Modes of Random Lasers

In conventional lasers, the optical cavity that confines the photons also determines essential characteristics of the lasing modes such as wavelength, emission pattern, ... In random lasers, which do not have mirrors or a well-defined cavity, light is confined within the gain medium by means of multiple scattering. The sharp peaks in the emission spectra of semiconductor powders, first observed in 1999, has therefore lead to an intense debate about the nature of the lasing modes in these so-called lasers with resonant feedback. In this paper, we review numerical and theoretical studies aimed at clarifying the nature of the lasing modes in disordered scattering systems with gain. We will discuss in particular the link between random laser modes near threshold (TLM) and the resonances or quasi-bound (QB) states of the passive system without gain. For random lasers in the localized regime, QB states and threshold lasing modes were found to be nearly identical within the scattering medium. These studies were later extended to the case of more lossy systems such as random systems in the diffusive regime where differences between quasi-bound states and lasing modes were measured. Very recently, a theory able to treat lasers with arbitrarily complex and open cavities such as random lasers established that the TLM are better described in terms of the so-called constant-flux states.Comment: Review paper submitted to Advances in Optics and Photonic

Investigating the functionality of an OCT4-short response element in human induced pluripotent stem cells.

Pluripotent stem cells offer great therapeutic promise for personalized treatment platforms for numerous injuries, disorders, and diseases. Octamer-binding transcription factor 4 (OCT4) is a key regulatory gene maintaining pluripotency and self-renewal of mammalian cells. With site-specific integration for gene correction in cellular therapeutics, use of the OCT4 promoter may have advantages when expressing a suicide gene if pluripotency remains. However, the human OCT4 promoter region is 4 kb in size, limiting the capacity of therapeutic genes and other regulatory components for viral vectors, and decreasing the efficiency of homologous recombination. The purpose of this investigation was to characterize the functionality of a novel 967bp OCT4-short response element during pluripotency and to examine the OCT4 titer-dependent response during differentiation to human derivatives not expressing OCT4. Our findings demonstrate that the OCT4-short response element is active in pluripotency and this activity is in high correlation with transgene expression in vitro, and the OCT4-short response element is inactivated when pluripotent cells differentiate. These studies demonstrate that this shortened OCT4 regulatory element is functional and may be useful as part of an optimized safety component in a site-specific gene transferring system that could be used as an efficient and clinically applicable safety platform for gene transfer in cellular therapeutics

River sediment geochemistry and provenance following the Mount Polley mine tailings spill, Canada:The role of hydraulic sorting and sediment dilution processes in contaminant dispersal and remediation

The failure of the Mount Polley tailings storage facility (TSF) in August 2014 was one of the largest magnitude failures on record, and released approximately 25 Mm3 of material, including c. 7.3 Mm3 of tailings into Hazeltine Creek, part of the Quesnel River watershed. This study evaluates the impact of the spill on the geochemistry of river channel and floodplain sediments and utilizes Pb isotope ratios and a multi-variate mixing model to establish sediment provenance. In comparison to sediment quality guidelines and background concentrations, Cu and V were found to be most elevated. Copper in river channel sediments ranged from 88-800 mg kg-1, with concentrations in sand-rich and clay/silt-rich sediments being statistically significantly different. Concentrations in river channel were believed to be influenced by hydraulic sorting during the rising and falling limbs of the flood wave caused by the tailings spill. Results highlight the importance of erosive processes, instigated by the failure, in incorporating soils and sediments into the sediment load transported and deposited within Hazeltine Creek. In this instance, these processes diluted tailings with relatively clean material that reduced metal concentrations away from the TSF failure. This does however, highlight environmental risks in similar catchments downstream of TSFs that contain metal-rich sediment within river channels and floodplain that have been contaminated by historical mining

DRP-1 is required for BH3 mimetic-mediated mitochondrial fragmentation and apoptosis

The concept of using BH3 mimetics as anticancer agents has been substantiated by the efficacy of selective drugs, such as Navitoclax and Venetoclax, in treating BCL-2-dependent haematological malignancies. However, most solid tumours depend on MCL-1 for survival, which is highly amplified in multiple cancers and a major factor determining chemoresistance. Most MCL-1 inhibitors that have been generated so far, while demonstrating early promise in vitro, fail to exhibit specificity and potency in a cellular context. To address the lack of standardised assays for benchmarking the in vitro binding of putative inhibitors before analysis of their cellular effects, we developed a rapid differential scanning fluorimetry (DSF)-based assay, and used it to screen a panel of BH3 mimetics. We next contrasted their binding signatures with their ability to induce apoptosis in a MCL-1 dependent cell line. Of all the MCL-1 inhibitors tested, only A-1210477 induced rapid, concentration-dependent apoptosis, which strongly correlated with a thermal protective effect on MCL-1 in the DSF assay. In cells that depend on both MCL-1 and BCL-XL, A-1210477 exhibited marked synergy with A-1331852, a BCL-XL specific inhibitor, to induce cell death. Despite this selectivity and potency, A-1210477 induced profound structural changes in the mitochondrial network in several cell lines that were not phenocopied following MCL-1 RNA interference or transcriptional repression, suggesting that A-1210477 induces mitochondrial fragmentation in an MCL-1-independent manner. However, A-1210477-induced mitochondrial fragmentation was dependent upon DRP-1, and silencing expression levels of DRP-1 diminished not just mitochondrial fragmentation but also BH3 mimetic-mediated apoptosis. These findings provide new insights into MCL-1 ligands, and the interplay between DRP-1 and the anti-apoptotic BCL-2 family members in the regulation of apoptosis

Origin and Fate of Vanadium in the Hazeltine Creek Catchment following the 2014 Mount Polley Mine Tailings Spill in British Columbia, Canada

This is the final version. Available on open access from American Chemical Society via the DOI in this recordResults are presented from the analysis of aqueous and solid-phase V speciation within samples collected from the Hazeltine Creek catchment affected by the August 2014 Mount Polley mine tailings dam failure, Canada. Electron microprobe and XANES analysis found that V is present as V3+ substituted into magnetite, and V3+ and V4+ substituted into titanite, both of which occur in the spilled Mount Polley tailings. Secondary Fe oxyhydroxides forming in inflow waters and on creek beds have V K-edge XANES spectra exhibiting E½ positions and pre-edge features consistent with the presence of V5+ species, suggesting sorption of this species on these secondary phases. PHREEQC modelling suggests that the stream waters mostly contain V5+, and the inflow and pore waters contain a mixture of V3+ and V5+. These data, and stream, inflow and pore water chemical data, suggest that dissolution of V(III)-bearing magnetite, V(III,IV)-bearing titanite, V(V)-bearing Fe(-Al-Si-Mn) oxhydroxides, V-bearing Al(OH)3 and/or -clay minerals may have occurred. In the circumneutral pH environment of Hazeltine Creek elevated V concentrations are likely naturally attenuated by formation of V(V)-bearing secondary Fe oxyhydroxide, Al(OH)3 or clay mineral colloids, suggesting that the V is not bioavailable. A conceptual model is presented describing the origin and fate of V in Hazeltine Creek that is applicable to other river systems.Natural Environment Research Council (NERC

Degradation of electroless Ni(P) under-bump metallization in Sn3.5Ag and Sn37Pb solders during high-temperature storage

The interfacial reaction between electroless Ni(P) under-bump metallization (UBM) and solders is studied. A P-rich layer forms in the UBM along the solder side after reflow and thermal aging. Crack formation inside the P-rich layer can sometimes penetrate throughout the entire UBM layer structure. The Ni(P) UBM degradation occurs earlier in the Sn3.5Ag solder than in Sn37Pb because of its higher reflow temperature. Despite the formation of a P-rich layer and cracks inside the UBM, it still keeps its original function within the high-temperature storage period in this study. Explanations for the formation of the P-rich layer and cracks in the UBM are outlined along with explanations for the Ni(P) UBM degradation process

Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells.

Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies. In this study, we demonstrate a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism

Gene expression by marrow stromal cells in a porous collagen-glycosaminoglycan scaffold is affected by pore size and mechanical stimulation.

Marrow stromal cell (MSC) populations, which are a potential source of undifferentiated mesenchymal cells, and culture scaffolds that mimic natural extracellular matrix are attractive options for orthopaedic tissue engineering. A type I collagen-glycosaminoglycan (CG) scaffold that has previously been used clinically for skin regeneration was recently shown to support expression of bone-associated proteins and mineralisation by MSCs cultured in the presence of osteogenic supplements. Here we follow RNA markers of osteogenic differentiation in this scaffold. We demonstrate that transcripts of the late stage markers bone sialoprotein and osteocalcin are present at higher levels in scaffold constructs than in two-dimensional culture, and that considerable gene induction can occur in this scaffold even in the absence of soluble osteogenic supplements. We also find that bone-related gene expression is affected by pore size, mechanical constraint, and uniaxial cyclic strain of the CG scaffold. The data presented here further establish the CG scaffold as a potentially valuable substrate for orthopaedic tissue engineering and for research on the mechanical interactions between cells and their environment, and suggest that a more freely-contracting scaffold with larger pore size may provide an environment more conducive to osteogenesis than constrained scaffolds with smaller pore sizes

Mobility shift-based electrophoresis coupled with fluorescent detection enables real-time enzyme analysis of carbohydrate sulfatase activity

Sulfated carbohydrate metabolism is a fundamental process, which occurs in all domains of life. Carbohydrate sulfatases are enzymes that remove sulfate groups from carbohydrates and are essential to the depolymerisation of complex polysaccharides. Despite their biological importance, carbohydrate sulfatases are poorly studied and challenges remain in accurately assessing the activity, specificity and kinetic parameters. Most notably, separation of desulfated products from sulfated substrates is currently a time-consuming process. In this paper, we describe the development of rapid capillary electrophoresis coupled to substrate fluorescence detection as a high-throughput and facile means of analysing carbohydrate sulfatase activity. The approach has utility for the determination of both kinetic and inhibition parameters and is based on existing microfluidic technology coupled to a new synthetic fluorescent 6S-GlcNAc carbohydrate substrate. Furthermore, we compare this technique in terms of both time and resources, to high performance anion exchange chromatography and NMR-based methods, which are the two current ‘gold standards’ for enzymatic carbohydrate sulfation analysis. Our study clearly demonstrates the advantages of mobility shift assays for the quantification of near real-time carbohydrate desulfation by purified sulfatases, and could support the search for small molecule inhibitors of these disease-associated enzymes. One sentence summary Sulfatases remove sulfate groups from biomolecules; in this study we report a rapid and robust capillary electrophoresis assay for the quantification of carbohydrate desulfation

Tips for Junior Doctors and Medical Students: Writing and Publishing Undergraduate Textbooks

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