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Detecting and improving the scientific understanding of global trends in complex Earth systems, such as climate, increasingly depend on assimilating datasets from multiple instruments and platforms over decadal timescales. Calibration accuracy, stability, and inter-consistency among different instruments are key to developing reliable composite data records from sensors in low Earth and geostationary orbits, however, achieving sufficiently low uncertainties for these performance metrics poses a significant challenge. Space-borne instruments commonly carry on-board references for calibration at various wavelengths, but these increase mass and mission complexity and are subject to degradation in the space environment. The Moon can be considered a natural solar diffuser which can be utilized as an on-orbit calibration target by most space-borne Earth-observing instruments. Since the lunar surface reflectance is effectively time-invariant, establishing the Moon as a high-accuracy calibration reference enables broad inter-calibration opportunities even between temporally non-overlapping instruments and provides an exo-atmospheric absolute radiometric standard. The ARCSTONE mission goal is to establish the Moon as a reliable reference for high-accuracy on-orbit calibration spanning the visible and near-infrared spectral regions. The ARCSTONE instrument is a compact spectrometer which will be packaged on a 6U CubeSat intended for low Earth orbit. It will measure the lunar spectral reflectance with accuracy < 0.5% (k=1), sufficient to establish an SI-traceable absolute lunar calibration standard referenced to the spectral solar irradiance across the 350 to 2300 nm spectral range. This lunar reference will help to enable high-accuracy absolute calibrations and inter-calibrations of past, current, and future Earth-observing sensors, meteorological imagers, and long-term climate monitoring satellite systems. The ARCSTONE team will present the development status of the instrument, results from laboratory characterizations and functional tests, and the planned path toward mission implementation.

Detecting and improving scientific understanding of global trends in complex Earth systems such as climate increasingly depend on assimilating datasets from multiple instruments and platforms over decadal timescales. Calibration accuracy, stability, and inter-consistency among different instruments are key to developing reliable composite data records from sensors in low Earth and geostationary orbits, but achieving sufficiently low uncertainties for these performance metrics poses a significant challenge. Space-borne instruments commonly carry on-board references for calibration at various wavelengths, but these increase mass and mission complexity, and are subject to degradation in the space environment. The Moon can be considered a natural solar diffuser which can be observed as a calibration target by most spaceborne Earth-observing instruments. Since the lunar surface reflectance is effectively time-invariant, establishing the Moon as a high-accuracy calibration reference enables broad inter-calibration opportunities even between temporally non-overlapping instruments, and well as provides an exo-atmospheric absolute radiometric standard. The ARCSTONE mission goal is to establish the Moon as a reliable reference for high-accuracy on-orbit calibration of reflected-solar instruments. The ARCSTONE instrument is a compact spectrometer on a CubeSat intended for low Earth orbit. It will measure the lunar spectral reflectance with accuracy < 0.5% (k=1), sufficient to establish an SI-traceable absolute lunar calibration standard referenced to the spectral solar irradiance across the 350 to 2300 nm spectral range. This lunar reference will help to enable high-accuracy absolute calibration and inter-calibration of past, current, and future Earth-observing sensors, meteorological imagers, and long-term climate monitoring satellite systems. The ARCSTONE team will present the instrument development status, its approach to calibration and characterization, and the planned path toward mission implementation.

It is assumed that the human genome encodes about 21,000 annotated protein-coding genes. However, over 60 million of small open reading frames (smORFs) are predicted to give rise to microproteins smaller than 100 amino acids, yet only very few have been characterized to date. Here we report an experimental validation of thousands of smORF-encoded peptides (SEPs) using advanced proteophylogenomics and quantitative peptidomics methods. We applied our pipeline to plasma and serum obtained from 60 healthy donors of both sexes, ages ranging from 20 to 50 years old. Our results revealed the existence of 6,533 predicted microproteins (median size of 51 amino acids), none of which are redundant to known protein-coding genes, and confirmed another 199 previously reported SEPs. Most are predicted to be intergenic, display ordered peptides with alpha helices, beta sheets or both, with an abundance of positive charges. Based on abundance, a unsupervised hierchical clustering analysis clearly distinguished gender and age, sugg esting that they likely reflect meaningful biological differences. Some smORFs showed genome-wide association hits (GWAS) that correlate with specific types of cancer, longevity and other traits and diseases, yet their functional role remains a mystery. Our study further expands our knowledge of the human peptidome that can be secreted into the bloodstream, which may contain factors relevant in cell and tissue homeostasis, physiology and possibly in aging. Certainly, these findings open a field to use SEPs as biomarkers for disease and hold the potential as novel biological therapeutics.

There is emerging evidence that dysregulation of the epigenome plays a dominant role in organismal decline during aging, but it is uncertain what causes this dysregulation. DNA damage is one possible driver of these epigenetic changes, as induction of DNA damage leads to an accelerated aging of the epigenomes of diverse organisms. However, the most convincing way to test this hypothesis is to evaluate epigenetic changes in model organisms with enhanced DNA repair. Generating such model organisms has proven difficult, because overexpression of endogenous DNA repair proteins often leads to genomic instability, likely due to stoichiometric imbalances in multi-protein DNA repair complexes. We hypothesized that DNA repair proteins from other species (i.e. “exogenous”) wouldn’t lead to this stoichiometric disruption and could improve mammalian genome stability. To identify such proteins, we generated and screened a library comprised of DNA repair genes from polyextremophiles that can survive extremely high levels of DNA damage. This screen identified six genes that more than tripled the viability of human cells exposed to high doses of H2O2. This enhanced survival likely results from improved DNA repair and protection mechanisms, as cells expressing these genes had fewer double-strand breaks following exposure to non-lethal doses of H2O2. We are currently testing if expression of these genes reduces epigenetic alterations following DNA damage, and if expression of these genes in yeast is able to affect epigenetic changes and lifespan. These experiments could provide powerful evidence of a connection between the stability of the genome and epigenome during aging.

ABI : ankle–brachial index ACCORD : Action to Control Cardiovascular Risk in Diabetes ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation AGREE : Appraisal of Guidelines Research and Evaluation AHA : American Heart Association apoA1 : apolipoprotein A1 apoB : apolipoprotein B CABG : coronary artery bypass graft surgery CARDS : Collaborative AtoRvastatin Diabetes Study CCNAP : Council on Cardiovascular Nursing and Allied Professions CHARISMA : Clopidogrel for High Athero-thrombotic Risk and Ischemic Stabilisation, Management, and Avoidance CHD : coronary heart disease CKD : chronic kidney disease COMMIT : Clopidogrel and Metoprolol in Myocardial Infarction Trial CRP : C-reactive protein CURE : Clopidogrel in Unstable Angina to Prevent Recurrent Events CVD : cardiovascular disease DALYs : disability-adjusted life years DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Trial ED : erectile dysfunction eGFR : estimated glomerular filtration rate EHN : European Heart Network EPIC : European Prospective Investigation into Cancer and Nutrition EUROASPIRE : European Action on Secondary and Primary Prevention through Intervention to Reduce Events GFR : glomerular filtration rate GOSPEL : Global Secondary Prevention Strategies to Limit Event Recurrence After MI GRADE : Grading of Recommendations Assessment, Development and Evaluation HbA1c : glycated haemoglobin HDL : high-density lipoprotein HF-ACTION : Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing HOT : Hypertension Optimal Treatment Study HPS : Heart Protection Study HR : hazard ratio hsCRP : high-sensitivity C-reactive protein HYVET : Hypertension in the Very Elderly Trial ICD : International Classification of Diseases IMT : intima-media thickness INVEST : International Verapamil SR/Trandolapril JTF : Joint Task Force LDL : low-density lipoprotein Lp(a) : lipoprotein(a) LpPLA2 : lipoprotein-associated phospholipase 2 LVH : left ventricular hypertrophy MATCH : Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke MDRD : Modification of Diet in Renal Disease MET : metabolic equivalent MONICA : Multinational MONItoring of trends and determinants in CArdiovascular disease NICE : National Institute of Health and Clinical Excellence NRT : nicotine replacement therapy NSTEMI : non-ST elevation myocardial infarction ONTARGET : Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial OSA : obstructive sleep apnoea PAD : peripheral artery disease PCI : percutaneous coronary intervention PROactive : Prospective Pioglitazone Clinical Trial in Macrovascular Events PWV : pulse wave velocity QOF : Quality and Outcomes Framework RCT : randomized clinical trial RR : relative risk SBP : systolic blood pressure SCORE : Systematic Coronary Risk Evaluation Project SEARCH : Study of the Effectiveness of Additional Reductions in Cholesterol and SHEP : Systolic Hypertension in the Elderly Program STEMI : ST-elevation myocardial infarction SU.FOL.OM3 : SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids Syst-Eur : Systolic Hypertension in Europe TNT : Treating to New Targets UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use VITATOPS : VITAmins TO Prevent Stroke VLDL : very low-density lipoprotein WHO : World Health Organization ### 1.1 Introduction Atherosclerotic cardiovascular disease (CVD) is a chronic disorder developing insidiously throughout life and usually progressing to an advanced stage by the time symptoms occur. It remains the major cause of premature death in Europe, even though CVD mortality has …