Signs of interaction of the NGC 1275 nucleus with the high-velocity system according to 0.7 sec seeing observations

The nucleus of the Seyfert galaxy NGC 1275 was observed in the B system on 1 December 1989 with seeing 0, 7 seconds using the Zeiss-1000 telescope on Mount Majdanak in Central Asia. Special methods of processing reveal low-contrast details. The nucleus and circumnucleus are stretched in NW-SE direction. There are two narrow filaments near the nucleus in position angles roughly 340 degrees and 320 degrees. The first is directed near the radio jet of the nucleus, the second has broken details curved to the NW or toward the high-velocity system of NGC 1275

DPYD and fluorouracil-based chemotherapy: Mini review and case report

5-Fluorouracil remains a foundational component of chemotherapy for solid tumour malignancies. While considered a generally safe and effective chemotherapeutic, 5-fluorouracil has demonstrated severe adverse event rates of up to 30%. Understanding the pharmacokinetics of 5-fluorouracil can improve the precision medicine approaches to this therapy. A single enzyme, dihydropyrimidine dehydrogenase (DPD), mediates 80% of 5-fluorouracil elimination, through hepatic metabolism. Importantly, it has been known for over 30-years that adverse events during 5-fluorouracil therapy are linked to high systemic exposure, and to those patients who exhibit DPD deficiency. To date, pre-treatment screening for DPD deficiency in patients with planned 5-fluorouracil-based therapy is not a standard of care. Here we provide a focused review of 5-fluorouracil metabolism, and the efforts to improve predictive dosing through screening for DPD deficiency. We also outline the history of key discoveries relating to DPD deficiency and include relevant information on the potential benefit of therapeutic drug monitoring of 5-fluorouracil. Finally, we present a brief case report that highlights a limitation of pharmacogenetics, where we carried out therapeutic drug monitoring of 5-fluorouracil in an orthotopic liver transplant recipient. This case supports the development of robust multimodality precision medicine services, capable of accommodating complex clinical dilemmas

Radiation Brightening from Virus-like Particles

Concentration quenching is a well-known challenge in many fluorescence imaging applications. Here we show that the optical emission from hundreds of chromophores confined onto the surface of a virus particle 28 nm diameter can be recovered under pulsed irradiation. We have found that, as one increases the number of chromophores tightly-bound to the virus surface, fluorescence quenching ensues at first, but when the number of chromophores per particle is nearing the maximum number of surface sites allowable, a sudden brightening of the emitted light and a shortening of the excited state lifetime are observed. This radiation brightening occurs only under short pulse excitation; steady-state excitation is characterized by conventional concentration quenching for any number of chromophores per particle. The observed suppression of fluorescence quenching is consistent with efficient, collective relaxation at room temperature. Interestingly, radiation brightening disappears when the emitters' spatial and/or dynamic heterogeneity is increased, suggesting that the template structural properties may play a role and opening a way towards novel, virus-enabled imaging vectors that have qualitatively different optical properties than state-of-the-art biophotonic agents

Color Effects Associated with the 1999 Microlensing Brightness Peaks in Gravitationally Lensed Quasar Q2237+0305

Photometry of the Q2237+0305gravitational lens in VRI spectral bands with the 1.5-m telescope of the high-altitude Maidanak observatory in 1995-2000 is presented. Monitoring of Q2237+0305 in July-October 2000, made at nearly daily basis, did not reveal rapid (night-to-night and intranight) variations of brightness of the components during this time period. Rather slow changes of magnitudes of the components were observed, such as 0.08 mag fading of B and C components and 0.05 mag brightening of D in R band during July 23 - October 7, 2000. By good luck three nights in 1999 were almost at the time of the strong brightness peak of image C, and approximately in the middle of the ascending slope of the image A brightness peak. The C component was the most blue one in the system in 1998 and 1999, having changed its (V-I) color from 0.56 mag to 0.12 mag since August 1997, while its brightness increased almost 1.2 mag during this time period. The A component behaved similarly between August 1998 and August 2000, having become 0.47 mag brighter in R, and at the same time, 0.15 mag bluer. A correlation between the color variations and variations of magnitudes of the components is demonstrated to be significant and reaches 0.75, with a regression line slope of 0.33. A color (V-I) vrs color (V-R) plot shows the components settled in a cluster, stretched along a line with a slope of 1.31. Both slopes are noticeably smaller than those expected if a standard galactic interstellar reddening law were responsible for the differences between the colors of images and their variations over time. We attribute the brightness and color changes to microlensing of the quasar's structure, which we conclude is more compact at shorter wavelengths, as predicted by most quasar models featuring an energizing central source.Comment: 14 pages, 7 figures, LaTeX, submitted to A&

Examining the Heterogeneous Genome Content of Multipartite Viruses BMV and CCMV by Native Mass Spectrometry

Since the concept was first introduced by Brian Chait and co-workers in 1991, mass spectrometry of proteins and protein complexes under non-denaturing conditions (native MS) has strongly developed, through parallel advances in instrumentation, sample preparation, and data analysis tools. However, the success rate of native MS analysis, particularly in heterogeneous mega-Dalton (MDa) protein complexes, still strongly depends on careful instrument modification. Here, we further explore these boundaries in native mass spectrometry, analyzing two related endogenous multipartite viruses: the Brome Mosaic Virus (BMV) and the Cowpea Chlorotic Mottle Virus (CCMV). Both CCMV and BMV are approximately 4.6 megadalton (MDa) in mass, of which approximately 1 MDA originates from the genomic content of the virion. Both viruses are produced as mixtures of three particles carrying different segments of the genome, varying by approximately 0.1 MDA in mass (~2%). This mixture of particles poses a challenging analytical problem for high-resolution native MS analysis, given the large mass scales involved. We attempt to unravel the particle heterogeneity using both Q-TOF and Orbitrap mass spectrometers extensively modified for analysis of very large assemblies. We show that manipulation of the charging behavior can provide assistance in assigning the correct charge states. Despite their challenging size and heterogeneity, we obtained native mass spectra with resolved series of charge states for both BMV and CCMV, demonstrating that native MS of endogenous multipartite virions is feasible. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-016-1348-6) contains supplementary material, which is available to authorized users