Neuroinflammation contributes to hypoxic-ischemic (HI) brain injury. Inter-alpha inhibitor proteins (IAIPs) have important immunomodulatory properties. Human (h) plasma-derived IAIPs reduce brain injury and improve neurobehavioral outcomes after HI. However, the effects of hIAIPs on neuroinflammatory biomarkers after HI have not been examined. We determined whether hIAIPs attenuated HI-related neuroinflammation. Postnatal day-7 rats exposed to sham-placebo, or right carotid ligation and 8% oxygen for 90 minutes with placebo, and hIAIP treatment were studied. hIAIPs (30 mg/kg) or PL was injected intraperitoneally immediately, 24, and 48 hours after HI. Rat complete blood counts and sex were determined. Brain tissue and peripheral blood were prepared for analysis 72 hours after HI. The effects of hIAIPs on HI-induced neuroinflammation were quantified by image analysis of positively stained astrocytic (glial fibrillary acid protein [GFAP]), microglial (ionized calcium binding adaptor molecule-1 [Iba-1]), neutrophilic (myeloperoxidase [MPO]), matrix metalloproteinase-9 (MMP9), and MMP9-MPO cellular markers in brain regions. hIAIPs reduced quantities of cortical GFAP, hippocampal Iba-1-positive microglia, corpus callosum MPO, and cortical MMP9-MPO cells and the percent of neutrophils in peripheral blood after HI in male, but not female rats. hIAIPs modulate neuroinflammatory biomarkers in the neonatal brain after HI and may exhibit sex-related differential effects.
An array of 50μm×50μm polymer waveguides with 45° total internal reflection (TIR) wideband coupling mirrors were fabricated by soft molding to achieve fully embedded boardlevel optoelectronic interconnects. The 45° TIR coupling mirrors were formed at the ends of the waveguides to provide surface normal light coupling between waveguides and optoelectronic devices. Three-dimensional optoelectronic interconnects were replicated in one-step transfer by the soft molding technique. The measured propagation loss of the multimode waveguide was 0.16dB∕cm at 850nm wavelength. The coupling efficiency of the silver-coated 45° micromirrors buried under the top cladding was 92% with low polarization sensitivity.
Electro-optic signal modulation provides a key functionality in modern technology and information networks. Photonic integration has enabled not only miniaturizing photonic components, but also provided performance improvements due to co-design addressing both electrical and optical device rules. However, the millimeter-to-centimeter large footprint of many foundry-ready photonic electro-optic modulators significantly limits on-chip scaling density. To address these limitations, here we experimentally demonstrate a coupling-enhanced electroabsorption modulator by heterogeneously integrating a novel dual-gated indium-tin-oxide (ITO) phase-shifting tunable absorber placed at a silicon directional coupler region. Our experimental modulator shows a 2 dB extinction ratio for a just 4 µm short device at 4 volt bias. Since no material nor optical resonances are deployed, this device shows spectrally broadband operation as demonstrated here across the entire C-band. In conclusion we demonstrate a modulator utilizing strong index-change from both real and imaginary part of active material enabling compact and high-performing modulators using semiconductor foundry-near materials.
When a mutation in an essential gene shows a temperature-sensitive phenotype, one usually assumes that the protein is inactive at nonpermissive temperature. DNA gyrase is an essential bacterial enzyme composed of two subunits, GyrA and GyrB. The gyrB652 mutation results from a single base change that substitutes a serine residue for arginine 436 (R436-S) in the GyrB protein. At 42°C, strains with the gyrB652 allele stop DNA replication, and at 37°C, such strains grow but have RecA-dependent SOS induction and show constitutive RecBCD-dependent DNA degradation. Surprisingly, the GyrB652 protein is not inactive at 42°C in vivo or in vitro and it doesn't directly produce breaks in chromosomal DNA. Rather, this mutant has a low k cat compared to wild-type GyrB subunit. With more than twice the normal mean number of supercoil domains, this gyrase hypomorph is prone to fork collapse and topological chaos near the terminus of DNA replication.Temperature-sensitive (TS) mutants have been used to study complex biochemical pathways in prokaryotic and eukaryotic organisms alike. By comparing phenotypes of a TS mutant at permissive and restrictive temperatures, important insights can be obtained about the progression of intermediates through a biochemical pathway. For example, TS mutants guided early studies of DNA replication and provided the initial evidence for three different cellular polymerases (28). TS mutants also showed that replication involves numerous genes, and a large mutant collection guided the in vitro reconstruction of replication initiation and elongation (44,72). In bacteriophages and Mu, TS repressors were found that undergo a change in protein conformation causing repressor-DNA complexes to dissociate at nonpermissive temperatures (24,31,69). Physiological studies after shifts from permissive to nonpermissive temperature revealed relevant promoters and important biochemical steps necessary for the onset of the lytic cycle in phage development (19,30). Thus, it has become expected that when a gene confers a TS phenotype, the cause is a temperature-dependent change in the mutant protein's structure or catalytic activity.DNA gyrase has a unique and essential role in prokaryotic replication and transcription. The enzyme catalyzes the introduction of negative supercoils into covalently closed DNA molecules at the expense of ATP binding and hydrolysis. The enzyme is essential in most prokaryotes and is a critical target for antimicrobial chemotherapy. The quinolone antibiotics are among the most potent antibacterial agents known, and they kill bacteria by turning DNA gyrase (and the closely related enzyme topoisomerase IV [Topo IV]) into a DNA-reactive cytotoxin (23).Gyrase plays at least two essential roles in chromosome structure and function. First, it condenses DNA by converting relaxed DNA molecules into a dynamic, underwound, and plectonemically supercoiled state (12). DNA in living cells is compartmentalized into subchromosomal regions called domains, and the dynamic superhelical structure within a doma...
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