Planning for 1000 Years: The Råängen Experiment

While traditional forms of urban planning are oriented towards the future, the recent turn towards experimental and challenge-led urban developments is characterized by an overarching presentism. We explore in this article how an experimental approach to urban planning can consider the long-term through setting-up ‘conversations with a future situation.’ In doing so, we draw on a unique experiment: Råängen, a piece of farmland in Lund (Sweden) owned by the Cathedral. The plot is part of Brunnshög, a large urban development program envisioned to accommodate homes, workspaces, and world-class research centers in the coming decades. We trace how Lund Cathedral became an unusual developer involved in ‘planning for thousand years,’ deployed a set of art commissions to allow reflections about values, belief, time, faith, and became committed to play a central role in the development process. The art interventions staged conversations with involved actors as well as publics geographically and temporally far away. The Råängen case illustrates how long-term futures can be fruitfully brought to the present through multiple means of imagination. A key insight for urban planning is how techniques of financial discounting and municipal zoning plans could be complemented with trust in reflective conversations in which questions are prioritized over answers

On-line estimation of local oscillator noise and optimisation of servo parameters in atomic clocks

For atomic frequency standards in which fluctuations of the local oscillator (LO) frequency are the dominant noise source, we examine the role of the the servo algorithm that predicts and corrects these frequency fluctuations. We derive the optimal linear prediction algorithm, showing how to measure the relevant spectral properties of the noise and optimise servo parameters while the standard is running, using only the atomic error signal. We find that, for realistic LO noise spectra, a conventional integrating servo with a properly chosen gain performs nearly as well as the optimal linear predictor. Using simple analytical models and numerical simulations, we establish optimum probe times as a function of clock atom number and of the dominant noise type in the local oscillator. We calculate the resulting LO-dependent scaling of achievable clock stability with atom number for product states as well as for maximally-correlated states.Alexander von Humboldt foundationEMPIREU/HORIZON 2020DFG/CRC/1128DFG/CRC/122

Coherent photo-thermal noise cancellation in a dual-wavelength optical cavity for narrow-linewidth laser frequency stabilisation

Optical resonators are used for the realisation of ultra-stable frequency lasers. The use of high reflectivity multi-band coatings allows the frequency locking of several lasers of different wavelengths to a single cavity. While the noise processes for single wavelength cavities are well known, the correlation caused by multi-stack coatings has as yet not been analysed experimentally. In our work, we stabilise the frequency of a $729\,$nm and a $1069\,$nm laser to one mirror pair and determine the residual-amplitude modulation (RAM) and photo-thermal noise (PTN). We find correlations in PTN between the two lasers and observe coherent cancellation of PTN for the $1069\,$nm coating. We show that the fractional frequency instability of the $729\,$nm laser is limited by RAM at $1\times10^{-14}$. The instability of the $1069\,$nm laser is at $3\times10^{-15}$ close to the thermal noise limit of $1.5\times10^{-15}$.Comment: 17 pages, 5 figure

Coherent photo-thermal noise cancellation in a dual-wavelength optical cavity for narrow-linewidth laser frequency stabilisation

Optical resonators are used for the realisation of ultra-stable frequency lasers. The use of high reflectivity multi-band coatings allows the frequency locking of several lasers of different wavelengths to a single cavity. While the noise processes for single wavelength cavities are well known, the correlation caused by multi-stack coatings has as yet not been analysed experimentally. In our work, we stabilise the frequency of a 729 nm and a 1069 nm laser to one mirror pair and determine the residual-amplitude modulation (RAM) and photo-thermal noise (PTN). We find correlations in PTN between the two lasers and observe coherent cancellation of PTN for the 1069 nm coating. We show that the fractional frequency instability of the 729 nm laser is limited by RAM at 1 × 10−14. The instability of the 1069 nm laser is at 3 × 10−15 close to the thermal noise limit of 1.5 × 10−1

Features of ZED1227: The first-in-class tissue transglutaminase inhibitor undergoing clinical evaluation for the treatment of celiac disease

ZED1227 is a small molecule tissue transglutaminase (TG2) inhibitor. The compound selectively binds to the active state of TG2, forming a stable covalent bond with the cysteine in its catalytic center. The molecule was designed for the treatment of celiac disease. Celiac disease is an autoimmune-mediated chronic inflammatory condition of the small intestine affecting about 1–2% of people in Caucasian populations. The autoimmune disease is triggered by dietary gluten. Consumption of staple foods containing wheat, barley, or rye leads to destruction of the small intestinal mucosa in genetically susceptible individuals, and this is accompanied by the generation of characteristic TG2 autoantibodies. TG2 plays a causative role in the pathogenesis of celiac disease. Upon activation by Ca2+, it catalyzes the deamidation of gliadin peptides as well as the crosslinking of gliadin peptides to TG2 itself. These modified biological structures trigger breaking of oral tolerance to gluten, self-tolerance to TG2, and the activation of cytotoxic immune cells in the gut mucosa. Recently, in an exploratory proof-of-concept study, ZED1227 administration clinically validated TG2 as a “druggable” target in celiac disease. Here, we describe the specific features and profiling data of the drug candidate ZED1227. Further, we give an outlook on TG2 inhibition as a therapeutic approach in indications beyond celiac disease

Exposure to Inhalable, Respirable, and Ultrafine Particles in Welding Fume

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m−3 for inhalable and 1.29 mg m−3 for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m−3). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements <LOD from the regression equation with manganese to estimate determinants of the exposure to welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging

In-vivo somatostatin-receptor expression in small cell lung cancer as a prognostic image biomarker and therapeutic target

Background: Given the dismal prognosis of small cell lung cancer (SCLC), novel therapeutic targets are urgently needed. We aimed to evaluate whether SSTR expression, as assessed by positron emission tomography (PET), can be applied as a prognostic image biomarker and determined subjects eligible for peptide receptor radionuclide therapy (PRRT). Methods: A total of 67 patients (26 females; age, 41–80 years) with advanced SCLC underwent SSTR-directed PET/computed tomography (somatostatin receptor imaging, SRI). SRI-avid tumor burden was quantified by maximum standardized uptake values (SUVmax) and tumor-to-liver ratios (T/L) of the most intense SCLC lesion. Scan findings were correlated with progression-free (PFS) and overall survival (OS). In addition, subjects eligible for SSTR-directed radioligand therapy were identified, and treatment outcome and toxicity profile were recorded. Results: On a patient basis, 36/67 (53.7%) subjects presented with mainly SSTR-positive SCLC lesions (>50% lesions positive); in 10/67 patients (14.9%), all lesions were positive. The median SUVmax was found to be 8.5, while the median T/L was 1.12. SRI-uptake was not associated with PFS or OS, respectively (SUVmax vs. PFS, ρ = 0.13 with p = 0.30 and vs. OS, ρ = 0.00 with p = 0.97; T/L vs. PFS, ρ = 0.07 with p = 0.58 and vs. OS, ρ = −0.05 with p = 0.70). PRRT was performed in 14 patients. One patient succumbed to treatment-independent infectious complications immediately after PRRT. In the remaining 13 subjects, disease control was achieved in 5/13 (38.5%) with a single patient achieving a partial response (stable disease in the remainder). In the sub-group of responding patients, PFS and OS were 357 days and 480 days, respectively. Conclusions: SSTR expression as detected by SRI is not predictive of outcome in patients with advanced SCLC. However, it might serve as a therapeutic target in selected patient

Sepsis and delayed cerebral ischemia are associated and have a cumulative effect on poor functional outcome in aneurysmal subarachnoid hemorrhage

ObjectiveAlthough sepsis and delayed cerebral ischemia (DCI) are severe complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) and share pathophysiological features, their interrelation and additive effect on functional outcome is uncertain. We investigated the association between sepsis and DCI and their cumulative effect on functional outcome in patients with aSAH using current sepsis-3 definition.MethodsPatients admitted to our hospital between 11/2014 and 11/2018 for aSAH were retrospectively analyzed. The main explanatory variable was sepsis, diagnosed using sepsis-3 criteria. Endpoints were DCI and functional outcome at hospital discharge (modified Rankin Scale (mRS) 0–3 vs. 4–6). Propensity score matching (PSM) and multivariable logistic regressions were performed.ResultsOf 238 patients with aSAH, 55 (23.1%) developed sepsis and 74 (31.1%) DCI. After PSM, aSAH patients with sepsis displayed significantly worse functional outcome (p &lt; 0.01) and longer ICU stay (p = 0.046). Sepsis was independently associated with DCI (OR = 2.46, 95%CI: 1.28–4.72, p &lt; 0.01). However, after exclusion of patients who developed sepsis before (OR = 1.59, 95%CI: 0.78–3.24, p = 0.21) or after DCI (OR = 0.85, 95%CI: 0.37–1.95, p = 0.70) this statistical association did not remain. Good functional outcome gradually decreased from 56.3% (76/135) in patients with neither sepsis nor DCI, to 43.8% (21/48) in those with no sepsis but DCI, to 34.5% (10/29) with sepsis but no DCI and to 7.7% (2/26) in patients with both sepsis and DCI.ConclusionOur study demonstrates a strong association between sepsis, DCI and functional outcome in patients with aSAH and suggests a complex interplay resulting in a cumulative effect towards poor functional outcome, which warrants further studies