The PEST sequence does not contribute to the stability of the cystic fibrosis transmembrane conductance regulator.

Background  

Endoplasmic reticulum retention of misfolded cystic fibrosis transmembrane conductance regulator (CFTR) mutants and their rapid degradation is the major cause of cystic fibrosis (CF). An important goal is to understand the mechanism of how the misfolded proteins are recognized, retained, and targeted for degradation.     

Terpsichorean movements of pentaammineruthenium on pyrimidine and isocytosine ligands

Pentaammineruthenium moves on ambidentate nitrogen heterocycles by both rotation and linkage isomerization, which may affect the biological activity of potential ruthenium metallopharmaceuticals. The rapid rotation rates of [(NH3)5RuIII] coordinated to the exocyclic nitrogens of isocytosine (ICyt) and 6-methylisocytosine (6MeICyt) have been determined by 1H NMR. Since these rotamers can be stabilized by hydrogen bonding between the coordinated ammines and the N1 and N3 endocyclic nitrogens, rotamerization is under pH control. Spectrophotometrically (UV-vis) measured pKa values for the two endocyclic sites for the ICyt complex are 2.78 and 9.98, and for 6MeICyt are 3.06 and 10.21, which are probably weighted averages for ionization from N3 and N1, respectively. Activation parameters for the rotamerizations were determined by variable-temperature NMR at pKa1 < pH < pKa2 for the complexes with (ICyt-kappa N2)-, (6MeICyt kappa N2)-, and 2AmPym kappa N2. For [(6MeICyt kappa N2)(-)-(NH3)5RuIII]2+, delta H* = 1.6 kcal/mol, delta S* = -37 cal/mol K, and Ea = 2.2 kcal/mol. Due to strong RuIII-N pi-bonding, the activation enthalpies are approximately 10 kcal lower than the expected values for the free ligands. Rotameric structure is correlated with pKa values, pH-dependent reduction potentials, and 1H NMR parameters. Linkage isomers of [(2AmPym)(NH3)5Ru]n+ are reported in which RuII is coordinated to the endocyclic nitrogen (N1) and RuIII to the exocyclic nitrogen (N2). The rate constant for the kappa N2-->kappa N1 isomerization as part of an ECE mechanism is 3.9 s-1 at pH 3. The pH dependence of the acid-catalyzed hydrolysis of [(2AmPym kappa N1)(NH3)5Ru]2+ is determined.     

Approximately straight kink theories

A precise meaning is given to the idea of a kink theory approximating a vectoror vector-bundle-valued theory. It is shown that vector theories taking values in a vector bundle with groupSO(n- s,s;), acting naturally, do not approximate any kink theory. It is further shown that, where a kink theory is approximated by a vector bundle theory, the field equations in the vector theory can give rise to field equations in the kink theory. The theory of Skyrme and the sine-Gordon theory are of this form. An example is given of a nonlinear modification of electromagnetism having solitonlike solutions.     

A Facile One Stage Synthesis of Oxazolines Under Microwave Irradiation

A rapid, high yielding procedure for the synthesis of 2-substituted oxazolines has been achieved under microwave irradiation from alkyl and aryl nitriles and β-amino alcohols using a mild Lewis acid catalyst.     

Electromagnetic Interference in Measurements of Radial Stress During Split Hopkinson Pressure Bar Experiments

Split Hopkinson pressure bar experiments on soils are often carried out using a rigid steel confining ring to provide plane strain conditions, and measurements of the circumferential strain in the ring can be used to infer the radial stress on the surface of the specimen. Previous experiments have shown evidence of irregular electromagnetic interference in measurements of radial stress, which obscures the signals and impedes analysis. The development of robust constitutive models for soils in blast and impact events relies on the accurate characterisation of this behaviour, and so it is necessary to isolate and remove the source of interference. This paper uses an induction coil to identify the source of the anomalous signals, which are found to be due to induced currents in the gauge lead wires from the movement of magnetised pressure bars (martensitic stainless steel, 440C). Comparative experiments on sand and rubber specimens are used to show that the deforming soil specimen does not make a significant contribution to this activity, and recommendations are made on reducing electromagnetic interference to provide reliable radial stress measurements.     

High iso Aldehyde Selectivity in the Hydroformylation of Short‐Chain Alkenes

The hydroformylation of propene to give predominantly iso‐butanal has been achieved; class‐leading selectivity is possible even at higher temperatures that deliver fast conversion. Racemic rhodium complexes of bidentate phospholane phosphites derived from tropos‐biphenols and unusual solvent systems are the key to the selectivity observed.