Measurement of the charged pion mass using X-ray spectroscopy of exotic atoms

The $5g-4f$ transitions in pionic nitrogen and muonic oxygen were measured simultaneously by using a gaseous nitrogen-oxygen mixture at 1.4\,bar. Due to the precise knowledge of the muon mass the muonic line provides the energy calibration for the pionic transition. A value of (139.57077\,$\pm$\,0.00018)\,MeV/c$^{2}$ ($\pm$\,1.3ppm) is derived for the mass of the negatively charged pion, which is 4.2ppm larger than the present world average

Age-related macular degeneration: suitability of optogenetic therapy for geographic atrophy

Age-related macular degeneration (AMD) is a growing public health concern given the aging population and it is the leading cause of blindness in developed countries, affecting individuals over the age of 55 years. AMD affects the retinal pigment epithelium (RPE) and Bruch’s membrane in the macula, leading to secondary photoreceptor degeneration and eventual loss of central vision. Late AMD is divided into two forms: neovascular AMD and geographic atrophy (GA). GA accounts for around 60% of late AMD and has been the most challenging subtype to treat. Recent advances include approval of new intravitreally administered therapeutics, pegcetacoplan (Syfovre) and avacincaptad pegol (Iveric Bio), which target complement factors C3 and C5, respectively, which slow down the rate of enlargement of the area of atrophy. However, there is currently no treatment to reverse the central vision loss associated with GA. Optogenetics may provide a strategy for rescuing visual function in GA by imparting light-sensitivity to the surviving inner retina (i.e., retinal ganglion cells or bipolar cells). It takes advantage of residual inner retinal architecture to transmit visual stimuli along the visual pathway, while a wide range of photosensitive proteins are available for consideration. Herein, we review the anatomical changes in GA, discuss the suitability of optogenetic therapeutic sensors in different target cells in pre-clinical models, and consider the advantages and disadvantages of different routes of administration of therapeutic vectors

Sixfold improved single particle measurement of the magnetic moment of the antiproton

Our current understanding of the Universe comes, among others, from particle physics and cosmology. In particle physics an almost perfect symmetry between matter and antimatter exists. On cosmological scales, however, a striking matter/antimatter imbalance is observed. This contradiction inspires comparisons of the fundamental properties of particles and antiparticles with high precision. Here we report on a measurement of the g-factor of the antiproton with a fractional precision of 0.8 parts per million at 95% confidence level. Our value /2=2.7928465(23) outperforms the previous best measurement by a factor of 6. The result is consistent with our proton g-factor measurement gp/2=2.792847350(9), and therefore agrees with the fundamental charge, parity, time (CPT) invariance of the Standard Model of particle physics. Additionally, our result improves coefficients of the standard model extension which discusses the sensitivity of experiments with respect to CPT violation by up to a factor of 20.EU/ERC/290870-MEFUCOMax-Planck SocietyHelmholtz-GemeinschaftRIKEN Initiative Research Unit ProgramRIKEN President FundingRIKEN Pioneering Project FundingRIKEN FPR FundingRIKEN JRA ProgramMEXT/24000008Max-Planck SocietyEU/ERC Advanced Grant/290870-MEFUCOHelmholtz-GemeinschaftCERN-fellowship program

Unique and conserved MicroRNAs in wheat chromosome 5D revealed by next-generation sequencing

MicroRNAs are a class of short, non-coding, single-stranded RNAs that act as post-transcriptional regulators in gene expression. miRNA analysis of Triticum aestivum chromosome 5D was performed on 454 GS FLX Titanium sequences of flow sorted chromosome 5D with a total of 3,208,630 good quality reads representing 1.34x and 1.61x coverage of the short (5DS) and long (5DL) arms of the chromosome respectively. In silico and structural analyses revealed a total of 55 miRNAs; 48 and 42 miRNAs were found to be present on 5DL and 5DS respectively, of which 35 were common to both chromosome arms, while 13 miRNAs were specific to 5DL and 7 miRNAs were specific to 5DS. In total, 14 of the predicted miRNAs were identified in wheat for the first time. Representation (the copy number of each miRNA) was also found to be higher in 5DL (1,949) compared to 5DS (1,191). Targets were predicted for each miRNA, while expression analysis gave evidence of expression for 6 out of 55 miRNAs. Occurrences of the same miRNAs were also found in Brachypodium distachyon and Oryza sativa genome sequences to identify syntenic miRNA coding sequences. Based on this analysis, two other miRNAs: miR1133 and miR167 were detected in B. distachyon syntenic region of wheat 5DS. Five of the predicted miRNA coding regions (miR6220, miR5070, miR169, miR5085, miR2118) were experimentally verified to be located to the 5D chromosome and three of them : miR2118, miR169 and miR5085, were shown to be 5D specific. Furthermore miR2118 was shown to be expressed in Chinese Spring adult leaves. miRNA genes identified in this study will expand our understanding of gene regulation in bread wheat

Improved limit on the directly measured antiproton lifetime

Continuous monitoring of a cloud of antiprotons stored in a Penning trap for 405 days enables us to set an improved limit on the directly measured antiproton lifetime. From our measurements we extract a storage time of 3.15x108 equivalent antiproton-seconds, resulting in a lower lifetime limit of Tp > 10.2,a with a confidence level of 68%. This result improves the limit on charge-parity-time violation in antiproton decays based on direct observation by a factor of 7

Atomoxetine and citalopram alter brain network organization in Parkinson's disease.

Parkinson's disease has multiple detrimental effects on motor and cognitive systems in the brain. In contrast to motor deficits, cognitive impairments in Parkinson's disease are usually not ameliorated, and can even be worsened, by dopaminergic treatments. Recent evidence has shown potential benefits from restoring other neurotransmitter deficits, including noradrenergic and serotonergic transmission. Here, we study global and regional brain network organization using task-free imaging (also known as resting-state), which minimizes performance confounds and the bias towards predetermined networks. Thirty-three patients with idiopathic Parkinson's disease were studied three times in a double-blinded, placebo-controlled counter-balanced crossover design, following placebo, 40 mg oral atomoxetine (selective noradrenaline reuptake inhibitor) or 30 mg oral citalopram (selective serotonin reuptake inhibitor). Neuropsychological assessments were performed outside the scanner. Seventy-six controls were scanned without medication to provide normative data for comparison to the patient cohort. Graph theoretical analysis of task-free brain connectivity, with a random 500-node parcellation, was used to measure the effect of disease in placebo-treated state (versus unmedicated controls) and pharmacological intervention (drug versus placebo). Relative to controls, patients on placebo had executive impairments (reduced fluency and inhibitory control), which was reflected in dysfunctional network dynamics in terms of reduced clustering coefficient, hub degree and hub centrality. In patients, atomoxetine improved fluency in proportion to plasma concentration (P = 0.006, r 2 = 0.24), and improved response inhibition in proportion to increased hub Eigen centrality (P = 0.044, r 2 = 0.14). Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering (P = 0.01, r 2 = 0.22), modularity (P = 0.043, r 2 = 0.14) and path length (P = 0.006, r 2 = 0.25) increased in patients with milder forms of Parkinson's disease, but decreased in patients with more advanced disease (Unified Parkinson's Disease Rating Scale motor subscale part III > 30). This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. We propose that hub connectivity contributes to cognitive performance in Parkinson's disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function

Perspectives on weak interactions in complex materials at different length scales

Nanocomposite materials consist of nanometer-sized quantum objects such as atoms, molecules, voids or nanoparticles embedded in a host material. These quantum objects can be exploited as a super-structure, which can be designed to create material properties targeted for specific applications. For electromagnetism, such targeted properties include field enhancements around the bandgap of a semiconductor used for solar cells, directional decay in topological insulators, high kinetic inductance in superconducting circuits, and many more. Despite very different application areas, all of these properties are united by the common aim of exploiting collective interaction effects between quantum objects. The literature on the topic spreads over very many different disciplines and scientific communities. In this review, we present a cross-disciplinary overview of different approaches for the creation, analysis and theoretical description of nanocomposites with applications related to electromagnetic properties

Fibroblast activation protein-α expression in fibroblasts is common in the tumor microenvironment of colorectal cancer and may serve as a therapeutic target

Background: Colorectal cancer (CRC) is still one of the leading causes of cancer death worldwide, emphasizing the need for further diagnostic and therapeutic approaches. Cancer invasion and metastasis are affected by the tumor microenvironment (TME), with cancer-associated fibroblasts (CAF) being the predominant cellular component. An important marker for CAF is fibroblast activation protein-α (FAP) which has been evaluated as therapeutic target for, e.g., radioligand therapy. The aim of this study was to examine CRC regarding the FAP expression as a candidate for targeted therapy.Methods: 67 CRC, 24 adenomas, 18 tissue samples of inflammation sites and 28 non-neoplastic, non-inflammatory tissue samples of colonic mucosa were evaluated for immunohistochemical FAP expression of CAF in tissue microarrays. The results were correlated with clinicopathological data, tumor biology and concurrent expression of additional immunohistochemical parameters.Results: 53/67 (79%) CRC and 6/18 (33%) inflammatory tissue specimens showed expression of FAP. However, FAP was only present in 1/24 (4%) adenomas and absent in normal mucosa (0/28). Thus, FAP expression in CRC was significantly higher than in the other investigated groups. Within the CRC cohort, expression of FAP did not correlate with tumor stage, grading or the MSI status. However, it was observed that tumors exhibiting high immunohistochemical expression of Ki-67, CD3, p53, and β-Catenin showed a significantly higher incidence of FAP expression.Conclusion: In the crosstalk between tumor cells and TME, CAF play a key role in carcinogenesis and metastatic spread. Expression of FAP was detectable in the majority of CRC but nearly absent in precursor lesions and non-neoplastic, non-inflammatory tissue. This finding indicates that FAP has the potential to emerge as a target for new diagnostic and therapeutic concepts in CRC. Additionally, the association between FAP expression and other immunohistochemical parameters displays the interaction between different components of the TME and demands further investigation

Perspectives on weak interactions in complex materials at different length scales

Nanocomposite materials consist of nanometer-sized quantum objects such as atoms, molecules, voids or nanoparticles embedded in a host material. These quantum objects can be exploited as a super-structure, which can be designed to create material properties targeted for specific applications. For electromagnetism, such targeted properties include field enhancements around the bandgap of a semiconductor used for solar cells, directional decay in topological insulators, high kinetic inductance in superconducting circuits, and many more. Despite very different application areas, all of these properties are united by the common aim of exploiting collective interaction effects between quantum objects. The literature on the topic spreads over very many different disciplines and scientific communities. In this review, we present a cross-disciplinary overview of different approaches for the creation, analysis and theoretical description of nanocomposites with applications related to electromagnetic properties