Wolstenholme and Vandiver primes

The Ramanujan Journal - A prime p is a Wolstenholme prime if $$\left( {\begin{array}{c}2p\\ p\end{array}}\right) \equiv 2$$ mod $$p^4$$ , or, equivalently, if p divides the numerator of the...     

Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by SN2 displacement and radical generation

The radical SAM (RS) proteins RlmN and Cfr catalyze methylation of carbons 2 and 8, respectively, of adenosine 2503 in 23S rRNA. Both reactions are similar in scope, entailing the synthesis of a methyl group partially derived from S-adenosylmethionine (SAM) onto electrophilic sp(2)-hybridized carbon atoms via the intermediacy of a protein S-methylcysteinyl (mCys) residue. Both proteins contain five conserved Cys residues, each required for turnover. Three cysteines lie in a canonical RS CxxxCxxC motif and coordinate a [4Fe-4S]-cluster cofactor; the remaining two are at opposite ends of the polypeptide. Here we show that each protein contains only the one "radical SAM" [4Fe-4S] cluster and the two remaining conserved cysteines do not coordinate additional iron-containing species. In addition, we show that, while wild-type RlmN bears the C355 mCys residue in its as-isolated state, RlmN that is either engineered to lack the [4Fe-4S] cluster by substitution of the coordinating cysteines or isolated from Escherichia coli cultured under iron-limiting conditions does not bear a C355 mCys residue. Reconstitution of the [4Fe-4S] cluster on wild-type apo RlmN followed by addition of SAM results in rapid production of S-adenosylhomocysteine (SAH) and the mCys residue, while treatment of apo RlmN with SAM affords no observable reaction. These results indicate that in Cfr and RlmN, SAM bound to the unique iron of the [4Fe-4S] cluster displays two reactivities. It serves to methylate C355 of RlmN (C338 of Cfr), or to generate the 5'-deoxyadenosyl 5'-radical, required for substrate-dependent methyl synthase activity.     

Synthesis of 5-, 6- and 7-substituted-2-aminoquinolines as SH3 domain ligands

The Src homology 3 (SH3) domains are small protein-protein interaction domains that mediate a range of important biological processes and are considered valuable targets for the development of therapeutic agents. We have been developing 2-aminoquinolines as ligands for SH3 domains--so far the only reported examples of entirely small-molecule ligands for the SH3 domains. The highest affinity 2-aminoquinolines so far identified are 6-substituted compounds. In this article, the synthesis of several new 2-aminoquinolines, including 5-, 6- and 7-substituted compounds, for Tec SH3 domain ligand binding studies is presented. As a part of the synthetic investigation, the utility of different methods for the synthesis of 2-aminoquinolines was explored and potentially powerful methods were identified for the synthesis of 2-aminoquinolines with diverse functionality. Of the compounds prepared, the 5-substituted-2-aminoquinolines generally bound with similar affinities to unsubstituted 2-aminoquinoline, whilst the 7-substituted compounds generally bound with similar or lower affinity than unsubstituted 2-aminoquinoline. However, the 6-substituted-2-aminoquinolines generally bound with significantly higher affinity than unsubstituted 2-aminoquinoline. In addition, one 6-substituted-N-benzylated-2-aminoquinoline was also tested for SH3 binding and some evidence for the formation of additional contacts at other regions of the SH3 domain was found. These results provide new and useful SAR information that should greatly assist with the challenge of developing high affinity small-molecule ligands for the SH3 domains.     

Correlation between structural and electrical profiles in ion-implanted GaAs

Abstract

Damaging effect of diatomic phosphorus ions implanted into silicon was compared with that of atomic ions in the range between 25 and 300 keV/atom. Dose was around 10¹⁴ ions/cm². Target temperature varied between 77 and 533 K. Below and at 300 K the “damage enhancement factor” defined as ratio of damage produced by equivalnet molecular and atomic ion implantation varied from 1 to 1.6 depending on incident energy. At elevated implantation temperature this factor increased by almost an order of magnitude. In interpretation of experimental results, fluctuations in damage structure inside the volume of collision cascades was proposed. Conclusions are believed to be relevant for other molecular implantation, e.g. for the BF₂ ⁺.     

Housing in the Dearne Valley: Doing Community OR with the Thurnscoe Tenants Housing Co-Operative Part 1 — The Involvement of the Community OR Unit

In this paper we describe the work of the Community Operational Research Unit with the Thurnscoe Tenants Housing Co-operative. We discuss the various stages through which this work has progressed, from the initial contacts with the Co-operative, through a period of acting as external consultants, to a continuing process of working as, essentially, internal consultants. A variety of the projects with which the Unit has been involved are outlined. These demonstrate the breadth and eclecticism of community operational research. No attempt is made to evaluate the involvement and contribution of the Community Operational Research Unit in a systematic way in this paper. This will be the subject of a subsequent paper.     

Measurement of Torsionally Induced Shear Stresses in Shrink-Fit Assemblies

Shear stresses along the shaft/hub interface in shrink-fit components, generated by torsional loads, can drive premature failure through fretting mechanisms. It is difficult to numerically predict these shear stresses, and the associated circumferential slip along the shaft/hub interface, due to uncertainties in frictional behaviour and the presence of steep stress gradients which can cause meshing problems. This paper attempts to provide validation of a numerical modelling methodology, based on finite element analysis, so the procedure may be used with confidence in fitness-for-purpose cases. Very few experimental techniques offer the potential to make measurements of stress and residual stress interior to metallic components. Even fewer techniques provide the possibility of measuring shear stresses. This paper reports the results of neutron diffraction measurements of shear stress and residual shear stress in a bespoke test specimen containing a shrink-fit. One set of measurements was made with a torsional load ‘locked-in’. A second set of measurements was made to determine the residual shear stress when the torsional load had been applied and removed. Overall, measurement results were consistent with numerical models, but the necessity for a small test specimen to allow penetration of the neutron beam to the measurement locations meant the magnitude of shear stresses was at the limits of what could be measured experimentally.     

Room‐Temperature Palladium‐Catalyzed C?H Activation: ortho‐Carbonylation of Aniline Derivatives

Pd and CO—ureally got me! The title reaction proceeds efficiently at 18 °C under CO (1 atm) with 5 % [Pd(OTs)₂(MeCN)₂] as precatalyst. Depending on the solvents used, either anthranilates or cyclic imides can be obtained in high yields (see picture, BQ=benzoquinone, Ts=4‐toluenesulfonyl).

     

Approaches to the quaternary stereocentre and to the heterocyclic core in diazonamide A using the Heck reaction and related coupling reactions

In model studies towards the quaternary centre at the heart of diazonamide A (early structure 2; revised structure 1), cyclisations of the alkene-substituted iodoaryls 4, 13, 18 and 23, under Heck reaction conditions, were shown to lead to the corresponding benzodihydrofuran 5, benzofuranone 14 and the oxindoles 19 and 24 respectively, in 50-80% yield. Further manipulation of the benzodihydrofuran 5 then led to the intermediates 30, 33 and 39, which make up parts of the oxazole-indole heterocyclic core in diazonamide A. Attempts to perform a corresponding 13-exo-trig Heck cyclisation from the precursor 46a, prepared from 44 and 45, leading to 47 were not successful. A similar outcome was obtained during attempts to effect Heck cyclisations from the ester 57 and the related ether 59. Treatment of the chromene-substituted iodoaryl 62 with Pd(OAc)2, PPh3 and Ag2CO3 led to the spirocycle 64 as a crystalline solid. X-Ray crystal structure analysis established that the quaternary centre in 64 had the same configuration as that present in diazonamide A (1).