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The Born–Oppenheimer ab initio equilibrium structures of propane (CH3)2CH2 and 2,2-difluoropropane (CH3)2CF2 were computed at the CCSD(T) level of theory using a basis set of quadruple zeta quality. The semiexperimental structure of propane was also determined from the ground state rotational constants corrected for rovibrational corrections calculated at the MP2 level of theory. Structural comparisons are made with other molecules and are discussed in terms of the quantum theory of atoms in molecules.

The equilibrium structures of silyl iodide, SiH3I, and silylene halides, SiHX (X = F, Cl, Br, I), were determined by using the mixed regression method, where approximate values of the rotational constants are supplemented by the structural parameters of a different origin. For this goal, it is shown that the r(Si-H) bond length can be determined by using the isolated SiH stretching frequency and that an accurate estimation of the bond angles is obtained by an MP2 calculation with a basis set of triple zeta quality. To check the accuracy of the experimental structures, they were also optimized by means of all electron CCSD(T) calculations using basis sets of quadruple zeta quality.

Patient-centric drug development is crucial to creating treatments that address unmet patient needs but is often ignored. The COPD Foundation's COPD360Net ® includes a multistakeholder approach for operationalizing patient-centric development of treatments where patients, caregivers, scientists, and clinicians review opportunities based on scientific merit, potential to address an unmet need, and feasibility of adoption. COPD360Net deploys large-scale online community surveys to review profiles of potential therapies based on those criteria. This approach was implemented to inform the development of an intranasal spray to prevent viral respiratory infections (VRIs), a major cause of exacerbations in people with chronic lung diseases. Insights included: Of the 376 respondents with COPD surveyed, frequent exacerbators reported strong interest in a new type of antiviral nasal spray to prevent VRI. Patient survey and advisory committee insights demonstrated that a pan antiviral nasal spray has potential high value to both clinicians and patients and informed the COPD360Net decision to partner on its development. Including patient perspectives from the outset can be conducted efficiently by mobilizing an engaged online patient community.

Considered as interactive media, electronic games have their sound features as strong support to obtain an expanded UX (user experience): as a feedback of the players’ actions or as a constructive element of the immersive atmosphere. The auditive interfaces are bridges of the designer-user communication which extrapolate the screen’s visual elements. Sound effects and soundtracks have yet an important role to the game identity construction, enabling the player to have full knowledge of the actions. This essay sought to evaluate the user’s ability to identify the game actions only through its respective sound effects, aiming to study the sound design role in the UX. To that, it was opted for the case study of the sound interface of the game Super Mario Bros., released by Nintendo to the NES console, in 1985, which gave birth to one of the most important game franchises of the history. The study is relevant for the development of new sound projects in video games, mainly taking into account the possibility of working inclusive aspects through the sound interface.

The study refers to the design of outlets plugs covers, taking into account ergonomic and usability criteria. The study was developed in two subjects of the Design undergraduate course (Product Design 1 and Ergonomics and Product Design), developed in an integrated way to corroborate content and design practices in solving a problem. In this case, the problem addressed included the risk of domestic accidents, especially involving children. The aim of the project was to develop a new, more efficient, safe and comfortable product. For this, we used the product development methodology proposed by Lobach (2000), together with tools presented by Baxter (2011) and Task Analysis (MORAES; MONT'ALVÃO, 2000). Validation tests such as the Erick Test (CAVALCANTI, 2003) and a Satisfaction Scale (SUS) (BROOKE, 1986) were applied after 3D printing of the prototype. The study results in a conceptual proposal for new outlets plugs covers that has been tested and evaluated by users from the developed prototype. The ergonomic and usability criteria in this product project guided the choice of alternatives in order to improve functional aspects and, consequently, the satisfaction of individuals.

The impact of respiratory virus infections on global health is felt not just during a pandemic, but endemic seasonal infections pose an equal and ongoing risk of severe disease. Moreover, vaccines and antiviral drugs are not always effective or available for many respiratory viruses. We investigated how induction of effective and appropriate antigen-independent innate immunity in the upper airways can prevent the spread of respiratory virus infection to the vulnerable lower airways. Activation of TLR2, when restricted to the nasal turbinates, resulted in prompt induction of innate immune–driven antiviral responses through action of cytokines, chemokines, and cellular activity in the upper but not the lower airways. We have defined how nasal epithelial cells and recruitment of macrophages work in concert and play pivotal roles to limit progression of influenza virus to the lungs and sustain protection for up to 7 days. These results reveal underlying mechanisms of how control of viral infection in the upper airways can occur and support the implementation of strategies that can activate TLR2 in nasal passages to provide rapid protection, especially for at-risk populations, against severe respiratory infection when vaccines and antiviral drugs are not always effective or available.

Background: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. Methods: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). Findings: We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=

Abstract Background Better choices of dietary lipid sources and substitution of refined by fortified oils could reduce the intake of saturated fatty acids (FA) and increase the intake of omega 3 FA concomitantly to healthy bioactive compounds. Methods The development of obesity and metabolic disturbances was explored in rats fed during 11 weeks with a high fat diet (HFD) in which the amount of saturated and polyunsaturated FA was respectively reduced and increased, using rapeseed oil as lipid source. This oil was used in a refined form (R) or fortified (10 fold increase in concentration) with endogenous micronutrients (coenzyme Q10 + tocopherol only (RF) only and also with canolol (RFC)). The effect of substituting palm by rapeseed oil was analysed using a student t test, oil fortification was analysed using ANOVA statistical test. Results Despite a similar weight gain, diets R, RF and RFC improved glucose tolerance (+ 10%) of the rats compared to a standard HFD with palm and sunflower oils as lipid source. Plasma glucose was lowered in RF and RFC groups (− 15 and 23% respectively), although triacylglycerol level was only reduced in group RFC (− 33%) compared to R. The fortification with canolol promoted the activation of Akt and AMP-activated protein kinase (AMPK) in skeletal muscle and subcutaneous adipose tissue respectively. Canolol supplementation also led to reduce p38 MAPK activation in skeletal muscle. Conclusions This study suggests that the presence of endogenous micronutrients in rapeseed oil promotes cellular adaptations to reverse glucose intolerance and improve the metabolism of insulin sensitive tissues.

Abstract Background Obesity progressively leads to cardiac failure. Omega-3 polyunsaturated fatty acids (PUFA) have been shown to have cardio-protective effects in numerous pathological situations. It is not known whether rapeseed oil, which contains α-linolenic acid (ALA), has a similar protective effect. Omega-3 PUFAs are sensitive to attack by reactive oxygen species (ROS), and lipid peroxidation products could damage cardiac cells. We thus tested whether dietary refined rapeseed oil (RSO) associated with or without different antioxidants (vitamin E, coenzyme Q10 and canolol) is cardio-protective in a situation of abdominal obesity. Methods Sixty male Wistar rats were subdivided into 5 groups. Each group was fed a specific diet for 11 weeks: a low-fat diet (3% of lipids, C diet) with compositionally-balanced PUFAs; a high-fat diet rich in palm oil (30% of lipids, PS diet); the PS diet in which 40% of lipids were replaced by RSO (R diet); the R diet supplemented with coenzyme Q10 (CoQ10) and vitamin E (RTC diet); and the RTC diet supplemented with canolol (RTCC diet). At the end of the diet period, the rats were sacrificed and the heart was collected and immediately frozen. Fatty acid composition of cardiac phospholipids was then determined. Several features of cardiac function (fibrosis, inflammation, oxidative stress, apoptosis, metabolism, mitochondrial biogenesis) were also estimated. Results Abdominal obesity reduced cardiac oxidative stress and apoptosis rate by increasing the proportion of arachidonic acid (AA) in membrane phospholipids. Dietary RSO had the same effect, though it normalized the proportion of AA. Adding vitamin E and CoQ10 in the RSO-rich high fat diet had a deleterious effect, increasing fibrosis by increasing angiotensin-2 receptor-1b (Ag2R-1b) mRNA expression. Overexpression of these receptors triggers coronary vasoconstriction, which probably induced ischemia. Canolol supplementation counteracted this deleterious effect by reducing coronary vasoconstriction. Conclusion Canolol was found to counteract the fibrotic effects of vitamin E + CoQ10 on cardiac fibrosis in the context of a high-fat diet enriched with RSO. This effect occurred through a restoration of cardiac Ag2R-1b mRNA expression and decreased ischemia.

Obesity is a risk factor for the development of type 2 diabetes (T2D), which is associated with cardiovascular diseases [...]

It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary α-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.

Diabetes is characterized by a high mortality rate which is often associated with heart failure. Green tea and eicosapentaenoic acid (EPA) are known to lessen some of the harmful impacts of diabetes and to exert cardio-protection. The aim of the study was to determine the effects of EPA, green tea extract (GTE), and a combination of both on the cardiac consequences of diabetes mellitus, induced in Wistar rats by injection of a low dose of streptozotocin (33 mg/kg) combined with a high fat diet. Cardiac mechanical function, coronary reactivity, and parameters of oxidative stress, inflammation, and energy metabolism were evaluated. In the context of diabetes, GTE alone limited several diabetes-related symptoms such as inflammation. It also slightly improved coronary reactivity and considerably enhanced lipid metabolism. EPA alone caused the rapid death of the animals, but this effect was negated by the addition of GTE in the diet. EPA and GTE combined enhanced coronary reactivity considerably more than GTE alone. In a context of significant oxidative stress such as during diabetes mellitus, EPA enrichment constitutes a risk factor for animal survival. It is essential to associate it with the antioxidants contained in GTE in order to decrease mortality rate and preserve cardiac function.

A Middle Miocene oil source rock has been identified by geochemicallogging of exploration wells in the Eastern Drava depression (EDD) and in the Slavonija-Srijem depression (SSD) at the south-east margin of the Pannonian Basin, Croatia. The source rock contains Type II to II/III kerogen and reaches early maturity stage at depths of about 2400 m. The Mesozoic sequences were found either to be absent or to be poor in organic matter within the analysed wells.According to C27-C28-C29 sterane and C27-C28-C29 monoaromaticsteroid distributions, gamacerane indices, C35 homohopane indicesand presence of C30 steranrs, the EDD and SSD oils wrre generatedfrom the same marine source rock. The distribution of homohopanesand high Ni/(Ni + V) porphyrin ratios indicates that the related sourcerock was deposited under suboxic conditions. The oils appear to havebeen generated from the source rock during the early to middle stagesof maturity. The oils are waxy, with pour points up to 30°C and sulphurcontents not exceeding 0.7%.

The aim of our study was to know whether high dietary energy intake (HDEI) with equilibrated and unbalanced diets in term of lipid composition modify the fatty acid profile of cardiac phospholipids and function of various cardiac cells and to know if the changes in membrane lipid composition can explain the modifications of cellular activity. Wistar rats were fed either a control or high-fat (HF) diet for 12 weeks and Zucker diabetic fatty (ZDF) rats as well as their lean littermate (ZL) a control diet between week 7 to 11 of their life. Energy intake and abdominal obesity was increased in HF-fed and ZDF rats. Circulating lipids were also augmented in both strains although hyperglycemia was noticed only in ZDF rats. HDEI induced a decrease in linoleate and increase in arachidonate in membrane phospholipids which was more pronounced in the ZDF rats compared to the HF-fed rats. In vivo cardiac function (CF) was improved in HF-fed rats whereas ex vivo cardiac function was unchanged, suggesting that environmental factors such as catecholamines stimulated the in vivo CF. The unchanged ex vivo CF was associated with an increased cardiac mass which indicated development of fibrosis and/or hypertrophy. The increased in vivo CF was sustained by an augmented coronary reserve which was related to the cyclooxygenase pathway and accumulation of arachidonate in membrane phospholipids. In conclusion, before triggering a diabetic cardiomyopathy, HDEI stimulated the CF. The development of cardiomyopathy seems to result from fibrosis and/or hypertrophy which augments myocardial stiffness and decreases contractility.

Le vieillissement s’accompagne d’une perte de masse musculaire qui contribue à l’affaiblissement des capacités de défenses de l’organisme, et à la réduction de la mobilité et de l’autonomie des personnes âgées. Ce travail a été entrepris pour déterminer si le stress oxydant pouvait être impliqué dans ce phénomène, et en particulier la mitochondrie, forte productrice d’espèces actives de l’oxygène. Nous avons montré dans les muscles glycolytiques que la production mitochondriale d’H2O2 (PMH) induite par le flux inverse d’électrons entre les complexes II et I augmentait avec l’âge. Dans les muscles oxydatifs, la PMH induite par un flux d’électrons à partir du complexe I augmentait également. La PMH semble donc augmenter avec l’âge dans tous les types musculaires et la réduction de l’activité de la GPX dans les muscles glycolytiques pourrait accroître les conséquences de ce phénomène. Cependant, d’autres paramètres mitochondriaux (respiration, activités des complexes II à IV) n’étaient pas modifiés. De plus, un stress calcique provoqué par l’injection d’un ionophore (A23187) n’a pas eu d’effet chez des rats jeunes, alors qu’il a induit une atrophie du muscle soleus et un accroissement de la PMH dans le muscle gastrocnemius chez les rats âgés. L’ensemble de nos résultats suggère donc que l’augmentation de la PMH au cours du vieillissement n’a pas d’effet majeur à court terme sur le vieillissement musculaire. Elle pourrait avoir un effet à long terme, notamment dans le grand âge et/ou contribuer à accentuer la fragilisation du tissu âgé, en particulier en réponse à un stress.