Antidromic latency variations of nigral compacta neurones

Summary Variations in the antidromic latency of substantia nigra compacta neurones were commonly observed following striatal stimulation. These results provide electrophysiological evidence for a branched unmyelinated nigrostriatal pathway and demonstrate that the antidromic criterion of constant latency is not valid for this type of pathway.     

Hydroxyproline production in chick fibroblast cultures

Zusammenfassung Kulturen von Hühnerherzfibroblasten wurden nach 10, 21 und 28 Tagenin vitro auf ihren Gehaltan Hydroxyprolin — einer wichtigen Aminosäure des Kollagens — untersucht. Nach 10, bzw. 21 Tagen ist eine signifikante, durch Prolinzugaben nicht beeinflussbare Vermehrung des zu 50% löslichen Hydroxyprolins feststellbar.

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Kantonsspital, Chur.     

Changing Arctic Ocean freshwater pathways

Freshening in the Canada basin of the Arctic Ocean began in the 1990s and continued to at least the end of 2008. By then, the Arctic Ocean might have gained four times as much fresh water as comprised the Great Salinity Anomaly of the 1970s, raising the spectre of slowing global ocean circulation. Freshening has been attributed to increased sea ice melting and contributions from runoff, but a leading explanation has been a strengthening of the Beaufort High--a characteristic peak in sea level atmospheric pressure--which tends to accelerate an anticyclonic (clockwise) wind pattern causing convergence of fresh surface water. Limited observations have made this explanation difficult to verify, and observations of increasing freshwater content under a weakened Beaufort High suggest that other factors must be affecting freshwater content. Here we use observations to show that during a time of record reductions in ice extent from 2005 to 2008, the dominant freshwater content changes were an increase in the Canada basin balanced by a decrease in the Eurasian basin. Observations are drawn from satellite data (sea surface height and ocean-bottom pressure) and in situ data. The freshwater changes were due to a cyclonic (anticlockwise) shift in the ocean pathway of Eurasian runoff forced by strengthening of the west-to-east Northern Hemisphere atmospheric circulation characterized by an increased Arctic Oscillation index. Our results confirm that runoff is an important influence on the Arctic Ocean and establish that the spatial and temporal manifestations of the runoff pathways are modulated by the Arctic Oscillation, rather than the strength of the wind-driven Beaufort Gyre circulation.     

A steady-state superradiant laser with less than one intracavity photon

The spectral purity of an oscillator is central to many applications, such as detecting gravity waves, defining the second, ground-state cooling and quantum manipulation of nanomechanical objects, and quantum computation. Recent proposals suggest that laser oscillators which use very narrow optical transitions in atoms can be orders of magnitude more spectrally pure than present lasers. Lasers of this high spectral purity are predicted to operate deep in the 'bad-cavity', or superradiant, regime, where the bare atomic linewidth is much less than the cavity linewidth. Here we demonstrate a Raman superradiant laser source in which spontaneous synchronization of more than one million rubidium-87 atomic dipoles is continuously sustained by less than 0.2 photons on average inside the optical cavity. By operating at low intracavity photon number, we demonstrate isolation of the collective atomic dipole from the environment by a factor of more than ten thousand, as characterized by cavity frequency pulling measurements. The emitted light has a frequency linewidth, measured relative to the Raman dressing laser, that is less than that of single-particle decoherence linewidths and more than ten thousand times less than the quantum linewidth limit typically applied to 'good-cavity' optical lasers, for which the cavity linewidth is much less than the atomic linewidth. These results demonstrate several key predictions for future superradiant lasers, which could be used to improve the stability of passive atomic clocks and which may lead to new searches for physics beyond the standard model.     

Direct and highly regioselective and enantioselective allylation of β-diketones

The enantioselective allylation of ketones is a problem of fundamental importance in asymmetric reaction design, especially given that only a very small number of methods can generate tertiary carbinols. Despite the vast amount of attention that synthetic chemists have given to this problem, success has generally been limited to just a few simple ketone types. A method for the selective allylation of functionally complex ketones would greatly increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective and enantioselective allylation of β-diketones. The strong tendency of β-diketones to act as nucleophilic species was overcome by using their enol form to provide the necessary Br?nsted-acid activation. This reaction significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed. It also overturns more than a century of received wisdom regarding the reactivity of β-diketones.     

Immune self-reactivity triggered by drug-modified HLA-peptide repertoire

Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to T?cells. HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen-derived peptide antigens selected by different HLA allotypes. A growing number of immunologically based drug reactions, including abacavir hypersensitivity syndrome (AHS) and carbamazepine-induced Stevens-Johnson syndrome (SJS), are associated with specific HLA alleles. However, little is known about the underlying mechanisms of these associations, including AHS, a prototypical HLA-associated drug reaction occurring exclusively in individuals with the common histocompatibility allele HLA-B*57:01, and with a relative risk of more than 1,000 (refs?6, 7). We show that unmodified abacavir binds non-covalently to HLA-B*57:01, lying across the bottom of the antigen-binding cleft and reaching into the F-pocket, where a carboxy-terminal tryptophan typically anchors peptides bound to HLA-B*57:01. Abacavir binds with exquisite specificity to HLA-B*57:01, changing the shape and chemistry of the antigen-binding cleft, thereby altering the repertoire of endogenous peptides that can bind HLA-B*57:01. In this way, abacavir guides the selection of new endogenous peptides, inducing a marked alteration in 'immunological self'. The resultant peptide-centric 'altered self' activates abacavir-specific T-cells, thereby driving polyclonal CD8 T-cell activation and a systemic reaction manifesting as AHS. We also show that carbamazepine, a widely used anti-epileptic drug associated with hypersensitivity reactions in HLA-B*15:02 individuals, binds to this allotype, producing alterations in the repertoire of presented self peptides. Our findings simultaneously highlight the importance of HLA polymorphism in the evolution of pharmacogenomics and provide a general mechanism for some of the growing number of HLA-linked hypersensitivities that involve small-molecule drugs.