Both the 1S-2S transition and the ground state hyperfine spectrum have been observed in trapped antihydrogen. The former constitutes the first observation of resonant interaction of light with an ...anti-atom, and the latter is the first detailed measurement of a spectral feature in antihydrogen. Owing to the narrow intrinsic linewidth of the 1S-2S transition and use of two-photon laser excitation, the transition energy can be precisely determined in both hydrogen and antihydrogen, allowing a direct comparison as a test of fundamental symmetry. The result is consistent with CPT invariance at a relative precision of around 2×10−10. This constitutes the most precise measurement of a property of antihydrogen. The hyperfine spectrum of antihydrogen is determined to a relative uncertainty of 4×10−4. The excited state and the hyperfine spectroscopy techniques currently both show sensitivity at the few 100 kHz level on the absolute scale. Here, the most recent work of the ALPHA collaboration on precision spectroscopy of antihydrogen is presented together with an outlook on improving the precision of measurements involving lasers and microwave radiation. Prospects of measuring the Lamb shift and determining the antiproton charge radius in trapped antihydrogen in the ALPHA apparatus are presented. Future perspectives of precision measurements of trapped antihydrogen in the ALPHA apparatus when the ELENA facility becomes available to experiments at CERN are discussed.
This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.
Thymidine Kinase 1 (TK1) plays an important role in DNA precursor synthesis and serum TK1 activity has been used as a biomarker for prognosis and therapy monitoring of different malignancies. AroCell ...has developed a dual monoclonal antibody ELISA for determination of TK1 protein in clinical samples. The purpose of the study is to validate the ELISA analytically in relation to the gold standard,
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H-deoxythymidine (dThd) phosphorylation assay for TK1 activity using sera from patients with different malignancies. The colorimetric TK 210 ELISA was validated analytically by assessment of precision, linearity, interfering substances, and stability. For the clinical validation, serum samples from patients with hematological malignancies (n = 100), breast cancer (n = 56), prostate cancer (n = 70) and blood donors (n = 159) were analyzed using TK 210 ELISA and TK1 activity by
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H-deoxythymidine (dThd) phosphorylation assay. The sandwich TK 210 ELISA was highly specific for TK1 protein having a detection limit of 0.12 ng/mL, with a functional sensitivity of 0.25 ng/mL. Within-run CVs ranged from 5.5% to 10% and between-run CVs ranged from 5% to 15%. The ratio of observed to expected dilutional parallelism of 5 serum samples was in the range of 80–120%. Samples exhibited stability through four freeze/thaw cycles and 5 days at 4°C. Further, the ROC curve analysis showed that TK 210 ELISA and
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H-dThd phosphorylation assay had similar sensitivity (62% vs 59%) in hematological malignancies. However, in the case of breast and prostate cancer sera, TK 210 ELISA had higher sensitivity (59% and 44%) compared to
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H-dThd phosphorylation assay (47% and 25%) at a specificity of 98%. These data demonstrate that the dual monoclonal antibody based AroCell TK 210 ELISA is a robust, accurate and precise tool for measuring TK1 protein in different malignancies that can improve the clinical applications of TK1 as a biomarker in cancer management.
Background
Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.
Objective
All‐cause mortality after hip fracture was investigated to assess its ...magnitude.
Methods
A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time‐dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random‐effects meta‐analysis.
Results
Hip fracture was positively associated with increased all‐cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76–2.57, after adjusting for potential confounders. This association was stronger amongst men HR: 2.39, 95% CI: 1.72–3.31 than amongst women HR: 1.92, 95% CI: 1.54–2.39, although this difference was not significant. Mortality was higher during the first year after the hip fracture HR: 2.78, 95% CI: 2.12–3.64, but it remained elevated without major fluctuations after longer time since hip fracture HR (95% CI): 1.89 (1.50–2.37) after 1–4 years; 2.15 (1.81–2.55) after 4–8 years; 1.79 (1.57–2.05) after 8 or more years.
Conclusion
In this large population‐based sample of older persons across eight cohorts, hip fracture was associated with excess short‐ and long‐term all‐cause mortality in both sexes.
Background and purpose
Methcathinone abuse is a new cause of manganism. The psychostimulant is prepared from pseudoephedrine using potassium permanganate as an oxidant. We describe the clinical, ...biological, neuroimaging characteristics and follow‐up results in a large Estonian cohort of intravenous methcathinone users.
Methods
During 2006–2012 we studied 38 methcathinone abusers with a mean age of 33 years. Subjects were rated by the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (HY), and Schwab and England (SE) rating scales. Twenty‐four cases were reassessed 9–70 (20 ± 15) months after the initial evaluation. Manganese (Mn) in plasma and hair was analysed by inductively coupled plasma‐atom emission spectrometry. Magnetic resonance imaging (MRI) was performed in 11, and single‐photon emission computed tomography (SPECT) with iodobenzamide (IBZM) in eight subjects.
Results
The average total UPDRS score was 43 ± 21. The most severely affected domains in UPDRS Part III were speech and postural stability, the least affected domain was resting tremor. At follow‐up there was worsening of HY and SE rating scales. Subjects had a higher mean level of Mn in hair (2.9 ± 3.8 ppm) than controls (0.82 ± 1.02 ppm), P = 0.02. Plasma Mn concentrations were higher (11.5 ± 6.2 ppb) in active than in former users (5.6 ± 1.8 ppb), P = 0.006. Active methcathinone users had increased MRI T1‐signal intensity in the globus pallidus, substantia nigra and periaquaductal gray matter. IBZM‐SPECT showed normal symmetric tracer uptake in striatum.
Conclusion
Methcathinone abusers develop a distinctive hypokinetic syndrome. Though the biomarkers of Mn exposure are characteristic only of recent abuse, the syndrome is not reversible.
The European Astronaut Centre (EAC) is currently constructing the European Lunar Exploration Laboratory (LUNA), a large training and operations facility to be located adjacent to EAC at the DLR ...(German Aerospace Centre) campus in Cologne, Germany. With an estimated representative lunar testbed area of approximately 660 m
, a large volume of lunar regolith simulant material is needed for this purpose. In this study, a basanitic sandy silt from a quarry located in the Siebengebirge Volcanic Field is evaluated as a large-volume source of material. The focus of this project has been to conduct a physical and chemical characterisation of the fine-grained material to be used in LUNA; the European Astronaut Centre lunar regolith simulant 1 (EAC-1 A). The physical characterisation tests undertaken include sphericity, density measurements, cohesion and static angle of repose, with mineralogical investigations via petrographical analysis with optical microscope and SEM, XRF, XRD and DSC measurements. The results of the EAC-1A tests are compared to published data on existing widely used lunar regolith simulants, namely JSC-1A, JSC-2A, NU-LHT-3M, DNA and FJS-1.
Magnetic reconnection is believed to be the main driver to transport solar wind into the Earth's magnetosphere when the magnetopause features a large magnetic shear. However, even when the magnetic ...shear is too small for spontaneous reconnection, the Kelvin-Helmholtz instability driven by a super-Alfvénic velocity shear is expected to facilitate the transport. Although previous kinetic simulations have demonstrated that the non-linear vortex flows from the Kelvin-Helmholtz instability gives rise to vortex-induced reconnection and resulting plasma transport, the system sizes of these simulations were too small to allow the reconnection to evolve much beyond the electron scale as recently observed by the Magnetospheric Multiscale (MMS) spacecraft. Here, based on a large-scale kinetic simulation and its comparison with MMS observations, we show for the first time that ion-scale jets from vortex-induced reconnection rapidly decay through self-generated turbulence, leading to a mass transfer rate nearly one order higher than previous expectations for the Kelvin-Helmholtz instability.
The hot topic of genetic modification and genome editing is sometimes presented as a rapid solution to various problems in the field of animal breeding and genetics. These technologies hold potential ...for future use in agriculture but we need to be aware of difficulties in large-scale application and integration in breeding schemes. In this review, we discuss applications of both classical genetic modifications (GM) using vectors and genome editing in dairy cattle breeding. We use an interdisciplinary approach considering both ethical and animal breeding perspectives. Decisions on how to make use of these techniques need to be made based not only on what is possible, but on what is reasonable to do. Principles of animal integrity, naturalness, risk perception, and animal welfare issues are examples of ethically relevant factors to consider. These factors also influence public perception and decisions about regulations by authorities. We need to acknowledge that we lack complete understanding of the genetic background of complex traits. It may be difficult, therefore, to predict the full effect of certain modifications in large-scale breeding programs. We present 2 potential applications: genome editing to dispense with dehorning, and insertion of human genes in bovine genomes to improve udder health as an example of classical GM. Both of these cases could be seen as beneficial for animal welfare but they differ in other aspects. In the former case, a genetic variant already present within the species is introduced, whereas in the latter case, transgenic animals are generated—this difference may influence how society regards the applications. We underline that the use of GM, as well as genome editing, of farm animals such as cattle is not independent of the context, and should be considered as part of an entire process, including, for example, the assisted reproduction technology that needs to be used. We propose that breeding organizations and breeding companies should take an active role in ethical discussions about the use of these techniques and thereby signal to society that these questions are being responsibly addressed.
Knowledge of the structure of amorphous solids can direct, for example, the optimization of pharmaceutical formulations, but atomic-level structure determination in amorphous molecular solids has so ...far not been possible. Solid-state nuclear magnetic resonance (NMR) is among the most popular methods to characterize amorphous materials, and molecular dynamics (MD) simulations can help describe the structure of disordered materials. However, directly relating MD to NMR experiments in molecular solids has been out of reach until now because of the large size of these simulations. Here, using a machine learning model of chemical shifts, we determine the atomic-level structure of the hydrated amorphous drug AZD5718 by combining dynamic nuclear polarization-enhanced solid-state NMR experiments with predicted chemical shifts for MD simulations of large systems. From these amorphous structures we then identify H-bonding motifs and relate them to local intermolecular complex formation energies.
Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain ...important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors.
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