SModelS: a tool for interpreting simplified-model results from the LHC and its application to supersymmetry

We present a general procedure to decompose Beyond the Standard Model (BSM) collider signatures presenting a $\mathbb {Z}_2$ symmetry into Simplified Model Spectrum (SMS) topologies. Our method provides a way to cast BSM predictions for the LHC in a model independent framework, which can be directly confronted with the relevant experimental constraints. Our concrete implementation currently focusses on supersymmetry searches with missing energy, for which a large variety of SMS results from ATLAS and CMS are available. As show-case examples we apply our procedure to two scans of the minimal supersymmetric standard model. We discuss how the SMS limits constrain various particle masses and which regions of parameter space remain unchallenged by the current SMS interpretations of the LHC results.     

Vitrifying star-shaped liquid crystals: synthesis and application in cholesteric polymer networks

In this paper, the formation of glass-forming reactive mesogens, that do not crystallize upon cooling, but vitrify and form supercooled LC phases, is described. These molecules exhibit broad range LC phases and enable us to carry out photopolymerization in a broad range of temperatures. From such reactive mesogens densely crosslinked networks in which the liquid crystalline order is permanently fixed are formed by photopolymerization. For this purpose eight novel low molecular mass LC materials with photopolymerizable acrylate groups have been synthesized and the detailed experimental procedures are given. The molecules have a star-shaped topology with three and four arms. The mesogenic units were varied by the addition of lateral groups in different positions. Comparing the twin molecules which we have described before with the novel three- and four-armed stars, we found that the supercooled LC phase in the three-armed stars has a stability superior to that in both twin molecules and four-armed stars. In the three-armed star triple-4 with a suitable substituent pattern, the supercooled nematic phase is stable at room temperature for at least nine months. Photo-DSC experiments show that the final conversion after 10 min of UV-irradiation for the threearmed star molecule triple-4 is as high as for the smaller molecules twin-4 and mono-4 over the whole temperature range. Doped with a suitable chiral molecule the novel nematics formed cholesteric phases which were used to make cholesteric polymer networks by photopolymerization.     

1,6-Anhydrofurawosen,XX.1 Synthese von Zuei 1,6:2,3-Dianhydrohexofuranosen Durch Payne-Oxidation von 1,6-Anhydro-5-O-Benzoyl-2,3-Didesoxy-β-D-Erythro- uno -α-L-Threo-Hex-2-Enofuranose

Abstract

The 5-0-benzoyl derivatives 3 and 4 derived from 1,6-anhydro-β-D-mannpfuranose and -α-L-gulofuranose are suitable educts for the preparation of the isomeric olefins 7 and 8 by Corey-Winter elimination via the thionocarbonates 5 and 6, respectively. 8 was prepared in higher yields also from 5-α-Benzoyl-1,6-anhydro-α-L-talofuranose (14) via 15. Payne oxidation of the unsaturated compounds 7 and 8 gave the exo epoxides 9 and 10 with D-allo and L-talo configuration.     

A Practical Synthesis of ω-Aminoalkanoic Acid Derivatives from Cycloalkanones

A practical synthetic route to N-Boc protected or Boc-amino acid coupled ω-aminoalkanoic acids is reported and exemplified by the preparation of 8-(t-butoxycarbonylamino)caprylic acid 2 and (N-t-butoxycarbonylphenylalanyl)-8-aminocaprylic acid 3. The sequence does not involve column chromatography, hydrogenation, azide or bromine related rearrangements, and therefore is amenable to scale-up. Homologues of the ω-aminoalkanoic acid derivatives may also be prepared by using different cycloalkanones.     

A comparative study of fragment screening methods on the p38�� kinase: new methods, new insights

The stress-activated kinase p38α was used to evaluate a fragment-based drug discovery approach using the BioFocus fragment library. Compounds were screened by surface plasmon resonance (SPR) on a Biacore(?) T100 against p38α and two selectivity targets. A sub-set of our library was the focus of detailed follow-up analyses that included hit confirmation, affinity determination on 24 confirmed, selective hits and competition assays of these hits with respect to a known ATP binding site inhibitor. In addition, functional activity against p38α was assessed in a biochemical assay using a mobility shift platform (LC3000, Caliper LifeSciences). A selection of fragments was also evaluated using fluorescence lifetime (FLEXYTE(?)) and microscale thermophoresis (Nanotemper) technologies. A good correlation between the data for the different assays was found. Crystal structures were solved for four of the small molecules complexed to p38α. Interestingly, as determined both by X-ray analysis and SPR competition experiments, three of the complexes involved the fragment at the ATP binding site, while the fourth compound bound in a distal site that may offer potential as a novel drug target site. A first round of optimization around the remotely bound fragment has led to the identification of a series of triazole-containing compounds. This approach could form the basis for developing novel and active p38α inhibitors. More broadly, it illustrates the power of combining a range of biophysical and biochemical techniques to the discovery of fragments that facilitate the development of novel modulators of kinase and other drug targets.     

Molecular recognition at the active site of catechol-O-methyltransferase (COMT): adenine replacements in bisubstrate inhibitors

L-Dopa, the standard therapeutic for Parkinson's disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of an activated methyl group from S-adenosylmethionine (SAM) to its catechol substrates, such as L-dopa, in the presence of magnesium ions. The molecular recognition properties of the SAM-binding site of COMT have been investigated only sparsely. Here, we explore this site by structural alterations of the adenine moiety of bisubstrate inhibitors. The molecular recognition of adenine is of special interest due to the great abundance and importance of this nucleobase in biological systems. Novel bisubstrate inhibitors with adenine replacements were developed by structure-based design and synthesized using a nucleosidation protocol introduced by Vorbrüggen and co-workers. Key interactions of the adenine moiety with COMT were measured with a radiochemical assay. Several bisubstrate inhibitors, most notably the adenine replacements thiopyridine, purine, N-methyladenine, and 6-methylpurine, displayed nanomolar IC(50) values (median inhibitory concentration) for COMT down to 6 nM. A series of six cocrystal structures of the bisubstrate inhibitors in ternary complexes with COMT and Mg(2+) confirm our predicted binding mode of the adenine replacements. The cocrystal structure of an inhibitor bearing no nucleobase can be regarded as an intermediate along the reaction coordinate of bisubstrate inhibitor binding to COMT. Our studies show that solvation varies with the type of adenine replacement, whereas among the adenine derivatives, the nitrogen atom at position 1 is essential for high affinity, while the exocyclic amino group is most efficiently substituted by a methyl group.     

Higher borides and oxygen-enriched Mg–B–O inclusions as possible pinning centers in nanostructural magnesium diboride and the influence of additives on their formation

The study of high pressure (2 GPa) synthesized MgB₂-based materials allows us to conclude that higher borides (with near MgB₁₂ stoichiometry) and oxygen-enriched Mg–B–O inclusions can be pinning centers in nanostructural magnesium diboride matrix (with average grain sizes of 15–37 nm). It has been established that additions of Ti or SiC as well as manufacturing temperature can affect the size, amount and distribution of these inclusions in the material structure and thus, influence critical current density. The superconducting behavior of materials with near MgB₁₂ stoichiometry of matrix is discussed.     

Effect of OH-content on thermal and chemical properties of SnOP2O5 glasses

Glasses with 55–60 mol% SnO and 40–45 mol% P₂O₅ have shown extremely large differences in the chemical and thermal properties depending on the temperature at which they were melted. Glasses prepared at low melting temperature, 450–550 °C, had low T_g, 150–200 °C, and low chemical stability. Glasses prepared at high melting temperature, 800–1200 °C, had much higher T_g, 250–300 °C, and much higher chemical stability. No significant differences were found by ¹¹⁹Sn Mössbauer and ³¹P Nuclear Magnetic Resonance spectroscopy. Large differences in the OH-content could be detected as the reason by infrared absorption spectroscopy, thermal analyses, and ¹H Nuclear Magnetic Resonance spectroscopy. In samples with low T_g, a broad OH – vibration band around 3000 nm with an absorption intensity >20 cm^?1, bands at 2140 nm with intensity ～5 cm^?1, at 2038 nm with intensity ～2.7 cm^?1, and at 1564 nm with intensity ～0.4 cm^?1 were measured. These samples have shown a mass loss of 3–4 wt% by thermal gravimetric analyses under argon in the temperature range 400–1000 °C. No mass loss and only one broad OH-band with a maximum at 3150 nm and low absorption intensity <4 cm^?1 could be detected in samples melted at high temperature, 1000–1200 °C, which have much higher T_g, ～300 °C, and much higher chemical stability.     

Fatty Acid Composition and Cytotoxic Activity of Lipid Extracts from Nannochloropsis gaditana Produced by Green Technologies

Microalgae are alternatives and sustainable sources of omega-3 long chain-polyunsaturated fatty acids (LC-PUFA). However, the eco-friendly extraction of these bioactives remains unexplored. In this work, the use of enzyme-based methods in combination with ultrasounds was evaluated as green approaches to extract the omega-3 lipids from Nannochloropsis gaditana. Three commercial enzymatic solutions (Viscozyme^® L, Celluclast^® 1.5 L, and Saczyme^®) were investigated, and results were compared with the traditional Folch method. A promising extraction approach was developed by using Saczyme^®, achieving a lipid yield of 25.7% ± 0.5, comparable to the traditional method (27.3% ± 0.7) (p > 0.05). Similar omega-3 content was found by GC–MS analysis for both lipid extracts (30.2% ± 2.4 and 29.3% ± 0.8 for the green and the traditional method, respectively), showing that the green approaches did not affect the fatty acid profile. Moreover, the cytotoxic activity of produced lipids was assessed by comparing human colon cancer cells (HCT-116) and epithelial nontumorigenic immortalized cells (HCEC-1CT). Results suggest that the lipid extracts have a selective effect, reducing the viability of the colon carcinoma cells but not the nontumorigenic cells. Thus, this study provides new eco-innovative approaches for extracting the omega-3 LC-PUFA from microalgae with promising biological properties.     

The Fascinating Flexibility and Coordination Modes of a Pentamethylene Connected Macrocyclic CNC Pincer Ligand

The coordination chemistry of an electron-rich macrocyclic CNC pincer-ligand consisting of two pentamethylene tethered N-heterocyclic carbene moieties on a carbazole backbone (bimca^C5) is investigated by mainly NMR spectroscopy and X-ray crystal structure analysis. A bridging coordination mode is found for the lithium complex. With the larger and softer potassium ion, the ligand adopts a facial coordination mode and a polymeric structure by intermolecular potassium nitrogen interactions. The facial coordination is also confirmed at a Cp*Ru fragment, while C-H activation under dehydrogenation at the alkyl chain is observed upon reaction with [Ru(PPh₃)₃Cl₂]. In contrast, Pd(OAc)₂ reacts under C-H activation at the central carbon atom of the pentamethylene tether to an alkyl-pincer macrocycle.