An Abstract Interpretation-based Model of Tracing Just-In-Time Compilation

Tracing just-in-time compilation is a popular compilation technique for the efficient implementation of dynamic languages, which is commonly used for JavaScript, Python and PHP. We provide a formal model of tracing JIT compilation of programs using abstract interpretation. Hot path detection corresponds to an abstraction of the trace semantics of the program. The optimization phase corresponds to a transform of the original program that preserves its trace semantics up to an observation modeled by some abstraction. We provide a generic framework to express dynamic optimizations and prove them correct. We instantiate it to prove the correctness of dynamic type specialization and constant variable folding. We show that our framework is more general than the model of tracing compilation introduced by Guo and Palsberg [2011] based on operational bisimulations.Comment: To appear in ACM Transactions on Programming Languages and System

Metal-Organic Frameworks in Germany: from Synthesis to Function

Metal-organic frameworks (MOFs) are constructed from a combination of inorganic and organic units to produce materials which display high porosity, among other unique and exciting properties. MOFs have shown promise in many wide-ranging applications, such as catalysis and gas separations. In this review, we highlight MOF research conducted by Germany-based research groups. Specifically, we feature approaches for the synthesis of new MOFs, high-throughput MOF production, advanced characterization methods and examples of advanced functions and properties

Tuning the Mechanical Response of Metal−Organic Frameworks by Defect Engineering

The incorporation of defects into crystalline materials provides an important tool to fine-tune properties throughout various fields of materials science. We performed high-pressure powder X-ray diffraction experiments, varying pressures from ambient to 0.4 GPa in 0.025 GPa increments to probe the response of defective UiO-66 to hydrostatic pressure for the first time. We observe an onset of amorphization in defective UiO-66 samples around 0.2 GPa and decreasing bulk modulus as a function of defects. Intriguingly, the observed bulk moduli of defective UiO-66­(Zr) samples do not correlate with defect concentration, highlighting the complexity of how defects are spatially incorporated into the framework. Our results demonstrate the large impact of point defects on the structural stability of metal–organic frameworks (MOFs) and pave the way for experiment-guided computational studies on defect engineered MOFs

Real-life data on potential drug-druginteractions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study

Background There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used. Aim To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study. Methods Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org) Results Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate- to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI. Conclusions Based on these results, we can estimate that 30 - 44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate- to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease

Oxy inflammation in diving activities

openGli esseri umani e la maggior parte degli organismi animali si sono adattati a vivere nell'atmosfera terrestre, dove la frazione di ossigeno ispirato (FiO2) è pari a circa 0,21. L'O2 è il terzo elemento più abbondante nell'universo, dopo l'idrogeno e l'elio come composti, compresi gli ossidi, che costituiscono il 50 % della crosta terrestre [1]. L'O2 comprende un terzo della massa corporea umana; rappresenta un componente essenziale di macromolecole come proteine, carboidrati, lipidi e nucleotidi. È il costituente principale dei composti inorganici di gusci, denti e ossa animali. L'O2 è l'accettore terminale degli elettroni nella fosforilazione ossidativa, fornendo la maggior parte dell'energia biologica praticamente in tutte le forme di vita animali. L'O2 è l'ultimo accettore di elettroni nei processi catabolici che convertono l'energia biochimica dai nutrienti in ATP, l'"unità di valuta" molecolare del trasferimento di energia intracellulare [2]. Questo processo avviene attraverso l'uso di portatori di elettroni, come la nicotinammide adenina dinucleotide (NAD+), che vengono ridotti nel processo ricevendo elettroni dalle molecole bersaglio e vengono ri-ossidati donando elettroni all'O2 attraverso la fosforilazione ossidativa [3]. Questo processo avviene tra la membrana mitocondriale interna ed esterna. La presenza di O2 nei tessuti umani consente alle cellule di produrre 38 ATP (adenosina trifosfato, noto come molecola di accumulo di energia) per molecola di glucosio attraverso il ciclo di Krebs e la fosforilazione ossidativa. La glicolisi anaerobica (manca di O2) fornisce solo l'energia per 2 ATP. Il metabolismo dei lipidi richiede anche ossigeno: il metabolismo del palmitato di acidi grassi, per esempio, produce 129 ATP mentre utilizza 31 mol di O2. Respirare aria a pressione iperbarica (la pressione ambientale aumenta di un'atmosfera ogni 10 m di profondità) [4] aumenta necessariamente la pressione parziale di O2 (pO2) nella circolazione con aumento del rilascio di radicali liberi e aumento della resistenza vascolare a causa della vasocostrizione legata all'iperossia [5]. La tossicità da O2 è una condizione derivante dagli effetti dannosi della respirazione di O2 ad un aumento della pressione parziale come in profondità, che porta a danni cellulari con effetti più spesso osservati nel sistema nervoso centrale (CNS) [6], nei polmoni [7] e negli occhi [8]. La tossicità del SNC è correlata al valore di pO2 e all'esposizione temporale [9]. Può verificarsi come conseguenza dell'esposizione a condizioni iperbariche che si manifestano con cambiamenti visivi come visione a tunnel, tinnito, nausea, contrazioni facciali (specialmente del viso), cambiamenti comportamentali (confusione, irritabilità, ansia), vertigini [10]. L'esposizione a livelli elevati di pO2 può anche portare a una patologia nota come tossicità polmonare da ossigeno (POT). I subacquei possono mostrare diversi sintomi tra cui irritazione tracheale, tosse, atelettasia, edema interstiziale, infiammazione e fibrosi [7].Humans and most animal organisms have adapted to live in the Earth's atmosphere, where the fraction of inspired oxygen (FiO2) equals approximately 0.21. O2 is the third-most abundant element in the universe, after hydrogen and helium as compounds, including oxides, which constitute 50 % of Earth's crust [1]. O2 comprises a third of the human body mass; it represents an essential component of macromolecules such as proteins, carbohydrates, lipids, and nucleotides. It is the principal constituent of inorganic compounds of animal shells, teeth, and bones. O2 is the terminal acceptor of electrons in oxidative phosphorylation, providing most of the biological energy in virtually all animal life forms. O2 is the last electron acceptor in the catabolic processes that convert biochemical energy from nutrients in ATP, the molecular "unit of currency" of intracellular energy transfer [2]. This process occurs through the use of electron carriers, such as nicotinamide adenine dinucleotide (NAD+), which are reduced in the process by receiving electrons from target molecules and are re-oxidized by donating electrons to O2 through oxidative phosphorylation [3]. This process occurs between the inner and the outer mitochondrial membrane. The presence of O2 in human tissues allows cells to produce 38 ATP (adenosine triphosphate, known as energy storage molecule) per glucose molecule through Krebs cycle and oxidative phosphorylation. Anaerobic (O2 lack) glycolysis only provides the energy for 2 ATP. Lipid metabolism also requires oxygen: metabolism of the fatty acid palmitate, for example, yields 129 ATP while utilizing 31 mol of O2. Breathing air at hyperbaric pressure (environmental pressure increases by one atmosphere every 10-m depth) [4] necessarily increases the O2 partial pressure (pO2) in the circulation with augmented free radicals release and increased vascular resistance due to hyperoxia-linked vasoconstriction [5]. O2 toxicity is a condition resulting from the harmful effects of breathing O2 at increased partial pressure such as at depth, leading to cell damage with effects most often seen in the central nervous system (CNS) [6], lungs [7], and eyes [8]. CNS toxicity is related to pO2 value and time exposure [9]. It can occur as consequence the exposure to hyperbaric conditions manifesting with visual changes such as tunnel vision, tinnitus, nausea, facial twitching (especially of the face), behavioural changes (confusion, irritability, anxiety), dizziness [10]. Exposure to high pO2 level may also lead to a pathology known as pulmonary oxygen toxicity (POT). Divers may show several symptoms including tracheal irritation, coughing, atelectasis, interstitial oedema, inflammation and fibrosis [7]

Tuning the properties of MOF‐808 via defect engineering and metal nanoparticle encapsulation

Defect engineering and metal encapsulation are considered as valuable approaches to fine‐tune the reactivity of metal–organic frameworks. In this work, various MOF‐808 (Zr) samples are synthesized and characterized with the final aim to understand how defects and/or platinum nanoparticle encapsulation act on the intrinsic and reactive properties of these MOFs. The reactivity of the pristine, defective and Pt encapsulated MOF‐808 is quantified with water adsorption and CO(2) adsorption calorimetry. The results reveal strong competitive effects between crystal morphology and missing linker defects which in turn affect the crystal morphology, porosity, stability, and reactivity. In spite of leading to a loss in porosity, the introduction of defects (missing linkers or Pt nanoparticles) is beneficial to the stability of the MOF‐808 towards water and could also be advantageously used to tune adsorption properties of this MOF family

Using water adsorption measurements to access the chemistry of defects in the metal–organic framework UiO-66

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