193 research outputs found
Quantifying the Structure of Misfolded Proteins Using Graph Theory
The structure of a protein molecule is highly correlated to its function. Some diseases such as cystic fibrosis are the result of a change in the structure of a protein so that this change interferes or inhibits its function. Often these changes in structure are caused by a misfolding of the protein molecule. To assist computational biologists, there is a database of proteins together with their misfolded versions, called decoys, that can be used to test the accuracy of protein structure prediction algorithms. In our work we use a nested graph model to quantify a selected set of proteins that have two single misfold decoys. The graph theoretic model used is a three tiered nested graph. Measures based on the vertex weights are calculated and we compare the quantification of the proteins with their decoys. Our method is able to separate the misfolded proteins from the correctly folded proteins
1964: Abilene Christian College Bible Lectures - Full Text
LEADERSHIP IN THE CHURCH”
Being the Abilene Christian College Annual Bible Lectures 1964
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ABILENE CHRISTIAN COLLEGE STUDENTS EXCHANGE
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Abilene, Texa
Radial distribution of stars, gas and dust in SINGS galaxies. I. Surface photometry and morphology
We present ultraviolet through far-infrared surface brightness profiles for
the 75 galaxies in the Spitzer Infrared Nearby Galaxies Survey (SINGS). The
imagery used to measure the profiles includes GALEX UV data, optical images
from KPNO, CTIO and SDSS, near-IR data from 2MASS, and mid- and far-infrared
images from Spitzer. Along with the radial profiles, we also provide
multi-wavelength asymptotic magnitudes and several non-parametric indicators of
galaxy morphology: the concentration index (C_42), the asymmetry (A), the Gini
coefficient (G) and the normalized second-order moment of the brightest 20% of
the galaxy's flux (M_20). Our radial profiles show a wide range of morphologies
and multiple components (bulges, exponential disks, inner and outer disk
truncations, etc.) that vary not only from galaxy to galaxy but also with
wavelength for a given object. In the optical and near-IR, the SINGS galaxies
occupy the same regions in the C_42-A-G-M_20 parameter space as other normal
galaxies in previous studies. However, they appear much less centrally
concentrated, more asymmetric and with larger values of G when viewed in the UV
(due to star-forming clumps scattered across the disk) and in the mid-IR (due
to the emission of Polycyclic Aromatic Hydrocarbons at 8.0 microns and very hot
dust at 24 microns).Comment: 66 pages in preprint format, 14 figures, published in ApJ. The
definitive publisher authenticated version is available online at
http://dx.doi.org/10.1088/0004-637X/703/2/156
Converting multilevel nonclassicality into genuine multipartite entanglement
Characterizing genuine quantum resources and determining operational rules for their manipulation are crucial steps to appraise possibilities and limitations of quantum technologies. Two such key resources are nonclassicality, manifested as quantum superposition between reference states of a single system, and entanglement, capturing quantum correlations among two or more subsystems. Here we present a general formalism for the conversion of nonclassicality into multipartite entanglement, showing that a faithful reversible transformation between the two resources is always possible within a precise resource-theoretic framework. Specializing to quantum coherence between the levels of a quantum system as an instance of nonclassicality, we introduce explicit protocols for such a mapping. We further show that the conversion relates multilevel coherence and multipartite entanglement not only qualitatively, but also quantitatively, restricting the amount of entanglement achievable in the process and in particular yielding an equality between the two resources when quantified by fidelity-based geometric measures
Functional Connectivity Analyses in Imaging Genetics: Considerations on Methods and Data Interpretation
Functional magnetic resonance imaging (fMRI) can be combined with genotype assessment to identify brain systems that mediate genetic vulnerability to mental disorders (“imaging genetics”). A data analysis approach that is widely applied is “functional connectivity”. In this approach, the temporal correlation between the fMRI signal from a pre-defined brain region (the so-called “seed point”) and other brain voxels is determined. In this technical note, we show how the choice of freely selectable data analysis parameters strongly influences the assessment of the genetic modulation of connectivity features. In our data analysis we exemplarily focus on three methodological parameters: (i) seed voxel selection, (ii) noise reduction algorithms, and (iii) use of additional second level covariates. Our results show that even small variations in the implementation of a functional connectivity analysis can have an impact on the connectivity pattern that is as strong as the potential modulation by genetic allele variants. Some effects of genetic variation can only be found for one specific implementation of the connectivity analysis. A reoccurring difficulty in the field of psychiatric genetics is the non-replication of initially promising findings, partly caused by the small effects of single genes. The replication of imaging genetic results is therefore crucial for the long-term assessment of genetic effects on neural connectivity parameters. For a meaningful comparison of imaging genetics studies however, it is therefore necessary to provide more details on specific methodological parameters (e.g., seed voxel distribution) and to give information how robust effects are across the choice of methodological parameters
Radial distribution of stars, gas and dust in SINGS galaxies. II. Derived dust properties
We present a detailed analysis of the radial distribution of dust properties
in the SINGS sample, performed on a set of UV, IR and HI surface brightness
profiles, combined with published molecular gas profiles and metallicity
gradients. The internal extinction, derived from the TIR-to-FUV luminosity
ratio, decreases with radius, and is larger in Sb-Sbc galaxies. The TIR-to-FUV
ratio correlates with the UV spectral slope beta, following a sequence shifted
to redder UV colors with respect to that of starbursts. The star formation
history (SFH) is identified as the main driver of this departure. We have also
derived radial profiles of the total dust mass surface density, the fraction of
the dust mass contributed by PAHs, the fraction of the dust mass heated by very
intense starlight and the intensity of the radiation field heating the grains.
The dust profiles are exponential, their radial scale-length being constant
from Sb to Sd galaxies (only ~10% larger than the stellar scale-length). Many
S0/a-Sab galaxies have central depressions in their dust radial distributions.
The PAH abundance increases with metallicity for 12+\log(O/H)<9, and at larger
metallicities the trend flattens and even reverses, with the SFH being a
plausible underlying driver for this behavior. The dust-to-gas ratio is also
well correlated with metallicity and therefore decreases with galactocentric
radius.Comment: 73 pages in preprint format, 21 figures, published in ApJ. The
definitive publisher authenticated version is available online at
http://dx.doi.org/10.1088/0004-637X/701/2/196
The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial
\ua9 2023, The Author(s).BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system–penetrant, type II RAF inhibitor tovorafenib (420 mg m−2 once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485
Mantle Pb paradoxes : the sulfide solution
Author Posting. © Springer, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 152 (2006): 295-308, doi:10.1007/s00410-006-0108-1.There is growing evidence that the budget of Pb in mantle peridotites is largely
contained in sulfide, and that Pb partitions strongly into sulfide relative to silicate melt. In
addition, there is evidence to suggest that diffusion rates of Pb in sulfide (solid or melt)
are very fast. Given the possibility that sulfide melt ‘wets’ sub-solidus mantle silicates,
and has very low viscosity, the implications for Pb behavior during mantle melting are
profound. There is only sparse experimental data relating to Pb partitioning between
sulfide and silicate, and no data on Pb diffusion rates in sulfides. A full understanding of
Pb behavior in sulfide may hold the key to several long-standing and important Pb
paradoxes and enigmas. The classical Pb isotope paradox arises from the fact that all
known mantle reservoirs lie to the right of the Geochron, with no consensus as to the
identity of the “balancing” reservoir. We propose that long-term segregation of sulfide
(containing Pb) to the core may resolve this paradox. Another Pb paradox arises from the fact that the Ce/Pb ratio of both OIB and MORB
is greater than bulk earth, and constant at a value of 25. The constancy of this “canonical
ratio” implies similar partition coefficients for Ce and Pb during magmatic processes
(Hofmann et al. 1986), whereas most experimental studies show that Pb is more
incompatible in silicates than Ce. Retention of Pb in residual mantle sulfide during
melting has the potential to bring the bulk partitioning of Ce into equality with Pb if the
sulfide melt/silicate melt partition coefficient for Pb has a value of ~ 14. Modeling shows
that the Ce/Pb (or Nd/Pb) of such melts will still accurately reflect that of the source, thus
enforcing the paradox that OIB and MORB mantles have markedly higher Ce/Pb (and
Nd/Pb) than the bulk silicate earth. This implies large deficiencies of Pb in the mantle
sources for these basalts. Sulfide may play other important roles during magmagenesis:
1). advective/diffusive sulfide networks may form potent metasomatic agents (in both
introducing and obliterating Pb isotopic heterogeneities in the mantle); 2). silicate melt
networks may easily exchange Pb with ambient mantle sulfides (by diffusion or
assimilation), thus ‘sampling’ Pb in isotopically heterogeneous mantle domains
differently from the silicate-controlled isotope tracer systems (Sr, Nd, Hf), with an
apparent ‘de-coupling’ of these systems.Our intemperance
should not be blamed on the support we gratefully acknowledge from NSF: EAR-
0125917 to SRH and OCE-0118198 to GAG
Genetic variants associated with longitudinal changes in brain structure across the lifespan
Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging
Національно-демократичні об'єднання та політичні партії в Україні кінця XIX - початку XX століття
Deep brain stimulation (DBS) has become increasingly important for the treatment and relief of neurological disorders such as Parkinson's disease, tremor, dystonia and psychiatric illness. As DBS implantations and any other stereotactic and functional surgical procedure require accurate, precise and safe targeting of the brain structure, the technical aids for preoperative planning, intervention and postoperative follow-up have become increasingly important. The aim of this paper was to give and overview, from a biomedical engineering perspective, of a typical implantation procedure and current supporting techniques. Furthermore, emerging technical aids not yet clinically established are presented. This includes the state-of-the-art of neuroimaging and navigation, patient-specific simulation of DBS electric field, optical methods for intracerebral guidance, movement pattern analysis, intraoperative data visualisation and trends related to new stimulation devices. As DBS surgery already today is an important technology intensive domain, an "intuitive visualisation" interface for improving management of these data in relation to surgery is suggested
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