In-Vitro Validated Methods for Encoding Digital Data in Deoxyribonucleic Acid (DNA)

Deoxyribonucleic acid (DNA) is emerging as an alternative archival memory technology. Recent advancements in DNA synthesis and sequencing have both increased the capacity and decreased the cost of storing information in de novo synthesized DNA pools. In this survey, we review methods for translating digital data to and/or from DNA molecules. An emphasis is placed on methods which have been validated by storing and retrieving real-world data via in-vitro experiments

Janus II: a new generation application-driven computer for spin-system simulations

This paper describes the architecture, the development and the implementation of Janus II, a new generation application-driven number cruncher optimized for Monte Carlo simulations of spin systems (mainly spin glasses). This domain of computational physics is a recognized grand challenge of high-performance computing: the resources necessary to study in detail theoretical models that can make contact with experimental data are by far beyond those available using commodity computer systems. On the other hand, several specific features of the associated algorithms suggest that unconventional computer architectures, which can be implemented with available electronics technologies, may lead to order of magnitude increases in performance, reducing to acceptable values on human scales the time needed to carry out simulation campaigns that would take centuries on commercially available machines. Janus II is one such machine, recently developed and commissioned, that builds upon and improves on the successful JANUS machine, which has been used for physics since 2008 and is still in operation today. This paper describes in detail the motivations behind the project, the computational requirements, the architecture and the implementation of this new machine and compares its expected performances with those of currently available commercial systems.Comment: 28 pages, 6 figure

Met signaling in cardiomyocytes is required for normal cardiac function in adult mice.

Hepatocyte growth factor (HGF) and its receptor, Met, are key determinants of distinct developmental processes. Although HGF exerts cardio-protective effects in a number of cardiac pathologies, it remains unknown whether HGF/Met signaling is essential for myocardial development and/or physiological function in adulthood. We therefore investigated the requirement of HGF/Met signaling in cardiomyocyte for embryonic and postnatal heart development and function by conditional inactivation of the Met receptor in cardiomyocytes using the Cre-α-MHC mouse line (referred to as α-MHCMet-KO). Although α-MHCMet-KO mice showed normal heart development and were viable and fertile, by 6 months of age, males developed cardiomyocyte hypertrophy, associated with interstitial fibrosis. A significant upregulation in markers of myocardial damage, such as β-MHC and ANF, was also observed. By the age of 9 months, α-MHCMet-KO males displayed systolic cardiac dysfunction. Mechanistically, we provide evidence of a severe imbalance in the antioxidant defenses in α-MHCMet-KO hearts involving a reduced expression and activity of catalase and superoxide dismutase, with consequent reactive oxygen species accumulation. Similar anomalies were observed in females, although with a slower kinetics. We also found that Met signaling down-regulation leads to an increase in TGF-β production and a decrease in p38MAPK activation, which may contribute to phenotypic alterations displayed in α-MHCMet-KO mice. Consistently, we show that HGF acts through p38α to upregulate antioxidant enzymes in cardiomyocytes. Our results highlight that HGF/Met signaling in cardiomyocytes plays a physiological cardio-protective role in adult mice by acting as an endogenous regulator of heart function through oxidative stress control.Comunidad de Madrid/Universidad Complutense de Madrid; Association Française contre les Myopathies; Seventh Framework Programme; Fondation pour la Recherche Médicale; Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación; Fondation Bettencourt Schueller; European Regional Development Fund; Junta de Andalucía; Junta de Castilla y Leó

Bsx, a novel hypothalamic factor linking feeding with locomotor activity, is regulated by energy availability

Es un estudio en modelos de rata acerca del papel de BSX, la actividad y la alimentación.We recently reported that the hypothalamic homeobox domain transcription factor Bsx plays an essential role in the central nervous system control of spontaneous physical activity and the generation of hyperphagic responses. Moreover, we found Bsx to be a master regulator for the hypothalamic expression of key orexigenic neuropeptide Y and agouti gene-related protein. We now hypothesized that Bsx, which is expressed in the dorsomedial and arcuate nucleus (ARC) of the hypothalamus, is regulated by afferent signals in response to peripheral energy balance. Bsx expression was analyzed using in situ hybridization in fed vs. fasted (24 h) and ghrelin vs. leptin-treated rats, as well as in mice deficient for leptin or the ghrelin signaling. Ghrelin administration increased, whereas ghrelin receptor antagonist decreased ARC Bsx expression. Leptin injection attenuated the fasting-induced increase in ARC Bsx levels but had no effect in fed rats. Dorsomedial hypothalamic nucleus Bsx expression was unaffected by pharmacological modifications of leptin or ghrelin signaling. Obese leptin-deficient (ob/ob) mice, but not obese melanocortin 4 receptor-knockout mice, showed higher expression of Bsx, consistent with dependency from afferent leptin rather than increased adiposity per se. Interestingly, exposure to a high-fat diet triggered Bsx expression, consistent with the concept that decreased leptin signaling due to a highfat diet induced leptin resistance. Our data indicate that ARC Bsx expression is specifically regulated by afferent energy balance signals, including input from leptin and ghrelin. Future studies will be necessary to test if Bsx may be involved in the pathogenesis of leptin resistance

Shedding light on the origin of 204Pb, the heaviest s-process–only isotope in the solar system

Asymptotic giant branch stars are responsible for the production of most of the heavy isotopes beyond Sr observed in the solar system. Among them, isotopes shielded from the ¿-process contribution by their stable isobars are defined as ¿-only nuclei. For a long time the abundance of 204Pb, the heaviest ¿-only isotope, has been a topic of debate because state-of-the-art stellar models appeared to systematically underestimate its solar abundance. Besides the impact of uncertainties from stellar models and galactic chemical evolution simulations, this discrepancy was further obscured by rather divergent theoretical estimates for the neutron capture cross section of its radioactive precursor in the neutron-capture flow, 204Tl (¿1/2=3.78¿¿yr), and by the lack of experimental data on this reaction. We present the first ever neutron capture measurement on 204Tl, conducted at the CERN neutron time-of-flight facility n_TOF, employing a sample of only 9 mg of 204Tl produced at the Institute Laue Langevin high flux reactor. By complementing our new results with semiempirical calculations we obtained, at the ¿-process temperatures of ¿¿¿˜8¿¿keV and ¿¿¿˜30¿¿keV, Maxwellian-averaged cross sections (MACS) of 580(168) mb and 260(90) mb, respectively. These figures are about 3% lower and 20% higher than the corresponding values widely used in astrophysical calculations, which were based only on theoretical calculations. By using the new 204Tl MACS, the uncertainty arising from the 204Tl¿(n,¿) cross section on the ¿-process abundance of 204Pb has been reduced from ~30% down to +8%/-6%, and the ¿-process calculations are in agreement with the latest solar system abundance of 204Pb reported by K. Lodders in 2021.We acknowledge the suggestions of three referees, which helped to improve the present article in several relevant aspects. We would like to acknowledge financial support from the Argos Scholarship of the Universtitat Politècnica de Catalunya (UPC) and the Consejo de Seguridad Nuclear (CSN), the Spanish Government Ministries MINECO (projects FPA2014- 52823-C2-1/2-P and FPA2017-83946-C2-1/2-P) and MCIU (projects PID2019–104714 GB-C21 and PID2022-138297NB-C21), the EC FP7 projects NeutAndalus (Grant No. 334315) and CHANDA (Grant No. 605203), and the n_TOF Collaboration and the Institut de Tècniques Energètiques (INTE) of the UPC. A. C. H. also recognizes the support from a Margarita Salas grant by the UPC (Agreement CG/2021/03/23) funded by the Ministerio de Universidades (Order UNI/551/2021) and by the European Union NextGenerationEU/PRTR. A. C. H. and C. D. P. acknowledge support from ERC Consolidator Grant HYMNS, Grant Agreement No. 681740. M. P. acknowledges significant support to NuGrid from STFC (through the University of Hull’s Consolidated Grant No. ST/R000840/1), from the ERC Consolidator Grant FIG. 3. Isotopic abundance ratios Nð204PbÞ=Nð150SmÞ in the star envelope at the end of the AGB phase, obtained using the MACS from Fig. 2 for the stellar models described in the text. All values are normalized to the solar system (ss) ratio [10], which is highlighted by the thick green bar with the green shaded band depicting its uncertainty. Solid error bars reflect only the uncertainty contribution from the cross section, while dashed error bars include also the uncertainty on the thermal dependency of the β− decay of 204Tl [31]. PHYSICAL REVIEW LETTERS 133, 052702 (2024) 052702-6 (Hungary) funding scheme (Project RADIOSTAR, G. A. n. 724560), from the ChETEC COST Action (CA16117), supported by the European Cooperation in Science and Technology, from the IReNA network supported by NSF AccelNet, from the National Science Foundation (NSF, USA) under Grant No. PHY-1430152 (JINA Center for the Evolution of the Elements), from the NKFI via K-project 138031 and the Lendület Program LP2023-10 of the Hungarian Academy of Sciences and from the European Union’s Horizon 2020 research and innovation programme (ChETEC-INFRA—Project No. 101008324). M. P. also acknowledges the access to VIPER, the University of Hull High Performance Computing Facility. C. L. W. acknowl- edges support from the Science and Technology Facilities Council UK (ST/M006085/1), and the European Research Council ERC-2015-STG No. 677497. The support of all funding agencies of the n_TOF participating institutes is acknowledged.Article signat per 134 autors/es: A. Casanovas-Hoste, C. Domingo-Pardo, J. Lerendegui-Marco, C. Guerrero, A. Tarifeño-Saldivia, M. Krtička, M. Pignatari, F. Calviño, D. Schumann, S. Heinitz, R. Dressler, U. Köster, O. Aberle, J. Andrzejewski, L. Audouin, V. Bécares, M. Bacak, J. Balibrea-Correa, M. Barbagallo, S. Barros, F. Bečvář, C. Beinrucker, E. Berthoumieux, J. Billowes, D. Bosnar, M. Brugger, M. Caamaño, M. Calviani, D. Cano-Ott, R. Cardella, D. M. Castelluccio, F. Cerutti, Y. H. Chen, E. Chiaveri, N. Colonna, G. Cortés, M. A. Cortés-Giraldo, L. Cosentino, L. A. Damone, M. Diakaki, E. Dupont, I. Durán, B. Fernández-Domínguez, A. Ferrari, P. Ferreira, P. Finocchiaro, V. Furman, K. Göbel, A. R. García, A. Gawlik-Ramięga, T. Glodariu, I. F. Gonçalves, E. González-Romero, A. Goverdovski, E. Griesmayer, F. Gunsing, H. Harada, T. Heftrich, J. Heyse, D. G. Jenkins, E. Jericha, F. Käppeler, Y. Kadi, T. Katabuchi, P. Kavrigin, V. Ketlerov, V. Khryachkov, A. Kimura, N. Kivel, M. Kokkoris, E. Leal-Cidoncha, C. Lederer-Woods, H. Leeb, S. Lo Meo, S. J. Lonsdale, R. Losito, D. Macina, J. Marganiec, T. Martínez, C. Massimi, P. Mastinu, M. Mastromarco, F. Matteucci, E. A. Maugeri, E. Mendoza, A. Mengoni, P. M. Milazzo, F. Mingrone, M. Mirea, S. Montesano, A. Musumarra, R. Nolte, A. Oprea, N. Patronis, A. Pavlik, J. Perkowski, I. Porras, J. Praena, J. M. Quesada, K. Rajeev, T. Rauscher, R. Reifarth, A. Riego-Perez, Y. Romanets, P. C. Rout, C. Rubbia, J. A. Ryan, M. Sabaté-Gilarte, A. Saxena, P. Schillebeeckx, S. Schmidt, P. Sedyshev, A. G. Smith, A. Stamatopoulos, G. Tagliente, J. L. Tain, L. Tassan-Got, A. Tsinganis, S. Valenta, G. Vannini, V. Variale, P. Vaz, A. Ventura, V. Vlachoudis, R. Vlastou, A. Wallner, S. Warren, M. Weigand, C. Weiss, C. Wolf, P. J. Woods, T. Wright, P. Žugec.Postprint (published version

Temporal sampling, resetting, and adaptation orchestrate gradient sensing in sperm

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Cell Biology 198 (2012): 1075-1091, doi:10.1083/jcb.201204024.Sperm, navigating in a chemical gradient, are exposed to a periodic stream of chemoattractant molecules. The periodic stimulation entrains Ca2+ oscillations that control looping steering responses. It is not known how sperm sample chemoattractant molecules during periodic stimulation and adjust their sensitivity. We report that sea urchin sperm sampled molecules for 0.2–0.6 s before a Ca2+ response was produced. Additional molecules delivered during a Ca2+ response reset the cell by causing a pronounced Ca2+ drop that terminated the response; this reset was followed by a new Ca2+ rise. After stimulation, sperm adapted their sensitivity following the Weber–Fechner law. Taking into account the single-molecule sensitivity, we estimate that sperm can register a minimal gradient of 0.8 fM/µm and be attracted from as far away as 4.7 mm. Many microorganisms sense stimulus gradients along periodic paths to translate a spatial distribution of the stimulus into a temporal pattern of the cell response. Orchestration of temporal sampling, resetting, and adaptation might control gradient sensing in such organisms as well.This work was supported by the German Research Foundation and the Fonds der Chemischen Industrie.2013-03-1

Violent Deaths of Iraqi Civilians, 2003–2008: Analysis by Perpetrator, Weapon, Time, and Location

Madelyn Hsiao-Rei Hicks and colleagues provide a detailed analysis of Iraqi civilian violent deaths during 2003-2008 of the Iraq war and show that of 92,614 deaths, unknown perpetrators caused 74% of deaths, Coalition forces 12%, and Anti-Coalition forces 11%

Hot, rocky and warm, puffy super-Earths orbiting TOI-402 (HD 15337)

Context: The Transiting Exoplanet Survey Satellite (TESS) is revolutionising the search for planets orbiting bright and nearby stars. In sectors 3 and 4, TESS observed TOI-402 (TIC-120896927), a bright V = 9.1 K1 dwarf also known as HD 15337, and found two transiting signals with periods of 4.76 and 17.18 days and radii of 1.90 and 2.21 R⊕, respectively. This star was observed prior to the TESS detection as part of the radial-velocity (RV) search for planets using the HARPS spectrometer, and 85 precise RV measurements were obtained before the launch of TESS over a period of 14 yr. Aims: In this paper, we analyse the HARPS RV measurements in hand to confirm the planetary nature of these two signals. Methods: HD 15337 happens to present a stellar activity level similar to the Sun, with a magnetic cycle of similar amplitude and RV measurements that are affected by stellar activity. By modelling this stellar activity in the HARPS radial velocities using a linear dependence with the calcium activity index log(RHK′), we are able, with a periodogram approach, to confirm the periods and the planetary nature of TOI-402.01 and TOI-402.02. We then derive robust estimates from the HARPS RVs for the orbital parameters of these two planets by modelling stellar activity with a Gaussian process and using the marginalised posterior probability density functions obtained from our analysis of TESS photometry for the orbital period and time of transit. Results: By modelling TESS photometry and the stellar host characteristics, we find that TOI-402.01 and TOI-402.02 have periods of 4.75642 ± 0.00021 and 17.1784 ± 0.0016 days and radii of 1.70 ± 0.06 and 2.52 ± 0.11 R⊕ (precision 3.6 and 4.2%), respectively. By analysing the HARPS RV measurements, we find that those planets are both super-Earths with masses of 7.20 ± 0.81 and 8.79 ± 1.68 M⊕ (precision 11.3 and 19.1%), and small eccentricities compatible with zero at 2σ. Conclusions: Although having rather similar masses, the radii of these two planets are very different, putting them on different sides of the radius gap. By studying the temporal evolution under X-ray and UV (XUV) driven atmospheric escape of the TOI-402 planetary system, we confirm, under the given assumptions, that photo-evaporation is a plausible explanation for this radius difference. Those two planets, being in the same system and therefore being in the same irradiation environment are therefore extremely useful for comparative exoplanetology across the evaporation valley and thus bring constraints on the mechanisms responsible for the radius gap