Mode combinability: Exploring convex combinations of permutation aligned models.

We explore element-wise convex combinations of two permutation-aligned neural network parameter vectors Θ and Θ of size d. We conduct extensive experiments by examining various distributions of such model combinations parametrized by elements of the hypercube [0,1] and its vicinity. Our findings reveal that broad regions of the hypercube form surfaces of low loss values, indicating that the notion of linear mode connectivity extends to a more general phenomenon which we call mode combinability.

Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo.

Incomplete reperfusion of the microvasculature ('no-reflow') after ischaemic stroke damages salvageable brain tissue. Previous ex vivo studies suggest pericytes are vulnerable to ischaemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains under-explored in vivo. Using longitudinal in vivo two-photon single-cell imaging over 7 days, we showed that 87% of pericytes constrict during cerebral ischaemia and remain constricted post reperfusion, and 50% of the pericyte population are acutely damaged.

Phase-separated ribosome-nascent chain complexes in genotoxic stress response.

Assemblysomes are EDTA- and RNase-resistant ribonucleoprotein (RNP) complexes of paused ribosomes with protruding nascent polypeptide chains. They have been described in yeast and human cells for the proteasome subunit Rpt1, and the disordered amino-terminal part of the nascent chain was found to be indispensable for the accumulation of the Rpt1-RNP into assemblysomes. Motivated by this, to find other assemblysome-associated RNPs we used bioinformatics to rank subunits of protein complexes according to their amino-terminal disorder propensity.

Grade Group accuracy is improved by extensive prostate biopsy sampling, but unrelated to prostatectomy specimen sampling or use of immunohistochemistry.

Assessing the accurate Grade Group of a prostate needle biopsy specimen is essential for choosing the adequate therapeutic modality for prostate cancer patients. However, it is well-known that biopsy Grade Group tends to up- or downgrade significantly at radical prostatectomy. We aimed to investigate the correlation between accuracy and biopsy core number, performed immunohistochemical staining (IHC) or prostatectomy specimen sampling, with the latest also being correlated with higher detection rates of adverse pathological features, e.

3D Scanner-Based Identification of Welding Defects-Clustering the Results of Point Cloud Alignment.

This paper describes a framework for detecting welding errors using 3D scanner data. The proposed approach employs density-based clustering to compare point clouds and identify deviations. The discovered clusters are then classified according to standard welding fault classes.

HCN channels at the cell soma ensure the rapid electrical reactivity of fast-spiking interneurons in human neocortex.

Accumulating evidence indicates that there are substantial species differences in the properties of mammalian neurons, yet theories on circuit activity and information processing in the human brain are based heavily on results obtained from rodents and other experimental animals. This knowledge gap may be particularly important for understanding the neocortex, the brain area responsible for the most complex neuronal operations and showing the greatest evolutionary divergence. Here, we examined differences in the electrophysiological properties of human and mouse fast-spiking GABAergic basket cells, among the most abundant inhibitory interneurons in cortex.

Machine learning framework to segment sarcomeric structures in SMLM data.

Object detection is an image analysis task with a wide range of applications, which is difficult to accomplish with traditional programming. Recent breakthroughs in machine learning have made significant progress in this area. However, these algorithms are generally compatible with traditional pixelated images and cannot be directly applied for pointillist datasets generated by single molecule localization microscopy (SMLM) methods.

Application of Lacunarity for Quantification of Single Molecule Localization Microscopy Images.

The quantitative analysis of datasets achieved by single molecule localization microscopy is vital for studying the structure of subcellular organizations. Cluster analysis has emerged as a multi-faceted tool in the structural analysis of localization datasets. However, the results it produces greatly depend on the set parameters, and the process can be computationally intensive.

Analysis of Ionizing Radiation Induced DNA Damage by Superresolution dSTORM Microscopy.

The quantitative detection of radiation caused DNA double-strand breaks (DSB) by immunostained γ-H2AX foci using direct stochastic optical reconstruction microscopy (dSTORM) provides a deeper insight into the DNA repair process at nanoscale in a time-dependent manner. Glioblastoma (U251) cells were irradiated with 250 keV X-ray at 0, 2, 5, 8 Gy dose levels. Cell cycle phase distribution and apoptosis of U251 cells upon irradiation was assayed by flow cytometry.

A New Modified Bipedicle Scrotal Skin Flap Technique for the Reconstruction of Penile Skin in Patients with Paraffin-Induced Sclerosing Lipogranuloma of the Penis.

Purpose: We introduce a new modified penile skin reconstruction technique to treat paraffin-induced sclerosing lipogranuloma of the penis.

Materials And Methods: From 2017 to 2020, 49 patients underwent the procedure. Complete removal of the lipogranuloma-involved penile skin was performed.

Syndecan-4 affects myogenesis via Rac1-mediated actin remodeling and exhibits copy-number amplification and increased expression in human rhabdomyosarcoma tumors.

Skeletal muscle demonstrates a high degree of regenerative capacity repeating the embryonic myogenic program under strict control. Rhabdomyosarcoma is the most common sarcoma in childhood and is characterized by impaired muscle differentiation. In this study, we observed that silencing the expression of syndecan-4, the ubiquitously expressed transmembrane heparan sulfate proteoglycan, significantly enhanced myoblast differentiation, and fusion.

Transient Hypoperfusion to Ischemic/Anoxic Spreading Depolarization is Related to Autoregulatory Failure in the Rat Cerebral Cortex.

Background: In ischemic stroke, cerebral autoregulation and neurovascular coupling may become impaired. The cerebral blood flow (CBF) response to spreading depolarization (SD) is governed by neurovascular coupling. SDs recur in the ischemic penumbra and reduce neuronal viability by the insufficiency of the CBF response.

Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study.

Background: Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19.

Methods: We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA).

Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study.

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients.

The antagonism of prostaglandin FP receptors inhibits the evolution of spreading depolarization in an experimental model of global forebrain ischemia.

Spontaneous, recurrent spreading depolarizations (SD) are increasingly more appreciated as a pathomechanism behind ischemic brain injuries. Although the prostaglandin F2α - FP receptor signaling pathway has been proposed to contribute to neurodegeneration, it has remained unexplored whether FP receptors are implicated in SD or the coupled cerebral blood flow (CBF) response. We set out here to test the hypothesis that FP receptor blockade may achieve neuroprotection by the inhibition of SD.

Microglia alter the threshold of spreading depolarization and related potassium uptake in the mouse brain.

Selective elimination of microglia from the brain was shown to dysregulate neuronal Ca signaling and to reduce the incidence of spreading depolarization (SD) during cerebral ischemia. However, the mechanisms through which microglia interfere with SD remained unexplored. Here, we identify microglia as essential modulators of the induction and evolution of SD in the physiologically intact brain in vivo.

Chitosan nanoparticles release nimodipine in response to tissue acidosis to attenuate spreading depolarization evoked during forebrain ischemia.

Stroke is an important cause of mortality and disability. Treatment options are limited, therefore the progress in this regard is urgently needed. Nimodipine, an L-type voltage-gated calcium channel antagonist dilates cerebral arterioles, but its systemic administration may cause potential side effects.

Quantification of DNA damage induced repair focus formation via super-resolution dSTORM localization microscopy.

In eukaryotic cells, each process, in which DNA is involved, should take place in the context of a chromatin structure. DNA double-strand breaks (DSBs) are one of the most deleterious lesions often leading to chromosomal rearrangement. In response to environmental stresses, cells have developed repair mechanisms to eliminate the DSBs.

Hyaluronan bound mature sperm count (HB-MaSC) is a more informative indicator of fertility than conventional sperm parameters: Correlations with Body Mass Index (BMI).

The relationship between overweight and male fertility is well studied, still the correlation of obesity and decreased sperm quality is a subject to debate. The widely used conventional spermatological examinations alone seem to be inadequate to assess fertilization potential. Hyaluronan Binding Assay (HBA) is one of the available validated tests that allows the functional examination of sperm.

The impact of dihydropyridine derivatives on the cerebral blood flow response to somatosensory stimulation and spreading depolarization.

Background And Purpose: A new class of dihydropyridine derivatives, which act as co-inducers of heat shock protein but are devoid of calcium channel antagonist and vasodilator effects, has recently been developed with the purpose of selectively targeting neurodegeneration. Here, we evaluated the action of one of these novel compounds LA1011 on neurovascular coupling in the ischaemic rat cerebral cortex. As a reference, we applied nimodipine, a vasodilator dihydropyridine and well-known calcium channel antagonist.

Susceptibility of the cerebral cortex to spreading depolarization in neurological disease states: The impact of aging.

Secondary injury following acute brain insults significantly contributes to poorer neurological outcome. The spontaneous, recurrent occurrence of spreading depolarization events (SD) has been recognized as a potent secondary injury mechanism in subarachnoid hemorrhage, malignant ischemic stroke and traumatic brain injury. In addition, SD is the underlying mechanism of the aura symptoms of migraineurs.

Large-conductance Ca-activated potassium channels are potently involved in the inverse neurovascular response to spreading depolarization.

Recurrent spreading depolarizations occur in the cerebral cortex from minutes up to weeks following acute brain injury. Clinical evidence suggests that the immediate reduction of cerebral blood flow in response to spreading depolarization importantly contributes to lesion progression as the wave propagates over vulnerable tissue zones, characterized by potassium concentration already elevated prior to the passage of spreading depolarization. Here we demonstrate with two-photon microscopy in anesthetized mice that initial vasoconstriction in response to SD triggered experimentally with 1 M KCl is coincident in space and time with the large extracellular accumulation of potassium, as shown with a potassium indicator fluorescent dye.

[Pharmacotherapy in patients with reduced kidney function].

Pharmacotherapy in patients with reduced kidney function Abstract. Pharmacotherapy in patients with chronic kidney disease (CKD) requires careful assessment of renal function and a profound knowledge of dose adaption principles and pharmacological characteristics of the drugs used. Of importance, non-renal clearance is also affected by impaired kidney function.

Systemic administration of l-kynurenine sulfate induces cerebral hypoperfusion transients in adult C57Bl/6 mice.

The kynurenine pathway is a cascade of enzymatic steps generating biologically active compounds. l-kynurenine (l-KYN) is a central metabolite of tryptophan degradation. In the mammalian brain, l-KYN is partly converted to kynurenic acid (KYNA), which exerts multiple effects on neurotransmission.

Contribution of prostanoid signaling to the evolution of spreading depolarization and the associated cerebral blood flow response.

The significance of prostanoid signaling in neurovascular coupling during somatosensory stimulation is increasingly more appreciated, yet its involvement in mediating the cerebral blood flow (CBF) response to spreading depolarization (SD) has remained inconclusive. Selective cyclooxygenase (COX) enzyme inhibitors (NS-398, SC-560) or an antagonist (L161,982) of the EP4 type prostaglandin E2 receptor were applied topically to a cranial window over the parietal cortex of isoflurane-anesthetized Sprague-Dawley rats (n = 60). Global forebrain ischemia was induced by occlusion of both common carotid arteries in half of the animals.