Replacement of dichloromethane within chromatographic purification : a guide to alternative solvents

Replacement of dichloromethane as the bulk medium within chromatographic purification has been evaluated with a broad range of molecules containing functionality common within Medicinal Chemistry programmes. Analysis of the data set has generated a set of general guidelines to assist in the selection of alternative solvents for CH2Cl2 as the bulk media in these ubiquitously employed processes

Characterizing Chromium Isotope Fractionation During Reduction of Cr(VI): Batch and Column Experiments

Chromium (VI) is a pervasive groundwater contaminant that poses a considerable threat to human health. Remediation techniques have focused on the reduction of the highly mobile Cr(VI) to the sparingly soluble, and less toxic, Cr(III) species. Traditionally, remediation performance has been evaluated through the measurement of Cr(VI) concentrations; however, this method is both costly and time-consuming, and provides little information regarding the mechanism of Cr(VI) removal. More recently, Cr isotope analysis has been proposed as a tool for tracking Cr(VI) migration in groundwater. Redox processes have been shown to produce significant Cr isotope fractionation, where enrichment in the ⁵³Cr/⁵²Cr ratio in the remaining Cr(VI) pool is indicative of a mass-transfer process. This thesis describes laboratory batch and column experiments that evaluate the Cr isotope fractionation associated with the reduction of Cr(VI) by various materials and under various conditions. Laboratory batch experiments were conducted to characterize the isotope fractionation during Cr(VI) reduction by granular zero-valent iron (ZVI) and organic carbon (OC). A decrease in Cr(VI) concentrations was accompanied by an increase in δ⁵³Cr values for the ZVI experiments. Data were fitted to a Rayleigh-type curve, which produced a fractionation factor α = 0.9994, suggesting a sorption-dominated removal mechanism. Scanning electron microscopy (SEM), X-ray absorption near-edge structure (XANES) spectroscopy, and X-ray photoelectron spectroscopy (XPS) indicated the presence of Cr(III) on the solid material, suggesting that reduction of Cr(VI) occurred. A series of batch experiments determined that reaction rate, experimental design, and pre-treatment of the ZVI had little to no effect on the Cr isotope fractionation. The interpretation of isotope results for the organic carbon experiments was complicated by the presence of both Cr(VI) and Cr(III) co-existing in solution, suggesting that further testing is required. A laboratory column experiment was conducted to evaluate isotopic fractionation of Cr during Cr(VI) reduction by OC under saturated flow conditions. Although decreasing dissolved Cr(VI) concentrations also were accompanied by an increase in δ⁵³Cr values, the isotope ratio values did not fit a Rayleigh-type fractionation curve. Instead, the data followed a linear regression equation yielding α = 0.9979. Solid-phase analysis indicated the presence of Cr(III) on the surface of the OC. Both the results of the solid-phase Cr and isotope analyses suggest a combination of Cr(VI) reduction mechanisms, including reduction in solution, and sorption prior to reduction. The linear characteristic of the δ⁵³Cr data may reflect the contribution of transport on Cr isotope fractionation

A Proteomics Approach Identifies Novel Resident Zebrafish Balbiani Body Proteins Cirbpa And Cirbpb

The Balbiani body (Bb) is the first marker of polarity in vertebrate oocytes. The Bb is a conserved structure found in diverse animals including insects, fish, amphibians, and mammals. During early zebrafish oogenesis, the Bb assembles as a transient aggregate of mRNA, proteins, and membrane-bound organelles at the presumptive vegetal side of the oocyte. As the early oocyte develops, the Bb appears to grow slowly until at the end of stage I of oogenesis it disassembles and deposits its cargo of localized mRNAs and proteins at the cortex. In fish and frogs, this cargo includes the germ plasm as well as gene products required to specify dorsal tissues of the future embryo. We demonstrate that the Bb is a stable, solid structure that forms a size exclusion barrier similar to other biological hydrogels. Despite its central role in oocyte polarity, little is known about the mechanism behind the Bb’s action. Analysis of the few known protein components of the Bb is insufficient to explain how the Bb assembles, translocates, and disassembles. We isolated Bbs from zebrafish oocytes and performed mass spectrometry to define the Bb proteome. We successfully identified 80 proteins associated with the Bb sample, including known Bb proteins and novel RNA-binding proteins. In particular, we identified Cirbpa and Cirbpb, which have both an RNA-binding domain and a predicted self-aggregation domain. In stage I oocytes, Cirbpa and Cirbpb localize to the Bb rather than the nucleus (as in somatic cells), indicating that they may have a specialized function in the germ line. Both the RNA-binding domain and the self-aggregation domain are sufficient to localize to the Bb, suggesting that Cirbpa and Cirbpb interact with more than just their mRNA targets within the Bb. We propose that Cirbp proteins crosslink mRNA cargo and proteinaceous components of the Bb as it grows. Beyond Cirbpa and Cirbpb, our proteomics dataset presents many candidates for further study, making it a valuable resource for building a comprehensive mechanism for Bb function at a protein level

P1: Effect of age, oestradiol levels and endometrial thickness on determining success of frozen embryo transfers

Introduction: Frozen-thawed embryo transfer (FET) is a widely used technique, with replacement of embryos during natural menstrual cycles or in cycles constructed by exogenous steroids having similar outcomes in many series. Multiple factors have been proposed to have a positive influence on the success rate of FET, including increased endometrial thickness, younger maternal age and lower circulating oestradiol. The impact of these variables in the context of constructed cycles, using GnRH agonists to facilitate suppression of ovarian function prior to exogenous steroid administration, is not known. The aim of this study was to determine the predictive ability of these indices on clinical outcomes

Harnessing ICTs : a Canadian First Nations experience; introduction to K-Net

Spanish version available in IDRC Digital Library: Cómo aprovechar las TICs : una experiencia de las Primeras Naciones Canadienses; introducción a K-NetThis document is an introduction to the work of K-Net, a program of Keewaytinook Okimakanak (KO) tribal council. K-Net is providing information and communication technologies (ICTs) to First Nations communities in remote regions of northwestern. Ontario, Canada. In less than a decade, KO communities have experienced a major technological transformation, and this case study series outlines some of the key lessons learned from their experience

Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis

Cannabis Use in an English Community: Acceptance, Anxieties, and the Liminality of Drug Prohibition

Cannabis occupies an ambiguous social, cultural, economic, and legal position, meaning that the way communities construct, interact with, and interpret drug markets is a complicated and uncertain process. This article seeks to explain these ambiguities by investigating the place of cannabis use in a UK borough, drawing on qualitative empirical data collated from a sample (N = 68) of practitioners, local residents, cannabis users, and their families. In doing so, the article employs the concept of liminality (whereby individuals and spaces occupy a position at both ends of a threshold) to explore how community behaviors and norms relate to issues of space, harm, and drug policy. The article contextualizes the position of cannabis use within the fieldwork site, exploring a series of competing contradictions that divided participants between the rhetoric and reality of drug prohibition. Drug prohibition suggests cannabis use to be dangerous, which prompted concern. However, the lived reality of prohibition for residents sat in stark juxtaposition: The drug was used commonly and publicly, was effectively decriminalized, and its use (reluctantly) accommodated. This malaise placed residents within what is described here as the liminality of drug prohibition, in which notions of the licit and illicit became blurred and whereby the illegality of cannabis augmented anxieties yet simultaneously proved a barrier to addressing them. In conclusion, the current study provides further evidence of prohibitionist drug policy proliferating rather than mitigating drug-related harms

Aktivnost Poslovnog udruženja

The authors thank the University of Strathclyde for a PhD studentship (KLW) and Merck KGaA, Darmstadt, Germany, for financial and material support.Palladium-catalyzed bond forming reactions, such as the SuzukiMiyaura and Mizoroki-Heck reactions, are some of the most broadly utilized reactions within the chemical industry. These reactions frequently employ hazardous solvents; however, to adhere to increasing sustainability pressures and restrictions regarding the use of such solvents, alternatives are highly sought after. Here we demonstrate the utility of dimethyl isosorbide (DMI) as a bio-derived solvent in several benchmark Pd-catalysed reactions: Suzuki– Miyaura (13 examples, 62–100% yield), Mizoroki–Heck (13 examples, 47– 91% yield), and Sonogashira (12 examples, 65–98% yield).PostprintPeer reviewe

Evaluation of alternative solvents in common amide coupling reactions : replacement of dichloromethane and N,N-dimethylformamide

A range of alternative solvents have been evaluated within amidation reactions employing common coupling reagents with a view to identifying suitable replacements for dichloromethane and N,N-dimethylformamid