Enantioselective Organocatalytic α-Fluorination of Aldehydes

The first direct enantioselective catalytic α-fluorination of aldehydes has been accomplished. The use of enamine catalysis has provided a new organocatalytic strategy for the enantioselective fluorination of aldehydes to generate α-fluoro aldehydes, an important chiral synthon for medicinal agent synthesis. The use of imidazolidinone 1 as the asymmetric catalyst has been found to mediate the fluorination of a large variety of aldehyde substrates with N-fluorobenzenesulfonimide serving as the electrophilic source of fluorine. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. While catalyst quantities of 20 mol % were generally employed in this study, successful halogenation can be accomplished using catalyst loadings as low as 2.5 mol %

Expanding the scope of N → S acyl transfer in native peptide sequences

Understanding the factors that influence N → S acyl transfer in native peptide sequences, and discovery of new reagents that facilitate it, will be key to expanding its scope and applicability. Here, through a study of short model peptides in thioester formation and cyclisation reactions, we demonstrate that a wider variety of Xaa-Cys motifs than originally envisaged are capable of undergoing efficient N → S acyl transfer. We present data for the relative rates of thioester formation and cyclisation for a representative set of amino acids, and show how this expanded scope can be applied to the production of the natural protease inhibitor Sunflower Trypsin Inhibitor-1 (SFTI-1)

On the locus formed by the maximum heights of projectile motion with air resistance

We present an analysis on the geometrical place formed by the set of maxima of the trajectories of a projectile launched in a media with linear drag. Such a place, the locus of apexes, is written in term of the Lambert $W$ function in polar coordinates, confirming the special role played by this function in the problem. In order to characterize the locus, a study of its curvature is presented in two parameterizations, in terms of the launch angle and in the polar one. The angles of maximum curvature are compared with other important angles in the projectile problem. As an addendum, we find that the synchronous curve in this problem is a circle as in the drag-free case.Comment: 7 pages, 6 color eps figures. Synchronous curve added. Typos and style corrected

Is copyright blind to the visual?

This article argues that, with respect to the copyright protection of works of visual art, the general uneasiness that has always pervaded the relationship between copyright law and concepts of creativity produces three anomalous results. One of these is that copyright lacks much in the way of a central concept of 'visual art' and, to the extent that it embraces any concept of the 'visual', it is rooted in the rhetorical discourse of the Renaissance. This means that copyright is poorly equipped to deal with modern developments in the visual arts. Secondly, the pervasive effect of rhetorical discourse appears to have made it particularly difficult for copyright law to strike a meaningful balance between protecting creativity and permitting its use in further creative works. Thirdly, just when rhetorical discourse might have been useful in identifying the significance and materiality of the unique one-off work of visual art, copyright law chooses to ignore its implications

The direct arylation of allylic sp3 C–H bonds via organic and photoredox catalysis

The direct functionalization of unactivated sp3 C–H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts1, the establishment of general and mild strategies for the engagement of sp3 C–H bonds in C–C bond forming reactions has proved difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene and methine carbons in a catalytic manner is a priority. Although protocols for direct oxidation and amination of allylic C–H bonds (that is, C–H bonds where an adjacent carbon is involved in a C = C bond) have become widely established2,3, the engagement of allylic substrates in C–C bond forming reactions has thus far required the use of pre-functionalized coupling partners4. In particular, the direct arylation of non-functionalized allylic systems would enable access to a series of known pharmacophores (molecular features responsible for a drug’s action), though a general solution to this long-standing challenge remains elusive. Here we report the use of both photoredox and organic catalysis to accomplish a mild, broadly effective direct allylic C–H arylation. This C–C bond forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants, and has been used in the direct arylation of benzylic C–H bonds

Neurobehavioral Abnormalities in Firest-Degree Relative of Individuals With Autism

CONTEXT: Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder. OBJECTIVE: To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism. DESIGN: Case-control comparison of neurobehavioral functions. SETTING: University medical center. PARTICIPANTS: Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8-54 years). MAIN OUTCOME MEASURES: Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors. RESULTS: On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another. CONCLUSIONS: Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism

The impact of atmospheric mountain lee waves on systematic geodetic errors observed using the Global Positioning System

The article discusses the first case law issued on the EU-Turkey deal that authoritatively answers the question whether Turkey constitutes a safe third country for refugees. In 390 out of 393 decisions Greek Asylum Appeals Committees ruled that the safe third country requirements are not fulfilled with respect to Turkey, essentially impeding the application of the EU-Turkey deal. The purpose of this article is, on the first level, through empirical research, to shed light on the reasoning of the decisions of the Appeals Committees and investigate the impact of the EU-Turkey agreement upon them. On a second level, it focuses on evaluating from the perspective of effective legal protection the legislative amendment, subsequent to these decisions, which modifies their composition. The analysis is of significant societal relevance, as it aspires to inform further law, policy, and jurisprudence in the field, especially since it provides access to sources that due to language and other practical barriers would remain far from the reach of legal and policy experts

Prevalence of face recognition deficits in middle childhood

Approximately 2-2.5% of the adult population is believed to show severe difficulties with face recognition, in the absence of any neurological injury – a condition known as developmental prosopagnosia (DP). However, to date no research has attempted to estimate the prevalence of face recognition deficits in children, possibly because there are very few child-friendly, well-validated tests of face recognition. In the current study, we examined face and object recognition in a group of primary school children (aged 5-11 years), to establish whether our tests were suitable for children; and to provide an estimate of face recognition difficulties in children. In Experiment 1 (n = 184), children completed a pre-existing test of child face memory, the CFMT-K, and a bicycle test with the same format. In Experiment 2 (n = 413), children completed three-alternative forced choice matching tasks with faces and bicycles. All tests showed good psychometric properties. The face and bicycle tests were well-matched for difficulty and showed a similar developmental trajectory. Neither the memory nor matching tests were suitable to detect impairments in the youngest groups of children, but both tests appear suitable to screen for face recognition problems in middle childhood. In the current sample, 1.2-5.2% of children showed difficulties with face recognition; 1.2-4% showed face-specific difficulties – that is, poor face recognition with typical object recognition abilities. This is somewhat higher than previous adult estimates: it is possible that face matching tests overestimate the prevalence of face recognition difficulties in children; alternatively, some children may “outgrow” face recognition difficulties

Sunflower trypsin inhibitor (SFTI-1) analogues of synthetic and biological origin via N -> S acyl transfer: potential inhibitors of human Kallikrein-5 (KLK5)

Sunflower Trypsin Inhibitor (SFTI-1) analogues have been prepared from simple linear precursors produced either by chemical synthesis or following purification from Escherichia coli. We have shown, for the first time that these linear SFTI-1 derived peptide sequences can be converted to circular peptides via selective consecutive acyl transfer reactions, and that the products derived from synthetic and bacterial origin are identical. Preliminary analysis of the semi-synthetic SFTI-1 analogues confirmed SFTI-I10H as an inhibitor of Kallikrein-5 (KLK5) protease that could also mediate its action on human keratinocytes. The preliminary results obtained serve as a useful starting point for the biological production of SFTI-1 based, selective KLK5 inhibitors for the treatment of atopic dermatitis