Differential Scattering Cross-Sections for the Different Product Vibrational States in the Ion-Molecule Reaction Ar+ + N2

The charge transfer reaction Ar+ + N2 --> Ar + N2+ has been investigated in a crossed beam experiment in combination with three-dimensional velocity map imaging. Angular differential state-to-state cross sections were determined as a function of the collision energy. We found that scattering into the first excited vibrational level dominates as expected, but only for scattering in the forward direction. Higher vibrational excitations up to v'=6 have been observed for larger scattering angles. For decreasing collision energy, scattering into higher scattering angles becomes increasingly important for all kinematically allowed quantum states. Our detailed measurements indicate that a quantitative agreement between experiment and theory for this basic ion-molecule reaction now comes within reach.Comment: accepted to Phys. Rev. Let

Gel meloksikama za topičku primjenu: In vitro i in vivo vrednovanje

Skin delivery of NSAIDs offers several advantages over the oral route associated with potential side effects. In the present investigation, topical gel of meloxicam (MLX) was formulated using N-methyl pyrrolidone (NMP) as a solubilizer and Carbopol Ultrez 10® as a gelling polymer. MLX gel was evaluated with respect to different physicochemical parameters such as pH, viscosity and spreadability. Irritation potential of MLX gel was studied on rabbits. Permeation of MLX gel was studied using freshly excised rat skin as a membrane. Anti-inflammatory activity of MLX gel was studied in rats and compared with the commercial formulation of piroxicam (Pirox® gel, 0.5 %, m/m). Accelerated stability studies were carried out for MLX gel for 6 months according to ICH guidelines. MLX gel was devoid of any skin irritation in rabbits. After 12 h, cumulative permeation of MLX through excised rat skin was 3.0 ± 1.2 mg cm2 with the corresponding flux value of 0.24 ± 0.09 mg cm2 h1. MLX gel exhibited significantly higher anti-inflammatory activity in rats compared to Pirox® gel. Physicochemically stable and non-irritant MLX gel was formulated which could deliver significant amounts of active substance across the skin in vitro and in vivo to elicit the anti-inflammatory activity.Primjena nesteroidnih protuupalnih lijekova na kožu ima nekoliko prednosti nad peroralnim načinom primjene uz koju se vežu određene nuspojave. U radu je opisana priprava gela meloksikama (MLX) za topičku primjenu. U pripravi gela korišten je N-metil pirolidon (NMP) kao otapalo i Carbopol ultrez 10® kao polimer za geliranje. Određivani su različiti fizikokemijski parametri kao što su pH, viskoznost i razmazljivost. Potencijalna iritacija MLX gela testirana je na kunićima, a svojstvo permeacije na svježim izrescima kože štakora. Protuupalno djelovanje praćeno je na štakorima i uspoređeno s registriranim pripravkom piroksikama (Pirox® gel, 0,5 % m/m). Testovi ubrzanog starenja MLX gela rađeni su tijekom 6 mjeseci prema ICH protokolu. Dobiveni rezultati ukazuju da MLX gel nimalo ne iritira kožu kunića. Kumulativna permeacija nakon 12 h bila je 3,0 ± 1,2 mg cm2, s odgovarajućem vrijednošću fluksa 0,24 ± 0,09 mg cm2 h1. MLX gel pokazao je značajno jače protuupalno djelovanje u odnosu na Pirox® gel. Pripravljeni gel je stabilan, ne iritira kožu, te in vitro i in vivo doprema kroz kožu ljekovitu tvar u dovoljnoj količini da ispolji protuupalno djelovanje

Exit Channel Dynamics in a Micro-Hydrated S N 2 Reaction of the Hydroxyl Anion

We report on the reaction dynamics of the monosolvated SN2 reaction of cold OH–(H2O) with CH3I that have been studied using crossed beam ion imaging. Two SN2 reaction channels are possible for this reaction: Formation of unsolvated I– and of solvated I–(H2O) products. We find a strong preference for the formation of unsolvated I– reaction products with respect to the energetically favored reaction toward solvated I–(H2O). Angle differential cross section measurements reveal similar velocity and angular distributions for all solvated and parts of the unsolvated reaction products. We furthermore find that the contribution of these two products to the total product flux can be described by the same collision energy dependence. We interpret our findings in terms of a joint reaction mechanism in which a CH3OH(H2O)···I– complex is formed that decays into either solvated or unsolvated products. Quantum chemical calculation are used to support this assumption

Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations

Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients’ prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field

Imaging Proton Transfer and Dihalide Formation Pathways in Reactions of F- + CH3I

Ion-molecule reactions of the type X(-) + CH3Y are commonly assumed to produce Y(-) through bimolecular nucleophilic substitution (SN2). Beyond this reaction, additional reaction products have been observed throughout the last decades and have been ascribed to different entrance channel geometries differing from the commonly assumed collinear approach. We have performed a crossed beam velocity map imaging experiment on the F(-) + CH3I reaction at different relative collision energies between 0.4 and 2.9 eV. We find three additional channels competing with nucleophilic substitution at high energies. Experimental branching ratios and angle- and energy differential cross sections are presented for each product channel. The proton transfer product CH2I(-) is the main reaction channel, which competes with nucleophilic substitution up to 2.9 eV relative collision energy. At this level, the second additional channel, the formation of IF(-) via halogen abstraction, becomes more efficient. In addition, we present the first evidence for an [FHI](-) product ion. This [FHI](-) product ion is present only for a narrow range of collision energies, indicating possible dissociation at high energies. All three products show a similar trend with respect to their velocity- and scattering angle distributions, with isotropic scattering and forward scattering of the product ions occurring at low and high energies, respectively. Reactions leading to all three reaction channels present a considerable amount of energy partitioning in product internal excitation. The internally excited fraction shows a collision energy dependence only for CH2I(-). A similar trend is observed for the isoelectronic OH(-) + CH3I system. The comparison of our experimental data at 1.55 eV collision energy with a recent theoretical calculation for the same system shows a slightly higher fraction of internal excitation than predicted, which is, however, compatible within the experimental accuracy

Imaging dynamic fingerprints of competing E2 and S(N)2 reactions

The competition between bimolecular nucleophilic substitution and base-induced elimination is of fundamental importance for the synthesis of pure samples in organic chemistry. Many factors that influence this competition have been identified over the years, but the underlying atomistic dynamics have remained difficult to observe. We present product velocity distributions for a series of reactive collisions of the type X- + RY with X and Y denoting the halogen atoms fluorine, chlorine and iodine. By increasing the size of the residue R from methyl to tert-butyl in several steps, we find that the dynamics drastically change from backward to dominant forward scattering of the leaving ion relative to the reactant RY velocity. This characteristic fingerprint is also confirmed by direct dynamics simulations for ethyl as residue and attributed to the dynamics of elimination reactions. This work opens the door to a detailed atomistic understanding of transformation reactions in even larger systems.The competition between chemical reactions critically affects our natural environment and the synthesis of new materials. Here, the authors present an approach to directly image distinct fingerprints of essential organic reactions and monitor their competition as a function of steric substitution

Reaction Dynamics of Temperature-Variable Anion Water Clusters Studied with Crossed Beams and by Direct Dynamics

We present a study of the different product channels in the reactions of OH− and OH−(H2O) with methyl iodide over a range of collision energies. Direct dynamics classical trajectory simulations are employed to obtain an atomistic comparison with the experimental results. For the experiments we have combined a crossed beam ion imaging setup with a multipole rf ion trap. The trap allows us to prepare the molecular and cluster ions with a controlled internal temperature and thus provides well-defined initial conditions for reaction experiments at low collision energy. Changing the internal temperature of the cluster ions was found to have a profound effect on their reactivity

Alternative splicing of the TNFSF13B (BAFF) pre-mRNA and expression of the BAFFX1 isoform in human immune cells

Human B cell activating factor (TNFSF13B, BAFF) is a tumor necrosis factor superfamily member. Binding its unique receptor (TNFRSF13C, BAFF-R) mediates gene expression and cell survival in B cells via activation of NF kappa B pathway. Furthermore, there is data indicating a role in T cell function. A functionally inhibitory isoform (Delta BAFF) resulting from the deletion of exon 3 in the TNFSF13B pre-RNA has already been reported. However, data on the complexity of post-transcriptional regulation is scarce. Here, we report molecular cloning of nine TNFSF13B transcript variants resulting from alternative splicing of the TNFSF13B pre-mRNA including BAFFX1. This variant is characterized by a partial retention of intron 3 of the TNFSF13B gene causing the appearance of a premature stop codon. We demonstrate the expression of the corresponding BAFFX1 protein in Jurkat T cells, in ex vivo human immune cells and in human tonsillar tissue. Thereby we contribute to the understanding of TNFSF13B gene regulation and reveal that BAFF is regulated through a post-transcriptional mechanism to a greater extent than reported to date