Miracle-dz/UniFAR-FTUs huggingface dataset:
Pixantrone induces cell death through mitotic perturbations and subsequent aberrant cell divisions

Pixantrone is a novel aza-anthracenedione active against aggressive lymphoma and is being evaluated for use against various hematologic and solid tumors. The drug is an analog of mitoxantrone, but displays less cardiotoxicity than mitoxantrone or the more commonly used doxorubicin. Although pixantrone is purported to inhibit topoisomerase II activity and intercalate with DNA, exact mechanisms of how it induces cell death remain obscure. Here we evaluated the effect of pixantrone on a panel of solid tumor cell lines to understand its mechanism of cell killing. Initial experiments with pixantrone showed an apparent discrepancy between its anti-proliferative effects in MTS assays (short-term) compared with clonogenic assays (long-term). Using live cell videomicroscopy to track the fates of cells, we found that cells treated with pixantrone underwent multiple rounds of aberrant cell division before eventually dying after approximately 5 d post-treatment. Cells underwent abnormal mitosis in which chromosome segregation was impaired, generating chromatin bridges between cells or within cells containing micronuclei. While pixantrone-treated cells did not display γH2AX foci, a marker of DNA damage, in the main nuclei, such foci were often detected in the micronuclei. Using DNA content analysis, we found that pixantrone concentrations that induced cell death in a clonogenic assay did not impede cell cycle progression, further supporting the lack of canonical DNA damage signaling. These findings suggest pixantrone induces a latent type of DNA damage that impairs the fidelity of mitosis, without triggering DNA damage response or mitotic checkpoint activation, but is lethal after successive rounds of aberrant division.
Dual-Polarized Quasi Yagi–Uda Antennas With Endfire Radiation for Millimeter-Wave MIMO Terminals

This paper presents a novel design of compact dual-polarized multi-input and multi-output (MIMO) antennas with endfire radiation for millimeter-wave wireless applications. The low-cost printed circuit board process serves as the basis for the design, fabrication, and measurement of the proposed dual-polarized quasi Yagi–Uda antennas. Addressing the potential antenna locations in a mobile terminal, this paper investigates both the corner and the lateral design of antenna modules. Each design incorporates dual-port dual-polarized antennas co-located in a compact area. The lateral design is further extended to a linear $1 \times 4$ array for high-gain and phased-scanning operation. Experimental results show that the proposed compact dual-polarized quasi Yagi–Uda antennas are very suitable for MIM terminals of next-generation (5G) mobile communications.
Bond Risk Premia, Macroeconomic Fundamentals and the Exchange Rate

We introduce a two-country no-arbitrage term-structure model to analyse the joint dynamics of bond yields, macroeconomic variables and the exchange rate. The model allows to understand how exogenous shocks to the exchange rate affect the yield curves, how bond yields co-move in different countries and how the exchange rate is influenced by the interactions between macroeconomic variables and time-varying bond risk premia. Estimating the model with US and German data, we obtain an excellent fit of the yield curves and we are able to account for up to 75 per cent of the variability of the exchange rate. We find that time-varying risk premia play a non-negligible role in exchange rate fluctuations, due to the fact that a currency tends to appreciate when risk premia on long-term bonds denominated in that currency rise. A number of other novel empirical findings emerge.
EDTA dependent pseudothrombocytopenia caused by antibodies against the cytoadhesive receptor of platelet gpIIB-IIIA.

AIMS--To clarify the mechanisms involved in the development of EDTA dependent pseudothrombocytopenia, particularly the platelet receptors. METHODS--Platelets were measured in 33 patients with pseudothrombocytopenia, using different anticoagulants to collect blood samples (direct test). The results were compared with the counts obtained by adding patients' serum or immunoglobulins to normal blood samples (indirect test). The role of platelet function was explored using ASA, PGE1, and apyrase as platelet inhibitors. The contribution of platelet receptor/s was investigated using antigens to gpIb-IX and gpIIb-IIIa monoclonal antibodies. Immunoglobulin class was estimated by the ability of IgG, IgA, and IgM antibodies to prevent platelet clumping. RESULTS--Agglutinating antibodies were IgA in 40%, IgG in 30%, and IgM in 10% of patients studied. Both patients' serum and immunoglobulins induced platelet clumping in normal samples anticoagulated with EDTA (indirect test). This was prevented by incubation of blood samples at 37 degrees C and almost completely inhibited by the platelet inhibitors ASA, PGE1, and apyrase. Pseudothrombocytopenia was also entirely prevented by an antigen to gpIIb-IIIa monoclonal antibody that recognises fibrinogen and the von Willebrand factor binding site. Pseudothrombocytopenia was almost completely abolished after the addition of RGD peptide, the recognition sequence of cytoadhesive proteins. CONCLUSIONS--These findings suggest that EDTA dependent pseudothrombocytopenia is caused by agglutinating antibodies that recognise cytoadhesive receptors on platelet gpIIb-IIIa and that an efficient platelet metabolism is required.
BldG and SCO3548 Interact Antagonistically To Control Key Developmental Processes in Streptomyces coelicolor

ABSTRACT The similarity of BldG and the downstream coexpressed protein SCO3548 to anti-anti-sigma and anti-sigma factors, respectively, together with the phenotype of a bldG mutant, suggests that BldG and SCO3548 interact as part of a regulatory system to control both antibiotic production and morphological differentiation in Streptomyces coelicolor. A combination of bacterial two-hybrid, affinity purification, and far-Western analyses demonstrated that there was self-interaction of both BldG and SCO3548, as well as a direct interaction between the two proteins. Furthermore, a genetic complementation experiment demonstrated that SCO3548 antagonizes the function of BldG, similar to other anti-anti-sigma/anti-sigma factor pairs. It is therefore proposed that BldG and SCO3548 form a partner-switching pair that regulates the function of one or more sigma factors in S. coelicolor. The conservation of bldG and sco3548 in other streptomycetes demonstrates that this system is likely a key regulatory switch controlling developmental processes throughout the genus Streptomyces.
Comparing Residents’ and Tourists’ Emotional Solidarity with One Another

This study is the first of its kind to examine residents’ and tourists’ degree of emotional solidarity experienced with one another in a destination—Galveston County, Texas. Two main purposes for this study are (1) to confirm the factor structure of the emotional solidarity scale for both residents and tourists while assessing psychometric properties of reliability and validity and (2) to compare residents’ and tourists’ emotional solidarity (based on resulting factors from confirmatory factor analysis) with one another. Ultimately, the scale produced the same factors (i.e., welcoming nature, emotional closeness, and sympathetic understanding) as in previous studies while exhibiting sound psychometric properties. Significant differences in mean factor scores were found for the factors welcoming nature and emotional closeness across residents and tourists. Implications, limitations, and future research directions are provided.
Integrated Genomic, Transcriptomic, and RNA-Interference Analysis of Genes in Somatic Copy Number Gains in Pancreatic Ductal Adenocarcinoma

Objectives This study used an integrated analysis of copy number, gene expression, and RNA interference screens for identification of putative driver genes harbored in somatic copy number gains in pancreatic ductal adenocarcinoma (PDAC). Methods Somatic copy number gain data on 60 PDAC genomes were extracted from public data sets to identify genomic loci that are recurrently gained. Array-based data from a panel of 29 human PDAC cell lines were used to quantify associations between copy number and gene expression for the set of genes found in somatic copy number gains. The most highly correlated genes were assessed in a compendium of pooled short hairpin RNA screens on 27 of the same human PDAC cell lines. Results A catalog of 710 protein-coding and 46 RNA genes mapping to 20 recurrently gained genomic loci were identified. The gene set was further refined through stringent integration of copy number, gene expression, and RNA interference screening data to uncover 34 candidate driver genes. Conclusions Among the candidate genes from the integrative analysis, ECT2 was found to have significantly higher essentiality in specific PDAC cell lines with genomic gains at the 3q26.3 locus, which harbors this gene, suggesting that ECT2 may play an oncogenic role in the PDAC neoplastic process.
A functional MRI study of happy and sad affective states induced by classical music

The present study investigated the functional neuroanatomy of transient mood changes in response to Western classical music. In a pilot experiment, 53 healthy volunteers (mean age: 32.0; SD = 9.6) evaluated their emotional responses to 60 classical musical pieces using a visual analogue scale (VAS) ranging from 0 (sad) through 50 (neutral) to 100 (happy). Twenty pieces were found to accurately induce the intended emotional states with good reliability, consisting of 5 happy, 5 sad, and 10 emotionally unevocative, neutral musical pieces. In a subsequent functional magnetic resonance imaging (fMRI) study, the blood oxygenation level dependent (BOLD) signal contrast was measured in response to the mood state induced by each musical stimulus in a separate group of 16 healthy participants (mean age: 29.5; SD = 5.5). Mood state ratings during scanning were made by a VAS, which confirmed the emotional valence of the selected stimuli. Increased BOLD signal contrast during presentation of happy music was found in the ventral and dorsal striatum, anterior cingulate, parahippocampal gyrus, and auditory association areas. With sad music, increased BOLD signal responses were noted in the hippocampus/amygdala and auditory association areas. Presentation of neutral music was associated with increased BOLD signal responses in the insula and auditory association areas. Our findings suggest that an emotion processing network in response to music integrates the ventral and dorsal striatum, areas involved in reward experience and movement; the anterior cingulate, which is important for targeting attention; and medial temporal areas, traditionally found in the appraisal and processing of emotions. Hum Brain Mapp 2007. © 2006 Wiley‐Liss, Inc.
Marine snow microbial communities: scaling of abundances with aggregate size

Marine aggregates are inhibited by diverse microbial communities, and the concentration of attached microbes typically exceeds concentrations in the ambient water by orders of magnitude. An extension of the classical Lotka-Volterra model, which includes 3 trophic levels (bacteria, flagellates, ciliates) and considers colonization, detachment, growth and predator-prey interactions on the surface of the particle, was used to examine the processes that govern abundances of attached micro-organisms. Effects of sinking on colonization rates as well as the spacial nature of natural aggregates were also taken into account. As input for the model, I used experimentally determined encounter and detachment rates, and density-dependent growth and grazing rates, as well as information on relevant properties of natural aggregates, all taken from the literature. The model reproduces the temporal development of attached populations of bacteria, flagellates, and ciliates, as observed in experimental systems, and also predicts steady-stale abundances of attached microorganisms that are close to those observed on field-collected aggregates. The model suggests that attached bacterial populations are controlled by flagellate grazing, while flagellate and ciliate populations are governed by colonization and detachment. The model also suggests that microbial populations are turned over rapidly (1 to 20 times d -1 ) due to continued colonization and detachment. The model overpredicts somewhat the scaling of microbial abundances with aggregate size observed in field-collected aggregates. This may be because it disregards the aggregation/disaggregation dynamics of aggregates, as well as interspecific interactions between bacteria.
Two Kinds of Metonymy

We propose a distinction between two kinds of metonymy: "referential" metonymy, in which the referent of an NP is shifted, and "predicative" metonymy, in which the referent of the NP is unchanged and the argument place of the predicate is shifted instead. Examples are, respectively, "The hamburger is waiting for his check" and "Which airlines fly from Boston to Denver". We also show that complications arise for both types of metonymy when multiple coercing predicates are considered. Finally, we present implemented algorithms handling these complexities that generate both types of metonymic reading, as well as criteria for choosing one type of metonymic reading over another.
An approach for modeling the name lookup problem in the C++ programming lanaguage

Formal grammars are well established for specifying the syntax of programming languages. However, the formal specification of programming language semantics has proven more elusive. A recent standard, the Unified Modeling Language (UML), has quickly become established as a common framework for the specification of large scale software applications. In this paper, we describe an approach for using the UML to solve the name lookup problem for the recently standardized C++ programming language. We apply our approach to C++ because a solution to the name lookup problem is required for parser construction and the development of analysis and testing tools.
Probing the Geometry of the Inner Vestibule of BK Channels with Sugars

The geometry of the inner vestibule of BK channels was probed by examining the effects of different sugars in the intracellular solution on single-channel current amplitude (unitary current). Glycerol, glucose, and sucrose decreased unitary current through BK channels in a concentration- and size-dependent manner, in the order sucrose > glucose > glycerol, with outward currents being reduced more than inward currents. The fractional decrease of outward current was more directly related to the fractional hydrodynamic volume occupied by the sugars than to changes in osmolality. For concentrations of sugars ≤1 M, the i/V plots for outward currents in the presence and absence of sugar superimposed after scaling, and increasing K+ i from 150 mM to 2 M increased the magnitudes of the i/V plots with little effect on the shape of the scaled curves. These observations suggest that sugars ≤1 M reduce outward currents mainly by entering the inner vestibule and reducing the movement of K+ through the vestibule, rather than by limiting diffusion-controlled access of K+ to the vestibule. With 2 M sucrose, the movement of K+ into the inner vestibule became diffusion limited for 150 mM K+ i and voltages >+100 mV. Increasing K+ i then relieved the diffusion limitation. An estimate of the capture radius based on the 5 pA diffusion-limited current for channels without the ring of negative charge at the entrance to the inner vestibule was 2.2 Å. Adding the radius of a hydrated K+ (6–8 Å) then gave an effective radius for the entrance to the inner vestibule of 8–10 Å. Such a functionally wide entrance to the inner vestibule together with our observation that even small concentrations of sugar in the inner vestibule reduce unitary current suggest that a wide inner vestibule is required for the large conductance of BK channels.
Symbolic computation in Java: an appraisement

Java, first developed as a programming interface for web browsers, is being pushed by a consortium of companies as a high level programming language for general programming. Sun Microsystems provides, in addition to a compiler into byte code for an interpreter (the Java virtual machine), a multitude of libraries, most notably an object hierarchy for building graphical user interfaces: the Abstract Windowing Toolkit and the Swing components from the Java Foundation Classes. Internet browsers contain Java virtual machines for interpreting byte code of Java programs that are embedded into Internet documents as applets. Java defines a standard framework for multi-threaded execution and for message passing via serialization and socket/datagram protocols. Java assists component composition in two ways. Java objects can discover how to invoke other Java objects at run-time through a process called reflection. Java also supports programming conventions (collectively referred to as “Java Beans”) for event-driven inter-component operation. The two together allow tools such as Java Studio [26] to provide convenient visual programming methods of connecting up Java software components. In short, Java is being vigorously developed and we ask the natural question whether Java is suited for symbolic computation and whether our discipline should take advantage of the plethora of freely available software. This article discusses Java as a symbolic computation development tool, expanding on the pioneering efforts of other researchers [39, 9]. We investigate if Java can compete with C++, or Maple/Mathematica/Axiom for efficient
On the modelling of transient scattering under ultra wideband short-pulse electromagnetic excitation

Accurate modelling of electromagnetic radiation, scattering and propagation using ultra wideband (UWB) sources has been of significant interest with ongoing application in areas such as short-range communications, through-the-wall imaging, ground-penetrating radar and medical imaging etc. Numerical modelling of these applications is vital to the evaluation and enhancement of their performance In this paper, a review of different methods for numerical modelling of the transient electromagnetic response under UWB short-pulse excitation is undertaken. The advantages, limitations and challenges of both direct and indirect time domain methods are described in detail and numerical examples of transient scattering demonstrate the use of an indirect time domain method.
Multiple Mitochondrial Introgression Events and Heteroplasmy in Trypanosoma cruzi Revealed by Maxicircle MLST and Next Generation Sequencing

Background Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution. In Trypanosoma cruzi, the causative agent of Chagas disease, the mitochondrial genome has a unique structural organization consisting of 20–50 maxicircles (∼20 kb) and thousands of minicircles (0.5–10 kb). T. cruzi is an early diverging protist displaying remarkable genetic heterogeneity and is recognized as a complex of six discrete typing units (DTUs). The majority of infected humans are asymptomatic for life while 30–35% develop potentially fatal cardiac and/or digestive syndromes. However, the relationship between specific clinical outcomes and T. cruzi genotype remains elusive. The availability of whole genome sequences has driven advances in high resolution genotyping techniques and re-invigorated interest in exploring the diversity present within the various DTUs. Methodology/Principal Findings To describe intra-DTU diversity, we developed a highly resolutive maxicircle multilocus sequence typing (mtMLST) scheme based on ten gene fragments. A panel of 32 TcI isolates was genotyped using the mtMLST scheme, GPI, mini-exon and 25 microsatellite loci. Comparison of nuclear and mitochondrial data revealed clearly incongruent phylogenetic histories among different geographical populations as well as major DTUs. In parallel, we exploited read depth data, generated by Illumina sequencing of the maxicircle genome from the TcI reference strain Sylvio X10/1, to provide the first evidence of mitochondrial heteroplasmy (heterogeneous mitochondrial genomes in an individual cell) in T. cruzi. Conclusions/Significance mtMLST provides a powerful approach to genotyping at the sub-DTU level. This strategy will facilitate attempts to resolve phenotypic variation in T. cruzi and to address epidemiologically important hypotheses in conjunction with intensive spatio-temporal sampling. The observations of both general and specific incidences of nuclear-mitochondrial phylogenetic incongruence indicate that genetic recombination is geographically widespread and continues to influence the natural population structure of TcI, a conclusion which challenges the traditional paradigm of clonality in T. cruzi.
Depoliticisation, Resilience and the Herceptin Post-Code Lottery Crisis: Holding Back the Tide

Research Highlights and Abstract This article: Covers new empirical terrain in the study of depoliticisation, with an in-depth case study of health technology regulation; Analyses depoliticisation from a novel analytical perspective, examining how depoliticised institutions are resilient to external pressure for politicisation; Posits a distinctive framework for analysing resilience, drawing on cognate literatures on policy networks and agencification; Raises interesting and distinctive questions about the nature of depoliticisation in advanced liberal democracies, arguing it is more contested than commonly acknowledged. Depoliticisation as a concept offers distinctive insights into how governments attempt to relieve political pressures in liberal democracies. Analysis has examined the effects of depoliticisation tactics on the public, but not how those tactics are sustained during moments of political tension. Drawing on policy networks and agencification literatures, this article examines how these tactics are resilient against pressure for politicisation. Using an in-depth case study of the controversial appraisal of cancer drug Herceptin in 2005/6 by the National Institute for Health and Clinical Excellence (NICE), the article examines how ‘resilient’ NICE was to external politicisation. It is argued that NICE was resilient because it was effectively ‘insulated’ by formal procedures and informal norms of deference to scientific expertise. This mechanism is termed ‘institutional double glazing’. The conclusion suggests developments to the conceptual and methodological framework of depoliticisation, and highlights theoretical insights into the nature of ‘anti-politics’ in contemporary democracies.