S. Cohen

Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL

Senescent cells, formed in response to physiological and oncogenic stresses, facilitate protection from tumourigenesis and aid in tissue repair. However, accumulation of such cells in tissues contributes to age-related pathologies. Resistance of senescent cells to apoptotic stimuli may contribute to their accumulation, yet the molecular mechanisms allowing their prolonged viability are poorly characterized. Here we show that senescent cells upregulate the anti-apoptotic proteins BCL-W and BCL-XL. Joint inhibition of BCL-W and BCL-XL by siRNAs or the small-molecule ABT-737 specifically induces apoptosis in senescent cells. Notably, treatment of mice with ABT-737 efficiently eliminates senescent cells induced by DNA damage in the lungs as well as senescent cells formed in the epidermis by activation of p53 through transgenic p14ARF. Elimination of senescent cells from the epidermis leads to an increase in hair-follicle stem cell proliferation. The finding that senescent cells can be eliminated pharmacologically paves the way to new strategies for the treatment of age-related pathologies.

Observation of the 1S–2S transition in trapped antihydrogen

The spectrum of the hydrogen atom has played a central part in fundamental physics over the past 200 years. Historical examples of its importance include the wavelength measurements of absorption lines in the solar spectrum by Fraunhofer, the identification of transition lines by Balmer, Lyman and others, the empirical description of allowed wavelengths by Rydberg, the quantum model of Bohr, the capability of quantum electrodynamics to precisely predict transition frequencies, and modern measurements of the 1S–2S transition by Hänsch to a precision of a few parts in 1015. Recent technological advances have allowed us to focus on antihydrogen—the antimatter equivalent of hydrogen. The Standard Model predicts that there should have been equal amounts of matter and antimatter in the primordial Universe after the Big Bang, but today’s Universe is observed to consist almost entirely of ordinary matter. This motivates the study of antimatter, to see if there is a small asymmetry in the laws of physics that govern the two types of matter. In particular, the CPT (charge conjugation, parity reversal and time reversal) theorem, a cornerstone of the Standard Model, requires that hydrogen and antihydrogen have the same spectrum. Here we report the observation of the 1S–2S transition in magnetically trapped atoms of antihydrogen. We determine that the frequency of the transition, which is driven by two photons from a laser at 243 nanometres, is consistent with that expected for hydrogen in the same environment. This laser excitation of a quantum state of an atom of antimatter represents the most precise measurement performed on an anti-atom. Our result is consistent with CPT invariance at a relative precision of about 2 × 10−10.

Observation of the hyperfine spectrum of antihydrogen

The observation of hyperfine structure in atomic hydrogen by Rabi and co-workers and the measurement of the zero-field ground-state splitting at the level of seven parts in 1013 are important achievements of mid-twentieth-century physics. The work that led to these achievements also provided the first evidence for the anomalous magnetic moment of the electron, inspired Schwinger’s relativistic theory of quantum electrodynamics and gave rise to the hydrogen maser, which is a critical component of modern navigation, geo-positioning and very-long-baseline interferometry systems. Research at the Antiproton Decelerator at CERN by the ALPHA collaboration extends these enquiries into the antimatter sector. Recently, tools have been developed that enable studies of the hyperfine structure of antihydrogen—the antimatter counterpart of hydrogen. The goal of such studies is to search for any differences that might exist between this archetypal pair of atoms, and thereby to test the fundamental principles on which quantum field theory is constructed. Magnetic trapping of antihydrogen atoms provides a means of studying them by combining electromagnetic interaction with detection techniques that are unique to antimatter. Here we report the results of a microwave spectroscopy experiment in which we probe the response of antihydrogen over a controlled range of frequencies. The data reveal clear and distinct signatures of two allowed transitions, from which we obtain a direct, magnetic-field-independent measurement of the hyperfine splitting. From a set of trials involving 194 detected atoms, we determine a splitting of 1,420.4 ± 0.5 megahertz, consistent with expectations for atomic hydrogen at the level of four parts in 104. This observation of the detailed behaviour of a quantum transition in an atom of antihydrogen exemplifies tests of fundamental symmetries such as charge–parity–time in antimatter, and the techniques developed here will enable more-precise such tests.

Antihydrogen accumulation for fundamental symmetry tests

Antihydrogen, a positron bound to an antiproton, is the simplest anti-atom. Its structure and properties are expected to mirror those of the hydrogen atom. Prospects for precision comparisons of the two, as tests of fundamental symmetries, are driving a vibrant programme of research. In this regard, a limiting factor in most experiments is the availability of large numbers of cold ground state antihydrogen atoms. Here, we describe how an improved synthesis process results in a maximum rate of 10.5 ± 0.6 atoms trapped and detected per cycle, corresponding to more than an order of magnitude improvement over previous work. Additionally, we demonstrate how detailed control of electron, positron and antiproton plasmas enables repeated formation and trapping of antihydrogen atoms, with the simultaneous retention of atoms produced in previous cycles. We report a record of 54 detected annihilation events from a single release of the trapped anti-atoms accumulated from five consecutive cycles.Antihydrogen studies are important in testing the fundamental principles of physics but producing antihydrogen in large amounts is challenging. Here the authors demonstrate an efficient and high-precision method for trapping and stacking antihydrogen by using controlled plasma.

Photofragment ionization-loss stimulated Raman spectroscopy of a hydrated neurotransmitter: 2-phenylethylamine–water

Different types of spectral signatures and their interpretation provide valuable information on intra- and inter-molecular interactions that lead to unique shapes of molecules and clusters. Here, ionization-loss stimulated Raman (ILSR) spectra of the 2-phenylethylamine–water (PEA–H2O) cluster were obtained by monitoring the spectral signatures of PEA and of CH2NH2–H2O (a hydrated portion of the PEA tail) fragment ions. The ILSR spectra of both fragments were found to be similar, indicating that they are actually reminiscent of the PEA–H2O cluster signature. Comparison of the photofragment spectra to anharmonic calculated Raman spectra of the different conformers of the PEA–H2O clusters, suggests a structure with PEA similar to that of the most stable gauche conformer, with H2O hydrogen bonded to the nitrogen lone pair.

Characterization of the 1S–2S transition in antihydrogen

In 1928, Dirac published an equation1 that combined quantum mechanics and special relativity. Negative-energy solutions to this equation, rather than being unphysical as initially thought, represented a class of hitherto unobserved and unimagined particles—antimatter. The existence of particles of antimatter was confirmed with the discovery of the positron2 (or anti-electron) by Anderson in 1932, but it is still unknown why matter, rather than antimatter, survived after the Big Bang. As a result, experimental studies of antimatter3–7, including tests of fundamental symmetries such as charge–parity and charge–parity–time, and searches for evidence of primordial antimatter, such as antihelium nuclei, have high priority in contemporary physics research. The fundamental role of the hydrogen atom in the evolution of the Universe and in the historical development of our understanding of quantum physics makes its antimatter counterpart—the antihydrogen atom—of particular interest. Current standard-model physics requires that hydrogen and antihydrogen have the same energy levels and spectral lines. The laser-driven 1S–2S transition was recently observed8 in antihydrogen. Here we characterize one of the hyperfine components of this transition using magnetically trapped atoms of antihydrogen and compare it to model calculations for hydrogen in our apparatus. We find that the shape of the spectral line agrees very well with that expected for hydrogen and that the resonance frequency agrees with that in hydrogen to about 5 kilohertz out of 2.5 × 1015 hertz. This is consistent with charge–parity–time invariance at a relative precision of 2 × 10−12—two orders of magnitude more precise than the previous determination8—corresponding to an absolute energy sensitivity of 2 × 10−20 GeV.The shape of the spectral line and the resonance frequency of the 1S–2S transition in antihydrogen agree very well with those of hydrogen.

Enhanced Control and Reproducibility of Non-Neutral Plasmas

The simultaneous control of the density and particle number of non-neutral plasmas confined in Penning-Malmberg traps is demonstrated. Control is achieved by setting the plasmas density by applying a rotating electric field while simultaneously fixing its axial potential via evaporative cooling. This novel method is particularly useful for stabilizing positron plasmas, as the procedures used to collect positrons from radioactive sources typically yield plasmas with variable densities and particle numbers; it also simplifies optimization studies that require plasma parameter scans. The reproducibility achieved by applying this technique to the positron and electron plasmas used by the ALPHA antihydrogen experiment at CERN, combined with other developments, contributed to a 10-fold increase in the antiatom trapping rate.

Fokker-Planck coefficients for a magnetized ion-electron plasma

The Fokker-Planck coefficients are developed for an ion-electron plasma in an ambient uniform magnetic field. The calculation is based on the binary collision model where a single encounter between an ion and an electron is first considered. The collision is taken as a perturbation to the free helical motion of the two particles involved, and the terms are kept up to the second order. The collision process is reformulated in terms of the changes of the perpendicular and parallel speeds and gyrophase shift. This new approach allows us to properly take into account the persisting helical motion in the magnetic field when the collisional interaction ceases.

Erratum: Observation of the hyperfine spectrum of antihydrogen

This corrects the article DOI: 10.1038/nature23446