Pathway to cryogen free production of hyperpolarized krypton-83 and xenon-129

yperpolarized (hp) 129Xe and hp 83Kr for magnetic resonance imaging (MRI) are typically obtained through spin-exchange optical pumping (SEOP) in gas mixtures with dilute concentrations of the respective noble gas. The usage of dilute noble gases mixtures requires cryogenic gas separation after SEOP, a step that makes clinical and preclinical applications of hp 129Xe MRI cumbersome. For hp 83Kr MRI, cryogenic concentration is not practical due to depolarization that is caused by quadrupolar relaxation in the condensed phase. In this work, the concept of stopped flow SEOP with concentrated noble gas mixtures at low pressures was explored using a laser with 23.3 W of output power and 0.25 nm linewidth. For 129Xe SEOP without cryogenic separation, the highest obtained MR signal intensity from the hp xenon-nitrogen gas mixture was equivalent to that arising from 15.561.9% spin polarized 129Xe in pure xenon gas. The production rate of the hp gas mixture, measured at 298 K, was 1.8 cm3/min. For hp 83Kr, the equivalent of 4.460.5% spin polarization in pure krypton at a production rate of 2 cm3/min was produced. The general dependency of spin polarization upon gas pressure obtained in stopped flow SEOP is reported for various noble gas concentrations. Aspects of SEOP specific to the two noble gas isotopes are discussed and compared with current theoretical opinions. A non-linear pressure broadening of the Rb D1 transition was observed and taken into account for the qualitative description of the SEOP process

Diet Significantly Influences the Immunopathology and Severity of Kidney Injury in Male C57Bl/6J Mice in a Model Dependent Manner

Diet is a leading causative risk factor for morbidity and mortality worldwide, yet it is rarely considered in the design of preclinical animal studies. Several of the nutritional inadequacies reported in Americans have been shown to be detrimental to kidney health; however, the mechanisms responsible are unclear and have been largely attributed to the development of diabetes or hypertension. Here, we set out to determine whether diet influences the susceptibility to kidney injury in male C57Bl/6 mice. Mice were fed a standard chow diet, a commercially available “Western” diet (WD), or a novel Americanized diet (AD) for 12 weeks prior to the induction of kidney injury using the folic acid nephropathy (FAN) or unilateral renal ischemia reperfusion injury (uIRI) models. In FAN, the mice that were fed the WD and AD had worse histological evidence of tissue injury and greater renal expression of genes associated with nephrotoxicity and monocyte infiltration as compared to mice fed chow. Mice fed the AD developed more severe renal hypertrophy following FAN, and gene expression data suggest the mechanism for FAN differed among the diets. Meanwhile, mice fed the WD had the greatest circulating interleukin-6 concentrations. In uIRI, no difference was observed in renal tissue injury between the diets; however, mice fed the WD and AD displayed evidence of suppressed inflammatory response. Taken together, our data support the hypothesis that diet directly impacts the severity and pathophysiology of kidney disease and is a critical experimental variable that needs to be considered in mechanistic preclinical animal studies

Pulmonary MRI contrast using Surface Quadrupolar Relaxation (SQUARE) of hyperpolarized 83Kr

Hyperpolarized 83Kr has previously been demonstrated to enable MRI contrast that is sensitive to the chemical composition of the surface in a porous model system. Methodological advances have lead to a substantial increase in the 83Kr hyperpolarization and the resulting signal intensity. Using the improved methodology for spin exchange optical pumping of isotopically enriched 83Kr, internal anatomical details of ex vivo rodent lung were resolved with hyperpolarized 83Kr MRI after krypton inhalation. Different 83Kr relaxation times were found between the main bronchi and the parenchymal regions in ex vivo rat lungs. The T1 weighted hyperpolarized 83Kr MRI provided a first demonstration of surface quadrupolar relaxation (SQUARE) pulmonary MRI contrast

The 2022 Outburst of IGR J17091-3624: Connecting the exotic GRS 1915+105 to standard black hole X-ray binaries

While the standard X-ray variability of black hole X-ray binaries (BHXBs) is stochastic and noisy, there are two known BHXBs that exhibit exotic `heartbeat'-like variability in their light curves: GRS 1915+105 and IGR J17091-3624. In 2022, IGR J17091-3624 went into outburst for the first time in the NICER/NuSTAR era. These exquisite data allow us to simultaneously track the exotic variability and the corresponding spectral features with unprecedented detail. We find that as in typical BHXBs, the outburst began in the hard state, then the intermediate state, but then transitioned to an exotic soft state where we identify two types of heartbeat-like variability (Class V and a new Class X). The flux-energy spectra show a broad iron emission line due to relativistic reflection when there is no exotic variability, and absorption features from highly ionized iron when the source exhibits exotic variability. Whether absorption lines from highly ionized iron are detected in IGR J17091-3624 is not determined by the spectral state alone, but rather is determined by the presence of exotic variability; in a soft spectral state, absorption lines are only detected along with exotic variability. Our finding indicates that IGR J17091-3624 can be seen as a bridge between the most peculiar BHXB GRS 1915+105 and `normal' BHXBs because it alternates between the conventional and exotic behavior of BHXBs. We discuss the physical nature of the absorbing material and exotic variability in light of this new legacy dataset.Comment: 23 pages, 15 figures, 2 tables, accepted to be published in Ap

Highly-coherent quasi-periodic oscillations in the 'heartbeat' black hole X-ray binary IGR J17091-3624

IGR J17091-3624 is a black hole X-ray binary (BHXB), often referred to as the 'twin' of GRS 1915+105 because it is the only other known BHXB that can show exotic 'heartbeat'-like variability that is highly structured and repeated. Here we report on observations of IGR J17091-3624 from its 2022 outburst, where we detect an unusually coherent quasi-periodic oscillation (QPO) when the broadband variability is low (total fractional rms $\lesssim$ 6%) and the spectrum is dominated by the accretion disk. Such spectral and variability behavior is characteristic of the soft state of typical BHXBs (i.e., those that do not show heartbeats), but we also find that this QPO is strongest when there is some exotic heartbeat-like variability (so-called Class V variability). This QPO is detected at frequencies between 5 and 8 Hz and has Q-factors (defined as the QPO frequency divided by the width) $\gtrsim$ 50, making it one of the most highly coherent low-frequency QPO ever seen in a BHXB. The extremely high Q factor makes this QPO distinct from typical low-frequency QPOs that are conventionally classified into Type-A/B/C QPOs. Instead, we find evidence that archival observations of GRS 1915+105 also showed a similarly high-coherence QPO in the same frequency range, suggesting that this unusually coherent and strong QPO may be unique to BHXBs that can exhibit 'heartbeat'-like variability.Comment: 11 pages, 10 figures, 2 tables, accepted to be published in Ap

Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)

\We present the sixth catalog of Kepler candidate planets based on nearly 4 years of high precision photometry. This catalog builds on the legacy of previous catalogs released by the Kepler project and includes 1493 new Kepler Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these candidates have best fit radii <1.5 R_earth. This brings the total number of KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many of these new candidates at the low signal-to-noise limit may be false alarms created by instrumental noise, and discuss our efforts to identify such objects. We re-evaluate all previously published KOIs with orbital periods of >50 days to provide a consistently vetted sample that can be used to improve planet occurrence rate calculations. We discuss the performance of our planet detection algorithms, and the consistency of our vetting products. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement Serie

ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2

ZNF804a was identified by a genome-wide association study (GWAS) in which a single nucleotide polymorphism (SNP rs1344706) in ZNF804a reached genome-wide statistical significance for association with a combined diagnosis of schizophrenia (SZ) and bipolar disorder. Although the molecular function of ZNF804a is unknown, the amino acid sequence is predicted to contain a C2H2-type zinc-finger domain and suggests ZNF804a plays a role in DNA binding and transcription. Here, we confirm that ZNF804a directly contributes to transcriptional control by regulating the expression of several SZ associated genes and directly interacts with chromatin proximal to the promoter regions of PRSS16 and COMT, the two genes we find upregulated by ZNF804a. Using immunochemistry we establish that ZNF804a is localized to the nucleus of rat neural progenitor cells in culture and in vivo. We demonstrate that expression of ZNF804a results in a significant increase in transcript levels of PRSS16 and COMT, relative to GFP transfected controls, and a statistically significant decrease in transcript levels of PDE4B and DRD2. Furthermore, we show using chromatin immunoprecipitation assays (ChIP) that both epitope-tagged and endogenous ZNF804a directly interacts with the promoter regions of PRSS16 and COMT, suggesting a direct upregulation of transcription by ZNF804a on the expression of these genes. These results are the first to confirm that ZNF804a regulates transcription levels of four SZ associated genes, and binds to chromatin proximal to promoters of two SZ genes. These results suggest a model where ZNF804a may modulate a transcriptional network of SZ associated genes

Cryogenics free production of hyperpolarized 129Xe and 83Kr for biomedical MRI applications

As an alternative to cryogenic gas handling, hyperpolarized (hp) gas mixtures were extracted directly from the spin exchange optical pumping (SEOP) process through expansion followed by compression to ambient pressure for biomedical MRI applications. The omission of cryogenic gas separation generally requires the usage of high xenon or krypton concentrations at low SEOP gas pressures to generate hp 129Xe or hp 83Kr with sufficient MR signal intensity for imaging applications. Two different extraction schemes for the hp gasses were explored with focus on the preservation of the nuclear spin polarization. It was found that an extraction scheme based on an inflatable, pressure controlled balloon is sufficient for hp 129Xe handling, while 83Kr can efficiently be extracted through a single cycle piston pump. The extraction methods were tested for ex vivo MRI applications with excised rat lungs. Precise mixing of the hp gases with oxygen, which may be of interest for potential in vivo applications, was accomplished during the extraction process using a piston pump. The 83Kr bulk gas phase T1 relaxation in the mixtures containing more than approximately 1% O2 was found to be slower than that of 129Xe in corresponding mixtures. The experimental setup also facilitated 129Xe T1 relaxation measurements as a function of O2 concentration within excised lungs

Life-Long Radar Tracking of Bumblebees

This work was supported by European Research Council Advanced Grant no. 339347