Investigation of the DYRK1A Regulation by LZTS2-SIPA1L1 Complex

A region on chromosome 21, the Down Syndrome critical region (DSCR), is associated with major defects found in Down Syndrome, such as craniofacial malformations. DYRK1A is a gene found on chromosome 21 within the DSCR that encodes an enzyme, dual specificity tyrosine-phosphorylation-regulated kinase 1A. DYRK1A is known to phosphorylate many substrate proteins and is thought to be involved in tumor suppression, neurological development, cell cycle regulation, and aging. Recently, the Litovchick lab and others reported that DYRK1A also plays a role in the double-strand break repair of DNA, which could lead to mutations and tumorigenesis, if deregulated. The Litovchick lab is currently investigating novel interactions of DYRK1A, and their implications for cancer. One of these proteins, DCAF7, is already a well-known DYRK1A interacting partner. Another less characterized protein is LZTS2, also known as LAPSER1 or leucine-zipper tumor suppressor 2. LZTS2 is found to be deleted in many human tumors and is known to bind a signaling intermediate SIPA1L1.2 Our preliminary data show that LZTS2 may promote DYRK1A phosphorylation, thereby regulating DYRK1A kinase activity. We suspect that SIPA1L1 may be involved in this interaction and, as this complex is known to be involved in the WNT pathway that plays a role in both cancer and orofacial formation, To test this hypothesis, we started characterization of the DYRK1A-LZTS2 interaction using ectopic expressions of the full-length LZTS2 and DYRK1A as well as their fragments expressed in human T98G cells. We will further perform experiments investigating the physical binding and functional interactions between DCAF7, SIPA1L1, and the DYRK1A-LZTS2 complex.https://scholarscompass.vcu.edu/uresposters/1442/thumbnail.jp

Level-Based Analysis of Genetic Algorithms and Other Search Processes

The fitness-level technique is a simple and old way to derive upper bounds for the expected runtime of simple elitist evolutionary algorithms (EAs). Recently, the technique has been adapted to deduce the runtime of algorithms with non-elitist populations and unary variation operators [2,8]. In this paper, we show that the restriction to unary variation operators can be removed. This gives rise to a much more general analytical tool which is applicable to a wide range of search processes. As introductory examples, we provide simple runtime analyses of many variants of the Genetic Algorithm on well-known benchmark functions, such as OneMax, LeadingOnes, and the sorting problem

Direct-Acting Antiviral Hepatitis C Treatment Cascade and Barriers to Treatment Initiation among US Men and Women with and without HIV

Background: People with HIV are disproportionately coinfected with hepatitis C virus (HCV) and experience accelerated liver-related mortality. Direct-acting antivirals (DAAs) yield high sustained virologic response (SVR) rates, but uptake is suboptimal. This study characterizes the DAA-era HCV treatment cascade and barriers among US men and women with or at risk for HIV. Methods: We constructed HCV treatment cascades using the Women's Interagency HIV Study (women, 6 visits, 2015-2018, n=2447) and Multicenter AIDS Cohort Study (men, 1 visit, 2015-2018, n=2221). Cascades included treatment-eligible individuals (ie, HCV RNA-positive or reported DAAs). Surveys captured self-reported clinical (eg, CD4), patient (eg, missed visits), system (eg, appointment access), and financial/insurance barriers. Results: Of 323/92 (women/men) treatment eligible, most had HIV (77%/70%); 69%/63% were black. HIV-positive women were more likely to attain cascade outcomes than HIV-negative women (39% vs 23% initiated, 21% vs 12% SVR); similar discrepancies were noted for men. Black men and substance users were treated less often. Women initiating treatment (vs not) reported fewer patient barriers (14%/33%). Among men not treated, clinical barriers were prevalent (53%). Conclusions: HIV care may facilitate HCV treatment linkage and barrier navigation. HIV-negative individuals, black men, and substance users may need additional support. Clinical trials registration: NCT00000797 (Women's Interagency HIV Study); NCT00046280 (Multicenter AIDS Cohort Study)

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc

Pion, kaon, proton and anti-proton transverse momentum distributions from p+p and d+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

Identified mid-rapidity particle spectra of $\pi^{\pm}$, $K^{\pm}$, and $p(\bar{p})$ from 200 GeV p+p and d+Au collisions are reported. A time-of-flight detector based on multi-gap resistive plate chamber technology is used for particle identification. The particle-species dependence of the Cronin effect is observed to be significantly smaller than that at lower energies. The ratio of the nuclear modification factor ($R_{dAu}$) between protons $(p+\bar{p})$ and charged hadrons ($h$) in the transverse momentum range $1.2<{p_{T}}<3.0$ GeV/c is measured to be $1.19\pm0.05$(stat)$\pm0.03$(syst) in minimum-bias collisions and shows little centrality dependence. The yield ratio of $(p+\bar{p})/h$ in minimum-bias d+Au collisions is found to be a factor of 2 lower than that in Au+Au collisions, indicating that the Cronin effect alone is not enough to account for the relative baryon enhancement observed in heavy ion collisions at RHIC.Comment: 6 pages, 4 figures, 1 table. We extended the pion spectra from transverse momentum 1.8 GeV/c to 3. GeV/

Azimuthal anisotropy at RHIC: the first and fourth harmonics

We report the first observations of the first harmonic (directed flow, v_1), and the fourth harmonic (v_4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v_2) generated at RHIC. From the correlation of v_2 with v_1 it is determined that v_2 is positive, or {\it in-plane}. The integrated v_4 is about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8) harmonics upper limits on the magnitudes are reported.Comment: 6 pages with 3 figures, as accepted for Phys. Rev. Letters The data tables are at http://www.star.bnl.gov/central/publications/pubDetail.php?id=3

Current assessment of the Red Rectangle band problem

In this paper we discuss our insights into several key problems in the identification of the Red Rectangle Bands (RRBs). We have combined three independent sets of observations in order to try to define the constraints guiding the bands. We provide a summary of the general behavior of the bands and review the evidence for a molecular origin of the bands. The extent, composition, and possible absorption effects of the bands are discussed. Comparison spectra of the strongest band obtained at three different spectral resolutions suggests that an intrinsic line width of individual rotational lines can be deduced. Spectroscopic models of several relatively simple molecules were examined in order to investigate where the current data are weak. Suggestions are made for future studies to enhance our understanding of these enigmatic bands

A Quantum-mechanical Approach for Constrained Macromolecular Chains

Many approaches to three-dimensional constrained macromolecular chains at thermal equilibrium, at about room temperatures, are based upon constrained Classical Hamiltonian Dynamics (cCHDa). Quantum-mechanical approaches (QMa) have also been treated by different researchers for decades. QMa address a fundamental issue (constraints versus the uncertainty principle) and are versatile: they also yield classical descriptions (which may not coincide with those from cCHDa, although they may agree for certain relevant quantities). Open issues include whether QMa have enough practical consequences which differ from and/or improve those from cCHDa. We shall treat cCHDa briefly and deal with QMa, by outlining old approaches and focusing on recent ones.Comment: Expands review published in The European Physical Journal (Special Topics) Vol. 200, pp. 225-258 (2011

Event-wise ⟨p\u3csub\u3et\u3c/sub\u3e⟩ fluctuations in Au-Au collisions at √s\u3csub\u3eNN\u3c/sub\u3e = 130 GeV

We present the first large-acceptance measurement of event-wise mean transverse momentum ⟨pt⟩ fluctuations for Au-Au collisions at nucleon-nucleon center-of-momentum collision energy √sNN = 130 GeV. The observed nonstatistical ⟨pt⟩ fluctuations substantially exceed in magnitude fluctuations expected from the finite number of particles produced in a typical collision. The r.m.s. fractional width excess of the event-wise ⟨pt⟩ distribution is 13.7±0.1(stat) ±1.3(syst)% relative to a statistical reference, for the 15% most-central collisions and for charged hadrons within pseudorapidity range |η|c. The width excess varies smoothly but nonmonotonically with collision centrality and does not display rapid changes with centrality which might indicate the presence of critical fluctuations. The reported ⟨pt⟩ fluctuation excess is qualitatively larger than those observed at lower energies and differs markedly from theoretical expectations. Contributions to ⟨pt⟩ fluctuations from semihard parton scattering in the initial state and dissipation in the bulk colored medium are discussed

Event-wise ⟨p\u3csub\u3et\u3c/sub\u3e⟩ fluctuations in Au-Au collisions at √s\u3csub\u3eNN\u3c/sub\u3e = 130 GeV

We present the first large-acceptance measurement of event-wise mean transverse momentum ⟨pt⟩ fluctuations for Au-Au collisions at nucleon-nucleon center-of-momentum collision energy √sNN = 130 GeV. The observed nonstatistical ⟨pt⟩ fluctuations substantially exceed in magnitude fluctuations expected from the finite number of particles produced in a typical collision. The r.m.s. fractional width excess of the event-wise ⟨pt⟩ distribution is 13.7±0.1(stat) ±1.3(syst)% relative to a statistical reference, for the 15% most-central collisions and for charged hadrons within pseudorapidity range |η|c. The width excess varies smoothly but nonmonotonically with collision centrality and does not display rapid changes with centrality which might indicate the presence of critical fluctuations. The reported ⟨pt⟩ fluctuation excess is qualitatively larger than those observed at lower energies and differs markedly from theoretical expectations. Contributions to ⟨pt⟩ fluctuations from semihard parton scattering in the initial state and dissipation in the bulk colored medium are discussed