A theoretical study of the photochemistry of 1,3-cyclopentadiene and its cyano derivatives bound to a water dimer: Assessing reactivity of ionized clusters and possible photoproducts.

We theoretically investigate the photoionization scenarios of molecular complexes involving cyclopentadiene and cyanocyclopentadiene bound to water dimers. Using electronic structure calculations within density-functional theory (DFT) and time dependent DFT (TD-DFT), we explore the potential photochemical pathways following ionization, and determine the charge transfer excitations related to the possible subsequent reactions. Our findings suggest that the investigated photochemical pathways of the hydrated complexes take place in two well-defined ultraviolet regions: (i) 8.2-9.5 eV for the cyclic compounds and (ii) 11.2-11.4 eV for the bound water dimer. We quantify how H-bonding effects can influence the photoionization channels. Before forming possible photoproducts, we also examine the regiospecificity of OH addition to 1,3-cyclopentadiene and its cyano derivatives We analyze our results in light of photoionization studies of jet-cooled molecular complexes and possible implications in astrochemical environments.

The Interplay between the Temperature and Pressure on the Reaction Pathways of the Prenol Oxidation by Hydroxyl Radicals.

Despite prenol emerging as a next-generation biofuel, some questions about its mechanism still need to be adequately proposed to rationalize its consumption and evaluate its efficiency in spark-ignition (SI) engines. Here, we present new insights into the reaction mechanism of prenol (3-methyl-2-buten-1-ol) with OH radicals as a function of temperature and pressure. We have determined that the different temperature and pressure conditions control the preferred products. At combustion temperatures and low pressures, OH-addition adducts are suppressed, increasing the formation of α and δ allylic radicals responsible for the auto-ignition.

Influence of Solvents and Halogenation on ESIPT of Benzimidazole Derivatives for Designing Turn-on Fluorescence Probes.

This work reports a theoretical investigation of the solvent polarity as well as the halogenation of benzimidazole derivatives during excited state intramolecular proton transfer (ESIPT). It details how the environment and halogen substitution may contribute to the efficiency of ESIPT upon keto-enol tautomerism and exploits this effect to design fluorescence sensing. For this purpose, we first examine the conformational equilibrium of benzimidazole derivatives containing different halogen atoms, which results in intramolecular proton transfer, using density-functional theory (DFT) combined with the polarizable continuum model (PCM). Then we evaluate the fluorescence of the benzimidazole derivatives in different dielectric constants within time-dependent DFT (TD-DFT) approaches. Our results quantitatively allow the determination of large Stokes shifts in nonpolar solvents around 100 nm. These theoretical results are in agreement with experimental solvatochromism studies of benzimidazoles. The effect of halogenation, with fluorine, chlorine, and bromine, is less important than solvent polarization when ESIPT takes place. Thus, halogenation can be properly chosen depending on the interest of the synthesis of benzimidazole-based turn-on fluorescence in appropriate solvents.

Predicting pressure-dependent rate constants for the furan + OH reactions and their impact under tropospheric conditions.

In this work, we have evaluated the influence of temperature and pressure on the mechanism of furan oxidation by the OH radical. The stationary points on the potential energy surface were described at the M06-2X/aug-cc-pVTZ level of theory. In the kinetic treatment at the high-pressure limit (HPL), we have combined the multistructural canonical variational theory with multidimensional small-curvature tunneling corrections and long-range transition state theory. The system-specific quantum Rice-Ramsperger-Kassel theory was employed to estimate the pressure-dependent rate. In the HPL, the OH addition on the α carbon is the dominant pathway in the mechanism, producing a product via the ring-opening process, also confirmed by the product branching ratio calculations. The overall rate constant, obtained by a kinetic Monte Carlo simulation, reads the form koverall=5.22×10-13T/3001.10⁡exp1247(K/T) and indicates that the furan oxidation by OH radicals is a pressure-independent reaction under tropospheric conditions.

Leverage demand-side policies for energy security.

Conventional supply-side approaches overlook potential benefits.

A Deeper Insight into the Supramolecular Activation of Oxidative Addition Reactions Involving Pincer-Rhodium(I) Complexes.

The factors governing the acceleration of the oxidative addition of methyl iodide to pincer rhodium(I)-complexes induced by coronene have been computationally explored in detail using quantum chemical methods. Both the parent reaction and the coronene-mediated process proceed via a stepwise SN2-type mechanism. It is found that the acceleration of the process derives from the formation of an initial supramolecular complex, mainly stabilized by electrostatic and π-π interactions, which significantly increases the electron richness of the complex. The impact of this effect on the reaction barrier has been quantitatively analyzed by applying the activation strain model in combination with the energy decomposition analysis method. In addition, the influence of other polycyclic aromatic hydrocarbons on the oxidative reaction has been also considered.

Understanding the reactivity and selectivity of Diels-Alder reactions involving furans.

The reactivity and endo/exo selectivity of the Diels-Alder cycloaddition reactions involving furan and substituted furans as dienes have been computationally explored. In comparison to cyclopentadiene, it is found that furan is comparatively less reactive and also less endo-selective in the reaction with maleic anhydride as the dienophile. Despite that, both the reactivity and the selectivity can be successfully modified by the presence of substituents at either 2- or 3-positions of the heterocycle. In this sense, it is found that the presence of strong electron-donor groups significantly increases the reactivity of the system while the opposite is found in the presence of electron-withdrawing groups. The observed trends in both the reactivity and selectivity are analyzed quantitatively in detail by means of the activation strain model of reactivity in combination with the energy decomposition analysis methods.

A new large-scale gravitational complex discovered in the Gulf of Squillace (central Mediterranean): tectonic implications.

Seismic reflection (2D/3D), borehole and bathymetric data are used to recognize a new gravitational complex in the Gulf of Squillace, Southern Italy, named the Squillace Complex. The complex has a NE-striking headwall connected to a basal detachment formed between Messinian evaporites and Tortonian shales. Its sense of movement changes to a W-E direction in the toe region. In plan view, the Squillace Complex is marked by the presence of sinuous and continuous seafloor scarps, just a few kilometers offshore, over an elongated morphological high. Seismic-well ties reveal that the complex was initiated in the Zanclean (~ 4 Ma) and continued its movement into the Gelasian (~ 2.1 Ma) at an average rate of 1.9 mm/year. Movement slowed down in the Calabrian (middle Pleistocene) and continued until the present day at a lower rate of 0.1 mm/year. Gravitational collapse of the Squillace Complex correlates with discrete contractional/transpressional events affecting the Calabrian region, which caused basin shortening and the temporary arrest of Calabrian Arc migration. These episodes resulted in tectonic uplift in the study area after 0.45 Ma (Late Pleistocene). Conversely, the complex's slower movement recorded since the Calabrian (middle Pleistocene) is associated with slab rollback of the Ionian plate under the Calabrian Arc.

Combined oil spill modelling and shoreline sensitivity analysis for contingency planning in the Irish Sea.

Offshore oil spills often result in severe environmental and socio-economic consequences. This work focuses on a busy, yet poorly studied part of NW Europe, the Irish Sea, to assess the impact of future oil spills on the nearby coast. By integrating numerical models and shoreline sensitivity analyses for two confined areas, Liverpool Bay and Milford Haven, this work acknowledges wind direction and speed as principal controls on the movement of oil under winter/storm conditions and in shallow waters. Ocean currents play a secondary role, but are significant in deeper waters and in low-wind summer conditions. The temporal elements used in the modelling thus stress that when the spill occurs is just as important as where. As a corollary, the fate of spilled oil is determined in this work for distinct scenarios and types. Response strategies are recommended to minimise the impact of future spills on coastal populations.

Multistructural partition function truncation and its effect on the thermal rate constants.

Thermal rate constants for the hydrogen abstraction reaction of methyl pentanoate were calculated using the multistructural canonical variational theory with small-curvature tunneling (MS-CVT/SCT). The conformational search for the stationary points generated by these reactions was performed with an algorithm that combines systematic and stochastic searches at dual-level. At the high-level (MPWB1K/6-31+G(d,p)), 244 geometries for methyl pentanoate and transition states were found. A systematic estimative of the efficiency of the truncation of multistructural rovibrational partition functions and its effects on thermal rate constants was carried out. In this analysis, we observed that rotation about -OCH3 group (ϕ4) of the ester generates unstable structures with little contribution to the magnitude of the partition function. We also estimate that the truncation of the partition functions in a small set of conformations can produce deviations up to 75% compared to converged theoretical results.

Photoabsorption of Microhydrated Naphthalene and Its Cyano-Substituted Derivatives: Probing Prereactive Models for Photodissociation in Molecular Clouds.

We investigate the photoionization pathways of naphthalene, 1-cyanonaphthalene, and 2-cyanonaphthalene upon complexation with the water dimer, aiming to understand the photodissociation process under conditions of the interstellar medium (ISM). We analyze the intermolecular bonding pattern, equilibrium rotational properties, energy complexation, far-IR spectra, and ionic trends of the possible photoproducts using dispersion-corrected density functional theory (DFT-D) and time-dependent DFT (TD-DFT). For the different configurations, we evaluate the possible charge-transfer (CT) excitations near the photoionization limit. Our results indicate that, in high-radiation regions of the ISM (>8.0 eV), CT excitations occur from localized occupied molecular orbitals (MOs) in the aromatic molecules to mixed unoccupied MOs in the complexes, favoring cationic aromatic species in these conditions. We notice that the photoabsorption spectra depend on the type of intermolecular interaction (H-bonds or O-H···π bonds) in the complexes, as well as the presence and position (1 or 2) of the cyano-functional group in naphthalene. For hydrated naphthalene, the O-H···π complexes assume a more relevant role for photodissociation. In the case of the cyano-substituted derivatives, the H-bonded structures are more favorable to be considered as prereactive models. However, the cyano group at position 2 indicates that CT excitations toward the water dimer are more likely to occur.

Transferrin receptor 2 deficiency promotes macrophage polarization and inflammatory arthritis.

OBJECTIVE: Rheumatoid arthritis is an inflammatory joint disease in which synovial iron deposition has been described. Transferrin receptor 2 (Tfr2) represents a critical regulator of systemic iron levels. Loss of Tfr2 function in humans and mice results in iron overload. As iron contributes to inflammatory processes, we investigated whether Tfr2-deletion affects the pathogenesis of inflammatory arthritis in an iron-dependent manner. METHODS: Using a global and conditional genetic disruption of Tfr2, we assessed the relevance of Tfr2 in K/BxN serum-transfer arthritis (STA) and macrophage polarization. RESULTS: Male Tfr2-/- mice subjected to STA developed pronounced joint swelling, and bone erosion as compared to Tfr2+/+ littermate-controls (P < 0.01). Furthermore, an increase of neutrophils and macrophages/monocytes was observed in the inflammatory infiltrate within the paws of Tfr2-/- mice. To elucidate whether Tfr2 in myeloid cells has a direct role in the pathogenesis of arthritis or whether the effects were mediated via the systemic iron overload, we induced STA in Tfr2fl/fl-LysMCre + mice, which showed normal iron-loading. Cre + female mice displayed increased disease development compared to Cre-controls. As macrophages regulate iron availability and innate immunity, we hypothesized that Tfr2-deficiency would polarize macrophages toward a pro-inflammatory state (M1) that contributes to arthritis progression. In response to IFN-γ stimulation, Tfr2-/- macrophages showed increased expression of M1-like cytokines, IFN-γ-target genes, nitric-oxide production, and prolonged STAT1 activation compared to Tfr2+/+ macrophages (P < 0.01), while pre-treatment with ruxolitinib abolished Tfr2-driven M1-like polarization. CONCLUSION: Taken together, these findings suggest a protective role of Tfr2 in macrophages on the progression of arthritis via suppression of M1-like polarization.

Tumour catabolism independent of malnutrition and inflammation in upper GI cancer patients revealed by longitudinal metabolomics.

BACKGROUND: The detrimental impact of malnutrition and cachexia in cancer patients subjected to surgical resection is well established. However, how systemic and local metabolic alterations in cancer patients impact the serum metabolite signature, thereby leading to cancer-specific differences, is poorly defined. In order to implement metabolomics as a potential tool in clinical diagnostics and disease follow-up, targeted metabolite profiling based on quantitative measurements is essential. We hypothesized that the quantitative metabolic profile assessed by 1 H nuclear magnetic resonance (NMR) spectroscopy can be used to identify cancer-induced catabolism and potentially distinguish between specific tumour entities. Importantly, to prove tumour dependency and assess metabolic normalization, we additionally analysed the metabolome of patients' sera longitudinally post-surgery in order to assess metabolic normalization. METHODS: Forty two metabolites in sera of patients with tumour entities known to cause malnutrition and cachexia, namely, upper gastrointestinal cancer and pancreatic cancer, as well as sera of healthy controls, were quantified by 1 H NMR spectroscopy. RESULTS: Comparing serum metabolites of patients with gastrointestinal cancer with healthy controls and pancreatic cancer patients, we identified at least 15 significantly changed metabolites in each comparison. Principal component and pathway analysis tools showed a catabolic signature in preoperative upper gastrointestinal cancer patients. The most specifically upregulated metabolite group in gastrointestinal cancer patients was ketone bodies (3-hydroxybutyrate, P < 0.0001; acetoacetate, P < 0.0001; acetone, P < 0.0001; false discovery rate [FDR] adjusted). Increased glycerol levels (P < 0.0001), increased concentration of the ketogenic amino acid lysine (P = 0.03) and a significant correlation of 3-hydroxybutyrate levels with branched-chained amino acids (leucine, P = 0.02; isoleucine, P = 0.04 [FDR adjusted]) suggested that ketone body synthesis was driven by lipolysis and amino acid breakdown. Interestingly, the catabolic signature was independent of the body mass index, clinically assessed malnutrition using the nutritional risk screening score, and systemic inflammation assessed by CRP and leukocyte count. Longitudinal measurements and principal component analyses revealed a quick normalization of key metabolic alterations seven days post-surgery, including ketosis. CONCLUSIONS: Together, the quantitative metabolic profile obtained by 1 H NMR spectroscopy identified a tumour-induced catabolic signature specific to upper gastrointestinal cancer patients and enabled monitoring restoration of metabolic homeostasis after surgery. This approach was critical to identify the obtained metabolic profile as an upper gastrointestinal cancer-specific signature independent of malnutrition and inflammation.

Overexpression of UCP3 decreases mitochondrial efficiency in mouse skeletal muscle in vivo.

Uncoupling protein-3 (UCP3) is a mitochondrial transmembrane protein highly expressed in the muscle that has been implicated in regulating the efficiency of mitochondrial oxidative phosphorylation. Increasing UCP3 expression in skeletal muscle enhances proton leak across the inner mitochondrial membrane and increases oxygen consumption in isolated mitochondria, but its precise function in vivo has yet to be fully elucidated. To examine whether muscle-specific overexpression of UCP3 modulates muscle mitochondrial oxidation in vivo, rates of ATP synthesis were assessed by 31 P magnetic resonance spectroscopy (MRS), and rates of mitochondrial oxidative metabolism were measured by assessing the rate of [2-13 C]acetate incorporation into muscle [4-13 C]-, [3-13 C]-glutamate, and [4-13 C]-glutamine by high-resolution 13 C/1 H MRS. Using this approach, we found that the overexpression of UCP3 in skeletal muscle was accompanied by increased muscle mitochondrial inefficiency in vivo as reflected by a 42% reduction in the ratio of ATP synthesis to mitochondrial oxidation.

Meniscal Bone Angle Is a Strong Predictor of Anterior Cruciate Ligament Injury.

Purpose: To evaluate the influence of lateral posterior tibial slope (LPTS) and meniscal bone angle (MBA) on primary anterior cruciate ligament (ACL) tear risk in an adult population through the LPTS-MBA ratio. Methods: A retrospective case-control study was performed with patients from a tertiary hospital who underwent primary ACL surgery and had preoperative magnetic resonance imaging (MRI). These subjects were matched by age and sex in a 1:1 ratio to patients who had an MRI without ACL tear. LPTS and MBA were measured on MRI scan. Quantitative data are presented in the median ± interquartile range (IQR). Identification of independent risk factors for primary ACL tear was performed using multivariable logistic regression. Receiver operating characteristics curves detected any variable with strong discriminative capacity. Results: In total, 95 patients with primary ACL tear confirmed on MRI were matched with 95 controls (N = 190). Nearly 80% were male subjects, with a median age of 26 years. In the ACL tear group, the median value of LPTS-MBA ratio was 0.20 (IQR 0.11-0.37) versus 0.12 (IQR 0.08-0.19) in the control group (P = .001). LPTS had a median value of 4.20° in the ACL tear group (IQR 2.05-7.35°) and 2.90° in the control group (IQR, 2.05-5.00°) (P = .026), whereas MBA was 19° (IQR, 16-24°) versus 26° (IQR, 24-30°) (P = .001), respectively. Logistic regression showed that LPTS (odds ratio 1.20, 95% confidence interval 1.03-1.42, P = .021) and MBA (odds ratio 0.78, 95% confidence interval 0.71-0.85, P = .001) were independent predictors. The area under the curve (AUC) of LPTS-MBA ratio was 0.69, greater than that of LPTS alone (AUC = 0.61) but lower than that for MBA (AUC = 0.82). Conclusions: In this study, a reduced MBA was the strongest predictive variable associated with a primary ACL tear. A threshold of 22.35° of MBA was associated with an increased risk of ACL tear, with a sensitivity of 70% and specificity of 84%. A cut-off of 0.22 of LPTS-MBA was associated with an increased risk of ACL tear, with a sensitivity of 55% and specificity of 87%. Level of Evidence: Level III, case-control study.

Prenol as a Next-Generation Biofuel or Additive: A Comprehension of the Hydrogen Abstraction Reactions by a H Atom.

Thermal rate coefficients for the hydrogen abstraction reactions of prenol (3-methyl-2-butenol) by a hydrogen atom were calculated with the multipath canonical variational theory with small-curvature tunneling (MP-CVT/SCT). The conformational search was performed with a dual-level approach, and the multistructural torsional anharmonicity effects were corrected through the rovibrational partition function calculated with the multistructural method based on a coupled torsional potential (MS-T(C)). This methodology allows us to estimate the thermal rate constants in the temperature range of 200-2500 K and fit them into two analytical expressions. Differences between the number of conformations on the torsional potential energy surfaces for prenol and the transition state decrease the thermal rate constants for the H-abstraction at the α carbon. An opposite behavior was detected for the abstractions on the δ site. The product branching ratios were calculated using single-structure and multipath approaches. The product distributions from the former are shown to be inadequate for studying the mechanism under combustion conditions. The values estimated from MP-CVT/SCT rate coefficients indicated that the radicals from (Rα) and (Rδ)/(Rδ') are formed in considerable amounts. These species are fundamental in comprehending the inhibition and promotion of the autoignition phenomena.

Two-photon polymerization simulation and fabrication of 3D microprinted suspended waveguides for on-chip optical interconnects.

Quantum and neuromorphic computational platforms in integrated photonic circuits require next-generation optical functionalities. Often, increasingly complex on-chip light-routing that allow superpositions not attainable by planar technologies are paramount e.g. for artificial neural networks. Versatile 3D waveguides are achievable via two-photon polymerization (TPP)-based microprinting. Here, a 3D morphology prediction tool which considers experimental TPP parameters, is presented, enabling on-chip 3D waveguide performance simulations. The simulations allow reducing the cost-intensive systematic experimental optimization process. Fabricated 3D waveguides show optical transmission properties in agreement with simulations, demonstrating that the developed morphology prediction methodology is beneficial for the development of versatile on-chip and potentially inter-chip photonic interconnect technology.

The evolution of knowledge on genes associated with human diseases.

Thousands of biomedical scientific articles, including those describing genes associated with human diseases, are published every week. Computational methods such as text mining and machine learning algorithms are now able to automatically detect these associations. In this study, we used a cognitive computing text-mining application to construct a knowledge network comprising 3,723 genes and 99 diseases. We then tracked the yearly changes on these networks to analyze how our knowledge has evolved in the past 30 years. Our systems approach helped to unravel the molecular bases of diseases and detect shared mechanisms between clinically distinct diseases. It also revealed that multi-purpose therapeutic drugs target genes that are commonly associated with several psychiatric, inflammatory, or infectious disorders. By navigating this knowledge tsunami, we were able to extract relevant biological information and insights about human diseases.

Metabolic regulation of prostate cancer heterogeneity and plasticity.

Metabolic reprogramming is one of the main hallmarks of cancer cells. It refers to the metabolic adaptations of tumor cells in response to nutrient deficiency, microenvironmental insults, and anti-cancer therapies. Metabolic transformation during tumor development plays a critical role in the continued tumor growth and progression and is driven by a complex interplay between the tumor mutational landscape, epigenetic modifications, and microenvironmental influences. Understanding the tumor metabolic vulnerabilities might open novel diagnostic and therapeutic approaches with the potential to improve the efficacy of current tumor treatments. Prostate cancer is a highly heterogeneous disease harboring different mutations and tumor cell phenotypes. While the increase of intra-tumor genetic and epigenetic heterogeneity is associated with tumor progression, less is known about metabolic regulation of prostate cancer cell heterogeneity and plasticity. This review summarizes the central metabolic adaptations in prostate tumors, state-of-the-art technologies for metabolic analysis, and the perspectives for metabolic targeting and diagnostic implications.

Differences in the torsional anharmonicity between reactant and transition state: the case of 3-butenal + H abstraction reactions.

Thermal rate coefficients for the hydrogen-abstraction reactions of 3-butenal by a hydrogen atom were obtained applying multipath canonical variational theory with small-curvature tunneling (MP-CVT/SCT). Torsional anharmonicity due to the hindered rotors was taken into account by calculating the rovibrational partition function using the extended two-dimensional torsional (E2DT) method. For comparison, rovibrational partition functions were also estimated using the multistructural method with torsional anharmonicity based on a coupled torsional potential (MS-T(C)). By contrast, with (E)-2-butenal reactions, the abstraction reactions of 3-butenal proceed via five reaction channels (R1)-(R5). In a conformational search, 45 distinguishable structures of transition states were found, including enantiomers, which were separated into six conformational reaction channels (CRCs). The individual reactive paths were constructed, the recrossing and semiclassical transmission coefficients estimated, and the multipath rate constants were obtained. High torsional barriers between the wells of CRC2/CRC6 indicate a harmonic behavior. Consequently, a difference between the torsional anharmonicity of 3-butenal and the transition states is responsible for the increase in the thermal rate constants for channel (R2). Analysis of the contributions of each conformer of the transition state shows an important contribution of the high-energy rotamers in the total flux of (R1)-(R5). After fitting the rate constants in a four-parameter equation, the activation energy estimation showed a strong temperature dependence.