The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 ± 0.02, ΔBE = −17.6 ± 1.2 mmol/L, mean ± SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 °C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.     

Astrocyte Ca2+ Waves and Subsequent Non-Synchronized Ca2+ Oscillations Coincide with Arteriole Diameter Changes in Response to Spreading Depolarization

Spreading depolarization (SD) is a wave of mass depolarization that causes profound perfusion changes in acute cerebrovascular diseases. Although the astrocyte response is secondary to the neuronal depolarization with SD, it remains to be explored how glial activity is altered after the passage of SD. Here, we describe post-SD high frequency astrocyte Ca²⁺ oscillations in the mouse somatosensory cortex. The intracellular Ca²⁺ changes of SR101 labeled astrocytes and the SD-related arteriole diameter variations were simultaneously visualized by multiphoton microscopy in anesthetized mice. Post-SD astrocyte Ca²⁺ oscillations were identified as Ca²⁺ events non-synchronized among astrocytes in the field of view. Ca²⁺ oscillations occurred minutes after the Ca²⁺ wave of SD. Furthermore, fewer astrocytes were involved in Ca²⁺ oscillations at a given time, compared to Ca²⁺ waves, engaging all astrocytes in the field of view simultaneously. Finally, our data confirm that astrocyte Ca²⁺ waves coincide with arteriolar constriction, while post-SD Ca²⁺ oscillations occur with the peak of the SD-related vasodilation. This is the first in vivo study to present the post-SD astrocyte Ca²⁺ oscillations. Our results provide novel insight into the spatio-temporal correlation between glial reactivity and cerebral arteriole diameter changes behind the SD wavefront.     

The Un(f)told Story of General Anesthesia

Inhalational anesthetics are routinely employed in clinical practice to accomplish general anesthesia. Concerns have recently emerged regarding the deleterious impact of these volatile agents on cognitive performance, immune functions, and tumor recurrence and metastasis. These agents have been shown to modify the gene‐expression pattern as well as cell signaling in tumor cells, but the underlying molecular mechanisms remain a matter of conjecture. Regulatory/signaling proteins either of cytosolic or membrane origin abundantly contain intrinsically disordered sequences, the conformational pliability of which is pivotal in their biological functions. It is well known that chloroform (an anesthetic itself), trifluoroethanol, hexafluoroisopropanol, and related haloalcohols markedly affect the structure of disordered proteins and protein regions by inducing folding, misfolding, or even aggregation. Taking into consideration the physicochemical similarities and protein interaction modes of these volatile solvents and inhaled anesthetics, it is postulated that administration of these drugs can also modify the secondary structure of disordered protein segments. Accordingly, pharmacological effects of anesthetics may, at least in part, be mediated by conformational perturbations of intrinsic disorder‐based regulatory protein networks of cells.     

The P-graph approach for systematic synthesis of wastewater treatment networks

Wastewater treatment consists of three or four sequential stages: preliminary, primary, secondary, and tertiary. Each stage can comprise multiple alternative technologies that can perform the same tasks with different efficiencies, operating times, and costs. Thus, we propose a systematic approach for designing wastewater treatment networks by utilizing principles of mathematical modeling and generating an exhaustive enumeration of all the possible technologies and their connections during the early stages of designing a treatment facility. Some of these structures are nonintuitive and include recycling, reprocessing, bypasses, and multiple technologies in parallel or series to remove the same contaminant. The nonintuitive structures with multiple technologies may provide a measure of resilience compared to typical heuristic designs. Thus, the combination of P-graph methodology and the sequence of treatment technologies predicted via the optimization algorithm from the maximal structure is based on holistic considerations and does not lead to suboptimal solutions.     

Interrelation between the climate-related sustainability and the financial reporting disclosures of the European automotive industry

The financial reports of the automotive companies' are measured in a standardized manner; therefore, they are transparent and comparable to each other, but this is not valid for the sustainability reports and it is not possible to compare their sustainability performances. Standard-setting organizations are currently searching for better reporting procedures. This study aims to investigate the connection between sustainability and financial reports for the most dominant European car manufacturers. It reviews the traceability of the sustainability elements back to the financial statements, which helps transparency, comparability, and impact measurement of the disclosed items and issues. This investigation allowed us to additionally review whether these companies are targeting to disclose the most harmful pollution impacts, or only focus to disclose the required obligatory items. Given the financial and sustainability reports magnitude manual testing would not provide complete and proper coverage, therefore we utilized an automated and AI-assisted content analysis with natural language processing. In this new review method, the sustainable elements of the textual reports were automatically retrieved following the 5-stage model of Landrum & Ohsowski (2018). The study highlights the lack of true sustainability information content of reports and the potential discrepancies and connections between the financial and the sustainability reports. Findings concluded that sustainability disclosures at the reviewed companies from several aspects could be improved and quantified, traced back to the financial disclosures, and to be comparable to each other if they apply a similar review method.

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NMR water self‐diffusion and relaxation studies on sodium polyacrylate solutions and gels in physiologic ionic solutions

Water self‐diffusion coefficients and longitudinal relaxation rates in sodium polyacrylate solutions and gels were measured by NMR, as a function of polymer content and structure in a physiological concentration range of monovalent and divalent cations, Ca²⁺ and Na⁺. Several physical models describing the self‐diffusion of the solvent were applied and compared. A free‐volume model was found to be in good agreement with the experimental results over a wide range of polymer concentrations. The longitudinal relaxation rate exhibited linear dependence on polymer concentration below a critical concentration and showed non‐linear behavior at higher concentrations. Both the water self‐diffusion and relaxation were less influenced by the polymer in the gel state than in the uncrosslinked polymer solutions. The effect of Na⁺ on the mobility of water molecules was practically undetectable. In contrast, addition of Ca²⁺ strongly increased the longitudinal relaxation rate while its effect on the self‐diffusion coefficient was much less pronounced. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 40001.     

SEM and EDS investigation of a pyrolytic carbon covered C/C composite maxillofacial implant retrieved from the human body after 8 years

The long term effect of the human body on a pyrolytic carbon covered C/C composite maxillofacial implant (CarBulat^Tm) was investigated by comparing the structure, the surface morphology and composition of an implant retrieved after 8 years to a sterilized, but not implanted one. Although the thickness of the carbon fibres constituting the implants did not change during the 8 year period, the surface of the implant retrieved was covered with a thin surface layer not present on the unimplanted implant. The composition of this layer is identical to the composition of the underlying carbon fibres. Calcium can only be detected on the surface as a trace element implying that the new layer is not formed by bone tissue. Residual soft tissue penetrating the bulk material between the carbon fibre bunches was found on the retrieved implant indicating the importance of the surface morphology in tissue growth and adhering to implants.     

Mass-velocity correlation in impact induced fragmentation of heterogeneous solids

We study the impact fragmentation of disordered solids by means of a discrete element model focusing on the velocity and mass-velocity correlation of fragments. Simulations are performed with plate-like objects varying the plate thickness and the impact velocity in broad ranges. Depending on the impact velocity the breakup process has two different outcomes: at low velocities the sample gets only damaged, to achieve fragmentation, where no large residues survive, the impact velocity has to surpass a critical value. In the fragmented phase the velocity components of fragments are power law distributed with a stretched exponential cutoff, where the impact velocity and plate thickness mainly control the standard deviation of the distributions. Mass velocity correlation is only pointed out for thin plates, while it disappears for three-dimensional bulk samples. In the damage phase of thin plates the mass and velocity of fragments proved to be strongly correlated, however, in the fragmented phase correlation occurs in the vicinity of the critical velocity and it is limited to the large fragments only. The correlation function decays as a power law with different exponents for small and large fragments in good agreement with recent experimental findings. We show that the mass-velocity correlation originates from the spatial dependence of the mass and velocity of pieces inside the fragmenting body.