Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific changes in the synthesis of mitochondrial DNA in chick embryo fibroblasts transformed by Rous sarcoma viruses

In chick-embryo fibroblasts infected with the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup A (wild type), or with a thermosensitive mutant of this virus, T5, the rates of mitochondrial DNA synthesis differ in cells that exhibit normal and malignant phenotypes. In wild type virus-infected cells grown at 36 or 41 degrees C, morphological transformation is expressed, the rate of 2-deoxy-D-[3H]glucose uptake is stimulated, and mitochondrial DNA synthesis in vivo is stimulated three- to fivefold over that in uninfected cells. In T5-infected cells these changes occur only at the permissive temperature (36 degrees C); a shift to the nonpermissive temperature (41 degrees C) causes the reversal of these effects, and the specific activity of purified mitochondrial DNA is characteristic of that from uninfected cells. In contrast, the specific activities of nuclear DNA purified from cells maximally transformed under the permissive conditions do not differ between wild type-infected and uninfected with the T5 virus. In parallel experiments with isolated mitochondria, the rate of mtDNA synthesis in vitro is again greater in mitochondria isolated from transformed cells. In addition, mitochondrial DNA synthesis in vitro in mitochondria from nontransformed and virus-transformed cells exhibits differential sensitivity to inhibition by mercaptoethanol. Furthermore, the ntDNAP polymerase activity in mitochondrial extracts prepared from cells with transformed phenotypes is about sevenfold higher than in extracts from cells with nontransformed phenotypes.
Estimating Software System Reliability: An Architecture-Based Approach

To ensure high reliability for large and complex software systems, fault tolerance mechanisms have been widely used in the system design processes. However, less attention has been paid to the analysis of the system reliability improvement concerning fault tolerance. Therefore, they might underestimate the system reliability. To remedy this, we extend architecture based reliability estimation to take account of failure recovery mechanisms. This has two elements. Firstly, from the view of correctness of components' I/O, we give an analytical model for the architecture-centric system to detailly illustrate the invocation among components. Second we leverage Discrete-Time Markov Chain (DTMC) to calculate the system reliability according to the analytical model. The results help to locate the crucial components that need to be combined with robust fault tolerance mechanisms to improve the system reliability efficiently. Case study shows how our approach can produce an accurate estimation of system reliability.
Spherical Layout Implementation using Centroidal Voronoi Tessellations

The 3D tree visualization faces multiple challenges: the election of an appropriate layout, the use of the interactions that make the data exploration easier and a metaphor that helps in the process of information understanding. A good combination of these elements will result in a visualization that effectively conveys the key features of a complex structure or system to a wide range of users and permits the analytical reasoning process. In previous works we presented the Spherical Layout, a technique for 3D tree visualization that provides an excellent base to achieve those key features. The layout was implemented using the TriSphere algorithm, a method that discretized the spheres's surfaces with triangles to achieve a uniform distribution of the nodes. The goal of this work was centered in a new algorithm for the implementation of the Spherical layout; we called it the Weighted Spherical Centroidal Voronoi Tessellations (WSCVT). In this paper we present a detailed description of this new implementation and a comparison with the TriSphere algorithm.
Hydrogen-bonding and packing features of membrane proteins: functional implications.

The recent structural elucidation of about one dozen channels (in which we include transporters) has provided further evidence that these membrane proteins typically undergo large movements during their function. However, it is still not well understood how these proteins achieve the necessary trade-off between stability and mobility. To identify specific structural properties of channels, we compared the helix-packing and hydrogen-bonding patterns of channels with those of membrane coils; the latter is a class of membrane proteins whose structures are expected to be more rigid. We describe in detail how in channels, helix pairs are usually arranged in packing motifs with large crossing angles (|tau| approximately 40 degrees ), where the (small) side chains point away from the packing core and the backbones of the two helices are in close contact. We found that this contributes to a significant enrichment of Calpha-H.O bonds and to a packing geometry where right-handed parallel (tau = -40 degrees +/- 10 degrees ) and antiparallel (tau = +140 degrees +/- 25 degrees ) arrangements are equally preferred. By sharp contrast, the interdigitation and hydrogen bonding of side chains in helix pairs of membrane coils results in narrowly distributed left-handed antiparallel arrangements with crossing angles tau = -160 degrees +/- 10 degrees (|tau| approximately 20 degrees ). In addition, we show that these different helix-packing modes of the two types of membrane proteins correspond to specific hydrogen-bonding patterns. In particular, in channels, three times as many of the hydrogen-bonded helix pairs are found in parallel right-handed motifs than are non-hydrogen-bonded helix pairs. Finally, we discuss how the presence of weak hydrogen bonds, water-containing cavities, and right-handed crossing angles may facilitate the required conformational flexibility between helix pairs of channels while maintaining sufficient structural stability.
Inducible nitric oxide synthase activity contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites

Background: Overexpression of inducible nitric oxide synthase (iNOS) and increased nitric oxide generation may be associated with the hyperdynamic circulation of patients with cirrhosis. We have, for the first time, used the highly selective iNOS inhibitor, 1400W, to determine whether iNOS activity contributes to the regulation of vascular tone in patients with cirrhosis and ascites. Methods: Bilateral forearm blood flow was measured using strain gauge plethysmography in eight patients with cirrhosis and ascites, and eight matched healthy volunteers during intrabrachial infusion of 1400W (0.1–1 μmol/min), NG-monomethyl-L-arginine (L-NMMA, a non-selective NOS inhibitor; 2–8 μmol), and norepinephrine (a control vasoconstrictor; 60–480 pmol/min). Results: In patients with cirrhosis, 1400W, L-NMMA, and norepinephrine caused dose dependent reductions in forearm blood flow: peak reductions of 11 (5)%, 37 (4)%, and 48 (5)%, respectively (p<0.05 for all). In contrast, 1400W had no effect on blood flow (+4 (8)%; NS) in healthy controls despite similar reductions in blood flow with L-NMMA and norepinephrine (39 (5)% and 49 (5)%, respectively; p<0.05 for both). Conclusions: We have, for the first time, demonstrated that 1400W causes peripheral vasoconstriction in patients with cirrhosis but not healthy matched controls. This suggests that iNOS contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites, and may contribute towards the hyperdynamic circulation associated with this condition.
Understanding HCI Education across Asia-Pacific

The emergence of Internet of Things, social media, mobile, ubiquitous, and wearable computing has brought human-computer interaction (HCI) body of knowledge to the fore and has rooted it as an established field of teaching and research. Due to its unique and diverse characteristics, there is a lack of awareness and understanding on the importance of HCI education. The unique characteristics, interdisciplinary nature and rapid evolution of HCI bring not only challenges but also innovations in teaching and designing HCI curriculum in this region. In this paper, we present the key findings from our first attempt to bring together HCI educators in Asia-Pacific and sharing the experiences and challenges in HCI Education.
Biotransformation of insulin glargine after subcutaneous injection in healthy subjects

Summary Objective: It is important to establish pharmacokinetic or pharmacodynamic differences between novel insulin analogues and human insulin. This study examined the primary metabolic degradation products of insulin glargine (LANTUS*) in humans. Design: In this single dose, open-label study, insulin glargine was administered subcutaneously at a dose of 0.6IU/kg; placebo was administered to one control subject. Patients: Four healthy male subjects, plus one control subject, aged 18–50 years were enrolled in this study. Measurements: Following insulin glargine administration, blood glucose levels were clamped at the subjects' fasting concentration for 6 h and the amount of 20% glucose infused to maintain this baseline concentration was recorded. Metabolite profiling was performed in plasma and injection site tissue using HPLC and radioimmunoassay (RIA). Pharmacokinetics were evaluated by RIA of serum and plasma immunoreactive insulin levels. The primary pharmacodynamic measure was the glucose infusion rate (GIR). Safety was evaluated by measuring blood glucose concentrations during the clamp and adverse events were observed by the investigator or reported by the subject. Results: Metabolic profiling revealed a clear pattern: insulin glargine is metabolised by sequential cleavage at the carboxy terminus of the B chain, to yield products M1 and M2, which are both structurally similar to human insulin. These degradation products are present both at the injection site and in plasma. Conclusion: Thus, during treatment with a subcutaneous injection of insulin glargine, metabolic degradation is likely to be initiated at the injection site and continued within the circulatory system.
Processing capacity limits are not explained by storage limits

Cowan's review shows that a short-term memory limit of four items is consistent with a wide range of phenomena in the field. However, he does not explain that limit, whereas an existing theory does offer an explanation for capacity limitations. Furthermore, processing capacity limits cannot be reduced to storage limits as Cowan claims.
Associations Between Incident Ischemic Stroke Events and Stroke and Cardiovascular Disease-Related Genome-Wide Association Studies Single Nucleotide Polymorphisms in the Population Architecture Using Genomics and Epidemiology Study

Background— Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored. Methods and Results— Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were associated with increased IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS. Conclusions— Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation.
Korean Students' Perceptions of Scientific Practices and Understanding of Nature of Science

Korean students have shown relatively little interest and confidence in learning science, despite being ranked in the top percentile in international evaluations of academic achievement in science such as the Trends in International Mathematics and Science Study. Although research indicates a positive relationship between student perceptions of science and their science learning, this area has not been sufficiently explored in Korea. Particularly, even though both students' perceptions of scientific practice and their understanding of the nature of science (NOS) are influenced by their science learning experiences at schools, little research examines how this perception, understanding, and experience are related to one another. This study aimed to uncover Korean students' perceptions of school scientific practice through exploring their drawings, writings, and responses to questionnaires. Participants were 500 Korean students in 3rd, 7th, and 10th grades who were asked to complete an open-ended questionnaire. The results indicated that Korean students typically viewed school scientific practices as experimental activities or listening to lecture; and that most participants held an insufficient understanding of the NOS. Overall, no significant relationship emerged between students' perceptions of school scientific practice and their understanding of the NOS. Our findings highlight the need to help both teachers and students understand the potential breadth of school scientific practices, beyond simple ‘activity mania. ’ This study also suggests that teachers must balance implicit and explicit instructional approaches to teaching about the NOS through scientific practices in school science contexts.
Right Dorsolateral Prefrontal Cortical Activity and Behavioral Inhibition

Individuals show marked variation in their responses to threat. Such individual differences in behavioral inhibition play a profound role in mental and physical well-being. Behavioral inhibition is thought to reflect variation in the sensitivity of a distributed neural system responsible for generating anxiety and organizing defensive responses to threat and punishment. Although progress has been made in identifying the key constituents of this behavioral inhibition system in humans, the involvement of dorsolateral prefrontal cortex (DLPFC) remains unclear. Here, we acquired self-reported Behavioral Inhibition System Sensitivity scores and high-resolution electroencephalography from a large sample (n = 51). Using the enhanced spatial resolution afforded by source modeling techniques, we show that individuals with greater tonic (resting) activity in right-posterior DLPFC rate themselves as more behaviorally inhibited. This observation provides novel support for recent conceptualizations of behavioral inhibition and clues to the mechanisms that might underlie variation in threat-induced negative affect.
Understanding Public Service Systems: Is There a Role for Complex Adaptive Systems Theory?

In spite of the introduction of a range of reforms generally referred to as “new public management” (NPM; Hood, 1991; Osborne & Gaebler, 1992), the delivery of public services continues to pose problems at local, national, and EU levels in terms of cost, outcome, configuration, and governance. Europe as a whole and its individual member states grapple with these issues with mixed success (Dunsire et al., 1994; Mackintosh, 1998; Hood, 2000; Kay, 2002). It is worth noting that, after 15 years of “new” public management, OECD figures show that taxes and government outlays as a proportion of GDP in the EU were roughly the same in 2002 as they were in 1987, although net government debt soared to 49 percent from 37 percent over the same period.
How Giardia Swim and Divide

ABSTRACT To determine how binuclear giardia swim, we used video microscopy to observe trophozoites of Giardia intestinalis, which were labeled with an amino-specific Alexa Fluor dye that highlighted the flagella and adherence disc. Giardia swam forward by means of the synchronous beating of anterior, posterolateral, and ventral flagella in the plane of the ventral disc, while caudal flagella swam in a plane perpendicular to the disc. Giardia turned in the plane of the disc by means of a rudder-like motion of its tail, which was constant rather than beating. To determine how giardia divide, we used three-dimensional confocal microscopy, the same surface label, nuclear stains, and antitubulin antibodies. Giardia divided with mirror-image symmetry in the plane of the adherence disc, so that the right nucleus of the mother became the left nucleus of the daughter. Pairs of nuclei were tethered together by microtubules which surrounded nuclei and prevented mother or daughter giardia from receiving two copies of the same nucleus. New adherence discs formed upon a spiral backbone of microtubules, which had a clockwise rotation when viewed from the ventral surface. These dynamic observations of the parasite begin to reveal how giardia swim and divide.
Coupling Transmission and Energy Markets Reduces Market Power

Transmission constraints fragment electricity markets and enhance regional market power of electricity generators. In continental Europe rights to access transmission between countries are auctioned to traders, which arbitrage separate energy spot markets of these countries. In Scandinavia the system operator integrates these markets and simultaneously clears energy spot markets of several countries and decides on optimal energy transmission. In any unconstrained or partially constrained network, integration mitigates market power of strategic generators and avoids inefficient production decisions. A testable prediction for both effects is applied to the Dutch-German and Norway-Sweden interconnection and supports the theory. In meshed networks, integration also mitigates market power when constraints are permanently binding. Le Chatelier’s principle extends to electricity networks in the presence of market power. Demand is more responsive to price changes and aggregate output increases if markets are integrated.
Targeting the IL‐4/IL‐13 signaling pathway sensitizes Hodgkin lymphoma cells to chemotherapeutic drugs

Hodgkin/Reed‐Sternberg lymphoma (HL) is a clonal B‐cell‐related malignancy. Although many patients with HL can be cured by the current regimen of high‐dose multi‐agent chemotherapy, the treatment causes high risks of later pathologies including secondary malignancies. This fact highlights the demand to develop rational treatment for HL. Survival and growth of HL cells are largely dependent on their microenvironment. In this study, using the HL cell lines L1236 and KM‐H2 as model systems, we investigated the role of IL‐4/IL‐13 signaling in regulation of drug sensitivity and resistance in HL. We show that specific blocking of IL‐4 and IL‐13‐mediated STAT6 activation by either an IL‐4‐binding fusion protein APG598 or an IL‐4R antagonist APG201 (R121D/Y124D) renders HL cells more prone to apoptotic killing by chemotherapeutic drugs such as Mitomycin C, 5‐Fluorouracil, Etopside, Doxorubicin and Paclitaxel. This effect is due to inhibition of STAT6‐mediated elevation of expression of the anti‐apoptotic Bcl‐2 family protein Bcl‐xL. Employing ChIP analysis in combination with APG201 or STAT6‐specific siRNA we identified a defined STAT6‐binding site in the Bcl‐xL promoter region from −1967 to −1957 of the transcription start site. Our data demonstrate that the IL‐4/IL‐13‐STAT6‐Bcl‐xL axis may be an important target for HL treatment. This study also suggests that combination of classical chemotherapeutic drugs with the IL‐4/IL‐13 antagonists may enhance efficacy and reduce risks of toxicity from high dose of drugs in HL treatment.
Common aging pathways in worms, flies, mice and humans

SUMMARY Development of functional genomics tools has made it possible to define the aging process by performing genome-wide scans for transcriptional differences between the young and the old. Global screens for age regulation have been performed for worms and flies, as well as many tissues in mice and humans. Recent work has begun to analyze the similarities and differences in transcriptional changes in aging among different species. Most age-related expression changes are specific for a given species, but genes in one pathway (the electron transport chain pathway) show common age regulation in species from worms to humans. Evolutionary theories of aging provide a basis to understand how age regulation of a genetic pathway might be preserved between distantly related species.
Nicotinic Modulation of GABAA Receptor Function in Single Dopaminergic Neurons Freshly-Dissociated from Rat Substantia Nigra Pars Compacta

Previous studies have shown that nicotine modulates GABAergic transmission onto dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc) mainly via presynaptic mechanisms. However, nicotinic modulation of postsynaptic GABAA receptor function in SNc DAergic neurons is unknown. Employing patch-clamp recording technique in single putative DAergic neurons freshly dissociated from rat SNc, we found that functional α4β2-nAChRs were well expressed on majority (77%) of putative SNc DAergic neurons recorded (type ID neurons), while functional α7-nAChRs were only detected in 23% of recorded putative SNc DAergic neurons (type IID neurons). Smoking relevant concentration of nicotine reversibly increased the amplitude of GABAA receptor-mediated wholecell currents in 63% of type ID neurons expressing α4β2-nAChRs, but not in those type IID neurons expressing α7-nAChRs, which suggests that postsynaptic GABAA receptors on putative SNc DAergic neurons that contain nAChR α4β2 subunits are significantly modulated by nicotine. Interestingly, nicotine at concentrations from 1 nM to 10 μM produced concentration-independent enhancement effects on GABAA receptor-mediated currents. There was no significant influence of pretreatment with either DHβE (a selective α4β2-nAChR antagonist) or 500 nM nicotine over the nicotinic modulation. In addition, 500 nM nicotine did not affect glutamate or glycine-induced current under our experimental conditions. Collectively, our results suggest that nicotine directly boosts the function of postsynaptic GABAA receptors, which in turn results in hyperpolarization and reduced excitability of putative SNc DAergic neurons through novel α4β2-nAChR-dependent pathways and/or additional postsynaptic mechanisms.
Personalized affective music player

We introduce and test an affective music player (AMP) that selects music for mood enhancement. Through a concise overview of content, construct, and ecological validity, we elaborate five considerations that form the foundation of the AMP. Based on these considerations, computational models are developed, using regression and kernel density estimation. We show how these models can be used for music selection and how they can be extended to fit in other systems. Subsequently, the success of the models is illustrated with a user test. The AMP augments music listening, where its techniques, in general, enable automated affect guidance. Finally, we argue that our AMP is readily applicable to real-world situations as it can 1) cope with noisy situations, 2) handle the large inter-individual differences apparent in the musical domain, and 3) integrate context or other information, all in real-time.