Gemini-South + FLAMINGOS Demonstration Science: Near-Infrared Spectroscopy of the z=5.77 Quasar SDSS J083643.85+005453.3

We report an infrared 1-1.8 micron (J+H-bands), low-resolution (R=450) spectrogram of the highest-redshift radio-loud quasar currently known, SDSS J083643.85+005453.3, obtained during the spectroscopic commissioning run of the FLAMINGOS multi-object, near-infrared spectrograph at the 8m Gemini-South Observatory. These data show broad emission from both CIV 1549 and CIII] 1909, with strengths comparable to lower-redshift quasar composite spectra. The implication is that there is substantial enrichment of the quasar environment, even at times less than a billion years after the Big Bang. The redshift derived from these features is z = 5.774 +/- 0.003, more accurate and slightly lower than the z = 5.82 reported in the discovery paper based on the partially-absorbed Lyman-alpha emission line. The infrared continuum is significantly redder than lower-redshift quasar composites. Fitting the spectrum from 1.0 to 1.7 microns with a power law f(nu) ~ nu^(-alpha), the derived power law index is alpha = 1.55 compared to the average continuum spectral index = 0.44 derived from the first SDSS composite quasar. Assuming an SMC-like extinction curve, we infer a color excess of E(B-V) = 0.09 +/- 0.01 at the quasar redshift. Only approximately 6% of quasars in the optically-selected Sloan Digital Sky Survey show comparable levels of dust reddening.Comment: 10 pages, 1 figure; to appear in the Astrophysical Journal Letter

Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex

<p>Abstract</p> <p>Background</p> <p>Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. However, regulation of caudal area formation by Fgf signaling remains unknown.</p> <p>Results</p> <p>In mutant mice with constitutive activation of Fgf receptor 3 (Fgfr3) in the forebrain, surface area of the caudolateral cortex was markedly expanded at early postnatal stage, while rostromedial surface area remained normal. Cortical thickness was also increased in caudal regions. The expression domain and levels of Fgf8, as well as overall patterning, were unchanged. In contrast, the changes in caudolateral surface area were associated with accelerated cell cycle in early stages of neurogenesis without an alteration of cell cycle exit. Moreover, a marked overproduction of intermediate neuronal progenitors was observed in later stages, indicating prolongation of neurogenesis.</p> <p>Conclusion</p> <p>Activation of Fgfr3 selectively promotes growth of caudolateral (occipitotemporal) cortex. These observations support the 'radial unit' and 'radial amplification' hypotheses and may explain premature sulcation of the occipitotemporal cortex in thanatophoric dysplasia, a human <it>FGFR3 </it>disorder. Together with previous work, this study suggests that formation of rostral and caudal areas are differentially regulated by Fgf signaling in the cerebral cortex.</p

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals.

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme

A conceptual design study for Subaru ULTIMATE GLAO

We report on the conceptual design study done for the Ground Layer Adaptive Optics system of the ULTIMATE-Subaru project. This is an ambitious instrument project, providing GLAO correction in a square field of view of 14 arcmin on a side, aiming to deliver improved seeing at the near infrared wavelength. Its client instruments are an imager and multi-IFU spectrograph at Cassegrain and a Multi-Object spectrograph at Nasmyth. In this paper, we introduce the ULTIMATE-Subaru project overview and its science case and report the results of the GLAO performance prediction based on the numerical simulation and conceptual design of the wavefront sensor systemThe development of ULTIMATE-Subaru is partly supported by the Japan Society for the Promotion of Science (Grant-in-Aid for Research #17H06129)

Mapping protein dynamics at high spatial resolution with temperature-jump X-ray crystallography

温度による酵素の構造変化を分子動画撮影 様々な生体高分子のダイナミクスを決定する新たな方法論. 京都大学プレスリリース. 2023-09-19.Understanding and controlling protein motion at atomic resolution is a hallmark challenge for structural biologists and protein engineers because conformational dynamics are essential for complex functions such as enzyme catalysis and allosteric regulation. Time-resolved crystallography offers a window into protein motions, yet without a universal perturbation to initiate conformational changes the method has been limited in scope. Here we couple a solvent-based temperature jump with time-resolved crystallography to visualize structural motions in lysozyme, a dynamic enzyme. We observed widespread atomic vibrations on the nanosecond timescale, which evolve on the submillisecond timescale into localized structural fluctuations that are coupled to the active site. An orthogonal perturbation to the enzyme, inhibitor binding, altered these dynamics by blocking key motions that allow energy to dissipate from vibrations into functional movements linked to the catalytic cycle. Because temperature jump is a universal method for perturbing molecular motion, the method demonstrated here is broadly applicable for studying protein dynamics

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Effects of empagliflozin on cardiovascular and renal outcomes in heart failure with reduced ejection fraction according to age: A secondary analysis of EMPEROR-Reduced

Aims Empagliflozin improves cardiovascular and renal outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but its efficacy and safety across patient's age is not well established. Methods and results We assessed the effects of empagliflozin (10 mg daily) versus placebo, on top of standard HF therapy, in symptomatic HFrEF patients with a left ventricular ejection fraction = 75 years). The primary endpoint was a composite of cardiovascular death or HF hospitalization. Key secondary endpoints included first and recurrent HF hospitalizations and slope of change in estimated glomerular filtration rate (eGFR); the latter was supported by an analysis of a renal composite endpoint (chronic dialysis or renal transplantation or profound and sustained reduction in eGFR). Of 3730 patients, 38% were = 75 years. Compared with placebo, empagliflozin reduced the primary endpoint consistently across the three age groups (hazard ratio 0.71 [95% confidence interval 0.57-0.89] for = 75 years, interaction p-trend test = 0.24). The effects of empagliflozin were also consistent across age groups for key secondary endpoints of first and recurrent HF hospitalization (p-trend = 0.30), the rate of decline in eGFR (p-trend = 0.78) and the renal composite (p-trend = 0.94). Adverse events (AEs), serious AEs and AEs leading to drug discontinuation increased with age in both treatment arms, but empagliflozin did not increase their incidence over placebo within each age group. Conclusion The efficacy and safety of empagliflozin in improving cardiovascular and renal outcomes in HFrEF was consistent across the spectrum of age, including older patients (aged >= 75)

The potential of behavioural activation for the treatment of chronic pain: An exploratory review

Background: A substantial proportion of the population have a persistent pain condition. In addition to considerable personal suffering, these conditions have a massive economic cost at a society level in terms of health expenditure and lost productivity. To address this immense public health problem, treatment approaches are needed that are based on scientifically supported theories and that are easy to disseminate and scalable. Method: An exploratory qualitative review of literature concerning the operant model of chronic pain, related psychological interventions, and a synopsis of existing intervention studies with a behavioural activation (BA) approach was undertaken. Results: Current treatments for chronic pain are multimodal, however early research showed promising results for operant-based behavioural intervention alone. Although originally developed for depression, BA is a good theoretical match for operant conceptions of chronic pain. Further, because of its relative simplicity, BA is appealing in terms of its potential ease of dissemination. Two case studies have used BA for individuals suffering from fibromyalgia and produced promising treatment outcomes. Conclusions: Further research investigating the efficacy of BA for chronic pain is justified. Such work should begin with more single subject experimental designs to explore how BA might be best applied and the generalisability of the approach

Novel biomarker-driven prognostic models to predict morbidity and mortality in chronic heart failure: the EMPEROR-Reduced trial

Aims: The aim of this study was to generate a biomarker-driven prognostic tool for patients with chronic HFrEF. Circulating levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) each have a marked positive relationship with adverse outcomes in heart failure with reduced ejection fraction (HFrEF). A risk model incorporating biomarkers and clinical variables has not been validated in contemporary heart failure (HF) trials. Methods and results: In EMPEROR-Reduced, 33 candidate variables were pre-selected. Multivariable Cox regression models were developed using stepwise selection for: (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all-cause death, and (iii) cardiovascular mortality. A total of 3730 patients were followed up for a median of 16 months, 823 (22%) patients had a primary outcome and 515 (14%) patients died, of whom 389 (10%) died from a cardiovascular cause. NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last HF hospitalization, longer time since HF diagnosis, lower systolic blood pressure, New York Heart Association (NYHA) Class III or IV, higher heart rate and peripheral oedema were key predictors (eight variables in total, all P 9 times higher than those in the bottom 10th. Empagliflozin benefitted patients across risk levels for the primary outcome. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality, followed by NYHA Class III or IV and ischaemic aetiology (four variables in total, all P < 0.001). The mortality risk model presented good event discrimination for all-cause and cardiovascular mortality (c-statistic = 0.69 for both). These simple models were externally validated in the BIOSTAT-CHF study, achieving similar c-statistics. Conclusions: The combination of NT-proBNP and hs-cTnT with a small number of readily available clinical variables provides prognostic assessment for patients with HFrEF. This predictive tool kit can be easily implemented for routine clinical use

Common variants at 2q11.2, 8q21.3, and 11q13.2 are associated with major mood disorders

Bipolar disorder (BPD) and major depressive disorder (MDD) are primary major mood disorders. Recent studies suggest that they share certain psychopathological features and common risk genes, but unraveling the full genetic architecture underlying the risk of major mood disorders remains an important scientific task. The public genome-wide association study (GWAS) data sets offer the opportunity to examine this topic by utilizing large amounts of combined genetic data, which should ultimately allow a better understanding of the onset and development of these illnesses. Genome-wide meta-analysis was performed by combining two GWAS data sets on BPD and MDD (19,637 cases and 18,083 controls), followed by replication analyses for the loci of interest in independent 12,364 cases and 76,633 controls from additional samples that were not included in the two GWAS data sets. The single-nucleotide polymorphism (SNP) rs10791889 at 11q13.2 was significant in both discovery and replication samples. When combining all samples, this SNP and multiple other SNPs at 2q11.2 (rs717454), 8q21.3 (rs10103191), and 11q13.2 (rs2167457) exhibited genome-wide significant association with major mood disorders. The SNPs in 2q11.2 and 8q21.3 were novel risk SNPs that were not previously reported, and SNPs at 11q13.2 were in high LD with potential BPD risk SNPs implicated in a previous GWAS. The genome-wide significant loci at 2q11.2 and 11q13.2 exhibited strong effects on the mRNA expression of certain nearby genes in cerebellum. In conclusion, we have identified several novel loci associated with major mood disorders, adding further support for shared genetic risk between BPD and MDD. Our study highlights the necessity and importance of mining public data sets to explore risk genes for complex diseases such as mood disorders