Norupberthelsen7107

This leads me to advance a possible strategy for historians to investigate big bioscience fields. Following Abir-Am, I propose to trace their genealogies back to the fluctuating semi-institutional gatherings and the institutional structures that sustained them. My research on Crick supports the view that such studies can bring insights into the question of why the contours of contemporary big bioscience endeavours have come to be shaped the way they are. Further, the essay provides a heuristic device for approaching these enquiries 'follow the cross-worlds influencers' who worked to build and organise these semi-institutional gatherings and institutional structures.

Cosmetic formulations are influenced by environmental impacts and ageing, resulting in rancidity and change of colour and structure. These changes are caused by free radicals (FRs). KG-501 The sensitivity of cosmetics generating FRs is a metric for its quality and should be determined.

Electron spin resonance spectroscopy in combination with UV irradiation tested cosmetics such as creams, milks, lotions and fragrances. The probes were directly measured without expensive preparation.

Nine formulations are tested for its radical generation and ranked corresponding to the radical power. The transformation of the FR properties of three formulations to skin is measured by the radical skin status factor (RSF) method. It shows that the higher the radical power (RP) is, the lower the radical status RSF of skin will be.

The knowledge of the sensitivity of cosmetics to generate FRs is necessary for its stabilization and prevention of potential damages to skin. It is a new way in development of cosmetics which has to be considered.

The knowledge of the sensitivity of cosmetics to generate FRs is necessary for its stabilization and prevention of potential damages to skin. It is a new way in development of cosmetics which has to be considered.Anthropogenic (137)Cs activity concentration, in surface sea water along the western and eastern coast of India has been estimated using the in-situ pre-concentration approach. Activity levels of (137)Cs ranges from 0.09-1.30Bqm(-3) with an overall mean of 0.69±0.29Bqm(-3). Latitudinal variation and higher depletion in activity concentration of (137)Cs at few locations were observed. Temporal change of (137)Cs in sea water along Indian coast unveils a lower effective half-life of 13.8±0.7y in comparison to Asia Pacific regional sea water. The results prevailed that the spatial distribution confers no fresh input of (137)Cs in Indian coastal region.Carboxylating enoyl-thioester reductases (ECRs) are a recently discovered class of enzymes. They catalyze the highly efficient addition of CO2 to the double bond of α,β-unsaturated CoA-thioesters and serve two biological functions. In primary metabolism of many bacteria they produce ethylmalonyl-CoA during assimilation of the central metabolite acetyl-CoA. In secondary metabolism they provide distinct α-carboxyl-acyl-thioesters to vary the backbone of numerous polyketide natural products. Different ECRs were systematically assessed with a diverse library of potential substrates. We identified three active site residues that distinguish ECRs restricted to C4 and C5-enoyl-CoAs from highly promiscuous ECRs and successfully engineered a selected ECR as proof-of-principle. This study defines the molecular basis of ECR reactivity, allowing for predicting and manipulating a key reaction in natural product diversification.During the last decade, maslinic acid has been evaluated for many biological properties, e.g. as an anti-tumor or an anti-viral agent but also as a nutraceutical. The potential of maslinic acid and related derivatives to act as inhibitors of acetyl- or butyryl-cholinesterase was examined in this communication in more detail. Cholinesterases do still represent an interesting group of target enzymes with respect to the investigation and treatment of the Alzheimer's disease and other dementia illnesses as well. Although other triterpenoic acids have successfully been tested for their ability to act as inhibitors of cholinesterases, up to now maslinic acid has not been part of such studies. For this reason, three series of maslinic acid derivatives possessing modifications at different centers were synthesized and subjected to Ellman's assay to determine their inhibitory strength and type of inhibitory action. While parent compound maslinic acid was no inhibitor in these assays, some of the compounds exhibited an inhibition of acetylcholinesterase in the single-digit micro-molar range. Two compounds were identified as inhibitors of butyrylcholinesterase showing inhibition constants comparable to those of galantamine, a drug often used in the treatment of Alzheimer's disease. Furthermore, additional selectivity as well as cytotoxicity studies were performed underlining the potential of several derivatives and qualifying them for further investigations. Docking studies revealed that the different kinetic behavior within the same compound series may be explained by the ability of the compounds to enter the active site gorge of AChE.New analogues (3a-l) of the previously described α4β2 selective ligand 3-(6-halopyridin-3-yl)-3,6-diazabicyclo[3.1.1]heptanes (2a,b) have been synthesized and their binding activity for neuronal acetylcholine receptor subtypes α4β2 and α7 were assayed. Six of these compounds (3a,b,c,j,k and l) showed high affinity and selectivity for α4β2 receptors. The phenylpyridyl-diazabicycloheptane 3c displayed Ki value of 11.17 pM for α4β2, in line with that of the halogenated homologues 3a,b, although it was characterized by an improved selectivity (Ki = 17 μM for α7 receptors). The influence of substitutions on the phenylpyridyl moiety on binding at both α4β2 and α7 receptors has been examined through the Topliss decision tree analysis. Substitution with electron-donating groups (as CH3 and OCH3) resulted in a good affinity for α4β2 receptors and substantially no affinity for α7. Amongst all the tested phenyl-substituted compounds, the p-NO2-phenyl substituted analogue 3j exhibited the highest α4β2 affinity, with Ki value comparable to that of 3c. Intrinsic α4β2 receptor mediated activity in [(3)H]-DA release assay was showed by compound 3a as well as by the reference analogue 2a, whereas phenyl substituted derivative 3c exhibited α4β2 antagonist activity.In our continuing search for safe and efficacious antifilarials, a series of novel chalcone-benzothiazole hybrids have been synthesized and evaluated for their Brugia malayi thymidylate kinase (BmTMK) enzyme inhibition activity. Their selectivity towards BmTMK was studied and compared to the human TMK (HsTMK) by an in silico method. Out of seventeen derivatives, compounds 34 and 42 showed higher interactions with the BmTMK active site. MolDock docking model revealed the interactions of these two derivatives and the results corroborated well with their in vitro antifilarial activities. Our studies suggest that these hybrids are selective towards the BmTMK enzyme and may serve as potential therapeutic agents against filariasis.A series of original 2-phenyl-3-(pyridin-4-yl)imidazo[1,2-a]pyrazines and the 3-iodo precursors, bearing a polar moiety at the C-8 position, was synthesized and evaluated for their antileishmanial activities. Two derivatives exhibited very good activity against the promastigote and the amastigote forms of Leishmania major in the micromolar to submicromolar ranges, coupled with a low cytotoxicity against macrophages and 3T3 mouse fibroblast cells. Through LmCK1 inhibition assay, investigations of the putative molecular target of these promising antileishmanial compounds will be discussed.The development of new stable 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins with high absorption properties at 650 nm, and their impressive photosensitizer ability against melanotic and amelanotic cancer cells is described. Comparison between a diester-substituted chlorin with the corresponding dihydroxymethyl derivative demonstrated that the increased hydrophilicity of the latter is crucial to ensure nanomolar activity against melanoma cells. The new photosensitizer leads to death of human melanoma cells being both apoptosis and necrosis in equal parts involved in the treatment response. The dihydroxymethyl-chlorin was particularly active against human melanocytic melanoma A375 cells, which can be viewed as a solution to overcome the resistance of melanotic melanoma to photodynamic therapy.The reaction of epichlorohydrin with concentrated sodium hydroxide in hexane under phase transfer conditions has surprisingly led to the formation of the symmetrical di(3-epoxyglycidyl-1-propenyl) ether 1 which contains both nucleophilic and electrophilic moieties. When it was reacted with n-butyllithium, intermediate 1 once again surprisingly generated epoxyglycidyl propargyl ether, which was further reacted in situ with a variety of benzaldehydes to furnish the corresponding substituted propargylic alcohols in good yields. While the reaction is operationally simple, it provides a powerful method for the synthesis of the important products from commodity materials such as epichlorohydrin. Moreover, these reactions may have revealed that some fundamental properties of the hydroxide anion in those once thought straightforward reactions are not well understood. A careful analysis of the experimental data suggests that an unprecedented concerted elimination of the epoxyglycidyl ether with sodium hydroxide may be operative and an alpha deprotonation followed by alpha elimination of the di(3-epoxyglycidyl-1-propenyl) ether with alkyllithium may have been involved.Methods for analysing water for viruses are known to have variable and relatively poor recovery efficiencies. Quantitative method recovery data are needed to correct virus enumeration results so that estimates of virus concentrations in surface waters for QMRA are not too low. Obtaining quantitative data representing method recoveries for different pathogenic viruses is a significant challenge. In this study, we investigated the use of mengovirus process control data for quantifying recovery efficiency of human adenovirus (AdV) and noroviruses GI (NoVGI) and GII (NoVGII) from surface waters. Samples were collected from the inlet to a drinking water treatment plant on the Glomma River, Norway. Performance of the sample concentration procedure was quantified by comparing the virus concentrations found in concentrated and unconcentrated samples. The mean recovery of viruses (1.2%, 0.31%, 0.15% and 0.053% for mengovirus (n = 86), AdV (n = 20), NoVGI (n = 33) and NoVGII (n = 21) respectively) estimated in this study were lower than expected, and the between sample variability in estimated recovery was very high, spanning around 6 orders of magnitude for mengovirus. Within-sample correlation between the estimated recovery of mengovirus and human viruses was poor, and therefore sample specific mengovirus data could not be used to correct all human virus concentrations. Instead beta distributions were fitted to human virus-specific recovery estimates. The magnitude and variability of virus concentration when corrected for the variable recovery efficiency was orders of magnitude higher than the uncorrected concentration. Better estimates of virus concentration could be achieved if a sample-specific spiking control could be developed that mimicked closely the behaviour of human viruses in environmental samples.