Two-step Pathway Research Articles

Formicamycin biosynthesis involves a unique reductive ring contraction.

Fasamycin natural products are biosynthetic precursors of the formicamycins. Both groups of compounds are polyketide natural products that exhibit potent antibacterial activity despite displaying different three-dimensional topologies. We show here that transformation of fasamycin into formicamycin metabolites requires two gene products and occurs via a novel two-step ring expansion-ring contraction pathway. Deletion of forX, encoding a flavin dependent monooxygenase, abolished formicamycin production and leads to accumulation of fasamycin E. Deletion of the adjacent gene forY, encoding a flavin dependent oxidoreductase, also abolished formicamycin biosynthesis and led to the accumulation of new lactone metabolites that represent Baeyer-Villiger oxidation products of the fasamycins. These results identify ForX as a Baeyer-Villiger monooxygenase capable of dearomatizing ring C of the fasamycins. Through in vivo cross feeding and biomimetic semi-synthesis experiments we showed that these lactone products represent biosynthetic intermediates that are reduced to formicamycins in a unique reductive ring contraction reaction catalyzed by ForY.

Effect of Fe and Mn Substitution in LaNiO3 on Exsolution, Activity, and Stability for Methane Dry Reforming

Perovskites LaNi0.8Fe0.2O3 and LaNi0.8Mn0.2O3 were synthesized using the co-precipitation method by substituting 20 mol.% of the Ni-site with Fe and Mn, respectively. Temperature programmed reduction (TPR) showed that the exsolution process in the Fe- and Mn-substituted perovskites followed a two-step and three-step reduction pathway, respectively. Once exsolved, the catalysts were found to be able to regenerate the original perovskite when exposed to an oxygen environment but with different crystallographic properties. The catalytic activity for both materials after exsolution was measured for the methane dry reforming (DRM) reaction at 650 °C and 800 °C. Catalyst resistance against nickel agglomeration, unwanted phase changes, and carbon accumulation during DRM were analyzed using X-ray diffraction (XRD), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). The presence Fe alloying in the catalyst particles after exsolution from LaNi0.8Fe0.2O3 led to a lower methane conversion compared to the catalyst derived from LaNi0.8Mn0.2O3 where no alloying occurred.

Conversion of D-fructose to 5-acetoxymethyl-2-furfural Using Immobilized Lipase and Cation Exchange Resin.

5-Acetoxymethyl-2-furfural (AMF) was prepared from D-fructose via 1,6-diacetylfructose (DAF) through a simple two-step reaction pathway. Immobilized enzyme (Novozym 435) was found to be the best enzymatic catalyst for the trans-esterification step (yielding 94.6% DAF). In the dehydration step, while soluble H2SO4 was found to be the best acidic catalyst (yielding 86.6% AMF), we opted to utilize heterogeneous cation exchange resin (Amberlyst 15) together with recyclable industrial solvents (1,4-dioxane) for a more sustainable AMF synthesis procedure. Although the total yield of AMF was a little lower, both the enzyme and the solid acid catalyst could be recycled for five cycles without a significant loss of activity, which has a major contribution to the cost-efficient aspect of the entire process.

Biosynthesis pathway of indole-3-acetyl-myo-inositol during development of maize (Zea mays L.) seeds

Indole-3-acetic acid (IAA) conjugation is one of the mechanisms responsible for auxin homeostasis. IAA ester conjugates biosynthesis has been studied during development of maize seeds where IAA-inositol (IAInos) and its glycosidic forms make up about 50 % of its ester conjugates pool. 1-O-indole-3-acetyl-β-d-glucose (IAGlc) synthase and indole-3-acetyl transferase (IAInos synthase) are key enzymes in a two-step pathway of IAInos synthesis. In the first reaction, IAA is glucosylated to a high energy acetal, 1-O-indole-3-acetyl-β-d-glucose by IAGlc synthase, whereas in the second step, IAInos synthase transfers IAA moiety to myo-inositol forming a stable auxin ester, indole-3-acetyl-myo-inositol (IAInos). It should be mentioned that IAGlc synthase catalyzes a reversible reaction with unfavourable equilibrium that delivers IAGlc for favourable transacylation to IAInos. This is the first study where IAGlc synthase and IAInos synthase are simultaneously analyzed by enzymatic activity assay and quantitative RT-PCR in maize seeds at four stages of development (13, 26, 39 and 52 Days After Flowering). Activity of IAGlc/IAInos synthases as well as their expression profiles during seed development were different. While both enzymatic activities and ZmIAIn expression were the highest in seeds at 26 DAF, the highest expression of ZmIAGlc was observed at 13 DAF. Protein gel blot analysis showed that IAInos synthase exists as a mixture of several isoforms at a similar protein level at particular stages of seed development. Neither of other ester conjugates of IAA (IAA-mannose) nor IAA-amino acids were detected at the stages studied. Catalytic activity of l-tryptophan aminotransferase involved in IAA biosynthesis as well as UDPG pyrophosphorylase, synthesizing UDPG as a substrate for IAGlc synthase, were also analyzed. l-tryptophan aminotransferase activity was the highest at 26 DAF. Changes in enzyme activity of UDPG pyrophosphorylase are difficult to interpret. Expression levels of ZmIPS and ZmIPP encoding two enzymes of myo-inositol biosynthesis pathway: inositol-x-phosphate synthase (IPS) and inositol-x-phosphate phosphatase (IPP), respectively, were analyzed. 26 DAF seeds displayed the highest expression level of ZmIPS, whereas transcription of ZmIPP was the highest at 13 DAF.

Microbial transformation of diosgenin to diosgenone by Wickerhamomyces anomalus JQ-1 obtained from Naxi traditional Jiu Qu

Diosgenone [(20S,22R,25R)-spirost-4-en-3-one, C27H40O3] has been considered as a potential therapeutic alternative remedy for malaria. An efficient and economical approach of microbial transformation with diosgenin to diosgenone by the yeast strain Wickerhamomyces anomalus JQ-1 from Naxi traditional Jiu Qu was developed in this study. Chromatographic analysis confirmed that 85% of 0.1 mM diosgenin was transformed to diosgenone within 72 h. This research demonstrates that diosgenin could be converted to diosgenone through two-step pathway including 3β-hydroxyl oxidation and double bond isomerization rather than through one-step pathway, which prompted a further inference that the oxidation activity in W. anomalus JQ-1 has the same function with the Oppenauer-type oxidation which can convert diosgenin into diosgenone. Gaining specific functional strains from traditional fermented products will be a potential direction and ethnobotanical researches could provide helps with discovery and utilization of microbial resources.

Carbon monoxide electroreduction as an emerging platform for carbon utilization

The electrochemical conversion of carbon dioxide to value-added chemical products has been heavily explored as a promising strategy for carbon utilization. However, the direct synthesis of multi-carbon (C2+) products suffers from undesired side reactions and relatively low selectivity. Electrochemically converting CO2 to single-carbon products is much more effective and being commercially deployed. Recent studies have shown that CO can be electrochemically transformed further to C2+ at high reaction rates, high C2+ selectivity and inherently improved electrolyte stability, raising the prospect of a two-step pathway to transform CO2. In this Perspective, the progress towards high-rate CO conversion is shown alongside mechanistic insights and device designs that can improve performance even further. A techno-economic analysis of the two-step conversion process and cradle-to-gate lifecycle assessment shows the economic feasibility and improved environmental impact of a high-volume commercial process generating acetic acid and ethylene compared to the current state of the art. Carbon monoxide can be electrochemically transformed to multi-carbon products selectively at high rates, raising the prospect of a two-step pathway to transform CO2 into value-added chemical products. This Perspective highlights recent progress complemented by a techno-economic analysis of the two-step conversion process and cradle-to-gate lifecycle assessment.

PBS3 and EPS1 Complete Salicylic Acid Biosynthesis from Isochorismate in Arabidopsis

Salicylic acid (SA) is an important phytohormone mediating both local and systemic defense responses in plants. Despite over half a century of research, how plants biosynthesize SA remains unresolved. In Arabidopsis, a major part of SA is derived from isochorismate, a key intermediate produced by the isochorismate synthase, which is reminiscent of SA biosynthesis in bacteria. Whereas bacteria employ an isochorismate pyruvate lyase (IPL) that catalyzes the turnover of isochorismate to pyruvate and SA, plants do not contain an IPL ortholog and generate SA from isochorismate through an unknown mechanism. Combining genetic and biochemical approaches, we delineated the SA biosynthetic pathway downstream of isochorismate in Arabidopsis. We found that PBS3, a GH3 acyl adenylase-family enzyme important for SA accumulation, catalyzes ATP- and Mg2+-dependent conjugation of L-glutamate primarily to the 8-carboxyl of isochorismate and yields the key SA biosynthetic intermediate, isochorismoyl-glutamate A. Moreover, we discovered that EPS1, a BAHD acyltransferase-family protein with a previously implicated role in SA accumulation upon pathogen attack, harbors a noncanonical active site and an unprecedented isochorismoyl-glutamate A pyruvoyl-glutamate lyase activity that produces SA from the isochorismoyl-glutamate A substrate. Together, PBS3 and EPS1 form a two-step metabolic pathway to produce SA from isochorismate in Arabidopsis, which is distinct from how SA is biosynthesized in bacteria. This study closes a major knowledge gap in plant SA metabolism and would help develop new strategies for engineering disease resistance in crop plants.

New two-step pathway for the production of acrylonitrile from propionic acid

Acrylonitrile is currently made from fossil resources. We investigated the synthesis of acrylonitrile from propionic acid in only two steps, which opens up a new route to acrylonitrile based on propionic acid obtained by fermentation. Propionic acid was initially converted to propionitrile with NH3 at 400 °C. Zeolite H-Y allows for >99% selectivity at 98% conversion. However, coking led to deactivation after 180 min on stream. The dehydrogenation of propionitrile to acrylonitrile was catalyzed by SnO/SiO2. The selectivity was 71% at 22% conversion, which gives already after first experiments an overall selectivity for acrylonitrile production from propionic acid of 71%.

Microbial 2-butanol production with Lactobacillus diolivorans

BackgroundBiobutanol has great potential as biofuel of the future. However, only a few organisms have the natural ability to produce butanol. Amongst them, Clostridium spp. are the most efficient producers. The high toxicity of biobutanol constitutes one of the bottlenecks within the biobutanol production process which often suffers from low final butanol concentrations and yields. Butanol tolerance is a key driver for process optimisation and, therefore, in the search for alternative butanol production hosts. Many Lactobacillus species show a remarkable tolerance to solvents and some Lactobacillus spp. are known to naturally produce 2-butanol from meso-2,3-butanediol (meso-2,3-BTD) during anaerobic sugar fermentations. Lactobacillus diolivorans showed already to be highly efficient in the production of other bulk chemicals using a simple two-step metabolic pathway. Exactly, the same pathway enables this cell factory for 2-butanol production.ResultsDue to the inability of L. diolivorans to produce meso-2,3-BTD, a two-step cultivation processes with Serratia marcescens has been developed. S. marcescens is a very efficient producer of meso-2,3-BTD from glucose. The process yielded a butanol concentration of 10 g/L relying on wild-type bacterial strains. A further improvement of the maximum butanol titer was achieved using an engineered L. diolivorans strain overexpressing the endogenous alcohol dehydrogenase pduQ. The two-step cultivation process based on the engineered strain led to a maximum 2-butanol titer of 13.4 g/L, which is an increase of 34%.ConclusionIn this study, L. diolivorans is for the first time described as a good natural producer for 2-butanol from meso-2,3-butanediol. Through the application of a two-step cultivation process with S. marcescens, 2-butanol can be produced from glucose in a one-vessel, two-step microbial process.

Assembling amorphous (Fe-Ni)Cox-OH/Ni3S2 nanohybrids with S-vacancy and interfacial effects as an ultra-highly efficient electrocatalyst: Inner investigation of mechanism for alkaline water-to-hydrogen/oxygen conversion

Rational design of earth-abundant electrocatalysts with ultra-high activity and durability for the electrochemical water-to-energy conversion systems is still a significant challenge. Herein, a hierarchical nanocluster hybrids of trimetallic (Fe-Ni)Cox−OH nanofilms decorated amorphous Ni3S2 with S-vacancy supported on nickel foam (NF) was proposed via rapid two-step electrodeposited pathway. By effectively breaking long-range-order of Ni3S2 to form S-vacant amorphous phase, combining with the strong electronic interactions between the (Fe-Ni)Cox−OH and Ni3S2, it resulted in favorable water adsorption ability, free-energy of H* adsorption (ΔGH*), and fast mass/charge transfer for hydrogen evolution process. The (Fe-Ni)Cox−OH/Ni3S2 nanohybrids displayed ultralow overpotential of 91 and 145 mV at 100 and 1400 mA·cm−2 respectively with admirable durability for 100 h at 200 mA·cm−2 in 1 M KOH, even exceeding Pt plate. The amorphous S-vacant Ni3S2 plays a crucial role for hydrogen evolution: compared with both original and defective Ni3S2, the free energy of disordering Ni3S2 for *H−OH and H* intermediates more tend to thermodynamical neutrality according to density functional theory (DFT) calculations. For water-to-oxygen evolution (η100 = 280 mV), in situ newly formed ultrathin NiOOH nanosheets on near-surface Ni3S2 layer coupling with (Fe-Ni)Cox−OH nanofilms can be identified as intrinsic OER active species; and the host metallic Ni3S2 phase provides wonderful conductivity. Impressively, the bifunctional (Fe-Ni)Cox−OH/Ni3S2 nanohybrid represents the best electrocatalyst so far, achieving cell-voltage of 1.45 and 1.61 V at 10 and 200 mA·cm−2 respectively with super stability for 100 h.

Probing the Crystal and Electronic Structures of Molybdenum Oxide in Redox Process: Implications for Energy Applications

Knowledge regarding the phase and valence state evolution of molybdenum (Mo) and its oxides during the redox reaction is essential for advancing their energy applications (e.g., electrocatalysis), which unfortunately remains largely unexplored. Herein, the effects of atomic and electronic structures on the electrocatalytic performance of Mo/oxides core–shell structures are investigated on the basis of the combination of ex situ and in situ experiments. First, a two-step reaction pathway is revealed during the oxidation of nanoscale Mo: the formation of amorphous MoO3 (A-MoO3) shells followed by the nucleation of crystalline α-MoO3. It is shown that the electrocatalytic performance of A-MoO3 is superior to that of α-MoO3, mainly due to more catalytically active sites in the former material. Furthermore, in situ transmission electron microscopy observations show that the A-MoO3 shell can be rapidly reduced into metallic MoO2 under reductive environment, which is likely to occur during the hydrogen evolution...

Deep endometriosis transvaginal ultrasound in the workup of patients with signs and symptoms of endometriosis: a cost analysis.

Deep endometriosis transvaginal ultrasound (DE TVS) is accurate in the detection of ovarian endometriosis and DE; however, realisation of its full potential and utilisation remains variable. As such, patients may require a two-step surgical approach (diagnostic followed by therapeutic laparoscopy) or experience incomplete surgical treatment. Besides the clinical implications, the economic impact of a two-step approach to diagnosis and treatment on the healthcare system is likely to be significant. We aim to compare the economic costs of two diagnostic models of care for patients with potential endometriosis. Cost analysis using Markov model with 12-month time horizon comparing the economic costs of two diagnostic models. The study used a hypothetical population of 1000 women visiting a public tertiary gynaecology clinic. Women with potential endometriosis. Estimates for endometriosis prevalence and severity were drawn from local Australian hospital data. The conventional model (M1) includes the basic TVS and diagnostic laparoscopy. The novel model (M2) includes the DE TVS. Probabilistic sensitivity analysis was conducted to capture the uncertainty in the information used to populate the models. Changes to government, health-service and patient costs with the adoption of the DE TVS compared with standard diagnostic methods. Costs are given in Australian dollars (AU$) and also in pound sterling (£). The total annual cost of the novel model (M2) is AU$12,547,724.03 (£6,826,673.63), cheaper than the conventional model (M1), which cost AU$13,472,161.67 (£7,329,620.15). For a population of 1000 women, the integration of the DE TVS may save healthcare costs of AU$924,437 (£502,946.17) annually. An endometriosis-focused ultrasound may negate a two-step surgery pathway, including diagnostic surgery, and save healthcare money.

Synthesis, physicochemical characteristics and antimicrobial studies of ethyl-substituted imidazolium-based surface active ionic liquids (SAILs)

A series containing higher members of ethyl-substituted imidazolium-based surface active ionic liquids (SAILs) [Cneim]Br, (n = 12, 14, 16) has been synthesized by a two-step reaction pathway. They were characterized by FT-IR, 1H NMR and 13C NMR and their effect on self-aggregation behavior in aqueous solution has been examined, employing conductometric and tensiometric methods besides fluorescence measurements and UV-visible spectroscopy. The conductivity data were recorded at different temperatures and thermodynamic parameters of micelle formation such as, standard Gibbs free energy (∆Gmo), standard enthalpy (∆Hmo), standard entropy (∆Smo) were evaluated. The process of micellization is entropy driven and supported by Gibbs free energy measurements. Interfacial parameters have also been evaluated by employing surface tension technique. The SAILs were also analyzed for their antimicrobial activity by taking eleven kinds of bacterial strains.

Topotactic Synthesis of Phosphabenzene-Functionalized Porous Organic Polymers: Efficient Ligands in CO2 Conversion.

Progress toward the preparation of porous organic polymers (POPs) with task-specific functionalities has been exceedingly slow-especially where polymers containing low-oxidation phosphorus in the structure are concerned. A two-step topotactic pathway for the preparation of phosphabenzene-based POPs (Phos-POPs) under metal-free conditions is reported, without the use of unstable phosphorus-based monomers. The synthetic route allows additional functionalities to be introduced into the porous polymer framework with ease. As an example, partially fluorinated Phos-POPs (F-Phos-POPs) were obtained with a surface area of up to 591 m2 g-1 . After coordination with Ru species, a Ru/F-Phos-POPs catalyst exhibited high catalytic efficiency in the formylation of amines (turnover frequency up to 204 h-1 ) using a CO2 /H2 mixture, in comparison with the non-fluorinated analogue (43 h-1 ) and a Au/TiO2 heterogeneous catalysts reported previously (<44 h-1 ). This work describes a practical method for synthesis of porous organic phosphorus-based polymers with applications in transition-metal-based heterogeneous catalysis.

Two-step d-ononitol epimerization pathway in Medicago truncatula.

Methylated inositol, d-pinitol (3-O-methyl-d-chiro-inositol), is a common constituent in legumes. It is synthesized from myo-inositol in two reactions: the first reaction, catalyzed by myo-inositol-O-methyltransferase (IMT), consists of a transfer of a methyl group from S-adenosylmethionine to myo-inositol with the formation of d-ononitol, while the second reaction, catalyzed by d-ononitol epimerase (OEP), involves epimerization of d-ononitol to d-pinitol. To identify the genes involved in d-pinitol biosynthesis in a model legume Medicago truncatula, we conducted a BLAST search on its genome using soybean IMT cDNA as a query and found putative IMT (MtIMT) gene. Subsequent co-expression analysis performed on publicly available microarray data revealed two potential OEP genes: MtOEPA, encoding an aldo-keto reductase and MtOEPB, encoding a short-chain dehydrogenase. cDNAs of all three genes were cloned and expressed as recombinant proteins in E.coli. In vitro assays confirmed that putative MtIMT enzyme catalyzes methylation of myo-inositol to d-ononitol and showed that MtOEPA enzyme has NAD+ -dependent d-ononitol dehydrogenase activity, while MtOEPB enzyme has NADP+ -dependent d-pinitol dehydrogenase activity. Both enzymes are required for epimerization of d-ononitol to d-pinitol, which occurs in the presence of NAD+ and NADPH. Introduction of MtIMT, MtOEPA, and MtOEPB genes into tobacco plants resulted in production of d-ononitol and d-pinitol in transformants. As this two-step pathway of d-ononitol epimerization is coupled with a transfer of reducing equivalents from NADPH to NAD+ , we speculate that one of the functions of this pathway might be regeneration of NADP+ during drought stress.

Catalysis for highly thermostable phenol-terephthalaldehyde polymer networks

There was a crucial need to eliminate formaldehyde (F) from high-performance thermoset formulations. The catalyzed reaction of innovative phenol (P)-terephthalaldehyde (TPA) resoles (basic conditions) was studied. For aerospace applications, alkali- or alkaline-earth-based catalysts should be avoided. To address this issue, we successfully employed DBU to catalyze the resole formation (with NaOH as reference system). The pre-polymerization (addition of phenol onto the first aldehyde of TPA) was performed in solution under mild conditions and followed by NMR and IR. Sodium hydroxide catalyzed rather effectively the reaction of ortho phenolic positions (1:1 ortho:para) whereas DBU catalyzed more para positions (ca. 1:2 ortho:para), because of the absence of chelating behavior of Na+. Based on non-isothermal DSC of the thermosets curing, we proposed a two-step mechanism pathway, directly arising from the multiple reactions occurring with TPA. The first reaction was assigned to the condensation reaction as its reactivity was enhanced by the unreacted aldehyde in para position (invariant aldehyde content measured in IR and weight loss recorded in TGA). The second was assigned to the addition of the phenol onto the second aldehyde (decrease of aldehyde and no weight loss). An in-depth non-isothermal thermo-kinetics study was efficient to compare both NaOH and DBU catalyzed reactions (isoconversional computational method of Vyazovkin). The isoconversional analysis allowed to discriminate the activation energies of the addition and condensation reactions (NaOH: 78 and 72 kJ·mol−1; DBU: 63 and 49 kJ·mol−1, respectively). Finally, TGA results showed that these new resoles presented increased thermal performances as compared to a commercial PF (Td10% ≥ 470 °C and char yield ≥ 64 wt%).

New insight into N2O formation from NH3 oxidation over MnOx/TiO2 catalyst

NH3 oxidation over MnOx/TiO2 catalyst was studied in the work, and new insights into the process were provided. According to specially designed experiments, probable N2O formation routes were put forward, and the oxidizer role that gaseous O2 and catalyst oxygen played in NH3 oxidation was analyzed by relevant characterization analysis. Experimental data demonstrated the promotion influence of O2 on NH3 oxidation and on NO and N2O formation. N2O derived from the direct reaction between NH3 and oxygen or the two-step pathway of the prerequisite formation of NO and then the following non-selective catalytic reduction of NO. Characterization results indicated that as O2 concentration increased, the participation of surface absorbed oxygen and lattice oxygen in NH3 oxidation decreased gradually, while the participation of gaseous O2 increased significantly. The work helped to better understand the mechanism of N2O formation from NH3 oxidation over MnOx/TiO2.

Steep-Slope Threshold Switch Enabled by Pulsed-Laser-Induced Phase Transformation.

Super-steep two-terminal electronic devices using NbO2, which abruptly switch from insulator to metal at a threshold voltage (Vth), offer diverse strategies for energy-efficient and high-density device architecture to overcome fundamental limitation in current electronics. However, the tight control of stoichiometry and high-temperature processing limit practical implementation of NbO2 as a component of device integration. Here, we demonstrate a facile room-temperature process that uses solid-solid phase transformation induced by pulsed laser to fabricate NbO2-based threshold switches. Interestingly, pulsed laser annealing under a reducing environment facilitates a two-step nucleation pathway (a-Nb2O5 → o-Nb2O5-δ → t-NbO2) of the threshold-enabled NbO2 phase mediated by oxygen vacancies in o-Nb2O5-δ. The laser-annealed devices with embedded NbO2 crystallites exhibit excellent threshold device performance with low off-current and high on/off current ratio. Our strategy that exploits the interactions of pulsed lasers with multivalent metal oxides can guide the development of a rational route to achieve NbO2-based threshold switches that are compatible with current semiconductor fabrication technology.

Review of the treatment milestones for stage I non-small cell lung cancer at a regional rural cancer center.

e18305 Background: Treatment milestones were reviewed for all stage I non-small cell lung cancer (NSCLC) patients treated at Northern Light Cancer Institute (NLCI), from 2010 to 2017. Cases in which the initial time to treatment (TTT) exceeded 6 months and those not seeking treatment were considered non-typical and were excluded from analysis, resulting in 502 cases for this time period. Methods: Analysis demonstrated that patients primarily took one of three different pathways in the diagnostic process. This process typically involved a CT scan, PET scan, and a biopsy. The three primary diagnostic pathways were: CT-PET-Biopsy (29.7%), CT-Biopsy-PET (14.3%), or CT-PET (no biopsy) (39.8%), accounting for 83.9% of eligible patients. The primary mode of treatment for most patients was surgery (63.7%). Patients not eligible for surgery received stereotactic body radiation therapy (SBRT) (26.7%). Results: Patients undergoing surgery experienced a shorter average TTT compared to patients receiving SBRT for all years except 2016. (p &lt; 0.05). Time to treatment for surgical patients was stable at approximately 70 days from 2011-2014, at which time there was an average 27.9 day increase by 2016. TTT for SBRT patients increased from a mean of 67.4 days in 2010 to a high of 110.8 days in 2015 before decreasing to 90.0 in 2016. The different diagnostic pathways did not significantly differ from each other in terms of 3 year average TTT (2015-2017) for surgical patients (p = 0.59). SBRT patients who had a two-step diagnostic pathway (CT-PET) had TTT that was 22.7 days shorter than the three step pathway of CT-PET-Biopsy (p = 0.02). Patients receiving SBRT had a 1.56 points average higher Charlson Comorbidity Index, and were an average of 4.5 years older than those receiving surgery. Conclusions: Differences in TTT between treatment modalities are likely related to patient comorbidities and additional time needed for radiation planning and simulation. The changes seen since 2015 were thought to be secondary to the emergence of prior-authorization for procedures. This was a quality study aiming to identify the current treatment milestones and related wait times for each treatment modality in an effort to further optimize patient care.

Polymorphic transition and nucleation pathway of barium dititanate (BaTi2O5) during crystallization from undercooled liquid

The nucleation pathway plays an important role in vitrification, preparation of glass-ceramic composites and synthesis of metastable materials. In this paper, we studied the nucleation pathway of a novel ferroelectric BaTi2O5 (BT2) during crystallization from undercooled liquid by aerodynamic levitation (ADL) containerless processing and structural analysis. An interesting polymorphic transition of BT2 regulated by the undercooling was observed during the crystallization process: the ferroelectric monoclinic phase (γ-BT2) was fabricated at low undercoolings and the paraelectric orthorhombic metastable phase (β-BT2) was obtained from hypercooled liquid. This polymorphic transition phenomenon corresponds to a non-classical nucleation pathway: metastable β-BT2 preferentially nucleates from undercooled melt and γ-BT2 is generated from β phase by solid-state phase transition. The two-step nucleation pathway stems from the structural heredity between the undercooled liquid and crystals. A stronger structural homology exists between the undercooled melt and β-BT2 than γ-BT2 based on diffraction data and atomic configurations analysis. This structural homology coupled with nucleation barrier calculation was used to elucidate the non-classical nucleation pathway of BT2 crystallization: the similarity of the structural unit (Ti-O polyhedra) between the undercooled liquid and the metastable β-BT2 reduces the nucleation barrier and contributes to the preferential precipitation of β-like clusters. This work reveals the formation route of BT2 from cooling melt, which not only benefits the synthesis and application of this novel functional material but also provides a guideline of the crystallization process of titanates from melt at atomic level.