Coherent multidimensional spectroscopy in the gas phase

Recent work applying multidimentional coherent electronic spectroscopy at dilute samples in the gas phase is reviewed. The development of refined phase-cycling approaches with improved sensitivity has opened-up new opportunities to probe even dilute gas-phase samples. In this context, first results of 2-dimensional spectroscopy performed at doped helium droplets reveal the femtosecond dynamics upon electronic excitation of cold, weakly-bound molecules, and even the induced dynamics from the interaction with the helium environment. Such experiments, offering well-defined conditions at low temperatures, are potentially enabling the isolation of fundamental processes in the excitation and charge transfer dynamics of molecular structures which so far have been masked in complex bulk environments.Comment: Invited Review Articl

Extracting the current-phase-relation of a monolithic three-dimensional nano-constriction using a DC-current-tunable superconducting microwave cavity

Superconducting circuits with nonlinear elements such as Josephson tunnel junctions or kinetic inductance nanowires are the workhorse for microwave quantum and superconducting sensing technologies. For devices, which can be operated at high temperatures and large magnetic fields, nano-constrictions as nonlinear elements are recently under intense investigation. Constrictions, however, are far less understood than conventional Josephson tunnel junctions, and their current-phase-relationships (CPRs) -- although highly important for device design -- are hard to predict. Here, we present a niobium microwave cavity with a monolithically integrated, neon-ion-beam patterned three-dimensional (3D) nano-constriction. By design, we obtain a DC-current-tunable microwave circuit and characterize how the bias-current-dependent constriction properties impact the cavity resonance. Based on the results of these experiments, we reconstruct the CPR of the nanoconstriction. Finally, we discuss the Kerr nonlinearity of the device, a parameter important for many high-dynamic-range applications and an experimental probe for the second and third derivatives of the CPR. Our platform provides a useful method to comprehensively characterize nonlinear elements integrated in microwave circuits and could be of interest for current sensors, hybrid quantum systems and parametric amplifiers. Our findings furthermore contribute to a better understanding of nano-fabricated 3D constrictions

Quantitative pharmacologic MRI: Mapping the cerebral blood volume response to cocaine in dopamine transporter knockout mice

The use of pharmacologic MRI (phMRI) in mouse models of brain disorders allows noninvasive in vivo assessment of drug-modulated local cerebral blood volume changes (ΔCBV) as one correlate of neuronal and neurovascular activities. In this report, we employed CBV-weighted phMRI to compare cocaine-modulated neuronal activity in dopamine transporter (DAT) knockout (KO) and wild-typemice. Cocaine acts to block the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT) that clear their respective neurotransmitters from the synapses, helping to terminate cognate neurotransmission. Cocaine consistently reduced CBV, with a similar pattern of regional ΔCBV in brain structures involved inmediating reward in both DAT genotypes. The largest effects (−20% to −30% ΔCBV) were seen in the nucleus accumbens and several cortical regions. Decreasing response amplitudes to cocaine were noted in more posterior components of the cortico-mesolimbic circuit. DAT KO mice had significantly attenuated ΔCBV amplitudes, shortened times to peak response, and reduced response duration in most regions. This study demonstrates that DAT knockout does not abolish the phMRI responses to cocaine, suggesting that adaptations to loss of DAT and/or retained cocaine activity in other monoamine neurotransmitter systems underlie these responses in DAT KO mice

Superconducting Josephson circuits for quantum hybrid systems with mechanical oscillators

Mechanische Oszillatoren bieten eine vielversprechende Plattform für die hochempfindliche Detektion von Beschleunigungen und Kräften, sowie für die Erforschung der Quantenphysik in bisher unerforschte Bereiche mit großen Massen und langen Kohärenzzeiten. Das starke Interesse an solchen Systemen erfordert immer bessere Sensitivitäten und Kopplung der Sensoren zur mechanischen Auslese. Eine der vielversprechendsten Möglichkeiten für die Detektion und Kontrolle mechanischer Oszillatoren stellen supraleitende Quantenintereferenz-Schwingkreise dar. Dafür sind allerdings starke externe Magnetfelder nötig, die mit den existierenden supraleitenden Bauelementen nicht kompatibel sind. Hierfür wurden im Rahmen der Arbeit Quantensensoren auf Basis Magnetfeld-toleranter Supraleiter entwickelt, die zur Kopplung an mechanischer Oszillatoren dienen. Diese supraleitenden Sensoren basieren auf Strom und Magnet -empfindlichen Mikrowellenresonatoren mit schwach nichlinearen Josephson-Kontakten aus Niob (Nb) und YBa2Cu3O7 (YBCO). Die Herstellung von Josephson-Kontakten aus diesen Materialien hat sich jedoch als herausfordernd erwiesen. Um dieses Problem anzugehen, wurde ein fokussierter Neon-Ionenstrahl zur Herstellung von monolithischen dreidimensionalen Nb-Nanoeinschnürungen verwendet. Im Fall von YBCO werden nahezu ideale SIS-Tunnelkontakte durch Bestrahlung mit einem fokussierten Helium-Ionenstrahl erhalten. Die resultierenden Mikrowellen-Resonatoren aus beiden Materialien wurden auf ihre Mikrowellen Eigenschaften und Responsivität untersucht

Hemicraniectomy for Dominant vs Nondominant Middle Cerebral Artery Infarction : A Systematic Review and Meta- Analysis

Objectives: Decompressive hemicraniectomy decreases mortality and severe disabil-ity from space-occupying middle cerebral artery infarction in selected patients. However, attitudes towards hemicraniectomy for dominant-hemispheric stroke have been hesitant. This systematic review and meta-analysis examines the associa-tion of stroke laterality with outcome after hemicraniectomy. Materials and methods: We performed a systematic literature search up to 6th February 2020 to retrieve original articles about hemicraniectomy for space-occupying middle cere-bral artery infarction that reported outcome in relation to laterality. The primary outcome was severe disability (modified Rankin Scale 4-6 or 5-6 or Glasgow Out -come Scale 1-3) or death. A two-stage combined individual patient and aggregate data meta-analysis evaluated the association between dominant-lateralized stroke and (a) short-term ( 3 months) outcome. We per -formed sensitivity analyses excluding studies with sheer mortality outcome, sec -ond-look strokectomy, low quality, or small sample size, and comparing populations from North America/Europe vs Asia/South America. Results: The analysis included 51 studies (46 observational studies, one nonrandomized trial, and four randomized controlled trials) comprising 2361 patients. We found no asso-ciation between dominant laterality and unfavorable short-term (OR 1.00, 95% CI 0.69-1.45) or long-term (OR 1.01, 95% CI 0.76-1.33) outcome. The results were unchanged in all sensitivity analyses. The grade of evidence was very low for short -term and low for long-term outcome. Conclusions: This meta-analysis suggests that patients with dominant-hemispheric stroke have equal outcome after hemicraniec-tomy compared to patients with nondominant stroke. Despite the shortcomings of the available evidence, our results do not support withholding hemicraniectomy based on stroke laterality.Peer reviewe

Coherent multidimensional spectroscopy of dilute gas-phase nanosystems

Two-dimensional electronic spectroscopy (2DES) is one of the most powerful spectroscopic techniques, capable of attaining a nearly complete picture of a quantum system including its couplings, quantum coherence properties and its real-time dynamics. While successfully applied to a variety of condensed phase samples, high precision experiments on isolated quantum systems in the gas phase have been so far precluded by insufficient sensitivity. However, such experiments are essential for a precise understanding of fundamental mechanisms and to avoid misinterpretations, e.g. as for the nature of quantum coherences in energy trans-port. Here, we solve this issue by extending 2DES to isolated nanosystems in the gas phase prepared by helium nanodroplet isolation in a molecular beam-type experiment. This approach uniquely provides high flexibility in synthesizing tailored, quantum state-selected model systems of single and many-body properties. For demonstration, we deduce a precise and conclusive picture of the ultrafast coherent dynamics in isolated high-spin Rb2 molecules and present for the first time a dynamics study of the system-bath interaction between a single molecule (here Rb3) and a superfluid helium environment. The results demonstrate the unique capacity to elucidate prototypical interactions and dynamics in tailored quantum systems and bridges the gap to experiments in ultracold quantum science

Subordinates’ Resistance and Managers’ Evaluations of Subordinates’ Performance

The authors explored the validity of two perspectives as to how managers evaluate subordinates who resist downward influence attempts: a uniformly dysfunctional perspective (i.e., managers regard all manifestations of resistance as indicators of ineffective influence and rate subordinates unfavorably when they resist) and a multifunctional perspective (i.e., managers regard some manifestations of resistance as more constructive than others and rate subordinates more favorably when they employ constructive resistance tactics). The results of two studies provided support for an interactive model, which predicts that the uniformly dysfunctional perspective is characteristic of lower quality leader-member exchange (LMX) relationships and that the multifunctional perspective is characteristic of higher quality leader-member exchanges

Subordinates’ Resistance and Managers’ Evaluations of Subordinates’ Performance

The authors explored the validity of two perspectives as to how managers evaluate subordinates who resist downward influence attempts: a uniformly dysfunctional perspective (i.e., managers regard all manifestations of resistance as indicators of ineffective influence and rate subordinates unfavorably when they resist) and a multifunctional perspective (i.e., managers regard some manifestations of resistance as more constructive than others and rate subordinates more favorably when they employ constructive resistance tactics). The results of two studies provided support for an interactive model, which predicts that the uniformly dysfunctional perspective is characteristic of lower quality leader-member exchange (LMX) relationships and that the multifunctional perspective is characteristic of higher quality leader-member exchanges

Comparative analysis of cell death induction by Taurolidine in different malignant human cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Taurolidine (TRD) represents an anti-infective substance with anti-neoplastic activity in many malignant cell lines. So far, the knowledge about the cell death inducing mechanisms and pathways activated by TRD is limited. The aim of this study was therefore, to perform a comparative analysis of cell death induction by TRD simultaneously in different malignant cell lines.</p> <p>Materials and methods</p> <p>Five different malignant cell lines (HT29/Colon, Chang Liver/Liver, HT1080/fibrosarcoma, AsPC-1/pancreas and BxPC-3/pancreas) were incubated with increasing concentrations of TRD (100 μM, 250 μM and 1000 μM) for 6 h and 24 h. Cell viability, apoptosis and necrosis were analyzed by FACS analysis (Propidiumiodide/AnnexinV staining). Additionally, cells were co-incubated with the caspase Inhibitor z-VAD, the radical scavenger N-Acetylcystein (NAC) and the Gluthation depleting agent BSO to examine the contribution of caspase activation and reactive oxygen species in TRD induced cell death.</p> <p>Results</p> <p>All cell lines were susceptible to TRD induced cell death without resistance toward this anti-neoplastic agent. However, the dose response effects were varying largely between different cell lines. The effect of NAC and BSO co-treatment were highly different among cell lines - suggesting a cell line specific involvement of ROS in TRD induced cell death. Furthermore, impact of z-VAD mediated inhibition of caspases was differing strongly among the cell lines.</p> <p>Conclusion</p> <p>This is the first study providing a simultaneous evaluation of the anti-neoplastic action of TRD across several malignant cell lines. The involvement of ROS and caspase activation was highly variable among the five cell lines, although all were susceptible to TRD induced cell death. Our results indicate, that TRD is likely to provide multifaceted cell death mechanisms leading to a cell line specific diversity.</p

The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression.

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise &lt;1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer