On Landau damping

Going beyond the linearized study has been a longstanding problem in the theory of Landau damping. In this paper we establish exponential Landau damping in analytic regularity. The damping phenomenon is reinterpreted in terms of transfer of regularity between kinetic and spatial variables, rather than exchanges of energy; phase mixing is the driving mechanism. The analysis involves new families of analytic norms, measuring regularity by comparison with solutions of the free transport equation; new functional inequalities; a control of nonlinear echoes; sharp scattering estimates; and a Newton approximation scheme. Our results hold for any potential no more singular than Coulomb or Newton interaction; the limit cases are included with specific technical effort. As a side result, the stability of homogeneous equilibria of the nonlinear Vlasov equation is established under sharp assumptions. We point out the strong analogy with the KAM theory, and discuss physical implications.Comment: News: (1) the main result now covers Coulomb and Newton potentials, and (2) some classes of Gevrey data; (3) as a corollary this implies new results of stability of homogeneous nonmonotone equilibria for the gravitational Vlasov-Poisson equatio

Efficient and irreversible antibody-cysteine bioconjugation using carbonylacrylic reagents.

There is considerable interest in the development of chemical methods for the precise, site-selective modification of antibodies for therapeutic applications. In this protocol, we describe a strategy for the irreversible and selective modification of cysteine residues on antibodies, using functionalized carbonylacrylic reagents. This protocol is based on a thiol-Michael-type addition of native or engineered cysteine residues to carbonylacrylic reagents equipped with functional compounds such as cytotoxic drugs. This approach is a robust alternative to the conventional maleimide technique; the reaction is irreversible and uses synthetically accessible reagents. Complete conversion to the conjugates, with improved quality and homogeneity, is often achieved using a minimal excess (typically between 5 and 10 equiv.) of the carbonylacrylic reagent. Potential applications of this method cover a broad scope of cysteine-tagged antibodies in various formats (full-length IgGs, nanobodies) for the site-selective incorporation of cytotoxic drugs without loss of antigen-binding affinity. Both the synthesis of the carbonylacrylic reagent armed with a synthetic molecule of interest and the subsequent preparation of the chemically defined, homogeneous antibody conjugate can be achieved within 48 h and can be easily performed by nonspecialists. Importantly, the conjugates formed are stable in human plasma. The use of liquid chromatography-mass spectrometry (LC-MS) analysis is recommended for monitoring the progression of the bioconjugation reactions on protein and antibody substrates with accurate resolution.We thank FAPESP (BEPE 2015/07509-1 and 2017/13168-8 to B.B., and 2013/25504-1 to A.C.B.B.), Xunta de Galicia (M.J.M.), FCT Portugal (FCT Investigator to G.J.L.B., IF/00624/2015), the EU (Marie Sklodowska-Curie ITN Protein Conjugates, GA 675007, including a PhD Studentship to X.F.), the Ministerio de Economía y Competitividad (projects CTQ2015-67727-R and UNLR13-4E-1931 to F.C. and CTQ2015-70524-R and RYC-2013-14706 to G.J.O.) and the Universidad de La Rioja (FPI Studentship to I.C.). We also thank S. Massa and N. Devoogdt (Vrije Universiteit Brussel (VUM), Brussels) for the generous gift of the Her2-targeting nanobody 2Rb17c, Genentech for providing Thiomab LC-V205C and trastuzumab antibodies, and D. Neri’s laboratory (Swiss Federal Institute of Technology (ETH Zürich), Zurich) for the generous gift of the F16 antibody. G.J.L.B. is a Royal Society University Research Fellow (UF110046 and URF/R/180019) and the recipient of a European Research Council Starting Grant (TagIt, GA 676832)

Previous tonsillectomy modifies odds of tonsil and base of tongue cancer

BACKGROUND: Tonsillectomy is a commonly performed surgical procedure that involves removal of the palatine tonsils. The purpose of this study is to examine the association between previous tonsillectomy and odds of oropharyngeal squamous cell carcinoma (OPSCC) in a large population-based case–control study. We hypothesise that previous tonsillectomy is associated with a decreased odds of tonsil cancer with no impact on the odds of developing base of tongue (BOT) cancer. METHODS: This was a population-based, frequency-matched case–control study with multinomial logistic regression, including 1378 controls, 108 BOT cancer cases, and 198 tonsil cancer cases. Demographic and risk factor data were collected using a structured questionnaire during an in-home visit conducted by trained nurse-interviewers. The human papillomavirus (HPV) tumour status was determined through Luminex-based multiplex PCR and p16 status by immunohistochemistry. RESULTS: Previous tonsillectomy was associated with a nearly two-fold increased odds of BOT cancer (OR=1.95, 95% CI 1.25–3.06, P=0.003) and a large decrease in the odds of tonsil cancer (OR=0.22, 95% CI 0.13–0.36, P<0.001). When HPV status was considered, tonsillectomy was associated with a decreased odds of HPV-positive tonsil cancer (OR=0.17, 95% CI 0.08–0.34, P<0.001) and an increased risk of HPV-positive BOT cancer (OR=2.46, 95% CI 1.22–4.95, P=0.012). When p16 status was considered, tonsillectomy was associated with an increased odds of p16-positive BOT cancer (OR=2.24, 95% CI 1.16–4.35, P=0.017) and a decreased odds of p16-positive tonsil cancer (OR=0.14, 95% CI 0.07–0.31, P<0.001). CONCLUSIONS: Previous tonsillectomy modifies the odds of both tonsil and BOT cancer, with decreased odds of tonsil cancer and increased odds of BOT cancer. A history of previous tonsillectomy may play a role in OPSCC risk stratification when considered along with other covariates such as sexual history, smoking status, and age