997 research outputs found
Schwermetallpfad Luft – Boden – Pflanze am Beispiel der Cadmiumbelastung durch den Truppenübungsplatz Wildflecken im Biosphärenreservat Rhön
Am Beispiel des Cadmiumaustrags durch den militärischen Übungsbetrieb wird durch eine begrenzte Untersuchung ein Beitrag zu der Frage geleistet, ob die militärische Nutzung des Truppenübungsplatzes Wildflecken mit dem Konzept des umgebenden Biosphärenreservats Rhön vereinbar ist. Es wurde in einer angrenzenden Fläche des Biosphärenreservats eine höhere Cadmiumbelastung festgestellt als auf einer Vergleichsfläche innerhalb des Truppenübungsplatzes. Geltende Grenz- und Richtwerte werden jedoch nicht überschritten
Prediction of Phase Behavior of Spray-Dried Amorphous Solid Dispersions: Assessment of Thermodynamic Models, Standard Screening Methods and a Novel Atomization Screening Device with Regard to Prediction Accuracy
The evaluation of drug–polymer miscibility in the early phase of drug development is essential to ensure successful amorphous solid dispersion (ASD) manufacturing. This work investigates the comparison of thermodynamic models, conventional experimental screening methods (solvent casting, quench cooling), and a novel atomization screening device based on their ability to predict drug–polymer miscibility, solid state properties (Tg value and width), and adequate polymer selection during the development of spray-dried amorphous solid dispersions (SDASDs). Binary ASDs of four drugs and seven polymers were produced at 20:80, 40:60, 60:40, and 80:20 (w/w). Samples were systematically analyzed using modulated differential scanning calorimetry (mDSC) and X-ray powder diffraction (XRPD). Principal component analysis (PCA) was used to qualitatively assess the predictability of screening methods with regards to SDASD development. Poor correlation was found between theoretical models and experimentally-obtained results. Additionally, the limited ability of usual screening methods to predict the miscibility of SDASDs did not guarantee the appropriate selection of lead excipient for the manufacturing of robust SDASDs. Contrary to standard approaches, our novel screening device allowed the selection of optimal polymer and drug loading and established insight into the final properties and performance of SDASDs at an early stage, therefore enabling the optimization of the scaled-up late-stage development
Direct and Distributed Strain Measurements Inside a Shotcrete Lining: Concept and Realisation
Development of a small-scale spray-drying approach for amorphous solid dispersions (ASDs) screening in early drug development
The present study details the development of a small-scale spray-drying approach
for the routine screening of amorphous solid dispersions (ASDs). This strategy
aims to overcome the limitations of standard screening methodologies like
solvent casting and quench cooling to predict drug-polymer miscibility of spraydried
solid dispersions (SDSDs) and therefore to guarantee appropriate carrier
and drug-loading (DL) selection. A DoE approach was conducted to optimize
process conditions of ProCept 4M8-TriX spray-drying to maximize the yield
from a 100 mg batch of Itraconazole/HPMCAS-LF and Itraconazole/Soluplus
40:60 (w/w). Optimized process parameters include: inlet temperature, pump
speed, drying and atomizing airflows. Identified process conditions derived from
the DoE analysis were further i) tested with Itraconazole, Naproxen and seven
polymers, ii) adapted for small cyclone use, iii) downscaled to 20 mg batch
production. Drug-polymer miscibility was systematically characterized using
modulated differential scanning calorimetry (mDSC). Spray-drying was
identified as a well-suited screening approach: mean yield of 10.1 to 40.6% and
51.1 to 81.0% were obtained for 20 and 100 mg ASD productions, respectively.
Additionally, this work demonstrates the interest to move beyond conventional
screening approaches and integrate spray-drying during screening phases so that
a greater prediction accuracy in terms of SDSDs miscibility and performance can
be obtained.
Keywords: amorphous solid dispersions; spray-dryer; design of experiments;
screening; miscibility; solvent casting; quench cooling; polymer
ERIS: revitalising an adaptive optics instrument for the VLT
ERIS is an instrument that will both extend and enhance the fundamental
diffraction limited imaging and spectroscopy capability for the VLT. It will
replace two instruments that are now being maintained beyond their operational
lifetimes, combine their functionality on a single focus, provide a new
wavefront sensing module that makes use of the facility Adaptive Optics System,
and considerably improve their performance. The instrument will be competitive
with respect to JWST in several regimes, and has outstanding potential for
studies of the Galactic Center, exoplanets, and high redshift galaxies. ERIS
had its final design review in 2017, and is expected to be on sky in 2020. This
contribution describes the instrument concept, outlines its expected
performance, and highlights where it will most excel.Comment: 12 pages, Proc SPIE 10702 "Ground-Based and Airborne Instrumentation
for Astronomy VII
Causes and Consequences of A Glutamine Induced Normoxic HIF1 Activity for the Tumor Metabolism
The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of
genes that are involved in metabolism under hypoxic conditions, but information regarding the
transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated
under normoxic and hypoxic conditions with various drugs that affect cellular metabolism. HIF1ff
was silenced by siRNA in normoxic/hypoxic tumor cells, before RNA sequencing and bioinformatics
analyses were performed while using the breast cancer cell line MDA-MB-231 as a model. Differentially
expressed genes were further analyzed and validated by qPCR, while the activity of the metabolites
was determined by enzyme assays. Under normoxic conditions, HIF1 activity was significantly
increased by (i) glutamine metabolism, which was associated with the release of ammonium, and
it was decreased by (ii) acetylation via acetyl CoA synthetase (ACSS2) or ATP citrate lyase (ACLY), respectively, and (iii) the presence of L-ascorbic acid, citrate, or acetyl-CoA. Interestingly, acetylsalicylic
acid, ibuprofen, L-ascorbic acid, and citrate each significantly destabilized HIF1ff only under normoxia.
The results from the deep sequence analyses indicated that, in HIF1-siRNA silenced MDA-MB-231
cells, 231 genes under normoxia and 1384 genes under hypoxia were transcriptionally significant
deregulated in a HIF1-dependent manner. Focusing on glycolysis genes, it was confirmed that HIF1
significantly regulated six normoxic and 16 hypoxic glycolysis-associated gene transcripts. However,
the results from the targeted metabolome analyses revealed that HIF1 activity affected neither the
consumption of glucose nor the release of ammonium or lactate; however, it significantly inhibited
the release of the amino acid alanine. This study comprehensively investigated, for the first time,
how normoxic HIF1 is stabilized, and it analyzed the possible function of normoxic HIF1 in the
transcriptome and metabolic processes of tumor cells in a breast cancer cell model. Furthermore, these
data imply that HIF1 compensates for the metabolic outcomes of glutaminolysis and, subsequently,
theWarburg effect might be a direct consequence of the altered amino acid metabolism in tumor cells
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Evidence both L-type and non-L-type voltage-dependent calcium channels contribute to cerebral artery vasospasm following loss of NO in the rat
We recently found block of NO synthase in rat middle cerebral artery caused spasm, associated with depolarizing oscillations in membrane potential (Em) similar in form but faster in frequency (circa 1 Hz) to vasomotion. T-type voltage-gated Ca2+ channels contribute to cerebral myogenic tone and vasomotion, so we investigated the significance of T-type and other ion channels for membrane potential oscillations underlying arterial spasm. Smooth muscle cell membrane potential (Em) and tension were measured simultaneously in rat middle cerebral artery. NO synthase blockade caused temporally coupled depolarizing oscillations in cerebrovascular Em with associated vasoconstriction. Both events were accentuated by block of smooth muscle BKCa. Block of T-type channels or inhibition of Na+/K+-ATPase abolished the oscillations in Em and reduced vasoconstriction. Oscillations in Em were either attenuated or accentuated by reducing [Ca2+]o or block of KV, respectively. TRAM-34 attenuated oscillations in both Em and tone, apparently independent of effects against KCa3.1. Thus, rapid depolarizing oscillations in Em and tone observed after endothelial function has been disrupted reflect input from T-type calcium channels in addition to L-type channels, while other depolarizing currents appear to be unimportant. These data suggest that combined block of T and L-type channels may represent an effective approach to reverse cerebral vasospasm
Completion of the 8 MW Multi-Frequency ECRH System at ASDEX Upgrade
Over the last 15 years, the Electron Cyclotron Resonance Heating (ECRH) system at the ASDEX Upgrade tokamak has been upgraded from a 2 MW, 2 s, 140 GHz system to an 8 MW, 10 s, dual frequency system (105/140 GHz). Eight gyrotrons were in routine operation during the current experimental campaign. All gyrotrons are step-tunable operating at 105 and 140 GHz with a maximum output power of about 1 MW and 10 s pulse length. The system includes 8 transmission lines, mainly consisting of oversized corrugated waveguides (I.D. = 87 mm) with overall lengths between 50 and 70 meters including quasi-optical sections at both ends. Further improvements of the transmission lines with respect to power handling and reliability are underway
Retinal Vascular Occlusion after COVID-19 Vaccination : More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study
Background: To investigate whether vaccination against SARS-CoV-2 is associated with
the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data
from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch
retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were
retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined
protocol. The relation to any previous vaccination was documented for the consecutive case series.
Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case–
control study using age- and sex-matched controls from the general population (study participants
from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was
conducted. Results: Four hundred and twenty-one subjects presenting during the index period
(61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO,
fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred
and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given
were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our
case–control analysis integrating population-based data from the GHS yielded no evidence of an
increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with
a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any
association between SARS-CoV-2 vaccination and a higher RVOD risk
Study of decays to the final state and evidence for the decay
A study of decays is performed for the first time
using data corresponding to an integrated luminosity of 3.0
collected by the LHCb experiment in collisions at centre-of-mass energies
of and TeV. Evidence for the decay
is reported with a significance of 4.0 standard deviations, resulting in the
measurement of
to
be .
Here denotes a branching fraction while and
are the production cross-sections for and mesons.
An indication of weak annihilation is found for the region
, with a significance of
2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html,
link to supplemental material inserted in the reference
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