Continuous size fractionation of magnetic nanoparticles by using simulated moving bed chromatography

The size fractionation of magnetic nanoparticles is a technical problem, which until today can only be solved with great effort. Nevertheless, there is an important demand for nanoparticles with sharp size distributions, for example for medical technology or sensor technology. Using magnetic chromatography, we show a promising method for fractionation of magnetic nanoparticles with respect to their size and/or magnetic properties. This was achieved by passing magnetic nanoparticles through a packed bed of fine steel spheres with which they interact magnetically because single domain ferro-/ferrimagnetic nanoparticles show a spontaneous magnetization. Since the strength of this interaction is related to particle size, the principle is suitable for size fractionation. This concept was transferred into a continuous process in this work using a so-called simulated moving bed chromatography. Applying a suspension of magnetic nanoparticles within a size range from 20 to 120 nm, the process showed a separation sharpness of up to 0.52 with recovery rates of 100%. The continuous feed stream of magnetic nanoparticles could be fractionated with a space-time-yield of up to 5 mg/(L∙min). Due to the easy scalability of continuous chromatography, the process is a promising approach for the efficient fractionation of industrially relevant amounts of magnetic nanoparticles.     

Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine. Neuroinflammation in general, and IL-6 signaling in particular, appear to play a major role in the pathobiology and pathophysiology of aneurysm formation and aneurysmal subarachnoid hemorrhage (SAH). Most importantly, elevated IL-6 CSF (rather than serum) levels appear to correlate with delayed cerebral ischemia (DCI, “vasospasm”) and secondary (“vasospastic”) infarctions. IL-6 CSF levels may also reflect other forms of injury to the brain following SAH, i.e., early brain damage and septic complications of SAH and aneurysm treatment. This would explain why many researchers have found an association between IL-6 levels and patient outcomes. These findings clearly suggest CSF IL-6 as a candidate biomarker in SAH patients. However, at this point, discrepant findings in variable study settings, as well as timing and other issues, e.g., defining proper clinical endpoints (i.e., secondary clinical deterioration vs. angiographic vasospasm vs. secondary vasospastic infarct) do not allow for its routine use. It is also tempting to speculate about potential therapeutic measures targeting elevated IL-6 CSF levels and neuroinflammation in SAH patients. Corticosteroids and anti-platelet drugs are indeed used in many SAH cases (not necessarily with the intention to interfere with detrimental inflammatory signaling), however, no convincing benefit has been demonstrated yet. The lack of a robust clinical perspective against the background of a relatively large body of data linking IL-6 and neuroinflammation with the pathophysiology of SAH is somewhat disappointing. One underlying reason might be that most relevant studies only report correlative data. The specific molecular pathways behind elevated IL-6 levels in SAH patients and their various interactions still remain to be delineated. We are optimistic that future research in this field will result in a better understanding of the role of neuroinflammation in the pathophysiology of SAH, which in turn, will translate into the identification of suitable biomarkers and even potential therapeutic targets.     

No Direct Postconditioning Effect of Poloxamer 188 on Mitochondrial Function after Ischemia Reperfusion Injury in Rat Isolated Hearts

Myocardial infarction is a leading cause for morbidity and mortality worldwide. The only viable treatment for the ischemic insult is timely reperfusion, which further exacerbates myocardial injury. Maintaining mitochondrial function is crucial in preserving cardiomyocyte function in ischemia reperfusion (IR) injury. Poloxamer (P) 188 has been shown to improve cardiac IR injury by improving cellular and mitochondrial function. The aim of this study was to show if P188 postconditioning has direct protective effects on mitochondrial function in the heart. Langendorff prepared rat hearts were subjected to IR injury ex-vivo and reperfused for 10 min with 1 mM P188 vs. vehicle. Cardiac mitochondria were isolated with 1 mM P188 vs. 1 mM polyethylene glycol (PEG) vs. vehicle by differential centrifugation. Mitochondrial function was assessed by adenosine triphosphate synthesis, oxygen consumption, and calcium retention capacity. Mitochondrial function decreased significantly after ischemia and showed mild improvement with reperfusion. P188 did not improve mitochondrial function in the ex-vivo heart, and neither further P188 nor PEG induced direct mitochondrial protection after IR injury in this model.     

Luminescent Amphiphilic Aminoglycoside Probes to Study Transfection

We report the characterization of amphiphilic aminoglycoside conjugates containing luminophores with aggregation-induced emission properties as transfection reagents. These inherently luminescent transfection vectors are capable of binding plasmid DNA through electrostatic interactions; this binding results in an emission “on” signal due to restriction of intramolecular motion of the luminophore core. The luminescent cationic amphiphiles effectively transferred plasmid DNA into mammalian cells (HeLa, HEK 293T), as proven by expression of a red fluorescent protein marker. The morphologies of the aggregates were investigated by microscopy as well as ζ-potential and dynamic light-scattering measurements. The transfection efficiencies using luminescent cationic amphiphiles were similar to that of the gold-standard transfection reagent Lipofectamine® 2000.     

Probing the Conformation States of Neurotensin Receptor 1 Variants by NMR Site-Directed Methyl Labeling

G protein-coupled receptors (GPCRs) are key players in mediating signal transduction across the cell membrane. However, due to their intrinsic instability, many GPCRs are not suitable for structural investigations. Various approaches have been developed in recent years to remedy this situation, ranging from the use of more native membrane mimetics to protein-stabilization methods. The latter approach typically results in GPCRs that contain various numbers of mutations. However, probing the functionality of such variants by in vitro and in vivo assays is often time consuming. In addition, to validate the suitability of such GPCRs for structural investigations, an assessment of their conformation state is required. NMR spectroscopy has been proven to be suitable to probe the conformation state of GPCRs in solution. Here, by using chemical labeling with an isotope-labeled methyl probe, we show that the activity and the conformation state of stabilized neurotensin receptor 1 variants obtained from directed evolution can be efficiently assayed in 2D NMR experiments. This strategy enables the quantification of the active and inactive conformation states and the derivation of an estimation of the basal as well as agonist-induced activity of the receptor. Furthermore, this assay can be used as a readout when re-introducing agonist-dependent signaling into a highly stabilized, and thus rigidified, receptor by mutagenesis. This approach will be useful in cases where low production yields do not permit the addition of labeled compounds to the growth medium and where 1D NMR spectra of selectively ¹⁹F-labeled receptors are not sufficient to resolve signal overlap for a more detailed analysis.     

Good ergonomics and team diversity reduce absenteeism and errors in car manufacturing

Prior research suggests that ergonomics work design and mixed teams (in age and gender) may compensate declines in certain abilities of ageing employees. This study investigates simultaneous effects of both team level factors on absenteeism and performance (error rates) over one year in a sample of 56 car assembly teams (N = 623). Results show that age was related to prolonged absenteeism and more mistakes in work planning, but not to overall performance. In comparison, high-physical workload was strongly associated with longer absenteeism and increased error rates. Furthermore, controlling for physical workload, age diversity was related to shorter absenteeism, and the presence of females in the team was associated with shorter absenteeism and better performance. In summary, this study suggests that both ergonomics work design and mixed team composition may compensate age-related productivity risks in manufacturing by maintaining the work ability of older employees and improving job quality.     

Dynamic thread mapping of shared memory applications by exploiting cache coherence protocols

In current computer architectures, the communication performance between threads varies depending on the memory hierarchy. This performance difference must be considered when mapping parallel applications to processor cores. In parallel applications based on the shared memory paradigm, the communication is difficult to detect because it is implicit. Furthermore, dynamic mapping introduces several challenges, since it needs to find a suitable mapping and migrate the threads with a low overhead during the execution of the application. We propose a mechanism to detect the communication pattern of shared memory applications by monitoring cache coherence protocols. We also propose heuristics that, combined with our communication detection mechanism, allow the mapping to be performed dynamically by the operating system. Experiments with the NAS Parallel Benchmarks showed a reduction of up to 13.9% of the execution time, 30.5% of the cache misses and 39.4% of the number of invalidation messages.     

Whispering gallery modes in photoluminescence and Raman spectra of a spherical microcavity with CdTe quantum dots: anti-Stokes emission and interference effects

We have studied the photoluminescence and Raman spectra of a system consisting of a polystyrene latex microsphere coated by CdTe colloidal quantum dots. The cavity-induced enhancement of the Raman scattering allows the observation of Raman spectra from only a monolayer of CdTe quantum dots. Periodic structure with very narrow peaks in the photoluminescence spectra of a single microsphere was detected both in the Stokes and anti-Stokes spectral regions, arising from the coupling between the emission of quantum dots and spherical cavity modes.