Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of the Pheroid delivery system on the in vitro metabolism and in vivo pharmacokinetics of artemisone

Objectives: The objectives were to determine the pharmacokinetics (PK) of artemisone and artemisone formulated in the Pheroid® drug delivery system in primates and to establish whether the formulation affects the in vitro metabolism of artemisone in human and monkey liver and intestinal microsomes. Methods: For the PK study, a single oral dose of artemisone was administered to vervet monkeys using a crossover design. Plasma samples were analyzed by means of liquid chromatography-tandem mass spectrometry. For the in vitro metabolism study, clearance was determined using microsomes and recombinant CYP3A4 enzymes, and samples were analyzed by means of ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Results: Artemisone and M1 plasma levels were unexpectedly low compared to those previously recorded in rodents and humans. The in vitro intrinsic clearance (CLint) of the reference formulation with monkey liver microsomes was much higher (1359.33 ± 103.24 vs 178.86 ± 23.42) than that of human liver microsomes. The in vitro data suggest that microsomal metabolism of artemisone is inhibited by the Pheroid delivery system. Conclusions: The in vivo results obtained in this study indicate that the Pheroid delivery system improves the PK profile of artemisone. The in vitro results indicate that microsomal metabolism of artemisone is inhibited by the Pheroid delivery system.
Dynamical, biological and anthropic consequences of equal lunar and solar angular radii

The nearly equal lunar and solar angular sizes as subtended at the Earth is generally regarded as a coincidence. This is, however, an incidental consequence of the tidal forces from these bodies being comparable. Comparable magnitudes implies strong temporal modulation, as the forcing frequencies are nearly but not precisely equal. We suggest that on the basis of palaeogeographic reconstructions, in the Devonian period, when the first tetrapods appeared on land, a large tidal range would accompany these modulated tides. This would have been conducive to the formation of a network of isolated tidal pools, lending support to A. S. Romer's classic idea that the evaporation of shallow pools was an evolutionary impetus for the development of chiridian limbs in aquatic tetrapodomorphs. Romer saw this as the reason for the existence of limbs, but strong selection pressure for terrestrial navigation would have been present even if the limbs were aquatic in origin. Since even a modest difference in the Moon's angular size relative to the Sun's would lead to a qualitatively different tidal modulation, the fact that we live on a planet with a Sun and Moon of close apparent size is not entirely coincidental: it may have an anthropic basis.
Role of the Streptococcus mutans gtf genes in caries induction in the specific-pathogen-free rat model

The role of each of the Streptococcus mutans gtf genes coding for glucan synthesis in cariogenesis was evaluated by using strain UA130 in the specific-pathogen-free (SPF) rat model system. Mutants defective in either or both of the genes required for insoluble glucan synthesis, the gtfB and gtfC genes, exhibited markedly reduced levels of smooth-surface carious lesions relative to that of the parental organism. Likewise, the mutant defective in the gtfD gene coding for the glucosyltransferase-S enzyme synthesizing water-soluble glucans also produced significantly fewer smooth-surface lesions than strain UA130. None of these mutations markedly altered the rate of sulcal caries induction relative to that of the parental organism. In addition, a mutant of strain UA130 defective in the gtfA gene was reexamined in the SPF rat model. In contrast to previous results from a gnotobiotic rat system, these mutants also induced significantly fewer smooth-surface carious lesions compared with that by strain UA130. These results suggest that all four genes are important for smooth-surface caries formation. Furthermore, these results are discussed relative to the differences in the diets utilized in the SPF and gnotobiotic rat model systems for assessing the virulence factors of S. mutans.
Speciation of OH reactivity above the canopy of an isoprene-dominated forest

Abstract. Measurements of OH reactivity, the inverse lifetime of the OH radical, can provide a top–down estimate of the total amount of reactive carbon in an air mass. Using a comprehensive measurement suite, we examine the measured and modeled OH reactivity above an isoprene-dominated forest in the southeast United States during the 2013 Southern Oxidant and Aerosol Study (SOAS) field campaign. Measured and modeled species account for the vast majority of average daytime reactivity (80–95 %) and a smaller portion of nighttime and early morning reactivity (68–80 %). The largest contribution to total reactivity consistently comes from primary biogenic emissions, with isoprene contributing ∼ 60 % in the afternoon, and ∼ 30–40 % at night and monoterpenes contributing ∼ 15–25 % at night. By comparing total reactivity to the reactivity stemming from isoprene alone, we find that ∼ 20 % of the discrepancy is temporally related to isoprene reactivity, and an additional constant ∼ 1 s−1 offset accounts for the remaining portion. The model typically overestimates measured OVOC concentrations, indicating that unmeasured oxidation products are unlikely to influence measured OH reactivity. Instead, we suggest that unmeasured primary emissions may influence the OH reactivity at this site.
Effects of growth hormone therapy on the developmental changes of follicle stimulating hormone and insulin‐like growth factor‐I serum concentrations in Turner's syndrome

OBJECTIVE The aim was to investigate whether, in the absence of gonads, GH could bring forward the age of neuroendocrine activation resulting in onset of puberty. DESIGN In girls with Turner's syndrome, we evaluated the effects of GH therapy on developmental changes in FSH serum concentrations used as an indicator of neuroendocrine maturation in the absence of gonads.
Klenow polymerase is preferable to T4 polymerase in end-labeling reactions.

For radioactive labeling or timming the 3' ends of linear dsDNA, the Klenow fragment of E. coli DNA-polymerase I or T4 DNA polymerase, which has a stronger 3'-5' exonucleolytic activity, are used (1). In order to find optimal conditions that ensure exclusive end-labeling of the adenovirus 5 (adS) DNA for footprinting purposes, we performed an analysis of the labeling reaction of the flush ends of adS DNA (indicated below) with the two polymerases: and labeled at the 3' ends by replacement of the terminal guanosine deoxynucleotide by a-32P-dGTP, as indicated in the legend of Fig. 1. The DNA was checked for unique end-labeling by digestion with HindI, which cleaves at a distance of 2.8 and 1.0 kb from the left and right ends, respectively 2). When two, three or four non-radioactive dNTPs are supplied in addition, the Klenow polymerase incorporates the a-32P-dGTP into the adS DNA and nuclear DNA, present in traces, in a time-dependent manner. However, is 2, becomes progressively non-selective, apparently because the nucleotides allow 'snapback' polymerization at internal strand-nicks despite the low incubation temperature.
Coosa: A Chiefdom in the Sixteenth-Century Southeastern United States

Abstract Sixteenth-century Spanish explorers regarded Coosa as one of the most important chiefdoms in the southeastern United States. Using both documentary and archaeological evidence, we have located the main town of Coosa and several tributary towns, as well as some of the frontiers of the chiefdom. The locations of these towns and frontiers are supported by the archaeological recovery of sixteenth-century European artifacts in the postulated area of the chiefdom.
An accurate and adaptable photogrammetric approach for estimating the mass and body condition of pinnipeds using an unmanned aerial system

Measurements of body size and mass are fundamental to pinniped population management and research. Manual measurements tend to be accurate but are invasive and logistically challenging to obtain. Ground-based photogrammetric techniques are less invasive, but inherent limitations make them impractical for many field applications. The recent proliferation of unmanned aerial systems (UAS) in wildlife monitoring has provided a promising new platform for the photogrammetry of free-ranging pinnipeds. Leopard seals (Hydrurga leptonyx) are an apex predator in coastal Antarctica whose body condition could be a valuable indicator of ecosystem health. We aerially surveyed leopard seals of known body size and mass to test the precision and accuracy of photogrammetry from a small UAS. Flights were conducted in January and February of 2013 and 2014 and 50 photogrammetric samples were obtained from 15 unrestrained seals. UAS-derived measurements of standard length were accurate to within 2.01 ± 1.06%, and paired comparisons with ground measurements were statistically indistinguishable. An allometric linear mixed effects model predicted leopard seal mass within 19.40 kg (4.4% error for a 440 kg seal). Photogrammetric measurements from a single, vertical image obtained using UAS provide a noninvasive approach for estimating the mass and body condition of pinnipeds that may be widely applicable.
Maternal Education, Home Environments and the Development of Children and Adolescents

We study the intergenerational effects of maternal education on children's cognitive achievement, behavioural problems, grade repetition and obesity. We address endogeneity of maternal schooling by instrumenting with variation in schooling costs when the mother grew up. Using matched data from the female participants of the National Longitudinal Survey of Youth 1979 (NLSY79) and their children, we can control for mother's ability and family background factors. Our results show substantial intergenerational returns to education. For children aged 7-8, for example, our IV results indicate that an additional year of mother's schooling increases the child's performance on a standardized math test by almost 0.1 of a standard deviation, and reduces the incidence of behavioural problems. Our data set allows us to study a large array of channels, which may transmit the effect of maternal education to the child, including family environment and parental investments at different ages of the child. We find that income effects, delayed childbearing, and assortative mating are likely to be important, and we show that maternal education leads to substantial differences in maternal labour supply. We investigate heterogeneity in returns, and we present results focusing both on very early stages in the child's life as well as adolescent outcomes. We present a falsification exercise to support the validity of our instruments, and our results are found to be robust in a sensitivity analysis. We discuss policy implications and relate our findings to intergenerational mobility.
Insulin Induces Suppressor of Cytokine Signaling-3 Tyrosine Phosphorylation through Janus-activated Kinase*

Suppressor of cytokine signaling (SOCS) proteins were originally described as cytokine-induced molecules involved in negative feedback loops. We have shown that SOCS-3 is also a component of the insulin signaling network (1). Indeed, insulin leads to SOCS-3 expression in 3T3-L1 adipocytes. Once produced, SOCS-3 binds to phosphorylated tyrosine 960 of the insulin receptor and inhibits insulin signaling. Now we show that in 3T3-L1 adipocytes and in transfected COS-7 cells insulin leads to SOCS-3 tyrosine phosphorylation. This phosphorylation takes place on Tyr204 and is dependent upon a functional SOCS-3 SH2 domain. Purified insulin receptor directly phosphorylates SOCS-3. However, in intact cells, a mutant of the insulin receptor, IRY960F, unable to bind SOCS-3, was as efficient as the wild type insulin receptor to phosphorylate SOCS-3. Importantly, IRY960F is as potent as the wild type insulin receptor to activate janus-activated kinase (Jak) 1 and Jak2. Furthermore, expression of a dominant negative form of Jak2 inhibits insulin-induced SOCS-3 tyrosine phosphorylation. As transfected Jaks have been shown to cause SOCS-3 phosphorylation, we propose that insulin induces SOCS-3 phosphorylation through Jak activation. Our data indicate that SOCS-3 belongs to a class of tyrosine-phosphorylated insulin signaling molecules, the phosphorylation of which is not dependent upon a direct coupling with the insulin receptor but relies on the Jaks.
Low power mapping optimization of loops for dual-Vdd CGRAs

Coarse Grained Reconfigurable Architecture (CGRA) is a promising platform based on its high performance and low power. Efficient compilers have been developed for improving loop mapping performance using modulo scheduling, and the Dual-Vdd technique is popularly used to reduce power consumption in CGRAs. To achieve the best mapping performance and lowest power consumption simultaneously, this paper formulates a joint optimization problem of performance and power efficiency of CGRAs and proposes a low power optimization approach integrating Dual-Vdd assignment into the loop pipelining mapping. The experimental results show that the proposed optimization approach could reduce the power by 22.5% on average without decreasing performance.
Mutations can cause light chains to be too stable or too unstable to form amyloid fibrils

Light chain (AL) amyloidosis is an incurable human disease, where the amyloid precursor is a misfolding‐prone immunoglobulin light‐chain. Here, we identify the role of somatic mutations in the structure, stability and in vitro fibril formation for an amyloidogenic AL‐12 protein by restoring four nonconservative mutations to their germline (wild‐type) sequence. The single restorative mutations do not affect significantly the native structure, the unfolding pathway, and the reversibility of the protein. However, certain mutations either decrease (H32Y and H70D) or increase (R65S and Q96Y) the protein thermal stability. Interestingly, the most and the least stable mutants, Q96Y and H32Y, do not form amyloid fibrils under physiological conditions. Thus, Q96 and H32 are key residues for AL‐12 stability and fibril formation and restoring them to the wild‐type residues preclude amyloid formation. The mutants whose equilibrium is shifted to either the native or unfolded states barely sample transient partially folded states, and therefore do not form fibrils. These results agree with previous observations by our laboratory and others that amyloid formation occurs because of the sampling of partially folded states found within the unfolding transition (Blancas‐Mejia and Ramirez‐Alvarado, Ann Rev Biochem 2013;82:745–774). Here we provide a new insight on the AL amyloidosis mechanism by demonstrating that AL‐12 does not follow the established thermodynamic hypothesis of amyloid formation. In this hypothesis, thermodynamically unstable proteins are more prone to amyloid formation. Here we show that within a thermal stability range, the most stable protein in this study is the most amyloidogenic protein.
Measuring neural efficiency of program comprehension

Most modern software programs cannot be understood in their entirety by a single programmer. Instead, programmers must rely on a set of cognitive processes that aid in seeking, filtering, and shaping relevant information for a given programming task. Several theories have been proposed to explain these processes, such as ``beacons,' for locating relevant code, and ``plans,'' for encoding cognitive models. However, these theories are decades old and lack validation with modern cognitive-neuroscience methods. In this paper, we report on a study using functional magnetic resonance imaging (fMRI) with 11 participants who performed program comprehension tasks. We manipulated experimental conditions related to beacons and layout to isolate specific cognitive processes related to bottom-up comprehension and comprehension based on semantic cues. We found evidence of semantic chunking during bottom-up comprehension and lower activation of brain areas during comprehension based on semantic cues, confirming that beacons ease comprehension.
Spatio-temporal data mining for maritime situational awareness

Maritime Situational Awareness (MSA) is the capability of understanding events, circumstances and activities within and impacting the maritime environment. Nowadays, the vessel positioning sensors provide a vast amount of data that could enhance the maritime knowledge if analysed and modelled. Vessel positioning data is dynamic and continuous on time and space, requiring spatio-temporal data mining techniques to derive knowledge. In this paper, several spatio-temporal data mining techniques are proposed to enhance the MSA, tackling existing challenges such as automatic maritime route extraction and synthetic representation, mapping vessels activities, anomaly detection or position and track prediction. The aim is to provide a more complete and interactive Maritime Situational Picture (MSP) and, hence, to provide more capabilities to operational authorities and policy-makers to support the decision-making process. The proposed approaches are evaluated on diverse areas of interest from the Dover Strait to the Icelandic coast.
Dental guards: An alternative solution for loose tooth

1. Liu D, Görges M, Jenkins SA. University of Queensland vital signs dataset: Development of an accessible repository of anesthesia patient monitoring data for research. Anesth Analg 2012;114:584-9. 2. Kennedy RR, French RA. The development of a system to guide volatile anaesthetic administration. Anaesth Intensive Care 2011;39:182-90. 3. van Schalkwyk JM, Lowes D, Frampton C, Merry AF. Does manual anaesthetic record capture remove clinically important data? Br J Anaesth 2011;107:546-52. 4. Peterfreund RA, Driscoll WD, Walsh JL, Subramanian A, Anupama S, Weaver M, et al. Evaluation of a mandatory quality assurance data capture in anesthesia: A secure electronic system to capture quality assurance information linked to an automated anesthesia record. Anesth Analg 2011;112:1218-25.
Energy based collision avoidance at the MAC layer for wireless sensor network

A Wireless Sensor Network (WSN) is a network of thousands of low-cost sensors which have a limited operating lifetime. A sensor node generally comprises four basic elements, including a transceiver unit, a detection unit, a processing unit, and an energy supply unit. One of the major challenges in the WSN is to increase the network life-time. Since the transmitting/receiving unit has the highest energy consumption, reducing it increases the network life-time significantly. In this work, we propose to differentiate resources or services in order to provide high performances of Quality of Service (QoS) to the prioritized node, since the Medium Access Control (MAC) layer is considered as the responsible that manages the access to the transmission channel. Therefore, we need to manage the quality of service of this layer in order to give high chance to nodes with a lower energy level to get access to the tranmission channel to send the data before their batteries run out. In this article, we present a new technique called Energy based Collision Avoidance (ECA-MAC), that handles WSN energy constraints and the QoS designed for versatile applications. ECA-MAC protocol aims at controlling the access to the medium according to nodes energy level and at reducing the collision using different Contention Windows (CW). Our simulation results show that ECA-MAC protocol improves the QoS in terms of Packet Delivery Ratio (PDR), message latency, and energy consumption.
Sensitivity of arabinosyladenine-resistant mutants of herpes simplex virus to other antiviral drugs and mapping of drug hypersensitivity mutations to the DNA polymerase locus

Seven herpes simplex virus mutants which have been previously shown to be resistant to arabinosyladenine were examined for their sensitivities to four types of antiviral drugs. These drugs were a pyrophosphate analog, four nucleoside analogs altered in their sugar moieties, two nucleoside analogs altered in their base moieties, and one altered in both. The seven mutants exhibited five distinct phenotypes based on their sensitivities to the drugs relative to wild-type strain KOS. All mutants exhibited resistance to acyclovir and arabinosylthymine, as well as marginal resistance to iododeoxyuridine, whereas all but one exhibited resistance to phosphonoformic acid. The mutants exhibited either sensitivity or hypersensitivity to other drugs tested--2'-nor-deoxyguanosine, 5-methyl-2'-fluoroarauracil, 5-iodo-2'-fluoroarauracil, and bromovinyldeoxyuridine--some of which differed only slightly from drugs to which the mutants were resistant. These results suggest ways to detect and treat arabinosyladenine-resistant isolates in the clinic. Antiviral hypersensitivity was a common phenotype. Mutations conferring hypersensitivity to 2'-nor-deoxyguanosine in mutant PAAr5 and to bromovinyldeoxyridine in mutant tsD9 were mapped to nonoverlapping regions of 1.1 and 0.8 kilobase pairs, respectively, within the herpes simplex virus DNA polymerase locus. Thus, viral DNA polymerase mediates sensitivity to these two drugs. However, we could not confirm reports of mutations in the DNA polymerase locus conferring resistance to these two drugs. All of the mutants exhibited altered sensitivity to two or more types of drugs, suggesting that single mutations affect recognition of the base, sugar, and triphosphate moieties of nucleoside triphosphates by viral polymerase.
Methods for user‐centered design and evaluation of text analysis tools in a digital history project

This paper reports on the user centered, formative evaluation of tools and the validation of models for the analysis of historical textbooks in the context of the digital history project Children and their World. The goal of the project is to create methods for computer‐supported, interactive analysis that can be applied to a large corpus of historical textbooks on history and geography (∼5000 volumes). A first version of a tool for text analysis has been created based on a user centered design process, including a contextual study on current work practices of historians, participative design workshops, and the prioritization of requirements with the project stakeholders. In addition, several generations of text models used in these tools have been iteratively evaluated by the historians in the project. In the context of a cooperative validation study, researchers have used these tools to examine existing hypotheses from the field. The method enables the validation of text models regarding established knowledge, provides additional insights into the requirements for tools and visualizations, and helps to strengthen the expert users' trust in the tools. Based on the findings, this paper proposes four principles for the analysis of a corpus of historical texts. Moreover, the methods presented are discussed regarding the application of user centered design in the context of digital humanities projects.