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.

Excretion kinetics of 1,3-dichlorobenzene and its urinary metabolites after controlled airborne exposure in human volunteers.

The solvent 1,3-dichlorobenzene (1,3-DCB) is formed during thermal decomposition of the initiator 2,4-dichlorobenzoylperoxide in the production of silicone rubber with potential exposure of production workers as shown in previous works. Despite a threshold limit value (MAK value) of 2 ppm in air, there are currently no data about the corresponding internal exposure that would allow for the derivation of a biological limit value. In the present study, we have investigated the absorption of 1,3-DCB and urinary kinetics of its metabolites in 10 human volunteers after controlled inhalative exposure. Due to the strong odour of 1,3-DCB, a subjective evaluation of odour nuisance was also performed. Ten male human volunteers (23-36 yrs.) were exposed 6 h/day to a concentration of 0.7 ppm and 1.5 ppm in the Aachen workplace simulation laboratory (AWSL) with one week between each experiment. In order to investigate potential dermal absorption, the volunteers were exposed to 1.5 ppm wearing a suitable filter mask that prevented inhalative exposure in a third exposure. 1,3-DCB in blood was measured after 3 and 6 h exposure and the urinary metabolites 3,5-dichlorocatechol (3,5-DCC), 2,4-dichlorophenol (2,4-DCP) and 3,5-dichlorophenol (3,5-DCP) were measured over 24 h after exposure via LC/MS/MS. There were clear dose-response relations for all investigated parameters. The maximum excretion of the metabolites was reached at the end of exposure and corresponded to 5.2 ± 0.7 mg/g crea, 1.5 ± 0.35 mg/g crea and 0.07 ± 0.011 mg/g crea at 0.7 ppm and to 12.0 ± 3 mg/g crea, 3.5 ± 1.1 mg/g crea and 0.17 ± 0.05 mg/g crea at 1.5 ppm for 3,5-DCC, 2,4-DCP and 3,5-DCP, respectively. The use of filter masks decreased the internal exposure for about 85-90%, indicating substantial dermal absorption. Odour perception did not show a dose-response, probably due to fast olfactory adaption. The human study presented here provides an excellent basis for deriving a biological limit value for 1,3-DCB.

Metabolic activation and toxicological evaluation of polychlorinated biphenyls in Drosophila melanogaster.

Degradation of polychlorinated biphenyls (PCBs) is initiated by cytochrome P450 (CYP) enzymes and includes PCB oxidation to OH-metabolites, which often display a higher toxicity than their parental compounds. In search of an animal model reflecting PCB metabolism and toxicity, we tested Drosophila melanogaster, a well-known model system for genetics and human disease. Feeding Drosophila with lower chlorinated (LC) PCB congeners 28, 52 or 101 resulted in the detection of a human-like pattern of respective OH-metabolites in fly lysates. Feeding flies high PCB 28 concentrations caused lethality. Thus we silenced selected CYPs via RNA interference and analyzed the effect on PCB 28-derived metabolite formation by assaying 3-OH-2',4,4'-trichlorobiphenyl (3-OHCB 28) and 3'-OH-4',4,6'-trichlorobiphenyl (3'-OHCB 28) in fly lysates. We identified several drosophila CYPs (dCYPs) whose knockdown reduced PCB 28-derived OH-metabolites and suppressed PCB 28 induced lethality including dCYP1A2. Following in vitro analysis using a liver-like CYP-cocktail, containing human orthologues of dCYP1A2, we confirm human CYP1A2 as a PCB 28 metabolizing enzyme. PCB 28-induced mortality in flies was accompanied by locomotor impairment, a common phenotype of neurodegenerative disorders. Along this line, we show PCB 28-initiated caspase activation in differentiated fly neurons. This suggested the loss of neurons through apoptosis. Our findings in flies are congruent with observation in human exposed to high PCB levels. In plasma samples of PCB exposed humans, levels of the neurofilament light chain increase after LC-PCB exposure, indicating neuronal damage. In summary our findings demonstrate parallels between Drosophila and the human systems with respect to CYP mediated metabolism and PCB mediated neurotoxicity.

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.

Human biomonitoring of polychlorinated biphenyls (PCBs) in plasma of former underground miners in Germany - A case-control study.

Polychlorinated biphenyls (PCBs) are very persistent organic pollutants of severe environmental concern due to their toxic properties. Former underground miners might have been exposed to this substance group due to the widespread use of PCBs in hydraulic oils from the late 1960s to the mid 1980s. We have conducted a blinded case-control study in order to evaluate the possibility of retrospective exposure assessment of PCBs using human biomonitoring in former underground miners decades after the last possible exposure. We have identified n = 34 male former underground miners and n = 136 age-matched male control persons from the database of patients of our occupational outpatient clinic aged between 47.9 and 83.7 years  at the time of sampling (June 2006-June 2016). These archived plasma samples have been blinded and analysed for 21 different PCB-congeners using a validated and quality controlled procedure using GC/MS (LOQ: 0.01 µg/L). Highly significant differences between cases and age-matched controls were only found for the PCB-congeners PCB 74 and PCB 114. The median (95th percentile) levels of PCB 74 in cases and controls were 0.126 µg/L plasma (0.899 µg/L plasma) vs. 0.058 µg/L plasma (0.368 µg/L plasma) and the 95th percentile levels for PCB 114 were 0.039 µg/L plasma vs. 0.017 µg/L plasma. Linear regression models revealed that this difference in plasma levels was unequivocally attributed to the underground mining activity. Thus, retrospective exposure assessment for underground miners by use of human biomonitoring seems feasible and further studies with a particular focus on this special group of workers should be performed.

Neuropsychological effects of occupational exposure to polychlorinated biphenyls.

In the context of a health surveillance program for former PCB-exposed workers of a transformer and capacitor recycling company in Germany, their family members, employees of surrounding companies and area residents a broad range of cognitive functions covering attention, executive processing, reasoning, memory and motor performance was examined. The study aimed at identifying potential adverse effects of PCB load on cognitive functions. Detailed analysis of PCB burden of the participants revealed rather high correlations of lower and higher chlorinated as well as dioxin-like PCBs. Nearly one half of the participants exhibited increased burden in all three PCB classes whereas only 33 out of 237 participants did not show any increased PCB burden. Thus, data analysis followed a two-fold strategy: (1) Based on studies providing data on PCB exposure of the German general population the PCB burden of every participant was classified as normal (percentile rank PR <95) or increased (PR ≥95). Increased burden with respect to lower (LPCBs) and higher chlorinated (HPCBs) as well as dioxin-like (dlPCBs) PCBs was assumed if a participant showed at least one congener surpassing the PR95 criterion for the respective congener class and (2) Overall plasma PCB level per congener class was used as measure of PCB load. In a multivariate approach using structural equation modelling and multiple regression analysis we found a significant impact of PCBs on word fluency and sensorimotor processing irrespective of the measure of PCB burden (PR95 criterion or overall plasma level). However, no effect of PCB burden on memory, attention, and cognitive flexibility could be demonstrated. Particularly, an increase of LPCBs was associated with an overall reduction of verbal fluency of letter and semantic word generation as well as word production based on a single or two alternating criteria. In addition, participants with increased burden of LPCBs exhibited a time-on-task effect in terms of a stronger decline of performance with increasing duration of the verbal fluency task. Moreover, we found adverse effects of HPCBs on Aiming and of dlPCBs on Line Tracking. Results are discussed in terms of (1) a decrease of cerebral dopamine (DA) with non-coplanar PCBs resulting in an impact on fronto-striatal cerebral structures subserving verbal fluency and motor processing, (2) a PCB-induced reduction of norepinephrine leading to the time-on-task effect with verbal fluency, and (3) adverse effects of PCBs on dopaminergic receptors in the cerebellum resulting in impaired fine motor function.

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.

Bilateral Ureteral Obstruction in Children after Appendectomy.

Acute renal failure due to bilateral ureteral obstruction is a rare complication after appendectomy in children. We report a case of bilateral ureteric obstruction in a 14-year-old boy nine days after surgery for an acute appendicitis. After saline-filling of the urinary bladder, transabdominal ultrasound demonstrated bilateral hydronephrosis of moderate degree. No abscess was found with CT but presence of millimetric stones on both distal ureters was shown, with bilateral calyceal dilatation. Cystoscopy revealed inflammatory changes in the bladder base. Following introduction of bilateral ureteric stents, there was rapid normalisation of urinary output and serum creatinine.

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.

Effect of occupational polychlorinated biphenyls exposure on quality-adjusted life years over time at the HELPcB surveillance program.

HELPcB (Health Effects in High-Level Exposure to Polychlorinated Biphenyls [PCB]) is a surveillance program for former PCB-exposed workers of a capacitor recycling company and other concerned individuals. The aim of this study was to examine the influence of polychlorinated biphenyls (PCB) on the health-related quality of life (HRQL) and on quality-adjusted life years (QALY). The EQ-5D-3L questionnaire was used to determine the HRQL. After three cross-sectional examinations at intervals of 1 yr, the longitudinal development of QALY was compared by repeated-measurement analysis of covariance (ANCOVA). The cohort was split at the 95th percentile of the comparison group for each PCB congener; known confounders such as age were taken into account. A significant difference in height and development of QALY over time was shown for the higher chlorinated non-dioxin-like PCB (hcPCB) congeners. A significant between-groups effect was found on PCB 153, PCB 180, and the sum of hcPCB. It was found that QALY decreased in the high-burden group and QALY stabilized after yr 2 in the normal-burden group. Taking the dimensions of the EQ-5D into account, the between-groups effect seems to be based predominantly on the dimension anxiety. The development of the within-group effect, however, seems to be based on the dimension mobility. This study detected a significant influence of hcPCB on the development of HRQL and QALYs over time according to the level of internal PCB burden.

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.

Search for light gauge bosons of the dark sector at the Mainz Microtron.

A new exclusion limit for the electromagnetic production of a light U(1) gauge boson γ' decaying to e + e- was determined by the A1 Collaboration at the Mainz Microtron. Such light gauge bosons appear in several extensions of the standard model and are also discussed as candidates for the interaction of dark matter with standard model matter. In electron scattering from a heavy nucleus, the existing limits for a narrow state coupling to e + e- were reduced by nearly an order of magnitude in the range of the lepton pair mass of 210 MeV/c2}

Intracellular electroporation site distributions: modeling examples for nsPEF and IRE pulse waveforms.

We illustrate expected electroporation (EP) responses to two classes of large electric field pulses by employing systems models, one of a cell in vitro and the other of multiple cells in vivo. The first pulse class involves "nsPEF" (nanosecond pulsed electric fields). The durations are less than a microsecond, but the magnitudes are extremely large, often 10 kV/cm or more, and all of the pores remain small. The second class involves "IRE" (irreversible electroporation). Durations are many microseconds to several milliseconds, but with magnitudes smaller than 10 kV/cm, and a wide range of pore sizes evolves. A key feature of both pulse classes is non-thermal cell killing by multiple pulses without delivering external drugs or genes. For small pulses the models respond passively (no pore creation) providing negative controls. For larger pulses transient aqueous pore populations evolve. These greatly increase local membrane conductance temporarily, causing rapid redistribution of fields near and within cells. This complex electrical behavior is generally not revealed by experiments reporting biological end points resulting from cumulative ionic and molecular transport through cell membranes. The underlying, heterogeneous pore population distributions are also not obtained from typical experiments. Further, traditional EP applications involving molecular delivery are usually assumed to create pores solely in the outer, plasma membrane (PM). In contrast, our examples support the occurrence of intracellular EP by both nsPEF and IRE, but with different intracellular spatial distributions of EP sites.

High-precision determination of the electric and magnetic form factors of the proton.

New precise results of a measurement of the elastic electron-proton scattering cross section performed at the Mainz Microtron MAMI are presented. About 1400 cross sections were measured with negative four-momentum transfers squared up to Q² = 1 (GeV/c)² with statistical errors below 0.2%. The electric and magnetic form factors of the proton were extracted by fits of a large variety of form factor models directly to the cross sections. The form factors show some features at the scale of the pion cloud. The charge and magnetic radii are determined to be ½ = 0.879(5)stat(4)syst(2)model(4)group fm and ½ = 0.777(13)stat(9)syst(5)model(2)group fm.

In silico estimates of cell electroporation by electrical incapacitation waveforms.

We use a system model of a cell and approximate magnitudes of electrical incapacitation (EI) device waveforms to estimate conditions that lead to responses with or without electroporation (EP) of cell membranes near electrodes. Single pulse waveforms of Taser X26 and Aegis MK63 devices were measured using a resistive load. For the present estimates the digitized waveforms were scaled in magnitude according to the inverse square radial distance from two tissue-penetrating electrodes, approximated as hemispheres. The corresponding tissue level electric fields were then used as inputs to the cell system model. A dynamic pore model for membrane electroporation (EP) was assigned to many different sites on the cell plasma membrane (PM). EI devices generate sufficiently large transmembrane voltage, U(m)(t), such that pores were created, evolving into a heterogeneous and time-dependent pore population. These approximate responses suggest that both waveforms can cause PM EP. Peripheral nerve damage by EP is a candidate side effect. More extensive EP is expected from the Taser X26 than the Aegis MK63, mainly due to the approximately eight-fold difference in the peak magnitudes. In silico examination of EI waveforms by multiscale modeling is warranted, and can involve whole body, tissue and cell level models that now exist and are rapidly being improved.

Trace eyeblink conditioning in patients with cerebellar degeneration: comparison of short and long trace intervals.

To elucidate whether the cerebellar cortex may contribute to trace eyeblink conditioning in humans, eight patients with degenerative cerebellar disorders (four with sporadic adult onset ataxia, three with autosomal dominant cerebellar ataxia type III and one with spinocerebellar ataxia type 6) and eight age- and sex-matched healthy control subjects were investigated. Individual high resolution three-dimensional MRI data sets were acquired. As revealed by volumetric measurements of the cerebellum using ECCET software, patients showed cerebellar atrophy to various degrees. No abnormalities were observed in the control subjects. Eyeblink conditioning was performed twice using a tone of 40 ms as conditioned stimulus, followed by a short (400 ms) and a long (1,000 ms) trace interval and an air-puff of 100 ms as unconditioned stimulus. Using the short trace interval, eyeblink conditioning was significantly impaired in cerebellar patients compared to controls, even in those who fulfilled criteria of awareness. Using the long trace interval no significant group differences could be observed. The present findings of impaired trace eyeblink acquisition in patients with cortical cerebellar degeneration suggest that the cerebellar cortex in humans, in addition to the interposed nucleus, is involved in trace eyeblink conditioning, if the trace interval is relatively short. Using a long trace interval, the cerebellum appears to be less important.

Long-range spatial correlations in the exciton energy distribution in GaAs/AlGaAs quantum wells.

Variations in the width of a quantum well (QW) are known to be a source of broadening of the exciton line. Using low temperature near-field optical microscopy, we have exploited the dependence of exciton energy on well width to show that in GaAs QWs, these seemingly random well-width fluctuations actually exhibit well-defined order-strong long-range correlations appearing laterally, in the plane of the QW, as well as vertically, between QWs grown one on top of the other. We show that these fluctuations are correlated with the commonly found mound structure on the surface. This is an intrinsic property of molecular beam epitaxial growth.