Advances in Parallel Heat Bath Configuration Interaction.

Heat-bath configuration interaction (HCI) is a deterministic method that approaches the full CI limit at greatly reduced computational cost. In this work, computational improvements to the HCI algorithm are introduced targeting speed, parallel efficiency, and memory requirements. The new implementation introduces a hash function to distribute determinants and takes advantage of MPI and OpenMP for parallelism allowing for a (22e,168o) active space to be studied, which explicitly includes 2.39 × 107 variational determinants and 8.95 × 1010 perturbative determinants. Benchmarks show up to 86% parallel efficiency of the perturbative step on 32 nodes (4096 cores) and a total efficiency of 74%. The new HCI implementation is benchmarked for accuracy against prior results and applied to study the triplet-quintet gap in the challenging [FeO(NH3)5]2+ complex.

Exchange correlation potentials from full configuration interaction in a Slater orbital basis.

Ryabinkin-Kohut-Staroverov (RKS) theory builds a bridge between wave function theory and density functional theory by using quantities from the former to produce accurate exchange-correlation potentials needed by the latter. In this work, the RKS method is developed and tested alongside Slater atomic orbital basis functions for the first time. To evaluate this approach, full configuration interaction computations in the Slater orbital basis are employed to give quality input to RKS, allowing full correlation to be present along with correct nuclei cusps and asymptotic decay of the wavefunction. SlaterRKS is shown to be an efficient algorithm to arrive at exchange-correlation potentials without unphysical artifacts in moderately-sized basis sets. Furthermore, enforcement of the nuclear cusp conditions will be shown to be vital for the success of the Slater-basis RKS method. Examples of weakly and strongly correlated molecular systems will demonstrate the main features of SlaterRKS.

The numerical evaluation of Slater integrals on graphics processing units.

This article presents SlaterGPU, a graphics processing unit (GPU) accelerated library that uses OpenACC to numerically compute Slater-type orbital (STO) integrals. The electron repulsion integrals (ERI) are computed under the RI approximation using the Coulomb potential of the Slater basis function. To fully realize the performance capabilities of modern GPUs, the Slater integrals are evaluated in mixed-precision, resulting in speedups for the ERIs of over 80×. Parallelization on multiple GPUs allows for integral throughput of over 3 million integrals per second. This places STO integral throughput within reach of single-threaded, conventional Gaussian integration schemes. To test the quality of the integrals, the fluorine exchange reaction barrier in fluoromethane was computed using heat-bath configuration interaction (HBCI). In addition, the singlet-triplet gap of cyclobutadiene was examined using HBCI in a triple- ζ , polarized basis set. These benchmarks demonstrate the library's ability to generate the full set of integrals necessary for configuration interaction with up to 6 h functions in the auxiliary basis.

Fully variational incremental CASSCF.

The complete-active-space self-consistent field (CASSCF) method is a canonical electronic structure theory that holds a central place in conceptualizing and practicing first principles simulations. For application to realistic molecules, however, the CASSCF must be approximated to circumvent its exponentially scaling computational costs. Applying the many-body expansion-also known as the method of increments-to CASSCF (iCASSCF) has been shown to produce a polynomially scaling method that retains much of the accuracy of the parent theory and is capable of treating full valence active spaces. Due to an approximation made in the orbital gradient, the orbital parameters of the original iCASSCF formulation could not be variationally optimized, which limited the accuracy of its nuclear gradient. Herein, a variational iCASSCF is introduced and implemented, where all parameters are fully optimized during energy minimization. This method is able to recover electronic correlations from the full valence space in large systems, produce accurate gradients, and optimize stable geometries as well as transition states. Demonstrations on challenging test cases, such as the oxoMn(salen)Cl complex with 84 electrons in 84 orbitals and the automerization of cyclobutadiene, show that the fully variational iCASSCF is a powerful tool for describing challenging molecular chemistries.

An Open-Shell Coronoid with Hybrid Chichibabin-Schlenk Conjugation.

A hexaradicaloid molecule with alternating Kekulé and non-Kekulé connectivities between adjacent spin centers was obtained by fusing two conjugation motifs in Chichibabin and Schlenk hydrocarbons into a coronoid structure. 1 H NMR, ESR, and SQUID experiments and computational analyses show that the system has a singlet ground state with a significant hexaradicaloid character (γ0 =0.826, γ1 =γ2 =0.773). It has multiple thermally accessible high-spin states (up to the septet), with uniform energy gaps of ca 1.0 kcal mol-1 between consecutive multiplicities. In line with its open-shell character, the coronoid has a small electronic band gap (ca. 0.8 eV) and undergoes two consecutive one-electron oxidations at low potentials, yielding cationic forms with extended near-infrared absorption. The hexaradicaloid, which combines open-shell and macrocyclic contributions to its π conjugation, is an example of a design strategy for multistate spin switches and redox-amphoteric NIR dyes.

Ginsenoside Re protects methamphetamine-induced dopaminergic neurotoxicity in mice via upregulation of dynorphin-mediated κ-opioid receptor and downregulation of substance P-mediated neurokinin 1 receptor.

BACKGROUND: We previously reported that ginsenoside Re (GRe) attenuated against methamphetamine (MA)-induced neurotoxicity via anti-inflammatory and antioxidant potentials. We also demonstrated that dynorphin possesses anti-inflammatory and antioxidant potentials against dopaminergic loss, and that balance between dynorphin and substance P is important for dopaminergic neuroprotection. Thus, we examined whether GRe positively affects interactive modulation between dynorphin and substance P against MA neurotoxicity in mice. METHODS: We examined changes in dynorphin peptide level, prodynorphin mRNA, and substance P mRNA, substance P-immunoreactivity, homeostasis in enzymatic antioxidant system, oxidative parameter, microglial activation, and pro-apoptotic parameter after a neurotoxic dose of MA to clarify the effects of GRe, prodynorphin knockout, pharmacological inhibition of κ-opioid receptor (i.e., nor-binaltorphimine), or neurokinin 1 (NK1) receptor (i.e., L-733,060) against MA insult in mice. RESULTS: GRe attenuated MA-induced decreases in dynorphin level, prodynorphin mRNA expression in the striatum of wild-type (WT) mice. Prodynorphin knockout potentiated MA-induced dopaminergic toxicity in mice. The imbalance of enzymatic antioxidant system, oxidative burdens, microgliosis, and pro-apoptotic changes led to the dopaminergic neurotoxicity. Neuroprotective effects of GRe were more pronounced in prodynorphin knockout than in WT mice. Nor-binaltorphimine, a κ-opioid receptor antagonist, counteracted against protective effects of GRe. In addition, we found that GRe significantly attenuated MA-induced increases in substance P-immunoreactivity and substance P mRNA expression in the substantia nigra. These increases were more evident in prodynorphin knockout than in WT mice. Although, we observed that substance P-immunoreactivity was co-localized in NeuN-immunreactive neurons, GFAP-immunoreactive astrocytes, and Iba-1-immunoreactive microglia. NK1 receptor antagonist L-733,060 or GRe selectively inhibited microgliosis induced by MA. Furthermore, L-733,060 did not show any additive effects against GRe-mediated protective activity (i.e., antioxidant, antimicroglial, and antiapoptotic effects), indicating that NK1 receptor is one of the molecular targets of GRe. CONCLUSIONS: Our results suggest that GRe protects MA-induced dopaminergic neurotoxicity via upregulatgion of dynorphin-mediated κ-opioid receptor and downregulation of substance P-mediated NK1 R.

The decline of malaria in Vietnam, 1991-2014.

BACKGROUND: Despite the well-documented clinical efficacy of artemisinin-based combination therapy (ACT) against malaria, the population-level effects of ACT have not been studied thoroughly until recently. An ideal case study for these population-level effects can be found in Vietnam's gradual adoption of artemisinin in the 1990s. METHODS AND RESULTS: Analysis of Vietnam's national annual malaria reports (1991-2014) revealed that a 10% increase in artemisinin procurement corresponded to a 32.8% (95% CI 27.7-37.5%) decline in estimated malaria cases. There was no consistent national or regional effect of vector control on malaria. The association between urbanization and malaria was generally negative and sometimes statistically significant. CONCLUSIONS: The decline of malaria in Vietnam can largely be attributed to the adoption of artemisinin-based case management. Recent analyses from Africa showed that insecticide-treated nets had the greatest effect on lowering malaria prevalence, suggesting that the success of interventions is region-specific. Continuing malaria elimination efforts should focus on both vector control and increased access to ACT.

Nanosecond laser flash photolysis of a 6-nitroindolinospiropyran in solution and in nanocrystalline suspension under single excitation conditions.

Nanosecond transient absorption spectroscopy was used to study the photochemical ring-opening reaction for a 6-nitroindolinospiropyran (SP1) in solution and in nanocrystalline (NC) suspension at 298 K. We measured the kinetics in argon purged and air saturated acetonitrile and found that the presence of oxygen affected two out of the three components of the kinetic decay at 440 nm. These are assigned to the triplet excited states of the Z- and E-merocyanines (3Z-MC* and 3E-MC*). In contrast, a long-lived growth component at 550 nm and the decay of a band centered at 590 nm showed no dependence on oxygen and are assigned, respectively, to the ground state Z- and E-merocyanines (Z-MC0 and E-MC0). Laser flash photolysis studies performed in NC suspensions initially showed a very broad, featureless absorption spectrum that decayed uniformly for ca. 70 ns before revealing a more defined spectrum that persisted for greater than 4 ms and is consistent with a mixture of the more stable Z- and E-MC0 structures. We performed quantum mechanical calculations on the interconversion of E- and Z-MCs on the S0 and S1 potential energy surfaces. The computed UV-vis spectra for a scan along the Z → E interconversion reaction coordinate show substantial absorptivity from 300-600 nm, which suggests that the broad, featureless transient absorption spectrum results from the contribution of the transition structure and other high-energy species during the Z to E isomerization.

YY-1224, a terpene trilactone-strengthened Ginkgo biloba, attenuates neurodegenerative changes induced by ß-amyloid (1-42) or double transgenic overexpression of APP and PS1 via inhibition of cyclooxygenase-2.

BACKGROUND: Ginkgo biloba has been reported to possess free radical-scavenging antioxidant activity and anti-inflammatory properties. In our pilot study, YY-1224, a terpene trilactone-strengthened extract of G. biloba, showed anti-inflammatory, neurotrophic, and antioxidant effects. RESULTS: We investigated the pharmacological potential of YY-1224 in ß-amyloid (Aß) (1-42)-induced memory impairment using cyclooxygenase-2 (COX-2) knockout (-/-) and APPswe/PS1dE9 transgenic (APP/PS1 Tg) mice. Repeated treatment with YY-1224 significantly attenuated Aß (1-42)-induced memory impairment in COX-2 (+/+) mice, but not in COX-2 (-/-) mice. YY-1224 significantly attenuated Aß (1-42)-induced upregulation of platelet-activating factor (PAF) receptor gene expression, reactive oxygen species, and pro-inflammatory factors. In addition, YY-1224 significantly inhibited Aß (1-42)-induced downregulation of PAF-acetylhydrolase-1 (PAF-AH-1) and peroxisome proliferator-activated receptor γ (PPARγ) gene expression. These changes were more pronounced in COX-2 (+/+) mice than in COX-2 (-/-) mice. YY-1224 significantly attenuated learning impairment, Aß deposition, and pro-inflammatory microglial activation in APP/PS1 Tg mice, whereas it significantly enhanced PAF-AH and PPARγ expression. A preferential COX-2 inhibitor, meloxicam, did not affect the pharmacological activity by YY-1224, suggesting that the COX-2 gene is a critical mediator of the neuroprotective effects of YY-1224. The protective activity of YY-1224 appeared to be more efficacious than a standard G. biloba extract (Gb) against Aß insult. CONCLUSIONS: Our results suggest that the protective effects of YY-1224 against Aß toxicity may be associated with its PAF antagonistic- and PPARγ agonistic-potential as well as inhibition of the Aß-mediated pro-inflammatory switch of microglia phenotypes through suppression of COX-2 expression.

Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK.

BACKGROUND: Activation of NADPH oxidase (PHOX) plays a critical role in mediating dopaminergic neuroinflammation. In the present study, we investigated the role of PHOX in methamphetamine (MA)-induced neurotoxic and inflammatory changes in mice. METHODS: We examined changes in mitogen-activated protein kinases (MAPKs), mitochondrial function [i.e., mitochondrial membrane potential, intramitochondrial Ca(2+) accumulation, mitochondrial oxidative burdens, mitochondrial superoxide dismutase expression, and mitochondrial translocation of the cleaved form of protein kinase C delta type (cleaved PKCδ)], microglial activity, and pro-apoptotic changes [i.e., cytosolic cytochrome c release, cleaved caspase 3, and terminal deoxynucleotidyl transferase dUDP nick-end labeling (TUNEL) positive populations] after a neurotoxic dose of MA in the striatum of mice to achieve a better understanding of the effects of apocynin, a non-specific PHOX inhibitor, or genetic inhibition of p47phox (by using p47phox knockout mice or p47phox antisense oligonucleotide) against MA-induced dopaminergic neurotoxicity. RESULTS: Phosphorylation of extracellular signal-regulated kinases (ERK1/2) was most pronounced out of MAPKs after MA. We observed MA-induced phosphorylation and membrane translocation of p47phox in the striatum of mice. The activation of p47phox promoted mitochondrial stresses followed by microglial activation into the M1 phenotype, and pro-apoptotic changes, and led to dopaminergic impairments. ERK activated these signaling pathways. Apocynin or genetic inhibition of p47phox significantly protected these signaling processes induced by MA. ERK inhibitor U0126 did not exhibit any additional positive effects against protective activity mediated by apocynin or p47phox genetic inhibition, suggesting that ERK regulates p47phox activation, and ERK constitutes the crucial target for apocynin-mediated inhibition of PHOX activation. CONCLUSIONS: Our results indicate that the neuroprotective mechanism of apocynin against MA insult is via preventing mitochondrial burdens, microglial activation, and pro-apoptotic signaling process by the ERK-dependent activation of p47phox.

Liposomal melatonin rescues methamphetamine-elicited mitochondrial burdens, pro-apoptosis, and dopaminergic degeneration through the inhibition PKCδ gene.

We have demonstrated that mitochondrial oxidative damage and PKCδ overexpression contribute to methamphetamine-induced dopaminergic degeneration. Although it is recognized that antioxidant melatonin is effective in preventing neurotoxicity induced by methamphetamine, its precise mechanism remains elusive. C57BL/6J wild-type mice exhibited a similar degree of dopaminergic deficit when methamphetamine was administered during light and dark phases. Furthermore, dopaminergic neuroprotection by genetic inhibition of PKCδ during the light phase was comparable to that during the dark phase. Thus, we have focused on the light phase to examine whether melatonin modulates PKCδ-mediated neurotoxic signaling after multiple high doses of methamphetamine. To enhance the bioavailability of melatonin, we applied liposomal melatonin. Treatment with methamphetamine resulted in hyperthermia, mitochondrial translocation of PKCδ, oxidative damage (mitochondria > cytosol), mitochondrial dysfunction, pro-apoptotic changes, ultrastructural mitochondrial degeneration, dopaminergic degeneration, and behavioral impairment in wild-type mice. Treatment with liposomal melatonin resulted in a dose-dependent attenuation against degenerative changes induced by methamphetamine in wild-type mice. Attenuation by liposomal melatonin might be comparable to that by genetic inhibition (using PKCδ((-/-)) mice or PKCδ antisense oligonucleotide). However, liposomal melatonin did not show any additional protective effects on the attenuation by genetic inhibition of PKCδ. Our results suggest that the circadian cycle cannot be a key factor in modulating methamphetamine toxicity under the current experimental condition and that PKCδ is one of the critical target genes for melatonin-mediated protective effects against mitochondrial burdens (dysfunction), oxidative stress, pro-apoptosis, and dopaminergic degeneration induced by methamphetamine.

Inhibition of protein kinase (PK) Cδ attenuates methamphetamine-induced dopaminergic toxicity via upregulation of phosphorylation of tyrosine hydroxylase at Ser40 by modulation of protein phosphatase 2A and PKA.

Recently, we proposed that inhibition of protein kinase (PK) Cδ may be a useful target for protection against methamphetamine (MA)-induced dopaminergic toxicity. We demonstrated that treatment with MA resulted in a significant decrease in phosphorylation of tyrosine hydroxylase (TH) at Ser(40) in the striatum, but not in the phosphorylation of TH at Ser(31) . In the present study, treatment with rottlerin (1.5 or 3.0 µg, i.c.v, once a day for 5 days), a PKCδ inhibitor, or a PKCδ antisense oligonucleotide (ASO; 2.5 µg/µl, i.c.v., 3 times) significantly attenuated MA-induced reductions in the phosphorylation of TH at Ser(40) and in the expression of PKA in the striatum of mice. This attenuation was significantly counteracted by H89 (10 or 30 ng, i.c.v., 1 h after the last MA administration), a PKA inhibitor. Treatment with rottlerin or ASO significantly attenuated the MA-induced increase in protein phosphatase (PP) 2A activity. FTY720 (1 or 5 mg/kg, i.p., 1 h after the last MA administration), a PP2A activator, significantly reversed the recovery in TH phosphorylation mediated by inhibition of PKCδ after MA treatment. Both H89 and FTY720 counteracted the recovery of MA-induced behavioural impairments induced by PKCδ inhibition. The effects, mediated by rottlerin or ASO in MA-treated wild-type mice were comparable with those in MA-treated PKCδ(-/-) mice. However, neither inhibition of the mitogen-activated protein kinase subfamily (extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38) nor inhibition of calcium calmodulin kinase II significantly altered PKCδ inhibition-mediated attenuation of MA-induced impairment of TH phosphorylation. The results suggest that genetic or pharmacological inhibition of PKCδ requires modulation of PKA expression and/or PP2A activity to attenuate the impairment of TH phosphorylation at Ser(40) and behavioural activity induced by MA.

Melatonin attenuates memory impairment induced by Klotho gene deficiency via interactive signaling between MT2 receptor, ERK, and Nrf2-related antioxidant potential.

BACKGROUND: We demonstrated that oxidative stress plays a crucial role in cognitive impairment in klotho mutant mice, a genetic model of aging. Since down-regulation of melatonin due to aging is well documented, we used this genetic model to determine whether the antioxidant property of melatonin affects memory impairment. METHODS: First, we examined the effects of melatonin on hippocampal oxidative parameters and the glutathione/oxidized glutathione (GSH/GSSG) ratio and memory dysfunction of klotho mutant mice. Second, we investigated whether a specific melatonin receptor is involved in the melatonin-mediated pharmacological response by application with melatonin receptor antagonists. Third, we examined phospho-extracellular-signal-regulated kinase (ERK) expression, nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, Nrf2 DNA binding activity, and glutamate-cysteine ligase (GCL) mRNA expression. Finally, we examined effects of the ERK inhibitor SL327 in response to antioxidant efficacy and memory enhancement mediated by melatonin. RESULTS: Treatment with melatonin resulted in significant attenuations of oxidative damage, a decrease in the GSH/GSSG ratio, and a significant amelioration of memory impairment in this aging model. These effects of melatonin were significantly counteracted by the selective MT2 receptor antagonist 4-P-PDOT. Importantly, 4-P-PDOT or SL327 also counteracted melatonin-mediated attenuation in response to the decreases in phospho-ERK expression, Nrf2 nuclear translocation, Nrf2 DNA-binding activity, and GCL mRNA expression in the hippocampi of klotho mutant mice. SL327 also counteracted the up-regulation of the GSH/GSSG ratio and the memory enhancement mediated by melatonin in klotho mutant mice. CONCLUSIONS: Melatonin attenuates oxidative stress and the associated memory impairment induced by klotho deficiency via signaling interaction between the MT2 receptor and ERK- and Nrf2-related antioxidant potential.

Protocol for producing hyperpolarized 13C-bicarbonate for clinical MRI of extracellular pH in aggressive tumors.

Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) 13C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule 13C-glycerol carbonate (13C-GLC), the post-dissolution reaction, and converting HP 13C-GLC to an injectable HP 13C-bicarbonate solution. We then detail procedures for MRI data acquisition to generate tumor pH maps for assessing tumor aggressiveness. For complete details on the use and execution of this protocol, please refer to Mu et al.1.

The seroprevalence of toxocariasis and related risk factors in children in Ho Chi Minh City, Vietnam: results from a school-based cross-sectional study.

BACKGROUND: Children are especially vulnerable to Toxocara infection and its severe complications; however, there have not been any published data on the disease prevalence and treatment effectiveness in the population of Vietnamese children. This study was conducted to determine the prevalence of toxocariasis and explore factors associated with Toxocara infection in children aged 3-15 y in Ho Chi Minh City, Vietnam. METHODS: We conducted a cross-sectional study using a multistage cluster sampling approach in public schools. Blood samples were collected, and toxocariasis cases were confirmed, based on a history of contact with dogs/cats and positive anti-Toxocara antibody detection via ELISA. We calculated the percentage of seropositive children across gender, grade levels, districts and caregiver education. Multiple regression models were employed to identify potential risk factors. RESULTS: Anti-Toxocara antibodies were found in 14.2% of the 986 children studied. Significant variations in seropositivity were observed across grade levels, districts and caregiver education levels. Multivariable analysis identified caregiver education, contact with dogs/cats and improper handling of pet feces as seropositivity risk factors. CONCLUSION: This was the first community-based prevalence study of toxocariasis in a pediatric population in Vietnam. Implementation of preventive measures such as public education, routine fecal examinations and chemotherapeutic treatment of animals is highly recommended.

Ginsenoside Re protects against kainate-induced neurotoxicity in mice by attenuating mitochondrial dysfunction through activation of the signal transducers and activators of transcription 3 signaling.

It was demonstrated that ginsenosides exert anti-convulsive potentials and interleukin-6 (IL-6) is protective from excitotoxicity induced by kainate (KA), a model of temporal lobe epilepsy. Ginsenosides-mediated mitochondrial recovery is essential for attenuating KA-induced neurotoxicity, however, little is known about the effects of ginsenoside Re (GRe), one of the major ginsenosides. In this study, GRe significantly attenuated KA-induced seizures in mice. KA-induced redox changes were more evident in mitochondrial fraction than in cytosolic fraction in the hippocampus of mice. GRe significantly attenuated KA-induced mitochondrial oxidative stress (i.e. increases in reactive oxygen species, 4-hydroxynonenal, and protein carbonyl) and mitochondrial dysfunction (i.e. the increase in intra-mitochondrial Ca2+ and the decrease in mitochondrial membrane potential). GRe or mitochondrial protectant cyclosporin A restored phospho-signal transducers and activators of transcription 3 (STAT3) and IL-6 levels reduced by KA, and the effects of GRe were reversed by the JAK2 inhibitor AG490 and the mitochondrial toxin 3-nitropropionic acid (3-NP). Thus, we used IL-6 knockout (KO) mice to investigate whether the interaction between STAT3 and IL-6 is involved in the GRe effects. Importantly, KA-induced reduction of manganese superoxide dismutase (SOD-2) levels and neurodegeneration (i.e. astroglial inhibition, microglial activation, and neuronal loss) were more prominent in IL-6 KO than in wild-type (WT) mice. These KA-induced detrimental effects were attenuated by GRe in WT and, unexpectedly, IL-6 KO mice, which were counteracted by AG490 and 3-NP. Our results suggest that GRe attenuates KA-induced neurodegeneration via modulating mitochondrial oxidative burden, mitochondrial dysfunction, and STAT3 signaling in mice.

Advanced Hyperpolarized 13C Metabolic Imaging Protocol for Patients with Gliomas: A Comprehensive Multimodal MRI Approach.

This study aimed to implement a multimodal 1H/HP-13C imaging protocol to augment the serial monitoring of patients with glioma, while simultaneously pursuing methods for improving the robustness of HP-13C metabolic data. A total of 100 1H/HP [1-13C]-pyruvate MR examinations (104 HP-13C datasets) were acquired from 42 patients according to the comprehensive multimodal glioma imaging protocol. Serial data coverage, accuracy of frequency reference, and acquisition delay were evaluated using a mixed-effects model to account for multiple exams per patient. Serial atlas-based HP-13C MRI demonstrated consistency in volumetric coverage measured by inter-exam dice coefficients (0.977 ± 0.008, mean ± SD; four patients/11 exams). The atlas-derived prescription provided significantly improved data quality compared to manually prescribed acquisitions (n = 26/78; p = 0.04). The water-based method for referencing [1-13C]-pyruvate center frequency significantly reduced off-resonance excitation relative to the coil-embedded [13C]-urea phantom (4.1 ± 3.7 Hz vs. 9.9 ± 10.7 Hz; p = 0.0007). Significantly improved capture of tracer inflow was achieved with the 2-s versus 5-s HP-13C MRI acquisition delay (p = 0.007). This study demonstrated the implementation of a comprehensive multimodal 1H/HP-13C MR protocol emphasizing the monitoring of steady-state/dynamic metabolism in patients with glioma.

Tetrafluorenofulvalene as a sterically frustrated open-shell alkene.

Electronic and steric effects are known to greatly influence the structure, characteristics and reactivity of organic compounds. A typical π bond is weakened by oxidation (corresponding to the removal of electrons from bonding orbitals), by reduction (through addition of electrons to antibonding orbitals) and by unpairing of the bonding electrons, such as in the triplet state. Here we describe tetrafluorenofulvalene (TFF), a twisted, open-shell alkene for which these general rules do not hold. Through the synthesis, experimental characterization and computational analysis of its charged species spanning seven redox states, the central alkene bond in TFF is shown to become substantially stronger in the tri- and tetraanion, generated by chemical reduction. Furthermore, although its triplet state contains a weaker alkene bond than the singlet, in the quintet state its bond order increases substantially, yielding a flatter structure. This behaviour originates from the doubly bifurcated topology of the underlying spin system and can be rationalized by the balancing effects of benzenoid aromaticity and spin pairing.

Phosphine substitution and linkage isomerization in cyclopentadienylruthenium bis(triphenylphosphine)thiocyanide and selenocyanide, CpRu(PPh3)2NCS and CpRu(PPh3)2SeCN.

The reaction between CpRu(PPh3)2NCS (1a) and PMePh2 yields CpRu(PPh3)(PMePh2)NCS (2a) while CpRu(PPh3)(PMePh2)Cl reacts with SCN- to form the S-bonded isomer, CpRu(PPh3)(PMePh2)SCN (2b). Compound 1a and the linkage isomers of 2 were characterized by X-ray crystallography. The kinetics of the reaction between 1a and PMePh2 under pseudo-first order conditions in THF and in fluorobenzene to form 2a are consistent with a dissociative interchange mechanism. Activation parameters for the reaction are: ΔH† = 15.7 ± 0.6 kcal mol-1 and ΔS† = -35 ± 2 cal mol-1 K-1 in THF vs. ΔH† = 24.8 ± 1.2 kcal mol-1 and ΔS† = -6 ± 4 cal mol-1 K-1 in C6H5F. In the presence of added SCN-, the rate of phosphine substitution is unchanged but a mixture of 2a and 2b is observed. The selenocyanate derivative, CpRu(PPh3)2SeCN (3b), crystallizes as the Se-bonded linkage isomer. Compound 3b reacts with PMePh2 under pseudo-first order conditions in fluorobenzene to form CpRu(PPh3)(PMePh2)SeCN (4b) at a much faster rate than 1a with activation parameters: ΔH† = 30.9 ± 4.8 kcal mol-1 and ΔS† = 22.4 ± 15.9 cal mol-1 K-1 with no evidence for linkage isomerization to the N-bonded products.

Late Onset of Organizing Pneumonia Following SARS-CoV-2 Infection: A Case Report of Successful Management and Review Literature.

A late consequence of COVID-19, organizing pneumonia is characterized by significant imaging and pathological abnormalities. The goals of this study are to better understand these abnormalities. The use of corticoid continues to be the recommended course of treatment for COVID-19. On the other hand, it is not clear whether or not corticoid has the same impact on organizing pneumonia after COVID-19. A 53-year-old male patient was identified with organized pneumonia following COVID-19 infection. He was diagnosed after experiencing severe respiratory symptoms several days with no improvement. We initiated a high dose of corticoid based on imaging and pathological findings and observed a significant response. In addition, we looked into the research that has been done concerning the diagnosis and treatment of this peculiar ailment. Patients who have been diagnosed with pneumonia after COVID 19 are required to undergo a reevaluation that includes a chest CT scan, and some of these patients may be candidates for an early lung biopsy. The most effective and convincing therapy for COVID-19-induced organizing pneumonia is corticoid treatment at a dose equivalent to 0.5 mg/kg/day of prednisone.