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We discuss the potential of light-nuclei measurements in heavy-ion collisions at intermediate energies for the search of the hypothetical QCD critical end-point. A previous proposal based on neutron density fluctuations has brought appealing experimental evidences of a maximum in the ratio of the number of tritons times protons, divided over deuterons square, O tpd. However these results are difficult to reconcile with the state-of-the-art statistical thermal model predictions. Based on the idea that the QCD critical point can lead to a substantial attraction among nucleons, we propose new light-nuclei multiplicity ratios involving He in which the maximum would be more noticeable. We argue that the experimental extraction is feasible by presenting these ratios formed from actual measurements of total and differential yields at low and high collision energies from FOPI and ALICE experiments, respectively. We also illustrate the possible behavior of these ratios at intermediate energies applying a semiclassical method based on flucton paths using the preliminary NA49 and STAR data for O tpd as input.
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative movement disorder caused by expansion of CAG repeats in the ATXN2 gene beyond 33 units, while healthy individuals carry 22-23 repeats. First symptoms of SCA2 include uncoordinated movement, ataxic gait and slowing of the saccadic eye movements in line with the early pronounced atrophy of cerebellum, spinal cord and brainstem. Cerebellar Purkinje cells and spinal cord motor neurons are the most affected cells from ATXN2 expansions. Later on, patients manifest distal amyotrophy, problems in breathing and swallowing, depression and cognitive decline caused by widespread degeneration throughout the brain. The striking loss of mass in the brain, due to severe myelin fat atrophy, is accompanied by a similar reduction in the peripheral fat stores. After the devastating progression of disease, the severity and duration of which depends on the CAG repeat size, genetic background and environmental factors, patients succumb to SCA2 mostly because of respiratory failure at the terminal stage. Larger repeat sizes lead to an earlier manifestation of the disease and a more rapid progression. Aside from SCA2, intermediate-length and short pathogenic CAG expansions in ATXN2 between 26-39 repeats significantly increase the risk of developing other neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), fronto-temporal lobar dementia (FTLD) or Parkinson plus tauopathies like progressive supranuclear palsy (PSP) in various cohorts across the world.
Ataxin-2 (ATXN2) is a ubiquitously expressed cytosolic protein most famous for its involvement in neurodegenerative disease caused by the expanded poly-glutamine (polyQ) domain corresponding to a genomic (CAG)n tract. This N-terminal polyQ domain has no known function, other than increasing the aggregation propensity of mutant ATXN2 and facilitating interaction with other polyQ containing proteins, leading to their sequestration. The progressive accumulation of ATXN2 into cytosolic foci, and also that of its interaction partners over time, underlies the molecular pathomechanism. Next to polyQ domain, ATXN2 also contains a Like-Sm domain (Lsm), an Lsm-associated domain (LsmAD), multiple proline-rich domains (PRD) and a Poly(A)-Binding-Protein (PABP)-interacting motif (PAM2).
Through its Lsm/LsmAD domains, ATXN2 directly binds to a large number of transcripts, regulating their quality and translation rate. In a similar fashion, through its direct interaction with PABP via PAM2 motif, ATXN2 indirectly modifies the fate of even larger number of transcripts and global translation. Several PRDs scattered across the protein help ATXN2 associate with growth factor receptors and other endocytosis factors, modulating nutrient uptake and downstream signaling.
ATXN2 is a stress response factor. Therefore, its involvement in nutrient uptake plays a crucial part in cell’s capability to overcome non-permissive conditions. Upon nutrient deprivation, oxidative stress, proteotoxicity, heat stress or Ca2+ imbalance, ATXN2 relocalizes into cytosolic ribonucleoprotein particles known as stress granules (SGs), together with PABP, several eukaryotic translation initiation factors, many other RNA-binding proteins (RBP) with their target transcripts and the small ribosomal subunit. Collectively, they modulate the stability of the trapped transcripts, favoring the maturation and translation of IRES-dependent stress response proteins instead, according to the specific need. Many RBPs interact either directly or in an RNA-dependent manner in the SGs, and due to the large number of ALS-causing mutations identified in them (such as TDP-43, FUS, TIA-1, hnRNPA2/B1), SGs became a hot topic in neuropathology. Acute SGs serve to halt translation and growth, and to spend energy only for survival until stress disappears. However, chronic SG assembly eventually activates apoptotis leading to cell death. While the polyQ expansions in ATXN2 enhance SG stability, reduce their dissociation rate after stress, and lead to aberrant post-translational modifications of other SG components like TDP-43, complete loss of ATXN2 delays SG formation and results in easily dissolvable foci.
Most of the stressors that induce SG formation eventually converge on energetic deficit. Therefore, it is logical that the ultimate task of SGs is to stop further growth when it cannot be afforded. In yeast, the molecular mechanism underlying this growth arrest was explained as sequestration of the master growth regulator complex, Target-of-Rapamycin Complex 1 (TORC1), into SGs in an ATXN2-dependent manner. The repressor effect of ATXN2 on mammalian TORC1 (mTORC1) and global protein translation had already been documented in earlier studies; complete loss of ATXN2 function in knock-out mouse (Atxn2-KO) resulted in mTORC1 hyperactivity and transcriptional upregulation of multiple ribosomal subunits indicating an increased need for these machines. ...
Čibiraitė-Lukenskienė, Dovilé ; Ikamas, Kęstutis ; Lisauskas, Tautvydas ; Krozer, Viktor ; Roskos, Hartmut ; Lisauskas, Alvydas
This work presents, to our knowledge, the first completely passive imaging with human-body-emitted radiation in the lower THz frequency range using a broadband uncooled detector. The sensor consists of a Si CMOS field-effect transistor with an integrated log-spiral THz antenna. This THz sensor was measured to exhibit a rather flat responsivity over the 0.1–1.5-THz frequency range, with values of the optical responsivity and noise-equivalent power of around 40 mA/W and 42 pW/√Hz, respectively. These values are in good agreement with simulations which suggest an even broader flat responsivity range exceeding 2.0 THz. The successful imaging demonstratestheimpressivethermalsensitivitywhichcanbeachievedwithsuchasensor. Recording of a 2.3×7.5-cm2-sized image of the fingers of a hand with a pixel size of 1 mm2 at a scanning speed of 1 mm/s leads to a signal-to-noise ratio of 2 and a noise-equivalent temperature difference of 4.4 K. This approach shows a new sensing approach with field-effect transistors as THz detectors which are usually used for active THz detection.
Evidence is increasingly pointing towards a significant global decline in biodiversity. The drivers of this decline are numerous, including habitat change and overexploitation, rapid deforestation, pollution, exotic species and disease, and finally climate change as an emerging driver of biodiversity change (Nakamura, et al., 2013; Hancocks, 2001; Pereira, Navarro & Martins, 2012). Raising public awareness of the need to conserve biological diversity is essential to safeguard the richness of life forms all over the world (Lindemann-Matthies, 2002). In this regard, institutions such as science museums, zoos and aquariums have the potential to play an important role (Rennie & Stocklmayer, 2003). Especially, zoos can provide a productive learning environment (Miles & Tout, 1992), facilitating the promotion of public conservation awareness and the adoption of pro-environmental behaviours that would reduce negative human impacts on biodiversity (Barongi, et al., 2015).
Based on these concepts, my study contributes to the developing field of visitor studies. Taking as reference non-zoo visitors and zoo visitors, I have focused on reviewing some aspects of conservation education, such as people's awareness of conservation, people's interest in animals and people's feelings towards animals and attitudes towards zoos. The study identified differences between non-regular and regular zoo visitors in interests in animals, as well as visitor attitudes towards conservation issues and zoos. Therefore, the present study indicated that positive emotional reactions and, in particular, a perceived sense of connection to the animal were linked and depended on the frequency of zoo visits. It was as well remarkable, that conservation awareness was influenced by the interest in animals, the interest in visiting zoos, the attitudes towards these institutions, and the age and the country of origin. All these variables had a greater effect in the conservation consciousness of the participants. Additionally interestingly, the main reason for visiting zoos in every country was to learn something about animals. This highlights the educational role of zoos and broadly supports the idea that people want to visit zoos to learn something about animals, in turn facilitating pro-conservation learning and changes in attitude. They are uniquely positioned to interact with visitors, communities, and society and to contribute by providing an informative and entertaining environment. Visiting zoos could led to contribute to promoting animal connectedness and interest in species.
Zöllner, Johann Philipp ; Misselwitz, Björn ; Mauroschat, Thomas ; Roth, Christian ; Steinmetz, Helmuth ; Rosenow, Felix ; Strzelczyk, Adam
Recent data have suggested that performing recanalizing therapies in ischemic stroke might lead to an increased risk of acute symptomatic seizures. This applies to both intravenous thrombolysis and mechanical thrombectomy. We therefore determined the frequency of acute symptomatic seizures attributable to these two recanalization therapies using a large, population-based stroke registry in Central Europe. We performed two matched 1:1 case–control analyses. In both analyses, patients were matched for age, stroke severity on admission and pre-stroke functional status. The first analysis compared patients treated with intravenous thrombolysis to a non-recanalization control group. To isolate the effect of mechanical thrombectomy, we compared patients with both mechanical thrombectomy and intravenous thrombolysis to those with only intravenous thrombolysis treatment in a second analysis. From 135,117 patients in the database, 13,356 patients treated with only intravenous thrombolysis, and 1013 patients treated with both intravenous thrombolysis and mechanical thrombectomy were each matched to an equivalent number of controls. Patients with intravenous thrombolysis did not suffer from clinically apparent acute symptomatic seizures significantly more often than non-recanalized patients (treatment = 199; 1.5% vs. control = 237; 1.8%, p = 0.07). Mechanical thrombectomy in addition to intravenous thrombolysis also was not associated with an increased risk of acute symptomatic seizures, as the same number of patients suffered from seizures in the treatment and control group (both n = 17; 1.7%, p = 1). In a large population-based stroke registry, the frequency of clinically apparent acute symptomatic seizures was not increased in patients who received either intravenous thrombolysis alone or in conjunction with mechanical thrombectomy.
Zöllner, Johann Philipp ; Misselwitz, Björn ; Kaps, Manfred ; Stein, Marco ; Konczalla, Jürgen ; Roth, Christian ; Krakow, Karsten ; Steinmetz, Helmuth ; Rosenow, Felix ; Strzelczyk, Adam
The National Institutes of Health Stroke Scale (NIHSS) score is the most frequently used score worldwide for assessing the clinical severity of a stroke. Prior research suggested an association between acute symptomatic seizures after stroke and poorer outcome. We determined the frequency of acute seizures after ischemic stroke in a large population-based registry in a central European region between 2004 and 2016 and identified risk factors for acute seizures in univariate and multivariate analyses. Additionally, we determined the influence of seizures on morbidity and mortality in a matched case–control design. Our analysis of 135,117 cases demonstrated a seizure frequency of 1.3%. Seizure risk was 0.6% with an NIHSS score at admission <3 points and increased up to 7.0% with >31 score points. Seizure risk was significantly higher in the presence of acute non-neurological infections (odds ratio: 3.4; 95% confidence interval: 2.8–4.1). A lower premorbid functional level also significantly increased seizure risk (OR: 1.7; 95%CI: 1.4–2.0). Mortality in patients with acute symptomatic seizures was almost doubled when compared to controls matched for age, gender, and stroke severity. Acute symptomatic seizures increase morbidity and mortality in ischemic stroke. Their odds increase with a higher NIHSS score at admission.
A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)
(2020)
Zöllner, Johann Philipp ; Franz, David Neal ; Hertzberg, Christoph ; Nabbout, Rima ; Rosenow, Felix ; Sauter, Matthias ; Schubert-Bast, Susanne ; Wiemer-Kruel, Adelheid ; Strzelczyk, Adam
Objective: This review will summarize current knowledge on the burden of illness (BOI) in tuberous sclerosis complex (TSC), a multisystem genetic disorder manifesting with hamartomas throughout the body, including mainly the kidneys, brain, skin, eyes, heart, and lungs.
Methods: We performed a systematic analysis of the available literature on BOI in TSC according to the PRISMA guidelines. All studies irrespective of participant age that reported on individual and societal measures of disease burden (e.g. health care resource use, costs, quality of life) were included.
Results: We identified 33 studies reporting BOI in TSC patients. Most studies (21) reported health care resource use, while 14 studies reported quality of life and 10 studies mentioned costs associated with TSC. Only eight research papers reported caregiver BOI. Substantial BOI occurs from most manifestations of the disorder, particularly from pharmacoresistant epilepsy, neuropsychiatric, renal and skin manifestations. While less frequent, pulmonary complications also lead to a high individual BOI. The range for the mean annual direct costs varied widely between 424 and 98,008 International Dollar purchasing power parities (PPP-$). Brain surgery, end-stage renal disease with dialysis, and pulmonary complications all incur particularly high costs. There is a dearth of information regarding indirect costs in TSC. Mortality overall is increased compared to general population; and most TSC related deaths occur as a result of complications from seizures as well as renal complications. Long term studies report mortality between 4.8 and 8.3% for a follow-up of 8 to 17.4 years.
Conclusions: TSC patients and their caregivers have a high burden of illness, and TSC patients incur high costs in health care systems. At the same time, the provision of inadequate treatment that does not adhere to published guidelines is common and centralized TSC care is received by no more than half of individuals who need it, especially adults. Further studies focusing on the cost effectiveness and BOI outcomes of coordinated TSC care as well as of new treatment options such as mTOR inhibitors are necessary.
This Dissertation deals with the development of FAIR-relevant X-ray diagnostics based on the interaction of lasers and particle beams with matter. The associated experimental methods are supposed to be employed in the HIHEX-experiments in the HHT-cave of the GSI Helmholtz Center for Heavy-Ion Research GmbH (GSI) in Phase-0 and in the APPA-cave at the Facility for Antiproton and Ion Research in Darmstadt, Germany.
Diagnostic of high aerial density targets that will be used in FAIR experiments demands intense and highly penetrating X-ray sources. Laser generated well-directe relativistic electron beams that interact with high Z materials is an excellent tool for generation of short-pulse high luminous sources of MeV-gammas.
In pilot experiments carried out at the PHELIX laser system, GSI Darmstadt, relativistic electrons were produced in a long scale plasma of near critical electron density (NCD) by the mechanism of the direct laser acceleration (DLA). Low density polymer foam layers preionised by a well-defined nanosecond laser pulse were used as NCD targets. The analysis of the measured electron spectra showed up to 10- fold increase of the electron "temperature" from T_Hot = 1–2 MeV, measured for the case of the interaction of 1–2 ×10^19 Wcm^(−2) ps-laser pulse with a planar foil, up to 14 MeV for the case when the relativistic laser pulse propagates through the by a ns-pulse preionised foam layer. In this case, up to 80–90 MeV electron energy was registered. An increase of the electron energy was accompanied by a strong increase of the number of relativistic electrons and well-defined directionality of the relativistic electron beam measured to be (12 ±1)° (FWHM). This directionality increases the gamma flux on target by far compared to the soft X-ray sources.
Additionally to laser based active diagnostics, passive techniques involving inherent X-ray fluorescence radiation of projectile and target emitted during heavy-ion target interaction can be used to measure the ion beam distribution on shot. This information is of great importance, since the target size is chosen to be smaller than the beam focus in order to ensure homogeneous heating of the HIHEX-target by the ion beam. High amounts of parasitic radiation and activation of experimental equipment is expected for experiments at the APPA-cave. For this reason, all electronic devices must be placed at a safe distance to the target chamber. In order to transport the signal over a large distance, the X-ray image of the target irradiated by heavy-ions has to be converted into an optical one.
For these purposes, the X-ray Conversion to Optical radiation and Transport (XCOT)-system was developed in the frame of a BMBF-project and commissioned in two beamtimes at the UNILAC, GSI during this work.
In experiments, we observed intense radiation of target atoms (K-shell transitions in Cu at 8–8.3 keV and L-shell transition in Ta) ionised in collisions with heavy ions as well as Doppler-shifted L-shell transitions of Au-projectiles passing through targets. This radiation can be used for monochromatic (dispersive elements like bent crystals) or polychromatic (pinhole) 2D X-ray mapping of the ion beam intensity distribution in the interaction region during the beam-target interaction. We measured the efficiency of the X-ray photon production depending on the target thickness and the number of ions passing through the target. The spatial resolution of the XCOT-system based on the multi-pinhole camera was measured to be (91±17) μm for the image magnification factor M = 2. It was considerably improved by application of a toroidally bent quartz crystal and reached 30 μm at M = 6. This resolution is optimal to image the distribution of a 1mm in diameter ion beam. As next step, the XCOT-system will be tested during the SIS18 beam-time at the HHT-experimental area.
The purpose of this study was to identify distinctive mental health profiles for industrial psychologists based on the Mental Health Continuum. Further, it aimed to determine how these profiles differ with respect to work-role fit, meaningfulness and work engagement. It also aimed to investigate whether industrial psychologists within managerial or specialist differ in respect of different types of mental health. An online cross-sectional survey design was employed to draw a census sample (n = 274) from all South African industrial psychologists. A biographical questionnaire, the Work-Role Fit Scale, the Psychological Meaningfulness Scale, the Work Engagement Scale, and the Mental Health Continuum–Short Form were administered. Descriptive statistics, correlations, latent profile analysis, MANOVAs and ANOVAs were computed. Three mental health profiles for industrial psychologists were identified: languishing, moderately mentally healthy and flourishing. Significant differences between the three mental health profiles and experiences of meaningful work-role fit and work engagement were found, but not between experiences of managerial roles. The results show that individuals with different mental health profiles, experience work and its related outcomes, differently. Therefore, in order to enhance meaningful work-role fit and work engagement of industrial psychologists, a one-size-fits-all model may not be appropriate.