Novel pericyclic routes to strained organic molecules: Theoretical and experimental studies

The chemistry of cyclobutyne (20) and 1,2-cyclobutadiene (21) has been investigated. Research efforts were focused on attempting to independently generate and trap these highly reactive species. The trapping experiments were inconclusive in each case. Calculations using MCSCF theory indicate that perfluorination of cyclobutyne will have a profound effect that stabilizes the cyclobutyne relative to rearrangement. However, experiments designed to generate and trap perfluorocyclobutyne (73) did not provide evidence for this compound. The development of new routes to strained organic compounds through the extension of known pericyclic reactions is described. These novel pericyclic reactions have been investigated by ab initio calculations and flash vacuum pyrolysis (FVP) experiments. MP4/6-31G*//MP2/6-31G* calculations support the possibility that strained six-membered rings can be prepared by replacement of a double bond with a triple bond in the prototypical Diels/Alder cycloaddition eq. (1) or electrocyclic reaction eq. (7). The novel cycloadditions explored involve the replacement of the traditional 1,3-butadiene component of (4+2) cycloadditions with vinylacetylene (19), 1,3-butadiyne (160), and strans-butadiene (233). Electrocyclic reactions of 1,2,3-cyclohexatriene (167), 1,2,4-cyclohexatriene (166), cyclohexen-3-yne (247), and 1,2,3,4-cyclohexatetraene (243) have been investigated. Experimental evidence is presented for the first example of intramolecular diyne + alkene and diyne + alkyne cycloadditions. The latter process is believed to give an o-benzyne intermediate, which is subsequently reduced to indan. This cycloaddition is unique in that it may be considered a cycloaromatization because an aromatic ring is directly generated. The mechanism and generality of diyne cycloadditions is examined

Vacuum Compatibility of 3D-Printed Materials

The fabrication fidelity and vacuum properties are tested for currently available 3D-printed materials including polyamide, glass, acrylic, and sterling silver. The silver was the only material found to be suitable to ultrahigh vacuum environments due to outgassing and sublimation observed in other materials.Comment: 3 pages, 2 figures, preprin

The Relative Role of Bacterial Cell Wall and Capsule in the Induction of Inflammation in Pneumococcal Meningitis

The relative contribution of bacterial components to the induction of inflammation during Streptococcus pneumoniae meningitis is unknown. Several strains of pneumococci with differences in cell surface characteristics (capsule or cell wall) were compared for the effect on the inflammatory response evoked during infection of the cerebrospinal fluid (CSF) in vivo. The presence of bacterial capsular polysaccharide was not necessary for bacterial growth in CSF in vivo but correlated with greater CSF bacterial density. CSF inflammatory changes began to appear when the bacterial concentration exceeded 105 cfu/ml, regardless of the pneumococcal strain. CSF inflammatory changes could be invoked by cisternal instillation of 105−106 cell equivalents of whole, heat-killed unencapsulated strains or their isolated cell walls but not by similar concentrations of heat-killed encapsulated strains or isolated capsular polysaccharide. Hypoglycorrhachia was observed only during inflammation caused by live bacteria. The inflammatory response characteristic of naturally acquired pneumococcal meningitis can be reproduced by challenge with both encapsulated and unencapsulated bacteria. The bacterial cell wall appears to be the most potent pneumococcal surface component in inducing CSF inflammatio

Two photon lithography for synthesis of fracture mechanical specimen

The design process of any mechanically loaded device must be guided by material properties, which also includes fracture mechanical considerations. 3D lithographical techniques, such as direct laser writing through two-photon polymerization, therefore, enable completely new possibilities regarding device geometry, as well as for sample fabrication and materials testing. Please click Download on the upper right corner to see the full abstract

Diffractive energy spreading and its semiclassical limit

We consider driven systems where the driving induces jumps in energy space: (1) particles pulsed by a step potential; (2) particles in a box with a moving wall; (3) particles in a ring driven by an electro-motive-force. In all these cases the route towards quantum-classical correspondence is highly non-trivial. Some insight is gained by observing that the dynamics in energy space, where $n$ is the level index, is essentially the same as that of Bloch electrons in a tight binding model, where $n$ is the site index. The mean level spacing is like a constant electric field and the driving induces long range hopping 1/(n-m).Comment: 19 pages, 11 figs, published version with some improved figure

The Induction of Meningeal Inflammation by Components of the Pneumococcal Cell Wall

Pneumococcal cell wall induces meningeal inflammation in rabbits injected intracisternally with >105 cell equivalents. Both of the major cell wall components, teichoic acid and peptidoglycan, contribute to this inflammatory activity although responses differ depending on the chemical nature, size, and complexity of these fractions. Challenge with teichoic acid (membrane or wall associated) results in greater inflammation at 5 hr than at 24 hr. Degraded teichoic acid is inactive. In contrast, the inflammation caused by whole cell wall or high-molecular-weight peptidoglycan-containing fractions increases in intensity from 5 to 24 hr. Peptidoglycan fractions lose activity at 24 hr when hydrolyzed to disaccharide-stem peptide moieties. Generation of free cell wall components in cerebrospinal fluid as, for example, during treatment with antibiotics that are bacteriolytic as well as bactericidal, could contribute to increased inflammation in the subarachnoid spac

On the X-rank with respect to linear projections of projective varieties

In this paper we improve the known bound for the $X$-rank $R_{X}(P)$ of an element $P\in {\mathbb{P}}^N$ in the case in which $X\subset {\mathbb P}^n$ is a projective variety obtained as a linear projection from a general $v$-dimensional subspace $V\subset {\mathbb P}^{n+v}$. Then, if $X\subset {\mathbb P}^n$ is a curve obtained from a projection of a rational normal curve $C\subset {\mathbb P}^{n+1}$ from a point $O\subset {\mathbb P}^{n+1}$, we are able to describe the precise value of the $X$-rank for those points $P\in {\mathbb P}^n$ such that $R_{X}(P)\leq R_{C}(O)-1$ and to improve the general result. Moreover we give a stratification, via the $X$-rank, of the osculating spaces to projective cuspidal projective curves $X$. Finally we give a description and a new bound of the $X$-rank of subspaces both in the general case and with respect to integral non-degenerate projective curves.Comment: 10 page

Autosomal Monoallelic Expression in the Mouse

Background: Random monoallelic expression defines an unusual class of genes displaying random choice for expression between the maternal and paternal alleles. Once established, the allele-specific expression pattern is stably maintained and mitotically inherited. Examples of random monoallelic genes include those found on the X-chromosome and a subset of autosomal genes, which have been most extensively studied in humans. Here, we report a genome-wide analysis of random monoallelic expression in the mouse. We used high density mouse genome polymorphism mapping arrays to assess allele-specific expression in clonal cell lines derived from heterozygous mouse strains. Results: Over 1,300 autosomal genes were assessed for allele-specific expression, and greater than 10% of them showed random monoallelic expression. When comparing mouse and human, the number of autosomal orthologs demonstrating random monoallelic expression in both organisms was greater than would be expected by chance. Random monoallelic expression on the mouse autosomes is broadly similar to that in human cells: it is widespread throughout the genome, lacks chromosome-wide coordination, and varies between cell types. However, for some mouse genes, there appears to be skewing, in some ways resembling skewed X-inactivation, wherein one allele is more frequently active. Conclusions: These data suggest that autosomal random monoallelic expression was present at least as far back as the last common ancestor of rodents and primates. Random monoallelic expression can lead to phenotypic variation beyond the phenotypic variation dictated by genotypic variation. Thus, it is important to take into account random monoallelic expression when examining genotype-phenotype correlation

Spartin activates atrophin-1-interacting protein 4 (AIP4) E3 ubiquitin ligase and promotes ubiquitination of adipophilin on lipid droplets

<p>Abstract</p> <p>Background</p> <p>Spartin protein is involved in degradation of epidermal growth factor receptor and turnover of lipid droplets and a lack of expression of this protein is responsible for hereditary spastic paraplegia type 20 (SPG20). Spartin is a multifunctional protein that associates with many cellular organelles, including lipid droplets. Recent studies showed that spartin interacts with E3 ubiquitin ligases that belong to the neural precursor cell-expressed developmentally downregulated gene (Nedd4) family, including atrophin-1-interacting protein 4 (AIP4/ITCH). However, the biological importance of the spartin-AIP4 interaction remains unknown.</p> <p>Results</p> <p>In this study, we show that spartin is not a substrate for AIP4 activity and that spartin's binding to AIP4 significantly increases self-ubiquitination of this E3 ligase, indicating that spartin disrupts the AIP4 autoinhibitory intramolecular interaction. Correspondingly, spartin has a seven times higher binding affinity to the WW region of AIP4 than the binding of the WW region has to the catalytic homologues of the E6-associated protein C-terminus (HECT) domain, as measured by enzyme-linked immunosorbent assay. We also show that spartin recruits AIP4 to lipid droplets and promotes ubiquitination of lipid droplet-associated protein, adipophilin, which regulates turnover of lipid droplets.</p> <p>Conclusions</p> <p>Our findings demonstrate that spartin acts as an adaptor protein that activates and recruits AIP4 E3 ubiquitin ligase to lipid droplets and by this means regulates the level of ubiquitination of adipophilin and potentially other lipid-associated proteins. We propose that this is one of the mechanisms by which spartin regulates lipid droplet turnover and might contribute to the pathology of SPG20.</p

Nonsteroidal Anti-Inflammatory Agents in the Therapy for Experimental Pneumococcal Meningitis

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of the cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhib-itors concurrently with the antibioti