A Measurement of Newton's Gravitational Constant

A precision measurement of the gravitational constant $G$ has been made using a beam balance. Special attention has been given to determining the calibration, the effect of a possible nonlinearity of the balance and the zero-point variation of the balance. The equipment, the measurements and the analysis are described in detail. The value obtained for G is 6.674252(109)(54) 10^{-11} m3 kg-1 s-2. The relative statistical and systematic uncertainties of this result are 16.3 10^{-6} and 8.1 10^{-6}, respectively.Comment: 26 pages, 20 figures, Accepted for publication by Phys. Rev.

Operational Experience with a Cryogenic Axial-Centrifugal Compressor

The Large Hadron Collider (LHC), presently under construction at CERN, requires large refrigeration capacity at 1.8 K. Compression of gaseous helium at cryogenic temperatures is therefore inevitable. Together with subcontractors, Linde Kryotechnik has developed a prototype machine. This unit is based on a cryogenic axial-centrifugal compressor, running on ceramic ball bearings and driven by a variable-frequency electrical motor operating at ambient temperature. Integrated in a test facility for superconducting magnets the machine has been commissioned without major problems and successfully gone through the acceptance test in autumn 1995. Subsequent steps were initiated to improve efficiency of this prototype. This paper describes operating experience gained so far and reports on measured performance prior to and after constructional modifications

Weak ferromagnetism with very large canting in a chiral lattice: (pyrimidine)2FeCl2

The transition metal coordination compound (pyrimidine)2FeCl2 crystallizes in a chiral lattice, space group I 4_1 2 2 (or I4_3 2 2). Combined magnetization, Mossbauer spectroscopy and powder neutron diffraction studies reveal that it is a canted antiferromagnet below T_N = 6.4 K with an unusually large canting of the magnetic moments of 14 deg. from their general antiferromagnetic alignment, one of the largest reported to date. This results in weak ferromagnetism with a ferromagnetic component of 1 mu_B. The large canting is due to the interplay between the antiferromagnetic exchange interaction and the local single-ion anisotropy in the chiral lattice. The magnetically ordered structure of (pyrimidine)2FeCl2, however, is not chiral. The implications of these findings for the search of molecule based materials exhibiting chiral magnetic ordering is discussed.Comment: 6 pages, 5 figure

Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions

<p>Abstract</p> <p>Background</p> <p>A method to estimate ease of synthesis (synthetic accessibility) of drug-like molecules is needed in many areas of the drug discovery process. The development and validation of such a method that is able to characterize molecule synthetic accessibility as a score between 1 (easy to make) and 10 (very difficult to make) is described in this article.</p> <p>Results</p> <p>The method for estimation of the synthetic accessibility score (SAscore) described here is based on a combination of fragment contributions and a complexity penalty. Fragment contributions have been calculated based on the analysis of one million representative molecules from PubChem and therefore one can say that they capture historical synthetic knowledge stored in this database. The molecular complexity score takes into account the presence of non-standard structural features, such as large rings, non-standard ring fusions, stereocomplexity and molecule size. The method has been validated by comparing calculated SAscores with ease of synthesis as estimated by experienced medicinal chemists for a set of 40 molecules. The agreement between calculated and manually estimated synthetic accessibility is very good with <it>r</it>²= 0.89.</p> <p>Conclusion</p> <p>A novel method to estimate synthetic accessibility of molecules has been developed. This method uses historical synthetic knowledge obtained by analyzing information from millions of already synthesized chemicals and considers also molecule complexity. The method is sufficiently fast and provides results consistent with estimation of ease of synthesis by experienced medicinal chemists. The calculated SAscore may be used to support various drug discovery processes where a large number of molecules needs to be ranked based on their synthetic accessibility, for example when purchasing samples for screening, selecting hits from high-throughput screening for follow-up, or ranking molecules generated by various <it>de novo </it>design approaches.</p

The next generation virus‐like particle platform for the treatment of peanut allergy

Background: Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus‐like particles (VLPs), is described here for the treatment of peanut allergy. Methods and Results: VLP Peanut consists of two proteins: a capsid subunit derived from Cucumber mosaic virus engineered with a universal T‐cell epitope (CuMV$_{TT}$) and a CuMV$_{TT}$ subunit fused with peanut allergen Ara h 2 (CuMV$_{TT}$‐Ara h 2), forming mosaic VLPs. Immunizations with VLP Peanut in both naïve and peanut‐sensitized mice resulted in a significant anti‐Ara h 2 IgG response. Local and systemic protection induced by VLP Peanut were established in mouse models for peanut allergy following prophylactic, therapeutic, and passive immunizations. Inhibition of FcγRIIb function resulted in a loss of protection, confirming the crucial role of the receptor in conferring cross protection against peanut allergens other than Ara h 2. Conclusion: VLP Peanut can be delivered to peanut‐sensitized mice without triggering allergic reactions, while remaining highly immunogenic and offering protection against all peanut allergens. In addition, vaccination ablates allergic symptoms upon allergen challenge. Moreover, the prophylactic immunization setting conferred the protection against subsequent peanut‐induced anaphylaxis, showing the potential for preventive vaccination. This highlights the effectiveness of VLP Peanut as a prospective break‐through immunotherapy vaccine candidate toward peanut allergy. VLP Peanut has now entered clinical development with the study PROTECT

Deformation-induced localized solid-state amorphization in nanocrystalline nickel

Although amorphous structures have been widely obtained in various multi-component metallic alloys, amorphization in pure metals has seldom been observed and remains a long-standing scientific curiosity and technological interest. Here we present experimental evidence of localized solid-state amorphization in bulk nanocrystalline nickel introduced by quasi-static compression at room temperature. High-resolution electron microscope observations illustrate that nano-scale amorphous structures present at the regions where severe deformation occurred, e.g. along crack paths or surrounding nano-voids. These findings have indicated that nanocrystalline structures are highly desirable for promoting solid-state amorphization, which may provide new insights for understanding the nature of the crystalline-to-amorphous transformation and suggested a potential method to produce elemental metallic glasses that have hardly been available hitherto through rapid solidification