and Baars 1993) • Neural assemblies bound by NMDA (Flohr 1995) • Certain neurochemical levels of activation (Hobson 1997) • Certain neurons in inferior temporal cortex (Sheinberg and Logothetis 1997) • Neurons in extrastriate visual cortex projecting to prefrontal areas (Crick and Koch 1995) • Visual processing within the ventral stream (Milner and Goodale 1995) (A longer list can be found in Chalmers 1998. Review articles on neural correlates of consciousness, especially visual consciousness, can be found in Crick and Koch 1998 and Milner 1995.)
Concurrent Hierarchical Reinforcement Learning

We consider applying hierarchical reinforcement learning techniques to problems in which an agent has several effectors to control simultaneously. We argue that the kind of prior knowledge one typically has about such problems is best expressed using a multithreaded partial program, and present concurrent ALisp, a language for specifying such partial programs. We describe algorithms for learning and acting with concurrent ALisp that can be efficient even when there are exponentially many joint choices at each decision point. Finally, we show results of applying these methods to a complex computer game domain.
Fast Spectrum Reuse and Power Control for Device-to-Device Communication

Future 5G mobile networks are expected to support high numbers of simultaneously connected devices and to achieve high system spectrum efficiency at low power consumption. To attain these goals, device-to-device (D2D) communication is a key component. We allow any cellular user equipment to share its radio resource with multiple D2D devices and then develop the MiSo algorithm, which considers spectrum reuse and power control jointly. Simulation results confirm that compared with several algorithms, MiSo achieves highest system throughput and power efficiency with shortest run time.
A hierarchical Bayesian approach to direction finding and beamforming

It is well known in array processing that general multiple signal model based approaches for direction of arrival estimation, such as maximum likelihood (ML) or maximum a posteriori (MAP) estimation, are optimal. The major drawbacks of these approaches, is that not only do we need to know the number of signals a priori, but these methods also involve multivariate nonlinear maximizations which can often lead to an unacceptably large computational overhead. In this paper we propose a hierarchical Bayesian analysis for high accuracy direction finding and the resolution of closely spaced signals. The approach is to use a one signal model posterior distribution to obtain an initial coarse location of the signals. We then take each peak found and analyze it locally with a two signal model. In this way the computational load is kept modest as the optimizations are carried out only locally around the peak and there is no need to know, a priori, the number of signals. It is shown that this approach also provides a basis for the development of robust beamformers through the use of Laplace asymptotic expansions.
A comparison of friction measurement results using two slipmeters

Assessment of floor slip slipperiness is of paramount importance in quantifying the risk of slipping and falling incidents. Friction measurement is one of the major approaches in assessing floor slipperiness. The Brungraber Mark II is one of the slipmeters commonly used in the USA. Operation of the Mark II requires repetitive strikes of the footwear pad on the floor for a single reading. One of the disadvantages of the Mark II is that the operator needs to lift a 4.54 kg weight and releases it with an awkward kneeing posture for every trial. To remedy this drawback, the designer of Mark II has fabricated a new slipmeter named Mark III. Instead of been driven by a 4.54 kg weight, the Mark III is activated by a spring. This requires less physical effort in both carrying and operating as compared to that of the Mark II. However, there is no published data examining the reliability and consistency of this new device. In this study, we compare the friction measurement results of the two slipmeters under four floors, four footwear materials, and three surface conditions.
Super Logic Programs

Recent extensive research on non-monotonic reasoning and logic programming has clearly demonstrated that logic programs are sufficiently expressive to allow formalizations of many important problems in non-monotonic reasoning, as well as providing an important test bed for new such formalizations. However, standard logic programs suffer from some important limitations. Most importantly, they are unable to handle disjunctive information and they allow only one type of negation. Consequently, considerable interest and research effort has been recently given to the problem of finding a suitable extension of the logic programming paradigm. We argue that in order to demonstrate that a class of programs can be justifiably called an extension of logic programs one should be able to show that their syntax resembles the syntax of logic programs but it applies to a significantly broader class of programs and that their semantics constitutes an intuitively natural extension of the semantics of normal logic programs. Moreover, their semantics should be closely related to other well-established non-monotonic formalisms and there should exist a reasonably simple procedural mechanism allowing us to compute it. In this paper we propose a specific class of such logic programs which will be called super logic programs. We show that the class of super logic programs satisfies all of the above conditions, and, in addition, is sufficiently flexible to allow various application-dependent extensions and modifications. We also provide a brief description of a Prolog implementation of a query-answering interpreter for super programs.
Selected problems of snow accumulation on glaciers during long-term studies in north-western Spitsbergen, Svalbard

ABSTRACT The primary objective of this work is to present the essential conditions and characteristics of changes in the dynamics of snow accumulation on glaciers of the Kaffiøyra region, an area of Svalbard, located in north-western Spitsbergen. Most of the research consisted in direct field measurements carried out in 1997–2014. The glaciers of the Kaffiøyra region have a large spatial diversity of snow cover thickness, and distinct changeability with change of altitude. Snow cover on the glaciers of the Kaffiøyra region shows some specific physical properties. Numerous ice layers were also found, as results prove seasonal warming to above 0°C. The mean snow density was 380 kg m−3 on the Waldemarbreen, 363 kg m−3 on the Irenebreen and 405 kg m−3 on the Elisebreen. The mean annual winter balance of the Waldemarbreen for the years 1996–2014 was 0.50 m w.e. The mean snow accumulation on the Irenebreen from 2002 to 2014 was 0.55 m w.e. , and on the Elisebreen, the mean value amounted to 0.67 m w.e. in 2006–2009. In the case of the Waldemarbreen, a slight increase in snow accumulation has been noted since 1997, and from the beginning of the twenty-first century the increase has been even more pronounced for glaciers of the Kaffiøyra region. This is the result of more frequent warmer periods during the winter season, which favours higher snowfall. The investigations of glacier snow accumulation and its properties in the Kaffiøyra region are especially important, being some of only a few long-term data series for snow on Svalbard.
Bioactive Constituents of Zanthoxylum rhetsa Bark and Its Cytotoxic Potential against B16-F10 Melanoma Cancer and Normal Human Dermal Fibroblast (HDF) Cell Lines

Zanthoxylum rhetsa is an aromatic tree, known vernacularly as “Indian Prickly Ash”. It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.
The diverse dietary profiles of MIS 3 cave bears from the Romanian Carpathians: insights from stable isotope (δ13C and δ15N) analysis

Late Pleistocene European cave bears (Ursus spelaeus) have been considered to be largely vegetarian, although stable isotope data (δ13C and δ15N values) from the Romanian Carpathians has suggested considerable dietary variation. Here we evaluate previous and additional adult cave bear isotopic data from four Marine Isotope Stage 3 (MIS 3) sites in the Carpathians. Peştera Urşilor (N = 35), Peştera Cioclovina (N = 32), Peştera Muierilor (N = 8), and Peştera cu Oase (N = 72) provide both a dichotomy between samples suggesting vegetarian diets (from Cioclovina and Muierilor) and more omnivorous diets (from Urşilor and Oase), and considerable isotopic variation within samples from each site. While an inference of a strictly vegetarian diet may apply to groups that lived in ecosystems which restricted the available animal protein for these large ursids, the within and between sample isotopic variation among the Carpathian cave bears indicates considerable flexibility in their sources of protein and hence in their dietary regimes. In addition, developmental assessment of Cioclovina isotopic profiles (neonates, juveniles, sub‐adults and adults) provides patterns of transfer of stable isotope signatures throughout immature life for both δ13C and δ15N (increase and decrease, respectively), whereas those from Urşilor show little developmental shift.
Time trends in allergic disorders in the UK

Background: Allergic disorders are common in the UK. This study reviews recent UK time trends in the prevalence, morbidity and mortality for allergic disorders, excluding asthma. Methods: A trend analysis was performed over recent decades of national, representative or repeat surveys, primary care consultations, prescriptions, hospital admissions, and mortality. Results: Serial surveys showed that the prevalence of diagnosed allergic rhinitis and eczema in children have both trebled over the last three decades. While these long term trends were paralleled by the prevalence of disease symptoms, more recent symptom prevalence data suggest a decline. Similarly, GP consultation rates rose by 260% for hay fever and by 150% for eczema overall during the period 1971–91, but rates have stabilised over the past decade. Hospital admissions for eczema have been stable since 1995, and hospital admissions for allergic rhinitis have fallen to about 40% of their 1990 levels. Since 1990, admissions for anaphylaxis have increased by 700%, for food allergy by 500%, for urticaria by 100%, and for angio-oedema by 40%. Prescriptions issued for all types of allergy have increased since 1991. Conclusions: The prevalence and healthcare usage for eczema and hay fever have increased substantially over recent decades, but may now be stabilising or even falling. In contrast, admissions for some systemic allergic diseases have risen sharply in the last decade which may indicate a rising incidence of these conditions. Although changes in treatment and other healthcare factors may have contributed to these trends, there may also be a change in the aetiology of allergic disease in the UK.
Amoeba A Distributed Operating System for the 1990 s Sape

n the nexi decdde, computer prices will drop 50 low that IO, 20, or persystem developed at the Free University and the Centre for Mathematics and ComT 1 haps IO0 powerful microprocessors per user will be feasible. All this computing power will have to be organized in a simple, efficient, and fault-tolerant system that is easy to use. The basic problem with current networks of PCs and workstations is that they are not transparent; that is, users are aware of the other machines. The user logs into one machine and uses that machine only, until doing a remote login to another machine. Few if any programs take advantage of multiple CPUs, even when all are idle. We envision a system for the 1990s that will appear to users as a single, 1970s centralized time-sharing system. Users will not know which processors their jobs are using (or even how many), where their files are stored (or how many replicated copies are maintained to provide high availability), or how processes and machines are communicating. All resources will be managed completely and automatically by a distributed operating system. Few such systems have been designed, The Amoeba distributed operating system appears to users as a centralized system, but it has the speed, fault tolerance, security safeguards, and flexibility required for the 1990s.
Expression of Fibroblast Growth Factor-21 in Muscle Is Associated with Lipodystrophy, Insulin Resistance and Lipid Disturbances in Patients with HIV

Background Fibroblast growth factor (FGF)-21 is a novel regulator of glucose and lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well understood. Patients with HIV-infection and lipodystrophy are characterised by various degree of lipid-driven insulin resistance. We hypothesized that muscle FGF-21 mRNA would be altered in HIV patients with lipodystrophy. Design Twenty-five HIV-infected men with lipodystrophy (LD) and 15 age-matched healthy controls, received an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp (50 mU/m2/min) combined with 6,6-H2 glucose infusion. Muscle biopsies were obtained and FGF-21 mRNA and glycogen synthase (GS) activity were measured. Results Subjects with HIV were insulin resistant compared with non-HIV subjects. Compared to controls, HIV subjects demonstrated a twofold increase of plasma FGF-21 from 70.4±56.8 pg/ml vs 109.1±71.8 pg/ml, respectively (p = 0.04) and an eight-fold increase in muscular FGF-21 mRNA expression (p = 0.001). Muscle FGF-21 mRNA correlated inversely with the rate of disappearance of glucose during insulin clamp (r = −0.54, p = 0.0009), and the GS fractional velocity in muscle (r = −0.39, p = 0.03), and directly with fasting insulin (r = 0.50, p = 0.0022), HOMA-IR (r = 0.47, p = 0.004), triglycerides (r = 0.60. P = 0.0001), waist-to-hip ratio (r = 0.51, p = 0.0001) and limb fat mass (−0.46, p = 0.004), but not to plasma FGF-21. Conclusion FGF-21 mRNA is increased in skeletal muscle in HIV patients and correlates to whole-body (primarily reflecting muscle) insulin resistance, but not to plasma FGF-21. Those findings add to the evidence that FGF-21 is a myokine and may suggest that muscle FGF-21 is working in a local manner.
Identification of innate immunity elicitors using molecular signatures of natural selection

The innate immune system is an ancient and broad-spectrum defense system found in all eukaryotes. The detection of microbial elicitors results in the up-regulation of defense-related genes and the elicitation of inflammatory and apoptotic responses. These innate immune responses are the front-line barrier against disease because they collectively suppress the growth of the vast majority of invading microbes. Despite their critical role, we know remarkably little about the diversity of immune elicitors. To address this paucity, we reasoned that hosts are more likely to evolve recognition to “core” pathogen proteins under strong negative selection for the maintenance of essential cellular functions, whereas repeated exposure to host–defense responses will impose strong positive selective pressure for elicitor diversification to avoid host recognition. Therefore, we hypothesized that novel bacterial elicitors can be identified through these opposing forces of natural selection. We tested this hypothesis by examining the genomes of six bacterial phytopathogens and identifying 56 candidate elicitors that have an excess of positively selected residues in a background of strong negative selection. We show that these positively selected residues are atypically clustered, similar to patterns seen in the few well-characterized elicitors. We then validated selected candidate elicitors by showing that they induce Arabidopsis thaliana innate immunity in functional (virulence suppression) and cellular (callose deposition) assays. These finding provide targets for the study of host–pathogen interactions and applied research into alternative antimicrobial treatments.
Water in soybean oil microemulsions as medium for electrochemical measurements

Microemulsions of water in soybean oil (w/o ME) were prepared with sodium dodecyl sulfate (SDS) as surfactant and amyl or isoamyl alcohol, as co-surfactants. Microemulsions containing 40.0% oil, 43.2% alcohol, 10.8% SDS and 6.0% water in weight, in the ratio 1:4 [SDS]:[alcohol] showed the highest thermodynamic stability. The aqueous droplet size and its diffusion coefficient Dw/o in the ME were determined through dynamic light scattering (DLS). Voltammetric measurements in the ME at a Pt disk ultramicroelectrode (ume) evidenced the oxidation of both water and ferrocene (Fc), and the reduction of oleic acid. The Dw/o values calculated from the limiting current being lower than the ones obtained from DLS indicate that water oxidation probably requires diffusion towards the electrode of both the droplets and the water molecules from inside the droplets. The results show that electroanalytical determinations can be carried out in w/o ME.
Identification of MicroRNAs Involved in Resistance to Sunitinib in Renal Cell Carcinoma Cells.

AIM To generate sunitinib-resistant renal cell carcinoma (RCC) cell lines and identify miRNAs contributing to sunitinib resistance. MATERIALS AND METHODS Two RCC cell lines, ACHN and RCC23, were cultured by continuous treatment with sunitinib for 3 months, with doses gradually increasing up to the 50% inhibitory concentration for each cell line. We performed microarray and quantitative real-time polymerase chain reaction analyses of sunitinib-resistant ACHN (SR-ACHN) and RCC23 (SR-RCC23) cells, as well of as sunitinib-sensitive ACHN and RCC23 cells. RESULTS SR-ACHN and SR-RCC23 cells exhibited significantly higher resistance to sunitinib treatment compared to sunitinib-sensitive cells. SR-ACHN and SR-RCC23 cells were hypertrophic and contained granules in the cytoplasm. When SR-ACHN and SR-RCC23 cells were compared to ACHN and RCC23 cells, expression of miR-575, miR-642b-3p, and miR-4430 was significantly increased, while that of miR-18a-5p, miR-29b-1-5p, miR-431-3p, and miR-4521 was significantly decreased. CONCLUSION These miRNAs may contribute to sunitinib resistance in humans.