Formal Analysis of a Fault-Tolerant Routing Algorithm for a Network-on-Chip

International audienceA fault-tolerant routing algorithm in Network-on-Chip architectures provides adaptivity for on-chip communications. Adding fault-tolerance adaptivity to a routing algorithm increases its design complexity and makes it prone to deadlock and other problems if improperly implemented. Formal verification techniques are needed to check the correctness of the design. This paper performs formal analysis on an extension of the link-fault tolerant Network-on-Chip architecture introduced by Wu et al. that supports multiflit wormhole routing. This paper describes several lessons learned during the process of constructing a formal model of this routing architecture. Finally, this paper presents how the deadlock freedom and tolerance to a single-link fault is verified for a two-by-two mesh version of this routing architecture

Effect of different standing poses on whole body volume acquisition by three-dimensional photonic scanning

The present study compared whole body volumes obtained by three-dimensional (3D) photonic scanning of two different poses and discussed its effect on body composition estimation. Pose A with large angles of shoulder abduction and feet separated and Pose B with shoulders abducted slightly, the elbows extended and heels together. 16 male and 13 female participants were scanned twice in each pose using a 3D scanner. The mean of whole body volume and the mean of body composition obtained with Pose B was corrected by a regression equation and compared with the results obtained from Pose A. After correction, the whole body volumes acquired with these two poses were similar [limit of agreement = (-0.71 l,0.71 l)] but the body compositions obtained with Pose A and Pose B were different [limit of agreement = (-4.4%, 4.4%)]. The results indicated that scanning using either pose gives reliable estimations for whole body volume and body composition. The whole body volume obtained from different poses can be adjusted using the regression equation but small volumetric differences translate into much more substantial differences in body fat percentage. Hence, it is recommended to use the same scanning pose consistently when monitoring individuals longitudinally

Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET

A bispecific antibody (BsAb) targeting the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) pathways represents a novel approach to overcome resistance to targeted therapies in patients with nonsmall cell lung cancer. In this study, we sequentially screened a panel of BsAbs in a combinatorial approach to select the optimal bispecific molecule. The BsAbs were derived from different EGFR and MET parental monoclonal antibodies. Initially, molecules were screened for EGFR and MET binding on tumor cell lines and lack of agonistic activity toward MET. Hits were identified and further screened based on their potential to induce untoward cell proliferation and crossphosphorylation of EGFR by MET via receptor colocalization in the absence of ligand. After the final step, we selected the EGFR and MET arms for the lead BsAb and added low fucose Fc engineering to generate amivantamab (JNJ-61186372). The crystal structure of the anti-MET Fab of amivantamab bound to MET was solved, and the interaction between the two molecules in atomic details was elucidated. Amivantamab antagonized the hepatocyte growth factor (HGF)-induced signaling by binding to MET Sema domain and thereby blocking HGF beta-chain-Sema engagement. The amivantamab EGFR epitope was mapped to EGFR domain III and residues K443, K465, I467, and S468. Furthermore, amivantamab showed superior antitumor activity over small molecule EGFR and MET inhibitors in the HCC827-HGF in vivo model. Based on its unique mode of action, amivantamab may provide benefit to patients with malignancies associated with aberrant EGFR and MET signaling.Transplantation and autoimmunit

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Stellar structure and compact objects before 1940: Towards relativistic astrophysics

Since the mid-1920s, different strands of research used stars as "physics laboratories" for investigating the nature of matter under extreme densities and pressures, impossible to realize on Earth. To trace this process this paper is following the evolution of the concept of a dense core in stars, which was important both for an understanding of stellar evolution and as a testing ground for the fast-evolving field of nuclear physics. In spite of the divide between physicists and astrophysicists, some key actors working in the cross-fertilized soil of overlapping but different scientific cultures formulated models and tentative theories that gradually evolved into more realistic and structured astrophysical objects. These investigations culminated in the first contact with general relativity in 1939, when J. Robert Oppenheimer and his students George Volkoff and Hartland Snyder systematically applied the theory to the dense core of a collapsing neutron star. This pioneering application of Einstein's theory to an astrophysical compact object can be regarded as a milestone in the path eventually leading to the emergence of relativistic astrophysics in the early 1960s.Comment: 83 pages, 4 figures, submitted to the European Physical Journal