X-shooter is the first 2nd generation instrument of the ESO Very Large Telescope (VLT). It is a very efficient, single-target, intermediate-resolution spectrograph that was installed at the ...Cassegrain focus of UT2 in 2009. The instrument covers, in a single exposure, the spectral range from 300 to 2500 nm. It is designed to maximize the sensitivity in this spectral range through dichroic splitting in three arms with optimized optics, coatings, dispersive elements and detectors. It operates at intermediate spectral resolution (R ~ 4000−17 000, depending on wavelength and slit width) with fixed échelle spectral format (prism cross-dispersers) in the three arms. It includes a 1.8″ × 4″ integral field unit as an alternative to the 11′′ long slits. A dedicated data reduction package delivers fully calibrated two-dimensional and extracted spectra over the full wavelength range. We describe the main characteristics of the instrument and present its performance as measured during commissioning, science verification and the first months of science operations.
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FMFMET, NUK, UL, UM, UPUK
Background and purpose
Hippocampal atrophy is presumably one morphological sign of critical illness encephalopathy; however, predictors have not yet been determined.
Methods
The data for this report ...derived from patients treated at the intensive care units (ICUs) of the University Hospital in Bonn in the years 2004–2006. These patients underwent structural magnetic resonance imaging 6–24 months after discharge. Volumes (intracranial, whole brain, white matter, grey matter, cerebral spinal fluid, bilateral hippocampus) were compared with healthy controls. Pro‐inflammatory parameters and ICU scoring systems were explored in conjunction with brain volumes. Cut‐scores were defined to differentiate patients with high from those with low inflammatory response.
Results
Hippocampal and white matter volume were reduced in critically ill patients compared with healthy controls. Procalcitonin showed a very strong correlation (r = −0.903, P = 0.01) and interleukin‐6 a moderate correlation (r = −0.538, P = 0.031) with hippocampal volume, but not with other brain volumes. C‐reactive protein was linked to grey matter volume. There was no correlation with systemic inflammatory response syndrome criteria (body temperature, heart rate, respiratory rate, white blood cell count) or for hippocampal or whole brain volume. Furthermore, parameters representing severity of disease (APACHE II score, SOFA score, duration of stay and duration of mechanical ventilation) were not associated with hippocampal or other brain volumes.
Conclusions
This analysis suggests that high levels of procalcitonin and interleukin‐6 in the blood serum of critically ill patients are associated with a high likelihood of hippocampal atrophy irrespective of the severity of disease measured by ICU scoring systems and other inflammatory parameters.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Brown bears are obese when they enter the den, and after 6 mo of hibernation and physical inactivity, bears show none of the adverse consequences of a sedentary lifestyle in humans, such as ...cardiovascular disease, type 2 diabetes, and kidney failure. The metabolic mechanisms that drive hibernation physiology in bears are poorly defined, but systemic endocrine regulators are likely involved. To investigate the potential role of steroid hormones, we quantified the total levels of 12 steroid hormones, the precursor cholesterol, sex hormone–binding globulin (SHBG), and corticosterone-binding globulin (CBG) in paired serum samples from subadult free-ranging Scandinavian brown bears during the active and hibernation states. During hibernation, androstenedione and testosterone were significantly decreased in subadult female bears (n=13), whereas they increased in all males but one (n=6) and therefore did not reach a significant difference. Despite this difference, SHBG increased more than 20-fold during hibernation for all bears. Compared with SHBG concentrations in humans, bear levels were very low in the active state, but during hibernation, levels equaled high levels in humans. The increased SHBG levels likely maintain a state of relative quiescence of the reproductive hormones in hibernating bears. Interestingly, the combination of SHBG and testosterone levels results in similar free bioavailable testosterone levels of 70–80 pM in both subadult and adult sexually active male bears, suggesting a role for SHBG in controlling androgen action during hibernation in males. Dehydroepiandrosterone sulfate, dihydrotestosterone, and estradiol levels were below the detection limit in all but one animal. The metabolically active glucocorticoids were significantly higher in both sexes during hibernation, whereas the inactive metabolite cortisone was reduced and CBG was low approaching the detection limit. A potential caveat is that the glucocorticoid levels might be affected by the ketamine applied in the anesthetic mixture for hibernating bears. However, increased hibernating cortisol levels have consistently been reported in both black bears and brown bears. Thus, we suggest that high glucocorticoid activity may support the hibernation state, likely serving to promote lipolysis and gluconeogenesis while limiting tissue glucose uptake to maintain a continuous glucose supply to the brain.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Atmospheric Remote-sensing Infrared Exoplanets Large-survey (ARIEL) is the fourth medium (M4) mission selected in the context of the ESA Cosmic Vision 2015–2025 programme, with a launch planned ...in 2028. During 4 years of flight operations, ARIEL will probe the chemical and physical properties of approximately 1000 known exoplanets by observing their atmosphere, to study how planetary systems form and evolve
1
,
2
. The mission is designed as a transit and eclipse spectroscopy survey, operated by a 1-m class telescope feeding two instruments, the Fine Guidance system (FGS) and the ARIEL InfraRed Spectrometer (AIRS), that accommodate photometric and spectroscopic channels covering the band from 0.5 to 7.8 μm in the visible to near-IR range
3
,
4
. The mission high sensitivity requirements ask for an extremely stable thermo-mechanical platform. The payload thermal control is based on a passive and active cooling approach. Passive cooling is achieved by a V-Groove shields system that exploits the L2 orbit favourable thermal conditions to cool the telescope and the optical bench to stable temperatures <60 K. The FGS focal planes operate at the optical bench temperature while the AIRS channel detectors require a colder reference, lower than 42 K. This is provided by an active cooling system based on a Neon Joule-Thomson cold end, fed by a mechanical compressor. In this paper we report the thermal architecture of the payload at the end of Phase B1 and present the requirements that drive the design together with the analyses results and the expected performances.
Abstract
We present the discovery of a highly irradiated and moderately inflated ultrahot Jupiter, TOI-1431b/MASCARA-5 b (HD 201033b), first detected by NASA’s Transiting Exoplanet Survey Satellite ...mission (TESS) and the Multi-site All-Sky Camera (MASCARA). The signal was established to be of planetary origin through radial velocity measurements obtained using SONG, SOPHIE, FIES, NRES, and EXPRES, which show a reflex motion of
K
= 294.1 ± 1.1 m s
−1
. A joint analysis of the TESS and ground-based photometry and radial velocity measurements reveals that TOI-1431b has a mass of
M
p
= 3.12 ± 0.18
M
J
(990 ± 60
M
⊕
), an inflated radius of
R
p
= 1.49 ± 0.05
R
J
(16.7 ± 0.6
R
⊕
), and an orbital period of
P
= 2.650237 ± 0.000003 days. Analysis of the spectral energy distribution of the host star reveals that the planet orbits a bright (
V
= 8.049 mag) and young (
0.29
−
0.19
+
0.32
Gyr) Am type star with
T
eff
=
7690
−
250
+
400
K, resulting in a highly irradiated planet with an incident flux of
〈
F
〉
=
7.24
−
0.64
+
0.68
×
10
9
erg s
−1
cm
−2
(
5300
−
470
+
500
S
⊕
) and an equilibrium temperature of
T
eq
= 2370 ± 70 K. TESS photometry also reveals a secondary eclipse with a depth of
127
−
5
+
4
ppm as well as the full phase curve of the planet’s thermal emission in the red-optical. This has allowed us to measure the dayside and nightside temperature of its atmosphere as
T
day
= 3004 ± 64 K and
T
night
= 2583 ± 63 K, the second hottest measured nightside temperature. The planet’s low day/night temperature contrast (∼420 K) suggests very efficient heat transport between the dayside and nightside hemispheres. Given the host star brightness and estimated secondary eclipse depth of ∼1000 ppm in the
K
band, the secondary eclipse is potentially detectable at near-IR wavelengths with ground-based facilities, and the planet is ideal for intensive atmospheric characterization through transmission and emission spectroscopy from space missions such as the James Webb Space Telescope and the Atmospheric Remote-sensing Infrared Exoplanet Large-survey.
Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier ...lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence supports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i) assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present the discovery of a highly irradiated and moderately inflated ultra-hot Jupiter, TOI-1431b/MASCARA-5b (HD 201033b), first detected by NASA's Transiting Exoplanet Survey Satellite mission ...(TESS) and the Multi-site All-Sky CAmeRA (MASCARA). The signal was established to be of planetary origin through radial velocity measurements obtained using SONG, SOPHIE, FIES, NRES, and EXPRES, which show a reflex motion of $K=294.1\pm1.1$ m s$^{-1}$. A joint analysis of the TESS and ground-based photometry and radial velocity measurements reveals that TOI-1431b has a mass of $M_{p}=3.12\pm0.18$ $\rm{M_J}$ ($990\pm60$ M$_{\oplus}$), an inflated radius of $R_{p}=1.49\pm0.05$ $\rm{R_J}$ ($16.7\pm0.6$ R$_{\oplus}$), and an orbital period of $P=2.650237\pm0.000003$ d. Analysis of the spectral energy distribution of the host star reveals that the planet orbits a bright ($\mathrm{V}=8.049$ mag) and young ($0.29^{+0.32}_{-0.19}$ Gyr) Am type star with $T_{\rm eff}=7690^{+400}_{-250}$ $\rm{K}$, resulting in a highly irradiated planet with an incident flux of $\langle F \rangle=7.24^{+0.68}_{-0.64}\times$10$^9$ erg s$^{-1}$ cm$^{-2}$ ($5300^{+500}_{-470}\mathrm{S_{\oplus}}$) and an equilibrium temperature of $T_{eq}=2370\pm70$ K. TESS photometry also reveals a secondary eclipse with a depth of $127^{+4}_{-5}$ppm as well as the full phase curve of the planet's thermal emission in the red-optical. This has allowed us to measure the dayside and nightside temperature of its atmosphere as $T_\mathrm{day}=3004\pm64$ K and $T_\mathrm{night}=2583\pm63$ K, the second hottest measured nightside temperature. The planet's low day/night temperature contrast ($\sim$420 K) suggests very efficient heat transport between the dayside and nightside hemispheres.
In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's ...disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration AT(N). This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Synthesis of proteins by automated flow chemistry Hartrampf, N; Saebi, A; Poskus, M ...
Science (American Association for the Advancement of Science),
2020-May-29, 2020-05-29, 20200529, Volume:
368, Issue:
6494
Journal Article
Peer reviewed
Open access
Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the ...direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome.
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