Curing study of a preimidized photosensitive polyimide

The effects of curing on removal of solvent and the development of chemical crosslinks were studied in a preimidized, intrinsically photosensitive polyimide. The polymer, Probimide 412, was in solution of γ-butyrolactone (GBL), and spun cast or doctor bladed to form samples for analysis. The films were systematically studied from soft (100°C) to hard bake (400°C), as the effects of cure environment (i.e., air vs. nitrogen) and UV exposure were monitored. The samples were characterized by thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and dynamic mechanical analysis (DMA). The index of refraction was measured by waveguide propagation mode determination. TGA results show that there is a distribution of solvent removal temperatures, probably due to polymer-solvent binding. Solvent is removed from the polymer as it is thermally cured from ∼150°C to 300°C, and UV curing aids in the removal of solvent. Chemical crosslinks induced by both thermal and UV curing increase the refractive index and darken the material. Crosslinking broadens the glass transition and reinforces the rubbery modulus. FTIR results show that thermally induced crosslinking occurs in the polymer at 400°C in nitrogen and at 300°C in air but does not occur appreciably at 300°C in nitrogen or at any lower temperature. Ultraviolet curing also crosslinks the polymer and is caused by hydrogen abstraction from alkyl substituents and subsequent crosslinking at the benzophenone carbonyl group. During thermal curing, although there is evidence from FTIR spectroscopy that a similar reaction may occur, there are probably multiple reactions simultaneously taking place.     

Guest editorial–special issue on ground control in mining in 2020

正Ground control is the science of studying and controlling the behavior of rock strata in response to mining operations.Ground-control-related research has seen significant advancements over the last 40 years, and these accomplishments are well documented in the proceedings of the annual International Conference on Ground Control in Mining (ICGCM)[1].     

Molecular Weight Patterns of Nägeli Amylodextrins

This research was designed to assess the utility of a four-column high performance size-exclusion chromatography (HPSEC) system to characterize starch-based carbohydrates of different sizes. Corn starches with varying amounts of amylose were treated with 16% sulfuric acid to create Nägeli amylodextrins. During treatment, sub-samples were taken at various intervals from 0–100 days. The washed, dried sub-samples were chromatographically analyzed using four Shodex lonpak columns linked in series. Chromatograms showed the progressive depolymerization of starch. Pullulan molecular weight standards were used to estimate amylodextrin molecular weights (MW). Number-average MWs of amylodextrins decreased as the original starches' amylopectin content decreased. A single HPSEC system can be effectively used to characterize carbohydrates ranging in size from starch to amylodextrins; and to monitor the acid (or enzyme) depolymerization of starches.     

Loss of αA or αB-Crystallin Accelerates Photoreceptor Cell Death in a Mouse Model of P23H Autosomal Dominant Retinitis Pigmentosa

Inherited retinal degenerations (IRD) are a leading cause of visual impairment and can result from mutations in any one of a multitude of genes. Mutations in the light-sensing protein rhodopsin (RHO) is a leading cause of IRD with the most common of those being a missense mutation that results in substitution of proline-23 with histidine. This variant, also known as P23H-RHO, results in rhodopsin misfolding, initiation of endoplasmic reticulum stress, the unfolded protein response, and activation of cell death pathways. In this study, we investigate the effect of α-crystallins on photoreceptor survival in a mouse model of IRD secondary to P23H-RHO. We find that knockout of either αA- or αB-crystallin results in increased intraretinal inflammation, activation of apoptosis and necroptosis, and photoreceptor death. Our data suggest an important role for the ⍺-crystallins in regulating photoreceptor survival in the P23H-RHO mouse model of IRD.     

Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases

Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood–brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies.     

The microRNA-455 Null Mouse Has Memory Deficit and Increased Anxiety,Targeting Key Genes Involved in Alzheimer’s Disease

The complete molecular mechanisms underlying the pathophysiology of Alzheimer’s disease (AD) remain to be elucidated. Recently, microRNA-455-3p has been identified as a circulating biomarker of early AD, with increased expression in post-mortem brain tissue of AD patients. MicroRNA-455-3p also directly targets and down-regulates APP, with the overexpression of miR-455-3p suppressing its toxic effects. Here, we show that miR-455-3p expression decreases with age in the brains of wild-type mice. We generated a miR-455 null mouse utilising CRISPR-Cas9 to explore its function further. Loss of miR-455 resulted in increased weight gain, potentially indicative of metabolic disturbances. Furthermore, performance on the novel object recognition task diminished significantly in miR-455 null mice (p = 0.004), indicating deficits in recognition memory. A slight increase in anxiety was also captured on the open field test. BACE1 and TAU were identified as new direct targets for miR-455-3p, with overexpression of miR-455-3p leading to a reduction in the expression of APP, BACE1 and TAU in neuroblastoma cells. In the hippocampus of miR-455 null mice at 14 months of age, the levels of protein for APP, BACE1 and TAU were all increased. Such findings reinforce the involvement of miR-455 in AD progression and demonstrate its action on cognitive performance.     

Role of Tyrosine Kinase Syk in Thrombus Stabilisation at High Shear

Understanding the pathways involved in the formation and stability of the core and shell regions of a platelet-rich arterial thrombus may result in new ways to treat arterial thrombosis. The distinguishing feature between these two regions is the absence of fibrin in the shell which indicates that in vitro flow-based assays over thrombogenic surfaces, in the absence of coagulation, can be used to resemble this region. In this study, we have investigated the contribution of Syk tyrosine kinase in the stability of platelet aggregates (or thrombi) formed on collagen or atherosclerotic plaque homogenate at arterial shear (1000 s⁻¹). We show that post-perfusion of the Syk inhibitor PRT-060318 over preformed thrombi on both surfaces enhances thrombus breakdown and platelet detachment. The resulting loss of thrombus stability led to a reduction in thrombus contractile score which could be detected as early as 3 min after perfusion of the Syk inhibitor. A similar loss of thrombus stability was observed with ticagrelor and indomethacin, inhibitors of platelet adenosine diphosphate (ADP) receptor and thromboxane A₂ (TxA₂), respectively, and in the presence of the Src inhibitor, dasatinib. In contrast, the Btk inhibitor, ibrutinib, causes only a minor decrease in thrombus contractile score. Weak thrombus breakdown is also seen with the blocking GPVI nanobody, Nb21, which indicates, at best, a minor contribution of collagen to the stability of the platelet aggregate. These results show that Syk regulates thrombus stability in the absence of fibrin in human platelets under flow and provide evidence that this involves pathways additional to activation of GPVI by collagen.