Research into chemical separation techniques for production of Bi-213 via irradiation of Ra-226 [abstract]

Abstract only availableBismuth 213 is an alpha radioimmunotherapeutic agent used in cancer treatment. Neutron bombardment of radium 226 is being investigated as an alternative method of producing Bi-213. For this project, a literature search of existing chemical separation steps for the production of Bis-213 for radioimmunotherapy was performed in order to optimize the combination of irradiation schemes with chemical separation steps. For the first step, the separation of actinium and radium from thorium 229 and recovery of radium for further irradiation, several successful methods were described in the literature. Organic cation exchange columns such as AG50W-X8 have traditionally been used to perform this step, but these suffer high radiolysis, which newer methods have tried to address. Some of these are an extraction chromatography method using a UTEVA column followed by a RE-resin column on a silica gel support, an inorganic titanium phosphate ion exchanger, and sublimation of the anhydrous chlorides of Th-229 and its daughter isotopes performed in a quartz tube, featuring complete separation of the elements while radium is retained at the bottom of the tube and available for further irradiation in one step. For the second part of the process, the elution of Bis-213 from an Ac-225 generator, quite a few successful techniques are described in the literature. Some of the better ones found are a multicolumn selectivity inversion generator, a renewable column, tandem column extraction chromatography, a PNNL automated generator, a MSKCC generator, an inorganic hydrated zirconium cation exchanger, and silica based resins, as well as the more traditional organic cation and anion exchange columns. A method using alpha recoil of Bis-213 from Ac-225 incorporated into a sealed isotope generator has the benefit of resulting in no radioactive, chemical, or mixed wastes, in contrast to chemical separation methods. In conclusion, several promising separation techniques were found in the literature

Bridgewater “Comments” on 80 Years of Men’s and Women’s Sports

Sports media is important because it shapes the perceptions, aspirations and dreams of the viewers (Angelini, 2008). It shows the viewers the skill and athletic achievement of both male and female athletes. The media allows viewers to witness the athletic prowess of their favorite athletes on TV and in print. Within sports media, the viewers are able to learn about the many different sports that are offered around the world. The viewers are able to get a sense about who the athletes are, their talents, their sport and their achievement. It is apparent that sports media has a huge impact on the people around the world who watch games, buy magazines, and endorse their favorite team by collecting team and player memorabilia

Discovery of an Enormous Lyα Nebula in a Massive Galaxy Overdensity at z = 2.3

Enormous Lyα nebulae (ELANe), unique tracers of galaxy density peaks, are predicted to lie at the nodes and intersections of cosmic filamentary structures. Previous successful searches for ELANe have focused on wide-field narrowband surveys or have targeted known sources such as ultraluminous quasi-stellar objects (QSOs) or radio galaxies. Utilizing groups of coherently strong Lyα absorptions, we have developed a new method to identify high-redshift galaxy overdensities and have identified an extremely massive overdensity, BOSS1441, at z = 2-3. In its density peak, we discover an ELAN that is associated with a relatively faint continuum. To date, this object has the highest diffuse Lyα nebular luminosity of L_(nebula) = 5.1 ± 0.1 x 10^(44) erg s^(−1). Above the 2σ surface brightness limit of SB Lyα = 4.8 x 10^(-18) erg s^(−1) cm^(−2) arcsec^(−2), this nebula has an end-to-end spatial extent of 442 kpc. This radio-quiet source also has extended C IV λ1549 and He II λ1640 emission on ≳ 30 kpc scales. Note that the Lyα, He II, and C IV emissions all have double-peaked line profiles. Each velocity component has an FWHM of ≈700–1000 km s^(−1). We argue that this Lyα nebula could be powered by shocks due to an active galactic nucleus–driven outflow or photoionization by a strongly obscured source

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Discovery of an Enormous Ly α Nebula in a Massive Galaxy Overdensity at z = 2.3

Enormous Ly alpha nebulae (ELANe), unique tracers of galaxy density peaks, are predicted to lie at the nodes and intersections of cosmic filamentary structures. Previous successful searches for ELANe have focused on wide-field narrowband surveys or have targeted known sources such as ultraluminous quasi-stellar objects (QSOs) or radio galaxies. Utilizing groups of coherently strong Ly alpha absorptions, we have developed a new method to identify high-redshift galaxy overdensities and have identified an extremely massive overdensity, BOSS1441, at z = 2-3. In its density peak, we discover an ELAN that is associated with a relatively faint continuum. To date, this object has the highest diffuse Ly alpha nebular luminosity of L-nebula = 5.1 +/- 0.1 x 10(44) erg s(-1). Above the 2 sigma surface brightness limit of SBLy alpha = 4.8 x 10(-18) erg s(-1) cm(-2) arcsec(-2), this nebula has an end-to-end spatial extent of 442 kpc. This radio-quiet source also has extended C IV lambda 1549 and He II lambda 1640 emission on greater than or similar to 30 kpc scales. Note that the Ly alpha, He II, and C IV emissions all have double-peaked line profiles. Each velocity component has an FWHM of approximate to 700-1000 km s(-1). We argue that this Lya nebula could be powered by shocks due to an active galactic nucleus-driven outflow or photoionization by a strongly obscured source.US NSF [AST 11-07682]; NSF [AST-1412981, AST-0908280]; National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF 2016R1C1B2007782]; NASA [ADP-NNX10AD47G]; Swiss National Science Foundation [PP00P2_163824]; JSPS [15H03645]; Kitt Peak National Observatory, National Optical Astronomy Observatory [2013A-0434, 2014A-0395]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Differential Processing of α- and β-Defensin Precursors by Matrix Metalloproteinase-7 (MMP-7)*

Proteolytic processing of defensins is a critical mode of posttranslational regulation of peptide activity. Because mouse α-defensin precursors are cleaved and activated by matrix metalloproteinase-7 (MMP-7), we determined if additional defensin molecules, namely human neutrophil defensin pro-HNP-1 and β-defensins, are targets for MMP-7. We found that MMP-7 cleaves within the pro-domain of the HNP-1 precursor, a reaction that does not generate the mature peptide but produces a 59-amino acid intermediate. This intermediate, which retains the carboxyl-terminal end of the pro-domain, had antimicrobial activity, indicating that the residues important for masking defensin activity reside in the amino terminus of this domain. Mature HNP-1 was resistant to processing by MMP-7 unless the peptide was reduced and alkylated, demonstrating that only the pro-domain of α-defensins is normally accessible for cleavage by this enzyme. From the 47-residue HBD-1 precursor, MMP-7 catalyzed removal of 6 amino acids from the amino terminus. Neither a 39-residue intermediate form of HBD-1 nor the mature 36-residue form of HBD-1 was cleaved by MMP-7. In addition, both pro-HBD-2, with its shorter amino-terminal extension, and pro-HBD-3 were resistant to MMP-7. However, human and mouse β-defensin precursors that lack disulfide bonding contain a cryptic MMP-7-sensitive site within the mature peptide moiety. These findings support and extend accumulating evidence that the native three-dimensional structure of both α- and β-defensins protects the mature peptides against proteolytic processing by MMP-7. We also conclude that sites for MMP-7 cleavage are more common at the amino termini of α-defensin rather than β-defensin precursors, and that catalysis at these sites in α-defensin pro-domains results in acquisition of defensin activity

International Society for Heart and Lung Transplantation consensus statement for the standardization of bronchoalveolar lavage in lung transplantation

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics