Heterogeneity and Disorder: Contributions of Rolf Landauer

Rolf Landauer made important contributions to many branches of science. Within the broad area of transport in disordered media, he wrote seminal papers on electrical conduction in macroscopically inhomogeneous materials, as well as fundamental analyses of electron transport in quantum mechanical systems with disorder on the atomic scale. We review here some of these contributions. We also briefly describe some main events in his personal and scientific life.Comment: 10 pages, 3 figures; presented on the occasion when Rolf Landauer was awarded, posthumously, the inaugural ETOPIM Medal at the ETOPIM 8 Conference, which took place during 7--12 June, 2009 in Rethymnon, Cret

Obscuration in the Host Galaxies of Soft X-ray Selected Seyferts

We define a new sample of 96 low-redshift (z<0.1), soft X-ray selected Seyferts from the catalog of the Einstein Slew Survey (Elvis etal. 1992, Plummer et al. 1994). We probe the geometry and column depth of obscuring material in the host-galaxy disks using galaxian axial ratios determined mainly from the Digitized Sky Survey. The distribution of host-galaxy axial ratios clearly shows a bias against edge-on spirals, confirming the existence of a geometrically thick layer of obscuring material in the host-galaxy planes. Soft X-ray selection recovers some of the edge-on objects missed in UV and visible surveys but still results in 30% incompleteness for Type 1's. We speculate that thick rings of obscuring material like the ones we infer for these Seyferts might be commonly present in early type spirals, sitting at the Inner Lindblad Resonances of the nonaxisymmetric potentials of the host galaxies.Comment: 14 pages including 2 tables and 3 eps figures, aas2pp4.sty, to appear in Ap

Nonlinear ac response of anisotropic composites

When a suspension consisting of dielectric particles having nonlinear characteristics is subjected to a sinusoidal (ac) field, the electrical response will in general consist of ac fields at frequencies of the higher-order harmonics. These ac responses will also be anisotropic. In this work, a self-consistent formalism has been employed to compute the induced dipole moment for suspensions in which the suspended particles have nonlinear characteristics, in an attempt to investigate the anisotropy in the ac response. The results showed that the harmonics of the induced dipole moment and the local electric field are both increased as the anisotropy increases for the longitudinal field case, while the harmonics are decreased as the anisotropy increases for the transverse field case. These results are qualitatively understood with the spectral representation. Thus, by measuring the ac responses both parallel and perpendicular to the uniaxial anisotropic axis of the field-induced structures, it is possible to perform a real-time monitoring of the field-induced aggregation process.Comment: 14 pages and 4 eps figure

Bromination Pattern of Hydroxylated Metabolites of BDE-47 Affects Their Potency to Release Calcium from Intracellular Stores in PC12 Cells

BACKGROUND: Brominated flame retardants, including the widely used polybrominated diphenyl ethers (PBDEs), have been detected in humans, raising concern about possible neurotoxicity. Recent research demonstrated that the hydroxylated metabolite 6-OH-BDE-47 increases neurotransmitter release by releasing calcium ions (Ca2+) from intracellular stores at much lower concentrations than its environmentally relevant parent congener BDE-47. Recently, several other hydroxylated BDE-47 metabolites, besides 6-OH-BDE-47, have been detected in human serum and cord blood. OBJECTIVE AND METHODS: To investigate the neurotoxic potential of other environmentally relevant PBDEs and their metabolites, we examined and compared the acute effects of BDE-47, BDE-49, BDE-99, BDE-100, BDE-153, and several metabolites of BDE-47-6-OH-BDE-47 (and its methoxylated analog 6-MeO-BDE-47), 6 -OH-BDE-49, 5-OH-BDE-47, 3-OH-BDE-47, and 4 -OH-BDE-49--on intracellular Ca2+ concentration ([Ca2+]i), measured using the Ca2+-responsive dye Fura-2 in neuroendocrine pheochromocytoma (PC12) cells. RESULTS: In contrast to the parent PBDEs and 6-MeO-BDE-47, all hydroxylated metabolites induced Ca2+ release from intracellular stores, although with different lowest observed effect concentrations (LOECs). The major intracellular Ca2+ sources were either endoplasmic reticulum (ER; 5-OH-BDE-47 and 6 -OH-BDE-49) or both ER and mitochondria (6-OH-BDE-47, 3-OH-BDE-47, and 4 -OH-BDE-49). When investigating fluctuations in [Ca2+]i, which is a more subtle end point, we observed lower LOECs for 6-OH-BDE-47 and 4 -OH-BDE-49, as well as for BDE-47. CONCLUSIONS: The present findings demonstrate that hydroxylated metabolites of BDE-47 cause disturbance of the [Ca2+]i. Importantly, shielding of the OH group on both sides with bromine atoms and/or the ether bond to the other phenyl ring lowers the potency of hydroxylated PBDE metabolites

MDHAQ/RAPID3 scores in patients with osteoarthritis are similar to or higher than in patients with rheumatoid arthritis: A cross-sectional study from current routine rheumatology care at four sites

Objective To compare patients with a primary diagnosis of osteoarthritis (OA) versus rheumatoid arthritis (RA) for scores on a patient self-report MDHAQ/RAPID3 (Multidimensional Health Assessment Questionnaire/Routine Assessment of Patient Index Data 3), and for physician global assessment (DOCGL). Methods All patients with all diagnoses complete an MDHAQ/RAPID3 at all routine rheumatology visits in the waiting area before seeing a rheumatologist at four sites, one in Australia and three in the USA. The two-page MDHAQ includes 0-10 scores for physical function (in 10 activities), pain and patient global assessment [on 0-10 visual analogue scales (VAS)], compiled into a 0-30 RAPID3, as well as fatigue and self-report painful joint count scales. Rheumatologists estimate a 0-10 DOCGL VAS. Demographic, MDHAQ/RAPID3 and DOCGL data from a random visit were compared in patients with RA versus patients with OA using multivariate analysis of variance, adjusted for age, disease duration and formal education level. Results Median RAPID3 was higher in OA versus RA at all four sites (11.7-16.8 vs 6.2-11.8) (p<0.001 at three sites). Median DOCGL in OA versus RA was 5 vs 4, 4 vs 3.7, 2.2 vs 2.5 and 2 vs 1. Patterns were similar for individual RAPID3 items, fatigue and painful joint scales, and in stratified analyses of patients aged 55-70. Conclusion Patient MDHAQ/RAPID3 and physician DOCGL indicate similar or higher disease burden in OA versus RA. Routine MDHAQ/RAPID3 allows direct comparisons of the two diseases. The findings suggest possible revision of current clinical and public policy views concerning OA

Awareness, views and experiences of Citizen Science among Swedish researchers — two surveys

In 2021 Sweden’s first national portal for citizen science will be launched to help researchers practice sustainable and responsible citizen science with different societal stakeholders. This paper present findings from two surveys on attitudes and experiences of citizen science among researchers at Swedish universities. Both surveys provided input to the development of the national portal, for which researchers are a key stakeholder group. The first survey (n=636) was exclusively focused on citizen science and involved researchers and other personnel at Swedish University of Agricultural Science (SLU). 63% of respondents at SLU had heard about citizen science (CS) prior to the survey; however a majority of these (61%) had not been involved in any CS initiative themselves. Dominant reasons for researchers choosing a CS approach in projects were to enable collection of large amounts of data (68%), improving the knowledge base (59%), improving data quality (25%), promote participants’ understanding in research (21%) and promote collaboration between the university and society (20%). The other survey (n=3 699) was on the broader topic of communication and open science, including questions on CS, and was distributed to researchers from all Swedish universities. 61% of respondents had not been engaged in any research projects where volunteers were involved in the process. A minority of the researchers had participated in projects were volunteers had collected data (18%), been involved in internal or external communication (16%), contributed project ideas (14%) and/or formulated research questions (11%). Nearly four out of ten respondents (37%) had heard about CS prior to the survey. The researchers were more positive towards having parts of the research process open to citizen observation, rather than open to citizen influence/participation. Our results show that CS is a far from well-known concept among Swedish researchers. And while those who have heard about CS are generally positive towards it, researchers overall are hesitant to invite citizens to take part in the research process

Evaluation of Dosing Guidelines for Gentamicin in Neonates and Children

Although aminoglycosides are frequently prescribed to neonates and children, the ability to reach effective and safe target concentrations with the currently used dosing regimens remains unclear. This study aims to evaluate the target attainment of the currently used dosing regimens for gentamicin in neonates and children. We conducted a retrospective single-center cohort study in neonates and children receiving gentamicin between January 2019 and July 2022, in the Beatrix Children’s Hospital. The first gentamicin concentration used for therapeutic drug monitoring was collected for each patient, in conjunction with information on dosing and clinical status. Target trough concentrations were ≤1 mg/L for neonates and ≤0.5 mg/L for children. Target peak concentrations were 8–12 mg/L for neonates and 15–20 mg/L for children. In total, 658 patients were included (335 neonates and 323 children). Trough concentrations were outside the target range in 46.2% and 9.9% of neonates and children, respectively. Peak concentrations were outside the target range in 46.0% and 68.7% of neonates and children, respectively. In children, higher creatinine concentrations were associated with higher gentamicin trough concentrations. This study corroborates earlier observational studies showing that, with a standard dose, drug concentration targets were met in only approximately 50% of the cases. Our findings show that additional parameters are needed to improve target attainment

Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours

BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users