Biomimetic total synthesis of meiogynin A, an inhibitor of Bcl-xL and Bak interaction

A short, convergent, and selective synthesis of meiogynin A, an inhibitor of the antiapoptotic protein Bcl-xL, has been performed. This synthesis, based on a biomimetic approach, allowed the determination of its absolute configuration. Three isomers of meiogynin A have also been elaborated. One of these was found to be three times more potent than the natural compound.     

Specific molecular and cellular events induced by irradiated X‐ray photoactivatable drugs raise the problem of co‐toxicities: particular consequences for anti‐cancer synchrotron therapy

Synchrotrons are capable of producing intense low‐energy X‐rays that enable the photoactivation of high‐Z elements. Photoactivation therapy (PAT) consists of loading tumors with photoactivatable drugs and thereafter irradiating them at an energy, generally close to the K‐edge of the element, that enhances the photoelectric effect. To date, three major photoactivatable elements are used in PAT: platinum (cisplatin and carboplatin), iodine (iodinated contrast agents and iododeoxyuridine) and gadolinium (motexafin gadolinium). However, the molecular and cellular events specific to PAT and the radiobiological properties of these photoactivatable drugs are still misknown. Here, it is examined how standard and synchrotron X‐rays combined with photoactivatable drugs impact on the cellular response of human endothelial cells. These findings suggest that the radiolysis products of the photoactivatable drugs may participate in the synergetic effects of PAT by increasing the severity of radiation‐induced DNA double‐strand breaks. Interestingly, subpopulation of highly damaged cells was found to be a cellular pattern specific to PAT. The data show that the efficiency of emerging anti‐cancer modalities involving synchrotron photoactivation strongly depends on the choice of photoactivatable drugs, and important series of experiments are required to secure their clinical transfer before applying to humans.     

Flow and heat transfer of non-Newtonian fluids in enameling dies

The present work analyses computationally the flow inside wire enameling dies within the framework of the lubrication theory approximation. Non-Newtonian flow behavior and heat transfer are accounted for as well. It is shown that the developed approach most accurately predicts the momentum and heat fluxes along the wire. As such it is proven as a reliable and computationally efficient tool for the design of flow optimized die shapes. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

On heterogeneous latent class models with applications to the analysis of rating scores

Discovering the preferences and the behaviour of consumers is a key challenge in marketing. Information about such topics can be gathered through surveys in which the respondents must assign a score to a number of items. A strategy based on different latent class models can be used to analyze such data and achieve this objective: it consists in identifying groups of consumers whose response patterns are similar and characterizing them in terms of preferences and covariates. The basic latent class model can be extended by including covariates to model differences in (1) latent class probabilities and (2) conditional probabilities. A strategy for fitting and choosing a suitable model among them is proposed taking into account identifiability issues, the identification of potential covariates and the checking of goodness-of-fit. The tools to perform this analysis are implemented in the R package covLCA available from CRAN. We illustrate and explain the application of this strategy using data about the preferences of Belgian households for supermarkets.     

Quantization and clustering with Bregman divergences

This paper deals with the problem of quantization of a random variable X taking values in a separable and reflexive Banach space, and with the related question of clustering independent random observations distributed as X. To this end, we use a quantization scheme with a class of distortion measures called Bregman divergences, and provide conditions ensuring the existence of an optimal quantizer and an empirically optimal quantizer. Rates of convergence are also discussed.     

Dual-Color Photoconvertible Fluorescent Probes Based on Directed Photooxidation Induced Conversion for Bioimaging

We herein present a new concept to produce dual-color photoconvertible probes based on a mechanism called Directed Photooxidation Induced Conversion (DPIC). As a support of this mechanism, styryl-coumarins ( SCs ) bearing Aromatic Singlet Oxygen Reactive Moieties (ASORMs) like furan and pyrrole have been synthesized. SCs are bright fluorophores, which undergo a hypsochromic conversion upon visible light irradiation due to directed photooxidation of the ASORM that leads to the disruption of conjugation. SC-P , a yellow emitting probe bearing a pyrrole moiety, converts to a stable blue emitting coumarin with a 68 nm shift allowing the photoconversion and tracking of lipid droplet in live cells. This new approach might pave the way to a new generation of photoconvertible dyes for advanced bioimaging applications.     

Potentiometric determination of mephedrone in oral fluids with ion-selective membranes

This work presents a potentiometric approach for the detection of two cathinone derivatives, namely mephedrone (4-MMC) and clephedrone (4-CMC). Contrary to neutral-carriers (dibenzo-18-crown-6-ether and calix[4]arene), cation-exchanger (tetraphenylborate sodium) as active component of ion-selective membrane showed near-Nernstian response (+47 mV/decade from 1.7 ⋅ 10⁻⁶ to 5.6 ⋅ 10⁻⁴ mol l⁻¹) and selectivity for 4-MMC in oral fluids (OF). The agreement between the quantitative results obtained with the potentiometric approach and the HPLC/MS-MS method determination of 4-MMC in OF shows the potential of the proposed potentiometric approach for forensic analysis.     

碳纤维阴极的电子发射机制

建立了金属阴极和碳纤维阴极的电子发射机制模型,发射后的阴极和碳纤维阴极的微观照片证实了模型的正确性。实验结果与分析表明：一种优化的阴极应该具备多种电子发射机制,整个阴极的电子发射更均匀,碳纤维阴极的电子发射不仅具有尖端的场发射,而且伴随着侧向的表面闪络(随纹)。此外和金属阴极相比较,处理后碳纤维阴极具有较慢的等离子体膨胀速度(≤1 cm/μs)并使该实验用微波源具有较宽的微波脉冲输出(≥200 ns)。     

One-pot synthesis of oxazoles using isocyanide surrogates

We wish to present herein a simple one-pot synthesis of 2,5-disubstituted oxazoles, starting from benzyl halides and acyl chlorides. The in situ formation of isocyanides, followed by the addition of an acyl chloride in the presence of a base leads to the desired oxazoles in good yields.     

Reductive transformations of unsaturated azabicyclic nitrolactams

Using different reducing methods unsaturated indolizidine and quinolizidine lactams substituted with a nitro group were transformed into various alkaloid-like derivatives. Hydrogen transfer and palladium catalyzed hydrogenation gave compounds of ketolactam or lactam type meanwhile the nitro group was eliminated. On the other hand, in presence of Raney-nickel catalyst the nitro compounds were reduced to diastereomeric amino derivatives whose stereochemistry was elucidated by NMR spectroscopy. Using sodium bis-dimethoxy-ethoxy-aluminum-hydride (Red-Al) as reducing agent an unexpected tricyclic azetidine was isolated and characterized.