Ariel - Volume 2 Number 8

Editors Richard J. Bonanno Robin A. Edwards Associate Editors Steven Ager Stephen Flynn Shep Dickman Tom Williams Lay-out Editor Eugenia Miller Contributing Editors Michael J. Blecker Milton Packe James J. Nocon Lynne Porter Editors Emeritus Delvyn C. Case, Jr. Paul M. Fernhof

Ariel - Volume 1 Number 3

Copyright 1969 Arie

Comparative proteogenomic analysis of right-sided colon cancer, left-sided colon cancer and rectal cancer reveals distinct mutational profiles

Right-sided colon cancer (RCC) has worse prognosis compared to left-sided colon cancer (LCC) and rectal cancer. The reason for this difference in outcomes is not well understood. We performed comparative somatic and proteomic analyses of RCC, LCC and rectal cancers to understand the unique molecular features of each tumor sub-types. Utilizing a novel in silico clonal evolution algorithm, we identified common tumor-initiating events involving APC, KRAS and TP53 genes in RCC, LCC and rectal cancers. However, the individual role-played by each event, their order in tumor development and selection of downstream somatic alterations were distinct in all three anatomical locations. Some similarities were noted between LCC and rectal cancer. Hotspot mutation analysis identified a nonsense mutation, APC R1450* specific to RCC. In addition, we discovered new significantly mutated genes at each tumor location, Further in silico proteomic analysis, developed by our group, found distinct central or hub proteins with unique interactomes among each location. Our study revealed significant differences between RCC, LCC and rectal cancers not only at somatic but also at proteomic level that may have therapeutic relevance in these highly complex and heterogeneous tumors.Merit Review Award, Medical Research Service, Department of Veterans AffairsUS Department of Veterans Affairs [I01 BX000545]; Veterans AffairsUS Department of Veterans Affairs [I01BX000545] Funding Source: NIH RePORTERPart of A. H.'s time was supported by a Merit Review Award (I01 BX000545), Medical Research Service, Department of Veterans Affairs

Ariel - Volume 2 Number 4

Copyright 1969 Arie

Threshold of a Random Laser with Cold Atoms

We address the problem of achieving an optical random laser with a cloud of cold atoms, in which gain and scattering are provided by the same atoms. The lasing threshold can be defined using the on-resonance optical thickness b0 as a single critical parameter. We predict the threshold quantitatively, as well as power and frequency of the emitted light, using two different light transport models and the atomic polarizability of a strongly-pumped two-level atom. We find a critical b0 on the order of 300, which is within reach of state-of-the-art cold-atom experiments. Interestingly, we find that random lasing can already occur in a regime of relatively low scattering.Comment: Note that Eq. (3) of the published version in PRL contains a misprint. The correct expression is given her

Ariel - Volume 2 Number 3

Editors Delvyn C. Case, Jr. Paul M. Fernhoff News Editors Richard Bonanno Daniel B. Gould Robin A. Edwards Lay-Out Editor Carol Dolinskas Sports Editor James J. Nocon Contributing Editors Michael J. Blecker Lin Sey Edwards Jack Guralnik W. Cherry Light Features Editor Steven A. Ager Donald A. Bergman Stephen P. Flynn Business Manager Nick Greg

The NANOGrav 15 yr Data Set: Constraints on Supermassive Black Hole Binaries from the Gravitational-wave Background

El conjunto de datos de 15 años de NANOGrav muestra evidencias de la presencia de un fondo de ondas gravitacionales (GWB) de baja frecuencia. Aunque muchos procesos físicos pueden originar estas ondas gravitacionales de baja frecuencia, aquí analizamos la señal como procedente de una población de agujeros negros binarios supermasivos (SMBH) distribuidos por todo el Universo. Demostramos que los modelos astrofísicos de poblaciones binarias SMBH son capaces de reproducir tanto la amplitud como la forma del espectro de ondas gravitacionales de baja frecuencia observado. Aunque múltiples variaciones del modelo son capaces de reproducir el espectro GWB con nuestra precisión de medida actual, nuestros resultados subrayan la importancia de modelar con precisión la evolución binaria para producir espectros GWB realistas. Además, aunque unos parámetros razonables son capaces de reproducir las observaciones de 15 años, la amplitud implícita del GWB requiere que un gran número de parámetros se sitúen en los límites de los valores esperados o que un pequeño número de parámetros difieran notablemente de las expectativas estándar. Aunque todavía no somos capaces de establecer definitivamente el origen de la señal GWB inferida, la consistencia de la señal con las expectativas astrofísicas ofrece una perspectiva tentadora para confirmar que las binarias SMBH son capaces de formarse, alcanzar separaciones de sub-segundos y finalmente unirse. A medida que la importancia aumente con el tiempo, las características de orden superior del espectro del GWB determinarán definitivamente la naturaleza del GWB y permitirán nuevas restricciones sobre las poblaciones de SMBH. © 2023The NANOGrav 15 yr data set shows evidence for the presence of a low-frequency gravitational-wave background (GWB). While many physical processes can source such low-frequency gravitational waves, here we analyze the signal as coming from a population of supermassive black hole (SMBH) binaries distributed throughout the Universe. We show that astrophysically motivated models of SMBH binary populations are able to reproduce both the amplitude and shape of the observed low-frequency gravitational-wave spectrum. While multiple model variations are able to reproduce the GWB spectrum at our current measurement precision, our results highlight the importance of accurately modeling binary evolution for producing realistic GWB spectra. Additionally, while reasonable parameters are able to reproduce the 15 yr observations, the implied GWB amplitude necessitates either a large number of parameters to be at the edges of expected values or a small number of parameters to be notably different from standard expectations. While we are not yet able to definitively establish the origin of the inferred GWB signal, the consistency of the signal with astrophysical expectations offers a tantalizing prospect for confirming that SMBH binaries are able to form, reach subparsec separations, and eventually coalesce. As the significance grows over time, higher-order features of the GWB spectrum will definitively determine the nature of the GWB and allow for novel constraints on SMBH populations. © 2023. The Author(s). Published by the American Astronomical Society

Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease

AbstractEmerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy

Exploring electronic effects on the partitioning of actinides(III) from lanthanides(III) using functionalised bis-triazinyl phenanthroline ligands

The first examples of 4,7-disubstituted 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzo-triazin-3-yl)-1,10- phenanthroline (CyMe4 -BTPhen) ligands are reported herein. Evaluating the kinetics, selectivity and stoichiometry of actinide(III) and lanthanide(III) radiotracer extractions has provided a mechanistic insight into the extraction process. For the first time, it has been demonstrated that metal ion extraction kinetics can be modulated by backbone functionalisation and a promising new CHON compliant candidate ligand with enhanced metal ion extraction kinetics has been identified. The effects of 4,7- functionalisation on the equilibrium metal ion distribution ratios are far more pronounced than those of 5,6-functionalisation. The complexation of Cm(III) with two of the functionalised ligands was investigated by TRLFS and, at equilibrium, species of 1:2 [M:L] stoichiometry were observed exclusively. A direct correlation between the ELUMO-EHOMO energy gap and metal ion extraction potential is reported, with DFT studies reaffirming experimental findings