Identifying the Unique Properties of α-Bi2Mo3O12 for the Activation of Propene

In order to understand the remarkable activity of α-Bi2Mo3O12 for selective oxidation and ammoxidation of propene, the propene activation ability of four molybdenum-based mixed metal oxides - Bi2Mo3O12, PbMoO4, Bi2Pb5Mo8O32, and MoO3 - was investigated using density functional theory. Propene activation is considered to occur via abstraction of a hydrogen atom from the methyl group of physisorbed propene by lattice oxygen. For each material, the apparent activation energy was estimated by summing the heat of adsorption of propene, the C-H bond dissociation energy, and the hydrogen attachment energy (HAE) for hydrogen addition to lattice oxygen; this sum provides a lower bound for the apparent activation energy. It was found that two structural features of oxide surfaces are essential to achieve low activation barriers: under-coordinated surface cation sites enable strong propene adsorption, and suitable 5- or 6-coordinate geometries at molybdenum result in favorable HAEs. The impact of molybdenum coordination on HAE was elucidated by carrying out a molecular orbital analysis using a cluster model of the molybdate unit. This effort revealed that, in 5- and 6-coordinate molybdates, oxygen donor atoms trans to molybdenyl oxo atoms destabilize the molybdate prior to H addition but stabilize the molybdate after H addition, thereby providing an HAE ∼15 kcal/mol more favorable than that on 4-coordinate molybdate oxo atoms. Bi3+ cations in Bi2Mo3O12 thus promote catalytic activity by providing both strong adsorption sites for propene and forcing molybdate into 5-coordinate geometries that lead to particularly favorable values of the HAE. (Graph Presented)

Validation of a clinical examination to differentiate a cervicogenic source of headache: a diagnostic prediction model using controlled diagnostic blocks

OBJECTIVES: Neck pain commonly accompanies recurrent headaches such as migraine, tension-type and cervicogenic headache. Neck pain may be part of the headache symptom complex or a local source. Patients commonly seek neck treatment to alleviate headache, but this is only indicated when cervical musculoskeletal dysfunction is the source of pain. Clinical presentation of reduced cervical extension, painful cervical joint dysfunction and impaired muscle function collectively has been shown to identify cervicogenic headache among patients with recurrent headaches. The pattern's validity has not been tested against the 'gold standard' of controlled diagnostic blocks. This study assessed the validity of this pattern of cervical musculoskeletal signs to identify a cervical source of headache and neck pain, against controlled diagnostic blocks, in patients with headache and neck pain. DESIGN: Prospective concurrent validity study that employed a diagnostic model building approach to analysis. SETTING: Hospital-based multidisciplinary outpatient clinic in Joliet, Illinois. PARTICIPANTS: A convenience sample of participants who presented to a headache clinic with recurrent headaches associated with neck pain. Sixty participants were enrolled and thirty were included in the analysis. OUTCOME MEASURES: Participants underwent a clinical examination consisting of relevant tests of cervical musculoskeletal dysfunction. Controlled diagnostic blocks of C2/C3-C3/C4 established a cervical source of neck pain. Penalised logistic regression identified clinical signs to be included in a diagnostic model that best predicted participants' responses to diagnostic blocks. RESULTS: Ten of thirty participants responded to diagnostic blocks. The full pattern of cervical musculoskeletal signs best predicted participants' responses (expected prediction error = 0.57) and accounted for 65% of the variance in responses. CONCLUSIONS: This study confirmed the validity of the musculoskeletal pattern to identify a cervical source of headache and neck pain. Adopting this criterion pattern may strengthen cervicogenic headache diagnosis and inform differential diagnosis of neck pain accompanying migraine and tension-type headache

Divergent Role of Gamma Interferon in a Murine Model of Pulmonary versus Systemic Klebsiella pneumoniae Infection

Klebsiella pneumoniae is a leading cause of both community-acquired and nosocomial gram-negative-bacterial pneumonia. A further clinical complication of pulmonary K. pneumoniae infection is dissemination of bacteria from the lung into the peripheral blood, resulting in bacteremia concurrent with the localized pulmonary infection. Here, we report studies detailing the divergent role of gamma interferon (IFN-γ) in pulmonary versus systemic K. pneumoniae infection. Intratracheal inoculation of IFN-γ knockout mice resulted in significantly increased mortality compared to that observed for wild-type infected animals. Increased mortality correlated with a 100-fold increase in pulmonary bacteria within 2 days postinfection and upregulation of lung-associated interleukin-10 (IL-10) mRNA. Interestingly, IFN-γ knockout mice had a twofold reduction in plasma aminospartate transferase activity, indicating diminished liver injury following peripheral blood bacterial dissemination. To study the host response towards blood-borne bacteria in the absence of the ongoing pulmonary infection, intravenous inoculation studies were initiated. IFN-γ knockout mice were no more susceptible to intravenous infection than their wild-type counterparts. The consistent observation in IFN-γ knockout mice was for improved survival correlating with increased clearance of blood- and liver-associated bacteria. Intravenous inoculation resulted in a two- to threefold increase in hepatic IL-10 production 24 and 48 h postinfection. Liver injury was also significantly reduced in IFN-γ knockout mice. These data indicate that IFN-γ secretion is a critical mediator in the resolution of localized gram-negative pulmonary pneumonia. Surprisingly, host responses towards systemic infection with the same bacteria appear to be IFN-γ independent

Increased Mortality and Dysregulated Cytokine Production in Tumor Necrosis Factor Receptor 1-Deficient Mice following Systemic Klebsiella pneumoniae Infection

A significant clinical complication of pulmonary infections with Klebsiella pneumoniae is peripheral blood dissemination, resulting in a systemic infection concurrent with the localized pulmonary infection. In this context, little is known about the role of tumor necrosis factor receptor 1 (TNFR1)-mediated innate immune responses during systemic Klebsiella infections. Mice lacking TNFR1 were significantly more susceptible to Klebsiella-induced mortality following intravenous inoculation. Bacterial clearance was impaired in TNFR1-deficient mice at early times following infection. Unexpectedly, bacterial burdens at the onset of mortality (days 2 to 3 postinfection) were not higher in mice lacking TNFR1. However, elevated production of liver-associated proinflammatory cytokines (interleukin-12, tumor necrosis factor alpha [TNF-α[, and gamma interferon [IFN-γ]) and chemokines (MIP-1α, MIP-2, and MCP-1) was observed within the first 24 h of infection. Additionally, excessive plasma-associated IFN-γ was also observed late in the course of infection (day 3). Spleen cells from day-3 infected TNFR1-deficient mice secreted markedly enhanced levels of IFN-γ when cultured in vitro. Additionally, there was a marked increase in the total number of activated lymphocyte subsets as indicated by CD69 upregulation. A notable exception was the sharp decrease in the frequency of splenic NK T cells in infected TNFR1 knockout (KO) mice. Anti-TNF-α therapy in TNFR1 KO mice significantly reduced chemokine production and liver injury. Combined, these data indicate a dysregulated antibacterial host response following intravenous Klebsiella infection in the absence of TNFR1 signaling, resulting in heightened cytokine production and hyperactivation of specific splenic lymphocyte subsets

Measuring the solubility of a quickly transforming metastable polymorph of carbamazepine

The solubility of the stable FIII polymorph of the pharmaceutical compound carbamazepine was measured by determining its solubility gravimetrically in ethanol and methanol. Where the metastable FI polymorph was suspended in a solution of ethanol, the stable FIII polymorph nucleated immediately initiating a solution mediated transformation from FI to FIII. This meant that the FI polymorph was not in thermodynamic equilibrium with the solution as FI was continually dissolving while FIII was growing. We show that the solubility of FI can be accurately measured by in situ microscopy using an adaption of the bracketing method and the results show that the solubility is close to but higher than the maximum solution concentration reached during the solution mediated transformation from FI to FIII carbamazepine in both solvents. The technique demonstrates a relatively simple and robust method for determining the solubility of a metastable crystalline phase which transforms quickly in solution

Sintering-Resistant Single-Site Nickel Catalyst Supported by Metal–Organic Framework

Developing supported single-site catalysts is an important goal in heterogeneous catalysis since the well-defined active sites afford opportunities for detailed mechanistic studies, thereby facilitating the design of improved catalysts. We present herein a method for installing Ni ions uniformly and precisely on the node of a Zr-based metal–organic framework (MOF), NU-1000, in high density and large quantity (denoted as Ni-AIM) using atomic layer deposition (ALD) in a MOF (AIM). Ni-AIM is demonstrated to be an efficient gas-phase hydrogenation catalyst upon activation. The structure of the active sites in Ni-AIM is proposed, revealing its single-site nature. More importantly, due to the organic linker used to construct the MOF support, the Ni ions stay isolated throughout the hydrogenation catalysis, in accord with its long-term stability. A quantum chemical characterization of the catalyst and the catalytic process complements the experimental results. With validation of computational modeling protocols, we further targeted ethylene oligomerization catalysis by Ni-AIM guided by theoretical prediction. Given the generality of the AIM methodology, this emerging class of materials should prove ripe for the discovery of new catalysts for the transformation of volatile substrates