Visualizing Intracellular Organelle and Cytoskeletal Interactions at Nanoscale Resolution on Millisecond Timescales.

In eukaryotic cells, organelles and the cytoskeleton undergo highly dynamic yet organized interactions capable of orchestrating complex cellular functions. Visualizing these interactions requires noninvasive, long-duration imaging of the intracellular environment at high spatiotemporal resolution and low background. To achieve these normally opposing goals, we developed grazing incidence structured illumination microscopy (GI-SIM) that is capable of imaging dynamic events near the basal cell cortex at 97-nm resolution and 266 frames/s over thousands of time points. We employed multi-color GI-SIM to characterize the fast dynamic interactions of diverse organelles and the cytoskeleton, shedding new light on the complex behaviors of these structures. Precise measurements of microtubule growth or shrinkage events helped distinguish among models of microtubule dynamic instability. Analysis of endoplasmic reticulum (ER) interactions with other organelles or microtubules uncovered new ER remodeling mechanisms, such as hitchhiking of the ER on motile organelles. Finally, ER-mitochondria contact sites were found to promote both mitochondrial fission and fusion.

Advances in the Direct Study of Carbon Burning in Massive Stars.

The ^{12}C+^{12}C fusion reaction plays a critical role in the evolution of massive stars and also strongly impacts various explosive astrophysical scenarios. The presence of resonances in this reaction at energies around and below the Coulomb barrier makes it impossible to carry out a simple extrapolation down to the Gamow window-the energy regime relevant to carbon burning in massive stars. The ^{12}C+^{12}C system forms a unique laboratory for challenging the contemporary picture of deep sub-barrier fusion (possible sub-barrier hindrance) and its interplay with nuclear structure (sub-barrier resonances). Here, we show that direct measurements of the ^{12}C+^{12}C fusion cross section may be made into the Gamow window using an advanced particle-gamma coincidence technique. The sensitivity of this technique effectively removes ambiguities in existing measurements made with gamma ray or charged-particle detection alone. The present cross-section data span over 8 orders of magnitude and support the fusion-hindrance model at deep sub-barrier energies.

Competition between Allowed and First-Forbidden ß Decay: The Case of

The ß decay of ^{208}Hg into the one-proton hole, one neutron-particle _{81}^{208}Tl_{127} nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Q_{ß} window, only three negative parity states are populated directly in the ß decay. The data provide a unique test of the competition between allowed Gamow-Teller and Fermi, and first-forbidden ß decays, essential for the understanding of the nucleosynthesis of heavy nuclei in the rapid neutron capture process. Furthermore, the observation of the parity changing 0^{+}→0^{-}ß decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.

Anomalies in the Charge Yields of Fission Fragments from the

Fast-neutron-induced fission of ^{238}U at an energy just above the fission threshold is studied with a novel technique which involves the coupling of a high-efficiency γ-ray spectrometer (MINIBALL) to an inverse-kinematics neutron source (LICORNE) to extract charge yields of fission fragments via γ-γ coincidence spectroscopy. Experimental data and fission models are compared and found to be in reasonable agreement for many nuclei; however, significant discrepancies of up to 600% are observed, particularly for isotopes of Sn and Mo. This indicates that these models significantly overestimate the standard 1 fission mode and suggests that spherical shell effects in the nascent fission fragments are less important for low-energy fast-neutron-induced fission than for thermal neutron-induced fission. This has consequences for understanding and modeling the fission process, for experimental nuclear structure studies of the most neutron-rich nuclei, for future energy applications (e.g., Generation IV reactors which use fast-neutron spectra), and for the reactor antineutrino anomaly.

94 ß-Decay Half-Lives of Neutron-Rich _{55}Cs to _{67}Ho: Experimental Feedback and Evaluation of the r-Process Rare-Earth Peak Formation.

The ß-decay half-lives of 94 neutron-rich nuclei ^{144-151}Cs, ^{146-154}Ba, ^{148-156}La, ^{150-158}Ce, ^{153-160}Pr, ^{156-162}Nd, ^{159-163}Pm, ^{160-166}Sm, ^{161-168}Eu, ^{165-170}Gd, ^{166-172}Tb, ^{169-173}Dy, ^{172-175}Ho, and two isomeric states ^{174m}Er, ^{172m}Dy were measured at the Radioactive Isotope Beam Factory, providing a new experimental basis to test theoretical models. Strikingly large drops of ß-decay half-lives are observed at neutron-number N=97 for _{58}Ce, _{59}Pr, _{60}Nd, and _{62}Sm, and N=105 for _{63}Eu, _{64}Gd, _{65}Tb, and _{66}Dy. Features in the data mirror the interplay between pairing effects and microscopic structure. r-process network calculations performed for a range of mass models and astrophysical conditions show that the 57 half-lives measured for the first time play an important role in shaping the abundance pattern of rare-earth elements in the solar system.

Role of the Δ Resonance in the Population of a Four-Nucleon State in the

The ^{54}Fe nucleus was populated from a ^{56}Fe beam impinging on a Be target with an energy of E/A=500 MeV. The internal decay via γ-ray emission of the 10^{+} metastable state was observed. As the structure of this isomeric state has to involve at least four unpaired nucleons, it cannot be populated in a simple two-neutron removal reaction from the ^{56}Fe ground state. The isomeric state was produced in the low-momentum (-energy) tail of the parallel momentum (energy) distribution of ^{54}Fe, suggesting that it was populated via the decay of the Δ^{0} resonance into a proton. This process allows the population of four-nucleon states, such as the observed isomer. Therefore, it is concluded that the observation of this 10^{+} metastable state in ^{54}Fe is a consequence of the quark structure of the nucleons.

Enhanced γ-Ray Emission from Neutron Unbound States Populated in ß Decay.

Total absorption spectroscopy is used to investigate the ß-decay intensity to states above the neutron separation energy followed by γ-ray emission in (87,88)Br and (94)Rb. Accurate results are obtained thanks to a careful control of systematic errors. An unexpectedly large γ intensity is observed in all three cases extending well beyond the excitation energy region where neutron penetration is hindered by low neutron energy. The γ branching as a function of excitation energy is compared to Hauser-Feshbach model calculations. For (87)Br and (88)Br the γ branching reaches 57% and 20%, respectively, and could be explained as a nuclear structure effect. Some of the states populated in the daughter can only decay through the emission of a large orbital angular momentum neutron with a strongly reduced barrier penetrability. In the case of neutron-rich (94)Rb the observed 4.5% branching is much larger than the calculations performed with standard nuclear statistical model parameters, even after proper correction for fluctuation effects on individual transition widths. The difference can be reconciled by introducing an enhancement of 1 order of magnitude in the photon strength to neutron strength ratio. An increase in the photon strength function of such magnitude for very neutron-rich nuclei, if it proves to be correct, leads to a similar increase in the (n,γ) cross section that would have an impact on r process abundance calculations.

Total Absorption Spectroscopy Study of (92)Rb Decay: A Major Contributor to Reactor Antineutrino Spectrum Shape.

The antineutrino spectra measured in recent experiments at reactors are inconsistent with calculations based on the conversion of integral beta spectra recorded at the ILL reactor. (92)Rb makes the dominant contribution to the reactor antineutrino spectrum in the 5-8 MeV range but its decay properties are in question. We have studied (92)Rb decay with total absorption spectroscopy. Previously unobserved beta feeding was seen in the 4.5-5.5 region and the GS to GS feeding was found to be 87.5(25)%. The impact on the reactor antineutrino spectra calculated with the summation method is shown and discussed.

Isomer decay spectroscopy of 164Sm and 166Gd: midshell collectivity around N=100.

Excited states in the N=102 isotones 166Gd and 164Sm have been observed following isomeric decay for the first time at RIBF, RIKEN. The half-lives of the isomeric states have been measured to be 950(60) and 600(140) ns for 166Gd and 164Sm, respectively. Based on the decay patterns and potential energy surface calculations, including ß6 deformation, a spin and parity of 6- has been assigned to the isomeric states in both nuclei. Collective observables are discussed in light of the systematics of the region, giving insight into nuclear shape evolution. The decrease in the ground-band energies of 166Gd and 164Sm (N=102) compared to 164Gd and 162Sm (N=100), respectively, presents evidence for the predicted deformed shell closure at N=100.

Hindered Gamow-Teller decay to the odd-odd N=Z (62)Ga: absence of proton-neutron T=0 condensate in A=62.

Search for a new kind of superfluidity built on collective proton-neutron pairs with aligned spin is performed studying the Gamow-Teller decay of the T=1, J(π)=0+ ground state of (62)Ge into excited states of the odd-odd N=Z nucleus (62)Ga. The experiment is performed at GSI Helmholtzzentrum für Shwerionenforshung with the (62)Ge ions selected by the fragment separator and implanted in a stack of Si-strip detectors, surrounded by the RISING Ge array. A half-life of T1/2=82.9(14) ms is measured for the (62)Ge ground state. Six excited states of (62)Ga, populated below 2.5 MeV through Gamow-Teller transitions, are identified. Individual Gamow-Teller transition strengths agree well with theoretical predictions of the interacting shell model and the quasiparticle random phase approximation. The absence of any sizable low-lying Gamow-Teller strength in the reported beta-decay experiment supports the hypothesis of a negligible role of coherent T=0 proton-neutron correlations in (62)Ga.

Half-life systematics across the N=126 shell closure: role of first-forbidden transitions in the ß decay of heavy neutron-rich nuclei.

This Letter reports on a systematic study of ß-decay half-lives of neutron-rich nuclei around doubly magic (208)Pb. The lifetimes of the 126-neutron shell isotone (204)Pt and the neighboring (200-202)Ir, (203)Pt, (204)Au are presented together with other 19 half-lives measured during the "stopped beam" campaign of the rare isotope investigations at GSI collaboration. The results constrain the main nuclear theories used in calculations of r-process nucleosynthesis. Predictions based on a statistical macroscopic description of the first-forbidden ß strength reveal significant deviations for most of the nuclei with N<126. In contrast, theories including a fully microscopic treatment of allowed and first-forbidden transitions reproduce more satisfactorily the trend in the measured half-lives for the nuclei in this region, where the r-process pathway passes through during ß decay back to stability.

Split-bolus single-phase versus single-bolus split-phase CT acquisition protocols for staging in patients with testicular cancer: A retrospective study.

INTRODUCTION: Computed tomography (CT) imaging has become indispensable in the management of medical oncology patients. Risks associated with high cumulative effective dose (CED) are relevant in testicular cancer patients. Split-bolus protocols, whereby the contrast medium injection is divided into two, followed by combining the required phase images in a single scan acquisition has been shown to provide images of comparable image quality and less radiation dose compared to single-bolus split-phase CT for various indications. We retrospectively evaluated the performance of split-bolus and single-bolus protocols in patients having follow-up CT imaging for testicular cancer surveillance. METHODS: 45 patients with testicular cancer undergoing surveillance CT imaging of the thorax, abdomen, and pelvis who underwent split-bolus and single-bolus protocols were included. Quantitative image quality analysis was conducted by placing region of interests in pre-defined anatomical sub-structures within the abdominal cavity. The signal-to-noise ratio (SNR) and radiation dose in the form of dose length product (DLP) and effective dose (ED) were recorded. RESULTS: The DLP and ED for the single-bolus, split-phase acquisition was 506 ± 89 mGy cm and 7.59 ± 1.3 mSv, respectively. For the split-bolus, single-phase acquisition, 397 ± 94 mGy∗cm and 5.95 ± 1.4 mSv, respectively (p < 0.000). This represented a 21.5 % reduction in radiation dose exposure. The SNR for liver, muscle and fat for the single-bolus were 7.4, 4.7 and 8, respectively, compared to 5.5, 3.8 and 7.4 in the split-bolus protocol (p < 0.001). CONCLUSION: In a testicular cancer patient cohort undergoing surveillance CT imaging, utilization of a split-bolus single-phase acquisition CT protocol enabled a significant reduction in radiation dose whilst maintaining subjective diagnostic acceptability. IMPLICATIONS FOR PRACTICE: Use of split-bolus, single-phase acquisition has the potential to reduce CED in surveillance of testicular cancer patients.

A plastic scintillator and HPGe ß-γ coincidence detection system.

A network of specialist laboratories support the International Monitoring System (IMS) of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) with re-measurements of radionuclide samples, including xenon gas. The measurement of four xenon fission product radionuclides (133Xe, 135Xe, 131mXe and 133mXe) can be used to detect an underground nuclear explosion. Laboratories use a range of techniques to measure the radionuclides, including beta-gamma (ß-γ) coincidence spectrometry. These highly-sensitive measurements are capable of detecting concentrations of down to 500 atoms of 133Xe in a few cm3 of xenon. In some detector systems, detection of the metastable isomers (131mXe and 133mXe) can be more challenging due to interferences between the signatures of different radionuclides. Recent work has shown that using high-purity Germanium (HPGe) high-resolution gamma detectors, these interferences can be reduced, lowering the dependence of the detection limits on radionuclide sample isotopic composition. One downside of these detectors is the reduction in detection efficiency, which impacts the overall detection sensitivity; so assessing different detector systems is a priority for radionuclide laboratories. This work presents a coincidence detector system comprising of a plastic scintillator gas cell and a large-crystal high-purity germanium detector. The energy resolution, coincidence detection efficiency, MDA and interference factors are determined from measurements of synthetic radioxenon gas samples.

Determination of the Terbium-152 half-life from mass-separated samples from CERN-ISOLDE and assessment of the radionuclide purity.

Terbium-152 is one of four terbium radioisotopes that together form a potential theranostic toolbox for the personalised treatment of tumours. As 152 Tb decay by positron emission it can be utilised for diagnostics by positron emission tomography. For use in radiopharmaceuticals and for activity measurements by an activity calibrator a high radionuclide purity of the material and an accurate and precise knowledge of the half-life is required. Mass-separation and radiochemical purification provide a production route of high purity 152Tb. In the current work, two mass-separated samples from the CERN-ISOLDE facility have been assayed at the National Physical Laboratory to investigate the radionuclide purity. These samples have been used to perform four measurements of the half-life by three independent techniques: high-purity germanium gamma-ray spectrometry, ionisation chamber measurements and liquid scintillation counting. From the four measurement campaigns a half-life of 17.8784(95) h has been determined. The reported half-life shows a significant difference to the currently evaluated half-life (ζ-score = 3.77), with a relative difference of 2.2 % and an order of magnitude improvement in the precision. This work also shows that under controlled conditions the combination of mass-separation and radiochemical separation can provide high-purity 152Tb.

New isomers in the full seniority scheme of neutron-rich lead isotopes: the role of effective three-body forces.

The neutron-rich lead isotopes, up to (216)Pb, have been studied for the first time, exploiting the fragmentation of a primary uranium beam at the FRS-RISING setup at GSI. The observed isomeric states exhibit electromagnetic transition strengths which deviate from state-of-the-art shell-model calculations. It is shown that their complete description demands the introduction of effective three-body interactions and two-body transition operators in the conventional neutron valence space beyond (208)Pb.

Head and Neck Merkel Cell Carcinoma: A 12-Year Single Institutional Experience.

Background: Merkel cell carcinoma (MCC) is an aggressive malignancy of presumed neuroendocrine origin. Most case series of MCC are limited by low case numbers and are not specific to head and neck tumours. The purpose of this study was to provide a focused review of head and neck MCC diagnosis and management in a single Irish institution. Methods: Patient's demographics, tumour characteristics, pathological diagnosis, surgical treatment, adjuvant treatment, subsequent management and clinical course were collected. Estimates of progression-free MCC survival rates were calculated by the Kaplan-Meier statistical model. A Pearson product-moment correlation coefficient examined the association between surgical margins and disease-free follow-up. Results: In total, 11 patients were treated for head and neck MCC with a mean age of 79.6 years (range = 69-91 years). The mean average follow-up duration of patients was 18.3 months. Of the cohort, 18% (n=2) had a sentinel node biopsy (SLNB). A selective neck dissection was subsequently performed in 18% (n=2). In total, 72% (n=8) of patients received adjuvant radiotherapy. Median disease-specific survival was 15 months for the SLNB group and 17 months for the non-SLNB group, not statistically significant (p=0.23). There was no significant association between surgical margins and disease-free follow (p=0.65). Conclusions: Our case series adds to a limited body of evidence of head and neck MCC. Surgery remains the treatment priority in localized disease, with an increasing role of SLNB for accurate prognostication and staging. Early management of stage I disease results in moderate long-term disease-free survivability.

Determination of the 161Tb half-life.

There is significant interest in the use of terbium radioisotopes for applications in cancer therapy and diagnosis. Of these, 161Tb, as a medium energy beta-emitter, is being investigated as a potential alternative to 177Lu. The relatively high proportion of conversion electron and Auger electron emissions per decay make 161Tb an attractive targeted therapeutic. As a product of nuclear fission, 161Tb is also of importance to nuclear forensics. The standard uncertainty of the current evaluated half-life of 6.89(2) d contributes significantly to the standard uncertainty of any decay corrected activity determination made. Furthermore, the accuracy of this evaluated half-life has been called into question by measurements reported in 2020 at the Institute of Radiation Physics (IRA), Switzerland, who reported a half-life of 6.953(2) d. In the current work, the half-life of the 161Tb ground state decay has been measured at three independent laboratories located in the United Kingdom and the United States of America for a total of six determinations using three independent measurement techniques; gamma-ray spectrometry, ionisation chamber measurement and liquid scintillation counting. The half-life determined for 161Tb of 6.9637(29) d confirms the observed 1% relative increase observed by IRA, though the reported half-lives in this work and at IRA are significantly different (ζ-score = 3.1).

Half-life determination of 155Tb from mass-separated samples produced at CERN-MEDICIS.

Terbium-155 has been identified for its potential for single-photon emission computed tomography (SPECT) in nuclear medicine. For activity measurements, an accurate and precise half-life of this radionuclide is required. However, the currently evaluated half-life of 5.32(6) d with a relative standard uncertainty of 1.1% determines the precision possible. Limited literature for the half-life measurements of this radionuclide is available and all reported investigations are prior to 1970. Further measurements are therefore needed to confirm the accuracy and improve the precision of the half-life for its use in the clinical setting. Two samples produced and mass separated at the CERN-MEDICIS facility have been measured at the National Physical Laboratory by two independent techniques: liquid scintillation counting and high-purity germanium gamma-ray spectrometry. A half-life of 5.2346(36) d has been determined from the weighted mean of the half-lives determined by the two techniques. The half-life reported in this work has shown a relative difference of 1.6% to the currently evaluated half-life and has vastly improved the precision.

Superresolution microscopy reveals actomyosin dynamics in medioapical arrays.

Arrays of actin filaments (F-actin) near the apical surface of epithelial cells (medioapical arrays) contribute to apical constriction and morphogenesis throughout phylogeny. Here, superresolution approaches (grazing incidence structured illumination, GI-SIM, and lattice light sheet, LLSM) microscopy resolve individual, fluorescently labeled F-actin and bipolar myosin filaments that drive amnioserosa cell shape changes during dorsal closure in Drosophila. In expanded cells, F-actin and myosin form loose, apically domed meshworks at the plasma membrane. The arrays condense as cells contract, drawing the domes into the plane of the junctional belts. As condensation continues, individual filaments are no longer uniformly apparent. As cells expand, arrays of actomyosin are again resolved-some F-actin turnover likely occurs, but a large fraction of existing filaments rearrange. In morphologically isotropic cells, actin filaments are randomly oriented and during contraction are drawn together but remain essentially randomly oriented. In anisotropic cells, largely parallel actin filaments are drawn closer to one another. Our images offer unparalleled resolution of F-actin in embryonic tissue, show that medioapical arrays are tightly apposed to the plasma membrane and are continuous with meshworks of lamellar F-actin. Medioapical arrays thereby constitute modified cell cortex. In concert with other tagged array components, superresolution imaging of live specimens will offer new understanding of cortical architecture and function.