Instrumentation-related uncertainty of reflectance and transmittance measurements with a two-channel spectrophotometer

Spectrophotometers are operated in numerous fields of science and industry for a variety of applications. In order to provide confidence for the measured data, analyzing the associated uncertainty is valuable. However, the uncertainty of the measurement results is often unknown or reduced to sample-related contributions. In this paper, we describe our approach for the systematic determination of the measurement uncertainty of the commercially available two-channel spectrophotometer Agilent Cary 5000 in accordance with the Guide to the expression of uncertainty in measurements. We focus on the instrumentation-related uncertainty contributions rather than the specific application and thus outline a general procedure which can be adapted for other instruments. Moreover, we discover a systematic signal deviation due to the inertia of the measurement amplifier and develop and apply a correction procedure. Thereby we increase the usable dynamic range of the instrument by more than one order of magnitude. We present methods for the quantification of the uncertainty contributions and combine them into an uncertainty budget for the device. © 2017 Author(s)

Polyene Macrolide Antifungal Drugs Trigger Interleukin-1β Secretion by Activating the NLRP3 Inflammasome

The use of antimycotic drugs in fungal infections is based on the concept that they suppress fungal growth by a direct killing effect. However, amphotericin and nystatin have been reported to also trigger interleukin-1β (IL-1β) secretion in monocytes but the molecular mechanism is unknown. Here we report that only the polyene macrolides amphotericin B, nystatin, and natamycin but none of the tested azole antimycotic drugs induce significant IL-1β secretion in-vitro in dendritic cells isolated from C57BL/6 mouse bone marrow. IL-1β release depended on Toll-like receptor-mediated induction of pro-IL-1β as well as the NLRP3 inflammasome, its adaptor ASC, and caspase-1 for enzymatic cleavage of pro-IL-1β into its mature form. All three drugs induced potassium efflux from the cells as a known mechanism for NLRP3 activation but the P2X7 receptor was not required for this process. Natamycin-induced IL-1β secretion also involved phagocytosis, as cathepsin activation as described for crystal-induced IL-1β release. Together, the polyene macrolides amphotericin B, nystatin, and natamycin trigger IL-1β secretion by causing potassium efflux from which activates the NLRP3-ASC-caspase-1. We conclude that beyond their effects on fungal growth, these antifungal drugs directly activate the host's innate immunity

Toll-Like Receptor Signaling and SIGIRR in Renal Fibrosis upon Unilateral Ureteral Obstruction

Innate immune activation via IL-1R or Toll-like receptors (TLR) contibutes to acute kidney injury but its role in tissue remodeling during chronic kidney disease is unclear. SIGIRR is an inhibitor of TLR-induced cytokine and chemokine expression in intrarenal immune cells, therefore, we hypothesized that Sigirr-deficiency would aggravate postobstructive renal fibrosis. The expression of TLRs as well as endogenous TLR agonists increased within six days after UUO in obstructed compared to unobstructed kidneys while SIGIRR itself was downregulated by day 10. However, lack of SIGIRR did not affect the intrarenal mRNA expression of proinflammatory and profibrotic mediators as well as the numbers of intrarenal macrophages and T cells or morphometric markers of tubular atrophy and interstitial fibrosis. Because SIGIRR is known to block TLR/IL-1R signaling at the level of the intracellular adaptor molecule MyD88 UUO experiments were also performed in mice deficient for either MyD88, TLR2 or TLR9. After UUO there was no significant change of tubular interstitial damage and interstitial fibrosis in neither of these mice compared to wildtype counterparts. Additional in-vitro studies with CD90+ renal fibroblasts revealed that TLR agonists induce the expression of IL-6 and MCP-1/CCL2 but not of TGF-β, collagen-1α or smooth muscle actin. Together, postobstructive renal interstitial fibrosis and tubular atrophy develop independent of SIGIRR, TLR2, TLR9, and MyD88. These data argue against a significant role of these molecules in renal fibrosis

Phytochemical Analysis Of Avicennia Officinalis Of Krishna Estuary

Phytochemical investigation on the aerial roots of Avicennia officinalis of Krishna estuary, India resulted in the isolation ofthree pentacyclic triterpenoids, betulin aldehyde (1), betulinic acid ( 2) and betulin ( 3). These are characterized byphysical and spectral data. All are known compounds but we are reporting first time from the Krishna estuary species.Compound ( 2) was also possess Cytotoxicity

Determination of boron in zirconium-niobium alloys by spectrophotometry

468-470Boron doped zirconium-niobium alloy rods are used as neutron reactivity control rods in advanced nuclear reactors. Accurate knowledge about the boron content in this alloy is an essential requirement prior to its usage in nuclear reactors. In view of the refractory nature of the alloy, boron determination in these type of matrices is a challenging task. Also due to non-availability of matrix matched reference materials, direct solid analysis cannot be resorted to. Quantitative dissolution of the matrix without losing any boron followed by its determination is the only alternative. In the present work, Zr-Nb sample was dissolved in (NH4)2SO4 and H2SO4 taking care to prevent the loss of boron. Boron was selectively separated employing batch extraction with 10% 2-ethyl hexane 1,3 diol in chloroform and determined spectrophotometrically as B-Curcumin complex. Absorbance was measured at 550 nm. The precision and accuracy of the method is 3%. The absolute detection limit of the method is 12 ng. The method has been evaluated by standard addition method and validated by ICP-AES technique

Continuous-Flow Visible Light Organophotocatalysis for Direct Arylation of 2H-Indazoles: Fast Access to Drug Molecules

A continuous-flow homogeneous photocatalytic method has been devised for the direct arylation of 2H-indazoles. This visible-light-promoted approach directly accesses a wide range of structurally diverse C3-arylated scaffolds of biological interest in a fast (1 min), single-step reaction by using eosin Y as an organophotocatalyst. Furthermore, a microreactor technology is also employed for the fast synthesis of liver X receptor inhibitor drugs with very good yields under metal-free conditions, whereas the reported methods required multiple steps and much longer reaction times (18-24 h).11Nscopu

Fast-Synthesis of alpha-Phosphonyloxy Ketones as Drug Scaffolds in a Capillary Microreactor

A simple, room temperature approach for the fast single-step synthesis of alpha-phosphonyloxy ketone, a drug scaffold, has been developed which involves highly reactive species i.e., 1,2-dicarbonyls that readily react with trialkyl phosphites and formic acids in batch as well as in continuous-flow with the flow rate of 3 ml/min (t (R) = similar to 4 s). The present approach reduced the synthesis time from hours to minutes in batch, which was further lowered to a few seconds precisely controlled by single capillary microfluidics. A wide range of 1,2-dicarbonyl derivatives were smoothly transformed to their corresponding alpha-phosphonyloxy ketones in moderate to good yields (50-82 %) under optimized flow-reaction conditions. Further, the alpha-phosphonyloxy ketones produced can be utilized in batch process to form benzoin, oxazole core, and alpha,alpha '-diarylated carbonyl compounds in 82 %, 50 %, and 54 % yields, respectively, which are alternative key precursors/scaffolds of natural products and active pharmaceutical ingredients (APIs).11Nsciescopu

Photocatalysis in a multi-capillary assembly microreactor: toward up-scaling the synthesis of 2H-indazoles as drug scaffolds

Visible-light-promoted direct arylation of 2H-indazoles using phenyldiazonium salt enabled a single-step and fast synthesis (65%) in a capillary microreactor, compared to the slow synthesis (18 h) in a flask. Moreover, scalable photocatalysis of a 2H-indazole based liver X-receptor modulator was performed by devising a compact multi-capillary assembly microreactor composed of vertically aligned 10 capillary tubes connected to 3D printed fluidic fixtures. Eventually, the assembly produced the drug on an similar to 4 gram scale per hour by a one-flow automated process taken for 2.2 min from synthesis to product separation, which would be a breakthrough approach for pharmaceutical production.11Nsciescopu