Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of CPD Ultraviolet Lesion Bypass in Chicken DT40 Cells: Polymerase η and PCNA Ubiquitylation Play Identical Roles

Translesion synthesis (TLS) provides a mechanism of copying damaged templates during DNA replication. This potentially mutagenic process may operate either at the replication fork or at post-replicative gaps. We used the example of T-T cyclobutane pyrimidine dimer (CPD) bypass to determine the influence of polymerase recruitment via PCNA ubiquitylation versus the REV1 protein on the efficiency and mutagenic outcome of TLS. Using mutant chicken DT40 cell lines we show that, on this numerically most important UV lesion, defects in polymerase η or in PCNA ubiquitylation similarly result in the long-term failure of lesion bypass with persistent strand gaps opposite the lesion, and the elevation of mutations amongst successful TLS events. Our data suggest that PCNA ubiquitylation promotes CPD bypass mainly by recruiting polymerase η, resulting in the majority of CPD lesions bypassed in an error-free manner. In contrast, we find that polymerase ζ is responsible for the majority of CPD-dependent mutations, but has no essential function in the completion of bypass. These findings point to a hierarchy of access of the different TLS polymerases to the lesion, suggesting a temporal order of their recruitment. The similarity of REV1 and REV3 mutant phenotypes confirms that the involvement of polymerase ζ in TLS is largely determined by its recruitment to DNA by REV1. Our data demonstrate the influence of the TLS polymerase recruitment mechanism on the success and accuracy of bypass.
A Nuclear Family A DNA Polymerase from Entamoeba histolytica Bypasses Thymine Glycol

Background Eukaryotic family A DNA polymerases are involved in mitochondrial DNA replication or translesion DNA synthesis. Here, we present evidence that the sole family A DNA polymerase from the parasite protozoan E. histolytica (EhDNApolA) localizes to the nucleus and that its biochemical properties indicate that this DNA polymerase may be involved in translesion DNA synthesis. Methodology and Results EhDNApolA is the sole family A DNA polymerase in E. histolytica. An in silico analysis places family A DNA polymerases from the genus Entamoeba in a separate branch of a family A DNA polymerases phylogenetic tree. Biochemical studies of a purified recombinant EhDNApolA demonstrated that this polymerase is active in primer elongation, is poorly processive, displays moderate strand displacement, and does not contain 3′–5′ exonuclease or editing activity. Importantly, EhDNApolA bypasses thymine glycol lesions with high fidelity, and confocal microscopy demonstrates that this polymerase is translocated into the nucleus. These data suggest a putative role of EhDNApolA in translesion DNA synthesis in E. histolytica. Conclusion This is the first report of the biochemical characterization of a DNA polymerase from E. histolytica. EhDNApolA is a family A DNA polymerase that is grouped into a new subfamily of DNA polymerases with translesion DNA synthesis capabilities similar to DNA polymerases from subfamily ν.
The Sound Space as Musical Instrument: Playing Corpus-Based Concatenative Synthesis

Corpus-based concatenative synthesis is a fairly recent sound synthesis method, based on descriptor analysis of any number of existing or live-recorded sounds, and synthesis by selection of sound segments from the database matching given sound characteristics. It is well described in the literature, but has been rarely examined for its capacity as a new interface for musical expression. The interesting outcome of such an examination is that the actual instrument is the space of sound characteristics, through which the performer navigates with gestures captured by various input devices. We will take a look at different types of interaction modes and controllers (positional, inertial, audio analysis) and the gestures they afford, and provide a critical assessment of their musical and expressive capabilities, based on several years of musical experience, performing with the CataRT system for real-time CBCS.
Home Dampness and Molds, Parental Atopy, and Asthma in Childhood: A Six-Year Population-Based Cohort Study

Previous studies of how parental atopy and exposure to dampness and molds contribute to the risk of asthma have been mainly cross-sectional or prevalent case–control studies, where selection and information bias and temporality constitute problems. We assessed longitudinally the independent and joint effects of parental atopy and exposure to molds in dwellings on the development of asthma in childhood. We conducted a population-based, 6-year prospective cohort study of 1,984 children 1–7 years of age at the baseline in 1991 (follow-up rate, 77%). The study population included 1,916 children without asthma at baseline and complete outcome information. The data collection included a baseline and follow-up survey. The outcome of interest was development of asthma during the study period. The studied determinants were parental allergic diseases and four indicators of exposure at baseline: histories of water damage, presence of moisture and visible molds, and perceived mold odor in the home. A total of 138 (7.2%) children developed asthma during the study period, resulting in an incidence rate of 125 cases per 10,000 person-years [95% confidence interval (CI), 104–146]. In Poisson regression adjusting for confounding, parental atopy [adjusted incidence rate ratio (IRR) 1.52; 95% CI, 1.08–2.13] and the presence of mold odor in the home reported at baseline (adjusted IRR 2.44; 95% CI, 1.07–5.60) were independent determinants of asthma incidence, but no apparent interaction was observed. The results of this cohort study with assessment of exposure before the onset of asthma strengthen the evidence on the independent effects of parental atopy and exposure to molds on the development of asthma.
Electroacupuncture enhances hippocampal NSCs proliferation in cerebral ischemia-reperfusion injured rats via activation of notch signaling pathway

The purpose of this study was to investigate the mechanisms by which electroacupuncture (EA) enhances hippocampal neural stem cells (NSCs) proliferation in cerebral ischemia-reperfusion (I/R) injured rats. A total of 72 male adult Sprague-Dawley rats were randomly divided into the sham operation control group (SC), the ischemia control group (IC) and the EA group. Middle cerebral artery occlusion (MCAO) was performed to establish the focal cerebral I/R injury model. Proliferation of hippocampal NSCs in cerebral I/R injured rats was determined by the Nestin immunohistochemical staining. Activation of the notch signaling pathway was detected by Western blotting and reverse transcription polymerase chain reaction analysis. The serum level of neurotrophic factors, e.g., the brain-derived neurotrophic factor (BDNF) and the Glial cell line-derived neurotrophic factor (GDNF), was measured using enzyme-linked immunosorbent assay (ELISA). The results showed that EA at Quchi (LI11) and Zusanli (ST36) acupoints significantly alleviated neurological deficits, reduced infarct volumes and promoted the proliferation of hippocampal NSCs in cerebral I/R injured rats. The crucial signaling molecules in the notch signaling pathway were activated and the secretion of BDNF and GDNF was increased upon EA. The protein and mRNA levels of Cyclin D1, Cdk4 and p-Rb were increased, while p21 and p27 transcripts were suppressed by notch signaling. These results suggest that the up-regulatory effect of EA on the notch signaling pathway and neurotrophic factor secretion may result in the promotion of NSCs proliferation and consequently a therapeutic effect on cerebral ischemia.
Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum

Dictyostelium cells are forest soil amoebae, which feed on bacteria and proliferate as solitary cells until bacteria are consumed. Starvation triggers a change in life style, forcing cells to gather into aggregates to form multicellular organisms capable of cell differentiation and morphogenesis. As a soil amoeba and a phagocyte that grazes on bacteria as the obligate source of food, Dictyostelium could be a natural host of pathogenic bacteria. Indeed, many pathogens that occasionally infect humans are hosted for most of their time in protozoa or free-living amoebae, where evolution of their virulence traits occurs. Due to these features and its amenability to genetic manipulation, Dictyostelium has become a valuable model organism for studying strategies of both the host to resist infection and the pathogen to escape the defense mechanisms. Similarly to higher eukaryotes, iron homeostasis is crucial for Dictyostelium resistance to invasive bacteria. Iron is essential for Dictyostelium, as both iron deficiency or overload inhibit cell growth. The Dictyostelium genome shares with mammals many genes regulating iron homeostasis. Iron transporters of the Nramp (Slc11A) family are represented with two genes, encoding Nramp1 and Nramp2. Like the mammalian ortholog, Nramp1 is recruited to phagosomes and macropinosomes, whereas Nramp2 is a membrane protein of the contractile vacuole network, which regulates osmolarity. Nramp1 and Nramp2 localization in distinct compartments suggests that both proteins synergistically regulate iron homeostasis. Rather than by absorption via membrane transporters, iron is likely gained by degradation of ingested bacteria and efflux via Nramp1 from phagosomes to the cytosol. Nramp gene disruption increases Dictyostelium sensitivity to infection, enhancing intracellular growth of Legionella or Mycobacteria. Generation of mutants in other “iron genes” will help identify genes essential for iron homeostasis and resistance to pathogens.
NGC 300 X-1 and IC 10 X-1: a new breed of black hole binary?

Context. IC 10 X-1 has recently been confirmed as a black hole (BH) + Wolf-Rayet (WR) X-ray binary, and NGC 300 X-1 is thought to be. The only other known BH+WR candidate is Cygnus X-3. IC 10 X-1 and NGC 300 X-1 have similar X-ray properties, with 0.3–10 keV luminosities ∼10 38 erg s −1 , and their X-ray lightcurves exhibit orbital periods ∼30 h. Aims. We investigate similarities between IC 10 X-1 and NGC 300 X-1, as well as differences between these systems and the known Galactic BH binary systems. Methods. We have examined all four XMM-Newton observations of NGC 300 X-1, as well as the single XMM-Newton observation of IC 10 X-1. For each observation, we extracted lightcurves and spectra from the pn, MOS1 and MOS2 cameras; power density spectra were constructed from the lightcurves, and the X-ray emission spectra were modeled. Results. Each source exhibits power density spectra that are well described by a power law with index, γ, ∼1. Such variability is characteristic of turbulence in wind accretion or disc-accreting X-ray binaries (XBs) in the high state. In this state, Galactic XBs with known BH primaries have soft, thermal emission; however the emission spectra of NGC 300 X-1 and IC 10 X-1 in the XMM-Newton observations are predominantly non-thermal. Furthermore, the Observation 1 spectrum of NGC 300 X-1 is strikingly similar to that of IC 10 X-1. Conclusions. The remarkable similarity between the behaviour of NGC 300 X-1 in Observation 1 and that of IC 10 X-1 lends strong evidence for NGC 300 X-1 being a BH+WR binary. Our spectral modeling rules out Bondi-Hoyle accretion onto a neutron star (NS) for NGC 300 X-1, but not a disc-accreting NS+WR system, nor a NS low mass X-ray binary (LMXB) that is merely coincident with the WR. We favour disc accretion for both systems, but cannot exclude Bondi-Hoyle accretion onto a BH. The unusual spectra of NGC 300 X-1 and IC 10 X-1 may be due to these systems existing in a persistently high state, whereas all known BH LMXBs are transient. The violent transition from low state to high state may temporarily eject the disc corona from the BH LMXBs, drastically reducing the non-thermal component. However, BH XBs in a persistent high state could retain their corona, and hence exhibit a large non-thermal component. LMC X-1 is a BH XB that has only been observed in the high state, and its spectrum is remarkably similar to those of NGC 300 X-1 in Observation 1 and IC 10 X-1. We therefore classify NGC 300 X-1, IC 10 X-1 and perhaps LMC X-1 as a new breed of BH XB, defined by their persistently high accretion rates and consequent stable disc configuration and corona. This scenario may also explain the lack of ultraluminous X-ray sources in the canonical soft state.
Projective resolutions for graph products

Let Γ be a finite graph together with a group Gv at each vertex v. The graph productG(Γ) is obtained from the free product of all Gv by factoring out by the normal subgroup generated by for all adjacent v, w. In this note we construct a projective resolution for G(Γ) given projective resolutions for each Gv, and obtain some applications.
Indexing Boolean Expressions

We consider the problem of efficiently indexing Disjunctive Normal Form (DNF) and Conjunctive Normal Form (CNF) Boolean expressions over a high-dimensional multi-valued attribute space. The goal is to rapidly find the set of Boolean expressions that evaluate to true for a given assignment of values to attributes. A solution to this problem has applications in online advertising (where a Boolean expression represents an advertiser's user targeting requirements, and an assignment of values to attributes represents the characteristics of a user visiting an online page) and in general any publish/subscribe system (where a Boolean expression represents a subscription, and an assignment of values to attributes represents an event). All existing solutions that we are aware of can only index a specialized sub-set of conjunctive and/or disjunctive expressions, and cannot efficiently handle general DNF and CNF expressions (including NOTs) over multi-valued attributes. In this paper, we present a novel solution based on the inverted list data structure that enables us to index arbitrarily complex DNF and CNF Boolean expressions over multi-valued attributes. An interesting aspect of our solution is that, by virtue of leveraging inverted lists traditionally used for ranked information retrieval, we can efficiently return the top-N matching Boolean expressions. This capability enables emerging applications such as ranked publish/subscribe systems [16], where only the top subscriptions that match an event are desired. For example, in online advertising there is a limit on the number of advertisements that can be shown on a given page and only the "best" advertisements can be displayed. We have evaluated our proposed technique based on data from an online advertising application, and the results show a dramatic performance improvement over prior techniques.
Intrinsic TNF/TNFR2 Interactions Fine-Tune the CD8 T Cell Response to Respiratory Influenza Virus Infection in Mice

TNF is an important inflammatory mediator and a target for intervention. TNF is produced by many cell types and is involved in innate inflammation as well as adaptive immune responses. CD8 T cells produce TNF and can also respond to TNF. Deficiency of TNF or TNFR2 has been shown to affect anti-viral immunity. However, as the complete knockout of TNF or its receptors has effects on multiple cell types as well as on lymphoid architecture, it has been difficult to assess the role of TNF directly on T cells during viral infection. Here we have addressed this issue by analyzing the effect of CD8 T cell intrinsic TNF/TNFR2 interactions during respiratory influenza infection in mice, using an adoptive transfer model in which only the T cells lack TNF or TNFR2. During a mild influenza infection, the capacity of the responding CD8 T cells to produce TNF increases from day 6 through day 12, beyond the time of viral clearance. Although T cell intrinsic TNF is dispensable for initial expansion of CD8 T cells up to day 9 post infection, intrinsic TNF/TNFR2 interactions potentiate contraction of the CD8 T cell response in the lung between day 9 and 12 post infection. On the other hand, TNF or TNFR2-deficient CD8 T cells in the lung express lower levels of IFN-γ and CD107a per cell than their wild type counterparts. Comparison of TNF levels on the TNFR2 positive and negative T cells is consistent with TNF/TNFR2 interactions inducing feedback downregulation of TNF production by T cells, with greater effects in the lung compared to spleen. Thus CD8 T cell intrinsic TNF/TNFR2 interactions fine-tune the response to influenza virus in the lung by modestly enhancing effector functions, but at the same time potentiating the contraction of the CD8 T cell response post-viral clearance.
Dynamical Collapse of Nonrotating Magnetic Molecular Cloud Cores: Evolution through Point-Mass Formation

We present a numerical simulation of the dynamical collapse of a nonrotating, magnetic molecular cloud core and follow the core's evolution through the formation of a central point mass and its subsequent growth into a 1 M☉ protostar. The epoch of point-mass formation (PMF) is investigated by a self-consistent extension of previously presented models of core formation and contraction in axisymmetric, self-gravitating, isothermal, magnetically supported interstellar molecular clouds. Prior to PMF, the core is dynamically contracting and is not well approximated by a quasi-static equilibrium model. Ambipolar diffusion, which plays a key role in the early evolution of the core, is unimportant during the dynamical pre-PMF collapse phase. However, the appearance of a central mass, through its effect on the gravitational field in the inner core regions, leads to a "revitalization" of ambipolar diffusion in the weakly ionized gas surrounding the central protostar. This process is so efficient that it leads to a decoupling of the field from the matter and results in an outward-propagating hydromagnetic C-type shock. The existence of an ambipolar diffusion-mediated shock of this type was predicted by Li & McKee, and we find that the basic shock structure given by their analytic model is well reproduced by our more accurate numerical results. Our calculation also demonstrates that ambipolar diffusion, rather than Ohmic diffusivity operating in the innermost core region, is the main field-decoupling mechanism responsible for driving the shock after PMF. The passage of the shock leads to a substantial redistribution, by ambipolar diffusion but possibly also by magnetic interchange, of the mass contained within the magnetic flux tubes in the inner core. In particular, ambipolar diffusion reduces the flux initially threading a collapsing ~1 M☉ core by a factor ≳103 by the time this mass accumulates within the inner radius (≃7.3 AU) of our computational grid. This reduction, which occurs primarily during the post-PMF phase of the collapse, represents a significant step toward the resolution of the protostellar magnetic flux problem. Our calculations indicate that a 1 M☉ protostar forms in ~1.5 × 105 yr for typical cloud parameters. The mass-accretion rate is time dependent, in part because of the C-shock that decelerates the infalling matter as it propagates outward: the accretion rate rises to ≃9.4 M☉ Myr-1 early on and decreases to ≃5.6 M☉ Myr-1 by the time a solar-mass protostar is formed. The infalling gas disk surrounding the protostar has a mass ~10-2 M☉ at radii r ≳ 500 AU. A distinguishing prediction of our model is that the rapid ambipolar diffusion after the formation of a protostar should give rise to large (≳1 km s-1), and potentially measurable, ion-neutral drift speeds on scales r ≲ 200 AU. The main features of our simulation, including the C-shock formation after PMF, are captured by a similarity solution that incorporates the effects of ambipolar diffusion.
Is X-linked methyl-CpG binding protein 2 a new target for the treatment of Parkinson's disease

X-linked methyl-CpG binding protein 2 mutations can induce symptoms similar to those of Parkinson's disease and dopamine metabolism disorders, but the specific role of X-linked methyl-CpG binding protein 2 in the pathogenesis of Parkinson's disease remains unknown. In the present study, we used 6-hydroxydopamine-induced human neuroblastoma cell (SH-SY5Y cells) injury as a cell model of Parkinson's disease. The 6-hydroxydopamine (50 μmol/L) treatment decreased protein levels for both X-linked methyl-CpG binding protein 2 and tyrosine hydroxylase in these cells, and led to cell death. However, overexpression of X-linked methyl-CpG binding protein 2 was able to ameliorate the effects of 6-hydroxydopamine, it reduced 6-hydroxydopamine-induced apoptosis, and increased the levels of tyrosine hydroxylase in SH-SY5Y cells. These findings suggesting that X-linked methyl-CpG binding protein 2 may be a potential therapeutic target for the treatment of Parkinson's disease.
COMPLEXITY METRIC FOR ANALOGY BASED EFFORT ESTIMATION

The problem of cost estimation in software engineering has been addressed by several researchers. Research shows that among many factors that affect the development cost, size of the product plays an important role. In addition to the size, product properties like complexity, cohesion and coupling are also mentioned as cost factors. We focus on the relationship between complexity of a product to its development cost. The aim of this research is to identify the use of complexity metrics as important parameters in similarity matching for retrieval of cases in case based effort estimation. The objective is to estimate the development effort of student programs based on the values of certain attributes using case based reasoning model. We have developed a case based estimation model using complexity metrics and have validated it upon student data. Our focus is on object oriented programs.
Inverse-Compton Emission from the Lobes of 3C 353

X-ray emission due to inverse-Compton scattering of microwave background photons by electrons in the lobes of powerful radio galaxies has now been seen in a large number of objects. Combining an inverse-Compton model for the lobe X-ray emission with information obtained from radio synchrotron emission provides a method of constraining the electron population and magnetic field energy density, which cannot be ac complished using the radio data alone. Using six frequencies of new and archival radio data and new XMM-Newtonobservations of the Fanaroff & Riley class II radio galaxy 3C 353, we show that inverse-Compton emission is detected in the radio lobes of this source at a lev el consistent with what is seen in other objects. We argue that variations in the X-ray/radi o ratio in the brighter eastern lobe require positionally varying magnetic field strength. We al so examine the X-ray nucleus and the cluster, Zw 1819.1-0108, spatially and spectrally.
Transoral Laryngeal Surgery Using the CO2 Laser: Laboratory Experiments and Clinical Experience

Since the introduction of the CO2 laser coupled to the Zeiss operating microscope in 1969, it has become apparent that this instrument is without equal for the carefully controlled removal of small laryngeal lesions. It has now also been shown experimentally and with some clinical confirmation that by using the CO2 laser transorally all of the standard types of partial and excisional laryngeal surgery may be accomplished with minimal morbidity and without the use of tracheotomy. The major exception is that replacement of soft tissue is not possible. Therefore, procedures that remove sufficient amounts of soft tissue to compromise the sphincter function of the larynx should not be done transorally with the CO2 laser.