Measurement of the α-Particle Monopole Transition Form Factor Challenges Theory: A Low-Energy Puzzle for Nuclear Forces?

We perform a systematic study of the α-particle excitation from its ground state 0_{1}^{+} to the 0_{2}^{+} resonance. The so-called monopole transition form factor is investigated via an electron scattering experiment in a broad Q^{2} range (from 0.5 to 5.0 fm^{-2}). The precision of the new data dramatically supersedes that of older sets of data, each covering only a portion of the Q^{2} range. The new data allow the determination of two coefficients in a low-momentum expansion, leading to a new puzzle. By confronting experiment to state-of-the-art theoretical calculations, we observe that modern nuclear forces, including those derived within chiral effective field theory that are well tested on a variety of observables, fail to reproduce the excitation of the α particle.

Toggle-like current-induced Bloch point dynamics of 3D skyrmion strings in a room temperature nanowire.

Research into practical applications of magnetic skyrmions, nanoscale solitons with interesting topological and transport properties, has traditionally focused on two dimensional (2D) thin-film systems. However, the recent observation of novel three dimensional (3D) skyrmion-like structures, such as hopfions, skyrmion strings (SkS), skyrmion bundles, and skyrmion braids, motivates the investigation of new designs, aiming to exploit the third spatial dimension for more compact and higher performance spintronic devices in 3D or curvilinear geometries. A crucial requirement of such device schemes is the control of the 3D magnetic structures via charge or spin currents, which has yet to be experimentally observed. In this work, we utilise real-space imaging to investigate the dynamics of a 3D SkS within a nanowire of Co8Zn9Mn3 at room temperature. Utilising single current pulses, we demonstrate current-induced nucleation of a single SkS, and a toggle-like positional switching of an individual Bloch point at the end of a SkS. The observations highlight the possibility to locally manipulate 3D topological spin textures, opening up a range of design concepts for future 3D spintronic devices.

The impact of accuracy and precision of analytical test methods on the determination of withdrawal periods.

Treatment of food-producing animals with veterinary medicinal products (VMPs) can result in residues in foodstuffs (e.g. eggs, meat, milk, or honey) representing a potential consumer health risk. To ensure consumer safety, worldwide regulatory concepts for setting safe limits for residues of VMPs e.g. as tolerances (US) or maximum residue limits (MRLs, EU) are used. Based on these limits so-called withdrawal periods (WP) are determined. A WP represents the minimum period of time required between the last administration of the VMP and the marketing of foodstuff. Usually, WPs are estimated using regression analysis based on residue studies. With high statistical confidence (usually 95% in the EU and 99% in the US) the residues in almost all treated animals (usually 95%) have to be below MRL when edible produce is harvested. Here, uncertainties from both sampling and biological variability are taken into account but uncertainties of measurement associated with the analytical test methods are not systematically considered. This paper describes a simulation experiment to investigate the extent to which relevant sources of measurement uncertainty (accuracy and precision) can impact the length of WPs. A set of real residue depletion data was artificially 'contaminated' with measurement uncertainty related to permitted ranges for accuracy and precision. The results show that both accuracy and precision had a noticeable effect on the overall WP. Due consideration of sources of measurement uncertainty may improve the robustness, quality and reliability of calculations upon which regulatory decisions on consumer safety of residues are based.

Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil.

Soil ecosystems harbor diverse microorganisms and yet remain only partially characterized as neither single-cell sequencing nor whole-community sequencing offers a complete picture of these complex communities. Thus, the genetic and metabolic potential of this "uncultivated majority" remains underexplored. To address these challenges, we applied a pooled-cell-sorting-based mini-metagenomics approach and compared the results to bulk metagenomics. Informatic binning of these data produced 200 mini-metagenome assembled genomes (sorted-MAGs) and 29 bulk metagenome assembled genomes (MAGs). The sorted and bulk MAGs increased the known phylogenetic diversity of soil taxa by 7.2% with respect to the Joint Genome Institute IMG/M database and showed clade-specific sequence recruitment patterns across diverse terrestrial soil metagenomes. Additionally, sorted-MAGs expanded the rare biosphere not captured through MAGs from bulk sequences, exemplified through phylogenetic and functional analyses of members of the phylum Bacteroidetes Analysis of 67 Bacteroidetes sorted-MAGs showed conserved patterns of carbon metabolism across four clades. These results indicate that mini-metagenomics enables genome-resolved investigation of predicted metabolism and demonstrates the utility of combining metagenomics methods to tap into the diversity of heterogeneous microbial assemblages.IMPORTANCE Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented Bacteroidetes phylum provided insights into conserved and clade-specific patterns of carbon metabolism.

New Insight in the Q

Virtual Compton scattering on the proton has been investigated at three yet unexplored values of the four-momentum transfer Q^{2}: 0.10, 0.20, and 0.45 GeV^{2}, at the Mainz Microtron. Fits performed using either the low-energy theorem or dispersion relations allowed the extraction of the structure functions P_{LL}-P_{TT}/ε and P_{LT}, as well as the electric and magnetic generalized polarizabilities α_{E1}(Q^{2}) and ß_{M1}(Q^{2}). These new results show a smooth and rapid falloff of α_{E1}(Q^{2}), in contrast to previous measurements at Q^{2}=0.33 GeV^{2}, and provide for the first time a precise mapping of ß_{M1}(Q^{2}) in the low-Q^{2} region.

First Measurement of the Q

We report on the first Q^{2}-dependent measurement of the beam-normal single spin asymmetry A_{n} in the elastic scattering of 570 MeV vertically polarized electrons off ^{12}C. We cover the Q^{2} range between 0.02 and 0.05 GeV^{2}/c^{2} and determine A_{n} at four different Q^{2} values. The experimental results are compared to a theoretical calculation that relates A_{n} to the imaginary part of the two-photon exchange amplitude. The result emphasizes that the Q^{2} behavior of A_{n} given by the ratio of the Compton to charge form factors cannot be treated independently of the target nucleus.

Flexible enzymatic activation of artificial polyketide extender units by Streptomyces cinnamonensis into the monensin biosynthetic pathway.

Streptomyces cinnamonensis A495 is a variant of the monensin producer which instead of the native polyether antibiotic gives rise to antibiotic and anti-tumour shunt-product premonensin. Through the supplementation of the fermentation medium with suitable precursors, premonensin can be derivatized via the incorporation of new-to-nature extender units into the biosynthetic machinery. Polyketide extender units require activation, typically in form of coenzyme A-thioesters. These are membrane impermeable and thus in the past an artificial mimic was employed. Here, we show the use and preliminary characterization of a highly substrate promiscuous new enzyme for the endogenous thioester formation in a Streptomyces strain. These intracellularly activated alternative extender units are significantly better incorporated into premonensin than the synthetically activated counterparts. SIGNIFICANCE AND IMPACT OF THE STUDY: Polyketide natural products are of enormous relevance in medicine. The hit-rate in finding active compounds for the potential treatment of various diseases among this substance family of microbial origin is high. However, most polyketides require derivatization to render them suitable for the application. Of relevance in this field is the incorporation of artificial substances into the biogenesis of polyketides, hampered by both the microbial metabolism and the complexity of the enzymes involved. This manuscript describes the straightforward and selective biosynthetic incorporation of synthetic substances into a reduced polyketide and showcases a promising new enzyme to aid this purpose.

Beam-Recoil Polarization Measurement of π

The helicity-dependent recoil proton polarizations P_{x}^{'} and P_{z}^{'} as well as the helicity-independent component P_{y} have been measured in the p(e[over →],e^{'}p[over →])π^{0} reaction at four-momentum transfer Q^{2}≃0.1 GeV^{2}, center-of-mass proton emission angle θ_{p}^{*}≃90°, and invariant mass W≃1440 MeV. This first precise measurement of double-polarization observables in the energy domain of the Roper resonance P_{11}(1440) by exploiting recoil polarimetry has allowed for the extraction of its scalar electroexcitation amplitude at an unprecedentedly low value of Q^{2}, establishing a powerful instrument for probing the interplay of quark and meson degrees of freedom in the nucleon.

Biosynthesis-driven structure-activity relationship study of premonensin-derivatives.

The controlled derivatization of natural products is of great importance for their use in drug discovery. The ideally rapid generation of compound libraries for structure-activity relationship studies is of particular concern. We here use modified biosynthesis for the generation of such a library of reduced polyketides to interfere with the oncogenic KRas pathway. The polyketide is derivatized via side chain alteration, and variations in its redox pattern and in its backbone chain length through manipulation in the corresponding polyketide synthase. Structural and biophysical analyses revealed the nature of the interaction between the polyketides and KRas-interacting protein PDE6δ. Non-natural polyketides with low nanomolar affinity to PDE6δ were identified.

Effective PEGylation of gold nanorods.

Standard procedures to coat gold nanorods (AuNR) with poly(ethylene glycol) (PEG)-based ligands are not reliable and high PEG-grafting densities are not achieved. In this work, the ligand exchange of AuNR with PEGMUA, a tailored PEG-ligand bearing a C10 alkylene spacer, is studied. PEGMUA provides AuNR with very high stability against oxidative etching with cyanide. This etching reaction is utilized to study the ligand exchange in detail. Ligand exchange is faster, less ligand consuming and more reproducible with assisting chloroform extraction. Compared to PEG ligands commonly used, PEGMUA provides much higher colloidal and chemical stability. Further analyses based on NMR-, IR- and UV/Vis-spectroscopy reveal that significantly higher PEG-grafting densities, up to ∼3 nm(-2), are obtained with PEGMUA. This demonstrates how the molecular structure of the PEG ligand can be used to dramatically improve the ligand exchange and to synthesize PEGylated AuNR with high chemical and colloidal stability and high PEG grafting densities. Such AuNR are especially interesting for applications in nanomedicine.

Observation of Λ(4)H Hyperhydrogen by Decay-Pion Spectroscopy in Electron Scattering.

At the Mainz Microtron MAMI, the first high-resolution pion spectroscopy from decays of strange systems was performed by electron scattering off a (9)Be target in order to study the Λ binding energy of light hypernuclei. Positively charged kaons were detected by a short-orbit spectrometer with a broad momentum acceptance at 0° forward angles with respect to the beam, efficiently tagging the production of strangeness in the target nucleus. Coincidentally, negatively charged decay pions were detected by two independent high-resolution spectrometers. About 10(3) pionic weak decays of hyperfragments and hyperons were observed. The pion momentum distribution shows a monochromatic peak at pπ≈133 MeV/c, corresponding to the unique signature for the two-body decay of hyperhydrogen Λ(4)H→(4)He+π(-), stopped inside the target. Its Λ binding energy was determined to be BΛ=2.12±0.01 (stat)±0.09 (syst)MeV with respect to the (3)H+Λ mass.

Search at the Mainz Microtron for light massive gauge bosons relevant for the muon g-2 anomaly.

A massive, but light, Abelian U(1) gauge boson is a well-motivated possible signature of physics beyond the standard model of particle physics. In this Letter, the search for the signal of such a U(1) gauge boson in electron-positron pair production at the spectrometer setup of the A1 Collaboration at the Mainz Microtron is described. Exclusion limits in the mass range of 40 MeV/c^{2} to 300 MeV/c^{2}, with a sensitivity in the squared mixing parameter of as little as ε^{2}=8×10^{-7} are presented. A large fraction of the parameter space has been excluded where the discrepancy of the measured anomalous magnetic moment of the muon with theory might be explained by an additional U(1) gauge boson.

Sensitivity of different generations and developmental stages in studies on reproductive toxicity.

Numerous studies on reproductive toxicity are expected to be necessary under the EU program on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH). Therefore, it is important to analyse existing testing strategies including also the recently implemented extended one-generation reproduction toxicity study (EOGRTS, OECD guideline 443). For this purpose the responsiveness of the different generations and developmental stages in studies on reproductive toxicity is analysed and critical targets of reproductive toxicity are identified by using the Fraunhofer FeDTex database. The F1 generation is identified as most responsive generation in more than 50% of one-generation and multi-generation reproduction studies. Within the F1 generation the adult stage is mostly affected compared to the prenatal or postnatal stage. The target analysis in F1 has revealed alterations in body weight as highly sensitive for all developmental stages. Other important targets are the liver, kidney, testes, prostate, sperm parameters as well as developmental landmarks. The findings in the F2 generation have shown a higher responsiveness than F1 only in 3% of the studies. Although in 29 studies new effects are observed in F2 offspring compared to F1 irrespective of dose levels, overall no severe new effects have emerged that would change classification and labelling and justify an F1 mating. The presented data support the importance of F1 for risk assessment and demonstrate that the study design of the EOGRTS is a suitable alternative to two-generation studies. However, compared to a conventional one-generation study the EOGRTS may identify additional effects but will change risk assessment with respect to NOELs only in rare cases.

Influence of age on the cell biological characteristics and the stimulation potential of male human tenocyte-like cells.

The incidence of rotator cuff tears and recurrent defects positively correlate with patient age. However, this observation has never been analysed at the cellular level. The present study aims to better understand this correlation by investigating cellular characteristics of rotator cuff tenocytes of different age groups. Additionally, previous studies reported on stimulating effects of Bone Morphogenetic Protein (BMP) -2 and BMP-7 on tenocytes. Thus, the second aim was to investigate, whether the stimulation potential of tenocytes demonstrates age-related differences. Tenocyte-like cells from supraspinatus tendons of young and aged patients were analysed for the following cell biological characteristics: cell density, cell growth, marker expression, collagen-I protein synthesis, stem cell phenotype, potential for multipotent differentiation and self-renewal. To analyse the stimulation potential, cells were treated with BMP-2 and BMP-7 in 2D-/3D-cultures. Measured parameters included cell activity, marker expression and collagen-I protein synthesis. An effect of age was seen for cell growth and stem cell potential but not on extracellular matrix level. Cells from both groups responded to BMP-7 by increasing cell activity, collagen-I expression and protein synthesis. BMP-2 led to smaller increases in these parameters when compared to BMP-7. In general, 3D-cultivation improved the stimulation compared to 2D-culture. The cell biological characteristics of tenocyte-like cells, considered important for successful restoration of the tendon-bone unit, were inferior in elderly donors. This may help explain higher rates of recurrent defects seen in elderly patients. Regarding the stimulation potential, on a cellular level young and aged patients may benefit from biological augmentation with BMPs.

[Case report of a rare occupational disease: a during life non-recognised occupational disease--talcosis]. / Fallbericht zu einer seltenen Berufskrankheit: Eine zu Lebzeiten nicht anerkannte Talkose.

Talc is a hydrated magnesium silicate used in the chemical, ceramic, cosmetic, leather, paper and building industries. Interstitial lung disease - talcosis - due to exclusive talc inhalation is a rare form of pneumoconiosis. More often, pulmonary disease due to talc is encountered after intravenous administration of talc during drug abuse. Talc can contain asbestos or quartz particles which induce asbestosis or silicosis. Here we present a case report about a worker who was exposed to talcum during his work in tire manufacturing. During his lifetime an occupational disease was not recognised. The deceased had been forwarded to cremation; the legally prescribed second inspection of the corpse induced the suspicion of an occupational disease and an autopsy was ordered. The autopsy revealed a lung fibrosis with honeycomb lung alterations and under polarised light a massive burden with birefringed crystalline particles could be visualised. Light and electron microscopic lung dust analyses could exclude an elevated asbestos lung burden. The element analysis of foreign body material in lung tissue confirmed its chemical composition of magnesium and silicon which was consistent with talc. Based on the pathological and mineralogical findings, the confirmed occupational exposure towards talc and, due to the exclusion of other possible causes (asbestos, quartz), the diagnose of a talc-induced interstitial lung fibrosis - talcosis - was established. This case emphasises the importance of pathological-anatomic examinations in combination with lung dust analysis to reveal occupational exposure as a cause of an interstitial lung disease.

[Alkaptonuria. Ochronotic arthropathy caused by hereditary metabolic disease]. / Alkaptonurie. Arthropathia ochronotica durch angeborenen Stoffwechseldefekt.

Alkaptonuria is a rare hereditary metabolic disease. We report the case of a 72-year-old woman who suffered from pain and limitation of motion in the major joints and spine since middle age because of osteoarthrosis deformans alkaptonurica.During knee replacement typical black coloration were detected. Early therapy can reduce disease progression but there is no way to heal alkaptonuria.

Cerebellar atrophy following mild head injury in a 4-year-old girl.

Cerebellar atrophy following severe head injury in infants has been described in imaging studies. We report the case of a 4-year-old girl who died of accidental hypothermia. Three weeks before, she had sustained head injury after falling on the back of her head with linear fracture of the occipital bone. Neuropathological examination of the girl's brain revealed cerebellar atrophy with specific loss of Purkinje cells. We present findings of detailed neuropathological studies and discuss possible mechanisms of posttraumatic cerebellar atrophy. To the best of our knowledge, cerebellar atrophy following mild head injury in man has not been described morphologically so far.